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Item 1A. Risk Factors

2022-03-22 compared with 2021-03-25 · 633 added, 750 removed, 63 unchanged (96% of the section changed)

Risks Relating to Our Business and Industry

Our business and operations may be

materially and adversely affected by the coronavirus pandemic.

In December 2019, a novel strain of coronavirus

that causes COVID-19 was reported to have surfaced in Wuhan, China and has since spread to other parts of the world, including

the United States.

In March 2020, the World Health Organization declared the outbreak a pandemic.

The coronavirus pandemic is affecting

the United States and global economies and as a result, government authorities have implemented restrictions and limited certain

operations, such as limits on the number of people at a gathering, travel restrictions and stay-at-home orders, to try to slow

the spread of coronavirus.

The Company’s facilities remain operational and are operating in accordance with federal and state

governmental authority guidelines and with the implementation of safety measures such as social distancing protocols, suspending

travel, the wearing of masks and frequently disinfecting our workspaces.

Employee personnel who do not need to be physically present

on our premises are continuing to work remotely, but have the ability to be on site as required.

While the majority of these mandates

have specific end dates, they may be modified or extended and as a result there is uncertainty regarding the length of time that

such measures will be place.

We believe the impact to our internal operations has not been material thus far, however, current

and future restrictions may further impact our operations and may slow or diminish our research and development activities.

a result of the coronavirus pandemic, certain of our third-party suppliers and service providers on which we rely have seen impacts

to their operations.

If the impact to their operations continue or extend, it may in turn affect our operations.

Company does not expect a material impact to its program’s anticipated timelines as a result of potential delays from our

third-party service providers and believes that we have a sufficient supply of our INTASYL compounds to conduct our ongoing preclinical

studies and initial clinical activities.

However, the ultimate impact to the third parties on which we rely is highly uncertain

and subject to change.

If the measures to contain the outbreak are extended or further expanded, it could reduce or delay the availability

of supplies and services that we purchase and outsource, which may in turn slow or delay our preclinical and clinical activities,

and/or result in higher costs.

The extent to which the coronavirus pandemic impacts our results will depend on future developments,

which are highly uncertain and cannot be predicted, including new information which may emerge concerning the severity of the coronavirus

and the actions to contain the coronavirus or treat its impact, among others.

Additionally, while the potential economic

impact brought by, and the duration of, the coronavirus pandemic is difficult to assess or predict, the impact of the coronavirus

pandemic on the global financial markets may reduce the Company’s ability to access capital and negatively affect our future

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.

candidates are in an early stage of development and may fail or experience significant delays or may never advance to the clinic,

which may materially and adversely impact our business.

All of our pipeline programs are currently

in the preclinical development stage and our future success heavily depends on the successful development of our INTASYL product

candidates, which may never occur.

These product candidates could be delayed, not advance into the clinic or unexpectedly fail

at any stage of development.

Before we can commence clinical trials for a product candidate, we must conduct extensive preclinical

and other non-clinical tests in order to support an IND application, including IND-enabling good laboratory practice toxicology

studies, in the United States or their equivalents with regulatory authorities in other jurisdictions.

Preclinical studies and

clinical trials are expensive, difficult to design and can take many years.

There is no assurance that we will be able to successfully

develop our product candidates, and we may focus our efforts and resources on product candidates that may prove to be unsuccessful.

We cannot be certain of the outcome of preclinical

testing and clinical studies and results from these studies may not predict the results that will be obtained in later phase trials

of our product candidates.

Even if we are able to complete our preclinical studies and planned clinical trials in line with our

projected timelines, results from such studies and trials may be not replicated in subsequent preclinical studies or clinical trial

Additionally, such studies may be delayed due to events beyond our control including as a result of natural disasters,

epidemics or pandemic outbreaks such as the novel coronavirus pandemic.

While the steps for us to initiate our clinical trials

with PH-762 in the second half of 2021 are continuing and ongoing, the FDA, or equivalent regulatory authority, may not accept

the results of our preclinical studies or proposed clinical study designs and may require the Company to complete additional preclinical

studies or impose stricter approval conditions than we expect.

As a result, we cannot guarantee that we will be able to submit

INDs, or similar applications, within our projected timelines, if at all, or that the FDA, or similar regulatory authorities, will

allow us to commence clinical trials.

We are dependent on collaboration

partners for the successful development of our adoptive cell therapy product candidates.

We are not 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.

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.

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

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

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

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

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.

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

1 unchanged sentence

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’

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, results of operations and prospects could be materially and adversely affected.

We rely upon third-party relationships

to conduct preclinical studies, and any future clinical trials, for our product candidates and may not be able to establish or

maintain the third-party relationships that are necessary to support their development.

We depend upon third-party CROs, medical

institutions, clinical investigators, consultants and other third parties to support our preclinical research efforts such as

through managing and conducting research studies, formulating our product candidates and manufacturing our product candidates

and expect to rely on the same for our future clinical trials.

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 and we cannot guarantee

that these parties will fulfill their obligations to us under these arrangements.

Furthermore, we compete with many other companies

for the resources of these third parties, some of which may be our competitors, and may detract from our programs.

Additionally,

as a result of the coronavirus pandemic, certain of our contracted CROs and other third parties are now facing impacts to their

operations, resulting in delays or interruptions.

We previously had been able to engage

with third-party service providers in areas with limited or no impact (e.g.

countries with limited or no restrictions), but

with the global spread of the virus and associated restrictions, this has been no longer possible.

The Company has also undertaken

efforts to mitigate potential future impact by identifying and engaging alternative third-party service providers and suppliers.

However, the ultimate impact to the third parties on which we rely is highly uncertain and subject to change.

If the measures

to contain the coronavirus outbreak are extended or further expanded, it could reduce or delay the availability of supplies and

services that we purchase and outsource, which may in turn slow or delay our preclinical and clinical activities, and/or result

in higher costs.

If these third parties do not successfully carry out their responsibilities, as well as within a timely

fashion, our preclinical and clinical development may be delayed, unsuccessful or otherwise adversely affected.

We cannot guarantee that we will be able

to successfully negotiate agreements with or maintain relationships with these third parties on favorable terms, if at all.

we are unable to obtain or maintain these agreements, we may not be able to develop, formulate, manufacture, obtain regulatory

approval(s) or commercialize our product candidates.

The third parties whom we rely on generally may terminate their agreements

with us at any time, subject to applicable notice periods, and we may not be able to readily terminate any such agreements with

contract partners even if such partners do not fulfill their obligations to us.

If we have to enter into alternative arrangements

it may delay or adversely affect the development of our product candidates and our business operations.

We rely upon third parties for the

manufacture of our product candidates.

We rely on third party suppliers and manufacturers

to provide us with the materials and services to manufacture our INTASYL compounds and product candidates for certain of our preclinical

research activities and expect that we will rely on them for the supply of our product candidates for our future clinical trials.

While we do have in-house expertise and capacity to manufacture our INTASYL compounds, we do not own or lease manufacturing facilities

or have our own supply source for the required materials.

Accordingly, we will be dependent upon third party suppliers and our

contract manufacturers to obtain supplies, and we will need to either develop, contract for, or otherwise arrange for the necessary

manufacturers for these supplies.

If for any reason we are unable to obtain the supplies for our INTASYL compounds from our current

manufacturer, we would have to seek to obtain it from another major manufacturer.

There is no assurance that we will be able to

timely secure needed supply arrangements on satisfactory terms, or at all.

We currently contract with multiple manufacturers

for the supply of our clinical product candidates to reduce the risk of supply interruption or availability.

However, there is

no assurance that our supply of our clinical drug product will not be limited, interrupted, of satisfactory quality or be available

at acceptable prices.

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.

While we believe that we currently have sufficient

supply of our INTASYL compounds to conduct our ongoing preclinical studies and initial clinical activities, we have begun to see

some of our third-party supplies on which we rely becoming impacted from the coronavirus pandemic, which may result in delays or

shortages due to ongoing efforts to address the pandemic.

The Company has also undertaken

efforts to mitigate potential future impact by identifying and engaging alternative third-party suppliers and manufacturers.

the ultimate impact to these third parties on which we rely is highly uncertain and subject to change.

If the measures to

contain the outbreak are extended or further expanded, it could reduce or delay the availability

of supplies and services that we purchase and outsource, which may in turn slow or delay our preclinical and clinical activities,

and/or result in higher costs.

Our failure to secure these arrangements as needed could have a material adverse effect on

our ability to complete the development of our clinical product candidates or, if we obtain regulatory approval, to commercialize

The FDA, or equivalent regulatory authority,

governs the manufacturing process for product candidates and will inspect the facilities at which the product manufactured.

of the product will not occur unless the manufacturing facilities are in compliance with the FDA’s cGMP regulations, or equivalent

foreign authority.

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.

Natural disasters, epidemic or pandemic

disease outbreaks, trade wars, political unrest or other events could disrupt our business or operations or those of our development

partners, manufacturers, regulators or other third parties with whom we conduct business now or in the future.

A wide variety of events beyond our control,

including natural disasters, epidemic or pandemic disease outbreaks (such as the coronavirus pandemic), trade wars, political unrest

or other events could disrupt our business or operations or those of our manufacturers, regulatory authorities, or other third

parties with whom we conduct business.

These events may cause businesses and government agencies to be shut down, supply chains

to be interrupted, slowed, or rendered inoperable, and individuals to become ill, quarantined, or otherwise unable to work and/or

travel due to health reasons or governmental restrictions.

These limitations could negatively affect our business operations and

continuity, and could negatively impact our development timelines and ability to timely perform basic business functions, including

making SEC filings and preparing financial reports.

If our operations or those of third parties with whom we have business are

impaired or curtailed as a result of these events, the development and commercialization of our products and product candidates

could be impaired or halted, which could have a material adverse impact on our business.

The approach we are taking to discover

and develop novel therapeutics using RNAi may never lead to marketable products.

Our research and development efforts and

our future success is based on our INTASYL technology platform.

We plan to develop our INTASYL products for the treatment of cancer

to be delivered via direct injection for use intratumorally and with ACT by isolating immune cells from patients, treating the

cells ex vivo and then returning them to the patient for treatment.

We believe that our INTASYL compounds may offer a new

treatment option to current standards of care, such as antibodies, and potentially with a more cost-effective approach.

development of our INTASYL compounds by us, or by our collaborative partners, is highly uncertain and depends on a number of factors,

many of which are beyond our control.

The scientific research used to support our efforts and approach to developing RNAi therapeutics

Decisions made by the Company to advance the development of our pipeline, including those related to our technology

or manufacturing processes, may show to be incorrect based on further work by us or our collaborators.

The use of RNAi

is a relatively new scientific discovery and the scientific evidence to support the feasibility of developing drugs based on these

discoveries, or INTASYL, is limited.

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 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.

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.

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.

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

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.

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

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.

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.

these third parties may face disruptions due to the coronavirus pandemic that may affect our ability to initiate and complete our clinical

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 (“ SCC s”), 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.

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

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.

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

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

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 INTASYL product candidates for.

As a result, our clinical trials may be delayed or we

may be required to incur more expense than we anticipated.

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 IRBs, which approve and continually review clinical investigations and protect the rights and welfare of human subjects.

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.

Clinical trials of a new drug candidate

require the enrollment of a sufficient number of subjects, including subjects 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.

the global spread of the coronavirus and the associated safety measures to contain the spread by governmental authorities, a delay

in the commencement of new clinical trials and in the enrollment and participation of patients in clinical trials may occur.

steps required for us to initiate our clinical trials with PH-762 in the second half of 2021 are continuing and ongoing, however,

the Company does not yet know the full extent of potential delays or impacts related to its planned clinical activities from the

coronavirus pandemic.

Preclinical studies and clinical trials

are lengthy and expensive, and their outcome is highly uncertain.

Historical failure rates are high due to 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 trial and refusing to approve a particular drug

candidate for any or all indications of use.

An additional number of factors could affect

the timing, cost or outcome of our drug development efforts, including the following:

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

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:

Delays in filing or acceptance of initial drug applications for our product candidates;

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Negative or inconclusive results from our clinical trials or the clinical trials of others for similar product candidates or inability to generate statistically significant data confirming the efficacy of the product being tested;

Changes in the FDA’s requirements for testing during the course of that testing;

The impact from the recent coronavirus pandemic;

Changes in the FDA’s requirements for testing during the course of that testing;

The impact from the ongoing coronavirus pandemic;

Reallocation of our limited financial and other resources to other clinical programs;

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.

The results of preclinical and initial clinical testing of these products

may not necessarily indicate the results that will be obtained from later or more extensive testing.

Preliminary observations

made in early stages of clinical trials with small numbers of subjects are inherently uncertain and initial clinical trial results

are not necessarily indicative of results that will be obtained when full data sets are analyzed or in subsequent clinical trials.

Because of these factors, it is difficult to predict the time and cost of the development of our product candidates.

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.

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.

We are dependent on the success of

our product candidates and even if we complete the necessary preclinical and clinical studies, we may not receive or be delayed

in receiving regulatory approval and as a result, we will not be able to commercialize or will be delayed in commercializing our

product candidates.

We have no commercial products and currently

generate no revenue from product sales and may never be able to develop marketable products.

The FDA or similar foreign governmental

agencies must approve our products in development before they can be marketed.

We, and any of our collaborators, must demonstrate

and establish our product candidate’s safety, purity and effectiveness to patients through extensive clinical trials before

we can submit an NDA or BLA to the FDA for approval.

Even if we complete the necessary preclinical and clinical studies, it is

possible that none of the product candidates that we may attempt to develop will obtain the appropriate regulatory approvals needed

to begin selling them or they may be subject to limitations on the indicated uses for which we may market the product.

The process for obtaining FDA and other

approval is both time consuming and costly, with no certainty of a successful outcome, and can often take years following the commencement

of clinical trials, depending on the complexity of the drug candidate.

Any analysis we perform of data from clinical activities

is subject to confirmation and interpretation by regulatory authorities, which could delay, limit or prevent regulatory approval.

The FDA has substantial discretion in the approval process and may deny our application, may decide our data is insufficient or

require additional information from us regarding our current or planned clinical trials at any time, and such information may be

costly to provide or cause potentially significant delays in development.

Any changes in marketing approval policies or regulatory

statutes and regulations during product development, trials and the review process, may cause delays in the approval of an application.

There is no assurance that we will be able to successfully develop any of our product candidates, and we may spend large amounts

of money trying to resolve these issues and may never succeed in doing so.

We have no experience in filing the applications

necessary to obtain marketing approval and expect that we will need to rely on CROs and regulatory consultants to assist us with

this process.

Regulatory approval also requires the submission about the product manufacturing process and inspection of the manufacturing

facilities, to the relevant regulatory authority.

Any product candidates we develop may not be effective, may prove to have undesirable

or unintended side effects, toxicities or other characteristics that may preclude our obtaining marketing approval or prevent or

limit commercial use.

If we experience delays or fail to obtain

marketing approval for any of our product candidates that we may develop, we would be prevented from being able to commercialize

our product candidates and our commercial prospects and ability to generate revenues may be materially impaired.

The FDA could impose a unique regulatory

regime for our therapeutics.

The compounds we intend to develop may represent

a new class of drug, and even though the first RNAi therapeutic was approved in August 2018, the FDA has not yet established any

definitive policies, practices or guidelines in relation to these drugs.

While we expect any product candidates that we develop

will be regulated as a new drug under the Federal Food, Drug, and Cosmetic Act, the FDA could decide to regulate them or other

products we may develop as biologics under the Public Health Service Act.

The lack of policies, practices or guidelines may hinder

or slow review by the FDA of any regulatory filings that we may submit.

Moreover, the FDA may respond to these submissions by defining

requirements that we may not have anticipated.

Even if we receive regulatory approval

to market our product candidates, our product candidates may not be accepted commercially, which may prevent us from becoming profitable.

Even if we receive regulatory approval for

a product candidate, we may not generate or sustain revenues from sales of the product.

The product candidates that we are developing

are based on new technologies and therapeutic approaches, which are largely unproven.

Additionally, RNAi products do not readily

cross the so-called blood brain barrier, are rapidly eliminated from circulating blood and, for various applications, are likely

to require injection or implantation, which will make them less convenient to administer than drugs administered orally.

Key participants

in the pharmaceutical marketplace, such as physicians, medical professionals working in large reference laboratories, public health

laboratories and hospitals, third-party payors and consumers may not accept products intended to improve therapeutic results based

on our technologies.

For example, RNAi products may be more expensive to manufacture than traditional small molecule drugs, which

may make them costlier than competing small molecule drugs.

As a result, it may be more difficult for us to convince the medical

community and third-party payors to accept and use our products or to provide favorable reimbursement.

If medical professionals

working with large reference laboratories, public health laboratories and hospitals choose not to adopt and use our technologies,

our products may not achieve broader market acceptance.

Additionally, although we expect that we

will have intellectual property protection for our technology, certain governments may elect to deny patent protection for drugs

targeting diseases with high unmet medical need (e.g., as in the case of HIV) and allow in their country internationally unauthorized

generic competition.

If this were to happen, our commercial prospects for developing any such drugs would be substantially diminished

in these countries.

We are dependent on technologies we

license, and if we lose the right to license such technologies or fail to license new technologies in the future, our ability to

develop new products would be harmed.

Many patents in the fields we are pursuing

have already been exclusively licensed to third parties, including our competitors.

If any of our existing licenses are terminated,

the development of the products 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.

We may be unable to protect our intellectual

property rights licensed from other parties;

our intellectual property rights may be inadequate to prevent third parties from using

our technologies or developing competing products;

and we may need to license additional intellectual property from others.

Therapeutic applications of gene silencing

technologies, formulations, delivery methods and other technologies that we license from third parties are claimed in a number

of pending patent applications, but 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 United States Patent and Trademark

Office and patent granting authorities in other countries have upheld stringent standards for the RNAi patents that have been prosecuted

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.

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

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 patent 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.

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 use our technologies freely.

Our efforts to enforce and maintain our intellectual

property rights may not be successful and may result in substantial costs and diversion of management time.

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.

There is no guarantee that future licenses

will be available from third parties for our product candidates on timely or satisfactory terms, or at all.

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.

Our success depends upon our ability to

obtain and maintain intellectual property protection for our products and technologies.

The applications based on RNAi technologies

claim many different methods, compositions and processes relating to the discovery, development, delivery and commercialization

of RNAi therapeutics.

Because this field is so new, very few of these patent applications have been fully processed by government

patent offices around the world, and there is a great deal of uncertainty about which patents will issue, when, to whom and with

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 RNAi field.

It is possible that we may become a party to such proceedings.

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

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The biotechnology and pharmaceutical industries

including immuno-oncology, have intense competition and contain a high degree of risk.

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

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.

We are subject to potential liabilities

from clinical testing and future product liability claims.

If any of our future products are alleged

to be defective, they may expose us to claims for personal injury by subjects in clinical trials of our products.

If our products

are approved by the FDA, users may claim that such products caused unintended adverse effects.

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.

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 and marketing of those products.

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.

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 drugs we develop may become subject

to unfavorable pricing regulations, third-party reimbursement practices or healthcare reform initiatives, which could have a material

adverse effect on our business.

If approved, we intend to sell our products

primarily to hospitals, oncologists and clinics, which receive reimbursement for the healthcare services they provide to their

patients from third-party payors, such as Medicare, Medicaid and other domestic and international government programs, private

insurance plans and managed care programs.

Most third-party payors may deny reimbursement if they determine that a medical product

was not used in accordance with cost-effective treatment methods, as determined by the third-party payor, was used for an unapproved

indication or if they believe the cost of the product outweighs its benefits.

Third-party payors also may refuse to reimburse for

experimental procedures and devices.

Furthermore, because our programs are still in development, we are unable at this time to

determine their cost-effectiveness and the level or method of reimbursement for them.

Increasingly, the third-party payors who

reimburse patients are requiring that drug companies provide them with predetermined discounts from list prices and are challenging

the prices charged for medical products.

If the price we are able to charge for any products we develop is inadequate in light

of our development and other costs, our profitability could be adversely affected.

We currently expect that any drugs we develop

may need to be administered under the supervision of a physician.

Under currently applicable law, drugs that are not usually self-administered

may be eligible for coverage by the Medicare program if:

They are “incidental”

to a physician’s services;

They are “reasonable and necessary”

for the diagnosis or treatment of the illness or injury for which they are administered according to accepted standards of medical practice;

They are not excluded as immunizations;

They have been approved by the FDA.

Insurers may refuse to provide insurance

coverage for newly approved drugs, including drugs in our clinical pipeline, or insurance coverage may be delayed or be more limited

than the purpose for which the drugs are approved by the FDA.

Moreover, eligibility for insurance coverage does not imply that

any drug will be reimbursed in all cases or at a rate that covers our costs, including research, development, manufacture, sale

and distribution costs.

Interim payments for new drugs, if applicable, may also not be sufficient to cover our costs and may not

be made permanent.

Reimbursement may be based on payments for other services and may reflect budgetary constraints or imperfections

in Medicare data.

Net prices for drugs may be reduced by mandatory discounts or rebates required by government healthcare programs

or private payors and by any future relaxation of laws that presently restrict imports of drugs from countries where they may be

sold at lower prices than in the United States.

Third-party payors often rely upon Medicare coverage policy and payment limitations

in setting their own reimbursement rates.

Our inability to promptly obtain coverage and profitable reimbursement rates from both

government-funded and private payors for new drugs that we develop could have a material adverse effect on our operating results,

our ability to raise capital needed to develop products and our overall financial condition.

Additionally, third-party payors are increasingly

attempting to contain healthcare costs by limiting both coverage and the level of reimbursement for medical products and services.

Levels of reimbursement may decrease in the future, and future legislation, regulation or reimbursement policies of third-party

payors may adversely affect the demand for and price levels of our products.

If our customers are not reimbursed for our products,

they may reduce or discontinue purchases of our products, which could have a material adverse effect on our business, financial

condition and results of operations.

Comprehensive healthcare reform legislation,

which became law in 2010, and any revisions to this legislation, could adversely affect our business and financial condition.

other provisions, the legislation provides that a “biosimilar”

product may be approved by the FDA on the basis of analytical

tests and certain clinical studies demonstrating that such product is highly similar to an existing, approved product and that

switching between an existing product and the biosimilar product will not result in diminished safety or efficacy.

This abbreviated

regulatory approval process may result in increased competition if we are able to bring a product to market.

The legislation also

includes more stringent compliance programs for companies in various sectors of the life sciences industry with which we may need

to comply and enhanced penalties for non-compliance with the new healthcare regulations.

Complying with new regulations may divert

management resources, and inadvertent failure to comply with new regulations may result in penalties being imposed on us.

Some states and localities have established

drug importation programs for their citizens, and federal drug import legislation has been introduced in Congress.

Prescription Drug Plan legislation, which became law in 2003, required the Secretary of Health and Human Services to promulgate

regulations for drug reimportation from Canada into the United States under some circumstances, including when the drugs are sold

at a lower price than in the United States.

The Secretary, however, retained the discretion not to implement a drug reimportation

plan, if the Secretary finds that the benefits do not outweigh the costs, and has so far declined to approve a reimportation plan.

Proponents of drug reimportation may attempt to pass legislation that would directly allow reimportation under certain circumstances.

Legislation or regulations allowing the reimportation of drugs, if enacted, could decrease the price we receive for any products

that we may develop and adversely affect our future revenues and prospects for profitability.

With the current U.S.

administration and

Congress, there may be additional legislative changes, including repeal and replacement of certain provisions of the Affordable

It remains to be seen, however, precisely what new legislation will provide, when it will be enacted and what impact

it will have on the availability of healthcare and containing or lowering the cost of healthcare.

Such reforms could have an adverse

effect on anticipated revenue from product candidates that we may successfully develop and for which we may obtain marketing approval

and may affect our overall financial condition and ability to develop product candidates.

Even if we obtain regulatory approvals,

our marketed drugs will be subject to ongoing regulatory review.

If we fail to comply with continuing U.S.

and foreign regulations,

we could lose our approvals to market drugs and our business would be materially and adversely affected.

Following regulatory approval of any drugs

we may develop, we will remain subject to continuing regulatory review, including the review of adverse drug experiences and clinical

results that are reported after our drug products are made available to patients.

This would include results from any post-marketing

tests or vigilance required as a condition of approval.

The manufacturer and manufacturing facilities we use to make any of our

drug products will also be subject to periodic review and inspection by the FDA.

The discovery of any new or previously unknown

problems with the product, manufacturer or facility may result in restrictions on the drug or manufacturer or facility, including

withdrawal of the drug from the market.

We would continue to be subject to the FDA requirements governing the labeling, packaging,

storage, advertising, promotion, recordkeeping and submission of safety and other post-market information for all of our product

candidates, even those that the FDA had approved.

If we fail to comply with applicable continuing regulatory requirements, we may

be subject to fines, suspension or withdrawal of regulatory approval, product recalls and seizures, operating restrictions and

other adverse consequences.

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.

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”

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

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 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.

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

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.

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

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

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

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,

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.

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 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.

to incur significant operating losses as we advance our product candidates through drug development and the regulatory process.

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.

will require substantial additional funds to complete our research and development activities.

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.

Based on our current operating plans and liquidity, we believe that

our existing cash at December 31, 2020 and the proceeds received from our capital raise activities subsequent to the balance

sheet date, 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, 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 conduct research and development to successfully develop our technologies;

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

To conduct research and development to successfully develop our product candidates;

To obtain regulatory approval for our products;

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To acquire new technologies, licenses or products.

In the future, we will need to obtain funding

from third parties, such as proceeds from the issuance of debt, sale of equity or strategic opportunities in order to fund our

planned expenditures, as well as to make acquisitions and other investments.

Historically, the Company’s primary source of

funding has been through the sale of its securities.

We cannot assure you that equity or debt 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.

Moreover, the global coronavirus pandemic has led to significant uncertainty and increased volatility

in the capital markets.

If these conditions in the capital markets continue for an extended period of time it may impact our ability

to raise capital.

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.

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,

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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

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.

In addition, 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.

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

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.

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.

Our financial

statements do not include any adjustments to, or classification of, recorded asset amounts and classification of liabilities that

might be necessary if we were unable to continue as a going concern.

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.

to utilize net operating loss carryforwards and other tax benefits may be limited.

We have historically

incurred net losses.

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.

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.

The Company has not conducted a study to assess whether a change of control, as defined

by Section 382 of the Code, has occurred and it is possible that we have experienced an ownership change limitation.

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.

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

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.

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.

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

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

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,

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:

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

Announcements regarding the initiation or completion, and the results of preclinical studies and clinical trials of our product candidates;

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to the operating performance of particular companies.

These broad market fluctuations may adversely affect the trading price of

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.

In addition, the limited trading volume of our stock may contribute to its volatility.

may incur significant costs from class action litigation due to our historical or expected stock volatility.

Our stock price has historically fluctuated

significantly and may continue to do so in the future.

This risk is relevant to us as in the past, following periods of volatility

in the market price of a particular company’s securities, litigation has often been brought against that company that issued

If litigation of this type is brought against us by any of our stockholders, even if the lawsuit is without merit, it

could be extremely expensive and divert management’s attention and the Company’s resources.

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

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

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’

interest in us.

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.

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

Alternatively, it may be necessary for us to raise additional funds through public or private financings.

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.

We do not anticipate paying cash dividends

in the foreseeable future.

Our business requires significant funding.

We currently plan to invest all available funds and future earnings in the development and growth of our business and do not anticipate

paying any cash dividends on our common stock in the foreseeable future.

As a result, capital appreciation, if any, of our common

stock will be the sole source of potential gain for our stockholders for the foreseeable future.

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.

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:

Authorize the issuance of “blank check”

preferred stock that our Board of Directors could issue to increase the number of outstanding shares and to discourage a takeover attempt;

Authorize the issuance of “blank check” preferred stock that our Board of Directors could issue to increase the number of outstanding shares and to discourage a takeover attempt;

Prohibit stockholder action by written consent, which requires all stockholder actions to be taken at a meeting of our stockholders;

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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.

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

UNRESOLVED STAFF COMMENTS

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What changed 10-K

Item 1A. Risk Factors