Item 1A. Risk Factors
Investing in our common stock involves a high
degree of risk. Before making an investment decision, you should carefully consider the risks described below before deciding whether
to invest in our common stock. Before you make a decision to buy our securities, in addition to the risks and uncertainties discussed
above under “Cautionary Note Regarding Forward-Looking Statements”, you should carefully consider the specific
risks set forth herein. If any of these risks actually occur, it may materially harm our business, financial condition, liquidity
and results of operations. As a result, the market price of our securities could decline, and you could lose all or part of your investment.
Additionally, the risks and uncertainties described below are not the only risks and uncertainties that we face. Additional risks and
uncertainties not presently known to us or that we currently believe to be immaterial may become material and adversely affect our business.
Risk Factor Summary
Below is a summary of the principal factors that
make an investment in our common stock speculative or risky. This summary does not address all of the risks that we face. Additional
discussion of the risks summarized in this risk factor summary, and other risks that we face, can be found below and should be carefully
considered, together with other information in this Quarterly Report on Form 10-Q and our other filings with the Securities and Exchange
Commission (the “SEC”) before making an investment decision regarding our common stock. Risk factors marked with an asterisk
(*) below include a substantive change from or an update to the risk factors included in our Annual Report on Form 10-K for the fiscal
year ended December 31, 2021, filed with the SEC on March 18, 2022.
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Risks Related to Our Financial Position and Need for
Additional Capital, including, among others, that: |
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We have incurred significant net losses and negative
operating cash flows since our inception. We expect to incur net losses for the foreseeable future and may never achieve or maintain
profitability. |
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We will need substantial additional
funding, which may not be available on acceptable terms, or at all. If we are unable to raise capital when needed, we would be forced
to delay, reduce or eliminate our research and product development programs or future commercialization efforts. |
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As a result of our history
of losses and negative cash flows from operations, our consolidated financial statements contain a statement regarding a substantial
doubt about our ability to continue as a going concern. |
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Risks Related to Discovery, Development, Manufacturing
and Commercialization, including, among others, that: |
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We are substantially dependent on the success of our
most advanced product candidate, JSP191. If we are unable to complete development of, obtain approval for and commercialize our product
candidates, including JSP191, in a timely manner or at all, our business will be harmed. |
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We may not be successful in our efforts to identify,
develop and commercialize additional product candidates. If these efforts are unsuccessful, we may never become a commercial stage
company or generate any revenues. |
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mRNA stem cell grafts are a novel technology that is
not yet clinically validated for human use. The approaches we are taking to create mRNA stem cell grafts are unproven and may never
lead to marketable products. |
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If any of our product candidates cause serious adverse
events, undesirable side effects or unexpected characteristics, such events, side effects or characteristics could delay or prevent
regulatory approval of the product candidate, limit our commercial potential or result in significant negative consequences following
any potential marketing approval. |
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Results of preclinical studies and early clinical trials
may not be predictive of results of future clinical trials, and such results do not guarantee approval of a product candidate by
regulatory authorities. In addition, our clinical trials to date have been limited in scope, and results received to date may not
be replicated in expanded or additional future clinical trials. |
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We have never obtained regulatory approval for a drug,
may never receive regulatory approval for any of our product candidates, and may therefore never generate revenues from product sales. |
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We face significant competition in an environment of
rapid technological change, and there is a possibility that our competitors may achieve regulatory approval before us or develop
therapies that are safer or more advanced or effective than ours, which may harm our financial condition and our ability to successfully
market or commercialize our product candidates. |
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Risks Related to Regulatory Review, including, among
others, that: |
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If clinical trials of our product candidates fail to
demonstrate safety and efficacy to the satisfaction of regulatory authorities or do not otherwise produce positive results, we may
incur additional costs or experience delays in completing, or ultimately be unable to complete, the development and commercialization
of such product candidates. |
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Stem cell transplant is a high-risk procedure
with curative potential that may result in complications or adverse events for patients in our clinical trials or for patients that
use any of our product candidates, if approved. |
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Risks Related to Our Relationships with Third Parties,
including, among others, that: |
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We rely on third parties to conduct our preclinical
and clinical trials and will rely on them to perform other tasks for us. If these third parties do not successfully carry out their
contractual duties, meet expected deadlines or comply with regulatory requirements, we may not be able to obtain regulatory approval
for or commercialize our product candidates and our business could be substantially harmed. |
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We currently rely on a single
manufacturer for our clinical supply of our product candidates. In the event of a loss of this manufacturer, or a failure by such
manufacturer to comply with FDA regulations, we may not be able to find an alternative source on commercially reasonable terms, or
at all. In addition, third-party manufacturers and any third-party collaborators may be unable to successfully scale-up manufacturing
of our current or future product candidates in sufficient quality and quantity, which would delay or prevent us from developing our
product candidates and commercializing approved products, if any. |
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Risks Related to Our Intellectual Property, including,
among others, that: |
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We are highly dependent on intellectual property licensed
from third parties, and termination of any of these licenses could result in the loss of significant rights, which would harm our
business. |
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Our commercial success depends on our ability to obtain,
maintain and protect our intellectual property and proprietary technology. |
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Risks Related to Ownership of Our Common Stock and
Warrants, including, among others, that we will incur significant increased expenses and administrative burdens as a public company,
which could negatively impact our business, financial condition and results of operations. |
Risks Related to Our Financial Position and Need for Additional
Capital
*We have incurred significant net losses and negative operating
cash flows since our inception. We expect to incur net losses for the foreseeable future and may never achieve or maintain profitability.
We are a clinical-stage biotechnology company
dedicated to enabling cures through hematopoietic stem cell therapy and have a limited operating history. Investment in biopharmaceutical
product development is highly speculative because it entails substantial upfront capital expenditures and significant risk that any potential
product candidate will fail to demonstrate adequate effect or an acceptable safety profile, gain regulatory approval and become commercially
viable. We have no products approved for commercial sale and have not generated any revenue from product sales to date, and we continue
to incur significant research and development and other expenses related to our ongoing operations. As a result, we are not profitable
and have incurred losses and negative operating cash flows in each period since our inception. For the nine months ended September 30,
2022 and 2021, we reported net losses of $24.5 million and $21.6 million, respectively. For the nine months ended September 30, 2022
and 2021, we reported negative operating cash flows of $33.2 million and $19.1 million, respectively. As of September 30, 2022, we had
an accumulated deficit of $91.9 million. We have devoted all of our efforts to organizing and staffing our company, business and scientific
planning, raising capital, acquiring and developing technology, identifying potential product candidates, undertaking research and preclinical
studies of potential product candidates, developing manufacturing capabilities and evaluating a clinical path for our pipeline programs.
We expect to continue to incur significant expenses and increasing operating losses for the foreseeable future, and we expect these losses
to increase as we continue our research and development of, and seek regulatory approvals for, our product candidates.
The net losses we incur may fluctuate significantly
from quarter to quarter. We anticipate that our expenses will increase substantially if and as we:
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continue the open label Phase 1/2 clinical trial
for JSP191 for SCID, and the open label Phase 1 clinical trial for JSP191 in patients with MDS or AML; |
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continue the clinical development of JSP191 in autoimmune
diseases and other indications; |
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continue our current research programs and development
of other potential product candidates from our current research programs; |
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seek to identify additional product candidates and
research programs; |
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initiate preclinical testing and clinical trials for
any other product candidates we identify and develop; |
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maintain, expand, enforce, defend and protect our intellectual
property portfolio, and provide reimbursement of third-party expenses related to our patent portfolio; |
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seek marketing approvals for any product candidates
that successfully complete clinical trials; |
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ultimately establish a sales, marketing and distribution
infrastructure to commercialize any product candidates for which we may obtain marketing approval; |
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adapt our regulatory compliance efforts to incorporate
requirements applicable to any approved product candidates; |
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further develop our genome engineering capabilities; |
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hire additional research and development and clinical
personnel; |
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hire commercial personnel and advance market access
and reimbursement strategies; |
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add operational, financial and management information
systems and personnel, including personnel to support our product development; |
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acquire or in-license product candidates, intellectual
property and technologies; |
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develop or in-license manufacturing and distribution
technologies; |
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should we decide to do so and receive approval for
any of our product candidates, build and maintain, or purchase and validate, commercial-scale manufacturing facilities designed
to comply with current Good Manufacturing Practices (“cGMP”) requirements; and |
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incur additional legal, accounting and other expenses
in operating as a public company. |
As a company, we have not completed clinical development
of any product candidate and expect that it will be several years, if ever, before we have a product candidate ready for commercialization.
To become and remain profitable, we must develop and, either directly or through collaborators, eventually commercialize a product or
products with significant market potential. This will require us to be successful in a range of challenging activities, including identifying
product candidates, completing preclinical testing and clinical trials of product candidates, obtaining marketing approval for these
product candidates, manufacturing, marketing and selling those products for which we may obtain marketing approval and satisfying any
post-marketing requirements.
We may never succeed in these activities and,
even if we do, may never generate revenues that are significant or large enough to achieve profitability. Our product candidates and
research programs are currently only in the early stages of development. Because of the numerous risks and uncertainties associated with
developing product candidates, we are unable to predict the extent of any future losses or when we will become profitable, if at all.
If we do achieve profitability, we may not be able to sustain or increase profitability on a quarterly or annual basis. Our failure to
become and remain profitable would decrease the value of our company and could impair our ability to raise capital, maintain our research
and development efforts, expand our business or continue our operations. A decline in the value of our company could also cause
you to lose all or part of your investment.
*We will need substantial additional funding, which may not
be available on acceptable terms, or at all. If we are unable to raise capital when needed, we would be forced to delay, reduce or eliminate
our research and product development programs or future commercialization efforts.
We expect to spend substantial amounts of cash
to conduct further research and development and preclinical testing and clinical trials of our product candidates, to seek regulatory
approvals for our product candidates and to launch and commercialize any product candidates for which we receive regulatory approval.
Furthermore, we expect to incur additional costs associated with operating as a public company. Accordingly, we will need to obtain substantial
additional funding in order to maintain our continuing operations. If we are unable to raise capital when needed or on attractive terms,
we would be forced to delay, reduce or eliminate our research and product development programs or future commercialization efforts. As
of September 30, 2022, our cash and cash equivalents were $51.0 million and we had an accumulated deficit of $91.9 million. Our future
financing requirements will depend on many factors, including:
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the initiation, progress, timing, costs and results
of preclinical studies and clinical trials for our product candidates, including any COVID-19-related delays or other effects
on our development programs; |
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the costs of continuing to build our technology platform,
including in-licensing additional genome engineering technologies for use in developing our product candidates; |
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the costs of developing, acquiring or in-licensing additional
targeted therapies to use in combination with JSP191 and other product candidates we may develop; |
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the costs of preparing, filing and prosecuting patent
applications, maintaining and enforcing our intellectual property and proprietary rights and defending intellectual property-related claims
in the United States and internationally; |
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the number and characteristics of product candidates
that we develop or may in-license; |
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our ability to establish and maintain collaborations
on favorable terms, if at all; |
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the achievement of milestones or occurrence of other
developments that trigger payments under any collaboration agreements we enter into; |
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the outcome, timing and cost of meeting regulatory
requirements established by the FDA, the European Medical Agency (the “EMA”) and other comparable foreign regulatory
authorities; |
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the cost and timing of completion of commercial-scale outsourced
manufacturing activities; |
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the cost of establishing sales, marketing and distribution
capabilities for any product candidates for which we may receive regulatory approval in regions where we choose to commercialize
our products on our own; and |
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the costs of operating as a public company. |
Conducting preclinical testing and clinical trials
is a time-consuming, expensive and uncertain process that takes years to complete, and we may never generate the necessary data
or results required to obtain marketing approval and achieve product sales. In addition, even if we successfully develop product candidates
and those are approved, we may not achieve commercial success. Our commercial revenues, if any, will be derived from sales of products
that we do not expect to be commercially available for several years, if at all. Accordingly, we will need to continue to rely
on additional financing to achieve our business objectives.
We
currently have an effective universal shelf registration statement on Form S-3, which we
filed with the SEC on October 7, 2022, and which was declared effective on October 18, 2022
and will expire on October 18, 2025. We may use the shelf registration statement on Form
S-3 to offer from time to time up to $150.0 million of securities, including any combination
of common stock, preferred stock, debt securities, warrants, rights, units and depositary
shares. On November 10, 2022, we entered into a Controlled Equity OfferingSM Sales
Agreement with Cantor Fitzgerald & Co. (the “Agent”), pursuant to which we
may offer and sell through or to the Agent, as sales agent or principal, shares of our voting
common stock from time to time (the “ATM Offering”). However, for so long as
the aggregate market value of our outstanding common stock held by non-affiliates is less
than $75.0 million, in no event will we be able to sell securities pursuant to the shelf
registration statement (including pursuant to the ATM Offering) with a value more than one-third
of the aggregate market value of our common stock held by non-affiliates in any 12-month
period.
If
we raise additional capital by issuing equity securities, the percentage ownership of our
existing stockholders may be reduced, and accordingly these stockholders may experience substantial
dilution. We may also issue equity securities that provide for rights, preferences and privileges
senior to those of our common stock. Given our need for cash and that equity issuances are
the most common type of fundraising for similarly situated companies, the risk of dilution
is particularly significant for our stockholders.
Any additional fundraising efforts may divert
our management from our day-to-day activities, which may adversely affect our ability to develop and commercialize product candidates.
We cannot be certain that additional funding will be available on acceptable terms, or at all. We have no committed source of additional
capital and, if we are unable to raise additional capital in sufficient amounts or on terms acceptable to us, we may have to significantly
delay, scale back or discontinue the development or commercialization of product candidates or other research and development initiatives.
Our license agreements and any future collaboration agreements may also be terminated if we are unable to meet the payment or other obligations
under the agreements. We could be required to seek collaborators for product candidates at an earlier stage than otherwise would be desirable
or on terms that are less favorable than might otherwise be available or relinquish or license on unfavorable terms our rights to product
candidates in markets where we otherwise would seek to pursue development or commercialization ourselves.
As a result of our recurring losses from operations
and recurring negative cash flows from operations, our management concluded that there is a substantial doubt about our ability to maintain
liquidity sufficient to operate our business effectively, which raise substantial doubt about our ability to continue as a going concern.
See the risk factor below titled, “As a result of our history of losses and negative cash flows from operations, our consolidated
financial statements contain a statement regarding a substantial doubt about our ability to continue as a going concern.” Based
on our current operating plan, we will need to raise additional financing to continue our products’ development for the foreseeable
future, and until we become profitable. If we are unable to obtain funding when and as needed on a timely basis, we may be required to
significantly curtail, delay or discontinue one or more of our research or development programs or the commercialization of any product
candidate, or be unable to expand our operations or otherwise capitalize on our business opportunities, as desired, which could materially
affect our business, financial condition and results of operations. Any of the above events could significantly harm our business, prospects,
financial condition and results of operations and cause the price of our common stock to decline.
We have a limited operating history and no history of commercializing
pharmaceutical products, which may make it difficult to evaluate the prospects for our future viability.
We are a clinical stage company. Old Jasper was
founded and commenced operations in March 2018. Our operations to date have been limited to organizing and staffing our company,
business planning, raising capital, acquiring and developing our technology, identifying potential product candidates and undertaking
preclinical studies and clinical trials. Although we have initiated clinical trials for JSP191, we have not yet demonstrated an ability
to successfully complete clinical trials of our product candidates; obtained marketing approvals; manufactured a commercial-scale medicine
or therapy, or arranged for a third party to do so on our behalf; or conducted sales and marketing activities necessary for successful
commercialization. Typically, it takes about 10 to 15 years to develop a new medicine from the time it is discovered
to when it is available for treating patients. Consequently, any predictions we make about our future success or viability may not be
as accurate as they could be if we had a longer operating history.
In addition, as a young business, we may encounter
unforeseen expenses, difficulties, complications, delays and other known and unknown factors. We will need to transition at some point
from a company with a research and development focus to a company capable of supporting commercial activities. We may not be successful
in such a transition.
We have never generated revenue from product sales and may never
be profitable.
Our ability to generate revenue from product sales
and achieve profitability depends on our ability, alone or with collaborators, to successfully complete the development of, and obtain
the regulatory approvals necessary to commercialize, product candidates. We do not anticipate generating revenues from product sales
for the next several years, if ever. Our ability to generate future revenue from product sales depends heavily on our, or our future
collaborators’, ability to successfully:
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identify product candidates and complete research and
preclinical and clinical development of any product candidates we may identify; |
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seek and obtain regulatory and marketing approvals
for any product candidates for which we complete clinical trials; |
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launch and commercialize any product candidates for
which we obtain regulatory and marketing approval by establishing a sales force, marketing and distribution infrastructure or, alternatively,
collaborating with a commercialization partner; |
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qualify for coverage and adequate reimbursement by
government and third-party payors for any product candidates for which we obtain regulatory and marketing approval; |
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develop, maintain, and enhance a sustainable, scalable,
reproducible, and transferable manufacturing process for the product candidates we may develop; |
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establish and maintain supply and manufacturing relationships
with third parties that can provide adequate, in both amount and quality, products and services to support clinical development and
the market demand for any product candidates for which we obtain regulatory and marketing approval; |
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obtain market acceptance of product candidates as viable
treatment options; |
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address competing technological and market developments; |
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implement internal systems and infrastructure, as needed; |
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negotiate favorable terms in any collaboration, licensing
or other arrangements into which we may enter, and perform our obligations in such arrangements; |
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maintain, protect, enforce, defend and expand our portfolio
of intellectual property rights, including patents, trade secrets and know-how, in the United States and internationally; |
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avoid and defend against third-party interference,
infringement and other intellectual property claims in the United States and internationally; and |
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attract, hire and retain qualified personnel. |
Even if one or more of the product candidates
we develop are approved for commercial sale, we anticipate incurring significant costs associated with commercializing any approved product
candidate. Our expenses could increase beyond expectations if we are required by the FDA, the EMA or other regulatory authorities to
perform clinical and other studies in addition to those that we currently anticipate.
Many of the factors listed above are beyond our
control, and could cause us to experience significant delays or prevent us from completing the development of our product candidates,
obtaining regulatory approvals or commercializing our product candidates. Even if we do achieve profitability, we may not be able to
sustain or increase profitability on a quarterly or annual basis. A failure to become or remain profitable could result in a decline
in the value of our company and could also cause you to lose all or part of your investment.
As a result of our history of losses and negative cash flows
from operations, our consolidated financial statements contain a statement regarding a substantial doubt about our ability to continue
as a going concern.
Our history of operating losses and negative cash
flows from operations combined with our anticipated use of cash to fund operations raises substantial doubt about our ability to continue
as a going concern beyond the 12-month period from the issuance date of our consolidated financial statements included in Part
I, Item 1 of this Quarterly Report on Form 10-Q. Based on our current operating plan, we will need to raise additional financing to continue
our products’ development for the foreseeable future, and until we become profitable. Our future viability as an ongoing business
is dependent on our ability to generate cash from our operating activities or to raise additional capital to finance our operations.
The perception that we might be unable to continue
as a going concern may also make it more difficult to obtain financing for the continuation of our operations on terms that are favorable
to us, or at all, and could result in the loss of confidence by investors and employees. Our consolidated financial statements do not
include any adjustments that might result from the outcome of this uncertainty. If we are unable to continue as a going concern, we may
have to liquidate our assets and may receive less than the value at which those assets are carried on our consolidated financial statements,
and it is likely that our investors will lose all or a part of their investment.
Our ability to utilize our net operating loss carryforwards
and certain other tax attributes to offset taxable income or taxes may be limited.
As
of December 31, 2021, we had net operating loss carryforwards for federal income tax
purposes of $53.1 million that can be carried forward indefinitely. As of December 31,
2021, we had net operating loss carryforwards for state income tax purposes of $45.4 million
that begin to expire in 2038. Portions of these net operating loss carryforwards could
expire unused and be unavailable to offset future income tax liabilities. Under the legislation
enacted in 2017, informally titled the Tax Cuts and Jobs Act (the “Tax Act”),
as modified by the Coronavirus Aid, Relief, and Economic Security Act (the “CARES Act”),
U.S. federal net operating losses incurred in taxable years beginning after December 31,
2017 may be carried forward indefinitely, but the deductibility of such federal net operating
losses in taxable years beginning after December 31, 2020 is limited. It is uncertain
how various states will respond to the Tax Act and the CARES Act. For state income tax purposes,
there may be periods during which the use of net operating loss carryforwards is suspended
or otherwise limited, which could accelerate or permanently increase state taxes owed. In
addition, under Sections 382 and 383 of the Internal Revenue Code of 1986, as amended
(the “Code”), and corresponding provisions of state law, if a corporation undergoes
an “ownership change,” which is generally defined as a greater than 50%
change, by value, in its equity ownership over a three-year period, the corporation’s
ability to use its pre-change net operating loss carryforwards and other pre-change tax attributes
to offset its post-change income or taxes may be limited. Our existing net operating loss
carryforwards may be subject to limitations arising out of previous ownership changes and
we may be limited as to the amount that can be utilized each year as a result of such previous
ownership changes, including our business combination with AMHC that was completed in September
2021 (the “Business Combination”) and related transactions. In addition, future
changes in our stock ownership, including future offerings, as well as other changes that
may be outside of our control, could result in additional ownership changes. We have completed
a Section 382 analysis covering taxable periods from our inception through the year
ended December 31, 2021. We experienced an ownership change on November 21, 2019
for both federal and California tax purposes related to our Series A redeemable convertible
preferred stock financing. Any net operating loss generated for taxable periods in 2018 and
through November 21, 2019 in excess of $2.87 million will be permanently limited
for California tax purposes. We reduced our California net operating loss deferred tax assets
balance by the permanently limited amount of $0.6 million. There would be no permanent
loss of federal net operating loss based on the limits. We experienced an additional ownership
change on September 24, 2021. However, we do not expect there are additional tax attributes
that will expire unused before the expiration periods. There is a full valuation allowance
for net deferred tax assets, including net operating loss carryforwards for the year ended
December 31, 2021.
Our business could be adversely affected by the effects of health
pandemics or epidemics, including the current COVID-19 pandemic and future outbreaks of the disease, in regions where we or third parties
on which we rely have concentrations of clinical trial sites or other business operations.
Our business could be adversely affected by the
effects of health pandemics or epidemics, including the current COVID-19 pandemic and future outbreaks of the disease, including any
variants thereof. For example, enrollment in clinical trials may be delayed. Although we have reopened our offices and some employees
have transitioned back to working on site, there is a lack of uniformity of restrictions and requirements among our clinical trial sites,
and future restrictions could be imposed. We are subject to risk of outbreaks at our facilities, and potential exposure to employee claims
regarding workplace safety, and unanticipated shutdowns or quarantines could be imposed in the future, which would disrupt our operations.
This uncertainty and the evolving nature of policies and restrictions may negatively impact productivity, disrupt our business and further
delay clinical programs and timelines, the magnitude of which will depend, in part, on the length and severity of the restrictions and
other limitations on our ability to conduct our business in the ordinary course, which could negatively impact our business, operating
results and financial condition.
The spread of COVID-19, which has caused a broad
impact globally, may affect us economically. While the potential economic impact brought by, and the duration of, the COVID-19 pandemic
may be difficult to assess or predict, it has resulted in significant disruption of global financial markets. This disruption, if sustained
or recurrent, could make it more difficult for us to access capital, which could in the future negatively affect our liquidity. In addition,
a recession or market correction resulting from the spread of COVID-19 or the global impacts thereof could materially affect our business
and the value of our common stock. The global COVID-19 pandemic continues to evolve, and its ultimate impact or that of any similar health
pandemic or epidemic is highly uncertain. We do not yet know the full extent of potential delays or impacts on our business, our planned
and ongoing clinical trials, the hospitals and healthcare systems or the global economy as a whole. These effects could have an adverse
impact on our operations, and we will continue to monitor the COVID-19 situation closely.
Business disruptions caused by natural or man-made disasters,
acts of war or other hostilities could seriously harm our future revenues and financial condition and increase our costs and expenses
generally.
Our corporate headquarters are located in the
San Francisco Bay Area, a region known for seismic activity. Our suppliers may also experience a disruption in their business as a result
of natural or man-made disasters. A significant natural or man-made disaster, such as an earthquake, prolonged or repeated power outage,
hurricane, flood, fire, drought or other extreme weather events and changing weather patterns, which are increasing in frequency due
to the impacts of climate change, could severely damage or destroy our headquarters or facilities or the facilities of our manufacturers
or suppliers, which could have a material and adverse effect on our business, financial condition and results of operations. In addition,
terrorist acts, acts of war or the outbreak of hostilities against the U.S. or other countries globally, could cause damage or disruption
to us, our employees, facilities, partners and suppliers, which could have a material adverse effect on our business, financial condition
and results of operations.
Risks Related to Discovery, Development, Manufacturing and Commercialization
We are substantially dependent on the success of our most advanced
product candidate, JSP191. If we are unable to complete development of, obtain approval for and commercialize our product candidates,
including JSP191, in a timely manner or at all, our business will be harmed.
Our future success is dependent on our ability
to timely advance and complete clinical trials, obtain marketing approval for and successfully commercialize our product candidates.
We are not permitted to market or promote JSP191 or any other product candidate before we receive marketing approval from the FDA and
comparable foreign regulatory authorities, and we may never receive such marketing approvals.
The success of our product candidates will depend
on several factors, including the following:
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the acceptance of individual investigational review
boards (“IRBs”) and scientific review committees at each clinical trial site as to the adequacy of the preclinical data
package to support clinical development of JSP191 and their overall general agreement with the use of JSP191 in the intended patient
population in the intended manner; |
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the willingness of clinical investigators to place
patients in the clinical trials, and the willingness of patients to enroll in a clinical trial studying a first-in-human cell therapy; |
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the initiation and successful patient enrollment and
completion of additional clinical trials of JSP191 on a timely basis; |
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the frequency and severity of adverse events in the
clinical trials; |
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the successful and timely completion of our ongoing
Phase 1/2 clinical trial of JSP191 for the treatment of SCID and the ongoing Phase 1 clinical trial of JSP191 for AML or MDS; |
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maintaining and establishing relationships with contract
research organizations (“CROs”) and clinical sites for the clinical development of JSP191 both in the United States and
internationally; |
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successful completion of toxicology studies, biodistribution
studies and minimally efficacious dose studies in animals, where applicable; |
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successful completion of clinical trials, under the
FDA’s current Good Clinical Practices (“cGCPs”) and the FDA’s current Good Laboratory Practices; |
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effective investigational new drug (“IND”)
applications or Clinical Trial Authorizations that allow commencement of our planned clinical trials or future clinical trials for
our product candidates; |
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the results of clinical trials conducted by third parties
in hematopoietic stem cell transplant (“HSCT”) if such trials result in changes to the standard of care for HSCT or otherwise
cause us to change our clinical trial protocols; |
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the efficacy, safety and tolerability profiles that
are satisfactory to the FDA, EMA or any comparable foreign regulatory authority for marketing approval; |
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the timely receipt of marketing approvals for our product
candidates from applicable regulatory authorities; |
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the extent of any required post-marketing approval
commitments to applicable regulatory authorities; |
|
● |
the maintenance of existing or the establishment of
new supply arrangements with third-party suppliers and manufacturers for clinical development of JSP191; |
|
● |
the maintenance of existing, or the establishment of
new, scaled production arrangements with third-party manufacturers to obtain finished products that are appropriate for commercial
sale of JSP191, if it is approved; |
|
● |
obtaining and maintaining patent protection, trade
secret protection and regulatory exclusivity, both in the United States and internationally; |
|
● |
a continued acceptable safety profile following any
marketing approval; |
|
● |
commercial acceptance by patients, the medical community
and third-party payors; |
|
● |
our ability to obtain coverage and adequate reimbursement
from third-party payors for our products, and patients’ willingness to pay out-of-pocket in the absence of such coverage and
adequate reimbursement; and |
|
● |
our ability to compete with other treatments. |
We do not have complete control over many of these
factors, including certain aspects of clinical development and the regulatory submission process, potential threats to our intellectual
property rights and the manufacturing, marketing, distribution and sales efforts of any future collaborator. If we are not successful
with respect to one or more of these factors in a timely manner or at all, we could experience significant delays or an inability to
successfully commercialize JSP191, which would materially harm our business. If we do not receive marketing approvals for JSP191, we
may not be able to continue our operations.
We may not be successful in our efforts to identify, develop
and commercialize additional product candidates. If these efforts are unsuccessful, we may never become a commercial stage company
or generate any revenues.
The success of our business depends primarily
upon our ability to identify, develop and commercialize additional product candidates based on, or complementary with, our technology
platform. While we are currently conducting a Phase 1/2 clinical trial of JSP191 as a conditioning agent prior to allogenic transplant
for SCID patients, a Phase 1 clinical trial of JSP191 as a conditioning agent prior to allogenic transplant for patients with AML
or MDS, and are planning a registrational clinical trial of JSP191 as a conditioning agent prior to allogenic transplant, all of our
other product development programs, including our mRNA stem cell grafts platform, are still in the research or preclinical stage of development.
Our research programs may fail to identify additional product candidates for clinical development for a number of reasons. Our research
methodology may be unsuccessful in identifying potential product candidates, our potential product candidates may be shown to have harmful
side effects in preclinical in vitro experiments or animal model studies, they may not show promising signals of efficacy in such experiments
or studies or they may have other characteristics that may make the product candidates impractical to manufacture, unmarketable or unlikely
to receive marketing approval. The historical failure rate for product candidates is high due to risks relating to safety, efficacy,
clinical execution, changing standards of medical care and other unpredictable variables. In addition, although we believe our technology
platform will position us to rapidly expand our portfolio of product candidates beyond our current product candidates, our ability to
expand our portfolio may never materialize.
If any of these events occur, we may be forced
to abandon our research or development efforts for a program or programs, which would have a material adverse effect on our business,
financial condition, results of operations and prospects. Research programs to identify new product candidates require substantial technical,
financial and human resources. We may focus our efforts and resources on potential programs or product candidates that ultimately prove
to be unsuccessful, which would be costly and time-consuming.
*We may expend our limited resources to pursue a particular
product candidate or indication and fail to capitalize on product candidates or indications that may be more profitable or for which
there is a greater likelihood of success.
Because we have limited financial and managerial
resources, we focus on research programs and product candidates that we identify for specific indications among many potential options.
As a result, we may forego or delay pursuit of opportunities with other product candidates 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 medicines
or profitable market opportunities. Our spending on current and future research and development programs and product candidates for specific
indications may not yield any commercially viable product candidates. If we do not accurately evaluate the commercial potential or target
market for a particular product candidate, we may relinquish valuable rights to that product candidate 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 product candidate. Any such event could have a material adverse effect on our business, financial condition, results of
operations and prospects.
mRNA stem cell grafts are a novel technology that is not yet
clinically validated for human use. The approaches we are taking to create mRNA stem cell grafts are unproven and may never lead to marketable
products.
We are developing mRNA stem cell grafts for transplant
into the human body. Although there have been significant advances in the field of use of RNA or DNA to edit cells ex vivo prior to transplant
in recent years, these technologies have only more recently been applied to HSCs, and our approach is new and unproven. The scientific
evidence to support the feasibility of developing mRNA stem cell grafts is both preliminary and limited. Successful development of mRNA
stem cell grafts by us will require solving a number of challenges, including:
|
● |
obtaining regulatory authorization from the FDA and
other regulatory authorities; |
|
● |
identifying appropriate molecular or genetic targets
for modification within HSCs; |
|
● |
developing and deploying consistent and reliable processes
for procuring cells from consenting third-party donors, isolating HSCs from such donor cells, modifying target molecules within such
HSCs, storing and transporting the resulting mRNA stem cell grafts for therapeutic use and finally infusing these mRNA stem cell
grafts into patients; |
|
● |
utilizing these mRNA stem cell graft product candidates
in combination or in sequence with companion therapeutics, which may increase the risk of adverse side effects; |
|
● |
avoiding potential complications of mRNA stem cell
graft transplants, including failure to engraft, rejection by host or lack of functionality, any of which could result in serious
side effects or death; |
|
● |
educating medical personnel regarding the potential
side effect profile of our product candidates, particularly those that may be unique to our mRNA stem cell grafts; |
|
● |
understanding and addressing variability in the quality
of a donor’s cells, which could ultimately affect our ability to manufacture product in a reliable and consistent manner; |
|
● |
developing processes for the safe administration of
mRNA stem cell graft product candidates, including long-term follow-up and registries, for all patients who receive these product
candidates; |
|
● |
relying on third parties to find suitable healthy donors; |
|
● |
manufacturing product candidates to our specifications
and in a timely manner to support our clinical trials and, if approved, commercialization; |
|
● |
sourcing clinical and, if approved by applicable regulatory
authorities, commercial supplies for the materials used to manufacture and process product candidates; |
|
● |
developing a manufacturing process and distribution
network that can provide a stable supply with a cost of goods that allows for an attractive return on investment; and |
|
● |
establishing sales and marketing capabilities ahead
of and after obtaining any regulatory approval to gain market acceptance, and obtaining coverage, adequate reimbursement and pricing
by third-party payors and governmental healthcare programs. |
We may decide to alter or abandon our initial
mRNA stem cell grafts platform as new data become available and we gain experience in developing mRNA stem cell grafts. We cannot be
sure that our programs will yield satisfactory products that are safe and effective, scalable or profitable in our initial indication
or any other indication we pursue.
Moreover, actual or perceived safety issues, including
as a result of adverse developments in our mRNA stem cell graft platform or in genome engineering programs undertaken by third parties
or of the adoption of novel approaches to treatment, may adversely influence the willingness of subjects to participate in our clinical
trials, or, if one of our product candidates is approved by applicable regulatory authorities, of physicians to subscribe to the novel
treatment mechanics or of patients to provide consent to receive a novel treatment despite its regulatory approval. The FDA or other
applicable regulatory authorities may require specific post-market studies or additional information that communicates the benefits or
risks of our products. New data may reveal new risks of our product candidates at any time prior to or after regulatory approval.
If any of our product candidates cause serious adverse events,
undesirable side effects or unexpected characteristics, such events, side effects or characteristics could delay or prevent regulatory
approval of the product candidate, limit our commercial potential or result in significant negative consequences following any potential
marketing approval.
Undesirable side effects or adverse events caused
by JSP191 and our other product candidates, and our mRNA stem cell grafts or other cell-based companion therapeutics we may develop,
could cause us or regulatory authorities to interrupt, delay or halt clinical trials and could result in a more restrictive label or
the delay or denial of regulatory approval by the FDA or comparable foreign regulatory authorities. Results of our clinical trials could
reveal a high and unacceptable severity and prevalence of side effects or unexpected characteristics. Treatment-related side effects
could also affect patient recruitment or the ability of enrolled patients to complete the trials or result in potential product liability
claims.
There have been no clinical trials of mRNA stem
cell grafts. In the genetic medicine field, there have been several significant adverse events from genetically engineered treatments
in the past, including reported cases of leukemia and death. There can be no assurance that our mRNA stem cell grafts will not cause
undesirable side effects, as improper modification of a patient’s DNA could lead to lymphoma, leukemia or other cancers, or other
aberrantly functioning cells.
A significant risk in any genetically engineered
product candidate is that “off-target” gene alterations may occur, which could cause serious adverse events, undesirable
side effects or unexpected characteristics. Although we and others have demonstrated the ability to improve the specificity of gene alterations
in a laboratory setting, we cannot be certain that off-target alterations will not occur in any of our planned or future clinical trials,
and the lack of observed side effects in preclinical studies does not guarantee that such side effects will not occur in human clinical
trials.
If any product candidates we develop are associated
with serious adverse events, undesirable side effects or unexpected characteristics, we may need to abandon their development or limit
development to certain uses or subpopulations in which the serious adverse events, undesirable side effects or other characteristics
are less prevalent, less severe or more acceptable from a risk-benefit perspective, any of which would have a material adverse effect
on our business, financial condition, results of operations, and prospects. Many product candidates that initially showed promise in
early stage testing have later been found to cause side effects that prevented further clinical development of the product candidates.
Results of preclinical studies and early clinical trials may
not be predictive of results of future clinical trials, and such results do not guarantee approval of a product candidate by regulatory
authorities. In addition, our clinical trials to date have been limited in scope, and results received to date may not be replicated
in expanded or additional future clinical trials.
The outcome of preclinical studies and early clinical
trials may not be predictive of the success of later clinical trials, and interim results of clinical trials do not necessarily predict
success in the results of completed clinical trials. There can be no assurance that any of our current or future preclinical and clinical
trials will ultimately be successful or support further preclinical or clinical development of any of our product candidates. Many companies
in the pharmaceutical and biotechnology industries have suffered significant setbacks in late-stage clinical trials after achieving positive
results in earlier development, and we could face similar setbacks. The design of a clinical trial can determine whether its results
will support approval of a product, and flaws in the design of a clinical trial may not become apparent until the clinical trial is well
advanced. Many companies that believed their product candidates performed satisfactorily in preclinical studies and clinical trials have
nonetheless failed to obtain regulatory approval for their product candidates. In addition, preclinical and clinical data are often susceptible
to varying interpretations and analyses, which may delay, limit or prevent regulatory approval. In addition, regulatory delays or rejections
may be encountered as a result of many factors, including changes in regulatory policy during the period of product development. Any
such adverse events may cause us to delay, limit or terminate planned clinical trials, any of which would have a material adverse effect
on our business, financial condition, results of operations and prospects.
In some instances, there can be significant variability
in safety or efficacy results between different clinical trials of the same product candidate due to numerous factors, including changes
in trial procedures set forth in protocols, differences in the size and type of the patient populations, changes in and adherence to
the dosing regimen and other clinical trial procedures and the rate of dropout among clinical trial participants. If we fail to receive
positive results in clinical trials of our product candidates, the development timeline and regulatory approval and commercialization
prospects for our most advanced product candidate, and, correspondingly, our business and financial prospects would be negatively impacted.
If we experience delays or difficulties in the enrollment of
patients in clinical trials, the cost of developing product candidates could increase and our receipt of necessary regulatory approvals
could be delayed or prevented.
Patient enrollment is a significant factor in
the timing of clinical trials. The timing of our clinical trials depends, in part, on the speed at which we can recruit patients to participate
in our trials. We or our collaborators may not be able to continue clinical trials for JSP191 or any other product candidates we identify
or develop if we are unable to locate and enroll a sufficient number of eligible patients to participate in these trials as required
by the FDA, the EMA or other analogous regulatory authorities outside the United States, or as needed to provide appropriate statistical
power for a given trial. Patients may be unwilling to participate in our clinical trials because of negative publicity from adverse events
related to the biotechnology, gene therapy or genome engineering fields, competitive clinical trials for similar patient populations,
clinical trials in competing products or for other reasons. As a result, the timeline for recruiting patients, conducting trials and
obtaining regulatory approval of product candidates may be delayed.
Patient enrollment is also affected by other factors,
including:
|
● |
severity of the disease under investigation; |
|
● |
size of the patient population and process for identifying
patients; |
|
● |
design of the trial protocol; |
|
● |
availability and efficacy of approved medications for
the disease under investigation; |
|
● |
availability of genetic testing for potential patients; |
|
● |
ability to obtain and maintain patient informed consent; |
|
● |
risk that enrolled patients will drop out before completion
of the trial; |
|
● |
eligibility and exclusion criteria for the trial in
question; |
|
● |
perceived risks and benefits of the product candidate
under trial; |
|
● |
perceived risks and benefits of genome engineering
as a treatment approach; |
|
● |
perceived risks and benefits of the companion therapeutics
that may be administered in combination or in sequence with JSP191; |
|
● |
efforts to facilitate timely enrollment in clinical
trials; |
|
● |
potential disruptions caused by the COVID-19 pandemic,
including difficulties in initiating clinical sites, enrolling and retaining participants, diversion of healthcare resources away
from clinical trials, travel or quarantine policies that may be implemented, and other factors; |
|
● |
patient referral practices of physicians; |
|
● |
ability to monitor patients adequately during and after
treatment; |
|
● |
proximity and availability of clinical trial sites
for prospective patients, especially for those conditions that have small patient pools; |
|
● |
the requirement for HSCT to be performed in centers
that specialize in this procedure; and |
|
● |
changes to diagnostic technologies, methodologies or
criteria used to identify HSCT patients at high risk for relapse. |
In addition, our clinical trials will compete
with other clinical trials for product candidates that are in the same therapeutic areas as our product candidates, and this competition
will reduce the number and types of patients available to us because some patients who have opted to enroll in our trials may instead
opt to enroll in a trial being conducted by a competitor. We may conduct some of our clinical trials at the same clinical trial sites
that some of our competitors use, which will reduce the number of patients who are available for our clinical trials at such clinical
trial sites.
Enrollment delays in our clinical trials may result
in increased development costs for JSP191 or any other product candidates we may develop, which would cause the value of our company
to decline and limit our ability to obtain additional financing. If we or our collaborators have difficulty enrolling a sufficient number
of patients to conduct our clinical trials as planned, we may need to delay, limit or terminate ongoing or planned clinical trials, any
of which would have an adverse effect on our business, financial condition, results of operations and prospects.
We have never obtained regulatory approval for a drug, may never
receive regulatory approval for any of our product candidates, and may therefore never generate revenues from product sales.
As a company, we have never obtained regulatory
approval for, or commercialized, a drug. It is possible that the FDA may refuse to accept any or all future product candidates for substantive
review or may conclude after review of our data that our application is insufficient to obtain regulatory approval for any current or
future product candidates. If the FDA does not approve any future product candidates, it may require that we conduct additional costly
clinical, preclinical or manufacturing validation studies before the FDA will reconsider one or more of our applications. Depending on
the extent of these or any other FDA-required studies, approval of any product candidates or other application that we submit may be
significantly delayed, possibly for several years, or may require us to expend more resources than we have available. Any failure
or delay in obtaining regulatory approvals would prevent us from commercializing JSP191 or any other product candidate, generating revenues
and achieving and obtaining or sustaining profitability. It is also possible that additional studies, if performed and completed, may
not be considered sufficient by the FDA to approve any new drug application or other application we submit. If any of these outcomes
occur, we may be forced to abandon the development of our product candidates, which would materially adversely affect our business and
could potentially cause us to cease operations. We face similar risks for our applications in foreign jurisdictions.
Our commercial success depends upon attaining significant market
acceptance of our product candidates, if approved, among physicians, patients, healthcare payers and operators of major clinics, and
we may not be successful in attaining such market acceptance.
Even with the requisite approvals from the FDA
in the U.S., the EMA in the European Union and other regulatory authorities internationally, the commercial success of our product candidates
will depend, in part, upon the degree of market acceptance by physicians, patients, third-party payors and others in the medical community.
Any product that we commercialize may not gain acceptance by physicians, patients, health care payors and others in the medical community.
If these products do not achieve an adequate level of acceptance, we may not generate significant product revenue and may not become
profitable. Efforts to educate the medical community and third-party payors on the benefits of our product candidates may require significant
resources, including our management’s time and financial resources, and may not be successful. Ethical, social and legal concerns
about genetic medicines generally and genome engineering technologies specifically could result in additional regulations restricting
or prohibiting the marketing of our product candidates. Even if any product candidate we develop receives marketing approval, it may
nonetheless fail to gain sufficient market acceptance by physicians, patients, healthcare payors and others in the medical community.
The degree of market acceptance of any product candidate we develop, if approved for commercial sale, will depend on a number of factors,
including:
|
● |
the efficacy and safety of such product candidate as
demonstrated in clinical trials; |
|
● |
the efficacy and safety of other products that are
used in combination or in sequence with our product candidates; |
|
● |
the potential and perceived advantages of our product
candidates compared to alternative treatments; |
|
● |
the limitation to our targeted patient population and
limitations or warnings contained in approved labeling by the FDA or other regulatory authorities; |
|
● |
the ability to offer our products for sale at competitive
prices; |
|
● |
convenience and ease of administration compared to
alternative treatments; |
|
● |
the clinical indications for which the product candidate
is approved by the FDA, the EMA or other regulatory agencies; |
|
● |
public attitudes regarding genetic medicine generally
and genome engineering technologies specifically; |
|
● |
the willingness of the target patient population to
try novel biologics and of physicians to prescribe these treatments, as well as their willingness to accept an intervention that
involves the alteration of the patient’s gene; |
|
● |
product labeling or product insert requirements of
the FDA, the EMA or other regulatory authorities, including any limitations or warnings contained in a product’s approved labeling; |
|
● |
relative convenience and ease of administration; |
|
● |
the strength of marketing and distribution support; |
|
● |
availability of third-party coverage and sufficiency
of reimbursement; and |
|
● |
the prevalence and severity of any side effects. |
Even if a product candidate is approved, such
product may not achieve an adequate level of acceptance, we may not generate significant product revenues, and we may not become profitable.
If we are unable to establish effective marketing and sales
capabilities or enter into agreements with third parties to market and sell our product candidates, if approved, we may not be able to
effectively market and sell our product candidates, if approved, or generate product revenues.
We have limited marketing capabilities and limited
experience in the sale, marketing or distribution of pharmaceutical products. In addition, we do not have a large sales, promotion and
marketing budget. As a result of our limited marketing capabilities, to achieve commercial success for any approved product for which
we retain sales and marketing responsibilities, we must either develop a sales and marketing organization or outsource these functions
to third parties. In the future, we may choose to build a focused sales, marketing and commercial support infrastructure to sell, or
participate in sales activities with our collaborators for, some of our product candidates if and when they are approved.
Factors that may inhibit our efforts to commercialize
our product candidates on our own include:
|
● |
our inability to recruit and retain adequate numbers
of effective sales, marketing, reimbursement, customer service, medical affairs and other support personnel; |
|
● |
the inability of sales personnel to obtain access to
physicians or educate adequate numbers of physicians on the benefits of prescribing any future products; |
|
● |
the inability of reimbursement professionals to negotiate
arrangements for formulary access, reimbursement and other acceptance by payors; |
|
● |
restricted or closed distribution channels that make
it difficult to distribute our product candidates to segments of the patient population; |
|
● |
the lack of complementary products to be offered by
sales personnel, which may put us at a competitive disadvantage relative to companies with more extensive product lines; and |
|
● |
unforeseen costs and expenses associated with creating
an independent commercialization organization. |
We may not be successful in entering into arrangements
with third parties to commercialize our product candidates or may be unable to do so on terms that are favorable to us. We may have little
control over such third parties, and any of them may fail to devote the necessary resources and attention to sell and market our products
effectively. If we do not establish commercialization capabilities successfully, either on our own or in collaboration with third parties,
we will not be successful in commercializing our product candidates.
We
face significant competition in an environment of rapid technological change, and there is a possibility that our competitors may achieve
regulatory approval before us or develop therapies that are safer or more advanced or effective than ours, which may harm our financial
condition and our ability to successfully market or commercialize our product candidates.
The
development and commercialization of new drug and biologic products is highly competitive. Moreover, the genome engineering and oncology
fields are characterized by rapidly changing technologies, significant competition and a strong emphasis on intellectual property. We
will face competition with respect to JSP191 and any other product candidates that we develop or commercialize in the future from major
pharmaceutical companies, specialty pharmaceutical companies and biotechnology companies worldwide. Potential competitors also include
academic institutions, government agencies and other public and private research organizations that conduct research, seek patent protection
and establish collaborative arrangements for research, development, manufacturing and commercialization.
There
are a number of large pharmaceutical and biotechnology companies that currently market and sell products or are pursuing the development
of products for the treatment of the disease indications for which we have product candidates and research programs. Some of these competitive
products and therapies are based on scientific approaches that are the same as or similar to our approach, and others are based on entirely
different approaches. Any product candidates that we successfully develop and commercialize will compete with existing therapies and
new therapies that may become available in the future that are approved to treat the same diseases for which we may obtain approval for
our product candidates. This may include other types of therapies, such as small molecule, antibody and/or protein therapies.
Many
of our current or potential competitors, either alone or with their collaboration partners, may have significantly greater financial
resources and expertise in research and development, manufacturing, preclinical testing, conducting clinical trials, obtaining regulatory
approvals and marketing approved products than we do. Mergers and acquisitions in the pharmaceutical, biotechnology and gene therapy
industries may result in even more resources being concentrated among a smaller number of our competitors. Smaller or early-stage companies
may also prove to be significant competitors, particularly through collaborative arrangements with large and established companies. These
competitors also compete with us in recruiting and retaining qualified scientific and management personnel and establishing clinical
trial sites and patient registration for clinical trials, as well as in acquiring technologies complementary to, or necessary for, our
programs. Our commercial opportunity could be reduced or eliminated if our competitors develop and commercialize product candidates that
are safer, more effective, have fewer or less severe side effects, are more convenient or are less expensive than our product candidates
or that would render our product candidates obsolete or non-competitive. Our competitors also may obtain FDA or other regulatory approval
for their product candidates more rapidly than we may obtain approval for ours, which could result in our competitors establishing a
strong market position before we are able to enter the market. Additionally, technologies developed by our competitors may render our
product candidates uneconomical or obsolete, and we may not be successful in marketing any product candidates against competitors.
Competitors
of JSP191 for our conditioning program for CD-117, a receptor for stem cell factor (“SCF”) that is expressed on the surface
of hematopoietic stem and progenitor cells, include the following:
|
● |
Magenta
Therapeutics, Inc., which is developing an Amanitin Anti-CD117 antibody drug conjugate and is in clinical development; |
|
● |
Gilead
Sciences, Inc., which is developing an antibody to CD117 that is not conjugated to any toxin and is used in combination with an antibody
to CD47 and has started initial Phase I clinical studies; |
|
● |
Actinium
Pharmaceuticals, Inc., which is developing an antibody to CD45 that is linked to radioisotope iodine-131 and is in Phase III
clinical studies; |
|
● |
Molecular
Templates Inc., which is developing an antibody to CD45 that is conjugated to engineered Shiga-toxin and is in preclinical development;
and |
|
● |
Celldex
Therapeutics, Inc., which is developing an antibody to inhibit tyrosine kinase KIT found in mast cells and is in Phase I/II
clinical studies in indications unrelated to conditioning. |
Competitors
for our mRNA stem cell grafts platform include the following:
|
● |
Gamida
Cell Ltd., which is developing an umbilical cord blood-derived cell product that uses a small molecule to inhibit differentiation
and enhance functionality of ex vivo-expanded HSCs; |
|
● |
ExCellThera
Inc., which is focused on ex vivo expansion of stem cells using a pyrimido-indole derivative small molecule; |
|
● |
Angiocrine
Bioscience, Inc., which is expanding cord blood and gene-modified HSCs using an endothelial cell feeder layer; |
|
● |
Sana
Biotechnology, Inc., which is developing hypoimmune cells designed to evade rejection and enable persistence of allogeneic cells; |
|
● |
Vor
Biopharma, Inc., which is developing treatment-resistant marrow cells that enable CD33 targeted therapy; and |
|
● |
Ensoma
Inc., which is developing viral vectors for delivery of cell modification payload, in vivo. |
Adverse
public perception of genetic medicines, and genome engineering in particular, may negatively impact regulatory approval of, and/or demand
for, our potential products.
Some
of our mRNA stem cell grafts or other cell-based therapeutics we develop may be created by altering the human genome. The clinical and
commercial success of our potential products will depend in part on public understanding and acceptance of the use of genome engineering
for the prevention or treatment of human diseases. Public attitudes may be influenced by claims that genome engineering is unsafe, unethical
or immoral, and, consequently, our current or future product candidates may not gain the acceptance of the public or the medical community.
Adverse public attitudes may adversely impact our ability to enroll clinical trials. Moreover, our success will depend upon physicians
prescribing, and their patients being willing to receive, treatments that involve the use of product candidates in lieu of, or in addition
to, existing treatments with which they are already familiar and for which greater clinical data may be available.
In
addition, genome engineering technology is subject to public debate and heightened regulatory scrutiny due to ethical concerns relating
to the application of genome engineering technology to human embryos or the human germline. For example, in the United States, germline
alteration for clinical application has been expressly prohibited since enactment of a December 2015 FDA ban on such activity. Prohibitions
are also in place in the United Kingdom, across most of Europe, in China and many other countries around the world. In the United States,
the National Institutes of Health has announced that the agency would not fund any use of gene engineering technologies in human embryos,
noting that there are multiple existing legislative and regulatory prohibitions against such work, including the Dickey-Wicker Amendment,
which prohibits the use of appropriated funds for the creation of human embryos for research purposes or for research in which human
embryos are destroyed. Adverse events in our preclinical studies or clinical trials or those of our competitors or of academic researchers
utilizing genome engineering technologies, even if not ultimately attributable to product candidates we may identify and develop, and
the accompanying publicity could result in increased governmental regulation, unfavorable public perception, potential regulatory delays
in the testing or approval of potential product candidates we may identify and develop, stricter labeling requirements for those product
candidates that are approved and a decrease in demand for any such product candidates.
If
product liability lawsuits are brought against us, we may incur substantial liabilities and may be required to limit commercialization
of our product candidates.
We
face an inherent risk of product liability exposure related to the testing in human clinical trials of our product candidates and will
face an even greater risk if we commercially sell any products that we may develop. For example, we may be sued if our product candidates
cause, or are perceived to cause, injury or are found to be otherwise unsuitable during clinical trials, 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. Claims could also be asserted under state consumer
protection acts. If we cannot successfully defend ourselves against claims that our product candidates or products caused injuries, we
could incur substantial liabilities or be required to limit commercialization of our product candidates. Even a successful defense would
require significant financial and management resources. Regardless of merit or eventual outcome, liability claims may result in:
|
● |
the
inability to commercialize any products that we may develop; |
|
● |
decreased
demand for our product candidates or products that we may develop; |
|
● |
injury
to our reputation and significant negative media attention; |
|
● |
withdrawal
of clinical trial participants; |
|
● |
significant
time and costs to defend the related litigation; |
|
● |
substantial
monetary awards to trial participants or patients; and |
Although
we maintain product liability insurance coverage, it may not be adequate to cover all liabilities that we may incur. We anticipate that
we will need to increase our insurance coverage as we continue clinical trials and if we successfully commercializes any product. Insurance
coverage is increasingly expensive. We may not be able to maintain insurance coverage at a reasonable cost or in an amount adequate to
satisfy any liability that may arise.
*Our product candidates are complex and difficult to manufacture.
We could experience delays in satisfying regulatory authorities or production problems that result in delays in our development or commercialization
programs, limit the supply of our product candidates, or otherwise harm our business.
Our
product candidates require processing steps that are more complex than those required for most chemical and other biological pharmaceuticals.
Moreover, unlike chemical and other biological pharmaceuticals, the physical and chemical properties of a gene-engineered cell therapies
cannot be fully characterized. As a result, assays of the finished product candidate may not be sufficient to ensure that the product
candidate will perform in the intended manner. Problems with the manufacturing process, even minor deviations from the normal process,
could result in product defects or manufacturing failures that result in lot failures, product recalls, product liability claims, insufficient
inventory or potentially delay progression of our clinical trials. If we successfully develop product candidates, we may encounter problems
achieving adequate quantities and quality of clinical-grade materials that meet FDA, EMA or other comparable applicable foreign standards
or specifications with consistent and acceptable production yields and costs. In addition, our product candidates will require complicated
delivery modalities, such as electroporation, which will introduce additional complexities into the manufacturing process.
mRNA
stem cell grafts consist of engineered human cells, and the process of manufacturing such product candidates is complex, concentrated
with a limited number of suppliers, highly regulated and subject to numerous risks. Manufacturing such product candidates involves harvesting
cells from a donor or from the patient, altering the cells ex vivo using genome engineering technology, cryopreservation, storage
and eventually shipment and infusing the cell product into the patient’s body. Our manufacturing process will be susceptible to
product loss or failure, or product variation that may negatively impact patient outcomes, due to logistical issues associated with the
collection of starting material from the donor, shipping such material to the manufacturing site, shipping the final product back to
the clinical trial recipient, preparing the product for administration, infusing the patient with the product, manufacturing issues or
different product characteristics resulting from the differences in donor starting materials, variations between reagent lots, interruptions
in the manufacturing process, contamination, equipment or reagent failure, improper installation or operation of equipment, vendor or
operator error, inconsistency in cell growth and variability in product characteristics. our manufacturing process, like that of a number
of other cell therapy companies, is also characterized by limited numbers of suppliers, and in some cases sole source suppliers, with
the manufacturing capabilities and know-how to create or source the materials, such as donor marrow cells and electroporation machines,
used in our cell manufacturing. While we pursue multiple sources for the critical components of our manufacturing process, we may not
be successful in securing these additional sources at all or on a timely basis. If microbial, viral or other contaminations are discovered
in our product candidates or in any of the manufacturing facilities in which our product candidates or other materials are made, such
manufacturing facilities may need to be closed for an extended period of time to investigate and remedy the contamination.
In
addition, the FDA, the EMA and other regulatory authorities may require us to submit samples of any lot of approved product together
with the protocols showing the results of applicable tests at any time. Under some circumstances, the FDA, the EMA or other regulatory
authorities may require that we not distribute a lot until the agency authorizes its release. Slight deviations in the manufacturing
process, including those affecting quality attributes and stability, may result in unacceptable changes in the product that could result
in lot failures or product recalls. Lot failures or product recalls could cause us to delay clinical trials or product launches, which
could be costly to us and otherwise harm our business, financial condition, results of operations and prospects.
Some
of the raw materials that we anticipate will be required in our manufacturing process are derived from biologic sources. Such raw materials
are difficult to procure and may be subject to contamination or recall. A material shortage, contamination, recall or restriction on
the use of biologically derived substances in the manufacture of our product candidates could adversely impact or disrupt the commercial
manufacturing or the production of clinical material, which could materially harm our development timelines and our business, financial
condition, results of operations and prospects.
Moreover,
the clinical development of our product candidates depends on the availability of certain materials and agents used in our clinical trials.
Specifically, our clinical trial protocols for JSP191-based conditioning include the administration of fludarabine, and the FDA recently
reported a shortage of fludarabine. Any failure or delays by us or by our clinical sites to obtain sufficient quantities of fludarabine
or other components and agents necessary for the conduct of our clinical trials, may delay our ability to enroll and treat patients in,
or complete, our current or future clinical trials of our product candidates on time, if at all.
If
we or any contract research organizations, contract manufacturers or suppliers that we engage fail to comply with environmental, health
and safety laws and regulations, we could become subject to fines or penalties or incur costs that could have a material adverse effect
on the success of our business.
We
and any contract research organizations, contract manufacturers and suppliers we engage are subject to numerous federal, state and local
environmental, health and safety laws, regulations and permitting requirements, including those governing laboratory procedures; the
generation, handling, use, storage, treatment and disposal of hazardous and regulated materials and wastes; the emission and discharge
of hazardous materials into the ground, air and water; and employee health and safety. Our operations involve the use of hazardous and
flammable materials, including chemicals and biological and radioactive materials. Our operations also produce hazardous waste. We generally
contract with third parties for the disposal of these materials and wastes. Although we believe that our and such third parties’
procedures for handling, storing and disposing of these materials and waste comply with legally prescribed standards, we cannot eliminate
the risk of 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. Under certain environmental
laws, we could be held responsible for costs relating to any contamination at our current or past facilities and at third-party facilities.
We also could incur significant costs associated with civil or criminal fines and penalties.
Compliance
with applicable environmental laws and regulations may be expensive, and current or future environmental laws and regulations may impair
our product development and research efforts. In addition, we cannot entirely eliminate the risk of accidental injury or contamination
from these materials or wastes. 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 carry specific biological or hazardous waste insurance coverage, and our property, casualty
and general liability insurance policies specifically exclude coverage for damages and fines arising from biological or hazardous waste
exposure or contamination. Accordingly, in the event of contamination or injury, we could be held liable for damages or be penalized
with fines in an amount exceeding our resources, and our clinical trials or regulatory approvals could be suspended, which could have
a material adverse effect on our business, financial condition, results of operations and prospects.
In
addition, we may incur substantial costs in order to comply with current or future environmental, health and safety laws, regulations
and permitting requirements. For example, our products are considered to contain genetically modified organisms or cells, which are regulated
in different ways depending upon the country in which preclinical research or clinical trials are conducted. These current or future
laws, regulations and permitting requirements may impair our research, development or production efforts. Failure to comply with these
laws, regulations and permitting requirements also may result in substantial fines, penalties or other sanctions or business disruption,
which could have a material adverse effect on our business, financial condition, results of operations and prospects.
Any
third-party contract research organizations, contract manufacturers and suppliers we engage will also be subject to these and other environmental,
health and safety laws and regulations. Liabilities they incur pursuant to these laws and regulations could result in significant costs
or an interruption in operations, which could have a material adverse effect on our business, financial condition, results of operations
and prospects.
Risks
Related to Regulatory Review
*If
clinical trials of our product candidates fail to demonstrate safety and efficacy to the satisfaction of regulatory authorities or do
not otherwise produce positive results, we may incur additional costs or experience delays in completing, or ultimately be unable to
complete, the development and commercialization of such product candidates.
Before
obtaining marketing approval from regulatory authorities for the sale of JSP191 and any other product candidates we identify and develop,
we must complete preclinical development and then conduct extensive clinical trials to demonstrate the safety and efficacy of such product
candidates in humans. Clinical testing is expensive, difficult to design and implement, can take many years to complete and is uncertain
as to outcome. A failure of one or more clinical trials can occur at any stage of testing. The outcome of preclinical testing and early
clinical trials may not be predictive of the success of later clinical trials, and interim results of a clinical trial do not necessarily
predict final results. Moreover, preclinical and clinical data are often susceptible to varying interpretations and analyses. Many companies
that have believed their product candidates performed satisfactorily in preclinical studies and clinical trials have nonetheless failed
to obtain marketing approval of their product candidates.
We
and our collaborators, if any, may experience numerous unforeseen events during, or as a result of, clinical trials that could delay
or prevent our ability to receive marketing approval or commercialize any product candidates, including:
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delays
in reaching a consensus with regulators on trial design; |
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regulators,
IRBs, independent ethics committees or scientific review boards may not authorize us or our investigators to commence a clinical
trial or conduct a clinical trial at a prospective trial site; |
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delays
in reaching or failing to reach agreement on acceptable clinical trial contracts or clinical trial protocols with prospective CROs
and clinical trial sites; |
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clinical
trials of product candidates may produce negative or inconclusive results, and we may decide, or regulators may require us, to conduct
additional clinical trials or abandon product development or research programs; |
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difficulty
in designing well-controlled clinical trials due to ethical considerations that may render it inappropriate to conduct a trial with
a control arm that can be effectively compared to a treatment arm; |
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difficulty
in designing clinical trials and selecting endpoints for diseases that have not been well-studied and for which the natural history
and course of the disease is poorly understood; |
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the
number of patients required for clinical trials of JSP191 and any other product candidates we may develop may be larger than we anticipate;
enrollment of suitable participants in these clinical trials, which may be particularly challenging for some of the rare genetically
defined diseases we are targeting in our most advanced programs, may be delayed or slower than we anticipate; or patients may drop
out of these clinical trials at a higher rate than we anticipate; |
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our
third-party contractors may fail to comply with regulatory requirements or meet their contractual obligations to us in a timely manner,
or at all; |
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regulators,
IRBs or independent ethics committees may require that we or our investigators suspend or terminate clinical research or clinical
trials for various reasons, including noncompliance with regulatory requirements, a finding of undesirable side effects or other
unexpected characteristics, or that the participants are being exposed to unacceptable health risks or after an inspection of our
clinical trial operations or trial sites; |
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the
cost of clinical trials may be greater than we anticipate; |
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the
supply or quality of product candidates or other materials necessary to conduct clinical trials may be insufficient or inadequate,
including as a result of delays in the testing, validation, manufacturing and delivery of product candidates to the clinical sites
by us or by third parties with whom we have contracted to perform certain of those functions; |
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delays
in having patients complete participation in a trial or return for post-treatment follow-up; |
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clinical
trial sites dropping out of a trial; |
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selection of clinical endpoints that require prolonged
periods of clinical observation or analysis of the resulting data; |
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occurrence of serious adverse events associated with
product candidates that are viewed to outweigh their potential benefits; |
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occurrence of serious adverse events in trials of the
same class of agents conducted by other sponsors; and |
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changes in regulatory requirements and guidance that
require amending or submitting new clinical protocols. |
If
we or our collaborators, if any, are required to conduct additional clinical trials or other testing of product candidates beyond those
that we currently contemplate, if we or our collaborators are unable to successfully complete clinical trials or other testing of product
candidates, or if the results of these trials or tests are not positive or are only modestly positive or if there are safety concerns,
we or our collaborators may:
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be delayed in obtaining marketing approval for any
such product candidates or not obtain marketing approval at all; |
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obtain approval for indications or patient populations
that are not as broad as intended or desired; |
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obtain approval with labeling that includes significant
use or distribution restrictions or safety warnings, including boxed warnings; |
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be subject to changes in the way the product is administered; |
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be required to perform additional clinical trials to
support approval or be subject to additional post-marketing testing requirements; |
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have regulatory authorities withdraw or suspend their
approval of the product or impose restrictions on its distribution in the form of a Risk Evaluation and Mitigation Strategy (“REMS”)
or through modification to an existing REMS; |
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experience damage to our reputation. |
Product
development costs will also increase if we or our collaborators experience delays in clinical trials or other testing or in obtaining
marketing approvals. We do not know whether any clinical trials will begin as planned, will need to be restructured or will be completed
on schedule, or at all. Significant clinical trial delays also could shorten any periods during which we may have the exclusive right
to commercialize product candidates, could allow our competitors to bring products to market before we do and could impair our ability
to successfully commercialize product candidates, any of which may harm our business, financial condition, results of operations and
prospects.
Further,
disruptions at the FDA and other agencies may prolong the time necessary for new drugs to be reviewed and/or approved by necessary government
agencies, which would adversely affect our business. For example, over the last several years, the U.S. government has shut
down several times and certain regulatory agencies, including the FDA, have furloughed critical employees and stopped critical activities.
If a prolonged government shutdown occurs, it could significantly impact the ability of the FDA to timely review and process our regulatory
submissions, which could have a material adverse effect on our business.
Stem
cell transplant is a high-risk procedure with curative potential that may result in complications or adverse events for patients in our
clinical trials or for patients that use any of our product candidates, if approved.
Stem
cell transplant has the potential to cure patients across multiple diseases, but its use carries with it risks of toxicity, serious adverse
events and death. Because many of our therapies are used to prepare or treat patients undergoing stem cell transplant, patients in our
clinical trials or patients that use any of our product candidates may be subject to many of the risks that are currently inherent to
this procedure. In particular, stem cell transplant involves certain known potential post-procedure complications that may manifest several weeks
or months after a transplant and that may be more common in certain patient populations. For example, up to 20% of patients
with inherited metabolic disorders treated with a transplant experience primary engraftment failure, resulting in severe complications,
including death. Another example is autoimmune cytopenia, a known and severe frequent complication of the transplant procedure in patients
with non-malignant diseases, such as inherited metabolic diseases, that can result in death. There is also a risk of graft-versus-host
disease, a potentially serious complication in which the grafted cells attack and damage the patient’s healthy cells, which can
be severe and sometimes life-threatening. If these or other serious adverse events, undesirable side effects, or unexpected characteristics
are identified during the development of any of our product candidates, we may need to limit, delay or abandon our further clinical development
of those product candidates, even if such events, effects or characteristics were the result of stem cell transplant or related procedures
generally, and not directly or specifically caused or exacerbated by our product candidates. All serious adverse events or unexpected
side effects are continually monitored per the clinical trial’s approved protocol. If serious adverse events are determined to
be directly or specifically caused or exacerbated by our product candidates, we would follow the trial protocol’s requirements,
which call for our data safety monitoring committee to review all available clinical data in making a recommendation regarding the trial’s
continuation.
Failure
to obtain marketing approval in foreign jurisdictions would prevent any product candidates we develop from being marketed in such jurisdictions,
which, in turn, would materially impair our ability to generate revenue.
In
order to market and sell any product candidates we develop in the European Union and many other foreign jurisdictions, we or our collaborators
must obtain separate marketing approvals and comply with numerous and varying regulatory requirements. The approval procedure varies
among countries and can involve additional testing. The time required to obtain approval may differ substantially from that required
to obtain FDA approval. The regulatory approval process outside the United States generally includes all of the risks associated
with obtaining FDA approval. In addition, in many countries outside the United States, it is required that the product be approved
for reimbursement before the product can be approved for sale in that country. We or our collaborators may not obtain approvals from
regulatory authorities outside the United States on a timely basis, if at all. Approval by the FDA does not ensure approval by regulatory
authorities in other countries or jurisdictions, and approval by one regulatory authority outside the United States does not ensure
approval by regulatory authorities in other countries or jurisdictions or by the FDA. We may not be able to file for marketing approvals
and may not receive necessary approvals to commercialize our product candidates in any jurisdiction, which would materially impair our
ability to generate revenue.
Additionally,
we could face heightened risks with respect to seeking marketing approval in the United Kingdom as a result of the recent withdrawal
of the United Kingdom from the European Union on December 31, 2020, commonly referred to as Brexit. Pursuant to the formal withdrawal
arrangements agreed between the United Kingdom and the European Union, the United Kingdom withdrew from the European Union, effective
December 31, 2020. On December 24, 2020, the United Kingdom and European Union entered into a Trade and Cooperation Agreement.
The agreement sets out certain procedures for approval and recognition of medical products in each jurisdiction.
Since
the regulatory framework for pharmaceutical products in the United Kingdom covering the quality, safety, and efficacy of pharmaceutical
products, clinical trials, marketing authorization, commercial sales, and distribution of pharmaceutical products is derived from European
Union directives and regulations, Brexit could materially impact the future regulatory regime that applies to products and the approval
of product candidates in the United Kingdom. Any delay in obtaining, or an inability to obtain, any marketing approvals, as a result
of Brexit or otherwise, would prevent us from commercializing any product candidates in the United Kingdom and/or the European Union
and restrict our ability to generate revenue and achieve and sustain profitability. If any of these outcomes occur, we may be forced
to restrict or delay efforts to seek regulatory approval in the United Kingdom and/or the European Union for any product candidates,
which could significantly and materially harm our business.
Even
if we complete the necessary clinical trials, we cannot predict when, or if, we will obtain regulatory approval to commercialize our
product candidates in the United States or any other jurisdiction, and any such approval may be for a more narrow indication than
we seek.
We
cannot commercialize a product candidate until the appropriate regulatory authorities have reviewed and approved the product candidate.
Even if our product candidates meet their safety and efficacy endpoints in clinical trials, the regulatory authorities may not complete
their review processes in a timely manner, or we may not be able to obtain regulatory approval. Additional delays may result if an FDA
Advisory Committee or other regulatory authority recommends non-approval or restrictions on approval. In addition, we may experience
delays or rejections based upon additional government regulation from future legislation or administrative action, or changes in regulatory
authority policy during the period of product development, clinical trials and the review process.
Regulatory
authorities also may approve a product candidate for more limited indications than requested or they may impose significant limitations
in the form of narrow indications, warnings or a REMS. These regulatory authorities may require labeling that includes precautions
or contra-indications with respect to conditions of use, or they may grant approval subject to the performance of costly post-marketing
clinical trials. In addition, regulatory authorities may not approve the labeling claims that are necessary or desirable for the successful
commercialization of our product candidates. Any of the foregoing scenarios could materially harm the commercial prospects for our product
candidates and materially adversely affect our business, financial condition, results of operations and prospects.
Marketing
approval by the FDA in the United States, if obtained, does not ensure approval by regulatory authorities in other countries or
jurisdictions. In addition, clinical trials conducted in one country may not be accepted by regulatory authorities in other countries,
and regulatory approval in one country does not guarantee regulatory approval in any other country. Approval processes vary among countries
and can involve additional product candidate testing and validation and additional administrative review periods. Seeking foreign regulatory
approval could result in difficulties and costs for us and require additional preclinical studies or clinical trials, which could be
costly and time-consuming. Regulatory requirements can vary widely from country to country and could delay or prevent the introduction
of our product candidates we may develop in those countries. The foreign regulatory approval process involves all of the risks associated
with FDA approval. We do not have any product candidates approved for sale in any jurisdiction, including international markets, and
we do not have experience in obtaining regulatory approval in international markets. If we fail to comply with regulatory requirements
in international markets or to obtain and maintain required approvals, or if regulatory approvals in international markets are delayed,
our target market will be reduced and our ability to realize the full market potential of our product candidates will be unrealized.
Even
if we obtain regulatory approval of any of our product candidates, the approved products may be subject to post-approval studies and
will remain subject to ongoing regulatory requirements. If we fail to comply, or if concerns are identified in subsequent studies, our
approval could be withdrawn, and our product sales could be suspended.
If
we are successful at obtaining regulatory approval for JSP191 or any of our other product candidates, regulatory agencies in the U.S. and
other countries where a product will be sold may require extensive additional clinical trials or post-approval clinical trials that are
expensive and time-consuming to conduct. These studies may be expensive and time-consuming to conduct and may reveal side effects or
other harmful effects in patients that use our therapeutic products after they are on the market, which may result in the limitation
or withdrawal of our drugs from the market. Alternatively, we may not be able to conduct such additional trials, which might force us
to abandon our efforts to develop or commercialize certain product candidates. Even if post-approval studies are not requested or required,
after our products are approved and are on the market, there might be safety issues that emerge over time that require a change in product
labeling, additional post-market studies or clinical trials, imposition of distribution and use restrictions under a REMS or withdrawal
of the product from the market, which would cause our revenue to decline.
Additionally,
any products that we may successfully develop will be subject to ongoing regulatory requirements after they are approved. These requirements
will govern the manufacturing, packaging, marketing, distribution, and use of our products. If we fail to comply with such regulatory
requirements, approval for our products may be withdrawn, and product sales may be suspended. We may not be able to regain compliance,
or we may only be able to regain compliance after a lengthy delay, significant expense, lost revenues and/or damage to our reputation.
The
regulatory landscape that will govern our product candidates is uncertain; regulations relating to more established cellular therapy
products are still developing, and changes in regulatory requirements could result in delays or discontinuation of development of our
product candidates or unexpected costs in obtaining regulatory approval. The FDA and other governing bodies may disagree with our regulatory
plan, and we may fail to obtain regulatory approval of our product candidates.
Because
our product candidates and technology platform involve genetic and cellular engineering, we are subject to many of the challenges and
risks that other genetically engineered biologics and cellular therapies face, including:
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regulatory requirements or guidance regarding the requirements
governing genetic and cellular engineering products have changed and may continue to change in the future; |
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to date, only a limited number of products that involve
genetic or cellular engineering have been approved globally; |
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improper modulation of a gene sequence, including unintended
alterations or insertion of a sequence into certain locations in a patient’s chromosomes, could lead to cancer, other aberrantly
functioning cells or other diseases, as well as death; |
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corrective expression of a missing protein, or deletion
of an existing protein, in patients’ cells could result in the protein or cell being recognized as foreign, and lead to a sustained
immunological reaction against the expressed protein or expressing cells, which could be severe or life-threatening; |
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regulatory agencies may require extended follow-up
observation periods of patients who receive treatment using genetic or cellular engineering products including, for example, the
FDA’s recommended 15-year follow-up observation period for these patients, and we will need to adopt such observation
periods for our product candidates if required by the relevant regulatory agency, which could vary by country or region; and |
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the fields of genetic and cellular engineering are
subject to a number of intellectual property disputes. |
The
regulatory requirements that will govern any mRNA stem cell grafts or other novel genetically engineered product candidates we develop
may change. Within the broader genetic medicine field, we are aware of a limited number of gene therapy products that have received marketing
authorization from the FDA and the EMA. Even with respect to more established products that fit into the categories of gene therapies
or cell therapies, the regulatory landscape is still developing. Regulatory requirements governing gene therapy products and cell therapy
products have changed frequently and will likely continue to change in the future. Moreover, there is substantial, and sometimes uncoordinated,
overlap in those responsible for regulation of existing gene therapy products and cell therapy products. For example, in the United States,
the FDA has established the Office of Tissues and Advanced Therapies (“OTAT”) within its Center for Biologics Evaluation
and Research (“CBER”) to consolidate the review of gene therapy and related products, and the Cellular, Tissue and Gene Therapies
Advisory Committee to advise CBER on its review. In addition to FDA oversight and oversight by IRBs under guidelines promulgated by the
National Institutes of Health (“NIH”), gene therapy clinical trials are also subject to review and oversight by an institutional
biosafety committee (“IBC”), a local institutional committee that reviews and oversees research utilizing recombinant or
synthetic nucleic acid molecules at that institution. Before a clinical study can begin at any institution, that institution’s
IRB and its IBC assess the safety of the research and identify any potential risk to public health or the environment. While
the NIH guidelines are not mandatory unless the research in question is being conducted at or sponsored by institutions receiving NIH
funding of recombinant or synthetic nucleic acid molecule research, many companies and other institutions not otherwise subject to the
NIH guidelines voluntarily follow them. Moreover, serious adverse events or developments in clinical trials of gene or cellular therapy
product candidates conducted by others may cause the FDA or other regulatory bodies to initiate a clinical hold on our clinical trials
or otherwise change the requirements for approval of any of our product candidates. Although the FDA decides whether individual gene
or cellular therapy protocols may proceed, the review process and determinations of other reviewing bodies can impede or delay the initiation
of a clinical trial even if the FDA has reviewed the trial and approved its initiation.
The
same applies in the European Union. The EMA’s Committee for Advanced Therapies (“CAT”) is responsible for assessing
the quality, safety and efficacy of advanced-therapy medicinal products. The role of the CAT is to prepare a draft opinion on an application
for marketing authorization for a cell or gene therapy or other novel therapeutic medicinal candidate that is submitted to the Committee
for Medicinal Products for Human Use (“CHMP”) before CHMP adopts its final opinion. In the European Union, the development
and evaluation of an advanced therapeutic medicinal product must be considered in the context of the relevant European Union guidelines.
The EMA may issue new guidelines concerning the development and marketing authorization for these medicinal products and require that
we comply with these new guidelines. As a result, the procedures and standards applied to gene and cell therapy products may be applied
to our mRNA stem cell grafts, but that remains uncertain at this point.
Adverse
developments in post-marketing experience or in clinical trials conducted by others of gene therapy products, cell therapy products or
products developed through the application of a genome engineering technology may cause the FDA, the EMA and other regulatory bodies
to revise the requirements for development or approval of our mRNA stem cell grafts may develop or limit the use of products utilizing
genome engineering technologies, either of which could materially harm our business. In addition, the clinical trial requirements of
the FDA, the EMA and other regulatory authorities and the criteria these regulators use to determine the safety and efficacy of a product
candidate vary substantially according to the type, complexity, novelty and intended use and market of the potential products. The regulatory
approval process for novel product candidates, such as our mRNA stem cell grafts, can be more expensive and take longer than for other,
better known or more extensively studied pharmaceutical or other product candidates. Regulatory agencies administering existing or future
regulations or legislation may not allow production and marketing of products utilizing genome engineering technology in a timely manner
or under technically or commercially feasible conditions. In addition, regulatory action or private litigation could result in expenses,
delays or other impediments to our product candidate development, research programs or the commercialization of resulting products.
The
regulatory review committees and advisory groups described above and the new guidelines they promulgate may lengthen the regulatory review
process, require us to perform additional studies or trials, increase our development costs, lead to changes in regulatory positions
and interpretations, delay or prevent approval and commercialization of these treatment candidates, or lead to significant post-approval
limitations or restrictions. Currently, OTAT requires a 15-year follow-up for each patient who receives a genetically engineered
cell or gene therapy. This requirement applies to all patients treated in trials during clinical development prior to approval. Following
approval, such prolonged follow-up could continue to be required. As we advance our product candidates and research programs, we will
be required to consult with these regulatory and advisory groups and to comply with applicable guidelines. If we fail to do so, we may
be required to delay or discontinue development of our mRNA stem cell grafts and any other product candidates we identify and develop.
Interim
“top-line” and preliminary results from our clinical trials that we may announce or publish from time to time may change
as more patient data become available and are subject to audit and verification procedures that could result in material changes in the
final data.
From
time to time, we may publish interim top-line or preliminary results from our preclinical studies and clinical trials, which are based
on a preliminary analysis of then-available data, and the results and related findings and conclusions are subject to change following
a more comprehensive review of the data related to the particular study or trial. In particular, we have announced, and may in the future
announce, interim results from our ongoing, open label Phase 1/2 and Phase 1 clinical trials of JSP191. Interim results from
clinical trials that we may complete are subject to the risk that one or more of the clinical outcomes may materially change as patient
enrollment continues and more patient data become available. Preliminary or top-line results also remain subject to audit and verification
procedures that may result in the final data being materially different from the preliminary data we previously published. As a result,
interim and preliminary data should be viewed with caution until the final data are available. Differences between preliminary or interim
data and final data could significantly harm our business prospects and may cause the trading price of our common stock to fluctuate
significantly.
Further,
others, including regulatory agencies, may not accept or agree with our assumptions, estimates, calculations, conclusions or analyses
or may interpret or weigh the importance of data differently, which could impact the value of the particular program, the approvability
or commercialization of the particular product candidate or product and us in general. In addition, the information we choose to publicly
disclose regarding a particular study or clinical trial is based on what is typically extensive information, investors or others may
not agree with what we determine is material or otherwise appropriate information to include in our disclosure, and any information we
determine not to disclose may ultimately be deemed significant with respect to future decisions, conclusions, views, activities or otherwise
regarding a particular product, product candidate or our business. If the interim, topline or preliminary data that we report differ
from actual results, or if others, including regulatory authorities, disagree with the conclusions reached, our ability to obtain approval
for, and commercialize, our product candidates may be harmed, which could harm our business, operating results, prospects or financial
condition.
Negative
public opinion of gene therapy and increased regulatory scrutiny of gene therapy and genetic research may adversely impact public perception
of our future product candidates.
Our
potential therapeutic products involve introducing genetic material into patients’ cells. The clinical and commercial success of
our potential products will depend in part on public acceptance of the use of gene therapy and gene regulation for the prevention or
treatment of human diseases. Public attitudes may be influenced by claims that gene therapy and gene regulation are unsafe, unethical
or immoral, and, consequently, our products may not gain the acceptance of the public or the medical community. Adverse public attitudes
may adversely impact our ability to enroll clinical trials. Moreover, our success will depend upon physicians prescribing, and their
patients being willing to receive, treatments that involve the use of product candidates we may develop in lieu of, or in addition to,
existing treatments with which they are already familiar and for which greater clinical data may be available.
More
restrictive government regulations or negative public opinion would have a negative effect on our business or financial condition and
may delay or impair the development and commercialization of our product candidates or demand for any products once approved. For example,
in 2003, trials using early versions of murine gamma-retroviral vectors, which integrate with, and thereby alter, the host cell’s
DNA, have led to several well-publicized adverse events, including reported cases of leukemia. Adverse events in our clinical trials,
even if not ultimately attributable to our product candidates, and the resulting publicity could result in increased governmental regulation,
unfavorable public perception, potential regulatory delays in the testing or approval of our product candidates, stricter labeling requirements
for those product candidates that are approved, and a decrease in demand for any such product candidates. The risk of cancer remains
a concern for gene therapy, and we cannot assure that it will not occur in any of our planned or future clinical trials. In addition,
there is the potential risk of delayed adverse events following exposure to gene therapy products due to persistent biological activity
of the genetic material or other components of products used to carry the genetic material. If any such adverse events occur, commercialization
of our product candidates or further advancement of our clinical trials could be halted or delayed, which would have a negative impact
on our business and operations.
We
may seek Fast Track or other accelerated review designations for some or all of our product candidates. We may not receive such designation,
and even for those product candidates for which we do, it may not lead to a faster development or regulatory review or approval process,
and will not increase the likelihood that product candidates will receive marketing approval.
We
may seek Fast Track or other accelerated review designations for some or all of our other product candidates. If a drug or biologic is
intended for the treatment of a serious or life-threatening condition or disease, and nonclinical or clinical data demonstrate the potential
to address an unmet medical need, the product may qualify for FDA Fast Track designation, for which sponsors must apply. If granted,
a Fast Track or other accelerated review designation makes a product candidate eligible for more frequent interactions with the FDA to
discuss the development plan and clinical trial design, as well as rolling review of the application, which means that we can submit
completed sections of our marketing application for review prior to completion of the entire submission. Marketing applications of product
candidates with a Fast Track or other accelerated review designation may qualify for priority review under the policies and procedures
offered by the FDA, but a Fast Track or other accelerated review designation does not assure any such qualification or ultimate marketing
approval by the FDA. The FDA has broad discretion with respect to whether or not to grant this designation. Thus, even if we believe
a particular product candidate is eligible for this designation, the FDA may decide not to grant it. Moreover, even if we do receive
a Fast Track or another accelerated review designation, we or our collaborators may not experience a faster development process, review
or approval compared to conventional FDA procedures. In addition, the FDA may withdraw a Fast Track or other accelerated review designation
if it believes that the designation is no longer supported by data from our clinical development program.
We
may seek priority review designation for our product candidates, but we might not receive such designation, and even if we do, such designation
may not lead to a faster development or regulatory review or approval process.
If
the FDA determines that a product candidate offers a treatment for a serious condition and, if approved, the product would provide a
significant improvement in safety or effectiveness, the FDA may designate the product candidate for priority review. A priority review
designation means that the goal for the FDA to review an application is six months, rather than the standard review period of ten months.
The FDA has broad discretion with respect to whether or not to grant priority review status to a product candidate, so even if we believe
a particular product candidate is eligible for such designation or status, the FDA may decide not to grant it. Moreover, a priority review
designation does not necessarily mean a faster development or regulatory review or approval process or necessarily confer any advantage
with respect to approval compared to conventional FDA procedures. Receiving priority review from the FDA does not guarantee approval
within the six-month review cycle or at all.
A
Breakthrough Therapy Designation by the FDA, even if granted for any of our product candidates, may not lead to a faster development
or regulatory review or approval process, and it does not increase the likelihood that our product candidates will receive marketing
approval.
We
may seek a Breakthrough Therapy Designation for our product candidates if the clinical data support such a designation for one or more
product candidates. A breakthrough therapy is defined as a drug or biologic that is intended, alone or in combination with one or more
other drugs or biologics, to treat a serious or life-threatening disease or condition and preliminary clinical evidence indicates that
the drug, or biologic, may demonstrate substantial improvement over existing therapies on one or more clinically significant endpoints,
such as substantial treatment effects observed early in clinical development. For product candidates that have been designated as breakthrough
therapies, interaction and communication between the FDA and the sponsor of the trial can help to identify the most efficient path for
clinical development while minimizing the number of patients placed in ineffective control regimens. Drugs and biologics designated as
breakthrough therapies by the FDA may also be eligible for accelerated approval.
Designation
as a breakthrough therapy is within the discretion of the FDA. Accordingly, even if we believe one of our product candidates meets
the criteria for designation as a breakthrough therapy, the FDA may disagree and determine not to make such designation. In any event,
the receipt of a Breakthrough Therapy Designation for a product candidate may not result in a faster development process, review or approval
compared to drugs considered for approval under non-expedited FDA review procedures and does not assure ultimate approval by the FDA. In
addition, even if one or more of our product candidates qualify as breakthrough therapies, the FDA may later decide that the product
no longer meets the conditions for such qualification.
The
regenerative medicine advanced therapy (“RMAT”) designation by the FDA for any of our product candidates may not lead to
a faster development or regulatory review or approval process, and it does not increase the likelihood that our product candidates will
receive marketing approval.
We
may seek an RMAT designation for our product candidates if the clinical data support such a designation for one or more product candidates.
An RMAT is defined as cell and gene therapies, therapeutic tissue engineering products, human cell and tissue products, and combination
products using any such therapies or products. Gene therapies, including genetically modified cells that lead to a durable modification
of cells or tissues may meet the definition of a regenerative medicine therapy. The RMAT program is intended to facilitate efficient
development and expedite review of RMATs, which are intended to treat, modify, reverse, or cure a serious or life-threatening disease
or condition and for which preliminary clinical evidence indicates that the drug has the potential to address unmet medical needs for
such disease or condition. A biologics license application for a regenerative medicine therapy that has received RMAT designation may
be eligible for priority review or accelerated approval. An RMAT may be eligible for priority review if it treats a serious condition
and, if approved, would provide a significant improvement in the safety or effectiveness of the treatment of the condition. An RMAT may
be eligible for accelerated approval through surrogate or intermediate endpoints reasonably likely to predict long-term clinical benefit
or reliance upon data obtained from a meaningful number of sites. Benefits of such designation also include early interactions with the
FDA to discuss any potential surrogate or intermediate endpoint to be used to support accelerated approval. A regenerative medicine therapy
with RMAT designation that is granted accelerated approval and is subject to post-approval requirements may fulfill such requirements
through the submission of clinical evidence from clinical trials, patient registries, or other sources of real world evidence, such as
electronic health records; the collection of larger confirmatory data sets; or post-approval monitoring of all patients treated with
such therapy prior to its approval.
Designation
as an RMAT is within the discretion of the FDA. Accordingly, even if we believe one of our product candidates meets the criteria
for designation as a RMAT, the FDA may disagree and instead determine not to make such designation. In any event, the receipt of RMAT
designation for our product candidates may not result in a faster development process, review or approval compared to drugs considered
for approval under conventional FDA procedures and does not assure ultimate approval by the FDA. In addition, even if one or more
of our product candidates qualify for RMAT designation, the FDA may later decide that the biological products no longer meet the conditions
for such qualification.
We
may not be able to obtain orphan drug exclusivity for one or more of our product candidates, and even if we do, that exclusivity may
not prevent the FDA or EMA from approving other competing products.
Under
the Orphan Drug Act of 1983, the FDA may designate a product as an orphan drug if it is a drug or biologic intended to treat
a rare disease or condition. A similar regulatory scheme governs approval of orphan products by the EMA in the European Union. Generally,
if a product candidate with an orphan drug designation subsequently receives the first marketing approval for the indication for which
it has such designation, the product is entitled to a period of marketing exclusivity, which precludes the FDA or EMA from approving
another marketing application for the same product for the same therapeutic indication for that time period. The applicable period is
seven years in the United States and ten years in the European Union. The exclusivity period in the European Union can
be reduced to six years if a product no longer meets the criteria for orphan drug designation, in particular if the product is sufficiently
profitable so that market exclusivity is no longer justified.
In
order for the FDA to grant orphan drug exclusivity to one of our products, the FDA must find that the product is indicated for the treatment
of a condition or disease with a patient population of fewer than 200,000 individuals annually in the United States. The FDA may
conclude that the condition or disease for which we may seek orphan drug exclusivity does not meet this standard. Even if we obtain orphan
drug exclusivity for a product, that exclusivity may not effectively protect the product from competition because different products
can be approved for the same condition. In particular, the concept of what constitutes the “same drug” for purposes of orphan
drug exclusivity remains in flux in the context of gene therapies, and the FDA issued recent draft guidance suggesting that it would
not consider two genetic medicine products to be different drugs solely based on minor differences in the transgenes or vectors within
a given vector class. In addition, even after an orphan drug is approved, the FDA can subsequently approve the same product for the same
condition if the FDA concludes that the later product is clinically superior in that it is shown to be safer, more effective or makes
a major contribution to patient care. Orphan drug exclusivity may also be lost if the FDA or EMA determines that the request for designation
was materially defective or if the manufacturer is unable to assure sufficient quantity of the product to meet the needs of the patients
with the rare disease or condition.
In
2017, Congress passed the FDA Reauthorization Act of 2017 (the “FDARA”). FDARA, among other things, codified the
FDA’s pre-existing regulatory interpretation to require that a drug sponsor demonstrate the clinical superiority of an orphan drug
that is otherwise the same as a previously approved drug for the same rare disease in order to receive orphan drug exclusivity. Under
omnibus legislation signed by President Trump on December 27, 2020, the requirement for a product to show clinical superiority applies
to any drug and biologic that received orphan drug designation before enactment of FDARA in 2017 but has not yet been approved or licensed
by the FDA. We do not know if, when, or how the FDA may change the orphan drug regulations and policies in the future, and it is
uncertain how any changes might affect our business. Depending on what changes the FDA may make to its orphan drug regulations and policies,
our business could be adversely impacted.
*Disruptions
at the FDA and other government agencies caused by funding shortages or global health concerns could hinder their ability to hire, retain
or deploy key leadership and other personnel, or otherwise prevent new or modified products from being developed, approved or commercialized
in a timely manner or at all, which could negatively impact our business.
The
ability of the FDA to review and approve new products can be affected by a variety of factors, including government budget and funding
levels, statutory, regulatory, and policy changes, the FDA’s ability to hire and retain key personnel and accept the payment of
user fees, and other events that may otherwise affect the FDA’s ability to perform routine functions. Average review times at the
agency have fluctuated in recent years as a result. In addition, government funding of other government agencies that fund research
and development activities is subject to the political process, which is inherently fluid and unpredictable. Disruptions at the FDA and
other agencies may also slow the time necessary for new biologics or modifications to cleared or approved biologics to be reviewed and/or
approved by necessary government agencies, which would adversely affect our business. For example, over the last several years,
including for 35 days beginning on December 22, 2018, the U.S. government has shut down several times and certain
regulatory agencies, such as the FDA, have furloughed critical FDA employees and stopped critical activities. If a prolonged government
shutdown occurs, it could significantly impact the ability of the FDA to timely review and process our regulatory submissions, which
could have a material adverse effect on our business.
Separately,
in response to the COVID-19 pandemic, on March 10, 2020, the FDA announced its intention to postpone most inspections of foreign
manufacturing facilities, and on March 18, 2020, the FDA temporarily postponed routine surveillance inspections of domestic manufacturing
facilities. Subsequently, on July 10, 2020, the FDA announced its intention to resume certain on-site inspections of domestic manufacturing
facilities subject to a risk-based prioritization system. Increased cases associated with a COVID-19 variant led the FDA to again pause
inspections, although the FDA announced in February 2022 that it would resume routine domestic surveillance inspections and that it would
proceed with certain foreign surveillance inspections where country conditions permit. 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.
Risks
Related to Our Relationships with Third Parties
We
rely on third parties to conduct our preclinical and clinical trials and will rely on them to perform other tasks for us. If these third
parties do not successfully carry out their contractual duties, meet expected deadlines or comply with regulatory requirements, we may
not be able to obtain regulatory approval for or commercialize our product candidates and our business could be substantially harmed.
Although
we have recruited a team that has experience with clinical trials, as a company, we have limited experience in conducting clinical trials.
Moreover, we do not have the ability to independently conduct preclinical studies and clinical trials, and we have relied upon, and plan
to continue to rely upon, medical institutions, clinical investigators, contract laboratories and other third parties, or our CROs, to
conduct preclinical studies and future clinical trials for our product candidates. We expect to rely heavily on these parties for execution
of preclinical and future clinical trials for our product candidates and control only certain aspects of their activities. Nevertheless,
we will be responsible for ensuring that each of our preclinical and clinical trials is conducted in accordance with the applicable protocol,
legal and regulatory requirements and scientific standards and our reliance on CROs will not relieve us of our regulatory responsibilities.
For any violations of laws and regulations during the conduct of our preclinical studies and clinical trials, we could be subject to
warning letters or enforcement action that may include civil penalties up to and including criminal prosecution.
We
and our CROs will be required to comply with regulations, including cGCPs for conducting, monitoring, recording and reporting the results
of preclinical and clinical trials to ensure that the data and results are scientifically credible and accurate and that the trial patients
are adequately informed of the potential risks of participating in clinical trials and their rights are protected. These regulations
are enforced by the FDA, the Competent Authorities of the Member States of the European Economic Area and comparable foreign regulatory
authorities for any drugs in clinical development. The FDA enforces cGCP regulations through periodic inspections of clinical trial sponsors,
principal investigators and trial sites. If we or our CROs fail to comply with applicable cGCPs, 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 you that, upon inspection, the FDA will determine that any of our
future clinical trials will comply with cGCPs. In addition, our clinical trials must be conducted with product candidates produced in
accordance with the requirements in the FDA’s current cGMPs requirements. Our failure or the failure of our CROs to comply with
these regulations may require us to repeat clinical trials, which would delay the regulatory approval process and could also subject
us to enforcement action.
Although
we intend to design our planned clinical trials for our product candidates, for the foreseeable future CROs will conduct all of our planned
clinical trials. As a result, many important aspects of our development programs, including their conduct and timing, will be outside
of our direct control. Our reliance on third parties to conduct future preclinical studies and clinical trials will also result in less day-to-day
control over the management of data developed through preclinical studies and clinical trials than would be the case if we were relying
entirely upon our own staff.
If
any of our relationships with these third-party CROs terminate, we may not be able to enter into arrangements with alternative CROs.
If CROs do not successfully carry out their contractual duties or obligations or meet expected deadlines, if they need to be replaced
or if the quality or accuracy of the clinical data they obtain is compromised due to the failure to adhere to our clinical protocols,
regulatory requirements or for other reasons, any preclinical studies or clinical trials with which such CROs are associated with may
be extended, delayed or terminated. In such cases, we may not be able to obtain regulatory approval for or successfully commercialize
our product candidates. As a result, our financial results and the commercial prospects for our product candidates in the subject indication
could be harmed, our costs could increase and our ability to generate revenue could be delayed.
We
currently rely on a single manufacturer for our clinical supply of our product candidates. In the event of a loss of this manufacturer,
or a failure by such manufacturer to comply with FDA regulations, we may not be able to find an alternative source on commercially reasonable
terms, or at all. In addition, third-party manufacturers and any third-party collaborators may be unable to successfully scale-up manufacturing
of our current or future product candidates in sufficient quality and quantity, which would delay or prevent us from developing our product
candidates and commercializing approved products, if any.
We
do not have any manufacturing facilities at the present time. We currently rely on third-party manufacturers, including Lonza Sales AG
(“Lonza”) as a single source supplier, for the manufacture and supply of our materials for preclinical studies, and expect
to continue to do so for future clinical testing and for commercial supply of JSP191 and any other product candidates that we may develop
and for which we or our collaborators obtain marketing approval. Our agreement with Lonza includes certain limitations on our ability
to enter into supply arrangements with any other supplier without Lonza’s consent. In addition, Lonza has the right to increase
the prices it charges us for certain supplies depending on a number of factors, some of which are outside of our control. We may be unable
to maintain or establish any agreements with third-party manufacturers or suppliers or to do so on acceptable terms. Even if we are able
to establish agreements with third-party manufacturers or suppliers, reliance on third-party manufacturers entails additional risks,
including:
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the possible breach of the manufacturing or supply
agreement by the third party; |
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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; and |
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reliance on the third party for regulatory compliance,
quality assurance, safety and pharmacovigilance and related reporting. |
In
addition, pursuant to our Exclusive License Agreement with Amgen Inc., Lonza Biologics, Inc. has been engaged to manufacture JSP191 for
us. The agreement provides that in the event we wish to change the manufacturer of JSP191 to a different party, we must obtain Amgen
Inc.’s prior consent. As a result, our ability to obtain any alternative supplier of JSP191 may be further limited.
Third-party
manufacturers may not be able to comply with cGMP regulations or similar regulatory requirements outside the United States. Our
failure, or the failure of our third-party manufacturers or suppliers, to comply with applicable regulations could result in sanctions
being imposed on us, including fines, injunctions, civil penalties, delays, suspension or withdrawal of approvals, license revocations,
seizures or recalls of product candidates or products, operating restrictions and criminal prosecutions, any of which could significantly
and adversely affect supplies of our products and harm our business, financial condition, results of operations and prospects.
Our
product candidates may compete with other product candidates and products for access to manufacturing facilities and other supplies.
There are a limited number of manufacturers that operate under cGMP regulations and that might be capable of manufacturing for us. Also,
prior to the approval of our product candidates, we would need to identify a contract manufacturer that could produce our products at
a commercial scale and that could successfully complete FDA pre-approval inspection and inspections by other health authorities. Agreements
with such manufacturers or suppliers may not be available to us at the time we would need to have that capability and capacity.
Any
performance failure on the part of our existing or future manufacturers or suppliers, or any decision by a manufacturer or supplier to
remove our products from the market or restrict access to our products, could delay clinical development or marketing approval. We do
not currently have arrangements in place for redundant or guaranteed supply for many of the materials we currently use in our clinical
trials or preclinical studies, and we may have difficulty or be unable to establish alternative sources of these materials.
We
may enter into collaborations with third parties for the research, development and commercialization of certain product candidates we
may develop. If any such collaborations are not successful, we may not be able to capitalize on the market potential of those product
candidates.
We
may seek third-party collaborators for the research, development and commercialization of certain product candidates we may develop.
If we enter into any such arrangements with any third parties, we will likely have limited control over the amount and timing of resources
that our collaborators dedicate to the development or commercialization our product candidates. Our ability to generate revenues from
these arrangements will depend on our collaborators’ abilities to successfully perform the functions assigned to them in these
arrangements. We cannot predict the success of any collaboration that we enter into.
Collaborations
involving our current or future product candidates or research programs pose numerous risks to us, including the following:
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Collaborators may not pursue development and commercialization
of our product candidates or may elect not to continue or renew development or commercialization programs based on clinical trial
results, changes in the collaborator’s strategic focus or available funding or external factors such as an acquisition that
diverts resources or creates competing priorities; |
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Collaborators may delay clinical trials, provide insufficient
funding for a clinical trial program, stop a clinical trial or abandon a product candidate, repeat or conduct new clinical trials
or require a new formulation of a product candidate for clinical testing; |
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Collaborators could independently develop, or develop
with third parties, products that compete directly or indirectly with our product candidates if the collaborators believe that competitive
products are more likely to be successfully developed or can be commercialized under terms that are more economically attractive
than ours; |
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Collaborators with marketing and distribution rights
to one or more products may not commit sufficient resources to the marketing and distribution of such products; |
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Collaborators may not properly obtain, maintain, enforce
or defend our intellectual property or proprietary rights or may use our proprietary information in such a way as to invite litigation
that could jeopardize or invalidate our proprietary information or expose us to potential litigation; |
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Disputes may arise between the collaborators and us
that result in the delay or termination of the research, development or commercialization of our products or product candidates or
that result in costly litigation or arbitration that diverts management attention and resources; |
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We may lose certain valuable rights under circumstances
identified in our collaborations, including if we undergo a change of control; and |
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Collaboration agreements may not lead to development
or commercialization of product candidates in the most efficient manner or at all. If a present or future collaborator of ours were
to be involved in a business combination, the continued pursuit and emphasis on our product development or commercialization program
under such collaboration could be delayed, diminished or terminated. |
If
our collaborations do not result in the successful development and commercialization of product candidates, or if one of our collaborators
terminates our agreement with us, we may not receive any future research funding or milestone or royalty payments under the collaboration.
If we do not receive the funding we expect under these agreements, our development of product candidates could be delayed, and we may
need additional resources to develop product candidates. In addition, if one of our collaborators terminates its agreement with us, we
may find it more difficult to find a suitable replacement collaborator or attract new collaborators, and our development programs may
be delayed or the perception of us in the business and financial communities could be adversely affected. All of the risks relating to
product development, regulatory approval and commercialization described in this Quarterly Report on Form 10-Q apply to the activities
of our collaborators.
These
relationships, or those like them, may require us to incur non-recurring and other charges, increase our near- and long-term expenditures,
issue securities that dilute our existing stockholders, or disrupt our management and business.
If
we are not able to establish collaborations on commercially reasonable terms, we may have to alter our development and commercialization
plans.
Our
product development and research programs and the potential commercialization of JSP191 or any other product candidates we may develop
will require substantial additional cash to fund expenses. For some of the product candidates we may develop, we may decide to collaborate
with other pharmaceutical and biotechnology companies for the development and potential commercialization of those product candidates.
We
would face significant competition in seeking appropriate collaborators. Whether we reach a definitive agreement for a collaboration
will depend, among other things, upon our assessment of the collaborator’s resources and expertise, the terms and conditions of
the proposed collaboration, and the proposed collaborator’s evaluation of a number of factors. Those factors may include the design
or results of clinical trials, the likelihood of approval by the FDA, the EMA or similar regulatory authorities outside the United States,
the potential market for the subject product candidate, the costs and complexities of manufacturing and delivering such product candidate
to patients, the potential of competing products, the existence of uncertainty with respect to our ownership of technology, which can
exist if there is a challenge to such ownership without regard to the merits of the challenge, and industry and market conditions generally.
The collaborator may also consider alternative product candidates or technologies for similar indications that may be available to collaborate
on and whether such a collaboration could be more attractive than the one with us.
We
may also be restricted under existing collaboration agreements from entering into future agreements on certain terms with potential collaborators.
Collaborations are complex and time-consuming to negotiate and document. In addition, there have been a significant number of recent
business combinations among large pharmaceutical companies that have resulted in a reduced number of potential future collaborators.
We
may not be able to negotiate collaborations on a timely basis, on acceptable terms, or at all. If we are unable to do so, we may have
to curtail the development of the product candidate for which we are seeking to collaborate, reduce or delay our development program
or one or more of our other development programs, delay our potential commercialization or reduce the scope of any sales or marketing
activities, or increase our expenditures and undertake development or commercialization activities at our own expense. If we elect to
increase our expenditures to fund development or commercialization activities on our own, we may need to obtain additional capital, which
may not be available to us on acceptable terms or at all. If we do not have sufficient funds, we may not be able to develop product candidates
or bring them to market and generate product revenue.
Risks
Related to Our Intellectual Property
We
are highly dependent on intellectual property licensed from third parties, and termination of any of these licenses could result in the
loss of significant rights, which would harm our business.
We
are dependent on the patents, know-how and proprietary technology licensed from third parties for the development and, if approved, commercialization
of JSP191. Any termination of these licenses, or a finding that such intellectual property lacks legal effect, could result in the loss
of significant rights and could harm our ability to commercialize our current or future product candidates.
For
example, we rely on our worldwide exclusive license agreement with Amgen Inc., whereby we license a patent portfolio from Amgen Inc.
applicable to our targeted conditioning program that contains patent families directed to humanized C-kit antibody. We also rely on our
license agreement with Stanford, whereby we license a patent portfolio applicable to our targeted conditioning and Stem Cell Graft programs
that contains patent families directed to immunodepletion of endogenous stem cell niche for engraftment.
Each
of our license agreements with third parties impose certain obligations on us, including obligations to use diligent efforts to meet
development thresholds and payment obligations. Non-compliance with such obligations may result in termination of the respective license
agreement or in legal and financial consequences. If any of our licensors terminates its respective license agreement, we may not be
able to develop or commercialize JSP191 or any other product candidates covered by these agreements. Termination of our license agreements
or reduction or elimination of our rights under them may result in us having to negotiate a new or reinstated agreement, which may not
be available to us on equally favorable terms, or at all, which may mean we are unable to develop, commercialize or sell the affected
product candidate or may cause us to lose our rights under the agreement.
In
addition, our licensors may make decisions in prosecuting, maintaining, enforcing and defending any licensed intellectual property rights
that may not be in our best interest. Moreover, if our licensors take any action with respect to any licensed intellectual property rights,
for example, any licensed patents or patent applications, that results in a successful challenge to the licensed intellectual property
by a third party, such patents may be invalidated or held to be unenforceable, and we may lose our rights under such patents, which could
materially harm our business.
Further,
the agreements under which we currently license intellectual property from third parties are complex, and certain provisions in such
agreements may be susceptible to multiple interpretations. Accordingly, disputes may arise between us and our licensors regarding intellectual
property subject to a license agreement. The resolution of any contract interpretation disagreement that may arise could narrow what
we believe to be the scope of our rights to the relevant intellectual property or technology, or increase what we believe to be our financial
or other obligations under the relevant agreement. If disputes over intellectual property that we have licensed prevent or impair our
ability to maintain our current licensing arrangements on acceptable terms, or are insufficient to provide us with the necessary rights
to use the intellectual property, we may be unable to successfully develop and commercialize the affected product candidates.
Our
commercial success depends on our ability to obtain, maintain and protect our intellectual property and proprietary technology.
Our
commercial success depends in large part on our ability to obtain, maintain and protect intellectual property rights through patents,
trademarks and trade secrets in the United States and other countries with respect to our proprietary product candidates. If we
do not adequately protect our intellectual property rights, competitors may be able to erode, negate or preempt any competitive advantage
we may have, which could harm our business and ability to achieve profitability.
To
protect our proprietary position, we own and have in-licensed certain intellectual property rights, including certain issued patents
and patent applications, and have filed and may file provisional and non-provisional patent applications in the United States or
abroad related to our product candidates that are important to our business. Provisional patent applications are not eligible to become
issued patents until, among other things, we file a non-provisional patent application within 12 months of the filing of one
or more of our related provisional patent applications. If we do not timely file non-provisional patent applications, we may lose our
priority date with respect to our provisional patent applications and any patent protection on the inventions disclosed in our provisional
patent applications. While we intend to timely file non-provisional patent applications relating to our provisional patent applications,
we cannot predict whether any such patent applications will result in the issuance of patents that provide us with any competitive advantage.
Moreover, the patent application and approval process is expensive and time-consuming. We may not be able to file and prosecute all necessary
or desirable patent applications at a reasonable cost or in a timely manner.
The
patent application, prosecution, and enforcement processes are subject to numerous risks and uncertainties, and there can be no assurance
that we, our licensors, or any of our future collaborators will be successful in protecting our product candidates by obtaining, defending,
and/or asserting patent rights. These risks and uncertainties include the following:
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the U.S. Patent and Trademark Office (the “USPTO”)
and various foreign governmental patent agencies require compliance with a number of procedural, documentary, fee payment and other
provisions during the patent process. There are situations in which noncompliance can result in abandonment or lapse of a patent
or patent application, resulting in partial or complete loss of patent rights in the relevant jurisdiction. In such an event, competitors
might be able to enter the market earlier than would otherwise have been the case; |
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patent applications may not result in any patents being
issued; |
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patents that may be issued or in-licensed may be challenged,
invalidated, modified, revoked, circumvented, found to be unenforceable or otherwise may not provide any competitive advantage; |
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our competitors, many of whom have substantially greater
resources and many of whom have made significant investments in competing technologies, may seek or may have already obtained patents
that will limit, interfere with or eliminate our ability to make, use, and sell our potential product candidates; |
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there may be significant pressure on the U.S. government
and international governmental bodies to limit the scope of patent protection both inside and outside the United States for
disease treatments that prove successful, as a matter of public policy regarding worldwide health concerns; and |
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countries other than the United States may have
patent laws less favorable to patentees than those upheld by U.S. courts, allowing foreign competitors a better opportunity
to create, develop and market competing product candidates. |
In
some instances, agreements through which we license intellectual property rights may not give us control over patent prosecution or maintenance,
so that we may not be able to control which claims or arguments are presented, how claims are amended, and may not be able to secure,
maintain or successfully enforce necessary or desirable patent protection from those patent rights. We cannot be certain that patent
prosecution and maintenance activities by our licensors have been or will be conducted in compliance with applicable laws and regulations
or will result in valid and enforceable patents.
Moreover,
some of our in-licensed patents and patent applications may be, and some of our future owned and licensed patents may be, co-owned with
third parties. If we are unable to obtain an exclusive license to any such third-party co-owners’ interest in such patents or patent
applications, such co-owners may be able to license their rights to other third parties, including our competitors, and our competitors
could market competing products and technology. In addition, we may need the cooperation of any such co-owners of our patents in order
to enforce such patents against third parties, and such cooperation may not be provided to us.
The
patent protection we obtain for our product candidates may not be sufficient enough to provide us with any competitive advantage or our
patents may be challenged.
Our
owned and licensed patents and pending patent applications, if issued, may not provide us with any meaningful protection or may not prevent
competitors from designing around our patent claims to circumvent our patents by developing similar or alternative technologies or therapeutics
in a non-infringing manner. For example, a third party may develop a competitive product that provides benefits similar to one or more
of our product candidates but falls outside the scope of our patent protection or license rights. If the patent protection provided by
the patents and patent applications we hold or pursue with respect to our product candidates is not sufficiently broad to impede such
competition, our ability to successfully commercialize our product candidates could be negatively affected, which would harm our business.
Currently, a significant portion of our patents and patent applications are in-licensed, though similar risks would apply to any patents
or patent applications that we now own or may own or in-license in the future.
It
is possible that defects of form in the preparation or filing of our patents or patent applications may exist, or may arise in the future,
for example with respect to proper priority claims, inventorship, claim scope or requests for patent term adjustments. If we or our partners,
collaborators, licensees or licensors, whether current or future, fail to establish, maintain or protect such patents and other intellectual
property rights, such rights may be reduced or eliminated. If our partners, collaborators, licensees or licensors, are not fully cooperative
or disagree with us as to the prosecution, maintenance or enforcement of any patent rights, such patent rights could be compromised.
If there are material defects in the form, preparation, prosecution or enforcement of our patents or patent applications, such patents
may be invalid and/or unenforceable, and such applications may never result in valid, enforceable patents. Any of these outcomes could
impair our ability to prevent competition from third parties, which may have an adverse impact on our business.
In
addition, the determination of patent rights with respect to clinical compositions of matter and treatment methods commonly involves
complex legal and factual questions, which are dependent upon the current legal and intellectual property context, extant legal precedent
and interpretations of the law by individuals. As a result, the issuance, scope, validity, enforceability and commercial value of our
patent rights are characterized by uncertainty.
Changes
in either the patent laws or interpretation of the patent laws in the United States and other countries may diminish the value of
our patents or narrow the scope of our patent protection. In addition, the laws of foreign countries may not protect our rights to the
same extent or in the same manner as the laws of the United States. For example, patent laws in various jurisdictions, including
significant commercial markets such as Europe, restrict the patentability of methods of treatment of the human body more than U.S. law
does. If these changes were to occur, they could have a material adverse effect on our ability to generate revenue.
Pending
patent applications cannot be enforced against third parties practicing the technology claimed in such applications unless and until
a patent issues from such applications. Assuming the other requirements for patentability are met, currently, the first party to file
a patent application is generally entitled to the patent. However, prior to March 16, 2013, in the United States, the first
party to invent was entitled to the patent. Publications of discoveries in the scientific literature often lag behind the actual discoveries,
and patent applications in the United States and other jurisdictions are not published until 18 months after filing, or
in some cases not at all. Therefore, we cannot be certain that we were the first to make the inventions claimed in our patents or pending
patent applications, or that we were the first to file for patent protection of such inventions. Similarly, we cannot be certain that
parties from whom we do or may license or purchase patent rights were the first to make relevant claimed inventions, or were the first
to file for patent protection for them. If third parties have filed prior patent applications on inventions claimed in our patents or
applications that were filed on or before March 15, 2013, an interference proceeding in the United States can be initiated
by such third parties to determine who was the first to invent any of the subject matter covered by the patent claims of our applications.
If third parties have filed such prior applications after March 15, 2013, a derivation proceeding in the United States can
be initiated by such third parties to determine whether our invention was derived from theirs.
Moreover,
because the issuance of a patent is not conclusive as to its inventorship, scope, validity or enforceability, our owned and licensed
patents or pending patent applications may be challenged in the courts or patent offices in the United States and abroad. There
is no assurance that all of the potentially relevant prior art relating to our patents and patent applications has been found. If such
prior art exists, it may be used to invalidate a patent, or may prevent a patent from issuing from a pending patent application. For
example, such patent filings may be subject to a third-party submission of prior art to the USPTO, or to other patent offices around
the world. Alternately or additionally, we may become involved in post-grant review procedures, oppositions, derivation proceedings,
ex parte reexaminations, inter parties review, supplemental examinations, or interference proceedings or challenges in district court,
in the United States or in various foreign patent offices, including both national and regional, challenging patents or patent applications
in which we have rights, including patents on which we rely to protect our business. An adverse determination in any such challenges
may result in loss of the patent or in patent claims being narrowed, invalidated or held unenforceable, in whole or in part, or in denial
of the patent application or loss or reduction in the scope of one or more claims of the patent application, any of 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. In addition, given the amount of time required for the development, testing and regulatory
review of new product candidates, patents protecting such candidates might expire before or shortly after such candidates are commercialized.
Issued
patents that we have or may obtain or license may not 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 patents by developing similar
or alternative technologies or products in a non-infringing manner. Our competitors may also seek approval to market their own products
similar to or otherwise competitive with our products. Alternatively, our competitors may seek to market generic versions of any approved
products or pursue similar strategies in the United States or other jurisdictions, in which they claim that patents owned or licensed
by us are invalid, unenforceable or not infringed. In these circumstances, we may need to defend or assert our patents, or both, including
by filing lawsuits alleging patent infringement. In any of these types of proceedings, a court or other agency with jurisdiction may
find our patents invalid or unenforceable, or that our competitors are competing in a non-infringing manner. Thus, even if we have valid
and enforceable patents, these patents still may not provide protection against competing products or processes sufficient to achieve
our business objectives. Any of the foregoing could have a material adverse effect on our business, financial condition, results of operations
and prospects.
Other
parties have developed or may develop technologies that may be related to or competitive with our approach, and may have filed or may
file patent applications and may have been issued or may be issued patents with claims that overlap or conflict with our patent applications,
either by claiming the same materials, formulations or methods, or by claiming subject matter that could dominate our patent position.
In addition, certain parts or all of the patent portfolios licensed to us are, or may be, licensed to third parties and such third parties
may have or may obtain certain enforcement rights. If the scope of the patent protection we or our licensors obtain is not sufficiently
broad, we may not be able to prevent others from developing and commercializing technology and products similar or identical to ours.
The degree of patent protection we require to successfully compete in the marketplace may be unavailable or severely limited in some
cases and may not adequately protect our rights or permit us to gain or keep any competitive advantage. We cannot provide any assurances
that any of our licensed patents have, or that any of our pending owned or licensed patent applications that mature into issued patents
will include, claims with a scope sufficient to protect our product candidates or otherwise provide any competitive advantage, nor can
we provide any assurance that our licenses will remain in force.
In
addition, there are situations in which noncompliance can result in abandonment or lapse of the patent or patent application, resulting
in partial or complete loss of patent rights in the relevant jurisdiction. Noncompliance events that could result in abandonment or lapse
of a patent or patent application include, but are not limited to, failure to respond to official actions within prescribed time limits,
non-payment of fees and failure to properly legalize and submit formal documents.
If
we are unable to protect the confidentiality of our trade secrets, our business and competitive position may be harmed.
In
addition to the protection afforded by patents, we rely upon trade secret protection, know-how and continuing technological innovation
to develop and maintain our competitive position. We seek to protect our proprietary technology and processes, in part, by entering into
confidentiality agreements with our contractors, collaborators, scientific advisors, employees and consultants and invention assignment
agreements with our consultants and employees. However, we may not obtain these agreements in all circumstances, and individuals with
whom we have these agreements may not comply with their terms. The assignment of intellectual property rights under these agreements
may not be self-executing or the assignment agreements may be breached, and we may be forced to bring claims against third parties, or
defend claims that they may bring against us, to determine the ownership of what we regard as our intellectual property. In addition,
we may not be able to prevent the unauthorized disclosure or use of our technical know-how or other trade secrets by the parties to these
agreements despite the existence of confidentiality agreements and other contractual restrictions. Monitoring unauthorized uses and disclosures
is difficult and we do not know whether the steps we have taken to protect our proprietary technologies will be effective. If any of
the contractors, collaborators, scientific advisors, employees and consultants who are parties to these agreements breaches or violates
the terms of any of these agreements, we may not have adequate remedies for any such breach or violation. As a result, we could lose
our trade secrets. Enforcing a claim against a third party that illegally obtained and is using our trade secrets, like patent litigation,
is expensive and time-consuming and the outcome is unpredictable. In addition, courts outside the United States are sometimes less
willing or unwilling to protect trade secrets. Any of the foregoing could have a material adverse effect on our business, financial condition,
results of operations, and prospects.
Moreover,
our trade secrets could otherwise become known or be independently discovered by our competitors or other third parties. Competitors
and other third parties could attempt to replicate some or all of the competitive advantages we derive from our development efforts,
willfully infringe our intellectual property rights, design around our protected technology or develop their own competitive technologies
that fall outside of our intellectual property rights. If any of our trade secrets were to be lawfully obtained or independently developed
by a competitor or other third party, 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 our trade secrets are not adequately protected or sufficient to provide an advantage over our competitors,
our competitive position could be adversely affected, as could our business. Additionally, if the steps taken to maintain our trade secrets
are deemed inadequate, we may have insufficient recourse against third parties for misappropriating our trade secrets.
If
our trademarks and trade names are not adequately protected, then we may not be able to build name recognition in our markets of interest
and our business may be adversely affected.
Our
current or future trademarks or trade names may be challenged, infringed, circumvented or declared generic or descriptive or determined
to be infringing on other marks. We may not be able to protect our rights to these trademarks and trade names or may be forced to stop
using these names, which we need for name recognition by potential partners or customers in our markets of interest. Our company name
and logo, as well as our product candidate names “JSP191” and “JSP502”, are not registered trademarks. If we
seek to register any of our trademarks, during trademark registration proceedings, we may receive rejections of our applications by the
USPTO or in other foreign jurisdictions. Although we would be given an opportunity to respond to those rejections, we may be unable to
overcome such rejections. In addition, in the USPTO and in comparable agencies in many foreign jurisdictions, third parties are given
an opportunity to oppose pending trademark applications and to seek to cancel registered trademarks. Opposition or cancellation proceedings
may be filed against our trademarks, and our trademarks may not survive such proceedings. If we are unable to establish name recognition
based on our trademarks and trade names, we may not be able to compete effectively and our business may be adversely affected. We may
license our trademarks and trade names to third parties, such as distributors. Although these license agreements may provide guidelines
for how our trademarks and trade names may be used, a breach of these agreements or misuse of our trademarks and tradenames by our licensees
may jeopardize our rights in or diminish the goodwill associated with our trademarks and trade names.
Moreover,
any name we have proposed to use with our product candidate in the United States must be approved by the FDA, regardless of whether
we have registered it, or applied to register it, as a trademark. Similar requirements exist in Europe. The FDA typically conducts a
review of proposed product names, including an evaluation of potential for confusion with other product names. If the FDA (or an equivalent
administrative body in a foreign jurisdiction) objects to any of our proposed proprietary product names, we may be required to expend
significant additional resources in an effort to identify a suitable substitute name that would qualify under applicable trademark laws,
not infringe the existing rights of third parties and be acceptable to the FDA. Furthermore, in many countries, owning and maintaining
a trademark registration may not provide an adequate defense against a subsequent infringement claim asserted by the owner of a senior
trademark. At times, competitors or other third parties may adopt trade names or trademarks similar to ours, thereby impeding our ability
to build brand identity and possibly leading to market confusion. In addition, there could be potential trade name or trademark infringement
claims brought by owners of other registered trademarks or trademarks that incorporate variations of our registered or unregistered trademarks or
trade names. If we assert trademark infringement claims, a court may determine that the marks we have asserted are invalid or unenforceable,
or that the party against whom we have asserted trademark infringement has superior rights to the marks in question. In this case, we
could ultimately be forced to cease use of such trademarks.
We
may not be successful in acquiring or in-licensing necessary rights to key technologies underlying JSP191 or any future product candidates
we may develop.
We
currently have rights to intellectual property, through licenses from third parties, to develop JSP191, and we expect to seek to expand
our intellectual property footprint related to our product candidate pipeline in part by in-licensing the rights to key technologies.
The future growth of our business will depend in part on our ability to in-license or otherwise acquire the rights to develop additional
product candidates and technologies. Although we have succeeded in licensing technologies from third-party licensors, including Amgen
Inc. and Stanford, in the past, we can give no assurance that we will be able to in-license or acquire the rights to other technologies
relevant to our product candidates from third parties on acceptable terms or at all.
In
order to market our product candidates, we may find it necessary or prudent to obtain licenses from such third-party intellectual property
holders. However, it may be unclear who owns the rights to intellectual property we wish to obtain, or we may be unable to secure such
licenses or otherwise acquire or in-license intellectual property rights from third parties that we identify as necessary for product
candidates we may develop and technology we employ. For example, we employ a range of genome engineering technologies that are owned
by third parties in our preclinical studies, as well as to manufacture the supply of mRNA stem cell grafts or other cell therapies used
for clinical trials and, if approved, for commercialization of our product candidates. We currently conduct our preclinical research
and clinical trials under 35 U.S.C. § 271(e)(1), which provides a safe harbor from patent infringement for uses of patented
technology reasonably related to the development and submission of information under a federal law which regulates the manufacture, use,
or sale of drugs.
The
licensing or acquisition of third-party intellectual property rights is a highly competitive area, and other companies may pursue strategies
to license or acquire third-party intellectual property rights that we may consider attractive or necessary. Such companies may have
a competitive advantage over us, e.g., due to their size, capital resources and greater clinical development and commercialization capabilities.
In addition, companies that perceive us to be a competitor may be unwilling to assign or license rights to us. We also may be unable
to license or acquire third-party intellectual property rights on terms that would allow us to make an appropriate return on our investment
or at all. If we are unable to successfully obtain rights to required third-party intellectual property rights or maintain the existing
intellectual property rights we have, we may have to abandon development of the relevant program or product candidate, which could have
a material adverse effect on our business, financial condition, results of operations and prospects.
Even
if we were able to obtain such a license, it could be non-exclusive, thereby giving our competitors and other third parties access to
the same technologies licensed to us, and it could require us to make substantial licensing and royalty payments. If we are unable to
obtain a necessary license to a third-party patent on commercially reasonable terms, we may be unable to commercialize our product candidates
or such commercialization efforts may be significantly delayed, which could in turn significantly harm our business.
Third-party
claims of intellectual property infringement, misappropriation or other violations may prevent or delay our product discovery and development
efforts and have a material adverse effect on our business.
Our
commercial success depends in part on us avoiding infringement, misappropriation and other violations of the patents and proprietary
rights of third parties. There is a substantial amount of litigation involving patents and other intellectual property rights in the
biotechnology and pharmaceutical industries, as well as administrative proceedings for challenging patents, including interference and
reexamination proceedings before the USPTO or oppositions and other comparable proceedings in foreign jurisdictions. Recently, under
U.S. patent reform, new procedures including inter partes review and post grant review have been implemented. This reform
will bring uncertainty to the possibility of challenge to our patents in the future. Numerous U.S.-and foreign-issued patents and pending
patent applications, which are owned by third parties, exist in the fields in which we are developing our product candidates, and third
parties may allege they have patent rights encompassing our product candidates, technologies or methods. Third parties may assert that
we are employing their proprietary technology without authorization and may file patent infringement claims or lawsuits against us, and
if we are found to infringe such third-party patents, we may be required to pay damages, cease commercialization of the infringing technology
or obtain a license from such third parties, which may not be available on commercially reasonable terms or at all.
There
may be third-party patents with patent rights to materials, formulations, methods of manufacture or methods of treatment related to the
use or manufacture of our product candidates. Because patent applications can take many years to issue, there may be currently pending
patent applications which may later result in issued patents that our product candidates may infringe. In addition, third parties may
obtain patents in the future and claim that use of our technologies infringes upon these patents. Further, we or our licensors may fail
to identify even those relevant third-party patents that have issued or may incorrectly interpret the relevance, scope or expiration
of such patents. The scope of a patent claim is determined by an interpretation of the law, the written disclosure in a patent and the
patent’s prosecution history. Our interpretation of the relevance or scope of a patent or a pending application may be incorrect.
If any third-party patents were held by a court of competent jurisdiction to cover the manufacturing process of our product candidates,
materials used in or formed during the manufacturing process or any final product itself, the holders of any such patents may be able
to block our ability to commercialize the product candidate unless we obtained a license under the applicable patents, or until such
patents expire or they are finally determined to be held invalid or unenforceable. Similarly, if any third-party patent were held by
a court of competent jurisdiction to cover aspects of our materials, formulations or methods, including without limitation, combination
therapy or patient selection methods, the holders of any such patent may be able to block our ability to develop and commercialize the
product candidate unless we obtained a license or until such patent expires or is finally determined to be held invalid or unenforceable.
Parties
making claims against us may seek and obtain injunctive or other equitable relief, which could effectively block our ability to further
develop and commercialize our product candidates. Defense of these claims, regardless of their merit, would involve substantial litigation
expense and would involve a substantial diversion of employee resources from our business. We may not have sufficient resources to bring
these actions to a successful conclusion, which may result in significant cost and may impede our inability to pursue any affected products
or product candidates. There could also be public announcements of the results of hearings, motions or other interim proceedings or developments.
If securities analysts or investors perceive these results to be negative, it could have a material adverse effect on the price of shares
of our common stock.
In
the event of a successful claim of infringement against us, we may have to pay substantial damages, including treble damages and attorneys’
fees for willful infringement, obtain one or more licenses from third parties, pay royalties or redesign our infringing products, which
may be impossible or require substantial time and monetary expenditure.
Some
intellectual property that we have in-licensed may have been discovered through government-funded programs and thus may be subject to
federal regulations such as “march-in” rights, certain reporting requirements and a preference for U.S.-based companies.
Compliance with such regulations may limit our exclusive rights and limit our ability to contract with non-U.S. manufacturers.
Any
of the intellectual property rights that we have licensed or may license in the future and that have been generated through the use of
U.S. government funding are subject to certain federal regulations. As a result, the U.S. government may have certain rights
to intellectual property embodied in our current or future product candidates pursuant to the Bayh-Dole Act of 1980 (“Bayh-Dole
Act”). These U.S. government rights in certain inventions developed under a government-funded program include a non-exclusive,
non-transferable, irrevocable worldwide license to use inventions for any governmental purpose. In addition, the U.S. government
would have the right to require us to grant exclusive, partially exclusive, or non-exclusive licenses to any such intellectual property
rights to a third party if it determines that:
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adequate steps have not been taken to commercialize
the invention; |
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government action is necessary to meet public health
or safety needs; or |
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government action is necessary to meet requirements
for public use under federal regulations (also referred to as “march-in rights”). |
The
U.S. government also has the right to take title to such intellectual property rights if we, or the applicable licensor, fail to
disclose the invention to the government and fail to file an application to register the intellectual property within specified time
limits. Intellectual property generated under a government-funded program is also subject to certain reporting requirements, compliance
with which may require us or the applicable licensor to expend substantial resources. We cannot be certain that our current or future
licensors will comply with the disclosure or reporting requirements of the Bayh-Dole Act at all times, or be able to rectify any lapse
in compliance with these requirements.
In
addition, the U.S. government requires that any products embodying the subject invention or produced through the use of the subject
invention be manufactured substantially in the United States. The manufacturing preference requirement can be waived if the owner
of the intellectual property can show that reasonable but unsuccessful efforts have been made to grant licenses on similar terms to potential
licensees that would be likely to manufacture substantially in the United States or that under the circumstances domestic manufacture
is not commercially feasible. This preference for U.S. manufacturers may limit our ability to contract with non-U.S. product
manufacturers for products covered by such intellectual property. To the extent any of our current or future intellectual property is
generated through the use of U.S. government funding, the provisions of the Bayh-Dole Act may similarly apply.
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 patents, trademarks, copyrights or other intellectual property. To counter infringement or unauthorized use, we may
be required to file infringement claims, which can be expensive and time-consuming and divert the time and attention of our management
and scientific personnel. Any claims we assert against perceived infringers could provoke these parties to assert counterclaims against
us alleging that we infringe their patents, in addition to counterclaims asserting that our patents are invalid or unenforceable, or
both. In any patent infringement proceeding, there is a risk that a court will decide that a patent of ours is invalid or unenforceable,
in whole or in part, and that we do not have the right to stop the other party from using the invention at issue. There is also a risk
that, even if the validity of such patents is upheld, the court will construe the patent’s claims narrowly or decide that we do
not have the right to stop the other party from using the invention at issue on the grounds that our patent claims do not cover the invention.
An adverse outcome in a litigation or proceeding involving our patents could limit our ability to assert our patents against those parties
or other competitors, and may curtail or preclude our ability to exclude third parties from making and selling similar or competitive
products. Any of these occurrences could adversely affect our competitive business position, business prospects and financial condition.
Similarly, if we assert trademark infringement claims, a court may determine that the marks we have asserted are invalid or unenforceable,
or that the party against whom we have asserted trademark infringement has superior rights to the marks in question. In this case, we
could ultimately be forced to cease use of such trademarks.
Even
if we establish infringement, the court may decide not to grant an injunction against further infringing activity and instead award only
monetary damages, which may or may not be an adequate remedy. Furthermore, because of the substantial amount of discovery required in
connection with intellectual property litigation, there is a risk that some of our confidential information could be compromised by disclosure
during litigation. There could also be public announcements of the results of hearings, motions or other interim proceedings or developments.
If securities analysts or investors perceive these results to be negative, it could have a material adverse effect on the price of shares
of our common stock. Moreover, there can be no assurance that we will have sufficient financial or other resources to file and pursue
such infringement claims, which typically last for years before they are concluded. Even if we ultimately prevail in such claims,
the monetary cost of such litigation and the diversion of the attention of our management and scientific personnel could outweigh any
benefit we receive as a result of the proceedings. Any of the foregoing may have a material adverse effect on our business, financial
condition, results of operations and prospects.
We
may not be able to protect our intellectual property rights throughout the world.
Filing,
prosecuting, maintaining, defending and enforcing patents on our product candidates in all countries throughout the world would be prohibitively
expensive, and our intellectual property rights in some countries outside the United States can be less extensive than those in
the United States. In addition, the laws of some foreign countries do not protect intellectual property rights to the same extent
as federal and state laws in the United States. Consequently, we may not be able to prevent third parties from practicing our inventions
in all countries outside the United States, or from selling or importing products made using our inventions in and into the United States
or other jurisdictions. Competitors may use our technologies in jurisdictions where we have not obtained patent protection to develop
their own drugs and may export otherwise infringing drugs to territories where we have patent protection, but enforcement rights are
not as strong as those in the United States. These drugs may compete with our product candidates and our patents or other intellectual
property rights may not be effective or sufficient to prevent them from competing.
Many
companies have encountered significant problems in protecting and defending intellectual property rights in foreign jurisdictions. The
legal systems of some countries do not favor the enforcement of patents and other intellectual property protection, which could make
it difficult for us to stop the infringement of our patents generally. Proceedings to enforce our patent rights in foreign jurisdictions
could result in substantial costs and divert our efforts and attention from other aspects of our business, could put our patents at risk
of being invalidated or interpreted narrowly and our patent applications at risk of not issuing and could provoke third parties to assert
claims against us. We may not prevail in any lawsuits that we initiate, and the damages or other remedies awarded, if any, may not be
commercially meaningful.
Many
countries have compulsory licensing laws under which a patent owner may be compelled under specified circumstances to grant licenses
to third parties. In addition, many countries limit the enforceability of patents against government agencies or government contractors.
In those countries, we may have limited remedies if patents are infringed or if we are compelled to grant a license to a third party,
which could materially diminish the value of those patents. This could limit our potential revenue opportunities. Accordingly, our efforts
to enforce our intellectual property rights around the world may be inadequate to obtain a significant commercial advantage from the
intellectual property that we develop or license, which could adversely affect our business, financial condition, results of operations,
and prospects.
If
we do not obtain patent term extension (PTE) and data exclusivity for JSP191 or any other product candidates we may develop, our
business may be materially harmed.
Depending
upon the timing, duration and conditions of any FDA marketing approval of our product candidates, one or more of our U.S. patents
may be eligible for limited patent term extension under the Drug Price Competition and Patent Term Restoration Act of 1984,
referred to as the Hatch-Waxman Amendments, and similar legislation in the European Union. The Hatch-Waxman Amendments permit a patent
term extension of up to five years for a patent covering an approved product as compensation for effective patent term lost during
product development and the FDA regulatory review process. However, we may not receive an extension if we fail to exercise due diligence
during the testing phase or regulatory review process, fail to apply within applicable deadlines, fail to apply prior to expiration of
relevant patents or otherwise fail to satisfy applicable requirements. Moreover, the length of the extension could be less than we request.
Only one patent per approved product can be extended; the extension cannot extend the total patent term beyond 14 years from
approval; and only those claims covering the approved drug, a method for using it or a method for manufacturing it may be extended. If
we are unable to obtain patent term extension or the term of any such extension is less than we request, the period during which we can
enforce our patent rights for the applicable product candidate will be shortened, and our competitors may obtain approval to market competing
products sooner. As a result, our revenue from applicable products could be reduced. Further, if this occurs, our competitors may take
advantage of our investment in development and trials by referencing our clinical and preclinical data and launch their product earlier
than might otherwise be the case, and our competitive position, business, financial condition, results of operations, and prospects could
be materially harmed.
Third
parties may assert that our employees or consultants have wrongfully used or disclosed confidential information or misappropriated trade
secrets.
We
employ individuals who were previously employed at universities or other biopharmaceutical companies, including our competitors or potential
competitors. Although we try to ensure that our employees and consultants do not use the proprietary information or know-how of others
in their work for us, we may be subject to claims that we or our employees, consultants or independent contractors have inadvertently
or otherwise used or disclosed intellectual property, including trade secrets or other proprietary information, of a former employer
or other third parties. We may also be subject to claims that patents and applications that we may file to protect inventions of our
employees or consultants are rightfully owned by their former employers or other third parties. Litigation may be necessary to defend
against these claims. If we fail in defending any such claims, in addition to paying monetary damages, we may lose valuable intellectual
property rights or personnel. Even if we are successful in defending against such claims, litigation could result in substantial costs
and be a distraction to management and other employees. Any of the foregoing would harm our business, financial condition, results of
operations, and prospects.
Risks
Related to Other Legal Compliance Matters
If
any of our product candidates are approved, an unfavorable reimbursement determination in any of the major markets could have a negative
impact on us. Further, an unfavorable change in such regimes (e.g., price controls) could have a negative impact on us.
The
regulations that govern marketing approvals, pricing, and reimbursement for new medicines vary widely from country to country. In the
U.S., recently enacted legislation may significantly change the approval requirements in ways that could involve additional costs and
cause delays in obtaining approvals. Some countries require approval of the sale price of a medicine before it can be marketed. In many
countries, the pricing review period begins after marketing or product licensing approval is granted. In some foreign markets, prescription
pharmaceutical pricing remains subject to continuing governmental control even after initial approval is granted. As a result, we might
obtain marketing approval for a medicine in a particular country, but then be subject to price regulations that delay our commercial
launch of the medicine, possibly for lengthy time periods, and negatively impact the revenues we are able to generate from the sale of
the medicine in that country. Adverse pricing limitations may hinder our ability to recoup our investment in one or more product candidates,
even if any product candidates we may develop obtain marketing approval.
Our
ability to commercialize any medicines successfully also will depend in part on the extent to which reimbursement for these medicines
and related treatments will be available from government health administration authorities, private health insurers, and other organizations.
Government authorities and third-party payors, such as private health insurers and health maintenance organizations, decide which medications
they will pay for and establish reimbursement levels. A primary trend in the U.S. healthcare industry and elsewhere is cost containment.
Government authorities and third-party payors have attempted to control costs by limiting coverage and the amount of reimbursement for
particular medications. For example, in May 2019, the Centers for Medicare & Medicaid Services (“CMS”) issued
a final rule to allow Medicare Advantage Plans the option of using step therapy, a type of prior authorization for Medicare Party B drugs,
beginning January 1, 2020. This final rule codified CMS’s policy change that was effective January 1, 2019.
Congress
and the Biden administration have each indicated that it will continue to seek new legislative and/or administrative measures to control
drug costs. Individual states in the U.S. have also increasingly passed legislation and implemented regulations designed to control
pharmaceutical 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.
At
the state level, legislatures have become increasingly aggressive in passing legislation and implementing regulations designed to control
pharmaceutical and biological product pricing. Some of these measures include price or patient reimbursement constraints, discounts,
restrictions on certain product access, marketing cost disclosure and transparency measures, and, in some cases, measures designed to
encourage importation from other countries and bulk purchasing. In addition, regional health care 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 health care programs. Also, increasingly, third-party payors are requiring that drug companies provide them with predetermined
discounts from list prices and are challenging the prices charged for medical products. We cannot be sure that reimbursement will be
available for any medicine that we commercialize and, if reimbursement is available, the level of reimbursement. Reimbursement may impact
the demand for, or the price of, any product candidate for which we obtain marketing approval. If reimbursement is not available or is
available only to limited levels, we may not be able to successfully commercialize any product candidate for which we obtain marketing
approval.
There
may be significant delays in obtaining reimbursement for newly approved medicines, and coverage may be more limited than the purposes
for which the medicine is approved by the FDA or similar regulatory authorities outside the U.S. Moreover, eligibility for reimbursement
does not imply that any medicine will be paid for in all cases or at a rate that covers our costs, including research, development, manufacture,
sale and distribution. Interim reimbursement levels for new medicines, if applicable, may also not be sufficient to cover our costs and
may not be made permanent. Reimbursement rates may vary according to the use of the medicine and the clinical setting in which it is
used, may be based on reimbursement levels already set for lower cost medicines and may be incorporated into existing payments for other
services. Net prices for medicines may be reduced by mandatory discounts or rebates required by government healthcare programs or private
payors and by any future relaxation of laws that presently restrict imports of medicines from countries where they may be sold at lower
prices than in the U.S. Any such reductions could negatively impact our net product sales, if any of our product candidates are
ever approved.
Any
product candidate for which we obtain marketing approval could be subject to restrictions or withdrawal from the market, and we may be
subject to substantial penalties if we fail to comply with regulatory requirements or if we experience unanticipated problems with our
medicines, when and if any of them are approved.
The
FDA and other regulatory agencies closely regulate the post approval marketing and promotion of medicines to ensure that they are marketed
only for the approved indications and in accordance with the provisions of the approved labeling. The FDA and other regulatory agencies
impose stringent restrictions on manufacturers’ communications regarding off label use, and if we do not market our medicines for
their approved indications, we may be subject to enforcement action for off label marketing by the FDA and other federal and state enforcement
agencies, including the Department of Justice. Violation of the Federal Food, Drug, and Cosmetic Act and other statutes, including the
False Claims Act, relating to the promotion and advertising of prescription products may also lead to investigations or allegations of
violations of federal and state healthcare fraud and abuse laws and state consumer protection laws.
In
addition, later discovery of previously unknown problems with our medicines, third-party manufacturers, or manufacturing processes, or
failure to comply with regulatory requirements, may yield various results, including:
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restrictions on such medicines, manufacturers, or manufacturing
processes; |
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restrictions on the labeling or marketing of a medicine; |
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restrictions on the distribution or use of a medicine; |
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requirements to conduct post
marketing clinical trials; |
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receipt of warning or untitled
letters; |
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withdrawal of the medicines
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 or revenue; |
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suspension or withdrawal of marketing approvals; |
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suspension of any ongoing clinical trials; |
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refusal to permit the import or export of our medicines; |
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injunctions or the imposition of civil or criminal
penalties. |
Any government investigation of alleged violations
of law could require us to expend significant time and resources in response and could generate negative publicity. The occurrence of
any event or penalty described above may inhibit our ability to commercialize any product candidates we develop and adversely affect
our business, financial condition, results of operations, and prospects.
Additionally, if any of our product candidates
receives marketing approval, the FDA could require it to adopt a Risk Evaluation and Mitigation Strategy, to ensure that the benefits
outweigh its risks, which may include, among other things, a medication guide outlining the risks of the product for distribution to
patients and a communication plan to healthcare practitioners. Furthermore, if we or others later identify undesirable side effects caused
by any of our product candidates, several potentially significant negative consequences could result, including:
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regulatory authorities may suspend or withdraw approvals
of such product candidate; |
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regulatory authorities may require additional warnings
on the label; |
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we may be required to change the way such product candidate
is administered or conduct additional clinical trials; |
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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. |
Our relationships with healthcare providers, including physicians,
and third-party payors will be subject to applicable anti-kickback, fraud and abuse, anti-bribery and other healthcare laws and regulations,
which could expose us to criminal sanctions, civil penalties, contractual damages, reputational harm and diminished profits and future
earnings.
Healthcare providers and third-party payors play
a primary role in the recommendation and prescription of any product candidates for which we obtain marketing approval. Our current and
future arrangements with healthcare providers, third-party payors and customers may expose us to broadly applicable fraud and abuse and
other healthcare laws and regulations that may constrain the business or financial arrangements and relationships through which we research
as well as market, sell and distribute our products for which we obtain marketing approval. Restrictions under applicable federal and
state healthcare laws and regulations, including certain laws and regulations applicable only if we have marketed products, include,
but are not limited to, the following:
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the federal healthcare program Anti-Kickback Statute,
which prohibits, among other things, persons or entities from knowingly and willfully soliciting, receiving, offering, or providing
any remuneration (including any kickback, bribe or certain rebates), directly or indirectly, in cash or in kind, to induce, or in
return for, either the referral of an individual, for the purchase, lease, order or recommendation of any item, good, facility or
service for which payment may be made, in whole or in part, under federal healthcare programs, such as Medicare and Medicaid. A person
or entity does not need to have actual knowledge of the statute or specific intent to violate it in order to have committed a violation; |
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federal false claims, including the False Claims Act
that can be enforced through whistleblower actions, false statements and civil monetary penalties laws, which prohibit, among other
things, any person or entity from knowingly presenting, or causing to be presented, a false or fraudulent claim for payment of government
funds or knowingly making, or causing to be made, a false record or statement material to a false or fraudulent claim to get a false
claim paid or to avoid, decrease or conceal an obligation to pay money to the federal government. In addition, the government may
assert that a claim including items and services resulting from a violation of the U.S. federal Anti-Kickback Statute constitutes
a false or fraudulent claim for purposes of the False Claims Act; |
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the federal Health Insurance Portability and Accountability
Act of 1996 (“HIPAA”), which, prohibits, among other things, executing, or attempting to execute, a scheme to defraud
any healthcare benefit program or making false, fictitious, or fraudulent statements in connection with the delivery of, or payment
for, healthcare benefits, items or services relating to healthcare matters. Similar to the federal Anti-Kickback Statute, a person
or entity does not need to have actual knowledge of the statute or specific intent to violate it in order to have committed a violation; |
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the federal false statements statute, which prohibits
knowingly and willfully falsifying, concealing, or covering up a material fact or making any materially false statement in connection
with the delivery of or payment for healthcare benefits, items, or services; |
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the federal Food, Drug, and Cosmetic Act, which among
other things, strictly regulates drug marketing, prohibits manufacturers from marketing such products for off-label use and regulates
the distribution of samples; |
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federal laws that require pharmaceutical manufacturers
to report certain calculated product prices to the government or provide certain discounts or rebates to government authorities or
private entities, often as a condition of reimbursement under government healthcare programs; |
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the federal Physician Payments Sunshine Act, which
requires certain manufacturers of drugs, devices, biologics and medical supplies for which payment is available under Medicare, Medicaid
or the Children’s Health Insurance Program (with certain exceptions) to report annually to the CMS within the U.S. Department
of Health and Human Services, information related to payments or other transfers of value made during the previous year to physicians,
(defined to include doctors, dentists, optometrists, podiatrists and chiropractors) and teaching hospitals, as well as ownership
and investment interests held by physicians and their immediate family members. Beginning in 2022, such obligations include
payments and other transfers of value provided in the previous year to certain other healthcare professionals, including physician
assistants, nurse practitioners, clinical nurse specialists, certified nurse anesthetists, anesthesiologist assistants and certified
nurse midwives; and |
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analogous state and foreign laws and regulations, such
as state anti-kickback and false claims laws, which may be broader in scope and apply to healthcare items or services that are reimbursed
by non-governmental third-party payors, including private insurers. |
Some state laws also require pharmaceutical companies
to comply with specific compliance standards, restrict financial interactions between pharmaceutical companies and healthcare providers
or require pharmaceutical companies to report information related to payments to health care providers or marketing expenditures. Certain
state laws also require the reporting of information related to drug pricing. Further, certain state and local laws require the registration
of pharmaceutical sales representatives.
Efforts to ensure that our business arrangements
with third parties will comply with applicable healthcare laws and regulations will involve substantial costs. Given the breadth of the
laws and regulations and evolving government interpretations of the laws and regulations, governmental authorities may possibly conclude
that our business practices, including certain of our advisory board arrangements with physicians, some of whom are compensated in the
form of stock or stock options, may not comply with healthcare laws and regulations. If our operations are found to be in violation of
any of the laws described above or any other government regulations that apply to us, we may be subject to significant penalties, including
administrative, civil and criminal penalties, damages, fines, disgorgement, exclusion from participation in government health care programs,
such as Medicare and Medicaid, imprisonment, integrity oversight and reporting obligations, contractual damages, reputational harm, diminished
profits and future earnings, and the curtailment or restructuring of our operations, any of which could adversely affect our business,
financial condition, results of operations, and prospects.
The European Union has strict laws governing the
provision of benefits or advantages to healthcare professionals in order to induce or encourage the prescription, recommendation, endorsement,
purchase, supply, order or use of medicinal products. Such laws and associated codes of practice set out the rules and requirements that
the provision of hospitality, sponsorship, gifts and promotional items must meet before they can be accepted by healthcare professionals.
The provision of benefits or advantages to healthcare professionals is also governed by the national anti-bribery laws of European Union
Member States. Infringement of these laws could result in substantial fines and imprisonment.
Payments made to healthcare professionals in certain
European Union Member States may be publicly disclosed. Moreover, agreements with healthcare professionals often must be the subject
of prior notification and approval by the healthcare professionals’ employer, his or her competent professional organization, and/or
the regulatory authorities of the individual European Union Member States. These requirements are provided in the national laws, industry
codes, or professional codes of conduct applicable in the European Union Member States. Failure to comply with these requirements could
result in reputational risk, public reprimands, administrative penalties, fines or imprisonment.
Healthcare and other reform legislation, may increase the difficulty
and cost for us and any collaborators we may have to obtain marketing approval of and commercialize JSP191 and any other product candidates
we may develop and affect the prices we, or they, may obtain.
In the United States and some foreign jurisdictions,
there have been, and continue to be, ongoing efforts to implement legislative and regulatory changes regarding the healthcare system.
Such changes could prevent or delay marketing approval of JSP191 and any other product candidates that we may develop, restrict or regulate
post-approval activities and affect our ability to profitably sell any product candidates for which we obtain marketing approval. Although
we cannot predict what healthcare or other reform efforts will be successful, such efforts may result in more rigorous coverage criteria,
in additional downward pressure on the price that we, or our future collaborators, may receive for any approved products or in other
consequences that may adversely affect our ability to achieve or maintain profitability.
Within the United States, the federal government
and individual states have aggressively pursued healthcare reform, as evidenced by the passing of the ACA and the ongoing efforts to
modify or repeal that legislation. The ACA substantially changed the way healthcare is financed by both governmental and private insurers
and contains a number of provisions that affect coverage and reimbursement of drug products and/or that could potentially reduce the
demand for pharmaceutical products such as increasing drug rebates under state Medicaid programs for brand name prescription drugs and
extending those rebates to Medicaid managed care and assessing a fee on manufacturers and importers of brand name prescription drugs
reimbursed under certain government programs, including Medicare and Medicaid. Other aspects of healthcare reform, such as expanded government
enforcement authority and heightened standards that could increase compliance-related costs, could also affect our business. There are,
and may continue to be, judicial challenges, including review by the United States Supreme Court. We cannot predict the ultimate
content, timing or effect of any changes to the ACA or other federal and state reform efforts. There is no assurance that federal or
state healthcare reform will not adversely affect our future business and financial results, and we cannot predict how future federal
or state legislative, judicial or administrative changes relating to healthcare reform will affect our business.
Federal and state governments have shown significant
interest in implementing cost-containment programs to limit the growth of government-paid healthcare costs, including price controls,
waivers from Medicaid drug rebate law requirements, restrictions on reimbursement and requirements for substitution of generic products
for branded prescription drugs. The private sector has also sought to control healthcare costs by limiting coverage or reimbursement
or requiring discounts and rebates on products. We are unable to predict what additional legislation, regulations or policies, if any,
relating to the healthcare industry or third party coverage and reimbursement may be enacted in the future or what effect such legislation,
regulations or policies would have on our business. Any cost containment measures could significantly decrease the available coverage
and the price we might establish for our potential products, which would have an adverse effect on our net revenues and operating results.
Legislative and regulatory proposals have been
made to expand post-approval requirements and restrict sales and promotional activities for biotechnology products. We cannot be sure
whether additional legislative changes will be enacted, or whether FDA regulations, guidance or interpretations for biological products
will be changed, or what the impact of such changes on the marketing approvals of our product candidates, if any, may be. In addition,
increased scrutiny by the U.S. Congress of the FDA’s approval and decision-making processes may significantly delay or prevent
marketing approval, as well as subject us to more stringent product labeling and post-marketing testing and other requirements.
*The prices of prescription pharmaceuticals in the United States
and foreign jurisdictions are subject to considerable legislative and executive actions and could impact the prices we obtain for our
products, if and when licensed.
The prices of prescription pharmaceuticals have
also been the subject of considerable discussion in the United States. To date, there have been several recent U.S. congressional
inquiries and proposed and enacted state and federal legislation designed to, among other things, bring more transparency to drug pricing,
review the relationship between pricing and manufacturer patient programs, reduce the costs of drugs under Medicare and reform government
program reimbursement methodologies for products. To those ends, in October 2020, the FDA issued final guidance that describes procedures
drug manufacturers can follow to facilitate importation of prescription drugs, including biological products, that are FDA-approved,
manufactured abroad, authorized for sale in any foreign country, and originally intended for sale in that foreign country.
At the state level, individual states are increasingly
aggressive in passing legislation and implementing 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. In addition, regional health
care organizations 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 health care programs. These measures could reduce the ultimate demand
for our products, once approved, or put pressure on our product pricing. We expect that additional state and federal healthcare reform
measures will be adopted in the future, any of which could limit the amounts that federal and state governments will pay for healthcare
products and services, which could result in reduced demand for our product candidates or additional pricing pressures.
In the European Union, similar political, economic
and regulatory developments may affect our ability to profitably commercialize our product candidates, if approved. In markets outside
of the United States and the European Union, reimbursement and healthcare payment systems vary significantly by country, and many
countries have instituted price ceilings on specific products and therapies. In some countries, particularly the countries of the European
Union, the pricing of prescription pharmaceuticals is subject to governmental control. In these countries, pricing negotiations with
governmental authorities can take considerable time after the receipt of marketing approval for a product. To obtain reimbursement or
pricing approval in some countries, we may be required to conduct a clinical trial that compares the cost-effectiveness of our product
candidates to other available therapies. If reimbursement of our products is unavailable or limited in scope or amount, or if pricing
is set at unsatisfactory levels, our business could be harmed, possibly materially.
In addition, on August 16, 2022, President Biden
signed into law the Inflation Reduction Act of 2022, which, among other things, includes policies that are designed to have a direct
impact on drug prices and reduce drug spending by the federal government, which shall take effect in 2023. Under the Inflation Reduction
Act of 2022, Congress authorized Medicare beginning in 2026 to negotiate lower prices for certain costly single-source drug and biologic
products that do not have competing generics or biosimilars. This provision is limited in terms of the number of pharmaceuticals whose
prices can be negotiated in any given year and it only applies to drug products that have been approved for at least 9 years and biologics
that have been licensed for 13 years. Drugs and biologics that have been approved for a single rare disease or condition are categorically
excluded from price negotiation. Further, the new legislation provides that if pharmaceutical companies raise prices in Medicare faster
than the rate of inflation, they must pay rebates back to the government for the difference. The new law also caps Medicare out-of-pocket
drug costs at an estimated $4,000 a year in 2024 and, thereafter beginning in 2025, at $2,000 a year.
Our
employees, principal investigators, consultants and commercial partners may engage in misconduct or other improper activities, including
non-compliance with regulatory standards and requirements and insider trading.
We are exposed to the risk of fraud or other misconduct
by our employees, consultants and commercial partners, and, if we commence clinical trials, our principal investigators. Misconduct by
these parties could include intentional failures to comply with FDA regulations or the regulations applicable in the European Union and
other jurisdictions, provide accurate information to the FDA, the EMA and other regulatory authorities, comply with healthcare fraud
and abuse laws and regulations in the United States and abroad, report financial information or data accurately or disclose unauthorized
activities to us. In particular, sales, marketing and business arrangements in the healthcare industry are subject to extensive laws
and regulations intended to prevent fraud, misconduct, kickbacks, self-dealing and other abusive practices. These laws and regulations
restrict or prohibit a wide range of pricing, discounting, marketing and promotion, sales commission, customer incentive programs and
other business arrangements. Such misconduct also could involve the improper use of information obtained in the course of clinical trials
or interactions with the FDA, the EMA or other regulatory authorities, which could result in regulatory sanctions and cause serious harm
to our reputation. We have adopted a code of conduct applicable to all of our employees, but it is not always possible to identify and
deter employee misconduct, and 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 government investigations or other actions or lawsuits stemming from a failure
to comply with these laws or regulations. If any such actions are instituted against us, and we are not successful in defending ourselves
or asserting our rights, those actions could have a significant impact on our business, financial condition, results of operations and
prospects, including the imposition of significant fines or other sanctions.
Laws and regulations governing any international operations
we may have in the future may preclude us from developing, manufacturing and selling certain product candidates outside of the United States
and require us to develop and implement costly compliance programs.
We may be subject to numerous laws and regulations
in each jurisdiction outside of the United States in which we may operate. The creation, implementation and maintenance of international
business practices compliance programs is costly and such programs are difficult to enforce, particularly where reliance on third parties
is required.
The Foreign Corrupt Practices Act (the “FCPA”),
prohibits any U.S. individual or business from paying, offering, authorizing payment or offering of anything of value, directly
or indirectly, to any foreign official, political party or candidate for the purpose of influencing any act or decision of the foreign
entity in order to assist the individual or business in obtaining or retaining business. The FCPA also obligates companies whose securities
are listed in the United States to comply with certain accounting provisions requiring us to maintain books and records that accurately
and fairly reflect all transactions of the corporation, including international subsidiaries, and to devise and maintain an adequate
system of internal accounting controls for international operations. The anti-bribery provisions of the FCPA are enforced primarily by
the Department of Justice. The SEC is involved with enforcement of the books and records provisions of the FCPA.
Similarly, the U.K. Bribery Act 2010
has extra-territorial effect for companies and individuals having a connection with the United Kingdom. The U.K. Bribery Act
prohibits inducements both to public officials and private individuals and organizations. Compliance with the FCPA and the U.K. Bribery
Act is expensive and difficult, particularly in countries in which corruption is a recognized problem. In addition, the FCPA presents
particular challenges in the pharmaceutical industry, because, in many countries, hospitals are operated by the government, and doctors
and other hospital employees are considered foreign officials. Certain payments to hospitals in connection with clinical trials and other
work have been deemed to be improper payments to government officials and have led to FCPA enforcement actions.
Various laws, regulations and executive orders
also restrict the use and dissemination outside of the United States, or the sharing with certain non-U.S. nationals, of information
classified for national security purposes, as well as certain products and technical data relating to those products. Our expansion outside
of the United States has required, and will continue to require, us to dedicate additional resources to comply with these laws,
and these laws may preclude us from developing, manufacturing or selling certain product candidates outside of the United States,
which could limit our growth potential and increase our development costs. The failure to comply with laws governing international business
practices may result in substantial penalties, including suspension or debarment from government contracting. Violation of the FCPA can
result in significant civil and criminal penalties. Indictment alone under the FCPA can lead to suspension of the right to do business
with the U.S. government until the pending claims are resolved. Conviction of a violation of the FCPA can result in long-term disqualification
as a government contractor. The termination of a government contract or relationship as a result of our failure to satisfy any of our
obligations under laws governing international business practices would have a negative impact on our operations and harm our reputation
and ability to procure government contracts. The SEC also may suspend or bar issuers from trading securities on U.S. exchanges for
violations of the FCPA’s accounting provisions.
Compliance with global privacy and data security requirements
could result in additional costs and liabilities to us or inhibit our ability to collect and process data globally, and the failure to
comply with such requirements could subject us to significant fines and penalties, which may have a material adverse effect on our business,
financial condition and results of operations.
The regulatory framework for the collection, use,
safeguarding, sharing, transfer, and other processing of information worldwide is rapidly evolving and is likely to remain uncertain
for the foreseeable future. Globally, virtually every jurisdiction in which we operate has established its own data security and privacy
frameworks with which we must comply. For example, the collection, use, disclosure, transfer, or other processing of personal data regarding
individuals in the European Union, including personal health data, is subject to the EU General Data Protection Regulation (the “GDPR”),
which took effect across all member states of the European Economic Area (the “EEA”) in May 2018. The GDPR is wide-ranging
in scope and imposes numerous requirements on companies that process personal data, including requirements relating to processing health
and other sensitive data, obtaining consent of the individuals to whom the personal data relates, providing information to individuals
regarding data processing activities, implementing safeguards to protect the security and confidentiality of personal data, providing
notification of data breaches, and taking certain measures when engaging third-party processors. The GDPR increases our obligations with
respect to clinical trials conducted in the EEA by expanding the definition of personal data to include coded data and requiring changes
to informed consent practices and more detailed notices for clinical trial subjects and investigators. In addition, the GDPR imposes
strict rules on the transfer of personal data to countries outside the European Union, including the United States, and, as a result,
increases the scrutiny that clinical trial sites located in the EEA should apply to transfers of personal data from such sites to countries
that are considered to lack an adequate level of data protection, such as the United States. The GDPR also permits data protection
authorities to require destruction of improperly gathered or used personal information and/or impose substantial fines for violations
of the GDPR, which can be up to four percent of global revenues or 20 million Euros, whichever is greater, and it also confers a
private right of action on data subjects and consumer associations to lodge complaints with supervisory authorities, seek judicial remedies,
and obtain compensation for damages resulting from violations of the GDPR. In addition, the GDPR provides that European Union member
states may make their own further laws and regulations limiting the processing of personal data, including genetic, biometric or health
data.
Further, Brexit has led and could also lead to
legislative and regulatory changes and may increase our compliance costs. As of January 1, 2021 and the expiry of transitional arrangements
agreed to between the United Kingdom and the European Union, data processing in the United Kingdom is governed by a United Kingdom version
of the GDPR (combining the GDPR and the Data Protection Act 2018), exposing us to two parallel regimes, each of which authorizes similar
fines and other potentially divergent enforcement actions for certain violations. On June 28, 2021, the European Commission adopted an
Adequacy Decision for the United Kingdom, allowing for the relatively free exchange of personal information between the European Union
and the United Kingdom, however, the European Commission may suspend the Adequacy Decision if it considers that the United Kingdom no
longer provides for an adequate level of data protection. Other jurisdictions outside the European Union are similarly introducing or
enhancing privacy and data security laws, rules and regulations.
Similar actions are either in place or under way
in the United States. There are a broad variety of data protection laws that are applicable to our activities, and a wide range
of enforcement agencies at both the state and federal levels that can review companies for privacy and data security concerns based on
general consumer protection laws. The Federal Trade Commission and state Attorneys General all are aggressive in reviewing privacy and
data security protections for consumers. New laws also are being considered at both the state and federal levels. For example, the California
Consumer Privacy Act — which went into effect on January 1, 2020 — is creating similar risks and obligations
as those created by the GDPR, though the California Consumer Privacy Act does exempt certain information collected as part of a clinical
trial subject to the Federal Policy for the Protection of Human Subjects (the Common Rule). In March 2020, the California State
Attorney General proposed varying versions of companion draft regulations which are not yet finalized. Despite the delay in adopting
regulations, the California State Attorney General commenced enforcement actions against violators beginning July 1, 2020. In addition,
a new California privacy law, the California Privacy Rights Act (the “CPRA”) was passed by California voters on November
3, 2020. The CPRA will create additional obligations with respect to processing and storing personal information that are scheduled to
take effect on January 1, 2023 (with certain provisions having retroactive effect to January 1, 2022). Further, a new Virginia privacy
law, Virginia Consumer Data Protection Act, or VCDPA, was signed into law on March 2, 2021 and is also scheduled to take effect on January
1, 2023, and the Colorado Privacy Act, or CPA, will take effect on July 1, 2023. The VCDPA and CPA will impose many similar obligations
regarding the processing and storing of personal information as the California Consumer Privacy Act and the CPRA. Many other states are
considering similar legislation. A broad range of legislative measures also have been introduced at the federal level. Accordingly, failure
to comply with federal and state laws (both those currently in effect and future legislation) regarding privacy and security of personal
information could expose us to fines and penalties under such laws. There also is the threat of consumer class actions related to these
laws and the overall protection of personal data. Even if we are not determined to have violated these laws, government investigations
into these issues typically require the expenditure of significant resources and generate negative publicity, which could harm our reputation
and business.
Given the breadth and depth of changes in data
protection obligations, preparing for and complying with these requirements is rigorous and time intensive and requires significant resources
and a review of our technologies, systems and practices, as well as those of any third-party collaborators, service providers, contractors
or consultants that process or transfer personal data collected in the European Union. The GDPR and other changes in laws or regulations
associated with the enhanced protection of certain types of sensitive data, such as healthcare data or other personal information from
our clinical trials, could require us to change our business practices and put in place additional compliance mechanisms, may interrupt
or delay our development, regulatory and commercialization activities and increase our cost of doing business, and could lead to government
enforcement actions, private litigation and significant fines and penalties against us and could have a material adverse effect on our
business, financial condition and results of operations.
We and our partners may be subject to stringent privacy laws,
information security laws, regulations, policies and contractual obligations related to data privacy and security, and changes in such
laws, regulations, policies or how they are interpreted or changes in contractual obligations could adversely affect our business.
There are numerous U.S. federal and state
data privacy and protection laws and regulations that apply to the collection, transmission, processing, storage and use of personally-identifying
information, which among other things, impose certain requirements relating to the privacy, security and transmission of personal information.
The legislative and regulatory landscape for privacy and data protection continues to evolve in jurisdictions worldwide, and there has
been an increasing focus on privacy and data protection issues with the potential to affect our business. Failure to comply with any
of these laws and regulations could result in enforcement action against us, including fines, imprisonment of company officials and public
censure, claims for damages by affected individuals, damage to our reputation and loss of goodwill, any of which could have a material
adverse effect on our business, financial condition, results of operations or prospects.
If we are unable to properly protect the privacy
and security of health-related information or other sensitive or confidential information in our possession, we could be found to have
breached our contracts. Further, if we fail to comply with applicable privacy laws, including applicable HIPAA privacy and security standards,
we could face significant administrative, civil and criminal penalties. Enforcement activity can also result in financial liability and
reputational harm, and responses to such enforcement activity can consume significant internal resources. In addition, state attorneys
general are authorized to bring civil actions seeking either injunctions or damages in response to violations that threaten the privacy
of state residents.
*Previously enacted state laws in California seek
to impose gender and diversity quotas for boards of directors of public companies headquartered in California.
In
September 2018, California enacted Senate Bill 826 (“SB 826”),
which generally required public companies with principal executive offices in California
to have at least two female directors on its board of directors if the company has at least
five directors, and at least three female directors on its board of directors if the company
has at least six directors. On May 13, 2022, the Los Angeles Superior Court declared SB 826
unconstitutional and, although the California Secretary of State has directed counsel to
file an appeal of decision, the State of California is currently precluded from enforcing
SB 826.
Additionally,
on September 30, 2020, California enacted Assembly Bill 979 (“AB 979”),
which generally required public companies with principal executive offices in California
to include specified numbers of directors from “underrepresented communities”.
A director from an “underrepresented community” means a director who self-identifies
as Black, African American, Hispanic, Latino, Asian, Pacific Islander, Native American, Native
Hawaiian, Alaska Native, gay, lesbian, bisexual or transgender. By December 31, 2021, each
public company with principal executive offices in California was required to have at least
one director from an underrepresented community. By December 31, 2022, a public company with
more than four but fewer than nine directors would be required to have a minimum of two directors
from underrepresented communities, and a public company with nine or more directors would
need to have a minimum of three directors from underrepresented communities. On April 1,
2022, the Los Angeles Superior Court declared AB 979 unconstitutional and, although the California
Secretary of State has filed a notice of appeal in the case, the State of California is currently
precluded from enforcing AB 979.
If the State of California successfully appeals
the court decisions regarding SB 826 or AB 979, we cannot assure that we can recruit, attract and/or retain qualified members of the
board and meet gender or diversity quotas as previously required by SB 826 or AB 979, and our board of directors does not currently
satisfy the quota previously required under SB 826 and, as currently constituted, would not satisfy the quota previously required by
December 31, 2022 under AB 979. A failure to comply with any such quota requirement could result in fines from the California Secretary
of State, and our reputation may be adversely affected.
*Investors’ expectations of our performance relating to
environmental, social and governance factors may impose additional costs and expose us to new risks.
There
is an increasing focus from certain investors, employees, regulators and other stakeholders
concerning corporate responsibility, specifically related to environmental, social and governance
(“ESG”) factors. Some investors and investor advocacy groups may use these factors
to guide investment strategies and, in some cases, investors may choose not to invest in
our company if they believe our policies relating to corporate responsibility are inadequate.
Third-party providers of corporate responsibility ratings and reports on companies have increased
to meet growing investor demand for measurement of corporate responsibility performance,
and a variety of organizations currently measure the performance of companies on such ESG
topics, and the results of these assessments are widely publicized. Investors, particularly
institutional investors, use these ratings to benchmark companies against their peers and
if we are perceived as lagging with respect to ESG initiatives, certain investors may engage
with us to improve ESG disclosures or performance and may also make voting decisions, or
take other actions, to hold us and our board of directors accountable. In addition, the criteria
by which our corporate responsibility practices are assessed may change, which could result
in greater expectations of us and cause us to undertake costly initiatives to satisfy such
new criteria. If we elect not to or are unable to satisfy such new criteria, investors may
conclude that our policies with respect to corporate responsibility are inadequate.
We may face reputational damage in the event our
corporate responsibility initiatives or objectives do not meet the standards set by our investors, stockholders, lawmakers, listing exchanges
or other constituencies, or if we are unable to achieve an acceptable ESG or sustainability rating from third-party rating services.
A low ESG or sustainability rating by a third-party rating service could also result in the exclusion of our common stock from consideration
by certain investors who may elect to invest with our competition instead. Ongoing focus on corporate responsibility matters by investors
and other parties as described above may impose additional costs or expose us to new risks. Any failure or perceived failure by us in
this regard could have a material adverse effect on our reputation and on our business, share price, financial condition, or results
of operations, including the sustainability of our business over time.
In addition, the SEC has announced proposed rules
that, among other matters, will establish a framework for reporting of climate-related risks. To the extent the proposed rules impose
additional reporting obligations, we could face increased costs. Separately, the SEC has also announced that it is scrutinizing existing
climate-change related disclosures in public filings, increasing the potential for enforcement if the SEC were to allege our existing
climate disclosures are misleading or deficient.
Risks Related to Employee Matters, Managing Growth and Information
Technology
If we lose key management personnel, or if we fail to recruit
additional highly skilled personnel, our ability to continue developing and to identify and develop new or next generation product candidates
will be impaired, which could result in delays in the development process, loss of market opportunities, make us less competitive and
have a material adverse effect on our business, financial condition and results of operations.
Our ability to compete in the highly competitive
biotechnology and pharmaceutical industries depends upon our ability to attract and retain highly qualified managerial, scientific and
medical personnel. We are highly dependent on our management, particularly our Chief Executive Officer, the members of our executive
team, and key scientific and medical personnel employees. The loss of the services of any of our executive officers, key employees, and
scientific and medical advisors, and our inability to find suitable replacements, could result in delays in product development and harm
our business.
We conduct our operations at our facility in the
San Francisco Bay Area. This region is headquarters to many other biopharmaceutical companies and many academic and research institutions.
Competition for skilled personnel in our market is intense and may limit our ability to hire and retain highly qualified personnel on
acceptable terms or at all.
To induce valuable employees to remain at our
company, in addition to salary and cash incentives, we have provided stock options that vest over time. The value to employees of stock
options that vest over time may be significantly affected by movements in our stock price that are beyond our control, and may at any
time be insufficient to counteract more lucrative offers from other companies. Despite our efforts to retain valuable employees, members
of our management, scientific and development teams may terminate their employment with us on short notice. In addition, we may experience
employee turnover as a result of the ongoing “great resignation” occurring throughout the U.S. economy, which has impacted
job market dynamics. New hires require training and take time before they achieve full productivity. New employees may not become as
productive as we expect, and we may be unable to hire or retain sufficient numbers of qualified individuals. Although we have employment
agreements with our key employees, these agreements provide for at-will employment, which means that any of our employees could leave
our employment at any time, with or without notice. We do not maintain “key man” insurance policies on the lives of these
individuals or the lives of any of our other employees. Our success also depends on our ability to continue to attract, retain and motivate
highly skilled junior, mid-level and senior managers as well as junior, mid-level and senior scientific and medical personnel.
We and our management have a limited track record as an operating
company. Failures in the operational execution of the expected business plans may have a material impact on our commercial prospects.
Further, if we are not able to attract and retain highly-qualified personnel, we may not be able to successfully implement our business
strategy.
Our management team has worked together for only
a limited period of time and has a limited track record of executing our business plan as a team. In addition, we have recently filled
a number of positions in our finance and accounting staff. Accordingly, certain key personnel have only recently assumed the duties and
responsibilities they are now performing, and it is difficult to predict whether our management team, individually and collectively,
will be effective in operating our business. These changes may cause speculation and uncertainty regarding our commercial prospects and
may cause or result in:
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disruption of our business or distraction of our employees
and management; |
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difficulty in recruiting, hiring, motivating, and retaining
talented and skilled personnel; |
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stock price volatility; and |
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difficulty in negotiating, maintaining, or consummating
business or strategic relationships or transactions. |
If we are unable to mitigate these risks or to
attract and retain highly qualified personnel, our revenue, operating results and financial condition may be adversely impacted.
*We will need to grow the size of our organization, and we may
experience difficulties in managing this growth.
As of September 30, 2022, we had 36 full-time
employees. As our development, manufacturing and commercialization plans and strategies develop and we continue our operations as a public
company, we expect to need and are actively recruiting additional managerial, operational, sales, marketing, financial and other personnel.
Future growth would impose significant added responsibilities on members of management, including:
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identifying, recruiting, integrating, maintaining and
motivating additional employees; |
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managing our internal development efforts effectively,
including the clinical, FDA and international regulatory review process for our product candidates, while complying with our contractual
obligations to contractors and other third parties; and |
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improving our operational, financial and management
controls, reporting systems and procedures. |
Our future financial performance and our ability
to commercialize our product candidates will depend, in part, on our ability to effectively manage any future growth, and our management
may also have to divert a disproportionate amount of time to managing these growth activities.
We currently rely, and for the foreseeable future
will continue to rely, in substantial part on certain independent organizations, advisors and consultants to provide certain services,
including substantially all aspects of regulatory approval, clinical management and manufacturing. We cannot assure you that the services
of independent organizations, advisors and consultants will continue to be available to us on a timely basis when needed, or that we
can find qualified replacements. In addition, if we are unable to effectively manage our outsourced activities or if the quality or accuracy
of the services provided by consultants is compromised for any reason, our clinical trials may be extended, delayed or terminated, and
we may not be able to obtain regulatory approval of our product candidates or otherwise advance our business. We cannot assure you that
we will be able to manage our existing consultants or find other competent outside contractors and consultants on economically reasonable
terms, or at all. If we are not able to effectively expand our organization by hiring new employees and expanding our groups of consultants
and contractors, or if we are not able to effectively build out new facilities to accommodate this expansion, we may not be able to successfully
implement the tasks necessary for further development and commercialization of our product candidates and, accordingly, may not achieve
our research, development and commercialization goals.
Our insurance policies may be inadequate and potentially expose
us to unrecoverable risks.
We have limited director and officer insurance
and commercial insurance policies. Any significant insurance claims would have a material adverse effect on our business, financial condition
and results of operations. Insurance availability, coverage terms and pricing continue to vary with market conditions. We endeavor to
obtain appropriate insurance coverage for insurable risks that we identify; however, we may fail to correctly anticipate or quantify
insurable risks; we may not be able to obtain appropriate insurance coverage; and insurers may not respond as we intend to cover insurable
events that may occur. We have observed rapidly changing conditions in the insurance markets relating to nearly all areas of traditional
corporate insurance. Such conditions have resulted in higher premium costs, higher policy deductibles and lower coverage limits. For
some risks, we may not have or maintain insurance coverage because of cost or availability.
Our internal computer systems, or those of our third-party vendors,
collaborators or other contractors or consultants, may fail or suffer security breaches, which could result in a material disruption
of our product development programs, compromise sensitive information related to our business or prevent us from accessing critical information,
potentially exposing us to liability or otherwise adversely affecting our business.
Our internal computer systems and those of our
current and any future third-party vendors, collaborators and other contractors or consultants are vulnerable to damage or interruption
from computer viruses, computer hackers, malicious code, employee theft or misuse, denial-of-service attacks, sophisticated nation-state
and nation-state-supported actors, unauthorized access, natural disasters, terrorism, war and telecommunication and electrical failures.
While we seek to protect our information technology systems from system failure, accident and security breach, if such an event were
to occur and cause interruptions in our operations, it could result in a disruption of our development programs and our business operations,
whether due to a loss of our trade secrets or other proprietary information or other disruptions. 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. If we were to experience a significant cybersecurity breach of our information systems or data, the costs associated
with the investigation, remediation and potential notification of the breach to counter-parties and data subjects could be material.
In addition, our remediation efforts may not be successful. If we do not allocate and effectively manage the resources necessary to build
and sustain the proper technology and cybersecurity infrastructure, we could suffer significant business disruption, including transaction
errors, supply chain or manufacturing interruptions, processing inefficiencies, data loss or the loss of or damage to intellectual property
or other proprietary information.
Although we take such steps to help protect confidential
and other sensitive information from unauthorized access or disclosure, our information technology and infrastructure may be vulnerable
to attacks by hackers or viruses, failures, or breaches due to third-party action, employee negligence or error, malfeasance, or other
incidents or disruptions. For example, we could be the target of phishing attacks seeking confidential information regarding our employees.
Furthermore, while we have implemented data privacy and security measures in an effort to comply with applicable laws and regulations
relating to privacy and data protection, some health-related and other personal information or confidential information may be transmitted
to us by third parties, who may not implement adequate security and privacy measures, and it is possible that laws, rules and regulations
relating to privacy, data protection, or information security may be interpreted and applied in a manner that is inconsistent with our
practices or those of third parties who transmit health-related and other personal information or confidential information to us.
To the extent that we or these third parties are
found to have violated such laws, rules or regulations or that any disruption or security breach were to result in a loss of, or damage
to, us or our third-party vendors’, collaborators’ or other contractors’ or consultants’ data or applications,
or inappropriate disclosure of confidential or proprietary information, we could incur liability including litigation exposure, penalties
and fines, we could become the subject of regulatory action or investigation, our competitive position could be harmed and the further
development and commercialization of our product candidates could be delayed. Any of the above could have a material adverse effect on
our business, financial condition, results of operations or prospects.
*Unstable market and economic conditions may have serious adverse
consequences on our business, financial condition and share price.
As widely reported, global credit and financial
markets have experienced volatility and disruptions in the past several years and especially in 2020 and 2021 and year to date 2022
due to the impacts of the COVID-19 pandemic, and, more recently, the ongoing conflict between Ukraine and Russia and the global impact
of restrictions and sanctions imposed on Russia, including severely diminished liquidity and credit availability, declines in consumer
confidence, declines in economic growth, increases in unemployment rates and uncertainty about economic stability. There can be no assurances
that further deterioration in credit and financial markets and confidence in economic conditions will not occur. Our general business
strategy may be adversely affected by any such economic downturn, volatile business environment or continued unpredictable and unstable
market conditions. If the current equity and credit markets deteriorate, it may make any necessary debt or equity financing more difficult,
more costly and more dilutive. Failure to secure any necessary financing in a timely manner and on favorable terms could have a material
adverse effect on our growth strategy, financial performance and share price and could require us to delay or abandon clinical development
plans.
*The impact of the Russian invasion of Ukraine on the global
economy, energy supplies and raw materials is uncertain, but may prove to negatively impact our business and operations.
The short and long-term implications of Russia’s
invasion of Ukraine are difficult to predict at this time. We continue to monitor any adverse impact that the outbreak of war in Ukraine
and the subsequent institution of sanctions against Russia by the United States and several European and Asian countries may have on
the global economy in general, on our business and operations and on the businesses and operations of our suppliers and other third parties
with which we conduct business. For example, a prolonged conflict may result in increased inflation, escalating energy prices and constrained
availability, and thus increasing costs, of raw materials. We will continue to monitor this fluid situation and develop contingency plans
as necessary to address any disruptions to our business operations as they develop. To the extent the war in Ukraine may adversely affect
our business as discussed above, it may also have the effect of heightening many of the other risks described herein. Such risks include,
but are not limited to, adverse effects on macroeconomic conditions, including inflation; disruptions to our technology infrastructure,
including through cyberattack, ransom attack, or cyber-intrusion; adverse changes in international trade policies and relations; disruptions
in global supply chains; and constraints, volatility, or disruption in the capital markets, any of which could negatively affect our
business and financial condition.
Risks Related to Ownership of Our Common Stock and Warrants
*If
our operations and performance do not meet the expectations of investors or securities analysts or for other reasons, the market price
of our securities may decline, and the market price of our common stock may continue to be volatile.
Any of the factors listed below could have a negative
impact on your investment in our securities, and our securities may trade at prices significantly below the price you paid for them.
In such circumstances, the trading price of our securities may not recover and may experience a further decline.
Factors affecting the trading price of our securities
may include:
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adverse regulatory decisions; |
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any delay in our regulatory filings for our product
candidates and any adverse development or perceived adverse development with respect to the applicable regulatory authority’s
review of such filings, including without limitation the FDA’s issuance of a “refusal to file” letter or a request
for additional information; |
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the impacts of the ongoing COVID-19 pandemic and related
restrictions; |
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the ongoing conflict between Ukraine and Russia and
the global impact of restrictions and sanctions imposed on Russia and the impact thereof on the markets generally, including any
adverse effects on macroeconomic conditions such as inflation; |
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the commencement, enrollment or results of any future
clinical trials we may conduct, or changes in the development status of our product candidates; |
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adverse results from, delays in or termination of clinical
trials; |
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unanticipated serious safety concerns related to the
use of our product candidates; |
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lower than expected market acceptance of our product
candidates following approval for commercialization; |
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changes in financial estimates by us or by any securities
analysts who might cover our stock; |
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changes in the market valuations of similar companies; |
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stock market price and volume fluctuations of comparable
companies and, in particular, those that operate in the biopharmaceutical industry; |
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publication of research reports about us or our industry
or positive or negative recommendations or withdrawal of research coverage by securities analysts; |
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announcements by us or our competitors of significant
acquisitions, strategic partnerships or divestitures; |
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announcements of investigations or regulatory scrutiny
of our operations or lawsuits filed against us; |
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investors’ general perception of our business
or management; |
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recruitment or departure of key personnel; |
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overall performance of the equity markets; |
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disputes or other developments relating to intellectual
property rights, including patents, litigation matters and our ability to obtain, maintain, defend, protect and enforce patent and
other intellectual property rights for our technologies; |
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significant lawsuits, including patent or stockholder
litigation; |
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proposed changes to healthcare
laws in the U.S. or foreign jurisdictions, or speculation regarding such changes; |
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general political and economic conditions; and |
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other events or factors, many of which are beyond our
control. |
In
addition, the stock market in general, Nasdaq and pharmaceutical companies in particular
have experienced extreme price and volume fluctuations that have often been unrelated or
disproportionate to the operating performance of these companies. The trading price of our
common stock is, and is likely to continue to be, volatile. For example, from September 24,
2021, the date of the closing of the Business Combination, to September 30, 2022, our closing
stock price ranged from $0.789 to $16.42 per share. Broad market and industry factors may
negatively affect the market price of our securities, regardless of our actual operating
performance. As a result of this volatility, our stockholders may not be able to sell their
common stock at or above the prices at which they purchased their shares. Moreover, in the
past, stockholders have initiated class action lawsuits against pharmaceutical and biotechnology
companies following periods of volatility in the market prices of these companies’
stock. Such litigation, if instituted against us, could cause us to incur substantial costs
and divert management’s attention and resources from our business.
Insiders have substantial control over us, which could limit
your ability to affect the outcome of key transactions, including a change of control.
As of September 30, 2022, our directors and executive
officers and their affiliates beneficially owned approximately 36.6% of the outstanding shares of our common stock. As a result, these
stockholders, if they act together, will be able to influence our management and affairs and all matters requiring stockholder approval,
including the election of directors and approval of significant corporate transactions, such as a merger or other sale of our company
or our assets. This concentration of ownership may have the effect of delaying or preventing a change in control of our company or discouraging
a potential acquirer from making a tender offer or otherwise attempting to obtain control, even if that change in control would benefit
our other stockholders. This significant concentration of ownership may also adversely affect the trading price for our common stock
because investors often perceive disadvantages in owning stock in companies with controlling stockholders.
We will incur significant increased expenses and administrative
burdens as a public company, which could negatively impact our business, financial condition and results of operations.
We face increased legal, accounting, administrative
and other costs and expenses as a public company that we did not incur as a private company. The Sarbanes-Oxley Act, including the requirements
of Section 404, as well as rules and regulations subsequently implemented by the SEC, the Dodd-Frank Wall Street Reform and Consumer
Protection Act of 2010 and the rules and regulations promulgated and to be promulgated thereunder, and the securities exchanges,
impose additional reporting and other obligations on public companies. Compliance with public company requirements will increase costs
and make certain activities more time-consuming. A number of those requirements will require us to carry out activities we had not done
previously. For example, we have adopted new charters for our board committees and adopted some new disclosure controls and procedures.
In addition, expenses associated with SEC reporting requirements will be incurred. Furthermore, if any issues in complying with those
requirements are identified (for example, if the auditors identify a material weakness or significant deficiency in the internal control
over financial reporting), we could incur additional costs rectifying those issues, and the existence of those issues could adversely
affect our reputation or investor perceptions of us. It may also be more expensive to obtain director and officer liability insurance.
Risks associated with our status as a public company may make it more difficult to attract and retain qualified persons to serve on our
board of directors or as executive officers. The additional reporting and other obligations imposed by these rules and regulations will
increase legal and financial compliance costs and the costs of related legal, accounting and administrative activities. These increased
costs will require us to divert a significant amount of money that could otherwise be used to expand our business and achieve strategic
objectives. Advocacy efforts by stockholders and third parties may also prompt additional changes in governance and reporting requirements,
which could further increase costs.
If we fail to comply with the continued listing requirements
of the Nasdaq Capital Market, our common stock may be delisted and the price of our common stock and our ability to access the capital
markets could be negatively impacted.
We must continue to satisfy the Nasdaq Capital
Market’s continued listing requirements, including, among other things, a minimum closing bid price requirement of $1.00 per share
for 30 consecutive business days. If a company fails for 30 consecutive business days to meet the $1.00 minimum closing bid price requirement,
The Nasdaq Stock Market LLC (“Nasdaq”) will send a deficiency notice to the company, advising that it has been afforded a
“compliance period” of 180 calendar days to regain compliance with the applicable requirements.
A delisting of our common stock from the Nasdaq
Capital Market could materially reduce the liquidity of our common stock and result in a corresponding material reduction in the price
of our common stock. In addition, delisting could harm our ability to raise capital through alternative financing sources on terms acceptable
to us, or at all, and may result in the potential loss of confidence by investors and employees.
On November 3, 2022, we received written notice
from Nasdaq indicating that, for the last 30 consecutive business days, the bid price for our common stock had closed below the minimum
$1.00 per share requirement for continued listing on the Nasdaq Capital Market under Nasdaq Listing Rule 5550(a)(2). In accordance with
Nasdaq Listing Rule 5810(c)(3)(A), we have been provided with an initial period of 180 calendar days, or until May 2, 2023, to regain
compliance. The written notice states that the Nasdaq staff will provide written notification that we have achieved compliance with Rule
5550(a)(2) if at any time before May 2, 2023, the bid price of our common stock closes at $1.00 per share or more for a minimum of ten
consecutive business days. We intend to monitor the bid price of our common stock and consider available options if our common stock
does not trade at a level likely to result in our regaining compliance with the Nasdaq Capital Market’s minimum bid price rule
by May 2, 2023, which may include, among other options, effectuating a reverse stock split. There is no guarantee that we will regain
compliance by May 2, 2023. If we do not regain compliance with Rule 5550(a)(2) by May 2, 2023, we may be afforded a second 180 calendar
day period to regain compliance. To qualify, we would be required to meet the continued listing requirement for market value of publicly
held shares and all other initial listing standards for the Nasdaq Capital Market, except for the minimum bid price requirement. In addition,
we would be required to notify Nasdaq of our intent to cure the deficiency during the second compliance period, which may include, if
necessary, implementing a reverse stock split.
Any failure to maintain compliance with continued
listing requirements of the Nasdaq Capital Market could result in delisting of our common stock from the Nasdaq Capital Market and negatively
impact our company and holders of our common stock, including by reducing the willingness of investors to hold our common stock because
of the resulting decreased price, liquidity and trading of our common stock, limited availability of price quotations and reduced news
and analyst coverage. Delisting may adversely impact the perception of our financial condition, cause reputational harm with investors,
our employees and parties conducting business with us and limit our access to debt and equity financing.
Our failure to timely and effectively implement controls and
procedures required by Section 404(a) of the Sarbanes-Oxley Act could negatively impact our business.
Absent an applicable exemption, we are required
to provide a management’s attestation on internal controls over financial reporting, and we were not previously required to do
this as a private company. The standards required for a public company under Section 404(a) of the Sarbanes-Oxley Act are significantly
more stringent than those required of us when we were a privately held company. Management may not be able to effectively and timely
implement controls and procedures that adequately respond to the increased regulatory compliance and reporting requirements. If we are
not able to implement the additional requirements of Section 404(a) in a timely manner or with adequate compliance, we may
not be able to assess whether our internal controls over financial reporting are effective, which may subject us to adverse regulatory
consequences and could harm investor confidence and the market price of our securities.
We are an “emerging growth company” within the meaning
of the Securities Act, and if we take advantage of certain exemptions from disclosure requirements available to emerging growth companies,
it could make our securities less attractive to investors and may make it more difficult to compare our performance to the performance
of other public companies.
We
are an “emerging growth company” as defined in Section 2(a)(19) of
the U.S. Securities Act of 1933, as amended (the “Securities Act”), as modified
by the JOBS Act. As such, we are eligible for and intend to take advantage of certain exemptions
from various reporting requirements applicable to other public companies that are not emerging
growth companies for as long as we continue to be an emerging growth company, including,
but not limited to, (a) not being required to comply with the auditor attestation requirements
of Section 404 of the Sarbanes-Oxley Act, (b) reduced disclosure obligations regarding
executive compensation in our periodic reports and proxy statements and (c) exemptions
from the requirements of holding a nonbinding advisory vote on executive compensation and
stockholder approval of any golden parachute payments not previously approved. As a result,
our stockholders may not have access to certain information they may deem important. We will
remain an emerging growth company until the earlier of (i) the last day of the
fiscal year (a) following November 22, 2024, (b) in which we have total annual
gross revenue of at least $1.235 billion, or (c) in which we are deemed to be a
large accelerated filer, which means the market value of our common equity that is held by
non-affiliates exceeds $700 million as of the last business day of our most recently
completed second fiscal quarter; and (ii) the date on which we have issued more than
$1.00 billion in non-convertible debt securities during the prior three-year period.
We cannot predict whether investors will find our securities less attractive because we will
rely on these exemptions. If some investors find our securities less attractive as a result
of our reliance on these exemptions, the trading prices of our securities may be lower than
they otherwise would be; there may be a less active trading market for our securities; and
the trading prices of our securities 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 opted to take advantage of the exemption for complying with new or revised accounting
standards within the same time periods as private companies, 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, can adopt the new or revised standard at the time private
companies adopt the new or revised standard. This may make comparison of our consolidated
financial statements with another public company that is neither an emerging growth company
nor an emerging growth company that has opted out of using the extended transition period
difficult or impossible because of the potential differences in accounting standards used.
Even after we no longer qualify as an emerging
growth company, we may continue to qualify as a “smaller reporting company,” which would allow us to continue to take advantage
of many of the same exemptions from disclosure requirements, including reduced disclosure obligations regarding executive compensation
in our periodic reports and proxy statements. If we cease to be an emerging growth company and do not qualify as a smaller reporting
company, we will no longer be able to take advantage of certain exemptions from reporting discussed above, including not being able to
take advantage of extended transition periods for the adoption of new or modified accounting standards, and, absent other exemptions
or relief available from the SEC, we will also be required to comply with the auditor attestation requirements of Section 404 of
the Sarbanes-Oxley Act if we are no longer a non-accelerated filer at such time. We will incur additional expenses in connection with
such compliance, and our management will need to devote additional time and effort to implement and comply with such requirements.
If securities or industry analysts do not publish or cease publishing
research or reports about us, our business, or our market, or if they change their recommendations regarding our securities adversely,
the price and trading volume of our securities could decline.
The trading market for our common stock will be
influenced by the research and reports that industry or financial analysts publish about us or our business. Securities and industry
analysts do not currently, and may never, publish research on us. If no or few analysts commence coverage of us, the trading price of
our securities would likely decrease. Even if we do obtain analyst coverage, if one or more of the analysts covering our business downgrade
their evaluations of our securities, the price of our securities could decline. If one or more of these analysts cease to cover our securities,
we could lose visibility in the market for our securities, which in turn could cause the price of our securities to decline.
*Future sales, or the perception of future sales, by us or our
stockholders in the public market, the issuance of rights to purchase our common stock, including pursuant to the Equity Incentive Plan
and the ESPP, and future exercises of registration rights could result in the additional dilution of the percentage ownership of our
stockholders and cause the market price for our common stock to decline.
The sale of shares of our common stock, convertible
securities or other equity securities in the public market, or the perception that such sales could occur, could harm the prevailing
market price of shares of our common stock. These sales, or the possibility that these sales may occur, also might make it more difficult
for us to sell equity securities in the future at a time and at a price that we deem appropriate. In addition, if we sell shares of our
common stock, convertible securities or other equity securities, investors may be materially diluted by subsequent sales. Such sales
may also result in material dilution to our existing stockholders, and new investors could gain rights, preferences, and privileges senior
to the holders of our common stock.
Pursuant to the Jasper Therapeutics, Inc. 2021
Equity Incentive Plan (the “Equity Incentive Plan”), which became effective on September 23, 2021, we are authorized
to grant equity awards to our employees, directors and consultants. In addition, pursuant to the Jasper Therapeutics, Inc. 2021 Employee
Stock Purchase Plan (the “ESPP”), which became effective on September 23, 2021, we are authorized to sell shares to
our employees. A total of up to 4,400,000 and up to 550,000 shares of our common stock were initially reserved for future issuance
under the Equity Incentive Plan and the ESPP, respectively. In addition, the Equity Incentive Plan and ESPP provide for annual automatic
increases in the number of shares reserved thereunder, in each case, beginning on January 1, 2022. On January 1, 2022, pursuant
to the foregoing provisions, 1,514,204 and 378,551 shares of common stock were added to the shares reserved for future issuance under
the Equity Incentive Plan and the ESPP, respectively. As a result of such annual increases, our stockholders may experience additional
dilution, which could cause the price of our common stock to fall.
On March 14, 2022, the Compensation Committee
of our board of directors adopted the 2022 Inducement Equity Incentive Plan (the “2022 Inducement Plan”). The maximum number
of shares available for grant under the 2022 Inducement Plan is 3,000,000 shares of common stock. The 2022 Inducement Plan has not been
and will not be approved by our stockholders. Under the 2022 Inducement Plan, we can grant nonstatutory stock options, restricted stock
awards, stock appreciation rights, restricted stock units, performance awards and other awards, but only to an individual, as a material
inducement to such individual to enter into employment with us or an affiliate of ours, who (i) has not previously been an employee or
director of ours or (ii) is rehired following a bona fide period of non-employment with us.
As of September 30, 2022, options to purchase
an aggregate of 2,561,687 shares of our common stock were outstanding that were previously issued under the Jasper Therapeutics, Inc.
2019 Equity Incentive Plan (the “2019 EIP”). We assumed the 2019 EIP in connection with the Business Combination and no further
awards will be granted under the 2019 EIP. However, shares of our common stock subject to outstanding awards granted under the 2019 EIP
that (a) are not issued because the award or any portion of the award expires or otherwise terminates without all of the shares
covered by the award having been issued, (b) are withheld or reacquired to satisfy the exercise, strike or purchase price or (c) are
withheld or reacquired to satisfy a tax withholding obligation will also be added to the number of shares of our common stock available
for issuance pursuant to the Equity Incentive Plan. As of September 30, 2022, a total of 106,268 shares of common stock had been added
to the number of shares of our common stock available for issuance pursuant to the Equity Incentive Plan as a result of the cancellation
of certain options previously granted under the 2019 EIP.
Pursuant to the Amended and Restated Registration
Rights Agreement entered into in connection with the Business Combination, certain of our stockholders can demand that we register their
registrable securities under certain circumstances and will each also have piggyback registration rights for these securities. In addition,
we are required to file and maintain an effective registration statement under the Securities Act covering such securities and certain
of our other securities. We filed a registration statement on October 18, 2021, which was first amended on March 29, 2022 and further
amended on October 7, 2022, in order to satisfy the foregoing obligations and we have currently registered for resale an aggregate of
31,019,499 shares of our common stock, including up to 4,999,863 shares of our common stock issuable upon exercise of our outstanding
warrants. The registration of these securities permits the public sale of such securities, subject to certain contractual restrictions
on transfer imposed by the Amended and Restated Registration Rights Agreement and the Business Combination Agreement, which contractual
restrictions on transfer terminated on March 23, 2022. The presence of these additional shares of our common stock trading in the public
market may have an adverse effect on the market price of our securities.
In the future, we may also issue our securities
in connection with investments or acquisitions. The amount of shares of our common stock issued in connection with an investment or acquisition
could constitute a material portion of our then-outstanding shares of our common stock. Any issuance of additional securities in connection
with investments or acquisitions may result in additional dilution to our stockholders.
Because there are no current plans to pay cash dividends on
our common stock for the foreseeable future, you may not receive any return on investment unless you sell shares of our common stock
for a price greater than that which you paid for it.
We may retain future earnings, if any, for future
operations, expansion and debt repayment and have no current plans to pay any cash dividends for the foreseeable future. Any decision
to declare and pay dividends as a public company in the future will be made at the discretion of our board of directors and will depend
on, among other things, our results of operations, financial condition, cash requirements, contractual restrictions and other factors
that our board of directors may deem relevant. In addition, our ability to pay dividends may be limited by covenants of any existing
and future outstanding indebtedness we or our subsidiaries incur. As a result, you may not receive any return on an investment in our
common stock unless you sell your shares of our common stock for a price greater than that which you paid for it.
Anti-takeover provisions in our Certificate of Incorporation
and under Delaware law could make an acquisition of us, which may be beneficial to our stockholders, more difficult and may prevent attempts
by our stockholders to replace or remove our current management.
Our Second Amended and Restated Certificate of
Incorporation (our “Certificate of Incorporation”) contains provisions that could delay or prevent a change of control of
us or changes in our board of directors that our stockholders might consider favorable. Some of these provisions include:
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a board of directors divided into three classes serving
staggered three-year terms, such that not all members of our board of directors will be elected at one time; |
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a prohibition on stockholder
action through written consent, which requires that all stockholder actions be taken at a meeting of our stockholders; |
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a requirement that special
meetings of stockholders be called only by the chairman of our board of directors, the chief executive officer, the president, or
by a majority of the total number of authorized directors; |
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advance notice requirements
for stockholder proposals and nominations for election to our board of directors; |
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a requirement that no member
of our board of directors may be removed from office by our stockholders except for cause and, in addition to any other vote required
by law, upon the approval of not less than two-thirds of all outstanding shares of our voting stock then entitled to vote in the
election of directors; |
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a requirement of approval
of not less than two-thirds of all outstanding shares of our voting stock to amend any bylaws by stockholder action or to amend specific
provisions of our Certificate of Incorporation; and |
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the authority of our board
of directors to issue preferred stock on terms determined by our board of directors without stockholder approval and which preferred
stock may include rights superior to the rights of the holders of our common stock. |
In
addition, because we are incorporated in the State of Delaware, we are governed by the provisions
of Section 203 of the General Corporation Law of the State of Delaware (“DGCL”),
which may prohibit certain business combinations with stockholders owning 15% or more
of our outstanding voting stock. These anti-takeover provisions and other provisions in our
Certificate of Incorporation and Second Amended and Restated Bylaws (our “Bylaws”)
could make it more difficult for stockholders or potential acquirors to obtain control of
our board of directors or initiate actions that are opposed by our then-current board of
directors and could also delay or impede a merger, tender offer, or proxy contest involving
us. These provisions could also discourage proxy contests and make it more difficult for
you and other stockholders to elect directors of your choosing or cause us to take other
corporate actions you desire. Any delay or prevention of a change of control transaction
or changes in our board of directors could cause the market price of our common stock to
decline.
Our Certificate of Incorporation provides that the Court of
Chancery of the State of Delaware is the exclusive forum for substantially all disputes between us and our stockholders, which could
limit our stockholders’ ability to obtain a favorable judicial forum for disputes with us or our directors, officers or employees.
Our Certificate of Incorporation provides that
the Court of Chancery of the State of Delaware is the exclusive forum for the following types of actions or proceedings under Delaware
statutory or common law: (i) any derivative action or proceeding brought on our behalf; (ii) any action or proceeding asserting
a claim of breach of a fiduciary duty owed by any of our current or former directors, officers, or other employees to us or our stockholders;
(iii) any action or proceeding asserting a claim against us or any of our current or former directors, officers, or other employees,
arising out of or pursuant to any provision of the DGCL, our Certificate of Incorporation or Bylaws; (iv) any action or proceeding
to interpret, apply, enforce, or determine the validity of our Certificate of Incorporation or Bylaws; (v) any action or proceeding
as to which the DGCL confers jurisdiction to the Court of Chancery of the State of Delaware; and (vi) any action asserting a claim
against us or any of our directors, officers, or other employees governed by the internal affairs doctrine, in all cases to the fullest
extent permitted by law and subject to the court’s having personal jurisdiction over the indispensable parties named as defendants.
These provisions would not apply to suits brought to enforce a duty or liability created by the Exchange Act. Furthermore, Section 22
of the Securities Act creates concurrent jurisdiction for federal and state courts over all such Securities Act actions. Accordingly,
both state and federal courts have jurisdiction to entertain such claims. To prevent having to litigate claims in multiple jurisdictions
and the threat of inconsistent or contrary rulings by different courts, among other considerations, our Certificate of Incorporation
provides that the federal district courts of the United States of America shall be exclusive forum for resolving any complaint asserting
a cause of action arising under the Securities Act, including all causes of action asserted against any defendant named in such complaint.
While the Delaware courts have determined that such choice of forum provisions are facially valid, a stockholder may nevertheless seek
to bring a claim in a venue other than those designated in the exclusive forum provisions. In such instance, we would expect to vigorously
assert the validity and enforceability of the exclusive forum provisions of our Certificate of Incorporation. This may require significant
additional costs associated with resolving such action in other jurisdictions, and the provisions may not be enforced by a court in those
other jurisdictions.
These exclusive forum provisions may limit a stockholder’s
ability to bring a claim in a judicial forum that it finds favorable for disputes with us or our directors, officers, or other employees
and may discourage these types of lawsuits. In addition, a stockholder that is unable to bring a claim in the judicial forum of its choosing
may be required to incur additional costs in the pursuit of actions that are subject to these exclusive forum provisions, particularly
if the stockholder does not reside in or near Delaware. Furthermore, the enforceability of similar choice of forum provisions in other
companies’ certificates of incorporation or bylaws has been challenged in legal proceedings, and it is possible that a court could
find these types of provisions to be inapplicable or unenforceable. If a court were to find the exclusive forum provision contained in
our Certificate of Incorporation to be inapplicable or unenforceable in an action, we may incur further significant additional costs
associated with resolving such action in other jurisdictions, all of which could seriously harm our business.
Any exercise of the outstanding warrants to purchase shares
of our common stock would increase the number of shares eligible for future resale in the public market and result in dilution to our
stockholders.
Outstanding
warrants to purchase shares of our common stock became exercisable in accordance with the
terms of the Warrant Agreement, dated November 19, 2019, between Continental Stock Transfer &
Trust Company, as warrant agent, and us (the “Warrant Agreement”) commencing
on October 24, 2021 (the “Public Warrants”). As of September 30, 2022, Public
Warrants to purchase 4,999,863 shares of our common stock were outstanding. The exercise
price of these Public Warrants is $11.50 per share. To the extent such Public Warrants are
exercised, additional shares of our common stock will be issued, which will result in dilution
to the holders of our common stock and increase the number of shares eligible for resale
in the public market. Sales of substantial numbers of such shares in the public market or
the fact that such Public Warrants may be exercised could adversely affect the prevailing
market prices of our common stock. However, there is no guarantee that the Public Warrants
will ever be in the money prior to their expiration, and as such, the Public Warrants may
expire worthless. See below risk factor, “The Public Warrants may never be in the
money, they may expire worthless and the terms of the Public Warrants may be amended in a
manner adverse to a holder if holders of at least 50% of the then-outstanding Public Warrants
approve of such amendment.”
The Public Warrants may never be in the money, they may expire
worthless and the terms of the Public Warrants may be amended in a manner adverse to a holder if holders of at least 50% of the then-outstanding
Public Warrants approve of such amendment.
The Public Warrants were issued in registered
form under the Warrant Agreement. The Warrant Agreement provides that the terms of the Public Warrants may be amended without the consent
of any holder to cure any ambiguity or correct any defective provision or correct any mistake, but requires the approval by the holders
of at least 50% of the then-outstanding Public Warrants to make any change that adversely affects the interests of the registered holders
of Public Warrants. Accordingly, we may amend the terms of the Public Warrants in a manner adverse to a holder if holders of at least
50% of the then-outstanding Public Warrants approve of such amendment. Although our ability to amend the terms of the Public Warrants
with the consent of at least 50% of the then-outstanding Public Warrants is unlimited, examples of such amendments could be amendments
to, among other things, increase the exercise price of the Public Warrants, convert the Public Warrants into cash, shorten the exercise
period, or decrease the number of shares of our common stock purchasable upon exercise of a Public Warrant.
We may redeem your unexpired Public Warrants prior to their
exercise at a time that is disadvantageous to you, thereby making your Public Warrants worthless.
We have the ability to redeem outstanding Public
Warrants at any time after they become exercisable and prior to their expiration, at a price of $0.01 per Public Warrant, provided that
the last reported sales price of our common stock equals or exceeds $18.00 per share (as adjusted for share subdivisions, share dividends,
rights issuances, subdivisions, reorganizations, recapitalizations, and the like) for any 20 trading days within a 30-trading-day period
ending on the third trading day prior to the date we send the notice of redemption to the warrantholders. If and when the Public
Warrants become redeemable by us, we may exercise our redemption right even if we are unable to register or qualify the underlying securities
for sale under all applicable state securities laws. Redemption of the outstanding Public Warrants could force you to: (i) exercise
your Public Warrants and pay the exercise price therefor at a time when it may be disadvantageous for you to do so; (ii) sell your
Public Warrants at the then-current market price when you might otherwise wish to hold your Public Warrants; or (iii) accept the
nominal redemption price that, at the time the outstanding Public Warrants are called for redemption, is likely to be substantially less
than the market value of your Public Warrants.
In addition, we may redeem your Public Warrants
at any time after they become exercisable and prior to their expiration at a price of $0.10 per Public Warrant upon a minimum of 30 days’
prior written notice of redemption; provided that holders will be able to exercise their Public Warrants prior to redemption for a number
of our common stock determined based on the redemption date and the fair market value of our common stock. The value received upon exercise
of the Public Warrants (1) may be less than the value the holders would have received if they had exercised their Public Warrants
at a later time where the underlying share price is higher and (2) may not compensate the holders for the value of the Public Warrants.