ITEM 1A. RISK FACTORS
An investment in our securities involves a
high degree of risk. You should consider carefully all of the risks described below, together with the other information contained in
this report, before making a decision to invest in our securities. If any of the following events occur, our business, financial condition
and operating results may be materially adversely affected. In that event, the trading price of our securities could decline, and you
could lose all or part of your investment.
Summary of Risk Factors
Risks Related to Commercialization and Manufacturing
Risks Related to Our Financial Position
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Risks Related to Our Business Development
Risks Related to Our Industry
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Risks Related to Our Intellectual Property
Risks Related to Government Regulation
Risks Related to Employee Matters and Growth
Management
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Risks Related to Our Common Stock
General Risk Factors
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Risks Related to Commercialization and Manufacturing
ZUNVEYL oral tablet formulation may fail
to achieve the broad degree of adoption and use by physicians, patients, hospitals, healthcare payors and others in the medical community
necessary for commercial success.
ZUNVEYL may fail to gain sufficient market acceptance
by physicians, patients, healthcare payors and others in the medical community. ZUNVEYL and most of our product candidates target mechanisms
for which there are limited or no currently approved products, which may result in slower adoption by physicians, patients and payors.
If ZUNVEYL or our other product candidates do not achieve an adequate level of acceptance, we may not generate significant product revenue
and we may not become profitable. The degree of market acceptance of our product candidates, if approved for commercial sale, will depend
on a number of factors, including:
● any FDA requirement to undertake a REMS;
● the effectiveness of our sales, marketing and distribution efforts;
● potential product liability claims.
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We cannot assure you that our current or future
product candidates, if approved, will achieve broad market acceptance among physicians, patients, healthcare payors and others in the
medical community. Even following the approval of ZUNVEYL or if we receive regulatory approval to market any of our future product candidates,
we cannot assure you that any such product candidate will be more effective than other commercially available alternatives or successfully
commercialized. Any approval we may obtain could be for indications or patient populations that are not as broad as intended or desired
or may require labeling that includes significant use or distribution restrictions or safety warnings. We may also be required to perform
additional or unanticipated clinical trials to obtain approval or be subject to additional post-marketing testing requirements to
maintain approval. In addition, regulatory authorities may withdraw their approval of a product or impose restrictions on its distribution,
such as in the form of a REMS. Any failure by our product candidates that obtain regulatory approval to achieve market acceptance
or commercial success would adversely affect our reputation, ability to raise additional capital, financial condition, results of operations
and business prospects.
The market opportunities for ZUNVEYL may
be smaller than we anticipate.
We have received FDA approval for ZUNVEYL for
mild-to-moderate dementia of the Alzheimer’s type in adults (Alzheimer’s disease). Our estimates of market potential
have been derived from a variety of sources, including scientific literature, patient foundations and market research and may prove to
be incorrect. Even if we obtain significant market share for ZUNVEYL, the potential target populations for mild-to-moderate Alzheimer’s
disease may be too small to consistently generate revenue, and we may never achieve profitability without obtaining marketing approval
for additional indications.
We rely on third-party suppliers to manufacture
our product candidates, and we intend to rely on third parties to produce commercial supplies of any approved product. The loss of these
suppliers, or their failure to comply with applicable regulatory requirements or to provide us with sufficient quantities at acceptable
quality levels or prices, or at all, would materially and adversely affect our business, financial condition, results of operations and
prospects.
We do not currently have nor do we plan to build
or acquire the infrastructure or capability internally to manufacture supplies of our product candidates or the materials necessary to
produce our product candidates for use in the conduct of our preclinical studies or clinical trials, and we lack the internal resources
and the capability to manufacture any of our product candidates on a preclinical, clinical or commercial scale. The facilities used by
our contract manufacturers to manufacture our product candidates are subject to various regulatory requirements and may be subject to
the inspection of the FDA or other regulatory authorities. We do not control the manufacturing processes of, and are completely dependent
on, our contract manufacturing partners for compliance with the regulatory requirements, known as cGMPs. If our contract manufacturers
cannot successfully manufacture material that conforms to our specifications and the strict regulatory requirements of the FDA or comparable
regulatory authorities in foreign jurisdictions, we may not be able to rely on their manufacturing facilities for the manufacture of our
product candidates. In addition, we have limited control over the ability of our contract manufacturers to maintain adequate quality control,
quality assurance and qualified personnel. If the FDA or a comparable foreign regulatory authority finds these facilities inadequate for
the manufacture of our product candidates or if such facilities are subject to enforcement action in the future or are otherwise inadequate,
we may need to find alternative manufacturing facilities, which would significantly impact our ability to develop, obtain future regulatory
approvals for or market our product candidates.
We currently rely on third parties at key stages in our supply chain.
For instance, the supply chains for our lead product candidate involve several manufacturers that specialize in specific operations of
the manufacturing process, specifically, raw materials manufacturing, drug substance manufacturing and drug product manufacturing. We
have a direct relationship with a manufacturer in Taiwan for our lead candidate, ALPHA-1062. As a result, the supply chain for the manufacturing
of our product candidates is complicated, and we expect the logistical challenges associated with our supply chain to grow more complex
as our product candidates are further developed.
We do not have any control over the process or
timing of the acquisition or manufacture of materials by our manufacturers. We generally do not begin preclinical or clinical trials unless
we believe we have access to a sufficient supply of a product candidate to complete such study. In addition, any significant delay in,
or quality control problems with respect to, the supply of a product candidate, or the raw material components thereof, for an ongoing
study could considerably delay completion of our preclinical or clinical trials, product testing and potential regulatory approval of
our product candidates.
We have not yet engaged all manufacturers for
the commercial supply of our product candidates. Although we intend to enter into such agreements prior to commercial launch of any of
our product candidates, we may be unable to enter into any such agreement or do so on commercially reasonable terms, which could have
a material adverse impact upon our business. Moreover, if there is a disruption to one or more of our third-party manufacturers’
or suppliers’ relevant operations, or if we are unable to enter into arrangements for the commercial supply of our product candidates,
we will have no other means of producing our product candidates until they restore the affected facilities or we or they procure alternative
manufacturing facilities or sources of supply. Our ability to progress our preclinical and clinical programs could be materially and adversely
impacted if any of the third-party suppliers upon which we rely were to experience a significant business challenge, disruption or
failure due to issues such as financial difficulties or bankruptcy, issues relating to other customers such as regulatory or quality compliance
issues, or other financial, legal, regulatory or reputational issues. Additionally, any damage to or destruction of our third-party manufacturers’
or suppliers’ facilities or equipment may significantly impair our ability to manufacture our product candidates on a timely basis.
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In addition, to manufacture our product candidates
in the quantities which we believe would be required to meet anticipated market demand, our third-party manufacturers would likely
need to increase manufacturing capacity and we may need to secure alternative sources of commercial supply, which could involve significant
challenges and may require additional regulatory approvals. In addition, the development of commercial-scale manufacturing capabilities
may require us and our third-party manufacturers to invest substantial additional funds and hire and retain the technical personnel
who have the necessary manufacturing experience. Neither we nor our third-party manufacturers may successfully complete any required
increase to existing manufacturing capacity in a timely manner, or at all. If our manufacturers or we are unable to purchase the raw materials
necessary for the manufacture of our product candidates on acceptable terms, at sufficient quality levels or in adequate quantities, if
at all, the commercial launch of our product candidates would be delayed or there would be a shortage in supply, which would impair our
ability to generate revenues from the sale of such product candidates, if approved.
We are subject to certain supply chain risks
inherent in manufacturing our lead product, ZUNVEYL, and future products with respect to Taiwan. Risks including periodic foreign economic
downturns and political instability, which may adversely affect our ability to obtain materials and conduct business in Taiwan.
Our sole manufacturing location for ZUNVEYL is
located in Taiwan. There are risks inherent in manufacturing internationally, including the following: different regulatory environments;
difficulties in enforcing agreements and collecting receivables through certain foreign legal systems; fluctuations in foreign currency
exchange rates; tax rates in certain foreign countries that may exceed those in the United States and foreign earnings that may be
subject to withholding requirements; the imposition of tariffs, exchange controls, or other trade restrictions; general economic and political
conditions in countries where we operate or where our customers reside; government control of capital transactions, including the borrowing
of funds for operations or the expatriation of cash; potential adverse tax consequences; security concerns and potential business interruption
risks associated with political or social unrest in foreign countries where our facilities or assets are located; difficulties associated
with managing a large organization spread throughout various countries; difficulties in enforcing intellectual property rights and weaker
intellectual property rights protection in some countries; required compliance with a variety of foreign laws and regulations; and differing
customer preferences. The factors described above may have a material adverse effect on our business, financial condition, and results
of operations.
Foreign economic downturns may affect our results
of manufacturing in the future. Additionally, other facts may have a material adverse effect on the Company’s business, financial
condition and results of operations, including:
● international economic and political changes;
● restrictions on transfers of funds and assets between jurisdictions; and
● China-Taiwan geo-political instability.
Our Taiwanese partners are critical to our supply
chain. Accordingly, our business, financial condition and results of operations may be affected by changes in governmental policies, taxation,
inflation or interest rates in Taiwan and by social instability and diplomatic and social developments in or affecting Taiwan which are
outside of our control. Since 1949, Taiwan and the Chinese mainland have been separately governed. The PRC claims that it is the only
legitimate government in China, including Taiwan and mainland China, and that Taiwan is part of China. Although significant economic and
cultural relations have been established between Taiwan and mainland China in the past few years, such as the adoption of the Economic
Cooperation Framework Agreement and memorandum regarding cross-strait financial supervision, we cannot assure you that relations
between Taiwan and mainland China will not become strained again. For example, the PRC government has refused to renounce the use of military
force to gain control over Taiwan and, in March 2005, passed an Anti-Secession Law that authorized non-peaceful means and
other necessary measures should Taiwan move to gain independence from the PRC. Past developments in relations between Taiwan and
mainland China have on occasion depressed the market prices of the securities of companies doing business in Taiwan. Such initiatives
and actions are commonly viewed as having a detrimental effect to reunification efforts between Taiwan and mainland China. Relations between
Taiwan and mainland China and other factors affecting military, political or economic conditions in Taiwan could materially and adversely
affect our financial condition and results of operations, as well as the market price and the liquidity of our ordinary stock.
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As the Company continues to manufacture in Taiwan,
our success will depend in part, on our ability to anticipate and effectively manage these risks. The impact of any one or more of these
factors could materially adversely affect our business, financial condition and results of operations.
If a situation arises that prohibits us from manufacturing
in Taiwan now or in the future, we do believe we would be able to find replacement third-party manufacturer in another country. The
Company has begun sourcing from manufacturers at different geographical regions to mitigate the situation, however this could deviate
from our current timelines and cost structure. We may be forced to either temporarily or permanently discontinue the manufacturing and
sale of our products which could expose us to legal liability, loss of reputation, and risk of loss or reduced profit.
Our product candidates have not previously
been manufactured on a commercial scale, and there are risks associated with scaling up manufacturing to commercial scale. In particular,
we are working on developing a larger scale manufacturing process that is more efficient and cost-effective to commercialize our potential
products, which may not be successful.
Our product candidates have not previously been
manufactured on a commercial scale, and there are risks associated with scaling up manufacturing to commercial scale including, among
others, cost overruns, potential problems with process scale-up, process reproducibility, stability issues, lot consistency and timely
availability of raw materials. There is no assurance that our third-party manufacturers will be successful in establishing a larger-scale commercial
manufacturing process for our product candidates which achieves our objectives for manufacturing capacity and cost of goods. In addition,
there is no assurance that our third-party manufacturers will be able to manufacture our product candidates to specifications acceptable
to the FDA or other regulatory authorities, to produce it in sufficient quantities to meet the requirements for the potential launch of
such products or to meet potential future demand. Our failure to properly or adequately scale up manufacturing for commercial scale would
adversely affect our business, results of operations and financial condition.
The manufacture of drugs is complex, and
our third-party manufacturers may encounter difficulties in production. If any of our third-party manufacturers encounter such difficulties,
our ability to provide adequate supply of our product candidates for clinical trials or our products for patients, could be delayed or
prevented.
Manufacturing drugs, especially in large quantities,
is complex and may require the use of innovative technologies. Each lot of an approved drug product must undergo thorough testing for
identity, strength, quality, purity and potency. Manufacturing drugs requires facilities specifically designed for and validated for this
purpose, as well as sophisticated quality assurance and quality control procedures. Slight deviations anywhere in the manufacturing process,
including filling, labeling, packaging, storage and shipping and quality control and testing, may result in lot failures or product recalls.
When changes are made to the manufacturing process, we may be required to provide preclinical and clinical data showing the comparable
quality and efficacy of the products before and after such changes. If our third-party manufacturers are unable to produce sufficient
quantities for clinical trials or for commercialization as a result of these challenges, or otherwise, our development and commercialization
efforts would be impaired, which would have an adverse effect on our business, financial condition, results of operations and growth prospects.
The successful commercialization of ZUNVEYL
and our other product candidates which may obtain approval will depend in part on the extent to which governmental authorities and health
insurers establish adequate coverage, reimbursement levels and pricing policies. Failure to obtain or maintain coverage and adequate reimbursement
for our product candidates, if approved, could limit our ability to market those drugs and decrease our ability to generate revenue.
The availability and adequacy of coverage and
reimbursement by governmental healthcare programs such as Medicare and Medicaid, private health insurers and other third-party payors
are essential for most patients to be able to afford prescription medications such as our product candidates, if approved. Our ability
to achieve acceptable levels of coverage and reimbursement for products by governmental authorities, private health insurers and other
organizations will have an effect on our ability to successfully commercialize our product candidates. Even if we obtain coverage for
our product candidates by a third-party payor, the resulting reimbursement payment rates may not be adequate or may require co-payments that
patients find unacceptably high. We cannot be sure that coverage and reimbursement in the United States, the European Union or elsewhere
will be available for our product candidates or any product that we may develop, and any reimbursement that may become available may be
decreased or eliminated in the future.
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Third-party payors increasingly are challenging
prices charged for biopharmaceutical products and services, and many third-party payors may refuse to provide coverage and reimbursement
for particular drugs or biologics when an equivalent generic drug, biosimilar or a less expensive therapy is available. It is possible
that a third-party payor may consider our product candidates as substitutable and only offer to reimburse patients for the cost of
the less expensive product. Even if we show improved efficacy or improved convenience of administration with our product candidates, pricing
of existing third-party therapeutics may limit the amounts we will be able to charge for our product candidates. These payors may
deny or revoke the reimbursement status of a given product or establish prices for new or existing marketed products at levels that are
too low to enable us to realize an appropriate return on our investment in our product candidates. If reimbursement is not available or
is available only at limited levels, we may not be able to successfully commercialize our product candidates and may not be able to obtain
a satisfactory financial return on our investment in the development of product candidates.
There is significant uncertainty related to the
insurance coverage and reimbursement of newly-approved products. In the United States, third-party payors, and governmental
healthcare plans, such as the Medicare and Medicaid programs, play an important role in determining the extent to which new drugs and
biologics will be covered. The Medicare and Medicaid programs increasingly are used as models in the United States for how private
payors and other governmental payors develop their coverage and reimbursement policies for drugs and biologics. Some third-party payors
may require pre-approval of coverage for new or innovative devices or drug therapies before they will reimburse healthcare providers
who use such therapies. We cannot predict at this time what third-party payors will decide with respect to the coverage and reimbursement
for our product candidates.
No uniform policy for coverage and reimbursement
for products exists among third-party payors in the United States. Therefore, coverage and reimbursement for products can differ
significantly from payor to payor. As a result, the coverage determination process is often a time-consuming and costly process that
will require us to provide scientific and clinical support for the use of our product candidates to each payor separately, with no assurance
that coverage and adequate reimbursement will be applied consistently or obtained in the first instance. Furthermore, rules and regulations
regarding reimbursement change frequently, in some cases on short notice, and we believe that changes in these rules and regulations are
likely.
Outside the United States, international
operations are generally subject to extensive governmental price controls and other market regulations, and we believe the increasing
emphasis on cost-containment initiatives in Europe and other foreign jurisdictions have and will continue to put pressure on the
pricing and usage of our product candidates. In many countries, the prices of medical products are subject to varying price control mechanisms
as part of national health systems. Other countries allow companies to fix their own prices for medical products, but monitor and control
company profits. Additional foreign price controls or other changes in pricing regulation could restrict the amounts that we are able
to charge for our product candidates. Accordingly, in markets outside the United States, the reimbursement for our product candidates
may be reduced compared with the United States and may be insufficient to generate commercially-reasonable revenue and profits.
Moreover, increasing efforts by governmental and
third-party payors in the United States and abroad to cap or reduce healthcare costs may cause such organizations to limit both
coverage and the level of reimbursement for newly approved products, and, as a result, they may not cover or provide adequate payment
for our product candidates. We expect to experience pricing pressures in connection with the sale of our product candidates due to the
trend toward managed health care, the increasing influence of health maintenance organizations and additional legislative changes. The
downward pressure on healthcare costs in general, particularly prescription drugs and biologics and surgical procedures and other treatments,
has become intense. As a result, increasingly high barriers are being erected to the entry of new products.
We currently have a small, newly formed
sales organization. If we are unable to establish sales capabilities on our own or through third parties, we may not be able to market
and sell ZUNVEYL or our other product candidates, if approved, effectively in the United States and foreign jurisdictions or generate
product revenue.
We have only recently established a small marketing and sales organization.
In order to commercialize ZUNVEYL and our other product candidates, which may obtain approval, in the United States and foreign jurisdictions,
we must build our marketing, sales, distribution, managerial and other non-technical capabilities or make arrangements with third
parties to perform these services, and we may not be successful in doing so. If any of our other product candidates receive regulatory
approval, we expect to expand our sales organization with technical expertise and supporting distribution capabilities to commercialize
each such product candidate, which will be expensive and time consuming. We have no prior experience in the marketing, sale and distribution
of biopharmaceutical products, and there are significant risks involved in building and managing a sales organization, including our ability
to hire, retain and incentivize qualified individuals, generate sufficient sales leads, provide adequate training to sales and marketing
personnel and effectively manage a geographically dispersed sales and marketing team. Any failure or delay in the development of our internal
sales, marketing and distribution capabilities would adversely impact the commercialization of these products. We may choose to collaborate
with third parties that have direct sales forces and established distribution systems, either to augment our own sales force and distribution
systems or in lieu of our own sales force and distribution systems. If we are unable to enter into such arrangements on acceptable terms
or at all, we may not be able to successfully commercialize our product candidates. If we are not successful in commercializing our product
candidates or any future product candidates, either on our own or through arrangements with one or more third parties, we may not be able
to generate any future product revenue and we would incur significant additional losses.
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Risks Related to Our Financial Condition
We are a commercial biopharmaceutical company
with one product approved for commercial sale and have incurred significant losses since our inception. We expect to incur significant
losses for the foreseeable future and our costs may increase substantially in the foreseeable future.
Since our inception, we have incurred significant net losses, and we
expect to continue to incur significant expenses and operating losses for the foreseeable future. Our net losses were approximately $20.6
million and $14.6 million for the years ended December 31, 2025, and 2024, respectively. As of December 31, 2025, we had
an accumulated deficit of approximately $97.1 million. We have only one product, ZUNVEYL formerly known as ALPHA-1062, approved for
commercialization.
We have devoted substantially all our financial resources and efforts
to the commercialization of ZUNVEYL and development of our other product candidates, including conducting preclinical studies and clinical
trials. We expect to continue to incur significant expenses and operating losses over the next several years and we continue the
commercial roll out of ZUNVEYL and pursue our other product candidates. Our net losses may fluctuate significantly from quarter to quarter
and year to year. We anticipate that our expenses will increase substantially for the foreseeable future as we:
● maintain, expand and protect our intellectual property portfolio;
● hire additional clinical, manufacturing and scientific personnel;
● scale up our clinical and regulatory capabilities.
Our ability to continue to generate
revenue and achieve profitability depends significantly on our ability to achieve commercial success with ZUNVEYL oral tablet
formulation, our one FDA approved product, and continued development and commercialization of our other product candidates, if
approved.
To date, we have generated approximately $6.8 million in revenue from
the commercialization of ZUNVEYL To continue to generate revenue and become and remain profitable, we must succeed in the commercialization
of ZUNVEYL and developing and eventually commercializing our other product candidates. This will require us to be successful in a range
of challenging activities, including commercial manufacturing, marketing and sales of ZUNVEYL, completing preclinical testing and clinical
trials of our other product candidates, obtaining regulatory approval of our other product candidates, and manufacturing, marketing and
selling any other product candidates for which we may obtain regulatory approval, as well as discovering and developing additional product
candidates. Outside of our commercial development activities for ZUNVEYL, we are only in the preliminary stages of most of these activities.
We may never succeed in these activities and, even if we do, may never generate any revenue or revenue that is significant enough to achieve
profitability. Even if we 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 depress the value of our Company and could impair our ability to raise capital, expand
our business, maintain our development efforts, obtain product approvals, diversify our offerings or continue our operations. A decline
in the value of our Company could also cause you to lose all or part of your investment.
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We have a limited operating history and
no prior history of commercializing products, which may make it difficult for an investor to evaluate the success of our business to
date and to assess our future viability.
We commenced operations in 2014, and our operations to date have been
largely focused on developing our clinical and preclinical product candidates, primarily ALPHA-1062. To date, we have successfully obtained
regulatory approval for only one product, ZUNVEYL oral tablets, and began to commercialize ZUNVEYL in 2025. Prior to beginning commercialization
efforts in 2025, we have no history of commercializing products. Consequently, any predictions made about our future success or viability
may not be as accurate as they could be if we had a longer operating history or a history of successfully developing and commercializing
products.
We may encounter unforeseen expenses, difficulties,
complications, delays and other known or unknown factors in achieving our business objectives. We may also need to transition from a company
with a research focus to a company capable of supporting commercial activities. Our inability to adequately address these risks and difficulties
or successfully make such a transition could adversely affect our business, financial condition, results of operations and growth prospects.
We will need substantial capital to meet
our financial obligations and to pursue our business objectives, including the continued commercialization of ZUNVEYL oral tablet formulation.
If we are unable to raise capital when needed, we could be forced to delay, reduce and/or eliminate one or more of our research and drug
development programs or future commercialization efforts.
Our operations have required substantial amounts of capital since inception,
and we expect our expenses to increase significantly in the foreseeable future. Developing commercial manufacturing, marketing and sales
is expensive and uncertain which could take a long time to complete. We may not achieve commercial success with ZUNVEYL. Similarly, identifying
potential product candidates and 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 regulatory approval and
achieve product sales. We expect to continue to incur significant expenses and operating losses over the next several years as we
continue our commercialization activities for ZUNVEYL and our ongoing clinical trials of our other product candidates, initiate future
clinical trials of our other product candidates, prepare for commercialization activities of our other product candidates and advance
any of our other product candidates we may develop or otherwise acquire. In addition, our product candidates, if approved, may not achieve
commercial success. Our revenue is primarily derived from sales of ZUNVEYL as a result of our commercial development activities. If we
obtain marketing approval for any other product candidates that we develop or otherwise acquire, we expect to incur significant commercialization
expenses related to product sales, marketing, distribution and manufacturing. We also expect an increase in our expenses associated with
creating additional infrastructure to support operations as a public company.
As of December 31, 2025, we had approximately $66.1 million
in unrestricted cash and cash equivalents and have not generated positive cash flows from operations. Based on our current business plans,
we believe our existing cash and cash equivalents, will be sufficient for us to fund our ongoing operating expenses, commercialization
expenses, and capital expenditures requirements through at least the next 12 months. We may need to raise additional capital to fund
our operations and commercial plans after 12 months. ZUNVEYL is expected to require substantial capital to continue our commercialization
efforts and bring the product to market in the US. We have based these estimates on assumptions that may prove to be incorrect or
require adjustment as a result of business decisions, and we could utilize our available capital resources sooner than we currently expect.
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Our future capital requirements will depend on
many factors, including, but not limited to:
● the costs, timing and outcome of regulatory review of our product candidates;
A change in the outcome of any of these or other
factors with respect to the development of any of our product candidates could significantly change the costs and timing associated with
the development of that product candidate.
We expect to incur significant commercialization expenses related to
product manufacturing, sales, marketing, distribution, and continued R&D of ZUNVEYL.
We may seek additional capital due to favorable
market conditions or strategic considerations even if we believe we have sufficient funds for our current or future operating plans. Attempting
to secure additional financing may divert our management from our day-to-day activities, which may adversely affect our ability
to develop our product candidates.
Additional funds may not be available on a timely
basis, on favorable terms, or at all, and such funds, if raised, may not be sufficient to enable us to continue to implement our long-term business
strategy. Further, our ability to raise additional capital may be adversely impacted by recent volatility in the equity markets in the
United States and worldwide. Our failure to raise capital as and when needed or on acceptable terms would have a negative impact
on our financial condition and our ability to pursue our business strategy, and we may have to delay, reduce the scope of, suspend or
eliminate one or more of our research-stage programs, clinical trials or future commercialization efforts.
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We expect to be exposed to fluctuations
in currency exchange rates, which could adversely affect our results of operations.
We incur expenses in U.S. dollars, Canadian
dollars, and Euros but our financial statements are denominated in U.S. dollars. Accordingly, we face exposure to adverse movements
in currency exchange rates. Our foreign operations that are contracted in foreign currencies will be exposed to foreign exchange rate
fluctuations as the financial results are translated from the local currency into U.S. dollars. Specifically, the U.S. dollar
cost of our operations in Canada, API manufacturing in Taiwan and manufacturing of ZUNVEYL in India is influenced by any movements
in the currency exchange rate. Such movements in the currency exchange rate may have a negative effect on our financial results. Currently,
our revenue generating agreements are settled in U.S. dollars, however, we may in the future enter into revenue contracts in foreign currencies
if and when we expand commercialization of ZUNVEYL. The extent contracts related to our operating costs or revenue are settled in a foreign
currency, if the U.S. dollar weakens against foreign currencies, the translation of these foreign currency denominated transactions
could result in increased revenue decreased operating expenses and increased net income (decreased net loss).
Similarly, if the U.S. dollar strengthens against foreign currencies, the translation of these foreign currency denominated transactions
could result in decreased revenue, increased operating expenses and decreased net income (increased net loss). As exchange
rates vary, sales and other operating results, when translated, may differ materially from our or the capital market’s expectations.
Risks Related to Our Business Development
Our business is heavily dependent on the
commercial success of ZUNVEYL oral tablet formulation, our only FDA approved product, and the development and commercialization of any
future product candidates that we may develop or acquire.
The NDA for ZUNVEYL oral tablets was approved by the FDA on July 26,
2024, but all our other product candidates are in the pre-clinical stage. The success of our business, including our ability to finance
our Company and generate revenue in the future, will primarily depend on the commercial success of ZUNVEYL, our only FDA approved and
commercially produced product, and the development, regulatory approval and commercialization of our other product candidates. We cannot
be certain that ZUNVEYL will experience commercial success or that our other product candidates will receive regulatory approval or be
successfully commercialized even if we receive regulatory approval.
The commercial success of ZUNVEYL and the clinical and commercial success
of any future product candidates that we may develop or acquire will depend on a number of factors, including the following:
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● the convenience of our treatment or dosing regimen;
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● a continued acceptable safety profile following any marketing approval;
● our ability to compete with other therapies;
These factors, many of which are beyond our control,
could cause us to experience significant delays or an inability to obtain future regulatory approvals or commercialize our product candidates.
Even if regulatory approvals are obtained, we may never be able to successfully commercialize any of our product candidates. Accordingly,
we cannot provide assurances that we will be able to generate sufficient revenue through the sale of our product candidates or any future
product candidates to continue our business or achieve profitability.
We may not successfully expand our pipeline
of product candidates. If we are not successful in identifying, developing, in-licensing, acquiring or/and commercializing additional
product candidates, our ability to expand our business and achieve our strategic objectives would be impaired.
Although a substantial amount of our effort will
focus on the continued development and potential approval of our current product candidates, a key element of our strategy is to identify,
develop and commercialize a portfolio of products that help the cognitive and functional symptoms of mild-to-moderate Alzheimer’s
disease. A component of our strategy is to evaluate our product candidates in multiple indications, such as mild-to-moderate Alzheimer’s
disease, moderate-to-severe Alzheimer’s disease, and TBI. However, we have not yet evaluated ALPHA-1062 or ALPHA-0602 in
all of these patient populations and we may find that while we have seen promising results in one neurodegenerative disease, that effect
is not replicated across other indications with promising similarities. Even if we successfully identify additional product candidates,
we may still fail to yield additional product candidates for development and commercialization for many reasons, including the following:
We therefore cannot provide any assurance that
we will be able to successfully identify, in-license or acquire additional product candidates, advance any of these additional product
candidates through the development process, successfully commercialize any such additional product candidates, if approved, or assemble
sufficient resources to identify, acquire, develop or, if approved, commercialize additional product candidates. If we are unable to successfully
identify, acquire, develop and commercialize additional product candidates, our commercial opportunities may be limited.
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We have initially concentrated our research
and development efforts on the treatment of Alzheimer’s Disease, a disease that has seen limited success in drug development.
Efforts by biopharmaceutical and pharmaceutical companies in treating
Alzheimer’s disease have seen limited success in drug development. Biogen’s Aduhelm, a monoclonal antibody administered via
infusion, received accelerated approval from the FDA on June 7, 2021, but Biogen has announced that it will discontinue marketing
Aduhelm by the end of 2024. Adlarity, transdermal formulation of donepezilfrom the markers of Corium, was the most recently
FDA approved symptomatic treatment in 8 years, in March 2022. We cannot be certain that our oral, small-molecule approach will
lead to the development of further approvable or marketable products. Since 2003, over 500 clinical studies in Alzheimer’s have
been completed and only Aduhelm, Adlarity and now our product ZUNVEYL have been approved by the FDA, compared to higher success rates
for all other drug candidates.
ZUNVEYL remains subject to regulatory oversight.
Even though we obtained regulatory approval for
ZUNVEYL, our lead product, it will be subject to ongoing regulatory requirements for manufacturing, labeling, packaging, storage, advertising,
promotion, sampling, record-keeping and submission of safety and other post-market information. FDA has required that we conduct
further root cause investigation into observe high variability of the dissolution data for ZUNVEYL oral tables and develop new dissolution
methods and acceptance criteria and to report to FDA by February 28, 2025. ZUNVEYL also remains subject to a post-approval safety
monitoring program, limitations on the approved indicated uses for which the product may be marketed or to the conditions of approval,
or contain requirements for potentially costly post-marketing testing and surveillance to monitor the quality, safety and efficacy
of the product. For example, the holder of an approved NDA is obligated to monitor and report adverse events and any failure of a product
to meet the specifications in the NDA. The holder of an approved NDA also must submit new or supplemental applications and obtain
FDA approval for certain changes to the approved product, product labeling or manufacturing process. Advertising and promotional materials
must comply with FDA rules and are subject to FDA review, in addition to other potentially applicable federal and state laws.
In addition, product manufacturers and their facilities
are subject to payment of user fees and continual review and periodic inspections by the FDA and other regulatory authorities. If we,
or a regulatory authority, discover previously unknown problems with a product, such as adverse events of unanticipated severity or frequency,
or problems with the facility where the product is manufactured or disagrees with the promotion, marketing or labeling of that product,
a regulatory authority may impose restrictions relative to that product, the manufacturing facility or us, including requiring recall
or withdrawal of the product from the market or suspension of manufacturing.
If we fail to comply with applicable regulatory
requirements of ZUNVEYL or any future product candidate, a regulatory authority may take enforcement actions, such as issuing warnings,
fines, or even revoking approval, which could result in delays, financial penalties, reputational damage, and potential legal liabilities
for our Company.
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 the commercial success of ZUNVEYL and adversely affect our business, financial condition, results of operations
and prospects.
We cannot predict the likelihood, nature or extent
of government regulation that may arise from future legislation or administrative action, either in the United States or abroad.
If we are slow or unable to adapt to changes in existing requirements or the adoption of new requirements or policies, or if we are not
able to maintain regulatory compliance, we may lose any marketing approval that we may have obtained and we may not achieve or sustain
profitability, which would materially and adversely affect our business, financial condition, results of operations and prospects.
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For our other product candidates, we may
encounter substantial delays in our preclinical studies, clinical trials and obtaining NDA approval or may not be able to conduct or complete
our preclinical studies or clinical trials or receive NDA approval on the timelines we expect, if at all.
Clinical trials are expensive and can take many years to complete,
and the outcome is inherently uncertain. The historical failure rate for product candidates in our industry is high. We cannot guarantee
that any clinical trials will be conducted as planned or completed on schedule, if at all. A failure of one or more clinical trials can
occur at any stage and our future clinical trials may not be successful. Clinical trials can be delayed or terminated for a variety of
reasons. Further, even once completed the process to receive an NDA can be delayed or unsuccessful.
The timing and success of obtaining NDA approval
can be affected by many factors including:
● identifying, recruiting and training suitable clinical investigators;
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● obtaining IRB approval at each trial site;
● recruiting an adequate number of suitable patients to participate in a trial;
● having subjects complete a trial or return for post-treatment follow-up;
● clinical sites deviating from trial protocol or dropping out of a trial;
● addressing subject safety concerns that arise during the course of a trial;
● adding a sufficient number of clinical trial sites; or
We may experience numerous adverse or unforeseen
events during, or as a result of, preclinical studies and clinical trials which could delay or prevent our ability to receive marketing
approval or commercialize our product candidates, including:
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● incur unplanned costs;
● obtain marketing approval in some countries and not in others;
● be subject to additional post-marketing testing requirements; or
● have the product removed from the market after obtaining marketing approval.
The outcome of preclinical testing and early
clinical trials may not be predictive of the success of later clinical trials, and the results of our clinical trials may not satisfy
the requirements of the FDA or other comparable foreign regulatory authorities.
We will be required to demonstrate with substantial
evidence through well-controlled clinical trials that our product candidates are safe and effective for use in a diverse population
before we can seek marketing approvals for their commercial sale. Success in preclinical studies and early-stage clinical trials
does not mean that future clinical trials will be successful. For instance, we do not know whether ALPHA-1062 will perform in future
clinical trials as ALPHA-1062 has performed in preclinical studies or earlier clinical trials. Product candidates in clinical trials
may fail to demonstrate sufficient safety and efficacy to the satisfaction of the FDA and other comparable foreign regulatory authorities
despite having progressed through preclinical studies. Regulatory authorities may also limit the scope of later-stage trials until
we have demonstrated satisfactory safety, which could delay regulatory approval, limit the size of the patient population to which we
may market our product candidates, or prevent regulatory approval.
In some instances, there can be significant variability
in safety and efficacy results between different clinical trials of the same product candidates due to numerous factors, including changes
in trial protocols, differences in size and type of the patient populations, differences in and adherence to the dose and dosing regimen
and other trial protocols and the rate of dropout among clinical trial participants. Patients treated with our product candidates may
also be undergoing other therapies and may be using other approved products or investigational new drugs, which can cause side effects
or adverse events that are unrelated to our product candidates. As a result, assessments of efficacy can vary widely for a particular
patient, and from patient to patient and site to site within a clinical trial. This subjectivity can increase the uncertainty of, and
adversely impact, our clinical trial outcomes.
We do not know whether any clinical trials we
may conduct will demonstrate consistent or adequate efficacy and safety sufficient to obtain approval to market any of our product candidates.
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We rely on third parties in the conduct
of all of our clinical trials. If these third parties do not successfully carry out their contractual duties, fail to comply with applicable
regulatory requirements or meet expected deadlines, we may be unable to obtain regulatory approval for our product candidates.
We currently do not have the ability to independently
conduct clinical trials that comply with the regulatory requirements known as good laboratory practice (“GLP”) requirements
or good clinical practice (“GCP”) requirements, respectively. The FDA and regulatory authorities in other jurisdictions require
us to comply with GCP requirements for conducting, monitoring, recording and reporting the results of clinical trials, in order to ensure
that the data and results are scientifically credible and accurate and that the trial subjects are adequately informed of the potential
risks of participating in clinical trials. We rely on medical institutions, clinical investigators, contract laboratories and other third
parties, such as CROs, to conduct GLP-compliant preclinical studies and GCP-compliant clinical trials on our product candidates
properly and on time. While we have agreements governing their activities, we control only certain aspects of their activities and have
limited influence over their actual performance. The third parties with whom we contract for execution of our GLP-compliant preclinical
studies and our GCP-compliant clinical trials play a significant role in the conduct of these studies and the subsequent collection
and analysis of data. These third parties are not our employees and, except for restrictions imposed by our contracts with such third
parties, we have limited ability to control the amount or timing of resources that they devote to our programs. Although we rely on these
third parties to conduct our GLP-compliant preclinical studies and GCP-compliant clinical trials, we remain responsible for
ensuring that each of our preclinical studies and clinical trials is conducted in accordance with its investigational plan and protocol
and applicable laws and regulations, and our reliance on the CROs does not relieve us of our regulatory responsibilities.
Many of the third parties with whom we contract
may also have relationships with other commercial entities, including our competitors, for whom they may also be conducting preclinical
studies, clinical trials or other drug development activities that could harm our competitive position. If the third parties conducting
our preclinical studies or our clinical trials do not adequately perform their contractual duties or obligations, experience significant
business challenges, disruptions or failures, do not meet expected deadlines, terminate their agreements with us or need to be replaced,
or if the quality or accuracy of the data they obtain is compromised due to their failure to adhere to our protocols or to GLPs or GCPs,
or for any other reason, we may need to enter into new arrangements with alternative third parties. This could be difficult, costly or
impossible, and our preclinical studies or clinical trials may need to be extended, delayed, terminated or repeated. As a result, we may
not be able to obtain regulatory approval in a timely fashion, or at all, for the applicable product candidate, our business, financial
results and the commercial prospects for our product candidates would be harmed, our costs could increase, and our ability to generate
revenues could be delayed.
Use of our therapeutic candidates could
be associated with side effects, adverse events or other properties or safety risks, which could delay or preclude approval, cause us
to suspend or discontinue clinical trials, abandon a therapeutic candidate, limit the commercial profile of an approved label or result
in other significant negative consequences that could severely harm our business, prospects, operating results and financial condition.
Adverse events or other undesirable side effects
caused by our product candidates or related to procedures conducted as part of the clinical trials 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 planned clinical trials could reveal a high and unacceptable severity
and prevalence of side effects or unexpected characteristics. If unacceptable side effects arise in the development of our product candidates,
we, the FDA, the IRBs at the institutions in which our studies are conducted or the Data Safety Monitoring Board, or DSMB, could suspend
or terminate our clinical trials or the FDA or comparable foreign regulatory authorities could order us to cease clinical trials or deny
approval of our product candidates for any or all targeted indications. Treatment-related side effects may not be appropriately recognized
or managed by the treating medical staff. We expect to have to train medical personnel using our product candidates to understand the
side effect profiles for our clinical trials and upon any commercialization of any of our product candidates. Inadequate training in recognizing
or managing the potential side effects of our product candidates could result in patient injury or death. Any of these occurrences may
materially and adversely affect our business, financial condition, results of operations and prospects.
In addition, our patient tolerability study and
other clinical trials may only include a limited number of subjects and limited duration of exposure to our product candidates. As a result,
our product candidates may cause unforeseen safety events when evaluated in larger patient populations. Further, clinical trials may not
be sufficient to determine the effect and safety consequences of taking our product candidates over a multi-year period.
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If following marketing approval of ZUNVEYL (which
was received on July 26, 2024) or of any of our future product candidates, we or others later identify undesirable and unforeseen
side effects caused by such product, a number of potentially significant negative consequences could result, including but not limited
to:
● we could be sued and held liable for harm caused to patients;
● the product may become less competitive; and
● our reputation may suffer.
Any of these events could prevent us from achieving
or maintaining market acceptance of the particular product candidate, if approved, and result in the loss of significant revenues to us,
which would materially and adversely affect our business, financial condition, results of operations and prospects.
Interim “top-line” and preliminary
data from studies or trials that we announce or publish from time to time may change as more 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 data from preclinical studies or clinical trials. Interim data are subject to the risk that one or more of the outcomes
may materially change as more data becomes available. We also make assumptions, estimations, calculations and conclusions as part of our
analyses of data, and we may not have received or had the opportunity to fully and carefully evaluate all data when we publish such data.
As a result, the “top-line” results that we report may differ from future results of the same studies, or different conclusions
or considerations may qualify such results once additional data have been received and fully evaluated. Preliminary or “top-line”
data 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.
Additionally, interim data 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 becomes available. Adverse differences between preliminary
or interim data and final data could significantly harm our business, financial condition, results of operations and prospects.
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 our Company 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, and you or others may not agree with what we determine is
the material or otherwise appropriate information to include in our disclosure. Any information we determine not to disclose may ultimately
be deemed significant by you or others with respect to future decisions, conclusions, views, activities or otherwise regarding a particular
product candidate or our business. If the top-line data that we report differ from final results, or if others, including regulatory
authorities, disagree with the conclusions reached, our ability to obtain approval for, and commercialize, product candidates may be harmed,
which could significantly harm our business, financial condition, results of operations and prospects.
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We have conducted, and in the future plan
to conduct, clinical trials for product candidates outside the United States, and the FDA and comparable foreign regulatory authorities
may not accept data from such trials.
We have conducted clinical trials of our product candidates outside
the United States, and plan to continue to do so in the future. For example, we initially conducted our bioavailability and bioequivalence
pivotal clinical trials of ALPHA-1062 in collaboration with Vimta Labs, Inc in Hyderabad, India. In addition, the Phase 1 single
and multiple ascending dose studies of ALPHA-1062 in healthy volunteers were conducted at the Centre for Human Disease Research (CHDR)
in the Netherlands. The acceptance of future study data from clinical trials conducted outside the United States or another jurisdiction
by the FDA, any comparable foreign regulatory authority may be subject to certain conditions or may not be accepted at all. In cases where
data from foreign clinical trials are intended to serve as the basis for marketing approval in the United States, the FDA will generally
not approve the application on the basis of foreign data alone unless:
● the data are applicable to the U.S. population and U.S. medical practice;
● the trials were performed pursuant to GCP requirements; and
Many foreign regulatory authorities have similar
requirements. In addition, foreign trials are subject to the applicable local laws of the foreign jurisdictions where the trials are conducted.
There can be no assurance that the FDA or any comparable foreign regulatory authority will accept data from future trials conducted outside
of the United States or the applicable jurisdiction. If the FDA or any comparable foreign regulatory authority does not accept such
data, it would result in the need for additional trials, which would be costly and time-consuming and delay aspects of our business
plan, and which may result in product candidates that we may develop not receiving approval or clearance for commercialization in the
applicable jurisdiction.
We may expend our limited resources to pursue
a particular product candidate and fail to capitalize on product candidates that may have been more profitable or for which there could
have been a greater likelihood of success.
Because we have limited financial and management
resources, we must focus on development programs and product candidates that we identify for specific diseases. As such, currently we
are primarily focused on the commercialization and further development of ZUNVEYL oral tablets. As a result, we may forego or delay the
pursuit of opportunities with other product candidates. For example, we plan to out-license ALPHA-1062IN for applications in
treating mild traumatic brain injury to a private entity formed by us for the purpose of raising private capital and developing the asset.