Investing in our common stock involves a high degree of risk. You
should carefully consider the risks and uncertainties described below, together with all of the other information in this Quarterly Report on Form
10-Q,
before making an investment decision. The risks and
uncertainties described below may not be the only ones we face. If any of the risks actually occur, our business, financial condition, operating results, cash flows and prospects could be materially and adversely affected. In
that event, the market price of our common stock could decline, and you could lose part or all of your investment.
Risks
Relating to our Financial Condition and Need for Additional Capital
We have a limited operating history and expect to generate significant
losses for the foreseeable future. If we do not generate significant revenue, we will not be profitable.
With the exception of two
years, we have incurred annual net operating losses since inception, and to date have generated only limited revenue from government contracts, service agreements, collaboration agreements, and reagent protein product sales. We have recognized net
losses of $31.2 million and $28.2 million for the nine months ended September 30, 2017 and the year ended December 31, 2015, respectively, and net income of $16.1 million and $5.5 million for the nine months ended September
30, 2016 and the year ending December 31, 2016, respectively. As of September 30, 2017, we had an accumulated deficit of $167.2 million and net working capital of $36.7 million. To date, we have funded our operations primarily
through the sale and issuance of common stock in our public offerings, revenue from our collaboration agreements, government contracts, service agreements, and reagent protein product sales, our prior credit facility and the private placement of
equity securities. As of September 30, 2017, we had capital resources consisting of cash and cash equivalents of $48.4 million. As we continue to develop and invest more resources into the development and commercialization of our
product candidates, our net operating losses will increase over the next several years. To become profitable, we must successfully develop and obtain regulatory approval for our product candidates, and effectively manufacture and commercialize the
product candidates we develop. If we obtain regulatory approval to market a product candidate, our future revenue will depend upon the size of any markets in which our product candidates may receive approval, and our and our collaboration
partners ability to achieve sufficient market acceptance, pricing, reimbursement from third-party payors, and adequate market share for our product candidates in those markets. We may never succeed in these activities and therefore may never
generate revenue that is significant or large enough to achieve profitability. Even if we do achieve profitability, we may not be able to sustain or increase profitability on a quarterly or annual basis. Our failure to become and remain profitable
could depress the market price of our common stock and could impair our ability to raise capital, expand our business, diversify our product offerings or continue our operations.
We will require substantial additional funds to seek and obtain regulatory approval for and commercialize our two most advanced product candidates and
our other product candidates and, if additional capital is not available, we may need to limit, scale back or cease our operations.
Since our inception, a significant portion of our resources have been dedicated to the preclinical and clinical development of our product
candidates, including PF708, Px563L/RPA563, PF582, and PF529. We believe that we will continue to expend substantial resources for the foreseeable future for the preclinical and clinical development of our current product pipeline, and the
development of any other indications and product candidates we may choose to pursue, either alone or with a strategic collaboration partner. These expenditures will include costs associated with research and development, conducting preclinical
studies and clinical studies, and manufacturing and supply as well as marketing and selling any products that receive marketing authorization. In addition, other unanticipated costs may arise. Because the outcome of any clinical trial is highly
uncertain, we cannot reasonably estimate the actual amounts necessary to successfully complete the development and commercialization of PF708, Px563L/RPA563, and our pipeline of other product candidates and preclinical products under development.
Following our strategic review in November 2017, we decided to pause our development activities for PF582 and PF529, and focus our efforts and resources elsewhere in the product portfolio until strategic partnerships for these candidates are forged.
In the future, we may be required to devote additional resources to the development of PF582 or PF529, or obtain a new collaboration partner on short notice, and the terms of any additional collaboration or other arrangements that we establish may
not be favorable to us. We may also need to obtain substantial additional sources of funding to
24
develop PF708 and Px563L/RPA563 as currently contemplated. If such additional funding is not available on favorable terms or at all, we may need to delay or reduce the scope of our PF708 and
Px563L/RPA563 development programs, or grant rights in the United States, as well as outside the United States, to our product candidates to one or more partners.
We believe that our available cash and cash equivalents, including the proceeds from any revenue from our government contracts, service
agreements, collaboration agreement, and reagent protein product sales will allow us to fund our operations for at least the next 12 months, including costs associated with the anticipated submission of the PF708 NDA to the FDA. However, changing
circumstances and risks and uncertainties associated with our product development efforts may cause us to consume capital significantly faster than we currently anticipate, and we may need to spend more money than currently expected. Our future
capital requirements may vary depending on the following:
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the timing and extent of spending on our research and development efforts, including with respect to PF708 and our other product candidates;
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our ability to enter into and maintain collaboration, licensing, commercialization and other arrangements and the terms and timing of such arrangements;
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the cost of manufacturing and commercialization activities, if any;
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the receipt of any collaboration or milestone payments;
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the scope, rate of progress, results and cost of our clinical trials, preclinical testing and other related activities;
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the emergence of competing technologies or other adverse market developments;
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the time and costs involved in seeking and obtaining regulatory and marketing approvals in multiple jurisdictions for our product candidates that successfully complete clinical trials;
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the cost of preparing, filing, prosecuting, defending and enforcing any patent claims and other intellectual property rights;
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the introduction of new product candidates and the number and characteristics of product candidates that we pursue;
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the timing, receipt and amount of sales, profit sharing or royalties, if any, from our potential products;
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if approved, the degree and rate of market acceptance of any products launched by us or our collaboration partner;
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the expansion of our sales and marketing activities; and
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the potential acquisition and
in-licensing
of other technologies, products or assets.
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If we were to experience any delays or encounter issues with any of the above, including clinical holds, failed studies, inconclusive or
hard-to-interpret
results, safety or efficacy issues, or other regulatory challenges that require longer
follow-up
of existing studies,
additional major studies, or additional supportive studies in order to pursue marketing approval, it could further increase the costs associated with the above and delay revenues.
We will need to raise additional capital to fund our operations in the near future. If we seek additional funding in the future, additional
funds may not be available to us on acceptable terms or at all. We may seek to raise additional funds through equity, equity-linked or debt financings. If we raise additional funds through the incurrence of indebtedness, such indebtedness would have
rights that are senior to holders of our equity securities and could contain covenants that restrict our operations. Any additional equity financing may be dilutive to our stockholders. If we are unable to obtain funding on a timely basis, we may be
required to significantly curtail the advancement of one or more of our product candidates. We also could be required to seek funds through arrangements with collaboration partners or others that may require us to relinquish rights to some of our
technologies or product candidates which we would otherwise pursue on our own.
Any further development of PF582 and PF529 will require significant
resources from us or another collaboration partner, and in the event that we do not find a collaboration partner, the development of PF582 and PF529 could be significantly delayed or result in the discontinuation of the development of PF582 and
PF529.
In November 2017, we completed our strategic review of PF582 and PF529, our biosimilar product candidates to Lucentis
®
and Neulasta
®
, respectively. The strategic review considered the timeline for development and cost of both programs. As a result of our
strategic review, we decided to pause development activities on PF582 and PF529 and focus development efforts elsewhere within the product portfolio while we continue to engage potential strategic partners to monetize PF582 and PF529. Further
development of
25
PF582 and PF529 will require significant resources from us or another collaboration partner. We or a new collaboration partner will be responsible for funding any new PF582 and PF529 development
and clinical trial activities going forward. Any such further development will require significant resources to develop and commercialize PF582 and PF529, and such further development may not be possible in the near term without a new
collaboration partner
.
There are no assurances that we will have access to additional capital or find a new collaboration partner or that the terms and timing of any such arrangements would be acceptable to us. As a result, we could
experience a significant delay in the PF582 and PF529 development processes. If we determine instead to discontinue the development of PF582 or PF529, we will not receive any future return on our investment from that product candidate.
Our quarterly operating results may fluctuate significantly.
Our operating results are subject to quarterly fluctuations. Our operating results are affected by numerous factors, including:
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variations in the level of expenses related to our PF708, Px563L/RPA563 and other development programs;
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addition or termination of clinical trials;
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any intellectual property infringement lawsuit in which we may become involved;
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regulatory developments affecting any of our products; and
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our execution of any service, collaborative, licensing or similar arrangements, and the timing of payments we may make or receive under these arrangements.
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If our quarterly operating results fall below the expectations of investors or securities analysts, the market price of our common stock could
decline substantially. Furthermore, any quarterly fluctuations in our operating results may, in turn, cause the market price of our stock to fluctuate substantially.
Risks Relating to our Business and our Industry
Our business operations are dependent upon our new senior management team and the ability of our other new employees to execute on our business strategy.
If we fail to attract, integrate, and keep senior management and key scientific personnel, we may be unable to successfully develop PF708, Px563L/RPA563 or any other product candidates, conduct our clinical trials and commercialize PF708,
Px563L/RPA563 or any other product candidates we develop.
Our success depends in part on our continued ability to attract,
integrate, retain, and motivate highly qualified management, clinical and scientific personnel, including our ability to develop an effective working relationship among senior management. Our senior management has substantially changed over the last
year, including, for example, the recent departures of our former chief executive officer, Bertrand Liang, former chief financial officer, Paul Wagner, and former chief manufacturing officer, Steven Sandoval. We have a new president and chief
executive officer, Eef Schimmelpennink, who started in August 2017 and we are currently undertaking a search for a new chief financial officer.
As new employees gain experience in their roles, we could experience inefficiencies or a lack of business continuity due to loss of historical
knowledge and a lack of familiarity of new employees with business processes, operating requirements, policies and procedures, and we may experience additional costs as new employees gain necessary experience. It is important to our success that
these key employees quickly adapt to and excel in their new roles. If they are unable to do so, our business and financial results could be materially adversely affected. In addition, the loss of the services of any member of our senior management
or our scientific or technical support staff might significantly delay or prevent the development of our products or achievement of other business objectives by diverting managements attention to transition matters and identification of
suitable replacements, if any, and could have a material adverse effect on our business.
We believe that our future success is highly
dependent upon the contributions of our senior management, particularly our Chief Executive Officer, Chief Business Officer, and Chief Medical and Scientific Officer, as well as our senior scientists and other members of our senior management team.
Employment agreements with our Chief Executive Officer, Chief Business Officer, and Chief Medical and Scientific Officer, as well as our offer letters with our senior scientists, all provide for
at-will
employment. The loss of services of any of these individuals could delay or prevent the successful development of our product pipeline, completion of our planned clinical trials or the
commercialization of PF708, Px563L/RPA563, or any other products we develop.
Competition for qualified personnel in the biotechnology and
pharmaceuticals industry is intense due to the limited number of individuals who possess the skills and experience required. To help attract, retain, and motivate qualified employees, we use share-based incentive awards such as employee stock
options. Other companies may provide more generous compensation and benefits,
26
more diverse opportunities and better chances for career advancement than we do. Some of these advantages may be more appealing to high-quality candidates and employees than those we have to
offer. In addition, the decline in our stock price has created additional challenges related to our ability to compete effectively with respect to equity compensation. We may need to hire additional personnel as we expand our clinical development
and commercial activities. We may not be able to attract and retain quality personnel on acceptable terms, or at all, which may cause our business and operating results to suffer.
If an improved version of a reference product, such as Forteo, is developed, or if the market for a reference product significantly declines, sales or
potential sales of our biosimilar and therapeutic equivalent product candidates may suffer.
Reference product sponsor companies
may develop improved versions of a reference product as part of a life cycle extension strategy, and may obtain regulatory approval of the improved version under a supplemental biologics license application, or BLA. If a reference product sponsor
company succeeds in obtaining an approval of an improved product, it may capture a significant share of the collective reference product market and significantly reduce the market for the reference product, and thereby the potential size of the
market for our biosimilar and therapeutic equivalent product candidates. In addition, the improved product may be protected by additional patent rights.
Additionally, competition in the pharmaceutical market is intense. Reference products face competition on numerous fronts as technological
advances are made that may offer patients a more convenient form of administration or increased efficacy, or as new products are introduced. As new products are approved that compete with the reference product to our biosimilar or therapeutic
equivalent product candidates, such as Forteo, sales of the reference products may be significantly and adversely impacted and may render the reference product obsolete. If the market for the reference product is impacted, we in turn may lose
significant market share or market potential for our products and product candidates. As a result, the value of our product pipeline could be negatively impacted and our business, prospects and financial condition could suffer.
Our product candidates, if approved, will face significant competition from the reference products and from other biosimilars and therapeutic equivalent
products of the reference products, and from other products. Our failure to effectively compete may prevent us from achieving significant market penetration and expansion.
We expect to enter highly competitive pharmaceutical markets. Successful competitors in the pharmaceutical market have the ability to
effectively discover, obtain patents, develop, test and obtain regulatory approvals for products, as well as the ability to effectively commercialize, market and promote approved products, including communicating the effectiveness, safety and value
of products to consumers and medical professionals. Numerous companies, universities, and other research institutions are engaged in developing, patenting, manufacturing and marketing of products competitive with those that we are developing. Many
of these potential competitors, such as Novartis AG, Genentech, Inc., a wholly-owned member of the Roche Group, Amgen Inc. and Eli Lilly and Company, are large, experienced companies that enjoy significant competitive advantages, such as
substantially greater financial, research and development, manufacturing, personnel and marketing resources. Recent and potential future merger and acquisition activity in the biotechnology and pharmaceutical industries are likely to result in even
more resources being concentrated among a smaller number of our competitors. These companies also maintain greater brand recognition and more experience and expertise in undertaking preclinical testing and clinical trials of product candidates, and
obtaining the U.S. Food and Drug Administration, or FDA, and other regulatory approvals of products. Established pharmaceutical companies may also invest heavily to accelerate discovery and development of novel compounds that could make our product
candidates obsolete.
In addition, our biosimilar, therapeutic equivalent and vaccine products may face competition from companies that
develop and commercialize biosimilars, therapeutic equivalent products and vaccines that compete directly with our products. See
Risks Related to Government Regulation If other therapeutic equivalent products to Forteo are approved
and successfully commercialized before PF708, our business would suffer.
Use of our product candidates could be associated with side
effects or adverse events.
Use of our product candidates could be associated with side effects or adverse events which can vary
in severity (from minor reactions to death) and frequency (infrequent or prevalent). Side effects or adverse events associated with the use of our product candidates may be observed at any time, including in clinical trials or when a product is
commercialized, and any such side effects or adverse events may negatively affect our and our collaboration partners ability to obtain and maintain regulatory approval or market our product candidates. Side effects such as toxicity or other
safety issues associated with the use of our product candidates could require us or our collaboration partner to perform additional studies or halt development or sale of these product candidates or expose us to product liability lawsuits which
would harm our business. We may be required by regulatory agencies to conduct additional
27
animal or human studies regarding the safety and efficacy of our product candidates which we have not planned or anticipated. We may also be required to change our product labeling, including
increasing the prominence and content of warnings and contraindications for our products. There can be no assurance that we will resolve any issues related to any product-related adverse events to the satisfaction of the FDA or any regulatory agency
in a timely manner or ever, which could harm our business, prospects and financial condition.
In addition, if we and any future
collaboration partner are successful in commercializing PF708, Px563L/RPA563 or any other product candidates, the FDA, European Medicines Agency, or EMA, European Economic Area Competent Authorities, or EEA Competent Authorities, and other foreign
regulatory agency regulations require that we timely report certain information about adverse medical events if those products may have caused or contributed to those adverse events. The timing of our obligation to report would be triggered by the
date we become aware of the adverse event as well as the nature of the event. We or our collaboration partner may fail to report adverse events we become aware of within the prescribed timeframe. We or our collaboration partner may also fail to
appreciate that we or our collaboration partner have become aware of a reportable adverse event, especially if it is not reported to us as an adverse event or if it is an adverse event that is unexpected or removed in time from the use of our
products. If we or our collaboration partner fail to comply with our reporting obligations, the FDA, the EMA, EEA Competent Authorities, or other foreign regulatory agencies could take action including criminal prosecution, the imposition of civil
monetary penalties, seizure of our products, or delay in approval or clearance of our products.
We currently rely on a limited number of third
parties for a substantial portion of our revenue. The loss of or a change in any of these third parties, including its creditworthiness, could materially reduce our revenue and adversely impact our financial position.
One third party accounted for more than 10% of our 2016 revenue, two third parties accounted for more than 10% of our 2015 revenue, and three
third parties accounted for more than 10% of our revenue in 2014. Pfizer accounted for more than 10% of our 2016 revenue, and Pfizer and the Biomedical Advanced Research and Development Authority, or BARDA, each accounted for more than 10% of our
revenue in 2015. BARDA, the National Institute of Allergy and Infectious Diseases, or NIAID, and Boehringer Ingelheim International GmbH each accounted for more than 10% of our revenue in 2014.
In August 2016, we entered into a termination agreement with Pfizer pursuant to which our development and license agreement was terminated and
all rights to PF582 returned to us. The termination accelerated recognition of $45.8 million of revenue that had been previously deferred and we will not recognize any additional future revenue under this agreement. Pfizer will no longer be
responsible for manufacturing, clinical studies and commercialization of PF582. We will not receive additional revenue from Pfizer.
In
addition, in August of 2017, we and Strides Arcolab entered into a termination agreement pursuant to which our joint venture was terminated. While there was no activity under the joint venture with Strides Arcolab to date, following the termination
we solely own the product candidates that were previously subject to the joint venture with Strides Arcolab.
The loss of any key
collaboration partner or any significant adverse change in the size or terms of a contract with a key third party, such as the termination of the development and license agreement with Pfizer in August 2016, could significantly reduce our revenue
over the short term. Moreover, having our revenue concentrated among a limited number of entities creates a concentration of financial risk for us, and in the event that any significant third party is unable to fulfill its payment obligations to us,
our operating results and cash position would suffer. See
Risks Relating to our Reliance on Third Parties We are substantially dependent on the expertise of Jazz to develop and commercialize some of our product candidates. If we fail
to maintain our current strategic relationship with Jazz, our business, commercialization prospects and financial condition may be materially adversely affected.
We may fail to select or capitalize on the most scientifically, clinically or commercially promising or profitable product candidates.
We continue to evaluate our business strategy and, as a result, may modify our strategy in the future. In this regard, we may, from time to
time, focus our product development efforts on different product candidates or may delay, suspend or terminate the future development of a product candidate at any time for strategic, business, financial or other reasons. For example, we decided to
pause development activities on PF582 and PF529 and focus development efforts elsewhere within the product portfolio while we continue to engage potential strategic partners to monetize PF582 and PF529. As a result of changes in our strategy, we
have and may in the future change or refocus our existing product development, commercialization and manufacturing activities. This could require changes in our facilities and our personnel. Any product development changes that we implement may not
be successful. In particular, we may fail to select or capitalize on the most scientifically, clinically or commercially promising or profitable product candidates. Our decisions to allocate our research and development, management and financial
resources toward particular product candidates may not lead to the development of viable commercial products and may divert resources from better opportunities. Similarly, our decisions to delay or terminate product development programs may also
prove to be incorrect and could cause us to miss valuable opportunities.
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We currently have limited marketing capabilities and no sales organization.
We currently have limited sales and marketing capabilities. We have no prior experience in the marketing, sale and distribution of
pharmaceutical products and there are significant risks involved in building and managing a sales organization, including our ability to hire, retain and incentivize qualified individuals, generate sufficient sales leads, provide adequate training
to sales and marketing personnel and effectively manage a geographically dispersed sales and marketing team.
For PF708, we will need to
identify potential sales, marketing and distribution partners or establish our own internal sales force. In the future, we may choose to collaborate with other third parties that have direct sales forces and established distribution systems, either
to augment our own sales force or in lieu of our own sales force. If we are unable to enter into such arrangements on acceptable terms or at all, we may not be able to successfully commercialize our product candidates. If we are not successful in
commercializing our product candidates, either on our own or through collaborations with one or more third parties, our future product revenue will suffer and we would incur significant additional losses.
We enter into various contracts in the normal course of our business that periodically incorporate provisions whereby we indemnify the other party to
the contract. In the event we would have to perform under these indemnification provisions, it could have a material adverse effect on our business, financial position and results of operations.
In the normal course of business, we periodically enter into academic, commercial and consulting agreements that contain indemnification
provisions. With respect to our academic agreements, we may be required to indemnify the institution and related parties from losses arising from claims relating to the products, processes or services made, used, sold or performed pursuant to the
agreements for which we have secured licenses, and from claims arising from our or our sublicensees exercise of rights under the agreement. With respect to commercial agreements entered into with our protein production customers, we typically
provide indemnification for claims from third parties arising out of any potential intellectual property infringement associated with our P
f
ēnex Expression Technology
®
in the
course of performing our services. With respect to our commercial agreements, the bulk of which are with contract manufacturers, we indemnify our vendors from third-party product liability claims which result from the production, use or consumption
of the product, as well as for certain alleged infringements of any patent or other intellectual property right by a third party. With respect to consultants, we indemnify them from claims arising from the good faith performance of their services.
In all of the above cases, we do not indemnify the parties for claims resulting from the negligence or willful misconduct of the indemnified party.
In certain circumstances, we maintain insurance coverage which we believe may limit our obligations under certain of these indemnification
provisions. However, we do not carry insurance for all risks that our business may encounter, including our obligations under certain indemnification provisions. To the extent we do not have insurance to cover certain indemnification obligations, we
are denied insurance coverage, or our obligation under an indemnification provision exceeds applicable insurance coverage, any significant, uninsured liability may require us to pay substantial amounts, which would adversely affect our working
capital and results of operations.
We may have difficulty expanding our operations successfully.
As we advance our product candidates through the development process, we will need to expand our development, regulatory, manufacturing,
quality, sales and marketing capabilities or contract with other organizations to provide these capabilities for us. As our operations expand, we expect that we will need to manage additional relationships with various collaboration partners,
suppliers and other organizations.
As of September 30, 2017, we had 71 full-time employees. Our management and personnel, systems
and facilities currently in place may not be adequate to support this future growth. Therefore, we will need to continue to expand our managerial, operational, finance and other resources to manage our operations and clinical trials, continue our
development activities and commercialize our product candidates, if approved. In order to effectively execute our growth strategy, we will be required to:
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manage our clinical trials effectively;
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identify, recruit, retain, incentivize and integrate additional employees;
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establish and maintain collaborations with third parties for the development and commercialization of our product candidates, or otherwise build and maintain a sales, marketing and distribution infrastructure to
commercialize any products for which we may obtain marketing approval;
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manage our internal development efforts effectively while carrying out our contractual obligations to third parties; and
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continue to improve our operational, financial and management controls, reporting systems and procedures.
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Due to our limited financial resources and our limited experience in managing a company with
such anticipated growth, we may not be able to effectively manage the expansion of our operations or recruit and train additional qualified personnel. In addition, this expansion of our operations may lead to significant costs and may divert our
management and business development resources. Any inability to manage growth could delay the execution of our development and strategic objectives, or disrupt our operations, which could materially impact our business, revenue, and operating
results.
The U.S. government holds certain intellectual property rights related to our Anthrax vaccines, Px563L and RPA563 and Malaria vaccine,
Px533.
Although we have intellectual property related to expression of recombinant protective antigen in
P. fluorescens
,
the U.S. government holds certain patents related to the recombinant protective antigen in RPA563 and Px563L, as well as certain license rights to intellectual property related to other Px563L components used to produce the final vaccine, which, if
exercised, could materially impact our business, revenue and operating results. We have rights to utilize this intellectual property held by the U.S. government by virtue of the Authorization and Consent clauses of our contracts with the U.S.
government.
Our contracts with the U.S. government, and our subcontracts with U.S. government contractors, require ongoing funding decisions by the
U.S. government; reduced or discontinued funding of these contracts could cause our financial condition and operating results to suffer materially.
Development of our anthrax vaccines, RPA563 and Px563L, is funded by BARDA and development of our
Px563L-SDI
anthrax vaccine and our malaria vaccine, Px533, is funded by NIAID. The funding for government programs is subject to Congressional appropriations, often made on a fiscal year basis, even for
programs designed to continue for several years. These appropriations can be subject to political considerations and stringent budgetary constraints. Additionally, our government-funded development contracts give the U.S. government the right,
exercisable in its sole discretion, to extend this contract for successive options following a base period of performance. The value of the services to be performed during these options may constitute the majority of the total value of the
underlying contract. If levels of government expenditures and authorizations for biodefense decrease or shift to programs in areas where we do not offer products or are not developing product candidates, or if the U.S. government otherwise declines
to exercise its options under its contracts with us, our business, revenue and operating results would suffer.
Our current contracts with
BARDA and NIAID are cost plus fixed fee contracts and potential future contracts with the U.S. government may also be structured this way. Under our cost plus fixed fee contracts, we are allowed to recover our approved costs plus a fixed fee. The
total price on a cost plus fixed fee contract is based primarily on allowable costs incurred, but generally is subject to contract funding limitations. U.S. government regulations require us to notify our customer of any cost overruns or underruns
on a cost plus contract. If we incur costs in excess of the funding limitation specified in the contract, we may not be able to recover those cost overruns.
Moreover, changes in U.S. government contracting policies could directly affect our financial performance. Factors that could materially
adversely affect our U.S. government contracting business include:
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budgetary constraints affecting U.S. government spending generally, or specific departments or agencies in particular;
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changes in U.S. government fiscal policies or available funding;
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changes in U.S. government defense and homeland security priorities;
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changes in U.S. government programs or requirements;
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adoption of new laws or regulations;
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technological developments;
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U.S. government shutdowns, threatened shutdowns or budget delays;
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competition and consolidation in our industry; and
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general economic conditions.
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These or other factors could cause U.S. government departments
or agencies to reduce their development funding or future purchases under contracts, to exercise their right to terminate contracts or fail to exercise their options to extend our contracts, any of which could have a material adverse effect on our
business, financial condition, operating results and ability to meet our financial obligations.
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Unfavorable provisions in government contracts, some of which are customary, may subject our business
to material limitations, restrictions and uncertainties and may have a material adverse impact on our financial condition and operating results.
Government contracts contain provisions that give the U.S. government substantial rights and remedies, many of which are not typically found
in commercial contracts, including provisions that allow the U.S. government to:
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terminate existing contracts, in whole or in part, for any reason or no reason;
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unilaterally reduce or modify the governments obligations under such contracts or subcontracts, without the contractors consent, including by imposing equitable price adjustments;
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audit contract-related costs and fees, including allocated indirect costs;
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claim rights, including intellectual property rights, in products and data developed under such agreements;
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under certain circumstances involving public health and safety, license inventions made under such agreements to third parties;
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suspend the contractor from receiving new contracts pending resolution of alleged violations of procurement laws or regulations;
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impose U.S. manufacturing requirements for products that embody inventions conceived or first reduced to practice under such contracts;
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suspend or debar the contractor from doing future business with the government;
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decline to exercise an option to continue a contract;
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exercise an option to purchase only the minimum amount, if any, specified in a contract;
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decline to exercise an option to purchase the maximum amount, if any, specified in a contract;
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claim rights to facilities or to products, including intellectual property, developed under the contract;
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require repayment of contract funds spent on construction of facilities in the event of contract default;
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take actions that result in a longer development timeline than expected;
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change the course of a development program in a manner that differs from the contracts original terms or from our desired development plan, including decisions regarding our partners in the program;
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pursue civil or criminal remedies under the False Claims Act, or FCA, and False Statements Act; and
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control or prohibit the export of products.
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Generally, government contracts, including our
contracts with BARDA and NIAID, contain provisions permitting unilateral termination or modification, in whole or in part, at the U.S. governments convenience. Under general principles of government contracting law, if the U.S. government
terminates a contract for convenience, the government contractor may recover only its incurred or committed costs, settlement expenses and profit on work completed prior to the termination. If the U.S. government terminates a contract for default,
the government contractor is entitled to recover costs incurred and associated profits on accepted items only and may be liable for excess costs incurred by the government in procuring undelivered items from another source. In addition, government
contracts normally contain additional requirements that may increase our costs of doing business, reduce our profits, and expose us to liability for failure to comply with these terms and conditions. These requirements include, for example:
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specialized accounting systems unique to government contracts;
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mandatory financial audits and potential liability for price adjustments or recoupment of government funds after such funds have been spent;
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public disclosures of certain contract information, which may enable competitors to gain insights into our research program;
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mandatory internal control systems and policies; and
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mandatory socioeconomic compliance requirements, including labor standards,
non-discrimination
and affirmative action programs and environmental compliance requirements.
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If we fail to maintain compliance with these requirements, we may be subject to potential
contract or FCA liability and to termination of our contracts.
Furthermore, we are required to enter into agreements and subcontracts
with third parties, including suppliers, consultants and other third-party contractors in order to satisfy our contractual obligations pursuant to our agreements with the United States government. Negotiating and entering into such arrangements can
be time-consuming and we may not be able to reach agreement with such third parties. Any such agreement must also be compliant with the terms of our government contract. Any delay or inability to enter into such arrangements or entering into such
arrangements in a manner that is
non-compliant
with the terms of our contract, may result in violations of our contract.
We may not have the right to prohibit the U.S. government from using certain technologies developed by us, and we may not be able to prohibit
third-party companies, including our competitors, from using those technologies in providing products and services to the U.S. government. The U.S. government generally takes the position that it has the right to royalty-free use of technologies
that are developed under U.S. government contracts.
Most U.S. government contracts grant the U.S. government the right to use on
a royalty free basis, for or on behalf of the U.S. government, any technologies developed and data first produced by the contractor under the government contract. If we were to develop technology under a contract with such a provision, we might not
be able to prohibit third parties, including our competitors, from using that technology in providing products and services to the U.S. government.
Our business is subject to audit by the U.S. government and a negative audit could adversely affect our business.
U.S. government agencies such as the Department of Health and Human Services, or HHS, and the Defense Contract Audit Agency, or the DCAA,
routinely audit and investigate government contractors and recipients of federal grants and contracts. These agencies review a contractors performance under its contracts, cost structure and compliance with applicable laws, regulations and
standards.
The HHS and the DCAA also review the adequacy of, and a contractors compliance with, its internal control systems and
policies, including the contractors accounting, purchasing, property, estimating, compensation and management information systems. Any costs found to be improperly allocated to a specific contract will not be reimbursed, while such costs
already reimbursed must be refunded. If an audit uncovers improper or illegal activities, we may be subject to civil and criminal penalties and administrative sanctions, including:
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termination of contracts;
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suspension of payments;
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suspension or prohibition from conducting business with the U.S. government.
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In addition, we
could suffer serious reputational harm if allegations of impropriety were made against us, which could cause our stock price to decrease.
The
United States governments determination to award a future contract may be challenged by an interested party, such as another bidder, at the United States Government Accountability Office, or the GAO, or in federal court. If such a challenge is
successful, any future contract we may be awarded may be terminated.
The laws and regulations governing the procurement of goods
and services by the U.S. government provide procedures by which other bidders and interested parties may challenge the award of a government contract. If we are awarded a government contract, such challenges or protests could be filed even if there
are not any valid legal grounds on which to base the protest. If any such protests are filed, the government agency may decide to suspend our performance under the contract while such protests are being considered by the GAO or the applicable
federal court, thus potentially delaying delivery of payment. In addition, we could be forced to expend considerable funds to defend any potential award. If a protest is successful, the government may be ordered to terminate the contract and
resolicit proposals. The government agencies with which we have contracts could even be directed to award a potential contract to one of the other bidders.
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Laws and regulations affecting government contracts make it more costly and difficult for us to
successfully conduct our business.
We must comply with numerous laws and regulations relating to the formation, administration
and performance of government contracts, which can make it more difficult for us to retain our rights under our government contracts, including our contracts with BARDA and NIAID. These laws and regulations affect how we conduct business with
government agencies. Among the most significant government contracting regulations that affect our business are:
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the Federal Acquisition Regulations, or FAR, and agency-specific regulations supplemental to the FAR, which comprehensively regulate the procurement, formation, administration and performance of government contracts;
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the Truth in Negotiations Act, which requires certification and disclosure of cost or pricing data in connection with contract negotiations;
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business ethics and public integrity obligations, which govern conflicts of interest and the hiring of former government employees, restrict the granting of gratuities and funding of lobbying activities and include
other requirements such as the Anti-Kickback Statute and Foreign Corrupt Practices Act;
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export and import control laws and regulations; and
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laws, regulations and executive orders restricting the use and dissemination of information classified for national security purposes and the exportation of certain products and technical data.
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Any material changes in applicable laws and regulations could restrict our ability to maintain our existing BARDA and NIAID contracts and
obtain new contracts, which could limit our ability to conduct our business and materially adversely affect our results of operations.
Agreements
with government agencies may lead to claims against us under the Federal False Claims Act, and these claims could result in substantial fines and other penalties.
The biopharmaceutical industry is, and in recent years has been, under heightened scrutiny as the subject of government investigations and
enforcement actions. Our government contracts are subject to substantial financial penalties under the Federal Civil Monetary Penalties Act and the FCA. Under the FCAs whistleblower provisions, private enforcement of fraud claims
against businesses on behalf of the U.S. government has increased due in part to amendments to the FCA that encourage private individuals to sue on behalf of the government. These whistleblower suits, known as qui tam actions, may be filed by
private individuals, including present and former employees. The FCA statute provides for treble damages and up to approximately $22,000 per false claim. If our operations are found to be in violation of any of these laws, or any other governmental
regulations that apply to us, we may be subject to penalties, including civil and criminal penalties, damages, fines, exclusion from the Medicare and Medicaid programs, and the curtailment or restructuring of our operations. Any penalties, damages,
fines, exclusions, curtailment, or restructuring of our operations could adversely affect our ability to operate our business and our financial results.
If product liability lawsuits are brought against us, we may incur substantial liabilities and may be required to limit commercialization of products we
develop.
We face a risk of product liability as a result of the clinical testing of our product candidates and will face an even
greater risk if we commercialize any products. For example, we may incur liability if any product we develop allegedly causes injury or is found to be otherwise unsuitable during product testing, manufacturing, marketing or sale. Any such product
liability claims may include allegations of defects in manufacturing, defects in design, a failure to warn of dangers inherent in the product, negligence, strict liability and a breach of warranties. Claims could also be asserted under state
consumer protection acts. If we cannot successfully defend ourselves against product liability claims, we may incur substantial liabilities or be required to limit commercialization of our products. Regardless of the merits or eventual outcome,
liability claims may result in:
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decreased demand for PF708, Px563L/RPA563 or any other product candidates or products we develop;
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injury to our reputation and significant negative media attention;
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withdrawal of clinical trial participants or cancellation of clinical trials;
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costs to defend the related litigation;
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a diversion of managements time and our resources;
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substantial monetary awards to trial participants or patients;
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regulatory investigations, product recalls, withdrawals or labeling, marketing or promotional restrictions;
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the inability to commercialize any products we develop.
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Our inability to obtain and maintain
sufficient product liability insurance at an acceptable cost and scope of coverage to protect against potential product liability claims could impact the commercialization of PF708, Px563L/RPA563 and any other products we develop. We currently carry
product liability insurance covering our clinical trials in the amount of $10.0 million in the aggregate. Although we maintain such insurance, any claim that may be brought against us could result in a court judgment or settlement that is in
excess of the limits of our insurance coverage. Our insurance policies also have various exclusions and deductibles, and we may be subject to a product liability claim for which we have no coverage. We will have to pay any amounts awarded by a court
or negotiated in a settlement that exceed our coverage limitations or that are not covered by our insurance, and we may not have, or be able to obtain, sufficient capital to pay such amounts. Moreover, in the future, we may not be able to maintain
insurance coverage at a reasonable cost or in sufficient amounts to protect us against losses. If and when we obtain approval for marketing PF708, Px563L/RPA563 or any other product candidates, we intend to expand our insurance coverage to include
the sale of such products; however, we may be unable to obtain this liability insurance on commercially reasonable terms.
Our employees,
independent contractors, principal investigators, CROs, consultants and collaboration partner may engage in misconduct or other improper activities, including noncompliance with regulatory standards and requirements and insider trading.
We are exposed to the risk that our employees, independent contractors, principal investigators, third-party clinical research organizations,
or CROs, consultants and collaboration partner may engage in fraudulent conduct or other illegal activity. Misconduct by these parties could include intentional, reckless and/or negligent conduct or unauthorized activities that violate:
(1) regulations of the FDA and comparable foreign authorities, including those laws requiring the reporting of true, complete and accurate information to such authorities; (2) manufacturing standards; (3) federal and state healthcare
fraud and abuse laws and regulations; or (4) laws that require the reporting of true and accurate financial information and data. In particular, sales, marketing and business arrangements in the healthcare industry are subject to extensive laws
and regulations intended to prevent fraud, misconduct, kickbacks, self-dealing and other abusive practices. These laws and regulations may restrict or prohibit a wide range of pricing, discounting, marketing and promotion, sales commission, customer
incentive programs and other business arrangements. These activities also include the improper use of information obtained in the course of clinical trials, which could result in regulatory sanctions and serious harm to our reputation. We have
adopted a Code of Ethics and Conduct, but it is not always possible to identify and deter misconduct by employees and other third parties, and the precautions we take to detect and prevent this activity may not be effective in controlling unknown or
unmanaged risks or losses or in protecting us from governmental investigations or other actions or lawsuits stemming from a failure to be in compliance with such laws or regulations. If any such actions are instituted against us, and we are not
successful in defending ourselves or asserting our rights, those actions could have a significant impact on our business including the imposition of significant civil, criminal and administrative penalties, damages, monetary fines, possible
exclusion from participation in Medicare, Medicaid and other federal healthcare programs, contractual damages, reputational harm, diminished profits and future earnings, and curtailment of our operations, any of which could adversely affect our
ability to operate our business and our results of operations.
Our cash and cash equivalents and short term investments could be adversely affected
if the financial institutions in which we hold our cash and cash equivalents and short term investments fail.
We regularly
maintain cash balances at third-party financial institutions in excess of the Federal Deposit Insurance Corporation, or FDIC, insurance limit. While we monitor the cash balances in our accounts and adjust the balances as appropriate, these balances
could be impacted, and there could be a material adverse effect on our business, if one or more of the financial institutions with which we deposit fails or is subject to other adverse conditions in the financial or credit markets. To date, we have
experienced no loss or lack of access to our invested cash or cash equivalents; however, we can provide no assurance that access to our invested cash and cash equivalents will not be impacted by adverse conditions in the financial and credit
markets.
We may be subject to information technology failures, including data protection breaches and cyber-attacks, that could disrupt our
operations, damage our reputation and adversely affect our business, operations, and financial results.
We rely on our
information technology systems for the effective operation of our business and for the secure maintenance and storage of confidential data relating to our business and third party businesses. Although we have implemented security controls to protect
our information technology systems, experienced programmers or hackers may be able to penetrate our security controls, and
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develop and deploy viruses, worms and other malicious software programs that compromise our confidential information or that of third parties and cause a disruption or failure of our information
technology systems. Any such compromise of our information technology systems could result in the unauthorized publication of our confidential business or proprietary information, result in the unauthorized release of customer, supplier or employee
data, result in a violation of privacy or other laws, expose us to a risk of litigation, or damage our reputation. The cost and operational consequences of implementing further data protection measures either as a response to specific breaches or as
a result of evolving risks, could be significant. In addition, our inability to use or access our information systems at critical points in time could adversely affect the timely and efficient operation of our business. Any delayed sales,
significant costs or lost customers resulting from these technology failures could adversely affect our business, operations and financial results.
Third parties with which we conduct business have access to certain portions of our sensitive data. In the event that these third parties do
not properly safeguard our data that they hold, security breaches could result and negatively impact our business, operations and financial results.
Our business involves the use of hazardous materials and we, our collaboration partner, and our third-party manufacturers and suppliers must comply with
environmental laws and regulations, which can be expensive and restrict how we do business.
Our research and development and
manufacturing activities and our third-party manufacturers and suppliers activities involve the controlled storage, use and disposal of hazardous materials owned by us, including small quantities of acetonitrile, methanol, ethanol,
ethidium bromide and compressed gases, and other hazardous compounds. We and our collaboration partner, manufacturers and suppliers are subject to laws and regulations governing the use, manufacture, storage, handling and disposal of these hazardous
materials. In some cases, these hazardous materials and various wastes resulting from their use are stored at our and our manufacturers facilities pending their use and disposal. We cannot eliminate the risk of contamination, which could cause
an interruption of our commercialization efforts, research and development efforts and business operations, environmental damage resulting in costly
clean-up
and liabilities under applicable laws and
regulations governing the use, storage, handling and disposal of these materials and specified waste products.
Although we believe that
the safety procedures utilized by us and our third-party manufacturers for handling and disposing of these materials generally comply with the standards prescribed by these laws and regulations, we cannot guarantee that this is the case or eliminate
the risk of accidental contamination or injury from these materials. In such an event, we may be held liable for any resulting damages and such liability could exceed our resources and state or federal or other applicable authorities may curtail our
use of certain materials and interrupt our business operations.
We are also subject to numerous environmental, health and workplace
safety laws and regulations, including those governing laboratory procedures, and the handling of biohazardous materials. Although we maintain workers compensation insurance to cover us for costs and expenses we may incur due to injuries to
our employees resulting from the use of these materials, this insurance may not provide adequate coverage against potential liabilities. For claims not covered by workers compensation insurance, we also maintain an employers liability
insurance policy in the amount of $1.0 million per occurrence and in the aggregate. We do not maintain insurance for environmental liability or toxic tort claims that may be asserted against us.
Environmental laws and regulations are complex, change frequently and have tended to become more stringent. We cannot predict the impact of
such changes and cannot be certain of our future compliance. Any inability to comply with environmental laws and regulations may adversely affect our business and operating results.
Changes in accounting principles, or interpretations thereof, could have a significant impact on our financial position and results of operations.
We prepare our consolidated financial statements in accordance with accounting principles generally accepted in the United States
of America, referred to as GAAP. These principles are subject to interpretation by the Securities and Exchange Commission, or SEC, and various bodies formed to interpret and create appropriate accounting principles. A change in these principles can
have a significant effect on our reported results and may even retroactively affect previously reported transactions. Additionally, the adoption of new or revised accounting principles may require that we make significant changes to our
systems, processes and controls.
It is not clear if or when these potential changes in accounting principles may become effective,
whether we have the proper systems and controls in place to accommodate such changes and the impact that any such changes may have on our financial position and results of operations.
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Risks Relating to our Reliance on Third Parties
We rely on third parties, and in some cases a single third party, to manufacture nonclinical and clinical supplies of our product candidates and to store
critical components of our product candidates for us. Our business could be harmed if those third parties fail to provide us with sufficient quantities of product candidates, or fail to do so at acceptable quality levels or prices.
We do not currently have the infrastructure or capability internally to manufacture supplies of our product candidates for use in clinical
studies, and we lack the resources and the capability to manufacture any of our product candidates on a clinical or commercial scale. We rely on third-party manufacturers, including with respect to PF708, to manufacture our product candidates for
preclinical and clinical studies. Successfully transferring complicated manufacturing techniques to manufacturing organizations and scaling up these techniques for commercial quantities will be time consuming and we may not be able to achieve such
transfer. Moreover, the market for contract manufacturing services for protein therapeutics is highly cyclical, with periods of relatively abundant capacity alternating with periods in which there is little available capacity. If our need for
contract manufacturing services increases during a period of industry-wide production capacity shortage, we may not be able to produce our product candidates on a timely basis or on commercially viable terms. Although we generally do not begin a
clinical study unless we believe we have a sufficient supply of a product candidate to complete such study, any significant delay or discontinuation in the supply of a product candidate for an ongoing clinical study due to the need to replace a
third-party manufacturer could considerably delay completion of our clinical studies, product testing, and potential regulatory approval of our product candidates, which could harm our business and results of operations.
Reliance on third-party manufacturers entails additional risks, including reliance on the third party for regulatory compliance and quality
assurance, the possible breach of the manufacturing agreement by the third party, and the possible termination or nonrenewal of the agreement by the third party at a time that is costly or inconvenient for us. In addition, third-party manufacturers
may not be able to comply with cGMP, or similar regulatory requirements outside the United States. Our failure, or the failure of our third-party manufacturers, to comply with applicable regulations could result in sanctions being imposed on us,
including fines, injunctions, civil penalties, delays, suspension or withdrawal of approvals, license revocation, seizures or recalls of products, operating restrictions and criminal prosecutions, any of which could significantly and adversely
affect supplies of our product candidates or any other product candidates or products that we may develop. Any failure or refusal to supply the components for our product candidates that are being developed could delay, prevent or impair clinical
development or commercialization efforts. If our manufacturers were to breach or terminate their manufacturing arrangements with us, the development or commercialization of the affected products or product candidates could be delayed, which could
have an adverse effect on our business. Any change in our manufacturers could be costly because the commercial terms of any new arrangement could be less favorable and because the expenses relating to the transfer of necessary technology and
processes could be significant.
If any of our product candidates are approved, in order to produce the quantities necessary to meet
anticipated market demand, any manufacturer that we engage may need to increase manufacturing capacity. If we or our manufacturers are unable to produce our product candidates in sufficient quantities to meet the requirements for the launch of these
products or to meet future demand, our revenue and gross margins could be adversely affected. Although we currently believe that we and our manufacturers will not have any material supply issues, we cannot be certain that we will be able to obtain
long-term supply arrangements for our product candidates or materials used to produce them on acceptable terms, if at all. If we are unable to arrange for third-party manufacturing, or to do so on commercially reasonable terms, we may not be able to
complete development of our products or market them.
We also rely on third parties to store master and working cell banks for our product
candidates. We have master and working cell banks and believe we would have adequate backup should any cell bank be lost in a catastrophic event. However, it is possible that we could lose multiple cell banks and have our manufacturing severely
impacted by the need to replace the cell banks, which could materially and adversely affect our business, financial condition and results of operations.
We are substantially dependent on the expertise of Jazz to develop and commercialize some of our product candidates. If we fail to maintain our current
strategic relationship with Jazz, our business, commercialization prospects and financial condition may be materially adversely affected.
Because we have limited or no capabilities for late-stage product development, manufacturing, sales, marketing and distribution, we may need
to enter into alliances with other companies to develop our product candidates. For example, we have entered into an agreement with Jazz Pharmaceuticals Ireland Limited, or Jazz, pursuant to which we will transfer the development, manufacturing and
commercialization of some of our products.
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In February 2015, we entered into a development and license agreement with Pfizer to develop
and commercialize PF582. In August 2016, we entered into a termination agreement with Pfizer pursuant to which the development and license agreement was terminated and all rights to PF582 have been returned to us. The termination accelerated
recognition of $45.8 million of revenue that had been previously deferred and we will not recognize any additional future revenue under the Pfizer development and license agreement. Following our strategic review in November 2017, we decided to
pause our development activities for PF582 and focus our efforts and resources elsewhere in our product portfolio. While we are seeking a new collaboration partner for the development and commercialization of PF582, there are no assurances that we
will find a new collaboration partner or that the terms and timing of any such arrangements would be acceptable to us.
In addition, in
August of 2017, we and Strides Arcolab entered into a termination agreement pursuant to which our joint venture was terminated. While there was no activity under the joint venture with Strides Arcolab to date, following the termination we solely own
the product candidates that were previously subject to the joint venture with Strides Arcolab.
In July 2016, we entered into a license
and option agreement with Jazz, pursuant to which we and Jazz are collaboratively developing certain hematology products, and Jazz has the exclusive right to manufacture and commercialize such products throughout the world. In addition,
pursuant to the agreement, we granted Jazz certain other rights to negotiate the exclusive right to develop, manufacture and commercialize throughout the world other hematology products that are currently or in the future may be developed by us. In
consideration for the exclusive licenses and other rights contained in the agreement, we received upfront and option payments totaling $15 million in July 2016, and may be eligible to receive additional payments of up to $166 million
based on the achievement of certain development, regulatory, and sales-related milestones, including up to $41 million for certain
non-sales-related
milestones. We may also be eligible to receive
tiered royalties on worldwide sales of any products resulting from the collaboration.
The prospects for the product candidates developed
under this collaboration depend on the expertise, development and commercial skills, and financial strength of Jazz. Our collaboration with Jazz or any future collaboration partner may not be successful, and we may not realize the expected benefits
from such collaborations, due to a number of important factors, including but not limited to the following:
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Jazz or any future collaboration partner may terminate their agreements with us prior to completing development or commercialization of our product candidates, in whole or in part, adversely impacting our potential
approval and revenue from licensed products;
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the timing and amount of any payments we may receive under these agreements will depend on, among other things, the efforts, allocation of resources, and successful commercialization of the relevant product candidates
by Jazz or any future collaboration partner, as applicable, under our agreements;
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the timing and amounts of expense reimbursement that we may receive are uncertain; or
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Jazz or any future collaboration partner may change the focus of their development or commercialization efforts or pursue or emphasize higher priority programs.
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A failure of Jazz or any future collaboration partner to successfully develop our product candidates which are covered by the collaboration,
or commercialize such product candidates, or the termination of our agreement with Jazz or any future collaboration partner, as applicable, may have a material adverse effect on our business, results of operations and financial condition.
Our existing product development and/or commercialization arrangements, and any that we may enter into in the future, may not be successful, which could
adversely affect our ability to develop and commercialize our product candidates.
We are a party to, and continue to seek
additional, collaboration arrangements with other pharmaceutical companies for the development and/or commercialization of our current and future product candidates. In such alliances, we would expect our collaboration partners to provide
substantial capabilities in clinical development, manufacturing, regulatory affairs, sales and marketing, both in the United States and internationally.
To the extent that we decide to enter into additional collaboration agreements, we will face significant competition in seeking appropriate
collaboration partners. Any failure to meet our clinical milestones with respect to an unpartnered product candidate would make finding a collaboration partner more difficult. Moreover, collaboration arrangements are complex and time consuming to
negotiate, document and implement, and we cannot guarantee that we can successfully maintain such relationships or that the terms of such arrangements will be favorable to us. If we fail to maintain, establish and implement collaboration or other
alternative arrangements, the value of our business and operating results will be adversely affected.
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We may not be successful in our efforts to establish, implement and maintain collaborations
or other alternative arrangements if we choose to enter into such arrangements. The terms of any collaboration or other arrangements that we may establish may not be favorable to us. The management of collaborations may take significant time and
resources that distract our management from other matters. Our ability to successfully collaborate with any current or future collaboration partners may be impaired by multiple factors including:
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a collaboration partner may shift its priorities and resources away from our programs due to a change in business strategies, or a merger, acquisition, sale or downsizing of its company or business unit;
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a collaboration partner may cease development in therapeutic areas which are the subject of alliances with us;
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a collaboration partner may change the success criteria for a particular program or product candidate thereby delaying or ceasing development of such program or candidate;
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a significant delay in initiation of certain development activities by a collaboration partner will also delay payments tied to such activities, thereby impacting our ability to fund our own activities;
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a collaboration partner could develop a product that competes, either directly or indirectly, with our current or future products, if any;
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a collaboration partner with commercialization obligations may not commit sufficient financial or human resources to the marketing, distribution or sale of a product;
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a collaboration partner with manufacturing responsibilities may encounter regulatory, resource or quality issues and be unable to meet demand requirements;
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a collaboration partner may exercise its rights under the agreement to terminate our collaboration;
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a dispute may arise between us and a collaboration partner concerning the research or development of a product candidate or commercialization of a product resulting in a delay in milestones, royalty payments or
termination of a program and possibly resulting in costly litigation or arbitration which may divert management attention and resources;
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the results of our clinical trials may not match our collaboration partners expectations, even if statistically significant;
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a collaboration partner may not adequately protect or enforce the intellectual property rights associated with a product or product candidate; and
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a collaboration partner may use our proprietary information or intellectual property in such a way as to invite litigation from a third party.
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Any such activities by our current or future collaboration partners could adversely affect us financially and could harm our business
reputation.
In addition to product development and commercialization capabilities, we may depend on our alliances with other companies to
provide substantial additional funding for development and potential commercialization of our product candidates. We may not be able to obtain funding on favorable terms from these alliances, and if we are not successful in doing so, we may not have
sufficient funds to develop a particular product candidate internally, or to bring product candidates to market. Failure to bring our product candidates to market will prevent us from generating sales revenue, and this may substantially harm our
business. Furthermore, any delay in entering into these alliances could delay the development and commercialization of our product candidates and reduce their competitiveness even if they reach the market. As a result, our business and operating
results may be adversely affected.
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We rely on CROs to conduct and oversee our planned clinical trials for our product candidates and
other clinical trials for product candidates we are developing or may develop in the future. If our CROs do not successfully carry out their contractual duties, meet expected deadlines, or otherwise conduct the trials as required or comply with
regulatory requirements, we and our collaboration partner may not be able to seek or obtain regulatory approval for or commercialize our product candidates when expected or at all, and our business could be substantially harmed.
We will continue to rely upon medical institutions, clinical investigators and contract laboratories to conduct our trials in accordance with
our clinical protocols and in accordance with applicable legal and regulatory requirements. These third parties play a significant role in the conduct of these trials and the subsequent collection and analysis of data from the clinical trials. These
third parties are not our employees, and except for remedies available to us under our agreements with such third parties, there is no guarantee that any such third party will devote adequate time and resources to our clinical trial. If our CRO or
any other third parties upon which we rely for administration and conduct of our clinical trials do not successfully carry out their contractual duties or obligations or meet expected deadlines, if they need to be replaced or if the quality or
accuracy of the clinical data they obtain is compromised due to the failure to adhere to our clinical protocols, regulatory requirements, or for other reasons, or if they otherwise perform in a substandard manner, our clinical trials may be
extended, delayed, suspended or terminated, and we may not be able to complete development of, seek or obtain regulatory approval for, or successfully commercialize our product candidates. We plan to rely heavily on these third parties for the
execution of clinical trials for products we are developing or may develop in the future, and will control only certain aspects of their activities. Nevertheless, we are responsible for ensuring that each of our clinical trials is conducted in
accordance with the applicable protocol, legal, regulatory and scientific standards, and our reliance on our CRO does not relieve us of our regulatory responsibilities.
We, our CRO and our collaboration partner are required to comply with Good Clinical Practice, or GCP, which are regulations and guidelines
enforced by regulatory authorities around the world for products in clinical development. Regulatory authorities enforce these GCP regulations through periodic inspections of clinical trial sponsors, principal investigators and clinical trial sites.
If we, our CRO or our collaboration partner fail to comply with applicable GCP regulations, the clinical data generated in clinical trials may be deemed unreliable and submission of marketing applications may be delayed or the regulatory authorities
may require us to perform additional clinical trials before accepting our applications for review or approving marketing applications. We cannot assure that, upon inspection, a regulatory authority will determine that any of our clinical trials
comply or complied with applicable GCP regulations. In addition, clinical trials must be conducted with product produced under current Good Manufacturing Practices, or cGMP, regulations, which are enforced by regulatory authorities. Any failure to
comply with these regulations may require us to repeat clinical trials, which would delay the regulatory approval process. Moreover, our business may be implicated if our CRO violates federal or state fraud and abuse or false claims laws and
regulations or healthcare privacy and security laws.
Comparative clinical trials require a substantial number of patients that can form
the basis for generating statistically significant results. Delays in site initiation or unexpectedly low patient enrollment rates may delay the results of the clinical trial. CROs may also generate higher costs than anticipated. As a result, our
results of operations and the commercial prospects for our product candidates would be harmed, our costs could increase, and our ability to generate revenue could be delayed. Further, if our relationship with our CRO is terminated, we may be unable
to enter into arrangements with an alternative CRO on commercially reasonable terms, or at all. Switching or adding CROs can involve substantial cost and require extensive management time and focus. In addition, there is a natural transition period
when a new CRO commences work. As a result, delays may occur, which can materially impact our ability to meet our desired clinical development timelines. Although we carefully manage our relationship with our CROs, there can be no assurance that we
will not encounter such challenges or delays in the future or that these delays or challenges will not have a material adverse impact on our business, prospects, financial condition or results of operations.
We rely on third-party suppliers, and in some instances a single third-party supplier, for the manufacture and supply of certain materials in our
protein production services, and these suppliers could cease to manufacture the materials, go out of business or otherwise not perform as anticipated.
We rely on third-party suppliers for our protein production services and in some instances a single third-party supplier, for the manufacture
and supply of certain materials. We currently rely, and expect to continue to rely, on a single-source supplier for the manufacture and supply of CRM197. To meet these demands, our supplier is in the process of increasing production capacity, and we
also have established a repository in the United States that is capable of storing a safety supply of CRM197 and the CRM197 cell bank. Furthermore, we have taken steps to identify alternate sources of supply sufficient to support future needs;
however, there may be delays in switching to these alternative suppliers if our contract with primary sources are terminated without notice. Regardless of the foregoing alternative measures, we cannot guarantee that we will have an adequate supply
of CRM197. If we are unable to secure
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adequate quantities of CRM197 from our primary supplier, from potential secondary suppliers or from our safety supply, we may be required to identify additional suppliers. If we are required to
engage additional suppliers, we may not be able to enter into an alternative supply arrangement on commercially reasonable terms, or at all. Even if we are able to identify additional suppliers and enter into agreements on commercially reasonable
terms, we may incur delays associated with identifying and qualifying additional suppliers and negotiating the terms of any supply contracts. These delays could adversely impact our business and negatively affect profitability of our protein
production services.
We have entered into collaborations with third parties in connection with the development of certain of our product
candidates. Even if we believe that the development of our technology and product candidates is promising, our partners may choose not to proceed with such development.
Our existing agreement with our collaboration partner, Jazz, and any future collaboration agreements we may enter into, are generally subject
to termination by the counterparty on short notice upon the occurrence of certain circumstances. Accordingly, even if we believe that the development of product candidates is worth pursuing, our partners may choose not to continue with such
development. If any of our collaborations are terminated, such as the termination of our collaboration with Pfizer in August 2016 and the termination of the joint venture agreement, or JVA, with Strides Arcolab in August 2017, we may be required to
devote additional resources to the development of our product candidates or seek a new collaboration partner on short notice, and the terms of any additional collaboration or other arrangements that we establish may not be favorable to us.
We are also at risk that our current and any potential collaborations or other arrangements may not be successful. Factors that may affect the
success of our collaborations include the following:
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our collaboration partners may incur financial and cash flow difficulties that force them to limit or reduce their participation in our joint projects;
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our collaboration partners may be pursuing alternative technologies or developing alternative products that are competitive to our technology and products, either on their own or in partnership with others;
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our collaboration partners may terminate their collaboration with us, which could make it difficult for us to attract new partners or adversely affect perception of us in the business and financial communities; and
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our collaboration partners may pursue higher priority programs or change the focus of their development programs, which could affect their commitment to us.
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If we cannot maintain successful collaborations, our business, financial condition and operating results may be adversely affected.
If we are unable to maintain our commercial supply agreements with key customers purchasing CRM197 or if third-party distributors of our reagent
proteins fail to perform as expected, sales revenue could decline.
We primarily sell CRM197 directly to biopharmaceutical
companies and currently have several commercial supply agreements in place for long-term supply of CRM197. To establish and maintain relationships with customers, we believe we need to maintain adequate supplies of CRM197, remain price competitive,
comply with regulatory regulations and provide high quality products. If we are unable to establish and maintain arrangements for the sale of CRM197, our revenue and profits would decline.
Although we sell our protein reagents through multiple sales channels, including our ecommerce website, we also sell our protein reagents to
some of our customers through third-party distributors. Many of such third parties also market and sell products from our competitors. Our third-party distributors may terminate their relationships with us at any time, or with short notice. Our
future performance will also depend, in part, on our ability to attract additional third-party distributors that will be able to market protein reagents effectively, especially in markets in which we have not previously distributed our protein
reagents. If our current third-party distributors fail to perform as expected, our revenue and results of operations could be harmed.
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Risks Relating to Our Intellectual Property
Our collaboration partner and other third parties may assert ownership or commercial rights to inventions we develop from our use of the materials which
they provide to us, or otherwise arising from our collaboration.
We collaborate with other companies and institutions with respect
to research and development matters. Also, we rely on numerous third parties to provide us with materials that we use to develop our technology. If we cannot successfully negotiate sufficient ownership, licensing and/or commercial rights to any
inventions that result from our use of any third-party collaborators materials, or if disputes arise with respect to the intellectual property developed with the use of a collaborators materials, or data developed in a
collaborators study, our ability to capitalize on the market potential of these inventions or developments may be limited or precluded altogether.
If our efforts to protect our intellectual property related to our platform technology and our current or future product candidates are not adequate, we
may not be able to compete effectively in our market.
We rely upon a combination of patents, trade secret protection and
confidentiality agreements to protect the intellectual property related to our current product candidates and our development programs. If we do not adequately protect our intellectual property, competitors may be able to use our technologies and
erode or negate any competitive advantage we may have, which could harm our business and ability to achieve profitability. In particular, our success depends in large part on our ability to obtain and maintain patent protection in the
United States and other countries with respect to our platform and product candidates. However, we may not be able to file and prosecute all necessary or desirable patent applications at a reasonable cost or in a timely manner. We may also fail
to identify patentable aspects of our research and development before it is too late to obtain patent protection. Any disclosure to or misappropriation by third parties of our confidential proprietary information could enable competitors to quickly
duplicate or surpass our technological achievements, eroding our competitive position in our market.
The patentability of inventions, and
the validity, enforceability and scope of patents in the biotechnology and pharmaceutical industry involve complex legal and scientific questions and can be uncertain. This uncertainty includes changes to the patent laws through either legislative
action to change statutory patent law or court action that may reinterpret existing law in ways affecting the scope or validity of issued patents. The patent applications that we own or license may fail to result in issued patents in the
United States or foreign countries. There is a substantial amount of prior art in the biotechnology and pharmaceutical fields, including scientific publications, patents and patent applications. Our ability to obtain and maintain valid and
enforceable patents depends on whether the differences between our technology and the prior art allow our technology to be patentable over the prior art. We may be unaware of certain prior art relating to our patent applications and patents, which
could prevent a patent from issuing from a pending patent application, or result in an issued patent being invalidated. Even if the patents do successfully issue, third parties may challenge the validity, enforceability or scope of such issued
patents or any other issued patents we own or license, which may result in such patents being narrowed, invalidated or held unenforceable.
Patents granted by the European Patent Office may be opposed by any person within nine months from the publication of their grant and, in
addition, may be challenged before national courts at any time. Furthermore, even if they are unchallenged, our patents and patent applications may not adequately protect our intellectual property or prevent others from designing around our claims.
If the breadth or strength of protection provided by the patents and patent applications we hold, license or pursue with respect to our product candidates is threatened, it could threaten our ability to commercialize our product candidates. In
addition, recent changes to the patent laws of the United States provide additional procedures for third parties to challenge the validity of issued patents based on patent applications filed after March 15, 2013. If the breadth or strength of
protection provided by the patents and patent applications we hold or pursue with respect to our current or future product candidates is challenged, then it could threaten our ability to commercialize our current or future product candidates, and
could threaten our ability to prevent competitive products from being marketed. Further, if we encounter delays in our clinical trials, the period of time during which we could market our current or future product candidates under patent protection
would be reduced. Since patent applications in the United States and most other countries are confidential for a period of time after filing, we cannot be certain that we were the first to either (i) file any patent application related to our
product candidates, or (ii) invent any of the inventions claimed in our patents or patent applications. Furthermore, for applications filed before March 16, 2013, or patents issuing from such applications, an interference proceeding can be
provoked by a third party, or instituted by the United States Patent and Trademark Office, or USPTO, to determine who was the first to invent any of the subject matter covered by the patent claims of our applications and patents. As of
March 16, 2013, the United States transitioned to a
first-to-file
system for deciding which party should be granted a patent when two or more
patent applications are filed by different parties claiming the same invention. A third party that files a patent application in the USPTO before us could therefore be awarded a patent covering an invention of ours even if we had made the invention
before it was made by the third party.
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The change to
first-to-file
from
first-to-invent
is one of the changes to the
patent laws of the United States resulting from the Leahy-Smith America Invents Act, or the Leahy-Smith Act, signed into law on September 16, 2011. Among some of the other significant changes to the patent laws are changes that limit where
a patentee may file a patent infringement suit and provide opportunities for third parties to challenge any issued patent in the USPTO. It is not yet clear what, if any, impact the Leahy-Smith Act will have on the operation of our business. However,
the Leahy-Smith Act and its implementation could increase the uncertainties and costs surrounding the prosecution of our patent applications and the enforcement or defense of our issued patents, all of which could have a material adverse effect on
our business and financial condition.
Even where laws provide protection, costly and time-consuming litigation could be necessary to
enforce and determine the scope of our proprietary rights, and the outcome of such litigation would be uncertain. Moreover, any actions we may bring to enforce our intellectual property against our competitors could provoke them to bring
counterclaims against us, and some of our competitors have substantially greater intellectual property portfolios than we have.
If we are unable to
protect the confidentiality of our trade secrets, the value of our technology could be materially adversely affected and our business would be harmed.
In addition to the protection afforded by patents, we also rely on trade secret protection and confidentiality agreements to protect
proprietary
know-how
that may not be patentable, processes for which patents may be difficult to obtain or enforce and any other elements of our product development processes that involve proprietary
know-how,
information or technology that is not covered by patents.
As part of our efforts to protect
our trade secrets and other confidential information, we require our employees, consultants, collaborators and advisors to execute confidentiality agreements upon the commencement of their relationships with us. These agreements require that all
confidential information developed by the individual or made known to the individual by us during the course of the individuals relationship with us be kept confidential and not disclosed to third parties. These agreements, however, may not
provide us with adequate protection against improper use or disclosure of confidential information, and these agreements may be breached. Adequate remedies may not exist in the event of unauthorized use or disclosure of our confidential information.
We also note in this respect that trade secret protection in foreign countries may not provide protection to the same extent as federal and state laws in the United States. A breach of confidentiality could significantly affect our competitive
position. In addition, in some situations, these agreements may conflict with, or be subject to, the rights of third parties with whom our employees, consultants, collaborators or advisors have previous employment or consulting relationships. To the
extent that our employees, consultants or contractors use any intellectual property owned by others in their work for us, disputes may arise as to the rights in any related or resulting
know-how
and
inventions. Also, third parties, including our competitors, may independently develop substantially equivalent proprietary information and technologies or otherwise lawfully gain access to our trade secrets and other confidential information. In
such a case, we would have no right to prevent such third parties from using such proprietary information or technologies to compete with us, which could harm our competitive position.
If we infringe or are alleged to infringe intellectual property rights of third parties, our business could be harmed.
Our research, development and commercialization activities may infringe or otherwise violate or be claimed to infringe or otherwise violate
patents owned or controlled by other parties. Our competitors have developed large portfolios of patents and patent applications in fields relating to our business and it may not always be clear to industry participants, including us, which patents
cover various types of products or methods of use. There may also be patent applications that have been filed but not published that, when issued as patents, could be asserted against us. The coverage of patents is subject to interpretation by the
courts, and the interpretation is not always uniform. If we are sued for patent infringement, we would need to demonstrate that our product candidates, products or methods either do not infringe the patent claims of the relevant patent or that the
patent claims are invalid, and we may not be able to do this. Proving that a patent is invalid is difficult. For example, in the United States, proving invalidity requires a showing of clear and convincing evidence to overcome the presumption of
validity enjoyed by issued patents. Also in proceedings before courts in Europe, the burden of proving invalidity of the patent usually rests on the party alleging invalidity. Third parties could bring claims against us that would cause us to incur
substantial expenses and, if successful against us, could cause us to pay substantial damages. Further, if a patent infringement suit were brought against us, we could be forced to stop or delay research, development, manufacturing or sales of the
product or product candidate that is the subject of the suit.
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As a result of patent infringement claims, or to avoid potential claims, we may choose or be
required to seek licenses from third parties. These licenses may not be available on acceptable terms, or at all. Even if we are able to obtain a license, the license would likely obligate us to pay license fees or royalties or both, and the rights
granted to us might be nonexclusive, which could result in our competitors gaining access to the same intellectual property. Ultimately, we could be prevented from commercializing a product, or be forced to cease some aspect of our business
operations, if, as a result of actual or threatened patent infringement claims, we are unable to enter into licenses on acceptable terms.
There has been substantial litigation and other proceedings regarding patent and other intellectual property rights in the pharmaceutical
industry. In addition to infringement claims against us, we may become a party to other patent litigation and other proceedings, including interference, derivation or post-grant proceedings declared or granted by the USPTO and similar proceedings in
foreign countries, regarding intellectual property rights with respect to our current or future products. Third parties may submit applications for patent term extensions in the United States and/or supplementary protection certificates in the
European Union, or EU, member States seeking to extend certain patent protection which, if approved, may interfere with or delay the launch of one or more of our biosimilar or vaccine products. The cost to us of any patent litigation or other
proceeding, even if resolved in our favor, could be substantial. Some of our competitors may be able to sustain the costs of such litigation or proceedings more effectively than we can because of their substantially greater financial resources.
Patent litigation and other proceedings may also absorb significant management time. Uncertainties resulting from the initiation and continuation of patent litigation or other proceedings could impair our ability to compete in the marketplace. The
occurrence of any of the foregoing could have a material adverse effect on our business, financial condition or results of operations. We may become involved in lawsuits to protect or enforce our inventions, patents or other intellectual property or
the patents of our licensors, which could be expensive and time consuming.
Competitors may infringe our intellectual property, including
our patents or the patents of our licensors. In addition, one or more of our third-party collaborators may have submitted, or may in the future submit, a patent application to the USPTO without naming a lawful inventor that developed the subject
matter in whole or in part while under an obligation to execute an assignment of rights to us. As a result, we may be required to file infringement or inventorship claims to stop third-party infringement, unauthorized use, or to correct
inventorship. This can be expensive, particularly for a company of our size, and time-consuming. Any claims that we assert against perceived infringers could also provoke these parties to assert counterclaims against us alleging that we infringe
their intellectual property rights. In addition, in an infringement proceeding, a court may decide that a patent of ours is not valid or is unenforceable, or may refuse to stop the other party from using the technology at issue on the grounds that
our patent claims do not cover its technology or that the factors necessary to grant an injunction against an infringer are not satisfied.
An adverse determination of any litigation or other proceedings could put one or more of our patents at risk of being invalidated, held
unenforceable or interpreted narrowly and could put our patent applications at risk of not issuing.
Interference, derivation or other
proceedings brought at the USPTO or any foreign patent authority may be necessary to determine the priority or patentability of inventions with respect to our patent applications or those of our licensors or collaborators. Litigation or USPTO
proceedings brought by us may fail. An unfavorable outcome in any such proceedings could require us to cease using the related technology or to attempt to license rights to it from the prevailing party, or could cause us to lose valuable
intellectual property rights. Our business could be harmed if the prevailing party does not offer us a license on commercially reasonable terms, if any license is offered at all. Even if we are successful, domestic or foreign litigation or USPTO or
foreign patent office proceedings may result in substantial costs and distraction to our management. We may not be able, alone or with our licensors or collaborators, to prevent misappropriation of our trade secrets, confidential information or
proprietary rights, particularly in countries where the laws may not protect such rights as fully as in the United States.
Furthermore, because of the substantial amount of discovery required in connection with intellectual property litigation or other proceedings,
there is a risk that some of our confidential information could be compromised by disclosure during this type of litigation or proceedings. In addition, during the course of this kind of litigation or proceedings, there could be public announcements
of the results of hearings, motions or other interim proceedings or developments or public access to related documents. If investors perceive these results to be negative, the market price for our common stock could be significantly harmed.
We may not be able to globally protect our intellectual property rights.
Filing, prosecuting and defending patents on product candidates in all countries throughout the world would be prohibitively expensive, and
our intellectual property rights in some countries outside the United States can be less extensive than those in the United States. In addition, the laws of some foreign countries do not protect intellectual property rights to the same extent
as federal and state laws in the United States and in some cases may even force us to grant a compulsory license to competitors or other third parties. Consequently, we may not be able to prevent third parties from practicing our inventions in all
countries outside the
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United States, or from selling or importing products made using our inventions in and into the United States or other jurisdictions. Competitors may use our technologies in jurisdictions
where we have not obtained patent protection to develop their own products and further, may export otherwise infringing products to territories where we have patent protection, but enforcement is not as strong as that in the United States. These
products may compete with our products and our patents or other intellectual property rights may not be effective or sufficient to prevent them from competing.
Many companies have encountered significant problems in protecting and defending intellectual property rights in foreign jurisdictions. The
legal systems of certain countries, particularly certain developing countries, do not favor the enforcement of patents and other intellectual property protection, particularly those relating to biopharmaceuticals, which could make it difficult for
us to stop the infringement of our patents or marketing of competing products in violation of our proprietary rights generally. Proceedings to enforce our patent rights in foreign jurisdictions could result in substantial costs and divert our
efforts and attention from other aspects of our business, could put our patents at risk of being invalidated or interpreted narrowly and our patent applications at risk of not issuing and could provoke third parties to assert claims against us. We
may not prevail in any lawsuits that we initiate and the damages or other remedies awarded, if any, may not be commercially meaningful. Accordingly, our efforts to enforce our intellectual property rights around the world may be inadequate to obtain
a significant commercial advantage from the intellectual property that we develop or license.
In addition, our ability to protect and
enforce our intellectual property rights may be adversely affected by unforeseen changes in domestic and foreign intellectual property laws.
Obtaining and maintaining patent protection depends on compliance with various procedural, document submission, fee payment and other requirements
imposed by governmental patent agencies, and our patent protection could be reduced or eliminated for
non-compliance
with these requirements.
Periodic maintenance fees, renewal fees, annuity fees and various other governmental fees on patents and/or applications will be due to be
paid to the USPTO and various governmental patent agencies outside of the United States in several stages over the lifetime of the patents and/or applications. The USPTO and various
non-U.S.
governmental
patent agencies require compliance with a number of procedural, documentary, fee payment and other similar provisions during the patent application process. In many cases, an inadvertent lapse can be cured by payment of a late fee or by other means
in accordance with the applicable rules. However, there are situations in which noncompliance can result in abandonment or lapse of the patent or patent application, resulting in partial or complete loss of patent rights in the relevant
jurisdiction. In such an event, our competitors might be able to use our technologies and this circumstance would have a material adverse effect on our business.
We may be subject to claims that our employees or consultants have wrongfully used or disclosed alleged trade secrets of former or other employers.
Many of our employees and consultants, including our senior management, have been employed or retained by other biotechnology or
pharmaceutical companies, including our competitors or potential competitors. Although we try to ensure that our employees and consultants do not use the proprietary information or
know-how
of others in their
work for us, we may be subject to claims that we or these employees or consultants have used or disclosed intellectual property, including trade secrets or other proprietary information, of any such employees or consultants former or
other employer. We are not aware of any material threatened or pending claims related to these matters, but in the future litigation may be necessary to defend against such claims. If we fail in defending any such claims, in addition to paying
monetary damages, we may lose valuable intellectual property rights or personnel. Even if we are successful in defending against such claims, litigation could result in substantial costs and be a distraction to management.
Risks Related to Government Regulation
The
approval processes of the FDA, EMA, and comparable foreign authorities are lengthy, time consuming and inherently unpredictable, and if we and our collaborators are ultimately unable to obtain regulatory approval for our product candidates, our
business will be substantially harmed.
The research, development, testing, manufacturing, labeling, packaging, approval,
promotion, advertising, storage, marketing, distribution, post-approval monitoring and reporting, and export and import of drug and biologic products are subject to extensive regulation by the FDA and other regulatory authorities in the
United States, by the EMA and EEA Competent Authorities in the EEA, and by other regulatory authorities in other countries, which regulations differ from country to country. Neither we nor any collaboration partner is permitted to market PF708,
Px563L/RPA563 or any other product candidates in the United States until
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approval from the FDA is received, or in the EEA until we receive EU Commission or EEA Competent Authority approvals, as applicable. The time required to obtain approval from regulatory
authorities is unpredictable, typically takes many years following the commencement of clinical trials, and depends upon numerous factors, including the substantial discretion of such 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 product candidates clinical development and may vary among jurisdictions, which may cause delays in the approval or the decision
not to approve an application. We and our collaboration partner have not submitted any market application to regulatory authorities or 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.
Applications for our
product candidates could fail to receive regulatory approval for many reasons, including but not limited to the following:
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the data collected from clinical studies of our product candidates may not be sufficient to support the submission of a BLA; a new drug application, or NDA, under the 505(b)(2) section of the Food, Drug, and Cosmetic
Act; a biosimilar product application under the 351(k) pathway of the Public Health Service Act, or PHSA, a biosimilar marketing authorization under Article 6 of Regulation (EC) No. 726/2004 and/or Article 10(4) of Directive 2001/83/EC in the
EEA, or other submission or to obtain regulatory approval in the United States, the EEA, or elsewhere;
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regulatory authorities may disagree with the design or implementation of our clinical trials and may, at any time, determine that the regulatory pathway that we have committed to for PF708, Px563L/RPA563 or any other
product candidate is inappropriate;
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the population studied in the clinical program may not be sufficiently broad or representative to assure efficacy and safety in the full population for which we seek approval;
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regulatory authorities may disagree with our interpretation of data from preclinical studies or clinical trials;
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we may be unable to demonstrate to the satisfaction of regulatory authorities that a product candidates risk-benefit ratio for its proposed indication is acceptable;
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regulatory authorities may fail to approve the manufacturing processes, test procedures and specifications, or facilities of third-party manufacturers with whom we contract for clinical and commercial supplies; and
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the approval policies or regulations of regulatory authorities may significantly change in a manner that renders our clinical data insufficient for approval.
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This lengthy approval process as well as the unpredictability of future clinical trial results may result in our failing to seek or obtain
regulatory approval to market PF708, Px563L/RPA563 or any other product candidates, which would significantly harm our business, results of operations and prospects. Moreover, any delays in the commencement or completion of clinical testing could
significantly impact our product development costs and could result in the need for additional financing.
In addition, even if we or our
collaboration partner were to obtain approval, regulatory authorities may approve any of our product candidates for fewer or more limited indications than requested, may grant approval contingent on the performance of costly post-marketing clinical
trials, or may approve a product candidate with a label that does not include the labeling claims necessary or desirable for the successful commercialization of that product candidate. Any of the foregoing scenarios could materially harm the
commercial prospects for our product candidates.
If we fail to obtain approval for our most advanced product candidates or if our most advanced
product candidates are not commercially successful, we may have to curtail our product development programs and our business would be materially harmed.
We have invested a significant portion of our time, financial resources and efforts in the development of our most advanced product candidates,
including PF708 and Px563L/RPA563. The clinical and commercial success of our product candidates will depend on a number of factors, including the following:
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timely and successful completion of all necessary clinical trials and our Study
PF708-301
in subjects with osteoporosis, which may be significantly slower or cost more than we
currently anticipate and will depend substantially upon the accurate and satisfactory performance of third-party contractors;
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our ability to find suitable collaboration partners to develop our product candidates or our ability to obtain substantial additional sources of funding to develop our product candidates;
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timely receipt of necessary marketing approvals from the FDA, the EU Commission, and similar foreign regulatory authorities;
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maintaining an acceptable safety and adverse event profile of our products following approval;
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achieving and maintaining compliance with all regulatory requirements applicable to our product candidates or any approved products;
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making arrangements with third-party manufacturers for, or establishing, commercial manufacturing capabilities;
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launching commercial sales of our products, if and when approved, whether alone or in collaboration with others;
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obtaining and maintaining patent and trade secret protection and regulatory exclusivity, where available, for our product candidates;
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the availability, perceived advantages, relative cost, relative safety and relative efficacy of alternative and competing treatments;
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acceptance of our products, if and when approved, by patients, the medical community and third-party payors; and
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the ability to raise additional capital on acceptable terms to achieve our goals.
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If we and
our collaboration partner are unable to seek and obtain regulatory approval for any of our product candidates in a timely manner or at all, we may never realize revenue from these products and we may have to curtail our other product development
programs. As a result, our business, financial condition and results of operations would be materially harmed.
Our ability to market our products
in the United States may be significantly delayed or prevented by the BPCIA patent dispute resolution mechanism.
The Biologics
Price Competition and Innovation Act of 2009, Title VII, Subtitle A of the Patient Protection and Affordable Care Act, collectively referred to as the Affordable Care Act, or ACA,
Pub.L.No.111-148,
124
Stat.119, Sections
7001-02
signed into law March 23, 2010, and codified in 42 U.S.C. §262, or the BPCIA, created an elaborate and complex patent dispute resolution mechanism for biosimilars that
could prevent us from launching our product candidates in the United States or could substantially delay such launches. The BPCIA mechanism required for 351(k) biosimilar applicants may pose greater risk as compared to the litigation risk to which
we might be exposed under a traditional 351(a) BLA regulatory pathway.
The BPCIA sets forth patent disclosure and briefing that are
demanding and time-sensitive. The following is an overview of the patent exchange and patent briefing procedures set forth in the BPCIA:
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Disclosure of the Biosimilar Application. Within 20 days after the FDA publishes a notice that its application has been accepted for review, a 351(k) biosimilar applicant can decide whether or not it chooses to provide
a copy of its application to the originator. If the applicant does not provide its application, the originator may file for a declaration of infringement, validity, or enforceability of any patent that claims the biological product or a use of
the biological product.
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Identification of Pertinent Patents. Within 60 days of the date of receipt of the application the originator must identify patents owned or controlled by the originator which it believes could reasonably be asserted
against the biosimilar applicant.
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Statement by the Biosimilar Applicant. Within 60 days of the date of receipt of the originators patent list, the biosimilar applicant must state either that it will not market its product until the relevant
patents have expired or alternatively provide its arguments that the patents are invalid, unenforceable or would not be infringed by the proposed biosimilar product candidate. The biosimilar applicant may also provide the originator with a list of
patents the biosimilar applicant believes the originator could reasonably assert against a person not licensed by the originator engaged in the making, using, offering to sell, selling, or importing into the United States of the reference product.
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Statement by the Originator. In the event the biosimilar applicant has asserted that the patents are invalid, unenforceable or would not be infringed by the proposed
follow-on
product, the originator must provide the biosimilar applicant with a response within 60 days. The response must provide the legal and factual basis of the opinion that such patent will be infringed by the commercial marketing of the proposed
biosimilar and a response to any arguments offered from the biosimilar applicant concerning validity and enforceability.
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Patent Resolution Negotiations. If the originator provides its detailed views that the proposed biosimilar would infringe valid and enforceable patents, then the parties are required to engage in good faith negotiations
to identify which of the discussed patents will be the subject of a patent infringement action. If the parties agree on the patents to be litigated, the originator firm must bring an action for patent infringement within 30 days.
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Simultaneous Exchange of Patents. If those negotiations do not result in an agreement within 15 days, then the biosimilar applicant must notify the originator of how many patents (but not the identity of those patents)
that it wishes to litigate. Within five days, the parties are then required to exchange lists identifying the patents to be litigated. The number of patents identified by the originator may not exceed the number provided by the biosimilar applicant.
However, if the biosimilar applicant previously indicated that no patents should be litigated, then the originator may identify one patent.
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Commencement of Patent Litigation. The originator must then commence patent infringement litigation within 30 days. That litigation will involve all of the patents on the originators list and all of the patents on
the
follow-on
applicants list. The
follow-on
applicant must then notify the FDA of the litigation. The FDA must then publish a notice of the litigation in the
Federal Register.
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Notice of Commercial Marketing. The BPCIA requires the biosimilar applicant to provide notice to the originator at least 180 days in advance of its first commercial marketing of its proposed
follow-on
biologic. The originator is allowed to seek a preliminary injunction blocking such marketing based upon any patents that either party had preliminarily identified, but were not subject to the initial phase
of patent litigation. The litigants are required to reasonably cooperate to expedite such further discovery as is needed with respect to the preliminary injunction motion.
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Biosimilar companies such as ours have the option of applying for U.S. regulatory approval for our products under either a traditional 351(a)
BLA approval route, or under the recently enacted streamlined 351(k) approval route established by the BPCIA. The factors underpinning such a decision are extremely complex and involve, among other things, balancing legal risk (in terms of, e.g.,
the degree and timing of exposure to potential patent litigation by the originator) versus regulatory risks (in terms of, e.g., the development costs and the differing scope of regulatory approval that may be afforded under 351(a) versus 351(k)).
A significant legal risk in pursuing regulatory approval under the 351(k) regulatory approval route is that the above-summarized patent
exchange process established by the BPCIA could result in the initiation of patent infringement litigation prior to FDA approval of a 351(k) application, and such litigation could result in blocking the market entry of our products. In particular,
while the 351(k) route is more attractive to us (versus 351(a)) for reasons related to development time and costs and the potential broader scope of eventual regulatory approval for our proposed biosimilar candidates, the countervailing risk in such
a regulatory choice is that the complex patent exchange process mandated by the BPCIA could ultimately prevent or substantially delay us from launching our products in the United States.
Moreover, the disclosure process set forth in Step 1 of the process outlined above, which is directed to disclosure by the biosimilar
applicant of not only its regulatory application but also the applicants manufacturing process, has the potential to afford originators an easier path than traditional infringement litigation for developing any factual grounds they may require
to support allegations of infringement. The rules established in the BPCIAs patent dispute procedures (versus the rules governing traditional patent infringement litigation) place biosimilar firms at a significant disadvantage by affording
originators a much easier mechanism for factual discovery, thereby increasing the risk that a biosimilar product could be blocked from the market more quickly than under traditional patent infringement litigation processes. However, a recent
decision by the United States Supreme Court held that no injunction is available under federal law to force compliance with the patent exchange and patent briefing process. The Supreme Court remanded the case to the Federal Circuit to answer:
(1) whether an injunction is available under state law; and (2) whether such a
state-law
injunction is preempted by federal law.
Preparing for and conducting the patent exchange, briefing and negotiation process outlined above will require extraordinarily sophisticated
legal counseling and extensive planning, all under extremely tight deadlines. Moreover, it may be difficult for us to secure such legal support if large, well-funded originators have already entered into engagements with highly qualified law firms
or if the most highly qualified law firms choose not to represent biosimilar applicants due to their long standing relationships with originators. Furthermore, we could be at a serious disadvantage in this process as an originator company, as
competitors may be able to apply substantially greater legal and financial resources to this process than we could.
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We are aware that some biosimilar companies, namely Sandoz International GmbH, or Sandoz, a
subsidiary of Novartis AG, and Celltrion, Inc. have engaged in legal challenges against originators to establish their right to bring declaratory judgment actions against such originators outside the complex framework of the BPCIA patent exchange
rules in order to challenge the validity of the originators patents
prior
to the filing of any biosimilar regulatory application. For example, in the Sandoz case against the originator Amgen (relating to Sandoz proposed etanercept
(Enbrel
®
) biosimilar) the federal district court ruled that Sandoz did not have the right to bring a declaratory judgment action against Amgen to challenge the validity of certain
Amgen-controlled patents directed to Enbrel
®
, but instead determined that Sandoz must use the patent exchange mechanism established in the BPCIA. Sandoz appealed this decision to the
United States Court of Appeals for the Federal Circuit, and on December 5, 2014 the Federal Circuit Court ruled that Sandoz had not met the legal requirements to pursue a declaratory judgment action against Amgen. The Federal Circuit court
did not address whether the patent resolution mechanism established in the BPCIA would preclude Sandoz from filing its declaratory judgment action against Amgen if and when it files an FDA application under the BPCIA for its etanercept biosimilar.
In October 2014, Amgen filed suit in federal district court against Sandoz alleging that Sandoz unlawfully refused to follow the patent
resolution provisions of the BPCIA in connection with Sandoz July 2014 regulatory approval application under 351(k) for its Neupogen
®
(filgrastim) biosimilar, Zarxio
®
. Amgen sought declaratory and injunctive relief. Following litigation at the federal district court and appeals to the Federal Circuit, on February 16, 2016, Sandoz petitioned the United
States Supreme Court for certiorari review of the Federal Circuit decision that biosimilar applicants must wait until FDA approval before providing
180-day
notice and Amgen filed a cross petition to review the
decision the patent exchange and briefing process is optional. On June 12, 2017, the Supreme Court issued a unanimous opinion in Amgen v. Sandoz holding that notice of commercial marketing may be given prior to FDA approval of the biosimilar
product. The Court also held that no injunction is available under federal law to force compliance with the patent exchange and patent briefing process. The Court remanded the case to the Federal Circuit to answer: (1) whether an injunction is
available under state law; and (2) whether such a
state-law
injunction is preempted by federal law.
If we file a 351(k) regulatory approval application for one or more of our products, we may consider it necessary or advisable to adopt the
strategy of selecting one or more patents of the originator to litigate in the above described BPCIA process (for example in steps 3 and 7, of the process, as outlined above), either to assert our
non-infringement
of such patents or to challenge their validity; but we may ultimately not be successful in that strategy and could be prevented from marketing the product in the United States.
Under the complex and uncertain rules of the BPCIA patent provisions, coupled with the inherent uncertainty surrounding the legal
interpretation of any originator patents that might be asserted against us in this new process, we see substantial risk that the BPCIA process may significantly delay or defeat our ability to market our products in the United States.
Our ability to market our therapeutic equivalent products in the United States may be significantly delayed or prevented by the Hatch-Waxman patent
dispute resolution mechanism, including a potential automatic 30 month stay of regulatory approval of our marketing applications.
The Hatch-Waxman Act.
The provisions of Section 505(b)(2) of the Federal Food, Drug, and Cosmetic Act, or FFDCA, were created, in
part, to help avoid unnecessary duplication of studies already performed on a previously approved (reference or listed) drug; the section gives the FDA express permission to rely on data not developed by the NDA applicant.
Indeed, an NDA filed under Section 505(b)(2) is one for which one or more of the investigations relied upon by the applicant for approval were not conducted by or for the applicant and for which the applicant has not obtained a right of
reference or use from the person by or for whom the investigations were conducted. We are pursuing a Section 505(b)(2) regulatory strategy for our PF708 product candidate and we plan to reference the Forteo (teriparatide) listed drug which is
marketed by Eli Lilly for the treatment of osteoporosis. It is possible that for one reason or another, we will not be able to establish that our PF708 product candidate is suitable for approval under the Section 505(b)(2) framework. In
addition, to the extent we rely on certain data and information that was submitted to the FDA related to the safety of Forteo, the FDA may likely require any approved labeling for PF708 to include certain safety information that is included in the
Forteo label, including contraindications, warnings, precautions and other safety information.
The owner of an NDA for a branded drug
product may list with the FDA certain patents whose claims allegedly cover the applicants branded product. Each of the patents listed in the application for the drug is then published in the Orange Book. Any applicant who files a 505(b)(2) NDA
referencing a drug listed in the Orange Book must certify to the FDA that: (1) no patent information on the drug product that is the subject of the application has been submitted to the FDA, referred to as a Paragraph I Certification;
(2) such patent has expired, referred to as a Paragraph II Certification; (3) the date on which such patent expires, referred to as a Paragraph III Certification; or (4) such patent is invalid or will not be infringed upon
by the manufacture, use or sale of the drug product for which the application is submitted, referred to as a Paragraph IV Certification.
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The applicant may also elect to submit a section viii statement certifying that
its proposed label does not contain, or carves out, any language regarding the patented
method-of-use
rather than certify to a listed
method-of-use
patent. An applicant submitting a Paragraph IV Certification must provide notice to each owner of the patent that is the subject of the certification and to the holder of the approved
branded drug to which the 505(b)(2) application references. If the reference branded drug holder and patent owners file a lawsuit directed to one of the Orange Book listed patents within 45 days of the receipt of the Paragraph IV
Certification notice, the FDA is prohibited from approving the 505(b)(2) application until the earlier of 30 months from the receipt of the Paragraph IV Certification, expiration of the patent, settlement of the lawsuit, or a decision in
the infringement case that is favorable to the applicant. In the event we commercially launch our PF708 product candidate at a time when one or more unexpired patents are listed in the Orange Book for a reference listed drug product, we see
substantial risk that the Paragraph IV certification process, including the likelihood of imposition of a 30 month stay and necessity of defending against accusation of patent infringement, may significantly delay or defeat our ability to
competitively market our PF708 product in the United States.
Non-Patent
Exclusivity and
Approval of Competing Products
. Additionally, a 505(b)(2) application also will not be approved until any applicable
non-patent
exclusivity listed in the Orange Book for the NDA branded reference drug has
expired as described in further detail below. Market and data exclusivity provisions under the FFDCA can delay the submission or the approval of certain applications for competing products. In addition to patent exclusivity, the holder of the NDA
for a reference listed drug may be entitled to a period of
non-patent
exclusivity, during which the FDA cannot approve another drug application that relies on the listed drug. For example, a pharmaceutical
manufacturer may obtain five years of
non-patent
exclusivity upon NDA approval of a new chemical entity, or NCE, which is a drug that contains an active moiety that has not been approved by the FDA in any
other NDA. An active moiety is defined as the molecule or ion responsible for the drug substances physiological or pharmacologic action. During the five-year exclusivity period, the FDA cannot accept for filing any application for
the same active moiety and that relies on the FDAs findings regarding that drug; the FDA may accept an application for filing after four years if the 505(b)(2) applicant makes a Paragraph IV Certification. A drug may obtain a three-year
period of exclusivity for a particular condition of approval, or change to a marketed product, such as a new formulation for a previously approved product, if one or more new clinical trials, other than bioavailability or bioequivalence studies, was
essential to the approval of the application and was conducted or sponsored by the applicant. Should this occur, the FDA would be precluded from approving any Abbreviated New Drug Application, or ANDA, that references such product until after that
three-year exclusivity period has run. However, unlike NCE exclusivity, the FDA can accept an application and begin the review process during the entire exclusivity period.
Clinical drug development involves a lengthy and expensive process with an uncertain outcome, and results of earlier studies and trials may not be
predictive of future trial results.
Clinical testing is expensive and can take many years to complete, and its outcome is
inherently uncertain. Furthermore, we rely on our collaboration partner, CROs, and clinical trial sites to ensure the proper and timely conduct of our clinical trials for our product candidates. While we have agreements governing the committed
activities of our collaboration partner and CROs, we have limited influence over their actual performance. A failure of one or more clinical trials can occur at any time during the trial process. The results of preclinical studies and early clinical
trials of our product candidates may not be predictive of the results of later-stage clinical trials. Product candidates that have shown promising results in early studies may still suffer significant setbacks in subsequent clinical studies. For
example, the results generated to date in the clinical trial for PF708 do not ensure that later clinical trials will demonstrate similar results. There is a high failure rate for drugs and biologics proceeding through clinical studies, and product
candidates in later stages of clinical trials may fail to show the desired safety and efficacy despite having progressed through preclinical studies and initial clinical trials. A number of companies in the biopharmaceutical industry have suffered
significant setbacks in advanced clinical trials due to lack of efficacy or adverse safety profiles, notwithstanding promising results in earlier clinical trials, and we cannot be certain that we will not face similar setbacks. Even if the clinical
trials for our product candidates are completed, nonclinical and clinical data are often susceptible to varying interpretations and analyses, and the results may not be sufficient to obtain regulatory approval for our product candidates.
We have in the past and may in the future experience delays in ongoing clinical trials for our product candidates, and we do not know whether
future clinical trials, if any, will begin on time, need to be redesigned, enroll an adequate number of patients on time or be completed on schedule, if at all. The commencement or completion of clinical trials can be delayed or aborted for a
variety of reasons, including delay or failure to:
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generate sufficient preclinical, toxicology, or other in vivo or in vitro data to support the initiation of human clinical studies;
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raise sufficient capital to fund a trial;
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obtain regulatory approval, or feedback on trial design, necessary to commence a trial;
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identify, recruit and train suitable clinical investigators;
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reach agreement on acceptable terms with prospective CROs and clinical trial sites, the terms of which can be subject to extensive negotiation and may vary significantly among different CROs and trial sites;
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obtain institutional review board, or IRB, approval at each site;
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identify, recruit, and enroll suitable patients to participate in a trial;
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have patients complete a trial or return for post-treatment
follow-up;
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ensure clinical sites observe trial protocol or continue to participate in a trial;
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address any patient safety concerns that arise during the course of a trial;
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address any conflicts with new or existing laws or regulations;
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add a sufficient number of clinical trial sites;
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manufacture sufficient quantities of product candidate for use in clinical trials; and
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avoid delays in manufacturing, testing, releasing, validating, or importing/exporting sufficient stable quantities of our product candidates for use in clinical studies, or the inability to do any of the foregoing.
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Patient enrollment is a significant factor in the completion of clinical trials and is affected by many factors, including
the size and nature of the patient population, the proximity of patients to clinical sites, the eligibility criteria for the trial, the design of the clinical trial, competing clinical trials and clinicians and patients perceptions as to
the potential advantages of the drug being studied in relation to other available therapies, including any new drugs or treatments that may be approved for the indications we are investigating.
We could also encounter delays if a clinical trial is suspended or terminated by us, by the IRBs of the institutions in which such trials are
being conducted, by the data safety monitoring board, for such trial or by the FDA or other regulatory authorities. Such authorities may suspend or terminate a clinical trial due to a number of factors, including failure to conduct the clinical
trial in accordance with regulatory requirements or our clinical protocols, inspection of the clinical trial operations or trial site by the FDA or other regulatory authorities resulting in the imposition of a clinical hold, unforeseen safety issues
or adverse side effects, failure to demonstrate a benefit from using a drug, changes in governmental regulations or administrative actions or lack of adequate funding to continue the clinical trial.
If we or our collaboration partner experience delays in the completion of, or termination of, any clinical trial of our product candidates,
the commercial prospects of our product candidates may be harmed, and our ability to generate product revenue from any of these product candidates will be delayed. In addition, any delays in completing clinical trials for our product candidates will
increase our costs, slow down our product candidate development and approval process and jeopardize our ability to commence product sales and generate revenue. Any of these occurrences may significantly harm our business, financial condition and
prospects. In addition, 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 our product candidates.
Even if PF708, Px563L/RPA563 or any of our other product candidates obtain regulatory approval, they may never achieve market acceptance or commercial
success.
Even if we or our collaboration partner obtain FDA or other regulatory approvals, PF708, Px563L/RPA563 or any of our
other product candidates may not achieve market acceptance among physicians and patients, and may not be commercially successful. The degree and rate of market acceptance of PF708, Px563L/RPA563 or any of our other product candidates for which we
receive approval depends on a number of factors, including:
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the safety and efficacy of the product as demonstrated in clinical trials;
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the clinical indications for which the product is approved;
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acceptance by physicians, major operators of clinics and patients of the product as a safe and effective treatment;
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proper training and administration of our products by physicians and medical staff;
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the potential and perceived advantages of our products over alternative treatments;
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the cost of treatment in relation to alternative treatments and willingness to pay for our products, if approved, on the part of physicians and patients;
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relative convenience and ease of administration;
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the prevalence and severity of adverse events; and
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the effectiveness of our sales and marketing efforts.
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Any failure by our product candidates
that obtain regulatory approval to achieve market acceptance or commercial success would materially adversely affect our results of operations and delay, prevent or limit our ability to generate revenue and continue our business.
The development, manufacture and commercialization of biosimilar, therapeutic equivalent, and vaccine products pose unique risks, and our failure to
successfully introduce biosimilar, therapeutic equivalent products, and vaccine products could have a negative impact on our business and future operating results.
We are actively working to develop multiple biosimilar, therapeutic equivalent products and vaccines, including our most advanced product
candidates, PF708, and Px563L/RPA563. The cost to develop each biosimilar, therapeutic equivalent, and vaccine product candidate could vary significantly and is highly dependent on the specific compound and the amount and type of clinical work that
will be necessary for regulatory approval. There can be no assurance that our clinical work will be successful, or that regulatory authorities will not require additional clinical development beyond that which we have planned. Additionally, we may
enter into alliances and collaborations to fund biosimilar and therapeutic equivalent product research and development activities, and the success of any such biosimilar or therapeutic equivalent product program may depend on our ability to realize
the benefits under such arrangements. Due to events beyond our control or the risks identified herein, we may be unable to fund all or some of our internal biosimilar, therapeutic equivalent, and vaccine product research and development initiatives,
which would have an adverse impact on our strategy and growth initiatives.
We intend to pursue market authorization globally when
commercially appropriate. Since October 2005, the EU has had a regulatory framework for the approval of biosimilar products and as of September 30, 2017, 39 biosimilar medicinal products, less three subsequently withdrawn, have been approved.
In the United States, an abbreviated pathway for approval of biosimilar products was established by the BPCIA, enacted on March 23, 2010, as part of the ACA. The BPCIA established this abbreviated pathway under section 351(k) of the PHSA.
Subsequent to the enactment of the BPCIA, the FDA issued draft guidance regarding the demonstration of biosimilarity as well as the submission and review of biosimilar applications. However, to date, only seven biosimilars have been approved by the
FDA, and no biosimilar product has been designated as interchangeable to the reference drug. Moreover, market acceptance of biosimilar products in the U.S. is unclear. Numerous states are considering or have already enacted laws that regulate or
restrict the substitution by state pharmacies of biosimilars for biological products already licensed by the FDA pursuant to BLAs, or reference products. Market success of biosimilar products will depend on demonstrating to patients,
physicians, payors, and relevant authorities that such products are safe and efficacious compared to other existing products.
We will
continue to analyze and incorporate into our biosimilar development plans any final regulations issued by the FDA, pharmacy substitution policies enacted by state governments, and other applicable requirements established by relevant authorities.
The costs of development and approval, along with the probability of success for our biosimilar product candidates, will be dependent upon application of any laws and regulations issued by the relevant regulatory authorities.
Biosimilar products may also be subject to extensive patent clearances and patent infringement litigation, which will likely delay and could
prevent the commercial launch of a product. Moreover, the BPCIA prohibits the FDA from accepting an application for a biosimilar candidate to a reference product within four years of the reference products licensure by the FDA. In addition,
the BPCIA provides innovative biologics with 12 years of exclusivity from the date of their licensure, during which time the FDA cannot approve any application for a biosimilar candidate to the reference product. The proposal to award biologic
manufacturers seven years of exclusivity rather than 12 years carried forward in President Obamas proposed budget for fiscal year 2017. He also proposed to prohibit additional periods of exclusivity due to minor changes in product
formulations, a practice often referred to as evergreening. We are also aware of congressional measures H.R. 5573 and S.3094 (PRICED ACT) introduced to both the House and Senate on June 23, 2016, seeking to shorten the
exclusivity period for brand name biological products from 12 to 7 years. It is possible that Congress may take these or other measures to reduce or eliminate periods of exclusivity.
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The BPCIA is complex and only beginning to be interpreted and implemented by the FDA. As a
result, its ultimate impact, implementation, and meaning is subject to significant uncertainty. Future implementation decisions by the FDA could result in delays in the development or commercialization of our product candidates or increased costs to
assure regulatory compliance, and could adversely affect our operating results by restricting or significantly delaying our ability to market new biosimilar products. In the EEA, holders of marketing authorizations of reference products (for which a
marketing authorization was applied for under the centralized procedure after November 20, 2005, or under the Decentralized, Mutual Recognition and national procedures, after October 30, 2005) enjoy eight years of data exclusivity during
which a
follow-on
product or biosimilar marketing authorization applicant cannot rely on the preclinical and clinical data included in the reference products dossier, and 10 years of marketing
exclusivity during which a
follow-on
product or biosimilar of the reference product cannot be placed in the EEA market. The marketing exclusivity period can be extended one additional year (to 11 years) if a
second indication of the reference product with significant clinical benefit is approved during the eight-year data exclusivity period. The data and marketing exclusivity periods start from the date of the initial authorization, which for reference
medicinal products authorized through the Centralized Procedure is the date of notification of the marketing authorization decision to the marketing authorization holder of the reference product.
We may rely on the Animal Rule in conducting trials, which could be time consuming and expensive.
To obtain FDA approval for our vaccine candidates RPA563 and/or Px563L, we may obtain clinical data from trials in healthy human subjects that
demonstrate adequate safety, and efficacy data from adequate and well-controlled animal studies under regulations issued by the FDA in 2002, often referred to as the Animal Rule. Among other requirements, the animal studies must
establish that the drug or biological product is reasonably likely to produce clinical benefits in humans. If we use this approach we may not be able to sufficiently demonstrate this correlation to the satisfaction of the FDA, as these corollaries
are difficult to establish and are often unclear. Because the FDA must agree that data derived from animal studies may be extrapolated to establish safety and effectiveness in humans, seeking approval under the Animal Rule may add significant time,
complexity and uncertainty to the testing and approval process. The FDA may decide that our data are insufficient for approval and require additional preclinical, clinical or other studies, refuse to approve RPA563 and/or Px563L, or place
restrictions on our ability to commercialize the products. In addition, products approved under the Animal Rule are subject to additional requirements including post-marketing study requirements, restrictions imposed on marketing or distribution or
requirements to provide information to patients. Further, regulatory authorities in other countries have not, at this time, established an Animal Rule equivalent, and consequently there can be no assurance that we will be able to make a submission
for marketing approval in foreign countries based on such animal data.
Additionally, few facilities in the U.S. and internationally may
have the capability to test animals involving exposure to anthrax or otherwise assist us in qualifying the requisite animal models, and we must compete with other companies for access to this limited pool of highly specialized resources. We
therefore may not be able to secure contracts to conduct the testing in a predictable timeframe or at all.
If we and our collaboration partner are
not able to demonstrate biosimilarity of our biosimilar product candidates to the satisfaction of regulatory authorities, we will not obtain regulatory approval for commercial sale of our biosimilar product candidates and our future results of
operations would be adversely affected.
Our future results of operations depend, to a significant degree, on our and our
collaboration partners ability to obtain regulatory approval for and commercialize our proposed biosimilar products. To obtain regulatory approval for the commercial sale of these product candidates, we will be required to demonstrate to the
satisfaction of regulatory authorities, among other things, that our proposed biosimilar products are highly similar to biological products already licensed by the FDA pursuant to Biologic License Applications, or BLAs, notwithstanding minor
differences in clinically inactive components, and that they have no clinically meaningful differences as compared to the marketed biological products in terms of the safety, purity and potency of the products. In the EEA, the similar nature of a
biosimilar and a reference product is demonstrated by comprehensive comparability studies covering quality, biological activity, safety and efficacy.
In addition, the FDA may determine that a proposed biosimilar product is interchangeable with a reference product, meaning that
the biosimilar product may be substituted by a pharmacist for the reference product without the intervention of the health care provider who prescribed the reference product, if the application includes sufficient information to show that the
product is biosimilar to the reference product and that it can be expected to produce the same clinical result as the reference product in any given patient. If the biosimilar product may be administered more than once to a patient, the applicant
must demonstrate that the risk in terms of safety or diminished efficacy of alternating or switching between the biosimilar and reference product is not greater than the risk of using the reference product without such alternation or switch. To make
a final determination of biosimilarity or interchangeability, regulatory
52
authorities may require additional confirmatory information beyond what we and our collaboration partner plan to initially submit in our applications for approval, such as more
in-depth
analytical characterization, animal testing, or further clinical studies. Provision of sufficient information for approval may prove difficult and expensive. We cannot predict whether any of our biosimilar
product candidates will meet regulatory authority requirements for approval as a biosimilar or interchangeable product. To date, the FDA has not approved a biosimilar product as being interchangeable to the reference drug.
Analytical assessments can identify potential differences between biosimilar candidates and reference products. Differences in the analytical
assessments may require clinical studies to reduce the residual uncertainties. In the event that regulatory authorities require us to conduct additional clinical trials or other lengthy processes, the commercialization of our proposed biosimilar
products could be delayed or prevented. Delays in the commercialization of, or the inability to obtain regulatory approval for, these products could adversely affect our operating results by restricting or significantly delaying our introduction of
new biosimilars.
If other therapeutic equivalent products to Forteo are approved and successfully commercialized before PF708, our business would
suffer.
Other companies may seek approval to manufacture and market therapeutic equivalent product versions of Forteo. If other
therapeutic equivalent product versions of Forteo, are approved and successfully commercialized before PF708, we may never achieve significant market share for PF708, our revenue would be reduced and, as a result, our business, prospects and
financial condition could suffer. In addition, the first biosimilar determined to be interchangeable with a particular reference product for any condition of use is eligible for a period of market exclusivity that delays an FDA determination that a
second or subsequent biosimilar product is interchangeable with that reference product for any condition of use until the earlier of: (1) one year after the first commercial marketing of the first interchangeable product; (2) 18 months
after resolution of a patent infringement suit instituted under 42 U.S.C. § 262(l)(6) against the applicant that submitted the application for the first interchangeable product, based on a final court decision regarding all of the patents
in the litigation or dismissal of the litigation with or without prejudice; (3) 42 months after approval of the first interchangeable product, if a patent infringement suit instituted under 42 U.S.C. § 262(l)(6) against the applicant that
submitted the application for the first interchangeable product is still ongoing; or (4) 18 months after approval of the first interchangeable product if the applicant that submitted the application for the first interchangeable product has not
been sued under 42 U.S.C. § 262(l)(6). A determination that another companys product is interchangeable with a reference product prior to approval of our biosimilar product candidate may therefore delay the potential determination
that our biosimilar product candidate is interchangeable with the reference product, which may materially adversely affect our results of operations and delay, prevent or limit our ability to generate revenue.
Failure to obtain regulatory approval in each regulatory jurisdiction would prevent us and our collaboration partner from marketing our products to a
larger patient population and reduce our commercial opportunities.
In order to market our products in the European Union, the
United States and other jurisdictions, we or our collaboration partner must obtain separate regulatory approvals and comply with numerous and varying regulatory requirements. The European Medicines Agency is responsible for the centralized procedure
for human medicines. This procedure results in a single marketing authorization that is valid in all European Union countries, as well as in Iceland, Liechtenstein and Norway. The time required to obtain approval abroad may differ from that required
to obtain FDA approval. The foreign regulatory approval process may include all of the risks associated with obtaining FDA approval and we may not obtain foreign regulatory approvals on a timely basis, if at all. Approval by the FDA does not ensure
approval by regulatory authorities in other countries, and approval by one foreign regulatory authority does not ensure approval by regulatory authorities in other foreign countries or by the FDA. We may not be able to file for regulatory approvals
and may not receive necessary approvals to commercialize our products within the United States or in any market outside the United States. Failure to obtain these approvals would materially and adversely affect our business, financial condition and
results of operations.
Even if we and our collaboration partner obtain regulatory approvals for our product candidates, we will be subject to
ongoing regulatory review.
Even if we and our collaboration partner obtain regulatory approval for our product candidates, any
products we develop will be subject to ongoing regulatory review with respect to manufacturing, labeling, packaging, storage, advertising, promotion, sampling, record-keeping, conduct of post-marketing studies, and submission of safety, efficacy,
and other post-market information, including both federal and state requirements in the United States and requirements of comparable foreign regulatory authorities. Manufacturers and manufacturers facilities are required to comply with
extensive FDA and comparable foreign regulatory authority requirements,
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including ensuring that quality control and manufacturing procedures conform to cGMP. As such, we and our contract manufacturers will be subject to continual and unannounced review and
inspections by the regulatory authorities governing the markets in which we wish to sell our products. Accordingly, we and others with whom we work must continue to expend time, money, and effort in all areas of regulatory compliance, including
manufacturing, production, and quality control.
Any regulatory approvals that we and our collaboration partner receive for our product
candidates may be subject to limitations on the approved indicated uses for which the product may be marketed or to the conditions of approval, or contain requirements for potentially costly post-marketing testing, including Phase 4 trials, and
surveillance to monitor the safety and efficacy or the safety, purity, and potency of the product candidate. We will be required to immediately report any serious and unexpected adverse events and certain quality or production problems with our
products to regulatory authorities along with other periodic reports. Any new legislation addressing drug or biologic product safety issues could result in delays in product development or commercialization, or increased costs to assure compliance.
We and our collaboration partner will have to comply with requirements concerning advertising and promotion for our products. Promotional communications with respect to prescription drug and biologic products are subject to a variety of legal and
regulatory restrictions and must be consistent with the information in the products approved label. As such, we will not be allowed to promote our products for indications or uses for which they do not have approval. The holder of an approved
NDA, BLA, 351(k) application or marketing authorization application must submit new or supplemental applications and obtain prior approval for certain changes to the approved product, product labeling, or manufacturing process. We could also be
asked to conduct post-marketing clinical studies to verify the safety and efficacy of our products in general or in specific patient subsets. An unsuccessful post-marketing study or failure to complete such a study could result in the withdrawal of
marketing approval.
If a regulatory agency discovers previously unknown problems with a product, such as adverse events of unanticipated
severity or frequency, or problems with the facility where the product is manufactured or disagrees with the promotion, marketing or labeling of a product, or if we or our collaboration partner fail to comply with applicable continuing regulatory
requirements, such regulatory agency may impose restrictions on that product or us, including requiring withdrawal of the product from the market. If we or our collaboration partner fail to comply with applicable regulatory requirements, a
regulatory agency or enforcement authority may subject us to administrative or judicially imposed sanctions or other actions, including, among other things:
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adverse publicity, fines or warning letters;
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civil or criminal penalties;
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suspending or withdrawing regulatory approval;
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suspending any of our ongoing clinical studies;
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refusing to approve pending applications or supplements to approved applications submitted by us;
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imposing restrictions on our operations, including closing our contract manufacturers facilities; or
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seizing or detaining products, or requiring a product recall.
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Any government investigation of
alleged violations of law could require us to expend significant time and resources in response, and could generate negative publicity. Any failure to comply with ongoing regulatory requirements may significantly and adversely affect our ability to
commercialize and generate revenue from our products. If regulatory sanctions are applied or if regulatory approval is withdrawn, the value of our company and our operating results will be adversely affected.
We will also be subject to various health care fraud and abuse laws, including anti-kickback, false claims and fraud laws, and physician payment
transparency laws, and any violations by us of such laws could result in fines or other penalties.
Although we currently do not
have any products on the market, if our product candidates are approved and we begin commercialization, we will be subject to healthcare regulation and enforcement by the federal government and the states and EEA and other foreign governments in
which we conduct our business. These laws include, without limitation, state and federal, as well as EEA and other foreign, anti-kickback, fraud and abuse, false claims, privacy and security and physician sunshine laws and regulations. The federal
Anti-Kickback Statute prohibits the offer, receipt, or payment of remuneration in exchange for or to induce the referral of patients or the use of products or services that would be paid for in whole or part by Medicare, Medicaid or other federal
health care programs. Remuneration has been broadly defined to include anything of value, including cash, improper discounts, and free or reduced price items and services. The government has enforced the Anti-Kickback Statute to reach large
settlements with healthcare companies based on sham research or consulting and other financial arrangements with physicians. Further, the ACA, among other
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things, amended the intent requirement of the federal Anti-Kickback Statute and certain criminal statutes governing healthcare fraud. A person or entity no longer needs to have actual knowledge
of the statute or specific intent to violate it. In addition, the ACA provided 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 FCA or federal civil money penalties statute. Many states have similar laws that apply to their state health care programs as well as private payors. Violations of the anti-kickback laws can result in exclusion from federal
health care programs and substantial civil and criminal penalties. The FCA imposes liability on persons who, among other things, present or cause to be presented false or fraudulent claims for payment by a federal health care program. The FCA has
been used to prosecute persons submitting claims for payment that are inaccurate or fraudulent, that are for services not provided as claimed, or for services that are not medically necessary. Actions under the FCA may be brought by the Attorney
General or as a qui tam action by a private individual in the name of the government. Violations of the FCA can result in significant monetary penalties and treble damages. The federal government is using the FCA, and the accompanying threat of
significant liability, in its investigation and prosecution of pharmaceutical and biotechnology companies throughout the country, for example, in connection with the promotion of products for unapproved uses and other sales and marketing practices.
The government has obtained multi-million and multi-billion dollar settlements under the FCA in addition to individual criminal convictions under applicable criminal statutes. In addition, companies have been forced to implement extensive corrective
action plans, and have often become subject to consent decrees or corporate integrity agreements, severely restricting the manner in which they conduct their business. Given the significant size of actual and potential settlements, it is expected
that the government will continue to devote substantial resources to investigating healthcare providers and manufacturers compliance with applicable fraud and abuse laws. If our future marketing or other arrangements were determined to
violate anti-kickback or related laws, including the FCA, then our revenue could be adversely affected, which would likely harm our business, financial condition, and results of operations.
In addition, there has been a recent trend of increased federal and state regulation of payments made to physicians and other healthcare
providers. The ACA, among other things, imposed new reporting requirements on drug commercial manufacturers for payments and other transfers of value made by them to physicians and teaching hospitals, as well as ownership and investment interests
held by physicians and their immediate family members. Failure to submit required information may result in civil monetary penalties of up to an aggregate of $150,000 per year (or up to an aggregate of $1 million per year for knowing
failures), for all payments, transfers of value or ownership or investment interests that are not timely, accurately and completely reported in an annual submission. Drug manufacturers must submit reports by the 90th day of each calendar
year. Certain states also mandate implementation of commercial compliance programs, impose restrictions on device manufacturer marketing practices and/or require the tracking and reporting of gifts, compensation and other remuneration to physicians.
The shifting commercial compliance environment and the need to build and maintain robust and expandable systems to comply with different
compliance and/or reporting requirements in multiple jurisdictions increase the possibility that a healthcare company may violate one or more of the requirements. If our operations are found to be in violation of any of such laws or any other
governmental regulations that apply to us, we may be subject to penalties, including, without limitation, civil and criminal penalties, damages, fines, the curtailment or restructuring of our operations, exclusion from participation in federal and
state healthcare programs and imprisonment, any of which could adversely affect our ability to operate our business and our financial results.
Also, the U.S. Foreign Corrupt Practices Act and similar worldwide anti-bribery laws generally prohibit companies and their intermediaries
from making improper payments to
non-U.S.
officials for the purpose of obtaining or retaining business. We cannot assure investors that our internal control policies and procedures will protect us from
reckless or negligent acts committed by our employees, future distributors, partners, collaborators or agents. Violations of these laws, or allegations of such violations, could result in fines, penalties or prosecution and have a negative impact on
our business, results of operations and reputation.
Legislative or regulatory healthcare reforms in the United States may make it more difficult
and costly for us to obtain regulatory approval of PF708, Px563L/RPA563 or any other product candidates and to produce, market, and distribute our products after approval is obtained, if any.
From time to time, legislation is drafted and introduced in Congress that could significantly change the statutory provisions governing the
regulatory approval, manufacturing, and marketing of regulated products or the reimbursement thereof. In addition, FDA regulations and guidance may be revised or reinterpreted by the FDA in ways that may significantly affect our business and our
products. Any new regulations or guidance, or revisions or reinterpretations of existing regulations or guidance, may impose additional costs or lengthen FDA review times for PF708, Px563L/RPA563 or any other product candidates. We cannot determine
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how changes in regulations, statutes, policies, or interpretations when and if issued, enacted or adopted, may affect our business in the future. Such changes could, among other things, require:
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changes to manufacturing methods;
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recalls, replacements, or discontinuance of one or more of our products; and
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additional recordkeeping.
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Such changes would likely require substantial time and impose
significant costs, and could materially harm our business and our financial results. In addition, delays in receipt of or failure to receive regulatory clearances or approvals for any other products would harm our business, financial condition, and
results of operations.
If efforts by manufacturers of reference products to delay or limit the use of biosimilars and therapeutic equivalent
products are successful, our sales of biosimilar and other therapeutic equivalent products may suffer.
Many manufacturers of
reference products have increasingly used legislative, regulatory and other means in attempts to delay regulatory approval of and competition from biosimilars and therapeutic equivalent products. These efforts have included sponsoring legislation to
prevent pharmacists from substituting biosimilars and therapeutic equivalent products for prescribed reference products or to make such substitutions more difficult by establishing notification, recordkeeping, and/or other requirements, as well as
seeking to prevent manufacturers of biosimilars and therapeutic equivalent products from referencing the branded products in biosimilar and therapeutic equivalent product labels and marketing materials. If these or other efforts to delay or block
competition are successful, we may be unable to sell our biosimilar and therapeutic equivalent product candidates, which could have a material adverse effect on our sales and profitability.
Our and our collaboration partners future sales will be dependent on the availability and level of coverage and reimbursement from third-party
payors who continue to implement cost-cutting measures and more stringent reimbursement standards.
In the United States and
internationally, our and our collaboration partners ability to generate revenue on future sales of our products will be dependent, in significant part, on the availability and level of coverage and reimbursement from third-party payors, such
as state and federal governments and private insurance plans. Insurers have implemented cost-cutting measures and other initiatives to enforce more stringent reimbursement standards and likely will continue to do so in the future. These measures
include the establishment of more restrictive formularies and increases in the
out-of-pocket
obligations of patients for such products. In addition, particularly in the
U.S. and increasingly in other countries, we will be required to provide discounts and pay rebates to state and federal governments and agencies in connection with purchases of our products that are reimbursed by such entities.
In addition, in the United States, the full impact of recent healthcare reform and other changes in the healthcare industry and in healthcare
spending is currently unknown. In March 2010, the ACA, as amended by the Health Care and Education Reconciliation Act, was enacted with a goal of reducing the cost of healthcare and substantially changing the way healthcare is financed by both
government and private insurers. The ACA, among other things, subjected biologic products to potential competition by lower-cost biosimilars and
follow-on
products, addressed a new methodology by which rebates
owed by manufacturers under the Medicaid Drug Rebate Program are calculated for drugs that are inhaled, infused, instilled, implanted or injected, increased the minimum Medicaid rebates owed by manufacturers under the Medicaid Drug Rebate Program
and extended the rebate program to individuals enrolled in Medicaid managed care organizations, established annual fees and taxes on manufacturers of certain prescription drugs, and created a new Medicare Part D coverage gap discount program, in
which manufacturers must agree to offer 50%
point-of-sale
discounts off negotiated prices of applicable reference product drugs to eligible beneficiaries during their
coverage gap period as a condition for the manufacturers outpatient drugs to be covered under Medicare Part D.
Other legislative
changes have been proposed and adopted in the U.S. since the ACA was enacted. On August 2, 2011, the Budget Control Act of 2011 created measures for spending reductions by Congress. A Joint Select Committee on Deficit Reduction, tasked with
recommending a targeted deficit reduction of at least $1.2 trillion for the years 2013 through 2021, was unable to reach required goals, thereby triggering the legislations automatic reduction to several government programs. This included
aggregate reductions of Medicare payments to providers of 2% per fiscal year, which went into effect on April 1, 2013 and will stay in effect through 2024 unless additional Congressional action is taken. On January 2, 2013, the
American Tax Payer Relief Act was signed into law, which, among other things, further reduced Medicare payments to several providers, including hospitals. We expect that additional healthcare reform measures will be adopted in the future, any of
which could limit the amounts that federal, state and foreign governments will pay for healthcare products and services, which could result in reduced demand for our products, if approved, or additional pricing pressures. Furthermore, the current
presidential administration and Congress are also expected to
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attempt broad sweeping changes to the current health care laws. We face uncertainties that might result from modification or repeal of any of the provisions of the ACA, including as a result of
current and future executive orders and legislative actions. The impact of those changes on us and potential effect on biosimilar manufacturing industry as a whole is currently unknown. But, any changes to the ACA are likely to have an impact on our
results of operations, and may have a material adverse effect on our results of operations. We cannot predict what other healthcare programs and regulations will ultimately be implemented at the federal or state level or the effect of any future
legislation or regulation in the United States may have on our business.
Foreign governments tend to impose strict price controls, which may
adversely affect our revenue, if any.
In some foreign countries, the pricing of prescription pharmaceuticals is subject to
governmental control. In these countries, pricing negotiations with governmental authorities can take considerable time after the receipt of marketing approval for a product. Our existing or future collaboration partners, if any, may elect to reduce
the price of our products in order to increase the likelihood of obtaining reimbursement approvals which could adversely affect our revenues and profits. To obtain reimbursement or pricing approval in some countries, we or our collaboration partner
may also be required to conduct a clinical trial that compares the cost-effectiveness of our product candidate to other available therapies. If reimbursement of our products is unavailable or limited in scope or amount, or if pricing is set at
unsatisfactory levels, our business could be adversely affected.
Risks Relating to Owning Our Common Stock
The market price of our stock may fluctuate significantly, and investors may have difficulty selling their shares.
Our stock is currently traded on NYSE American, but we can provide no assurance that we will be able to maintain an active trading market on
NYSE American or any other exchange in the future. The trading volume of our stock tends to be low relative to our total outstanding shares, and we have several stockholders who hold substantial blocks of our stock. As of September 30, 2017, we
had 23,548,280 shares of common stock outstanding, and stockholders holding at least 5% of our stock, individually or with affiliated persons or entities, collectively beneficially owned or controlled approximately 39% of such shares. Sales of large
numbers of shares by any of our large stockholders could adversely affect our trading price, particularly given our relatively small historic trading volumes. If stockholders holding shares of our common stock sell, indicate an intention to sell, or
if it is perceived that they will sell, substantial amounts of their common stock in the public market, the trading price of our common stock could decline.
Since shares of our common stock were sold in our initial public offering in July 2014 at a price of $6.00 per share, our stock price has
ranged from $2.94 to $24.41 through September 30, 2017. In addition to the factors discussed in this Risk Factors section and elsewhere in this quarterly report on Form
10-Q
factors that may
cause volatility in our share price include:
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actual or anticipated quarterly variation in our results of operations or the results of our competitors;
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announcements by us or our competitors of new commercial products, significant contracts, commercial relationships or capital commitments;
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issuance of new or changed securities analysts reports or recommendations for our stock;
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developments or disputes concerning our intellectual property or other proprietary rights;
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changes to our organization and management;
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commencement of, or our involvement in, litigation;
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market conditions in the relevant market;
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reimbursement or legislative changes in the relevant market;
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failure to complete significant sales;
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regulatory developments that may impact our product candidates;
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any future sales of our common stock or other securities;
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any major change to the composition of our board of directors or management; and
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general economic conditions and slow or negative growth of our markets.
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The stock market in general and market prices for the securities of biopharmaceutical
companies like ours in particular, have from time to time experienced volatility that often has been unrelated to the operating performance of the underlying companies. These broad market and industry fluctuations may adversely affect the market
price of our common stock, regardless of our operating performance.
We may be subject to securities litigation, which is expensive and could divert
management attention.
The market price of our common stock has been and will likely continue to be volatile, and in the past
companies that have experienced volatility in the market price of their stock have been subject to securities class action litigation. We may be the target of this type of litigation in the future. Securities litigation against us could result in
substantial costs and divert our managements attention from other business concerns, which could seriously harm our business.
If securities
or industry analysts publish unfavorable research about our business or cease to cover our business, our stock price and/or trading volume could decline.
The trading market for our common stock may rely, in part, on the research and reports that equity research analysts publish about us and our
business. We do not have any control of the analysts or the content and opinions included in their reports. The price of our stock could decline if one or more equity research analysts downgrade our stock or issue other unfavorable commentary or
research. If one or more equity research analysts cease coverage of our company or fails to publish reports on us regularly, demand for our stock could decrease, which in turn could cause our stock price or trading volume to decline.
If we sell shares of our common stock in future financings, stockholders may experience immediate dilution and, as a result, the market price of our
common stock may decline.
We may from time to time issue additional shares of common stock at a discount from the current trading
price of our common stock. As a result, our stockholders would experience immediate dilution upon the purchase of any shares of our common stock sold at such discount. In addition, as opportunities present themselves, we may enter into financing or
similar arrangements in the future, including the issuance of debt securities, preferred stock or common stock. If we issue common stock or securities convertible into common stock, our common stockholders would experience additional dilution and,
as a result, the market price of our common stock may decline.
Sales of substantial amounts of our common stock in the public markets, or the
perception that such sales might occur, could reduce the price that our common stock might otherwise attain and may dilute your voting power and your ownership interest in us.
Sales of a substantial number of shares of our common stock in the public market, or the perception that these sales might occur, could
depress the market price of our common stock and could impair our ability to raise capital through the sale of additional equity securities. We are unable to predict the effect that sales may have on the prevailing market price of our common stock.
We also register the offer and sale of all shares of common stock that we may issue under our equity compensation plans.
Furthermore,
certain of our executive officers have adopted, and other directors and executive officers may in the future adopt, written plans, known as Rule
10b5-1
Plans, under which they have contracted, or
may in the future contract, with a broker to sell shares of our common stock on a periodic basis to diversify their assets and investments. Sales of substantial amounts of our common stock in the public markets, including, but not limited to, sales
made by our executive officers and directors pursuant to Rule
10b5-1
Plans, or the perception that these sales could occur, could cause the market price of our common stock to decline.
We are an emerging growth company, and the reduced disclosure requirements applicable to emerging growth companies could make our common
stock less attractive to investors.
We are an emerging growth company, as defined in the Jumpstart Our Business
Startups, or JOBS, Act enacted in April 2012, and may remain an emerging growth company for up to five years following the completion of our initial public offering, although, if we have more than $1.0 billion in annual revenue, if
the market value of our common stock that is held by
non-affiliates
exceeds $700 million as of December 31 of any year, or we issue more than $1.0 billion of
non-convertible
debt over a three-year period before the end of that five-year period, we would cease to be an emerging growth company as of the following December 31. For as
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long as we remain an emerging growth company, we are permitted and intend to rely on exemptions from certain disclosure requirements that are applicable to other public companies that
are not emerging growth companies. These exemptions include:
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not being required to comply with the auditor attestation requirements in the assessment of our internal control over financial reporting;
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not being required to comply with any requirement that may be adopted by the Public Company Accounting Oversight Board regarding mandatory audit firm rotation or a supplement to the auditors report providing
additional information about the audit and the financial statements;
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reduced disclosure obligations regarding executive compensation; and
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exemptions from the requirements of holding a nonbinding advisory vote on executive compensation and shareholder approval of any golden parachute payments not previously approved.
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We have taken advantage of reduced reporting burdens in our reports filed with the Securities and Exchange Commission, or SEC. In addition,
the JOBS Act provides that an emerging growth company can take advantage of an extended transition period for complying with new or revised accounting standards, delaying the adoption of these accounting standards until they would apply to private
companies. We have elected to avail ourselves of this exemption and, as a result, our financial statements may not be comparable to the financial statements of reporting companies who are required to comply with the effective dates for new or
revised accounting standards that are applicable to public companies. We cannot predict whether investors will find our common stock less attractive as a result of our reliance on these exemptions. If some investors find our common stock less
attractive as a result, there may be a less active trading market for our common stock and the market price of our common stock may be reduced or more volatile.
If we fail to maintain effective internal control over financial reporting in the future, the accuracy and timing of our financial reporting may be
adversely affected.
In connection with our audit committee investigation as more fully described in Item 4,
Controls and
Procedures
, we identified a material weakness in our internal control over financial reporting. A material weakness is a significant deficiency, or a combination of significant deficiencies, in internal control over financial reporting
such that it is reasonably possible that a material misstatement of the annual or interim financial statements will not be prevented or detected on a timely basis. The material weakness that we previously identified related to a failure to maintain
an effective control environment as our former Chief Executive Officer failed to set an appropriate Tone at the Top. The material weakness was identified in connection with our Audit Committee Investigation, which found violations of our
Board Approval Process Policy and related violations of our Code of Ethics and Conduct by our former Chief Executive Officer. The investigation determined that our former Chief Executive Officer had not acted in accordance with our Board Approval
Process Policy and Code of Ethics and Conduct as a result of his failure to comply with certain board approval procedures for third-party contracts.
In response to this reported material weakness, we undertook the following steps in the first and second quarter of 2017: a change in our
Chief Executive Officer following the resignation of our former Chief Executive Officer on January 23, 2017; requiring documentation of approvals for contracts that are within the scope of the Board Approval Process Policy; increasing the
frequency of our internal audit testwork to assess the design, implementation, and operating effectiveness of our entity level and process level controls; and increasing communication with, and training of, employees regarding our commitment to
ethical standards and the integrity of our business practices, requirements for compliance with our Board Approval Process Policy and Code of Ethics and Conduct, including training of new hires and
re-training
of existing employees, and availability of and processes for reporting suspected violations of our Code of Ethics and Conduct. The remediation was completed as of June 30, 2017. However, completion of remediation does not provide assurance that
our controls will operate properly or that our financial statements will be free from error. There may be undetected material weaknesses in our internal control over financial reporting, as a result of which we may not detect financial statement
errors on a timely basis.
If we identify new material weaknesses in our internal control over financial reporting or we are unable to
successfully remediate any future material weaknesses in our internal control over financial reporting, the accuracy and timing of our financial reporting may be adversely affected, we may be unable to maintain compliance with securities laws and
NYSE American listing requirements regarding the timely filing of periodic reports, investors may lose confidence in our financial reporting, and our stock price may decline.
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Additionally, our independent registered public accounting firm is not required to and did
not perform an evaluation of our internal control over financial reporting during any period in accordance with the provisions of the Sarbanes-Oxley Act due to a transition period established by the rules of the SEC for newly public companies that
have not lost their emerging growth company status as defined in the JOBS Act. Had our independent registered public accounting firm performed an evaluation of our internal control over financial reporting in accordance with the
provisions of the Sarbanes-Oxley Act, additional control deficiencies amounting to significant deficiencies or material weaknesses may have been identified. We cannot be certain as to when we will be able to implement the requirements of
Section 404 of the Sarbanes-Oxley Act. If we fail to implement the requirements of Section 404 in a timely manner, we might be subject to sanctions or investigation by regulatory agencies such as the SEC. In addition, failure to comply
with Section 404 or the report by us of a significant deficiency or material weakness may cause investors to lose confidence in our financial statements, and the trading price of our common stock may decline. If we fail to remedy any
significant deficiency or material weakness, our financial statements may be inaccurate, our access to the capital markets may be restricted and the trading price of our common stock may decline.
Our ability to use our net operating loss carryforwards and certain other tax attributes may be limited.
We expect to generate a tax net operating loss for 2017. The 2016 net operating loss carryforwards, or NOLs, are available to offset future
taxable income, if any, until such unused losses expire. Under Sections 382 and 383 of the Internal Revenue Code of 1986, as amended, if a corporation undergoes an ownership change, generally defined as a greater than 50 percentage point
change (by value) in its equity ownership by certain stockholders over a three-year period, the corporations ability to use its
pre-change
NOLs and other
pre-change
tax attributes (such as research tax credits) to offset its post-change income or taxes may be limited. We may experience ownership changes in the future as a result of shifts in our stock
ownership. As a result, if or when we earn net taxable income, our ability to use our
pre-change
NOLs to offset such taxable income may be subject to limitations. Similar provisions of state tax law may also
apply to limit our use of accumulated state tax attributes. As a result, even if we attain profitability, we may be unable to use a material portion of our NOLs and other tax attributes, which could adversely affect our future cash flows.
We will incur increased costs as a result of operating as a public company and our management will be required to devote substantial time to new
compliance initiatives and corporate governance practices including maintaining an effective system of internal control over financial reporting.
As a public company, and increasingly after we are no longer an emerging growth company, we will incur significant legal,
accounting and other expenses that we did not incur as a private company. In addition, the Sarbanes-Oxley Act and rules subsequently implemented by the SEC, and the NYSE American impose numerous requirements on public companies, including
establishment and maintenance of effective disclosure and financial controls and corporate governance practices. Also, the Securities Exchange Act of 1934, as amended, or the Exchange Act, requires, among other things, that we file annual, quarterly
and current reports with respect to our business and operating results. Our management and other personnel will need to devote a substantial amount of time to comply with these laws and regulations. These requirements have increased and will
continue to increase our legal, accounting, and financial compliance costs and have made and will continue to make some activities more time consuming and costly. For example, we expect these rules and regulations to make it more difficult and more
expensive for us to obtain director and officer liability insurance, and we may be required to incur substantial costs to maintain the same or similar coverage. These rules and regulations could also make it more difficult for us to attract and
retain qualified persons to serve on our board of directors or our board committees or as executive officers. These rules and regulations are often subject to varying interpretations, in many cases due to their lack of specificity, and, as a result,
their application in practice may evolve over time as new guidance is provided by regulatory and governing bodies. This could result in continuing uncertainty regarding compliance matters and higher costs necessitated by ongoing revisions to
disclosure and changing governance practices.
The Sarbanes-Oxley Act requires, among other things, that we assess the effectiveness of
our internal control over financial reporting annually and the effectiveness of our disclosure controls and procedures quarterly. In particular, Section 404(a) of the Sarbanes-Oxley Act requires us to perform system and process evaluation and
testing of our internal control over financial reporting to allow management to report on the effectiveness of our internal control over financial reporting. Section 404(b) of Sarbanes-Oxley Act, or Section 404(b), also requires our
independent registered public accounting firm to attest to the effectiveness of our internal control over financial reporting. As an emerging growth company, we are availing ourselves of the exemption from the requirement that our
independent registered public accounting firm attest to the effectiveness of our internal control over financial reporting under Section 404(b). However, we may no longer avail ourselves of this exemption when we are no longer an emerging
growth company. When our independent registered public accounting firm is required to undertake an assessment of our internal control over financial reporting, the cost of our compliance with Section 404(b) will correspondingly increase.
Our compliance with
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applicable provisions of Section 404 requires us and will continue to require us to incur substantial accounting expense and expend significant management time on compliance-related issues
as we implement additional corporate governance practices and comply with reporting requirements.
Furthermore, investor perceptions of
our company may suffer if deficiencies are found, and this could cause a decline in the market price of our stock. Irrespective of any required compliance with Section 404, any failure of our internal control over financial reporting could have
a material adverse effect on our stated operating results and harm our reputation. If we are unable to implement these requirements effectively or efficiently, it could harm our operations, financial reporting, or financial results and could result
in an adverse opinion on our internal controls from our independent registered public accounting firm.
Our directors, executive officers and
principal stockholders will continue to have substantial control over us and could limit investors ability to influence the outcome of key transactions, including transactions that would cause a change of control.
As of September 30, 2017, our executive officers, directors and stockholders who owned more than 5% of our outstanding common stock and
their respective affiliates beneficially owned or controlled approximately 41% of the outstanding shares of our common stock. Accordingly, these executive officers, directors and stockholders and their respective affiliates, acting as a group, have
substantial influence over the outcome of corporate actions requiring stockholder approval, including the election of directors, any merger, consolidation or sale of all or substantially all of our assets or any other significant corporate
transactions. These stockholders may therefore delay or prevent a change of control of us, even if such a change of control would benefit our other stockholders. The significant concentration of stock ownership may adversely affect the trading price
of our common stock due to investors perception that conflicts of interest may exist or arise.
Claims for indemnification by our directors
and officers may reduce our available funds to satisfy successful third-party claims against us and may reduce the amount of money available to us.
Our amended and restated certificate of incorporation and amended and restated bylaws provide that we will indemnify our directors and
officers, in each case to the fullest extent permitted by Delaware law. In addition, as permitted by Section 145 of the Delaware General Corporation Law, our amended and restated bylaws and our indemnification agreements that we have entered
into with our directors and officers provide that:
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We will indemnify our directors and officers for serving us in those capacities, or for serving other business enterprises at our request, to the fullest extent permitted by Delaware law. Delaware law provides that a
corporation may indemnify such person if such person acted in good faith and in a manner such person reasonably believed to be in or not opposed to the best interests of the registrant and, with respect to any criminal proceeding, had no reasonable
cause to believe such persons conduct was unlawful.
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We may, in our discretion, indemnify employees and agents in those circumstances where indemnification is permitted by applicable law.
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We are required to advance expenses, as incurred, to our directors and officers in connection with defending a proceeding, except that such directors or officers shall undertake to repay such advances if it is
ultimately determined that such person is not entitled to indemnification.
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We will not be obligated pursuant to our amended and restated bylaws to indemnify a person with respect to proceedings initiated by that person against us or our other indemnitees, except with respect to proceedings
authorized by our board of directors or brought to enforce a right to indemnification.
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The rights conferred in our amended and restated bylaws are not exclusive, and we are authorized to enter into indemnification agreements with our directors, officers, employees and agents and to obtain insurance to
indemnify such persons.
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We may not retroactively amend our amended and restated bylaw provisions to reduce our indemnification obligations to directors, officers, employees and agents.
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To the extent that a claim for indemnification is brought by any of our directors or officers, it would reduce the amount of funds available
for use in our business.
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Anti-takeover provisions in our charter documents and under Delaware law could make an acquisition of
us, which may be beneficial to our stockholders, more difficult and may prevent attempts by our stockholders to replace or remove our current management and limit the market price of our common stock.
Provisions in our certificate of incorporation and bylaws may have the effect of delaying or preventing a change of control or changes in our
management. Our amended and restated certificate of incorporation and amended and restated bylaws include provisions that:
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authorize our board of directors to issue, without further action by the stockholders, up to 10,000,000 shares of undesignated preferred stock;
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require that any action to be taken by our stockholders be effected at a duly called annual or special meeting and not by written consent;
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specify that special meetings of our stockholders can be called only by our board of directors, the chairman of the board of directors, or the chief executive officer;
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establish an advance notice procedure for stockholder approvals to be brought before an annual meeting of our stockholders, including proposed nominations of persons for election to our board of directors;
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establish that our board of directors is divided into three classes, Class I, Class II and Class III, with each class serving staggered three-year terms;
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provide that our directors may be removed only for cause;
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provide that vacancies on our board of directors may be filled only by a majority of directors then in office, even though less than a quorum;
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specify that no stockholder is permitted to cumulate votes at any election of directors; and
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require a super-majority of votes to amend certain of the above-mentioned provisions.
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These
provisions may frustrate or prevent any attempts by our stockholders to replace or remove our current management 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. In addition, because we are incorporated in Delaware, we are governed by the provisions of Section 203 of the Delaware General Corporation Law, which limits the ability of stockholders owning in excess of 15% of our
outstanding voting stock to merge or combine with us.
We have broad discretion in the use of the net proceeds from our public offerings and may not
use them effectively.
We have broad discretion as to how to spend and invest the proceeds from our public offerings, and we may
spend or invest these proceeds in a way with which our stockholders disagree. Accordingly, investors will need to rely on our judgment with respect to the use of these proceeds and these uses may not yield a favorable return to our stockholders. In
addition, until the net proceeds are used, they may be placed in investments that do not produce significant income or that may lose value.
With
the exception of the issuance of shares of common stock to our preferred stockholders in connection with the payment of all accrued and unpaid dividends in connection with our initial public offering, we do not anticipate paying any cash dividends
in the foreseeable future.
At the closing of our initial public offering, our board of directors issued shares of common stock to
pay all accrued but unpaid dividends on our convertible preferred stock. With the exception of this dividend, we do not anticipate paying cash dividends on any classes of our capital stock in the foreseeable future. We currently intend to retain our
future earnings for the foreseeable future to fund the development and growth of our business. As a result, capital appreciation, if any, of our common stock will be the sole source of gain on an investment in our common stock for the foreseeable
future.