Investing
in our common stock involves a high degree of risk. We have described below a number of uncertainties and risks which, in addition
to uncertainties and risks presented elsewhere in this Quarterly Report, may adversely affect our business, operating results and
financial condition. The uncertainties and risks enumerated below as well as those presented elsewhere in this Quarterly
Report should be considered carefully when evaluating our company, business and the value of our securities.
Risks Relating to Our Stage of Development,
Capital Structure and Listing of Our Securities
We may not be able to continue as a going concern if we do
not obtain additional financing.
We have incurred losses since our inception and have not demonstrated
an ability to generate revenues from the sales of our proposed products. Our ability to continue as a going concern is dependent
on raising capital from the sale of our common stock and/or obtaining debt financing. Our cash, cash equivalents and short-term
investment balance at March 31, 2019 was approximately $4.0 million. Based on our current expected level of operating expenditures,
we expect to be able to fund our operations into the third quarter of 2019. Our ability to remain a going concern is wholly dependent
upon our ability to continue to obtain sufficient capital to fund our operations.
Accordingly, despite our ability to secure capital in the past,
there can be no assurance that additional equity or debt financing will be available to us when needed or that we may be able to
secure funding from any other sources. In the event that we are not able to secure funding, we may be forced to curtail operations,
delay or stop ongoing clinical trials, cease operations altogether or file for bankruptcy.
Our auditors have expressed substantial doubt about our ability
to continue as a going concern.
Our auditors’ report issued in connection
with our December 31, 2018 financial statements expressed an opinion that our capital resources as of the date of their audit report
were not sufficient to sustain operations or complete our planned activities for the upcoming year unless we raised additional
funds. Our current cash level raises substantial doubt about our ability to continue as a going concern past the third quarter
of 2019. If we do not obtain additional capital by such time, we may no longer be able to continue as a going concern and may cease
operation or seek bankruptcy protection.
If we are unable
to successfully retain and integrate a new management team, our business could be harmed.
Effective
January 1, 2019, we appointed Dr. Kenneth Carter as our Executive Chairman. In such role, Dr. Carter is our Principal Executive
and Accounting Officer. Our success depends largely on the development and execution of our business strategy by our senior management
team. We currently have a limited full-time executive team which may adversely affect our business. Additionally, the loss of any
members or key personnel would likely harm our ability to implement our business strategy and respond to the rapidly changing market
conditions in which we operate. There may be a limited number of persons with the requisite skills to serve in these positions,
and we cannot assure you that we would be able to identify or employ such qualified personnel on acceptable terms, if at all. We
cannot assure you that management will succeed in working together as a team. In the event we are unsuccessful, our business and
prospects could be harmed.
Our common stock does not currently
meet the continued listing requirements for the Nasdaq Capital Market and accordingly is subject to delisting.
On November 29, 2018, we received a written
notice from the Nasdaq Stock Market LLC that we are not in compliance with Nasdaq Listing Rule 5550(a)(2), as the minimum bid price
of our common stock had been below $1.00 per share for 30 consecutive business days. In accordance with Nasdaq Listing Rule 5810(c)(3)(A),
we have a period of 180 calendar days, or until May 28, 2019, to regain compliance with the minimum bid price requirement. To regain
compliance, the closing bid price of our common stock must meet or exceed $1.00 per share for at least ten consecutive business
days during this 180-calendar day period. In the event we do not regain compliance by May 28, 2019, we may be eligible for an additional
180-calendar day grace period if we meet the initial listing standards, with the exception of bid price, for the Nasdaq Capital
Market, and provide written notice to Nasdaq of our intention to cure the deficiency during the second compliance period, by effecting
a reverse stock split, if necessary.
If we do not regain compliance within the
allotted compliance period, including any extensions that may be granted by Nasdaq, Nasdaq will provide notice that our common
stock will be subject to delisting. We will then be entitled to appeal the determination to a Nasdaq Listing Qualifications Panel
and request a hearing. We cannot be sure that our share price will comply with the requirements for continued listing of our shares
on the Nasdaq Capital Market in the future or that we will comply with the other continued listing requirements. If our shares
lose their status on the Nasdaq Capital Market, we believe that our shares would likely be eligible to be quoted on the inter-dealer
electronic quotation and trading system operated by Pink OTC Markets Inc., commonly referred to as the Pink Sheets and now known
as the OTCQB market. These markets are generally considered not to be as efficient as, and not as broad as, the Nasdaq Capital
Market. If our common stock is delisted, this would, among other things, substantially impair our ability to raise additional funds
and could result in a loss of institutional investor interest and fewer development opportunities for us.
The liquidity of our common stock
and shareholder’s ability to sell their shares may be affected if we undertake a reverse stock split.
On November 29, 2018, we received a written
notice from the Nasdaq Stock Market LLC that we are not in compliance with Nasdaq Listing Rule 5550(a)(2), as the minimum bid price
of our common stock had been below $1.00 per share for 30 consecutive business days. In the event the price of our common stock
does not substantially appreciate to a price at or above $1.00, and remain above $1.00 for 10 consecutive business days, we may
be required to undertake a reverse stock split. In the event we are required to undertake a reverse stock split to regain compliance,
the liquidity of our common stock may be adversely affected given the corresponding reduction in the number of shares that will
be outstanding following the reverse stock split. In addition, the reverse stock split may increase the number of stockholders
who own odd lots (less than 100 shares) of our common stock, creating the potential for such stockholders to experience an increase
in the cost of selling their shares and greater difficulty effecting such sales.
In the event we are required to undertake
a reverse stock split, the market price of our common stock may decline.
On November 29, 2018, we received a written
notice from the Nasdaq Stock Market LLC that we are not in compliance with Nasdaq Listing Rule 5550(a)(2), as the minimum bid price
of our common stock was been below $1.00 per share for 30 consecutive business days.
In accordance with Nasdaq Listing Rule
5810(c)(3)(A), we have a period of 180 calendar days, or until May 28, 2019, to regain compliance with the minimum bid price requirement.
In the event the price of our common stock does not substantially appreciate to a price above $1.00, we may be required to undertake
a reverse stock split. Historically, after a reverse stock split, the market price of a company’s shares declines.
If our common stock were delisted from NASDAQ, the Company
would be subject to the risks relating to penny stocks
.
If our common stock were to be delisted from trading on NASDAQ and
the trading price of our common stock were below $5.00 per share on the date our common stock is delisted, trading in our common
stock would also be subject to the requirements of certain rules promulgated under the Securities Exchange Act of 1934, as amended
(the “Exchange Act”). These rules require additional disclosure by broker-dealers in connection with any trades involving
a stock defined as a "penny stock" and impose various sales practice requirements on broker-dealers who sell penny stocks
to persons other than established customers and accredited investors, generally institutions. These additional requirements may
discourage broker-dealers from effecting transactions in securities that are classified as penny stocks, which could severely limit
the market price and liquidity of such securities and the ability of purchasers to sell such securities in the secondary market.
A penny stock is defined generally as any non-exchange listed equity security that has a market price of less than $5.00 per share,
subject to certain exceptions.
We could become
the subject to securities litigation.
Commencing in 2017, we have seen a dramatic
decrease in the price of our common stock. Plaintiffs have often initiated securities class action litigation against a company
following periods of significant decreases in the market price of the company’s securities. Although management is not aware
of any threatened litigation, we may in the future be the target of similar litigation. Securities litigation could result in substantial
costs and liabilities and could divert management’s attention and resources from our operations and business.
We have a history
of losses.
Since
inception in 1996 through March 31, 2019, we have accumulated losses totaling approximately $216.7 million. As of March 31, 2019,
we had a working capital surplus of approximately $3.3 million and stockholders’ equity of approximately $3.3 million. Our
net losses for the two most recent fiscal years have been approximately $4.9 million and $15.7 million for 2018 and 2017, respectively.
To
date, we have not generated any revenue from the commercial sale of our proposed products. No assurances can be given as to exactly
when, if at all, we will be able to fully develop, commercialize, market, sell and/or derive any, let alone material, revenues
from our proposed products.
We will need to
raise additional capital to continue operations.
Since our inception, we have funded our
operations through the sale of our securities, credit facilities, the exercise of options and warrants, and to a lesser degree,
from grants and research contracts and other revenue generating activities such as licensing. As of March 31, 2019, we had cash,
cash equivalents and short-term investments on hand of approximately $4.0 million. We cannot assure you that we will be able to
secure additional capital through financing transactions, including issuance of debt, licensing agreements or grants. Our inability
to license our intellectual property, obtain grants or secure additional financing will materially impact our ability to fund our
current and planned operations.
We have spent and expect to continue spending
substantial cash in the research, development, clinical and pre-clinical testing of our proposed products with the goal of ultimately
obtaining FDA approval and equivalent international approvals to market such products. We will require additional capital to conduct
research and development, establish and conduct clinical and pre-clinical trials, enter into commercial-scale manufacturing arrangements
and to provide for marketing and distribution of our products. We cannot assure you that financing will be available if needed.
If additional financing is not available, we may not be able to fund our operations, develop or enhance our technologies, take
advantage of business opportunities or respond to competitive market pressures. If we exhaust our cash reserves and are unable
to secure additional financing, we may be unable to meet our obligations which could result in us initiating bankruptcy proceedings
or delaying or eliminating some or all of our research and product development programs.
Tianjin Pharmaceuticals Group International
Holdings Co., LTD, by virtue of its ownership of our securities, may be able to control the Company.
As of April 30, 2019, Tianjin Pharmaceuticals
Group International Holdings Co., LTD (“Tianjin”) owned 4,000,685 shares or approximately 19.99% of our issued and
outstanding common stock. Additionally, Tianjin owns 534,809 shares of our Series A Preferred Stock, which subject to certain conversion
limitations, are convertible into an additional 2,079,010 shares of our common stock. The terms and conditions of the Series A
Preferred Stock limit Tianjin ability to convert, without receiving shareholder approval, if it would result in Tianjin owning
in excess of 19.99% of the Company’s issued and outstanding common stock. The limitation is a condition imposed by the NASDAQ
Market Place Rules. Tianjin has requested, and the Company has approved, the inclusion of a proposal, in accordance with Nasdaq
Market Place Rule 5635(b), approving the full conversion of the Series A Preferred Stock. In the event the proposal is approved,
Tianjin could own approximately 30% of our issued and outstanding convertible stock.
Based on Tianjin’s current level
of stock ownership, Tianjin retains substantial ability to influence the election or removal of members of our board of directors,
and thereby control our management. Tianjin also has the ability to significantly control the outcome of corporate actions requiring
shareholder approval, including amending our certificate of incorporation, approving mergers or other changes of corporate control,
and approving going private transactions and other extraordinary transactions, any of which may be in opposition to the best interest
of the other shareholders and may negatively impact the value of your investment.
Risks Relating to Our
Business
Following our announcements regarding the negative results
from our Phase 2 study, we may not generate any future revenues from NSI-189 or its underlying intellectual property and securing
additional financing may be more difficult.
On July 25, 2017, we announced that our
Phase 2 study of NSI-189 in subjects with MDD failed to achieve statistical significance on its primary endpoint although a subsequent
evaluation of the data appeared directionally positive with regard to certain secondary endpoints. Following these clinical results,
generating any future revenues from NSI-189 or its underlying intellectual property is unlikely. Additionally, after similar results,
other companies in our industry have found it more difficult to raise capital and when they have been able to raise capital, it
has typically been on less favorable terms.
Our business is
dependent on the successful development of our product candidates.
Our business is significantly dependent
on our product candidates which are currently at different phases of pre-clinical and clinical development or that we may acquire
or in-license in the future. The process to approve our product candidates is time-consuming, involves substantial expenditures
of resources, and depends upon a number of factors, including the availability of alternative treatments, and the risks and benefits
demonstrated in our clinical trials. Our success will depend on our ability to achieve scientific and technological advances and
to translate such advances into FDA-approvable, commercially competitive products on a timely basis. Failure can occur at any stage
of the process. On July 25, 2017, we announced that our Phase 2 clinical trial of NSI-189 in MDD failed to achieve statistical
significance on its primary endpoint although a subsequent evaluation of the data appeared directionally positive with regard to
certain secondary endpoints. If we are not successful in developing our product candidates, we will have invested substantial amounts
of time and money without developing revenue-producing products. As we enter a more extensive clinical program for our product
candidates, the data generated in these studies may not be as compelling as the earlier results. This, in turn, could adversely
impact our ability to raise additional capital and pursue our business plan and planned research and development efforts.
Our proposed products are not likely to
be commercially available for at least several years, if at all. Our development schedules for our proposed products may be affected
by a variety of factors, including technological difficulties, clinical trial failures, regulatory hurdles, competitive products,
intellectual property challenges and/or changes in governmental regulation, many of which will not be within our control. Any delay
in the development, introduction or marketing of our product candidates could result either in such products being marketed at
a time when their cost and performance characteristics would not be competitive in the marketplace or in the shortening of their
commercial lives. In light of the long-term nature of our projects, the unproven technology involved, and the other factors described
elsewhere in this section, there can be no assurance that we will be able to successfully complete the development or marketing
of any of our proposed product candidates.
Our
business relies on technologies that we may not be able to commercially develop.
We have allocated the majority of our resources
to the development of our stem cell and small molecule technologies. Our ability to generate revenue and operate profitably will
depend on being able to develop these technologies for human applications. These are emerging technologies that may have limited
human application. On July 25, 2017, we announced that our Phase 2 clinical trial of NSI-189 in MDD failed to achieve statistical
significance on its primary endpoint although a subsequent evaluation of the data appeared directionally positive with regard to
certain secondary endpoints. We cannot guarantee that we will be able to develop our technologies or that if developed, our technologies
will result in commercially viable products or have any commercial utility or value. We anticipate that the commercial sale of
our proposed products and/or royalty/licensing fees related to our technologies, will be our primary sources of revenue. If we
are unable to develop our technologies, we may never realize any significant revenue. Additionally, given the uncertainty of our
technologies, product candidates and the need for government regulatory approval, we cannot predict when, or if ever, we will be
able to realize revenues related to our products. As a result, we will be primarily dependent on our ability to raise capital through
the sale of our securities for the foreseeable future.
Our stem cell therapy programs rely on experimental surgical
devices and highly invasive experimental surgical procedures.
We are subject to the risks inherent in the use and development
of experimental surgical devices and procedures. We have limited experience with medical devices and must rely on outside consultants
and manufacturers to develop and seek any required approvals for the device we use in connection with our stem cell therapy program.
Additionally, the surgical procedures required to administer our stem cell therapies are experimental, highly invasive and is required
to be performed by highly experienced neurosurgeons who have received special training. We cannot guarantee consistent and safe
performance of these devices or the surgical procedures. A surgery related adverse event may result in a clinical hold and may
have long-term and damaging effects on our ability to complete development of the stem cell therapy programs, including the completion
of any ongoing or planned clinical trials. Even if one or more of our programs is successful and receives marketing approval from
a regulatory authority, due to the specialized nature of the device and surgical procedure, there may not be sufficient train surgeons
to administer our therapy.
We are unable to predict when or
if we will be able to earn significant revenues.
Given the uncertainty of our technologies
and the need for government regulatory approval, we cannot predict when, or if ever, we will be able to realize revenues related
to our products. Our proposed products are not likely to be commercially available for at least several or more years, if ever.
Accordingly, we do not foresee generating any significant revenue during such time. As a result, we will be primarily dependent
on our ability to raise capital through the sale of our securities to fund our operations for the foreseeable future.
Our reliance on third parties to
manufacture and store our stem cells and small molecule compounds could adversely impact our business.
We currently outsource most of the manufacturing
of our stem cells and small molecule pharmaceutical compounds to third party contractors and as such have limited ability to adequately
control the manufacturing process and the safe storage thereof. Any manufacturing or storage irregularity, error, or failure to
comply with applicable regulatory procedure would require us to find new third parties to outsource our manufacturing and storage
responsibilities or our business would be impacted.
The manufacture of our therapeutic products
is a complicated and difficult process, dependent upon substantial know-how and subject to the need for continual process improvements.
In addition, our suppliers’ ability to scale-up manufacturing to satisfy the various requirements of our planned clinical
trials is uncertain. Additionally, many of the materials that we use to prepare our cell-based products are highly specialized,
complex and available from only a limited number of suppliers. The loss of one or more of these sources would likely delay our
ability to conduct planned clinical trials and otherwise adversely affect our business.
If
we are unable to complete pre-clinical and clinical testing and trials or if clinical trials of our product candidates are prolonged,
delayed, suspended, terminated or fail to reach their endpoints, our business and results of operations could be materially harmed.
Although we have commenced a number of
trials, the ultimate outcome of the trials is uncertain. On July 25, 2017, we announced that our Phase 2 clinical trial of NSI-189
in MDD failed to achieve statistical significance on its primary endpoint although a subsequent evaluation of the data appeared
directionally positive with regard to certain secondary endpoints. If we are unable to satisfactorily complete our other trials,
or if such trials also yield unsatisfactory results, we may be unable to obtain regulatory approval for and commercialize our proposed
products. No assurances can be given that our clinical trials will be completed or result in successful outcomes. A number of events,
including any of the following, could delay the completion of our planned clinical trials and negatively impact our ability to
obtain regulatory approval for, and to market and sell, a particular product candidate:
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conditions imposed on us by the FDA or
any foreign regulatory authority regarding the scope or design of our clinical trials;
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delays in obtaining, or our inability
to obtain, required approvals from institutional review boards, or IRBs, or other reviewing entities at clinical sites selected
for participation in our clinical trials;
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insufficient supply or deficient quality
of our product candidates or other materials necessary to conduct our clinical trials;
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delays in obtaining regulatory agency
agreement for the conduct of our clinical trials;
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lower than anticipated enrollment and
retention rate of subjects in clinical trials;
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serious and unexpected side effects experienced
by patients in our clinical trials which are related to the use of our product candidates; or
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failure of our third-party contractors
to meet their contractual obligations to us in a timely manner.
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Clinical trials may also be delayed or
terminated as a result of ambiguous or negative interim results. In addition, a clinical trial may be suspended or terminated by
us, the FDA, clinical trial site IRB’s, or a data safety monitoring board, or DSMB, overseeing the clinical trial at issue,
or other regulatory authorities due to a number of factors. Additionally, changes in regulatory requirements and guidance may occur
and we may need to amend clinical trial protocols to reflect these changes. Amendments may require us to resubmit our clinical
trial protocols to IRBs for reexamination, which may impact the cost, timing or successful completion of a clinical trial. We do
not know whether our clinical trials will be conducted as planned, will need to be restructured or will be completed on schedule,
if at all. Delays in our clinical trials will result in increased development costs for our drug candidates. In addition, if we
experience delays in the completion of, or if we terminate, any of our clinical trials, the commercial prospects for our drug candidates
may be harmed and our ability to generate product revenues will be jeopardized. Furthermore, many of the factors that cause, or
lead to, a delay in the commencement or completion of clinical trials may also ultimately lead to the denial of regulatory approval
of a drug candidate. If regulatory authorities do not approve our products or if we fail to maintain regulatory compliance, we
would be unable to commercialize our proposed products, and our business and results of operations could be materially harmed.
The results of pre-clinical
studies and clinical trials may not be predictive of the results of our later-stage clinical trials and our proposed products may
not have favorable results in later-stage clinical trials or receive regulatory approval.
Seemingly positive results from pre-clinical
studies or clinical studies should not be relied upon as evidence that our clinical trials will succeed. Even if our product candidates
achieve positive results in pre-clinical studies or during our Phase 1 and Phase 2 studies, we will be required to demonstrate
through further clinical trials that our product candidates are safe and effective for use in a diverse population before we can
seek regulatory approvals for their commercial sale. There is typically an extremely high rate of attrition from the failure of
product candidates as they proceed through clinical trials. If any product candidate fails to demonstrate sufficient safety and
efficacy in any clinical trial, then we may experience potentially significant delays in, or be required to abandon development
of that product candidate. Additionally, failure to demonstrate safety and efficacy results acceptable to the FDA in later stage
trials could impair our development prospects and even prevent regulatory approval of our current and future product candidates.
Any such delays or abandonment in our development efforts of any of our product candidates would materially impair our ability
to generate revenues.
We are subject to
numerous risks inherent in conducting clinical trials.
We outsource the management of our clinical
trials to third parties. Agreements with clinical investigators and medical institutions for clinical testing and with other third
parties for data management services, place substantial responsibilities on these parties that, if unmet, could result in delays
in, or termination of, our clinical trials. For example, if any of our clinical trial sites fail to comply with FDA-approved good
clinical practices, we may be unable to use the data gathered at those sites. If these clinical investigators, medical institutions
or other third parties do not carry out their contractual duties or obligations or fail to meet expected deadlines, or if the quality
or accuracy of the clinical data they obtain is compromised due to their failure to adhere to our clinical protocols or for other
reasons, our clinical trials may be extended, delayed or terminated, and we may be unable to obtain regulatory approval for, or
successfully commercialize, our proposed products. Delays in recruitment, lack of clinical benefit or unacceptable side effects
would delay or prevent the completion of our clinical trials.
We or our regulators may suspend or terminate
our clinical trials for a number of reasons. We may voluntarily suspend or terminate our clinical trials if at any time we believe
they present an unacceptable risk to the patients enrolled in our clinical trials or do not demonstrate clinical benefit. In addition,
regulatory agencies may order the temporary or permanent discontinuation of our clinical trials at any time if they believe that
the clinical trials are not being conducted in accordance with applicable regulatory requirements or that they present an unacceptable
safety risk to the patients enrolled in our clinical trials.
Our clinical trial operations are subject
to regulatory inspections at any time. If regulatory inspectors conclude that we or our clinical trial sites are not in compliance
with applicable regulatory requirements for conducting clinical trials, we may receive reports of observations or warning letters
detailing deficiencies, and we will be required to implement corrective actions. If regulatory agencies deem our responses to be
inadequate, or are dissatisfied with the corrective actions we or our clinical trial sites have implemented, our clinical trials
may be temporarily or permanently discontinued, we may be fined, we or our investigators may be precluded from conducting any ongoing
or any future clinical trials, the government may refuse to approve our marketing applications or allow us to manufacture or market
our products, and we may be criminally prosecuted.
The lengthy approval process as well as
the unpredictability of future clinical trial results may result in our failing to obtain regulatory approval for our proposed
products, which would materially harm our business, results of operations and prospects.
We may be subject to litigation that
will be costly to defend or pursue and uncertain in its outcome.
Our business may bring us into conflict
with licensees, licensors, or others with whom we have contractual or other business relationships or with our competitors or others
whose interests differ from ours. If we are unable to resolve these conflicts on terms that are satisfactory to all parties, we
may become involved in litigation brought by or against such parties. Any litigation is likely to be expensive and may require
a significant amount of management's time and attention, at the expense of other aspects of our business. The outcome of litigation
is always uncertain, and in some cases, could include judgments against us which could have a materially adverse effect on our
business.
We may not be able to obtain government
or third-party payor coverage and reimbursement.
Our ability to successfully commercialize
our product candidates, if approved, depends to a significant degree on the ability of patients to be reimbursed for the costs
of such products and related treatments. We cannot assure you that reimbursement in the U.S. or in foreign countries will be available
for any products developed, or, if available, will not decrease in the future, or that reimbursement amounts will not reduce the
demand for, or the price of, our products. There is considerable pressure to reduce the cost of therapeutic products. Government
and other third-party payors are increasingly attempting to contain health care costs by limiting both coverage and the level of
reimbursement for new therapeutic products and by refusing, in some cases, to provide any coverage for uses of approved products
for disease indications for which the FDA or other relevant authority has not granted marketing approval. Moreover, in some cases,
government and other third-party payors have refused to provide reimbursement for uses of approved products for disease indications
for which the FDA or other relevant authority has granted marketing approval. Significant uncertainty exists as to the reimbursement
status of newly approved health-care products or novel therapies such as ours. We cannot predict what additional regulation or
legislation relating to the health care industry or third-party coverage and reimbursement may be enacted in the future or what
effect such regulation or legislation may have on our business. If additional regulations are overly onerous or expensive or if
healthcare related legislation makes our business more expensive or burdensome than originally anticipated, we may be forced to
significantly downsize our business plans or completely abandon the current business model.
Our products may not be profitable due to manufacturing
costs and our inability to receive favorable pricing.
Our products may be significantly more
expensive to manufacture than other drugs or therapies currently on the market today due to a fewer number of potential manufacturers,
greater level of needed expertise and other general market conditions affecting manufacturers of our proposed products. Even if
we can receive approval for the reimbursement of our proposed products the amount of reimbursement may be significantly less than
the manufacturing costs of our products. Additionally, other market factors may limit the price which we can charge for our proposed
products while still being competitive. Accordingly, even if we are successful in developing our proposed products, we may not
be able to charge a high enough price for us to earn a profit.
We are dependent
on the acceptance of our products by the healthcare community.
Our product candidates, if approved for
marketing, may not achieve market acceptance since hospitals, physicians, patients or the medical community, in general, may decide
not to accept and utilize these products. The products that we are attempting to develop represent substantial departures from
established treatment methods and will compete with a number of more conventional therapies marketed by major pharmaceutical companies.
If the healthcare community does not accept our products for any reason, our business will be materially harmed.
We depend on a limited number of employees and consultants
for our continued operations and future success.
We are highly dependent on a limited number
of employees and outside consultants. Although we have entered into employment and consulting agreements with these
parties, these agreements can be terminated at any time. The loss of any of our employees or consultants could adversely
affect our opportunities and materially harm our future prospects. In addition, we anticipate growth and expansion into
areas and activities requiring additional expertise, such as clinical testing, regulatory compliance, manufacturing and marketing. We
anticipate the need for additional management personnel as well as the development of additional expertise by existing management
personnel. There is intense competition for qualified personnel in the areas of our present and planned activities, and there can
be no assurance that we will be able to attract and retain the qualified personnel necessary for the development our business.
The employment contract of Dr. Carter
contains significant anti-termination provisions which could make changes in management difficult or expensive.
We have entered into an employment agreement
with Dr. Carter, our Executive Chairman and Chief Financial Officer. This agreement may require the payment of severance in the
event he ceases to be employed. The provision makes the replacement of Dr. Carter very costly and could cause difficulty in effecting
any required changes in management or a change in control.
Our competition
has significantly greater experience and financial resources.
The biotechnology industry is characterized
by rapid technological developments and a high degree of competition. We compete against numerous companies, many of which have
substantially greater resources. Several such enterprises have initiated cell therapy research programs and/or efforts to treat
the same diseases which we target. Given our current stage of development and resources, it may be extremely difficult for us to
compete against more developed companies.
As a result, our proposed products could
become obsolete before we recoup any portion of our related research and development and commercialization expenses. Competition
in the biopharmaceutical industry is based significantly on scientific and technological factors. These factors include the availability
of patent and other protection for technology and products, the ability to commercialize technological developments and the ability
to obtain governmental approval for testing, manufacturing and marketing. We compete with specialized biopharmaceutical firms in
the United States, Europe and elsewhere, as well as a growing number of large pharmaceutical companies that are applying biotechnology
to their operations. Many major pharmaceutical companies have developed or acquired internal biotechnology capabilities or made
commercial arrangements with other biopharmaceutical companies. These companies, as well as academic institutions and governmental
agencies and private research organizations, also compete with us in recruiting and retaining highly qualified scientific personnel
and consultants. Our ability to compete successfully with other companies in the pharmaceutical field will also depend to a considerable
degree on the continuing availability of capital to us.
We believe that our proposed products under
development and in pre-clinical testing and clinical trials will address unmet medical needs for those indications for which we
are focusing our development efforts. Our competition will be determined in part by the potential indications for which our proposed
products are developed and ultimately approved by regulatory authorities. Additionally, the timing of market introduction of some
of our proposed products or of competitors’ products may be an important competitive factor. Accordingly, the relative speed
with which we can develop our proposed products, complete preclinical testing, clinical trials and approval processes and supply
commercial quantities to market is expected to be important competitive factors. We expect that competition among products approved
for sale will be based on various factors, including product efficacy, safety, reliability, availability, price and patent position.
Our outsource model depends on third parties to assist
in developing and testing our proposed products.
Our strategy for the development, clinical
and pre-clinical testing and commercialization of our proposed products is based on an outsource model. This model requires us
to engage third parties in order to further develop our technology and products as well as for the day to day operations of our
business. In the event we are not able to enter into such relationships in the future, our ability to operate and develop products
may be seriously hindered or we may be required to spend considerable time and resources to bring such functions in-house. Either
outcome could result in our inability to develop a commercially feasible product or in the need for substantially more working
capital to complete the research in-house.
The commercialization of therapeutic products exposes
us to product liability claims.
Product liability claims could result in
substantial litigation costs and damage awards against us. We attempt to mitigate this risk by obtaining and maintaining appropriate
insurance coverage. Historically, we have obtained liability insurance that covers our clinical trials. If we begin commercializing
products, we will need to increase our insurance coverage. We may not be able to obtain insurance on acceptable terms, if at all,
and the policy limits on our insurance policies may be insufficient to cover our potential liabilities.
We currently rely heavily upon third
party FDA-regulated manufacturers and suppliers for our products
We currently manufacture our cells both
in-house and on an outsource basis. We outsource the manufacturing of our pharmaceutical compound to third party manufacturers.
We manufacture cells in-house which are not required to meet stringent FDA requirements. We use these cells in our research and
collaborative programs. At present, we outsource all the manufacturing and storage of our stem cells and pharmaceuticals compound
to be used in clinical testing, and which are subject to higher FDA requirements, to Charles River Laboratories, Inc., of Wilmington,
Massachusetts (stem cells) and Albany Molecular Resources, Inc. (small molecule). Failure by our contract manufacturer to achieve
and maintain high manufacturing standards could result in patient injury or death, product recalls or withdrawals, delays or failures
in testing or delivery, cost overruns, or other problems that could seriously hurt our business. Contract manufacturers may encounter
difficulties involving production yields, quality control, and quality assurance. These manufacturers are subject to ongoing periodic
and unannounced inspections by the FDA and corresponding state and foreign agencies to ensure strict compliance with cGMPs, GTPs
and other applicable government regulations and corresponding foreign standards; however, we do not have control over third-party
manufacturers’ compliance with these regulations and standards.
Because manufacturing facilities are subject
to regulatory oversight and inspection, failure to comply with regulatory requirements could result in material manufacturing delays
and product shortages, which could delay or otherwise negatively impact our clinical trials and product development. Moreover,
we do not have quantity or volume commitment orders from these manufacturers, and we cannot assure you that the manufacturers will
be able to manufacture in the quantity we require on a timely basis or at all. In the event we are required to seek alternative
third-party suppliers or manufacturers, they may require us to purchase a minimum amount of materials or could require other unfavorable
terms. Any such event would materially impact our business prospects and could delay the development of our products. Moreover,
there can be no assurance that any manufacturer or supplier that we select will be able to supply our products in a timely or cost-effective
manner or in accordance with applicable regulatory requirements or our specifications. In addition, due to the novelty of our products
and product development, there can be no assurances that we would be able to find other suitable third-party FDA-regulated manufacturers
on a timely basis and at terms reasonable to us. Even if we were to locate alternative manufacturers there may be delays before
they are able to begin manufacturing. Failure to secure such third-party manufacturers or suppliers would materially impact our
business.
We
rely on third parties to conduct our clinical trials and perform data collection and analysis, which may result in costs and delays
that prevent us from successfully commercializing our product candidates.
We do not have the in-house capability
to conduct clinical trials for our product candidates. We rely, and will rely in the future, on medical institutions, clinical
investigators, contract research organizations, contract laboratories, and collaborators to perform data collection and analysis
and other aspects of our clinical trials. Our reliance on these third parties for clinical development activities results in reduced
control over these activities. Furthermore, these third parties may also have relationships with other entities, some of which
may be our competitors. Our preclinical activities or clinical trials conducted in reliance on third parties may be delayed, suspended,
or terminated if:
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the third parties do not successfully
carry out their contractual duties;
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the third parties fail to meet FDA and
other regulatory obligations or expected deadlines;
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we replace a third party for any reason;
or
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the quality or accuracy of the data obtained
by third parties is compromised due to their failure to adhere to clinical protocols, regulatory requirements, or for other reasons.
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Third party performance failures may increase
our development costs, delay our ability to obtain regulatory approval, and delay or prevent the commercialization of our product
candidates. While we believe that there are numerous alternative sources to provide these services, in the event that we seek such
alternative sources, we may not be able to enter into replacement arrangements without incurring delays or additional costs.
Risks Relating to Intellectual
Property
We may not be able to withstand challenges to our intellectual
property rights.
We rely on our intellectual property, including
issued and applied-for patents, as the foundation of our business. Our intellectual property rights may come under challenge. No
assurances can be given that our current and potential future patents will survive such challenges. These cases are complex, lengthy,
expensive, and could potentially be adjudicated adversely to our interests, removing the protection afforded by an issued patent.
The viability of our business would suffer if such patent protection were limited or eliminated. Moreover, the costs associated
with defending or settling intellectual property claims would likely have a material adverse effect on our business and future
prospects.
We may not be able to adequately protect against the piracy
of the intellectual property in foreign jurisdictions.
We conduct research in countries outside
of the U.S., including through our subsidiary in the People’s Republic of China. Several of our competitors are located in
these countries and may be able to access our technology or test results. The laws protecting intellectual property in some of
these countries may not adequately protect our trade secrets and intellectual property. The misappropriation of our intellectual
property may materially impact our position in the market and any competitive advantages, if any, that we may have.
We may infringe the intellectual
property rights of others and may not be able to obtain necessary licenses to third-party patents and other rights.
A number of companies, universities and
research institutions have filed patent applications or have received patents relating to technologies in our field. We cannot
predict which, if any, of these applications will issue as patents or how many of these issued patents will be found valid and
enforceable. There may also be existing issued patents on which we would infringe by the commercialization of our product candidates.
If so, we may be prevented from commercializing these products unless the third party is willing to grant a license to us. We may
be unable to obtain licenses to the relevant patents at a reasonable cost, if at all, and may also be unable to develop or obtain
alternative non-infringing technology. If we are unable to obtain such licenses or develop non-infringing technology at a reasonable
cost, our business could be significantly harmed. Also, any infringement lawsuits commenced against us may result in significant
costs, divert our management’s attention and result in an award against us for substantial damages, or potentially prevent
us from continuing certain operations.
Risks Relating to Our
Common Stock
The market price for our common shares is particularly
volatile.
The market for our common shares is characterized
by significant price volatility when compared to seasoned issuers, and we expect that our share price will continue to be more
volatile than those of a seasoned issuer. The volatility in our share price is attributable to a number of factors. Mainly however,
we are a speculative or “risky” investment due to our limited operating history, lack of significant revenues to date
and the uncertainty of FDA approval. By way of example, in October of 2018, we completed a registered direct offering of 3,000,000
shares of our common stock and a simultaneous private placement of 3,000,000 common stock purchase warrants. Shortly thereafter,
the market price or our common stock decreased substantially. As a consequence of this enhanced risk, more risk-adverse investors
may, under the fear of losing all or most of their investment in the event of negative news or lack of progress, be more inclined
to sell their shares on the market more quickly and at greater discounts than would be the case with the stock of a seasoned issuer.
Additionally, in the past, plaintiffs have often initiated securities class action litigation against a company following periods
of volatility in the market price of its securities. We may in the future be the target of similar litigation. Securities litigation
could result in substantial costs and liabilities and could divert management’s attention and resources.
The following factors may add to the volatility
in the price of our common shares: actual or anticipated variations in our quarterly or annual operating results; the results of
clinical trials for our product candidates; FDA’s determination with respect to filings for new clinical studies, new drug
applications and new indications; government regulations; announcements of significant acquisitions, strategic partnerships or
joint ventures; our capital commitments; offerings of our securities and additions or departures of our key personnel. Many of
these factors are beyond our control and may decrease the market price of our common shares, regardless of our operating performance.
We cannot make any predictions or projections as to what the prevailing market price for our common shares will be at any time,
including as to whether our common shares will sustain their current market prices, or as to what effect the sale of shares or
the availability of common shares for sale at any time will have on the prevailing market price.
Future sales of our common stock
could cause our stock price to fall.
In October of 2018, we completed a registered
direct offering of 3,000,000 shares of our common stock or approximately 20% of our issued and outstanding shares, as well as a
private placement of an equal number of common stock purchase warrants. Transactions that result in a large amount of newly issued
shares that are readily tradable, or other events that cause current stockholders to sell shares, could place downward pressure
on the trading price of our common stock. In addition, the lack of a robust trading market may require a stockholder who desires
to sell a large number of shares of common stock to sell the shares in increments over time to mitigate any adverse impact of the
sales on the market price of our stock. If our stockholders sell, or the market perceives that our stockholders intend to sell
for various reasons, substantial amounts of our common stock in the public market, including shares issued upon the exercise of
outstanding options or warrants, the market price of our common stock could fall. Sales of a substantial number of shares of our
common stock may make it more difficult for us to sell equity or equity-related securities in the future at a time and price that
we deem reasonable or appropriate. We may become involved in securities class action litigation that could divert management’s
attention and harm our business.
Certain of our outstanding common stock purchase warrants contain
price protection provisions (anti-dilution protection) in the event that we sell our securities at prices lower than the current
exercise price of such warrants, which may have a negative impact on the trading price of our common stock or impair our ability
to raise capital.
As of March 31, 2019, we had 2,982,709 common stock purchase warrants
outstanding that were issued in our May 2016 registered offering, May 2016 private placement and August 2017 registered offering
that all contain price protection provisions in the event that we sell securities at a price per share below their respective exercise
prices (collectively “Price Protection Warrants”). Pursuant to our October 2018 registered offering, the Price Protection
Warrants all had their exercise prices adjusted to $0.57 per share. On April 24, 2019, the closing price of our common stock was
$0.54. In the event that we sell securities at a price per share lower than the current exercise price of the Price Protection
Warrants, their exercise prices will be further reduced. Any future adjustments to the exercise prices of the Price Protection
Warrants may have a negative impact on the trading price of our common stock. Additionally, raising additional capital with new
investors may be difficult as a result of the adjustment feature.
The requirements
of being a public company may strain our resources, divert management’s attention and affect our ability to attract and retain
qualified board members.
As a public company, we incur significant
legal, accounting and other expenses that we would not incur as a private company, including costs associated with public company
reporting requirements. We also incur costs associated with the Sarbanes-Oxley Act of 2002, as amended, the Dodd-Frank Wall Street
Reform and Consumer Protection Act and related rules implemented or to be implemented by the SEC and the Nasdaq. The expenses incurred
by public companies generally for reporting, insurance and corporate governance purposes have been increasing. We expect these
rules and regulations to increase our legal and financial compliance costs and to make some activities more time-consuming and
costly. These laws and regulations could also make it more difficult or costly for us to obtain certain types of insurance, including
director and officer liability insurance, and we may be forced to accept reduced policy limits and coverage or incur substantially
higher costs to obtain the same or similar coverage. These laws and regulations could also make it more difficult for us to attract
and retain qualified persons to serve on our board of directors, our board committees or as our executive officers and may divert
management’s attention. Furthermore, if we are unable to satisfy our obligations as a public company, we could be subject
to delisting of our common stock, fines, sanctions and other regulatory action and potentially civil litigation.
We have never paid
a cash dividend and do not intend to pay cash dividends on our common stock in the foreseeable future.
We have never paid a cash dividend, nor
do we anticipate paying cash dividends in the foreseeable future. Accordingly, any return on your investment will be as a result
of the appreciation of our common stock if any.
Our anti-takeover provisions may
delay or prevent a change of control, which could adversely affect the price of our common stock.
Our amended and restated certificate of
incorporation and amended and restated bylaws contain provisions that may make it difficult to remove our board of directors and
management and may discourage or delay “change of control” transactions, which could adversely affect the price of
our common stock. These provisions include, among others:
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our board of directors is divided into
three classes, with each class serving for a staggered three-year term, which prevents stockholders from electing an entirely new
board of directors at an annual meeting;
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advance notice procedures that stockholders
must comply with in order to nominate candidates to our board of directors and propose matters to be brought before an annual meeting
of our stockholders may discourage or deter a potential acquirer from conducting a solicitation of proxies to elect the acquirer’s
own slate of directors or otherwise attempting to obtain control of our company; and
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our board of directors may, without stockholder
approval, issue series of preferred stock, or rights to acquire preferred stock, that could dilute the interest of, or impair the
voting power of, holders of our common stock or could also be used as a method of discouraging, delaying or preventing a change
of control.
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If securities or
industry analysts do not publish research reports, or publish unfavorable research about our business, the price and trading volume
of our common stock could decline.
The trading market for our common stock
will depend in part on the research and reports that securities or industry analysts publish about us and our business. We currently
have limited research coverage by securities and industry analysts. In the event an analyst downgrades our securities the price
of our securities would likely decline. If analysts cease to cover us or fails to publish regular reports on us, interest in our
securities could decrease, which could cause the price of our common stock and other securities and their trading volume to decline.
Our
board of directors has broad discretion to issue additional securities, which might dilute the net tangible book value per share
of our common stock for existing stockholders.
We are entitled under our certificate of
incorporation to issue up to 300,000,000 shares of common stock and 7,000,000 “blank check” shares of preferred stock.
Shares of our blank check preferred stock provide our board of directors with broad authority to determine voting, dividend, conversion,
and other rights. As of March 31, 2019, we have issued and outstanding 18,205,060 shares of common stock and we have 14,757,301
shares of common stock reserved for future grants under our equity compensation plans and for issuances upon the exercise or conversion
of currently outstanding options, warrants and convertible securities. As of March 31, 2019, we had 1,000,000 shares of preferred
stock issued and outstanding which are convertible into 3,887,387 shares of our common stock. Accordingly, we are entitled to issue
up to 267,037,639 additional shares of common stock and 6,000,000 additional shares of “blank check” preferred stock.
Our board may generally issue those common and preferred shares, or convertible securities to purchase those shares, without further
approval by our shareholders. Any preferred shares we may issue will have such rights, preferences, privileges and restrictions
as may be designated from time-to-time by our board, including preferential dividend rights, voting rights, conversion rights,
redemption rights and liquidation provisions. It is likely that we will be required to issue a large amount of additional securities
to raise capital in order to further our development and marketing plans. It is also likely that we will be required to issue a
large amount of additional securities to directors, officers, employees and consultants as compensatory grants in connection with
their services, both in the form of stand-alone grants or under our various stock plans. The issuance of additional securities
may cause substantial dilution to our shareholders.
Risks Related to Government Regulation
and Approval of our Product Candidates.
The regulatory approval processes
of the FDA and comparable foreign authorities are lengthy, time consuming and inherently unpredictable, and our products may not
receive regulatory approval.
The time required to obtain approval by the FDA and comparable foreign
authorities is inherently unpredictable but typically takes many years following the commencement of clinical trials and depends
upon numerous factors, including the substantial discretion of the regulatory authorities. In addition, approval policies, regulations,
or the type and amount of clinical data necessary to gain approval may change during the course of a drug candidate’s clinical
development and may vary among jurisdictions. We have not obtained regulatory approval for any product candidate and it is possible
that none of our existing product candidates or any product candidates we may seek to develop in the future will ever obtain regulatory
approval.
Our drug candidates could fail to receive regulatory approval for many reasons, including
the following:
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the FDA or comparable foreign regulatory authorities may disagree
with the design or implementation of our clinical trials;
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we may be unable to demonstrate to the satisfaction of the FDA
or comparable foreign regulatory authorities that a product candidate is safe and effective for its proposed indication;
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the results of clinical trials may not meet the level of statistical
significance required by the FDA or comparable foreign regulatory authorities for approval;
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we may be unable to demonstrate that a product candidate’s
clinical and other benefits outweigh its safety risks;
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the FDA or comparable foreign regulatory authorities may disagree
with our interpretation of data from preclinical studies or clinical trials;
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the data collected from clinical trials of our product candidates
may not be sufficient to support the submission of a BLA, NDA or other submission or to obtain regulatory approval in the United
States or elsewhere;
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the FDA or comparable foreign regulatory authorities may fail to
approve the manufacturing processes or facilities of third-party manufacturers with which we contract for clinical and commercial
supplies; or
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the approval policies or regulations of the FDA or comparable foreign
regulatory authorities may significantly change in a manner rendering our clinical data insufficient for approval.
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We are currently undertaking clinical trials
for our lead products candidates NSI-189 and NSI-566. We cannot assure you that we will successfully complete any clinical
trials in connection with such INDs. Further, we cannot predict when we might first submit any product license application
(NDA or BLA) for FDA approval or whether any such product license application will be granted on a timely basis, if at all.
Any delay in obtaining, or failure to obtain, such approvals could have a material adverse effect on the marketing of our products
and our ability to generate product revenue.
Development of our product candidates
is subject to extensive government regulation.
Our research and development efforts, as
well as any future clinical trials, and the manufacturing and marketing of any products we may develop, will be subject to, and
restricted by, extensive regulation by governmental authorities in the U.S. and other countries. The process of obtaining FDA and
other necessary regulatory approvals is lengthy, expensive and uncertain. FDA and other legal and regulatory requirements applicable
to our proposed products could substantially delay or prevent us from initiating additional clinical trials. We may fail to obtain
the necessary approvals to commence clinical testing or to manufacture or market our potential products in reasonable time frames,
if at all. In addition, the U.S. Congress and other legislative bodies may enact regulatory reforms or restrictions on the development
of new therapies that could adversely affect the regulatory environment in which we operate or the development of any products
we may develop.
A substantial portion of our research and
development entails the use of stem cells obtained from human tissue. The U.S. federal and state governments and other jurisdictions
impose restrictions on the acquisition and use of human tissue, including those incorporated in federal Good Tissue Practice, or
“GTP,” regulations. These regulatory and other constraints could prevent us from obtaining cells and other components
of our products in the quantity or of the quality needed for their development or commercialization. These restrictions change
from time to time and may become more onerous. Additionally, we may not be able to identify or develop reliable sources for the
cells necessary for our potential products — that is, sources that follow all state and federal laws and guidelines for cell
procurement. Certain components used to manufacture our stem and progenitor cell product candidates will need to be manufactured
in compliance with the FDA’s GMP. Accordingly, we will need to enter into supply agreements with companies that manufacture
these components to GMP standards. There is no assurance that we will be able to enter into any such agreements.
Noncompliance with applicable regulatory
requirements can subject us, our third party suppliers and manufacturers and our other collaborators to administrative and judicial
sanctions, such as, among other things, warning letters, fines and other monetary payments, recall or seizure of products, criminal
proceedings, suspension or withdrawal of regulatory approvals, interruption or cessation of clinical trials, total or partial suspension
of production or distribution, injunctions, limitations on or the elimination of claims we can make for our products, refusal of
the government to enter into supply contracts or fund research, or government delay in approving or refusal to approve new drug
applications.
We cannot predict if or when we will be able to commercialize
our products due to regulatory constraints.
Federal, state and local governments and
agencies in the U.S. (including the FDA) and governments in other countries have significant regulations in place that govern many
of our activities. We are, or may become, subject to various federal, state and local laws, regulations and recommendations
relating to safe working conditions, laboratory and manufacturing practices, the experimental use of animals and the use and disposal
of hazardous or potentially hazardous substances used in connection with its research and development work. The preclinical testing
and clinical trials of our proposed products are subject to extensive government regulation that may prevent us from creating commercially
viable products. In addition, our sale of any commercially viable product will be subject to government regulation from several
standpoints, including manufacturing, advertising, marketing, promoting, selling, labeling and distributing. If, and
to the extent that, we are unable to comply with these regulations, our ability to earn revenues, if any, will be materially and
negatively impacted.
If our clinical trials fail to demonstrate
that any of our product candidates are safe and effective for the treatment of particular diseases, the FDA may require us to conduct
additional clinical trials or may not grant us marketing approval for such product candidates for those diseases.
We are not permitted to market our product
candidates in the United States until we receive approval of a BLA or NDA from the FDA. Before obtaining regulatory approvals for
the commercial sale of any product candidate for a target indication, we must demonstrate with evidence gathered in preclinical
and well-controlled clinical trials, and, with respect to approval in the United States, to the satisfaction of the FDA and, with
respect to approval in other countries, similar regulatory authorities in those countries, that the product candidate is safe and
effective for use for that target indication and that the manufacturing facilities, processes and controls used to produce the
product are compliant with applicable statutory and regulatory requirements. Our failure to adequately demonstrate the safety and
effectiveness of any of our product candidates for the treatment of particular diseases may delay or prevent our receipt of the
FDA’s approval and, ultimately, may prevent commercialization of our product candidates for those diseases. The FDA has substantial
discretion in deciding whether, based on the benefits and risks in a particular disease, any of our product candidates should be
granted approval for the treatment of that particular disease. Even if we believe that a clinical trial or trials has demonstrated
the safety and statistically significant efficacy of any of our product candidates for the treatment of a disease, the results
may not be satisfactory to the FDA. Preclinical and clinical data can be interpreted by the FDA and other regulatory authorities
in different ways, which could delay, limit or prevent regulatory approval. If regulatory delays are significant or regulatory
approval is limited or denied altogether, our financial results and the commercial prospects for those of our product candidates
involved will be harmed, and our prospects for profitability will be significantly impaired.
Satisfaction of these and other regulatory
requirements is costly, time consuming, uncertain, and subject to unanticipated delays. Despite our efforts, our drug candidates
may not:
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offer improvement over existing comparable
products;
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be proven safe and effective in clinical
trials; or
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meet applicable regulatory standards.
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In addition, in the course of its review
of a BLA or NDA or other regulatory application, the FDA or other regulatory authorities may conduct audits of the practices and
procedures of a company and its suppliers and contractors concerning manufacturing, clinical study conduct, non-clinical studies
and several other areas. If the FDA and/or other regulatory authorities conducts an audit relating to a BLA, NDA or other regulatory
application and finds a significant deficiency in any of these or other areas, the FDA or other regulatory authorities could delay
or not approve such BLA, NDA or other regulatory application. If regulatory delays are significant or regulatory approval is limited
or denied altogether, our financial results and the commercial prospects for those of our products or product candidates involved
will be harmed, and our prospects for profitability will be significantly impaired.
Both before and after marketing approval,
our product candidates are subject to extensive and rigorous ongoing regulatory requirements and continued regulatory review, and
if we fail to comply with these continuing requirements, we could be subject to a variety of sanctions.
Both before and after the approval of our
product candidates, we, our product candidates, our operations, our facilities, our suppliers, and our contract manufacturers,
contract research organizations, and contract testing laboratories are subject to extensive regulation by governmental authorities
in the United States and other countries, with regulations differing from country to country. In the United States, the FDA regulates,
among other things, the pre-clinical testing, clinical trials, manufacturing, safety, efficacy, potency, labeling, packaging, adverse
event reporting, storage, record keeping, quality systems, advertising, promotion, sale and distribution of therapeutic products.
These requirements include submissions of safety and other post-marketing information and reports, registration, as well as continued
compliance with cGMP, requirements and current good clinical practice, or cGCP, requirements for any clinical trials that we conduct
post-approval. Failure to comply with applicable requirements could result in, among other things, one or more of the following
actions: restrictions on the marketing of our products or their manufacturing processes, notices of violation, untitled letters,
warning letters, civil penalties, fines and other monetary penalties, unanticipated expenditures, delays in approval or refusal
to approve a product candidate, suspension or withdrawal of regulatory approvals, product, seizure or detention, voluntary or mandatory
product recalls and related publicity requirements, interruption of manufacturing or clinical trials, operating restrictions, injunctions,
import or export bans, and criminal prosecution. We or the FDA, or an institutional review board, may suspend or terminate human
clinical trials at any time on various grounds, including a finding that subjects are being exposed to an unacceptable health risk.
The FDA’s policies may change, and additional government regulations
may be enacted that could prevent, limit or delay regulatory approval of our drug candidates. If we are slow or unable to adapt
to changes in existing or new requirements or policies, or if we are not able to maintain regulatory compliance, we may lose any
marketing approval that we may have obtained, which would adversely affect our business, prospects and ability to achieve or sustain
profitability.
If side effects are identified during the time our drug candidates
are in development or after they are approved and on the market, we may choose or be required to perform lengthy additional clinical
trials, discontinue development of the affected drug candidate, change the labeling of any such products, or withdraw any such
products from the market, any of which would hinder or preclude our ability to generate revenues.
Undesirable side effects caused by our drug candidates could cause
us or regulatory authorities to interrupt, delay or halt clinical trials and could result in a more restrictive label or the delay
or denial of regulatory approval by the FDA or other comparable foreign authorities. Drug-related side effects could affect patient
recruitment or the ability of enrolled patients to complete a trial or result in potential product liability claims. Any of these
occurrences may harm our business, financial condition and prospects significantly. Even if any of our drug candidates receives
marketing approval, as greater numbers of patients use a drug following its approval, an increase in the incidence of side effects
or the incidence of other post-approval problems that were not seen or anticipated during pre-approval clinical trials could result
in a number of potentially significant negative consequences, including:
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regulatory authorities may withdraw their approval of the product;
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regulatory authorities may require the addition of labeling statements,
such as warnings or contradictions;
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we may be required to change the way the product is administered,
conduct additional clinical trials or change the labeling of the product;
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we could be sued and held liable for harm caused to patients; and
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our reputation may suffer.
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Any of these events could substantially increase the costs and expenses
of developing, commercializing and marketing any such drug candidates or could harm or prevent sales of any approved products.
Even if our product candidates receive regulatory approval
in the United States, we may never receive approval or commercialize our products outside of the United States.
In order to market any products outside of the United States, we
must establish and comply with numerous and varying regulatory requirements of other countries regarding safety and efficacy. Approval
procedures vary among countries and can involve additional product testing and additional administrative review periods. The time
required to obtain approval in other countries might differ from that required to obtain FDA approval. The regulatory approval
process in other countries may include all of the risks detailed above regarding FDA approval in the United States as well as other
risks. Regulatory approval in one country does not ensure regulatory approval in another, but a failure or delay in obtaining regulatory
approval in one country may have a negative effect on the regulatory process in others. Failure to obtain regulatory approval in
other countries or any delay or setback in obtaining such approval would impair our ability to develop foreign markets for our
drug candidates.
Our product candidates for which we intend to seek approval
as biologic products may face competition sooner than anticipated.
We expect our stem cell product candidates to be regulated by the
FDA as biologic products and we intend to seek approval for these products pursuant to the BLA pathway. The Biologics Price Competition
and Innovation Act of 2009, or BPCIA, created an abbreviated pathway for the approval of biosimilar and interchangeable biologic
products. The abbreviated regulatory pathway establishes legal authority for the FDA to review and approve biosimilar biologics,
including the possible designation of a biosimilar as “interchangeable” based on its similarity to an existing brand
product. Under the BPCIA, an application for a biosimilar product cannot be approved by the FDA until 12 years after the original
branded product was approved under a BLA. The law is complex and is still being interpreted and implemented by the FDA. As a result,
its ultimate impact, implementation, and meaning are subject to uncertainty. While it is uncertain when such processes intended
to implement BPCIA may be fully adopted by the FDA, any such processes could have a material adverse effect on the future commercial
prospects for our biologic products.
We believe that any of our product candidates
approved as a biologic product under a BLA should qualify for the 12-year period of exclusivity. However, there is a risk that
this exclusivity could be shortened due to congressional action or otherwise, or that the FDA will not consider our drug candidates
to be reference products for competing products, potentially creating the opportunity for generic competition sooner than anticipated.
Moreover, the extent to which a biosimilar, once approved, will be substituted for any one of our reference products in a way that
is similar to traditional generic substitution for non-biologic products is not yet clear, and will depend on a number of marketplace
and regulatory factors that are still developing.
We are subject to healthcare laws, regulation and enforcement
and our failure to comply with those laws could adversely affect our business, operations and financial condition.
Even though we do not and will not control referrals of healthcare
services or bill directly to Medicare, Medicaid or other third-party payors, certain federal and state healthcare laws and regulations
pertaining to fraud and abuse and patients’ rights are and will be applicable to our business. We could be subject to healthcare
fraud and abuse and patient privacy regulation by both the federal government and the states in which we conduct our business.
The regulations that may affect our ability to operate include, without limitation:
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the federal Anti-Kickback Statute, which prohibits, among other things, any person from knowingly
and willfully offering, soliciting, receiving or providing remuneration, directly or indirectly, to induce either the referral
of an individual, for an item or service or the purchasing or ordering of a good or service, for which payment may be made under
federal healthcare programs such as the Medicare and Medicaid programs;
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the federal False Claims Act, which prohibits, among other things, individuals or entities from
knowingly presenting, or causing to be presented, false claims, or knowingly using false statements, to obtain payment from the
federal government, and which may apply to entities that provide coding and billing advice to customers;
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federal criminal laws that prohibit executing a scheme to defraud any healthcare benefit program
or making false statements relating to healthcare matters;
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the federal physician sunshine requirements under the ACA, which require manufacturers of drugs,
devices, biologics, and medical supplies to report annually to the Centers for Medicare & Medicaid Services information related
to payments and other transfers of value to physicians, other healthcare providers, and teaching hospitals, and ownership and investment
interests held by physicians and other healthcare providers and their immediate family members; and
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HIPAA, which governs the conduct of certain electronic healthcare transactions and protects the
security and privacy of protected health information.
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In addition, recent healthcare reform legislation has strengthened
these laws. For example, the ACA, among other things, amended the intent requirement of the Federal Anti-Kickback Statute and criminal
healthcare fraud statutes. A person or entity no longer needs to have actual knowledge of the statute or specific intent to violate
it. In addition, the ACA provides that the government may assert that a claim including items or services resulting from a violation
of the Federal Anti-Kickback Statute constitutes a false or fraudulent claim for purposes of the False Claims Act.
These laws and regulations are broad in scope and they are subject
to change and evolving interpretations, which could require us to incur substantial costs associated with compliance or to alter
one or more of our sales or marketing practices. In addition, any action against us for violation of these laws, even if we successfully
defend against it, could cause us to incur significant legal expenses and divert our management’s attention from the operation
of our business. If our operations are found to be in violation of any of the laws described above or any other governmental regulations
that apply to us, we may be subject to penalties, including civil and criminal penalties, damages, fines, the exclusion from participation
in federal and state healthcare programs, imprisonment, or the curtailment or restructuring of our operations, any of which could
adversely affect our ability to operate our business and our financial results.
Failure to comply with domestic and international privacy and security
laws can result in the imposition of significant civil and criminal penalties. The costs of compliance with these laws, including
protecting electronically stored information from cyberattacks, and potential liability associated with failure to do so could
adversely affect our business, financial condition and results of operations. We are subject to various domestic and international
privacy and security regulations, including but not limited to HIPAA. HIPAA mandates, among other things, the adoption of uniform
standards for the electronic exchange of information in common healthcare transactions, as well as standards relating to the privacy
and security of individually identifiable health information, which require the adoption of administrative, physical and technical
safeguards to protect such information. In addition, many states have enacted comparable laws addressing the privacy and security
of health information, some of which are more stringent than HIPAA.
