Item 1. BUSINESS
Overview
We are a biopharmaceutical company primarily
focused on the development and commercialization of proprietary biopharmaceutical products. We are developing prescription drugs
for central nervous system (“CNS”) disorders and our current focus is the development of drugs with lower potential
for abuse than currently available drugs. Our clinical-stage product currently under development is Abuse-Deterrent Amphetamine Immediate-Release
(“ADAIR”), a proprietary, abuse-deterrent oral formulation of immediate-release (short-acting) dextroamphetamine
for the treatment of attention-deficit/hyperactivity disorder (“ADHD”), and narcolepsy. It is estimated that
over 5 million Americans abuse prescription ADHD stimulants annually.
We intend to develop ADAIR for registration
through the Section 505(b)(2) approval pathway, which we expect to obviate the need for large Phase 2 and Phase 3
efficacy and safety studies. See the sections entitled “Business — Section 505(b)(2) Pathway”
and “Business — Clinical Development” in this Annual Report for more information regarding Section 505(b)(2)
of the FDCA. Although the FDA does not approve of a drug using the Section 505(b)(2) pathway until submission and acceptance
of a new drug application (“NDA”), based on discussions held with FDA at a pre-IND meeting in January 2017 and
the minutes from such meeting, we believe the Section 505(b)(2) regulatory pathway is appropriate and will be acceptable to the
FDA. We expect to request additional labeling based on studies that demonstrate the abuse-deterrent characteristics of the product
as they relate to snorting, and possibly IV injection. While dextroamphetamine is approved by the FDA, our reformulation, ADAIR,
is not. Prescription drug abuse is a large and growing problem in the United States and globally.
We filed our Investigational New Drug (“IND”),
application for ADAIR in June 2018 and the IND was cleared in July 2018. Subsequently, we have successfully completed
a Phase 1 pivotal bioequivalence study of ADAIR and a Phase 1 food effect study. The bioequivalence study enrolled 24
subjects and the food effect study enrolled 22 subjects. Both studies were conducted by Altasciences, a contract research organization
(“CRO”).
In 2019, we conducted a Phase 1 proof-of-concept
intranasal human abuse potential study designed to compare ADAIR when insufflated (snorted) as compared to the reference comparator,
crushed immediate release dextroamphetamine sulfate tablets. The study enrolled 16 subjects and was conducted at a single site
by BioPharma Services, a CRO with experience conducting similar trials. The study measured the pharmacokinetic levels of dextroamphetamine
of the two compounds when snorted, the subjective “drug-liking” of the two drugs, and the willingness of recreational
drug users to take each product again. The results of this study demonstrated that as compared to standard dextroamphetamine, ADAIR,
when snorted, demonstrated an attenuated pharmacokinetic profile and lower drug liking and other abuse liability scores, using
standard measures for human abuse potential studies. We have used the results of this proof of concept abuse study to design a
larger intranasal abuse study that we will conduct prior to seeking approval of ADAIR. We designed the study to follow the model
used in intranasal abuse studies that have been conducted for abuse deterrent opioids and following guidance issued by the FDA
for such studies. We began enrollment of subjects in this pivotal abuse study during the fourth quarter of 2020.We recently completed
a preclinical embryofetal study which showed no evidence of developmental effects and no clinical observations other than those
associated with the pharmacological effects of dextroamphetamine. We are currently conducting a 13-week preclinical toxicology
study on the final formulation of ADAIR. We also plan to conduct additional preclinical studies of unintended routes of administration
such as IV and intranasal administration.
On January 6, 2020, Vallon entered into
a license agreement with Medice, who is affiliated with one of our principal stockholders, Salmon Pharma, and represented by one
member of our board of directors, which grants Medice an exclusive license, with the right to grant sublicenses, to develop, use,
manufacture, market and sell ADAIR throughout Europe. Medice currently markets several ADHD products in Europe and is the ADHD
market leader in Europe based on branded prescription market share. Medice is responsible for obtaining regulatory approval of
ADAIR in the licensed territory. Under the license agreement, Medice paid Vallon a minimal upfront payment and will pay milestone
payments of up to $6.3 million in the aggregate upon first obtaining regulatory approval to market and sell ADAIR in any country,
territory or region in the licensed territory and upon achieving certain annual net sales thresholds. Medice will also pay tiered
royalties on annual net sales of ADAIR at rates in the low double-digits. The initial term of the license agreement will expire
five years after the date on which Medice first obtains regulatory approval in any country, territory or region in the licensed
territory.
We plan to develop other abuse-deterrent
products that have potential for abuse in their current forms, beginning with the development of an abuse deterrent formulation
of Ritalin® (“ADMIR”), for which we are conducting formulation development work.
The U.S. market for ADHD treatment was estimated
to be approximately $9 billion annually, which accounted for over 80% of the global ADHD market in 2019, and the European
Union (“EU”) market for ADHD treatment was estimated to be approximately $700 million annually. We plan
to target the U.S. ADHD market once we receive FDA approval of ADAIR, followed by the EU market for ADHD with our partner, Medice,
who is affiliated with one of our principal stockholders, Salmon Pharma, and represented by one member of our board of directors,
once regulatory approval has been granted in the EU.
The ADAIR assets were acquired by us on June 22,
2018 pursuant to the terms and conditions of the Amended and Restated Asset Purchase Agreement with Arcturus Therapeutics, Ltd.
(“Arcturus”), and Amiservice Development Ltd., dated as of June 22, 2018 (the “Asset Purchase
Agreement”). In exchange for the ADAIR assets, we issued 843,750 shares of our common stock to Arcturus, which comprised
30% of our then-outstanding common stock on a fully diluted basis.
Reverse Split
On February 10, 2021, the Company filed
a certificate of amendment to its amended and restated certificate of incorporation with the Secretary of State of the State of
Delaware, which effected a one-for-40 reverse stock split (the “reverse split”) of its issued and outstanding
shares of common stock at 11:59 PM Eastern Time on that date. As a result of the reverse split, every 40 shares of common stock
issued and outstanding were reclassified into one share of common stock. No fractional shares were issued in connection with the
reverse split and any fractional shares were rounded up to the nearest whole share.
The reverse split did not change the par
value of the common stock or the authorized number of shares of common stock. The reverse split affected all stockholders uniformly
and did not alter any stockholder’s percentage interest in equity. All outstanding options and other securities entitling
their holders to purchase or otherwise receive shares of common stock have been adjusted as a result of the reverse split, as required
by the terms of each security. The number of shares available to be awarded under the Company’s 2018 Equity Incentive Plan
have also been appropriately adjusted.
All share and per share amounts contained
in this Annual Report on Form 10-K give retroactive effect to the reverse split.
Our Strategy and Pipeline
Stimulant abuse is a large and growing public
health challenge, yet the immediate-release segment of the ADHD market is entirely devoid of any abuse-deterrent products. We intend
to address this need by through our abuse-deterrent pharmaceutical products, such as ADAIR and other products we opt to pursue
in the future, including ADMIR. The following table summarizes our current product candidate portfolio:
Our near-term strategic milestones include:
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seeking the necessary regulatory approvals to complete
the clinical development of ADAIR for the treatment of ADHD and, if successful, file for marketing approval in the United States
and other territories;
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preparing to commercialize ADAIR by establishing independent
distribution capabilities or in conjunction with other biopharmaceutical companies in the United States and other key markets,
such as the license agreement with Medice;
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commencing development of other abuse-deterrent products such as ADMIR; and
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continuing our business development activities and seek partnering, licensing, merger and acquisition opportunities or other transactions to further develop our pipeline and drug-development capabilities and take advantage of our financial resources for the benefit of increasing stockholder value.
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Section 505(b)(2) Pathway
NDAs for most new drug products are based
on two adequate and well-controlled 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 an NDA for a drug for which the investigations to show whether the drug is safe and effective
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 in part on safety and effectiveness data that were not developed by the applicant. 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.
We expect that our clinical trials described
under the section entitled “Business — Clinical Development” will provide sufficient data to support
an NDA filing with the FDA.
Prescription Stimulant Abuse and Misuse
Abuse and Misuse
Stimulants are among the most widely abused
substances. This class of drugs includes amphetamines and methylphenidate. Both of these substances are placed in Schedule II
of the U.S. Controlled Substances Act (“CSA”) and the rules and regulation of the U.S. Drug Enforcement Administration
(“DEA”), which is reserved for drugs that carry the highest risk of abuse and dependence that have been approved
for medicinal use.
While the most severe public health and societal
problems related to stimulants result from abuse of illicitly manufactured stimulants including methamphetamine, and various synthetic
stimulants, prescription stimulants are also widely misused and abused for non-medical uses.
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Abuse — means the harmful or hazardous use of psychoactive substances, including alcohol and illicit drugs, and may include misusing a prescribed drug, through snorting, smoking or injecting, that is meant to be administered orally, to “get high” or produce “euphoria.”
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Misuse
— means the use of a substance or drug for a purpose not consistent with legal or medical guidelines. For example,
ADHD medication may be misused through taking high dosages of the drug to enhance alertness and counteract fatigue and sleepiness
in order to meet occupational demands, increase alertness while driving, or improve academic performance.
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Misuse and/or abuse can produce severe adverse
consequences, and on rare occasions also death, and contributes to diversion of medicines from prescribed users, as well as illicit
marketing. Furthermore, nonmedical use of prescription stimulants, even for the intent of occasional enhancement of alertness and
performance, can also lead to more harmful patterns of use of stimulants and other addictive substances.
Prevalence
According to a 2017 report by the National
Survey on Drug Use and Health (the “NSDUH”) over 5 million individuals ages 12 years or older in the
United States misused prescription stimulants in the previous year. This figure has been rising over time and this represents approximately
2% of the U.S. population in that age group. Rates of misuse of prescription stimulants increase from age 12 and peak at age 21,
where an estimated 10% of the population reported misuse of prescription stimulants, before declining in older adults.
Harmful Effects of Stimulant Abuse
Acute
Acute stimulant intoxication may result in
a number of cardiovascular-related adverse events, including chest pain, myocardial infarction, palpitations, arrhythmias, thromboembolism,
tachycardia, sinus bradycardia, ventricular premature depolarization, ventricular tachycardia degeneration (resulting in the need
for defibrillation), asystole, peripheral vascular abnormalities, and/or sudden death from respiratory or cardiac arrest, as well
as other adverse events such as strokes, seizures, pneumothorax, headaches, and tinnitus. Acute stimulant intoxication is also
associated with several psychiatric symptoms, including rambling speech, transient ideas, paranoid thoughts, auditory hallucinations,
tactile hallucinations, and psychosis.
High dosages of amphetamines and other stimulants
can lead to aggressive or violent behavior (which may lead to self-harm or harm to others), intense temporary anxiety resembling
panic disorder, or generalized anxiety disorder or mania, as well as paranoid thoughts and psychotic episodes that resemble schizophrenia.
Taking extremely high doses of stimulants may also result in dangerously high body temperatures, irregular heartbeat, cardiovascular
problems, and seizures.
Chronic
Extended abuse of stimulants can lead to
psychological symptoms, such as hostility or paranoid psychosis. In addition to health status, the consequences of such substance
use impact the individuals using drugs, their families and society at large, with severe repercussions possible at both the individual
and public health level resulting from the chronic abuse and/or misuse of stimulants, such as teenage pregnancy, domestic violence,
motor vehicle accidents, crime, poor work performance, and impaired personal relationships. Stimulant misuse is also correlated
with a higher risk for substance use, with some evidence suggesting greater severity relative to controls, although it remains
unclear whether the misuse of controlled medications precedes other substance use behaviors.
Long-term stimulant abuse can lead to stimulant
use disorder, which may be characterized by chaotic behavior, social isolation, aggressive behavior, and sexual dysfunction. Individuals
exposed to amphetamine-type stimulants have been reported to develop stimulant use disorder in as rapidly as one week.
Furthermore, individuals may increase their
stimulant use in an effort to increase the euphoria, energy, and social and vocational interactions that they feel while using
the medications. Individuals may crush and snort or inject the stimulants in order to produce even greater effects. Tolerance will
develop with repeated use, and individuals often increase the frequency and amount of use in order to achieve a similar sense of
euphoria.
Once tolerance has developed, individuals
may experience withdrawal symptoms (hypersomnia, increased appetite, and dysphoria) if they try to stop using the medication. Stimulant
withdrawal can lead to depression, suicidal thoughts, irritability, anhedonia, emotional lability, and disturbances in attention
and concentration. There may be temporary depressive symptoms that may meet the criteria for major depressive episode. The effects
of withdrawal often lead individuals to abuse the medications again.
About ADHD and Existing Treatment Options
ADHD Condition and Impact
ADHD is defined as a persistent pattern of
inattention and/or hyperactivity-impulsivity that interferes with functioning or development. ADHD causes significant impairment
during a patient’s childhood, and throughout the patient’s lifespan, as well as increased morbidity, mortality and
psychosocial adversity.
Once believed to only affect children, ADHD
is now known to persist into adolescence and adulthood in a sizeable number of cases. The following table illustrates how the nature
of ADHD symptoms changes with age:
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Children
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Adolescents
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Adults
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Hyperactive
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Easily
distracted
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Shifts
activities
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Aggressive
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Inattentive
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Easily
bored
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Low
frustration tolerance
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Impatient
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Impulsive
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Approximately 50-60% of adults who suffered
from ADHD as children continue to have symptoms of the disorder as adults, with over 90% experiencing inattention symptoms and
about 35% experiencing hyperactivity-impulsivity symptoms. As the majority of sufferers of ADHD age, their symptoms tend toward
impatience, restlessness, boredom, and low concentration levels away from the more aggressive hyperactivity and impulsive behavior
evident in children.
Although the definitive causes of ADHD are
still unclear, current research suggests that ADHD is caused by an interaction between environmental factors and genetic predispositions.
Biologic factors that reportedly increase the risk of having ADHD include maternal smoking, drug or alcohol abuse during pregnancy,
brain injury, and exposure to toxins.
ADHD is believed to be one of the most under-diagnosed
and under-treated mental health conditions facing children and adults. ADHD increases health risks, adverse social externalities
and economic costs as illustrated in the following table. Despite the disorder being highly treatable, most adults with ADHD remain
undiagnosed and untreated.
The following table illustrates the effects on society when
ADHD remains untreated:
Healthcare
System
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Patient
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Family
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Increased ER visits
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Increased criminal activity
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Increased divorce/separation
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Increased car accidents
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Increased incarceration
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More sibling fights
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School
and Occupation
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Society
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Employer
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High
rates of expulsion
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Substance
use disorders:
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Increased
parental absenteeism and
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High
drop-out rates
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Higher
risk and earlier onset
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lower
productivity
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Lower
occupational status
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Less
likely to quit in adulthood
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Existing Treatment Options
Current management of ADHD frequently includes
a combination of educational support, behavioral interventions, and pharmacotherapy. The current standard of care is the stimulant
class of medications including immediate- and extended-release methylphenidate and amphetamine. Amphetamine products comprise the
majority of the U.S. ADHD market and immediate-release amphetamines are the fastest growing segment of such market.
Stimulant products represent more than 90%
of prescriptions of ADHD products in the United States.
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Methylphenidate
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Amphetamine
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(Approx.
30%)
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(Approx.
60%)
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Immediate-Release
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Ritalin®
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Dexedrine®
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(Approx.
40%)
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Adderall®
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Extended-Release
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Concerta®
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Adderall
XR®
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(Approx.
50%)
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Ritalin
LA®
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Vyvanse®
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Immediate-release (or short-acting) tablets
and capsules release the active ingredient within a short period of time, such as 30 minutes and demonstrate efficacy that lasts
for four to six hours. The patents covering most of these formulations have expired and most of these medications are now available
in generic forms.
Extended-release (or long acting) tablets
and capsules release the active ingredient at a sustained and controlled release rate over the course of the day, typically demonstrating
efficacy for 10 to 14 hours. Some of these are currently covered by patents and are not available in generic form.
The four highest-selling drugs for the treatment
of ADHD in 2019 on a worldwide basis are shown below:
Brand
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2019 Global Sales
(in millions)
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Vyvanse®
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$
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2,514
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Concerta®
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$
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696
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Strattera®
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$
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243
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Adderall XR®
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$
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223
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As of 2019, the two best-selling medications
were Vyvanse® and Concerta®, which are both extended-release stimulants. These and other extended-release stimulants are
prescribed for both adults and children. For children in particular, the long-acting formulation is preferred because it eliminates
the need for the child to take several doses during the school day.
Despite the popularity of the long-acting
drugs, we believe there is a growing market opportunity for immediate-release treatments among children and adults with ADHD. For
instance, some patients taking the extended-release drugs benefit from the addition of a short-acting stimulant taken in the evening
to supplement the medication given earlier in the day. This allows the patient to alleviate their ADHD symptoms for an evening
meeting or class, without keeping the patient awake all night. In addition, the immediate-release products can be useful when evaluating
whether an individual will be able to tolerate a particular stimulant or respond to a dosage titration.
Finally, some individuals with ADHD
prefer to manage their symptoms with medication only on an as-needed basis, and the immediate-release formulations give the
patient more flexibility with the dosing frequency. For instance, many patients experience varying degrees of side effects to
stimulant medication, including headaches, jitteriness, irritability, sleep problems, and decreased appetite, and some report
that stimulants decrease their creativity and spontaneity. For these reasons, many adults — who now
comprise more than 50% of the U.S. prescriptions for ADHD medication — prefer the short-acting
formulations. Therefore, although short-acting stimulants are only approved for use in children and adolescents, part of our
long-term plan involves seeking approval for use of short-acting stimulants in adults as well.
ADHD Market
According to IQVIA (formerly, IMS Health),
the U.S. market for ADHD treatment was estimated to be approximately $9 billion annually, which accounted for over 80% of
the global ADHD market in 2019. The difference in market sizes between the U.S. and other countries is driven by different rates
of diagnosis and treatment, different pricing, and the number of available brand name medications (non-U.S. markets are dominated
by generic drugs). Global prevalence rates of the disease are estimated to be approximately 8-10% of school-aged children and approximately
4-5% of the adult population. Adult diagnosis and treatment, which has grown at approximately 10% annually over the last few years,
is forecasted to grow in the near future due to increased disease awareness and less sociological stigmatization towards the condition.
In the United States, the rate of treatment with prescription medications is approximately 70% in children and 45% in adults. In
2019, over 75 million prescriptions were filled in the United States for approved ADHD medications, whereas less than 44 million
prescriptions were filled in 2009. The U.S. market is projected to continue to grow in mid-single digits, driven by an increased
prescription rate for adult ADHD. The growth of immediate-release amphetamines averaged over 7% annually from 2014-19 and is projected
to continue to grow faster than the overall ADHD market in the foreseeable future. In 2019, 28 million prescriptions were
filled in the United States for immediate-release stimulants, such as Adderall and Ritalin. Immediate release amphetamine stimulants,
the segment which we are primarily targeting, currently represent approximately 30% of the ADHD medications market (prescriptions
and patients) and continue to gain market share.
The international ADHD market is projected
to grow at a faster rate than the U.S. market in part because disease recognition and acceptance is expected to increase in both
Japan and Europe. The estimated growth rate for the non-U.S. markets is also higher due to the recent launches of major ADHD drugs
that have already been marketed in the United States, such as Vyvanse and Intuniv.
Potential for Abuse
Stimulant abuse is unique and challenging
because the abuse and addiction risks of stimulants are not restricted to those who are prescribed the medications. Published data
reports that stimulants are almost twice as likely to be diverted (i.e., given away or sold) as other scheduled medications,
such as opioid, sleep or anxiety medications. It has been reported that between 25-60% of teenagers and college students with ADHD
have been approached at some point to give away or sell their prescription stimulants and over 60% of college students with ADHD
admit to having diverted their ADHD prescription medication.
Approximately 90% of those who misuse/abuse
stimulants do so with prescription amphetamines based on data from the NSDUH.
The number of emergency room visits associated
with non-medical use of prescription stimulants increased more than four-fold from 2004 to 2011, according to the Drug Abuse Warning
Network (“DAWN”), and most of this increase was associated with amphetamine-based prescription stimulants.
Speed of onset and route of administration
has been accepted as being important in evaluating the potential for abuse of certain medications, such as stimulants.
In general, the oral route is associated
with lower abuse liability because of slower absorption rates and slower onset of effects compared to other routes of administration.
Inhalation, snorting, and intravenous (“IV”) injection of drugs are associated with far more rapid absorption
and faster onset of effects when compared to oral ingestion. In general, oral use of stimulants results in the slowest rate of
absorption, while snorting is relatively faster; smoking and IV injection of stimulants evoke even more rapid absorption and more
intense and rapid physiological and subjective responses. Published studies report that 40% or more of people who misuse or abuse
prescription stimulants, do so by IV injection or snorting. These methods of abuse drive a more rapid increase in dopamine levels
that drive the subjective, or re-enforcing effects of these drugs. Consequently, these abuse routes are thought to bring the abuser
one step closer to addiction and dependence. In addition, the quick entry of the drug into the bloodstream increases the risk of
chest pain, rapid / irregular heartbeat, heart attack, seizures, hallucinations, hostile/aggressive behavior, suicidal thoughts
and behaviors, and stroke.
Immediate-release stimulants, including amphetamines,
are more prone to abuse than extended-release stimulants and are the fastest growing market in the ADHD market in recent years.
Amphetamine tablets are easy to crush into a powder suitable for snorting, or mixing with water and injecting. On the other hand,
long-acting stimulant capsules are abused less frequently because they contain a combination of immediate-release and extended-release
beads with different release profiles that are difficult to crush into a form that can be snorted, smoked, or mixed with water
and injected.
The rate of amphetamine use disorders doubled between 2010 and
2016:
Amphetamine forms molecules that are highly
soluble in lipids, which are then rapidly transported to the brain through the blood-brain barrier. Routes of administration that
deliver the drug directly into the bloodstream and bypass the digestive system (i.e., snorting, smoking, and IV injection)
would be expected to cause faster onset of psychoactive effects. Therefore, reducing the risk of abuse via snorting, smoking, and
injection is a potential public health goal because the speed of the absorption of stimulants is an important determinant of a
product’s abuse potential, as is the case for opioids, and is also related to the overall potential risks of the drug product.
Many people who use amphetamines and other
stimulants for recreational use prefer routes of administration that provide rapid onset of effects. In order to achieve its maximum
pharmacologic effect, the largest quantity of drug must be delivered into the CNS in the shortest possible time. For instance,
a published study found that the reinforcing properties of methylphenidate occur when the drug elicits a large and fast dopamine
increase but has only therapeutic properties when there is a slow, steady-state increase in dopamine caused by the drug. This leads
drug abusers to progress from relatively safe methods of self-administration, such as oral ingestion of marketed doses of stimulants,
to increasingly higher dosages and more dangerous routes of administration, such as smoking, snorting, and injecting.
Our Solutions
ADAIR
Stimulant abuse is large and growing public
health challenge, yet the immediate-release segment of the ADHD market is entirely devoid of any abuse-deterrent products. This
unmet need led to the design of ADAIR as an oral formulation of an immediate-release dextroamphetamine. This included the development
and in vitro testing of multiple formulations, followed by the selection of the optimal, proprietary formulation of ADAIR that
is intended to introduce certain barriers to abuse of immediate-release dextroamphetamine.
ADAIR is an oral, semi-solid, liquid-filled,
hard gelatin capsule of dextroamphetamine sulfate, the active ingredient. This formulation resists manipulation and preparation
for snorting, and provides meaningful barriers to injection — demonstrated through a set of abuse-deterrence
studies conducted in collaboration with M.W. Encap Limited, an affiliate of Lonza Group AG.
After subjecting ADAIR to grinding,
crushing, or cutting the capsule following thermal pre-treatment, minimal quantities of particles could appreciably pass
through a 500 micrometer (“µm”) filter (a particle size deemed suitable for snorting). In contrast,
42-47% of the physically manipulated immediate-release dextroamphetamine reference tablet could pass through a 500 µm
filter, suggesting that it could be readily crushed and snorted.
We also subjected ADAIR to multiple forms
of manipulation, but none of those yielded ADAIR particles that could be easily expelled from a syringe. ADAIR mixed in water yielded
a viscous, cloudy material, which was usually impossible, and at other times difficult, to syringe. Texture analysis demonstrated
that the force required to push the plunger with a manipulated ADAIR-filled syringe is far greater than that with manipulated immediate-release
dextroamphetamine reference tablet.
In comparison with the immediate-release
dextroamphetamine reference tablet, ADAIR demonstrated reduced syringe-ability across a range of volumes of water (2, 5, and 10
milliliters), needle gauges (26, 23, 20, and 18 gauge), in ambient or hot water, and when passed through a cigarette filter.
We believe these studies demonstrate that,
as compared to the immediate-release dextroamphetamine reference tablet, ADAIR could display deterrence properties against abuse
through snorting or IV injection.
Our abuse-deterrent formulation may not meaningfully
discourage oral ingestion to enhance occupational or academic performance, or misuse; however, depending on the properties of the
formulation, an abuse-deterrent formulation could reduce the risks of adverse effects by anyone who would attempt to abuse it by
snorting, smoking, or injecting, and reduce the contribution of prescription stimulants to problems associated with stimulant abuse.
In addition, the general pharmacologic rationale
for abuse-deterrent stimulants is similar to the rationale of abuse-deterrent opioids used to treat and manage pain as described
in the FDA 2015 Guidance on Abuse-Deterrent Opioid. The FDA clearly articulated the rationale for the development of abuse-deterrent
technologies, as well as cited its limitations, in its 2015 Guidance, pp. 1-2:
Prescription opioid products are an important component
of modern pain management. However, abuse and misuse of these products have created a serious and growing public health problem.
One potentially important step towards the goal of creating safer opioid analgesics has been the development of opioids that are
formulated to deter abuse. FDA considers the development of these products a high public health priority. Because opioid products
are often manipulated for purposes of abuse by different routes of administration or to defeat extended-release (ER) properties,
most abuse-deterrent technologies developed to date are intended to make manipulation more difficult or to make abuse of the manipulated
product less attractive or less rewarding. It should be noted that these technologies have not yet proven successful at
deterring the most common form of abuse — swallowing a number of intact capsules or tablets to achieve
a feeling of euphoria. Moreover, the fact that a product has abuse-deterrent properties does not mean that there is no risk of
abuse. It means, rather, that the risk of abuse is lower than it would be without such properties. Because opioid
products must in the end be able to deliver the opioid to the patient, there may always be some abuse of these products.
Although ADAIR is very difficult to manipulate
into a form that can be snorted, it is not impossible to do so. In order to conduct human abuse studies, Vallon hired a third-party
drug laboratory that was able to develop a time- consuming and laborious process to convert ADAIR into a form that could be insufflated.
The medical literature reports that recreational abusers of prescription medications are typically not willing to spend more than
a few minutes preparing a drug for misuse or abuse and our own research with recreational stimulant users documented that they
would not be willing to spend more than 10-12 minutes preparing a drug like ADAIR for snorting. In addition, although ADAIR is
difficult to solubilize into a form that can be injected, sophisticated drug abusers may be able to develop methods to manipulate
ADAIR into a form that can be injected.
Regulatory communications regarding the application
of abuse-deterrent technologies for prescription stimulants continue to emerge. In 2014, Janet Woodcock, M.D., Director, Center
for Drug Evaluation and Research, stated that the FDA encourages the development of abuse-deterrent formulations for controlled
substances, while also noting that the science surrounding abuse-deterrent technology is relatively new. In public meetings, FDA
officials have made comments related to interest in the application of abuse-deterrent technologies for stimulants, as well as
other drugs of abuse. In practice, the FDA engages with sponsors of abuse-deterrent formulations on a product-by-product basis,
sometimes requiring an abuse-deterrent assessment as part of the development to inform approval and labeling processes by the FDA.
In September 2019, the FDA issued a Federal Register notice to seek public comment on the development and evaluation of abuse
deterrent formulations (ADF) of ADHD stimulants and whether such products could play a role in addressing public health concerns
related to prescription stimulant misuse and abuse signaling their interest in this field.
Lastly, based on market research conducted
by us in conjunction with U.S. health insurers, who collectively manage over 100 million covered lives, a strong majority
of insurers are receptive of the ADAIR product concept and indicate that they would be willing to have ADAIR, if approved, placed
on their prescription drug formulary and to reimburse the costs for ADAIR through their respective health insurance plans. In addition,
the continuing and heightened publicity surrounding the national opioid epidemic continues to result in heightened sensitivity
by many health care professionals to prescribe, and pharmacies to dispense, medications with the potential for abuse.
Development of ADMIR
ADMIR is an abuse deterrent formulation of
Ritalin for which we are conducting formulation development work. We have developed several prototype formulations that we are
continuing to refine. If our formulation development work is successful, we anticipate requesting a pre-IND meeting with the FDA
and filing an IND in 2021. ADMIR is designed to have abuse deterrent properties that are similar to ADAIR.
Clinical Development
We aim to be the first company to introduce
a proprietary abuse-deterrent immediate-release dextroamphetamine drug to the market and leverage our agility, flexibility, and
know-how to utilize such a position for the benefit of patients, physicians, and our community.
We filed our Investigational New Drug (“IND”)
application for ADAIR in June 2018 and the IND was cleared in July 2018. Subsequently, we have successfully completed
three Phase 1 clinical studies.
Phase 1 Bioequivalence Study
In December 2018, we completed a Phase 1
pivotal bioequivalence study of ADAIR, which was conducted by Altasciences. The study enrolled 24 subjects, who were dosed with
10 mg of ADAIR and reference dextroamphetamine orally on a single occasion for each study drug. There were no serious adverse events
(“SAEs”) during the study. The primary objective of the study was to evaluate and compare the pharmacokinetics
(“PK”) of ADAIR capsules to dextroamphetamine tablets under fasting conditions. The secondary objectives of
the study were to evaluate the safety and tolerability of the test and reference formulations in healthy subjects. The study met
the primary endpoint demonstrating bioequivalence and met the secondary endpoints.
Food Effect Study
In December 2018, we completed a Phase 1
food effect study of ADAIR, which was conducted by Altasciences. The study enrolled 22 subjects who were dosed with 10 mg of ADAIR
orally twice, once when subjects were fasting and once when they had been fed. One SAE (miscarriage) was reported during the study.
A 33-year-old African American female subject had an unplanned pregnancy reported one week after the last study drug dose. The
miscarriage occurred at pregnancy day 35. The investigator considered the SAE possibly related to drug treatment. However, because
of the timing, background incidence, and risk factors (including age and race), we concluded that this SAE was unlikely to be related
to the study drug.
The primary objective of this study was to
evaluate and compare the PK of d-amphetamine from an abuse-deterrent capsule formulation of dextroamphetamine sulfate when dosed
under fasting and fed conditions. The secondary objective was to evaluate the safety and tolerability of the investigational product
in healthy subjects. The study met both the primary and secondary endpoints.
Human Abuse Proof of Concept Study
I n November 2019, we completed a Phase 1
proof-of-concept intranasal human abuse potential study designed to compare ADAIR when insufflated (snorted) as compared to the
reference comparator, crushed immediate release dextroamphetamine sulfate tablets. The study was conducted by BioPharma Services
and enrolled 16 subject who received one dose of ADAIR and reference dextroamphetamine administered intranasally each at a dose
of 30 mg. The primary objective was to assess safety and tolerability of manipulated ADAIR and crushed dextroamphetamine sulfate
IR (“DEX”), when administered intranasally to non-dependent, recreational stimulant users. The secondary objectives
were to evaluate and compare the PK profiles of ADAIR and DEX when administered intranasally to non-dependent, recreational stimulant
users. The exploratory objectives of this study were to assess and compare abuse liability of ADAIR and DEX when administered intranasally
to non- dependent, recreational stimulant to users. There were no SAEs in connection with this trial. The study met the primary,
secondary and exploratory endpoints.
The results of this study demonstrate that
as compared to DEX, ADAIR, when snorted, demonstrated an attenuated pharmacokinetic profile and lower drug liking and other abuse
liability scores, using standard measures for human abuse potential studies.
We have used the results of this proof of
concept abuse study to design a larger intranasal abuse study that we will conduct prior to seeking approval of ADAIR. We designed
the study to follow the model used in intranasal abuse studies that have been conducted for abuse deterrent opioids and following
guidance issued by the FDA for such studies.
Preclinical Studies and Other Clinical Development Plans
We recently completed a preclinical embryofetal
study which showed no evidence of developmental effects and no clinical observations other than those associated with the pharmacological
effects of dextroamphetamine. We are currently conducting a 13-week preclinical toxicology study on the final formulation of ADAIR.
We also plan to conduct additional preclinical studies of unintended routes of administration such as IV and intranasal administration.
We plan to develop other abuse-deterrent
products that have potential for abuse in their current forms, beginning with the development of an abuse deterrent formulation
of Ritalin® (“ADMIR”), for which we are conducting formulation development work.
We expect that our clinical trials described
above will provide sufficient data to support an NDA filing with the FDA.
Government Regulation and Product Approval
Clinical trials, the drug approval process,
and the marketing of drugs are intensively regulated in the United States and in all major foreign countries. In the United States,
the FDA regulates drugs under the Federal Food, Drug, and Cosmetic Act (“FDCA”), and related regulations. Drugs
are also subject to other federal, state, and local statutes and regulations. Failure to comply with the applicable U.S. regulatory
requirements at any time during the product development process, approval process or after approval may subject an applicant to
administrative or judicial sanctions. These sanctions could include the imposition by the FDA Institutional Review Board (“IRB”)
of a clinical hold on trials, the FDA’s refusal to approve pending applications or supplements, withdrawal of an approval,
warning letters, product recalls, product seizures, total or partial suspension of production or distribution, injunctions, fines,
civil penalties or criminal prosecution. Any agency or judicial enforcement action could have a material adverse effect on us.
The FDA and comparable regulatory agencies
in state and local jurisdictions and in foreign countries impose substantial requirements upon the clinical development, manufacture
and marketing of biopharmaceutical products. These agencies and other federal, state, and local entities regulate research and
development activities and the testing, manufacture, quality control, safety, effectiveness, labeling, storage, distribution, record
keeping, approval, advertising, and promotion of ADAIR or any other product we develop in the future.
The FDA’s policies may change, and
additional government regulations may be enacted that could prevent or delay regulatory approval of any candidate drug product
or approval of new disease indications or label changes. We cannot predict the likelihood, nature or extent of adverse governmental
regulation that might arise from future legislative or administrative action, either in the United States or abroad.
Marketing Approval
The process required by the FDA before new
drugs may be marketed in the United States generally involves the following:
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nonclinical laboratory and animal tests;
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submission of an IND application, which must become effective before clinical trials may begin;
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adequate and well-controlled human clinical trials to establish the safety and efficacy of the proposed drug for its intended
use or uses;
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pre-approval inspection of manufacturing facilities and clinical trial sites; and
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FDA approval of an NDA which must occur before a drug can be marketed or sold.
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The testing and approval process requires
substantial time and financial resources, and we cannot be certain that any approvals will be granted on a timely basis if at all.
We will need to successfully complete additional
clinical trials in order to be in a position to submit an NDA to the FDA. Future trials may not begin or be completed on schedule,
if at all. Trials can be delayed for a variety of reasons, including delays in:
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obtaining regulatory approval to commence a study;
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reaching agreement with third-party clinical trial sites and vendors and their subsequent performance in conducting accurate
and reliable studies on a timely basis;
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obtaining institutional review board approval to conduct a study at a prospective site;
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recruiting subjects to participate in a study; and
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We must reach an agreement with the FDA on
the proposed protocols for our future clinical trials in the United States. A separate submission to the FDA must be made for each
successive clinical trial to be conducted during product development. Further, an independent IRB for each site proposing to conduct
the clinical trial must review and approve the plan for any clinical trial before it commences at that site. Informed consent must
also be obtained from each study subject. Regulatory authorities, an IRB, a data safety monitoring board, or the sponsor may suspend
or terminate a clinical trial at any time on various grounds, including a finding that the participants are being exposed to an
unacceptable health risk.
ADAIR
ADAIR was specifically designed to limit
abuse by snorting or injecting. A pre-IND meeting with the FDA was held on January 26, 2017 to discuss the details of the
development program using the Section 505(b)(2) approval pathway. The FDA provided guidance on the necessary steps towards
an NDA.
The development plan for ADAIR is to conduct
clinical trials and if those trials are successful, seek marketing approval from the FDA. To achieve this objective, the following
development plan was proposed by Arcturus and reviewed by the FDA:
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Filing an IND application;
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Conducting a pivotal bioequivalence study in healthy volunteers comparing ADAIR and its reference listed drug;
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Conducting a food effect study comparing ADAIR when taken orally after a period of fasting to ADAIR taken after consuming a
high fat meal;
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Conducting further laboratory studies and Human Abuse Potential (HAP) studies (if feasible) to evaluate ADAIR’s abuse
deterrent characteristics in order to establish labeling language regarding abuse deterrence against snorting and injecting; and
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Conducting a 13-week preclinical toxicology study and preclinical embryofetal study on the final formulation of ADAIR.
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An NDA would be filed to the FDA only after
achieving success in each of the above milestones and any additional milestones the FDA may request.
As with similar products, the ADAIR development
program requires special regulatory management and controls, this may raise further risks to the program, including:
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Good communication and collaboration with multiple departments within the FDA, e.g., Division of Psychiatry Products, Office
of Pharmaceutical Quality, Control Substance Staff, Office of Surveillance and Epidemiology, and also outside the Agency with the
DEA since dextroamphetamine is classified as a Schedule II drug product.
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Following NDA submission, the FDA may call for an expert Advisory Committee (as seen with recent NDA applications for Abuse-Deterrent
Opioids products). Such committees, which are partially open to the public, are called to discuss the overall risk-benefit profile
of the product, and whether the applicant has demonstrated abuse-deterrent properties for their product that would support labeling.
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FDA Post-Approval Requirements
Any products manufactured or
distributed by us pursuant to FDA approvals are subject to continuing regulation by the FDA, including requirements for
record-keeping and reporting of adverse experiences with the drug. Drug manufacturers are required to register their
facilities with the FDA and certain state agencies and are subject to periodic unannounced inspections by the FDA and certain
state agencies for compliance with cGMPs, which impose certain quality processes, manufacturing controls, and documentation
requirements upon us and our third-party manufacturers in order to ensure that the product is safe, has the identity and
strength, and meets the quality and purity characteristics that it purports to have. Under the federal Prescription Drug
Marketing Act, the sampling and distribution and tracking of drugs is regulated. It is designed to discourage the sale of
counterfeit, adulterated, misbranded, subpotent, and expired prescription drugs. Certain states also impose requirements on
manufacturers and distributors to establish the pedigree of product in the chain of distribution, including some states that
require manufacturers and others to adopt new technology capable of tracking and tracing product as it moves through the
distribution chain. We cannot be certain that we or our present or future suppliers will be able to comply with the cGMP and
other FDA regulatory requirements. If our present or future suppliers are not able to comply with these requirements, the FDA
may halt our clinical trials, fail to approve any NDA or other application, require us to recall a drug from distribution,
shut down manufacturing operations or withdraw approval of the NDA for that drug. Noncompliance with cGMP or other
requirements can result in issuance of warning letters, civil and criminal penalties, seizures, and injunctive action.
The FDA may request, or we may propose, to
implement a risk management program to educate physicians and parents or patients of appropriate use of ADAIR, and to monitor the
real-world use and reports of abuse of ADAIR following its approval. Such risk management programs are common with many medications
with abuse potential including many approved ADHD products.
Labeling, Marketing and Promotion
The FDA closely regulates the labeling, marketing,
and promotion of drugs. While doctors are free to prescribe any drug approved by the FDA for any use, a company can only make claims
relating to the safety and efficacy of a drug that are consistent with FDA approval and may only actively market a drug only for
the particular use and treatment approved by the FDA. In addition, any claims we make for our products in advertising or promotion
must be appropriately balanced with important safety information and otherwise be adequately substantiated. Failure to comply with
these requirements can result in adverse publicity, warning letters, corrective advertising, injunctions, and potential civil and
criminal penalties. Government regulators recently have increased their scrutiny of the promotion and marketing of drugs.
Pediatric Research Equity Act
The Pediatric Research Equity Act (“PREA”)
amended the FDCA to authorize the FDA to require certain research into drugs used in pediatric patients. The intent of the PREA
is to compel sponsors whose drugs have pediatric applicability to study those drugs in pediatric populations, rather than ignoring
pediatric indications for adult indications that could be more economically desirable. The Secretary of Health and Human Services
may defer or waive these requirements under specified circumstances. The FDA may decide that an NDA will be approved only following
completion of additional pediatric studies.
Anti-Kickback and False Claims Laws
In the United States, the research, manufacturing,
distribution, sale and promotion of drug products and medical devices are potentially subject to regulation by various federal,
state and local authorities in addition to the FDA, including the Centers for Medicare & Medicaid Services, other divisions
of the U.S. Department of Health and Human Services (e.g., the Office of Inspector General), the U.S. Department of Justice, state
Attorneys General, and other state and local government agencies. For example, sales, marketing, and scientific/educational grant
programs must comply with the Anti-Kickback Statute, the False Claims Act, as amended, the privacy regulations promulgated under
HIPAA, and similar state laws. Pricing and rebate programs must comply with the Medicaid Drug Rebate Program requirements of the
Omnibus Budget Reconciliation Act of 1990, as amended, and the Veterans Health Care Act of 1992, as amended. If products are made
available to authorized users of the Federal Supply Schedule of the General Services Administration, additional laws and requirements
apply. All of these activities are also potentially subject to federal and state consumer protection and unfair competition laws.
In the United States, we are subject to complex
laws and regulations pertaining to healthcare “fraud and abuse,” including, but not limited to, the Anti-Kickback Statute,
the federal False Claims Act, and other state and federal laws and regulations. The Anti-Kickback Statute makes it illegal for
any person, including a prescription drug manufacturer (or a party acting on its behalf) to knowingly and willfully solicit, receive,
offer, or pay any remuneration that is intended to induce the referral of business, including the purchase, order, or prescription
of a particular drug, for which payment may be made under a federal healthcare program, such as Medicare or Medicaid.
The federal civil False Claims Act prohibits,
among other things, any person or entity from knowingly presenting, or causing to be presented, a false or fraudulent claim for
payment to or approval by the federal government or knowingly making, using or causing to be made or used a false record or statement
material to a false or fraudulent claim to the federal government. A claim includes “any request or demand” for money
or property presented to the U.S. government. Violations of the False Claims Act can result in very significant monetary penalties
and treble damages. The federal government is using the False Claims Act, and the accompanying threat of significant liability,
in its investigation and prosecution of pharmaceutical companies throughout the country, for example, in connection with the promotion
of products for unapproved uses and other sales and marketing practices. The government has obtained multi-million and multi-billion-dollar
settlements under the False Claims Act in addition to individual criminal convictions under applicable criminal statutes. In addition,
the federal civil monetary penalties statute imposes penalties against any person or entity that, among other things, is determined
to have presented or caused to be presented a claim to a federal health program that the person knows or should know is for an
item or service that was not provided as claimed or is false or fraudulent. Given the significant size of actual and potential
settlements, it is expected that the government will continue to devote substantial resources to investigating healthcare providers’
and manufacturers’ compliance with applicable fraud and abuse laws.
The federal Health Insurance Portability
and Accountability Act of 1996 (“HIPAA”), also created new federal criminal statutes that prohibit knowingly
and willfully executing, or attempting to execute, a scheme to defraud any healthcare benefit program, including private third-party
payors and knowingly and willfully falsifying, concealing or covering up a material fact or making any materially false, fictitious
or fraudulent statement in connection with the delivery of or payment for healthcare benefits, items or services. Similar to the
Anti-Kickback Statute a person or entity does not need to have actual knowledge of these statutes or specific intent to violate
them in order to have committed a violation.
There are also an increasing number of state
laws that require manufacturers to make reports to states on pricing and marketing information. Many of these laws contain ambiguities
as to what is required to comply with the laws. In addition, a similar federal requirement Section 6002 of the Patient Protection
and Affordable Care Act, as amended by the Health Care and Education Affordability Reconciliation Act (the “Affordable
Care Act”) commonly referred to as the “Physician Payments Sunshine Act” requires manufacturers to track
and report to the federal government certain payments and “transfers of value” made to physicians and teaching hospitals,
as well as ownership and investment interests held by physicians and their immediate family members, made in the previous calendar
year. There are a number of states that have various types of reporting requirements as well. These laws may affect our sales,
marketing, and other promotional activities by imposing administrative and compliance burdens on us. In addition, given the lack
of clarity with respect to these laws and their implementation, our reporting actions could be subject to the penalty provisions
of the pertinent state, and soon federal, authorities.
Patient Protection and Affordable Health Care Act
In March 2010, the Affordable Care Act
was enacted, which includes measures that have or will significantly change the way health care is financed by both governmental
and private insurers. The fees, discounts, and other provisions of this law are expected to have a significant negative effect
on the profitability of pharmaceuticals.
This legislation is expected to impact the
scope of healthcare insurance, the insurance refunds from the insurance companies and possibly also on the costs of medical products.
Other Regulations
We are also subject to numerous federal,
state and local laws relating to such matters as safe working conditions, manufacturing practices, environmental protection, fire
hazard control, and disposal of hazardous or potentially hazardous substances. We may incur significant costs to comply with such
laws and regulations now or in the future.
Manufacturing
We do not currently own or operate any manufacturing
facilities and we do not have any experience with commercial-scale manufacturing. We currently rely, and expect to continue to
rely for the foreseeable future, on a third-party manufacturer to produce our product candidates for preclinical and clinical testing,
as well as for commercial manufacture if our product candidates receive marketing approval.
Although we do not have a long-term commercial
supply arrangement in place with any of our contract manufacturers, it is our goal to contract with at least one manufacturer in
the United States for the commercial supply of ADAIR for the U.S. market.
Our third-party manufacturers, their facilities,
and all pharmaceutical products used in our clinical trials are required to comply with cGMP. The cGMP regulations include requirements
relating to organization of personnel, buildings and facilities, equipment, control of components and drug product containers and
closures, production and process controls, packaging and labeling controls, holding and distribution, laboratory controls, records
and reports, and returned or salvaged products. The manufacturing facilities for our products must meet, and continue to meet,
cGMP requirements and FDA satisfaction before any product is approved and we can manufacture commercial products. Contract manufacturers
often encounter difficulties involving production yields, quality control and quality assurance, as well as shortages of qualified
personnel.
Sales and Marketing
We retain advisors and consultants to support
our pre-commercialization activities. However, we currently do not have any internal sales or distribution infrastructure. In the
event that we receive regulatory approval for ADAIR or any other product we may develop, we intend, where appropriate, to pursue
commercialization relationships with biopharmaceutical companies and other strategic partners providing for distribution through
their sales and marketing organizations, or to build an internal commercial infrastructure.
Medice License Agreement
On January 6, 2020, Vallon entered into
a license agreement with Medice, who is affiliated with one of our principal stockholders, Salmon Pharma, and represented by one
member of our board of directors, which grants Medice an exclusive license, with the right to grant sublicenses, to develop, use,
manufacture, market and sell ADAIR throughout Europe. Medice currently markets several ADHD products in Europe and is the ADHD
market leader in Europe based on branded prescription market share. Medice is responsible for obtaining regulatory approval of
ADAIR in the licensed territory. Under the license agreement, Medice paid Vallon a minimal upfront payment and will pay milestone
payments of up to $6.3 million in the aggregate upon first obtaining regulatory approval to market and sell ADAIR in any country,
territory or region in the licensed territory and upon achieving certain annual net sales thresholds. For the term of the license
agreement, Medice will also pay tiered royalties on annual net sales of ADAIR at rates between 10% and 20%. The initial term of
the license agreement will expire five years after the date on which Medice first obtains regulatory approval in any country,
territory or region in the licensed territory. Medice has the option to extend the term of the license agreement for additional
periods of five years each. Medice has the right to terminate the license agreement at any time upon 12 months’
prior written notice to Vallon. Vallon has the right to terminate the license agreement immediately upon notice if Medice challenges
the validity, enforceability or patentability of any patent right comprising the licensed intellectual property. Either party may
terminate the license agreement if the other party materially breaches its obligations under the license agreement, provided that
the terminating party gives the breaching party notice of the breach and a specified opportunity to cure the breach, or upon the
other party’s bankruptcy.
Intellectual Property
We strive to pursue, maintain and defend
patent rights developed internally and to protect the technology, inventions and improvements that are commercially important to
the development of our business. We currently have two issued U.S. patents directed to specific ADAIR formulations (i.e., composition
of matter) and one pending patent application for ADAIR that is under examination with the U.S. PTO. The U.S. patents will expire
in 2037. Our international PCT application has entered national phase is under examination in several foreign countries and territories,
including the EU, Canada, Japan and China. We also rely on know-how relating to our proprietary technology and product candidates
and continuing innovation to develop, strengthen and maintain our proprietary position. We also plan to rely on data exclusivity,
market exclusivity and patent term extensions when available.
We cannot be sure that any additional
patents will be granted with respect to any of our pending patent applications or with respect to any patent applications we
may file in the future. There is also a significant risk that any issued patents will have substantially narrower claims than
those that are currently sought. Even with respect to any patents that may be issued to us, we cannot be sure that any such
patents will be commercially useful in protecting our technology. Our first two issued patents with respect to ADAIR expire
in 2037. Our commercial success will depend in part on our ability to obtain and maintain patent and other proprietary
protection for our technology, inventions and improvements; to defend and enforce our proprietary rights, including any
patents that we may own in the future; and to operate without infringing the valid and enforceable patents and other
proprietary rights of third parties. Intellectual property rights may not address all potential
threats to our competitive advantage. For a more comprehensive discussion of the risks related to our intellectual property,
please see “Risk Factors — Risks Relating to Intellectual Property.”
With respect to our product candidates and
processes we intend to develop and commercialize in the normal course of business, we intend to pursue patent protection covering,
when possible, compositions, methods of use, dosing and formulations. We or our licensors also may pursue patent protection with
respect to manufacturing and drug development processes and technologies. Obtaining and maintaining patent protection depends on
compliance with various procedural, document submission, fee payment, and other requirements imposed by governmental patent agencies.
We or our licensors may not be able to obtain patent protections for our compositions, methods of use, dosing and formulations,
manufacturing and drug development processes and technologies throughout the world. Issued patents can provide protection for varying
periods of time, depending upon the date of filing of the patent application, the date of patent issuance and the legal term of
patents in the countries in which they are obtained. In general, patents issued for applications filed in the United States can
provide exclusionary rights for 20 years from the earliest effective filing date. In addition, in certain instances, the term
of an issued U.S. patent that is directed to or claims an FDA-approved product can be extended to recapture a portion of the term
effectively lost as a result of the FDA regulatory review period, which is called “patent term extension.” The restoration
period cannot be longer than five years and the total patent term, including the restoration period, must not exceed 14 years
following FDA approval. The term of patents outside of the United States varies in accordance with the laws of the foreign jurisdiction,
but typically is also 20 years from the earliest effective filing date. However, the actual protection afforded by a patent
varies on a product-by-product basis, from country-to-country, and depends upon many factors, including the type of patent, the
scope of its coverage, the availability of regulatory-related extensions, the availability of legal remedies in a particular country,
and the validity and enforceability of the patent. The laws of some foreign countries may not protect intellectual property rights
to the same extent as the laws of the U.S.
Our success also depends in part on our ability
to preserve trade secrets; prevent third parties from infringing upon our proprietary rights; and operate our business without
infringing the patents and proprietary rights of third parties, both in the United States and internationally. We also protect
our proprietary technology and processes, in part, by confidentiality and invention assignment agreements with our employees, consultants,
scientific advisors and other contractors. These agreements may be breached, and we may not have adequate remedies for any breach.
In addition, our trade secrets may otherwise become known or be independently discovered by competitors. To the extent that our
employees, consultants, scientific advisors or other contractors use intellectual property owned by others in their work for us,
disputes may arise as to the rights in related or resulting know-how and inventions.
The patent positions of companies like ours
are generally uncertain and involve complex legal and factual questions. No consistent policy regarding the scope of claims allowable
in patents in the field of biopharmaceuticals has emerged in the United States. The relevant patent laws and their interpretation
outside of the United States is also uncertain. Changes in either the patent laws or their interpretation in the United States
and other countries may diminish our ability to protect our technology or product candidates and could affect the value of such
intellectual property. In particular, our ability to stop third parties from making, using, selling, offering to sell or importing
products that infringe our intellectual property will depend in part on our success in obtaining and enforcing patent claims that
cover our technology, inventions and improvements.
Competition
No immediate-release prescription stimulant
product with abuse-deterrent labeling currently exists on the market in the United States or internationally, however, we face
competition from established biopharmaceutical companies that currently market a wide range of drugs to treat ADHD. All of these
competitors have far greater marketing and research capabilities than we do. We also face potential competition from academic institutions,
government agencies, and private and public research institutions, among others, which may in the future develop products to treat
ADHD. Any of these companies and institutions may have products in development that are superior to ADAIR.
In addition, the biotechnology and pharmaceutical
industries are characterized by rapid technological advancement, significant competition and an emphasis on intellectual property.
Any product candidates that we successfully develop and commercialize will compete with current therapies and new therapies that
may become available in the future. Our commercial opportunity would be reduced significantly if our competitors develop and commercialize
products that are safer, more effective and convenient, have fewer side effects and/or are less expensive than the expected price
of ADAIR. Public announcements regarding the development of competing drugs could adversely affect the price of our stock and the
commercial potential of ADAIR.
Neither the FDA nor any other regulatory
agency has approved any abuse-deterrent immediate-release stimulant. One company has submitted an application to the FDA for the
approval of an immediate release stimulant designed to resist physical manipulation. An FDA advisory committee recently recommended
against the approval of this product because it did not meet the primary endpoint of its human abuse liability study and based
on safety concerns that are specific to the formulation in the other product that do not apply to ADAIR. The formulation technology
and active ingredient in that product is distinct from that in ADAIR. While we are aware of several abuse-deterrent long-acting
stimulants under development, we do not believe that ADAIR will compete directly with those products because they are designed
to last longer and compete in a different segment of the ADHD market for a different patient population than ADAIR.
Third-Party Reimbursement
Sales of biopharmaceutical products depend
in significant part on the availability of coverage and adequate reimbursement by third-party payors, such as state and federal
governments, including Medicare and Medicaid, managed care providers, and private insurance plans. Decisions regarding the extent
of coverage and amount of reimbursement to be provided for ADAIR will be made on a plan by plan basis.
Within the Medicare program, as a self-administered
drug, ADAIR would be reimbursed under the expanded prescription drug benefit known as Medicare Part D. This program is a voluntary
Medicare benefit administered by private plans that operate under contracts with the federal government. These Part D plans
negotiate discounts with drug manufacturers, which may be passed on to each of the plan’s enrollees. Historically, Part D
beneficiaries have been exposed to significant out-of-pocket costs after they surpass an annual coverage limit and until they reach
a catastrophic coverage threshold. However, changes made by recent legislation will reduce this patient coverage gap, known as
the donut hole, by reducing patient responsibility in that coverage range. Because the vast majority of patients treated with ADHD
medications are under 65 years old, Medicare has a relatively small impact on ADHD medications and this would also be expected
for ADAIR.
An ongoing trend has been for third-party
payors, including the U.S. government, to apply downward pressure on the reimbursement of biopharmaceutical products. Also, the
trend towards managed health care in the United States and the concurrent growth of organizations such as health maintenance organizations
tend to result in lower reimbursement for biopharmaceutical products. We expect that these trends will continue as these payors
implement various proposals or regulatory policies, including various provisions of the recent health reform legislation that affect
reimbursement of these products. There are currently, and we expect that there will continue to be, a number of federal and state
proposals to implement controls on reimbursement and pricing, directly and indirectly.
There is an emerging trend in state legislation
requiring the addition of abuse-deterrent formulations of opioid painkillers to be added to managed care formularies. Because there
are no stimulants currently approved with similar abuse-deterrent labeling, such legislation has not had an impact on stimulants;
however, this could favorably impact the reimbursement of a product like ADAIR in the future.
Asset Purchase Agreement
As described above, the ADAIR assets were
acquired by us pursuant to the terms and conditions of the Asset Purchase Agreement. In exchange for the ADAIR assets, we issued
843,750 shares of our common stock on June 22, 2018 to Arcturus Inc., which comprised approximately 30% of our then-outstanding
common stock on a fully diluted basis.
The Asset Purchase Agreement also gives
Arcturus the right to appoint one director to serve as a member of our board of directors, which was effective immediately upon
the closing of the transaction contemplated by the Asset Purchase Agreement. Thereafter, Arcturus is entitled to appoint one director
for so long as it owns at least 10% of the company securities on a fully diluted basis.
Employees and Human Capital Resources
We recognize that attracting, motivating
and retaining talent is vital to our continued success. We aim to create an equitable, inclusive and empowering environment in
which our employees can grow and advance their careers, with the overall goal of developing, expanding and retaining our workforce
to support our current pipeline and future business goals. We value innovation, passion, data-driven decision making, persistence
and honesty, and are building a diverse environment where our employees and consultants can thrive and be inspired to make exceptional
contributions.
Our current management team, board of directors,
and scientific advisors have significant experience in development and marketing of pharmaceutical product candidates from early
stage discovery to clinical trials, regulatory approval and commercialization. As of March 15, 2021, we had two full-time employees.
We also regularly work with several independent consultants and other contract organizations to support our business and we regularly
evaluate additional talent to help support our product development, financial, and other capabilities.
Our human capital resources objectives include
identifying, recruiting, retaining, and incentivizing our existing and new employees. We maintain an equity incentive plan, the
principal purposes of which are to attract, retain and reward personnel through the granting of stock-based compensation awards,
in order to increase stockholder value and the success of our company by motivating such individuals to perform to the best of
their abilities and achieve our objectives. To facilitate talent attraction and retention, we strive to make our company a safe
and rewarding workplace, with opportunities for our employees to grow and develop in their careers, supported by competitive compensation,
benefits and health and wellness programs, and by programs that build connections between our employees.
In addition, as a result of the COVID-19
pandemic, we have taken steps to protect the health and safety of our employees in line with directives from state and the applicable
local governments, as well as guidance from the CDC.
Facilities
Our executive offices are located at 100
N. 18th Street, Suite 300, Philadelphia, PA 19103. We believe that our current office space will be adequate for the next 12 months.
We have no plans to lease additional space in the next twelve months. Should we be required to obtain additional space in
the future, we believe we can obtain the required facilities at competitive rates. We do not own any real property.
Corporate Information
Vallon Pharmaceuticals, Inc. was incorporated
in Delaware on January 11, 2018, and completed its organization, formation and initial capitalization activities effective
as of June 7, 2018. Our telephone number is 267-207-3606, and our email address is info@vallon-pharma.com. Our website address
is https://www.vallon-pharma.com. Our Annual Reports on Form 10-K, Quarterly Reports on Form 10-Q, Current Reports on Form 8-K,
including exhibits, proxy and information statements and amendments to those reports filed or furnished pursuant to Sections 13(a),
14, and 15(d) of the Securities Exchange Act of 1934, as amended (the “Exchange Act”), are available through the “Investors”
portion of our website after we file such material with the SEC. The information contained on, or that can be accessed through,
our website is not part of this Annual Report and is not incorporated by reference. We have included our website address herein
solely as an inactive textual reference. Our filings with the SEC may be
accessed through the SEC’s Interactive Data Electronic Applications system at https://www.sec.gov.
We are an “emerging growth company,”
as defined in Section 2(a) of the Securities Act of 1933, as amended (the “Securities Act”), as modified
by the Jumpstart Our Business Startups Act of 2012 (the “JOBS Act”). Emerging growth companies can delay adopting
new or revised accounting standards until such time as those standards apply to private companies. Therefore, we may not be subject
to the same new or revised accounting standards as other public companies that are not “emerging growth companies.”
For as long as we continue to be an emerging growth company, we also 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 stockholder vote on executive compensation and any golden parachute payments not previously approved,
exemption from the requirement of auditor attestation in the assessment of our internal control over financial reporting and exemption
from any requirement that may be adopted by the Public Company Accounting Oversight Board regarding mandatory audit firm rotation
or a supplement to the auditor’s report providing additional information about the audit and the financial statements (auditor
discussion and analysis). 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 the end of the second
fiscal quarter, (ii) the end of the fiscal year in which we have total annual gross revenues 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) the end of the fiscal year following the fifth anniversary of the date of the first sale of our Common Stock
pursuant to an effective registration statement filed under the Securities Act.
Item 1A. RISK FACTORS
You should consider carefully the following
risks described below, together with the other information contained in this Annual Report and in our other public filings, in
evaluating our business. If any of the following risks actually occurs, our business, financial condition, results of operations
and future growth prospects would likely be materially and adversely affected. In these circumstances, the market price of our
common stock would likely decline.
Summary of Risk Factors
The following is a
summary of the principal risks described below in Part I, Item 1A “Risk Factors” in this Annual Report on Form 10-K.
We believe that the risks described in the “Risk Factors” section are material to investors, but other factors not
presently known to us or that we currently believe are immaterial may also adversely affect us. The following summary should not
be considered an exhaustive summary of the material risks facing us, and it should be read in conjunction with the “Risk
Factors” section and the other information contained in this Annual Report on Form 10-K.
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We anticipate future losses and negative cash flow, and it is uncertain if or when we will become profitable.
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We are a clinical-stage company with no approved products and a lack of operating history, which makes it difficult to assess
our future viability.
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As a result of our limited operating history, we may not be able to correctly estimate our future revenues, operating expenses,
need for investment capital, or stability of operations, which could lead to cash shortfalls.
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We do not currently have any drug products for sale, and only one clinical stage product under development, ADAIR. Our prospects
currently depend largely on the success of ADAIR, which is still in clinical development, and we may not be able to generate revenues
from ADAIR.
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If serious adverse or unacceptable side effects are identified during the development of ADAIR or any potential future products,
such as ADMIR, we may need to abandon or limit our development of some of such products.
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If ADAIR does not achieve broad market acceptance, the revenues that we generate from its sales will be limited.
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If we obtain approval to commercialize ADAIR, or any other future product, such as ADMIR, outside of the U.S., a variety of
risks associated with international operations could materially adversely affect our business.
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If the government or third-party payors fail to provide adequate coverage and payment rates for ADAIR or any future products,
such as ADMIR, we may develop, license or acquire, if any, our revenue and prospects for profitability will be limited.
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If we are unable to establish sales, marketing, and distribution capabilities or to enter into agreements with third parties
to market and sell ADAIR or any other future product, such as ADMIR, we may not be successful in commercializing ADAIR or any other
future product if and when they are approved.
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We will require substantial additional funding, which may not be available to us on acceptable terms, or at all, and, if not
so available, may require us to delay, limit, reduce or cease our operations.
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We will continue to incur significant increased costs as a result of operating as a public company, and our management will
be required to devote substantial time to new compliance initiatives.
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We may not receive regulatory approval for ADAIR or any future product, such as ADMIR, or its or their approvals may be delayed,
which would have a material adverse effect on our business and financial condition.
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Even if ADAIR or any other proposed product that we develop, such as ADMIR, receives marketing approval, we will continue to
face extensive regulatory requirements and the product may still face future development and regulatory difficulties.
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The abuse, misuse or off-label use of our products may harm our image in the marketplace, result in injuries that lead to product
liability suits or result in costly investigations, fines or sanctions by regulatory bodies if we are deemed to have engaged in
the promotion of these uses, any of which could be costly to our business.
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We have filed multiple patent applications and have two issued patents by the U.S. PTO. These or any other patent applications
may not result in issued patents, and as a result we may have limited protection of our proprietary technology in the marketplace.
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If we are unable to obtain and maintain patent protection for our technology and products or if the scope of the patent protection
obtained is not sufficiently broad, our competitors could develop and commercialize technology and products similar or identical
to ours, and our ability to successfully commercialize our technology and products may be impaired.
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Because it is difficult and costly to protect our proprietary rights, we may not be able to ensure their protection.
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If we cannot continue to satisfy the listing requirements of The Nasdaq Capital Market and other rules, including the director
independence requirements, our securities may be delisted, which could negatively impact the price of our securities and your ability
to sell them.
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Our stock may be subject to substantial price and volume fluctuations due to a number of factors, many of which are beyond
our control and may prevent our stockholders from reselling our common stock at a profit.
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Risks Relating to Our Business and Industry
We anticipate future losses and negative cash flow, and
it is uncertain if or when we will become profitable.
We do not expect to generate any significant
revenues until we successfully complete development of our first product, including obtaining all required regulatory approvals,
and we are able to successfully commercialize the product through sales and licensing. As of the date of this Annual Report, our
product candidates are still in development and have not been approved by the FDA.
We have not yet demonstrated our ability
to generate revenue, and we may never be able to produce revenues or operate on a profitable basis. We have incurred losses since
our inception (January 11, 2018) and expect to experience operating losses and negative cash flow for the foreseeable future.
ADAIR or any other future product, such as ADMIR, may never be approved or become commercially viable. Even if we and any collaborators
are able to commercialize our technology, which may include licensing, we may never recover our research and development expenses.
We are a clinical-stage company with no approved products
and a lack of operating history, which makes it difficult to assess our future viability.
We were incorporated on January 11,
2018, and our operations to date have been limited to organizing and staffing our company, acquiring rights to ADAIR, preparing
and filing an IND application for ADAIR, conducting four Phase I studies and working on the commercial formulation and manufacturing
of ADAIR. We have not yet demonstrated an ability to successfully overcome many of the risks and uncertainties frequently encountered
by companies in new and rapidly evolving fields, particularly in the biopharmaceutical area. For example, to execute our business
plan, we will need to successfully:
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obtain adequate financing on terms that are acceptable to us;
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execute product development activities;
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obtain required regulatory approvals for the development and commercialization of ADAIR or any other future product, such as
ADMIR;
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maintain, leverage, and expand our intellectual property portfolio;
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build and maintain robust sales, distribution, and marketing capabilities, either on our own or in collaboration with strategic
partners;
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gain market acceptance for ADAIR or any other future product, such as ADMIR;
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develop and maintain any strategic relationships we elect to enter into; and
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manage our spending as costs and expenses increase due to clinical trials, regulatory approvals, and commercialization.
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If we are unsuccessful in accomplishing these
objectives, we may not be able to develop ADAIR or any other future product, such as ADMIR, raise capital, expand our business,
or continue our operations.
Further, our lack of operating history makes
it difficult to evaluate our business and prospects. Our prospects must be considered in light of the risks, uncertainties, expenses,
and difficulties frequently encountered by companies in their early stages of development, particularly companies in the biopharmaceutical
industry. As a young business, we may encounter unforeseen expenses, difficulties, complications, delays, and other known and unknown
factors. We will need to expand our capabilities to support commercial activities. We may not be successful in adding such capabilities.
The historical information in this Annual Report may not be indicative of our future financial condition and future performance.
We expect our financial condition and operating results to continue to fluctuate significantly from quarter to quarter and year
to year due to a variety of factors, many of which are beyond our control. Accordingly, you should not rely upon our past results
of as an indication of future operating performance.
As a result of our limited operating history, we may not
be able to correctly estimate our future revenues, operating expenses, need for investment capital, or stability of operations,
which could lead to cash shortfalls.
We have a limited operating history from
which to evaluate our business. As a result, our historical financial data is of limited value in estimating future operating expenses.
In addition, although we are a clinical-stage company, we have not yet completed all of the non-clinical safety studies for ADAIR
or other pivotal clinical trials. We also have not obtained regulatory approvals for any of our products, manufactured a commercial
scale product, arranged for a third party to do so on our behalf, or conducted sales and marketing activities necessary for successful
product commercialization. Therefore, our budgeted operating expense levels are based in part on our expectations concerning the
FDA approval process and expenses related to development of other product candidates. Failing to reach our short-term developmental
milestones within anticipated timelines due to delays caused by the COVID-19 outbreak, serious adverse or unacceptable side effects
caused by our product candidates, or other events, many of which may be beyond our control, may cause our financial condition and
operating results to continue to fluctuate significantly from quarter to quarter and year to year.
We do not currently have any drug products for sale, and
only one clinical stage product under development, ADAIR. Our prospects currently depend largely on the success of ADAIR, which
is still in clinical development, and we may not be able to generate revenues from ADAIR.
We do not have any prescription drug products
that have been approved by the FDA, or any similar regulatory authority. Our business success depends on our ability to obtain
regulatory approval for and successfully commercialize our only product currently under development, ADAIR, which will require
substantial investment, access to sufficient commercial manufacturing capacity, and significant marketing efforts before we can
generate any revenue from sales of ADAIR, if it is ever approved for commercialization.
We have only one other prescription drug
candidate in early development today and so our business prospects currently depend primarily on the successful development, regulatory
approval, and commercialization of ADAIR, which may never occur. Even though ADAIR is in the clinical development stage, it has
an uncertain chance of successfully completing clinical development and gaining regulatory approval. Any significant delays in
obtaining approval for and commercializing ADAIR will have a substantial adverse impact on our business and financial condition.
Even if approved, we may be unable to successfully
commercialize ADAIR and we may never generate meaningful revenues. Our ability to generate revenues from ADAIR will depend on our
ability to:
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hire, train, deploy, and support our sales force, including any contract sales force engaged;
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create market demand for ADAIR through our own marketing and sales activities, and any other promotional arrangements we may
later establish;
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obtain sufficient quantities of ADAIR from our third-party manufacturers as required to meet commercial demand at launch and
thereafter;
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establish and maintain agreements with wholesalers, distributors and group purchasing organizations on commercially reasonable
terms; and
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maintain patent protection and regulatory exclusivity for ADAIR.
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In addition, if the market for ADAIR develops less
rapidly than we anticipate, we may not have the ability to shift our resources to the development of alternative products.
If serious adverse or unacceptable side effects are identified
during the development of ADAIR or any potential future products, such as ADMIR, we may need to abandon or limit our development
of some of such products.
If ADAIR or potential future products, such
as ADMIR, are associated with undesirable side effects in preclinical studies or clinical trials or have characteristics that are
unexpected, we may need to abandon their development or limit development to more narrow 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. In our
industry, many compounds that initially showed promise in early stage testing have later been found to cause side effects that
prevented further development of the compound. In the event that our clinical trials reveal a high and unacceptable severity and
prevalence of side effects, our trials could be suspended or terminated, and the FDA or comparable foreign regulatory authorities
could order us to cease further development or deny approval of ADAIR or potential future products for any or all targeted indications.
The FDA could also issue a letter requesting additional data or information prior to making a final decision regarding whether
or not to approve a product. The number of requests for additional data or information issued by the FDA in recent years has
increased, and resulted in substantial delays in the approval of several new drugs. Undesirable side effects caused by ADAIR or
potential future products could also result in the inclusion of unfavorable information in our product labeling, denial of regulatory
approval by the FDA, or other regulatory authorities for any or all targeted indications, and in turn prevent us from commercializing
and generating revenues from the sale of ADAIR or potential future products. Drug-related side effects could affect patient recruitment
or the ability of enrolled patients to complete the trial and could result in potential product liability claims.
Additionally, if one or more of our current
or potential future products, including ADAIR or ADMIR, receive marketing approval and we or others later identify undesirable
side effects caused by this product, a number of potentially significant negative consequences could result, including:
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regulatory authorities may require the addition of unfavorable labeling statements, specific warnings, or a contraindication;
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regulatory authorities may suspend or withdraw their approval of the product, or require it to be removed from the market;
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we may be required to change the way the product is administered, conduct additional clinical trials, or change the labeling
of the product; or
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our reputation may suffer.
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Any of these events could prevent us from
achieving or maintaining market acceptance of ADAIR or potential future products, such as ADMIR, or could substantially increase
our commercialization costs and expenses, which in turn could delay or prevent us from generating significant revenues from its
sale.
If ADAIR does not achieve broad market acceptance, the
revenues that we generate from its sales will be limited.
The commercial success of ADAIR, if approved
by the FDA, will depend upon its acceptance by the medical community, our ability to ensure that the drug is included in hospital
formularies, and coverage and reimbursement for ADAIR by third-party payors, including government payors. The degree of market
acceptance of ADAIR or any other product we may license or acquire will depend on a number of factors, including, but not necessarily
limited to:
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the efficacy and safety as demonstrated in clinical trials;
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the timing of market introduction of such proposed product as well as competitive products;
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the clinical indications for which the drug is approved;
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acceptance by physicians and patients of the drug as a safe and effective treatment;
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the safety of such proposed product seen in a broader patient group, including its use outside the approved indications;
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the availability, cost, and potential advantages of alternative treatments, including less expensive generic drugs;
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the availability of adequate reimbursement and pricing by third-party payors and government authorities;
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the relative convenience and ease of administration of the proposed product for clinical practices;
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the product labeling or product insert required by the FDA or regulatory authority in other countries;
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the approval, availability, market acceptance, and reimbursement for a companion diagnostic, if any;
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the prevalence and severity of adverse side effects;
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the effectiveness of our sales and marketing efforts;
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limitations or warnings contained in the product’s FDA-approved labeling;
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changes in the standard of care for the targeted indications for ADAIR or any future product, such as ADMIR, which could reduce
the marketing impact of any superiority claims that we could make following FDA approval; and
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potential advantages over, and availability of, alternative treatments.
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If any proposed product that we develop does
not provide a treatment regimen that is as beneficial as, or is not perceived as being as beneficial as, the current standard of
care or otherwise does not provide patient benefit, that proposed product, if approved for commercial sale by the FDA or other
regulatory authorities, likely will not achieve market acceptance. Our ability to effectively promote and sell ADAIR and any other
product we may license or acquire will also depend on pricing and cost effectiveness, including our ability to produce a product
at a competitive price and achieve acceptance of the product onto hospital formularies, as well as our ability to obtain sufficient
third-party coverage or reimbursement. Since many hospitals are members of group purchasing organizations, which leverage the purchasing
power of a group of entities to obtain discounts based on the collective buying power of the group, our ability to attract customers
will also depend on our ability to effectively promote ADAIR or any other future product to group purchasing organizations. We
will also need to demonstrate acceptable evidence of safety and efficacy, as well as relative convenience and ease of administration.
Market acceptance could be further limited depending on the prevalence and severity of any expected or unexpected adverse side
effects associated with ADAIR or any other future product, such as ADMIR. If ADAIR or any other future product are approved but
do not achieve an adequate level of acceptance by physicians, health care payors, and patients, we may not generate sufficient
revenue from these products, and we may not become or remain profitable. In addition, our efforts to educate the medical community
and third-party payors on the benefits of ADAIR or any other future product may require significant resources and may never be
successful.
If we obtain approval to commercialize ADAIR, or any other
future product, such as ADMIR, outside of the U.S., a variety of risks associated with international operations could materially
adversely affect our business.
If ADAIR, or any other future product, such
as ADMIR, is approved for commercialization outside the U.S., such as pursuant to the license agreement with Medice, who is affiliated
with one of our principal stockholders, Salmon Pharma, and represented by one member of our board of directors, we will likely
enter into agreements with third parties to market such product outside the U.S. We expect that we will be subject to additional
risks related to entering into or maintaining international business relationships, including:
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different regulatory requirements for drug approvals in foreign countries;
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differing U.S. and foreign drug import and export rules, particularly regarding controlled substances and scheduled products,
such as ADAIR;
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reduced protection for intellectual property rights in foreign countries;
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unexpected changes in tariffs, trade barriers, and regulatory requirements;
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different reimbursement systems;
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economic weakness, including inflation, or political instability in particular foreign economies and markets;
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compliance with tax, employment, immigration, and labor laws for employees living or traveling abroad;
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foreign taxes, including withholding of payroll taxes;
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foreign currency fluctuations, which could result in increased operating expenses and reduced revenues, and other obligations
incident to doing business in another country;
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workforce uncertainty in countries where labor unrest is more common than in the United States;
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production shortages resulting from any events affecting raw material supply or manufacturing capabilities abroad;
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potential liability resulting from development work conducted by these distributors; and
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business interruptions resulting from geopolitical actions, including war and terrorism, or natural disasters.
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Any government investigation of alleged violations
of law could require us to expend significant time and resources in response, and could generate negative publicity. Any failure
to comply with ongoing regulatory requirements may significantly and adversely affect our ability to commercialize and generate
revenues from ADAIR or any other future product, such as ADMIR. If regulatory sanctions are applied or if regulatory approval is
withdrawn, the value of our company and our operating results will be adversely affected.
If the government or third-party payors fail to provide
adequate coverage and payment rates for ADAIR or any future products, such as ADMIR, we may develop, license or acquire, if any,
our revenue and prospects for profitability will be limited.
In both domestic and foreign markets, our
sales of any future products, such as ADMIR, will depend in part upon the availability of coverage and reimbursement from third-party
payors. Such third-party payors include government health programs such as Medicare, Medicaid, managed care providers, private
health insurers and other organizations. Accordingly, ADAIR or any other future product that we may develop, in-license or acquire,
if approved, will face competition from other therapies and drugs for these limited payor financial resources. We may need to conduct
post-marketing studies in order to demonstrate the cost-effectiveness of any future products to the satisfaction of insurers, hospitals,
other target customers and their third-party payors. Such studies might require us to commit a significant amount of management
time and financial and other resources. Any of our future products might not ultimately be considered cost-effective. Adequate
third-party coverage and reimbursement might not be available to enable us to maintain price levels sufficient to realize an appropriate
return on investment in product development.
If we are unable to establish sales, marketing, and distribution
capabilities or to enter into agreements with third parties to market and sell ADAIR or any other future product, such as ADMIR,
we may not be successful in commercializing ADAIR or any other future product if and when they are approved.
Other than the license agreement with
Medice, we currently do not have a marketing or sales organization for the marketing, sales and distribution of
biopharmaceutical products. In order to commercialize any product that receives marketing approval, we would need to build
marketing, sales, distribution, managerial, and other non-technical capabilities or make arrangements with third parties to
perform these services, and we may not be successful in doing so. In the event of successful development and regulatory
approval of ADAIR or another future product, such as ADMIR, we expect to build a targeted specialist sales force to market or
co-promote the product. There are risks involved with establishing our own sales, marketing, and distribution capabilities.
For example, recruiting and training a sales force is expensive and time consuming and could delay any product launch. If the
commercial launch of a product for which we recruit a sales force and establish marketing capabilities is delayed or does not
occur for any reason, we would have prematurely or unnecessarily incurred these commercialization expenses. This may be
costly, and our investment would be lost if we cannot retain or reposition our sales and marketing personnel.
Factors that may inhibit our efforts to commercialize
our products, if any, on our own include, but are not necessarily limited to:
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our inability to recruit, train, and retain adequate numbers of effective sales and marketing personnel;
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the inability of sales personnel to obtain access to physicians or persuade adequate numbers of physicians to prescribe any
future products;
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the lack of complementary or other products to be offered by sales personnel, which may put us at a competitive disadvantage
from the perspective of sales efficiency relative to companies with more extensive product lines; and
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unforeseen costs and expenses associated with creating an independent sales and marketing organization.
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As an alternative to establishing our own
sales force, we may choose to partner with third parties that have well-established direct sales forces to sell, market, and distribute
our products.
We rely on a limited number of suppliers and manufacturers
for ADAIR and expect to continue to do so for any future product that we may develop, including ADMIR, and for commercialization
of our products. This reliance on a limited number of third parties increases the risk that we will not have sufficient quantities
of ADAIR or such quantities at an acceptable cost, which could delay, prevent or impair our development or commercialization efforts.
The manufacture of biopharmaceutical products
requires significant expertise and capital investment, including the development of advanced manufacturing techniques and process
controls and the use of specialized processing equipment. We have entered into an agreement to complete precommercial manufacturing
development activities with one contract manufacturer and expect to contract with them for the commercial manufacture of ADAIR.
However, we have not yet negotiated and signed a commercial supply agreement. The inability of a third-party manufacturer to successfully
manufacture ADAIR may materially harm our business and financial condition, and frustrate future development and any commercialization
efforts for this product.
We do not have any of our own manufacturing
facilities or personnel. We rely, and expect to continue to rely, on third parties for the manufacture of ADAIR or any other future
product, such as ADMIR, for clinical testing, as well as for commercial manufacture if any of ADAIR or any other future product
receive marketing approval. This reliance on third parties increases the risk that we will not have sufficient quantities of ADAIR
or any other future product or such quantities at an acceptable cost or quality, which could delay, prevent, or impair our development
or commercialization efforts.
We also expect to rely on third-party manufacturers
or third-party collaborators for the manufacture of commercial supply of any product for which our collaborators or we obtain marketing
approval. We may be unable to establish any agreements with third-party manufacturers or to do so on acceptable terms. Even if
we are able to establish agreements with third-party manufacturers, reliance on third-party manufacturers entails additional risks,
including, but not necessarily limited to:
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reliance on the third party for regulatory compliance and quality assurance;
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the possible breach of the manufacturing agreement by the third party;
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manufacturing delays if our third-party manufacturers give greater priority to the supply of other products over ADAIR or any
other future product, such as ADMIR, or otherwise do not satisfactorily perform according to the terms of the agreement between
us;
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the possible misappropriation of our proprietary information, including our trade secrets and know-how; and
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the possible termination or nonrenewal of the agreement by the third party at a time that is costly or inconvenient for us.
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All of our contract manufacturers must comply
with strictly enforced federal, state, and foreign regulations, including current Good Manufacturing Practice (“cGMP”)
requirements enforced by the FDA through its facilities inspection program. We do not control the manufacturing process of, and
are completely dependent on, our contract manufacturers for compliance with cGMP regulations for manufacture of ADAIR or any other
future product, such as ADMIR. Our failure, or the failure of our third-party manufacturers, to comply with applicable regulations
or similar regulatory requirements outside the U.S. could result in sanctions being imposed on us, including clinical holds, fines,
injunctions, civil penalties, suspension of production, delays, suspension or withdrawal of approvals, license revocation, seizures
or recalls of products, operating restrictions and criminal prosecutions, any of which could significantly and adversely affect
supplies of our products. Any manufacturing defect or error discovered after products have been produced and distributed could
result in even more significant consequences, including costly recall procedures, re-stocking costs, damage to our reputation,
and potential for product liability claims.
ADAIR and any products that we may develop
may compete with other products for access to manufacturing facilities. There are a limited number of manufacturers that operate
under cGMP regulations and that might be capable of manufacturing for us. Any performance failure on the part of our existing or
future manufacturers could delay clinical development or marketing approval. We do not currently have arrangements in place for
redundant supply or a second source for bulk drug substance. If our current contract manufacturers cannot perform as agreed, we
may be required to replace such manufacturers. We may incur added costs and delays in identifying and qualifying any replacement
manufacturers. The DEA restricts the importation of a controlled substance finished drug product when the same substance is commercially
available in the United States, which could reduce the number of potential alternative manufacturers for ADAIR.
Our current and anticipated future dependence
upon others for the manufacture of ADAIR or any other future products, such as ADMIR, may adversely affect our future profit margins
and our ability to commercialize any products that receive marketing approval on a timely and competitive basis.
We also expect to rely on other third parties
to store and distribute drug supplies for our clinical trials. Any performance failure on the part of our distributors could delay
clinical development or marketing approval of ADAIR or any other future product, such as ADMIR, or commercialization of any of
our products, producing additional losses and depriving us of potential product revenue.
Public health crises such as pandemics or similar outbreaks
could materially and adversely affect our preclinical and clinical trials, business, financial condition and results of operations.
In March 2020, the World Health Organization
declared COVID-19 a global pandemic and the United States declared a national emergency with respect to COVID-19. In response to
the COVID-19 pandemic, “shelter in place” orders and other public health guidance measures have been implemented across
much of the United States and Europe, including in the locations of our principal place of business, clinical trial sites, and
locations of our key vendors and partners. Our clinical development program and preclinical study timelines may be negatively affected
by COVID-19, which could materially and adversely affect our business, financial condition and results of operations. Further,
due to “shelter in place” orders and other public health guidance measures, we and our third-party vendors and suppliers
have implemented remote working policies. Our third-party vendors’ and suppliers’, and our increased reliance on personnel
working from home may negatively impact productivity, or disrupt, delay or otherwise adversely impact our business. For example,
the COVID-19 pandemic caused some delays at our clinical trial sites, contract research organizations (“CROs”),
and third-party manufacturers, which in turn resulted in some delays in the FDA approval process; however, these delays have been
largely remediated.
As a result of the COVID-19 pandemic, or
similar pandemics, and related “shelter in place” orders and other public health guidance measures, we have and may
in the future experience disruptions that could materially and adversely impact our clinical trials, business, financial condition
and results of operations. Potential disruptions include but are not limited to:
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delays or difficulties in enrolling patients in our clinical trials;
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delays or difficulties in initiating or expanding clinical trials, including delays or difficulties with clinical site initiation
and recruiting clinical site investigators and clinical site staff;
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increased rates of patients withdrawing from our clinical trials following enrollment as a result of contracting COVID-19 or
other health conditions or being forced to quarantine;
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interruption of key clinical trial activities, such as clinical trial site data monitoring and efficacy, safety and translational
data collection, processing and analyses, due to limitations on travel imposed or recommended by federal, state or local governments,
employers and others or interruption of clinical trial subject visits, which may impact the collection and integrity of subject
data and clinical study endpoints;
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delays or disruptions in preclinical experiments and IND-enabling studies due to restrictions of on-site staff and unforeseen
circumstances at CROs and vendors, including any delays caused by the COVID-19 outbreak;
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interruption or delays in the operations of the FDA and comparable foreign regulatory agencies;
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interruption of, or delays in receiving, supplies of our product candidates from our contract manufacturing organizations due
to staffing shortages, production slowdowns or stoppages and disruptions in delivery systems;
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delays in receiving approval from local regulatory authorities to initiate our planned clinical trials;
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limitations on employee or other resources that would otherwise be focused on the conduct of our clinical trials and pre-clinical
work, including because of sickness of employees or their families, the desire of employees to avoid travel or contact with large
groups of people, an increased reliance on working from home, school closures or mass transit disruptions;
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changes in regulations as part of a response to the COVID-19 pandemic which may require us to change the ways in which our
clinical trials are conducted, which may result in unexpected costs, or to discontinue the clinical trials altogether;
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delays in necessary interactions with regulators, ethics committees and other important agencies and contractors due to limitations
in employee resources or forced furlough of government or contractor personnel; and
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refusal of the FDA to accept data from clinical trials in affected geographies outside the United States.
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These and other factors arising from the
COVID-19 global pandemic could worsen in countries that are already afflicted with COVID-19, could continue to spread to additional
countries or could return to countries where the pandemic has been partially contained, each of which could further adversely impact
our ability to conduct clinical trials and our business generally, and could materially and adversely affect our business, financial
condition and results of operations.
The COVID-19 global pandemic continues to
rapidly evolve. The extent to which the outbreak may affect our clinical trials, business, financial condition and results of operations
will depend on future developments, which are highly uncertain and cannot be predicted at this time, such as the ultimate geographic
spread of the disease, the duration of the outbreak, travel restrictions and actions to contain the outbreak or treat its impact,
such as social distancing and quarantines or lock-downs in the United States and other countries, business closures or business
disruptions and the effectiveness of actions taken in the United States and other countries to contain and treat the disease. Future
developments in these and other areas present material uncertainty and risk with respect to our clinical trials, business, financial
condition and results of operations.
Our future growth may depend on our ability to identify
and acquire or in-license products and if we do not successfully identify and acquire or in-license related product candidates
and products or integrate them into our operations, we may have limited growth opportunities.
An important part of our business strategy
is to continue to develop a pipeline of product candidates and products by acquiring or in-licensing products, businesses or technologies
that we believe are a strategic fit with our business. Future in-licenses or acquisitions, however, may entail numerous operational
and financial risks, including:
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exposure to unknown liabilities;
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disruption of our business and diversion of our management’s time and attention to develop acquired products or technologies;
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difficulty or inability to secure financing to fund development activities for such acquired or in-licensed technologies in
the current economic environment;
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incurrence of substantial debt or dilutive issuances of securities to pay for acquisitions;
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higher than expected acquisition and integration costs;
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increased amortization expenses;
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difficulty and cost in combining the operations and personnel of any acquired businesses with our operations and personnel;
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impairment of relationships with key suppliers or customers of any acquired businesses due to changes in management and ownership;
and
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inability to retain key employees of any acquired businesses.
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We have limited resources to identify and
execute the acquisition or in-licensing of third-party products, businesses and technologies and integrate them into our current
infrastructure. In particular, we may compete with larger biopharmaceutical companies and other competitors in our efforts to establish
new collaborations and in-licensing opportunities. These competitors likely will have access to greater financial resources than
us and may have greater expertise in identifying and evaluating new opportunities. Moreover, we may devote resources to potential
acquisitions or in-licensing opportunities that are never completed, or we may fail to realize the anticipated benefits of such
efforts.
Expanding our product offerings may not be profitable.
We may choose to develop new products to
offer. We are currently developing an abuse deterrent formulation of Ritalin, ADMIR, another commonly prescribed product for the
treatment of ADHD. Developing new products involves inherent risks, including our inability to estimate demand for the new offerings,
competition from more established market participants, and a lack of market understanding. In addition, expanding into new geographic
areas and/or expanding product offerings will be challenging and may require integrating new employees into our culture as well
as assessing the demand in the applicable market.
We may expend our limited resources to pursue a particular
proposed product or indication, and fail to capitalize on a different proposed product or indication that may have been more profitable
or for which there would have been a greater likelihood of success.
Because we have limited financial and managerial
resources, we focus on research programs and proposed products that we identify for specific indications. As a result, we may forego
or delay pursuit of opportunities with other proposed products, or for other indications, that later prove to have greater commercial
potential. Our resource allocation decisions may cause us to fail to capitalize on viable commercial products or profitable market
opportunities. Our spending on current and future research and development programs and proposed products for specific indications
may not yield any commercially viable products. If we do not accurately evaluate the commercial potential or target market for
a particular proposed product, we may relinquish valuable rights to that proposed product through collaboration, licensing, or
other royalty arrangements in cases in which it would have been more advantageous for us to retain sole development and commercialization
rights to such proposed product.
If we fail to effectively manage our growth, our business
and reputation, results of operations, and financial condition may be adversely affected.
We may experience a rapid growth in operations,
which may place significant demands on our management team and our operational and financial infrastructure. As we continue to
grow, we must effectively identify, integrate, develop and motivate new employees, and maintain the beneficial aspects of our corporate
culture. To attract top talent, we believe we will have to offer attractive compensation packages. The risks of over-hiring or
overcompensating and the challenges of integrating a rapidly growing employee base may impact profitability.
Additionally, if we do not effectively
manage our growth, the quality of our services could suffer, which could adversely affect our business and reputation,
results of operations, and financial condition. If operational, technology, and infrastructure improvements are not
implemented successfully, our ability to manage our growth will be impaired and we may have to make significant additional
expenditures to address these issues. To effectively manage our growth, we will need to continue to improve our operational,
financial, and management controls and our reporting systems and procedures. This will require that we refine our information
technology systems to maintain effective online services and enhance information and communication systems to ensure that our
employees effectively communicate with each other and our growing base of customers. These system enhancements and
improvements will require significant incremental and ongoing capital expenditures and allocation of valuable management and
employee resources. If we fail to implement these improvements and maintenance programs effectively, our ability to manage
our expected growth and comply with the rules and regulations that are applicable to publicly reporting companies will be
impaired and we may incur additional expenses.
We may not be able to manage our business effectively
if we are unable to attract and retain key personnel.
Our key employees currently include David
Baker, our President and Chief Executive Officer, and Ms. Penny Toren, our Senior Vice President, Regulatory Affairs &
Program Management, who is responsible for regulatory affairs, and consulting arrangements with individuals such as our Chief Medical
Officer, Dr. Timothy Whitaker, who is responsible for overseeing clinical development of our product candidates. Our future
growth and success depend on our ability to recruit, retain, manage, and motivate our employees and key consultants. The loss of
the services of our Chief Executive Officer, or any of our key employees or the inability to hire or retain experienced management
personnel could adversely affect our ability to execute our business plan and harm our operating results. Although we have employment
agreements in place with management, these agreements are terminable at will with minimal notice.
Because of the specialized scientific and
managerial nature of our business, we rely heavily on our ability to attract and retain qualified scientific and technical consultants.
We may not be able to attract or retain qualified management and commercial, scientific, and clinical personnel in the future due
to the intense competition for qualified personnel among biotechnology, pharmaceutical, and other businesses. In addition, the
loss of one or more of our senior executive officers or key consultants could be detrimental to us if we cannot recruit suitable
replacements in a timely manner.
We do not currently carry “key person”
insurance on the lives of members of senior management. The competition for qualified personnel in the biopharmaceutical field
is intense.
If we are not able to attract and retain
necessary personnel to accomplish our business objectives, we may experience constraints that will significantly impede the achievement
of our development objectives, our ability to raise additional capital and our ability to implement our business strategy.
Our directors, consultants and advisors are not obligated
to commit their time and attention exclusively to our business and therefore they may encounter conflicts of interest with respect
to the allocation of time and business opportunities between our operations and those of other businesses.
Our directors are not obligated to commit
their time and attention exclusively to our business and, accordingly, they may encounter conflicts of interest in allocating their
own time, or any business opportunities which they may encounter, between our operations and those of other businesses.
Currently, our full-time employees consist
of David Baker, who is our President and Chief Executive Officer, and Penny Toren, who is Senior Vice President, Regulatory Affairs,
and our key consultants consist of Dr. Timothy Whitaker, our Chief Medical Officer, as well as consultants for finance, bookkeeping,
pre-clinical and formulation development, chemistry manufacturing and controls (CMC), and clinical operations. Currently, consulting
arrangements with individuals, such as Dr. Whitaker, only require them to devote an average of approximately 10 to 20 hours
per week to our business. In addition, our consultants and advisors may have other clients or projects that grow in scope or they
may acquire new clients and projects that require more of their time that may come at our expense. We also currently rely on consultants
for clinical operations, statistical support, and preclinical development. If the execution of our business plan demands more time
than is currently committed by any of our officers, directors, consultants or advisors, they will be under no obligation to commit
such additional time, and their failure to do so may adversely affect our ability to carry on our business and successfully execute
our business plan.
Additionally, all of our officers and
directors, in the course of their other business activities, may become aware of investments, business opportunities, or
information which may be appropriate for presentation to us as well as to other entities to which they owe a fiduciary duty.
They may also in the future become affiliated with entities that are engaged in business or other activities similar to those
we intend to conduct. As a result, they may have conflicts of interest in determining to which entity particular
opportunities or information should be presented. If, as a result of such conflict, we are deprived of investment, business
or information, the execution of our business plan and our ability to effectively compete in the marketplace may be adversely
affected.
Our employees may engage in misconduct or other improper
activities, including noncompliance with regulatory standards and requirements, which could have a material adverse effect on our
business.
We are exposed to the risk of employee fraud
or other misconduct. Misconduct by employees could include intentional failures to comply with FDA regulations, provide accurate
information to the FDA, comply with manufacturing standards we have established, comply with federal and state health-care fraud
and abuse laws and regulations, report financial information or data accurately or disclose unauthorized activities to us under
the Federal Physician Payments Sunshine Act and similar state laws. In particular, sales, marketing, and business arrangements
in the healthcare industry are subject to extensive laws and regulations intended to prevent fraud, kickbacks, self-dealing, making
or contributing to the making of a false claim for reimbursement to federal, state or private payors, and other abusive practices.
These laws and regulations may restrict or prohibit a wide range of pricing, discounting, marketing and promotion, sales commission,
customer incentive programs, and other business arrangements. Employee misconduct could also involve the improper use of information
obtained in the course of clinical trials, which could result in regulatory sanctions and serious harm to our reputation. The precautions
we take to detect and prevent this activity may not be effective in controlling unknown or unmanaged risks or losses or in protecting
us from governmental investigations or other actions or lawsuits stemming from a failure to comply with such 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 significant impact on our business and results of operations, including the imposition of significant fines
or other sanctions.
Our management has limited experience in managing the
day to day operations of a public company and, as a result, we may incur additional expenses associated with the management of
our company.
Our Chief Executive Officer is responsible
for the operations and reporting of our company. The requirements of operating as a small public company are new to our management.
This may require us to obtain outside assistance from legal, accounting, investor relations, or other professionals that could
be more costly than planned. We may also be required to hire additional staff to comply with additional SEC reporting requirements.
These compliance costs will make some activities significantly more time-consuming and costly. If we lack cash resources to cover
these costs in the future, our failure to comply with reporting requirements and other provisions of securities laws could negatively
affect our stock price and adversely affect our potential results of operations, cash flow, and financial condition after we commence
operations.
Our market is subject to intense competition. If we are
unable to compete effectively, ADAIR or any other proposed product that we develop may be rendered noncompetitive or obsolete.
There are a number of existing treatments
for ADHD currently on the market, all of which are marketed by pharmaceutical companies that are far larger and more experienced
than we are. Patients and doctors are often unwilling to change medications, and this factor will make it difficult for ADAIR or
any other proposed product to penetrate the market. Further, our industry is highly competitive and subject to rapid and significant
technological change. Our potential competitors include large pharmaceutical and biotechnology companies, specialty pharmaceutical
and generic drug companies, academic institutions, government agencies and research institutions. All of these competitors currently
engage in, have engaged in or may engage in the future in the development, manufacturing, marketing and commercialization of new
pharmaceuticals, some of which may compete with ADAIR or other proposed product we may have in the future. Smaller or early stage
companies may also prove to be significant competitors, particularly through collaborative arrangements with large, established
companies. These companies may have products in development that are superior to ADAIR or any other future product, such as ADMIR.
Key competitive factors affecting the commercial success of ADAIR and any other proposed product that we may develop in the future
are likely to be efficacy, time of onset, safety and tolerability profile, reliability, convenience of dosing, price, and reimbursement.
Many of our potential competitors have
substantially greater financial, technical, and human resources than we do and significantly greater experience in the
discovery and development of drug candidates, obtaining FDA and other regulatory approvals of products, and the
commercialization of those products. Established competitors may invest heavily to quickly discover and develop novel
compounds that could make ADAIR or other proposed product we may develop obsolete. Other companies may be developing abuse
deterrent formulations of ADHD treatments that may be approved and marketed before ADAIR, limiting the commercial potential
of ADAIR. Accordingly, our competitors may be more successful than us in obtaining FDA and other marketing approvals, or more
favorable language in the prescription information, for their drugs, and achieving widespread market acceptance. Our
competitors’ drugs may be more effective, or more effectively marketed and sold, than any drug we may commercialize and
may render ADAIR or any other proposed product that we develop obsolete or non-competitive before we can recover the expenses
of developing and commercializing the product. We anticipate that we will face intense and increasing competition as new
drugs enter the market and advanced technologies become available. Finally, the development of new treatment methods for the
diseases we are targeting could render ADAIR or any other proposed product that we develop non-competitive or obsolete.
We face potential product liability exposure, and if successful
claims are brought against us, we may incur substantial liability for ADAIR or other proposed product we may license or acquire
and may have to limit their commercialization.
The use of ADAIR and any other proposed product
we may license or acquire in clinical trials and the sale of any products for which we obtain marketing approval expose us to the
risk of product liability claims. For example, we may be sued if any product we develop allegedly causes injury or is found to
be otherwise unsuitable during clinical testing, manufacturing, marketing, or sale. Any such product liability claims may include
allegations of defects in manufacturing, defects in design, a failure to warn of dangers inherent in the product, negligence, strict
liability, or a breach of warranties. Product liability claims might be brought against us by consumers, health care providers,
or others using, administering, or selling our products. If we cannot successfully defend ourselves against these claims, we will
incur substantial liabilities. Regardless of merit or eventual outcome, liability claims may result in:
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withdrawal of clinical trial participants;
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termination of clinical trial sites or entire trial programs;
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decreased demand for any proposed product or products that we may develop;
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initiation of investigations by regulators;
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impairment of our business reputation;
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costs of related litigation;
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substantial monetary awards to patients or other claimants;
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reduced resources of our management to pursue our business strategy; and
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the inability to commercialize ADAIR or any future product, such as ADMIR.
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We will obtain limited product liability insurance coverage
for any and all of our clinical trials. However, our insurance coverage may not reimburse us or may not be sufficient to reimburse
us for any expenses or losses we may suffer. Moreover, insurance coverage is becoming increasingly expensive, and, in the future,
we may not be able to maintain insurance coverage at a reasonable cost or in sufficient amounts to protect us against losses due
to liability. When needed, we intend to expand our insurance coverage to include the sale of commercial products if we obtain
marketing approval for ADAIR or any other future product in development, such as ADMIR, but we may be unable to obtain commercially
reasonable product liability insurance for any product approved for marketing. On occasion, large judgments have been awarded
in class action lawsuits based on drugs that had unanticipated side effects. A successful product liability claim or series of
claims brought against us could cause our stock price to fall and, if judgments exceed our insurance coverage, could decrease
our cash and adversely affect our business.
Our internal computer systems, or those used by third-party
CROs, manufacturers, or other contractors or consultants, may fail or suffer security breaches.
Despite the implementation of security
measures, our internal computer systems and those of our future CROs, manufacturers, and other contractors and consultants
are vulnerable to damage from computer viruses and unauthorized access. Although to our knowledge we have not experienced any
such material system failure or security breach to date, if such an event were to occur, it could result in a material
disruption of our development programs and our business operations. For example, the loss of clinical trial data from future
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 (such as individually identifiable
health information), we could incur significant liabilities and the further development and commercialization of ADAIR or any
other future product, including ADMIR, could be delayed.
Medice may not successfully develop or commercialize ADAIR
in Europe.
On January 6, 2020, Vallon entered into
a license agreement with Medice, who is affiliated with one of our principal stockholders, Salmon Pharma, and represented by one
member of our board of directors, which grants Medice an exclusive license, with the right to grant sublicenses, to develop, use,
manufacture, market and sell ADAIR throughout Europe. Medice may be unsuccessful with the development program for ADAIR as required
to gain regulatory approval in European countries. The requirements for approval by European regulatory agencies may be deemed
too onerous and expensive to continue the development of ADAIR in Europe. Even if Medice is successful in gaining approval of ADAIR
in European countries, it may be unsuccessful in gaining favorable reimbursement of ADAIR by national payors of prescription medications
in Europe. Medice may not generate sufficient sales of ADAIR in Europe to support continued commercialization. All of the commercial
risks for ADAIR in the United States may also apply to Europe. In addition, Medice may not devote adequate marketing and sales
efforts to generate meaningful sales of ADAIR in Europe. The ADHD market in Europe is substantially smaller than in the United
States, estimated to be approximately $700 million annually as compared to $9 billion in the United States. Dextroamphetamine
products as a class capture much lower market share in Europe as compared to the United States. If European regulatory authorities
reject the approval of ADAIR in Europe, this may reflect poorly on ADAIR and diminish sales growth or overall sales in the United
States.
Risks Relating to Finances and Capital Requirements
We will require substantial additional funding, which
may not be available to us on acceptable terms, or at all, and, if not so available, may require us to delay, limit, reduce or
cease our operations.
Our operations have consumed substantial
amounts of cash since our inception. As of December 31, 2020, we had an accumulated deficit of $12.6 million and our net loss
was $4.8 million for the year ended December 31, 2020. We expect to continue to incur significant expenses and increasing operating
losses for the foreseeable future. Our business will require additional capital for implementation of our long-term business plan
and product development and commercialization.
Our ability to raise additional funds may
be adversely impacted by potential worsening global economic conditions and the recent disruptions to, and volatility in, the credit
and financial markets in the United States and worldwide resulting from the ongoing COVID-19 pandemic. As we require additional
funds, we may seek to fund our operations through the sale of additional equity securities, debt financing and/or strategic collaboration
agreements. We cannot be sure that additional financing from any of these sources will be available when needed or that, if available,
the additional financing will be obtained on favorable terms.
Our future funding requirements will depend on many factors,
including, but not limited to:
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the progress, timing, scope, and costs of our clinical trials, including the ability to timely enroll patients in our potential
future clinical trials;
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the outcome, timing, and cost of regulatory approvals by the FDA and comparable regulatory authorities, including the potential
that the FDA or comparable regulatory authorities may require that we perform more studies than those that we currently expect;
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the number and characteristics of ADAIR or any other future product, such as ADMIR, that we may in-license and develop;
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our ability to successfully commercialize ADAIR or any other future product, such as ADMIR;
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the amount of sales and other revenues from ADAIR or any other future product, such as ADMIR, that we may commercialize, if
any, including the selling prices for such potential product and the availability of adequate third-party reimbursement;
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selling and marketing costs associated with our potential products, including the cost and timing of expanding our marketing
and sales capabilities;
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the terms and timing of any potential future collaborations, licensing or other arrangements that we may establish;
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cash requirements of any future acquisitions and/or the development of other products;
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the costs of operating as a public company;
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the cost and timing of completion of commercial-scale, outsourced manufacturing activities;
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the time and cost necessary to respond to technological and market developments;
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any disputes which may occur between us and Arcturus, employees, collaborators or other prospective business partners; and
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the costs of filing, prosecuting, defending, and enforcing any patent claims and other intellectual property rights.
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If we raise additional funds by selling shares
of our common stock or other equity-linked securities, the ownership interest of our current stockholders will be diluted. We may
seek to access the public or private capital markets whenever conditions are favorable, even if we do not have an immediate need
for additional capital at that time. If we raise additional funds through collaborations, strategic alliances or marketing, distribution
or licensing arrangements with third parties, we may have to relinquish valuable rights to our technologies, future revenue streams
or products or to grant licenses on terms that may not be acceptable to us. If we raise additional funds through debt financing,
we may have to grant a security interest on our assets to the future lenders, our debt service costs may be substantial, and the
lenders may have a preferential position in connection with any future bankruptcy or liquidation involving the company.
If we are unable to raise additional capital
when needed, we may be required to curtail the development of our technology or materially curtail or reduce our operations. We
could be forced to sell or dispose of our rights or assets. Any inability to raise adequate funds on commercially reasonable terms
could have a material adverse effect on our business, results of operations, and financial condition, including the possibility
that a lack of funds could cause our business to fail and our company to dissolve and liquidate with little or no return to investors.
We will continue to incur significant increased costs
as a result of operating as a public company, and our management will be required to devote substantial time to new compliance
initiatives.
As a public company, we incur significant
legal, accounting, and other expenses under the Securities Exchange Act of 1934, as amended (“Exchange Act”),
the Sarbanes-Oxley Act, and other applicable securities rules and regulations. In addition, we are subject to the requirements
of The Nasdaq Capital Market.
These rules impose various requirements on
public companies, including requiring establishment and maintenance of effective disclosure and financial controls and appropriate
corporate governance practices. Our management and other personnel have devoted and will continue to devote a substantial amount
of time to these compliance initiatives. Moreover, these rules and regulations increase our legal and financial compliance costs
and make some activities more time-consuming and costly. For example, these rules and regulations make it more difficult and more
expensive for us to obtain director and officer liability insurance, and we may be required to accept reduced policy limits and
coverage or incur substantially higher costs to obtain the same or similar coverage. In addition, the listing requirements of The
Nasdaq Capital Market require that we satisfy certain corporate governance requirements relating to director independence, stockholder
meetings, approvals and voting, soliciting proxies, conflicts of interest and a code of conduct. Our management and other personnel
need to devote a substantial amount of time to ensure that we comply with all of these requirements. As a result, it may be difficult
for us to attract and retain qualified persons to serve on our board of directors, our board committees or as executive officers.
The Sarbanes-Oxley Act of 2002
requires, among other things, that we maintain effective internal controls for financial reporting and disclosure controls
and procedures. As a result, we are required to periodically perform an evaluation of our internal controls over financial
reporting to allow management to report on the effectiveness of those controls, as required by Section 404 of the
Sarbanes-Oxley Act. Additionally, our independent auditors may be required to perform a similar evaluation and report on the
effectiveness of our internal controls over financial reporting. These efforts to comply with Section 404 and related
regulations have required, and continue to require, the commitment of significant financial and managerial resources. While
we anticipate maintaining the integrity of our internal controls over financial reporting and all other aspects of
Section 404, we cannot be certain that a material weakness will not be identified when we test the effectiveness of our
control systems in the future. If a material weakness is identified, we could be subject to sanctions or investigations by
the U.S. Securities and Exchange Commission (the “SEC”), or other regulatory authorities, which would
require additional financial and management resources, costly litigation or a loss of public confidence in our internal
controls, which could have an adverse effect on the market price of our stock. See the risk factor entitled “Financial
reporting obligations of being a public company in the United States require well defined disclosure and financial controls
and procedures that we did not have as a private company and that are expensive and time-consuming requiring our management
to devote substantial time to compliance matters.” in this Annual Report for more information on our internal controls
over financial reporting.
We are an “emerging growth company” and we
cannot be certain if the reduced disclosure requirements applicable to emerging growth companies will make our securities less
attractive to investors.
We are an “emerging growth company,”
as defined in the JOBS Act. Emerging growth companies can delay adopting new or revised accounting standards until such time as
those standards apply to private companies. As an emerging growth company, we are not being required to comply with the auditor
attestation requirements of Section 404 of the Sarbanes-Oxley Act, we have reduced disclosure obligations regarding executive
compensation in our periodic reports and proxy statements, and we are exempt from the requirements of holding a nonbinding advisory
vote on executive compensation and stockholder approval of any golden parachute payments not previously approved. Additionally,
as an emerging growth company, we have elected to delay the adoption of new or revised accounting standards that have different
effective dates for public and private companies until those standards apply to private companies. As such, our financial statements
may not be comparable to companies that comply with public company effective dates. We cannot predict if investors will find our
stock less attractive because we may rely on these provisions. If some investors find our stock less attractive as a result, there
may be a less active trading market for our shares and our stock price may be more volatile.
Further, Section 102(b)(1) of the JOBS
Act exempts emerging growth companies from being required to comply with new or revised financial accounting standards until private
companies (that is, those that have not had a Securities Act registration statement declared effective or do not have a class of
securities registered under the Exchange Act) are required to comply with the new or revised financial accounting standards. The
JOBS Act provides that a company can elect to opt out of the extended transition period and comply with the requirements that apply
to non-emerging growth companies but any such an election to opt out is irrevocable. We have elected not to opt out of such extended
transition period which means that when a standard is issued or revised and it has different application dates for public or private
companies, we, as an emerging growth company, will not adopt the new or revised standard until the time private companies are required
to adopt the new or revised standard. This may make comparison of our financial statements with another public company which is
neither an emerging growth company nor an emerging growth company which has opted out of using the extended transition period difficult
or impossible because of the potential differences in accountant standards used.
After we become a reporting company under
the Exchange Act, 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 the end of the second fiscal
quarter, (ii) the end of the fiscal year in which we have total annual gross revenues 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) the end of the fiscal year following the fifth anniversary of the date of the first sale of our Common Stock pursuant
to an effective registration statement filed under the Securities Act.
Our ability to utilize our net operating loss (“NOL”)
carryforwards may be limited.
As of December 31, 2020, we had
NOL carryforwards available to reduce future taxable income, if any, for federal and state income tax purposes of
$11.6 million. The federal net operating loss carryforwards do not expire. If not utilized, the state and local losses
begin to expire in the year ending December 31, 2038. Our ability to utilize NOL carryforward amounts to reduce taxable
income in future years may be limited for various reasons, including if future taxable income is insufficient to
recognize the full benefit of such NOL carryforward amounts prior to their expiration. Additionally, our ability to fully
utilize these U.S. tax assets can also be adversely affected by “ownership changes” within the meaning of
Section 382 of the Internal Revenue Code of 1986, as amended (the “Code”), in a three-year period.
Any ownership change is generally defined as a greater than 50% increase in equity ownership by “5%
stockholders,” as that term is defined for purposes of Section 382 of the Code in any three-year period. Further,
we may experience an ownership change in the future as a result of further shifts in our stock ownership. As a result, if we
earn net taxable income, our ability to use our pre-change NOL carryforwards to offset U.S. federal taxable income may be
subject to limitations, which could potentially result in increased future tax liability to us. In addition, at the state
level, there may be periods during which the use of NOL carryforwards is suspended or otherwise limited, which could
accelerate or permanently increase state taxes owed.
The report of our independent registered public accounting
firm included a “going concern” explanatory paragraph.
The report of our independent registered
public accounting firm on our financial statements as of and for the year ended December 31, 2020 included an explanatory
paragraph indicating that there is substantial doubt about our ability to continue as a going concern. We have financed our working
capital requirements to date by raising capital through private placements of shares of our common stock, issuing of short-term
and convertible notes, and the proceeds from our initial public offering completed in February 2021. If we are unable to raise
sufficient capital as and when needed, our business, financial condition and results of operations will be materially and adversely
affected, and we will need to significantly modify our operational plans to continue as a going concern. If we are unable to continue
as a going concern, we may have to liquidate our assets, and the values we receive for our assets in liquidation or dissolution
could be significantly lower than the values reflected in our financial statements. The inclusion of a going concern explanatory
paragraph by our independent registered public accounting firm, our lack of cash resources and our potential inability to continue
as a going concern may materially adversely affect our share price and our ability to raise new capital, enter into critical contractual
relations with third parties and otherwise execute our development strategy.
Risks Relating to Regulatory Matters
We may not receive regulatory approval for ADAIR or any
future product, such as ADMIR, or its or their approvals may be delayed, which would have a material adverse effect on our business
and financial condition.
ADAIR and any other future product, such
as ADMIR, as well as the activities associated with their development and commercialization, including their design, testing, manufacture,
safety, efficacy, recordkeeping, labeling, storage, approval, advertising, promotion, sale and distribution, are subject to comprehensive
regulation by the FDA and other regulatory agencies in the United States and by the European Medicines Agency, and similar regulatory
authorities outside the U.S. Failure to obtain marketing approval for ADAIR or any future product will prevent us from commercializing
such products. We have not received approval to market ADAIR from regulatory authorities in any jurisdiction. We have only limited
experience in filing and supporting the applications necessary to gain marketing approvals and expect to rely on third-party contract
research organizations and regulatory consultants to assist us in this process. Securing marketing approval requires the submission
of extensive preclinical and clinical data and supporting information to regulatory authorities for each therapeutic indication
to establish the proposed product’s safety and efficacy. Securing marketing approval also requires the submission of information
about the product manufacturing process to, and inspection of manufacturing facilities by, the regulatory authorities. ADAIR or
any future product may not be effective, may be only moderately effective or may prove to have undesirable or unintended side effects,
toxicities or other characteristics that may preclude our obtaining marketing approval or prevent or limit commercial use. If ADAIR
or any future product receives marketing approval, the accompanying label may limit the approved use of our drug, which could limit
sales of the product. We may never succeed in convincing regulatory agencies to allow us to promote the abuse deterrent properties
of ADAIR, even if we are successful in demonstrating these characteristics in studies. The FDA and other regulatory agencies may
never allow us to study ADAIR in human abuse liability studies, thereby limiting our ability to generate differentiating data and
claims.
The process of obtaining marketing
approvals, both in the United States and abroad, is expensive, may take many years if approval is granted at all, and
can vary substantially based upon a variety of factors, including the type, complexity and novelty of the proposed product
involved. Changes in marketing approval policies during the development period, changes in or the enactment of additional
statutes or regulations, or changes in regulatory review for each submitted product application, may cause delays in the
approval or rejection of an application. Regulatory authorities have substantial discretion in the approval process and may
refuse to accept any application or may decide that our data is insufficient for approval and require additional preclinical
studies and/or clinical trials. In addition, varying interpretations of the data obtained from preclinical studies and/or
clinical testing could delay, limit, or prevent marketing approval of a proposed product. Any marketing approval we
ultimately obtain may be limited or subject to restrictions or post-approval commitments that render the approved product not
commercially viable.
If we experience delays in obtaining approval
or if we fail to obtain approval of our proposed product or any future product, the commercial prospects for our proposed product
may be harmed and our ability to generate revenue will be materially impaired.
In addition, even if we obtain approval,
regulatory authorities may approve our proposed product or any future product for fewer or more limited indications than we request,
may not approve the price we intend to charge for our product, may grant approval contingent on the performance of costly post-marketing
clinical trials, or may approve a proposed product with a label that does not include the labeling claims necessary or desirable
for the successful commercialization of that product. Any of these scenarios could compromise the commercial prospects for our
proposed product or any future product.
Separately, in response to the global pandemic
of COVID-19, on March 10, 2020 the FDA announced its intention to postpone most foreign inspections of manufacturing facilities
and products, and subsequently, on March 18, 2020, the FDA announced its intention to temporarily postpone routine surveillance
inspections of domestic manufacturing facilities. The FDA reiterated its stance to Congress on June 2, 2020 stating, “only
inspections deemed mission-critical will be considered on a case-by-case basis as this outbreak continues to unfold.” On
August 20, 2020, and subsequently updated on January 29, 2021, the FDA’s Guidance for Industry against stated, “foreign
pre-approval and for-cause inspection assignments that are not deemed mission-critical remain temporarily postponed, while those
deemed mission-critical will still be considered for inspection on a case-by-case basis.”
Regulatory authorities outside the United
States may adopt similar restrictions or other policy measures in response to the COVID-19 pandemic. If a prolonged government
shutdown occurs, or if global health concerns continue to prevent the FDA or other regulatory authorities from conducting their
regular inspections, reviews, or other regulatory activities, it could significantly impact the ability of the FDA or other regulatory
authorities to timely review and process our regulatory submissions, which could have a material adverse effect on our business.
If the FDA becomes unable to continue its current level of performance, we could experience delays and setbacks for our product
candidates, including ADAIR and ADMIR, and for any approvals we may seek which could adversely affect our business.
Even if ADAIR or any other proposed product that we develop,
such as ADMIR, receives marketing approval, we will continue to face extensive regulatory requirements and the product may still
face future development and regulatory difficulties.
ADAIR and any other proposed product we may
develop, such as ADMIR, or license or acquire, will also be subject to ongoing requirements and review of the FDA and other regulatory
authorities. These requirements include labeling, packaging, storage, advertising, promotion, record-keeping and submission of
safety and other post-market information and reports, registration and listing requirements, cGMP requirements relating to manufacturing,
quality control, quality assurance and corresponding maintenance of records and documents, and requirements regarding the distribution
of samples to physicians and recordkeeping of the drug.
The FDA may also impose requirements for
costly post-marketing studies or clinical trials and surveillance to monitor the safety or efficacy of the product. 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. The FDA imposes stringent restrictions on manufacturers’ communications
regarding off-label use and if we do not market ADAIR or any other future product for only their approved indications, we may be
subject to enforcement action for off-label marketing. Violations of the FDCA, relating to the promotion of prescription drugs
may lead to investigations alleging violations of federal and state health care fraud and abuse laws, false claims acts, as well
as state consumer protection laws.
In addition, later discovery of previously
unknown adverse events or other problems with ADAIR or any other future product, manufacturers or manufacturing processes, or failure
to comply with regulatory requirements, may yield various results, including:
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restrictions on such products, operations, manufacturers, or manufacturing processes;
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restrictions on the labeling or marketing of a product;
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restrictions on product distribution or use;
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requirements to conduct post-marketing studies or clinical trials;
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withdrawal of the products from the market;
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refusal to approve pending applications or supplements to approved applications that we submit;
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fines, restitution, or disgorgement of profits;
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suspension or withdrawal of marketing or regulatory approvals;
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suspension of any ongoing clinical trials;
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refusal to permit the import or export of ADAIR or any other future product, such as ADMIR;
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injunctions or the imposition of civil or criminal penalties.
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In addition, manufacturers of drug products
and their facilities are subject to continual review and periodic inspections by the FDA and other regulatory authorities for compliance
with cGMP and other regulations.
The FDA’s policies may change, and
additional government regulations may be enacted that could prevent, limit or delay regulatory approval of our proposed product.
If we are slow or unable to adapt to changes in existing requirements or the adoption of new requirements or policies, or if we
are not able to maintain regulatory compliance, we may lose any marketing approval that we may have obtained.
The abuse, misuse or off-label use of our products may
harm our image in the marketplace, result in injuries that lead to product liability suits or result in costly investigations,
fines or sanctions by regulatory bodies if we are deemed to have engaged in the promotion of these uses, any of which could be
costly to our business.
The products we market will be approved by
the FDA for specific treatments. We will train our marketing and direct sales force to not promote our products for uses outside
of the FDA-approved indications for use, known as “off-label uses.” We cannot, however, prevent a physician from using
our products off-label, when in the physician’s independent professional medical judgement, he or she deems it appropriate.
There may be increased risk of injury to patients if physicians attempt to use our products off-label. Furthermore, the use of
our products for indications other than those approved by the FDA or approved by any foreign regulatory body may not effectively
treat such conditions, which could harm our reputation in the marketplace among physicians and patients. In addition, although
ADAIR is very difficult to manipulate into a form that can be snorted, it is not impossible to do so, as was shown by a third-party
drug laboratory, hired by us in preparation for human abuse studies, that was able to develop a time-consuming and laborious process
to convert ADAIR into a form that could be insufflated. In addition, although ADAIR is difficult to solubilize into a form that
can be injected, sophisticated drug abusers may be able to develop methods to manipulate ADAIR into a form that can be injected.
We cannot assure you that users of ADAIR or such other products we may develop in the future will not manipulate our products with
the intention of abusing our products. Such abuse of our products may harm our image in the marketplace and damage our reputation.
If the FDA or any foreign regulatory
body determines that our promotional materials or training constitute promotion of an off-label use, it could request that we
modify our training or promotional materials or subject us to regulatory or enforcement actions, including the issuance of an
untitled letter, a warning letter, injunction, seizure, civil fine or criminal penalties. It is also possible that other
federal, state or foreign enforcement authorities might take action if they consider our business activities to constitute
promotion of an off-label use, which could result in significant penalties, including, but not limited to, criminal, civil
and administrative penalties, damages, fines, disgorgement, exclusion from participation in government healthcare programs,
and the curtailment of our operations.
In addition, physicians may misuse our products
if they are not adequately trained, potentially leading to injury and an increased risk of product liability. If our products are
misused or used with improper technique, we may become subject to costly litigation by our customers or their patients. As described
elsewhere, product liability claims could divert management’s attention from our core business, be expensive to defend and
result in sizeable damage awards against us that may not be covered by insurance.
Our current and future relationships with customers and
third-party payors in the United States and elsewhere may be subject, directly or indirectly, to applicable anti-kickback, fraud
and abuse, false claims, transparency, health information privacy and security, and other healthcare laws and regulations, which
could expose us to criminal sanctions, civil penalties, contractual damages, reputational harm, administrative burdens, and diminished
profits and future earnings.
Healthcare providers, physicians and third-party
payors in the United States and elsewhere will play a primary role in the recommendation and prescription of any product 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, including, without limitation, the federal Anti-Kickback Statute and
the federal False Claims Act, which may constrain the business or financial arrangements and relationships through which we sell,
market, and distribute any product for which we obtain marketing approval. In addition, we may be subject to transparency laws
and patient privacy regulation by U.S. federal and state governments and by governments in foreign jurisdictions in which we conduct
our business. The applicable federal, state, and foreign healthcare laws and regulations that may affect our ability to operate
include, but are not necessarily limited to:
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the federal Anti-Kickback Statute, which prohibits, among other things, persons from knowingly and willfully soliciting, offering,
receiving or providing remuneration, directly or indirectly, in cash or in kind, to induce or reward, or in return for, either
the referral of an individual for, or the purchase, order or recommendation of, any good or service, for which payment may be made
under federal and state healthcare programs, such as Medicare and Medicaid;
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federal civil and criminal false claims laws and civil monetary penalty laws, including the federal False Claims Act, which
impose criminal and civil penalties, including civil whistleblower or qui tam actions, against individuals or entities for knowingly
presenting, or causing to be presented, to the federal government, including the Medicare and Medicaid programs, 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 (“HIPAA”), which imposes
criminal and civil liability for executing a scheme to defraud any healthcare benefit program or making false statements relating
to healthcare matters;
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HIPAA, as amended by the Health Information Technology for Economic and Clinical Health Act of 2009 (“HITECH”)
and their respective implementing regulations, which impose obligations on covered healthcare providers, health plans, and healthcare
clearinghouses, as well as their business associates that create, receive, maintain or transmit individually identifiable health
information for or on behalf of a covered entity, with respect to safeguarding the privacy, security and transmission of individually
identifiable health information;
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the federal Open Payments program, which requires manufacturers of drugs, devices, biologics and medical supplies for which
payment is available under Medicare, Medicaid or the Children’s Health Insurance Program, with specific exceptions, to report
annually to the Centers for Medicare & Medicaid Services (“CMS”) information related to “payments
or other transfers of value” made to physicians, which is defined to include doctors, dentists, optometrists, podiatrists
and chiropractors, and teaching hospitals and applicable manufacturers and applicable group purchasing organizations to report
annually to CMS ownership and investment interests held by the physicians and their immediate family members. Data collection began
on August 1, 2013 with requirements for manufacturers to submit reports to CMS by March 31, 2014 and 90 days after
the end each subsequent calendar year. Disclosure of such information was made by CMS on a publicly available website beginning
in September 2014; and
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analogous state and foreign laws and regulations, such as state anti-kickback and false claims laws, which may apply to sales
or marketing arrangements and claims involving healthcare items or services reimbursed by non-governmental third-party payors,
including private insurers; state and foreign laws that require pharmaceutical companies to comply with the pharmaceutical industry’s
voluntary compliance guidelines and the relevant compliance guidance promulgated by the federal government or otherwise restrict
payments that may be made to healthcare providers; state and foreign laws that require drug manufacturers to report information
related to payments and other transfers of value to physicians and other healthcare providers or marketing expenditures; and state
and foreign laws governing the privacy and security of health information in certain circumstances, many of which differ from each
other in significant ways and often are not preempted by HIPAA, thereby complicating compliance efforts.
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Efforts to ensure that our business arrangements
with third parties will comply with applicable healthcare laws and regulations may involve substantial costs. It is possible that
governmental authorities will conclude that our business practices may 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, including, without limitation, damages, fines, imprisonment, exclusion from participation
in government healthcare programs, such as Medicare and Medicaid, and the curtailment or restructuring of our operations, which
could have a material adverse effect on our business. If any of the physicians or other healthcare providers or entities with whom
we expect to do business, including our collaborators, is found not to be in compliance with applicable laws, it may be subject
to criminal, civil or administrative sanctions, including exclusions from participation in government healthcare programs, which
could also materially affect our business.
Regulatory approval for any approved product is limited
by the FDA to those specific indications and conditions for which clinical safety and efficacy have been demonstrated.
Any regulatory approval is limited to those
specific diseases and indications for which a product is deemed to be safe and effective by the FDA. In addition to the FDA approval
required for new formulations, any new indication for an approved product also requires FDA approval. If we are not able to obtain
FDA approval for any desired future indications for ADAIR or any other future product, such as ADMIR, our ability to effectively
market and sell ADAIR or any other future product may be reduced, and our business may be adversely affected.
While physicians may choose to prescribe
drugs for uses that are not described in the product’s labeling and for uses that differ from those tested in clinical studies
and approved by the regulatory authorities, our ability to promote the products is limited to those indications that are specifically
approved by the FDA. These “off-label” uses are common across medical specialties and may constitute an appropriate
treatment for some patients in varied circumstances. Regulatory authorities in the United States generally do not regulate the
behavior of physicians in their choice of treatments. Regulatory authorities do, however, restrict communications by pharmaceutical
companies on the subject of off-label use. If our promotional activities fail to comply with these regulations or guidelines, we
may be subject to warnings from, or enforcement action by, these authorities. In addition, our failure to follow FDA rules and
guidelines relating to promotion and advertising may cause the FDA to send a Warning Letter to the Company (which becomes public)
alleging violations of the FDCA and subjecting the Company to other potential enforcement such as to suspend or withdraw an approved
product from the market, require a recall or institute fines, or could diminish our reputation and result in disgorgement of money,
operating restrictions, injunctions, or criminal prosecution, any of which could harm our business.
Public concern regarding the safety of drug products such
as ADAIR could delay or limit our ability to obtain regulatory approval, result in the inclusion of unfavorable information in
our labeling, or require us to undertake other activities that may entail additional costs.
In light of widely publicized events
concerning the safety risk of certain drug products, the FDA, members of Congress, the Government Accountability Office,
medical professionals and the general public have raised concerns about potential drug safety issues. These events have
resulted in the withdrawal of drug products, revisions to drug labeling that further limit use of the drug products and the
establishment of risk management programs. The Food and Drug Administration Amendments Act of 2007
(“FDAAA”) grants significant expanded authority to the FDA, much of which is aimed at improving the safety
of drug products before and after approval. In particular, this law authorizes the FDA to, among other things, require
post-approval studies and clinical trials, mandate changes to drug labeling to reflect new safety information and require
risk evaluation and mitigation strategies for certain drugs, including certain currently approved drugs. It also
significantly expands the federal government’s clinical trial registry and results databank, which we expect will
result in significantly increased government oversight of clinical trials. Under the FDAAA, companies that violate these and
other provisions of this law are subject to substantial civil monetary penalties, among other regulatory, civil and criminal
penalties. The increased attention to drug safety issues may result in a more cautious approach by the FDA in its review of
data from our preclinical studies and clinical trials. Data from preclinical studies and clinical trials may receive greater
scrutiny, particularly with respect to safety, which may make the FDA or other regulatory authorities more likely to require
additional preclinical studies and/or clinical trials. If the FDA requires us to conduct additional preclinical studies or
clinical trials prior to approving ADAIR, our ability to obtain approval of this proposed product will be delayed. If the FDA
requires us to provide additional preclinical studies and/or clinical data following the approval of ADAIR, the indications
for which this proposed product is approved may be limited or there may be specific warnings or limitations on dosing, and
our efforts to commercialize ADAIR may be otherwise adversely impacted.
If we experience delays or difficulties in the enrollment
of patients in clinical trials, our receipt of necessary regulatory approvals could be delayed or prevented.
We may not be able to continue existing clinical
trials, or initiate new clinical trials, for our proposed product if we are unable to locate and enroll a sufficient number of
eligible patients to participate in these trials as required by the FDA or similar regulatory authorities outside the U.S. Some
of our competitors have ongoing clinical trials for proposed products that treat the same indications as our proposed product,
and patients who would otherwise be eligible for our clinical trials may instead enroll in clinical trials of our competitors’
proposed products. Available therapies for the indications we are pursuing can also affect enrollment in our clinical trials. Patient
enrollment is affected by other factors including, but not necessarily limited to:
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the severity of the disease under investigation;
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the eligibility criteria for the study in question;
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the perceived risks and benefits of the proposed product under study;
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the efforts to facilitate timely enrollment in clinical trials;
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the patient referral practices of physicians;
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the ability to monitor patients adequately during and after treatment;
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the proximity and availability of clinical trial sites for prospective
patients; and
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the availability of other approved drugs to treat the same condition, thereby creating competition
for our clinical trial enrollment and reducing the incentive for prospective patients to participate in our trials.
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Our inability to enroll a sufficient number
of patients for our clinical trials would result in significant delays and could require us to abandon one or more clinical trials
altogether. Enrollment delays in our clinical trials may result in increased development costs for ADAIR or any future product,
such as ADMIR, which would cause the value of our company to decline and limit our ability to obtain additional financing.
Current and future legislation may increase the difficulty
and cost for us to obtain marketing approval of and commercialize ADAIR or any other proposed product that we develop and affect
the prices we may set.
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
prevent or delay marketing approval for ADAIR or any other proposed product that we develop, restrict or regulate post-approval
activities and affect our ability to profitably sell ADAIR or any other proposed product for which we obtain marketing approval.
Legislative and regulatory proposals have
been made to expand post-approval requirements, restrict sales and promotional activities for pharmaceutical products, and regulate
pricing. We are not sure whether additional legislative changes will be enacted, or whether the FDA regulations, guidance or interpretations
will be changed, or what the impact of such changes on the marketing approvals of our proposed product, if any, may be. In addition,
increased scrutiny by the U.S. Congress of the FDA’s approval process may significantly delay or prevent marketing approval,
as well as subject us to more stringent product labeling and post-marketing testing and other requirements.
Recently enacted legislation, future legislation and healthcare
reform measures may increase the difficulty and cost for us to obtain marketing approval for and commercialize ADAIR and for any
future product, such as ADMIR, and may affect the prices we may set.
In the United States and some foreign jurisdictions,
there have been, and we expect there will continue to be, a number of legislative and regulatory changes to the healthcare system,
including cost-containment measures that may reduce or limit coverage and reimbursement for newly approved drugs and affect our
ability to profitably sell ADAIR and for any future product, such as ADMIR, for which we obtain marketing approval. In particular,
there have been and continue to be a number of initiatives at the U.S. federal and state levels that seek to reduce healthcare
costs, restrict or regulate post-approval activities and improve the quality of healthcare.
In the United States, the Medicare Prescription
Drug, Improvement, and Modernization Act of 2003 (the “MMA”) 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 drugs. In addition, this legislation authorized Medicare Part D prescription drug plans
to limit the number of drugs that will be covered in any therapeutic class. As a result of this legislation and the expansion of
federal coverage of drug products, we expect that there will be additional pressure to contain and reduce costs. These cost reduction
initiatives and other provisions of this legislation could decrease the coverage and price that we receive for any approved products
and could seriously harm our business. While the MMA applies only to drug benefits for Medicare beneficiaries, private payors often
follow Medicare coverage policy and payment limitations in setting their own reimbursement rates, and any reduction in reimbursement
that results from the MMA may result in a similar reduction in payments from private payors.
For example, in March 2010, the Affordable
Care Act, was enacted in the United States. Among the provisions of the Affordable Care Act of importance to ADAIR and for any
future product, the Affordable Care Act: establishes an annual, nondeductible fee on any entity that manufactures or imports specified
branded prescription drugs and biologic agents; extends manufacturers’ Medicaid rebate liability to covered drugs dispensed
to individuals who are enrolled in Medicaid managed care organizations; expands eligibility criteria for Medicaid programs; expands
the entities eligible for discounts under the Public Health program; increases the statutory minimum rebates a manufacturer must
pay under the Medicaid Drug Rebate Program; creates a new Medicare Part D coverage gap discount program; establishes a new
Patient-Centered Outcomes Research Institute to oversee, identify priorities in and conduct comparative clinical effectiveness
research, along with funding for such research; and establishes a Center for Medicare Innovation at CMS to test innovative payment
and service delivery models to lower Medicare and Medicaid spending.
At this time, we are unsure of the full impact
that the Affordable Care Act will have on our business. There have been judicial and political challenges to certain aspects of
the Affordable Care Act. For example, since January 2017, President Trump has signed two executive orders and other directives
designed to delay, circumvent, or loosen certain requirements of the Affordable Care Act. Concurrently, Congress has considered
legislation that would repeal or repeal and replace all or part of the Affordable Care Act. While Congress has not passed comprehensive
repeal legislation, two bills affecting the implementation of certain taxes under the Affordable Care Act have been signed into
law. The Tax Cuts and Jobs Act of 2017 (the “Tax Act”) included a provision repealing, effective January 1,
2019, the tax-based shared responsibility payment imposed by the Affordable Care Act on certain individuals who fail to maintain
qualifying health coverage for all or part of a year that is commonly referred to as the “individual mandate.” On January 22,
2018, President Trump signed a continuing resolution on appropriations for fiscal year 2018 that delayed the implementation of
certain Affordable Care Act-mandated fees, including the so-called “Cadillac” tax on certain high cost employer-sponsored
insurance plans, the annual fee imposed on certain health insurance providers based on market share. The Bipartisan Budget Act
of 2018 (the “BBA”) among other things, amends the Affordable Care Act, effective January 1, 2019, to close
the coverage gap in most Medicare drug plans, commonly referred to as the “donut hole,” by increasing from 50 percent
to 70 percent the point-of-sale discount that is owed by pharmaceutical manufacturers who participate in Medicare Part D.
In July 2018, CMS published a final rule permitting further collections and payments to and from certain Affordable Care Act
qualified health plans and health insurance issuers under the Affordable Care Act risk adjustment program in response to the outcome
of federal district court litigation regarding the method CMS uses to determine this risk adjustment. On December 14, 2018,
a U.S. District Court Judge in the Northern District of Texas (“Texas District Court Judge”) ruled that the
individual mandate is a critical and inseverable feature of the ACA, and therefore, because it was repealed as part of the Tax
Act, the remaining provisions of the ACA are invalid as well. While the Texas District Court Judge, as well as the Trump Administration
and CMS, have stated that the ruling will have no immediate effect, it is unclear how this decision, subsequent appeals, and other
efforts to repeal and replace the ACA will impact the ACA and our business.
In addition, other legislative changes have
been proposed and adopted since the Affordable Care Act was enacted. The Coronavirus Aid, Relief, and Economic Security Act, which
was signed into law on March 27, 2020, designed to provide financial support and resources to individuals and businesses affected
by the COVID-19 pandemic, suspended these reductions from May 1, 2020 through December 31, 2020, and extended the sequester
by one year, through 2030. In addition, on January 2, 2013, the American Taxpayer Relief Act of 2012 was signed into law,
which, among other things, reduced Medicare payments to several providers, including hospitals, and increased the statute of limitations
period for the government to recover overpayments to providers from three to five years.
Further, there has been heightened governmental
scrutiny in the United States of pharmaceutical pricing practices in light of the rising cost of prescription drugs. Such scrutiny
has resulted in several recent congressional inquiries and proposed and enacted federal and state legislation designed to, among
other things, bring more transparency to product pricing, review the relationship between pricing and manufacturer patient programs,
and reform government program reimbursement methodologies for products.
At the federal level, the Trump administration’s
budget proposal for fiscal year 2019 contains further drug price control measures that could be enacted during the 2019 budget
process or in other future legislation, including, for example, measures to permit Medicare Part D plans to negotiate the
price of certain drugs under Medicare Part B, to allow some states to negotiate drug prices under Medicaid and to eliminate
cost sharing for generic drugs for low-income patients. Additionally, the Trump administration released a “Blueprint”
to lower drug prices through proposals to increase manufacturer competition, increase the negotiating power of certain federal
healthcare programs, incentivize manufacturers to lower the list price of their products and reduce the out of pocket costs of
drug products paid by consumers. The U.S. Department of Health and Human Services has begun the process of soliciting feedback
on some of these measures and, at the same time, is implementing others under its existing authority. Although some of these, and
other, proposals will require authorization through additional legislation to become effective, Congress and the Trump administration
have each indicated that it will continue to seek new legislative and/or administrative measures to control drug costs.
At the state level, legislatures have increasingly
passed legislation and implemented regulations designed to control pharmaceutical and biological product pricing, including price
or patient reimbursement constraints, discounts, restrictions on certain product access and marketing cost disclosure and transparency
measures, and, in some cases, designed to encourage importation from other countries and bulk purchasing. Legally mandated price
controls on payment amounts by third-party payors or other restrictions could harm our business, results of operations, financial
condition and prospects. In addition, regional healthcare authorities and individual hospitals are increasingly using bidding procedures
to determine what pharmaceutical products and which suppliers will be included in their prescription drug and other healthcare
programs. This could reduce the ultimate demand for ADAIR and for any future product, such as ADMIR, if approved, or put pressure
on our product pricing, which could negatively affect our business, results of operations, financial condition and prospects.
We expect that the Affordable Care Act, these
new laws and other healthcare reform measures that may be adopted in the future may result in additional reductions in Medicare
and other healthcare funding, more rigorous coverage criteria, new payment methodologies and additional downward pressure on the
price that we receive for any approved product. Any reduction in reimbursement from Medicare or other government programs may result
in a similar reduction in payments from private payors. The implementation of cost containment measures or other healthcare reforms
may prevent us from being able to generate revenue, attain profitability or commercialize ADAIR and for any future product, such
as ADMIR, if approved.
We rely, and expect to continue to rely, on third parties
to conduct our clinical trials, and those third parties may not perform satisfactorily, including failing to meet deadlines for
the completion of such trials or complying with applicable regulatory requirements.
We rely on third-party contract research
organizations and clinical research organizations to conduct our clinical trials for ADAIR and for any future product, such as
ADMIR. We expect to continue to rely on third parties, such as contract research organizations, clinical research organizations,
clinical data management organizations, medical institutions and clinical investigators, to conduct all of our clinical trials.
The agreements with these third parties might terminate for a variety of reasons, including a failure to perform by the third parties.
If we need to enter into alternative arrangements, that could delay our product development activities.
Our reliance on these third parties for research
and development activities will reduce our control over these activities but will not relieve us of our responsibilities. For example,
we will remain responsible for ensuring that each of our clinical trials are conducted in accordance with the general investigational
plan and protocols for the trial and in accordance with good laboratory practice, as appropriate. Moreover, the FDA requires us
to comply with standards, commonly referred to as good clinical practices (“GCPs”) 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 trial participants are protected. Regulatory authorities enforce these requirements through periodic
inspections of trial sponsors, clinical investigators, and trial sites. If we or any of our clinical research organizations fail
to comply with applicable GCPs, the clinical data generated in our clinical trials may be deemed unreliable and the FDA or comparable
foreign regulatory authorities may require us to perform additional clinical trials before approving our marketing applications.
We cannot assure investors that upon inspection by a given regulatory authority, such regulatory authority will determine that
any of our clinical trials complies with GCP regulations. In addition, our clinical trials must be conducted with product produced
under cGMP regulations. Our failure to comply with these regulations may require us to repeat clinical trials, which would delay
the regulatory approval process. We also are 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.
The third parties with whom we have contracted
to help perform our clinical trials may also have relationships with other entities, some of which may be our competitors. If these
third parties 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 will not be able to obtain, or may be delayed in obtaining,
marketing approvals for our proposed product and will not be able to, or may be delayed in our efforts to, successfully commercialize
our proposed product.
If any of our relationships with these third-party
contract research organizations or clinical research organizations terminates, we may not be able to enter into arrangements with
alternative contract research organizations or clinical research organizations or to do so on commercially reasonable terms. Switching
or adding additional contract research organizations or clinical research organizations involves additional cost and requires management
time and focus. In addition, there is a natural transition period when a new contract research organization or clinical research
organization commences work. As a result, delays could occur, which could compromise our ability to meet our desired development
timelines. Though we carefully manage our relationships with our contract research organizations or clinical research organizations,
there can be no assurance that we will not encounter similar challenges or delays in the future.
We rely on clinical data and results obtained by third
parties that could ultimately prove to be inaccurate or unreliable.
As part of our strategy to mitigate development
risk, we seek to develop proposed products with validated mechanisms of action, and we utilize biomarkers to assess potential clinical
efficacy early in the development process. This strategy necessarily relies upon clinical data and other results obtained by third
parties that may ultimately prove to be inaccurate or unreliable. Further, such clinical data and results may be based on products
or proposed products that are significantly different from ADAIR or any future product, such as ADMIR. If the third-party data
and results we rely upon prove to be inaccurate, unreliable or not applicable to ADAIR or any future product, we could make inaccurate
assumptions and conclusions about our proposed product and our research and development efforts could be compromised.
If we 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.
We are subject to numerous environmental,
health, and safety laws and regulations, including those governing laboratory procedures and the handling, use, storage, treatment,
and disposal of hazardous materials and wastes. Our operations involve the use of hazardous and flammable materials, including
chemicals and biological materials. Our operations also produce hazardous waste products. We generally contract with third parties
for the disposal of these materials and wastes. We cannot eliminate the risk of contamination or injury from these materials. Although
we believe that the safety procedures for handling and disposing of these materials comply with the standards prescribed by these
laws and regulations, we cannot eliminate the risk of accidental contamination or injury from these materials. In the event of
contamination or injury resulting from our use of hazardous materials, we could be held liable for any resulting damages, and any
liability could exceed our resources. We also could incur significant costs associated with civil or criminal fines and penalties
for failure to comply with such laws and regulations.
Although we maintain workers’ compensation
insurance to cover us for costs and expenses we may incur due to injuries to our employees resulting from the use of hazardous
materials, this insurance may not provide adequate coverage against potential liabilities. We do not maintain insurance for environmental
liability or toxic tort claims that may be asserted against us in connection with our storage or disposal of biological, hazardous
or radioactive materials.
In addition, we may incur substantial costs
in order to comply with current or future environmental, health and safety laws and regulations. These current or future laws and
regulations may impair our research, development or production efforts. Our failure to comply with these laws and regulations also
may result in substantial fines, penalties or other sanctions.
If the FDA does not conclude that ADAIR is sufficiently
bioequivalent, or demonstrate comparable bioavailability to its reference listed drug (“RLD “), or if the FDA otherwise
does not conclude that ADAIR satisfies the requirements of Section 505(b)(2) of the FDCA, approval pathway, the approval pathway
for this proposed product will likely take significantly longer, cost significantly more and entail significantly greater complications
and risks than anticipated, and the FDA may not approve this proposed product.
A key element of our strategy is to seek
FDA approval for ADAIR through Section 505(b)(2) approval pathway. Section 505(b)(2) of the FDCA permits the filing
of an NDA that contains full safety and efficacy reports but where at least some of the information required for approval comes
from studies not conducted by or for the applicant. Such information could include the FDA’s findings of safety and efficacy
in the approval of a similar drug, and for which the applicant has not obtained a right of reference and/or published literature.
Such reliance is typically predicated on a showing of bioequivalence or comparable bioavailability to an approved drug.
If the FDA does not allow us to pursue the
Section 505(b)(2) approval pathway for ADAIR, or if we cannot demonstrate bioequivalence or comparable bioavailability of
ADAIR to an approved product, we may need to conduct additional clinical trials, provide additional data and information, and meet
additional standards for regulatory approval. If this were to occur, the time and financial resources required to obtain FDA approval
for ADAIR would increase. Moreover, our inability to pursue the Section 505(b)(2) approval pathway could result in new competitive
products reaching the market sooner than ADAIR, which could have a material adverse effect on our competitive position and our
business prospects. Even if we are allowed to pursue the Section 505(b)(2) approval pathway, we cannot assure investors that
ADAIR will receive the requisite approval for commercialization on a timely basis, if at all.
In addition, notwithstanding the approval
of a number of products by the FDA under the Section 505(b)(2) approval pathway over the last few years, pharmaceutical
companies and others have objected to the FDA’s interpretation of Section 505(b)(2). If the FDA’s interpretation
of Section 505(b)(2) is successfully challenged, the FDA may change its policies and practices with respect to the Section 505(b)(2)
approval pathway, which could delay or even prevent the FDA from approving any NDA that we submit under Section 505(b)(2).
Even if ADAIR is approved under Section 505(b)(2),
the approval may be subject to limitations on the indicated uses for which the product may be marketed or to other conditions of
approval, or may contain requirements for costly post-marketing testing and surveillance to monitor the safety or efficacy of the
product, including additional clinical trials.
ADAIR contains a controlled substance, the manufacture,
use, sale, importation, exportation, and distribution of which are subject to regulation by state, federal, and foreign law enforcement
and other regulatory agencies.
ADAIR contains, and any future product, such
as ADMIR, if any, may contain, controlled substances which are subject to state, federal, and foreign laws and other regulations
regarding their manufacturing, use, sale, importation, exportation, and distribution. ADAIR’s active ingredient, dextroamphetamine,
is classified as a controlled substance under the CSA, and regulations of the DEA. A number of states also independently regulate
these drugs as controlled substances. Controlled substances are classified by the DEA as Schedule I, II, III, IV, or V substances,
with Schedule I substances considered to present the highest risk of substance abuse and Schedule V substances the lowest
risk. The active ingredient in ADAIR, dextroamphetamine, is listed by the DEA as a Schedule II controlled substance under
the CSA. For our current proposed product, and any potential future product, such as ADMIR, containing a controlled substance,
we and our suppliers, manufacturers, contractors, customers, and distributors are required to obtain and maintain applicable registrations
from state, federal, and foreign law enforcement and regulatory agencies and comply with their laws and regulations regarding the
manufacturing, use, sale, importation, exportation, and distribution of controlled substances. An example of such practice is that
all Schedule II drug prescriptions must be signed by a physician, physically presented to a pharmacist and may not be refilled
without a new prescription. Furthermore, the amount of Schedule II substances that can be obtained for clinical trials and
commercial distribution is limited by the CSA and DEA regulations. We may not be able to obtain sufficient quantities of these
controlled substances in order to complete our clinical trials or meet commercial demand, even if ADAIR is approved for marketing.
In addition, controlled substances are subject
to regulations governing manufacturing, labeling, packaging, testing, dispensing, production and procurement quotas, recordkeeping,
reporting, handling, shipment, and disposal. These regulations increase the personnel needs and the expense associated with development
and commercialization of proposed products that include controlled substances. The DEA and some states conduct periodic inspections
of registered establishments that handle controlled substances.
Failure to obtain and maintain required registrations
or to comply with any applicable regulations, including quotas imposed by the DEA, could delay or preclude us from developing and
commercializing our proposed product that contains a controlled substance and subject us to enforcement action. The DEA may seek
civil penalties, refuse to renew necessary registrations, or initiate proceedings to revoke those registrations. In some circumstances,
violations could lead to criminal proceedings. Because of their restrictive nature, these regulations could limit commercialization
of our proposed product containing controlled substances.
If we, our drug products or the manufacturing
facilities for our drug products fail to comply with applicable regulatory requirements, a regulatory agency may:
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issue warning letters or untitled letters;
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seek an injunction or impose civil or criminal penalties or monetary
fines;
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suspend or withdraw marketing approval;
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suspend any ongoing clinical trials;
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refuse to approve pending applications or supplements to applications;
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suspend or impose restrictions on operations, including costly new
manufacturing requirements;
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seize or detain products, refuse to permit the import or export of
products or request that we initiate a product recall; or
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refuse
to allow us to enter into supply contracts, including government contracts.
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We cannot predict the likelihood, nature
or extent of government regulation that may arise from future legislation or administrative action, either in the United States
or abroad. If we are slow or unable to adapt to changes in existing requirements or the adoption of new requirements or policies,
or if we are not able to maintain regulatory compliance, we may lose any marketing approval that we may have been obtained and
we may not achieve or sustain profitability, which would adversely affect our business.
The FDA may not approve product labeling for ADAIR that
would permit us to market and promote our product in the United States by describing its abuse-deterrent features.
We have invested resources conducting Laboratory
Manipulation and Extraction Studies (Category 1), and may spend substantial additional resources conducting Pharmacokinetic Studies
(Category 2) and Clinical Abuse Potential Studies (Category 3) to support ADAIR’s abuse-deterrence characteristics, and we
believe such studies are consistent with the April 2015 final FDA guidance on opioid medications (the “2015 FDA Guidance”),
as no guidance exists on stimulants. However, we have not yet received regulatory approval to market ADAIR and additional data
may emerge that could change the FDA’s position on the proposed product label, and there can be no assurance that ADAIR or
our other current or any future product, such as ADMIR, will receive FDA-approved product labeling that describes abuse-deterrent
features of such product given the current absence of specific FDA guidance on development of abuse-deterrent amphetamines. Our
failure to achieve FDA approval of product labeling containing information on abuse-deterrence characteristics of ADAIR will prevent
or substantially limit our promotion of the abuse-deterrent features of ADAIR. This type of limitation would make it difficult
for us to differentiate ADAIR from other amphetamine-containing products, may cause us to lower the price of our product to the
extent that there are competing products with abuse-deterrent claims on their product labels and as a result, our product would
be less competitive in the market. The FDA closely regulates promotional materials and other promotional activities, even if the
FDA initially approves product labeling that includes a description of the abuse- deterrent characteristics of ADAIR and therefore
the FDA may object to our marketing claims and product advertising campaigns. This could lead to the issuance of warning letters
or untitled letters, suspension or withdrawal of our product from the market, recalls, fines, disgorgement of money, operating
restrictions, injunctions, and civil or criminal prosecution. Any of these consequences would harm the commercial success of ADAIR
or any other future product.
Even if any other proposed products are approved
for marketing with certain abuse-deterrence claims, the 2015 FDA Guidance may not apply to such proposed product, as the said guidance
is not binding law and may be superseded or modified at any time. Also, if the FDA determines that our post-marketing data do not
demonstrate that the abuse-deterrent properties result in reduction of abuse, or demonstrate a shift to routes of abuse that present
a greater risk, the FDA may find that product labeling revisions are needed, and may require the removal of our abuse-deterrence
claims. Although ADAIR is very difficult to manipulate into a form that can be snorted, it is not impossible to do so, as was shown
by a third-party drug laboratory, hired by us in preparation for human abuse studies, that was able to develop a time-consuming
and laborious process to convert ADAIR into a form that could be insufflated. In addition, although ADAIR is difficult to solubilize
into a form that can be injected, sophisticated drug abusers may be able to develop methods to manipulate ADAIR into a form that
can be injected.
Further, in October 2020, an FDA advisory
committee reviewed another abuse deterrent stimulant which relied on different delivery technology and a different active molecule
than ADAIR. The advisory committee recommended against the approval of the other product, voting that the benefits did not outweigh
the risks. In particular, the advisory committee determined that the other product had not established that it could deter the
risk of intranasal abuse based on the results of its human abuse liability study because it failed the study’s primary endpoint.
Further the advisory committee voted that the safety of the other product had not been adequately characterized because of safety
concerns with two inactive ingredients contained in the other product. ADAIR does not contain either of these inactive ingredients.
Nevertheless, we may not be able to conduct a successful pivotal human abuse trial and an FDA advisory committee could vote that
the benefits of ADAIR or ADMIR do not outweigh the risks.
We may need to comply with the requirements of the Drug
Supply Chain Security Act, which outlines critical steps required to build an electronic, interoperable system to identify and
trace certain prescription drugs as they are distributed in the United States.
We may need to comply with the requirements
of the Drug Supply Chain Security Act, including those related to product tracing, verification, and authorized trading partners.
Signed into law in 2013, the Drug Supply Chain Security Act, amended the FDCA, and is being implemented over a 10-year period.
The law’s requirements include the ability to quarantine and promptly investigate a suspect product, such as a potentially
counterfeit, diverted or stolen product, to determine if it is illegitimate, and notify our trading partners and the FDA of any
illegitimate product. Such compliance may be time consuming and expensive to implement. Also, in the event that we fail to comply
with these requirements, we may face regulatory actions that could affect our ability to commercialize ADAIR.
Even if ADAIR or any other future product, such as ADMIR,
we may develop receives marketing approval, there could be adverse effects not discovered during development.
Even if any of our proposed products receive
marketing approval, we or others may later identify undesirable side-effects caused by the product or problems with our third-party
manufacturers or manufacturing processes, and in either event a number of potentially significant negative consequences could result,
including:
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regulatory authorities may suspend or withdraw their approval of the
product;
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regulatory authorities may require the addition of labeling statements,
such as warnings or contraindications or distribution and use restrictions;
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regulatory authorities may require us to issue specific communications
to healthcare professionals, such as “Dear Doctor” letters;
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regulatory authorities may issue negative publicity regarding the
affected product, including safety communications;
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we may be required to change the way the product is administered,
conduct additional clinical trials or restrict the distribution or use of the product;
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we could be sued and held liable for harm caused to patients; and
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our reputation may suffer.
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Any of these events could prevent us from
achieving or maintaining market acceptance of the affected product and could substantially increase commercialization costs or
even force us to cease operations.
Our products may cause or contribute to adverse medical
events that we are required to report to the FDA and if we fail to do so, we would be subject to sanctions that would materially
harm our business.
Post-marketing safety data collection and
adverse event reporting are critical elements of FDA’s oversight of drugs and therapeutic biologics available to the American
public. The testing that helps to establish the safety of products, such as drugs and therapeutic biologics, is typically conducted
on small groups before FDA approves the products for sale. Some problems can remain unknown, only to be discovered when a product
is used by a large number of people. An adverse event is any unanticipated experience or side effect associated with the use of
a drug or therapeutic biologic in humans, whether or not it is considered related to the product. An adverse event could occur:
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with use in professional practice;
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from overdose whether accidental or intentional;
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due to lack of expected effectiveness.
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During inspections, FDA investigators will
review a company’s post-marketing adverse event information to ensure compliance with federal laws and regulations.
Our marketed products are subject to adverse
event reporting (ADR) which require that we report to the FDA events related to our products. The timing of our obligation to report
under the ADR regulations is triggered by the date we become aware of the adverse event as well as the nature of the event. We
may fail to report adverse events of which we become aware within the prescribed timeframe. We may also fail to recognize that
we have become aware of a reportable adverse event, especially if it is not reported to us as an adverse event or if it is an adverse
event that is unexpected or removed in time from the use of our products. If we fail to comply with our reporting obligations,
the FDA could take action, including warning letters, untitled letters, administrative actions, criminal prosecution, imposition
of civil monetary penalties, revocation of our device clearances or approvals, seizure of our products, or delay in clearance or
approval of future products.
Our products may in the future be subject to product recalls.
A recall of our products, either voluntarily or at the direction of the FDA or another governmental authority, or the discovery
of serious safety issues with our products, could have a significant adverse impact on us.
The FDA and similar foreign governmental
authorities have the authority to require the recall of commercialized products in the event of material deficiencies or defects
in their design or manufacture. A government-mandated or voluntary recall could occur as a result of an unacceptable risk to health,
contaminated product, manufacturing errors, or labeling defects or other deficiencies and issues. Recalls of any of our products
would divert managerial and financial resources and have an adverse effect on our reputation, results of operations and financial
condition, which could impair our ability to produce our products in a cost-effective and timely manner in order to meet our customers’
demands. We may also be subject to liability claims, be required to bear other costs, or take other actions that may have a negative
impact on our future sales and our ability to generate profits.
Changes in regulatory requirements and guidance or unanticipated
events during our clinical trials may occur, which may result in necessary changes to clinical trial protocols, which could result
in increased costs to us, delay our development timeline or reduce the likelihood of successful completion of our clinical trials.
Changes in regulatory requirements and guidance
or unanticipated events during our clinical trials may occur, as a result of which we may need to amend clinical trial protocols.
Amendments may require us to resubmit our clinical trial protocols to IRBs for review and approval, which may impact the cost,
timing or successful completion of a clinical trial. If we experience delays in completion of, or if we terminate, any of our clinical
trials, the commercial prospects for our proposed product would be harmed and our ability to generate product revenue would be
delayed, possibly materially.
Our amended and restated certificate of incorporation
designate specific courts as the exclusive forum for certain litigation that may be initiated by the Company’s stockholders,
which could limit its stockholders’ ability to obtain a favorable judicial forum for disputes with us.
Pursuant to our amended and restated certificate
of incorporation, unless we consent in writing to the selection of an alternative forum, the Court of Chancery of the State of
Delaware is the sole and exclusive forum for any state law claims for (1) any derivative action or proceeding brought on our
behalf; (2) any action asserting a claim of or based on a breach of a fiduciary duty owed by any director, officer or other
employee of ours to us or our stockholders; (3) any action asserting a claim pursuant to any provision of the Delaware General
Corporation Law, our amended and restated certificate of incorporation; or (4) any action asserting a claim governed by the
internal affairs doctrine (the “Delaware Forum Provision”). The Delaware Forum Provision will not apply to any
causes of action arising under the Securities Act or the Exchange Act. Our amended and restated certificate of incorporation further
provide that unless we consent in writing to the selection of an alternative forum, the federal district courts of the United States
of America shall be the sole and exclusive forum for resolving any complaint asserting a cause of action arising under the Securities
Act (the “Federal Forum Provision”). In addition, our amended and restated certificate of incorporation provide
that any person or entity purchasing or otherwise acquiring any interest in shares of our capital stock is deemed to have notice
of and consented to the Delaware Forum Provision and the Federal Forum Provision; provided, however, that stockholders cannot and
will not be deemed to have waived our compliance with the federal securities laws and the rules and regulations thereunder.
We recognize that the Delaware Forum Provision
in our amended and restated certificate of incorporation may impose additional litigation costs on stockholders in pursuing any
such claims, particularly if the stockholders do not reside in or near the State of Delaware. Additionally, the forum selection
clauses in our amended and restated certificate of incorporation may limit our stockholders’ ability to bring a claim in
a judicial forum that they find favorable for disputes with us or our directors, officers or employees, which may discourage the
filing of lawsuits against us and our directors, officers and employees, even though an action, if successful, might benefit our
stockholders. In addition, while the Delaware Supreme Court ruled in March 2020 that federal forum selection provisions purporting
to require claims under the Securities Act be brought in federal court are “facially valid” under Delaware law, there
is uncertainty as to whether other courts will enforce our Federal Forum Provision. If the Federal Forum Provision is found to
be unenforceable, we may incur additional costs associated with resolving such matters. The Federal Forum Provision may also impose
additional litigation costs on stockholders who assert that the provision is not enforceable or invalid. The Court of Chancery
of the State of Delaware and the United States District Court may also reach different judgments or results than would other courts,
including courts where a stockholder considering an action may be located or would otherwise choose to bring the action, and such
judgments may be more or less favorable to us than our stockholders.
Risks Relating to Intellectual Property
We have filed multiple patent applications and have two
issued patents by the U.S. PTO. These or any other patent applications may not result in issued patents, and as a result we may
have limited protection of our proprietary technology in the marketplace.
We have had two patents granted and one additional
patent application directed to ADAIR for ADHD and narcolepsy filed in the United States, and we are seeking patent protection for
ADAIR internationally in several foreign countries and territories, including the EU, Canada, Japan and China. The U.S. patents
will expire in 2037. It is impossible to predict whether or how our PCT application will result in any issued patent. Even if the
pending application issues, it may issue with claims significantly narrower than those we currently seek.
The patent position of biotechnology and
biopharmaceutical companies is generally uncertain because it involves complex legal and factual considerations. The standards
applied by the U.S. PTO and foreign patent offices in granting patents are not always applied uniformly or predictably. For example,
there is no uniform worldwide policy regarding patentable subject matter or the scope of claims allowable in biotechnology and
biopharmaceutical patents. Consequently, a patent may not issue from our pending patent applications. Therefore, we do not know
the degree of future protection that we will have on any proprietary product or technology that we have or may develop.
If we are unable to obtain and maintain patent protection
for our technology and products or if the scope of the patent protection obtained is not sufficiently broad, our competitors could
develop and commercialize technology and products similar or identical to ours, and our ability to successfully commercialize our
technology and products may be impaired.
Our commercial success will depend in part
on obtaining and maintaining patent protection and trade secret protection in the United States and other countries with respect
to ADAIR or any other future product, such as ADMIR, that we may license or acquire and the methods we use to manufacture them,
as well as successfully defending these patents and trade secrets against third-party challenges. We seek to protect our proprietary
position by filing patent applications in the United States and abroad related to our proposed products. We will only be able to
protect our technologies from unauthorized use by third parties to the extent that valid and enforceable patents or trade secrets
cover them.
The patent prosecution process is expensive
and time-consuming, and we may not be able to file and prosecute all necessary or desirable patent applications at a reasonable
cost or in a timely manner. It is also possible that we will fail to identify patentable aspects of our research and development
output before it is too late to obtain patent protection. If our licensors or we fail to obtain or maintain patent protection or
trade secret protection for ADAIR or any other future product, such as ADMIR, we may license or acquire, third parties could use
our proprietary information, which could impair our ability to compete in the market and adversely affect our ability to generate
revenues and achieve profitability. Moreover, should we enter into other collaborations we may be required to consult with or cede
control to collaborators regarding the prosecution, maintenance, and enforcement of our patents. Therefore, these patents and applications
may not be prosecuted and enforced in a manner consistent with the best interests of our business.
The patent position of biotechnology and
biopharmaceutical companies generally is highly uncertain, involves complex legal and factual questions, and has in recent years
been the subject of much litigation. In addition, no consistent policy regarding the breadth of claims allowed in biopharmaceutical
or biotechnology patents has emerged to date in the United States. The patent situation outside the U.S. is even more uncertain.
The laws of foreign countries may not protect our rights to the same extent as the laws of the U.S. For example, European patent
law restricts the patentability of methods of treatment of the human body more than U.S. law does. 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 eighteen (18) months after a first filing, or in some cases at all. Therefore, we cannot know
with certainty whether we or our licensors were the first to make the inventions claimed in our owned or licensed patents or pending
patent applications, or whether we were the first to file for patent protection of such inventions. In the event that a third
party has also filed a U.S. patent application relating to our proposed products or a similar invention, we may have to participate
in interference proceedings declared by the U.S. PTO to determine priority of invention in the United
States. The costs of these proceedings could be substantial, and it is possible that our efforts would be unsuccessful, resulting
in a material adverse effect on our U.S. patent position. As a result, the issuance, scope, validity, enforceability, and commercial
value of our patent rights are highly uncertain. Our pending and future patent applications may not result in patents being issued
which protect our technology or products, in whole or in part, or which effectively prevent others from commercializing competitive
technologies and products. 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.
Recent patent reform legislation could increase
the uncertainties and costs surrounding the prosecution of our patent applications and the enforcement or defense of our issued
patents. On September 16, 2011, the Leahy-Smith America Invents Act (the “Leahy-Smith Act”) was signed
into law. The Leahy-Smith Act includes a number of significant changes to U.S. patent law. These include provisions that affect
the way patent applications are prosecuted and may also affect patent litigation. The U.S. PTO recently developed new regulations
and procedures to govern administration of the Leahy-Smith Act, and many of the substantive changes to patent law associated with
the Leahy-Smith Act, and in particular, the first to file provisions, only became effective on March 16, 2013. Accordingly,
it is not clear what, if any, impact the Leahy-Smith Act will have on the operation of our business. However, the Leahy-Smith Act
and its implementation could increase the uncertainties and costs surrounding the prosecution of our patent applications and the
enforcement or defense of our issued patents, all of which could have a material adverse effect on our business and financial condition.
Moreover, we may be subject to a third-party
pre-issuance submission of prior art to the U.S. PTO, or become involved in opposition, derivation, reexamination, inter
parties review, post-grant review or interference proceedings challenging our patent rights or the patent rights of others.
An adverse determination in any such submission, patent office trial, proceeding or litigation could reduce the scope of, render
unenforceable, 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. In addition, if the breadth or strength of protection provided by our patents and patent applications is threatened,
it could dissuade companies from collaborating with us to license, develop or commercialize current or future product.
Even if our patent applications issue as
patents, they may not issue in a form that will provide us with any meaningful protection, prevent competitors from competing with
us or otherwise provide us with any competitive advantage. Our competitors may be able to circumvent our owned or licensed patents
by developing similar or alternative technologies or products in a non-infringing manner.
The issuance of a patent does not foreclose
challenges to its inventorship, scope, validity or enforceability. Therefore, our owned and licensed patents may be challenged
in the courts or patent offices in the United States and abroad. Such challenges may result in loss of exclusivity or freedom to
operate or in patent claims being narrowed, invalidated or held unenforceable, in whole or in part, 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 products. Given the amount of time required for the development, testing, and regulatory review
of new proposed products, patents protecting such proposed products might expire before or shortly after such proposed products
are commercialized. As a result, our owned and licensed patent portfolio may not provide us with sufficient rights to exclude others
from commercializing products similar or identical to ours.
Because it is difficult and costly to protect our proprietary
rights, we may not be able to ensure their protection.
The degree of future protection for our proprietary
rights is uncertain, because legal means afford only limited protection and may not adequately protect our rights or permit us
to gain or keep our competitive advantage. For example:
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our licensors might not have been the first to make the inventions
covered by each of our pending patent applications and issued patents;
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our licensors might not have been the first to file patent applications
for these inventions;
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others may independently develop similar or alternative technologies
or duplicate ADAIR or any future product, such as ADMIR;
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it is possible that none of the pending patent applications licensed
to us will result in issued patents;
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the issued patents covering ADAIR or any future product, such as ADMIR,
may not provide a basis for market exclusivity for active products, may not provide us with any competitive advantages, or may
be challenged by third parties;
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we may not develop additional proprietary technologies that are patentable;
or
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patents of others may have an adverse effect on our
business.
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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 our issued patents
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. Any claims we assert against perceived infringers could provoke these parties to assert counterclaims
against us alleging that we infringe their patents. In addition, in a patent infringement proceeding, a court may decide that a
patent of ours is invalid or unenforceable, in whole or in part, construe the patent’s claims narrowly or refuse to stop
the other party from using the technology at issue on the grounds that our patents do not cover the technology in question. An
adverse result in any litigation proceeding could put one or more of our patents at risk of being invalidated, rendered unenforceable,
or interpreted narrowly.
If we are sued for infringing intellectual property rights
of third parties, it will be costly and time consuming, and an unfavorable outcome in any litigation would harm our business.
Our ability to develop, manufacture, market
and sell ADAIR or any other future product, such as ADMIR, that we may license or acquire depends upon our ability to avoid infringing
the proprietary rights of third parties. Numerous U.S. and foreign issued patents and pending patent applications, which are owned
by third parties, exist in the general fields of ADHD and cover the use of numerous compounds and formulations in our targeted
markets. Because of the uncertainty inherent in any patent or other litigation involving proprietary rights, we and our licensors
may not be successful in defending intellectual property claims by third parties, which could have a material adverse effect on
our results of operations. Regardless of the outcome of any litigation, defending the litigation may be expensive, time-consuming
and distracting to management. In addition, because patent applications can take many years to issue, there may be currently
pending applications, unknown to us, which may later result in issued patents that ADAIR may infringe. There could also be existing
patents of which we are not aware that ADAIR may inadvertently infringe
There is a substantial amount of litigation
involving patent and other intellectual property rights in the biotechnology and biopharmaceutical industries generally. If a third
party claims that we infringe on their patents or misappropriated their technology, we could face a number of issues, including:
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infringement and other intellectual property claims, which, with or
without merit, can be expensive and time consuming to litigate and can divert management’s attention from our core business;
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substantial damages for past infringement which we may have to pay
if a court decides that our product infringes on a competitor’s patent;
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a court prohibiting us from selling or licensing our product unless
the patent holder licenses the patent to us, which it would not be required to do;
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if a license is available from a patent holder, we may have to pay
substantial royalties or grant cross licenses to our patents; and
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redesigning our processes so they do not infringe,
which may not be possible or could require substantial funds and time.
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Intellectual property litigation could cause us to spend
substantial resources and distract our personnel from their normal responsibilities.
Even if resolved in our favor, litigation
or other legal proceedings relating to intellectual property claims may cause us to incur significant expenses, and could distract
our technical and management personnel from their normal responsibilities. In addition, there could be public announcements of
the results of hearings, motions or other interim proceedings or developments and if securities analysts or investors perceive
these results to be negative, it could have a substantial adverse effect on the price of our common stock. Such litigation or proceedings
could substantially increase our operating losses and reduce the resources available for development activities or any future sales,
marketing or distribution activities. We may not have sufficient financial or other resources to conduct such litigation or proceedings
adequately. Some of our competitors may be able to sustain the costs of such litigation or proceedings more effectively than we
can because of their greater financial resources. Uncertainties resulting from the initiation and continuation of patent litigation
or other proceedings could compromise our ability to compete in the marketplace.
We may need to license certain intellectual property from
third parties, and such licenses may not be available or may not be available on commercially reasonable terms.
A third party may hold intellectual property,
including patent rights that are important or necessary to the development and commercialization of ADAIR or any other future product,
such as ADMIR. It may be necessary for us to use the patented or proprietary technology of third parties to commercialize ADAIR
or any other future product. If we are unable to obtain a license from these third parties, or unable to obtain a license, on commercially
reasonable terms, our business could be harmed.
If we fail to comply with our obligations in our intellectual
property licenses and funding arrangements with third parties, we could lose rights that are important to our business.
In the future, we may become party to licenses
that are important for product development and commercialization. If we fail to comply with our obligations under current or future
license and funding agreements, our counterparties may have the right to terminate these agreements, in which event we might not
be able to develop, manufacture or market any product or utilize any technology that is covered by these agreements or may face
other penalties under the agreements. Such an occurrence could materially and adversely affect the value of a proposed product
being developed under any such agreement or could restrict our drug discovery activities. Termination of these agreements or reduction
or elimination of our rights under these agreements may result in our having to negotiate new or reinstated agreements with less
favorable terms, or cause us to lose our rights under these agreements, including our rights to important intellectual property
or technology.
We may be subject to claims that our employees have wrongfully
used or disclosed alleged trade secrets of their former employers.
As is common in the biotechnology and biopharmaceutical
industry, we employ individuals who were previously employed at other biotechnology or biopharmaceutical companies, including our
competitors or potential competitors. Although no claims against us are currently pending, we may be subject to claims that these
employees or we have inadvertently or otherwise used or disclosed trade secrets or other proprietary information of their former
employers. Litigation may be necessary to defend against these claims. Even if we are successful in defending against these claims,
litigation could result in substantial costs and be a distraction to management.
If we are unable to protect the confidentiality of our
trade secrets, our business and competitive position would be harmed.
In addition to seeking patent protection
for ADAIR or any future product, such as ADMIR, we also rely on trade secrets, including unpatented know-how, technology, and other
proprietary information, to maintain our competitive position, particularly where we do not believe patent protection is appropriate
or obtainable. However, trade secrets are difficult to protect. We limit disclosure of such trade secrets where possible, but we
also seek to protect these trade secrets, in part, by entering into non-disclosure and confidentiality agreements with parties
who do have access to them, such as our employees, our licensors, corporate collaborators, outside scientific collaborators, contract
manufacturers, consultants, advisors, and other third parties. We also enter into confidentiality and invention or patent assignment
agreements with our employees and consultants. Despite these efforts, any of these parties may breach the agreements and may unintentionally
or willfully disclose our proprietary information, including our trade secrets, and we may 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. In addition, some courts inside and outside the U.S. are less willing or
unwilling to protect trade secrets. Moreover, if any of our trade secrets were to be lawfully obtained or independently developed
by a competitor, we would have no right to prevent them, or those to whom they communicate it, 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, our competitive
position would be harmed.
Risks Relating to Securities Markets and Our Common Stock
An active, liquid and orderly market for our common stock
may not be maintained.
Prior to our February 2021 initial public
offering, there had been no public market for our common stock. Our common stock only recently began trading on the Nasdaq Capital
Market, but we can provide no assurance that we will be able to develop and sustain an active trading market for our common stock.
Even if an active trading market is developed, it may not be sustained. The lack of an active market may impair your ability to
sell your shares at the time you wish to sell them or at a price that you consider reasonable. An inactive market may also impair
our ability to raise capital by selling shares and may impair our ability to acquire other businesses or technologies using our
shares as consideration, which, in turn, could materially adversely affect our business.
If we cannot continue to satisfy the listing requirements
of The Nasdaq Capital Market and other rules, including the director independence requirements, our securities may be delisted,
which could negatively impact the price of our securities and your ability to sell them.
Although common stock is listed on The Nasdaq
Capital Market, we may be unable to continue to satisfy the listing requirements and rules, including the director independence
requirements and certain financial metrics for our stockholders’ equity and market value of listed securities or net income
from continuing operations. If we are unable to satisfy The Nasdaq Capital Market criteria for maintaining our listing, our securities
could be subject to delisting. If The Nasdaq Capital Market delists our securities, we could face significant consequences, including:
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a limited availability for market quotations for our securities;
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reduced liquidity with respect to our securities;
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a determination that our common stock is a “penny stock,”
which will require brokers trading in our common stock to adhere to more stringent rules and possibly result in reduced trading;
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activity in the secondary trading market for our common stock;
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limited amount of news and analyst coverage; and
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a decreased ability to issue additional securities or obtain additional financing in the future.
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In addition, we would no longer be subject
to The Nasdaq Capital Market rules, including rules requiring us to have a certain number of independent directors and to meet
other corporate governance standards.
Our stock may be subject to substantial price and volume
fluctuations due to a number of factors, many of which are beyond our control and may prevent our stockholders from reselling our
common stock at a profit.
The market prices for securities of biotechnology
and biopharmaceutical companies have historically been highly volatile, and the market has from time to time experienced significant
price and volume fluctuations that are unrelated to the operating performance of particular companies. In particular, the trading
prices for pharmaceutical, biopharmaceutical and biotechnology companies have been highly volatile as a result of the COVID-19
pandemic.
The market price of our common stock is likely
to be highly volatile and may fluctuate substantially due to many factors, including:
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results from, and any delays in, our clinical trials for our product
candidates, including ADAIR and ADMIR, or any other future clinical development programs, including any delays related to the COVID-19
pandemic;
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announcements concerning the progress of our efforts
to obtain regulatory approval for and commercialize ADAIR or any future product, including ADMIR, including any requests we receive
from the FDA for additional studies or data that result in delays in obtaining regulatory approval or launching such proposed product,
if approved;
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market conditions in the biopharmaceutical and biotechnology sectors
or the economy as a whole;
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price and volume fluctuations in the overall stock market;
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the failure of ADAIR or any future product, such as ADMIR, if approved,
to achieve commercial success;
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announcements of the introduction of new products by us or our competitors;
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developments concerning product development results or intellectual
property rights of others;
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litigation or public concern about the safety of our potential products;
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actual fluctuations in our quarterly operating results, and concerns
by investors that such fluctuations may occur in the future;
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deviations in our operating results from the estimates of securities
analysts or other analyst comments;
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additions or departures of key personnel;
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health care reform legislation, including measures directed at controlling
the pricing of biopharmaceutical products, and third-party coverage and reimbursement policies;
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developments concerning current or future strategic collaborations;
and
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discussion of us or our stock price by the financial
and scientific press and in online investor communities.
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In addition, the stock markets have experienced
extreme price and volume fluctuations that have affected and continue to affect the market prices of equity securities of many
biopharmaceutical companies. If we were to become involved in securities litigation, it could subject us to substantial costs,
divert resources and the attention of management from our business and adversely affect, our business, operating results, financial
condition and cash flows.
If securities or industry analysts do not publish or cease
publishing research or reports about us, our business or our market, or if they adversely change their recommendations or publish
negative reports regarding our business or our common stock, a liquid trading market, if any, for our common stock may not develop,
and if it does, our share price and trading volume could decline.
The trading market for our common stock will
be influenced by the research and reports that industry or securities analysts may publish about us, our business, our market or
our competitors. We do not have any control over these analysts and analysts may not provide favorable coverage, or any coverage
at all. If any of the analysts that do cover us make an adverse recommendation regarding our stock, or provide more favorable relative
recommendations about our competitors, our stock price would likely decline. If any analyst who may cover us were to cease coverage
of our company or fail to regularly publish reports on us, we could lose visibility in the financial markets, which in turn could
cause our share price or trading volume to decline.
Because we do not intend to declare cash dividends on
our common stock in the foreseeable future, stockholders must rely on appreciation of the value of our common stock for any return
on their investment.
We have never declared or paid cash dividends
on our common stock. We currently anticipate that we will retain future earnings for the development, operation and expansion of
our business and do not anticipate declaring or paying any cash dividends in the foreseeable future.
Our significant stockholders may exert a substantial influence
on actions requiring a stockholder vote, potentially in a manner that you do not support.
As of March 15, 2021, Medice, through its
affiliated entity, Salmon Pharma owns approximately 22.4% of our issued and outstanding shares of common stock, and accordingly
controls approximately 22.4% of our voting power. In addition, Arcturus owns approximately 12.4% of our issued and outstanding
shares of common stock, and accordingly controls approximately 12.4% of our voting power. Members of our board of directors and
management beneficially own approximately 39.4% of our issued and outstanding shares of common stock, and accordingly will control
approximately 39.4% of our voting power, assuming exercise of all stock options exercisable within 60 days of March 15, 2021.
If Salmon Pharma, Arcturus or any member of our board or management acquires additional shares of common stock in the aftermarket
or in privately negotiated transactions, this would increase their control. Factors that would be considered in making such additional
purchases would include consideration of the current trading price of our common stock.
Salmon Pharma and Arcturus’s large
ownership stake may allow it to exert a substantial influence on actions requiring a stockholder vote, potentially in a manner
that you do not support, including amendments to our amended and restated certificate of incorporation, election of our board of
directors, removal of any of our directors, adoption of measures that could delay or prevent a change in control or impede a merger,
takeover, or other business combination involving us, and approval of other major corporate transactions. In addition, Salmon Pharma
and Arcturus’s stock ownership may discourage a potential acquirer from making a tender offer or otherwise attempting to
obtain control of us, which in turn could reduce our stock price or prevent our stockholders from realizing a premium over our
stock price. Accordingly, our stockholders other than Salmon Pharma and Arcturus may be unable to influence management and exercise
control over our business.
Our charter documents and Delaware law may inhibit a takeover
that stockholders consider favorable.
Certain provisions of our amended and restated
certificate of incorporation and our amended and restated bylaws and applicable provisions of Delaware law may delay or discourage
transactions involving an actual or potential change in control or change in our management, including transactions in which stockholders
might otherwise receive a premium for their shares, or transactions that our stockholders might otherwise deem to be in their best
interests. The provisions in our amended and restated certificate of incorporation and amended and restated bylaws:
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limit who may call stockholder meetings;
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do not provide for cumulative voting rights;
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provide that all vacancies may be filled only by the affirmative vote
of a majority of directors then in office, even if less than a quorum;
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provide that the Court of Chancery of the State of Delaware will be
the exclusive forum for certain legal claims; and
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provide that the federal district courts of the United
States of American will be the exclusive forum for legal claims under the Securities Act.
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In addition, once we become a publicly traded
corporation, Section 203 of the Delaware General Corporation Law may limit our ability to engage in any business combination
with a person who beneficially owns 15% or more of our outstanding voting stock unless certain conditions are satisfied. This
restriction lasts for a period of three years following the share acquisition. These provisions may have the effect of entrenching
our management team and may deprive you of the opportunity to sell your shares to potential acquirers at a premium over prevailing
prices. This potential inability to obtain a control premium could reduce the price of our common stock. See Exhibit 4.5 “Description
of Capital Stock” for additional information.
Financial reporting obligations of being a public company
in the United States require well defined disclosure and financial controls and procedures that are expensive and time-consuming
requiring our management to devote substantial time to compliance matters.
As a publicly traded company, we incur significant
legal, accounting and other expenses that we did not incur as a privately held company prior to the completion of our initial public
offering in February 2021. For example, as a privately held company, we were not required to have, and did not have, well defined
disclosure and financial controls and procedures or systems of internal controls over financial reporting that are generally required
of publicly held companies. We determined that our internal controls over financial reporting include material weaknesses that
need to be remedied. Although we intend to take steps to remedy these material weaknesses in order to assure compliance with our
future financial reporting obligations, there can be no assurance that we will be able to do so in a timely manner or at all.
These reporting obligations associated with
being a public company in the United States require significant expenditures and place significant demands on our management and
other personnel, including costs resulting from our reporting obligations under the Exchange Act and the rules and regulations
regarding corporate governance practices, including those under the Sarbanes-Oxley Act, the Dodd-Frank Wall Street Reform and
Consumer Protection Act, as amended, (the “Dodd-Frank Act”), and the listing requirements of The Nasdaq Capital
Market. These rules require the establishment and maintenance of effective disclosure and financial controls and procedures, internal
control over financial reporting and changes in corporate governance practices, among many other complex rules that are often
difficult to implement, monitor and maintain compliance with. Moreover, despite recent reforms made possible by the JOBS Act,
the reporting requirements, rules, and regulations may make some activities more time-consuming and costly, particularly after
we are no longer an “emerging growth company.” In addition, we expect these rules and regulations to make it more
difficult and more expensive for us to maintain director and officer liability insurance. Our management and other personnel need
to devote a substantial amount of time to ensure that we comply with all of these requirements and to keep pace with new regulations,
otherwise we may fall out of compliance and risk becoming subject to litigation or being delisted, among other potential problems.
If we fail to comply with the rules under
the Sarbanes-Oxley Act related to accounting controls and procedures in the future, or, if we discover additional material weaknesses
and other deficiencies in our internal control and accounting procedures, our stock price could decline significantly and raising
capital could be more difficult. Section 404 of the Sarbanes-Oxley Act requires annual management assessments of the effectiveness
of our internal control over financial reporting after a transition period ending with our second annual report on Form 10-K filed
under Section 13(a) of the Exchange Act. If we fail to comply with the rules under the Sarbanes-Oxley Act related to disclosure
controls and procedures in the future, or, if in the future we discover additional material weaknesses and other deficiencies in
our internal control and accounting procedures, our stock price could decline significantly and raising capital could be more difficult.
Raising additional capital may cause dilution to our stockholders
restrict our operations, or require us to relinquish rights to our technologies or product candidates.
Until such time, if ever, as we can generate
substantial revenue, we may finance our cash needs through a combination of equity offerings, debt financings, marketing and distribution
arrangements and other collaborations, strategic alliances and licensing arrangements or other sources. We do not currently have
any committed external source of funds. In addition, we may seek additional capital due to favorable market conditions or strategic
considerations, even if we believe that we have sufficient funds for our current or future operating plans.
To the extent that we raise additional capital
through the sale of equity or convertible debt securities, your ownership interest will be diluted, and the terms of these securities
may include liquidation or other preferences that adversely affect your rights as a common stockholder. Debt financing and preferred
equity 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 raise additional funds through
collaborations, strategic alliances or marketing, distribution or licensing arrangements with third parties, we may be required
to relinquish valuable rights to our technologies, intellectual property, future revenue streams or product candidates or grant
licenses on terms that may not be favorable to us. If we are unable to raise additional funds through equity or debt financings
when needed, we may be required to delay, limit, reduce or terminate product candidate development or future commercialization
efforts.