ITEM 1A. RISK FACTORS
Risks Relating to Our Business and Industry
Our business and operations may be materially
and adversely affected by the coronavirus pandemic.
Our business and operations may be materially and adversely affected by the ongoing coronavirus pandemic. From the first signs of the
pandemic, we have taken proactive measures to protect the health and safety of our employees, such as working remotely and flexible scheduling,
and our facilities have remained largely operational. The implementation of preventative and precautionary measures that we, companies
we do business with and government authorities have taken to mitigate the spread of coronavirus have impacted, and may further impact
or disrupt our business and operations. The effects of these measures and the extent of their impact will depend, in part, on the length
and severity of the restrictions and the limitations on our ability to conduct our business in the ordinary course. These and future measures
may negatively affect our business, results of operations, financial condition and cash flows.
As a result of the coronavirus pandemic, limited
availability of certain services and supplies required for our preclinical programs significantly impacted our operations, causing delays
to our clinical program timelines. The Company has undertaken efforts to mitigate potential future impacts by identifying and engaging
alternative third-party service providers, however, if measures to overcome the pandemic continue or are insufficient, the availability
of required services and supplies could be further delayed, which may in turn further slow or delay our preclinical and clinical activities.
Additionally, the commencement of new clinical trials and the enrollment of patients in clinical trials have been affected by the coronavirus
pandemic and while the steps to initiate our clinical trials are continuing and ongoing, the Company does not yet know the full extent
of similar potential delays on our clinical trial activities.
We cannot predict the impact that the progression
of the pandemic will have on future operations or financial results due to a number of factors including, but not limited to, the health
and safety of our employees, the ability of the Company’s third-party providers to continue to operate, the availability of services
and supplies for our programs, the ability to commence our clinical trials and the clinical sites to enroll patients, and the length of
the coronavirus pandemic. The extent to which the coronavirus impacts our business, preclinical studies and clinical trials will depend
on future developments, which are highly uncertain and cannot be predicted, including new information which may emerge concerning the
severity of COVID-19, including mutations or variants, and the actions to contain the pandemic or treat its impact, among others. As
a result, we may experience additional disruptions that could severely impact our business, preclinical studies and clinical trials, including
delays in regulatory approvals to initiate any planned clinical trials, delays or difficulties in enrolling patients, interruptions or
delays in preclinical studies due to limited operations at our facilities or the companies we do business with, and lack of availability
or delays in supplies needed to conduct our preclinical and clinical activities.
The pandemic has impacted and may further impact
the global economy and capital markets. Moreover, it has led to significant uncertainty and increased volatility in the capital markets.
If these conditions in the capital markets continue it may reduce the Company’s ability to access capital and negatively affect
our future liquidity. As a result, we may be compelled to take actions to preserve our cash flow.
The coronavirus pandemic continues to evolve and
change rapidly. The ultimate impact of the coronavirus pandemic, or a similar public health emergency, is highly uncertain and subject
to change. The Company does not yet know the full extent of potential delays or impacts on its business, financing activities, preclinical
studies, clinical trial activities or the global economy as a whole. However, these effects could have a material impact on the Company’s
liquidity, results of operations and financial condition.
We are dependent on the success of our INTASYL
technology platform, and our product candidates based on this platform, which is unproven and may never lead to approved and marketable
products.
Our research and development efforts have been
focused on the development of product candidates based on our INTASYL technology platform. We have invested, and we expect to continue
to invest, significant financial resources and efforts developing our product candidates. The ability to generate revenue is highly dependent
on the successful development, regulatory approval and commercialization of our INTASYL product candidates by us or by collaborative partners,
which may not occur for the foreseeable future, if ever, and is highly uncertain and depends on a number of factors, many of which are
beyond our control. Therefore, it is difficult to accurately predict challenges we may face with our product candidates as they move through
the discovery, preclinical and clinical development stages. We may spend large amounts of money trying to develop our INTASYL platform
technology and may never succeed in doing so. In addition, our research methodology may be unsuccessful in identifying product candidates
and results from preclinical and clinical studies may not predict the results that will be obtained in later phase trials of our product
candidates or our product candidates may interact with patients in unforeseen or harmful ways that may make it impractical to manufacture,
market or receive regulatory approval. If we are not successful in bringing an INTASYL product candidate to market, it could negatively
impact our business and financial condition and we may not be able to identify and successfully implement an alternative product development
strategy.
Our product candidates
are in an early stage of development and we may fail, experience significant delays, never advance to the clinic or not be successful
in our efforts to identify or discover additional product candidates, which may materially and adversely impact our business.
Our success depends heavily
on the successful development of our product candidates, which may never occur. Our product candidates could be delayed, not advance into
the clinic, or unexpectedly fail at any stage of development. Our ability to identify, develop and commercialize product candidates is
dependent on extensive preclinical and other non-clinical tests in order to support an investigational new drug (“IND”)
application in the United States, or the equivalent with regulatory authorities in other jurisdictions. These research programs to identify
new product candidates require substantial financial and human resources, are difficult to design and can take many years.
We cannot be certain of the outcome of our research
studies and the results from these studies may not predict the results that will be obtained in later stages of development and we may
focus our efforts and resources on product candidates that may prove to be unsuccessful. There is no assurance that we will be able to
successfully develop our product candidates, and we may forego opportunities with certain product candidates or for indications that later
prove to have greater commercial potential. If we are not able to successfully develop our product candidates, we may be forced to abandon
or delay our development efforts, which may materially and adversely affect our business, financial condition, and results of operations.
We are dependent on collaboration partners
for the successful development of our adoptive cell therapy product candidates.
As we do not have direct access to the patient
or donor cells used in cell therapy, we are not considered a cell therapy company and expect to depend on third-party collaborators to
support the clinical development of our ACT product candidates. We have entered into a clinical collaboration development agreement with
AgonOx, Inc. for the clinical development of our PH-762 product candidate in ACT and have entered into research agreements with our academic
and industry collaborators, each of which is terminable by the relevant party at any time, subject to applicable notice periods. The success
of our collaborations depends upon the efforts of our collaboration partners, and their performance in achieving the development activities
to the extent they are responsible under our collaboration agreements. Each of our partners may not be successful in performing these
activities, including completing the required preclinical studies and other information to be included in an IND application (or foreign
equivalent), obtaining approval to initiate clinical trials, conducting the necessary clinical trials and arranging for the manufacturing
or contract research organization (“CRO”) relationships and obtaining marketing authorization. Our partners work with
other companies, potentially including some of our competitors, and their corporate objectives may not align with ours, they may change
their strategic focus or pursue alternative technologies. If our collaborations are not successful or a partner terminates our collaboration
agreement, our business, financial condition, results of operations could be materially and adversely affected.
Further, we may not be successful in negotiating
agreements with these collaborators or with future collaborators for the development and commercialization of our ACT product candidates
through collaborations such as joint development or licensing agreements. Our ability to successfully negotiate such agreements will depend
on, among other things, potential partners’ evaluation of the superiority of our technology over competing technologies, the quality
of preclinical data that we have generated, the perceived risks specific to developing our product candidates and our partners’
own strategic and corporate objectives. If we fail to negotiate these agreements, we may not be able commence clinical trials with our
ACT product candidates or we may be required to obtain licenses from cell therapy companies and our business, financial condition, and
results of operations could be materially and adversely affected.
If we experience delays or difficulties in
identifying and enrolling patients in clinical trials, it may lead to delays in generating clinical data and the receipt of necessary
regulatory approvals.
Clinical trials of a new drug candidate require
the enrollment of a sufficient number of patients, including patients who are suffering from the disease or condition the drug candidate
is intended to treat and who meet other eligibility criteria. Rates of subject enrollment are affected by many factors, and delays in
subject enrollment can result in increased costs and longer development times, which could materially and adversely impact our business
and financial condition. We may experience slower than expected patient enrollment, including as a result of the coronavirus pandemic,
in our current or future clinical trials. In addition, clinical trials for drug candidates that treat the same indications as our product
candidates may result in subjects who would otherwise be eligible for our clinical trials instead enrolling in clinical trials for other
drug candidates.
Topline data may not accurately reflect or
may materially differ from the complete results of a study or clinical trial.
From time to time, we may publicly disclose topline
or interim data from our preclinical and clinical studies based on a preliminary analysis of then-available data, of which the results,
related findings and conclusions are subject to change following a more comprehensive review of the data related to the particular study
or trial. 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. Preliminary observations made in early stages of preclinical studies
and clinical trials are not necessarily indicative of results that will be obtained when full data sets are analyzed or in subsequent
preclinical and clinical studies and may not be replicated in subsequent studies. As a result, topline data may differ from future results
from the same studies or different conclusions may qualify such results once additional data has been received and evaluated. Topline
or interim data also remain subject to audit and verification procedures that may result in the final data being materially different
from the preliminary data that we publicly disclose and should be viewed with caution until the complete data is available.
Further, the U.S. Food and Drug Administration
(“FDA”), or equivalent foreign regulatory authority, may not accept the results of our preclinical or clinical studies
and may require us to complete additional studies or impose stricter approval conditions than we expect, which could impact the value
of a particular program, the approvability or commercialization of the particular product candidate or product and our Company in general.
Because of these factors, it is difficult to predict the time and cost of the development of our product candidates. Any delay or failure
in obtaining required approvals may prevent us from completing our preclinical or clinical studies and could have a material adverse effect
on our ability to initiate or commercialize any drug candidate on a timely basis, or at all. Additionally, preclinical studies and clinical
trials are lengthy and expensive and if our cash resources become limited we may not be able to commence, continue or complete our clinical
trials. If the topline data we report differs from future analysis of results, or if others, including regulatory authorities, disagree
with the conclusions reached, our business, financial condition, and results of operations could be materially and adversely affected.
We rely upon third-parties to conduct our
clinical trials and other studies for our product candidates, and if they do not successfully fulfill their obligations, the development
of our product candidates may be materially impacted.
We depend upon third-party CROs, medical institutions,
clinical investigators, consultants and other third-parties to support and conduct our clinical trials and rely on these third-party CROs
for the execution of certain of our preclinical studies and expect to continue to do so. Because we rely on these third-parties, we cannot
necessarily control the timing, quality of work or amount of resources that our contract partners will devote to these activities. We
and our CROs are responsible for ensuring that our clinical trials are conducted in accordance with applicable regulations and protocols.
If we or our CROs fail to comply with these applicable regulations, the FDA, or equivalent foreign regulatory authority, may not accept
these data and may require us to complete additional studies. which could result in significant additional costs and delays to us. Further,
these third parties may face disruptions due to the coronavirus pandemic that may affect our ability to initiate and complete our clinical
studies.
As we only control certain aspects of their activities,
we cannot guarantee that these partners will fulfill their obligations to us under these arrangements. If these third-parties do not successfully
carry out their responsibilities, as well as within a timely fashion, our clinical trials and preclinical studies may be delayed, unsuccessful
or otherwise adversely affected. If we have to enter into alternative arrangements it may delay or adversely affect the development of
our product candidates and our business operations. This could be difficult, costly or impossible, and our preclinical or clinical trials
may need to be extended, delayed, terminated or repeated, and we may not be able to obtain regulatory approval in a timely fashion, or
at all, for the applicable drug candidate, or to commercialize such drug candidate being tested in such trials.
France adopted the General Data Protection
Regulation, a data privacy regulation, and as we are conducting a clinical study in France we are required to follow this law, which,
if violated could subject us to significant fines.
The collection and use of personal health data
and other personal information in the European Union is governed by the provisions of the European General Data Protection Regulation
(EU) 2016/679 (“GDPR”), which came into force in May 2018 and related implementing laws in individual EU Member States.
The GDPR imposes a number of strict obligations
and restrictions on the ability to process (processing includes collection, analysis and transfer of) personal data of individuals within
the European Union and in the EEA, including health data from clinical trials and adverse event reporting. The GDPR also includes requirements
relating to the consent of the individuals to whom the personal data relates, the information provided to the individuals prior to processing
their personal data or personal health data, notification of data processing obligations to the national data protection authorities and
the security and confidentiality of the personal data. EU Member States may also impose additional requirements in relation to health,
genetic and biometric data through their national implementing legislation.
Under the GDPR, personal data can only be transferred
within the EU Member States and the three additional European Economic Area countries (Norway, Iceland and Liechtenstein) that have adopted
a national law implementing the GDPR. Appropriate safeguards are required to enable cross-border transfers of personal data from the EU
and EEA Member States to a “third country” (a country outside the EU or EEA). This status has a number of significant practical
consequences, in particular for international data transfers, competent supervisory authorities and enforcement of the GDPR.
In conclusion, the GDPR prohibits the transfer
of personal data to countries outside of the European Union/EEA (including the United States) that are not considered by the European
Commission to provide an adequate level of data protection, except if the data controller meets very specific requirements such as the
use of standard contractual clauses (“SCCs”), issued by the European Commission. In this respect recent legal developments
in Europe have created complexity and compliance uncertainty regarding certain transfers of personal data from the EU/EEA. For example,
following the Schrems II decision of the Court of Justice of the European Union on July 16, 2020, in which the Court invalidated the Privacy
Shield under which personal data could be transferred from the EU/EEA to United States entities who had self-certified under the Privacy
Shield scheme, there is uncertainty as to the general permissibility of international data transfers under the GDPR. The Court did not
invalidate the then current SCCs, but ruled that data exporters relying on these SCCs are required to verify, on a case-by-case basis,
if the law of the third country ensures an adequate level of data protection that is essentially equivalent to that guaranteed in the
EU/EEA. In light of the implications of this decision we may face difficulties regarding the transfer of personal data from the European
Union/EEA to third countries. However, on June 4, 2021 the EU Commission issued a new set of SCCs for data transfers from controllers
or processors in the EU/EEA to controllers or processors established outside the EU/EEA. These SCCs replace the old sets of SCCs that
were adopted under the previous European Data Protection Directive 95/46. Since September 27, 2021, it is no longer possible to conclude
contracts incorporating these previous versions of the SCCs. In addition, for contracts concluded before September 27, 2021, it is still
possible to rely on the previous SCCs until the end of an additional 15 months transitional period (until December 27, 2022), provided
that the processing operations which are the subject matter of the contract remain unchanged and reliance on previous SCCs ensures that
the transfer is subject to appropriate safeguards. On November 11, 2021, the European Data Protection Board has adopted recommendations
on such appropriate safeguards that supplement transfer mechanisms. These recommendations aim to assist data exporters with their duty
to identify and implement appropriate supplementary measures where they are needed to ensure an essentially equivalent level of protection
to the personal data they transfer to third countries.
Failure to comply with the requirements of the
GDPR and the related national data protection laws of the EU Member States may result in significant monetary fines for noncompliance
of up to €20 million or 4% of the annual global revenues of the noncompliant company, whichever is greater, other administrative
penalties and a number of criminal offenses (punishable by uncapped fines) for organizations and in certain cases their directors and
officers as well as civil liability claims from individuals whose personal data was processed. Data protection authorities from the different
EU Member States may still implement certain variations, enforce the GDPR and national data protection laws differently, and introduce
additional national regulations and guidelines, which adds to the complexity of processing personal data in the European Union. Guidance
developed at both EU level and at the national level in individual EU Member States concerning implementation and compliance practices
are often updated or otherwise revised. Ensuring compliance with GDPR is time-intensive and may increase the cost of doing business, and
failure to comply with these laws may have a material impact on our operations and financial condition.
There is, moreover, a growing trend towards required
public disclosure of clinical trial data in the European Union which adds to the complexity of obligations relating to processing health
data from clinical trials. Such public disclosure obligations are provided in the new EU Clinical Trials Regulation, EMA disclosure initiatives
and voluntary commitments by industry. Failing to comply with these obligations could lead to government enforcement actions and significant
penalties against us, harm to our reputation, and adversely impact our business and operating results. The uncertainty regarding the interplay
between different regulatory frameworks, such as the Clinical Trials Regulation and the GDPR, further adds to the complexity that we face
with regard to data protection regulation.
On June 28, 2021 the European Commission adopted
two adequacy decisions for the United Kingdom – one under the GDPR and the other for the Law Enforcement Directive. Personal data
may now freely flow from the European Union to the United Kingdom since the United Kingdom is deemed to have an adequate data protection
level. Additionally, following the UK's withdrawal from the European Union and the EEA, companies also have to comply with the UK’s
data protection laws (including the UK GDPR, which is based on the EU GDPR), the latter regime having the ability to separately fine up
to the greater of £17.5 million or 4% of global turnover. The adequacy decisions include a ‘sunset clause’ which entails
that the decisions will automatically expire four years after their entry into force.
A number of different factors could prevent
us from advancing into clinical development, obtaining regulatory approval, and ultimately commercializing our product candidates on a
timely basis, or at all.
Before obtaining regulatory approval for the sale
of any drug candidate, we must conduct extensive preclinical tests and successful clinical trials to demonstrate the safety and efficacy
of our product candidates in humans. Before human clinical trials may commence, we must submit to the FDA an IND application, or foreign
equivalent. An IND application involves the completion of preclinical studies and the submission of the results, together with proposed
clinical protocols, manufacturing information, analytical data and other data in the IND submission. The FDA may require us to complete
additional preclinical studies or disagree with our clinical trial study design. Also, animal models may not exist for some of the disease
areas we choose to develop our product candidates for. As a result, our clinical trials may be delayed or we may be required to incur
more expense than we anticipated.
Clinical trials require the review and oversight
of Institutional Review Boards (“IRB”), which approve and continually review clinical investigations and protect the
rights and welfare of human subjects. Before our clinical trials can begin, we must also submit to the FDA a clinical protocol accompanied
by the approval of the IRB at the institution(s) participating in the clinical trial. An inability or delay in obtaining IRB approval
could prevent or delay the initiation and completion of our clinical trials, and the FDA may decide not to consider any data or information
derived from a clinical investigation not subject to initial and continuing IRB review and approval.
Preclinical studies and clinical trials are lengthy
and expensive, and their outcome is highly uncertain. Historical failure rates are high due to a number of factors, such as safety and
efficacy of drug candidates. We, our collaborators, the FDA, or an IRB may suspend clinical trials of a drug candidate at any time for
various reasons, including if we or they believe the subjects participating in such trials are being exposed to unacceptable health risks.
Among other reasons, adverse side effects of a drug candidate on subjects in a clinical trial could result in the FDA or other regulatory
authorities suspending or terminating the clinical trial and refusing to approve a particular drug candidate for any or all indications
of use.
We also are subject to numerous foreign regulatory
requirements governing the conduct of clinical trials, manufacturing and marketing authorization, pricing and third-party reimbursement.
The foreign regulatory approval process includes all of the risks associated with the FDA approval described above, as well as risks attributable
to the satisfaction of local regulations in foreign jurisdictions. Approval by the FDA does not assure approval by regulatory authorities
outside of the United States.
An additional number of factors could affect the
timing, cost or outcome of our drug development efforts, including the following:
· Difficulty in securing centers to conduct clinical trials;
· The cost of our clinical trials being greater than we anticipate;
· The impact from the ongoing coronavirus pandemic;
· Adverse results obtained by other companies developing similar drugs.
A failure of any preclinical study or clinical
trial can occur at any stage of testing. Any delay or failure in obtaining required approvals may prevent us from completing our preclinical
or clinical studies and could have a material adverse effect on our ability to initiate or commercialize any drug candidate on a timely
basis, or at all. Additionally, preclinical studies and clinical trials are lengthy and expensive and if our cash resources become limited
we may not be able to commence, continue or complete our clinical trials, which could have a material impact on our business, financial
condition, and results of operations.
We are subject to significant competition
and may not be able to compete successfully.
The biotechnology and pharmaceutical industries
have intense competition and contain a high degree of risk and there are many other companies actively engaged in the discovery, development
and commercialization of products that may compete with our product candidates. We face a number of competitors that have substantially
greater experience and greater research and development capabilities, staffing, financial, manufacturing, marketing, technical and other
resources than us, and we may not be able to successfully compete with them. These companies include large and small pharmaceutical and
biotechnology companies, academic institutions, government agencies and other private and public research organizations.
In addition, even if we are successful in developing
our product candidates, in order to compete successfully we may need to be first to market or to demonstrate that our products are superior
to therapies based on different technologies. Some of our competitors may develop and commercialize products that are introduced to market
earlier than our product candidates or on a more cost-effective basis. A number of our competitors have already commenced clinical testing
of product candidates and may be more advanced than we are in the process of developing products. If we are not first to market or are
unable to demonstrate superiority, on a cost-effective basis or otherwise, any products for which we are able to obtain approval may
not be successful.
Our competitors also compete with us in acquiring
technologies complementary to our INTASYL technology. We may face competition with respect to product efficacy and safety, ease of use
and adaptability to modes of administration, acceptance by physicians, timing and scope of regulatory approvals, reimbursement coverage,
price and patent position, including dominant patent positions of others. If we are not able to successfully obtain regulatory approval
or commercialize our product candidates, we may not be able to establish market share and generate revenues from our technology.
If we fail to attract, hire and retain
qualified personnel, we may not be able to design, develop, market or sell our products or successfully manage our business.
We have a small management team and are particularly
dependent on our core management team. Accordingly, our business prospects are dependent on the principal members of our executive team,
the loss of whose services could make it difficult for us to manage our business successfully and achieve our business objectives. While
we have entered into employment agreements with each of our executive officers, they could leave at any time, in addition to our other
employees, who are all “at will” employees. Our ability to identify, attract, retain and integrate additional qualified key
personnel is also critical to our success. Competition for skilled research, product development, regulatory and technical personnel is
intense, and we may not be able to recruit and retain the personnel we need. The loss of the services of any key research, product development,
regulatory and technical personnel, or our inability to hire new personnel with the requisite skills, could restrict our ability to develop
our product candidates.
We are subject to potential liabilities from
clinical testing and future product liability claims.
The use of our product candidates
in clinical trials and, if any of our product candidates receive regulatory approval, the sale of our product candidates for commercial
use expose us to the risk or product liability claims. Product liability claims may be brought against us by patients, healthcare providers,
consumers or others who come into contact with our product candidates or approved products. We will seek to obtain clinical trial insurance
for clinical trials that we conduct, as well as liability insurance for any products that we market. However, there is no assurance that
we will be able to obtain insurance in the amounts we seek, or at all. We anticipate that licensees who develop our products will carry
liability insurance covering the clinical testing of our product candidates and the marketing of those product candidates, if approved.
There is no assurance, however, that any insurance maintained by us or our licensees will prove adequate in the event of a claim against
us. If we cannot successfully defend against product liability claims, we could incur substantial liabilities. Even if claims asserted
against us are unsuccessful, they may divert management’s attention from our operations and we may have to incur substantial costs
to defend such claims. Any of these outcomes could materially impact our business and financial condition.
We rely upon third parties for the manufacture
of the clinical supply for our product candidates.
We rely on third-party suppliers and manufacturers
to provide us with the materials and services to manufacture our product candidates for certain preclinical studies and for our clinical
trials, and we expect that we will continue to rely on third-party manufacturers for the supply of our product candidates in the future.
We have limited in-house manufacturing capabilities and resources, and we do not own or lease manufacturing facilities or have our own
supply source for the required materials to manufacture our compounds. Further, we have limited current good manufacturing practice (“cGMP”)
manufacturing capabilities and limited experience in scale-up of clinical supply as our internal capabilities are limited to small-scale
production of research material. Accordingly, we are dependent upon third-party suppliers and contract manufacturers to obtain supplies
and manufacture our product candidates and we will need to either develop, contract for, or otherwise arrange for the necessary manufacturers
for these supplies.
There are a limited number of manufacturers
that make oligonucleotides and we currently contract with multiple manufacturers for the supply of our product candidates to reduce
the risk of supply interruption or availability. However, there is no assurance that our supply of our product candidates will not
be limited, interrupted, of satisfactory quality or be available at acceptable prices. For example, constraints on the supply chain
and availability of resources due to the ongoing effort to address the coronavirus pandemic have resulted in delays and shortages at
manufacturing facilities. While we have engaged with multiple manufacturers for the supply of our product candidates, there can be no
assurance that our efforts will be successful. If for any reason we are unable to obtain the clinical supply of our product
candidates from our current manufacturers, we would have to seek to contract with another major manufacturer. If we or any of these
manufacturers is unable or unwilling to increase its manufacturing capacity or if we are unable to establish alternative
arrangements on a timely basis or on acceptable terms, the development and commercialization of such an approved product may be
delayed or there may be a shortage in supply. Any inability to manufacture our product candidates or future approved drugs in
sufficient quantities when needed would seriously harm our business.
Approval of any of our product candidates will
not occur unless the manufacturing facilities are in compliance with the FDA’s cGMP regulations, or a foreign equivalent’s
regulations, in order to ensure that drug products are safe and that they consistently meet applicable requirements and specifications.
These requirements are enforced by the FDA and other regulatory authorities through periodic inspections of the manufacturing facilities
and can result in enforcement action, such as warning letters, fines and suspension of production if they are found to not be in compliance
with the regulations. If our suppliers or manufacturers do not comply with the FDA or foreign regulations for our product candidates,
we may experience delays in timing or supply, be forced to manufacture our product candidates ourselves or seek to enter contract with
another supplier or manufacturer. If we are required to switch suppliers or manufacturers, we will be required to verify that the new
supplier or manufacturer maintains facilities and processes in line with cGMP regulations, which may result in delays, additional expenses,
and may have a material adverse effect on our ability to complete the development of our product candidates.
Risks Relating to Our Intellectual Property
We may be involved in litigation to protect
our patents and intellectual property rights and our ability to protect our patents and intellectual property rights is uncertain and
may subject us to potential liabilities.
We have filed patent applications, have pending
patents that we have licensed and those that we own and expect to continue to file patent applications. We may also need to license patents
and patent applications from research sponsored by us with third-parties. There is no assurance that these applications will result in
any issued patents or that those patents would withstand possible legal challenges or protect our technologies from competition. The patent
granting authorities have upheld stringent standards for the RNAi patents that have been prosecuted so far and, consequently, pending
patents that we have licensed and those that we own may continue to experience long and difficult prosecution challenges and may ultimately
issue with much narrower claims than those in the pending applications.
In addition, others may challenge the patents or
patent applications that we currently license or may license in the future or that we own and, as a result, these patents could be narrowed,
invalidated or rendered unenforceable, which would negatively affect our ability to exclude others from using the technologies described
in these patents. There is no assurance that these patents or other pending applications or issued patents we license or that we own will
withstand possible legal challenges. Moreover, the laws of some foreign countries may not protect our proprietary rights to the same extent
as do the laws of the United States. Our efforts to enforce and maintain our intellectual property rights may not be successful and may
result in substantial costs and diversion of management and key employee’s time. If we are unable to defend our licensed or owned
intellectual property, it may have a materially and adverse impact on our business, results of operations and financial condition.
Third-parties may claim that we infringe
their patents, which may result in substantial liabilities and prevent us from pursuing the development of our product candidates.
Because the field we operate in is relatively new,
is constantly changing and patent applications are still being processed by government patent offices around the world, there is a great
deal of uncertainty about which patents will issue, when, to whom and with what claims. Although we are not aware of any blocking patents
or other proprietary rights, it is likely that there will be significant litigation and other proceedings, such as interference and opposition
proceedings in various patent offices, relating to patent rights in the field we operate. Further, many patents in the fields we are pursuing
have already been exclusively licensed to third-parties, including our competitors. It is possible that we may become a party to such
proceedings.
If a claim should be brought against us and we
are found to infringe the rights of others, we may be required to pay substantial damages, be forced to stop the development of product
candidates affected by the claim, and/or establish licenses or similar arrangements. Furthermore, any such licenses may not be available
when needed, on commercially reasonable terms or at all. Whether an infringement claim is successful or not, the cost of these proceedings
may be significant and divert the attention of management and other key employees. As a result, we cannot be certain that our patents
or those we license will not be challenged by others, which could have a material adverse effect on our business, results of operations
and financial condition.
We are dependent on the patents we own and
the technologies we license, and if we fail to maintain our patents or lose the right to license such technologies, our ability to develop
new products would be harmed.
Our success depends upon our ability to obtain
and maintain intellectual property protection for our product candidates. Any patents issued to us or our licensors may not provide us
with any competitive advantages, and there is no assurance that the patents of others will not have an adverse effect on our ability to
do business or to continue to develop our product candidates freely. Pending patents that we have licensed and those that we own may continue
to experience long and difficult prosecution challenges and may ultimately issue with much narrower claims than those in the pending applications.
Because of the extensive time required for development, testing, and regulatory review of a potential product, it is possible that, before
any of our product candidates can be commercialized, any related patent may expire or remain in force for only a short period following
commercialization, thus reducing any advantage provided by the patent. Further, even if our rights are valid, enforceable and broad in
scope, competitors may develop products based on technology that is not covered by our licenses or patents or patent applications that
we own. If we are unable to derive value from our licensed or owned intellectual property, it may have a materially and adverse impact
on our business, results of operations and financial condition.
Third parties may hold or seek to obtain additional
patents that could make it more difficult or impossible for us to develop products based on our technologies without obtaining a license
to such patents, which licenses may not be available on attractive terms, or at all. If there is any dispute or issue of non-performance
between us and the respective licensing partner regarding the rights or obligations under the license agreements, the ability to develop
and commercialize the affected product candidate may be adversely affected. Moreover, if any of our existing licenses are terminated,
the development of the product candidates contemplated by the licenses could be delayed or terminated and we may not be able to negotiate
additional licenses on acceptable terms, if at all, which would have a material adverse effect on our business. To the extent that we
are required and are able to obtain multiple licenses from third parties to develop or commercialize a product candidate, the aggregate
licensing fees and milestones and royalty payments made to these parties may materially reduce our economic returns or even cause us to
abandon development or commercialization of a product candidate.
Risks Relating to Our Financial Condition
We have a history
of net losses, and we expect to continue to incur net losses for the foreseeable future and may not achieve or maintain profitability.
We have generated significant
losses to date, have not generated any product revenue and may not generate product revenue in the foreseeable future, or ever. We expect
to incur significant operating losses as we advance our product candidates through drug development and the regulatory process. Our
ability to achieve profitability, if ever, will depend on, among other things, us or our collaborators, obtaining regulatory approvals
and successfully commercializing our drug candidates. Even if we are able to successfully commercialize our drug candidates, we may not
be able to achieve or sustain profitability, which could have a material adverse effect on our business, financial condition and results
of operations.
We
will require substantial additional funds to complete our research and development activities.
We have used
substantial funds to develop our product candidates and will need to raise additional substantial funds to continue our drug development
efforts and support our operations. Our future capital requirements and the period for which our existing resources are able to support
our operations may vary significantly from what we expect. We anticipate that we will need to raise substantial amounts of
money to fund a variety of future activities integral to the development of our business, which may include but is not limited to the
following:
· To obtain regulatory approval for our products;
· To manufacture products ourselves or through third parties;
· To acquire new technologies, licenses or products.
In the future, we will be dependent on obtaining
funding from third parties, such as proceeds from the issuance of debt, sale of equity or strategic opportunities, in order to maintain
our operations. We cannot assure you that additional financing will be available to us on acceptable terms, or at all. If we cannot,
or are limited in the ability to, issue equity, incur debt or enter into strategic collaborations, we may be unable to fund the discovery
and development of our product candidates, address gaps in our product offerings or improve our technology. If we fail to obtain additional
funding when needed, we may ultimately be unable to continue to develop and potentially commercialize our product candidates, and we
may be forced to scale back or terminate our operations or seek to merge with or be acquired by another company.
Future financing may be obtained through,
and future development efforts may be paid for by, the issuance of debt or equity, which may have an adverse effect on our stockholders
or may otherwise adversely affect our business.
If we raise funds through the issuance of debt
or equity, any debt securities or preferred stock issued will have rights, preferences and privileges senior to those of holders of our
common stock in the event of a liquidation. In such event, there is a possibility that once all senior claims are settled, there may be
no assets remaining to pay out to the holders of common stock. The terms of debt securities may also impose restrictions on our operations,
which may include limiting our ability to incur additional indebtedness, to pay dividends on or repurchase our capital stock, or to make
certain acquisitions or investments. In addition, we may be subject to covenants requiring us to satisfy certain financial tests and ratios,
and our ability to satisfy such covenants may be affected by events outside of our control. If we raise funds through the issuance of
additional equity, whether through private placements or public offerings, such an issuance would dilute current stockholders’ ownership
in us, perhaps substantially. The issuance of a significant amount of shares of common stock could cause the market price of our common
stock to decline or become highly volatile.
We expect to continue to incur significant
research and development expenses, which may make it difficult for us to attain profitability, and may lead to uncertainty as to our
ability to continue as a going concern.
We expend substantial funds to develop our technologies,
and additional substantial funds will be required for further research and development, including preclinical testing and clinical trials
of any product candidates, and to manufacture and market any products that are approved for commercial sale. Because the successful development
of our products is uncertain, we are unable to precisely estimate the actual funds we will require to develop and potentially commercialize
them. In addition, we may not be able to generate enough revenue, even if we are able to commercialize any of our product candidates,
to become profitable.
Based on
our current operating plans and liquidity, we believe that our existing cash at December 31, 2021 will be sufficient to fund our currently
planned operations for at least the next 12 months from the date of release of the associated financial statements. However, if
we are unable to achieve or sustain profitability or to secure additional financing, we may not be able to meet our obligations as they
come due, raising substantial doubts as to our ability to continue as a going concern. Any such inability to continue as a going concern
may result in our common stockholders losing their entire investment. There is no guarantee that we will become profitable or secure additional
financing. Changes in our operating plans, our existing and anticipated working capital needs, the acceleration or modification of our
expansion plans, increased expenses, potential acquisitions or other events will all affect our ability to continue as a going concern.
Our ability to utilize
net operating loss carryforwards and other tax benefits may be limited.
We have historically incurred
net losses and may never achieve or sustain profitability. Under the Internal Revenue Code of 1986, as amended (the “Code”),
a corporation is generally allowed a deduction for net operating losses carried forward from a prior taxable year. Under that provision,
we can carryforward our net operating losses to offset our future taxable income, if any, until such net operating losses are used or
expire. As a result of the Tax Cuts and Jobs Act of 2017 legislation, net operating losses incurred in tax years beginning after December
31, 2017 may be carried forward indefinitely and can offset up to 80% of future taxable income. Under the Coronavirus Aid, Relief, and
Economic Security Act of 2020, net operating losses arising in years beginning 2018 through 2020 may be carried back five years and the
80% net operating loss deduction limit is temporarily lifted for net operating loss carryforwards to years beginning before January 1,
2021. These net operating loss carryforwards could expire unused before offsetting potential future income tax liabilities.
Additionally, an ownership
change, as defined by Section 382 of the Code, results from transactions increasing the ownership of certain stockholders or public groups
in the stock of a corporation by more than 50% over a three-year period. If the Company has experienced a change of control, as defined
by Section 382 of the Code, at any time since inception, utilization of the Company’s net operating loss carryforwards would be
subject to an annual limitation. Any limitation may result in expiration of a portion of the net operating loss carryforwards before utilization.
During 2021, the Company completed an assessment of the available net operating loss carryforwards under Section 382 and determined that
the Company underwent multiple ownership changes during the period from 2012 to 2021. As a result, our net operating losses are subject
to substantial annual limitations under Section 382 due to these ownership changes. The Company has adjusted its net operating loss carryforwards
to address the impact of the 382 ownership change. We may experience ownership changes in the future as a result of subsequent shifts
in our stock ownership, some of which may be outside of our control. If an ownership change occurs and our ability to use our net operating
loss carryforwards is materially limited, it would harm our future operating results by effectively increasing our future tax obligations.
Risks Relating to Our Securities
The price of our common stock has been and
may continue to be volatile.
Our stock price has historically fluctuated widely
and is likely to continue to be volatile. Because we are at an early stage of development and in the absence of product revenue as a measure
of operating performance, we anticipate that the market price for our common stock may be influenced by, but not limited to, such factors
as:
· Regulatory or legal developments in the United States and other countries;
· The recruitment or departure of key personnel;
· To acquire new technologies, licenses or products;
· Natural disasters and calamities, including the coronavirus pandemic; and
· General economic, industry and market conditions.
The stock markets, in general, and the markets
for drug delivery and pharmaceutical company stocks, in particular, have experienced extreme volatility, that has often been unrelated
to the operating performance of particular companies. These broad market fluctuations may adversely affect the trading price of our common
stock and could result in the loss of all or part of your investment. In addition, the limited trading volume of our stock may contribute
to its volatility. Moreover, our stock has recently traded below $1.00 for an extended period of time. If we are unable to trade above
$1.00 for a certain period of time (which may require a reverse split of our outstanding common stock), The Nasdaq Stock Market may delist
our common stock. Delisting our common stock from Nasdaq would adversely affect our trading volume and would likely negatively impact
our trading price.
Our Board of Directors has the authority
to issue shares of “blank check” preferred stock and the terms of the preferred stock may reduce the value of our common stock.
We are authorized to issue up to 10,000,000 shares
of preferred stock in one or more series. Our Board of Directors may determine the terms of future preferred stock offerings without further
action by our stockholders. The issuance of our preferred stock could affect the rights of existing stockholders or reduce the value of
our outstanding preferred stock or common stock. In particular, rights granted to holders of certain series of preferred stock may include
voting rights, preferences as to dividends and liquidation, conversion and redemption rights and restrictions on our ability to merge
with or sell our assets to a third party.
We may acquire other businesses or form joint
ventures that may be unsuccessful and could dilute your ownership interest in the Company.
As part of our business strategy, we may pursue
future acquisitions of other complementary businesses and technology licensing arrangements. We also may pursue strategic alliances. We
have limited experience with respect to acquiring other companies and with respect to the formation of collaborations, strategic alliances
and joint ventures. We may not be able to integrate such acquisitions successfully into our existing business, and we could assume unknown
or contingent liabilities. We also could experience adverse effects on our reported results of operations from acquisition related charges,
amortization of acquired technology and other intangibles and impairment charges relating to write-offs of goodwill and other intangible
assets from time to time following the acquisition. Integration of an acquired company requires management resources that otherwise would
be available for ongoing development of our existing business. We may not realize the anticipated benefits of any acquisition, technology
license or strategic alliance. There is no assurance that we will be successful in developing such assets, and a failure to successfully
develop such assets could diminish our prospects.
To finance future acquisitions, we may choose to
issue shares of our common stock or preferred stock as consideration, which would dilute current stockholders’ ownership interest
in us. Alternatively, it may be necessary for us to raise additional funds through public or private financings. Additional funds may
not be available on terms that are favorable to us and, in the case of equity financings, may result in dilution to our stockholders.
Any future acquisitions by us also could result in large and immediate write-offs, the incurrence of contingent liabilities or amortization
of expenses related to acquired intangible assets, any of which could harm our operating results.
Provisions of our certificate of incorporation
and bylaws and Delaware law might discourage, delay or prevent a change of control of the Company or changes in our management and, as
a result, depress the trading price of our common stock.
Our certificate of incorporation and bylaws contain
provisions that could discourage, delay or prevent a change of control of the Company or changes in our management that the stockholders
of the Company may deem advantageous. These provisions:
Although we believe these provisions collectively
provide for an opportunity to receive higher bids by requiring potential acquirers to negotiate with our Board of Directors, they would
apply even if the offer may be considered beneficial by some stockholders. In addition, these provisions may frustrate or prevent any
attempts by our stockholders to replace or remove our current management team by making it more difficult for stockholders to replace
members of our Board of Directors, which is responsible for appointing the members of our management.
Moreover, because we are incorporated in Delaware,
we are governed by the provisions of Section 203 of the Delaware General Corporation Law, which prohibits a person who owns in excess
of 15% of our outstanding voting stock from merging or combining with us for a period of three years after the date of the transaction
in which the person acquired in excess of 15% of our outstanding voting stock, unless the merger or combination is approved in a prescribed
manner.
ITEM 1B. UNRESOLVED STAFF COMMENTS
None.
ITEM 2. PROPERTIES
On December 17, 2013, we entered into a lease
(the “Lease”), as subsequently amended on January 22, 2019, with 257 Simarano Drive, LLC, Brighton Properties, LLC,
Robert Stubblebine 1, LLC and Robert Stubblebine 2, LLC to lease office and laboratory space in the building known as the “Main
Building” located at 257 Simarano Drive, Marlborough, Massachusetts, covering 7,581 square feet. The premises are used by the Company
for office and laboratory space. The term of the Lease commenced on April 1, 2014 and expires on March 31, 2024, for a total
of a ten year lease term. The base rent for the premises is $124,865 per annum, payable on a monthly basis. Each year thereafter, the
base rent shall increase by approximately 3% over the base rent from the prior year. With six months’ advance notice, either party
had the option to terminate the lease on March 31, 2021, paying the non-terminating party six months’ rent as a penalty or on March
31, 2022, paying the non-terminating party three months’ rent as a penalty. The option to terminate the Lease early was not exercised
by either party and has expired.
We believe that our facilities are suitable for
our current needs.
ITEM 3. LEGAL PROCEEDINGS
From time to time, we may become a party to various
legal proceedings and complaints arising in the ordinary course of business. There are none deemed to be material at this time.
ITEM 4. MINE SAFETY DISCLOSURES
Not applicable.
PART II.
Market Information
Our common stock is listed on The Nasdaq Capital
Market under the symbol “PHIO.”
Holders
At March 11, 2022, there were approximately
17 holders of record of our common stock. Because many of our shares are held by brokers and other institutions on behalf of stockholders,
we are unable to estimate the total number of individual stockholders represented by these holders of record.
Dividends
We have never paid any cash dividends and do not
anticipate paying any cash dividends on our common stock in the foreseeable future. We expect to retain future earnings, if any, for use
in our development activities and the operation of our business. The payment of any future dividends will be subject to the discretion
of our board of directors and will depend upon, among other things, our results of operations, financial condition, cash requirements,
prospects and other factors that our board of directors may deem relevant.
Securities Authorized for Issuance Under Equity Compensation Plans
See Item 12 to this Annual Report on Form 10-K
for additional information about the securities authorized for issuance under our equity compensation plans.
Recent Sales of Unregistered Sales of Securities
No sales or issues of unregistered securities occurred
that have not previously been disclosed in a Quarterly Report on Form 10-Q or in a Current Report on Form 8-K.
Purchases of Equity Securities by the Issuer and Affiliated Purchases
We did not repurchase any shares of our common
stock during the years ended December 31, 2021 or 2020.
ITEM 6. RESERVED
The following discussion of our financial condition
and results of operations should be read in conjunction with our consolidated financial statements and the notes to those consolidated
financial statements included in Item 8 of this Annual Report on Form 10-K. This discussion contains forward-looking statements that
involve significant risks and uncertainties. As a result of many factors, such as those set forth under “Risk Factors” and
elsewhere in this Annual Report on Form 10-K, our actual results may differ materially from those anticipated in these forward-looking
statements. Please refer to the discussion under the heading “Forward-Looking Statements” above.
Overview
Phio Pharmaceuticals Corp. (“Phio,”
“we,” “our” or the “Company”) is seeking to address the biggest challenges in
immuno-oncology by creating new pathways to a cancer-free future for patients. We are developing therapeutics that leverage our INTASYLTM
technology to target both tumor and immune cells by regulating genes to strengthen a patient’s immune system while weakening tumor
defense mechanisms. With our INTASYL self-delivering RNAi technology, we aim to bring the benefits of RNA therapeutics into cancer care
where other modalities may fall short.
We
are developing a pipeline of immuno-oncology therapies using our INTASYL technology that has the ability to attack cancers in multiple
ways. Our INTASYL-based therapeutics are used to: (1) strengthen immune cells, for example those administered as part of adoptive cell
therapy (“ACT”), and (2) directly modify cells in the tumor microenvironment (the “TME”) to weaken
a tumor’s defense. These two strategies allow for multiple therapeutic applications of our INTASYL products.
In contrast to other RNA
technologies and platforms, the self-delivering nature of our INTASYL platform makes it ideally suited for use with ACT treatments, as
well as for direct therapeutic use. By using INTASYL technology during the manufacturing of ACT cell products we can improve the phenotype
and function of these cells, potentially leading to better therapeutic outcomes. Multiple inhibitory mechanisms restrain immune cells
from effectively eradicating tumors, including immune checkpoints, reduced cell fitness and cell persistence. Furthermore, the immunosuppressive
TME can pose a formidable barrier to immune cell infiltration and function. By using INTASYL based drugs administered directly, we can
also reprogram cells in the TME to help overcome these immunosuppressive mechanisms.
INTASYL Use To Improve
Adoptive Cell Therapy Products
ACT consists of the administration of immune cells
with antitumor properties to patients to fight cancer after growing the cells in a lab to large numbers. These cells can be derived from