ITEM 1A. RISK FACTORS
Our business faces significant risks. You should
carefully consider the risks described below, together with all of the other information included in our filings with the United States
Securities and Exchange Commission (SEC) when evaluating our business. If any of the following risks actually occurs, our business, financial
condition or results of operations could be materially adversely affected and the trading price of shares of our common stock could decline.
The occurrence of any of the following risks could cause our actual results to differ materially from those contained in forward-looking
statements we have made in this report and those we may make from time to time.
Summary of Risks
This section provides a summary of the risks
that may impact our performance in the future. For details of our various risk factors and their impacts, see “Risk Factors Discussion.”
Our risk factors are organized into the following
categories: 1) Risks related to our business, 2) Risks related to clinical and regulatory matters, 3) Risks related to our intellectual
property, 4) Risks related to government regulations, 5) Risks related to our reliance on third parties, and 6) Risks related to ownership
of our common stock.
Risks related to our business
Business risks include risks associated with our products (including
as a result of terminating the development of our prior drug candidates and refocusing on new drug candidates) and regulatory approval,
licensing agreements, historical losses, managing growth, acquisitions, and economic uncertainty or downturns. In general, the risks related
to our business can cause variability in the future profits of the Company.
Risks related to clinical and regulatory
matters
Clinical and regulatory matters include risks associated with clinical
trials and the future ability to commercially market the product. In order for any of our products to be commercialized and produce future
profits, successful trials need to be completed with supporting data to receive regulatory approval. Failing to complete the trial will
significantly increase our cost of doing business. Developments from competitors and the ability to obtain market exclusivity could also
negatively impact future profits.
Risks related to our intellectual property
Our products depend upon securing and protecting
critical intellectual property. Patent positions are highly uncertain and involve complex legal and factual questions. Infringing upon
patents or trade secrets could force us to cease or alter our product development efforts or obtain a license to continue to develop
or sale our products. These risks could not only impact the future profits of the company but also create adverse publicity for us.
Risks related to government regulations
Regulatory matters present ongoing risks due to the evolving, complex,
and often uncertain nature of the healthcare regulatory and political landscape in which we operate. In this environment, we are required
to comply with various federal and state pharmaceutical and healthcare laws and regulations, and to maintain secure systems to protect
sensitive confidential information. Complying with the various regulations can increase our cost of doing business. We could also face
potential fines or reputational risk if we do not comply. Litigation or investigations can increase costs, negatively affect our operating
results and create adverse publicity for us.
Risks related to our reliance on third
parties
The Company relies on third parties to conduct non-clinical and clinical
studies, as well as to manufacture our product candidates. Third parties’ failure to perform the trials as contractually required
could impact our ability to obtain regulatory approval. If our third-party manufacturers fail to meet our requirements and strict regulatory
requirements, our product development and commercialization efforts may be materially harmed.
Risks related to ownership of our common
stock
Common stocks risks include risks associated
with the limited market for our common stock, a potential issuance of a substantial number of additional shares, stock price volatility,
and reporting requirements of federal securities laws. The net effect of these risks can include reductions in future profits, additional
operating expenses, inability to meet liquidity needs, inability to access capital and increased cost of capital.
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Risk Factors Discussion
Risks Related to Our Business
Ending Development of Our Former Drug Candidates May Adversely Affect
Our Business and Financial Condition
We terminated the development of our former primary drug candidate,
esmethadone (d-methadone, dextromethadone, or REL-1017) as a potential treatment for major depressive disorder (MDD), which had been the
cornerstone of our research and development efforts. This decision was made due to an interim analysis indicating that our Phase 3 study
of esmethadone, Reliance II, was futile and unlikely to meet the primary efficacy endpoint with statistical significance. We also recently
terminated development of REL-P11, a modified-release formulation of psilocybin, as an investigational agent for the treatment of metabolic
disease. These determinations resulted in the loss of significant time, resources and capital invested in the development of esmethadone
and REL-P11. There can be no assurance that our refocusing on our new drug candidates will successfully offset these setbacks.
Our Refocusing on New Drug Candidates Involves
Significant Uncertainty and Risk
We are now focusing our efforts on the development
of two new drug candidates, NDV-01 and sepranolone. These drug candidates are in early stages of development, and we have limited data
regarding their safety, efficacy or commercial viability. The transition to these new candidates requires us to redirect resources, establish
new research protocols and secure additional regulatory approvals, all of which may increase our operational costs and extend our development
timeline. The mechanisms of action and therapeutic potential of our new drug candidates are different from those of our prior drug candidates.
There is no guarantee that our experience with the prior drug candidates will translate to success with the new ones. Investors should
be aware that our refocused strategy is largely untested, and we may encounter unforeseen scientific, regulatory, or market challenges
that could materially impact our business prospects. If either or both new drug candidates fail to demonstrate sufficient promise in
clinical trials, we may face further delays and/or an inability to sustain our operations.
Our business depends on the success of
our drug candidates. If we are unable to obtain regulatory approval for and successfully commercialize our drug candidates or other future
product candidates, or we experience significant delays in doing so, our business will be materially harmed.
The primary focus of our product development
is NDV-01 and sepranolone.
This may make an investment in our Company riskier
than similar companies that have multiple product candidates in advanced stages of active development and that therefore may be able
to better sustain a setback of a product candidate. Our operating history with our new drug candidates, NDV-01 and sepranolone, is limited.
This lack of historical data and experience makes it difficult to predict the likelihood of success in development, regulatory approval,
or commercialization. Successful continued development and ultimate regulatory approval of our drug candidates is critical to the future
success of our business. We have invested, and will continue to invest, a significant portion of our time and financial resources in
the clinical development of our drug candidates. If we cannot successfully develop, obtain regulatory approval for and commercialize
our drug candidates, we may not be able to continue our operations. The future regulatory and commercial success of our drug candidates
is subject to a number of risks, including the following:
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Our drug candidates and any future product candidates
will be subject to rigorous and extensive clinical trials and extensive regulatory approval processes implemented by the FDA and comparable
foreign regulatory authorities before obtaining marketing approval, if at all, from these regulatory authorities. The drug development
and approval process is lengthy and expensive, and approval is never certain. Investigational new drugs, such as our drug candidates
may not prove to be safe and effective in clinical trials. We have limited experience as a company in conducting later stage clinical
trials required to obtain regulatory approval. We may be unable, if at all, to conduct future clinical trials at preferred sites, enlist
clinical investigators, enroll sufficient numbers of participants or begin or successfully complete clinical trials in a timely fashion.
In addition, 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. Because we have limited experience as a company
designing clinical trials, we may be unable to design and execute clinical trials to support regulatory approval.
There is a high failure rate for drugs and biological products proceeding
through clinical trials. Failure can occur at any time during the clinical trial process. The results of non-clinical studies and early
clinical trials of our drug candidates or any future product candidate may not be predictive of the results of later-stage clinical studies
or trials and the results of studies or trials in one set of patients or line of treatment may not be predictive of those obtained in
another. In fact, many companies in the pharmaceutical and biotechnology industries have suffered significant setbacks in late stage clinical
trials even after achieving promising results in non-clinical studies and earlier stage clinical trials. In addition, data obtained from
non-clinical and clinical activities are subject to varying interpretations, which may delay, limit or prevent regulatory approval. Owing
in part to the complexity of biological pathways, our drug candidates or any future product candidate may not demonstrate in patients
the biochemical and pharmacological properties we anticipate based on laboratory studies or earlier stage clinical trials, and they may
interact with human biological systems or other drugs in unforeseen, ineffective or harmful ways. The number of patients exposed to product
candidates and the average exposure time in the clinical development programs may be inadequate to detect rare adverse events or findings
that may only be detected once a product candidate is administered to more patients and for greater periods of time. If we are unable
to successfully demonstrate the safety and efficacy of our drug candidates or other future product candidates and receive the necessary
regulatory approvals, our business will be materially harmed.
Even if we do receive regulatory approval to
market our drug candidates or other future product candidates, any such approval may be subject to limitations on the indicated uses
or patient populations for which we may market the products. Accordingly, even if we are able to obtain the requisite financing to continue
to fund our development programs, we may be unable to successfully develop or commercialize our drug candidates or other future product
candidates. If we or any of our future development collaborators are unable to develop, or obtain regulatory approval for, or, if approved,
successfully commercialize our drug candidates or other future product candidates, we may not be able to generate sufficient revenue
to continue our business.
Preliminary or top-line results may not
accurately reflect the complete results of the clinical study.
Preliminary or top-line data remain subject to
audit and verification procedures that may result in the final data being materially different from the preliminary or top-line data.
As a result, preliminary or top-line data should be viewed with caution until the final data are available.
We May Require Substantial Additional Funding,
Which May Not Be Available on Favorable Terms, or at All
The termination of development of our former drug candidates and the
pivot to new candidates may increase our need for additional capital to fund ongoing research, clinical trials and operational expenses.
There is no guarantee that we will be able to secure additional funding on acceptable terms, or at all, particularly given the perceived
risk associated with our recent strategic shift. Failure to obtain sufficient capital could force us to curtail operations, delay development
or seek alternative strategies, such as liquidation or bankruptcy.
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We have generated no revenue from commercial
sales to date and our future profitability is uncertain.
We have a limited operating history, and our
business is subject to all of the risks inherent in the establishment of a new business enterprise. Our likelihood of success must be
considered in light of the problems, expenses, difficulties, complications and delays frequently encountered in connection with this.
Since we began our business, we have focused on research, development and clinical trials of product candidates, and have incurred significant
losses since inception and generated no product revenues. If we continue to incur operating losses and fail to become a profitable company,
we may be unable to continue our operations. We expect to continue to operate at a net loss for at least the next several years as we
continue our research and development efforts, continue to conduct clinical trials and develop manufacturing, sales, marketing and distribution
capabilities. There can be no assurance that the products under development by us will be approved for sales in the US or elsewhere.
Furthermore, there can be no assurance that if such products are approved they will be successfully commercialized, and the extent of
our future losses and the timing of our profitability are highly uncertain.
International commercialization of our
product candidates faces significant obstacles.
We may plan to commercialize some of our products
internationally through collaborative relationships with foreign partners. We have limited foreign regulatory, clinical and commercial
resources. Future partners are critical to our international success. We may not be able to enter into collaboration agreements with
appropriate partners for important foreign markets on acceptable terms, or at all. Future collaborations with foreign partners may not
be effective or profitable for us. We will need to obtain approval from the appropriate regulatory, pricing and reimbursement authorities
to market any of our proposed products internationally, and we may be unable to obtain foreign regulatory approvals. Pursuing foreign
regulatory approvals will be time-consuming and expensive. The regulations can vary among countries and foreign regulatory authorities
may require different or additional clinical trials than we conducted to obtain FDA approval for our product candidates. In addition,
adverse clinical trial results, such as death or injury due to side effects, could jeopardize not only regulatory approval, but if approval
is granted, may also lead to marketing restrictions. Our product candidates may also face foreign regulatory requirements applicable
to controlled substances.
We have a history of losses and we may never achieve or sustain
profitability.
We have incurred substantial losses since our
inception, and we may not achieve profitability for the foreseeable future, if at all. Since inception, we have an accumulated deficit
of approximately $698.3 million at December 31, 2025. The Company had cash, cash equivalents and short-term investments of approximately
$93.0 million at December 31, 2025. Even if we succeed in developing and commercializing one or more of our product candidates, we expect
to incur substantial net losses and negative cash flows for the foreseeable future due in part to increasing research and development
expenses, including clinical trials, and increasing expenses from leasing additional facilities and hiring additional personnel. As a
result, we will need to generate significant revenues in order to achieve and maintain profitability. We may not be able to generate these
revenues or achieve profitability in the future. Even if we do achieve profitability, we may not be able to sustain or increase profitability.
We have a limited operating history upon
which to base an investment decision.
Our limited operating history may limit your
ability to evaluate our prospects due to our limited historical financial data and our unproven potential to generate profits. You should
evaluate the likelihood of financial and operational success in light of the risks, uncertainties, expenses and difficulties associated
with an early-stage business, many of which may be beyond our control, including:
● our potential inability to obtain regulatory approvals, and
● our potential inability to manufacture, sell and market our products.
Our operations have been limited to organizing and staffing, on a limited
basis, our company, acquiring, developing and securing our proprietary technology and undertaking non-clinical studies and clinical trials
of our principal product candidates. These operations provide a limited basis for you to assess our ability to commercialize our product
candidates and the advisability of investing in our common stock.
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Our ability to use our net operating loss
carryforwards and certain other tax attributes may be limited.
As of December 31, 2025, we had Federal and State
net operating loss (NOL) carryforwards of approximately $246,410,000, and $2,719,000, respectively, which begin expiring in 2027, 2032
and 2032, respectively. Under U.S. federal tax legislation enacted in 2017, informally titled the Tax Cuts and Jobs Act, or Tax Act, federal
NOLs incurred in 2018 and in future years may be carried forward indefinitely, but the deductibility of such federal NOLs is limited to
80% of taxable income in the year. Under Sections 382 and 383 of the U.S. Internal Revenue Code of 1986, as amended, if a corporation
undergoes an “ownership change” (generally defined as a greater than 50 percentage-point cumulative change (by value) in the
equity ownership of certain stockholders over a rolling three-year period), the corporation’s ability to use its pre-change NOLs
and other pre-change tax attributes to offset its post-change taxable income or taxes may be limited. We may also experience ownership
changes as a result of stock offerings or as a result of subsequent shifts in our stock ownership, some of which are outside our control.
The Company completed an analysis and determined that there have been multiple changes of ownership as defined by Section 382 of the IRC.
As a result the utilization of the NOLs are limited annually. Due to the annual limitation some of the NOLs will expire unused regardless
of future taxable income.
We may not be successful in hiring and
retaining key employees.
Our future operations and successes depend in
large part upon the continued service of key members of our senior management team whom we are highly dependent upon to manage our business,
specifically Dr. Sergio Traversa, our Chief Executive Officer and our executive team. If any terminates employment with us, such a departure
would have a material adverse effect on our business.
Our future success also depends on our ability to identify, attract,
hire or engage, retain and motivate other well-qualified managerial, technical, clinical and regulatory personnel. Our success depends
heavily on the expertise of our management team and scientific personnel. The pivot to new drug candidates may require specialized knowledge
or skills that our current team lacks. If we lose key personnel or fail to attract and retain qualified replacements, our ability to execute
our revised strategy could be compromised, leading to delays or failure in our development program. We currently only have 17 full time
employees and are likely to hire additional qualified personnel with expertise in non-clinical pharmacology and toxicology, pharmaceutical
development, clinical research, regulatory affairs, manufacturing, sales and marketing. We compete for qualified individuals with numerous
biopharmaceutical companies, universities and other research institutions. Competition for such individuals, particularly in the United
States, is intense, and we may not be able to hire sufficient personnel to support our efforts. There can be no assurance that these professionals
will be available in the market, or that we will be able to retain existing professionals or to meet or to continue to meet their compensation
requirements. Furthermore, the cost base in relation to such compensation, which may include equity compensation, may increase significantly,
which could have a material adverse effect on us. Failure to establish and maintain an effective management team and work force could
adversely affect our ability to operate, grow and manage our business.
Managing our growth as we expand operations
may strain our resources.
We expect to need to grow rapidly in order to
support ongoing and additional, larger, and potentially international, pivotal clinical trials of our drug candidates, which will place
a significant strain on our financial, managerial and operational resources. In order to achieve and manage growth effectively, we must
continue to improve and expand our operational and financial management capabilities. Moreover, we will need to increase staffing and
to train, motivate and manage our employees.
We may expand our business through the
acquisition of rights to new drug candidates that could disrupt our business, harm our financial condition and may also dilute current
stockholders’ ownership interests in our company.
Our business strategy includes expanding our
products and capabilities, and we may seek acquisitions of drug candidates or technologies to do so. Acquisitions involve numerous risks,
including substantial cash expenditures; potentially dilutive issuance of equity securities; incurrence of debt and contingent liabilities,
some of which may be difficult or impossible to identify at the time of acquisition; difficulties in assimilating the acquired technologies
or the operations of the acquired companies; diverting our management’s attention away from other business concerns; risks of entering
markets in which we have limited or no direct experience; and the potential loss of our key employees or key employees of the acquired
companies.
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We cannot assure you that any acquisition will
result in short-term or long-term benefits to us. We may incorrectly judge the value or worth of an acquired product, company or business.
In addition, our future success would depend in part on our ability to manage the rapid growth associated with some of these acquisitions.
We cannot assure you that we will be able to make the combination of our business with that of acquired products, businesses or companies
work or be successful. Furthermore, the development or expansion of our business or any acquired products, business or companies may
require a substantial capital investment by us. We may not have these necessary funds or they might not be available to us on acceptable
terms or at all. We may also seek to raise funds by selling shares of our preferred or common stock, which could dilute each current
stockholder’s ownership interest in us.
Business interruptions could limit our ability
to operate our business.
Our operations as well as those of our collaborators
on which we depend are vulnerable to damage or interruption from computer viruses, human error, natural disasters, electrical and telecommunication
failures, international acts of terror and similar events. We have not established a formal disaster recovery plan and our back-up operations
and our business interruption insurance may not be adequate to compensate us for losses we may suffer. A significant business interruption
could result in losses or damages incurred by us and require us to cease or curtail our operations.
Risks Related to Clinical and Regulatory Matters
If we or our potential collaborators fail
to obtain the necessary regulatory approvals, or if such approvals are limited, we and our potential collaborators will not be allowed
to commercialize our drug candidates, and we will not generate product revenues.
Satisfaction of all regulatory requirements for
commercialization of a drug candidate typically takes many years, is dependent upon the type, complexity and novelty of the drug candidate,
and requires the expenditure of substantial resources for research and development. Our research and clinical approaches may not lead
to drugs that the FDA considers safe for humans and effective for indicated uses we are studying. The FDA may require studies in addition
to those we are conducting, in which case we or our collaborators would have to expend additional time and resources and would likely
delay the date of potentially receiving regulatory approval. The approval process may also be delayed by changes in government regulation,
future legislation or administrative action or changes in FDA policy that occur prior to or during our regulatory review. Delays in obtaining
regulatory approvals would:
Even if we or our collaborators comply with all
FDA regulatory requirements, our drug candidates may never obtain regulatory approval. If we or our collaborators fail to obtain regulatory
approval for any of our drug candidates we will have fewer commercial products, if any, and corresponding lower product revenues, if any.
Even if our drug candidates receive regulatory approval, such approval may involve limitations on the indications and conditions of use
or marketing claims for our products. Further, later discovery of previously unknown problems or adverse events could result in additional
regulatory restrictions, including withdrawal of products. The FDA may also require us or our collaborators to commit to perform lengthy
Phase IV post-approval clinical efficacy or safety studies. Our expending additional resources on such trials would have an adverse effect
on our operating results and financial condition.
In jurisdictions outside the United States, we
or our collaborators must receive marketing authorizations from the appropriate regulatory authorities before commercializing our drugs.
Regulatory approval processes outside the United States generally include all of the aforementioned requirements and risks associated
with FDA approval.
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If we or our collaborators are unable to
design, conduct and complete successful clinical trials, our drug candidates will not be able to receive regulatory approval.
Before obtaining regulatory approvals for the commercial sale of any
of our product candidates, we must demonstrate through lengthy, complex and expensive non-clinical testing and clinical trials that the
product is both safe and effective for use in each target indication.
Results from early clinical trials may not support moving a drug candidate
to later-stage clinical trials. Phase 3 clinical trials may not demonstrate the safety or efficacy of our drug candidates. Success in
non-clinical studies and early clinical trials does not ensure that later clinical trials will be successful. Results of later clinical
trials may not replicate the results of prior clinical trials and non-clinical studies.
We or our collaborators may have to commit substantial time and additional
resources to conducting further non-clinical studies and clinical trials before obtaining FDA approval for any of our drug candidates.
Clinical trials are very expensive and difficult
to design and implement, in part because they are subject to rigorous requirements. The clinical trial process also consumes a significant
amount of time. Furthermore, if participating patients in clinical trials suffer drug-related adverse reactions during the course of such
clinical trials, or if we, our collaborators or the FDA believe that participating patients are being exposed to unacceptable health risks,
such clinical trials will have to be suspended or terminated. Failure can occur at any stage of the clinical trials, and we or our collaborators
could encounter problems that cause abandonment or repetition of clinical trials.
We have a limited history of developing drug candidates.
We do not know whether any of our ongoing or planned clinical trials will result in marketable drugs.
In addition, completion of clinical trials can
be delayed by numerous factors, including:
● slower than expected rates of patient recruitment and enrollment;
● unanticipated patient dropout rates; and
Any of these delays could significantly impact
the timing, approval and commercialization of our drug candidates and could significantly increase our overall costs of drug development.
We cannot predict whether regulatory agencies
will determine that the data from our clinical trials support marketing approval.
The FDA’s and other regulatory agencies’ decisions to approve
our product candidates will depend on our ability to demonstrate, through adequate well-controlled clinical trials, that the product candidate
is effective. However, there is a possibility that our data may fail to show a clinically meaningful response rate or a statistically
significant difference between the product candidate and the control. Alternatively, there is a possibility that our data may be statistically
significant, but that the actual clinical benefit of the product candidates may not be considered to be clinically significant, clinically
relevant or clinically meaningful. Even if we believe that the data from our trials will support marketing approval in the United States
or in Europe, we cannot predict whether the agencies will agree with our analysis and approve our applications.
Developments by competitors may establish
standards of care that affect our ability to conduct our clinical trials as planned.
Changes in standards related to clinical trial
design could affect our ability to design and conduct clinical trials as planned. In that case, both the cost and the amount of time required
to conduct a clinical trial could increase.
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Conducting clinical trials of our drug
candidates or commercial sales of a drug candidate may expose us to expensive product liability claims and we may not be able to maintain
product liability insurance on reasonable terms or at all.
The risk of product liability is inherent in
the testing of pharmaceutical products. If we cannot successfully defend ourselves against product liability claims, we may incur substantial
liabilities or be required to limit or terminate testing of one or more of our drug candidates. Our inability to obtain sufficient product
liability insurance at an acceptable cost to protect against product liability claims could prevent or inhibit the commercialization
of our drug candidates. We currently carry clinical trial insurance but do not carry product liability insurance. If we successfully
commercialize our drug candidates, we may face product liability claims, regardless of FDA approval for commercial manufacturing and
sale. We may not be able to obtain such insurance at a reasonable cost, if at all. Even if our agreements with any current or future
corporate collaborators entitle us to indemnification against product liability losses, such indemnification may not be available or
adequate should any claim arise.
If our drug candidates receive regulatory
approval, we and our collaborators will also be subject to ongoing FDA obligations and continued regulatory review, such as continued
safety reporting requirements, and we and our collaborators may also be subject to additional FDA post-marketing obligations or new regulations,
all of which may result in significant expense and limit our and our collaborators’ ability to commercialize our drugs.
Any regulatory approvals that our drug candidates
receive may also be subject to limitations on the indicated uses for which the drug may be marketed or contain requirements for costly
post-marketing follow-up studies. In addition, if the FDA approves any of our drug candidates, the manufacturing processes, labeling,
packaging, distribution, post-approval monitoring and adverse event reporting, storage, import, export, advertising, promotion and record
keeping for the drug will be subject to extensive and ongoing regulatory requirements. The FDA has significant post-market authority,
including the authority to require labeling changes based on new safety information and to require post-market studies or clinical trials
to evaluate safety risks related to the use of a product or to require withdrawal of the product from the market. The manufacturing facilities
used to manufacture our product candidates will also be subject to periodic review and inspection by the FDA and other regulatory agencies,
including for continued compliance with cGMPs requirements. The discovery of any new or previously unknown problems with our third-party
manufacturers, manufacturing processes or facilities may result in restrictions on the product, manufacturer or facility, including withdrawal
of the product from the market. Any product promotion and advertising will also be subject to regulatory requirements and continuing
regulatory review. The FDA imposes stringent restrictions on manufacturers’ communications regarding use of their products. If
we promote our product candidates in a manner inconsistent with FDA-approved labeling or otherwise not in compliance with FDA regulations,
we may be subject to enforcement action. If we or our collaborators, manufacturers or service providers fail to comply with applicable
continuing regulatory requirements in the United States or foreign jurisdictions in which we seek to market our products, we or they
may be subject to, among other things, fines, warning or untitled letters, holds on clinical trials, suspension or withdrawal of regulatory
approval, product recalls and seizures, administrative detention of products, refusal to permit the import or export of products, operating
restrictions, injunction, civil penalties and criminal prosecution.
The FDA’s policies may change and additional
government regulations may be enacted that could prevent or delay regulatory approval of our drug candidates. We cannot predict the likelihood,
nature or extent of adverse government regulation that may arise from future legislation or administrative action, either in the United
States or abroad.
Fast Track Designation may not lead to a faster development
or regulatory review or approval process.
We may seek Fast Track Designation for our product candidates. Fast
Track Designation is granted if a drug is intended for the treatment of a serious or life-threatening condition and the drug demonstrates
the potential to address unmet medical needs for this condition. Fast Track Designation does not guarantee a faster development process,
review or approval compared to conventional FDA procedures. The FDA may withdraw Fast Track Designation if it believes that the designation
is no longer supported by data from our clinical development program.
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Even if we obtain orphan drug designation in the United States for
any of our drug product candidates, we may not obtain or maintain orphan drug exclusivity for that drug candidate, and we may not obtain
orphan drug designation or exclusivity for any of our product candidates or indications.
The FDA may designate drugs for relatively small
patient populations as orphan drugs. Under the Orphan Drug Act, the FDA may designate a product as an orphan drug if it is a drug intended
to treat a rare disease or condition, which is generally defined as a patient population of fewer than 200,000 individuals in the United
States.
Generally, if a product with an orphan drug designation
subsequently receives the first marketing approval for the indication for which it has such designation, the active ingredient is entitled
to a period of marketing exclusivity, which precludes the FDA from approving another marketing application for the same active ingredient
for the same disease for seven years. Orphan drug exclusivity may be lost if the FDA determines that the request for designation was
materially defective or if the manufacturer is unable to assure sufficient quantity of the drug to meet the needs of patients with the
rare disease or condition.
If the product candidate were to obtain orphan
drug exclusivity upon approval, such exclusivity would prevent the FDA from approving another application to market a drug containing
the same active moiety for the same orphan indication, except in very limited circumstances, including when the FDA concludes that the
later drug is safer, more effective or makes a major contribution to patient care. In addition, a designated orphan drug may not receive
orphan drug exclusivity if it is approved for a use that is broader than the indication for which it received orphan designation.
Even if we receive orphan drug designation for
a product candidate, we may not be the first to obtain marketing approval for this active moiety for the orphan-designated indication
due to the uncertainties associated with developing pharmaceutical product candidates. Further, even if we obtain orphan drug exclusivity
for a product, that exclusivity may not effectively protect the product from competition because different drugs with different active
moieties can be approved for the same condition or a drug with the same active moiety can be approved for a different indication. Orphan
drug designation by the FDA neither shortens the development time or regulatory review time of a drug nor gives the drug any advantage
in the regulatory review or approval process. In addition, even if we intend to seek orphan drug designation for other product candidates
or indications, we may never receive such designations or obtain orphan drug exclusivity.
We may not be able to obtain marketing
exclusivity under the Hatch-Waxman Amendments or equivalent regulatory data exclusivity protection in other jurisdictions for our products.
We intend to rely, in part, on Hatch-Waxman exclusivity for the commercialization
of our products in the United States, if approved. The Hatch-Waxman Amendments provide marketing exclusivity to the first applicant to
gain approval of an NDA under specific provisions of the FDCA. If FDA were to determine that we do not meet the requirements of an NCE,
we may not be able to obtain 5-year exclusivity for the product.
There can be no assurance that European authorities
will grant data exclusivity for any of our product candidates. Even if European data exclusivity is granted, this may not protect us from
direct competition. A competitor(s) with a generic version of our product may be able to obtain approval of its product during our
product’s period of data exclusivity, by submitting a marketing authorization application (MAA) with a less than full package of
nonclinical and clinical data.
We may need to focus our future efforts
in new therapeutic areas where we have little or no experience.
If our drug development efforts fail, or if the competitive landscape
or investment climate for a therapeutic area is less attractive, we may need to change the company’s strategic focus to include
development of our product candidates, or of newly acquired product candidates. We have very limited drug development experience and we
may be unsuccessful in making this change to a company with a focus in other areas, or a company with a focus in multiple therapeutic
areas.
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If a supplier of an active pharmaceutical
ingredient (API) or a pharmaceutical excipient fails to provide us sufficient quantities, we may not be able to obtain an alternative
supply on a timely or acceptable basis.
Our APIs and pharmaceutical excipients are multisource,
although not all sources have an active Drug Master File (DMF) with the FDA. A DMF is a submission to the FDA used to provide confidential
detailed information about facilities, processes, or articles used in the manufacturing, processing, packaging, and storing of drugs to
support drug development and approval. In addition, some of the countries for our multisource APIs may not be same as our drug manufacturing
locations. Thus, any disruption in supply from our preferred vendors could result in significant delays with our pharmaceutical development,
clinical trials, NDA submission, NDA approval or commercial sale of the finished product due to contract delays, the need to manufacture
a new batch of API, out of specification API, the need for import and export permits, and the failure of the newly sourced API to perform
to the standards of the previously sourced API.
Modifications to our products, if approved,
may require new NDA approvals.
After a product candidate receives FDA approval,
expanded uses or uses in new indications of our products may require additional clinical trials and new regulatory approvals, including
additional IND submissions before we can begin clinical development and supplemental NDA approval prior to marketing and sales. If we
are required to conduct additional clinical studies, it would require additional expenditures and impact our operating results. Delays
in obtaining required future approvals could adversely affect our ability to introduce new or enhanced products in a timely manner, which
in turn would harm our future growth.
Delays in the commencement or completion
of pharmaceutical development, manufacturing or clinical testing could result in increased costs to us and delay our ability to generate
revenues.
We do not know whether our pharmaceutical development, manufacturing
or clinical testing will be on time or be completed on schedule, if at all. For example, we may encounter delays during the manufacture
of pilot scale batches including delays with our contract development or manufacturing organization, sourcing satisfactory quantities
of APIs, narcotic import and export permits, sourcing of excipients, contract disputes with our third party vendors and manufacturers,
or failure of the product to meet specification. Similar delays may occur during cGMP manufacture of the product.
The commencement and completion of clinical trials
can be disrupted for a variety of reasons, including difficulties in:
● recruiting and enrolling patients to participate in a clinical trial;
● obtaining regulatory approval to commence a clinical trial;
● manufacturing sufficient quantities of a product candidate;
● diversion of controlled substances by clinical trial personnel.
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A clinical trial may also be suspended or terminated
by us, the FDA or other regulatory authorities due to a number of factors, including:
● unforeseen safety issues; or
In addition, changes in regulatory requirements
and guidance may occur and we may need to amend clinical trial protocols to reflect these changes, which could impact the cost, timing
or successful completion of a clinical trial. If we experience delays in the commencement or completion of our clinical trials, the commercial
prospects for our product candidates will be harmed, and our ability to generate product revenues will be delayed. Many of the factors
that cause, or lead to, a delay in the commencement or completion of clinical trials may also lead to the denial of regulatory approval
of a product candidate.
Conducting successful clinical studies
may require the enrollment of large numbers of patients, and suitable patients may be difficult to identify and recruit.
Patient enrollment in clinical trials and completion
of patient participation and follow-up depends on many factors, including the size of the patient population; the nature of the trial
protocol; the attractiveness of, or the discomforts and risks associated with, the treatments received by enrolled subjects; the availability
of appropriate clinical trial investigators; support staff; the number of ongoing clinical trials in the same indication that compete
for the same patients; and proximity of patients to clinical sites and ability to comply with the eligibility and exclusion criteria
for participation in the clinical trial and patient compliance. For example, patients may be discouraged from enrolling in our clinical
trials if the trial protocol requires them to undergo extensive post-treatment procedures or follow-up to assess the safety and effectiveness
of our products or if they determine that the treatments received under the trial protocols are not attractive or involve unacceptable
risks or discomforts. Patients may also not participate in our clinical trials if they choose to participate in contemporaneous clinical
trials of competitive products.
Adverse safety outcomes could affect our
ability to conduct our clinical trials or obtain approval of our product candidates.
Serious injury or death resulting from a failure
of one of our drug candidates during current or future clinical trials could result in the FDA halting or delaying our clinical trials
or denying or delaying clearance or approval of a product. Even though an adverse event may not be the result of the failure of our drug
candidate, FDA or an IRB could delay or halt a clinical trial for an indefinite period of time while an adverse event is reviewed, and
likely would do so in the event of multiple such events. Any delay or termination of our current or future clinical trials as a result
of the risks summarized above, including delays in obtaining or maintaining required approvals from IRBs, delays in patient enrollment,
the failure of patients to continue to participate in a clinical trial, and delays or termination of clinical trials as a result of protocol
modifications or adverse events during the trials, may cause an increase in costs and delays in the submission of any NDAs to the FDA,
delay the approval and commercialization of our products or result in the failure of the clinical trial, which could adversely affect
our business, operating results and prospects. Lengthy delays in the completion of clinical trials of our products would adversely affect
our business and prospects and could cause us to cease operations.
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Our products will face significant competition
in the markets for such products, and if they are unable to compete successfully, our business will suffer.
Our products candidates face, and will continue to face, intense competition
from large pharmaceutical companies, specialty pharmaceutical and biotechnology companies as well as academic and research institutions.
We compete in an industry that is characterized by: (i) rapid technological change, (ii) evolving industry standards, (iii) emerging competition
and (iv) new product introductions. Our competitors have existing products and technologies that will compete with our products and technologies
and may develop and commercialize additional products and technologies that will compete with our products and technologies. Because several
competing companies and institutions have greater financial resources than us, they may be able to: (i) provide broader services and product
lines, (ii) make greater investments in research and development, (R&D), and (iii) carry on larger R&D initiatives. Our
competitors also have greater development capabilities than we do and have substantially greater experience in undertaking non-clinical
and clinical testing of products, obtaining regulatory approvals, and manufacturing and marketing pharmaceutical products. They also have
greater name recognition and better access to customers than us. Our chief competitors include companies such as Johnson and Johnson,
CG Oncology, UroGen, Soleno Therapeutics, Aardvark Therapeutics, and Protara Therapeutics, among others.
We may be exposed to liability claims associated
with the use of hazardous materials and chemicals.
Our research and development activities involve
the controlled use of hazardous materials and chemicals. Although we believe that our safety procedures for using, storing, handling and
disposing of these materials comply with federal, state and local laws and regulations, we cannot completely eliminate the risk of accidental
injury or contamination from these materials. In the event of such an accident, we could be held liable for any resulting damages and
any liability could materially adversely affect our business, financial condition and results of operations. In addition, the federal,
state and local laws and regulations governing the use, manufacture, storage, handling and disposal of hazardous or radioactive materials
and waste products may require us to incur substantial compliance costs that could materially adversely affect our business and financial
condition.
We may incur substantial liabilities and
may be required to limit commercialization of our products in response to product liability lawsuits.
The testing and marketing of medical products
entail an inherent risk of product liability. We may be held liable if serious adverse reactions from the use of our product candidates
occur. If we cannot successfully defend ourselves against product liability claims, we may incur substantial liabilities or be required
to limit commercialization of our product candidates. Our inability to obtain sufficient product liability insurance at an acceptable
cost to protect against potential product liability claims could prevent or inhibit the commercialization of pharmaceutical products we
develop, alone or with corporate collaborators. We currently do not carry product liability insurance. We, or any corporate collaborators,
may not be able to obtain insurance at a reasonable cost, if at all. Even if our agreements with any future corporate collaborators entitle
us to indemnification against losses, such indemnification may not be available or adequate if any claim arises.
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Risks Related to Our Intellectual Property
Our business depends upon securing and
protecting critical intellectual property.
Our commercial success will depend in part on
our obtaining and maintaining patent, trade secret, copyright and trademark protection of our technologies in the United States and other
jurisdictions as well as successfully enforcing this intellectual property and defending this intellectual property against third-party
challenges. We will only be able to protect our technologies from unauthorized use by third parties to the extent that valid and enforceable
intellectual property protection, such as patents or trade secrets, cover them. In particular, we place considerable emphasis on obtaining
patent and trade secret protection for significant new technologies, products and processes. Furthermore, the degree of future protection
of our proprietary rights is uncertain because legal means afford only limited protection and may not adequately protect our rights or
permit us to gain or keep our competitive advantage. Moreover, the degree of future protection of our proprietary rights is uncertain
for products that are currently in the early stages of development because we cannot predict which of these products will ultimately
reach the commercial market or whether the commercial versions of these products will incorporate proprietary technologies.
Our patent position is highly uncertain
and involves complex legal and factual questions.
Accordingly, we cannot predict the breadth of
claims that may be allowed or enforced in our patents or in third-party patents. For example, we or our licensors might not have been
the first to make the inventions covered by each of our pending patent applications and issued patents; we or our licensors might not
have been the first to file patent applications for these inventions; others may independently develop similar or alternative technologies
or duplicate any of our technologies; it is possible that none of our pending patent applications or the pending patent applications
of our licensors will result in issued patents; our issued patents and issued patents of our licensors may not provide a basis for commercially
viable technologies, or may not provide us with any competitive advantages, or may be challenged and invalidated by third parties; and,
we may not develop additional proprietary technologies that are patentable.
As a result, our owned and licensed patents may
not be valid and we may not be able to obtain and enforce patents and to maintain trade secret protection for the full commercial extent
of our technology. The extent to which we are unable to do so could materially harm our business.
Unpatented trade secrets, improvements, confidential
know-how and continuing technological innovation are important to our scientific and commercial success. Although we attempt to and will
continue to attempt to protect our proprietary information through reliance on trade secret laws and the use of confidentiality agreements
with our corporate partners, collaborators, employees and consultants and other appropriate means, these measures may not effectively
prevent disclosure of our proprietary information, and, in any event, others may develop independently, or obtain access to, the same
or similar information.
Certain of our patent rights are licensed to
us by third parties. If we fail to comply with the terms of these license agreements, our rights to those patents may be terminated,
and we will be unable to conduct our business.
If we are found to be infringing on patents
or trade secrets owned by others, we may be forced to cease or alter our product development efforts, obtain a license to continue the
development or sale of our products, and/or pay damages.
Our manufacturing processes and potential products
may violate proprietary rights of patents that have been or may be granted to competitors, universities or others, or the trade secrets
of those persons and entities. As the pharmaceutical industry expands and more patents are issued, the risk increases that our processes
and potential products may give rise to claims that they infringe the patents or trade secrets of others. These other persons could bring
legal actions against us claiming damages and seeking to enjoin clinical testing, manufacturing and marketing of the affected product
or process. If any of these actions are successful, in addition to any potential liability for damages, we could be required to obtain
a license in order to continue to conduct clinical tests, manufacture or market the affected product or use the affected process. Required
licenses may not be available on acceptable terms, if at all, and the results of litigation are uncertain. If we become involved in litigation
or other proceedings, it could consume a substantial portion of our financial resources and the efforts of our personnel.
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Our ability to protect and enforce our
patents does not guarantee that we will secure the right to commercialize our patents.
A patent is a limited monopoly right conferred
upon an inventor, and his successors in title, in return for the making and disclosing of a new and non-obvious invention. This monopoly
is of limited duration but, while in force, allows the patent holder to prevent others from making and/or using his invention. While
a patent gives the holder this right to exclude others, it is not a license to commercialize the invention, where other permissions may
be required for permissible commercialization to occur. For example, a drug cannot be marketed without the appropriate authorization
from the FDA, regardless of the existence of a patent covering the product. Further, the invention, even if patented itself, cannot be
commercialized if it infringes the valid patent rights of another party.
Intellectual property rights do not necessarily
address all potential threats to our competitive advantage.
The degree of future protection afforded by our
intellectual property rights is uncertain because intellectual property rights have limitations, and may not adequately protect our business,
or permit us to maintain our competitive advantage. The following examples are illustrative:
Risks Related to Government Regulation
We may undertake international operations,
which will subject us to risks inherent with operations outside of the United States.
Although we do not have any foreign operations
at this time, we intend to seek to obtain market clearances in foreign markets that we deem to generate significant opportunities. However,
even with the cooperation of a commercialization partner, conducting drug development in foreign countries involves inherent risks, including,
but not limited to: difficulties in staffing, funding and managing foreign operations; unexpected changes in regulatory requirements;
export restrictions; tariffs and other trade barriers; difficulties in protecting, acquiring, enforcing and litigating intellectual property
rights; fluctuations in currency exchange rates; and potentially adverse tax consequences.
If we were to experience any of the difficulties
listed above, or any other difficulties, any international development activities and our overall financial condition may suffer and
cause us to reduce or discontinue our international development and registration efforts.
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We depend on our information technology
systems and those of our third-party collaborators, service providers, contractors or consultants. Our internal computer systems, or
those of our third-party collaborators, service providers, contractors or consultants, may fail or suffer security breaches, disruptions,
or incidents, which could result in a material disruption of our development programs or loss of data or compromise the privacy, security,
integrity or confidentiality of sensitive information related to our business and have a material adverse effect on our reputation, business,
financial condition or results of operations.
In the ordinary course of our business, we collect, store and transmit
large amounts of confidential information, including intellectual property, proprietary business information and personal information.
Our internal technology systems and infrastructure, and those of our current or future third-party collaborators, service providers, contractors
and consultants are vulnerable to damage from computer viruses, unauthorized access or use resulting from malware, natural disasters,
terrorism, war and telecommunication and electrical failures, denial-of-service attacks, cyber-attacks or cyber-intrusions over the internet,
hacking, phishing and other social engineering attacks, persons inside our organizations (including employees or contractors), loss or
theft, or persons with access to systems inside our organization. Attacks on information technology systems are increasing in their frequency,
levels of persistence, sophistication and intensity, and they are being conducted by increasingly sophisticated and organized foreign
governments, groups and individuals with a wide range of motives and expertise. Threat actors are increasingly leveraging artificial intelligence
and automation to enhance the scale, speed, and effectiveness of these attacks, making them more difficult to detect and prevent. In addition
to extracting or accessing sensitive information, such attacks could include the deployment of harmful malware, ransomware, denial-of-service
attacks, social engineering and other means to affect service reliability and threaten the security, confidentiality, integrity and availability
of information. The prevalent use of mobile devices that access sensitive information also increases the risk of data security incidents
which could lead to the loss of confidential information or other intellectual property. Cybersecurity incidents affecting these third