Indicate by check mark whether the registrant
is a large accelerated filer, an accelerated filer, a non-accelerated filer, a smaller reporting company, or an emerging growth
company. See the definitions of “large accelerated filer,” “accelerated filer,” “smaller reporting
company,” and “emerging growth company” in Rule 12b-2 of the Exchange Act.
If an emerging growth company, indicate
by check mark if the registrant has elected not to use the extended transition period for complying with any news or revised financial
accounting standards provided pursuant to Section 13(a) of the Exchange Act. ¨
The aggregate market value of the voting
and non-voting common equity held by non-affiliates computed by reference to the price at which the common equity was last sold
as of June 30, 2019 (based on the closing price of $4.30 on June 28, 2019, the last trading day of the registrant’s most
recently completed second fiscal quarter), was approximately $31,000,000. Common stock held by each officer and director and by
each person known to the registrant who owned 10% or more of the outstanding common stock have been excluded in that such persons
may be deemed to be affiliates. This determination of affiliate status is not necessarily a conclusive determination for other
purposes.
The number of outstanding shares of the
registrant’s common stock was 19,776,019 as of March 25, 2020.
Portions of the registrant’s proxy
statement for its 2020 Annual Meeting of Stockholders currently scheduled to be held on June 11, 2020 are incorporated by reference
into Part III hereof.
PART I
CAUTIONARY NOTE REGARDING FORWARD-LOOKING
STATEMENTS
This report contains
a number of “forward-looking statements.” Specifically, all statements other than statements of historical facts included
in this report regarding our financial position, business strategy and plans and objectives of management for future operations
are forward-looking statements. These forward-looking statements are based on the beliefs of management at the time these statements
were made, as well as assumptions made by and information available to management at that time. When used in this report and the
documents incorporated by reference herein, the words “anticipate,” “believe,” “estimate,”
“expect,” “may,” “might,” “will,” “continue” and “intend,”
and words or phrases of similar import, as they relate to our financial position, business strategy and plans, or objectives of
management, are intended to identify forward-looking statements. These statements reflect our view, as of the date hereof, with
respect to future events and are subject to risks, uncertainties and assumptions related to various factors.
You should understand
that the following important factors, in addition to those discussed in our periodic reports to be filed with the Securities and
Exchange Commission, or the SEC, under the Securities Exchange Act of 1934, as amended, or the Exchange Act, could affect our future
results and could cause those results to differ materially from those expressed in such forward-looking statements:
|
·
|
fluctuations in our financial results
and stock price, particularly given market conditions and the potential economic impact of COVID 19;
|
|
·
|
our need to raise additional money to
fund our operations for the next twelve months as a going concern;
|
|
·
|
risks of our clinical trials including,
but not limited to, the costs, design, initiation and enrollment (which could be adversely impacted by the coronavirus pandemic
and resulting social distancing), timing, progress and results of such trials;
|
|
·
|
our expectations related to the use of
proceeds from our financings;
|
|
·
|
our expectations regarding our ability
to fund our operating expenses and capital expenditure requirements with our cash on hand and proceeds from our financings;
|
|
·
|
our estimates regarding expenses, future
revenue, timing of any future revenue, capital requirements and needs for additional financing;
|
|
·
|
the potential advantages of our reprioritized
pipeline;
|
|
·
|
our estimates regarding cost savings related
to our reprioritized pipeline;
|
|
·
|
our estimates regarding the potential
market opportunity for our product candidates;
|
|
·
|
our ability to develop and implement our
anticipated commercialization, marketing and manufacturing capabilities and strategies;
|
|
·
|
the potential advantages of our product
candidates;
|
|
·
|
the rate and degree of market acceptance
and clinical utility of our products;
|
|
·
|
our intellectual property position;
|
|
·
|
our ability to identify additional products,
product candidates or technologies with significant commercial potential that are consistent with our commercial objectives;
|
|
·
|
our ability to attract and retain key
personnel;
|
|
·
|
the impact of government laws and regulations;
|
|
·
|
our competitive position;
|
|
·
|
developments relating to our competitors
and our industry;
|
|
·
|
our ability to maintain and establish
collaborations or obtain additional funding;
|
|
·
|
general or regional economic conditions;
|
|
·
|
changes in U.S. GAAP; and
|
|
·
|
changes in the legal, regulatory and legislative
environments in the markets in which we operate, including impacts of United States government shut-downs on our ability to raise
money and obtain regulatory approval for our products.
|
Although we believe
that our expectations (including those on which our forward-looking statements are based) are reasonable, we cannot assure you
that those expectations will prove to be correct. Should any one or more of these risks or uncertainties materialize, or should
any underlying assumptions prove incorrect, actual results may vary materially from those described in our forward-looking statements.
Except for our ongoing
obligations to disclose material information under the federal securities laws, we undertake no obligation to publicly update or
revise any forward-looking statements, whether as a result of new information, future events or any other reason. All subsequent
forward-looking statements attributable to us or any person acting on our behalf are expressly qualified in their entirety by the
cautionary statements contained or referred to herein. In light of these risks, uncertainties and assumptions, the forward-looking
events discussed in this report and the documents incorporated by reference herein might not occur.
Corporate Information
We were organized as
a corporation under the laws of the State of Florida on March 12, 2014 under the name “PGP Holdings V, Inc.” On May
5, 2014, we changed our name to Eyenovia, Inc. On October 6, 2014, we reincorporated in the State of Delaware by merging into Eyenovia,
Inc., a Delaware corporation. Our principal executive office is located at 295 Madison Avenue, Suite 2400, New York, NY 10017,
and our phone number is 917-289-1117. Our website is http://www.eyenoviabio.com. Information contained on, or
that can be accessed through, our website is not incorporated by reference into this report, and you should not consider information
on our website to be part of this report.
Overview
We are a clinical stage
ophthalmic biopharmaceutical company developing a pipeline of microdose therapeutics utilizing our patented piezo-print delivery
technology, branded the OptejetTM. Eyenovia aims to achieve clinical microdosing of next-generation formulations of
well-established ophthalmic pharmaceutical agents using its high-precision targeted ocular delivery system, which has the potential
to replace conventional eye dropper delivery and improve safety, tolerability, patient compliance and topical delivery success
for ophthalmic eye treatments. In the clinic, the Optejet has demonstrated the ability to horizontally deliver ophthalmic medication
with a success rate significantly higher than that of traditional eye drops (~90% vs. ~ 50%). Eyenovia’s technology also
can deliver up to a 75% reduction in ocular drug and preservative exposure and has demonstrated significant improvement in the
therapeutic index in drugs used for mydriasis and IOP lowering through three Phase II and two Phase III trials. Using the Optejet,
Eyenovia is developing the next generation of smart ophthalmic therapeutics which target new indications or new combinations where
there are currently no comparable drug therapies approved by the United States Food and Drug Administration, or the FDA. Eyenovia’s
microdose therapeutics follow the FDA-designated pharmaceutical registration and regulatory process. Its products are classified
by the FDA as drugs, and not medical devices or drug-device combination products.
On October 29, 2019,
we announced that we were advancing the development of our MicroLine program for the improvement in the near vision in patients
with presbyopia towards Phase III clinical studies. As a result of prioritizing MicroLine, in tandem with our MicroPine (progressive
myopia) and MicroStat (mydriasis) programs, Eyenovia deferred development activities for its MicroProst (glaucoma and ocular hypertension)
and MicroTears (red eye and itch relief lubrication) programs.
Presbyopia is a non-preventable,
age-related hardening of the lens, which causes the gradual loss of the eye’s ability to focus on nearby objects. There currently
are no known FDA-approved drugs for the improvement of near vision in patients with presbyopia, although other companies have related
therapies in their pipeline. Eyenovia plans to initiate and complete its Phase III VISION trials for MicroLine in 2020.
MicroPine is the Company’s
first-in-class topical therapy for the treatment of progressive myopia, a back-of-the-eye ocular disease associated with pathologic
axial elongation and sclero-retinal stretching affecting approximately five million people in the United States. In February 2019,
the FDA accepted Eyenovia’s investigational new drug application, or IND, to initiate its Phase III registration trial of
MicroPine (the CHAPERONE study) to reduce the progression of myopia in children. Eyenovia enrolled its first patient in the CHAPERONE
study in June 2019 and expects to complete enrollment in 2020.
MicroStat is Eyenovia’s
fixed combination formulation of phenylephrine-tropicamide for mydriasis, designed to be a novel approach for the estimated 80
million office-based comprehensive and diabetic eye exams performed every year in the United States. Eyenovia has completed its
Phase III trials for MicroStat and announced positive results from these studies, known as MIST-1 and MIST-2. With the primary
objectives of its Phase III program for MicroStat met, Eyenovia plans to submit a new drug application, or NDA, to the FDA in 2020
for marketing approval in the United States.
Results from Eyenovia’s
previous Phase II clinical trials have been published in peer-reviewed literature. Two studies evaluating mydriatic agents demonstrated
how the Optejet consistently delivered precision dosing at the volume of the eye’s natural tear film capacity of 6-8 µL,
which reduced ocular and systemic drug and preservative exposure, while demonstrating pupil dilation comparable to conventional
eye drops with fewer side effects. In the third study, Eyenovia evaluated usability, patient tolerability and IOP lowering of microdosed
latanoprost administered with the Optejet. In this study, eyes receiving microdosed latanoprost achieved IOP reduction consistent
with published literature on latanoprost eye drops, and administration of the medication was successful in a single attempt in
more than 90% of cases. Based on the results from these clinical trials, we are advancing MicroLine, MicroPine, MicroStat, and
MicroProst (should we resume the program) utilizing the 505(b)(2) pathway. Where possible, we also intend to use this pathway for
future clinical trials in new indications with significant unmet needs.
The following summarizes
our product pipeline and anticipated milestones:
Product
Candidate
|
|
Indication
|
|
Next Expected Milestones
|
MicroLine
|
|
Presbyopia
|
|
Initiate and Complete Phase III VISION Trials (2020)
|
MicroPine
|
|
Pediatric Myopia Progression
(Near-Sightedness)
|
|
Complete CHAPERONE Trial Enrollment (2020)
|
MicroStat
|
|
Mydriasis (Eye Dilation)
|
|
File NDA (2020)
|
Our Strategy
Our goal is to become
a leading ophthalmic biopharmaceutical company focused on developing and commercializing a strong pipeline of first-in-class microdose
therapeutics and a digital health platform for interactive patient care. The key elements of our strategy to achieve this goal
are:
Establish a portfolio
of first-in-class piezo-print micro-therapeutic products for multiple eye treatments through the 505(b)(2) pathway with the FDA. We
are focused on integrating our next-generation technology with therapeutic compounds already well established in the topical treatment
of ophthalmic indications. We believe that the 505(b)(2) registration pathway, which reduces development risk compared to new molecular
entity programs by working with known compounds with well-established safety and efficacy profiles, will be available for our development
pipeline. We believe our pipeline of patented micro-therapeutic product candidates will be highly differentiated by our improved
tolerability and enhanced compliance profile and that our late-stage development programs could lead to NDA submissions in novel
indications where the products can have unique dosing and therapeutic profiles. We believe that this could lead to favorable pricing
and a reduced risk of generic substitution.
Improve clinical
outcomes and patient experiences while providing an improved tolerability profile with our microdose therapeutics. We
believe the Optejet will allow for high precision targeted microdosing for multiple eye treatments, while eliminating ophthalmic
over-dosing and reducing ocular exposure to toxic preservatives and pharmacologic ingredients compared to conventional eye drop
delivery mechanisms. Our clinical trials have demonstrated similar efficacy to eye drops, improved side effect profile and enhanced
patient experience with the Optejet as compared to conventional eye drops.
Leverage our
electronic, smartphone-enabled “e-health” technology to introduce and develop patient-specific compliance monitoring
program. The Optejet’s mobile e-health technology is designed to track when a patient administers treatments,
allowing physicians to monitor patient compliance more accurately. We believe this could enhance patient compliance and improve
compliance monitoring by empowering patients and physicians with access to dynamic, real-time monitoring and compliance data for
a more intelligent, informed and personalized therapeutic paradigm.
Develop microdose
treatments for other ophthalmic diseases independently or in collaboration with third parties. The Optejet also may
be suitable for new molecular entities and applications. Leveraging our existing platform technology, Eyenovia plans to continue
developing, either independently or through strategic relationships with third parties, other product candidates for various eye
diseases that can be administered using the Optejet and additional applications for the Optejet. We have entered into an exclusive
agreement with Senju Pharmaceuticals Co., Ltd., a leading ophthalmology company in Japan, for the Asian development and commercial
rights of our therapies and technology.
Develop solutions
for ophthalmic conditions with high unmet needs and no approved therapy. We plan to target chronic ophthalmic conditions
with a high unmet medical need. By leveraging our piezo-print microdosing technology, we aim to reach conditions where there are
no approved drug therapies. For example, our MicroPine program involves a proprietary formulation of low-dose atropine intended
to slow myopia progression in the pediatric population. There are currently no commercially-available therapies in the United States
to treat this indication.
Limitations of Conventional Eye Therapies
Our microdosing platform
technology aims to address the following issues associated with conventional eye drop-based therapies:
Dosing,
administration and waste of medication
Multiple third-party
studies have confirmed challenges with administering conventional eye drops, which include overdosing, poor compliance, imprecise
dosing, variability in drop size, and difficulty with self-administration. One study in patients who were experienced in using
eye drops and undergoing treatment for glaucoma for at least six months documented that nine out of 10 patients were unable
to administer treatment correctly at the end of the six-month study. Patients on average administered almost twice the necessary
number of drops with a mean number of drops instilled at 1.8 (+/1 1.2) and one patient administered up to 8 drops at one time.
In addition, approximately 75% of patients risked bottle contamination or potential ocular trauma by having the eye drop container
touch their eyes. Another larger study in 139 patients demonstrated that the proportion of patients who were able to correctly
administer their eye drops was only 22%–30%. Similarly, other studies have demonstrated that the vast majority of patients
either overdose or do not administer the required therapy to the eye correctly, which leads to unnecessary waste of medication.
Side
effects associated with conventional macrodose therapies
Topical eye therapies
are administered using traditional eye drop pipette approaches. While average tear volume of the eye is 6–8 µL, current
eyedrop therapies can involve administration of 30–50 µL of liquid containing preservatives and pharmaceutical ingredients.
Thus, traditional drops can severely overdose the eye, which, depending on the ingredients, can be associated with ocular side
effects including hyperemia, or increased blood flow to the eye, redness, discomfort, stinging, blurred vision, burning, itching,
excessive tearing, eye pain, iris pigment changes, foreign body sensation, pigment discoloration, periorbital dermatitis and sunken
eye. For some topical medications, there also can be cardiovascular side effects such as changes in heart rate and arrhythmia that
are caused when medications are absorbed into the circulation system from overdosing both through conjunctiva absorption and when
drugs flow into the nose through the naso-lacrimal duct and are absorbed into the systemic circulation or swallowed. For example,
phenylephrine can cause cardiovascular adverse reactions including an increase in blood pressure, syncope, myocardial infarction,
tachycardia, arrhythmia and subarachnoid hemorrhage. Severe respiratory reactions and cardiac reactions, including death due to
bronchospasm in patients with asthma, and rarely death in association with cardiac failure, have been reported following systemic
or ophthalmic administration of timolol maleate.
MicroStat contains
phenylephrine and tropicamide. However, as demonstrated in our Phase III study for this product candidate, patients administering
MicroStat reported few ocular adverse events and no systemic adverse events when they administered our microdosed product candidate.
Compared with historical data for traditional eye drops, MicroStat appeared to be much better tolerated, with low systemic absorption
of phenylephrine alone.
With the Optejet, we
believe that the known adverse event profile of pilocarpine, including headaches, also may be moderated to make MicroLine the preferred
choice for presbyopia over potential pilocarpine drop options. The same is true with MicroPine, where we believe that microdosing
may result in a better tolerated product for children.
Our Solution: The Optejet
The Optejet dispenser
delivers doses of 6 – 8 µL, directly coating the corneal surface where 80% of intraocular drug penetration
occurs. We believe that microdosing may reduce drug and toxic preservative exposure by more than 75%, thus reducing ocular irritation,
and resulting in potentially gentler treatments without compromising the desired clinical effect. Our approach could also reduce
inadvertent waste associated with poor administration of conventional macrodose drops.
We believe that we
are one of the only companies with clinical stage technology for targeted microdosing of ophthalmic investigational therapies having
fully completed the Phase III clinical studies needed to serve as the basis for an NDA submission. The Optejet is based on piezo-print
technology, which is also used for pixel-sharp high-precision inkjet printing. The technology is optimized for and applied in ophthalmic
delivery to achieve microdosing that can be many times more precise than conventional eye droppers. In addition, our smart, electronic
system provides the capability to track when patients administer their medications and deliver this information to patients and
physicians via Bluetooth connectivity. Thus, physicians can make decisions regarding therapeutic regimens with knowledge of patient
compliance.
The FDA has provided
written feedback that our clinical development activities will be treated as drug development programs, because only the drug comes
into contact with the eye. Consequently, we do not anticipate needing separate FDA approval for the Optejet dispenser or being
required to comply with FDA medical device regulations.
Microdose administration
of topical ophthalmic drugs with the Optejet has been tested in preclinical models and clinical trials and shown to provide many
advantages over administrations of eye drops. Key advantages of the Optejet include:
Dose reduction: Our microdose
delivery technology is designed to achieve precise volumetric control at the microliter level to deliver 6–8 µL, which
is the physiologic capacity of the tear film. This compares favorably to the volume of an eye drop (30–50 µL), which
can result in overdosing, ocular toxicity and systemic leaching into the plasma.
Targeted dose
instillation: The Optejet allows for targeted delivery to the ocular surface and cornea, avoiding the conjunctival cul-de-sac.
The micro-jet spray created by the piezo-electric vibrations is columnated and focused to provide accurate delivery to the corneal
surface where the majority of ocular penetration occurs. Additionally, the Optejet is designed with an LED targeting mechanism
to facilitate proper positioning and objective alignment, thus increasing the likelihood of successful dose delivery.
Speed of delivery:
Our piezo-print technology is similar to high-precision ink-jet printing. Unlike a simple aerosolized mechanism, the Optejet is
designed with ejection control that creates a fast and targeted micro-jet delivery. Solution is dispensed to the ocular surface
in less than 100 milliseconds between the time the first droplet hits the corneal surface to the completion of dose delivery, which
is faster than the average involuntary blink response time.
Smart electronics:
A key feature of the Optejet is the embedded electronic, smartphone enabled “e-health” system, which we believe is
the first intelligent electronic delivery system for ophthalmic therapies. Our electronic functions are designed to enable patients
and physicians to track when doses are administered. We believe this technology will improve compliance and chronic disease management
by empowering patients and physicians with access to dynamic, real time monitoring and compliance data for a more intelligent and
personalized therapeutic paradigm.
Clinical Trial Results
We have an established
platform for microdose administration of ophthalmic solutions. Our preclinical and clinical studies suggest that a microdose of
approximately 8 µL of medication results in clinical efficacy comparable to that of traditional eye drops, with the advantages
of fewer ocular side effects and less systemic exposure. We can use our platform technology with either new or existing molecular
entities. We have chosen the latter path for our initial pipeline product candidates.
Prior to initiation
of our Phase III clinical studies, we conducted multiple preclinical and early phase studies to validate our piezo-print microdose
delivery platform. Data from a canine model of glaucoma demonstrated more than 40% IOP lowering effect at microdose of 8–9
µL latanoprost. Another independent microdose study published in the Journal of Investigative Ophthalmology and Visual Science
in 2014 further demonstrated that 3 µL microdose with timolol 0.5% can reduce systemic plasma levels of the drug by a factor
of 17.
Diurnal IOP Lowering Effect of a Microdose
of Latanoprost Delivered by Pipette vs. Piezo-Print Dispenser in a Canine Model
IOP Lowering Effect of Micro-Therapeutic
Dose of Latanoprost in Canine Model
The
Phase II EYN-1601 clinical trial compared the mydriatic effect of phenylephrine 10% microdosed (~7 µL in volume) with the
Optejet (EYN) to phenylephrine 10% (PE 10%) and phenylephrine 2.5% (PE 2.5%) eye drops (each ~32 µL in volume) in 24 eyes.
At 75-minute peak dilation, our microdose provided similar mydriatic results (at approximately 1/4 of the dose exposure) to the
10% phenylephrine drops, and superior activity compared to 2.5% phenylephrine drops.
Shown below is mean
pupil diameter change from baseline for the 24 eyes studied. The asterisk at t=75 min indicates EYN is statistically better than
PE 2.5% (p=0.009).
Pupil
Diameter, Increase from Baseline, MM
This study was also
informative with regard to systemic drug exposure of these topical treatments. As shown below, microdosed phenylephrine 10% (EYN1)
demonstrated 35–40% lower plasma levels as compared with phenylephrine 10% eye drops (PE 10%).
As shown in the table
below, there were also fewer ocular adverse events in the microdosed group (EYN) suggesting an improvement in tolerability as compared
to 10% phenylephrine eye drops (PE 10%).
OCULAR ADVERSE EVENTS BY TREATMENT
|
Adverse Event Description
|
|
PE 10%
(Eyedrops)
|
|
|
EYN
(PE 10% microdose)
|
|
Ocular blurriness
|
|
|
1
|
|
|
|
0
|
|
Ocular burning/stinging/irritation
|
|
|
4
|
|
|
|
1
|
|
Ocular dryness
|
|
|
2
|
|
|
|
0
|
|
Subtotal by Treatment Group
|
|
|
7
|
|
|
|
1
|
|
The EYE-103 study investigated
a combination of phenylephrine and tropicamide microdose treatment administered using the Optejet compared to conventional eye
drops in 102 subjects (204 eyes). In this study, microdosing produced equivalent pupil dilation to eye drops and 91% of participants
preferred medication administration with the Optejet versus eye drops (6% preferred eye drops, while 3% expressed no preference
[p < 0.0001]). On a scale of 1 to 10, with 10 being most favorable, general satisfaction scores were higher with Optejet administration
versus eye drops (9.8 ± 0.6 for Optejet vs 5.8 ± 3.0 for eye drops). Ocular comfort scores were nearly two times
better with the Optejet than with eye drops.
In 2018, Eyenovia completed
a third early phase trial (EYN-POC-PG-21) to extend the findings of the two previous trials evaluating Optejet administration of
mydriatic agents. This study was a single-center, open-label, prospective, crossover design evaluating the usability, patient tolerability,
and proof-of-concept of microdose administration of commercial latanoprost 0.005% using the Optejet. Thirty healthy volunteer subjects
(60 eyes) were evaluated for eligibility and consented to study participation. Subsequently, at each of three treatment visits,
IOP was measured in the morning. Afterwards, on Treatment Days 1 and 2, a single 8-µL microdose of latanoprost 0.005% ophthalmic
solution was administered to each eye using the Optejet. On the morning of Treatment Day 3, each subject received 2 × 8-µL
Optejet microdoses (administered approximately 5 minutes apart) in one eye and the other eye received a single eye drop of latanoprost
0.005% ophthalmic solution. For each treatment day, IOP was measured 1, 7, 12, and 24 hours after receiving medication and a mean
diurnal IOP (DIOP) was calculated from the four readings. As shown below, mean DIOP after medication administration on Days 1 and
2 was lowered by 25.0% and 28.7%, respectively.
Mean bilateral DIOP and percent change
in DIOP in eyes dosed using the Optejet through
Treatment Day 2 (N = 29 pairs of eyes
from 29 evaluable subjects)
As shown below, on
Day 3, mean DIOP was 35.5% lower than baseline for eyes receiving microdose latanoprost 0.005% using the Optejet, and 35.0% lower
than baseline for eyes receiving a single drop of latanoprost 0.005%.
DIOP
at Day 3 (N=29 Eyes of 29 Subjects per Treatment)
No clinically significant
changes were noted in slit lamp observations (including hyperemia) for any subjects who received study treatment and no adverse
events were reported. Subjects reported no-to-negligible ocular discomfort after medication administration using the Optejet.
Investigator-administered
medication using the Optejet was evaluated in 60 eyes (1 spray/eye) on Days 1 and 2, and in 30 eyes (2 sprays/eye) on Day 3. Optejet
administration was successful on the first attempt in 172 of the 180 cases (96%). Subject head movement and/or blinking and investigator
proficiency with Optejet use resulted in the need for additional administration in the remaining 4% of cases, the majority of which
(6/8) occurred on Day 1. Administration success was achieved on the first attempt on all Day 3 cases. There were no reports of
unintentional overdosing, tear fluid overflow, or the dispenser nozzle touching the eye.
In a separate evaluation,
subjects were trained on Optejet self-administration with sterile water and then asked to demonstrate Optejet use in each eye during
the afternoon of each treatment day. By the afternoon of Day 3, qualified Eyenovia representatives judged that almost 90% of subjects
were able to demonstrate accurate self-administration using the Optejet.
This study demonstrated
Optejet medication administration to be easy to perform, safe, and comfortable to study subjects. Additionally, Optejet microdose
administration of 0.005% latanoprost resulted in mean DIOP reduction similar to reported literature for use of latanoprost 0.005%
ophthalmic solution administered as traditional eye drops.
Based on the results
of these studies further validating microdose delivery of ophthalmic medication, we initiated Phase III programs in mydriasis in
late 2018 and progressive myopia in 2019.
Our Product Candidates
In 2019, Eyenovia advanced
the development of its MicroLine program for the improvement in near vision in patients with presbyopia towards Phase III clinical
studies. As a result of prioritizing MicroLine, in tandem with its MicroPine (progressive myopia) and MicroStat (mydriasis) programs,
the Company deferred development activities for its MicroProst (glaucoma and ocular hypertension) and MicroTears (red eye and itch
relief lubrication) programs.
MicroLine
MicroLine is our proprietary
microdosed version of pilocarpine, a common ophthalmic medication that can dose-dependently induces miosis, or a contraction of
the pupil. It is a direct acting cholinergic parasympathomimetic agent that stimulates muscarinic acetylcholine receptors present
on smooth muscles, including those in the iris and ciliary body. As a result, pilocarpine causes contraction of the iris sphincter
muscle, which causes miosis.
Reducing pupil size
with pilocarpine has been shown to improve near visual acuity in individuals who have presbyopia. In Benozzi et al, 2012, subjects
aged 45‒50 years who bilaterally self-administered both pilocarpine 1% and diclofenac 0.1% eyedrops every 6 hours during
the day for up to 5 years reported good improvement in near vision without compromising distance vision. Thus, pilocarpine’s
miotic effect may be useful in treating the increasingly compromised near vision that parallels the development of presbyopia.
Background of
Presbyopia and Market Opportunity
Presbyopia is the gradual
decrease in the ability of the eye’s natural lens to accommodate in near vision, resulting in a loss of focus on near objects.
In general, onset is around age 40 and is almost universal in adults over the age of 60. In the United States, there are approximately
113 million people with presbyopia; 20 million of them are between the ages of 45 and 65.
For many people, presbyopia
is among the first overt signs of aging. There are psychological factors accompanying the use of spectacles and bifocals for the
first time, as well as situational inconvenience for either not being able to see well or having to use a vision aiding device.
With MicroLine, we plan to introduce a pharmaceutical option for improving near vision that can work as a companion to spectacles,
for when patients wish not to use their reading glasses. Our market research indicates high interest in the product concept among
people aged 45 – 60 years, representing a potential market of presbyopes of up to 15 million people.
Phase III Clinical
Development Programs
We plan to evaluate
whether topical ocular microdosing of pilocarpine using the Optejet dispenser in presbyopic individuals can effectively improve
near vision without compromising distance vision and without causing the undesirable side effects of traditionally administered
pilocarpine. Our two Phase III studies, VISION-1 and VISION-2, are planned to enroll and complete in 2020. These studies will evaluate
the safety, tolerability, and efficacy of an Optejet-administered microdosing of pilocarpine 1% (approximately 0.080 mg/dose) and
2% (approximately 0.160 mg/dose) ophthalmic solutions versus placebo.
MicroPine
A key therapeutic program
for Eyenovia is our first-in-class topical treatment for progressive myopia, a back-of-the-eye disease.
Background of
Progressive Myopia and Market Opportunity
Myopia is an ocular
disorder that results in blurry vision when looking at distant objects. This happens when the eyeball is too long or corneal curvature
is too steep causing light entering the eye to be incorrectly focused. Myopia is one of the most common refractive errors seen
in children. Myopia that is present in young children tends to increase through the school years. As myopia progresses, so does
the risk of retinal detachment, cataracts, myopia maculopathy and even blindness. It is estimated that there are over 80 million
children diagnosed with myopia worldwide and over 12 million in the United States between the ages of 5 and 13. Progressive myopia
is estimated to affect close to half of these children in the United States.
Examples of Retinal Changes Due to Myopia
Progressive Myopia with Retinal Atrophy
Changes
While currently there are no FDA-approved
therapies for myopia progression, there is growing evidence of the therapeutic benefit of topical atropine ophthalmic solution,
an anticholinergic agent used for pupil dilation and treatment of lazy eye, as a treatment to slow progression. Academic groups
have demonstrated that low dose atropine solution reduces myopia progression 60-70%, with sustained effect through three years.
A recent therapeutic evidence assessment and review by the American Academy of Ophthalmology, indicates Level 1 (highest) evidence
of efficacy for low dose atropine for reduction of progressive myopia (Ophthalmology 2017;124:1857-1866; Ophthalmology 2016; 123(2)
391:399)). While atropine 1% ophthalmic solution is FDA-approved and commercially available in the United States for pupil dilation
and treatment of lazy eye, commonly reported side effects such as burning and stinging during drop administration, and blurred
vision and light sensitivity associated with its use make it undesirable for the treatment of progressive myopia in the pediatric
population, thus impeding the drug’s clinical utility and adoption for myopia progression.
Our MicroPine program involves the development
of a micro-formulation (dilute and low volume) of atropine ophthalmic solution for reduction of myopia progression in children.
Phase III Clinical
Development Program
The FDA accepted Eyenovia’s
IND to initiate our single Phase III registration trial of MicroPine (the CHAPERONE study) to reduce the progression of myopia
in children. Eyenovia enrolled its first patient in the CHAPERONE study in June 2019 and expects to complete enrollment in 2020.
The trial is a U.S.-based, multi-center, randomized, double-masked study enrolling more than 400 children and adolescents. Participants
will be equally randomized to receive nightly treatment with either of two MicroPine treatment concentrations or a placebo control
arm. The primary assessment of efficacy is based on reduction in myopia progression after 3 years of medication use. If the primary
objectives of our Phase III study are met, we plan to submit an NDA based on this study as well as existing literature demonstrating
the efficacy of low-dose atropine to reduce the progression of myopia in children to the FDA for marketing approval of MicroPine
to slow the progression of myopia under the 505(b)(2) pathway.
MicroStat
MicroStat is the potentially
first-in-class fixed combination micro-formulation product candidate for mydriasis (eye dilation) intended to facilitate the estimated
80 million office-based comprehensive and diabetic eye exams and four million ophthalmic surgical dilations performed every year
in the United States. Our fixed combination product has been developed to facilitate efficient pupil dilation with the potential
to reduce unintended effects of conventionally administered mydriatic agents. We believe the market for MicroStat exceeds $250
million in the United States alone.
Background of Mydriasis and Market
Opportunity
There are more than
an estimated 80 million topical mydriatic applications performed every year as a required part of the comprehensive dilated eye
exam and standard retina fundoscopy for diabetic retinopathy screening, macular degeneration evaluation, glaucoma optic disc evaluation
and many other back-of-the-eye conditions. There are an additional estimated four million applications for ocular surgery. Most
optometrist and ophthalmologist offices maintain bottles of both phenylephrine and tropicamide eyedrops and use the drops in combination.
Each bottle is used on multiple patients, which carries a risk of contamination and ocular infection. The bottles are purchased
directly from suppliers and are not subject to insurance reimbursement. Our combination therapy, if approved, will allow the purchase
of one product for eye dilation. Additionally, the Optejet does not come in direct contact with the eye, thus minimizing the risk
of infection.
Most dilated eye
exams require two separate topical pharmacologic agents/drops be administered sequentially (tropicamide, followed by
phenylephrine). All current mydriatic formulations use conventional macrodose drop delivery (30–50 µL), which can
significantly overdose the ocular surface whose physiologic capacity is only 6–8 µL. Studies demonstrate that
standard macrodosed pharmacologic dilation is associated with significant ocular discomfort and mild-moderate eye pain. On
the standard visual analogue scale for pain, such discomfort can exceed the levels of pain associated with a flu vaccine
subcutaneous injection. Additionally, there are systemic safety concerns with mydriatic macrodosing for retinopathy of
prematurity retinal screening and pediatric dilated eye exams. Studies comparing microdosed phenylephrine and cyclopentolate
to traditional eye drops (30–50 µL drop size) in premature babies and in full-term infants have shown equivalent
pupil dilation with drop sizes ranging from 5–8 µL while reducing systemic levels by more than 50%.
With millions of patients
exposed to mydriatic pharmacologic agents every year, we are developing a microdose alternative whereby the Optejet can be deployed
to reduce ocular and systemic exposure by more than 75%. This potential improvement stems from lowering the dose from the 30–50
µL in standard drops to just 8 µL with MicroStat combined with targeted delivery to the ocular surface. We expect to
achieve similar mydriatic activity as drops without the high incidence of unwanted side effects.
Pharmacologic mydriasis: dilated pupil
after application
Phase III Clinical Development Program
We initiated Phase
III clinical trials of fixed-combination phenylephrine 2.5% and tropicamide 1% administered using the Optejet for mydriasis in
November 2018.
The MicroStat program
consisted of two Phase III randomized, controlled, cross-over clinical studies evaluating pupil dilation with our fixed combination
product (MicroStat) in comparison with the individual drug components (phenylephrine 2.5% and tropicamide 1%, respectively) (the
MIST-1 study), and with a placebo (the MIST-2 study). The primary endpoint for each study was the mean change in pupil diameter
at 35 minutes post-drug administration.
The MIST-1 study was
a double-masked, active-controlled, three-period cross-over superiority study evaluating MicroStat ophthalmic solution versus the
two individual drug components contained in MicroStat (phenylephrine 2.5% and tropicamide 1% ophthalmic solutions). All study drugs
were administered using the Optejet.
Volunteer participants
were evaluated for study eligibility during a screening visit and enrolled after providing study consent. Subjects meeting all
inclusion/exclusion criteria were scheduled for three treatment visits, which occurred at least two days, but no more than seven
days apart. At each treatment visit, baseline measurements were taken, then one of the three study drugs was administered to both
eyes in two separate instances, approximately five minutes apart. Afterwards, efficacy and safety assessments were performed at
specific time intervals, including pupil diameter measured by digital pupillometry in highly photopic conditions established by
using a fully-charged transilluminator at the brightest setting. Subjects were equally randomized to receive all three treatments
according to one of the six possible sequences of study drug administration.
The MIST-1 study was
double-masked so that there were no differences in drug presentation. Study drug administration was performed by seven different
trained personnel during the trial. To maintain masking, personnel who administered study drug were not allowed to perform post-drug
administration ophthalmic assessments.
A total of 64 subjects
were randomized to receive the study drug. Two subjects withdrew after the first treatment visit; therefore, the resulting per-protocol
analysis population consisted of 62 subjects (124 eyes). Mean pupil diameter for each eye at baseline and at 35 minutes post-drug
administration is shown graphically below. At 35 minutes, the treatment group difference between MicroStat and tropicamide 1% was
0.440 mm (SE 0.1839), which was statistically significant (p = 0.0183). The treatment group difference between MicroStat and phenylephrine
2.5% at the same timepoint was 3.638 mm (SE 0.1817), which was also statistically significant (p <0.0001). Since the null hypothesis
was rejected for both sets of comparisons, the primary endpoint was met.
Pupil Diameter by Treatment at Baseline
and 35 Minutes
(PP Population)
Mean ± Standard Deviation
Tx A = phenylephrine 2.5%-tropicamide
1%; Tx B = tropicamide 1%; Tx C = phenylephrine 2.5%.
As
shown below, at 35 minutes post-drug administration, MicroStat achieved a clinically meaningful pupil diameter ≥ 6.0 mm in
95.2% of right eyes and 93.5% of left eyes compared to a lower proportion for tropicamide 1% (79.0% and 77.4% of right and left
eyes, respectively) and for phenylephrine 2.5% (1.6% for both right and left eyes). MicroStat also achieved a pupil diameter ≥
7.0 mm in 67.7% of right and left eyes compared to a lower proportion for tropicamide 1% (43.5% and 41.9% or right and left eyes,
respectively) and for phenylephrine 2.5% (0% for right and left eyes).
Proportion of Eyes Achieving Pupil Diameter
≥ 6.0 mm and ≥ 7.0 mm at 35 Minutes
(PP Population)
35 Min Post Dose
|
|
MicroStat
|
|
|
Tropicamide 1%
|
|
|
Phenylephrine 2.5%
|
|
Combined
Visits
(1, 2, 3)
|
|
OD
(N=62)
|
|
|
OS
N=62)
|
|
|
OD
(N=62)
|
|
|
OS
N=62)
|
|
|
OD
(N=62)
|
|
|
OS
N=62)
|
|
Pupil diameter ≥ 6.0 mm
|
|
|
59 (95.2
|
)%
|
|
|
58 (93.5
|
)%
|
|
|
49 (79.0
|
)%
|
|
|
48 (77.4
|
)%
|
|
|
1 (1.6
|
)%
|
|
|
1 (1.6
|
)%
|
Pupil diameter < 6.0 mm
|
|
|
3 (4.8
|
)%
|
|
|
4 (6.5
|
)%
|
|
|
13 (21.0
|
)%
|
|
|
14 (22.6
|
)%
|
|
|
61 (98.4
|
)%
|
|
|
61 ( 98.4
|
)%
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Pupil diameter ≥ 7.0 mm
|
|
|
42 (67.7
|
)%
|
|
|
42 (67.7
|
)%
|
|
|
27 (43.5
|
)%
|
|
|
26 (41.9
|
)%
|
|
|
0
|
|
|
|
0
|
|
Pupil diameter < 7.0 mm
|
|
|
20 (32.3
|
)%
|
|
|
20 (32.3
|
)%
|
|
|
35 (56.5
|
)%
|
|
|
36 (58.1
|
)%
|
|
|
62 (100.0
|
)%
|
|
|
62 (100.0
|
)%
|
The rate of treatment
emergent adverse events, or TEAEs, was low, and consistent with those observed with commercially available dilating eye drops (e.g.
blurry vision and stinging). Two TEAEs were reported in the MicroStat eyes, while four TEAEs were reported in each of the other
two treatment groups. All events were mild in nature. No non-ocular adverse events were reported.
The MIST-2 Study was
a multi-center, double-masked, placebo-controlled, three-period crossover superiority study evaluating MicroStat ophthalmic solution
versus placebo. Both study drugs were administered using the Optejet.
Volunteer participants
were evaluated for study eligibility during a screening visit and enrolled after providing study consent. Subjects meeting all
inclusion/exclusion criteria were scheduled for three treatment visits, which occurred at least two days, but no more than seven
days apart. A two-sequence, three-period crossover design was used. At each treatment visit, baseline measurements were taken,
then either the investigational drug or the placebo was administered to both eyes in two separate instances, approximately five
minutes apart. Only one study drug was administered per treatment visit, and subjects were equally randomized to one of two sequences,
ABB and BAA, where A was the Eyenovia fixed combination and B was placebo. Afterwards, efficacy and safety assessments were performed
at specific time intervals, including pupil diameter measured by digital pupillometry in highly photopic conditions established
by using a fully-charged transilluminator at the brightest setting.
Like MIST-1, this study
was double-masked so that there were no differences in drug presentation. Study drug administration was performed by five different
trained personnel and, to maintain masking, personnel who administered study drug were not allowed to perform post-drug administration
ophthalmic assessments.
A total of 70 subjects
at two investigational sites were randomized to receive study drug. One subject withdrew after the first treatment visit; therefore,
the resulting per-protocol analysis population consisted of 69 subjects (138 eyes). Mean pupil diameter for each eye at baseline
and at 35 minutes post-drug administration is shown graphically below. At 35 minutes, the treatment group difference between MicroStat
and placebo was 4.63 mm (SE 0.0544), which was highly statistically significant (p < 0.0001); consequently, the null hypothesis
was rejected and the primary endpoint was met.
Pupil Diameter by Eye and Treatment at
Baseline and 35 Minutes
(PP Population)
Mean ± Standard Deviation
As shown in the table below, at 35 minutes
post-drug administration, MicroStat achieved a clinically meaningful pupil diameter ≥ 6.0 mm in 92.8%% of right eyes and
94.2% of left eyes and pupil diameter ≥ 7.0 mm in 69.6% of right and 68.1% of left eyes. None of the eyes in the placebo
group achieved similar dilation.
Proportion of Eyes Achieving Pupil Diameter
≥ 6.0 mm and ≥ 7.0 mm at 35 Minutes
(PP Population)
35
Min Post Dose
|
|
MicroStat
|
|
|
Placebo
|
|
Combined
Visits (1, 2, 3)
|
|
OD
(N=69)
|
|
|
OS
(N=69)
|
|
|
OD
(N=69)
|
|
|
OS
(N=69)
|
|
Pupil
diameter ≥ 6.0 mm
|
|
|
64
(92.8
|
)%
|
|
|
65
(94.2
|
)%
|
|
|
0
|
|
|
|
0
|
|
Pupil
diameter < 6.0 mm
|
|
|
5
(7.2
|
)%
|
|
|
4
(5.8
|
)%
|
|
|
69
(100.0
|
)%
|
|
|
69
(100.0
|
)
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Pupil
diameter ≥ 7.0 mm
|
|
|
48
(69.6
|
)%
|
|
|
47
(68.1
|
)%
|
|
|
0
|
|
|
|
0
|
|
Pupil
diameter < 7.0 mm
|
|
|
21
(30.4
|
)%
|
|
|
22
(31.9
|
)%
|
|
|
69
(100.0
|
)%
|
|
|
69
(100.0
|
)
|
Two TEAEs (one event of mild instillation
site pain and one event of moderate photophobia) were reported in the MicroStat group, while none were reported with the use of
placebo. No non-ocular adverse events were reported. Essentially pain-free mydriasis was achieved without the use of a topical
anesthetic, which is often the practice.
The outcomes of MIST-1
and MIST-2 are consistent. As shown below, in both studies, MicroStat achieved a mean change in pupil size between 4.6 mm and 4.8
mm at 35 minutes post-dose. In both studies, between 93% and 95% of eyes treated with the fixed combination mydriatic drug achieved
a pupil diameter ≥ 6.0 mm at this same timepoint. Additionally, in MIST-1, the median time to maximum post-baseline pupil
diameter with ≥ 1.0 mm increase from baseline for fixed combination solution was 73.0 minutes, while in MIST-2, it was 71.0
minutes.
Efficacy of MicroStat in MIST-1 and MIST-2
Studies (PP Populations)
|
|
MIST-1
|
|
MIST-2
|
Mean change in pupil diameter from baseline at 35 minutes
|
|
4.6 mm right eyes
4.7 mm left eyes
|
|
4.7 mm right eyes
4.8 mm left eyes
|
Proportion of eyes with pupil diameter ≥ 6.0 mm at 35 minutes
|
|
95.2% of right eyes
93.5% of left eyes
|
|
92.8% of right eyes
94.2% of left eyes
|
Median time to maximum post-baseline pupil diameter with ≥ 1.0 mm increase from baseline
|
|
73.0 minutes
|
|
71.0 minutes
|
The consistency of
these results validates the robustness of the study designs and demonstrates the impressive treatment effect of MicroStat. More
generally, these outcomes serve to further validate the bioavailability and efficacy of Optejet drug administration to the ocular
surface.
With the primary objectives
of our Phase III program met, we plan to submit an NDA to the FDA for marketing approval in the United States in 2020. Outside
the United States, we have entered into a licensing partnership for MicroStat with Senju Pharmaceuticals for commercialization
in Asia, including China, Japan and India.
Our Technology
The Optejet comes in
two parts:
|
·
|
the base contains the electronic components which enable generation of control signals designed to ensure consistent, accurate columnated arrays of micro-droplets, as well as dose tracking via Bluetooth connectivity; and
|
|
·
|
the disposable cartridge which contains the drug formulation in a primary drug container, targeted dosing system and piezo-driven ejector nozzle, and comes in one-month doses.
|
For
administration of our product candidates, the patient receives both the base and the disposable cartridge. For refills, the
patient receives only the disposable cartridge. Patients deliver their dose by attaching the cartridge to the base, pressing
an activation button which loads a single drug dose, then, holding it between one and two inches from the eye while looking
directly into an illuminated circle, pressing a second button to emit the micro-droplet delivered medication. The
micro-droplets are emitted in a quickly repeating array, that in aggregate form a micro-jet. Solution is dispensed to the
ocular surface in less than 100 milliseconds between the time the first droplet hits the corneal surface to the completion of
dose delivery, which is faster than the average involuntary blink response time. The patient feels a wet sensation on
the eye, but does not experience any pain, as demonstrated in studies to date. Several acute clinical trials have been
performed to date that demonstrate the Optejet’s usability. As a precise and quick-delivered microdose, it does not
drip down the face or drain down the naso-lacrimal duct thereby minimizing delivery of extra product or preservatives to the
eye. The rechargeable base has intelligent power management and precision designed circuitry that maximizes battery life
allowing for infrequent recharging, while providing consistent dose delivery over the life of each cartridge.
Our system is based
on piezo-driven printer technology, which is also used for high-precision ink jet printing. In ink jet printing, piezo technology
enables ink to be sprayed with precision to form letters and numbers on paper. Our patented system takes aspects of piezo driven
printer technology, and applies it to the delivery of therapeutics to the eye.
Sales and Marketing
In light of our development
stage, our commercial organization is focused on establishing relationships with potential strategic partners, key opinion leaders
and medical organizations. These relationships will be important to the rapid acceptance and uptake of our products once they become
available. We are also assessing sales, reimbursement and distribution strategies to maximize the value of our assets in development.
We have licensed commercialization rights in Asia to Senju Pharmaceuticals and have retained global commercial rights for our product
candidates in all other regions. As partial consideration, Senju Pharmaceuticals purchased $5 million of our Series A preferred
stock in April 2015 (which subsequently converted to shares of our common stock in connection with our initial public offering).
Pursuant to the exclusive license agreement, Senju Pharmaceuticals also agreed to pay us royalties equal to 5% of the net sales
(excluding manufacturing costs, rebates and other charges) for the licensed products sold by Senju Pharmaceuticals on a semi-annual
basis until the expiration of all patents or pending patent applications covering such licensed product, at which time the royalty
rate will be reduced to 1%. The royalty payment will continue, on a country-by-country basis, until the latter of the 10th year
of the first commercial sale of a licensed product in any country or the expiration of the licensed patents. Upon expiration of
the agreement, Senju Pharmaceuticals will own an exclusive, fully paid up, irrevocable and perpetual license. The exclusive license
agreement may be terminated by either party for any material breach by the other party that is not cured within 90 If so terminated
by Senju Pharmaceuticals, the license will survive the termination with no further payment obligations to us. days of receipt of
written notice by the breaching party. If so terminated by us, the license will terminate and Senju Pharmaceuticals will transfer
all rights to regulatory approvals to us, with no refund or recovery of any development costs. Senju Pharmaceuticals may also terminate
the exclusive license agreement without cause upon 60 days written notice on a country-by-country basis, in which event Senju Pharmaceuticals
will transfer all rights to regulatory approvals pertaining to any licensed product to us.
If our product candidates
receive marketing approval, we plan to commercialize them in the United States through a combination of distributors, specialty
pharmacies and our own specialty sales force. We expect to work with distribution companies or through other marketing arrangements
in the European Union and other regions outside the United States We believe that the U.S. commercial organization will initially
consist of approximately 15 sales and marketing professionals and, upon approval of MicroPine, grow to approximately 100 individuals
calling on ophthalmologists and optometrists. We expect to make hires and sign distribution agreements for commercialization following
NDA approval of any of our product candidates. Our management team and directors, which would lead the commercialization planning
of our lead product candidates, have substantial experience in the commercialization of ophthalmic therapeutics.
Manufacturing
We currently rely on
a combination of limited internal manufacturing capacity and third-party manufacturers located in the United States and abroad
to produce the product candidates for our clinical trials. We manage such production with all our vendors on a purchase order basis.
Relationships with vendors of critical components are governed by applicable service and supply agreements or purchase order terms.
We do not currently have long-term agreements with these manufacturers or any other third-party suppliers. We intend to procure
quantities on a purchase order basis for our clinical and initial commercial production. If any of our existing third-party suppliers
should become unavailable to us for any reason, we believe that there are a number of potential replacements, although we might
experience a delay in our ability to obtain alternately sourced quantities of materials or services due to their unique and specialized
nature. We also do not have any current contractual relationships for the manufacture of commercial supplies of our product candidates
if they are approved. With respect to commercial production of our product candidates in the future, we plan to outsource production
of the majority of the product candidates if they are approved for marketing by the applicable regulatory authorities.
Competition
The biotechnology and
pharmaceutical industries are characterized by rapidly advancing technologies, intense competition and a strong emphasis on proprietary
products. While we believe that our technologies, knowledge, experience and scientific resources provide us with competitive advantages,
we face potential competition from many different sources. Any product candidates that we successfully develop and commercialize
may also compete with existing therapies and new therapies that may become available in the future.
Our potential competitors
include large pharmaceutical and biotechnology companies, and specialty pharmaceutical and generic or biosimilar drug companies.
Many of our competitors have significantly greater financial and human resources and expertise in research and development, manufacturing,
preclinical testing, conducting clinical trials, obtaining regulatory approvals and marketing approved products than we do. Smaller
and other early stage companies may also prove to be significant competitors, particularly through collaborative arrangements with
large and established companies. These third parties compete with us in recruiting and retaining qualified scientific and management
personnel, establishing clinical trial sites and patient enrollment for clinical trials, as well as in acquiring products, product
candidates or other technologies that we may target to in-license or acquire in pursuit of our updated business plan.
For MicroStat, we are
not aware of any micro-therapeutics nor of any existing FDA-approved phenylephrine-tropicamide topical fixed combination even in
standard macrodose. There are competitive macrodose drop formulations of individual therapeutics such as phenylephrine and tropicamide
for mydriasis by companies such as Akorn, Alcon and others, as well as pharmacies that compound the combination on an individual
basis for physicians.
For MicroLine, we are
not aware of FDA-approved drugs for the improvement of near vision in patients with presbyopia. There are other pharmaceutical
companies developing therapies for presbyopia, none of which makes use of microdosing technology or deliver medication as a spray.
We expect that both
MicroStat and MicroLine would be “cash pay” products, as MicroStat is purchased directly by offices and used routinely
in eye exams, and MicroLine would be considered an “aesthetic” prescription product not generally covered by third
party insurance.
For MicroPine, we are
not aware of any FDA-approved drugs to slow the progression of myopia. There are other versions of traditional eye drop atropine
under development by other pharmaceutical companies for this indication. There also are versions of compounded topical atropine
that have not been tested for their safety or efficacy that are dispensed on an individual basis to patients.
Intellectual Property
Our success may depend
on our ability to obtain, maintain and enforce our proprietary rights related to our products and other technologies. We must also
operate without infringing the proprietary rights of others while preventing others from infringing our proprietary rights. We
will seek to protect our proprietary position by, among other methods, filing U.S. and foreign patent applications. We may also
rely on trade secrets and know-how for some proprietary methods, methods of manufacture, and systems and devices. We continue innovating
our technologies, and will file appropriate U.S. and foreign patent applications for our future innovations.
Patents
As of December 31,
2019, we owned nine U.S. issued and allowed utility patents, one issued design patent, and eight pending U.S. patent applications,
as well as 53 issued foreign patents, 31 pending foreign patent applications, and one pending international PCT application.
Patent coverage within
the portfolio includes issued and pending patent applications disclosing and claiming the following devices and methods:
|
·
|
A piezoelectric device configured to generate an ejected stream of droplets is the subject of one patent family. The device ejects droplets having an average ejected droplet diameter greater than 20 microns and an average initial droplet ejecting velocity between 0.5 m/s and 10 m/s. Furthermore, the stream of droplets is generated with low entrained airflow so that at least 75% of the mass is deposited on the eye. U.S. patents for these devices are expected to expire in 2031.
|
|
·
|
A method of delivering a medicament or solution to an eye with a piezo-ejector device is the subject of another patent family. The method involves delivering an average droplet size of 20 microns to 100 microns in diameter with an average initial droplet ejecting velocity between 1 m/s and 10 m/s to the eye. About 85% to 100% of the ejected mass of droplets is deposited on the eye. U.S. patents for these methods are expected to expire in 2031.
|
|
·
|
A device having a piezo-ejector that generates a directed stream of droplets through specially shaped openings in the piezo-ejector is the subject of still another patent family. The openings provide laminar flow through the openings. Laminar flow is provided by shaping the openings with a gradual slope change so that an external entry radius has a circular shape which reduces airflow while providing laminar flow through the openings. U.S. patents related to these devices are expected to expire in 2033.
|
|
·
|
A piezo-electric ejector device having a microcontroller which auto-tunes the ejector mechanism is the subject of another patent family. The device generates at least one cycle in a range of drive signal frequencies and obtains time-energy product feedback from a decay signal emitted by the actuator. U.S. patents related to these devices are expected to expire in 2033.
|
|
·
|
A method of monitoring the treatment of ophthalmic subjects by capturing images of the eye is the subject of another patent family. Images of the eye are taken which are sufficient to obtain information about the diagnosis or health of the eye. The data is stored and analyzed to monitor treatment. U.S. patents related to this method are expected to expire in 2031.
|
|
·
|
A fluid ejector having a fluid loading plate in parallel arrangement with an ejector mechanism is the subject of patent family patented in Europe. The fluid loading plate forms a capillary separation with the ejector mechanism to generate capillary fluid flow. The fluid loading plate is also attached to the reservoir (at a fluid reservoir interface) and to the ejector mechanism (at an ejector mechanism interface) and may have one or more fluid channels from the fluid reservoir interface to the ejector mechanism interface. The ejector produces a stream of droplets having a droplet diameter greater than 15 microns with the stream having low entrained airflow so that the pressure of the stream will be substantially imperceptible.
|
The expiry of any patent
depends upon the legal term for patents in that particular country. In the United States, the patent term is generally 20 years
from the earliest claimed filing date of a non-provisional patent application. In the United States, a patent’s term may
be lengthened by patent term adjustment which compensates a patentee for administrative delays by the United States Patent and
Trademark Office, or the USPTO, in examining and granting a patent. A patent term may also be shortened if a patent is terminally
disclaimed over another patent or application.
The Drug Price Competition
and Patent Term Restoration Act of 1984, or the Hatch-Waxman Act, permits a patent term extension of up to five years beyond the
expiration date of a U.S. patent as partial compensation for the length of time the drug is under regulatory review while the patent
is in force.
A patent term extension
cannot extend the remaining term of a patent beyond a total of 14 years from the date of product approval, only one patent applicable
to each regulatory review period may be extended and only those claims covering the approved drug, a method for using it or a method
for manufacturing it may be extended. We cannot provide any assurance that any patent term extension with respect to any U.S. patent
will be obtained and, if obtained, the duration of such extension. Similar patent term extension/reduction provisions are available
in the European Union and other jurisdictions. In the future, if and when our product candidates receive approval by the FDA or
foreign regulatory authorities, we will apply for patent term extensions on issued patents covering our products to the extent
available under the applicable law, depending upon the length of any such clinical trials for any product and other factors. The
expiration dates referred to above are without regard to potential patent term extension or other market exclusivity that may be
available to us. However, we cannot provide any assurances that any such patent term extension of a foreign patent will be obtained
and, if obtained, the duration of such extension.
In Asia, we have been
granted a patent in each of China and South Korea and two patents in Japan that describe a piezoelectric device configured to generate
an ejected stream of droplets with a particular droplet diameter and ejection velocity. We also have seven additional patents granted
in China, five additional patents granted in Japan, and four patents granted in Singapore, all related to aspects of the piezoelectric
device and methods of using the device.
Trademarks
Our products are marketed
under trademarks and service marks that are owned by us. The following words are trademarks in our Company’s trademark portfolio
and are the subject of either registration, or application for registration, in the United States: EYENOVIA®, OPTEJET™,
EYELATOVA™, EYETANO™.
In addition to the
trademarks noted above, we will file trademark applications for new trademarks registrations to protect our market positions in
the United States and other jurisdictions on an ongoing basis.
Proprietary Technology
In addition to patents,
we may rely on trade secrets and proprietary know-how to protect our technology. We endeavor to protect our proprietary technology
and processes in the appropriate manner to maintain their secrecy including confidentiality agreements when dealing with third
parties. We also seek to preserve the integrity and confidentiality of our data and trade secrets by maintaining physical security
of our premises and physical and electronic security of our information technology systems. We also require invention assignment
agreements with our employees, consultants, and contractors.
Government Regulation and Product Approvals
Government authorities
in the United States, at federal, state and local levels, and in other countries and jurisdictions, including the European Union,
extensively regulate, among other things, the research, development, testing, manufacture, quality control, approval, packaging,
storage, recordkeeping, labeling, advertising, promotion, distribution, marketing, post-approval monitoring and reporting, and
import and export of pharmaceutical products. The processes for obtaining regulatory approvals in the United States and in foreign
countries and jurisdictions, along with subsequent compliance with applicable statutes and regulations and other regulatory authorities,
require the expenditure of substantial time and financial resources.
Review and Approval of Drugs in the
United States
In the United States,
the FDA regulates drug products under the Food, Drug, and Cosmetic Act, or FDCA, and implementing regulations. The process of obtaining
regulatory approvals and the subsequent compliance with appropriate federal, state, local and foreign statutes and regulations
requires the expenditure of substantial time and financial resources. The failure to comply with applicable requirements under
the FDCA and other applicable laws at any time during the product development process, approval process or after approval may subject
an applicant and/or sponsor to a variety of administrative or judicial sanctions, including refusal by the FDA to approve pending
applications, withdrawal of an approval, imposition of a clinical hold, issuance of warning letters and other types of letters,
voluntary product recalls, product seizures, total or partial suspension of production or distribution, injunctions, fines, refusals
of government contracts, restitution, disgorgement of profits, or civil or criminal investigations and penalties brought by the
FDA and the Department of Justice or other governmental entities.
An applicant seeking
approval to market and distribute a new drug product in the United States must typically undertake the following:
|
·
|
completion of preclinical laboratory tests, animal studies and formulation studies in compliance with the FDA’s good laboratory practice, or GLP, regulations;
|
|
·
|
submission to the FDA of an IND which must take effect before human clinical trials may begin;
|
|
·
|
approval by an institutional review board, or IRB, an independent committee charged with protecting the rights and welfare of human research subjects participating in clinical trials, before each clinical trial site may initiate clinical trial enrollment;
|
|
·
|
performance of adequate and well-controlled human clinical trial(s) in accordance with good clinical practices, or GCP, to establish the safety and efficacy of the proposed drug product for each indication;
|
|
·
|
preparation and submission to the FDA of an NDA;
|
|
·
|
review of the product by an FDA advisory committee, where appropriate or if applicable;
|
|
·
|
satisfactory completion of one or more FDA inspections of the manufacturing facility or facilities at which the product, or components thereof, are produced to assess compliance with current Good Manufacturing Practices, or cGMP, requirements and to assure that the facilities, methods and controls are adequate to preserve the product’s identity, strength, quality and purity;
|
|
·
|
satisfactory completion of FDA audits of selected clinical trial sites to assure compliance with GCPs and the integrity of the clinical data;
|
|
·
|
payment of user fees, with few exceptions, and securing FDA approval of the NDA; and
|
|
·
|
compliance with any post-approval requirements, including Risk Evaluation and Mitigation Strategies, or REMS, and post-approval studies required by the FDA.
|
Preclinical Studies
Preclinical studies
include laboratory evaluation of the purity and stability of the manufactured drug substance or active pharmaceutical ingredient
and the formulated drug or drug product, as well as in vitro and animal studies to assess the safety and activity
of the drug for initial testing in humans and to establish a rationale for therapeutic use. The conduct of preclinical studies
is subject to federal regulations and requirements, including GLP regulations. The results of the preclinical tests, together with
manufacturing information, analytical data, any available clinical data or literature and plans for clinical trials, among other
things, are submitted to the FDA as part of an IND. Some long-term preclinical testing, such as animal tests of reproductive adverse
events and carcinogenicity, may continue after the IND is submitted.
The IND and IRB
Processes
An IND is an exemption
from the FDCA that allows an unapproved drug to be shipped in interstate commerce for use in an investigational clinical trial
and a request for FDA authorization to administer an investigational drug to humans. Such authorization must be secured prior to
interstate shipment and administration of any new drug that is not the subject of an approved NDA. In support of a request for
an IND, applicants must submit a protocol for each clinical trial and any subsequent protocol amendments must be submitted to the
FDA as part of the IND. In addition, the results of the preclinical tests, together with manufacturing information, analytical
data, any available clinical data or literature and plans for clinical trials, among other things, are submitted to the FDA as
part of an IND. The FDA requires a 30-day waiting period after the acceptance of each IND before clinical trials may begin. This
waiting period is designed to allow the FDA to review the IND to determine whether human research subjects will be exposed to unreasonable
health risks. At any time during this 30-day period, the FDA may raise concerns or questions about the conduct of the clinical
trials as outlined in the IND and impose a clinical hold. In this case, the IND sponsor and the FDA must resolve any outstanding
concerns before clinical trials can begin.
Following
commencement of a clinical trial under an IND, the FDA may also place a clinical hold or partial clinical hold on that
clinical trial. A clinical hold is an order issued by the FDA to the sponsor to delay a proposed clinical investigation or to
suspend an ongoing investigation. A partial clinical hold is a delay or suspension of only part of the clinical work
requested under the IND. For example, a specific protocol or part of a protocol is not allowed to proceed, while other
protocols may do so. No more than 30 days after imposition of a clinical hold or partial clinical hold, the FDA will provide
the sponsor a written explanation of the basis for the hold. Following issuance of a clinical hold or partial clinical hold,
an investigation may only resume after the FDA has notified the sponsor that the investigation may proceed. The FDA will base
that determination on information provided by the sponsor correcting the deficiencies previously cited or otherwise
satisfying the FDA that the investigation can proceed.
A sponsor may choose,
but is not required, to conduct a foreign clinical study under an IND. When a foreign clinical study is conducted under an IND,
all FDA IND requirements must be met unless waived. When the foreign clinical study is not conducted under an IND, the sponsor
must ensure that the study complies with FDA certain regulatory requirements in order to use the study as support for an IND or
application for marketing approval. Specifically, such studies must be conducted in accordance with good clinical practice, or
GCP, including review and approval by an independent ethics committee, or IEC, and informed consent from subjects. The FDA’s
regulations are intended to help ensure the protection of human subjects enrolled in non-IND foreign clinical studies, as well
as the quality and integrity of the resulting data. They further help ensure that non-IND foreign studies are conducted in a manner
comparable to that required for IND studies.
In addition to the
foregoing IND requirements, an IRB representing each institution participating in the clinical trial must review and approve the
plan for any clinical trial before it commences at that institution, and the IRB must conduct continuing review and reapprove the
study at least annually. The IRB must review and approve, among other things, the study protocol and informed consent information
to be provided to study subjects. An IRB must operate in compliance with FDA regulations. An IRB can suspend or terminate approval
of a clinical trial at its institution, or an institution it represents, if the clinical trial is not being conducted in accordance
with the IRB’s requirements or if the product candidate has been associated with unexpected serious harm to patients.
Additionally, some
clinical trials are overseen by an independent group of qualified experts organized by the trial sponsor, known as a data safety
monitoring board or committee. This group provides authorization for whether or not a clinical trial may move forward at designated
check points based on access that only the group maintains to available data from the study. Suspension or termination of development
during any phase of clinical trials can occur if it is determined that the participants or patients are being exposed to an unacceptable
health risk. Other reasons for suspension or termination may be made by us based on evolving business objectives and/or competitive
climate.
Information about certain
clinical trials must be submitted within specific timeframes to the National Institutes of Health, or NIH, for public dissemination
on its ClinicalTrials.gov website.
Human Clinical
Trials in Support of an NDA
Clinical trials involve
the administration of the investigational product to human subjects under the supervision of qualified investigators in accordance
with GCP requirements, which include, among other things, the requirement that all research subjects provide their informed consent
in writing before their participation in any clinical trial. Clinical trials are conducted in accordance with written study protocols
detailing, among other things, study objectives, participant inclusion and exclusion criteria, the parameters to be used in monitoring
safety and the effectiveness criteria to be evaluated.
Human clinical trials
are typically conducted in three sequential phases, which may overlap or be combined:
|
·
|
Phase I. The drug is initially introduced into healthy human subjects or, in certain indications such as cancer, patients with the target disease or condition and tested for safety, dosage tolerance, absorption, metabolism, distribution, excretion and, if possible, to gain an early indication of its effectiveness and to determine optimal dosage.
|
|
·
|
Phase II. The drug is administered to a limited patient population to identify possible adverse effects and safety risks, to preliminarily evaluate the efficacy of the product for specific targeted diseases and to determine dosage tolerance and optimal dosage.
|
|
·
|
Phase III. The drug is administered to an expanded patient population, generally at geographically dispersed clinical trial sites, in well-controlled clinical trials to generate enough data to statistically evaluate the efficacy and safety of the product for approval, to establish the overall risk-benefit profile of the product and to provide adequate information for the labeling of the product.
|
Progress reports
detailing the results of the clinical trials must be submitted at least annually to the FDA and more frequently if serious
adverse events occur. In addition, IND safety reports must be submitted to the FDA for any of the following: serious and
unexpected suspected adverse reactions; findings from other studies or animal or in vitro testing that
suggest a significant risk in humans exposed to the drug; and any clinically important increase in the case of a serious
suspected adverse reaction over that listed in the protocol or investigator brochure. Phase I, Phase II and Phase III
clinical trials might not be completed successfully within any specified period, or at all. Furthermore, the FDA or the
sponsor may suspend or terminate a clinical trial at any time on various grounds, including a finding that the research
subjects are being exposed to an unacceptable health risk. Similarly, an IRB can suspend or terminate approval of a clinical
trial at its institution, or an institution it represents, if the clinical trial is not being conducted in accordance with
the IRB’s requirements or if the drug has been associated with unexpected serious harm to patients. The FDA will
typically inspect one or more clinical sites to assure compliance with GCP and the integrity of the clinical data
submitted.
Concurrent with clinical
trials, companies often complete additional animal studies and must also develop additional information about the chemistry and
physical characteristics of the drug as well as finalize a process for manufacturing the product in commercial quantities in accordance
with cGMP requirements. The manufacturing process must be capable of consistently producing quality batches of the drug candidate
and, among other things, must develop methods for testing the identity, strength, quality, purity, and potency of the final drug.
Additionally, appropriate packaging must be selected and tested and stability studies must be conducted to demonstrate that the
drug candidate does not undergo unacceptable deterioration over its shelf life.
Submission of
an NDA to the FDA
Assuming successful
completion of required clinical testing and other requirements, the results of the preclinical studies and clinical trials, together
with detailed information relating to the product’s chemistry, manufacture, controls and proposed labeling, among other things,
are submitted to the FDA as part of an NDA requesting approval to market the drug product for one or more indications. Under federal
law, the submission of most NDAs is subject to an application user fee, which for federal fiscal year 2019 is $2,588,478 for an
application requiring clinical data. The sponsor of an approved NDA is also subject to an annual prescription drug program fee,
which for fiscal year 2019 is $309,915. Certain exceptions and waivers are available for some of these fees, such as an exception
from the application fee for drugs with orphan designation and a waiver for certain small businesses. Eyenovia is currently eligible
for a waiver of the application fees under the small business provisions.
The FDA conducts a
preliminary review of an NDA within 60 days of its receipt and informs the sponsor by the 74th day after the FDA’s receipt
of the submission to determine whether the application is sufficiently complete to permit substantive review. The FDA may request
additional information rather than accept an NDA for filing. In this event, the application must be resubmitted with the additional
information. The resubmitted application is also subject to review before the FDA accepts it for filing. Once the submission is
accepted for filing, the FDA begins an in-depth substantive review. The FDA has agreed to certain performance goals in the review
process of NDAs. Most such applications are meant to be reviewed within 10 months from the date of filing, and most applications
for “priority review” products are meant to be reviewed within six months of filing. For applications of drug products
that are not new molecular entities, FDA aims to conduct standard reviews within 10 months of receipt of the NDA and priority reviews
within six months of receipt of the NDA. The review process may be extended by the FDA for three additional months to consider
new information or clarification provided by the applicant to address an outstanding deficiency identified by the FDA following
the original submission.
Before approving an
NDA, the FDA typically will inspect the facility or facilities where the product is or will be manufactured. These pre-approval
inspections may cover all facilities associated with an NDA submission, including drug component manufacturing (such as active
pharmaceutical ingredients), finished drug product manufacturing, and control testing laboratories. The FDA will not approve
an application unless it determines that the manufacturing processes and facilities are in compliance with cGMP requirements and
adequate to assure consistent production of the product within required specifications. Additionally, before approving an NDA,
the FDA will typically inspect one or more clinical sites to assure compliance with GCP.
In addition, as a condition
of approval, the FDA may require an applicant to develop a REMS. REMS use risk minimization strategies beyond the professional
labeling to ensure that the benefits of the product outweigh the potential risks. To determine whether a REMS is needed, the FDA
will consider the size of the population likely to use the product, seriousness of the disease, expected benefit of the product,
expected duration of treatment, seriousness of known or potential adverse events, and whether the product is a new molecular entity.
REMS can include medication guides, physician communication plans for healthcare professionals, and elements to assure safe use,
or ETASU. ETASU may include, but are not limited to, special training or certification for prescribing or dispensing, dispensing
only under certain circumstances, special monitoring, and the use of patient registries. The FDA may require a REMS before approval
or post-approval if it becomes aware of a serious risk associated with use of the product. The requirement for a REMS can materially
affect the potential market and profitability of a product.
The FDA may refer an
application for a novel drug to an advisory committee or explain why such referral was not made. Typically, an advisory committee
is a panel of independent experts, including clinicians and other scientific experts, that reviews, evaluates and provides a recommendation
as to whether the application should be approved and under what conditions. The FDA is not bound by the recommendations of an advisory
committee, but it considers such recommendations carefully when making decisions.
The FDA’s
Decision on an NDA
On the basis of the
FDA’s evaluation of the NDA and accompanying information, including the results of the inspection of the manufacturing facilities,
the FDA may issue an approval letter or a complete response letter. An approval letter authorizes commercial marketing of the product
with specific prescribing information for specific indications. A complete response letter generally outlines the deficiencies
in the submission and may require substantial additional testing or information in order for the FDA to reconsider the application.
If and when those deficiencies have been addressed to the FDA’s satisfaction in a resubmission of the NDA, the FDA will issue
an approval letter. The FDA has committed to reviewing such resubmissions in two or six months depending on the type of information
included. Even with submission of this additional information, the FDA ultimately may decide that the application does not satisfy
the regulatory criteria for approval.
If the FDA approves
a product, it may limit the approved indications for use for the product, require that contraindications, warnings or precautions
be included in the product labeling, require that post-approval studies, including Phase IV clinical trials, be conducted to further
assess the drug’s safety after approval, require testing and surveillance programs to monitor the product after commercialization,
or impose other conditions, including distribution restrictions or other risk management mechanisms, including REMS, which can
materially affect the potential market and profitability of the product. The FDA may prevent or limit further marketing of a product
based on the results of post-market studies or surveillance programs. After approval, many types of changes to the approved product,
such as adding new indications, manufacturing changes and additional labeling claims, are subject to further testing requirements
and FDA review and approval.
Post-Approval
Requirements
Drugs manufactured
or distributed pursuant to FDA approvals are subject to pervasive and continuing regulation by the FDA, including, among other
things, requirements relating to recordkeeping, periodic reporting, product sampling and distribution, advertising and promotion
and reporting of adverse experiences with the product. After approval, most changes to the approved product, such as adding new
indications or other labeling claims, are subject to prior FDA review and approval.
In addition, drug manufacturers
and other entities involved in the manufacture and distribution of approved drugs are required to register their establishments
with the FDA and state agencies, and are subject to periodic unannounced inspections by the FDA and these state agencies for compliance
with cGMP requirements. Changes to the manufacturing process are strictly regulated and often require prior FDA approval before
being implemented. FDA regulations also require investigation and correction of any deviations from cGMP and impose reporting and
documentation requirements upon the sponsor and any third-party manufacturers that the sponsor may decide to use. Accordingly,
manufacturers must continue to expend time, money, and effort in the area of production and quality control to maintain cGMP compliance.
Once an approval is
granted, the FDA may withdraw the approval if compliance with regulatory requirements and standards is not maintained or if problems
occur after the product reaches the market. Later discovery of previously unknown problems with a product, including adverse events
of unanticipated severity or frequency, or with manufacturing processes, or failure to comply with regulatory requirements, may
result in revisions to the approved labeling to add new safety information; imposition of post-market studies or clinical trials
to assess new safety risks; or imposition of distribution or other restrictions under a REMS program. Other potential consequences
include, among other things:
|
·
|
restrictions on the marketing or manufacturing of the product, complete withdrawal of the product from the market or product recalls;
|
|
·
|
fines, warning letters or holds on post-approval clinical trials;
|
|
·
|
refusal of the FDA to approve pending NDAs or supplements to approved NDAs, or suspension or revocation of product approvals;
|
|
·
|
product seizure or detention, or refusal to permit the import or export of products; or
|
|
·
|
injunctions or the imposition of civil or criminal penalties.
|
The FDA strictly regulates
marketing, labeling, advertising and promotion of products that are placed on the market. Drugs may be promoted only for the approved
indications and in accordance with the provisions of the approved label. The FDA and other agencies actively enforce the laws and
regulations prohibiting the promotion of off-label uses, and a company that is found to have improperly promoted off-label uses
may be subject to significant liability.
In addition, the distribution
of prescription pharmaceutical products is subject to the Prescription Drug Marketing Act, or PDMA, which regulates the distribution
of drugs and drug samples at the federal level, and sets minimum standards for the registration and regulation of drug distributors
by the states. Both the PDMA and state laws limit the distribution of prescription pharmaceutical product samples and impose requirements
to ensure accountability in distribution.
Section 505(b)(2)
NDAs
NDAs for most new drug
products are based on two full clinical trials which must contain substantial evidence of the safety and efficacy of the proposed
new product. These applications are submitted under Section 505(b)(1) of the FDCA. The FDA is, however, authorized to approve an
alternative type of NDA under Section 505(b)(2) of the FDCA. This type of application allows the applicant to rely, in part, on
the FDA’s previous findings of safety and efficacy for a similar product, or published literature. Specifically, Section
505(b)(2) applies to NDAs for a drug for which the investigations made to show whether or not the drug is safe for use and effective
in use and relied upon by the applicant for approval of the application “were not conducted by or for the applicant and for
which the applicant has not obtained a right of reference or use from the person by or for whom the investigations were conducted.”
Thus, Section 505(b)(2)
authorizes the FDA to approve an NDA based on safety and effectiveness data that were not developed by the applicant. NDAs filed
under Section 505(b)(2) may provide an alternate and potentially more expeditious pathway to FDA approval for new or improved formulations
or new uses of previously approved products. If the Section 505(b)(2) applicant can establish that reliance on the FDA’s
previous approval is scientifically appropriate, the applicant may eliminate the need to conduct certain preclinical studies or
clinical trials of the new product. The FDA may also require companies to perform additional studies or measurements to support
the change from the approved product. The FDA may then approve the new drug candidate for all or some of the label indications
for which the referenced product has been approved, as well as for any new indication sought by the Section 505(b)(2) applicant.
Abbreviated New
Drug Applications for Generic Drugs
In 1984, with passage
of the Hatch-Waxman Amendments to the FDCA, Congress authorized the FDA to approve generic drugs that are the same as drugs previously
approved by the FDA under the NDA provisions of the statute. To obtain approval of a generic drug, an applicant must submit an
abbreviated new drug application, or ANDA, to the agency. In support of such applications, a generic manufacturer may rely on the
preclinical and clinical testing previously conducted for a drug product previously approved under an NDA, known as the reference-listed
drug, or RLD.
Specifically, in order
for an ANDA to be approved, the FDA must find that the generic version is identical to the RLD with respect to the active ingredients,
the route of administration, the dosage form, and the strength of the drug. At the same time, the FDA must also determine that
the generic drug is “bioequivalent” to the innovator drug. Under the statute, a generic drug is bioequivalent to an
RLD if “the rate and extent of absorption of the drug do not show a significant difference from the rate and extent
of absorption of the listed drug.”
Upon approval of an
ANDA, the FDA indicates whether the generic product is “therapeutically equivalent” to the RLD in its publication Approved
Drug Products with Therapeutic Equivalence Evaluations, also referred to as the Orange Book. Clinicians and pharmacists consider
a therapeutic equivalent generic drug to be fully substitutable for the RLD. In addition, by operation of certain state laws and
numerous health insurance programs, the FDA’s designation of therapeutic equivalence often results in substitution of the
generic drug without the knowledge or consent of either the prescribing clinicians or patient.
Under the Hatch-Waxman
Amendments, the FDA might not approve an ANDA until any applicable period of non-patent exclusivity for the RLD has expired. The
FDCA provides a period of five years of non-patent data exclusivity for a new drug containing a new chemical entity. For the purposes
of this provision, a new chemical entity, or NCE, is a drug that contains no active moiety that has previously been approved by
the FDA in any other NDA. An active moiety is the molecule or ion responsible for the physiological or pharmacological action of
the drug substance. In cases where such NCE exclusivity has been granted, an ANDA may not be filed with the FDA until the expiration
of five years unless the submission is accompanied by a Paragraph IV certification, in which case the applicant may submit its
application four years following the original product approval.
The FDCA also
provides for a period of three years of exclusivity if the NDA includes reports of one or more new clinical investigations,
other than bioavailability or bioequivalence studies, that were conducted by or for the applicant and are essential to
the approval of the application. This three-year exclusivity period often protects changes to a previously approved drug
product, such as a new dosage form, route of administration, combination or indication. Three-year exclusivity would be
available for a drug product that contains a previously approved active moiety, provided the statutory requirement for a new
clinical investigation is satisfied. Unlike five-year NCE exclusivity, an award of three-year exclusivity does not block the
FDA from accepting ANDAs seeking approval for generic versions of the drug as of the date of approval of the original drug
product. The FDA typically makes decisions about awards of data exclusivity shortly before a product is approved.
Hatch-Waxman Patent Certification
and the 30-Month Stay
Upon approval of an
NDA or a supplement thereto, NDA sponsors are required to list with the FDA each patent with claims that cover the applicant’s
product or an approved method of using the product. Each of the patents listed by the NDA sponsor is published in the Orange Book.
When an ANDA applicant files its application with the FDA, the applicant is required to certify to the FDA concerning any patents
listed for the reference product in the Orange Book, except for patents covering methods of use for which the ANDA applicant is
not seeking approval. To the extent that the Section 505(b)(2) applicant is relying on studies conducted for an already approved
product, the applicant is required to certify to the FDA concerning any patents listed for the approved product in the Orange Book
to the same extent that an ANDA applicant would.
Specifically, the applicant
must certify with respect to each patent that:
|
·
|
the required patent information has not been filed;
|
|
·
|
the listed patent has expired;
|
|
·
|
the listed patent has not expired, but will expire on a particular date and approval is sought after patent expiration; or
|
|
·
|
the listed patent is invalid, unenforceable or will not be infringed by the new product.
|
A certification that
the new product will not infringe the already approved product’s listed patents or that such patents are invalid or unenforceable
is called a Paragraph IV certification. If the applicant does not challenge the listed patents or indicates that it is not seeking
approval of a patented method of use, the ANDA application will not be approved until all the listed patents claiming the referenced
product have expired (other than method of use patents involving indications for which the ANDA applicant is not seeking approval).
If the ANDA applicant
has provided a Paragraph IV certification to the FDA, the applicant must also send notice of the Paragraph IV certification to
the NDA and patent holders once the ANDA has been accepted for filing by the FDA. The NDA and patent holders may then initiate
a patent infringement lawsuit in response to the notice of the Paragraph IV certification. The filing of a patent infringement
lawsuit within 45 days after the receipt of a Paragraph IV certification automatically prevents the FDA from approving the ANDA
until the earlier of 30 months after the receipt of the Paragraph IV notice, expiration of the patent, or a decision in the infringement
case that is favorable to the ANDA applicant.
To the extent that
the Section 505(b)(2) applicant is relying on studies conducted for an already approved product, the applicant is required to certify
to the FDA concerning any patents listed for the approved product in the Orange Book to the same extent that an ANDA applicant
would. As a result, approval of a Section 505(b)(2) NDA can be stalled until all the listed patents claiming the referenced product
have expired, until any non-patent exclusivity, such as exclusivity for obtaining approval of a new chemical entity, listed in
the Orange Book for the referenced product has expired, and, in the case of a Paragraph IV certification and subsequent patent
infringement suit, until the earlier of 30 months, settlement of the lawsuit or a decision in the infringement case that is favorable
to the Section 505(b)(2) applicant.
Pediatric Studies
and Exclusivity
Under the Pediatric
Research Equity Act of 2003, an NDA or supplement thereto must contain data that are adequate to assess the safety and effectiveness
of the drug product for the claimed indications in all relevant pediatric subpopulations, and to support dosing and administration
for each pediatric subpopulation for which the product is safe and effective. With enactment of the Food and Drug Administration
Safety and Innovation Act, or FDASIA, in 2012, sponsors must also submit pediatric study plans prior to the assessment data. Those
plans must contain an outline of the proposed pediatric study or studies the applicant plans to conduct, including study objectives
and design, any deferral or waiver requests, and other information required by regulation. The applicant, the FDA, and the FDA’s
internal review committee must then review the information submitted, consult with each other, and agree upon a final plan. The
FDA or the applicant may request an amendment to the plan at any time.
The FDA may, on its
own initiative or at the request of the applicant, grant deferrals for submission of some or all pediatric data until after approval
of the product for use in adults, or full or partial waivers from the pediatric data requirements. Additional requirements and
procedures relating to deferral requests and requests for extension of deferrals are contained in FDASIA. Unless otherwise required
by regulation, the pediatric data requirements do not apply to products with orphan designation.
Pediatric exclusivity
is another type of non-patent marketing exclusivity in the United States and, if granted, provides for the attachment of an additional
six months of marketing protection to the term of any existing regulatory exclusivity, including the non-patent and orphan exclusivity.
This six-month exclusivity may be granted if an NDA sponsor submits pediatric data that fairly respond to a written request
from the FDA for such data. The data do not need to show the product to be effective in the pediatric population studied; rather,
if the clinical trial is deemed to fairly respond to the FDA’s request, the additional protection is granted. If reports
of requested pediatric studies are submitted to and accepted by the FDA within the statutory time limits, whatever statutory or
regulatory periods of exclusivity or patent protection cover the product are extended by six months. This is not a patent term
extension, but it effectively extends the regulatory period during which the FDA cannot approve another application.
Patent Term Restoration
and Extension
A patent claiming a
new drug product may be eligible for a limited patent term extension under the Hatch-Waxman Amendments, which permits a patent
restoration of up to five years for patent term lost during product development and the FDA regulatory review. The restoration
period granted is typically one-half the time between the effective date of an IND and the submission date of an NDA, plus the
time between the submission date of an NDA and the ultimate approval date. Patent term restoration cannot be used to extend the
remaining term of a patent past a total of 14 years from the product’s approval date. Only one patent applicable to an approved
drug product is eligible for the extension, and the application for the extension must be submitted prior to the expiration of
the patent in question. A patent that covers multiple drugs for which approval is sought can only be extended in connection with
one of the approvals. The USPTO reviews and approves the application for any patent term extension or restoration in consultation
with the FDA. We cannot provide any assurance that any patent term extension with respect to any U.S. patent will be obtained and,
if obtained, the duration of such extension, in connection with any of our product candidates.
The 21st Century
Cures Act
On December 13, 2016,
President Obama signed the 21st Century Cures Act, or the Cures Act, into law. The Cures Act is designed to modernize and personalize
healthcare, spur innovation and research, and streamline the discovery and development of new therapies through increased federal
funding of particular programs. It authorizes increased funding for the FDA to spend on innovation projects. The new law also amends
the Public Health Service Act, or the PHSA, to reauthorize and expand funding for the NIH. The Act establishes the NIH Innovation
Fund to pay for the cost of development and implementation of a strategic plan, early stage investigators and research. It also
charges NIH with leading and coordinating expanded pediatric research. Further, the Cures Act directs the Centers for Disease Control
and Prevention to expand surveillance of neurological diseases.
With amendments to
the FDCA and the PHSA, Title III of the Cures Act seeks to accelerate the discovery, development, and delivery of new medicines
and medical technologies. To that end, and among other provisions, the Cures Act reauthorizes the existing priority review voucher
program for certain drugs intended to treat rare pediatric diseases until 2020; creates a new priority review voucher program for
drug applications determined to be material national security threat medical countermeasure applications; revises the FDCA to streamline
review of combination product applications; requires FDA to evaluate the potential use of “real world evidence”
to help support approval of new indications for approved drugs; provides a new “limited population” approval pathway
for antibiotic and antifungal drugs intended to treat serious or life-threatening infections; and authorizes FDA to designate a
drug as a “regenerative advanced therapy,” thereby making it eligible for certain expedited review and approval designations.
Review and Approval of Drug Products
in the European Union
In order to market
any product outside of the United States, a company must also comply with numerous and varying regulatory requirements of other
countries and jurisdictions regarding quality, safety and efficacy and governing, among other things, clinical trials, marketing
authorization, commercial sales and distribution of products. Whether or not it obtains FDA approval for a product, the company
would need to obtain the necessary approvals by the comparable foreign regulatory authorities before it can commence clinical trials
or marketing of the product in those countries or jurisdictions. The approval process ultimately varies between countries and jurisdictions
and can involve additional product testing and additional administrative review periods. The time required to obtain approval in
other countries and jurisdictions might differ from and be longer than that required to obtain FDA approval. Regulatory approval
in one country or jurisdiction does not ensure regulatory approval in another, but a failure or delay in obtaining regulatory approval
in one country or jurisdiction may negatively impact the regulatory process in others.
Procedures Governing
Approval of Drug Products in the European Union
Pursuant to the
European Clinical Trials Directive, a system for the approval of clinical trials in the European Union has been implemented
through national legislation of the member states. Under this system, an applicant must obtain approval from the competent
national authority of a European Union member state in which the clinical trial is to be conducted. Furthermore, the
applicant may only start a clinical trial after a competent ethics committee has issued a favorable opinion. Clinical trial
application must be accompanied by an investigational medicinal product dossier with supporting information prescribed by the
European Clinical Trials Directive and corresponding national laws of the member states and further detailed in applicable
guidance documents.
To obtain marketing
approval of a product under European Union regulatory systems, an applicant must submit a marketing authorization application,
or MAA, either under a centralized or decentralized procedure. The centralized procedure provides for the grant of a single marketing
authorization by the European Commission that is valid for all European Union member states. The centralized procedure is compulsory
for specific products, including for medicines produced by certain biotechnological processes, products designated as orphan
medicinal products, advanced therapy products and products with a new active substance indicated for the treatment of certain diseases.
For products with a new active substance indicated for the treatment of other diseases and products that are highly innovative
or for which a centralized process is in the interest of patients, the centralized procedure may be optional.
Under the centralized
procedure, the Committee for Medicinal Products for Human Use, or the CHMP, established at the European Medicines Agency, or EMA,
is responsible for conducting the initial assessment of a product. The CHMP is also responsible for several post-authorization
and maintenance activities, such as the assessment of modifications or extensions to an existing marketing authorization. Under
the centralized procedure in the European Union, the maximum timeframe for the evaluation of an MAA is 210 days, excluding clock
stops, when additional information or written or oral explanation is to be provided by the applicant in response to questions of
the CHMP. Accelerated evaluation might be granted by the CHMP in exceptional cases, when a medicinal product is of major interest
from the point of view of public health and in particular from the viewpoint of therapeutic innovation. In this circumstance, the
EMA ensures that the opinion of the CHMP is given within 150 days.
The decentralized procedure
is available to applicants who wish to market a product in various European Union member states where such product has not received
marketing approval in any European Union member states before. The decentralized procedure provides for approval by one or more
other, or concerned, member states of an assessment of an application performed by one member state designated by the applicant,
known as the reference member state. Under this procedure, an applicant submits an application based on identical dossiers and
related materials, including a draft summary of product characteristics, and draft labeling and package leaflet, to the reference
member state and concerned member states. The reference member state prepares a draft assessment report and drafts of the related
materials within 210 days after receipt of a valid application. Within 90 days of receiving the reference member state’s
assessment report and related materials, each concerned member state must decide whether to approve the assessment report and related
materials.
If a member state cannot
approve the assessment report and related materials on the grounds of potential serious risk to public health, the disputed points
are subject to a dispute resolution mechanism and may eventually be referred to the European Commission, whose decision is binding
on all member states.
Within this framework,
manufacturers may seek approval of hybrid medicinal products under Article 10(3) of Directive 2001/83/EC. Hybrid applications rely,
in part, on information and data from a reference product and new data from appropriate preclinical tests and clinical trials.
Such applications are necessary when the proposed product does not meet the strict definition of a generic medicinal product, or
bioavailability studies cannot be used to demonstrate bioequivalence, or there are changes in the active substance(s), therapeutic
indications, strength, pharmaceutical form or route of administration of the generic product compared to the reference medicinal
product. In such cases the results of tests and clinical trials must be consistent with the data content standards required in
the Annex to the Directive 2001/83/EC, as amended by Directive 2003/63/EC.
Hybrid
medicinal product applications have automatic access to the centralized procedure when the reference product was authorized for
marketing via that procedure. Where the reference product was authorized via the decentralized procedure, a hybrid application
may be accepted for consideration under the centralized procedure if the applicant shows that the medicinal product constitutes
a significant therapeutic, scientific or technical innovation, or the granting of a community authorization for the medicinal product
is in the interest of patients at the community level.
Clinical Trial
Approval in the European Union
Requirements for the
conduct of clinical trials in the European Union including Good Clinical Practice, or GCP, are set forth in the Clinical Trials
Directive 2001/20/EC and the GCP Directive 2005/28/EC. Pursuant to Directive 2001/20/EC and Directive 2005/28/EC, as amended, a
system for the approval of clinical trials in the European Union has been implemented through national legislation of the E.U.
member states. Under this system, approval must be obtained from the competent national authority of each E.U. member state in
which a study is planned to be conducted. To this end, a clinical trial application is submitted, which must be supported by an
investigational medicinal product dossier, or IMPD, and further supporting information prescribed by Directive 2001/20/EC and Directive
2005/28/EC and other applicable guidance documents. Furthermore, a clinical trial may only be started after a competent ethics
committee has issued a favorable opinion on the clinical trial application in that country.
In April 2014, the
E.U. passed the new Clinical Trials Regulation, (EU) No 536/2014, which will replace the current Clinical Trials Directive 2001/20/EC.
To ensure that the rules for clinical trials are identical throughout the European Union, the new E.U. clinical trials legislation
was passed as a regulation that is directly applicable in all E.U. member states. All clinical trials performed in the European
Union are required to be conducted in accordance with the Clinical Trials Directive 2001/20/EC until the new Clinical Trials Regulation
(EU) No 536/2014 becomes applicable. According to the current plans of EMA, the new Clinical Trials Regulation will become applicable
in 2019. The Clinical Trials Directive 2001/20/EC will, however, still apply three years from the date of entry into application
of the Clinical Trials Regulation to (i) clinical trials applications submitted before the entry into application and (ii) clinical
trials applications submitted within one year after the entry into application if the sponsor opts for old system.
The new Clinical Trials
Regulation aims to simplify and streamline the approval of clinical trial in the European Union. The main characteristics of the
regulation include: a streamlined application procedure via a single entry point, the E.U. portal; a single set of documents
to be prepared and submitted for the application as well as simplified reporting procedures that will spare sponsors from submitting
broadly identical information separately to various bodies and different member states; a harmonized procedure for the assessment
of applications for clinical trials, which is divided in two parts (Part I is assessed jointly by all member states concerned,
and Part II is assessed separately by each member state concerned); strictly defined deadlines for the assessment of clinical trial
applications; and the involvement of the ethics committees in the assessment procedure in accordance with the national law of the
member state concerned but within the overall timelines defined by the Clinical Trials Regulation.
Periods of Authorization
and Renewals
Marketing authorization
is valid for five years in principle and the marketing authorization may be renewed after five years on the basis of a re-evaluation
of the risk-benefit balance by the EMA or by the competent authority of the authorizing member state. To this end, the marketing
authorization holder must provide the EMA or the competent authority with a consolidated version of the file in respect of quality,
safety and efficacy, including all variations introduced since the marketing authorization was granted, at least six months before
the marketing authorization ceases to be valid. Once renewed, the marketing authorization is valid for an unlimited period, unless
the European Commission or the competent authority decides, on justified grounds relating to pharmacovigilance, to proceed with
one additional five-year renewal. Any authorization which is not followed by the actual placing of the drug on the European Union
market (in case of centralized procedure) or on the market of the authorizing member state within three years after authorization
ceases to be valid (the so-called sunset clause).
Data and Market
Exclusivity in the European Union
In the European Union,
new chemical entities qualify for eight years of data exclusivity upon marketing authorization and an additional two years of market
exclusivity. This data exclusivity, if granted, prevents regulatory authorities in the European Union from referencing the innovator’s
data to assess a generic (abbreviated) application for eight years, after which generic marketing authorization can be submitted,
and the innovator’s data may be referenced, but not approved for two years. The overall 10-year period will be extended to
a maximum of 11 years if, during the first eight years of those 10 years, the marketing authorization holder obtains an authorization
for one or more new therapeutic indications which, during the scientific evaluation prior to their authorization, are held to bring
a significant clinical benefit in comparison with existing therapies. Even if a compound is considered to be a new chemical entity
and the sponsor is able to gain the prescribed period of data exclusivity, another company nevertheless could also market another
version of the product if such company can complete a full MAA with a complete database of pharmaceutical test, preclinical tests
and clinical trials and obtain marketing approval of its product.
Regulatory Requirements
after Marketing Authorization
As in the United States,
both marketing authorization holders and manufacturers of medicinal products are subject to comprehensive regulatory oversight
by the EMA and the competent authorities of the individual E.U. Member States both before and after grant of the manufacturing
and marketing authorizations. The holder of an E.U. marketing authorization for a medicinal product must, for example, comply with
E.U. pharmacovigilance legislation and its related regulations and guidelines which entail many requirements for conducting pharmacovigilance,
or the assessment and monitoring of the safety of medicinal products. The manufacturing process for medicinal products in the European
Union is also highly regulated and regulators may shut down manufacturing facilities that they believe do not comply with regulations.
Manufacturing requires a manufacturing authorization, and the manufacturing authorization holder must comply with various requirements
set out in the applicable E.U. laws, including compliance with E.U. cGMP standards when manufacturing medicinal products and active
pharmaceutical ingredients.
In the European
Union, the advertising and promotion of approved products are subject to E.U. Member States’ laws governing promotion
of medicinal products, interactions with clinicians, misleading and comparative advertising and unfair commercial practices.
In addition, other legislation adopted by individual E.U. Member States may apply to the advertising and promotion of
medicinal products. These laws require that promotional materials and advertising in relation to medicinal products comply
with the product’s Summary of Product Characteristics, or SmPC, as approved by the competent authorities. Promotion of
a medicinal product that does not comply with the SmPC is considered to constitute off-label promotion, which is prohibited
in the European Union.
Pharmaceutical Coverage, Pricing and
Reimbursement
Significant uncertainty
exists as to the coverage and reimbursement status of products approved by the FDA and other government authorities. Sales of products
will depend, in part, on the extent to which third-party payors, including government health programs in the United States such
as Medicare and Medicaid, commercial health insurers and managed care organizations, provide coverage, and establish adequate reimbursement
levels for, such products. The process for determining whether a payor will provide coverage for a product may be separate from
the process for setting the price or reimbursement rate that the payor will pay for the product once coverage is approved. Third-party
payors are increasingly challenging the prices charged, examining the medical necessity, and reviewing the cost-effectiveness of
medical products and services and imposing controls to manage costs. Third-party payors may limit coverage to specific products
on an approved list, or formulary, which might not include all of the approved products for a particular indication.
In order to secure
coverage and reimbursement for any product that might be approved for sale, a company may need to conduct expensive pharmacoeconomic
studies in order to demonstrate the medical necessity and cost-effectiveness of the product, in addition to the costs required
to obtain FDA or other comparable regulatory approvals. Nonetheless, product candidates might not be considered medically necessary
or cost effective. Additionally, a payor’s decision to provide coverage for a drug product does not imply that an adequate
reimbursement rate will be approved. Further, one payor’s determination to provide coverage for a drug product does not assure
that other payors will also provide coverage for the drug product. Third-party reimbursement might not be sufficient to maintain
price levels high enough to realize an appropriate return on investment in product development.
The containment of
healthcare costs also has become a priority of federal, state and foreign governments and the prices of drugs have been a focus
in this effort. Governments have shown significant interest in implementing cost-containment programs, including price controls,
restrictions on reimbursement and requirements for substitution of generic products. Adoption of price controls and cost-containment
measures, and adoption of more restrictive policies in jurisdictions with existing controls and measures, could further limit a
company’s revenue generated from the sale of any approved products. Coverage policies and third-party reimbursement rates
may change at any time. Even if favorable coverage and reimbursement status is attained for one or more products for which a company
or its collaborators receive regulatory approval, less favorable coverage policies and reimbursement rates may be implemented in
the future.
Outside the United
States, ensuring adequate coverage and payment for our product candidates will face challenges. Pricing of prescription pharmaceuticals
is subject to governmental control in many countries. Pricing negotiations with governmental authorities can extend well beyond
the receipt of regulatory marketing approval for a product and may require us to conduct a clinical trial that compares the cost
effectiveness of our product candidates or products to other available therapies. The conduct of such a clinical trial could be
expensive and result in delays in our commercialization efforts.
In the European Union,
pricing and reimbursement schemes vary widely from country to country. Some countries provide that drug products may be marketed
only after a reimbursement price has been agreed. Some countries may require the completion of additional studies that compare
the cost-effectiveness of a particular drug candidate to currently available therapies. For example, the European Union provides
options for its member states to restrict the range of drug products for which their national health insurance systems provide
reimbursement and to control the prices of medicinal products for human use. European Union member states may approve a specific
price for a drug product or it may instead adopt a system of direct or indirect controls on the profitability of the company placing
the drug product on the market. Other member states allow companies to fix their own prices for drug products, but monitor and
control company profits. The downward pressure on healthcare costs in general, particularly prescription drugs, has become intense.
As a result, increasingly high barriers are being erected to the entry of new products. In addition, in some countries, cross-border
imports from low-priced markets exert competitive pressure that may reduce pricing within a country. Any country that has price
controls or reimbursement limitations for drug products might not allow favorable reimbursement and pricing arrangements.
Healthcare Law and Regulation
Arrangements with healthcare
providers, pharmacists, consultants, third-party payors and customers are subject to broadly applicable healthcare laws and regulations
that may constrain our business and/or financial arrangements. Applicable federal and state healthcare laws and regulations include
without limitation the following:
|
·
|
the federal Anti-Kickback Statute, which prohibits persons and entities from knowingly and willfully soliciting, offering, receiving or providing remuneration, directly or indirectly, in cash or in kind, if one purpose of the remuneration is to induce or reward either the referral of an individual for, or the purchase, order or recommendation of, any good or service, for which payment may be made, in whole or in part, under a federal healthcare program such as Medicare and Medicaid;
|
|
·
|
the federal civil and criminal false claims laws, including the civil False Claims Act, and civil monetary penalties laws, which prohibit individuals or entities from, among other things, knowingly presenting, or causing to be presented, to the federal government, claims for payment that are false or fraudulent or making a false statement to avoid, decrease or conceal an obligation to pay money to the federal government;
|
|
·
|
the federal Health Insurance Portability and Accountability Act of 1996, or HIPAA, which created additional federal criminal laws that prohibit, among other things, knowingly and willingly executing, or attempting to execute, a scheme to defraud any healthcare benefit program or making false statements relating to healthcare matters;
|
|
·
|
the Health Information Technology for Economic and Clinical Health Act and its implementing regulations, which amended HIPAA to impose additional obligations, including mandatory contractual terms regarding the privacy, security and transmission of individually identifiable health information;
|
|
·
|
the federal transparency requirements known as the federal Physician Payments Sunshine Act, under the Patient Protection and Affordable Care Act, as amended by the Health Care and Education Reconciliation Act of 2010, or the Affordable Care Act, which requires certain manufacturers of drugs, devices, biologics and medical supplies to report annually to the Centers for Medicare & Medicaid Services, or CMS, within the United States Department of Health and Human Services, information related to payments and other transfers of value to clinicians and teaching hospitals and clinician ownership and investment interests; and
|
|
·
|
analogous state and foreign laws and regulations, such as state anti-kickback and false claims laws, which may apply to healthcare items or services that are reimbursed by non-governmental third-party payors, including private insurers.
|
Some state laws require
pharmaceutical companies to comply with the pharmaceutical industry’s voluntary compliance guidelines and the relevant
compliance guidance promulgated by the federal government in addition to requiring drug manufacturers to report information related
to payments to clinicians and other healthcare providers or marketing expenditures. State and foreign laws also govern the privacy
and security of health information in some circumstances, many of which differ from each other in significant ways and often are
not preempted by HIPAA, thus complicating compliance efforts.
Changes in the Healthcare Marketplace
A primary trend in
the U.S. healthcare industry and elsewhere is cost containment. There have been several federal and state proposals during the
last few years regarding the pricing of pharmaceutical and biopharmaceutical products, limiting coverage and reimbursement for
drugs and other medical products, government control, and other changes to the healthcare system in the United States.
The Patient Protection
and Affordable Care Act of 2010, or ACA, included provisions related to the coverage of and payment for prescription drugs under
government healthcare programs. With regard to pharmaceutical products, among other things, the ACA was designed to expand and
increase industry rebates for drugs covered under Medicaid programs, impose an annual fee on branded pharmaceutical manufacturers
and make changes to the coverage requirements under the Medicare Part D program. Although the ACA has been the target of numerous
repeal efforts, cost containment for prescription drugs remains a priority under the current administration and the elements of
the ACA intended to curb drug prices have higher levels of political support than some other aspects of the law. Among the provisions
of the ACA of importance to our potential drug candidates are:
|
·
|
an annual, nondeductible fee on any entity that manufactures or imports specified branded prescription drugs and biologic products, apportioned among these entities according to their market share in certain government healthcare programs, although this fee would not apply to sales of certain products approved exclusively for orphan indications;
|
|
·
|
expansion of eligibility criteria for Medicaid programs by, among other things, allowing states to offer Medicaid coverage to certain individuals with income at or below 133% of the federal poverty level, thereby potentially increasing a manufacturer’s Medicaid rebate liability;
|
|
·
|
expanded manufacturers’ rebate liability under the Medicaid Drug Rebate Program by increasing the minimum rebate for both branded and generic drugs and revising the definition of “average manufacturer price,” or AMP, for calculating and reporting Medicaid drug rebates on outpatient prescription drug prices and extending rebate liability to prescriptions for individuals enrolled in Medicare Advantage plans;
|
|
·
|
addressed a new methodology by which rebates owed by manufacturers under the Medicaid Drug Rebate Program are calculated for drugs that are inhaled, infused, instilled, implanted or injected;
|
|
·
|
expanded the types of entities eligible for the 340B drug discount program;
|
|
·
|
established the Medicare Part D coverage gap discount program by requiring manufacturers to provide a 50% point-of-sale-discount off the negotiated price of applicable brand drugs to eligible beneficiaries during their coverage gap period as a condition for the manufacturers’ outpatient drugs to be covered under Medicare Part D;
|
|
·
|
a new Patient-Centered Outcomes Research Institute to oversee, identify priorities in, and conduct comparative clinical effectiveness research, along with funding for such research;
|
|
·
|
the Independent Payment Advisory Board, or IPAB, which has authority to recommend certain changes to the Medicare program to reduce expenditures by the program that could result in reduced payments for prescription drugs. However, the IPAB implementation has been not been clearly defined. The ACA provided that under certain circumstances, IPAB recommendations will become law unless Congress enacts legislation that will achieve the same or greater Medicare cost savings; and
|
|
·
|
established the Center for Medicare and Medicaid Innovation within CMS to test innovative payment and service delivery models to lower Medicare and Medicaid spending, potentially including prescription drug spending. Funding has been allocated to support the mission of the Center for Medicare and Medicaid Innovation from 2011 to 2019.
|
Pharmaceutical pricing
has been a focus of the Trump administration, which has also continued efforts to repeal the ACA. It remains to be seen, however,
what impact new legislation, if passed, will have on the availability of healthcare and containing or lowering the cost of healthcare.
The elimination of the ACA’s individual mandate, which imposed penalties to individuals who failed to obtain insurance coverage,
could ultimately result in fewer individuals having health insurance coverage, which changes to the ACA’s minimum coverage
requirements may lead to policies with less generous benefits. While the timing and scope of any potential future legislation to
repeal and replace ACA provisions is highly uncertain in many respects, it is also possible that some of the ACA provisions that
generally are not favorable for the research-based pharmaceutical industry could also be repealed along with ACA coverage expansion
provisions.
Employees
As of March 25, 2020,
we had 27 full-time and two part-time employees. We also engage various consultants and contractors.
Available Information
Our Annual Reports
on Form 10-K, Quarterly Reports on Form 10-Q, Current Reports on Form 8-K, and amendments to those reports filed or furnished pursuant
to Section 13(a) or 15(d) of the Exchange Act, are available free of charge on our website at www.eyenoviabio.com as soon as reasonably
practicable after electronically filing or furnishing such material to the SEC. The SEC maintains a website (www.sec.gov) that
includes our reports, proxy statements and other information.
Investing in our
common stock involves a high degree of risk. You should carefully consider the risks described below, as well as the other information
in this report, including our financial statements and the related notes and “Management’s Discussion and Analysis
of Financial Condition and Results of Operations,” before deciding whether to invest in our common stock. The occurrence
of any of the events or developments described below could harm our business, financial condition, results of operations and growth
prospects. In such an event, the market price of our common stock could decline and you might lose all or part of your investment.
RISKS RELATED TO OUR FINANCIAL POSITION
AND NEED FOR ADDITIONAL CAPITAL
We might not be able to continue
as a going concern which would likely cause our stockholders to lose most or all of their investment.
Our audited financial
statements for the year ended December 31, 2019 were prepared under the assumption that we would continue as a going concern. However,
our independent registered public accounting firm included a “going concern” explanatory paragraph in its report on
our financial statements for the year ended December 31, 2019, indicating that, without additional sources of funding, our cash
at December 31, 2019 is not sufficient for us to operate as a going concern for a period of at least one year from the date that
the financial statements included in this Annual Report on Form 10-K are issued. Management’s plans concerning these matters,
including our need to raise additional capital, are described in Note 2 – Summary of Significant Accounting Policies –
Liquidity and Going Concern of our financial statements included within this Annual Report on Form 10-K, however, management cannot
assure you that its plans will be successful. In light of the foregoing, there is substantial doubt about our ability to continue
as a going concern. If we cannot continue as a viable entity, our stockholders would likely lose most or all of their investment
in us.
We need to raise additional capital
in order to continue developing our product candidates into next year. Such funding might not be available on acceptable terms,
or at all. Failure to obtain this necessary capital may force us to delay, limit or terminate certain of our product development
efforts to continue operations.
We require substantial
additional funding to continue our research and development activities into next year. We also need substantial funding to advance
our commercialization efforts, and fund our operating expenses and other activities. If additional capital is not available when
needed, including because of general market conditions, we may need to significantly scale back or reprioritize our research and
development activities or cease our operations.
We will require substantial
funds to discover, develop, protect and conduct research and development for our product candidates, including preclinical testing
for future product candidates and clinical trials of any of our product candidates, and to manufacture and market any such product
that may be approved for commercial sale. Even if we are successful in raising additional capital, such funds may prove to be insufficient
for these activities. Our financing needs may change substantially because of research and development costs, competition, clinical
trials and costs arising from additional regulatory approvals. We might not succeed in raising needed additional funds. The timing
of our need for additional funds will depend on a number of factors, which factors are difficult to predict or may be outside of
our control, including:
|
·
|
the resources, time and costs required
to initiate and complete our research and development, to initiate and complete preclinical studies and clinical trials and to
obtain regulatory approvals for our product candidates;
|
|
·
|
progress in our research and development
programs;
|
|
·
|
the timing, receipt and amount of milestone,
royalty and other payments from future collaborators, if any; and
|
|
·
|
costs necessary to protect our intellectual
property.
|
If our estimates and
predictions relating to any of these factors are incorrect, we may need to modify our operating plan. Additional funds might not
be available to us on acceptable terms, or at all, when needed.
Raising additional capital may cause
dilution to our existing stockholders, restrict our operations or require us to relinquish rights to our technologies.
Until such time as
we can generate substantial product revenues, we may attempt to finance our cash needs through equity offerings (such as our recent
approximately $6 million private placement), debt financings, government and/or other third-party grants or other third-party funding,
marketing and distribution arrangements and other collaborations, strategic alliances and licensing arrangements. To the extent
that we raise additional capital through the sale of equity or convertible debt securities, our investors’ ownership interest
will be diluted. Debt financing, if available, may involve agreements that include covenants limiting or restricting our ability
to take specific actions, such as incurring additional debt, making capital expenditures or declaring dividends. If we are unable
to obtain funding on a timely basis, we may be required to significantly curtail one or more clinical research or development programs,
which would adversely impact potential revenues, results of operations and financial condition.
If we raise additional
capital through future collaborations, strategic alliances or third-party licensing arrangements, we may have to relinquish valuable
rights to our intellectual property, future revenue streams, research programs or product candidates, or grant licenses on terms
that might not be favorable to us.
We have incurred operating losses
since our inception. We expect to continue to incur losses for the foreseeable future and might never achieve or maintain profitability.
We have incurred net
losses of approximately $57.7 million since inception, have not generated any product sales revenue and have not achieved
profitable operations. Our net losses were approximately $21.2 million and $17.3 million for the years ended December 31, 2019
and 2018, respectively. We expect to continue to incur substantial losses in future periods while we continue to test and prepare
our product candidates for the market. It could be several years, if ever, before we have a commercialized drug. The net losses
we incur may fluctuate significantly from quarter to quarter and year to year. We anticipate that our expenses will increase substantially
if, and as, we:
|
·
|
continue the ongoing and clinical development
of our product candidates;
|
|
·
|
initiate preclinical studies and clinical
trials for any additional product candidates that we may pursue in the future;
|
|
·
|
seek marketing approvals for our current
and future product candidates that successfully complete clinical trials;
|
|
·
|
continue to develop a sales, marketing
and distribution infrastructure to commercialize any product candidate for which we may obtain marketing approval;
|
|
·
|
develop, maintain, expand and protect
our intellectual property portfolio;
|
|
·
|
implement operational, financial and management
systems; and
|
|
·
|
attract, hire and retain additional administrative,
clinical, regulatory and scientific personnel.
|
Even if we are able to generate revenues
from the sale of our potential products, we might not become profitable and may need to obtain additional funding to continue operations.
If we fail to become profitable or are unable to sustain profitability on a continuing basis, then we may be unable to continue
our operations at planned levels and be forced to reduce our operations. Even if we do achieve profitability, we might not be able
to sustain or increase profitability on a quarterly or annual basis. Our failure to become and remain profitable would decrease
the value of our company and could impair our ability to raise capital, expand our business or continue our operations. In addition,
because of the numerous risks and uncertainties associated with product development, we are unable to predict the timing or amount
of increased expenses, or when, or if, we will be able to achieve or maintain profitability.
Our relatively short operating history
may make it difficult for investors to evaluate the success of our business to date and to assess our future viability.
We are a clinical-stage
company which commenced active operations in 2014. Our operations to date have been limited to organizing and staffing our company,
business planning, raising capital and developing our product candidates. We have not yet demonstrated our ability to obtain regulatory
approval, manufacture a commercial scale product or arrange for a third party to do so on our behalf, or conduct sales and marketing
activities necessary for successful product commercialization. Consequently, any predictions about our future success or viability
might not be as accurate as they could be if we had a longer operating history.
In addition, as a new
business, we may encounter unforeseen expenses, difficulties, complications, delays and other known and unknown factors. We will
need to transition from a company with a product development focus to a company capable of supporting commercial and manufacturing
activities. We might not be successful in such a transition.
If we are unable to use carryforward
tax losses or benefit from favorable tax legislation to reduce our taxes, our business, results of operations and financial condition
may be adversely affected.
We have incurred significant
net operating losses since our inception in July 2014. As of December 31, 2019, we had federal net operating loss carry-forwards
of approximately $45.0 million, of which, approximately $10.8 million will expire at various dates from 2034 to 2037 for federal
purposes. If we are unable to use carryforward tax losses to reduce our future taxable basis for corporate tax purposes, our business,
results of operations and financial condition may be adversely affected.
Net operating
loss and tax credit carry-forwards are subject to review and possible adjustment by the Internal Revenue Service and state
tax authorities and may become subject to an annual limitation in the event of certain cumulative changes in the ownership
interest of significant stockholders over a three-year period in excess of 50%, as defined under Sections 382 and 383 of the
Internal Revenue Code of 1986, as amended, as well as similar state provisions. This could limit the amount of tax attributes
that can be utilized annually to offset future taxable income or tax liabilities. Pre-July 15, 2019, net operating loss
carryforwards of approximately $35,000,000 are subject to an annual limitation of approximately $918,000.
The federal and state
income tax returns are generally subject to tax examinations. To the extent we have tax attribute carryforwards, the tax years
in which the attribute was generated may still be adjusted upon examination by the Internal Revenue Service or state tax authorities
to the extent utilized in a future period. Any unfavorable tax adjustment could have a significant impact on our results of operations
and future cash flows. Furthermore, if the United States government decides to eliminate, or reduce the scope or the rate of any
tax benefit, either of which it could decide to do at any time, our results of operations could be adversely affected.
RISKS RELATED TO DEVELOPMENT AND COMMERCIALIZATION
OF OUR PRODUCT CANDIDATES
We may encounter substantial delays
in or failure of our clinical trials.
If the clinical trials
that we are required to conduct to gain regulatory approval are delayed or unsuccessful, we might not be able to market our product
candidates. Additionally, because our product candidates are based on new technologies, we expect that our human clinical trials
will require extensive research and development and have substantial manufacturing and processing costs. Accordingly, our clinical
trial costs could be significantly higher than other conventional therapeutic technologies or drug products and could be delayed
if we do not have adequate means to fund them.
We may experience delays
in any phase of the development and commercial launch of product candidates, including during research and development and clinical
trials. Implementing a clinical trial is time-consuming and expensive, particularly human clinical trials, and the outcome of any
clinical trial is uncertain. The completion of any of these clinical trials may be delayed or halted for numerous reasons, including,
but not limited to, the following:
|
·
|
patients do not enroll in our clinical
trials (including due to any adverse impacts of the coronavirus pandemic and resulting social distancing and shelter in place orders)
or results from patients are not received at the expected rate;
|
|
·
|
patients discontinue participation in
a clinical trial prior to the scheduled endpoint set forth in the clinical protocol at a higher than expected rate, especially
if such discontinuations interfere with our ability to assess the efficacy of our drug candidate;
|
|
·
|
patients experience adverse events from
our treatment;
|
|
·
|
patients get hurt during a clinical trial
for a variety of reasons that might not be related to our product candidates, including the advanced stage of their disease and
other medical problems;
|
|
·
|
third-party clinical investigators do
not perform the clinical trials in accordance with the anticipated schedule or consistent with the clinical trial protocol and
good clinical practices or other third-party organizations do not perform data collection and analysis in a timely or accurate
manner;
|
|
·
|
the FDA, IRBs, European Union regulatory
authorities, or the European Medicines Agency, and national authorities, or other regulatory authorities do not approve a clinical
trial protocol or place a clinical trial on hold;
|
|
·
|
enrollment and sample size of our clinical
trials may be substantially different than estimated which may lead to longer timelines and larger expenses;
|
|
·
|
third-party clinical investigators engage
in activities that, even if not directly associated with our clinical trials, result in their debarment, loss of licensure, or
other legal or regulatory sanction;
|
|
·
|
regulatory inspections of manufacturing
facilities, which may, among other things, require us to undertake corrective action or suspend the clinical trials;
|
|
·
|
changes in governmental regulations or
administrative actions;
|
|
·
|
the interim results of the clinical trial,
if any, are inconclusive or negative; and
|
|
·
|
the study design, although approved and
completed, is inadequate to demonstrate effectiveness and safety.
|
Our dependence upon
clinical trials in developing product candidates may impede them from reaching advanced stages of development and might prevent
all or part of our commercial operations. To date, the situations regarding potential delays in research and development activities
and clinical trials have yet to occur in a manner which adversely affects our research and development activities.
We may find it difficult to enroll
or maintain participation of an adequate number of patients in our clinical trials, which could delay or prevent us from proceeding
with clinical trials of our product candidates.
Identifying and qualifying
patients to participate in our clinical trials is critical to our success. Patient enrollment depends on many factors, including
the size and nature of the patient population, eligibility criteria for the clinical trial, the proximity of patients to clinical
sites and their ability and willingness to participate in our trials (which may be adversely affected due to personal or environmental
factors, including pandemics like COVID-19 and the resulting social distancing and shelter in place orders), the design of the
clinical protocol, the availability of competing clinical trials, the availability of new drugs approved for the indication the
clinical trial is investigating, and clinicians’ and patients’ perceptions as to the potential advantages of the drug
being studied in relation to other available therapies. Any inability to locate, enroll and maintain participation of a sufficient
number of patients in our clinical trials would result in significant delays, could require us to abandon one or more clinical
trials altogether and could delay or prevent our receipt of necessary regulatory approvals. Delays in our clinical trials may also
result in increased development costs for our product candidates, which would cause the value of our company to decline and limit
our ability to obtain additional financing.
In addition, any negative
results we may report in clinical trials of our product candidates may make it difficult or impossible to recruit and retain patients
in other clinical trials of that same product candidate. Delays in the enrollment for any clinical trial of our product candidates
will increase our costs, slow down our product development and approval process and delay or potentially jeopardize our ability
to commence product sales and generate revenue. In addition, some of the factors that cause, or lead to, a delay in the commencement
or completion of clinical trials may also ultimately lead to the denial of regulatory approval of our product candidates.
We might not be able to develop marketable
products utilizing our technology and we might not be able to identify and successfully implement an alternative product development
strategy.
The approach we have
adopted to discover and develop product candidates is new and may never lead to marketable products. We have concentrated our efforts
on developing therapeutic product candidates utilizing new advanced technology for drug delivery. To our knowledge, no person or
company has developed any therapeutic product utilizing the same technology and no such ophthalmic micro-therapeutic product has
been approved for marketing to date. We are leading a new field of ophthalmic micro-therapeutic research and development and the
scientific discoveries that form the basis for our efforts to develop products are relatively new. The scientific evidence to support
the feasibility of developing such products and treatments based on these discoveries is limited. Our focus solely on developing
products utilizing our proprietary technology, as opposed to more traditional technology, increases the risks associated with investing
in our stock. If we are unsuccessful in developing product candidates utilizing our technology or finding additional applications
for our technology, we may be required to change the scope and direction of our product development activities. If we are not able
to identify and successfully implement an alternative product development strategy, our business may fail.
Ophthalmic micro-therapeutic research
and development is a highly uncertain undertaking. Our development efforts may be delayed for any number of reasons, in which case
potential marketing approval or commercialization of our proprietary technology could be delayed or prevented.
Our research and development
activities to develop ophthalmic microdose therapeutics utilizing our proprietary technology may be impeded due to scientific or
technological difficulties or our lack of complete understanding of the challenges. Our research and development activities might
not give rise to a marketable product and we might not succeed in developing a marketable product in a timely manner or in accordance
with our estimated budgets. Even if we are successful in developing such products, there is no certainty that our products, when
developed, will be found to be sufficiently effective and safe for use to receive regulatory approval for marketing, which would
adversely impact our potential revenues, results of operations and financial condition.
Even if we complete the necessary
preclinical studies for any new product candidates and clinical trials for existing product candidates, the marketing approval
process is expensive, time-consuming and uncertain and may prevent us from obtaining approvals for the commercialization of some
or all of our product candidates. If we are not able to obtain, or if there are delays in obtaining, required regulatory approvals,
we will not be able to commercialize our product candidates, and our ability to generate revenue would be materially impaired.
Our business depends
on the success of our lead research and development programs which will require additional clinical testing before we can seek
regulatory approval and potentially launch commercial sales. In addition, we do not have any products that have gained regulatory
approval. Our business and future success depends on our ability to obtain regulatory approval of and then successfully commercialize
our lead product candidates. We are currently preparing for Phase III clinical trials for MicroLine and MicroPine and our ability
to develop, obtain regulatory approval for, and successfully commercialize, current and any future product candidates will depend
on several factors, including the following:
|
·
|
further ascertaining the FDA’s expectations
with respect to the nonclinical and clinical testing requirements across the development programs;
|
|
·
|
successful completion of our current clinical
trials or other clinical trials, which will depend substantially upon the satisfactory performance of third-party contractors;
|
|
·
|
successful achievement of the objectives
of planned clinical trials, including manufacturability qualification of devices;
|
|
·
|
receipt of marketing approvals from the
FDA, and similar regulatory authorities outside the United States;
|
|
·
|
establishing commercial manufacturing
and supply arrangements;
|
|
·
|
establishing a manufacturing and commercial
infrastructure;
|
|
·
|
acceptance of the products by patients,
the medical community and third-party payors;
|
|
·
|
establishing market share while competing
with other therapies;
|
|
·
|
successfully executing any pricing and/or
reimbursement strategy;
|
|
·
|
a continued acceptable safety and adverse
event profile of the products following regulatory approval; and
|
|
·
|
qualifying for, identifying, registering,
maintaining, enforcing and defending intellectual property rights and claims covering the products.
|
Our business strategy
includes developing several pipeline product candidates over the next approximately 3-4 years which will require additional clinical
development, regulatory review and approval in multiple jurisdictions, substantial investment, access to sufficient commercial
manufacturing capacity and significant marketing efforts before we can generate any revenue from product sales. We are not permitted
to market or promote any of our product candidates before we receive regulatory approval from the FDA or comparable foreign regulatory
authorities, and we may never receive such regulatory approval for any of our product candidates. If we are unable to develop or
receive marketing approval in a timely manner or at all, we could experience significant delays or an inability to commercialize
the product, which would materially and adversely affect our business, financial condition and results of operations.
Our product candidates may cause
undesirable side effects or have other properties that could delay or prevent their regulatory approval, limit the commercial potential
or result in significant negative consequences following any potential marketing approval.
If our product candidates
are associated with undesirable side effects or have characteristics that are unexpected, we may need to abandon our development
or limit development to certain uses or subpopulations in which the undesirable side effects or other characteristics are less
prevalent, less severe or more acceptable from a risk-benefit perspective. Any serious adverse or undesirable side effects identified
during the development of our product candidates could interrupt, delay or halt clinical trials and could result in the denial
of regulatory approval by the FDA or other regulatory authorities for any or all targeted indications, and in turn prevent us from
commercializing our product candidates and generating revenues from their sale. In addition, if any of our product candidates receive
regulatory approval and we or others later identify undesirable adverse effects caused by the product, we could face one or more
of the following consequences:
|
·
|
regulatory authorities may require the
addition of labeling statements, such as a boxed warning or a contraindication, or other safety labeling changes;
|
|
·
|
regulatory authorities may require a Risk
Evaluation and Mitigation Strategy;
|
|
·
|
regulatory authorities may withdraw their
approval of the product;
|
|
·
|
regulatory authorities may seize the product;
|
|
·
|
we may be required to change the way that
the product is administered, or conduct additional clinical trials or we may need to recall the product;
|
|
·
|
we may be subject to litigation or product
liability claims fines, injunctions or criminal penalties; and
|
|
·
|
our reputation may suffer.
|
If the market opportunities for our
product candidates are smaller than we believe they are, our product revenues may be adversely affected and our business may suffer.
We are currently focusing
our research and product development efforts on our MicroLine, MicroPine and MicroStat products. Our understanding of both the
number of people who have needs for these products, as well as the subset of people who have the potential to benefit from current
product candidates, are based on estimates in published literature. While we believe these estimates are reasonable, they may prove
to be incorrect and new studies may reduce the estimated incidence or prevalence of presbyopia, progressive myopia and mydriasis.
The number of patients in the United States and elsewhere may turn out to be lower than expected or these patients might not be
otherwise amenable to our product candidates or may become increasingly difficult to identify and access, all of which would adversely
affect our business, financial condition, results of operations and prospects.
The commercial success of our product
candidates will depend on the degree of market acceptance among ophthalmologists and optometrists, patients, patient advocacy groups,
third-party payors and the medical community.
Even if we receive
regulatory approval to market our product candidates, our product candidates might not gain market acceptance upon their commercial
introduction, which could prevent us from becoming profitable.
We may have difficulties
convincing the medical community, third-party payors and consumers to accept and use any of our product candidates that may be
approved for commercialization in the future. Other factors that we believe will affect market acceptance of our product candidates
include:
|
·
|
the timing of our receipt of any marketing
approvals, the terms of any approvals and the countries in which approvals are obtained;
|
|
·
|
safety, efficacy and ease of administration
of our product candidates;
|
|
·
|
the success of physician education programs;
|
|
·
|
the availability of any government and
third-party payor reimbursement;
|
|
·
|
the pricing of our product candidates,
particularly as compared to alternative treatment methods and medications;
|
|
·
|
the extent to which alternative treatment
methods and medications are more readily available as compared to the availability of any product candidates that we may develop
in the future; and
|
|
·
|
the prevalence and severity of any adverse
effects.
|
We face significant competition in
an environment of rapid technological change and the possibility that our competitors may achieve regulatory approval before us
or develop therapies that are more advanced or effective than ours, which may adversely affect our financial condition and our
ability to successfully market or commercialize our product candidates.
The specialty pharma
market is highly competitive. If we are unable to compete effectively with any existing products, new treatment methods and new
technologies, we may be unable to commercialize therapeutic products that we may develop in the future.
The specialty pharma
market is subject to rapid technological change and is significantly affected by existing rival products and medical procedures,
new product introductions and the market activities of other participants. Pharmaceutical and biotechnology companies, academic
institutions, governmental agencies and other public and private research organizations may pursue the research and development
of technologies, drugs or other therapeutic products for the treatment of some or all of the diseases we are targeting. We may
also face competition from products which have already been approved and accepted by the medical community for the treatment of
these same indications.
As a result of any
of the foregoing factors, our competitors may develop or commercialize products with significant advantages over any therapeutic
products that we may develop. If our competitors are more successful in commercializing their products than we are, their success
could adversely affect our competitive position and harm our business prospects.
If we fail to establish an effective
distribution process our business may be adversely affected.
We have limited resources
for the sale, marketing and distribution of drug products. To achieve commercial success for the product candidates for which we
obtain marketing approval, we will need to establish and maintain an adequate sales force, and marketing and distribution capabilities,
either ourselves or through collaborations or other arrangements with third parties. In addition, failure to secure contracts with
wholesalers, retailers, or specialty pharmacies could negatively impact the distribution of our potential products, and failure
to coordinate financial systems could negatively impact our ability to accurately report product revenue. If we are unable to effectively
establish and manage the distribution process, the commercial launch and sales of our potential products may be delayed or severely
compromised and our results of operations may be harmed.
We are exposed to the risk of claims
seeking monetary damages by individuals and the risk of investigations by regulatory authorities, which could cause us to incur
substantial liabilities and to limit commercialization of any products that we develop.
We are exposed to the
risk of claims seeking monetary damages being filed against us for loss or harm suffered by participants of our clinical trials
or for loss or harm suffered by users of any drug that may receive approval for commercialization in the future. In either event,
the FDA or the regulatory authorities of other countries or regions may commence investigations of the safety and effectiveness
of any such clinical trial or commercialized drug, the manufacturing processes and facilities or marketing programs utilized in
respect of any such clinical trial or drug. Such investigations may result in mandatory or voluntary recalls of any commercialized
drug or other significant enforcement action such as limiting the indications for which any such drug may be used, or suspension
or withdrawal of approval for any such drug. Investigations by the FDA or any other regulatory authority in other countries or
regions also could delay or prevent the completion of any of our other clinical development programs.
Product liability lawsuits against
us could divert our resources and could cause us to incur substantial liabilities and to limit commercialization of any products
that we develop.
We face an inherent
risk of product liability exposure related to the use of our product candidates that we develop in human clinical trials. We face
an even greater risk if we commercially sell any products that we develop. If we cannot successfully defend ourselves against claims
that our product candidates or products caused injuries, we will incur substantial liabilities. Regardless of merit or eventual
outcome, liability claims may result in:
|
·
|
decreased demand for any product candidates
or products that we develop;
|
|
·
|
injury to our reputation and significant
negative media attention;
|
|
·
|
withdrawal of clinical trial participants;
|
|
·
|
significant costs to defend the related
litigation;
|
|
·
|
substantial monetary awards to clinical
trial participants or patients;
|
|
·
|
reduced time and attention of our management
to pursue our business strategy; and
|
|
·
|
the inability to commercialize any products
that we develop.
|
Our insurance policies
might not fully cover the risk of loss associated with our operations. We may need to increase our insurance coverage as we expand
or undertake new our clinical trials for existing and future product candidates. We will need to further increase our insurance
coverage if we commence commercialization of any of the product candidates for which we obtain marketing approval. Insurance coverage
is increasingly expensive. We might not be able to maintain insurance coverage at a reasonable cost or in an amount adequate to
satisfy any liability that may arise. In the event that we are required to pay damages for any such claim, we may be forced to
seek bankruptcy or to liquidate because our asset and revenue base may be insufficient to satisfy the payment of damages and any
insurance that we have obtained or may obtain for product or clinical trial liability might not provide sufficient coverage against
potential liabilities.
RISKS RELATED TO REGULATORY APPROVAL
OF OUR PRODUCT CANDIDATES AND
OTHER LEGAL COMPLIANCE MATTERS
If we are not able to obtain, or
if there are delays in obtaining, required regulatory approvals, we might not be able to commercialize our product candidates,
and our ability to generate revenue would be materially impaired.
Our product candidates
are subject to extensive and burdensome governmental regulations relating to product development, manufacturing, marketing and
commercialization, and sale, in addition to the laws and regulations applicable to clinical trials. Rigorous preclinical testing
and clinical trials and related regulatory approval processes are required in the United States and in many foreign jurisdictions
before a new product may be offered or sold. Satisfaction of these and other regulatory requirements is costly, time-consuming,
uncertain and subject to unanticipated delays.
In the United States,
the product candidates we intend to develop and market are regulated by the FDA under its drug development and review process.
The time required to obtain FDA and other approvals for our product candidates is unpredictable. Before such product candidates
can be marketed, we must obtain FDA approval of an IND permitting the conduct of clinical trials, then we must successfully complete
human testing, and the FDA must approve our NDA. Even after successful completion of clinical testing, there is a risk that the
FDA may request further information from us, disagree with our findings or otherwise undertake a lengthy review of our submission.
It is possible that
FDA will not approve any application we submit. It is possible that none of the product candidates that we may develop will obtain
the appropriate regulatory approvals necessary for us to commence the offer and sale of such products. Any delay or failure in
obtaining required approvals could have a material adverse effect on our ability to generate revenues from a particular prospective
product.
Failure to obtain marketing approval
in foreign jurisdictions would prevent our product candidates from being marketed in such jurisdictions.
Because we intend to
market any therapy that we may develop in jurisdictions in addition to the United States, such as the European Union and Asia,
we will likely incur the same costs or more in satisfying foreign regulatory requirements governing the conduct of clinical trials,
manufacturing and marketing and commercialization of our product candidates. Approval by the FDA by itself does not assure approval
by regulatory authorities outside the United States and approval by one regulatory authority outside the United States does not
ensure approval by regulatory authorities in other countries or jurisdictions or by the FDA. Each of these foreign regulatory approval
processes includes all of the risks associated with the FDA approval process, as well as risks attributable to having to satisfy
local regulations within each of these foreign jurisdictions. In addition, any failure or delay in obtaining regulatory approval
in one country may negatively affect the regulatory process in other countries. Our inability to obtain regulatory approval outside
the United States may adversely compromise our business prospects.
The terms of approvals, ongoing regulations
and post-marketing restrictions for our products may limit how we manufacture and market our products, which could materially impair
our ability to generate revenue.
Once marketing approval
has been granted, an approved product and its manufacturer and marketer are subject to ongoing review and extensive regulation.
The FDA closely regulates the post-approval marketing and promotion of drugs to ensure drugs are marketed only for the approved
indications and in accordance with the provisions of the approved labeling and regulatory requirements. The FDA imposes stringent
restrictions on manufacturers’ communications regarding off-label use and if we do not restrict the marketing of our products
only to their approved indications, we may be subject to enforcement action for off-label marketing. We, and any potential collaborators
we may have in the future, must therefore comply with requirements concerning advertising and promotion for any of our products
for which we or our collaborators obtain marketing approval. Thus, if any of our product candidates receive marketing approval,
the accompanying label may limit the approved use of our product, which could limit sales of the product.
In addition,
manufacturers of approved products and those manufacturers’ facilities are required to comply with extensive FDA
requirements, including ensuring that quality control and manufacturing procedures conform to cGMP requirements applicable to
drug manufacturers, which include requirements relating to quality control and quality assurance as well as the corresponding
maintenance of records and documentation and reporting requirements. We, any contract manufacturers we may engage in the
future, our future collaborators and their contract manufacturers will also be subject to other regulatory requirements,
including submissions of safety and other post-marketing information and reports, registration and listing requirements,
requirements regarding the distribution of samples to clinicians, recordkeeping, and costly post-marketing studies or
clinical trials and surveillance to monitor the safety or efficacy of the product such as the requirement to implement a risk
evaluation and mitigation strategy. Our third party manufacturers’ inability to satisfy the chemistry, manufacturing
and control concerns of regulatory bodies such as the FDA would either prevent us from completing clinical trials or prevent
us from obtaining regulatory approval for marketing, either of which would significantly compromise our business
prospects.
We may be subject to substantial
penalties if we fail to comply with regulatory requirements or if we experience unanticipated problems with our products.
Violations of the Food
Drug and Cosmetics Act (“FDCA”) relating to the promotion or manufacturing of drug products may lead to investigations
by the FDA, Department of Justice, and/or state Attorneys General alleging violations of federal and state healthcare fraud and
abuse laws, as well as state consumer protection laws. In addition, later discovery of previously unknown adverse events or other
problems with our products, manufacturers or manufacturing processes, or failure to comply with regulatory requirements, may yield
various results, including:
|
·
|
restrictions on such products, manufacturers
or manufacturing processes;
|
|
·
|
restrictions on the labeling or marketing
of a product;
|
|
·
|
restrictions on product distribution or
use;
|
|
·
|
requirements to conduct post-marketing
studies or clinical trials;
|
|
·
|
withdrawal of the products from the market;
|
|
·
|
refusal to approve pending applications
or supplements to approved applications that we submit;
|
|
·
|
fines, restitution or disgorgement of
profits or revenues;
|
|
·
|
suspension or withdrawal of marketing
approvals;
|
|
·
|
refusal to permit the import or export
of our products;
|
|
·
|
product seizure or detention; or
|
|
·
|
injunctions or the imposition of civil
or criminal penalties.
|
We are subject to federal and state
healthcare fraud and abuse laws, false claims laws and health information privacy and security laws. If we are unable to comply,
or have not fully complied, with such laws, we could face substantial penalties.
We are subject to U.S.
federal and state and also foreign healthcare fraud and abuse laws and regulations. Any finding of our failure to comply with such
laws and regulations could have a material adverse effect on our business.
Our operations may
be directly or indirectly affected by various broad U.S. federal and state healthcare fraud and abuse laws. These include the U.S.
federal anti-kickback statute, which prohibits any person from knowingly and willfully offering, paying, soliciting or receiving
remuneration, directly or indirectly, in return for or to induce the referring, ordering, leasing, purchasing or arranging for
or recommending the ordering, purchasing or leasing of an item or service for which payment may be made under U.S. federal healthcare
programs, such as the Medicare and Medicaid programs. The U.S. federal anti-kickback statute is very broad in scope, and many of
its provisions have not been uniformly or definitively interpreted by existing case law or regulations. In addition, many states
have adopted laws similar to the U.S. federal anti-kickback statute, and some of these laws are broader than that statute in that
their prohibitions are not limited to items or services paid for by a U.S. federal healthcare program but, instead, apply regardless
of the source of payment. Violations of these laws could result in fines, imprisonment or exclusion from government-sponsored programs.
Additionally, our relationships
with customers and third-party payors will be subject to applicable anti-kickback, fraud and abuse and other healthcare laws and
regulations, which may expose us to criminal sanctions, civil penalties, program exclusion, contractual damages, reputational harm
and diminished profits and future earnings.
Healthcare providers,
physicians and third-party payors play a primary role in the recommendation of any product candidates for which we obtain marketing
approval. Our future arrangements with third-party payors and customers may expose us to broadly applicable fraud and abuse and
other healthcare laws and regulations that may constrain the business or financial arrangements and relationships through which
we plan to market, sell and distribute products for which we obtain marketing approval.
Some state laws require
pharmaceutical companies to comply with the pharmaceutical industry’s voluntary compliance guidelines and the relevant compliance
guidance promulgated by the federal government and federal and state laws may require drug manufacturers to report information
related to payments and other transfers of value to physicians and other healthcare providers or marketing expenditures. State
and foreign laws also govern the privacy and security of health information in some circumstances, many of which differ from each
other in significant ways and often are not preempted by the Health Insurance Portability and Accountability Act, thus complicating
compliance efforts.
Efforts to ensure that
our business arrangements with third parties comply with applicable healthcare laws and regulations will involve substantial costs.
It is possible that governmental authorities will conclude that our business practices might not comply with current or future
statutes, regulations or case law involving applicable fraud and abuse or other healthcare laws and regulations. If our operations
are found to be in violation of any of these laws or any other governmental regulations that may apply to us, we may be subject
to significant civil, criminal and administrative penalties, damages, fines, exclusion from government funded healthcare programs,
such as Medicare and Medicaid, and the curtailment or restructuring of our operations. If any of the physicians or other providers
or entities with whom we expect to do business are found to be not in compliance with applicable laws, they may be subject to criminal,
civil or administrative sanctions, including exclusions from government funded healthcare programs.
Recently enacted and future legislation
may affect our ability to commercialize our products and the prices we obtain for any products that are approved in the United
States or foreign jurisdictions, which would harm our business.
In the United States
and some foreign jurisdictions, there have been a number of legislative and regulatory changes and proposed changes regarding the
healthcare system that could affect our ability to profitably sell or commercialize our product candidates for which we obtain
marketing approval. The pharmaceutical industry has been a particular focus of these efforts and have been significantly affected
by legislative initiatives. Current laws, as well as other healthcare reform measures that may be adopted in the future, may result
in more rigorous coverage criteria and in additional downward pressure on the price that we receive for any FDA approved product.
The United States Medicare
Prescription Drug, Improvement, and Modernization Act of 2003, or the Medicare Modernization Act, changed the way Medicare covers
and pays for pharmaceutical products. The legislation expanded Medicare coverage for drug purchases by the elderly and introduced
a new reimbursement methodology based on average sales prices for clinician administered drugs. In addition, this legislation provided
authority for limiting the number of drugs that will be covered in any therapeutic class. Cost reduction initiatives in this and
similar legislation could decrease the coverage and price that we receive for any approved products. While the Medicare Modernization
Act applies only to drug benefits for Medicare beneficiaries, private payors often follow Medicare coverage policy and payment
limitations in setting their own reimbursement rates. Therefore, any reduction in reimbursement that results from changes in laws
applicable to federal and state healthcare programs may result in similar reduction in payment from private payors.
As is discussed above,
several provisions of the ACA are important to our business, including, without limitation, our ability to commercialize our product
candidates and the prices we may obtain for any of our product candidates that are approved for sale. Provisions of the ACA that
are potentially important to our business include:
|
·
|
an annual, nondeductible fee on any entity
that manufactures or imports specified branded prescription drugs and biologic products;
|
|
·
|
an increase in the statutory minimum rebates
a manufacturer must pay under the Medicaid Drug Rebate Program;
|
|
·
|
a new Medicare Part D coverage gap discount
program, in which participating manufacturers must agree to offer 50% point-of-sale discounts off negotiated drug prices during
the coverage gap period as a condition for the manufacturer’s outpatient drugs to be covered under Medicare Part D;
|
|
·
|
expansion of healthcare fraud and abuse
laws, including the federal False Claims Act and the federal Anti-Kickback Statute, and the addition of new government investigative
powers, and enhanced penalties for noncompliance;
|
|
·
|
extension of manufacturers’ Medicaid
rebate liability;
|
|
·
|
expansion of eligibility criteria for
Medicaid programs; and
|
|
·
|
expansion of the entities eligible for
discounts under the Public Health Service pharmaceutical pricing program.
|
In addition, other legislative changes have
been proposed and adopted since the ACA was enacted. The Budget Control Act of 2011, for instance, included measures for spending
reductions by Congress. A Joint Select Committee on Deficit Reduction, tasked with recommending a targeted deficit reduction of
at least $1.2 trillion for the years 2013 through 2021, was unable to reach required goals, thereby triggering the legislation’s
automatic reduction to several government programs (“Sequestration”) . These changes included aggregate reductions
to Medicare payments to providers of up to 2% per fiscal year, which went into effect in April 2013 and will remain in effect through
2027 unless additional Congressional action is taken. The American Taxpayer Relief Act of 2012, among other things, reduced Medicare
payments to several providers and increased the statute of limitations period for the government to recover overpayments to providers
from three to five years. These and similar laws, including ongoing legislative efforts to promote transparency and contain costs
related to pharmaceutical prices, may result in additional reductions in Medicare and other third-party rates and otherwise affect
the prices we may obtain for any of our product candidates for which we may obtain regulatory approval or the frequency with which
any such product candidate is prescribed or used.
Continued efforts to
repeal or replace the ACA and other efforts to reform the healthcare marketplace and delivery system, could have an adverse effect
on anticipated revenue from product candidates that we may successfully develop and for which we may obtain marketing approval
and may affect our overall financial condition and ability to develop or commercialize product candidates. We expect that future
reform efforts will continue to prioritize reductions in Medicare and other healthcare spending, more rigorous coverage criteria,
new payment methodologies and additional downward pressure on the price that we receive for any approved product and/or the level
of reimbursement physicians receive for administering any approved product we might bring to market. Reductions in reimbursement
levels may negatively impact the prices we receive or the frequency with which any products we may develop are prescribed or administered.
Any reduction in reimbursement from Medicare or other government programs may result in a similar reduction in payments from private
payors.
The costs of prescription
pharmaceuticals has also been the subject of considerable discussion in the United States, and members of Congress and the Administration
have stated that they will address such costs through new legislative and administrative measures. To date, there have been several
laws passed under the new administration aimed at curbing the cost of drugs, and additional legislation has been proposed on this
subject.
The pricing of prescription
pharmaceuticals is also subject to governmental controls outside the United States, which vary widely from country to country.
As a result, we might obtain regulatory approval for a product in a particular country, but then be subjected to pricing regulations
in that country that delay the commercial launch of the product and negatively impact the revenues able to be generated from the
sale of the product in that country. In these countries, pricing negotiations with governmental authorities can take considerable
time after the receipt of marketing approval for a product. To obtain reimbursement or pricing approval in some countries, we may
be required to conduct a clinical trial that compares the cost-effectiveness of our product candidates to other available therapies.
If reimbursement of our products is unavailable or limited in scope or amount, or if pricing is set at unsatisfactory levels, our
ability to generate revenues and become profitable could be impaired.
We are subject to anti-corruption
laws, as well as export control laws, customs laws, sanctions laws and other laws governing our operations. If we fail to comply
with these laws, we could be subject to civil or criminal penalties, other remedial measures and legal expenses, be precluded from
developing manufacturing and selling products outside the United States or be required to develop and implement costly compliance
programs, which could adversely affect our business, results of operations and financial condition.
Our operations are
subject to anti-corruption laws, including the United Kingdom Bribery Act 2010, or Bribery Act, the United States Foreign Corrupt
Practices Act, or FCPA, and other anti-corruption laws that apply in countries where we do business and may do business in the
future. The Bribery Act, FCPA and these other laws generally prohibit us, our officers, and our employees and intermediaries from
bribing, being bribed or making other prohibited payments to government officials or other persons to obtain or retain business
or gain some other business advantage. Compliance with the FCPA, in particular, is expensive and difficult, particularly in countries
in which corruption is a recognized problem. In addition, the FCPA presents particular challenges in the pharmaceutical industry,
because, in many countries, hospitals are operated by the government, and doctors and other hospital employees are considered foreign
officials. Certain payments to hospitals in connection with clinical trials and other work have been deemed to be improper payments
to government officials and have led to FCPA enforcement actions.
We may in the
future operate in jurisdictions that pose a high risk of potential Bribery Act or FCPA violations, and we may participate in
collaborations and relationships with third parties whose actions could potentially subject us to liability under the Bribery
Act, FCPA or local anti-corruption laws. In addition, we cannot predict the nature, scope or effect of future regulatory
requirements to which our international operations might be subject or the manner in which existing laws might be
administered or interpreted. If we expand our operations outside of the United States, we will need to dedicate additional
resources to comply with numerous laws and regulations in each jurisdiction in which we plan to operate.
We are also subject
to other laws and regulations governing our international operations, including regulations administered by the governments of
the United Kingdom and the United States, and authorities in the European Union, including applicable export control regulations,
economic sanctions on countries and persons, customs requirements and currency exchange regulations, collectively referred to as
the Trade Control laws. In addition, various laws, regulations and executive orders also restrict the use and dissemination outside
of the United States, or the sharing with certain non-United States nationals, of information classified for national security
purposes, as well as certain products and technical data relating to those products. If we expand our presence outside of the United
States, it will require us to dedicate additional resources to comply with these laws, and these laws may preclude us from developing,
manufacturing, or selling certain products and product candidates outside of the United States, which could limit our growth potential
and increase our development costs.
We might not be completely
effective in ensuring our compliance with all applicable anti-corruption laws, including the Bribery Act, the FCPA or other legal
requirements, including Trade Control laws. If we are not in compliance with the Bribery Act, the FCPA and other anti-corruption
laws or Trade Control laws, we may be subject to criminal and civil penalties, disgorgement and other sanctions and remedial measures,
and legal expenses, which could have an adverse impact on our business, financial condition, results of operations and liquidity.
The SEC also may suspend or bar issuers from trading securities on United States exchanges for violations of the FCPA’s accounting
provisions. Any investigation of any potential violations of the Bribery Act, the FCPA, other anti-corruption laws or Trade Control
laws by U.K., U.S. or other authorities could also have an adverse impact on our reputation, our business, results of operations
and financial condition.
RISKS RELATED TO OUR BUSINESS OPERATIONS
AND MANAGING GROWTH
We are highly dependent on the services
of our senior management team, including our Chief Executive Officer and Chief Medical Officer, Dr. Ianchulev, and if we are not
able to retain these members of our management team or recruit and retain additional management, clinical and scientific personnel,
our business will be harmed.
We are highly dependent
on our senior management team, including our Chief Executive Officer and Chief Medical Officer, Dr. Ianchulev. The employment agreements
we have with our executive officers do not prevent such persons from terminating their employment with us at any time. The loss
of the services of any of these persons could impede the achievement of our research, development and commercialization objectives.
In addition, we are
dependent on our continued ability to attract, retain and motivate highly qualified additional management, clinical and scientific
personnel. If we are not able to retain our management and to attract, on acceptable terms, additional qualified personnel necessary
for the continued development of our business, we might not be able to sustain our operations or grow.
We might not be able
to attract or retain qualified personnel in the future due to the intense competition for qualified personnel among biotechnology,
pharmaceutical and other businesses. Many of the other pharmaceutical companies that we compete against for qualified personnel
and consultants have greater financial and other resources, different risk profiles and a longer history in the industry than we
do. They also may provide more diverse opportunities and better chances for career advancement. Some of these characteristics may
be more appealing to high-quality candidates and consultants than what we have to offer. If we are unable to continue to attract,
retain and motivate high-quality personnel and consultants to accomplish our business objectives, the rate and success at which
we can discover and develop drug candidates and our business will be limited and we may experience constraints on our development
objectives.
Our future performance
will also depend, in part, on our ability to successfully integrate newly hired executive officers into our management team and
our ability to develop an effective working relationship among senior management. Our failure to integrate these individuals and
create effective working relationships among.
We have limited corporate infrastructure
and may experience difficulties in managing growth.
As of March 25, 2020,
we had only 27 full time employees and we rely on third-party contractors for the provision of professional and other services.
As our development and commercialization plans and strategies develop, we expect to need additional managerial, operational, sales,
marketing, financial, legal and other resources. Our management may need to divert a disproportionate amount of its attention away
from our day-to-day operations and devote a substantial amount of time to managing these growth activities. We might not be able
to effectively manage the expansion of our operations, which may result in weaknesses in our infrastructure, operational inefficiencies,
loss of business opportunities, loss of employees and reduced productivity among remaining employees. Our expected growth could
require significant capital expenditures and may divert financial resources from other projects, such as the development of our
current and potential future drug candidates. If our management is unable to effectively manage our growth, our expenses may increase
more than expected, our ability to generate and grow revenue could be reduced and we might not be able to implement our business
strategy. Our future financial performance, our ability to commercialize drug candidates, develop a scalable infrastructure and
compete effectively will depend, in part, on our ability to effectively manage any future growth.
Our employees, third-party clinical
investigators, consultants, licensors and strategic partners may engage in misconduct or other improper activities, including non-compliance
with regulatory standards and requirements and insider trading.
We are exposed to the
risk of fraud or other misconduct by our employees, third-party clinical investigators, consultants, licensors and strategic partners.
Misconduct by these parties could include intentional failures to comply with FDA regulations or the regulations applicable in
other jurisdictions, provide accurate information to the FDA and other regulatory authorities, comply with healthcare fraud and
abuse laws and regulations in the United States and abroad, report financial information or data accurately or disclose unauthorized
activities to us. In particular, sales, marketing and business arrangements in the healthcare industry are subject to extensive
laws and regulations intended to prevent fraud, misconduct, kickbacks, self-dealing and other abusive practices. These laws and
regulations restrict or prohibit a wide range of pricing, discounting, marketing and promotion, sales commission, customer incentive
programs and other business arrangements. Such misconduct also could involve the improper use of information obtained in the course
of clinical trials or interactions with the FDA or other regulatory authorities, which could result in regulatory sanctions and
cause serious harm to our reputation. It is not always possible to identify and deter employee misconduct, and the precautions
we take to detect and prevent this activity might not be effective in controlling unknown or unmanaged risks or losses or in protecting
us from government investigations or other actions or lawsuits stemming from a failure to comply with these laws or regulations.
If any such actions are instituted against us and we are not successful in defending ourselves or asserting our rights, those actions
could have a negative impact on our business, financial condition, results of operations and prospects, including the imposition
of significant fines or other sanctions.
We rely upon information technology
and any failure, inadequacy, interruption or security lapse of that technology, including any cyber security incidents, could harm
our ability to operate our business effectively.
Our business operations
could suffer in the event of system failure. Despite the implementation of security measures, our internal computer systems and
those of our contract research organizations, and other contractors and consultants are vulnerable to damage from computer viruses,
unauthorized access, natural disasters, terrorism, war and telecommunication and electrical failures. If such an event were to
occur and cause interruptions in our operations, it could result in a material disruption of our drug development programs. For
example, the loss of clinical trial data from completed or ongoing or planned clinical trials could result in delays in our regulatory
approval efforts and significantly increase our costs to recover or reproduce the data. To the extent that any disruption or security
breach were to result in a loss of or damage to our data or applications, or inappropriate disclosure of confidential or proprietary
information, we could incur liability and further development of our product candidates could be delayed.
RISKS RELATED TO OUR DEPENDENCE ON THIRD
PARTIES
We have limited clinical trial experience.
We may rely upon third parties in conducting our clinical trials, and those third parties might not perform satisfactorily, including
failing to meet deadlines for the completion of such clinical trials.
We have limited experience
in conducting and managing the clinical trials necessary to obtain regulatory approvals for our product candidates. We rely on
third parties for certain clinical development activities. Reliance on third parties reduces our control over these activities
and does not relieves us of our responsibilities. For example, we remain responsible for ensuring that each of our clinical trials
is conducted in accordance with the general investigational plan and protocols for the clinical trial. Moreover, the FDA requires
us to comply with standards, commonly referred to as good clinical practices for conducting, recording and reporting the results
of clinical trials to assure that data and reported results are credible and accurate and that the rights, integrity and confidentiality
of clinical trial participants are protected. We are also required to register ongoing clinical trials and post the results of
completed clinical trials on a government-sponsored database, ClinicalTrials.gov, within specified timeframes. Failure to do so
can result in fines, adverse publicity and civil and criminal sanctions. If any third parties we engage do not successfully carry
out their contractual duties, meet expected deadlines or conduct our clinical trials in accordance with regulatory requirements
or our stated protocols, we might not be able to obtain, or may be delayed in obtaining, marketing approvals for our product candidates
and will not be able to, or may be delayed in our efforts to, successfully commercialize our product candidates. If these third
parties do not successfully carry out their contractual duties or meet expected deadlines, we may be required to replace them,
which may delay the affected clinical trial.
We contract with third parties for
the manufacture of our product candidates including to provide materials required for the production of the Optejet and for our
research and development activities. This reliance on third parties increases the risk that we will not have sufficient quantities
of our product candidates or such quantities at an acceptable cost, which could delay, prevent or impair our development or commercialization
efforts.
We do not currently
operate adequate internal manufacturing facilities for clinical or commercial production of our product candidates. We rely on
a number of third parties for the supply of parts, formulations, active pharmaceutical ingredients, and other materials required
for our manufacturing, research and development activities. If we were unable to reach agreements with these third parties, or
if we were unable to maintain contractual relationships with these third parties, our research and development activities would
be delayed.
We rely on third parties
to provide the materials required for our research and development activities. Obtaining these materials can require various approvals
as well as reaching a purchase or commercial agreement on acceptable terms with the provider of the materials. We might not be
able to reach agreements with a sufficient number of suppliers or do so on acceptable terms. If we are unable to reach acceptable
agreements with a sufficient number of suppliers of materials, our research and development activities will be delayed and our
ability to implement our business plan will be compromised.
Our manufacturing process
is a complicated and expensive and it requires months of advance planning. We rely on a limited number of manufacturers for our
supply. If we were unable to acquire the necessary amount of deliverables to complete our clinical trials, our progress could be
delayed substantially.
Additional potential
risks related to reliance on third-party manufacturers include:
|
·
|
manufacturing delays if our third-party manufacturers are compromised
due to environmental or political factors or health epidemics such as the coronavirus, they do not satisfactorily perform according
to the terms of their agreements with us, or they give greater priority to the supply of other products over our product candidates
or otherwise;
|
|
·
|
delays in obtaining regulatory approval
for our product candidates, if our third-party manufacturers fail to satisfy or comply with regulatory requirements;
|
|
·
|
the possible termination or nonrenewal
of the agreement by the third party at a time that is costly or inconvenient for us;
|
|
·
|
the possible breach of the manufacturing
agreement by the third party;
|
|
·
|
product loss due to contamination, equipment
failure or improper installation or operation of equipment or operator error;
|
|
·
|
the failure of the third-party manufacturer
to comply with applicable regulatory requirements; and
|
|
·
|
the possible misappropriation of our proprietary
information, including our trade secrets and know-how.
|
If we, our service providers or our
third-party manufacturers fail to comply with environmental, health and safety laws and regulations, we could become subject to
fines or penalties or incur costs that could harm our business.
If we, our service
providers, or any third-party manufacturers fail to comply with laws regulating the protection of the environment and health and
human safety, we could be subject to enforcement actions and our business prospects could be adversely affected.
Our research and development
activities, and the research and development activities of our service providers and third-party manufacturers, may involve the
use of hazardous materials and chemicals or the maintenance of various flammable and toxic chemicals. Failure to adequately handle
and dispose of these materials could lead to liabilities for resulting damages, which could be substantial. We also may be subject
to numerous environmental, health and workplace safety laws and regulations, including those governing laboratory procedures, exposure
to blood-home pathogens and the handling of bio-hazardous materials.
If we, our service
providers, or any third-party manufacturers fail to comply with applicable federal, state or foreign laws or regulations, we could
be subject to enforcement actions, which could adversely affect our ability to develop, market and sell our product candidates
successfully and could harm our reputation and lead to reduced acceptance of our product candidates. These enforcement actions
may include:
|
·
|
restrictions on, or prohibitions against,
marketing our product candidates;
|
|
·
|
restrictions on importation of our product
candidates;
|
|
·
|
suspension of review or refusal to approve
new or pending applications;
|
|
·
|
suspension or withdrawal of product approvals;
|
|
·
|
civil and criminal penalties and fines.
|
RISKS RELATED TO OUR INTELLECTUAL PROPERTY
AND POTENTIAL LITIGATION
Our success depends on our ability
to protect our intellectual property and proprietary technology.
Our success depends
in large part on our ability to obtain and maintain patent, trade secret and other intellectual property protection in the United
States and other countries with respect to our proprietary product candidates. If we do not adequately protect our intellectual
property rights, competitors may be able to erode, negate or preempt any competitive advantage we may have, which could harm our
business and ability to achieve profitability. To protect our proprietary position, we file patent applications in the United States
and abroad related to our novel product candidates that are important to our business. The patent application and approval process
is expensive and time-consuming and we might not be able to file and prosecute all necessary or desirable patent applications at
a reasonable cost or in a timely manner.
If the scope of the
patent protection we obtain is not sufficiently broad, we might not be able to prevent others from developing and commercializing
technology and products similar or identical to ours. The degree of patent protection we require to successfully compete in the
marketplace may be unavailable or severely limited in some cases and might not adequately protect our rights or permit us to gain
or keep any competitive advantage. Although we enter into non-disclosure and confidentiality agreements with parties who have access
to confidential or patentable aspects of our research and development output, such as our employees, contractors and other third
parties, any of these parties may breach the agreements and disclose such output before a patent application is filed, thereby
jeopardizing our ability to seek patent protection. In addition, publications of discoveries in the scientific literature often
lag behind the actual discoveries, and patent applications in the United States and other jurisdictions are typically not published
until 18 months after filing, or in some cases not at all. Therefore, we cannot be certain that we were the first to make the inventions
claimed in our patents or pending patent applications, or that we were the first to file for patent protection of such inventions.
The patent position
of biotechnology and pharmaceutical companies generally is highly uncertain, involves complex legal and factual questions, and
has been the subject of much litigation in recent years. As a result, the issuance, scope, validity, enforceability, and commercial
value of our patent rights may be uncertain. Our pending and future patent applications might not result in patents being issued
which protect our technology or product candidates or which effectively prevent others from commercializing competitive technologies
and product candidates. In addition, the coverage claimed in a patent application can be significantly reduced before the patent
is issued, and its scope can be reinterpreted after issuance. Even if our patent applications issue as patents, they might not
issue in a form that will provide us with any meaningful protection, prevent competitors or other third parties from competing
with us, or otherwise provide us with any competitive advantage. In addition, changes in either the patent laws or interpretation
of the patent laws in the United States and other countries may diminish the value of our patents or narrow the scope of our patent
protection. In addition, the laws of foreign countries might not protect our rights to the same extent or in the same manner as
the laws of the United States. For example, patent laws in various jurisdictions, including significant commercial markets such
as Europe, restrict the patentability of methods of treatment of the human body more than United States law does.
Some of our future
patents and patent applications may be co-owned with third parties. If we are unable to obtain an exclusive license to any such
third-party co-owners’ interest in such patents or patent applications, such co-owners may be able to license their rights
to other third parties, including our competitors, and our competitors could market competing products and technology. In addition,
we would need the cooperation of any such co-owners of our patents in order to enforce such patents against third parties, and
such cooperation might not be provided to us. Furthermore, we, or any future partners, collaborators, or licensees, may fail to
identify patentable aspects of inventions made in the course of development and commercialization activities before it is too late
to obtain patent protection on them. Therefore, we may miss potential opportunities to strengthen our patent position. Any of the
foregoing could have a material adverse effect on our business, financial condition, results of operations, and prospects.
Our patents covering our proprietary
technology maybe subject to challenge, narrowing, circumvention and invalidation by third parties.
Any of our patents
may be challenged, narrowed, circumvented, or invalidated by third parties. The issuance of a patent is not conclusive as to its
inventorship, scope, validity, or enforceability, and our patents may be challenged in the courts or patent offices in the United
States and abroad. We may be subject to a third party preissuance submission of prior art to the USPTO or become involved in opposition,
derivation, revocation, reexamination, post-grant and inter partes review, or interference proceedings challenging our patent
rights or the patent rights of others. An adverse determination in any such submission, proceeding or litigation could reduce the
scope of, or invalidate, our patent rights, allow third parties to commercialize our technology or products and compete directly
with us, without payment to us, or result in our inability to manufacture or commercialize products without infringing third-party
patent rights. Moreover, we may have to participate in interference proceedings declared by the USPTO to determine priority of
invention or in post-grant challenge proceedings, such as oppositions in a foreign patent office, that challenge priority of invention
or other features of patentability. Such challenges may result in loss of patent rights, loss of exclusivity, or in patent claims
being narrowed, invalidated, or held unenforceable, which could limit our ability to stop others from using or commercializing
similar or identical technology and products, or limit the duration of the patent protection of our technology and product candidates.
Such proceedings also may result in substantial cost and require significant time from our scientists and management, even if the
eventual outcome is favorable to us.
In addition, our competitors
and other third parties may be able to circumvent our patents by developing similar or alternative technologies or products in
a non-infringing manner. For example, a third party may develop a competitive therapy that provides benefits similar to our product
candidates but that uses a technology that falls outside the scope of our patent protection. Our competitors may also seek approval
to market generic versions of any approved products and in connection with seeking such approval may claim that our patents are
invalid, unenforceable or not infringed. In these circumstances, we may need to defend or assert our patents, or both, including
by filing lawsuits alleging patent infringement. In any of these types of proceedings, a court or other agency with jurisdiction
may find our patents invalid or unenforceable, or that our competitors are competing in a non-infringing manner. Thus, even if
we have valid and enforceable patents, these patents still might not provide protection against competing products or processes
sufficient to achieve our business objectives. If the patent protection provided by the patents and patent applications we hold
or pursue with respect to our product candidates is not sufficiently broad to impede such competition, our ability to successfully
commercialize our product candidates could be negatively affected, which could have a material adverse effect on our business,
financial condition, results of operations, and prospects.
We cannot be sure that we were the
first to make the technologies claimed in our patents or patent applications or that we were the first to file for patent protection.
Assuming the other
requirements for patentability are met, currently, the first to file a patent application is generally entitled to the patent.
However, prior to March 16, 2013, in the United States, the first to invent was entitled to the patent. Publications of discoveries
in the scientific literature often lag behind the actual discoveries, and patent applications in the United States and other jurisdictions
are not published until 18 months after filing, or in some cases not at all. Therefore, we cannot be certain that we were the first
to make the inventions claimed in our patents or pending patent applications, or that we were the first to file for patent protection
of such inventions. Similarly, we cannot be certain that parties from whom we may license or purchase patent rights were the first
to make relevant claimed inventions or were the first to file for patent protection for them. If third parties have filed patent
applications on inventions claimed in our patents or applications on or before March 15, 2013, an interference proceeding in the
United States can be initiated by such third parties to determine the first to invent any of the subject matter covered by the
patent claims of our applications. If third parties have filed such applications after March 15, 2013, a derivation proceeding
in the United States can be initiated by such third parties to determine whether our invention was derived from theirs.
The patent application process is
subject to numerous risks and there can be no assurance that we will be successful in obtaining patents for which we have applied.
Pending patent applications
cannot be enforced against third parties practicing the technology claimed in such applications unless and until a patent issues
from such applications. The patent application process is subject to numerous risks and uncertainties, and there can be no assurance
that we or any of our future development partners will be successful in protecting our product candidates by obtaining and defending
patents. These risks and uncertainties include the following:
|
·
|
the USPTO and various foreign governmental
patent agencies require compliance with a number of procedural, documentary, fee payment and other provisions during the patent
process. There are situations in which noncompliance can result in abandonment or lapse of a patent or patent application, resulting
in partial or complete loss of patent rights in the relevant jurisdiction. In such an event, competitors might be able to enter
the market earlier than would otherwise have been the case;
|
|
·
|
the coverage claimed in a patent application
can be significantly reduced before the patent is issued, and its scope can be reinterpreted after issuance;
|
|
·
|
patent applications might not result in
any patents being issued;
|
|
·
|
patents that may be issued or in-licensed
may be challenged, invalidated, modified, revoked, circumvented, narrowed, found to be unenforceable or otherwise might not provide
any competitive advantage;
|
|
·
|
our competitors, many of whom have substantially
greater resources and many of whom have made significant investments in competing technologies, may seek or may have already obtained
patents that will limit, interfere with or eliminate our ability to make, use, and sell our potential product candidates;
|
|
·
|
there may be significant pressure on the
U.S. government and international governmental bodies to limit the scope of patent protection both inside and outside the United
States for disease treatments that prove successful, as a matter of public policy regarding worldwide health concerns; and
|
|
·
|
countries other than the United States
may have patent laws less favorable to patentees than those upheld by United States courts, allowing foreign competitors a better
opportunity to create, develop and market competing product candidates.
|
Any of the foregoing
events could have a material adverse effect on our business, financial condition, results of operations, and prospects.
It is difficult and costly to protect
our intellectual property and our proprietary technologies, and we might not be able to ensure their protection.
Our commercial success
will depend in part on obtaining and maintaining patent protection and trade secret protection for the composition, use and structure
of our products and product candidates, the methods used to manufacture them, the related therapeutic targets and associated methods
of treatment as well as on successfully defending these patents against potential third-party challenges. Our ability to protect
our products and product candidates from unauthorized making, using, selling, offering to sell or importing by third parties is
dependent on the extent to which we have rights under valid and enforceable patents that cover these activities.
The ultimate determination
by the USPTO or by a court or other trier of fact in the United States, or corresponding foreign national patent offices or courts,
on whether a claim meets all requirements of patentability cannot be assured. Although we have conducted searches for third-party
publications, patents and other information that may affect the patentability of claims in our various patent applications and
patents, we cannot be certain that all relevant information has been identified. Accordingly, we cannot predict the breadth of
claims that may be allowed or enforced in our patents or patent applications, in our licensed patents or patent applications or
in third-party patents.
We cannot provide assurances
that any of our patent applications will be found to be patentable, including over our own prior art patents, or will issue as
patents. Neither can we make assurances as to the scope of any claims that may issue from our pending and future patent applications
nor to the outcome of any proceedings by any potential third parties that could challenge the patentability, validity or enforceability
of our patents and patent applications in the United States or foreign jurisdictions. Any such challenge, if successful, could
limit patent protection for our products and product candidates and/or materially harm our business.
The degree of future
protection for our proprietary rights is uncertain because legal means afford only limited protection and might not adequately
protect our rights or permit us to gain or keep our competitive advantage. For example:
|
·
|
we might not be able to generate sufficient
data to support full patent applications that protect the entire breadth of developments in one or more of our programs;
|
|
·
|
it is possible that one or more of our
pending patent applications will not become an issued patent or, if issued, that the patent(s) will be insufficient to protect
our technology, provide us with a basis for commercially viable products or provide us with any competitive advantages;
|
|
·
|
if our pending applications issue as patents,
they may be challenged by third parties as not infringed, invalid or unenforceable under United States or foreign laws; or
|
|
·
|
if issued, the patents under which we
hold rights might not be valid or enforceable.
|
In addition, to the
extent that we are unable to obtain and maintain patent protection for one of our products or product candidates or in the event
that such patent protection expires, it may no longer be cost-effective to extend our portfolio by pursuing additional development
of a product or product candidate for follow-on indications. Any of the foregoing could have a material adverse effect on our business,
financial condition, results of operations, and prospects.
Obtaining and maintaining patent
protection of our technologies depends on compliance with various procedural, document submission, fee payment and other requirements
imposed by governmental patent agencies, and our patent protection could be reduced or eliminated for non-compliance with these
requirements.
Periodic maintenance
fees, renewal fees, annuity fees and various other governmental fees on patents and applications are required to be paid to the
USPTO and various governmental patent agencies outside of the United States in several stages over the lifetime of the patents
and applications. The USPTO and various non- U.S. governmental patent agencies require compliance with a number of procedural,
documentary, fee payment and other similar provisions during the patent application process and after a patent has issued. There
are situations in which non-compliance can result in abandonment or lapse of the patent or patent application, resulting in partial
or complete loss of patent rights in the relevant jurisdiction. Under the terms of some of our licenses or future licenses, we
may not have the ability to maintain or prosecute patents in the portfolio, and must therefore rely on third parties to comply
with these requirements. Failure by us or our licensors to maintain protection of our patent portfolio could have a material adverse
effect on our business, financial condition, results of operations, and prospects.
In addition, it is
possible that defects of form in the preparation or filing of our patents or patent applications may exist, or may arise in the
future, for example with respect to proper priority claims, inventorship, claim scope, or requests for patent term adjustments.
If we fail to establish, maintain or protect such patents and other intellectual property rights, such rights may be reduced or
eliminated. If any of our present or future partners, collaborators, licensees, or licensors, are not fully cooperative or disagree
with us as to the prosecution, maintenance or enforcement of any patent rights, such patent rights could be compromised. If there
are material defects in the form, preparation, prosecution, or enforcement of our patents or patent applications, such patents
may be invalid and/or unenforceable, and such applications may never result in valid, enforceable patents. Any of these outcomes
could impair our ability to prevent competition from third parties, which may have a material adverse effect on our business, financial
condition, results of operations, and prospects.
Patent terms may be inadequate to
protect our competitive position on our products for an adequate amount of time and if we do not obtain protection under the Hatch-Waxman
Amendments and similar non- U.S. legislation for extending the term of patents covering each of our product candidates, our business
may be materially harmed.
Patents have a limited
lifespan. In the United States, the natural expiration of a patent is generally 20 years after it is filed. Various extensions
may be available, however, the life of a patent, and the protection it affords, is limited. Given the amount of time required for
the development, testing and regulatory review of new product candidates, patents protecting such candidates might expire before
or shortly after such candidates are commercialized. As a result, our patent portfolio might not provide us with adequate and continuing
patent protection sufficient to exclude others from commercializing products similar to our product candidates.
Depending upon the
timing, duration and conditions of FDA marketing approval of our product candidates, one or more of our U.S. patents may be eligible
for limited patent term extension under the Drug Price Competition and Patent Term Restoration Act of 1984, referred to as the
Hatch-Waxman Amendments and similar legislation in the European Union. The Hatch-Waxman Amendments permit a patent term extension
of up to five years for a patent covering an approved product as compensation for effective patent term lost during product development
and the FDA regulatory review process. A patent term extension cannot extend the remaining term of a patent beyond a total of 14
years from the date of product approval, only one patent may be extended and only those claims covering the approved drug, a method
for using it, or a method for manufacturing it may be extended. However, we might not receive an extension if we fail to apply
within applicable deadlines, fail to apply prior to expiration of relevant patents or otherwise fail to satisfy applicable requirements.
Moreover, the length of the extension could be less than we request. If we are unable to obtain patent term extension or the term
of any such extension is less than we request, the period during which we can enforce our patent rights for that product will be
shortened and our competitors may obtain approval to market competing products sooner. As a result, our revenue from applicable
products could be reduced and could have a material adverse effect on our business, financial condition, results of operations,
and prospects.
Changes to the patent law in the
United States or other jurisdictions could diminish the value of patents in general, thereby impairing our ability to protect our
products.
Our success is heavily
dependent on intellectual property, particularly patents. Obtaining and enforcing patents in the biopharmaceutical industry involves
both technological and legal complexity and is therefore costly, time consuming and inherently uncertain. The Leahy-Smith America
Invents Act, or the America Invents Act, reformed U.S. patent law in part by changing the U.S. patent system from a “first
to invent” system to a “first inventor to file” system, expanding the definition of prior art, and developing
a post-grant review system. This legislation changed U.S. patent law in a way that may weaken our ability to obtain patent protection
in the United States for those applications filed after March 16, 2013.
Further, the America
Invents Act created new procedures to challenge the validity of issued patents in the United States, including post-grant review
and inter partes review proceedings, which some third parties have been using to cause the cancellation of selected or all
claims of issued patents of competitors. For a patent with an effective filing date of March 16, 2013 or later, a petition for
post-grant review can be filed by a third party in a nine-month window from issuance of the patent. A petition for inter partes
review can be filed immediately following the issuance of a patent if the patent has an effective filing date prior to March 16,
2013. A petition for inter partes review can be filed after the nine-month period for filing a post-grant review petition
has expired for a patent with an effective filing date of March 16, 2013 or later. Post-grant review proceedings can be brought
on any ground of invalidity, whereas inter partes review proceedings can only raise an invalidity challenge based on published
prior art and patents. These adversarial actions at the USPTO review patent claims without the presumption of validity afforded
to U.S. patents in lawsuits in U.S. federal courts, and use a lower burden of proof than used in litigation in U.S. federal courts.
Therefore, it is generally considered easier for a competitor or third party to have a U.S. patent invalidated in a USPTO post-grant
review or inter partes review proceeding than invalidated in a litigation in a U.S. federal court. If any of our patents
are challenged by a third party in such a USPTO proceeding, there is no guarantee that we, our licensors or collaborators will
be successful in defending the patent, which would result in a loss of the challenged patent right to us.
In addition, recent
court rulings in cases such as Association for Molecular Pathology v. Myriad Genetics, Inc., BRCA1- & BRCA2-Based Hereditary
Cancer Test Patent Litigation, Promega Corp. v. Life Technologies Corp. and Abbvie Deutschland GmbH v. Janssen Biotech, Inc.
have narrowed the scope of patent protection available in certain circumstances and weakened the rights of patent owners in certain
situations. In addition to increasing uncertainty with regard to our ability to obtain patents in the future, this combination
of events has created uncertainty with respect to the value of patents once obtained. Depending on future actions by the U.S. Congress,
the U.S. courts, the USPTO and the relevant law-making bodies in other countries, the laws and regulations governing patents could
change in unpredictable ways that would weaken our ability to obtain new patents or to enforce our existing patents and patents
that we might obtain in the future. Any changes to patent law in the United States or other jurisdictions that impairs our ability
to protect our product candidates could have a material adverse effect on our business, financial condition, results of operations,
and prospects.
We might not be able to enforce our
intellectual property rights throughout the world.
Filing, prosecuting,
enforcing and defending patents on our product candidates in all countries throughout the world would be prohibitively expensive,
and our intellectual property rights in some foreign countries can be less extensive than those in the United States. The requirements
for patentability may differ in certain countries, particularly in developing countries; thus, even in countries where we do pursue
patent protection, there can be no assurance that any patents will issue with claims that cover our products.
Moreover, our ability
to protect and enforce our intellectual property rights may be adversely affected by unforeseen changes in foreign intellectual
property laws. Many companies have encountered significant problems in protecting and defending intellectual property rights in
certain foreign jurisdictions. The legal systems of some countries, including India, China and other developing countries, do not
favor the enforcement of patents and other intellectual property rights. This could make it difficult for us to stop the infringement
of our patents or the misappropriation of our other intellectual property rights. For example, many foreign countries have compulsory
licensing laws under which a patent owner must grant licenses to third parties. Consequently, we might not be able to prevent third
parties from practicing our inventions in certain foreign countries. Competitors may use our technologies in jurisdictions where
we have not obtained patent protection to develop and market their own products and, further, may export otherwise infringing products
to territories where we have patent protection, if our ability to enforce our patents to stop infringing activities is inadequate.
These products may compete with our products, and our patents or other intellectual property rights might not be effective or sufficient
to prevent them from competing.
Agreements through
which we license patent rights might not give us sufficient rights to permit us to pursue enforcement of our licensed patents or
defense of any claims asserting the invalidity of these patents (or control of enforcement or defense) of such patent rights in
all relevant jurisdictions as requirements may vary.
Proceedings to enforce
our patent rights in foreign jurisdictions, whether or not successful, could result in substantial costs and divert our efforts
and resources from other aspects of our business. Moreover, such proceedings could put our patents at risk of being invalidated
or interpreted narrowly and our patent applications at risk of not issuing and could provoke third parties to assert claims against
us. We might not prevail in any lawsuits that we initiate and the damages or other remedies awarded, if any, might not be commercially
meaningful. Furthermore, while we intend to protect our intellectual property rights in major markets for our products, we cannot
ensure that we will be able to initiate or maintain similar efforts in all jurisdictions in which we may wish to market our products.
Accordingly, our efforts to protect our intellectual property rights in such countries may be inadequate. Any of the foregoing
could have a material adverse effect on our business, financial condition, results of operations, and prospects.
If we are sued for infringing, misappropriating,
or otherwise violating intellectual property rights of third parties, such litigation could be costly and time consuming and could
prevent or delay us from developing or commercializing our product candidates.
Our commercial success
depends, in part, on our ability to develop, manufacture, market and sell our product candidates without infringing, misappropriating,
or otherwise violating the intellectual property and other proprietary rights of third parties. Third parties may have U.S. and
non- U.S. issued patents and pending patent applications relating to compounds, methods of manufacturing compounds and/or methods
of use for the treatment of the disease indications for which we are developing our product candidates that may cover our product
candidates or approach to complement inhibition. If any third-party patents or patent applications are found to cover our product
candidates or their methods of use or manufacture, or our approach to complement inhibition, we might not be free to manufacture
or market our product candidates as planned without obtaining a license, which might not be available on commercially reasonable
terms, or at all.
There is a substantial
amount of intellectual property litigation in the biotechnology and pharmaceutical industries, and we may become party to, or threatened
with, litigation or other adversarial proceedings regarding intellectual property rights with respect to our product candidates,
including interference and post-grant proceedings before the USPTO. There may be third-party patents or patent applications with
claims to materials, formulations, methods of manufacture or methods for treatment related to the composition, use or manufacture
of our product candidates. We cannot guarantee that any of our patent searches or analyses including, but not limited to, the identification
of relevant patents, the scope of patent claims or the expiration of relevant patents are complete or thorough, nor can we be certain
that we have identified each and every patent and pending application in the United States and abroad that is relevant to or necessary
for the commercialization of our product candidates in any jurisdiction. Because patent applications can take many years to issue,
there may be currently pending patent applications which may later result in issued patents that our product candidates may be
accused of infringing. In addition, third parties may obtain patents in the future and claim that use of our technologies infringes
upon these patents. Accordingly, third parties may assert infringement claims against us based on intellectual property rights
that exist now or arise in the future. The outcome of intellectual property litigation is subject to uncertainties that cannot
be adequately quantified in advance. The pharmaceutical and biotechnology industries have produced a significant number of patents,
and it might not always be clear to industry participants, including us, which patents cover various types of products or methods
of use or manufacture. The scope of protection afforded by a patent is subject to interpretation by the courts, and the interpretation
is not always uniform. If we are sued for patent infringement, we would need to demonstrate that our product candidates, products
or methods either do not infringe the patent claims of the relevant patent or that the patent claims are invalid or unenforceable,
and we might not be able to do this. Proving invalidity is difficult. For example, in the United States, proving invalidity requires
a showing of clear and convincing evidence to overcome the presumption of validity enjoyed by issued patents. Even if we are successful
in these proceedings, we may incur substantial costs and the time and attention of our management and scientific personnel could
be diverted in pursuing these proceedings, which could significantly harm our business and operating results. In addition, we might
not have sufficient resources to bring these actions to a successful conclusion. Further, the outcome of intellectual property
litigation is subject to uncertainties that cannot be adequately quantified in advance, including the demeanor and credibility
of witnesses and the identity of any adverse party. This is especially true in intellectual property cases that may turn on the
testimony of experts as to technical facts upon which experts may reasonably disagree.
If we are found to
infringe, misappropriate, or otherwise violate a third party’s intellectual property rights, we could be forced, including
by court order, to cease developing, manufacturing or commercializing the infringing product candidate or product. Alternatively,
we may be required to obtain a license from such third party in order to use the infringing technology and continue developing,
manufacturing or marketing the infringing product candidate or product. However, we might not be able to obtain any required license
on commercially reasonable terms or at all. Even if we were able to obtain a license, it could be non-exclusive, thereby giving
our competitors access to the same technologies licensed to us; alternatively or additionally it could include terms that impede
or destroy our ability to compete successfully in the commercial marketplace. In addition, we could be found liable for monetary
damages, including treble damages and attorneys’ fees if we are found to have willfully infringed a patent. A finding of
infringement could prevent us from commercializing our product candidates or force us to cease some of our business operations,
which could harm our business. Claims that we have misappropriated the confidential information or trade secrets of third parties
could have a similar negative impact on our business. Any of the foregoing could have a material adverse effect on our business,
financial condition, results of operations, and prospects.
We may be subject to claims by third
parties asserting that our employees or we have misappropriated their intellectual property, or claiming ownership of what we regard
as our own intellectual property and proprietary technology.
Many of our current
and former employees and our licensors’ current and former employees, including our senior management, were previously employed
at universities or at other biotechnology or pharmaceutical companies, including some which may be competitors or potential competitors.
Although we try to ensure that our employees do not use the proprietary information or know-how of others in their work for us,
we may be subject to claims that we or these employees have used or disclosed intellectual property, including trade secrets or
other proprietary information, of any such third party. Litigation may be necessary to defend against such claims. If we fail in
defending any such claims, in addition to paying monetary damages, we may lose valuable intellectual property rights or personnel
or sustain damages. Such intellectual property rights could be awarded to a third party, and we could be required to obtain a license
from such third party to commercialize our technology or products. Such a license might not be available on commercially reasonable
terms or at all. Even if we are successful in defending against such claims, litigation could result in substantial costs and be
a distraction to management.
In addition, while
we typically require our employees, consultants and contractors who may be involved in the development of intellectual property
to execute agreements assigning such intellectual property to us, we may be unsuccessful in executing such an agreement with each
party who in fact develops intellectual property that we regard as our own, which may result in claims by or against us related
to the ownership of such intellectual property. If we fail in prosecuting or defending any such claims, in addition to paying monetary
damages, we may lose valuable intellectual property rights. Even if we are successful in prosecuting or defending against such
claims, litigation could result in substantial costs and be a distraction to our senior management and scientific personnel. Any
of the foregoing could have a material adverse effect on our business, financial condition, results of operations, and prospects.
We may become involved in lawsuits
to protect or enforce our patents or other intellectual property, which could be expensive, time consuming and unsuccessful.
Competitors may infringe,
misappropriate, or otherwise violate our patents, trademarks, copyrights or other intellectual property. To counter infringement
or unauthorized use, we may be required to file infringement claims, which can be expensive and time consuming and divert the time
and attention of our management and scientific personnel. Any claims we assert against perceived infringers could provoke these
parties to assert counterclaims against us alleging that we infringe their patents, in addition to counterclaims asserting that
our patents are invalid or unenforceable, or both. In any patent infringement proceeding, there is a risk that a court will decide
that a patent of ours is invalid or unenforceable, in whole or in part, and that we do not have the right to stop the other party
from using the invention at issue. There is also a risk that, even if the validity of such patents is upheld, the court will construe
the patent’s claims narrowly or decide that we do not have the right to stop the other party from using the invention at
issue on the grounds that our patent claims do not cover the invention. An adverse outcome in a litigation or proceeding involving
one or more of our patents could limit our ability to assert those patents against those parties or other competitors, and may
curtail or preclude our ability to exclude third parties from making and selling similar or competitive products. Similarly, if
we assert trademark infringement claims, a court may determine that the marks we have asserted are invalid or unenforceable, or
that the party against whom we have asserted trademark infringement has superior rights to the marks in question. In this case,
we could ultimately be forced to cease use of such trademarks.
Further, the outcome
of intellectual property litigation is subject to uncertainties that cannot be adequately quantified in advance, including the
demeanor and credibility of witnesses and the identity of any adverse party. This is especially true in intellectual property cases
that may turn on the testimony of experts as to technical facts upon which experts may reasonably disagree.
Even if we establish
infringement, the court may decide not to grant an injunction against further infringing activity and instead award only monetary
damages, which might not be an adequate remedy. Furthermore, because of the substantial amount of discovery required in connection
with intellectual property litigation, there is a risk that some of our confidential information could be compromised by disclosure
during litigation. There could also be public announcements of the results of hearings, motions or other interim proceedings or
developments. If securities analysts or investors perceive these results to be negative, it could adversely affect the price of
our common shares. Moreover, there can be no assurance that we will have sufficient financial or other resources to file and pursue
such infringement claims, which typically last for years before they are concluded. Even if we ultimately prevail in such claims,
the monetary cost of such litigation and the diversion of the attention of our management and scientific personnel could outweigh
any benefit we receive as a result of the proceedings. Any such litigation could have a material adverse effect on our business,
financial condition, results of operations, and prospects.
If we fail to comply with our obligations
under our existing and any future intellectual property licenses with third parties, we could lose license rights that are important
to our business.
We may be reliant upon
licenses to certain patent rights and proprietary technology form third parties that are important or necessary to the development
of our product candidates. These and other licenses might not provide exclusive rights to use such intellectual property and technology
in all relevant fields of use and in all territories in which we may wish to develop or commercialize our technology and products
in the future. As a result, we might not be able to prevent competitors from developing and commercializing competitive products
in territories included in all of our licenses. Our licensors may have relied on third party consultants or collaborators or funds
from third parties such that our licensors are not the sole and exclusive owners of the patents we in-license. This could have
a material adverse effect on our competitive position, business, financial conditions, results of operations and prospects.
In addition, the agreements
under which we license patent rights might not give us control over patent prosecution or maintenance, so that we might not be
able to control which claims or arguments are presented and might not be able to secure, maintain, or successfully enforce necessary
or desirable patent protection from those patent rights. We cannot be certain that patent prosecution and maintenance activities
by our licensors will be conducted in compliance with applicable laws and regulations or will result in valid and enforceable patents.
Even if we are permitted to pursue such enforcement or defense, we will require the cooperation of our licensors, and cannot guarantee
that we would receive it and on what terms. We cannot be certain that our licensors will allocate sufficient resources or prioritize
their or our enforcement of such patents or defense of such claims to protect our interests in any licensed patents. If we cannot
obtain patent protection, or enforce existing or future patents against third parties, it could have a material adverse effect
on our business, financial condition, results of operations, and prospects.
Further, the agreements
under which we currently license intellectual property or technology to or from third parties are complex, and certain provisions
in such agreements may be susceptible to multiple interpretations. The resolution of any contract interpretation disagreement that
may arise could narrow what we believe to be the scope of our rights to the relevant intellectual property or technology, or increase
what we believe to be our financial or other obligations under the relevant agreement, either of which could have a material adverse
effect on our business, financial conditions, results of operations, and prospects. Moreover, if disputes over intellectual property
that we license prevent or impair our ability to maintain our licensing arrangements on commercially acceptable terms, we may be
unable to successfully develop and commercialize the affected product candidates, which could have a material adverse effect on
our business, financial conditions, results of operations, and prospects. Disputes may arise regarding intellectual property subject
to a licensing agreement, including:
|
·
|
the scope of rights granted under the
license agreement and other interpretation-related issues;
|
|
·
|
the extent to which our technology and
processes infringe on intellectual property of the licensor that is not subject to the licensing agreement;
|
|
·
|
the sublicensing of patent and other rights
under current and any future collaborative development relationships;
|
|
·
|
our diligence obligations under any license
agreement and what activities satisfy such obligations;
|
|
·
|
the inventorship and ownership of inventions
and know-how resulting from the joint creation or use of intellectual property by our license counterparties and us and our partners;
and
|
|
·
|
the priority of invention of patented
technology.
|
In spite of our efforts,
our license counterparties might conclude that we have materially breached our license agreements and might therefore terminate
the license agreements, which may remove our ability to develop and commercialize the product candidates and technology covered
by these license agreements. If any in-licenses are terminated, competitors would have the freedom to seek regulatory approval
of, and to market, products identical to ours. It is possible that we may be unable to obtain any additional licenses that we require
at a reasonable cost or on reasonable terms, if at all. In that event, we may be required to expend significant time and resources
to redesign our product candidates, technology, or the methods for manufacturing them or to develop or license replacement technology,
all of which might not be feasible on a technical or commercial basis. If we are unable to do so, we may be unable to develop or
commercialize the affected product candidates, which could harm our business, financial condition, results of operations, and prospects
significantly. Any of these events could have a material adverse effect on our competitive position, business, financial conditions,
results of operations, and prospects.
If we are unable to protect the confidentiality
of our trade secrets, the value of our technology could be negatively impacted and our business would be harmed.
In addition to the
protection afforded by patents, we also rely on trade secret protection for certain aspects of our intellectual property. However,
trade secrets are difficult to protect. We seek to protect these trade secrets, in part, by entering into non-disclosure and confidentiality
agreements with parties who have access to them, such as our employees, consultants, independent contractors, advisors, contract
manufacturers, suppliers and other third parties. We also enter into confidentiality and invention or patent assignment agreements
with employees and certain consultants. Any party with whom we have executed such an agreement may breach that agreement and disclose
our proprietary information, including our trade secrets, and we might not be able to obtain adequate remedies for such breaches.
Enforcing a claim that a party illegally disclosed or misappropriated a trade secret is difficult, expensive and time-consuming,
and the outcome is unpredictable. Additionally, if the steps taken to maintain our trade secrets are deemed inadequate, we may
have insufficient recourse against third parties for misappropriating the trade secret. Further, if any of our trade secrets were
to be lawfully obtained or independently developed by a competitor, we would have no right to prevent such third party, or those
to whom they communicate such technology or information, from using that technology or information to compete with us. If any of
our trade secrets were to be disclosed to or independently developed by a competitor, it could have a material adverse effect on
our business, financial condition, results of operations, and prospects.
If our trademarks and trade names
are not adequately protected, then we might not be able to build name recognition in our marks of interest and our business may
be adversely affected.
Our trademarks or trade
names, including OptejetTM, may be challenged, infringed, circumvented or declared generic or determined to be infringing
on other marks. We rely on both registration and common law protection for our trademarks. We might not be able to protect our
rights to these trademarks and trade names or may be forced to stop using these names, which we need for name recognition by potential
partners or customers in our markets of interest. During trademark registration proceedings, we may receive rejections. Although
we would be given an opportunity to respond to those rejections, we may be unable to overcome such rejections. In addition, in
the USPTO and in comparable agencies in many foreign jurisdictions, third parties are given an opportunity to oppose pending trademark
applications and to seek to cancel registered trademarks. Opposition or cancellation proceedings may be filed against our trademarks,
and our trademarks might not survive such proceedings. If we are unable to establish name recognition based on our trademarks and
trade names, we might not be able to compete effectively and our business may be adversely affected.
RISKS RELATED TO OWNERSHIP OF OUR COMMON
STOCK
Our management and members of our
Board of Directors have the ability to substantially influence all matters submitted to stockholders for approval.
As of March 25,
2020, our management and members of our Board of Directors, in the aggregate, beneficially owned shares representing
approximately 23% of our capital stock. As a result, they can substantially influence all matters submitted to our
stockholders for approval, as well as our management and affairs. For example, these persons would substantially influence
the election of directors and approval of any merger, consolidation or sale of all or substantially all of our assets. This
concentration of voting power could delay or prevent an acquisition of our company on terms that other stockholders desire or
result in management of our company that our public stockholders disagree with.
A significant portion of our total
outstanding shares may be sold into the market in the near future, which could cause the market price of our common stock to drop
significantly, even if our business is performing well.
Sales of a substantial
number of shares of our common stock in the public market could occur at any time, subject to certain restrictions. These sales,
or the perception in the market that holders of a large number of shares intend to sell shares, could reduce the market price
of our common stock. As of March 25, 2020, we had 19,776,019 shares of common stock outstanding, including 2,675,293 shares of
common stock that were issued in our recent private placement. The shares of common stock issued in our private placement and
3,344,154 shares of common stock issuable upon exercise of warrants also issued in that private placement may be resold without
restriction upon effectiveness of the resale registration statement regarding such securities that we are required to file with
the SEC within the next 30 days.
The price of our common stock may
be volatile and fluctuate substantially, which could result in substantial losses for purchasers of our common stock.
The stock market historically
has experienced extreme price and volume fluctuations, such as those seen in February 2020 as a result of concerns the coronavirus
will impact the economy worldwide. As a result of this volatility and because the public market for our stock is new, you might
not be able to sell your common stock at or above the price at which you purchase it. From our IPO in January 2018 through March
25, 2020, the per share trading price of our common stock has been as high as $10.74 and as low as $1.77. It might continue to
fluctuate significantly in response to various factors, some of which are beyond our control. These factors include:
|
·
|
general economic, industry and market
conditions, including as a result of the coronavirus pandemic;
|
|
·
|
our ability to successfully conduct clinical
trials and submit NDAs;
|
|
·
|
results of clinical trials of our product
candidates or those of our competitors;
|
|
·
|
the success of competitive products or
technologies;
|
|
·
|
commencement or termination of collaborations;
|
|
·
|
regulatory or legal developments in the
United States and other countries;
|
|
·
|
developments or disputes concerning patent
applications, issued patents or other proprietary rights;
|
|
·
|
the recruitment or departure of key personnel;
|
|
·
|
the level of expenses related to any of
our product candidates or clinical development programs;
|
|
·
|
the results of our efforts to discover,
develop, acquire or in-license additional product candidates;
|
|
·
|
actual or anticipated changes in estimates
as to financial results, development timelines or recommendations by securities analysts;
|
|
·
|
our inability to obtain or delays in obtaining
adequate product supply for any approved product or inability to do so at acceptable prices;
|
|
·
|
disputes or other developments relating
to proprietary rights, including patents, litigation matters and our ability to obtain patent protection for our technologies;
|
|
·
|
significant lawsuits, including patent
or stockholder litigation;
|
|
·
|
variations in our financial results or
those of companies that are perceived to be similar to us;
|
|
·
|
changes in the structure of healthcare
payment systems;
|
|
·
|
market conditions in the pharmaceutical
and biotechnology sectors;
|
|
·
|
the other factors described in this “Risk
Factors” section.
|
We have broad discretion in the use
of our cash, including the net proceeds from our financings, and might not use them effectively.
Our management will
have broad discretion in the application of our cash, including the net proceeds from our December 2018 follow-on and July 2019
public offerings of common stock, and recent private placement, and could spend our cash in ways that do not improve our results
of operations or enhance the value of our common stock. The failure by our management to apply these funds effectively could result
in financial losses that could have a material adverse effect on our business, cause the price of our common stock to decline and
delay the development of our product candidates. Pending their use, we may invest our cash, including the net proceeds from our
financings, in a manner that does not produce income or that loses value.
Our business is subject to changing
regulations regarding corporate governance, disclosure controls, internal control over financial reporting, and other compliance
areas that will increase both our costs and the risk of noncompliance.
As a public company,
we are subject to the reporting requirements of the Exchange Act, the Sarbanes-Oxley Act of 2002, or the Sarbanes-Oxley Act, the
Dodd-Frank Act, and the rules and regulations of our stock exchange. The requirements of these rules and regulations will increase
our legal, accounting, and financial compliance costs, will make some activities more difficult, time-consuming, and costly, and
may also place undue strain on our personnel, systems, and resources.
The Sarbanes-Oxley
Act requires, among other things, that we maintain effective disclosure controls and procedures and internal control over financial
reporting. Commencing with our fiscal year ending December 31, 2018, we performed system and process evaluation and testing of
our internal control over financial reporting so that management could report on the effectiveness of our internal control over
financial reporting, as required by Section 404 of the Sarbanes-Oxley Act. Our compliance with Section 404 of the Sarbanes-Oxley
Act requires that we incur substantial accounting expense and expend significant management efforts. Prior to our IPO, we had never
been required to test our internal controls within a specified period.
We are required to
disclose changes made to our internal control and procedures on a quarterly basis. However, our independent registered public accounting
firm will not be required to formally attest to the effectiveness of our internal control over financial reporting pursuant to
Section 404 of the Sarbanes-Oxley Act until we are no longer an “emerging growth company” as defined in the Jumpstart
Our Business Startups Act of 2012 (JOBS Act), if we take advantage of the exemption available under the JOBS Act to the auditor
attestation requirement in Section 404(b) of the Sarbanes-Oxley Act. If we are not able to comply with the requirements of Section
404 of the Sarbanes-Oxley Act in a timely manner, the market price of our stock could decline and we could be subject to sanctions
or investigations by the stock exchange on which our common stock is listed, the SEC, or other regulatory authorities, which would
require additional financial and management resources.
Failure to develop and maintain adequate
financial controls could cause us to have material weaknesses, which could adversely affect our operations and financial position.
As previously reported,
in the fourth quarter of 2017, we identified certain material weaknesses in internal controls including regarding insufficient
segregation of duties in our finance and accounting function because of our limited personnel, properly identifying all related
party relationships and transactions so that they could be evaluated for disclosure in our public filings, properly communicating
the terms of certain agreements entered into by us to the Board of Directors in order for the Board to take the appropriate actions,
and adequately recording research and development expenses in our internal books and records to permit timely and accurate financial
reporting. While we have remedied these weaknesses, we might in the future discover other material weaknesses that require additional
remediation. In addition, an internal control system, no matter how well-designed, cannot provide absolute assurance that misstatements
due to error or fraud will not occur or that all control issues and instances of fraud will be detected. If we are not able to
comply with the requirements of Section 404 of the Sarbanes-Oxley Act in a timely manner, or if we are unable to maintain proper
and effective internal controls, we might not be able to produce timely and accurate financial statements. If that were to happen,
the market price of our stock could decline and we could be subject to sanctions or investigations by the stock exchange on which
our common stock is listed, the SEC, or other regulatory authorities.
Any failure to develop
or maintain effective controls, or any difficulties encountered in their implementation or improvement, could harm our operating
results or cause us to fail to meet our reporting obligations. Any failure to implement and maintain effective internal controls
also could adversely affect the results of periodic management evaluations regarding the effectiveness of our internal control
over financial reporting that we are required to include in our periodic reports filed with the SEC under Section 404 of the Sarbanes-Oxley
Act. Ineffective disclosure controls and procedures or internal control over financial reporting could also cause investors to
lose confidence in our reported financial and other information, which would likely have a negative effect on the trading price
of our common stock. Implementing any appropriate changes to our internal controls may require specific compliance training of
our directors, officers, and employees, entail substantial costs in order to modify our existing accounting systems, and take a
significant period of time to complete. Such changes may not be effective, however, in maintaining the adequacy of our internal
controls, and any failure to maintain that adequacy, or consequent inability to produce accurate financial statements on a timely
basis, could increase our operating costs and could materially impair our ability to operate our business. In the event that we
are not able to demonstrate compliance with Section 404 of the Sarbanes-Oxley Act in a timely manner, that our internal controls
are perceived as inadequate, or that we are unable to produce timely or accurate financial statements, investors may lose confidence
in our operating results and our stock price could decline.
We are an “emerging growth
company” and the reduced disclosure requirements applicable to emerging growth companies may make our common stock less attractive
to investors.
We are an emerging
growth company. Under the JOBS Act, emerging growth companies can delay adopting new or revised accounting standards until such
time as those standards apply to private companies. We have elected to avail ourselves of this exemption from new or revised accounting
standards.
For as long as we continue
to be an emerging growth company, we intend to take advantage of certain other exemptions from various reporting requirements that
are applicable to other public companies including, but not limited to, reduced disclosure obligations regarding executive compensation
in our periodic reports and proxy statements, exemptions from the requirements of holding a nonbinding advisory vote on executive
compensation and stockholder approval of any golden parachute payments not previously approved, and exemptions from the requirements
of auditor attestation reports on the effectiveness of our internal control over financial reporting. We cannot predict if investors
will find our common stock less attractive because we will rely on these exemptions. If some investors find our common stock less
attractive as a result, there may be a less active trading market for our common stock and our stock price may be more volatile.
We will remain an emerging
growth company until the earliest of (i) the end of the fiscal year in which the market value of our common stock that is held
by non-affiliates exceeds $700 million as of June 30 of that fiscal year, (ii) the end of the fiscal year in which we have total
annual gross revenue of $1.07 billion or more during such fiscal year, (iii) the date on which we issue more than $1 billion in
non-convertible debt in a three-year period, or (iv) December 31, 2023.
Provisions in our corporate charter
documents and under Delaware law could make an acquisition of us, which may be beneficial to our stockholders, more difficult and
may prevent attempts by our stockholders to replace or remove our current management.
Provisions in our certificate
of incorporation, and our bylaws may discourage, delay or prevent a merger, acquisition or other change in control of us that stockholders
may consider favorable, including transactions in which you might otherwise receive a premium for your shares. These provisions
also could limit the price that investors might be willing to pay in the future for shares of our common stock, thereby depressing
the market price of our common stock. In addition, because our Board of Directors is responsible for appointing the members of
our management team, these provisions may frustrate or prevent any attempts by our stockholders to replace or remove our current
management by making it more difficult for stockholders to replace members of our Board. Among other things, these provisions:
|
·
|
allow the authorized number of our directors
to be changed only by resolution adopted by a majority of our Board;
|
|
·
|
limit the manner in which stockholders
can remove directors from the Board, as may be permitted by law;
|
|
·
|
establish advance notice requirements
for stockholder proposals that can be acted on at stockholder meetings and nominations to our Board;
|
|
·
|
limit who may call stockholder meetings;
|
|
·
|
authorize our Board to issue preferred
stock without stockholder approval, which could be used to institute a stockholder rights plan, or so-called “poison pill,”
that would work to dilute the stock ownership of a potential hostile acquirer, effectively preventing acquisitions that have not
been approved by our Board; and
|
|
·
|
require all stockholder action to take
place at duly called stockholder meetings and disallow the ability of our stockholders to act by majority written consent.
|
Moreover, because we
are incorporated in Delaware, we are governed by the provisions of Section 203 of the Delaware General Corporation Law, which prohibits
a person who owns in excess of 15% of our outstanding voting stock from merging or combining with us for a period of three years
after the date of the transaction in which the person acquired in excess of 15% of our outstanding voting stock, unless the merger
or combination is approved in a prescribed manner.
Our certificate
of incorporation provides that the Court of Chancery of the State of Delaware is, to the fullest extent permitted by law, the sole
and exclusive forum for substantially all disputes between us and our stockholders. These choice of forum provisions could limit
the ability of stockholders to obtain a favorable judicial forum for disputes with us or our directors, officers or employees.
Unless we consent to
the selection of an alternative forum, our certificate of incorporation provides that the Court of Chancery of the State of Delaware,
or the Court of Chancery, will be, to the fullest extent permitted by law, the sole and exclusive forum for any derivative action
or proceeding brought on our behalf; any action asserting a claim of breach of fiduciary duty owed by any of our directors, officers
or other employees or agent to the Company or our stockholders; any action asserting a claim against us arising pursuant to the
Delaware General Corporation Law, or DGCL, or our certificate of incorporation or bylaws; any action to enforce or determine the
validity of our certificate of incorporation or bylaws; or any action asserting a claim against us that is governed by the internal
affairs doctrine. Since the choice of forum provisions are only applicable to “the fullest extent permitted by law,”
as provided in our certificate of incorporation, the provisions do not designate the Court of Chancery as the exclusive forum for
any derivative action or other claim for which the applicable statute creates exclusive jurisdiction in another forum. As such,
the choice of forum provisions do not apply to any actions arising under the Securities Act of 1933, as amended or the Exchange
Act.
These
choice of forum provisions may limit a stockholder’s ability to bring a claim in a judicial forum that it finds favorable
for disputes with us or our directors, officers or other employees, which may discourage such lawsuits against us and our directors,
officers and other employees. Alternatively, if a court were to find the choice of forum provisions contained in our certificate
of incorporation to be inapplicable or unenforceable in an action, we may incur additional costs associated with resolving such
action in other jurisdictions, which could materially adversely affect our business, financial condition and operating results.
Because we do not anticipate paying
any cash dividends on our common stock in the foreseeable future, capital appreciation, if any, will be your sole source of gain.
We have never declared
or paid cash dividends on our common stock. We currently intend to retain all of our future earnings, if any, to finance the growth
and development of our business. In addition, the terms of any future debt agreements may preclude us from paying dividends. As
a result, capital appreciation, if any, of our common stock will be your sole source of gain for the foreseeable future.
If securities analysts do not continue
to publish research or reports about our business or if they publish negative evaluations of our stock, the price of our stock
could decline.
The trading market
for our common stock will rely, in part, on the research and reports that industry or financial analysts publish about us or our
business. If securities analysts do not continue coverage of us, the trading price of our stock could decrease. Additionally, if
one or more of the analysts covering our business downgrade their evaluations of our stock, the price of our stock could decline.
If one or more of these analysts cease to cover our stock, we could lose visibility in the market for our stock, which in turn
could cause our stock price to decline.
NOTES TO FINANCIAL STATEMENTS
FOR THE YEARS ENDED DECEMBER 31, 2019
AND 2018
Note 1 – Business Organization and Nature of Operations
Eyenovia, Inc. (“Eyenovia”
or the “Company”) was organized as a corporation under the laws of the State of Florida on March 12, 2014 under
the name, PGP Holdings V, Inc. On May 5, 2014, PGP Holdings V, Inc. changed its name to Eyenovia, Inc. On October 6,
2014, Eyenovia, Inc. reincorporated in the State of Delaware by merging into Eyenovia, Inc., a Delaware corporation.
Eyenovia. Inc. (“Eyenovia”
or the “Company”) is a clinical stage ophthalmic biopharmaceutical company developing a pipeline of microdose
therapeutics utilizing its patented piezo-print delivery technology, branded the OptejetTM. Eyenovia aims to achieve
clinical microdosing of next-generation formulations of well-established ophthalmic pharmaceutical agents using its high-precision
targeted ocular delivery system, which has the potential to replace conventional eye dropper delivery and improve safety, tolerability,
patient compliance and topical delivery success for ophthalmic eye treatments. In the clinic, the Optejet has demonstrated the
ability to horizontally deliver opthalmic medication with a success rate significantly higher than that of traditional eye drops
(~ 90% vs. ~ 50%). Using its proprietary delivery technology, Eyenovia is developing the next generation of smart ophthalmic therapies
which target new indications or new combinations where there are currently no comparable drug therapies approved by the U.S. Food
and Drug Administration (the “FDA”). Eyenovia’s microdose therapeutics follow the FDA-designated pharmaceutical
registration and regulatory process. Its products are classified by the FDA as drugs, and not medical devices or drug-device combination
products.
Note
2 – Summary of Significant Accounting Policies
Liquidity and Going Concern
The Company has not yet generated
revenues or achieved profitability and expects to continue to incur cash outflows from operations. The Company expects that
its research and development and general and administrative expenses will continue to increase and, as a result, it will
eventually need to generate significant product revenues to achieve profitability. These circumstances raise substantial
doubt about the Company’s ability to continue as a going concern within one year after the date that the financial
statements are issued. Implementation of the Company’s plans and its ability to continue as a going concern will depend
upon the Company’s ability to raise further capital, through the sale of additional equity or debt securities or
otherwise, to support its future operations.
The Company’s operating needs include
the planned costs to operate its business, including amounts required to fund working capital and capital expenditures. The Company’s
future capital requirements and the adequacy of its available funds will depend on many factors, including the Company’s
ability to successfully commercialize its products and services, competing technological and market developments, and the need
to enter into collaborations with other companies or acquire other companies or technologies to enhance or complement its product
and service offerings. If the Company is unable to secure additional capital, it may be required to curtail its research and development
initiatives and take additional measures to reduce costs in order to conserve its cash.
On October 29, 2019, the Company announced that it is advancing
its MicroLine program for the improvement in near vision in patients with presbyopia towards Phase III clinical studies. As a result
of prioritizing MicroLine, in tandem with its Mircropine (progressive myopia) and MicroStat (mydriasis) programs, the Company deferred
development activities for its MicroProst (glaucoma and ocular hypertension) and MicroTears (red eye and itch relief lubrication)
programs. The Company believes the re-prioritization of its programs will yield overall cost savings of approximately $1.5 million
to $1.9 million in 2020.
EYENOVIA, INC.
NOTES TO FINANCIAL STATEMENTS
FOR THE YEARS ENDED DECEMBER 31, 2019
AND 2018
Note 2 – Summary of Significant
Accounting Policies – Continued
Use of Estimates
Preparation of financial statements in
conformity with accounting principles generally accepted in the United States of America (“U.S. GAAP”) requires management
to make estimates, judgments and assumptions that affect the amounts reported in the financial statements and the amounts disclosed
in the related notes to the financial statements. The Company bases its estimates and judgments on historical experience and on
various other assumptions that it believes are reasonable under the circumstances. The amounts of assets and liabilities reported
in the Company’s balance sheets and the amounts of expenses reported for each of the periods presented are affected by estimates
and assumptions, which are used for, but not limited to, fair value calculations for equity securities, establishment of valuation
allowances for deferred tax assets, stock-based compensation, the recoverability and useful lives of long-lived assets and the
recovery of deferred costs. Certain of the Company’s estimates could be affected by external conditions, including those
unique to the Company and general economic conditions. It is reasonably possible that actual results could differ from those estimates.
See Note 2 - Summary of Significant Accounting
Policies — Stock-Based Compensation for additional discussion of the use of estimates in estimating the fair
value of the Company’s common stock.
Cash and Cash Equivalents
The Company considers all highly liquid
investments with an original maturity of three months or less to be cash equivalents in the financial statements.
The Company has cash deposits and U.S.
treasury bills in a financial institutions which, at times, may be in excess of Federal Deposit Insurance Corporation (“FDIC”)
insurance limits. The Company has not experienced losses in such accounts and periodically evaluates the creditworthiness of its
financial institutions. As of December 31, 2019 and 2018, the Company had cash and cash equivalent balances in excess of FDIC insurance
limits of $13,902,601 and $19,478,200, respectively.
Property and Equipment, Net
Property and equipment are stated at cost,
net of accumulated depreciation, which is recorded commencing at the in-service date using the straight-line method at rates sufficient
to charge the cost of depreciable assets to operations over their estimated useful lives, which range from 2 to 5 years. Leasehold
improvements are amortized over the lesser of (a) the useful life of the asset; or (b) the remaining lease term. Maintenance and
repairs are charged to operations as incurred. The Company capitalizes costs attributable to the betterment of property and equipment
when such betterment extends the useful life of the assets.
Impairment of Long-lived Assets
The Company reviews for the impairment
of long-lived assets whenever events or changes in circumstances indicate that the carrying amount of an asset might not be recoverable.
An impairment would be recognized when estimated future cash flows expected to result from the use of the asset and its eventual
disposition are less than its carrying amount. The Company did not record any impairment losses during the years ended December
31, 2019 and 2018.
Deferred Offering Costs
Deferred offering costs, which primarily
consist of direct, incremental professional fees incurred in connection with the Company’s IPO as well as other private equity
offerings are capitalized as non-current assets on the balance sheet. Upon the closing of the offering, the deferred offering costs
are offset against the offering proceeds. The Company had $0 in deferred offering costs at December 31, 2019 and 2018.
EYENOVIA, INC.
NOTES TO FINANCIAL STATEMENTS
FOR THE YEARS ENDED DECEMBER 31, 2019
AND 2018
Note 2 – Summary of Significant
Accounting Policies – Continued
Preferred Stock
The Company applies the accounting standards
for distinguishing liabilities from equity when determining the classification and measurement of its preferred stock. Preferred
shares subject to mandatory redemption are classified as liability instruments and are measured at fair value. Conditionally redeemable
preferred shares (including preferred shares that feature redemption rights that are either within the control of the holder or
subject to redemption upon the occurrence of uncertain events not solely within the Company’s control) are classified as
temporary equity. At all other times, preferred shares are classified as stockholders’ equity.
Fair Value of Financial Instruments
The Company measures the fair value of
financial assets and liabilities based on ASC 820 “Fair Value Measurements and Disclosures” (“ASC 820”),
which defines fair value, establishes a framework for measuring fair value, and expands disclosures about fair value measurements.
ASC 820 defines fair value as the exchange
price that would be received for an asset or paid to transfer a liability (an exit price) in the principal or most advantageous
market for the asset or liability in an orderly transaction between market participants on the measurement date. ASC 820 also establishes
a fair value hierarchy, which requires an entity to maximize the use of observable inputs and minimize the use of unobservable
inputs when measuring fair value. ASC 820 describes three levels of inputs that may be used to measure fair value:
Level 1 — quoted prices in active
markets for identical assets or liabilities;
Level 2 — quoted prices for similar
assets and liabilities in active markets or inputs that are observable; and
Level 3 — inputs that are unobservable
(for example, cash flow modeling inputs based on assumptions).
The carrying amounts of the Company’s
financial instruments, such as cash and cash equivalents, due from related party, accounts payable, accrued expenses and other
current liabilities approximate fair values due to the short-term nature of these instruments.
Income Taxes
The Company is subject to Federal, New
York State and City, and State of California income taxes and files tax returns in those jurisdictions.
The Company recognizes deferred tax assets
and liabilities for the expected future tax consequences of items that have been included or excluded in the consolidated financial
statements or tax returns. Deferred tax assets and liabilities are determined on the basis of the difference between the tax basis
of assets and liabilities and their respective financial reporting amounts (“temporary differences”) at enacted tax
rates in effect for the years in which such temporary differences are expected to reverse.
The Company utilizes a recognition threshold
and measurement process for financial statement recognition and measurement of a tax position taken or expected to be taken in
a tax return.
The Company’s policy is to classify
assessments, if any, for tax-related interest as interest expense and penalties as general and administrative expenses in the consolidated
statements of operations.
EYENOVIA, INC.
NOTES TO FINANCIAL STATEMENTS
FOR THE YEARS ENDED DECEMBER 31, 2019
AND 2018
Note 2 – Summary of Significant
Accounting Policies - Continued
Research and Development
Research and development expenses are charged
to operations as incurred. The Company records prepaid expenses on its balance sheet for the payment of research and development
expenses in advance of services being provided.
Stock-Based Compensation
The Company measures the cost of services
received in exchange for an award of equity instruments based on the fair value of the award. The fair value of the award is measured
on the grant date and the fair value amount is then recognized over the period during which services are required to be provided
in exchange for the award, usually the vesting period. Upon the exercise of an option, the Company issues new shares of common
stock out of the shares reserved for issuance under its equity plans.
Net Loss Per Common Share
Basic net loss per common share is computed
by dividing net loss by the weighted average number of common shares outstanding during the period. Diluted loss per share reflects
the potential dilution that could occur if securities or other instruments to issue common stock were exercised or converted into
common stock.
The following securities are excluded from
the calculation of weighted average dilutive common shares because their inclusion would have been anti-dilutive:
|
|
December 31,
|
|
|
|
2019
|
|
|
2018
|
|
Options
|
|
|
2,237,438
|
|
|
|
2,220,868
|
|
Restricted stock units
|
|
|
60,355
|
|
|
|
20,165
|
|
Total potentially dilutive shares
|
|
|
2,297,793
|
|
|
|
2,241,033
|
|
Subsequent Events
The Company has evaluated subsequent events
through the date which the financial statements were issued. Based upon the evaluation, the Company did not identify any recognized
or non-recognized subsequent events that would have required adjustment or disclosure in the financial statements, except as disclosed.
EYENOVIA, INC.
NOTES TO FINANCIAL STATEMENTS
FOR THE YEARS ENDED DECEMBER 31, 2019
AND 2018
Note 2 – Summary of Significant Accounting Policies
– Continued
Recently Issued Accounting Pronouncements
In February 2016, the FASB issued Accounting
Standards Update (“ASU”) 2016-02, “Leases (Topic 842)” (“ASU 2016-02”). ASU 2016-02 requires
that a lessee recognize the assets and liabilities that arise from operating leases. A lessee should recognize in the statement
of financial position a liability to make lease payments (the lease liability) and a right-of-use asset representing its right
to use the underlying asset for the lease term. For leases with a term of 12 months or less, a lessee is permitted to make an accounting
policy election by class of underlying asset not to recognize lease assets and lease liabilities. In transition, lessees and lessors
are required to recognize and measure leases at the beginning of the earliest period presented using a modified retrospective approach.
This amendment will be effective for fiscal years beginning after December 15, 2020, and interim periods within fiscal years beginning
after December 15, 2021. The FASB issued ASU No. 2019-01 “Leases (Topic 842) Codification Improvements” in March 2019
and ASU No. 2018-10 “Codification Improvements to Topic 842, Leases” and ASU No. 2018-11 “Leases (Topic 842)
Targeted Improvements” in July 2018, and ASU No. 2018-20 “Leases (Topic 842) - Narrow Scope Improvements for Lessors”
in December 2018. ASU 2019-01, ASU 2018-10 and ASU 2018-20 provide certain amendments that affect narrow aspects of the guidance
issued in ASU 2016-02. ASU 2018-11 allows all entities adopting ASU 2016-02 to choose an additional (and optional) transition method
of adoption, under which an entity initially applies the new leases standard at the adoption date and recognizes a cumulative-effect
adjustment to the opening balance of retained earnings in the period of adoption. The Company is currently evaluating ASU 2016-02
and its impact on its financial position, results of operations, and cash flows.
In July 2017, the FASB issued ASU No. 2017-11,
“Earnings Per Share (Topic 260) and Derivatives and Hedging (Topic 815)- Accounting for Certain Financial Instruments with
Down Round Features” (“ASU 2017-11”). Equity-linked instruments, such as warrants and convertible instruments
may contain down round features that result in the strike price being reduced on the basis of the pricing of future equity offerings.
Under ASU 2017-11, a down round feature will no longer require a freestanding equity-linked instrument (or embedded conversion
option) to be classified as a liability that is remeasured at fair value through the income statement (i.e. marked-to-market).
However, other features of the equity-linked instrument (or embedded conversion option) must still be evaluated to determine whether
liability or equity classification is appropriate. Equity classified instruments are not marked-to-market. For earnings per share
("EPS") reporting, the ASU requires companies to recognize the effect of the down round feature only when it is triggered
by treating it as a dividend and as a reduction of income available to common shareholders in basic EPS. The amendments in this
ASU are effective for all entities for fiscal years, and interim periods within those fiscal years, beginning after December 15,
2019. The Company does not expect the adoption of ASU 2017-11 will have a material impact on its financial position, results of
operations, and cash flows.
In August 2018, the FASB issued ASU No.
2018-13, “Fair Value Measurement (Topic 820): Disclosure Framework—Changes to the Disclosure Requirements for Fair
Value Measurement” (“ASU 2018-13”). The amendments in ASU 2018-13 modify the disclosure requirements on fair
value measurements based on the concepts in the FASB Concepts Statement, including the consideration of costs and benefits. The
amendments on changes in unrealized gains and losses, the range and weighted average of significant unobservable inputs used to
develop Level 3 fair value measurements, and the narrative description of measurement uncertainty should be applied prospectively
for only the most recent interim or annual period presented in the initial fiscal year of adoption. All other amendments should
be applied retrospectively to all periods presented upon their effective date. The amendments are effective for fiscal years beginning
after December 15, 2020. Early adoption is permitted, including adoption in an interim period. The Company is currently evaluating
ASU 2018-13 and its impact on its financial position, results of operations and cash flows.
EYENOVIA, INC.
NOTES TO FINANCIAL STATEMENTS
FOR THE YEARS ENDED DECEMBER 31, 2019
AND 2018
Note 2 – Summary of Significant
Accounting Policies – Continued
Recently Issued Accounting Pronouncements
- Continued
In
December 2019, the FASB issued ASU 2019-12, “Income Taxes (Topic 740): Simplifying the Accounting for Income Taxes,”
which is intended to simplify various aspects related to accounting for income taxes. ASU 2019-12 removes certain exceptions to
the general principles in Topic 740 and also clarifies and amends existing guidance to improve consistent application. ASU 2019-12
is effective for fiscal years beginning after December 15, 2021. The Company is currently evaluating ASU 2019-12 and its impact
financial position, results of operations, and cash flows.
Recently Adopted Accounting Pronouncements
In August 2016, the Financial Accounting
Standards Board (“FASB”) issued Accounting Standards Update (“ASU”) 2016-15, “Statement of Cash Flows
(Topic 230) Classification of Certain Cash Receipts and Cash Payments” (“ASU 2016-15”). The new standard will
make eight targeted changes to how cash receipts and cash payments are presented and classified in the statement of cash flows.
The new standard is effective for fiscal years beginning after December 15, 2018. The new standard requires adoption on a retrospective
basis unless it is impracticable to apply, in which case a company would be required to apply the amendments prospectively as of
the earliest date practicable. The Company adopted this standard on January 1, 2019 and it did not have a material impact on the
Company’s financial position, results of operations or cash flows.
In June 2018, the FASB issued ASU No. 2018-07,
“Compensation — Stock Compensation (Topic 718)” (“ASU 2018-07”). ASU 2018-07 is intended to reduce
cost and complexity of financial reporting for non-employee share-based payments. Currently, the accounting requirements for non-employee
and employee share-based payments are significantly different. ASU 2018-07 expands the scope of Topic 718, which currently only
includes share-based payments to employees, to include share-based payments to non-employees for goods or services. Consequently,
the accounting for share-based payments to non-employees and employees will be substantially aligned. This ASU supersedes Subtopic
505-50, “Equity — Equity-Based Payments to Nonemployees.” The amendments to ASU 2018 - 07 are effective for fiscal
years beginning after December 15, 2019, and interim periods within fiscal years beginning after December 15, 2020. Early adoption
is permitted, but no earlier than a company’s adoption date of ASU No. 2014-09, (Topic 606), “Revenue from Contracts
with Customers.” The Company adopted this standard on January 1, 2019 and it did not have a material impact on the Company’s
financial position, results of operations or cash flow.
Note 3 – Prepaid Expenses and
Other Current Assets
As of December 31, 2019 and 2018, prepaid
expenses and other current assets consisted of the following:
|
|
December 31,
|
|
|
|
2019
|
|
|
2018
|
|
Payroll tax receivable
|
|
$
|
95,233
|
|
|
$
|
-
|
|
Prepaid insurance expenses
|
|
|
33,923
|
|
|
|
39,465
|
|
Prepaid research and development expenses
|
|
|
17,978
|
|
|
|
-
|
|
Prepaid patent expenses
|
|
|
12,404
|
|
|
|
10,562
|
|
Prepaid conference expenses
|
|
|
10,600
|
|
|
|
7,000
|
|
Prepaid rent and security deposit
|
|
|
2,463
|
|
|
|
75,729
|
|
Other
|
|
|
24,079
|
|
|
|
-
|
|
Total prepaid expenses and other current assets
|
|
$
|
196,680
|
|
|
$
|
132,756
|
|
EYENOVIA, INC.
NOTES TO FINANCIAL STATEMENTS
FOR THE YEARS ENDED DECEMBER 31, 2019
AND 2018
Note 4 – Property and Equipment,
Net
As of December 31, 2019 and 2018, property
and equipment consisted of the following:
|
|
December 31,
|
|
|
|
2019
|
|
|
2018
|
|
Equipment
|
|
$
|
229,529
|
|
|
$
|
62,886
|
|
Leasehold improvements
|
|
|
82,500
|
|
|
|
40,000
|
|
|
|
|
312,029
|
|
|
|
102,886
|
|
Less: accumulated depreciation and amortization
|
|
|
(81,491
|
)
|
|
|
(66,148
|
)
|
Property and equipment, net
|
|
$
|
230,538
|
|
|
$
|
36,738
|
|
Depreciation and amortization expense was
$15,343 and $19,129 for the years ended December 31, 2019 and 2018, respectively, of which $9,762 and $17,966 was included within
research and development expenses and $5,581 and $1,163 was included in general and administrative expenses in the statements of
operations for the years ended December 31, 2019 and 2018, respectively.
Note 5 – Accrued Expenses and
Other Current Liabilities
As of December 31, 2019 and 2018, accrued
expenses and other current liabilities consisted of the following:
|
|
December 31,
|
|
|
|
2019
|
|
|
2018
|
|
Accrued research and development expenses
|
|
$
|
208,175
|
|
|
$
|
375,204
|
|
Accrued professional services
|
|
|
97,396
|
|
|
|
111,728
|
|
Credit card payable
|
|
|
56,979
|
|
|
|
9,466
|
|
Leasehold improvements
|
|
|
42,500
|
|
|
|
-
|
|
Accrued franchise tax
|
|
|
40,995
|
|
|
|
-
|
|
Accrued travel and entertainment expenses
|
|
|
7,385
|
|
|
|
-
|
|
Accrued legal expenses
|
|
|
-
|
|
|
|
168,650
|
|
Other
|
|
|
-
|
|
|
|
12,165
|
|
Total accrued expenses and other current liabilities
|
|
$
|
453,430
|
|
|
$
|
677,213
|
|
Note 6 – Accrued Compensation
As of December 31, 2019 and 2018, accrued compensation consisted
of the following:
|
|
December 31,
|
|
|
|
2019
|
|
|
2018
|
|
Accrued bonus expenses
|
|
$
|
897,839
|
|
|
$
|
694,490
|
|
Accrued payroll expenses
|
|
|
19,034
|
|
|
|
217,614
|
|
Total accrued compensation
|
|
$
|
916,873
|
|
|
$
|
912,104
|
|
EYENOVIA, INC.
NOTES TO FINANCIAL STATEMENTS
FOR THE YEARS ENDED DECEMBER 31, 2019
AND 2018
Note
7 – Income Taxes
The provision for income taxes consists
of the following expenses (benefits):
|
|
For the Years Ended
|
|
|
|
December 31,
|
|
|
|
2019
|
|
|
2018
|
|
Deferred tax provision (benefit):
|
|
|
|
|
|
|
|
|
Federal
|
|
$
|
(4,999,920
|
)
|
|
$
|
(3,516,722
|
)
|
State and local
|
|
|
68,762
|
|
|
|
(47,238
|
)
|
|
|
|
(4,931,158
|
)
|
|
|
(3,563,960
|
)
|
Change in valuation allowance
|
|
|
4,931,158
|
|
|
|
3,563,960
|
|
Provision for income taxes
|
|
$
|
-
|
|
|
$
|
-
|
|
The provision for income taxes differs
from the United States Federal statutory rate as follows:
|
|
For the Years Ended
|
|
|
|
December 31,
|
|
|
|
2019
|
|
|
2018
|
|
Federal statutory rate
|
|
|
21.0
|
%
|
|
|
21.0
|
%
|
State tax rate, net of federal benefit
|
|
|
0.1
|
%
|
|
|
0.3
|
%
|
Permanent differences
|
|
|
(0.2
|
)%
|
|
|
(0.8
|
)%
|
Research & development tax credits
|
|
|
3.0
|
%
|
|
|
2.8
|
%
|
Prior period adjustments and other
|
|
|
(0.6
|
)%
|
|
|
(2.6
|
)%
|
Change in valuation allowance
|
|
|
(23.3
|
)%
|
|
|
(20.7
|
)%
|
Effective income tax rate
|
|
|
0.0
|
%
|
|
|
0.0
|
%
|
Deferred tax assets consist of the following:
|
|
As of December 31,
|
|
|
|
2019
|
|
|
2018
|
|
Net operating loss carryforwards
|
|
$
|
9,479,512
|
|
|
$
|
5,453,854
|
|
Stock-based compensation expense
|
|
|
943,370
|
|
|
|
616,207
|
|
Property and equipment
|
|
|
(14,030
|
)
|
|
|
2,486
|
|
Intangibles
|
|
|
328,773
|
|
|
|
310,230
|
|
Research and development tax credits
|
|
|
1,584,753
|
|
|
|
1,008,443
|
|
Deferred tax assets
|
|
|
12,322,378
|
|
|
|
7,391,220
|
|
Valuation allowance
|
|
|
(12,322,378
|
)
|
|
|
(7,391,220
|
)
|
Deferred tax assets, net
|
|
$
|
-
|
|
|
$
|
-
|
|
EYENOVIA, INC.
NOTES TO FINANCIAL STATEMENTS
FOR THE YEARS ENDED DECEMBER 31, 2019 AND 2018
Note
7 – Income Taxes – Continued
As of December 31, 2019, the Company had
approximately $45,000,000 of domestic Federal net operating loss carryforwards ("NOLs") that may be available to offset
future Federal taxable income. Approximately $10,800,000 of those NOLs will expire during the years ranging from 2034 to 2037.
The remaining NOLs of approximately $34,200,000 have no expiration dates. Internal Revenue Code Section 382 limits the utilization
of approximately $35,000,000 of those NOLs to approximately $918,000 on an annual basis as a result of ownership changes that occurred
through July 15, 2019. As of December 31, 2019, the Company had minimal state net operating loss carryforwards that may be available
to offset future state taxable income as it conducted most of its operations in Nevada which does not tax corporate income.
The Company has assessed the likelihood
that deferred tax assets will be realized in accordance with the provisions of ASC 740 Income Taxes ("ASC 740").
ASC 740 requires that such a review considers all available positive and negative evidence, including the scheduled reversal of
deferred tax liabilities, projected future taxable income, and tax planning strategies. ASC 740 requires that a valuation allowance
be established when it is “more likely than not” that all, or a portion of, deferred tax assets will not be realized.
After the performance of such reviews as of December 31, 2019 and 2018, management believes that uncertainty exists with respect
to future realization of its deferred tax assets and has, therefore, established a full valuation allowance as of those dates.
Management has evaluated and concluded
that there were no material uncertain tax positions requiring recognition in the Company’s consolidated financial statements
as of December 31, 2019 and 2018. The Company does not expect any significant changes in its unrecognized tax benefits within twelve
months of the reporting date.
No tax audits were commenced or were in
process during the years ended December 31, 2019 and 2018. No tax related interest or penalties were incurred during the years
ended December 31, 2019 and 2018. The Company's State of California income tax returns beginning with the year ended December 31,
2015 remain subject to examination. The Company's Federal and New York State and City income tax returns beginning with the year
ended December 31, 2016 remain subject to examination.
Note 8 – Commitments and Contingencies
Operating Leases
On August 8, 2018, the Company entered
into a lease agreement to lease approximately 3,800 square feet of office space in New York, NY. The monthly base rent ranges from
$19,633 to $22,486 per month over the term of the lease for a total base rent lease commitment of approximately $1,236,000. The
lease expires on September 30, 2023. The security deposit is approximately $118,000.
Future minimum payments under this operating lease agreement
are as follows as:
For the Year Ending
December 31,
|
|
Minimum Lease Payments
|
|
2020
|
|
$
|
244,853
|
|
2021
|
|
|
251,586
|
|
2022
|
|
|
258,505
|
|
2023
|
|
|
198,157
|
|
|
|
$
|
953,101
|
|
See Note 9 – Related Party Transactions
– Lease Agreements for details of a lease agreement with a related party.
EYENOVIA, INC.
NOTES TO FINANCIAL STATEMENTS
FOR THE YEARS ENDED DECEMBER 31, 2019 AND 2018
Note 8 – Commitments and Contingencies
- Continued
Employment Agreements
Effective February 15, 2019, the Company
entered into at-will executive employment agreements with Tsontcho Ianchulev, its Chief Executive Officer and Chief Medical Officer,
John Gandolfo, its Chief Financial Officer, Jennifer Clasby, its Vice President, Clinical Operations, Luke Clauson, its Vice President,
Research and Development and Manufacturing (“VP of R&D”), and Michael Rowe, now its Vice President, Commercial.
Each of the employment agreements provides
that if the executive’s employment is terminated by the Company without “Cause” or the executive suffers an “Involuntarily
Termination” (each as defined in the employment agreements), provided that the executive has signed a full release of all
claims, the executive will be entitled to receive: (i) severance pay equal to three months of his or her then-current base salary
(currently estimated at approximately $419,000 in the aggregate), and (ii) a reimbursement for health insurance benefits under
COBRA for the executive and his or her spouse and dependents for a period of three months or until the executive becomes eligible
for comparable insurance benefits from another employer, whichever is earlier.
Each of the employment agreements also
provides that if, within 12 months following any “Corporate Transaction” (as defined in the employment agreements)
of the Company, the executive’s employment is terminated by the Company without Cause or the executive suffers an Involuntary
Termination, provided that the executive has signed a full release of all claims, the executive will be entitled to receive, in
lieu of what is described in the above paragraph: (i) severance pay equal to 12 months of his or her then-current base salary (currently
estimated at approximately $1,677,000 in the aggregate), and (ii) a reimbursement for health insurance benefits under COBRA for
the executive and his or her spouse and dependents for a period of 12 months or until the executive becomes eligible for comparable
insurance benefits from another employer, whichever is earlier.
Litigations, Claims and Assessments
In the normal course of business, the Company
may be involved in legal proceedings, claims and assessments arising in the ordinary course of business. The Company records legal
costs associated with loss contingencies as incurred and accrues for all probable and estimable settlements.
The Company, its Chief Executive Officer
and members of its Board of Directors were named as defendants in a legal proceeding filed in the United States District Court
for the District of New Jersey on September 2, 2014 in connection with the Company’s Asset Purchase Agreement with Corinthian
Ophthalmic, Inc. (“Corinthian”). A shareholder of Corinthian alleged a fraudulent transfer and sought to recover the
purchase price of its Corinthian shares and other damages in aggregate amount of approximately $1.1 million. The court conducted
a pretrial conference on January 22, 2018 and entered a final pretrial order on January 23, 2018. On October 29, 2018, the parties
entered into a Settlement Agreement pursuant to which the defendants agreed to pay the Corinthian shareholder $600,000 in exchange
for the release of all related claims. While the Company is indemnified by Corinthian and Corinthian's applicable insurance policy
provides coverage of $10 million, in an effort to avoid the additional legal costs and other resources required with a trial, the
Company contributed $150,000 of the settlement amount (the remaining $450,000 was paid by Corinthian's insurance carrier), which
was paid on October 29, 2018.
Note
9 – Related Party Transactions
Consulting Agreements
A company in which a member of the Company’s
Board of Directors is part owner is a party to a consulting agreement with the Company dated July 6, 2017 that provides for the
payment of $9,567 per month, and $250 per hour for any additional work, for advisory services performed by such director. The Company
incurred expenses of $213,521 and $162,929 for the years ended December 31, 2019 and 2018, respectively, related to the agreement
which was included within general and administrative expenses on the statements of operations.
EYENOVIA, INC.
NOTES TO FINANCIAL STATEMENTS
FOR THE YEARS ENDED DECEMBER 31, 2019 AND 2018
Note 9 – Related Party Transactions
– Continued
Lease Agreements
The Company paid $4,000 per month as of
January 2018, respectively, to a company controlled by a member of its Board of Directors for office space in New York, NY for
its Chief Executive Officer (“CEO”). The Company left the space on August 31, 2018. The Company’s rent expense
for this space amounted to $0 and $32,000 for the years ended December 31, 2019 and 2018, respectively, related to the office space,
which was included within general and administrative expenses on the statements of operations.
The Company’s Vice President of Research
and Development and Manufacturing (“VP of R&D”) owns a company that entered into a lease agreement with the Company
on September 15, 2016 to lease 953 square feet of space located in Reno, Nevada with respect to its research and development activities.
The initial monthly base rent was $3,895 per month over the term of the lease and the security deposit was $3,895. On September
15, 2018, the Company amended the lease agreement to extend it until September 14, 2020 and increase the monthly base rent and
security deposit to $4,012. The Company made $82,500 of leasehold improvements related to this lease which are included on the
balance sheet. The Company’s rent expense for this space amounted to $48,144 and $47,270 for the years ended December
31, 2019 and 2018, respectively.
Research and Development Activities
The VP of R&D is the sole owner and
President of a company that performs contract engineering services for the Company. During the years ended December 31, 2019 and
2018, the Company recognized research and development expense of $851,746 and $863,355, respectively, related to services provided
by such vendor. The Company had a liability of $89,052 and $100,667 to the vendor as of December 31, 2019 and 2018, respectively.
The Company recognized $186,160 and $182,275
of compensation expense related to the VP of R&D’s salary during the years ended December 31, 2019 and 2018, respectively.
License Agreement
During 2015, the Company entered into a
license agreement with Senju Pharmaceuticals Co., Ltd. (“Senju”) whereby the Company agreed to grant to Senju an exclusive,
royalty-bearing license for its microdose product candidates for Asia to sublicense, develop, make, have made, manufacture, use,
import, market, sell, and otherwise distribute the microdose product candidates. In consideration for the license, Senju agreed
to pay to Eyenovia five percent (5%) royalties for the term of the license agreement. The agreement will continue in full force
and effect, on a country-by-country basis, until the latest to occur of: (i) the tenth (10th) anniversary of the first commercial
sale of a microdose product candidate in Asia; or (ii) the expiration of the licensed patents. As of the date of this filing, there
had been no commercial sales of a microdose product candidate in Asia, so no royalties had been earned. Senju is owned by the family
of a former member of the Company’s Board of Directors and, together, they beneficially own greater than 5% of the Company’s
common stock.
Note 10 – Stockholders’ Equity
Reverse Stock Split
Effective January 8, 2018, pursuant
to authority granted by the stockholders of the Company, the Company implemented a 1-for-3.75 reverse split of the Company’s
issued and outstanding common stock and preferred stock (the “Reverse Split”). The number of authorized shares remained
unchanged. All share and per share information has been retroactively adjusted to reflect the Reverse Split for all periods presented,
unless otherwise indicated.
EYENOVIA, INC.
NOTES TO FINANCIAL STATEMENTS
FOR THE YEARS ENDED DECEMBER 31, 2019 AND 2018
Note 10 – Stockholders’
Equity – Continued
Authorized Capital
The Company is authorized to issue 90,000,000
shares of common stock, par value of $0.0001 per share, and 6,000,000 shares of preferred stock, par value of $0.0001
per share. The holders of the Company’s common stock are entitled to one vote per share. The Board of Directors is empowered,
without stockholder approval, to issue preferred stock with dividend, liquidation, redemption, voting or other rights.
Equity Incentive Plans
On January 5, 2018, the Company’s
Board of Directors and stockholders approved an amendment to the Company’s 2014 Equity Incentive Plan (“2014 Plan”)
to increase the number of shares of common stock authorized under the 2014 Plan from 1,733,333 shares to 1,866,667 shares. As of
December 31, 2019, there were 15,333 shares available for future issuance under the 2014 Plan.
On March 6, 2018, the Company’s Board
of Directors adopted the 2018 Omnibus Stock Incentive Plan (“2018 Plan”), which stockholders approved on June 11, 2018.
The 2018 Plan was subsequently amended by the Board on April 5, 2019 and approved by stockholders on June 11, 2019 (the “2018
Plan, as amended”). The 2018 Plan, as amended, provides for the issuance of incentive stock options, nonstatutory stock options,
rights to purchase common stock, stock appreciation rights, restricted stock and restricted stock units (“RSUs”)
to employees, directors and consultants of the Company and its affiliates. The 2018 Plan, as amended, terminates on June 11, 2028.
The 2018 Plan, as amended, requires the exercise price of stock options to be greater than or equal to the fair value of the Company’s
common stock on the date of grant. There are 1,250,000 shares of common stock authorized under the 2018 Plan, as amended. As of
December 31, 2019, there were 106,074 shares available for future issuance under the 2018 Plan, as amended.
Public Offerings
On January 29, 2018, the Company consummated
its IPO of 2,730,000 shares of its common stock at an offering price of $10.00 per share, generating $27.3 million and $24.5 million
in gross and net proceeds, respectively. Underwriting discounts, commissions and other offering expenses were approximately $2.8
million, which were recorded as a reduction of additional paid-in capital.
On December 21, 2018, the Company consummated
a follow-on public offering of 1,380,000 shares of its common stock at an offering price of $2.45 per share, generating $3.4 million
and $2.8 million in gross and net proceeds, respectively. Underwriting discounts, commissions and other offering expenses were
approximately $0.6 million, which were recorded as a reduction of additional paid-in capital.
On July 15, 2019, the Company closed an
underwritten public offering of 4,388,490 shares of its common stock at a public offering price of $2.78 per share. The Company
granted the underwriters a 30-day over-allotment option to purchase up to an additional 658,273 shares of the Company’s common
stock at the same price, which was exercised in full on July 16, 2019. Including the over-allotment shares, the Company issued
a total of 5,046,763 shares in the underwritten public offering, and received gross proceeds of approximately $14.0 million and
net proceeds of approximately $13.0 million, after deducting underwriting discounts, commissions and other offering expenses, which
were recorded as a reduction of additional paid-in capital.
EYENOVIA, INC.
NOTES TO FINANCIAL STATEMENTS
FOR THE YEARS ENDED DECEMBER 31, 2019 AND 2018
Note 10 – Stockholders’
Equity – Continued
Series A and Series A-2 Convertible
Preferred Stock
The Series A and Series A-2 Convertible
Preferred Stock did not contain a redemption provision and an overall analysis of its features performed by the Company determined
that it was more akin to equity and, therefore, it has been classified within stockholders’ equity on the balance sheet.
While the embedded conversion option (“ECO”) was subject to an anti-dilution price adjustment, since the ECO was clearly
and closely related to the equity host, it was not required to be bifurcated and accounted for as a derivative liability under
ASC 815. The Company determined that the preferred stock did not contain a beneficial conversion feature because the conversion
price exceeded the estimated fair value of the Company’s common stock as of the commitment date.
The Series A and Series A-2 Convertible
Preferred Stock was convertible, at the option of the holder, at any time into shares of common stock on a one-for-one basis. In
the event of any issuances by the Company for less than the in-force conversion price, the preferred stock conversion price would
be reduced on a weighted average basis. Each share of preferred stock was automatically convertible into shares of common stock
at the then effective conversion price: (i) immediately prior to the closing of a firm commitment underwritten initial public
offering provided that (A) the aggregate offering price, net of underwriters’ discounts and expenses, was at least $2.00
per share of common stock and (B) the aggregate proceeds of such offering were not less than $20,000,000; or (ii) the date specified
by written consent or agreement of the holders of at least 75% of the then outstanding shares of preferred stock. All of the Series
A and Series A-2 Convertible Preferred Stock converted immediately prior to the Company’s IPO. See Note 10 – Stockholders’
Equity – Conversion of Preferred Stock for additional details.
Series B Convertible Preferred Stock
The Series B Convertible Preferred did
not contain a redemption provision and an overall analysis of its features performed by the Company determined that it was more
akin to equity and therefore, has been classified within stockholders’ equity on the balance sheet. While the embedded conversion
option (“ECO”) was subject to an anti-dilution price adjustment, since the ECO was clearly and closely related to the
equity host, it was not required to be bifurcated and accounted for as a derivative liability under ASC 815. The Company determined
that the Series B Convertible Preferred did not contain a beneficial conversion feature, since the conversion price exceeded the
estimated fair value of the Company’s common stock as of the commitment date.
The Series B Convertible Preferred Stock
was convertible, at the option of the holder, at any time into shares of common stock on a one-for-one basis, subject to certain
adjustments. In the event of any issuances by the Company for less than the in-force conversion price, the Series B Convertible
Preferred Stock conversion price would be reduced on a weighted average basis. Each share of Series B Convertible Preferred Stock
was automatically convertible into shares of common stock at the then effective conversion price: (i) immediately prior to the
closing of a firm commitment underwritten initial public offering provided that (A) the aggregate offering price, net of underwriters'
discounts and expenses, is at least $2.00 per share of common stock and (B) the aggregate proceeds of such offering are not less
than $20,000,000; or (ii) the date specified by written consent or agreement of the holders of at least 75% of the then outstanding
shares of preferred stock. All of the Series B Convertible Preferred Stock converted immediately prior to the Company’s IPO.
See Note 10 – Stockholders’ Equity – Conversion of Preferred Stock for additional details.
Conversion of Preferred Stock
Immediately prior to the closing of the
IPO on January 29, 2018, all outstanding shares of preferred stock were automatically converted into an aggregate of 4,702,116
shares of the Company’s common stock.
EYENOVIA, INC.
NOTES TO FINANCIAL STATEMENTS
FOR THE YEARS ENDED DECEMBER 31, 2019 AND 2018
Note 10 – Stockholders’
Equity – Continued
Stock-Based Compensation Expense
The Company records stock-based compensation
expense related to stock options and RSUs. For the years ended December 31, 2019 and 2018, the Company recorded expense of $2,511,944
($1,459,055 of which was included within research and development expenses and $1,052,889 was included within general and administrative
expenses on the statements of operations) and $1,615,470 ($818,239 of which was included within research and development expenses
and $797,231 was included within general and administrative expenses on the statements of operations), respectively. As of December
31, 2019, there was $3,249,222 of unrecognized stock-based compensation expense which will be recognized over a weighted average
period of 1.9 years.
Restricted Stock Units
On July 24, 2018, the Company granted an
aggregate of 20,165 RSUs to its directors under the 2018 Plan. The grants vest on the earlier of (i) the one-year anniversary of
the date of grant and (ii) the date of the 2019 annual stockholders meeting, subject to the grantee remaining on the Board until
then. The RSUs had a grant date fair value of $125,000, which was recognized over the vesting period.
On August 16, 2019, the Company granted
to members of its Board of Directors an aggregate of 40,190 restricted stock units (“RSUs”) under the 2018 Plan, as
amended. The grants vest on the earlier of (i) the one-year anniversary of the date of grant and (ii) the date of the 2020 annual
stockholders meeting, subject to the grantee remaining on the Board until then. The RSUs had a grant date fair value of $125,000,
which will be recognized over the vesting period.
Stock Options
On April 16, 2018, the Compensation Committee
of the Board of Directors approved the grant of ten-year stock options to purchase 175,668 shares of common stock to Company employees
and consultants under the 2014 Plan. The stock options will vest in equal monthly increments over 36 months beginning on the one-month
anniversary of the date of grant, subject to continued service to the Company, and have an exercise price of $8.72 per share, which
was the closing stock price on the date of grant. The stock options had a grant date fair value of $1,412,700, which the Company
expects to recognize over the vesting period.
During the year ended December 31, 2018,
the Company granted ten-year stock options to purchase an aggregate of 395,999 shares of common stock to its employees, consultants
and directors under the 2018 Plan. Of the 395,999 shares, (i) 313,674 vest over three years from the date of grant with one-third
vesting on the one-year anniversary of the date of grant and the balance vesting monthly over the remaining 24 months, subject
to continued service to the Company, (ii) 60,000 vest monthly over 36 months beginning on the one-month anniversary of the date
of grant, subject to continued service to the Company, and (iii) 22,325 vest on the earlier of the one-year anniversary of the
date of grant and the date of the 2019 annual stockholders meeting, subject to continued service to the Company. The stock options
have exercise prices ranging from $5.10 per share to $6.30 per share, which represents the Company’s closing stock price
on the date of grant. The stock options had a grant date value of $2,237,800, which the Company expects to recognize over the vesting
period.
On January 2, 2019, stock options to purchase
180,000 and 133,686 shares of common stock with an exercise price of $1.24 and $1.95 per share, respectively, were exercised for
aggregate proceeds of $483,888. In connection with the exercise of the stock options, the Company remitted a portion of an employee’s
payroll taxes of $62,193 to the Internal Revenue Service. The Company was reimbursed in full by the employee.
On January 14, 2019, the Company granted
ten-year stock options to purchase an aggregate of 11,000 shares of common stock to its employees under the 2018 Plan. The 11,000
shares vest over three years from the date of grant with one-third vesting on the one-year anniversary of the date of grant and
the balance vesting monthly over the remaining 24 months, subject to continued service to the Company. The stock options have an
exercise price of $2.74 per share, which represents the Company’s closing stock price on the date of grant. The stock options
had a grant date value of $27,500, which the Company expects to recognize over the vesting period.
EYENOVIA, INC.
NOTES TO FINANCIAL STATEMENTS
FOR THE YEARS ENDED DECEMBER 31, 2019 AND 2018
Note 10 – Stockholders’
Equity – Continued
Stock Options - Continued
On February 6, 2019, stock options to purchase
an aggregate of 320,001 shares of common stock with an exercise price of $1.24 per share were exercised on a cashless basis, which
resulted in the issuance of an aggregate of 236,466 shares of common stock.
On February 13, 2019, the Board of Directors
of the Company approved the acceleration and immediate vesting of 124,210 stock options originally granted to Dr. Ianchulev on
July 24, 2018 in connection with his employment. In connection with the acceleration and immediate vesting, the Company recognized
$609,322 of stock-based compensation expense during the year ended December 31, 2019 , which represents the remaining unamortized
grant date fair value of the award.
On May 14, 2019, stock options to purchase
34,815 shares of common stock with an exercise price of $1.95 per share were exercised for aggregate proceeds of $67,889.
On August 16, 2019, the Company granted
ten-year stock options to purchase an aggregate of 681,572 shares of common stock to its employees, consultants and directors under
the 2018 Plan, as amended. Of the 681,572 shares, (i) 636,287 vest over three years from the date of grant with one-third vesting
on the one-year anniversary of the date of grant and the balance vesting monthly over the remaining 24 months, subject to continued
service to the Company and (ii) 45,285 vest on the earlier of the one-year anniversary of the date of grant and the date of the
2020 annual stockholders meeting, subject to continued service to the Company. The stock options have an exercise price of $3.11
per share, which represents the Company’s closing stock price on the date of grant. The stock options had a grant date value
of $1,909,700, which the Company expects to recognize over the vesting period.
In applying the Black-Scholes option pricing
model to stock options granted, the Company used the following approximate assumptions:
|
|
For the Year Ended
|
|
|
|
December 31,
|
|
|
|
2019
|
|
|
2018
|
|
Expected term (years)
|
|
5.50 - 10.00
|
|
|
5.50 - 10.00
|
|
Risk free interest rate
|
|
1.42 - 2.53%
|
|
|
2.69 - 3.24%
|
|
Expected volatility
|
|
134 - 139%
|
|
|
140 - 141%
|
|
Expected dividends
|
|
0.00%
|
|
|
0.00%
|
|
The Company has computed the fair
value of stock options granted using the Black-Scholes option pricing model. Option forfeitures are accounted for at the time
of occurrence. The expected term used for options issued is the estimated period of time that options granted are expected to
be outstanding. The Company utilizes the “simplified” method to develop an estimate of the expected term of “plain
vanilla” option grants. The Company does not currently have a sufficient trading history to support its historical volatility
calculations. Accordingly, the Company is utilizing an expected volatility figure based on a review of the historical volatility
of three comparable entities over a period of time equivalent to the expected life of the instrument being valued. The risk-free
interest rate was determined from the implied yields from U.S. Treasury zero-coupon bonds with a remaining term consistent with
the expected term of the instrument being valued.
The weighted average estimated grant date
fair value of the stock options granted for the years ended December 31, 2019 and 2018 was approximately $3.10 and $6.39 per share,
respectively.
EYENOVIA, INC.
NOTES TO FINANCIAL STATEMENTS
FOR THE YEARS ENDED DECEMBER 31, 2019
AND 2018
Note 10 – Stockholders’
Equity – Continued
Stock Options – Continued
A summary of the option activity during
the year ended December 31, 2019 is presented below:
|
|
|
|
|
|
|
|
Weighted
|
|
|
|
|
|
|
|
|
|
Weighted
|
|
|
Average
|
|
|
|
|
|
|
|
|
|
Average
|
|
|
Remaining
|
|
|
Aggregate
|
|
|
|
Number of
|
|
|
Exercise
|
|
|
Life
|
|
|
Intrinsic
|
|
|
|
Options
|
|
|
Price
|
|
|
In Years
|
|
|
Value
|
|
Outstanding January 1, 2019
|
|
|
2,220,868
|
|
|
$
|
3.01
|
|
|
|
|
|
|
|
|
|
Granted
|
|
|
692,572
|
|
|
|
3.10
|
|
|
|
|
|
|
|
|
|
Exercised
|
|
|
(668,502
|
)
|
|
|
1.42
|
|
|
|
|
|
|
|
|
|
Forfeited
|
|
|
(7,500
|
)
|
|
|
4.73
|
|
|
|
|
|
|
|
|
|
Outstanding December 31, 2019
|
|
|
2,237,438
|
|
|
$
|
3.51
|
|
|
|
8.1
|
|
|
$
|
3,559,915
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Exercisable December 31, 2019
|
|
|
1,183,637
|
|
|
$
|
3.33
|
|
|
|
7.3
|
|
|
$
|
2,222,680
|
|
The following table presents information
related to stock options as of December 31, 2019:
Options Outstanding
|
|
|
Options Exercisable
|
|
|
|
|
|
|
|
Weighted
|
|
|
|
|
|
|
|
Outstanding
|
|
|
Average
|
|
|
Exercisable
|
|
Exercise
|
|
|
Number of
|
|
|
Remaining Life
|
|
|
Number of
|
|
Price
|
|
|
Options
|
|
|
In Years
|
|
|
Options
|
|
$
|
1.24
|
|
|
|
260,000
|
|
|
|
5.2
|
|
|
|
260,000
|
|
$
|
1.95
|
|
|
|
700,281
|
|
|
|
7.5
|
|
|
|
545,170
|
|
$
|
2.74
|
|
|
|
6,000
|
|
|
|
-
|
|
|
|
-
|
|
$
|
3.11
|
|
|
|
681,572
|
|
|
|
-
|
|
|
|
-
|
|
$
|
4.00
|
|
|
|
2,000
|
|
|
|
8.9
|
|
|
|
723
|
|
$
|
5.10
|
|
|
|
6,000
|
|
|
|
8.7
|
|
|
|
2,667
|
|
$
|
5.19
|
|
|
|
16,500
|
|
|
|
8.7
|
|
|
|
6,875
|
|
$
|
5.25
|
|
|
|
26,668
|
|
|
|
6.8
|
|
|
|
21,249
|
|
$
|
6.20
|
|
|
|
311,499
|
|
|
|
8.6
|
|
|
|
224,438
|
|
$
|
6.30
|
|
|
|
60,000
|
|
|
|
8.5
|
|
|
|
28,333
|
|
$
|
8.72
|
|
|
|
166,918
|
|
|
|
8.3
|
|
|
|
94,182
|
|
|
|
|
|
|
2,237,438
|
|
|
|
7.3
|
|
|
|
1,183,637
|
|
EYENOVIA, INC.
NOTES TO FINANCIAL STATEMENTS
FOR THE YEARS ENDED DECEMBER 31, 2019
AND 2018
Note 11 – Employee Benefit Plans
401(k) Plan
In April 2019, the Company adopted the
Eyenovia 401(k) Plan (the “Plan”), which went into effect in May 2019. All Company employees are able to participate
in the Plan, subject to eligibility requirements as outlined in the Plan documents. Under the terms of the Plan, eligible employees
are able to defer a percentage of their pay every pay period up to annual limitations set by Congress and the Internal Revenue
Service under Section 401(k) of the Internal Revenue Code. For 2019, the Company’s Board of Directors has approved a matching
contribution equal to 100% of elective deferrals up to 4% of eligible earnings with the matching contribution subject to certain
vesting requirements as outlined in the Plan documents. For the year ended December 31, 2019, the Company recorded expense of $71,285
associated with its matching contributions, respectively.
Note
12 – Subsequent Events
Stock Options
On January 31, 2020, the Company granted
ten-year stock options to purchase 25,000 shares of common stock to its employees under the 2018 Plan, as amended. The shares vest
over three years from the date of grant with one-third vesting on the one-year anniversary of the date of grant and the balance
vesting monthly over the remaining 24 months. The stock options have an exercise price of $4.68 per share, which represents the
Company’s closing stock price on the date of grant.
Securities Purchase Agreement
On March 24, 2020, the Company closed on
a private placement of approximately $6.0 million of Units. Each Unit consists of (i) one share of the Company’s common stock,
(ii) a one-year warrant to purchase 0.5 of a share of common stock (“Class A Warrant”), and (iii) a five-year warrant
to purchase 0.75 of a share of common stock (“Class B Warrant”) (collectively, the Class A Warrants and Class B Warrants,
the “Warrants”). The Units were sold to the public at a price of $2.21425 per Unit and to certain directors and executive
officers at a price of $2.42625 per Unit. The Company generated approximately $5.3 million of net proceeds in the offering after
deducting placement agent fees and offering expenses. In the offering, the Company issued an aggregate of 2,675,293 shares of common
stock, Class A Warrants to purchase up to 1,337,659 shares of common stock, and Class B Warrants to purchase up to 2,006,495 shares
of common stock. The exercise price of the Class A Warrants issued to the public is $2.058 per share and the exercise price of
the Class A Warrants issued to the directors and officers is $2.27 per share. The exercise price of the Class B Warrants issued
to the public is $2.4696 per share and the exercise price of the Class B Warrants issued to the directors and officers is $2.724
per share.
In connection with the offering, on March
23, 2020, the Company also entered into a Registration Rights Agreement with the investors. Pursuant to the Registration Rights
Agreement, the Company must file with the SEC, no later than 30 days following the date on which the Company files its Form 10-K
for the year ended December 31, 2019 with the SEC, a registration statement on Form S-3 covering the shares of common stock issued
in the offering and the shares of common stock underlying the Warrants.