UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
WASHINGTON, D.C. 20549
FORM 10-K
☒ ANNUAL REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934
For the fiscal year ended December 31, 2019
OR
☐ TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934
For the transition period from
to
Commission File Number: 001-37798
Selecta Biosciences, Inc.
(Exact name of registrant as specified in its charter)
Delaware
(State or other jurisdiction of
incorporation or organization)
480 Arsenal
Way
Watertown MA
(Address of principal executive offices)
26-1622110
(I.R.S. Employer Identification No.)
02472
(Zip Code)
(617) 923-1400
Registrant’s telephone number, including area code
Securities registered pursuant to Section 12(b) of the Act:
Title of each class
Trading Symbol(s)
Name of each exchange on which registered
Common Stock, $0.0001 par value per share
SELB
The Nasdaq Global Market
Securities registered pursuant to Section 12(g) of the Act: None
Indicate by check mark if the registrant is a well-known seasoned issuer, as defined in Rule 405 of the Securities Act.
Indicate by check mark if the registrant is not required to file reports pursuant to Section 13 or Section 15(d) of the Act.
Yes o No ☒
Yes o No ☒
Indicate by check mark whether the registrant: (1) has filed all reports required to be filed by Section 13 or 15(d) of the Securities Exchange Act of 1934
during the preceding 12 months (or for such shorter period that the registrant was required to file such reports); and (2) has been subject to such filing
requirements for the past 90 days. Yes ☒ No o
Indicate by check mark whether the registrant has submitted electronically and posted on its corporate web site, if any, every Interactive Data File required
to be submitted and posted pursuant to Rule 405 of Regulation S-T (§232.405 of this chapter) during the preceding 12 months (or for such shorter period
that the registrant was required to submit and post such files).
Yes ☒ No o
Indicate by check mark whether the registrant is a large accelerated filer, an accelerated filer, a non-accelerated filer, a smaller reporting company, or an
emerging growth company. See the definitions of “large accelerated filer,” “accelerated filer,” “smaller reporting company,” and "emerging growth
company" in Rule 12b-2 of the Exchange Act.
Large accelerated filer ☐
Non-accelerated filer ☐
Accelerated filer ☒
Smaller reporting company ☒
Emerging growth company ☒
If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new
or revised financial accounting standards provided pursuant to section 13(a) of the Exchange Act. ☒
Indicate by check mark whether the registrant is a shell company (as defined in Rule 12b-2 of the Exchange Act). Yes ☐ No ☒
The aggregate market value of the voting and non-voting common equity held by non-affiliates of the registrant on June 28, 2019, based on the closing
price of $1.79 per share of the registrant's common stock as reported by the Nasdaq Global Market, was approximately $58.5 million.
As of March 6, 2020 the registrant had 86,420,195 shares of common stock, par value $0.0001 per share, outstanding.
Portions of the registrant’s definitive Proxy Statement relating to its 2020 Annual Meeting of Stockholders to be filed with the Securities and Exchange
Commission are incorporated by reference into Part III of this Annual Report on Form 10-K.
DOCUMENTS INCORPORATED BY REFERENCE
Item 1.
Item 1A.
Item 1B.
Item 2.
Item 3.
Item 4.
Item 5.
Item 6.
Item 7.
Item 7A.
Item 8.
Item 9.
Item 9A.
Item 9B.
Item 10.
Item 11.
Item 12.
Item 13.
Item 14.
Item 15.
Item 16.
Business
Risk Factors
Unresolved Staff Comments
Properties
Legal Proceedings
Mine Safety Disclosures
TABLE OF CONTENTS
Part I
Part II
Market for Registrant's Common Equity, Related Stockholder Matters and Issuer Purchases of Equity Securities
Selected Consolidated Financial Data
Management's Discussion and Analysis of Financial Condition and Results of Operations
Quantitative and Qualitative Disclosures About Market Risk
Financial Statements and Supplementary Data
Changes in and Disagreements With Accountants on Accounting and Financial Disclosure
Controls and Procedures
Other Information
Part III
Directors, Executive Officers and Corporate Governance
Executive Compensation
Security Ownership of Certain Beneficial Owners and Management and Related Stockholder Matters
Certain Relationships and Related Transactions, and Director Independence
Principal Accountant Fees and Services
Exhibits and Financial Statement Schedules
Form 10-K Summary
Signatures
Part IV
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FORWARD-LOOKING STATEMENTS
This Annual Report on Form 10-K contains forward-looking statements. We intend such forward-looking statements to be covered by the safe harbor
provisions for forward-looking statements contained in Section 27A of the Securities Act of 1933, as amended (the “Securities Act”), and Section 21E of
the Securities Exchange Act of 1934, as amended (the “Exchange Act”). All statements other than statements of historical facts contained in this Annual
Report, including statements regarding our future results of operations and financial position, business strategy, prospective products, product approvals,
research and development costs, timing and likelihood of success, the plans and objectives of management for future operations and future results of
anticipated products are forward-looking statements. These statements involve known and unknown risks, uncertainties and other important factors that
may cause our actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or
implied by the forward-looking statements.
In some cases, you can identify forward-looking statements by terms such as “may,” “will,” “should,” “expect,” “plan,” “anticipate,” “could,”
“intend,” “target,” “project,” “contemplate,” “believe,” “estimate,” “predict,” “potential”, or “continue” or the negative of these terms or other similar
expressions. The forward-looking statements in this Annual Report are only predictions. We have based these forward-looking statements largely on our
current expectations and projections about future events and financial trends that we believe may affect our business, financial condition and results of
operations. These forward-looking statements speak only as of the date of this Annual Report and are subject to a number of important factors that could
cause actual results to differ materially from those in the forward-looking statements, including the factors described under the sections in this Annual
Report titled “Risk Factors” and “Management’s Discussion and Analysis of Financial Condition and Results of Operations” as well as the following:
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our status as a development-stage company and our expectation to incur losses in the future;
our ability to continue as a going concern, our future capital needs and our need to raise additional funds;
our ability to build a pipeline of product candidates and develop and commercialize drugs;
our unproven approach to therapeutic intervention;
our ability to enroll patients in clinical trials, timely and successfully complete those trials and receive necessary regulatory approvals;
our ability to have continued access to manufacturing facilities and to receive or manufacture sufficient quantities of our product candidates;
our ability to maintain our existing or future collaborations or licenses, including our ability to reach an agreement regarding an acceptable amendment
of our exclusive patent license agreement with the Massachusetts Institute of Technology;
our ability to protect and enforce our intellectual property rights;
federal, state, and foreign regulatory requirements, including FDA regulation of our product candidates;
our ability to obtain and retain key executives and attract and retain qualified personnel;
developments relating to our competitors and our industry, including the impact of government regulation; and
our ability to successfully manage our growth.
Moreover, we operate in an evolving environment. New risk factors and uncertainties may emerge from time to time, and it is not possible for
management to predict all risk factors and uncertainties.
You should read this Annual Report and the documents that we reference in this Annual Report completely and with the understanding that our actual
future results may be materially different from what we expect. We qualify all of our forward-looking statements by these cautionary statements. Except as
required by applicable law, we do not plan to publicly update or revise any forward-looking statements contained herein, whether as a result of any new
information, future events, changed circumstances or otherwise.
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Item 1. Business
OVERVIEW
PART I
We are a clinical-stage biopharmaceutical company using our ImmTOR™ platform, designed to induce tolerance to novel biologic therapies that would
otherwise be limited by immunogenicity with the goal of effectively and safely treating rare and serious diseases. Many such diseases are treated with
biologic therapies that are foreign to the patient’s immune system and therefore elicit an undesired immune response. Of particular concern are anti-drug
antibodies, or ADAs, which are often produced by the immune system in response to biologic therapy and can adversely affect the efficacy and safety of
treatment. Our proprietary tolerogenic ImmTOR platform encapsulates an immunomodulator in biodegradable nanoparticles and is designed to mitigate the
formation of ADAs by inducing antigen-specific immune tolerance to biologic drugs. ADAs can start developing in the body with the first dose of a
biologic therapy and can render subsequent doses ineffective or unsafe, potentially depriving patients of life-saving therapeutic options and limiting the
likelihood of success for many otherwise promising novel biologic drugs and technologies. We believe ImmTOR has potential to enhance the efficacy
without compromising the safety of existing approved biologic drugs, improve product candidates under development, and enable novel therapeutic
modalities, such as re-administration of systemic gene therapy. We intend to build a product pipeline by combining our ImmTOR platform with a range of
biologics. Additionally, we plan to seek collaborations and license agreements to broaden our applications for our ImmTOR platform.
Our lead product candidate, SEL-212, is a proprietary combination of a therapeutic uricase enzyme (pegadricase) and our ImmTOR platform that is
designed to durably control serum uric acid, or SUA, levels in patients with chronic refractory gout through monthly administration. Our preclinical data
indicated that ImmTOR, when co-administered with pegadricase, induced antigen-specific immune tolerance to pegadricase and substantially reduced the
formation of associated ADAs. Our Phase 1 data showed that ImmTOR mitigated the formation of ADAs against pegadricase after a single dose of SEL-
212. Clinical data from our Phase 2 dose-finding study suggested the potential of monthly doses of SEL-212 to durably control serum uric acid levels by
mitigating the formation of anti-pegadricase antibodies. Initial tissue imaging studies by dual energy computerized tomography (DECT) scans also
provided evidence regarding the potential of SEL-212 to eliminate tissue deposits of uric acid crystals. This data also showed a low rate of gout flares.
Based on our Phase 2 clinical data and feedback received during our end-of-Phase 2 meeting from the U.S. Food and Drug Administration, or FDA, we
commenced enrollment in our Phase 2 head-to-head (COMPARE) clinical trial of SEL-212, utilizing revised stopping rules, compared to the current FDA-
approved uricase therapy, KRYSTEXXA® (pegloticase) in March 2019. We initiated dosing in May 2019. In December 2019, we completed enrollment in
this study. In the first quarter of 2020, we received feedback from the FDA on our planned Phase 3 program for SEL-212, which will consist of two
placebo-controlled trials, each with a six month primary endpoint, one of which will have a six-month placebo-controlled extension. We plan to commence
the Phase 3 clinical program in SEL-212 in the second half of 2020. We will require additional resources to complete the planned Phase 3 clinical program
for SEL-212. We expect our clinical and, if approved, marketing strategy for SEL-212 to initially focus on the estimated 160,000 patients in the United
States with chronic refractory gout, and to focus on those patients that are being treated by rheumatologists.
We are also applying our ImmTOR platform in an effort to mitigate the formation of ADAs when dosing gene therapy. Most gene therapies use a viral
vector, such as an adeno-associated virus, or AAV, vector to place corrective genetic material into cells to treat genetic diseases. One of the key hurdles for
the gene therapy field is to overcome immunogenicity against the viral vector. ADAs form in response to the first administration of a gene therapy vector
and prevent effective subsequent doses of gene therapy. The ability to provide repeat doses may be particularly important for pediatric patients to receive
continued treatment benefit later in life as gene expression wanes due to cellular turnover as patients grow. The ability to re-administer gene therapies also
could provide the potential for dose titration and could be advantageous for diseases where the goal is to transfect a high number of cells.
Our investigational gene therapy program targets the treatment of rare genetic diseases, including methylmalonic acidemia, or MMA. We are collaborating
with Asklepios BioPharmaceutical, Inc., or AskBio to develop a treatment for MMA, which, if successfully developed and approved, could have the
potential to prevent undesired immune responses to the vector and transgene that can occur with the first dose of gene therapy by using our ImmTOR
platform. We plan to enter the clinic under this collaboration in 2020. For more information, see "Licenses and Collaborations - AskBio” below.
In addition to developing this non-immunogenic therapeutic product candidate, we intend to continue expanding our proprietary immune tolerance pipeline
and pursue out-licensing opportunities for select applications of our ImmTOR platform. In December 2016, we entered into a license agreement, or the
Spark License Agreement, with Spark Therapeutics, Inc., or Spark, that provides Spark with exclusive worldwide rights to our ImmTOR platform to
research, develop and commercialize gene therapies for Factor VIII, an essential blood clotting protein relevant to the treatment of hemophilia A. For more
information,
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see “Licenses and Collaborations - Spark Therapeutics" below. Additionally, in December 2019 we entered into a license agreement, or the AskBio License
Agreement, with AskBio, that provides AskBio with exclusive worldwide rights to our ImmTOR platform to research, develop and commercialize certain
adeno-associated virus, or AAV gene therapy products targeting the glucosidase alpha, acid, or GAA gene, or derivatives thereof, to treat Pompe Disease.
For more information, see "Licenses and Collaborations - AskBio” below.
In September 2018, we announced a collaboration with the European consortium, CureCN, for an ImmTOR+AAV gene therapy combination product
candidate in Crigler-Najjar syndrome. We expect the CureCN consortium to obtain scientific advice from the German drug regulatory authority in 2020.
OUR STRATEGY
Our goal is to become the first biopharmaceutical company to develop and commercialize targeted therapies that are designed to more effectively and
safely treat rare and serious diseases by inducing immune tolerance to potent but immunogenic biologic therapies. In addition, we intend to maximize the
value of our ImmTOR platform by collaborating with or licensing our ImmTOR platform out to biopharmaceutical companies on programs that can benefit
from our technology but that are outside our area of focus. The key elements of our strategy include the following.
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Advance the development of SEL-212 for the treatment of chronic refractory gout. We believe SEL-212 has the potential, if successfully
developed and approved, to become the first monthly biologic treatment that durably controls uric acid while also dissolving harmful deposits of
uric acid crystals for patients with chronic refractory gout. We have completed Phase 1 and Phase 2 dose-finding clinical programs, comprised of
two Phase 1 clinical studies and an open-label, multiple ascending dose Phase 2 clinical program. We completed enrollment of our Phase 2 head-
to-head (COMPARE) clinical study against KRYSTEXXA in December 2019 and expect to report top-line data in the third quarter of 2020. The
two-armed, open label trial has enrolled approximately 150 patients, randomized 1:1, with one arm receiving KRYSTEXXA (as set forth in the
prescribing information) and the other arm receiving six monthly doses of SEL-212. The primary endpoint in the study is the percentage of
patients in each arm that maintain SUA control below 6.0 mg/dL, for at least 80% of the time during months three and six. In the first quarter of
2020, we received feedback from the FDA on our planned Phase 3 clinical program for SEL-212, which will consist of two placebo-controlled
trials, each with a six month primary endpoint, one of which will have a six-month placebo-controlled extension. We plan to commence the Phase
3 clinical program in SEL-212 in the second half of 2020. We will require additional resources to complete the planned Phase 3 clinical program
for SEL-212.
Transform gene therapy by enabling repeated administration of systemically-administered AAV gene therapy vectors. One of the key
challenges for the gene therapy field is the inability to administer more than one dose of AAV systemically due to the formation of neutralizing
anti-AAV antibodies. We believe redosing has the potential to enable dose titration of gene therapy to achieve therapeutic expression of the
transgene, to restore therapeutic expression in pediatric patients that have lost expression of the transgene due to target organ growth. A 2018
publication in Nature Communications provided peer-reviewed preclinical data supporting ImmTOR’s potential to mitigate the formation of
neutralizing anti-AAV antibodies and enable productive AAV vector redosing in mice and nonhuman primates. In August 2019, we entered into a
feasibility study and license agreement with AskBio, or the AskBio Collaboration Agreement, pursuant to which we and AskBio will conduct
proof of concept studies to potentially validate the use of our ImmTOR platform in conjunction with an AAV gene therapy to mitigate the
formation of neutralizing anti-AAV capsid antibodies, which currently precludes redosing.
Leverage ImmTOR to develop additional novel uses and classes of non-immunogenic biologics. We intend to use our ImmTOR platform to
develop a range of proprietary, non-immunogenic biologic therapeutic candidates. In each case, ImmTOR would be evaluated for its potential to
mitigate undesired immune response to the biologic therapy with the goal of improving efficacy and/or safety. Our strategy is to develop
proprietary treatments for rare and serious diseases by combining ImmTOR with biologics that have been in-licensed or provided through research
collaborations.
Establish infrastructure and capabilities to develop and commercialize our products in rare and orphan diseases. While we believe our
ImmTOR platform may be broadly applicable across disease areas, we intend to focus our proprietary efforts on developing and commercializing
proprietary ImmTOR-enabled products for rare and serious diseases where there is high unmet medical need. Therapies for treating these diseases
require focused commercial efforts and coordination with patient groups and investigators.
Selectively pursue licensing opportunities and maximize the value of our ImmTOR programs for immune tolerance. In addition to our own
product development efforts and those on which we are collaborating, we are in discussions with potential licensees to pursue novel therapies that
would utilize our ImmTOR platform. For example,
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in December 2016, we entered into the Spark License Agreement to develop gene therapies for certain targets utilizing our ImmTOR platform.
Additionally, in December 2019, we entered into the AskBio License Agreement to develop a gene therapy product for the treatment of Pompe
Disease utilizing our ImmTOR platform.
OVERVIEW OF THE HUMAN IMMUNE SYSTEM
The human immune system is an integrated system of specialized immune cells, cell products and tissues that protect against infectious disease and cancer.
The immune system recognizes antigens, which are substances, such as proteins, enzymes or complex sugars. These antigens can be endogenous, or self-
antigens, which are produced by the body, or exogenous antigens derived from foreign sources, such as viruses, fungi or bacteria. The human immune
system has evolved to recognize and destroy potentially harmful substances. To function effectively, the immune system must discern between harmful
antigens and innocuous antigens. The immune system maintains a delicate balance between effector cells, which mount immune responses to antigens that
represent potential threats, and regulatory cells, which mitigate undesired and potentially harmful immune responses through immune tolerance. Depending
upon the characteristics of the antigen and the context in which the antigen is encountered, the immune system must determine whether to mount a
defensive (effector) or regulatory (tolerogenic) immune response.
Antigens are processed in lymphoid organs, such as lymph nodes and the spleen, where the immune system determines whether to mount a defensive or
regulatory response through a process called “antigen presentation.” In connection with antigen presentation, dendritic cells process the antigens and
present them to T cells. When presented, antigens perceived as harmful induce a stimulatory response that can result in the activation of cytolytic T cells or
helper T cells, the latter of which help to induce B cells to produce antibodies. The role of cytolytic T cells is to kill cells that harbor intracellular antigens,
such as viruses. The role of antibodies is to neutralize or eliminate extracellular antigens on cell surfaces or in interstitial fluids, such as plasma. Figure 1
below depicts both antigen presentation and the related immune responses.
Figure 1. Antigen Presentation and Related Tolerogenic or Stimulatory Immune Response
There are a number of adverse outcomes that can occur when the immune system mounts an undesired response to an innocuous foreign antigen or a self-
antigen. For example, food allergy occurs when the immune system mounts an immune response to innocuous food antigens. Another example of
undesired immunogenicity occurs when the immune system is exposed to a biologic treatment, recognizes it as a foreign antigen and instructs the body to
mount a defense by forming ADAs to the biologic, which can compromise a therapy’s desired beneficial effect. Undesired immunogenicity is common
with biologic therapies, such as in enzyme and protein replacement therapies, and in novel technologies, such as gene therapy and antibody-drug
conjugates.
OUR ImmTOR PLATFORM
Our ImmTOR platform is based in part on the pioneering research performed by our co-founders at Harvard University, Massachusetts Institute of
Technology, or MIT, and Brigham and Women’s Hospital, or Brigham. In connection with our company’s founding, we licensed multiple patent families
related to aspects of our ImmTOR platform pursuant to an agreement
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with MIT. We believe one of the key insights from this research is that nanoparticles are uniquely suited to deliver precise instructions to the immune
system as a result of the natural predisposition of the immune system to interrogate nanoparticles, such as viruses. We have aggressively sought to extend
and protect the proprietary intellectual property underlying the composition and use of ImmTOR for antigen-specific immunotolerance. For more
information, see "Intellectual Property" below.
We are currently developing our ImmTOR platform for:
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combination with a uricase enzyme for the treatment of chronic refractory gout;
combination with gene therapies for the treatment of rare diseases;
potential application with other marketed products, product candidates in development and novel biologic drugs that would otherwise be too
immunogenic to develop
Our nanoparticles are designed to remain intact after injection into the body and accumulate selectively in lymphoid organs, which include lymph nodes
and the spleen, where the immune response is coordinated. The nanoparticles are designed to be processed by specialized immune cells, such as dendritic
cells and other antigen-presenting cells that initiate and regulate immune responses, where they deliver the immunomodulator in a coordinated and targeted
manner. Depending on the type of immunomodulator encapsulated in the nanoparticles, our technology can be used to induce a tolerogenic response to
mitigate the formation of ADAs against a biologic drug or to treat allergies and autoimmune diseases.
OUR ANTIGEN-SPECIFIC IMMUNE TOLERANCE PROGRAM
Our antigen-specific tolerance programs utilize ImmTOR, our biodegradable nanoparticle encapsulating the immunomodulator rapamycin. Rapamycin is a
small molecule approved for the prevention of organ rejection in kidney transplant patients. To mitigate the formation of ADAs and induce immune
tolerance in the body, we co-administer our ImmTOR with a free antigen, such as a biologic drug, which is depicted in Figure 2 below.
Figure 2. Co-Administration of ImmTOR with a Biologic Drug
ImmTOR is designed to be co-administered (prior to the biologic drug) at the beginning of therapy with a biologic drug to mitigate the formation of ADAs
without requiring the alteration of the drug or its dose regimen. As a result, we believe our ImmTOR may provide us with significant opportunities in the
areas of immune tolerance and ADA prevention because ImmTOR is designed to be co-administered at the beginning of therapy with many different
biologic drugs. Importantly, we believe each pairing of ImmTOR with a biologic drug also offers us the opportunity to pursue a distinct proprietary product
candidate, which we believe has the potential to be separately patented, approved and marketed. ImmTOR is manufactured in facilities subject to current
good manufacturing practice, or cGMP, requirements using well-defined commercial operations, which, we believe, further enhances the scalability of our
tolerance programs.
During preclinical studies, we observed that delivering an antigen together with ImmTOR provided the appropriate signals in vivo to induce regulatory T
cells, which, in turn, inhibited effector immune responses, such as the formation of ADAs. In our preclinical studies, we observed that ImmTOR labeled
with a fluorescent dye selectively accumulated in lymphoid organs where it was processed by antigen-presenting cells. Figure 3 below depicts a model of
how ImmTOR would be taken up by a dendritic cell in the spleen. We believe that when delivered in the context of our ImmTOR, both the biologic drug
and ImmTOR are taken up and processed by dendritic cells in a manner that may induce regulatory T cells, which can potentially block the activation of
helper T cells, mitigating the formation of ADAs.
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Figure 3. ImmTOR and Antigen/Biologic Drug Presentation and Related Immune Tolerance Induction
Limitations of existing therapies
All biologics, even those comprised of human protein sequences, have the potential to induce ADAs. Whether a biologic drug elicits an ADA response
depends on both product-specific factors, such as propensity to form aggregates, the route of administration and mechanism of action, as well as patient-
specific factors, such as genetics, underlying disease and medications. For instance, many enzyme and protein replacement therapies used in the treatment
of rare and serious diseases have a particularly high rate of immunogenicity because patients are genetically deficient in the target protein and, as a result,
the therapeutic protein can be recognized as foreign by the patient’s immune system.
The formation of ADAs can lead to neutralization of efficacy, modification of pharmacokinetics and pharmacodynamics as well as allergic responses.
Immunogenicity remains a significant hurdle for the development of safe and effective biologic treatments and has become a key concern for regulators, as
evidenced by over 100 approved biologics that describe immunogenicity in their labels or clinical literature. According to product package inserts,
approximately 50 currently marketed biologics report an incidence of ADAs affecting over 20% of patients. Among these biologics are Factor VIII
products, such as Advate® (antihemophilic factor) for the treatment of hemophilia A and antibody therapeutics with fully human sequences, such as
Humira® (adalimumab). We believe that immunogenicity also is a leading cause of product development failure for biopharmaceutical companies and that
this issue is hampering the development of novel platform technologies, such as gene therapy and gene editing.
Undesired immunogenicity represents a significant hurdle that can hamper the clinical development of new biologic platforms. For example, in gene
therapy, viral vectors are required to transport the genetic material into cells. The viral origin of these vectors explains their immunogenicity, which has led
drug developers to limit applications to situations where the required frequency and site of administration are conducive to manageable immune responses.
Treatment and product development failure resulting from undesired immunogenicity has been recognized by regulators and patient advocacy
organizations. In June 2014, the FDA and the National Organization for Rare Diseases, or NORD, co-sponsored a workshop on undesired immune
responses to enzyme replacement therapies and called on the biopharmaceutical industry to take a more proactive approach to addressing immunogenicity
to biologics.
Currently, we believe there are no comprehensive solutions to the complications of immunogenicity. Drug developers often stop the development of
biologics that show an undesired immune response during preclinical and/or clinical development. In some cases, biopharmaceutical companies may
attempt to reduce undesired immune responses by re-engineering the biologic through protein pegylation, removal or modification of immunogenic
epitopes, or other mechanisms. However, these approaches are limited in their effectiveness. Physicians may try to address the issue of undesired immune
responses by increasing the dose of the biologic, which can be prohibitively expensive and may present greater safety concerns, or in life-threatening
situations, by using global immunosuppressive combination therapies. We believe that our tolerogenic ImmTOR platform could offer an
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entirely new and effective treatment alternative for undesired immune responses, including with respect to the formation of ADAs, but potentially also for
autoimmune diseases and allergies.
OUR ImmTOR PROGRAMS DESIGNED TO INDUCE ANTIGEN-SPECIFIC IMMUNE TOLERANCE
We believe our ImmTOR platform designed to induce antigen-specific immune tolerance has a broad range of potential applications. We are currently
pursuing targeted product development strategies for multiple applications in which we believe ImmTOR products could be highly differentiated.
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Therapeutic enzymes. Therapeutic enzymes are a frequently used class of biologic drugs to treat rare diseases. Through our analysis of biologic
drugs, including our preclinical studies, we have observed that enzymes are especially prone to undesired immune responses. Our lead product
candidate, SEL-212, includes pegadricase, a pegylated uricase enzyme, which is an example of an immunogenic enzyme for which we are
applying ImmTOR with the intention of improving the enzyme’s efficacy and safety. We intend to seek opportunities to secure supply of and, if
appropriate, licenses to these or other enzymes that we would evaluate in combination with ImmTOR.
Gene therapies. We believe gene therapies have the potential to address key unmet medical needs for many rare genetic diseases, but undesired
immune responses to the viral vectors used for gene replacement, augmentation and editing may be restricting their broader use. Through our
analysis of genetic diseases, we have identified applications and patient segments that we believe would benefit from our ImmTOR platform. We
intend to develop ImmTOR -enabled non-immunogenic gene therapy candidates which are designed to be utilized with AAV vectors (e.g., AAV8,
AAV5). We believe our product candidates have the potential to mitigate the problem of pre-existing immunogenicity to the gene therapy vector
and to prevent undesired immune responses to the vector and transgene that can occur with the first dose of gene therapy by using our ImmTOR
platform. Our initial area of focus is on genetic metabolic diseases, but may also include lysosomal storage diseases and genetic muscular diseases.
We believe we are the first company to systematically pursue the development of gene therapy product candidates with the goal of enabling repeat
administration. We have engaged third parties with experience in gene therapy and rare diseases to support the development of our proprietary
products. We also have licensed our ImmTOR platform to Spark Therapeutics and AskBio for the development of gene therapies for certain pre-
specified targets. For more information, see "Licenses and Collaborations - Spark Therapeutics" and “Licenses and Collaborations - AskBio.”
Other products and product candidates affected by undesired immune responses. We have generated preclinical data which we believe suggests a
broad potential benefit of ImmTOR for immune tolerance. For many biologic drugs, undesired immune responses limit efficacy and cause safety
concerns. We intend to strategically out-license ImmTOR platform for use with other products that are outside our focus to larger
biopharmaceutical companies. We believe our ImmTOR platform may also be of interest to biopharmaceutical companies with novel biologic
development concepts or product candidates in clinical development that have demonstrated initial efficacy but are experiencing issues with safety
or sustained efficacy due to inhibitory ADAs.
SEL-212 for the treatment of chronic refractory gout
Overview
SEL-212 is our proprietary product candidate under development for the treatment of chronic refractory gout. SEL-212 consists of ImmTOR co-
administered with pegadricase, a pegylated uricase. We believe that our SEL-212 has the potential, if successfully developed and approved, to offer a
uniquely effective treatment for patients with chronic refractory gout, while also providing evidence regarding the utility of our ImmTOR platform
platform. Pegylated uricase, in the form of the approved drug KRYSTEXXA, has demonstrated the ability to significantly reduce uric acid levels and
dissolve the harmful uric acid crystals that are the manifestations of gout upon initial treatment in patients. However, we believe broad commercial
adoption has not been achieved primarily due to undesired immune responses. Based on the data received from our preclinical, Phase 1, Phase 2 dose-
finding clinical studies, and certain data disclosed from the ongoing Phase 2 head-to-head (COMPARE) clinical study, we believe that by leveraging our
ImmTOR platform to mitigate the formation of ADAs following the dosing of our pegylated uricase, pegadricase, SEL-212, if successfully developed and
approved, could enable the removal of uric acid crystals.
The market for gout therapy
Gout is a painful and potentially disabling form of arthritis resulting from excess accumulation of uric acid and deposition of uric acid crystals in joints and
soft tissues, including those of the kidney and heart, causing harmful inflammation. Gout is caused by an overproduction of uric acid, a natural byproduct
of purine metabolism that is produced after consumption of food with high levels of purines such as seafood, meat, yeast and certain vegetables, and/or an
inability of the kidneys to excrete
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adequate amounts of uric acid from the body. High concentrations of serum uric acid lead to formation of uric acid crystals in joints and tissues, causing
pain, inflammation and joint damage, and increase the risk for other conditions, including cardiovascular, cardiometabolic, joint and kidney disease.
There are approximately 8.3 million and 10.0 million gout sufferers in the United States and the European Union, respectively. The first line of treatments
for gout are allopurinol and febuxostat. Both drugs are xanthine oxidase inhibitors, oral drugs that reduce the synthesis of uric acid. Lesinurad and
probenecid are oral gout drugs that increase the rate of excretion of uric acid through the kidneys, and are used almost exclusively in combination with
these first line treatments. While these oral treatments are designed to prevent the formation of uric acid deposits, they are not well suited to reduce existing
uric acid deposits in joints and tissues.
Gout is a spectrum of disease that is typically diagnosed through the measurement of uric acid levels in the blood and/or the identification of uric acid
crystals from a visible tophus. High concentrations of serum uric acid increase the risk of co-morbidities, including cardiovascular, cardiometabolic, joint
and kidney disease. Patients who are unable to reduce their SUA levels below 6.0 mg/dL with oral drugs are diagnosed with refractory gout. Patients who
have uric acid deposits, or tophi, in soft tissues, joints, the urinary tract, the digestive tract or the heart and a persistently elevated uric acid level when left
untreated are diagnosed with chronic refractory gout. Tophi are a source of inflammation and pain. Chronic refractory gout constitutes a subset of gout
patients exhibiting chronic high serum uric acid levels and painful and damaging uric acid deposits. In total, we estimate that there are approximately
160,000 chronic refractory gout patients in the U.S.
Figure 4 below illustrates the association between gout and diseases of the heart, vascular system, metabolic process, kidney and joints.
Figure 4. Co-Morbidities Associated with Gout
Based on our preclinical studies, clinical data from our Phase 1b, Phase 2 dose-finding, ongoing Phase 2 head-to-head (COMPARE) clinical studies, and
market research, we believe that SEL-212 may potentially address several key unmet needs in the treatment of chronic refractory gout: the durable control
of serum uric acid levels, the elimination of painful and damaging uric acid deposits, reduction in incidence and severity of flares, and once-monthly
dosing.
Our product development strategy is designed to address these unmet medical needs while improving the dosing regimen to a once-monthly treatment. We
completed enrollment for our Phase 2 head-to-head (COMPARE) clinical study against KRYSTEXXA, which is intended to evaluate the differences
between KRYSTEXXA and SEL-212 with respect to SUA control, flare rates and dosing convenience, in December 2019. We expect to report top-line
data from the COMPARE trial in the third quarter of 2020. In the first quarter of 2020, we received feedback from the FDA on our planned Phase 3 clinical
program for SEL-212, which will consist of two placebo-controlled trials, each with a six month primary endpoint, one of which will have a six-month
placebo-controlled extension. We plan to commence the Phase 3 clinical program in SEL-212 in the second half of 2020, following which, if successful, we
plan to seek regulatory approval for the treatment of refractory gout based on an endpoint of reduction of SUA levels below 6.0 mg/dL for 80% of the time
during month six. We intend for the Phase 3 protocols to include patients with chronic refractory gout. During our market research, physicians expressed
their preference for a product that could be dosed monthly. If approved, we plan to position SEL-212 as a debulking therapy for gout
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that has the potential to remove harmful uric acid deposits over a limited number of once-monthly doses and subsequently allow patients to switch to oral
gout maintenance therapy unless and until such patients experience a subsequent manifestation of uric acid deposits. We do not believe that oral therapy
would completely prevent the build-up over time of uric acid crystals in patients with a history of chronic refractory gout and, as a result, we anticipate that
treatment with SEL-212, if approved, would be required intermittently in such patients. We believe that SEL-212, if approved, may be effective in
removing harmful uric acid deposits in most patients with chronic refractory gout over multiple courses of treatment in their lifetimes. Figure 5 below
depicts this positioning strategy as a sample diagram illustrating what we believe to be a shift in the treatment paradigm for chronic refractory gout.
Figure 5. Sample Treatment Course for Chronic Refractory Gout.
We expect our clinical and marketing strategy for SEL-212 to initially focus on the estimated 160,000 patients in the United States with chronic refractory
gout, and to focus on those who are being treated by rheumatologists. If SEL-212 is approved, we expect our strategy for marketing SEL-212 to
rheumatologists will be to promote a switch from oral therapies to SEL-212 for patients with SUA levels chronically above 6.0 mg/dL or those diagnosed
with chronic refractory gout. Some rheumatologists have begun to utilize imaging technologies recommended by the guideline writing associations for
rheumatology, including the American College of Rheumatology and the European League Against Rheumatism. In particular, DECT, can enable the
visualization and quantification of uric acid deposits in joints and in tissues as depicted in Figure 6 below. Figure 6 below depicts a patient, using DECT
imaging, with heavy urate burden at onset of study and almost a complete resolution of this after five months.
Figure 6. Tophi / Uric Acid Deposits (shown in green) Visualized Using Dual Energy Computed Tomography Imaging
SEL-212 components
Our SEL-212 consists of ImmTOR co-administered with pegadricase. Our ImmTOR consists of nanoparticles composed of poly(D,L-lactide), or PLA, and
poly(D,L-lactide)-block-poly(ethylene-glycol), or PLA-PEG, encapsulating rapamycin. Our
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pegadricase consists of a uricase modified with poly(ethylene-glycol), or PEG. The components of SEL-212 are depicted in Figure 7 below.
Figure 7. Components of SEL-212
Our pegadricase is a pegylated version of the therapeutic enzyme uricase, which we have licensed from Shenyang Sunshine Pharmaceutical Co., Ltd., or
3SBio, exclusively for all markets, except Japan and Greater China, and exclusively for Japan only in combination with our ImmTOR platform. Uricase is
an enzyme endogenous to all mammals, except for humans and certain primates, which converts uric acid to the more soluble metabolite, allantoin. There
is a natural limit to the amount of uric acid that can be excreted by the kidneys, which decreases with age and can be reduced by some medications. By
converting uric acid to allantoin, uricase provides an additional way for the body to reduce uric acid.
ImmTOR is our biodegradable nanoparticle that encapsulates rapamycin, also referred to as sirolimus. Rapamycin is the active ingredient of Rapamune, an
immunosuppressant which has extensive prior use in humans and is currently FDA-approved as a prophylaxis of organ rejection in kidney transplant
patients aged 13 or older. PLA is part of the broader poly(lactic-co-glycolic acid), or PLGA, family of biodegradable polymers that have more than 30
years of commercial use and are formulation components in a number of approved products. Polyethylene glycol, or PEG, has been widely studied in
clinical trials and is also a formulation component in many approved biologic products. In our preclinical studies, ImmTOR co-administered at the
initiation of treatment with a biologic drug substantially reduced the formation of associated ADAs and induced antigen-specific immune tolerance to the
biologic drug.
Clinical development
For chronic refractory gout, we are executing a clinical development program that seeks to evaluate SEL-212’s ability to durably reduce SUA levels below
6.0 mg/dL. The saturation point of uric acid, or the maximum level at which uric acid will remain soluble in plasma, is 6.8 mg/dL. When uric acid rises
above 6.8 mg/dL, uric acid microcrystals begin to form and settle in joints and other tissues, creating an inflammatory response that is diagnosed as gout.
This inflammatory response is the source of highly debilitating gout flares experienced by patients. When serum uric acid levels drop below the level of 6.0
mg/dL, microcrystals will begin to dissolve and, over time, gout symptoms will resolve. Therefore, a serum uric acid level of less than 6.0 mg/dL is defined
as the target for uric acid-lowering treatments by organizations such as the American College of Rheumatology and the European League Against
Rheumatism. The FDA and EMA have also considered the maintenance of serum uric acid levels below 6.0 mg/dL to be an acceptable primary endpoint in
clinical trials for urate lowering therapies. Available oral gout therapies are designed to prevent the formation of uric acid microcrystals but are not
effective in rapidly removing existing crystalized deposits. In severe gout patients who have significant deposits of uric acid crystals, known as tophi, it is
of clinical benefit to significantly reduce serum uric acid levels (i.e. below 0.1 mg/dL) for a period of time in order to rapidly dissolve the uric acid crystals.
As of March 8, 2020, we had dosed approximately 300 patients in multiple clinical studies in patients with gout or elevated levels of serum uric acid. We
initiated our clinical program in the U.S. in the second quarter of 2015 with a multicenter Phase 1a trial of pegadricase in patients with serum uric acid
levels greater than 6.0 mg/dL. We completed the patient treatment portion of our Phase 1a trial in November 2015, initiated a Phase 1b trial in December
2015 and reported data from both Phase 1 clinical trials in December 2016. In our Phase 1b trial, we demonstrated that a single dose of SEL-212 was
capable of lowering serum uric acid levels below 0.1 mg/dL for at least 30 days, at therapeutic doses which is correlated with the inhibition of uricase-
specific ADAs. We initiated patient recruitment in an open label multi-dose Phase 2 clinical trial of SEL-212 in patients with symptomatic gout and
elevated uric acid levels in October 2016. This study was conducted at multiple clinical sites in the U.S. In May 2019, we initiated patient recruitment for
our Phase 2 head-to-head (COMPARE) clinical study
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against KRYSTEXXA, which is intended to evaluate the differences between KRYSTEXXA and SEL-212 with respect to SUA control. We have
completed our initial end-of-Phase 2 meeting with the FDA and believe we have established a path forward for potential BLA submission. Additionally, in
the first quarter of 2020, we received feedback from the FDA on our planned Phase 3 clinical program for SEL-212, which will consist of two placebo-
controlled trials, each with a six month primary endpoint, one of which will have a six-month placebo-controlled extension.
Phase 1, Phase 2 dose-finding, and Phase 2 head-to-head (COMPARE) clinical trials
SEL-212 was evaluated in a Phase 1 and Phase 2 dose-finding clinical program that included a Phase 1a and Phase 1b clinical trial in patients with high
uric acid levels as well as a Phase 2 clinical trial in patients with symptomatic gout and high uric acid levels. Each Phase 1 clinical trial was designed with
the primary objective to evaluate the safety and tolerability of SEL-212 and its individual components. Additional objectives of the Phase 1 clinical trials
included identifying a pegadricase dose that was capable of lowering serum uric acid levels over a period of one month, evaluating the immunogenicity of
pegadricase after a single dose and demonstrating that ImmTOR co-administered with pegadricase reduced uric acid levels and mitigated the formation of
uricase-specific ADAs. The Phase 2 clinical trial evaluated the effect of multiple doses over an extended period of time on serum uric acid and the
formation of ADAs in patients. We commenced patient recruitment in the multiple ascending dose Phase 2 clinical trial in October 2016 and received final
data from this trial in December 2018. We completed enrollment of our Phase 2 head-to-head (COMPARE) clinical study against KRYSTEXXA in
December 2019 and expect to report top-line data in the third quarter of 2020. The two-armed, open label trial has enrolled approximately 150 patients,
randomized 1:1, with one arm receiving KRYSTEXXA (as set forth in the prescribing information) and the other arm receiving six monthly doses of SEL-
212. The primary endpoint in the study is the percentage of patients in each arm that maintain SUA control below 6.0 mg/dL, for at least 80% of the time
during months three and six. We plan to commence the Phase 3 clinical program in SEL-212 in the second half of 2020. We will require additional
resources to complete the planned Phase 3 clinical program for SEL-212.
Phase 1a clinical trial
The Phase 1a clinical trial for SEL-212 was conducted at multiple sites in the United States and was a single ascending dose trial of pegadricase alone in 22
patients with elevated serum uric acid levels greater than 6.0 mg/dL. At the outset of the trial, each of five cohorts received a single intravenous infusion of
pegadricase at ascending dose levels. We monitored the patients during a 30-day period post-infusion. We commenced enrollment of the clinical trial in the
second quarter of 2015 and completed the treatment portion of the trial in November 2015. We observed that pegadricase showed no serious adverse
events, or SAEs, and was well tolerated at the five dose levels tested. Additionally, we observed that pegadricase rapidly reduced and sustained average
serum uric acid levels below 6.0 mg/dL for each cohort for 14 to 30 days, depending on the dose level. Consistent with our preclinical studies in animals,
pegadricase induced uricase-specific ADAs in all patients with varying levels in this Phase 1a trial.
Figure 8 below indicates the serum uric acid and uricase-specific ADA levels for each patient in Cohort #3 of the Phase 1a clinical trial, which received a
single dose of 0.4 mg/kg of pegadricase. The serum uric acid levels were measured at baseline and days seven, 14, 21 and 30 and uricase-specific ADA
levels at baseline and days seven, 14 and 30 following the single intravenous injection of pegadricase. We did not measure uricase-specific ADA levels at
day 21 in the Phase 1a clinical trial. Patient number two in this cohort developed a relatively low level uricase-specific ADA titer of 40 and maintained uric
acid levels below 0.5 mg/dL through the thirtieth day after dosing. By contrast, the remaining four patients in the cohort developed levels of uricase-
specific ADAs greater than 1,000 titer and uric acid levels above 5 mg/dL by the thirtieth day after dosing. Based on the results from our Phase 1a clinical
trial, we observed that pegadricase at the 0.4 mg/kg dose is capable of achieving and maintaining a reduction of serum uric acid below the target of 6.0
mg/dL for a 30-day period in the absence of inhibitory uricase-specific ADAs.
Figure 8. Phase 1a Clinical Trial: Serum Uric Acid and Uricase-Specific ADA Levels of the Third Cohort
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Based on our analysis of the Phase 1a clinical trial data, we selected the pegadricase dose of 0.4 mg/kg from Cohort #3 of the Phase 1a clinical trial for
further study in the Phase 1b clinical trial.
Phase 1b clinical trial
In December 2015, we initiated our Phase 1b clinical trial at multiple sites in the United States. The clinical trial enrolled 63 patients with serum uric acid
levels greater than 6.0 mg/dL. One group of five patients received a single 0.4 mg/kg dose of pegadricase alone, which we refer to as the Pegadricase
Cohort. Four groups of patients, each containing two placebo-control patients and five test article patients, received a placebo or a single intravenous
infusion of ImmTOR alone at the following ascending dose levels: 0.03 mg/kg, 0.1 mg/kg, 0.3 mg/kg and 0.5 mg/kg, which we refer to collectively as the
ImmTOR Cohorts. Four groups of patients received a single intravenous infusion of ImmTOR at ascending dose levels of 0.03 mg/kg (5 patients), 0.1
mg/kg (10 patients), 0.15 mg/kg (5 patients) or 0.3 mg/kg (5 patients) with a fixed dose of pegadricase of 0.4 mg/kg, which we collectively call the SEL-
212 cohorts. All patients were followed for at least 30 days after their initial dose.
Figure 9 below depicts the serum uric acid levels of the Pegadricase Cohort (depicted in red symbols), the ImmTOR Cohorts (depicted in blue symbols),
and the SEL‑212 Cohorts (depicted in green symbols) from the Phase 1b clinical trial. Serum uric acid levels were measured at baseline and days seven, 14,
21, 30 and longer for some patients that maintained serum uric acid control at day 21. As expected, ImmTOR alone had no relevant effect on reducing
serum uric acid levels across the ImmTOR Cohorts, as such levels remained relatively constant during the 30‑day period. Patients in the Pegadricase
Cohort showed an immediate drop in uric acid levels after dosing, with uric acid levels returning close to or above baseline levels by day 21 in four of the
five patients, similar to what was observed in Cohort #3 in the Phase 1a study. In contrast, patients in the SEL-212 Cohort receiving the lowest dose of
ImmTOR (0.03 mg/kg) co-administered with pegadricase (0.4 mg/kg), showed four out of five patients maintaining serum uric acid levels below 6.0 mg/dL
through day 21 after dosing. SEL-212 patients receiving ImmTOR at 0.1 mg/kg co-administered with 0.4 mg/kg of pegadricase, showed seven out of 10
patients maintained levels of serum uric acid of less than 0.1 mg/dL through day 30. SEL-212 patients receiving ImmTOR at 0.15 mg/kg co-administered
with 0.4 mg/kg of pegadricase, showed all five patients maintaining levels of serum uric acid of less than 6.0 mg/dL through day 30. Finally, SEL-212
patients receiving ImmTOR at 0.3 mg/kg c- administered with 0.4 mg/kg of pegadricase, showed all five patients maintaining levels of serum uric acid of
less than 0.1 mg/dL through day 30. These results indicated that SEL-212 showed a dose-dependent reduction in serum uric acid levels.
Figure 9. Phase 1b Clinical Trial: Uric Acid Levels Across All Phase 1b Cohorts
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Figure 10 below depicts the serum uric acid levels at day 30 next to the corresponding day 30 uricase-specific ADA titer for all patients in the Pegadricase
Cohort and in the SEL-212 Cohorts at the three higher dose levels. Four of the five patients treated with 0.4 mg/kg pegadricase alone showed their serum
uric return to baseline by day 30 and all five showed uricase specific ADA titers greater than 1000. Seven of 10 SEL-212 patients treated with 0.1 mg/kg
ImmTOR and 0.4 mg/kg pegadricase showed serum uric acid levels below 0.1 mg/dL with corresponding low or negative uricase specific ADA titers at
day 30. All five SEL-212 patients treated with 0.15 mg/kg ImmTOR and 0.4 mg/kg pegadricase showed serum uric acid below 6 mg/dL at day 30. One
patient developed uricase specific ADA titers greater than 1000 but still maintained his serum uric acid below the target threshold of 6 mg/dL at day 30.
The other four patients showed no ADA titers and had serum uric acid levels below 0.1 mg/dL. Finally, all five SEL-212 patients treated with 0.3 mg/kg
ImmTOR and 0.4 mg/kg pegadricase showed serum uric acid below 0.1 mg/dL at day 30 with corresponding low or negative ADA titers. The one patient
with an ADA titer of 120 at baseline showed the same titer at baseline and at each time point tested, indicating that this patient had pre-existing low titer of
antibody that was cross-reactive with pegadricase at baseline. These results indicated that SEL-212 mitigated the formation of uricase-specific ADAs which
correlated with sustained control of serum uric acid levels through at least day 30 after a single dose.
Figure 10. Comparison of Phase 1b Uric Acid and Uricase‑Specific ADA Levels
Certain patients in the SEL-212 Cohort were requested to return for additional visits on days 37, 44, and/or 51 because their serum uric acid levels were
still under control (<6 mg/dL) at day 21. Not all patients were able to return for the additional visits. The data for those who could return are in included in
Figure 11 below. The data show that uric acid levels eventually returned to baseline, as expected after a single dose of pegadricase. Importantly, no
emergence of ADAs was detected in those patients who exhibited low or no ADA titers at day 30. These data suggest that the treatment with ImmTOR
controlled immune responses to pegadricase for up to 51 days after dosing. The data also support monthly dosing in the Phase 2 multiple dose trial of SEL-
212.
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Figure 11. Comparison of Phase 1b Uric Acid and Uricase‑Specific ADA Levels
At the completion of our Phase 1b program for SEL-212 we had dosed a total of 64 patients in the trial with either SEL-212 (ImmTOR and pegadricase),
ImmTOR alone, pegadricase alone or placebo. The median serum acid level of patients enrolled was 7.3 mg/dL, with a mean of 7.4 mg/dL at baseline.
Patients presented with an average of 5.3 co-morbidities, such as hypertension and diabetes.
We have generally observed that SEL‑212 and its components, ImmTOR and pegadricase, have been well tolerated in this patient population. There were a
total of six SAEs in the Phase 1b trial. Of the six SAEs, three were determined to not to be related to study drug by investigators. Of the remaining three
SAEs that were determined to possibly or likely be related to study drug, two were cases of stomatitis that occurred at the highest dose of ImmTOR tested
(0.5 mg/kg), leading us to define 0.3 mg/kg as the maximum tolerated dose of ImmTOR in this patient population. The remaining SAE was a case of drug
hypersensitivity that occurred at a dose of 0.1 mg/kg of ImmTOR in combination with 0.4 mg/kg of pegadricase. In all cases, the patient fully recovered
from the SAE without residual effects.
Phase 2 dose-finding clinical trial
In the fourth quarter of 2016, we began enrolling patients with symptomatic gout and elevated serum uric acid levels in an open-label, multiple ascending
dose Phase 2 clinical trial of SEL-212. The primary and secondary endpoints for this trial included safety, tolerability, pharmacokinetics, and reduction of
serum uric acid and ADA levels. We have also collected data regarding flares and other patient-related observations. We enrolled patients in multiple
ascending dose cohorts with the primary goal of identifying the dose regimens to advance into our ongoing Phase 2 head-to-head (COMPARE) clinical
study and planned Phase 3 clinical program.
A total of 152 patients were dosed in the Phase 2 trial at 15 active U.S. clinical sites and the treatment phase of all SEL-212 cohorts had been completed.
The following is a summary of clinical activity from the trial as defined by the primary clinical endpoint (i.e., serum uric acid levels below 6 mg/dL):
•
•
•
Control and 0.05 mg/kg ImmTOR Dose Cohorts (cohorts receiving five monthly doses of pegadricase alone or three monthly doses of 0.2 mg/kg
or 0.4 mg/kg of pegadricase + 0.05 mg/kg of ImmTOR followed by two monthly doses of pegadricase alone): Dosing of patients in the control
cohorts receiving pegadricase alone was stopped early due to a loss of clinical activity caused by the immunogenicity of the enzyme. Clinical
activity was lost by week 12 in the majority of patients receiving pegadricase in combination with the 0.05 mg/kg dose of ImmTOR.
0.08 and 0.1 mg/kg ImmTOR Dose Cohorts (cohorts receiving three monthly doses of 0.2 mg/kg or 0.4 mg/kg of pegadricase + 0.08 or 0.10 mg/kg
of ImmTOR followed by two monthly doses of pegadricase alone): A majority of patients in these cohorts maintained clinical activity while
receiving the combination therapy through week 12. These results were consistent with the level of clinical activity observed through day 30 at a
similar SEL-212 dose level in our Phase 1b trial. At the 0.1 mg/kg dose level, half of the patients that maintained clinical activity through week 12
also maintained clinical activity through week 20.
0.125 and 0.15 mg/kg ImmTOR Dose Cohorts (cohorts receiving three monthly doses of pegadricase +0.125 or 0.15 mg/kg of ImmTOR followed
by two monthly doses of pegadricase alone): A majority of patients in these cohorts maintained clinical activity while receiving the combination
therapy through week 12. These results were consistent with the level of clinical activity observed through day 30 at a similar SEL-212 dose level
in our Phase 1b trial.
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Approximately 81% of evaluable patients (N=27) receiving up to 0.15 mg/kg ImmTOR in combination with 0.2 or 0.4 mg/kg of pegadricase
followed by 2 monthly doses of pegadricase alone had serum uric acid control below 6 mg/dL at week 12.
•
0.10 and 0.15 mg/kg ImmTOR 5 Combination Dose Cohorts (cohorts receiving five monthly doses of pegadricase +0.10 or 0.15 mg/kg of
ImmTOR ): Five monthly doses of SEL-212 resulted in sustained serum uric acid control and was well tolerated over the entire treatment period.
100% of the patients that had serum uric acid levels below 6 mg/dL at 12 weeks maintained control through 20 weeks. Approximately 66% of
evaluable patients (21/32) completed week 20 with serum uric acid levels below 6 mg/dL. (Figure 12).
Figure 12. Five Combination Doses Controlled Serum Uric Acid <6 mg/dL at Week 20 in 66% of Patients
Data from the trial suggested that ADA levels were strongly correlated with serum uric acid levels. We have observed that ImmTOR reduced the formation
of ADAs in a dose-dependent manner, which we believe enabled pegadricase to maintain clinical activity for extended durations as compared to
pegadricase administered without ImmTOR.
Data from the trial suggest that sustained control of serum uric acid near 0 mg/dL led to reduction in uric acid deposits as measured by DECT imaging.
Approximately 29% of patients who received SEL-212 reported a gout flare during their first month of the trial. This was followed by a decline in flare
rates during the remainder of the therapy (Figure 13). By comparison, 50% of patients reported a flare during the first month in the control cohorts
receiving pegadricase alone before treatment was stopped due to loss of efficacy and safety.
Figure 13. Percentage of Patients Reporting a Gout Flare per Month
SEL-212 was generally well tolerated at clinically active doses following repeated administrations in the trial. Twenty patients reported a total of 23 SAEs
in the Phase 2 clinical trial. Nine SAEs were reported in the five dose combination cohorts, seven of which were reported to be not related or unlikely
related to study drug, and two of which were infusion reactions. All SAEs were successfully treated without further issues.
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Phase 2 head-to-head (COMPARE) clinical trial
In March 2019, we initiated a Phase 2 head-to-head clinical trial of SEL-212 (COMPARE), in which SEL-212 is being compared against the current FDA-
approved therapy for chronic refractory gout, KRYSTEXXA, in multiple clinical sites in the United States. We completed enrollment of this study in
December 2019 and expect to report top-line data in the third quarter of 2020. The two-armed, open label trial has enrolled approximately 150 patients,
randomized 1:1, with one arm receiving KRYSTEXXA (as set forth in the prescribing information) and the other arm receiving six monthly doses of SEL-
212. The primary endpoint in the study is the percentage of patients in each arm that maintain SUA control below 6.0 mg/dL, for at least 80% of the time
during months three and six.
Our ImmTOR programs for immune tolerance in gene therapy
Overview
Although gene therapy has made significant progress over the last several years, it faces certain limitations due to undesired immunogenicity to either the
AAV vector or the encoded transgene.
Gene vector-specific ADAs frequently occur for patients who receive gene therapy and have been found to prevent the AAV vector from reaching its target
cell. It is unknown exactly how long these neutralizing ADAs prevent redosing of gene therapy. However, it has been observed in studies with animals and
humans that high titer AAV-specific ADAs develop and persist for more than 10 years, preventing vector readministration. In addition, cellular immune
responses have been found to correlate with liver inflammation and loss of gene expression.
Because of the induction of lasting antibodies against AAV, we believe many gene therapy companies have focused on the single localized dose in diseases
of the eye and central nervous system for which immunogenicity is perceived to be less of an issue. We believe that many gene therapy applications may
require or would benefit from multiple doses, especially therapies designed to treat diseases via intravenous administration. Some of these rare genetic
deficiencies are best treated when patients are infants or small children in order to prevent developmental defects. However, pediatric patients may have a
higher need for repeat dosing due to higher cell turnover as the patient grows. Accordingly, we believe that a solution enabling repeat dosing would
significantly expand the number of diseases and patients that could be treated with gene therapies.
SEL-302 for the Treatment of Methylmalonic Acidemia
In August 2019, we entered into the AskBio Collaboration Agreement, pursuant to which we and AskBio will conduct proof of concept studies to
potentially validate the use of our ImmTOR platform in conjunction with an AAV gene therapy to mitigate the formation of neutralizing anti-AAV capsid
antibodies, which currently precludes redosing. One of the product candidates under this collaboration is a gene therapy candidate for MMA, which can
cause severe developmental defects and premature death as a result of an accumulation of toxic metabolites. We previously conducted preclinical studies
for this product candidate based on SEL-302 and will leverage that previous work within the collaboration.
SEL-313 for the Treatment of OTC Deficiency
For our second gene therapy program, we plan to develop another product candidate for the treatment of ornithine transcarbamylase, or OTC, deficiency,
which is another metabolic disorder. We are pursuing this second potential indication through collaborations with third parties with preclinical and clinical
experience in this area.
Hemophilia A
On December 2, 2016, or the Spark Signing Date, we entered into the Spark License Agreement to collaborate on the development of gene therapies for
certain targets utilizing our ImmTOR platform. Under the terms of the Spark License Agreement, we granted Spark certain exclusive, worldwide, royalty-
bearing licenses to our intellectual property and know-how relating to our ImmTOR platform to research, develop and commercialize gene therapies for
hemophilia A, which is the initial target under the Spark License Agreement.
For more information about the Spark License Agreement, see the discussion under “Licenses and Collaborations - Spark” below.
Crigler Najjar Syndrome
In September 2018, we announced a collaboration with the European consortium, CureCN, for an ImmTOR+AAV gene therapy combination product
candidate in Crigler-Najjar syndrome, a rare genetic disorder characterized by an inability to properly convert and clear bilirubin from the body. The
consortium plans to utilize our ImmTOR platform in combination with their AAV gene therapy with the potential to re-dose patients who are not producing
enough enzyme post their first dose of AAV gene therapy. We expect the CureCN consortium to obtain scientific advice from the German drug regulatory
authority in 2020.
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MANUFACTURING
We manufacture ImmTOR using a scalable, self-assembly nanoemulsion process with well-defined, pharmaceutical unit operations. This proprietary,
highly specialized and precisely controlled manufacturing process enables us to reproducibly manufacture ImmTOR across many production scales, from
milligram-scale at the laboratory bench to hundreds of grams to multi-kilogram scale for commercial production. This well-defined process has been
produced at multiple scales. We have also developed and executed the required detailed analytic characterization of our products.
For the SEL-212 program, we have increased ImmTOR production to a 50-gram scale and have developed an approximately 400-gram scale process,
which, at the current projected clinical dose, we believe would be suitable for commercialization. The process is designed such that this same equipment is
capable of potentially producing up to a one kilogram batch size scale. As our nanoparticle manufacturing process is compact, and therefore also portable,
our strategy is to transfer our custom designed process skids to a contract manufacturing organization, or CMO, and have the CMO produce the
nanoparticles, under our direction. This is the strategy we use for production of clinical supplies for clinical trials and would be the expected strategy for
commercial production.
The pegadricase enzyme for SEL-212 is produced by fermentation in E. Coli and is sourced from 3SBio in China. 3SBio is a Chinese pharmaceutical
company that produces multiple approved products in China and also has product sales in other countries around the world. 3SBio supplies the pegadricase
used in the current clinical trials of SEL-212 in the United States. Through a licensing arrangement, we own exclusive worldwide rights to pegadricase
outside of China, with co-ownership of rights in Japan and with 3SBio owning all rights in China. Under this arrangement, 3SBio has agreed to supply us
with pegadricase. We also have selected a back-up supplier for pegadricase in the United States.
LICENSES AND COLLABORATIONS
AskBio
Feasibility Study and License Agreement
In August 2019, we entered into the AskBio Collaboration Agreement. Pursuant to the AskBio Collaboration Agreement, we and AskBio agreed to license
intellectual property rights to each other as part of a collaboration to research, develop, and commercialize certain AAV gene therapy products utilizing our
ImmTOR platform to enable re-dosing of such AAV gene therapy products to treat serious rare and orphan genetic diseases for which there is a significant
unmet medical need. Pursuant to the AskBio Collaboration Agreement, we and AskBio will conduct proof of concept studies, or POC Studies, to validate
the use of ImmTOR in conjunction with AAV for the treatment of MMA, based on our product candidate, SEL-302, to mitigate the formation of
neutralizing anti-AAV capsid antibodies. If the POC Studies are successful, or the parties otherwise elect to do so, the parties will proceed with a
collaboration to pursue the development and commercialization of AAV gene therapy products utilizing ImmTOR for the treatment of certain agreed
serious rare and orphan genetic diseases. If the POC Studies fail to demonstrate a proof of concept, and the parties do not mutually agree in writing to
proceed with the collaboration, the Agreement will expire. We plan to enter the clinic under this collaboration in 2020.
We and AskBio will share responsibility for the research, development and commercialization of products developed under this collaboration. The parties
will also share research, development and commercialization costs equally for all collaboration products, but with a right of either party to opt out of certain
products, and thereby no longer be required to share costs for such products. Each party will receive a percentage of net profits for each product sold under
the collaboration equal to the percentage of shared costs borne by such party in the development of such product. Pursuant to the AskBio Collaboration
Agreement, AskBio is responsible for manufacturing the AAV capsids and AAV vectors and we are responsible for manufacturing ImmTOR.
License Agreement for Pompe Disease
In December 2019, we entered into the AskBio License Agreement. Pursuant to the AskBio License Agreement, AskBio exercised its option to exclusively
license our intellectual property rights covering ImmTOR to research, develop, and commercialize certain AAV gene therapy products utilizing ImmTOR,
and targeting the GAA gene, or derivatives thereof, to treat Pompe Disease, which we refer to as the Licensed Products.
Pursuant to the AskBio License Agreement, AskBio agreed to pay to us upfront fees of an aggregate of $7.0 million. Also pursuant to the AskBio License
Agreement, AskBio agreed to make additional payments to us based on the achievement of certain development and commercial milestones of up to an
aggregate of $237.0 million. AskBio will also be obligated to make tiered royalty payments, at percentages in the mid-to-high single digits, to us based on
achievement of certain sales milestones.
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We will supply AskBio with our ImmTOR platform and AskBio will be responsible for all preclinical, clinical and commercial manufacture and supply of
Licensed Products (other than ImmTOR) and carry out all other activities related to the research, development, and commercialization of Licensed Products
at its sole expense, including all regulatory activities related thereto.
The AskBio License Agreement contains other customary terms and conditions, including representations and warranties, covenants, termination, and
indemnification obligations in favor of each party.
Spark Therapeutics
In December 2016, we entered into the Spark License Agreement to develop gene therapies for certain targets utilizing our ImmTOR platform.
Under the terms of the Spark License Agreement, we granted Spark certain exclusive, worldwide, royalty-bearing licenses to our intellectual property and
know-how relating to our ImmTOR platform to research, develop and commercialize gene therapies for Factor VIII, an essential blood clotting protein
relevant to the treatment of hemophilia A, which is the initial target under the license agreement.
Pursuant to the Spark License Agreement, Spark made an upfront payment to us of $15.0 million. Additionally, Spark purchased an aggregate of $15.0
million of our common stock in connection with the Spark License Agreement. We will be eligible to receive up to an aggregate of $430.0 million in
milestone payments, with up to $65.0 million being based on Spark’s achievement of specified development and regulatory milestones and up to $365.0
million for commercial milestones, as well as tiered royalties on global net sales at percentages ranging from mid-single to low-double digits. Until
December 2019, Spark had the right to fund up to 50.0% of any development or regulatory milestone payable to us by issuing us shares of Spark’s common
stock having a fair market value equal to the percentage of such development or regulatory milestone, as applicable.
In addition, until December 2019, Spark was eligible to exercise options to research, develop and commercialize gene therapies utilizing our ImmTOR
platform for up to four additional targets. Spark did not exercise any of these options prior to the termination of the election period.
Each party is responsible for its own costs and expenses incurred in connection with its respective activities under the Spark License, except that Spark has
agreed to reimburse us for FTE and out-of-pocket costs incurred in performing certain tasks or assistance specifically requested by Spark. We retain the
responsibility to manufacture Spark’s preclinical, clinical and commercial requirements for the ImmTOR platform, subject to the terms of the Spark
License.
The Spark License Agreement will continue on a country-by-country and product-by-product basis until the expiration of Spark’s royalty payment
obligations with respect to such product in such country unless earlier terminated by the parties. The Spark License Agreement may be terminated by Spark
for convenience upon ninety days’ notice. Either party may terminate the Spark License Agreement on a target-by-target basis for material breach with
respect to such target.
In connection with the Spark License Agreement, we also entered into a stock purchase agreement with Spark, pursuant to which Spark has purchased in
the aggregate $15.0 million of our common stock including (i) 197,238 shares for an aggregate purchase price of $5.0 million on the Spark Signing Date,
(ii) 324,362 shares for an aggregate purchase price of $5.0 million on June 8, 2017, and (iii) 205,254 shares for an aggregate purchase price of $5.0 million
on October 31, 2017.
Massachusetts Institute of Technology
In November 2008, we entered into a license agreement with MIT, which we refer to as the MIT License. We amended the MIT License in January 2010,
November 2012, August 2013, November 2016 and December 2019. Under the MIT License, we acquired an exclusive worldwide license, with the right to
grant sublicenses, to develop, make, sell, use and import certain licensed products that are therapeutic or prophylactic vaccines and use certain licensed
processes in the exercise of rights to the licensed products, the manufacture, sale and practice of which are covered by patent rights owned or controlled by
MIT, including patents jointly owned with Brigham, the President and Fellows of Harvard College, the Immune Disease Institute and the Children’s
Medical Center Corporation. Our exclusivity is subject to certain retained rights of these institutions and other third parties.
Upon our entry into the MIT License, we paid MIT a non-refundable license issue fee, reimbursed certain of MIT’s costs and issued shares of our common
stock to MIT and the other institutional patent owners which were subject to certain anti-dilution, registration and other protective rights. We are obligated
to pay MIT creditable annual maintenance fees, low-single-digit running royalty on annual net sales, developmental milestones up to an aggregate of $1.5
million, a mid-single digit percentage of certain payments we receive from corporate partners and a specified percentage of certain income received from
sublicensees after 2009 between 10% and 30%. We may terminate the MIT License at any time upon six months written notice. MIT has the right to
terminate the MIT License immediately upon written notice to us if we cease to carry on our business related to the MIT License, fail to maintain insurance
as required under the MIT License, file for bankruptcy, fail to pay amounts due under the MIT License, challenge or assist others in bringing a challenge to
MIT’s patents or fail to cure material breach within 60
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days’ written notice thereof. Absent early termination, the MIT License will continue until the expiration or abandonment of the last to expire patent right
subject to the MIT License.
MIT may terminate the MIT License if we fail to meet a diligence obligation, including the initiation of a Phase 3 clinical trial by a specified date in the
fourth quarter of 2019. In December 2019, we entered into the Fourth Amendment to the MIT License, which we refer to as the MIT Amendment. Pursuant
to the MIT Amendment, the provision of the MIT License under which we were obligated to initiate a Phase 3 clinical trial for a licensed product by a
specified date in the fourth quarter of 2019 is tolled until the earlier of (i) a specified date in the second quarter of 2020 or (ii) the effective date of a written
amendment to the MIT License. Further, pursuant to the MIT Amendment, the parties agreed to negotiate in good faith to enter into a future amendment to
the MIT License subject to our providing MIT with an amended diligence plan.
Shenyang Sunshine Pharmaceutical Co., Ltd.
In May 2014, we entered into a license agreement with 3SBio, as amended in May 2017, which we refer to as the 3SBio License. Pursuant to the 3SBio
License, we were granted an exclusive license to certain pegadricase-related patents and related “know-how” owned or in-licensed by 3SBio for the
worldwide (except for Greater China and Japan) development and commercialization of products based thereupon for human therapeutic, diagnostic and
prophylactic use. We are also granted a worldwide (except for Greater China) exclusive license to develop, commercialize and manufacture or have
manufactured products combining our proprietary ImmTOR platform with pegadricase or related compounds supplied by 3SBio (or otherwise supplied if
our rights to manufacture are in effect) for human therapeutic, diagnostic and prophylactic use. We were also granted a co-exclusive license to manufacture
and have manufactured pegadricase and related compounds for our preclinical and clinical use or, if the 3SBio License is terminated for 3SBio’s material
breach, for any use under the 3SBio License. In addition, the 3SBio License, as amended, permits us to utilize one or more third parties to provide up to
20% of our commercial supply of pegadricase. Otherwise, except in the case of a supply shortage on the part of 3SBio, we are obligated to obtain at least
80% of our supply of such compounds for Phase 3 clinical trials and commercial use from 3SBio under the terms of supply agreements to be negotiated.
Under the 3SBio License we have paid to 3SBio an aggregate of $3.0 million in upfront and milestone-based payments. We are required to make future
payments to 3SBio contingent upon the occurrence of events related to the achievement of clinical and regulatory approval milestones of up to an aggregate
of $21.0 million for products containing our ImmTOR platform, and up to an aggregate of $41.5 million for products without our ImmTOR platform. We
are also required to pay 3SBio tiered royalties on annual worldwide net sales related to the pegadricase component of products at percentages ranging from
the low-to-mid single digits for products containing our ImmTOR platform, and from the mid-single digits to low or low-to-mid teens for products without
our ImmTOR platform, subject to specified reductions. These royalties are payable, on a country-by-country and product-by-product basis until the later of
(i) the date that all of the patent rights for that product have expired in that country, or (ii) a specified number of years from the first commercial sale of
such product in such country.
The 3SBio License expires on the date of expiration of all of our royalty payment obligations unless earlier terminated by either party for an uncured
material default or for the other party’s bankruptcy. We may also terminate the 3SBio License on a country-by-country or product-by-product basis for any
reason effective upon 60 days’ prior written notice to 3SBio or, with respect to a given product, immediately upon written notice to 3SBio if we identify a
safety or efficacy concern related to such product.
BIND
In December 2008, we entered into a cross-license agreement with BIND Therapeutics, Inc. (formerly BIND Biosciences, Inc.), or BIND, which we refer
to as the BIND Agreement. Pursuant to the BIND Agreement, BIND granted us a perpetual, irrevocable, royalty-free worldwide non-exclusive license
under certain of BIND’s existing and future patent rights to make, have made, use, sell, offer for sale and import products and services covered by such
patents and patent applications in the field of certain prophylactic and therapeutic vaccines. The time period for adding new patent rights, not included in
the families of previously licensed patent rights, to our license grant from BIND has expired. Pursuant to the BIND Agreement, we granted BIND a
perpetual, irrevocable, royalty-free, worldwide non-exclusive license under certain of our current and future patent rights to make, have made, use, sell,
offer for sale and import products and services covered by such patents and patent applications in all other fields, in each case, excluding certain future
patent rights of each party related to novel targeting agents. The time period for adding new patent rights, not included in the families of previously
licensed patent rights, to BIND’s license grant from us has expired.
We have paid BIND an upfront license issuance fee and reimbursed certain of BIND’s fees in connection with the entry into the BIND Agreement. No
royalties or other payments are due to or by either party. The BIND Agreement expires upon expiration of the last patent right covered by the BIND
Agreement. Neither party may unilaterally terminate the BIND Agreement for any reason. If either party materially breaches the BIND Agreement, fails to
expend a specified amount in research and development activities related to the BIND Agreement, undergoes bankruptcy or insolvency, or undergoes a
change of control,
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the future patent rights to be included in the license grant to the party breaching, failing to expend such amounts or undergoing such event under the BIND
Agreement will no longer be granted to the breaching party.
In connection with BIND’s entry into bankruptcy proceeding in 2016, Pfizer purchased substantially all of the assets of BIND, including those pertaining to
the BIND Agreement.
Massachusetts Eye and Ear Infirmary
In May 2016, we entered into a license agreement with the Massachusetts Eye and Ear Infirmary and The Schepens Eye Research Institute, Inc., or,
collectively, MEE, which we refer to as the MEE License. Under the MEE License, we were granted an exclusive commercial worldwide license, with the
right to grant sublicenses through multiple tiers, to make, have made, use, offer to sell, sell and import certain products and to practice certain processes,
the sale, use or practice of which are covered by patents and proprietary know-how owned or controlled by MEE, for use of Anc80 gene therapy vectors for
gene augmentation therapies expressing certain target sequences. On September 16, 2019, in accordance with the terms of the MEE License, we notified
MEE of our intention to terminate the MEE License, effective December 15, 2019.
INTELLECTUAL PROPERTY
We endeavor to protect our nanoparticle technology, which we consider fundamental to our business, by seeking, maintaining and defending patent rights,
whether developed internally or licensed from third parties, relating to our program, product candidates, their methods of use and the processes for their
manufacture. Our practice is to strive to protect our intellectual property by, among other methods, pursuing and obtaining patent protection in the United
States and in jurisdictions outside of the United States related to our proprietary technology, inventions, improvements, programs and product candidates
that are commercially important to the operation and growth of our business. We also rely on trade secrets and know-how relating to our proprietary
technology, programs and product candidates, continuing innovation and in-licensing opportunities to maintain, advance and fortify our proprietary position
in our nanoparticle-based immunotherapy program and product candidates. Our commercial success will depend in part on our ability to obtain and
maintain patent and other proprietary protection for our program technology, inventions and improvements; to preserve the confidentiality of our trade
secrets; to maintain our licenses to use intellectual property owned or controlled by third parties; to defend and enforce our proprietary rights, including our
patents; and to operate without infringing the patents and proprietary rights of third parties.
We have developed and in-licensed numerous patents and patent applications and possess substantial know-how and trade secrets relating to our
nanoparticle-based immunotherapy technology, program and product candidates. Our patent portfolio contains a number of issued patents in the United
States and certain foreign jurisdictions. We also own a number of pending patent applications in the United States and certain foreign jurisdictions. These
patents and patent applications include claims directed to:
•
•
tolerance immunotherapy programs;
immune stimulation programs;
• methods and compositions incorporating our proprietary nanoparticles in a variety of tolerance applications, including:
• mitigating or treating anti-drug antibodies associated with protein drugs, such as for chronic refractory gout, covering ImmTOR co-
administered with pegadricase, which related patents are expected to expire between 2032 and 2038, and
•
genetic therapies (such as viral delivery of genes), covering ImmTOR co-administered with a viral vector, which related patents are
expected to expire between 2032 and 2039; and
•
development and commercialization of SEL-212, including both composition of matter and method of treatment claims (there are multiple patent
families that cover the SEL-212 product, one of which is a licensed, issued U.S. patent that covers the SEL-212 product, which expires in 2021).
In addition, we have exclusively or non-exclusively licensed intellectual property, including U.S. issued patents, foreign issued patents, and pending
applications in both the U.S. and foreign jurisdictions. The licensed patents and patent applications cover various aspects of the technology being
developed by us, including claims directed to compositions of matter and methods of use, and have been filed in various countries worldwide including in
North America, Europe and Asia, with material expiration dates varying from 2021 to, if claims are issued, 2028. In addition to filing and prosecuting
patent applications in the United States, we often file analogous patent applications in the European Union and in additional foreign countries where we
believe such filing is likely to be beneficial, including but not limited to Australia, Brazil, China, Europe, South Korea, Mexico, India, Israel and Japan.
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Each patent’s term depends upon the laws of the countries in which they are obtained. The patent term in most countries in which we file is 20 years from
the earliest date of filing of a non-provisional patent application. Notably, the term of U.S. patents may be extended due to delays incurred due to
compliance with FDA or by delays encountered during prosecution that are caused by the USPTO. For example, the Hatch-Waxman Act permits a patent
term extension for FDA-approved drugs of up to five years beyond the expiration of the patent, depending upon the length of time the drug is under
regulatory review. There is a limit to the amount of time a patent may be extended in the United States; no patent extension can extend the remaining term
of a patent beyond a total of 14 years from the date of product approval and only one patent applicable to an approved drug may be extended. Similar
patent term extensions are available in Europe and other jurisdictions for patents that cover regulatory-approved drugs. Currently, we own or license patents
and patent applications with expected material expiration dates ranging from 2021 to 2039. However, the actual patent protection period varies on a
product-by-product basis, from country-to-country, and depends upon many factors, including the type of patent, the scope of its coverage, the availability
of regulatory-related extensions, the availability of legal remedies in a particular country and the validity and enforceability of the patent.
COMPETITION
The biotechnology and pharmaceutical industries are characterized by rapidly advancing technologies, intense competition and a strong emphasis on
proprietary products. We face potential competition from many different sources, including pharmaceutical and biotechnology companies, academic
institutions and governmental agencies and public and private research institutions. Product candidates that we successfully develop and commercialize
may compete with existing therapies and new therapies that may become available in the future.
Our competitors may have significantly greater financial resources, established presence in the market, expertise in research and development,
manufacturing, preclinical and clinical testing, obtaining regulatory approvals and reimbursement and marketing approved products than we do. These
competitors also compete with us in recruiting and retaining qualified scientific, sales, marketing and management personnel, establishing clinical trial sites
and patient registration for clinical trials, as well as in acquiring technologies complementary to, or necessary for, our programs. Smaller or early-stage
companies may also prove to be significant competitors, particularly through collaborative arrangements with large and established companies.
The key competitive factors affecting the success of SEL-212, and any other tolerance or immune stimulation product candidates that we develop, if
approved, are likely to be their efficacy, safety, convenience, price, the level of generic competition and the availability of reimbursement from government
and other third-party payors.
Our commercial opportunity could be reduced or eliminated if our competitors develop and commercialize products that are more effective, have fewer or
less severe side effects, are more convenient or are less expensive than any products that we may develop. Our competitors also may obtain FDA or other
regulatory approval for their products more rapidly than we may obtain approval for ours. In addition, our ability to compete may be affected in many cases
by insurers or other third-party payors seeking to encourage the use of generic or biosimilar products. SEL-212 may compete with others in the gout
market, including KRYSTEXXA, which contains a pegylated uricase similar to the pegadricase component of SEL-212 and is indicated for the treatment of
refractory gout. Horizon Pharma plc, whose affiliates own KRYSTEXXA, may find other approaches to eliminate undesired immunogenicity to
KRYSTEXXA. Long-term treatment with global immunosuppressive products may increase the susceptibility to contract infections, tumors and may lead
to organ failure. Large companies with active research to prevent the formation of ADAs and treat allergies or autoimmune diseases include Sanofi,
Pfizer Inc., or Pfizer, and Merck & Co., Inc., or Merck. Small, early-stage biopharmaceutical companies active in the research for new technologies to
induce antigen-specific immune tolerance include Anokion SA, AnTolRx Inc., Apitope International NV, Caladrius Biosciences, Cour Pharmaceutical
Development Company, Inc., Dendright International, Inc., Parvus Therapeutics, REGiMMUNE Corporation, Rubius Therapeutics, Inc., Tolerion, Inc.,
Topas Therapeutics GmbH, SQZ Biotechnologies and Txcell SA. However, we believe that most of these companies are focused on autoimmune and
inflammatory diseases rather than immune tolerance to biologics.
GOVERNMENT REGULATION
Government authorities in the United States, at the federal, state and local level, and in other countries extensively regulate, among other things, the
research, development, testing, manufacturing, quality control, approval, labeling, packaging, storage, record-keeping, promotion, advertising, distribution,
post-approval monitoring and reporting, marketing and export and import of products such as those we are developing.
Our most advanced product candidate, SEL-212, is subject to regulation in the United States as a combination product. If marketed individually, each
component would be subject to different regulatory pathways and would require approval of independent marketing applications by the FDA. A
combination product, however, is assigned to a Center that will have primary jurisdiction over its regulation based on a determination of the combination
product’s primary mode of action, which is the single mode of action that provides the most important therapeutic action. In the case of our SEL-212, we
believe that the
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primary mode of action is attributable to the biologic component of the product. In the case of SEL-212, which we believe will be regulated as a therapeutic
biologic, the FDA’s Center for Drug Evaluation and Research, or CDER, will have primary jurisdiction over premarket development. We expect to seek
approval of SEL-212 through a single Biologics License Application, or BLA, reviewed by CDER, and we do not expect that the FDA will require a
separate marketing authorization for each constituent of SEL-212.
Biological products are subject to regulation under the Federal Food, Drug, and Cosmetic Act, or FD&C Act, and the Public Health Service Act, or PHS
Act, and other federal, state, local and foreign statutes and regulations. SEL-212 and any other product candidates that we develop must be approved by the
FDA before they may be legally marketed in the United States and by the appropriate foreign regulatory agency before they may be legally marketed in
foreign countries.
U.S. biological products development process
The process required by the FDA before a biologic, including a gene therapy, may be marketed in the United States generally involves the following:
•
•
•
•
•
•
•
completion of extensive nonclinical testing, sometimes referred to as preclinical testing, including laboratory tests, animal trials and formulation
studies in accordance with applicable regulations, including good laboratory practices, or GLPs, and applicable requirements for humane use of
laboratory animals;
submission to the FDA of an IND, which must become effective before human clinical trials may begin;
performance of adequate and well-controlled human clinical trials according to good clinical practice, or GCP, regulations and any additional
requirements for the protection of human research subjects and their health information, to establish the safety, purity and potency of the proposed
biological product for its intended use;
submission to the FDA of a BLA for marketing approval that includes substantive evidence of safety, purity, and potency from results of
nonclinical testing and clinical trials;
satisfactory completion of an FDA inspection of the manufacturing facility or facilities where the biological product is produced to assess
compliance with cGMP requirements to assure that the facilities, methods and controls are adequate to preserve the biological product’s identity,
strength, quality and purity;
potential FDA audit of the nonclinical and clinical study sites that generated the data in support of the BLA; and
FDA review and approval, or licensure, of the BLA.
Before testing any biological product candidate in humans, the product candidate enters the preclinical testing stage. Preclinical tests, also referred to as
nonclinical studies, include laboratory evaluations of product chemistry, toxicity and formulation, as well as animal studies to assess the potential safety
and activity of the product candidate. The conduct of the preclinical tests must comply with federal regulations and requirements including GLPs.
The clinical study sponsor must submit the results of the preclinical tests, together with manufacturing information, analytical data, any available clinical
data or literature and a proposed clinical protocol, to the FDA as part of the IND. Some preclinical testing may continue even after the IND is submitted.
The IND automatically becomes effective 30 days after receipt by the FDA, unless the FDA places the clinical study on a clinical hold within that 30-day
time period. In such a case, the IND sponsor and the FDA must resolve any outstanding concerns before the clinical study can begin. The FDA may also
impose clinical holds on a biological product candidate at any time before or during clinical trials due to safety concerns or non-compliance. If the FDA
imposes a clinical hold, trials may not recommence without FDA authorization and then only under terms authorized by the FDA.
In addition to the submission of an IND to the FDA, supervision of certain human gene transfer trials may also require evaluation and assessment by an
institutional biosafety committee, or IBC, a local institutional committee that reviews and oversees research utilizing recombinant or synthetic nucleic acid
molecules at that institution. The IBC assesses the safety of the research and identifies any potential risk to public health or the environment, and such
review may result in some delay before initiation of a clinical trial.
Clinical trials involve the administration of the biological product candidate to healthy volunteers or patients under the supervision of qualified
investigators, generally physicians not employed by or under the study sponsor’s control. Clinical trials are conducted under protocols detailing, among
other things, the objectives of the clinical study, dosing procedures, patient selection and exclusion criteria, and the parameters to be used to monitor patient
safety, including stopping rules that assure a clinical study will be stopped if certain adverse events should occur. Each protocol and any amendments to the
protocol must be submitted to the FDA as part of the IND. Clinical trials must be conducted and monitored in accordance with the FDA’s regulations
comprising the GCP requirements, including the requirement that all research patients provide informed consent. Further, each clinical study must be
reviewed and approved by an independent institutional review board, or IRB, at or
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servicing each institution at which the clinical study will be conducted. Human clinical trials are typically conducted in three sequential phases that may
overlap or be combined:
•
•
•
Phase I. The biological product candidate is initially introduced into healthy human patients and tested for safety. In the case of some products for
severe or life-threatening diseases, especially when the product may be too inherently toxic to ethically administer to healthy volunteers, the initial
human testing is often conducted in patients.
Phase II. The biological product candidate is evaluated in a limited patient population to identify possible adverse effects and safety risks, to
preliminarily evaluate the efficacy of the product for specific targeted diseases and to determine dosage tolerance, optimal dosage and dosing
schedule.
Phase III. Clinical trials are undertaken to further evaluate dosage, clinical efficacy, potency, and safety in an expanded patient population at
geographically dispersed clinical study sites. These clinical trials are intended to establish the overall risk/benefit ratio of the product and provide
an adequate basis for product labeling.
Post-approval clinical trials, sometimes referred to as Phase IV clinical trials, may be conducted after initial marketing approval. These clinical trials are
used to gain additional experience from the treatment of patients in the intended therapeutic indication, particularly for long-term safety follow-up.
During all phases of clinical development, regulatory agencies require extensive monitoring and auditing of all clinical activities, clinical data, and clinical
study investigators. The FDA or the sponsor or its data safety monitoring board may suspend a clinical study at any time on various grounds, including a
finding that the research patients or patients are being exposed to an unacceptable health risk. Similarly, an IRB can suspend or terminate approval of a
clinical study at its institution if the clinical study is not being conducted in accordance with the IRB’s requirements or if the biological product candidate
has been associated with unexpected serious harm to patients.
There are also requirements governing the reporting of ongoing clinical trials and completed clinical trial results to public registries. Sponsors of clinical
trials of FDA-regulated products, including biologics, are required to register and disclose certain clinical trial information, which is publicly available at
www.clinicaltrials.gov. Concurrent with clinical trials, companies usually complete additional animal trials and must also develop additional information
about the physical characteristics of the biological product candidate as well as finalize a process for manufacturing the product in commercial quantities in
accordance with GMP requirements.
U.S. review and approval processes
After the completion of clinical trials of a biological product candidate, FDA approval of a BLA must be obtained before commercial marketing of the
biological product. The BLA must include results of product development, laboratory and animal trials, human trials, information on the manufacture and
composition of the product, proposed labeling and other relevant information. In addition, under the Pediatric Research Equity Act, or PREA, a BLA or
supplement to a BLA must contain data to assess the safety and effectiveness of the biological product candidate for the claimed indications in all relevant
pediatric subpopulations and to support dosing and administration for each pediatric subpopulation for which the product is safe and effective. The Food
and Drug Administration Safety and Innovation Act, or FDASIA, requires that a sponsor who is planning to submit a marketing application for a drug or
biological product that includes a new active ingredient, new indication, new dosage form, new dosing regimen or new route of administration submit an
initial Pediatric Study Plan, or PSP, within sixty days after a Type C meeting or as may be agreed between the sponsor and FDA. Unless otherwise required
by regulation, PREA does not apply to any biological product for an indication for which orphan designation has been granted.
Under the Prescription Drug User Fee Act, or PDUFA, as amended, each BLA must be accompanied by a user fee. The FDA adjusts the PDUFA user fees
on an annual basis. Fee waivers or reductions are available in certain circumstances, including a waiver of the application fee for the first application filed
by a small business. Additionally, no user fees are assessed on BLAs for products designated as orphan drugs, unless the product also includes a non-
orphan indication.
Within 60 days following submission of the application, the FDA reviews a BLA submitted to determine if it is substantially complete before the agency
accepts it for filing. The FDA may refuse to file any BLA that it deems incomplete or not properly reviewable at the time of submission and may request
additional information. In this event, the BLA must be resubmitted with the additional information. Once the submission is accepted for filing, the FDA
begins an in-depth substantive review of the BLA. The FDA reviews the BLA to determine, among other things, whether the proposed product is safe, pure
and potent for its intended use and whether the product is being manufactured in accordance with cGMP requirements to assure and preserve the product’s
identity, safety, strength, quality, potency and purity. The FDA may refer applications for novel biological products or biological products that present
difficult questions of safety or efficacy to an advisory committee, typically a panel that includes clinicians and other experts, for review, evaluation and a
recommendation as to whether the application should be approved and under what conditions. The FDA is not bound by the recommendations of an
advisory committee, but it considers such recommendations carefully when making decisions. During the biological product approval process, the FDA
also will determine whether a Risk Evaluation and Mitigation Strategy, or REMS, is necessary to assure the safe use of the biological
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product candidate. If the FDA concludes a REMS is needed, the sponsor of the BLA must submit a proposed REMS; the FDA will not approve the BLA
without a REMS, if required.
Before approving a BLA, the FDA will inspect the facilities at which the product is manufactured. The FDA will not approve the product unless it
determines that the manufacturing processes and facilities are in compliance with cGMP requirements and adequate to assure consistent production of the
product within required specifications. Additionally, before approving a BLA, the FDA will typically inspect one or more clinical sites to assure that the
clinical trials were conducted in compliance with IND study requirements and GCP requirements.
Notwithstanding the submission of relevant data and information, the FDA may ultimately decide that the BLA does not satisfy its regulatory criteria for
approval and deny approval. Data obtained from clinical trials are not always conclusive and the FDA may interpret data differently than the applicant
interprets the same data. If the FDA decides not to approve the BLA in its present form, the FDA will issue a complete response letter that usually
describes all of the specific deficiencies in the BLA identified by the FDA. Additionally, the complete response letter may include recommended actions
that the applicant might take to place the application in a condition for approval. If a complete response letter is issued, the applicant may either resubmit
the BLA, addressing all of the deficiencies identified in the letter, or withdraw the application.
If a product receives regulatory approval, the approval may be significantly limited to specific diseases and dosages or the indications for use may
otherwise be limited, which could restrict the commercial value of the product. Further, the FDA may require that certain contraindications, warnings or
precautions be included in the product labeling. The FDA may impose restrictions and conditions on product distribution, prescribing, or dispensing in the
form of a REMS, or otherwise limit the scope of any approval. In addition, the FDA may require post marketing clinical trials, sometimes referred to as
Phase IV clinical trials, designed to further assess a biological product’s safety and effectiveness, and testing and surveillance programs to monitor the
safety of approved products that have been commercialized.
One of the performance goals agreed to by the FDA under the PDUFA is to review 90% of standard BLAs in 10 months from the filing date and 90% of
priority BLAs in six months from the filing date, whereupon a review decision is to be made. The FDA does not always meet its PDUFA goal dates for
standard and priority BLAs.
Orphan designation
The FDA may grant orphan designation to drugs or biologics intended to treat a rare disease or condition that affects fewer than 200,000 individuals in the
United States, or if it affects more than 200,000 individuals in the United States, there is no reasonable expectation that the cost of developing and
marketing the product for this type of disease or condition will be recovered from sales in the United States. Orphan designation must be requested before
submitting a BLA. After the FDA grants orphan designation, the identity of the therapeutic agent and its potential orphan use are disclosed publicly by the
FDA. Orphan designation does not convey any advantage in or shorten the duration of the regulatory review and approval process.
In the United States, orphan designation entitles a party to financial incentives such as opportunities for grant funding towards clinical trial costs, tax
advantages and user-fee waivers. In addition, if a product receives the first FDA approval for the indication for which it has orphan designation, the product
is entitled to orphan exclusivity, which means the FDA may not approve any other application to market the same product for the same indication for a
period of seven years, except in limited circumstances, such as a showing of clinical superiority over the product with orphan exclusivity or where the
manufacturer with orphan exclusivity is unable to assure sufficient quantities of the approved orphan designated product. Competitors, however, may
receive approval of different products for the indication for which the orphan product has exclusivity or obtain approval for the same product but for a
different indication for which the orphan product has exclusivity. Orphan product exclusivity also could block the approval of one of our products for seven
years if a competitor obtains approval of the same biological product as defined by the FDA or if our product candidate is determined to be contained
within the competitor’s product for the same indication or disease. If a drug or biological product designated as an orphan product receives marketing
approval for an indication broader than what is designated, it may not be entitled to orphan product exclusivity.
We have not requested orphan designation for our product candidates, but depending on the proposed indication for which we intend to develop our future
products, we may in the future request such designation.
Expedited development and review programs
The FDA has a Fast Track program that is intended to expedite or facilitate the process for reviewing new biological products that meet certain criteria.
Specifically, new biological products are eligible for Fast Track designation if they are intended to treat a serious or life-threatening disease or condition
and demonstrate the potential to address unmet medical needs for the disease or condition. Fast Track designation applies to the combination of the product
and the specific indication for which it is being studied. The sponsor of a new biologic may request that the FDA designate the biologic as a Fast Track
product at any time during the clinical development of the product. The FDA may consider for review sections of the marketing application for a Fast
Track product on a rolling basis before the complete application is submitted, if the sponsor provides a schedule for the
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submission of the sections of the application, the FDA agrees to accept sections of the application and determines that the schedule is acceptable, and the
sponsor pays any required user fees upon submission of the first section of the application.
Any product submitted to the FDA for marketing, including under a Fast Track program, may be eligible for other types of FDA programs intended to
expedite development and review, such as priority review and accelerated approval. Any product is eligible for priority review if it treats a serious
condition and, if approved, would provide a significant improvement in safety or effectiveness compared to marketed products. The FDA will attempt to
direct additional resources to the evaluation of an application for a new biological product designated for priority review in an effort to facilitate the review.
Additionally, a product may be eligible for accelerated approval. Biological products studied for their safety and effectiveness in treating serious or life-
threatening illnesses and that provide meaningful therapeutic benefit over existing treatments may be eligible for accelerated approval, which means that
they may be approved on the basis of adequate and well-controlled clinical studies establishing that the product has an effect on a surrogate endpoint that is
reasonably likely to predict a clinical benefit, or on the basis of an effect on a clinical endpoint other than survival or irreversible morbidity or mortality or
other clinical benefit, taking into account the severity, rarity, or prevalence of the condition and the availability or lack of alternative treatments. As a
condition of approval, the FDA may require that a sponsor of a biological product subject to accelerated approval perform adequate and well-controlled
post-marketing clinical studies. In addition, the FDA currently requires as a condition for accelerated approval pre-approval of promotional materials,
which could adversely impact the timing of the commercial launch of the product. Fast Track designation, priority review and accelerated approval do not
change the standards for approval but may expedite the development or approval process.
In addition, under the provisions of FDASIA, the FDA established a Breakthrough Therapy Designation which is intended to expedite the development and
review of products that treat serious or life-threatening diseases or conditions. A breakthrough therapy is defined as a drug that is intended, alone or in
combination with one or more other drugs, to treat a serious or life-threatening disease or condition, and preliminary clinical evidence indicates that the
drug may demonstrate substantial improvement over existing therapies on one or more clinically significant endpoints, such as substantial treatment effects
observed early in clinical development. The designation includes all of the features of Fast Track designation, as well as more intensive FDA interaction
and guidance. The Breakthrough Therapy Designation is a distinct status from both accelerated approval and priority review, but these can also be granted
to the same product candidate if the relevant criteria are met. The FDA must take certain actions, such as holding timely meetings and providing advice,
intended to expedite the development and review of an application for approval of a breakthrough therapy. Requests for breakthrough therapy designation
will be reviewed within 60 days of receipt, and FDA will either grant or deny the request.
Fast Track designation, priority review, accelerated approval and breakthrough therapy designation do not change the standards for approval but may
expedite the development or approval process. Even if we receive one of these designations for our product candidates, the FDA may later decide that our
product candidates no longer meet the conditions for qualification. In addition, these designations may not provide us with a material commercial
advantage.
Post-approval requirements
Maintaining substantial compliance with applicable federal, state and local statutes and regulations requires the expenditure of substantial time and
financial resources. Rigorous and extensive FDA regulation of biological products continues after approval, particularly with respect to cGMP
requirements. Manufacturers of our products are required to comply with applicable requirements in the cGMP regulations, including quality control and
quality assurance and maintenance of records and documentation. Other post-approval requirements applicable to biological products include record-
keeping requirements, reporting of adverse effects and reporting updated safety and efficacy information.
We also must comply with the FDA’s advertising and promotion requirements, such as those related to direct-to-consumer advertising, the prohibition on
promoting products for uses or in patient populations that are not described in the product’s approved labeling (known as “off-label use”), industry-
sponsored scientific and educational activities and promotional activities involving the internet. Discovery of previously unknown problems or the failure
to comply with the applicable regulatory requirements may result in restrictions on the marketing of a product or withdrawal of the product from the market
as well as possible civil or criminal sanctions. Failure to comply with the applicable U.S. requirements at any time during the product development process,
approval process or after approval, may subject an applicant or manufacturer to administrative or judicial civil or criminal sanctions and adverse publicity.
FDA sanctions could include refusal to approve pending applications, withdrawal of an approval, clinical hold, warning or untitled letters, product recalls,
product seizures, total or partial suspension of production or distribution, injunctions, fines, refusals of government contracts, mandated corrective
advertising or communications with doctors, debarment, restitution, disgorgement of profits, or civil or criminal penalties.
Biological product manufacturers and other entities involved in the manufacture and distribution of approved biological products are required to register
their establishments with the FDA and certain state agencies, and are subject to periodic unannounced inspections by the FDA and certain state agencies for
compliance with cGMP requirements and other laws. Accordingly, manufacturers must continue to expend time, money and effort in the area of production
and quality control to
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maintain cGMP compliance. In addition, changes to the manufacturing process or facility generally require prior FDA approval before being implemented
and other types of changes to the approved product, such as adding new indications and additional labeling claims, are also subject to further FDA review
and approval.
Biosimilars and exclusivity
The Patient Protection and Affordable Care Act, or ACA, signed into law on March 23, 2010, includes a subtitle called the Biologics Price Competition and
Innovation Act of 2009, or BPCIA, which created an abbreviated approval pathway for biological products that are biosimilar to or interchangeable with an
FDA-licensed reference biological product.
Biosimilarity, which requires that there be no clinically meaningful differences between the biological product and the reference product in terms of safety,
purity and potency, can be shown through analytical studies, animal studies and a clinical study or studies. Interchangeability requires that a product is
biosimilar to the reference product and the product must demonstrate that it can be expected to produce the same clinical results as the reference product in
any given patient and, for products that are administered multiple times to an individual, the biologic and the reference biologic may be alternated or
switched after one has been previously administered without increasing safety risks or risks of diminished efficacy relative to exclusive use of the reference
biologic. However, complexities associated with the larger, and often more complex, structures of biological products, as well as the processes by which
such products are manufactured, pose significant hurdles to implementation of the abbreviated approval pathway that are still being worked out by the
FDA.
Under the BPCIA, an application for a biosimilar product may not be submitted to the FDA until four years following the date that the reference product
was first licensed by the FDA. In addition, the approval of a biosimilar product may not be made effective by the FDA until 12 years from the date on
which the reference product was first licensed. During this 12-year period of exclusivity, another company may still market a competing version of the
reference product if the FDA approves a full BLA for the competing product containing the sponsor’s own preclinical data and data from adequate and
well-controlled clinical trials to demonstrate the safety, purity and potency of their product. The BPCIA also created certain exclusivity periods for certain
biosimilars approved as interchangeable products. At this juncture, it is unclear whether products deemed “interchangeable” by the FDA will, in fact, be
readily substituted by pharmacies, which are governed by state pharmacy law.
A biological product can also obtain pediatric market exclusivity in the United States. Pediatric exclusivity, if granted, adds six months to existing
exclusivity periods and patent terms. This six-month exclusivity, which runs from the end of other exclusivity protection or patent term, may be granted
based on the voluntary completion of a pediatric study in accordance with an FDA-issued "Written Request" for such a study.
The BPCIA is complex and continues to be interpreted and implemented by the FDA. As a result, the ultimate impact, implementation and meaning of the
BPCIA is subject to significant uncertainty.
Government regulation outside of the United States
In addition to regulations in the United States, we will be subject to a variety of regulations in other jurisdictions governing, among other things, clinical
studies and any commercial sales and distribution of our products. Because biologically sourced raw materials are subject to unique contamination risks,
their use may be restricted in some countries.
Whether or not we obtain FDA approval for a product, we must obtain the requisite approvals from regulatory authorities in foreign countries prior to the
commencement of clinical studies or marketing of the product in those countries. Certain countries outside of the United States have a similar process that
requires the submission of a clinical study application much like the IND prior to the commencement of human clinical studies. In the European Union, for
example, a clinical trial authorization, or CTA, must be submitted to each country’s national health authority and an independent ethics committee, much
like the FDA and the IRB, respectively. Once the CTA is approved in accordance with a country’s requirements, clinical study development may proceed.
The requirements and process governing the conduct of clinical studies, product licensing, pricing and reimbursement vary from country to country. In all
cases, the clinical studies are conducted in accordance with GCP and the applicable regulatory requirements and the ethical principles that have their origin
in the Declaration of Helsinki.
In the European Economic Area, or EEA, which is composed of the 27 Member States of the European Union plus Norway, Iceland and Liechtenstein, and
the United Kingdom (until the end of the transition period on 31 December 2020 provided for in Withdrawal Agreement between the EU and the UK)
medicinal products can only be commercialized after obtaining a Marketing Authorization, or MA.
There are two types of MAs.
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The Community MA, which is issued by the European Commission through the Centralized Procedure, based on the opinion of the Committee for
Medicinal Products for Human Use, or CHMP, of the European Medicines Agency, or EMA, and which is valid throughout the entire territory of
the EEA. The Centralized Procedure is mandatory for
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certain types of products, such as biotechnology medicinal products, orphan medicinal products, advanced therapy medicinal products (such as
gene therapy, somatic cell therapy and tissue engineered products), and medicinal products that contain a new active substance indicated for the
treatment of AIDS, cancer, neurodegenerative disorders, diabetes, auto-immune and viral diseases. The Centralized Procedure is optional for
products containing a new active substance not yet authorized in the EEA, or for products that constitute a significant therapeutic, scientific or
technical innovation or which are in the interest of public health in the EU. Under the Centralized Procedure the maximum timeframe for the
evaluation of a marketing authorization application is 210 days (excluding clock stops, when additional written or oral information is to be
provided by the applicant in response to questions asked by the CHMP). Accelerated evaluation might be granted by the CHMP in exceptional
cases, when the authorization of a medicinal product is of major interest from the point of view of public health and in particular from the
viewpoint of therapeutic innovation. Under the accelerated procedure the standard 210 days review period is reduced to 150 days.
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National MAs, which are issued by the competent authorities of the Member States of the EEA and only cover their respective territory, are
available for products not falling within the mandatory scope of the Centralized Procedure. Where a product has already been authorized for
marketing in a Member State of the EEA, this National MA can be recognized in another Member States through the Mutual Recognition
Procedure. If the product has not received a National MA in any Member State at the time of application, it can be approved simultaneously in
various Member States through the Decentralized Procedure.
To obtain regulatory approval of an investigational biological product under European Union regulatory systems, we must submit a marketing authorization
application, which is similar to the U.S. BLA. The European Union also provides opportunities for market exclusivity. For example, in the European
Union, upon receiving marketing authorization, new chemical entities generally receive eight years of data exclusivity and an additional two years of
market exclusivity. If granted, data exclusivity prevents regulatory authorities in the European Union from referencing the innovator’s data to assess a
generic or biosimilar application. During the additional two-year period of market exclusivity, a generic marketing authorization can be submitted, and the
innovator’s data may be referenced, but no generic or biosimilar product can be marketed until the expiration of the market exclusivity. However, there is
no guarantee that a product will be considered by the European Union’s regulatory authorities to be a new chemical entity, and products may not qualify for
data exclusivity. Products receiving orphan designation in the European Union can receive ten years of market exclusivity, during which time no marketing
authorization application shall be accepted and no marketing authorization shall be granted for a similar medicinal product for the same indication. An
orphan product can also obtain an additional two years of market exclusivity in the European Union for pediatric studies. No extension to any
supplementary protection certificate can be granted on the basis of pediatric studies for orphan indications.
The criteria for designating an “orphan medicinal product” in the European Union are similar in principle to those in the United States. Under Article 3 of
Regulation (EC) 141/2000, a medicinal product may be designated as orphan if (1) it is intended for the diagnosis, prevention or treatment of a life-
threatening or chronically debilitating condition; (2) either (a) such condition affects no more than five in 10,000 persons in the European Union when the
application is made, or (b) the product, without the benefits derived from orphan status, would not generate sufficient return in the European Union to
justify investment; and (3) there exists no satisfactory method of diagnosis, prevention or treatment of such condition authorized for marketing in the
European Union, or if such a method exists, the product will be of significant benefit to those affected by the condition, as defined in Regulation (EC)
847/2000. Orphan medicinal products are eligible for financial incentives such as reduction of fees or fee waivers and are, upon grant of a marketing
authorization, entitled to ten years of market exclusivity for the approved therapeutic indication. The application for orphan drug designation must be
submitted before the application for marketing authorization. The applicant will receive a fee reduction for the marketing authorization application if the
orphan drug designation has been granted, but not if the designation is still pending at the time the marketing authorization is submitted. Orphan drug
designation does not convey any advantage in, or shorten the duration of, the regulatory review and approval process.
The 10-year market exclusivity may be reduced to six years if, at the end of the fifth year, it is established that the product no longer meets the criteria for
orphan designation, for example, if the product is sufficiently profitable not to justify maintenance of market exclusivity. Additionally, marketing
authorization may be granted to a similar product for the same indication at any time if the:
•
•
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second applicant can establish that its product, although similar, is safer, more effective or otherwise clinically superior;
applicant consents to a second orphan medicinal product application; or
applicant cannot supply enough orphan medicinal product.
For other countries outside of the European Union, such as countries in Eastern Europe, Latin America or Asia, the requirements governing the conduct of
clinical studies, product licensing, pricing and reimbursement vary from country to
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country. In all cases, again, the clinical studies are conducted in accordance with GCP and the applicable regulatory requirements and the ethical principles
that have their origin in the Declaration of Helsinki.
When conducting clinical trials in the EU, we must adhere to the provisions of the European Union Clinical Trials Directive (Directive 2001/20/EC) and
the laws and regulations of the EU Member States implementing them. These provisions require, among other things, that the prior authorization of an
Ethics Committee and the competent Member State authority is obtained before commencing the clinical trial. In April 2014, the EU passed the Clinical
Trials Regulation (Regulation 536/2014), which will replace the current Clinical Trials Directive. To ensure that the rules for clinical trials are identical
throughout the European Union, the EU Clinical Trials Regulation was passed as a regulation that is directly applicable in all EU member states. All
clinical trials performed in the European Union are required to be conducted in accordance with the Clinical Trials Directive until the Clinical Trials
Regulation becomes applicable. According to the current plans of the EMA, the Clinical Trials Regulation is expected to become applicable in 2020.
We are also subject to data privacy and security laws in the jurisdictions outside of the U.S. in which we are established, run clinical trials or in which we
sell or market our products once approved. For example, in Europe we are subject to Regulation (EU) 2016/679 (General Data Protection Regulation or
GDPR) in relation to our collection, control, processing and other use of personal data (i.e. data relating to an identifiable living individual). We process
personal data in relation to participants in our clinical trials in the EEA., including the health and medical information of these participants. The GDPR is
directly applicable in each E.U. Member State, however, it provides that E.U. Member States may introduce further conditions, including limitations which
could limit our ability to collect, use and share personal data (including health and medical information), or could cause our compliance costs to increase,
ultimately having an adverse impact on our business. The GDPR imposes onerous accountability obligations requiring data controllers and processors to
maintain a record of their data processing and implement policies as part of its mandated privacy governance framework. It also requires data controllers to
be transparent and disclose to data subjects (in a concise, intelligible and easily accessible form) how their personal information is to be used, imposes
limitations on retention of personal data; defines for the first time pseudonymized (i.e., key-coded) data; introduces mandatory data breach notification
requirements; and sets higher standards for data controllers to demonstrate that they have obtained valid consent for certain data processing activities. We
are also subject to E.U. rules with respect to cross-border transfers of personal data out of the E.U. and EEA. We are subject to the supervision of local data
protection authorities in those E.U. jurisdictions where we are established or otherwise subject to the GDPR. Fines for certain breaches of the GDPR are
significant: up to the greater of EUR 20 million or 4% of total global annual turnover. In addition to the foregoing, a breach of the GDPR could result in
regulatory investigations, reputational damage, orders to cease/ change our use of data, enforcement notices, as well potential civil claims including class
action type litigation where individuals suffer harm. Moreover, the United Kingdom leaving the E.U. could also lead to further legislative and regulatory
changes. It remains unclear how the United Kingdom data protection laws or regulations will develop in the medium to longer term and how data transfer
to the United Kingdom from the E.U. will be regulated, especially following the United Kingdom's departure from the E.U. on January 31, 2020 without a
deal. However, the United Kingdom has transposed the GDPR into domestic law with the Data Protection Act 2018, which remains in force following the
United Kingdom's departure from the EU.
If we fail to comply with applicable foreign regulatory requirements, we may be subject to, among other things, fines, suspension or withdrawal of
regulatory approvals, product recalls, seizure of products, operating restrictions and criminal prosecution.
Other healthcare laws
In addition to FDA restrictions on marketing of pharmaceutical and biological products, other U.S. federal and state healthcare regulatory laws restrict
business practices in the biopharmaceutical industry, which include, but are not limited to, state and federal anti-kickback, false claims, data privacy and
security, and physician payment and drug pricing transparency laws.
The federal Anti-Kickback Statute prohibits, among other things, any person or entity from knowingly and willfully offering, paying, soliciting, receiving
or providing any remuneration, directly or indirectly, overtly or covertly, to induce or in return for purchasing, leasing, ordering, or arranging for or
recommending the purchase, lease, or order of any item or service reimbursable, in whole or in part, under Medicare, Medicaid or other federal healthcare
programs. The term “remuneration” has been broadly interpreted to include anything of value. The Anti-Kickback Statute has been interpreted to apply to
arrangements between pharmaceutical manufacturers on the one hand and prescribers, purchasers and formulary managers on the other. In addition, a
person or entity does not need to have actual knowledge of the statute or specific intent to violate it in order to have committed a violation. The majority of
states also have anti-kickback laws, which establish similar prohibitions and in some cases may apply to items or services reimbursed by any third-party
payor, including commercial insurers.
The federal false claims and civil monetary penalties laws, including the civil False Claims Act, prohibit any person or entity from, among other things,
knowingly presenting, or causing to be presented, a false, fictitious or fraudulent claim for payment to, or approval by, the federal government or
knowingly making, using, or causing to be made or used a false record or statement material to a false or fraudulent claim to the federal government, or
from knowingly making a false statement to
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avoid, decrease or conceal an obligation. A claim includes “any request or demand” for money or property presented to the U.S. government. Violation of
the federal Anti-Kickback Statute may also constitute a false or fraudulent claim for purposes of the federal civil False Claims Act. Actions under the civil
False Claims Act 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
civil False Claims Act can result in very significant monetary penalties and treble damages. In addition, the civil monetary penalties statute imposes
penalties against any person who is determined to have presented or caused to be presented a claim to a federal health program that the person knows or
should know is for an item or service that was not provided as claimed or is false or fraudulent. Many states also have similar fraud and abuse statutes or
regulations that apply to items and services reimbursed under Medicaid and other state programs, or, in several states, apply regardless of the payor. Given
the significant size of actual and potential settlements, it is expected that the government authorities will continue to devote substantial resources to
investigating healthcare providers’ and manufacturers’ compliance with applicable fraud and abuse laws.
The federal Health Insurance Portability and Accountability Act of 1996, or HIPAA, prohibits, among other actions, knowingly and willfully executing, or
attempting to execute, a scheme to defraud any healthcare benefit program, including private third-party payors, knowingly and willfully embezzling or
stealing from a healthcare benefit program, willfully obstructing a criminal investigation of a healthcare offense, and knowingly and willfully falsifying,
concealing or covering up a material fact or making any materially false, fictitious or fraudulent statement in connection with the delivery of or payment for
healthcare benefits, items or services. A person or entity does not need to have actual knowledge of the statute or specific intent to violate it in order to have
committed a violation.
In addition, there has been a recent trend of increased federal and state regulation of payments made to physicians and certain other healthcare providers.
The ACA imposed, among other things, new annual reporting requirements through the Physician Payments Sunshine Act for covered manufacturers for
certain payments and “transfers of value” provided to physicians (defined to include doctors, dentists, optometrists, podiatrists and chiropractors), certain
other health care professionals beginning in 2022, and teaching hospitals, as well as ownership and investment interests held by physicians and their
immediate family members. Failure to submit timely, accurately and completely the required information for all payments, transfers of value and ownership
or investment interests may result in civil monetary penalties. In addition, certain states require implementation of compliance programs and compliance
with the pharmaceutical industry’s voluntary compliance guidelines and the relevant compliance guidance promulgated by the federal government, impose
restrictions on marketing practices, and/or tracking and reporting of pricing information and marketing expenditure as well as gifts, compensation and other
remuneration or items of value provided to physicians and other healthcare professionals and entities.
Violation of any of such laws or any other governmental regulations that may apply to us can result in penalties, including, without limitation,
administrative, civil and criminal penalties, damages, fines, disgorgement, contractual damages, reputational harm, diminished profits and future earnings,
the curtailment or restructuring of our operations, exclusion from participation in federal and state healthcare programs and individual imprisonment.
To the extent that any of our product candidates, once approved, are sold in a foreign country, we may be subject to similar foreign laws and regulations,
which may include, for instance, applicable post-marketing requirements, including safety surveillance, anti-fraud and abuse laws, and implementation of
corporate compliance programs and reporting of payments or other transfers of value to healthcare professionals.
We may also be subject to data privacy and security regulation by both the federal government and the states in which we conduct our business. HIPAA, as
amended by the Health Information Technology for Economic and Clinical Health Act, or HITECH, and their respective implementing regulations, impose
specified requirements relating to the privacy, security and transmission of individually identifiable health information held by covered entities and their
business associates. Among other things, HITECH made HIPAA’s security standards directly applicable to, as well as imposed certain other privacy
obligations on, “business associates,” defined as independent contractors or agents of covered entities that create, receive, maintain or transmit protected
health information in connection with providing a service for or on behalf of a covered entity. HITECH also increased the civil and criminal penalties that
may be imposed against covered entities, business associates and possibly other persons, and gave state attorneys general new authority to file civil actions
for damages or injunctions in federal courts to enforce the federal HIPAA laws and seek attorney’s fees and costs associated with pursuing federal civil
actions. Even when HIPAA does not apply, according to the Federal Trade Commission or the FTC, failing to take appropriate steps to keep consumers’
personal information secure constitutes unfair acts or practices in or affecting commerce in violation of Section 5(a) of the Federal Trade Commission Act,
or the FTCA, 15 U.S.C § 45(a). The FTC expects a company’s data security measures to be reasonable and appropriate in light of the sensitivity and
volume of consumer information it holds, the size and complexity of its business, and the cost of available tools to improve security and reduce
vulnerabilities. Individually identifiable health information is considered sensitive data that merits stronger safeguards. The FTC’s guidance for
appropriately securing consumers’ personal information is similar to what is required by the HIPAA Security Rule.
In addition, certain state laws govern the privacy and security of health information in certain circumstances, many of which differ from each other in
significant ways and may not have the same requirements, thus complicating compliance efforts. By
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way of example, the California Consumer Privacy Act, or CCPA, which went into effect January 1, 2020, among other things, creates new data privacy
obligations for covered companies and provides new privacy rights to California residents, including the right to opt out of certain disclosures of their
information. The CCPA also creates a private right of action with statutory damages for certain data breaches, thereby potentially increasing risks
associated with a data breach. Although the law includes limited exceptions, including for “protected health information” maintained by a covered entity or
business associate, it may regulate or impact our processing of personal information depending on the context.
Coverage and reimbursement
Significant uncertainty exists as to the coverage and reimbursement status of any pharmaceutical or biological products for which we obtain regulatory
approval. In the United States and markets in other countries, patients who are prescribed treatments for their conditions and providers performing the
prescribed services generally rely on third-party payors to reimburse all or part of the associated healthcare costs. Patients are unlikely to use our products
unless coverage is provided and reimbursement is adequate to cover a significant portion of the cost of our products. Moreover, for drugs and biologics
administered under the supervision of a physician, obtaining coverage and adequate reimbursement may be particularly difficult because of the higher
prices often associated with such products. Sales of any products for which we receive regulatory approval for commercial sale will therefore depend, in
part, on the availability of coverage and adequate reimbursement from third-party payors. Third-party payors include government authorities, managed care
plans, private health insurers and other organizations.
The process for determining whether a third-party payor will provide coverage for a pharmaceutical or biological product typically is separate from the
process for setting the price of such product or for establishing the reimbursement rate that the payor will pay for the product once coverage is approved.
Third-party payors may limit coverage to specific products on an approved list, also known as a formulary, which might not include all of the FDA-
approved products for a particular indication. A decision by a third-party payor not to cover our product candidates could reduce physician utilization of
our products once approved and have a material adverse effect on our sales, results of operations and financial condition. Moreover, a third-party payor’s
decision to provide coverage for a pharmaceutical or biological product does not imply that an adequate reimbursement rate will be approved. Adequate
third-party reimbursement may not be available to enable us to maintain price levels sufficient to realize an appropriate return on our investment in product
development. Additionally, coverage and reimbursement for products can differ significantly from payor to payor. One third-party payor’s decision to cover
a particular medical product or service does not ensure that other payors will also provide coverage for the medical product or service, or will provide
coverage at an adequate reimbursement rate.
The containment of healthcare costs is a priority of federal, state and foreign governments, and the prices of pharmaceutical or biological products have
been a focus in this effort. Third-party payors are increasingly challenging the prices charged for medical products and services, examining the medical
necessity and reviewing the cost-effectiveness of pharmaceutical or biological products, medical devices and medical services, in addition to questioning
safety and efficacy. If these third-party payors do not consider our products to be cost-effective compared to other available therapies, they may not cover
our products after FDA approval or, if they do, the level of payment may not be sufficient to allow us to sell our products at a profit.
Healthcare reform
A primary trend in the U.S. healthcare industry and elsewhere is cost containment. Government authorities and other third-party payors have attempted to
control costs by limiting coverage and the amount of reimbursement for particular medical products. For example, the ACA, among other things, increased
the minimum Medicaid rebates owed by most manufacturers under the Medicaid Drug Rebate Program; introduced 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;
extended the Medicaid Drug Rebate Program to utilization of prescriptions of individuals enrolled in Medicaid managed care plans; subjected drug
manufacturers to new annual fees based on pharmaceutical companies’ share of sales to federal healthcare programs; and created a new Patient Centered
Outcomes Research Institute to oversee, identify priorities in, and conduct comparative clinical effectiveness research, along with funding for such
research.
Since its enactment, there have been judicial and Congressional challenges to certain aspects of the ACA. By way of example, the Tax Cuts and Jobs Acts
was enacted, which, among other things, removes penalties for not complying with the individual mandate to carry health insurance. Further, on December
14, 2018, a U.S. District Court Judge in the Northern District of Texas, ruled that the individual mandate is a critical and inseverable feature of the ACA,
and therefore, because it was repealed as part of the Tax Cuts and Jobs Acts, the remaining provisions of the ACA are invalid as well. On December 18,
2019, the U.S. Court of Appeals for the 5th Circuit ruled that the individual mandate was unconstitutional and remanded the case back to the District Court
to determine whether the remaining provisions of the ACA are invalid as well. It is unclear how these decisions, subsequent appeals, if any, and other
efforts to challenge, repeal or replace the ACA will impact the law.
In addition, other legislative changes have been proposed and adopted in the United States since the ACA was enacted. This included aggregate reductions
of Medicare payments to providers of 2% per fiscal year, which went into effect on April 1, 2013
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and, due to subsequent legislative amendments, will stay in effect through 2027 unless additional Congressional action is taken. On January 2, 2013, the
American Taxpayer Relief Act was signed into law, which, among other things, further reduced Medicare payments to several providers, including
hospitals and imaging centers, and increased the statute of limitations period for the government to recover overpayments to providers from three to five
years. Recently there has also been heightened governmental scrutiny over the manner in which manufacturers set prices for their marketed products, which
has resulted in several Congressional inquiries and proposed and enacted legislation designed to, among other things, bring more transparency to product
pricing, review the relationship between pricing and manufacturer patient programs, and reform government program reimbursement methodologies.
We expect that additional state and federal healthcare reform measures will be adopted in the future, any of which could limit the amounts that federal and
state governments will pay for healthcare products and services, which could result in reduced demand for our products once approved or additional pricing
pressures. The implementation of cost containment measures or other healthcare reforms may prevent us from being able to generate revenue, attain
profitability or commercialize our drugs.
Employees
As of January 31, 2020, we had 39 full-time employees, 27 of whom were primarily engaged in research and development activities. A total of 12
employees have either one or both an M.D. or Ph.D. degree. None of our employees are represented by a labor union and we consider our employee
relations to be good.
Corporate Information
We were incorporated in Delaware in 2007. Our principal executive offices are located at 480 Arsenal Way, Watertown, MA 02472 and our telephone
number is (617) 923-1400. Our website address is www.selectabio.com. Information contained on or accessible through our website is not a part of this
Annual Report on Form 10-K, and the inclusion of our website address in this Annual Report on Form 10-K is an inactive textual reference only.
Available Information
We file electronically with the SEC, our annual reports on Form 10-K, quarterly reports on Form 10-Q, current reports on Form 8-K, proxy statements and
other information. Our SEC filings are available to the public over the Internet at the SEC's website at http://www.sec.gov. We make available on our
website at www.selectabio.com, under “Investors,” free of charge, copies of these reports as soon as reasonably practicable after filing or furnishing these
reports with the SEC.
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Item 1A. Risk Factors
Investing in our common stock involves a high degree of risk. You should consider carefully the risks described below, together with the other information
included or incorporated by reference in this Annual Report on Form 10-K. If any of the following risks occur, our business, financial condition, results of
operations and future growth prospects could be materially and adversely affected. In these circumstances, the market price of our common stock could
decline. Other events that we do not currently anticipate or that we currently deem immaterial may also affect our business, prospects, financial condition
and results of operations.
RISKS RELATED TO OUR FINANCIAL POSITION AND NEED FOR ADDITIONAL CAPITAL
We are a development‑stage company and have incurred significant losses since our inception. We expect to incur losses for the foreseeable future and
may never achieve or maintain profitability.
Since inception, we have incurred significant operating losses in every year. Our net loss was $55.4 million for the year ended December 31, 2019 and
$65.3 million for each of the years ended December 31, 2018 and 2017, respectively. As of December 31, 2019, we had an accumulated deficit of $335.8
million. To date, we have financed our operations primarily through the public offering and private placements of our securities, funding received from
research grants and collaboration arrangements and our credit facility. We currently have no source of product revenue, and we do not expect to generate
product revenue for the foreseeable future. All of our revenue to date has been collaboration and grant revenue. We have devoted substantially all of our
financial resources and efforts to developing our ImmTOR platform, identifying potential product candidates and conducting preclinical studies and our
clinical trials. We are in the early stages of development of most of our product candidates, and we have not completed development of any ImmTOR-
enabled therapies. We expect to continue to incur significant expenses and operating losses for the foreseeable future. We expect that our expenses will
increase substantially as we:
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conduct additional clinical trials of SEL‑212, our lead product candidate;
continue the research and development of our other product candidates;
seek to enhance our ImmTOR platform and discover and develop additional product candidates;
seek to maintain and enter into collaboration, licensing and other agreements, including, but not limited to research and development, and/or
commercialization agreements;
seek regulatory approvals for any product candidates that successfully complete clinical trials;
potentially establish a sales, marketing and distribution infrastructure and scale up external manufacturing capabilities to commercialize any products
for which we may obtain regulatory approval;
- maintain, expand and protect our intellectual property portfolio, including through licensing arrangements;
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add clinical, scientific, operational, financial and management information systems and personnel, including personnel to support our product
development and potential future commercialization efforts and to support our operations as a public company; and
experience any delays or encounter any issues with any of the above, including, but not limited to, failed studies, complex results, safety issues or other
regulatory, manufacturing or scale-up challenges.
To become and remain profitable, we must succeed in developing and eventually commercializing products that generate significant revenue. This will
require us to be successful in a range of challenging activities, including completing preclinical testing and clinical trials of our product candidates,
discovering additional product candidates, obtaining regulatory approval and securing reimbursement for these product candidates, manufacturing,
marketing and selling any products for which we may obtain regulatory approval, and establishing and managing our collaborations at various stages of a
product candidate’s development. We are only in the preliminary stages of most of these activities. We may never succeed in these activities and, even if we
do, may never generate revenues that are significant enough to achieve profitability.
Because of the numerous risks and uncertainties associated with pharmaceutical and biological product development, we are unable to accurately predict
the timing or amount of increased expenses or when, or if, we will be able to achieve profitability. If we are required by the FDA or other regulatory
authorities to perform studies in addition to those currently expected, or if there are any delays in completing our clinical trials or the development of any of
our product candidates, our expenses could increase and revenue could be further delayed.
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 would depress our value and could impair our ability to raise capital, expand our business, maintain our research and development efforts,
diversify our product offerings or continue our operations.
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We will need substantial additional funding in order to complete development of our product candidates and commercialize our products, if approved.
If we are unable to raise capital when needed, we could be forced to delay, reduce or eliminate our product development programs or
commercialization efforts.
We expect our expenses to increase in connection with our ongoing activities, particularly as we conduct our clinical trials of SEL‑212, continue to develop
our gene therapy program, including our collaboration with AskBio, and continue research and development for our other product candidates. In addition,
if we obtain regulatory approval for any of our product candidates, we expect to incur significant commercialization expenses related to product
manufacturing, marketing, sales and distribution. Accordingly, we will need to obtain substantial additional funding to continue operations. If we are
unable to raise capital when needed or on attractive terms, we could be forced to delay, reduce or eliminate our clinical trials, our other research and
development programs or any future commercialization efforts.
We believe that our existing cash, cash equivalents, investments, and restricted cash as of December 31, 2019 will enable us to fund our operating expenses
and capital expenditure requirements into the first quarter of 2021. We plan to commence our Phase 3 clinical program in SEL-212 in the second half of
2020. Because our current operating plan does not contain sufficient resources, we will require additional external sources of capital to complete the
planned Phase 3 clinical program for SEL-212. We have based this estimate on assumptions that may prove to be wrong, and we could use our capital
resources sooner than we currently expect. Because of the uncertainty in securing additional capital, we have concluded that substantial doubt exists with
respect to our ability to continue as a going concern within one year after the date of the filing of this Annual Report on Form 10-K.
Moreover, under the terms of the MIT License, MIT may terminate the MIT License if we fail to meet a diligence obligation, including the initiation of a
Phase 3 clinical trial by a specified date in the fourth quarter of 2019. If we are unable to reach an agreement with MIT regarding an acceptable amendment
of the MIT License and if we are unable to cure the breach, which is currently tolled until the earlier of (i) a specified date in the second quarter of 2020 or
(ii) the effective date of a written amendment to the MIT Agreement, there could be a material adverse effect on our business. See “Business - Licenses and
Collaborations – Massachusetts Institute of Technology.”
Our future capital requirements will depend on many factors, including:
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the scope, progress, results and costs of our clinical trials of SEL‑212;
the number of product candidates that we pursue;
our collaboration agreements remaining in effect, our entering into additional collaboration agreements and our ability to achieve milestones under
these agreements;
the cost of manufacturing clinical supplies of our product candidates;
our headcount growth and associated costs;
the scope, progress, results and costs of preclinical development, laboratory testing and clinical trials for our other product candidates;
the costs, timing and outcome of regulatory review of our product candidates;
the costs and timing of future commercialization activities, including manufacturing, marketing, sales and distribution, for any of our product
candidates for which we receive marketing approval;
the revenue, if any, received from commercial sales of our product candidates for which we receive marketing approval;
the costs and timing of preparing, filing and prosecuting patent applications, maintaining and enforcing our intellectual property rights and defending
any intellectual property‑related claims;
the effect of competing technological and market developments; and
the extent to which we acquire or invest in businesses, products and technologies, including entering into licensing or collaboration arrangements for
product candidates.
Any additional fundraising efforts may divert our management from their day‑to‑day activities, which may adversely affect our ability to develop and
commercialize our product candidates. In addition, we cannot guarantee that future financing will be available in sufficient amounts or on terms acceptable
to us, if at all. Moreover, the terms of any financing may adversely affect the holdings or the rights of our stockholders, and the issuance of additional
securities, whether equity or debt, by us, or the possibility of such issuance, may cause the market price of our shares to decline. The sale of additional
equity or convertible securities would dilute all of our stockholders. The incurrence of indebtedness could result in increased fixed payment obligations and
we may be required to agree to certain restrictive covenants, such as limitations on our ability to incur additional debt, limitations on our ability to acquire,
sell or license intellectual property rights and other operating restrictions
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that could adversely impact our ability to conduct our business. We could also be required to seek funds through arrangements with collaborators or others
at an earlier stage than otherwise would be desirable and we may be required to relinquish rights to some of our technologies or product candidates or
otherwise agree to terms unfavorable to us, any of which may have a material adverse effect on our business, operating results and prospects.
If we are unable to obtain funding on a timely basis, we may be required to significantly curtail, delay or discontinue one or more of our research or
development programs, including our clinical trial programs, or the commercialization of any product candidates, or be unable to sustain or expand our
operations or otherwise capitalize on our business opportunities, as desired, which could materially affect our business, financial condition and results of
operations.
Our recurring losses from operations and negative cash flows from operations raise substantial doubt regarding our ability to continue as a going
concern.
As of December 31, 2019 and December 31, 2018, we had an accumulated deficit of $335.8 million and $280.4 million, respectively. We anticipate
operating losses to continue for the foreseeable future due to, among other things, costs related to research, development of our product candidates,
conducting preclinical studies and clinical trials, and our administrative organization. We will require substantial additional financing to fund our operations
and to continue to execute our strategy, and we will pursue a range of options to secure additional capital. These conditions raise substantial doubt about
our ability to continue as a going concern within one year after the date of filing this Annual Report on Form 10-K.
We are exploring various sources of funding such as strategic collaborations and the issuance of equity to fund our operations. If we raise additional funds
through strategic collaborations and alliances, which may include existing collaboration partners, we may have to relinquish valuable rights to our
technologies or product candidates, or, grant licenses on terms that are not favorable to us. To the extent that we raise additional capital through the sale of
equity, the ownership interest of our existing shareholders will be diluted and other preferences may be necessary that adversely affect the rights of existing
shareholders. Because our current operating plan does not contain sufficient resources, we will require additional external sources of capital to complete the
planned Phase 3 clinical program for SEL-212. If we are unable to raise sufficient capital, we intend to curtail expenses contemplated by the current
operating plan, and we may be required to delay, limit, reduce or terminate our product development efforts or grant rights to develop and market product
candidates that we would otherwise prefer to develop and market ourselves. If the foregoing plans are unsuccessful and we are unable to continue as a
going concern, you could lose all or part of your investment in the company.
Our limited operating history may make it difficult for you to evaluate the success of our business to date and to assess our future viability.
We commenced active operations in 2007, and our operations to date have been limited to developing and researching our ImmTOR platform and related
products and programs, building our intellectual property portfolio, developing our supply chain, planning our business, raising capital and providing
general and administrative support for these operations. Other than SEL-212, our lead product candidate, our other product candidates are still in preclinical
development. While we have completed our early development clinical trials and a Phase 2 clinical trial for SEL‑212, we have not completed a clinical trial
for any other product candidate, nor have we demonstrated our ability to successfully complete any Phase 3 or other pivotal clinical trials, obtain regulatory
approvals, manufacture a commercial scale product, or arrange for a third party to do so on our behalf, or conduct sales and marketing activities necessary
for successful product commercialization. Additionally, we expect our financial condition and operating results to continue to fluctuate significantly from
quarter‑to‑quarter and year‑to‑year due to a variety of factors, many of which are beyond our control. Consequently, any predictions you make about our
future success or viability may not be as accurate as they could be if we had a longer operating history.
The terms of our credit facility place restrictions on our operating and financial flexibility. If we raise additional capital through debt financing, the
terms of any new debt could further restrict our ability to operate our business.
On September 12, 2017, we entered into a term loan facility of up to $21.0 million with Silicon Valley Bank, or SVB. The term loan facility is governed by
a loan and security agreement, dated September 12, 2017, between us and SVB, which was funded in full on September 13, 2017. The term loan facility
with SVB is secured by a lien on substantially all of our assets, other than intellectual property, provided that such lien on substantially all assets includes
any rights to payments and proceeds from the sale, licensing or disposition of intellectual property. We also granted SVB a negative pledge with respect to
our intellectual property.
The term loan facility contains customary covenants and representations, including but not limited to financial reporting obligations and limitations on
dividends, indebtedness, collateral, investments, distributions, transfers, mergers or acquisitions, taxes, corporate changes, deposit accounts, and
subsidiaries. The term loan facility also contains other customary provisions, such as expense reimbursement, non-disclosure obligations as well as
indemnification rights for the benefit of SVB. The events of default under the term loan facility include, but are not limited to, our failure to make any
payments of principal or interest under the term loan facility or other transaction documents, our breach or default in the performance of any covenant
under the
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term loan facility or other transaction documents, the occurrence of a material adverse effect, making a false or misleading representation or warranty in
any material respect under the term loan facility, our insolvency or bankruptcy, any attachment or judgment on our assets of at least approximately $0.3
million, or the occurrence of any default under any of our agreements or obligations involving indebtedness in excess of approximately $0.3 million. If an
event of default occurs, SVB is entitled to take enforcement action, including acceleration of amounts due under the term loan facility. If we raise any
additional debt financing, the terms of such additional debt could further restrict our operating and financial flexibility.
Changes in U.S. tax law may materially adversely affect our financial condition, results of operations and cash flows.
The Tax Cuts and Jobs Act of 2017, or TCJA, has significantly changed the U.S. federal income taxation of U.S. corporations. The TCJA remains unclear
in many respects and has been, and may continue to be, the subject of amendments and technical corrections, as well as interpretations and implementing
regulations by the Treasury and Internal Revenue Service, which have lessened or increased certain adverse impacts of the TCJA and may do so in the
future. We continue to work with our tax advisors and auditors to determine the full impact that the TCJA will have on us. We urge our investors to consult
with their legal and tax advisors with respect to the TCJA.
Our ability to use our net operating loss and research and development tax credit carryforwards to offset future taxable income may be subject to
certain limitations.
We have net operating loss carryforwards, or NOLs, for federal and state income tax purposes that may be available to offset our future taxable income, if
any. In general, under Sections 382 and 383 of the U.S. Internal Revenue Code of 1986, as amended, or the Code, a corporation that undergoes an
“ownership change” is subject to limitations on its ability to use its pre‑change NOLs to offset future taxable income. If the U.S. Internal Revenue Service,
or IRS, challenges our analysis that existing NOLs will not expire before utilization due to previous ownership changes, or if we undergo an ownership
change in connection with or after a public offering, our ability to use our NOLs could be limited by Section 382 of the Code. Future changes in our stock
ownership, some of which are outside of our control, could result in an ownership change under Sections 382 and 383 of the Code. Furthermore, our ability
to use NOLs of companies that we may acquire in the future may be subject to limitations. As a result, we may not be able to use a material portion of the
NOLs reflected on our balance sheet, even if we attain profitability. The reduction of the corporate tax rate under the TCJA may cause a reduction in the
economic benefit of our NOLs and other deferred tax assets available to us. Under the TCJA, although the treatment of NOLs arising on or before
December 31, 2017 has generally not changed, NOLs arising on or after January 1, 2018 will generally only be able to offset 80% of taxable income. This
change may require us to pay federal income taxes in future years despite generating a loss for federal income tax purposes in prior years.
RISKS RELATED TO THE DISCOVERY, DEVELOPMENT AND REGULATORY APPROVAL OF OUR PRODUCT CANDIDATES
Our product candidates are based on our ImmTOR platform, which is an unproven approach designed to induce antigen‑specific immune tolerance to
biologic drugs. We are very early in most of our clinical development efforts and may not be successful in our efforts to use our ImmTOR platform to
build a pipeline of product candidates and develop marketable drugs.
All of our product candidates are derived from our ImmTOR platform, which is an unproven approach to induce antigen‑specific immune tolerance and to
mitigate the immunogenicity of biologic therapies currently being implemented to treat patients. We are primarily developing our ImmTOR platform to
improve and enable activity in biologics that are designed to treat rare and serious diseases, with an initial focus on developing SEL‑212 for the treatment
of chronic refractory gout. We are also leveraging our ImmTOR platform to pursue programs in additional therapeutic areas with a focus on gene therapy.
We are developing two gene therapy product candidates for rare inborn errors of metabolism. Our lead gene therapy program, known as SEL-302, is a
potential gene therapy product candidate for MMA. In August 2019, we entered into a feasibility study and license agreement with AskBio, the AskBio
Collaboration Agreement, pursuant to which we and AskBio agreed to conduct proof of concept studies to potentially validate the use of our ImmTOR
platform in conjunction with an AAV gene therapy for the treatment of MMA, based on SEL-302, to mitigate the formation of neutralizing anti-AAV
capsid antibodies. If the proof of concept studies are successful, we will proceed with a collaboration to pursue the development and commercialization of
AAV gene therapy product candidates utilizing ImmTOR for the treatment of certain agreed serious rare and orphan genetic diseases. Our second gene
therapy product candidate, known as SEL-313, is being developed to treat ornithine transcarbamylase deficiency. In September 2018, we announced a
collaboration with the European consortium, CureCN, for an ImmTOR+AAV gene therapy combination product candidate in Crigler-Najjar syndrome, a
rare genetic disorder characterized by an inability to properly convert and clear bilirubin from the body. We expect the CureCN consortium to obtain
scientific advice from the German drug regulatory authority in 2020.
We are at an early stage of development of most of our product candidates and our technology has not yet led to, and may never lead to, approvable or
marketable drugs. We may have problems identifying new product candidates and applying our
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technologies to these other areas. Even if we are successful in identifying new product candidates, they may not be suitable for clinical development,
including as a result of harmful side effects, limited efficacy or other characteristics that indicate that they are unlikely to be products that will receive
marketing approval and achieve market acceptance. The success of our product candidates will depend on several factors, including the following:
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design, initiation and completion of preclinical studies and clinical trials with positive results;
reliance on third parties (including but not limited to collaborators, licensees, clinical research organizations and contract manufacturing
organizations);
receipt of marketing approvals from applicable regulatory authorities;
obtaining and maintaining patent and trade secret protection and regulatory exclusivity for our product candidates;
- making arrangements with third-party manufacturers for, or establishing, commercial manufacturing capabilities, or establishing such capabilities
ourselves;
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launching commercial sales of our products, if and when approved, whether alone or in collaboration with others;
our existing collaboration agreements remaining in effect and our ability to enter into new collaborations throughout the development process as
appropriate, from preclinical studies through to commercialization;
acceptance of our products, if and when approved, by patients and the medical community;
effectively competing with other therapies;
obtaining and maintaining coverage and adequate reimbursement by third‑party payors, including government payors, for our products, if approved;
protecting our rights in our intellectual property portfolio;
operating without infringing or violating the valid and enforceable patents or other intellectual property of third parties;
- maintaining an acceptable safety profile of our products following approval; and
- maintaining and growing an organization of scientists and business people who can develop and commercialize our product candidates and technology.
If we do not successfully develop and commercialize product candidates based upon our technological approach, we will not be able to obtain future
revenues, which would result in significant harm to our financial position and adversely affect our stock price.
As a result, we cannot be certain that our approach, or our development of SEL-212, will lead to the development or approval of marketable products. In
addition:
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due to the unproven nature of our ImmTOR therapeutics, there may be different efficacy and safety rates in various indications;
the FDA or other regulatory agencies may lack experience in evaluating the efficacy and safety of products based on ImmTOR or a biologic sourced
from China or other jurisdictions, which could result in a longer‑than‑expected regulatory review process, increase our expected development costs or
delay or prevent commercialization of our product candidates; and
in the event of a biologics license application, or BLA, for SEL‑212 or another product and a pre‑approval inspection by the FDA of the facilities of
Shenyang Sunshine Pharmaceutical Co., Ltd., or 3SBio, or any other third party manufacturers we may use, the FDA may not approve the facility for
production or may make observations that will take significant time for 3SBio or such other manufacturer to address.
The occurrence of any of the foregoing, would effectively prevent or delay approval of our lead and other product candidates.
We are applying our ImmTOR platform to antigen-specific immune tolerance for gene therapy involving gene augmentation, replacement or editing.
Regulatory authorities in the United States and European Union have limited experience in reviewing and approving gene therapy products, which
could affect the time and data required to obtain marketing authorization of any of our product candidates.
Our future success depends in part on our successful development of viable gene therapy product candidates utilizing ImmTOR platform. We may
experience problems or delays in developing such product candidates and any such problems or delays (i) may result in unanticipated costs and time to
develop our product candidates and/or (ii) may not be resolved in a satisfactory manner.
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The process of obtaining marketing approvals, both in the United States and abroad, is expensive and may take many years. If additional clinical trials are
required for certain jurisdictions, these trials can vary substantially based upon a variety of factors, including the type, complexity and novelty of the
product candidates involved, and may ultimately be unsuccessful. Changes in marketing approval policies during the development period, changes in or the
enactment or promulgation of additional statutes or regulations, respectively, or changes in the regulatory review process for each submitted product
application, may cause delays in the review and approval of an application.
The regulatory approval process and clinical trial requirements for novel product candidates can be more expensive and take longer than for other, better
known or more extensively studied product candidates, and we cannot predict how long it will take or how much it will cost to complete clinical
developments and obtain regulatory approvals for a gene therapy product candidate in either the United States or the European Union or how long it will
take to commercialize a gene therapy product candidate, if and when approved. Regulatory requirements governing gene therapy products have changed
frequently and may continue to change in the future. For example, the FDA established the Office of Tissues and Advanced Therapies within its Center for
Biologics Evaluation and Research, or CBER, to consolidate the review of gene therapy and related products, and the Cellular, Tissue and Gene Therapies
Advisory Committee to advise CBER on its review. These and other regulatory review agencies, committees and advisory groups and the requirements and
guidelines they promulgate may lengthen the regulatory review process, require us to perform additional preclinical studies or clinical trials, increase our
development costs, lead to changes in regulatory positions and interpretations, delay or prevent approval and commercialization of these treatment
candidates or lead to significant post-approval limitations or restrictions.
Additionally, under the National Institutes of Health, or NIH, Guidelines for Research Involving Recombinant DNA Molecules, or the NIH Guidelines,
supervision of human gene transfer trials includes evaluation and assessment by an institutional biosafety committee, or IBC, a local institutional
committee that reviews and oversees research utilizing recombinant or synthetic nucleic acid molecules at that institution. The IBC assesses the safety of
the research and identifies any potential risk to public health or the environment, and such review may result in some delay before initiation of a clinical
trial. While the NIH Guidelines are not mandatory unless the research in question is being conducted at or sponsored by institutions receiving NIH funding
of recombinant or synthetic nucleic acid molecule research, many companies and other institutions not otherwise subject to the NIH Guidelines voluntarily
follow them.
A similar framework is in place in the European Union, or the EU. The European Medicines Agency, or the EMA, has a Committee for Advanced
Therapies, or CAT, that is responsible for assessing the quality, safety and efficacy of advanced-therapy medicinal products. Advanced-therapy medical
products include gene therapy medicine, somatic-cell therapy medicines and tissue-engineered medicines. The role of the CAT is to prepare a draft opinion
on an application for marketing authorization for a gene therapy medicinal candidate that is submitted to the EMA. In the EU, the development and
evaluation of a gene therapy medicinal product must be considered in the context of the relevant EU guidelines. The EMA may issue new guidelines
concerning the development and marketing authorization for gene therapy medicinal products and require that we comply with these new guidelines.
Similarly, complex regulatory environments exist in other jurisdictions in which we might consider seeking regulatory approvals for our product
candidates, further complicating the regulatory landscape. As a result, the procedures and standards applied to gene therapy products and cell therapy
products may be applied to any of our gene therapy or genome editing product candidates, but that remains uncertain at this point.
The clinical trial requirements of the FDA, the EMA and other regulatory authorities and the criteria these regulators use to evaluate the safety and efficacy
of a product candidate vary substantially according to the type, complexity, novelty and intended use and market of the potential products. The regulatory
approval process for product candidates created with novel genome editing technology such as ours can be more lengthy, rigorous and expensive than the
process for other better known or more extensively studied product candidates and technologies. Since we are developing novel treatments for diseases in
which there is little clinical experience with new endpoints and methodologies, there is heightened risk that the FDA, the EMA or comparable regulatory
bodies may not consider the clinical trial endpoints to provide clinically meaningful results, and the resulting clinical data and results may be more difficult
to analyze. This may be a particularly significant risk for many of the genetically defined diseases for which we may develop product candidates alone or
with collaborators due to small patient populations for those diseases, and designing and executing a rigorous clinical trial with appropriate statistical
power is more difficult than with diseases that have larger patient populations. Regulatory agencies administering existing or future regulations or
legislation may not allow production and marketing of products utilizing genome editing technology in a timely manner or under technically or
commercially feasible conditions. Even if our product candidates obtain required regulatory approvals, such approvals may later be withdrawn as a result of
changes in regulations or the interpretation of regulations by applicable regulatory agencies.
Changes in applicable regulatory guidelines may lengthen the regulatory review process for our product candidates, require additional studies or trials,
increase development costs, lead to changes in regulatory positions and interpretations, delay or prevent approval and commercialization of such product
candidates, or lead to significant post-approval limitations or restrictions. Additionally, adverse developments in clinical trials conducted by others of gene
therapy products or products
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created using genome editing technology, or adverse public perception of the field of genome editing, may cause the FDA, the EMA and other regulatory
bodies to revise the requirements for approval of any product candidates we may develop or limit the use of products utilizing genome editing technologies,
either of which could materially harm our business. Furthermore, regulatory action or private litigation could result in expenses, delays or other
impediments to our research programs or the development or commercialization of current or future product candidates.
As we advance any gene therapy product candidates, we will be required to consult with various regulatory authorities, and we must comply with
applicable laws, rules, and regulations, which may change from time to time including during the course of development of our product candidates. If we
fail to do so, we may be required to delay or discontinue the clinical development of certain of our product candidates. These additional processes may
result in a review and approval process that is longer than we otherwise would have expected. Even if we comply with applicable laws, rules, and
regulations, and even if we maintain close coordination with the applicable regulatory authorities with oversight over our product candidates, our
development programs may fail to succeed. Regulatory authorities have substantial discretion in the approval process and may refuse to accept a marketing
application as deficient or may decide that our data is insufficient for approval and require additional preclinical, clinical or other studies. In addition,
varying interpretations of the data obtained from preclinical and clinical testing could delay, limit or prevent marketing approval of a product candidate.
Delay or failure to obtain, or unexpected costs in obtaining, the regulatory approval necessary to bring a potential product to market would materially and
adversely affect our business, financial condition, results of operations and prospects.
Clinical drug development involves a lengthy and expensive process, with an uncertain outcome. We may incur additional costs or experience delays in
completing, or ultimately be unable to complete, the development and commercialization of our product candidates.
Our lead product candidate, SEL-212, was evaluated in a Phase 2 clinical program that was initiated in October 2016 and the final patient's last visit
occurred in January 2019. In March 2019, we initiated COMPARE, a Phase 2 clinical trial designed to directly compare the safety, efficacy and tolerability
of SEL-212 to the currently FDA-approved uricase therapy, KRYSTEXXA, for the treatment of patients with chronic refractory gout, and completed our
targeted enrollment of the COMPARE trial in December 2019. We are preparing for the start of a pivotal Phase 3 program for SEL-212.
In May 2017 we licensed LMB-100, a potent immunotoxin, from the National Cancer Institute (NCI) and a Phase 1 clinical trial of LMB-100 plus
ImmTOR (SEL-403) initiated in March 2018 by NCI in patients with malignant pleural or peritoneal mesothelioma who had undergone at least one
regimen of chemotherapy under a Cooperative Research and Development Agreement (CRADA) between the NCI and the Company. In October 2018, the
NCI informed the Company of a Grade 5 Serious Adverse Event (patient death) in this clinical trial related to pneumonitis, which was deemed by the trial
investigator to be probably related to SVP-Rapamycin and possibly related to the patient’s pleural mesothelioma condition. This patient had received
previous therapies, including two courses of radiation therapy and three different immune check point inhibitors, which have been reported to be associated
with pneumonitis. However, the possible relationship to SVP-Rapamycin could not be excluded. Pneumonitis has been reported in patients receiving daily
oral rapamycin. In addition, a Serious Adverse Event (pericardial effusion) was seen in one of the other three patients dosed in the SEL-403 clinical trial.
Pericardial effusion can also be a side effect of immunotoxin therapies targeting mesothelin. The FDA placed the IND for SEL-403 on full clinical hold in
response to adverse events observed during the Phase 1 trial. Selecta has terminated the license of LMB-100 from NCI, effective April 9, 2019 and is no
longer pursuing this product candidate.
Aside from these programs, our other product candidates are in preclinical development. It is impossible to predict when or if any of our product candidates
will prove effective and safe in humans or will receive regulatory approval, and the risk of failure through the development process is high. Before
obtaining marketing approval from regulatory authorities for the sale of any product candidate, we must complete preclinical development and then
conduct extensive clinical trials to demonstrate the safety and efficacy of our product candidates in humans. Preclinical development is costly and
inherently uncertain. For example, we have invested significant resources in our preclinical gene therapy program, which has demonstrated the potential for
treatment of rare inborn errors of metabolism. Early preclinical results may not be predictive of future results, however, if our technology proves to be
ineffective or unsafe as a result of, among other things, adverse side effects, pre-existing anti-drug antibodies that can neutralize the viral vector and block
gene transfer, or cellular immune response to the transduced cells, we may incur additional costs or experience delays in completing, or ultimately be
unable to complete, the clinical development and commercialization of our product candidates.
Before obtaining marketing approval from regulatory authorities for the sale of our product candidates, we must conduct extensive clinical trials to
demonstrate the safety and efficacy of the product candidate for its intended indications. Clinical testing is expensive, difficult to design and implement,
can take many years to complete and its outcome is inherently uncertain. A failed clinical trial can occur at any stage of testing. Moreover, the outcome of
preclinical testing and early clinical trials may not be predictive of the success of later clinical trials, and interim results of a clinical trial do not necessarily
predict final results. For example, the clinical trial results from our Phase 2 head-to-head (COMPARE) study of SEL-212, including
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interim results, may not be predictive of future results. Moreover, we may not be able to complete, or may be required to deviate from the current clinical
trial protocol for a variety of reasons.
Many companies in the pharmaceutical and biotechnology industries have suffered significant setbacks in clinical trials after achieving positive results in
preclinical development or early-stage clinical trials, and we cannot be certain that we will not face similar setbacks. These setbacks have been caused by,
among other things, preclinical findings made while clinical trials were underway or safety or efficacy observations made in clinical trials, including
adverse events. SAEs caused by, or other unexpected properties of, any product candidates that we may choose to develop could cause us, an institutional
review board or regulatory authority to interrupt, delay or halt clinical trials of one or more of such product candidates and could result in a more restrictive
label or the delay or denial of marketing approval by the FDA or comparable non-U.S. regulatory authorities. If any product candidate that we may choose
to develop is associated with SAEs or other unexpected properties, we may need to abandon development or limit development of that product candidate to
certain uses or subpopulations in which those undesirable characteristics would be expected to be less prevalent, less severe or more tolerable from a risk-
benefit perspective. For example, in the SEL-403 Phase 1 clinical trial, a Grade 5 SAE (patient death) occurred that was deemed by the trial investigator to
be probably related to SVP-Rapamycin and possibly related to the patient's pleural mesothelioma condition which led the Company to abandon
development of SEL-403. In the SEL-212 Phase 1/2 clinical program, multiple SAEs have occurred, and future SAEs may occur causing the Company to
incur additional costs or experience delays in completing, or causing the Company to ultimately be unable to complete, the development and
commercialization of our product candidates, and delay or prevent our ability to obtain FDA approval. Moreover, preclinical and clinical data is often
susceptible to varying interpretations and analyses, and many companies that believed their product candidates performed satisfactorily in preclinical
studies and clinical trials nonetheless failed to obtain FDA or other regulatory authority approval. If we fail to produce positive results in clinical trials of
our product candidates, the development timeline and regulatory approval and commercialization prospects for our product candidates, and,
correspondingly, our business and financial prospects, would be negatively impacted.
In addition, we cannot be certain as to what type and how many clinical trials the FDA will require us to conduct before we may gain regulatory approval
to market SEL-212 or any of our other product candidates in the United States or other countries, if any. Prior to approving a new therapeutic product, the
FDA generally requires that safety and efficacy be demonstrated in two adequate and well-controlled clinical trials. We expect that we may need to conduct
more than one Phase 3 trial for SEL-212 for a chronic refractory gout indication in order to gain approval from the FDA. Even if we conduct more than one
Phase 3 trial for SEL-212, the FDA may not accept the data, and may delay, limit or deny approval of SEL-212. Additional clinical trials could cause us to
incur significant development costs, delay or prevent the commercialization of SEL-212 or otherwise adversely affect our business.
We may experience numerous unforeseen events during, or as a result of, clinical trials that could delay or prevent our ability to receive marketing approval
for, or commercialize, our product candidates, including:
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clinical trials of our product candidates may produce unfavorable, incomplete or inconclusive results;
regulators or institutional review boards may not authorize us or our investigators to commence a clinical trial or conduct a clinical trial at a
prospective trial site;
we may experience delays in reaching, or fail to reach, agreement on acceptable terms with contract research organizations, or CROs, or clinical trial
sites;
we may be unable to recruit suitable patients to participate in a clinical trial, the number of patients required for clinical trials of our product candidates
may be larger than we expect, enrollment in these clinical trials may be slower than we expect or participants may drop out of these clinical trials at a
higher rate than we expect;
the number of clinical trial sites required for clinical trials of our product candidates may be larger than we expect;
our third‑party contractors may fail to comply with regulatory requirements or meet their contractual obligations to us in a timely manner, or at all;
we may have to suspend or terminate clinical trials of our product candidates for various reasons, including a finding that the participants are being
exposed to unacceptable health risks;
investigators, regulators, data safety monitoring boards or institutional review boards may require that we or our investigators suspend or terminate
clinical research, or we may decide to do so ourselves;
investigators may deviate from the trial protocol, fail to conduct the trial in accordance with regulatory requirements or misreport study data;
the cost of clinical trials of our product candidates may be greater than we expect or we may have insufficient resources to pursue or complete certain
aspects of our clinical trial programs or to do so within the timeframe we planned;
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the supply or quality of raw materials or manufactured product candidates (whether provided by us or third parties) or other materials necessary to
conduct clinical trials of our product candidates may be insufficient, inadequate or not available at an acceptable cost, or in a timely manner, or we may
experience interruptions in supply;
regulators may revise the requirements for approving our product candidates, or such requirements may not be as we expect;
the FDA or comparable foreign regulatory authorities may disagree with our clinical trial design or our interpretation of data from preclinical studies
and clinical trials, or may change the requirements for approval even after it has reviewed and commented on the design of our clinical trials; and
regarding trials managed by our existing or any future collaborators, our collaborators may face any of the above issues, and may conduct clinical trials
in ways they view as advantageous to them but potentially suboptimal for us.
If we are required to conduct additional clinical trials or other testing of our product candidates beyond those that we currently contemplate, if we are
unable to successfully complete clinical trials of our product candidates or other testing, if the results of these trials or tests are not positive or are only
modestly positive or if there are safety concerns, or if we are forced to delay or abandon certain clinical trials or other testing in order to conserve capital
resources, we may:
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be delayed in obtaining marketing approval for our product candidates, if at all;
lose the support of collaborators, requiring us to bear more of the burden of research and development;
not obtain marketing approval at all;
obtain marketing approval in some countries and not in others;
obtain approval for indications or patient populations that are not as broad as intended or desired;
obtain approval with labeling that includes significant use or distribution restrictions or safety warnings;
be subject to additional post‑marketing testing requirements; or
have a product removed from the market after obtaining marketing approval.
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 a Data Safety Monitoring Board for such trial or by the FDA or comparable foreign regulatory authorities. Such authorities may impose such a
suspension or termination 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 comparable foreign 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. In addition, changes in regulatory requirements and policies may occur,
and we may need to amend clinical trial protocols to comply with these changes. Amendments may require us to resubmit our clinical trial protocols to
IRBs for reexamination, which may impact the costs, timing or successful completion of a clinical trial.
Our product development costs will increase if we experience delays in clinical testing or in obtaining marketing approvals. We do not know whether any
of our preclinical studies or clinical trials will begin as planned, will need to be restructured or will be completed on schedule, or at all. Significant
preclinical or clinical trial delays also could shorten any periods during which we may have the exclusive right to commercialize our product candidates or
allow our competitors to bring products to market before we do, potentially impairing our ability to successfully commercialize our product candidates and
harming our business and results of operations.
If we experience delays or difficulties in the enrollment of patients in clinical trials, our receipt of necessary regulatory approvals could be delayed or
prevented.
We may not be able to initiate or continue clinical trials for our product candidates if we are unable to locate and enroll a sufficient number of eligible
patients to participate in these trials as required by the FDA or similar regulatory authorities outside the United States. In addition, from time to time our
competitors have ongoing clinical trials for product candidates that treat the same indications as our product candidates, and patients who would otherwise
be eligible for our clinical trials may instead enroll in clinical trials of our competitors’ product candidates.
We are initially developing our lead product candidate, SEL‑212, for the treatment of chronic refractory gout, which affects approximately 160,000 patients
in the United States. Accordingly, there is a limited number of patients who could enroll in our clinical studies.
In addition to the size of the patient population, patient enrollment is also affected by other factors including:
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the severity of the disease under investigation;
the patient eligibility criteria for the study in question;
the perceived risks and benefits of the product candidate under study;
the availability of other treatments for the disease under investigation;
the existence of competing clinical trials;
our efforts to facilitate timely enrollment in clinical trials;
investigators engagement with, or enthusiasm about, the trial;
our payments for participating in clinical trials;
the patient referral practices of physicians;
the design of the trial;
the ability to monitor patients adequately during and after treatment; and
the proximity and availability of clinical trial sites for prospective patients.
In addition, our clinical trials will compete with other clinical trials for product candidates that are in the same therapeutic areas as our product candidates,
and this competition will reduce the number and types of patients available to us, because some patients who might have opted to enroll in our trials may
instead opt to enroll in a trial being conducted by one of our competitors. Since the number of qualified clinical investigators is limited, we expect to
conduct some of our clinical trials at the same clinical trial sites that some of our competitors use, which will reduce the number of patients who are
available for our clinical trials at such clinical trial site. Our inability to enroll a sufficient number of patients for our clinical trials would result in
significant delays and could require us to abandon one or more clinical trials altogether. Enrollment delays in our clinical trials may result in increased
development costs for our product candidates, which could cause the value of our common stock to decline and limit our ability to obtain additional
financing.
We may conduct clinical trials for product candidates at sites outside the United States, and the FDA may not accept data from trials conducted in such
locations or the complexity of regulatory burdens may otherwise adversely impact us.
Opening trial sites outside the United States may involve additional regulatory, administrative and financial burdens, including compliance with foreign and
local requirements relating to regulatory submission and clinical trial practices. Although the FDA may accept data from clinical trials conducted outside
the United States, acceptance of these data is subject to certain conditions imposed by the FDA. For example, the clinical trial must be well designed and
conducted and performed by qualified investigators in accordance with good clinical practices, or GCPs, and the FDA must be able to validate the data
from the trial through an onsite inspection, if necessary. Generally, the patient population for any clinical trials conducted outside the United States must be
representative of the population for which we intend to seek approval in the United States. In addition, while these clinical trials are subject to the
applicable local laws, FDA acceptance of the data will be dependent upon its determination that the trials also complied with all applicable U.S. laws and
regulations. Nonetheless, there can be no assurance that the FDA will accept data from trials conducted outside the United States. If the FDA does not
accept the data from any trial that we conduct outside the United States, it would likely result in the need for additional clinical trials, which would be
costly and time-consuming and delay or permanently halt our development of any applicable product candidates.
In addition, the conduct of clinical trials outside the United States could have a significant impact on us. Risks inherent in conducting international clinical
trials include:
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foreign regulatory requirements that could burden or limit our ability to conduct our clinical trials;
increased costs and heightened supply constraints associated with the acquisition of standard of care drugs and/or combination or comparator agents
for which we may bear responsibility in certain jurisdictions;
administrative burdens of conducting clinical trials under multiple foreign regulatory schema;
foreign exchange fluctuations;
- more burdensome manufacturing, customs, shipment and storage requirements;
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cultural differences in medical practice and clinical research;
lack of consistency in standard of care from country to country;
diminished protection of intellectual property in some countries; and
changes in country or regional regulatory requirements.
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We may not be able to obtain orphan drug designation for our product candidates, and even if we do, we may be unable to maintain the benefits
associated with orphan drug designation, including the potential for market exclusivity.
Regulatory authorities in some jurisdictions, including the United States and Europe, may designate drugs for relatively small patient populations as orphan
drugs. We expect to seek orphan drug designation for several of our product candidates. Under the Orphan Drug Act of 1983, the FDA may designate a
product as an orphan product if it is intended to treat a rare disease or condition, which is generally defined as a patient population of fewer than 200,000
individuals in the United States, or a patient population of greater than 200,000 individuals in the United States, but for which there is no reasonable
expectation that the cost of developing the drug or biologic will be recovered from sales in the United States.
In the United States, orphan designation entitles a party to financial incentives such as opportunities for grant funding towards clinical trial costs, tax
advantages and user‑fee waivers. In addition, if a product candidate that has orphan designation subsequently receives the first FDA approval for the
disease for which it has such designation, the product is entitled to orphan drug exclusivity, which means that the FDA may not approve any other
applications, including a full BLA or full new drug application, or NDA, to market the same biologic or drug for the same indication for seven years,
except in limited circumstances, such as a showing of clinical superiority to the product with orphan drug exclusivity or where the manufacturer is unable
to assure sufficient product quantity.
The applicable exclusivity period is ten years in the European Union, but such exclusivity period can be reduced to six years if a product no longer meets
the criteria for orphan designation or if the product is sufficiently profitable so that market exclusivity is no longer justified.
Even if we obtain orphan drug exclusivity for a product, that exclusivity may not effectively protect the product from competition because different drugs
can be approved for the same condition. Even after an orphan drug is approved, the FDA can subsequently approve the same drug for the same condition if
the FDA concludes that the later drug is clinically superior if it is shown to be safer, more effective or makes a major contribution to patient care. Orphan
drug designation neither shortens the development time or regulatory review time of a drug or biologic nor gives the drug or biologic any advantage in the
regulatory review or approval process.
Interim, top-line and preliminary data from our clinical trials that we announce or publish from time to time may change as more patient data become
available and are subject to audit and verification procedures that could result in material changes in the final data.
From time to time, we may publish interim, top-line or preliminary data from our clinical studies, which is based on a preliminary analysis of then-
available data, and the results and related findings and conclusions are subject to change following a full analyses of all data related to the particular trial.
We also make assumptions, estimations, calculations and conclusions as part of our analyses of data, and we may not have received or had the opportunity
to fully and carefully evaluate all data. As a result, the top-line results that we report may differ from future results of the same studies, or different
conclusions or considerations may qualify such results, once additional data have been received and fully evaluated. Preliminary or “top-line” data also
remain subject to audit and verification procedures that may result in the final data being materially different from the preliminary data we previously
published. As a result, preliminary and top-line data should be viewed with caution until the final data are available. We may also disclose interim data
from our clinical trials. Interim data from clinical trials that we may complete are subject to the risk that one or more of the clinical outcomes may
materially change as patient enrollment continues and more patient data become available. Adverse differences between preliminary or interim data and
final data could significantly harm our business prospects.
Further, others, including regulatory agencies, may not accept or agree with our assumptions, estimates, calculations, conclusions or analyses or may
interpret or weigh the importance of data differently, which could impact the value of the particular program, the approvability or commercialization of the
particular product candidate or product and our company in general. In addition, the information we choose to publicly disclose regarding a particular study
or clinical trial is based on what is typically extensive information, and you or others may not agree with what we determine is the material or otherwise
appropriate information to include in our disclosure. Any information we determine not to disclose may ultimately be deemed significant by you or others
with respect to future decisions, conclusions, views, activities or otherwise regarding a particular product candidate or our business. If the interim, top-line,
or preliminary data that we report differ from final results, or if others, including regulatory authorities, disagree with the conclusions reached, our ability to
obtain approval for, and commercialize, product candidates may be harmed, which could seriously harm our business.
The regulatory approval processes of the FDA and comparable foreign authorities are lengthy, time consuming and inherently unpredictable, and if we
are ultimately unable to obtain regulatory approval for our product candidates, our business will be substantially harmed.
The time required to obtain approval by the FDA and comparable foreign authorities is unpredictable but typically takes many years following the
commencement of clinical trials and depends upon numerous factors, including the substantial discretion of
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the regulatory authorities. In addition, approval policies, regulations, or the type and amount of clinical data necessary to gain approval may change during
the course of a product candidate’s clinical development and may vary among jurisdictions. We have not obtained regulatory approval for any product
candidate and it is possible that SEL-212 or any other product candidates we may seek to develop in the future will ever obtain regulatory approval. Neither
we nor any future collaborator is permitted to market any of our product candidates in the United States until we receive regulatory approval of a Biologics
License Application, or BLA, from the FDA.
Prior to obtaining approval to commercialize a product candidate in the United States or abroad, we or our collaborators must demonstrate with substantial
evidence from well-controlled clinical trials, and to the satisfaction of the FDA or foreign regulatory agencies, that such product candidates are safe and
effective, or in the case of biologics, safe, pure, and potent, for their intended uses. Results from nonclinical studies and clinical trials can be interpreted in
different ways. Even if we believe the nonclinical or clinical data for our product candidates are promising, such data may not be sufficient to support
approval by the FDA and other regulatory authorities. The FDA may also require us to conduct additional preclinical studies or clinical trials for our
product candidates either prior to or post-approval, or it may object to elements of our clinical development program.
The FDA or any foreign regulatory bodies can delay, limit or deny approval of our drug or device product candidates or require us to conduct additional
nonclinical or clinical testing or abandon a program for, including the following:
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the FDA or comparable foreign regulatory authorities may disagree with the design or implementation of our clinical trials;
we may be unable to demonstrate to the satisfaction of the FDA or comparable foreign regulatory authorities that a product candidate is safe and
effective for its proposed indication;
the results of clinical trials may not meet the level of statistical significance required by the FDA or comparable foreign regulatory authorities for
approval;
serious and unexpected drug-related side effects experienced by participants in our clinical trials or by individuals using drugs similar to our
product candidates;
we may be unable to demonstrate that a product candidate’s clinical and other benefits outweigh its safety risks;
the FDA or comparable foreign regulatory authorities may disagree with our interpretation of data from preclinical studies or clinical trials;
the data collected from clinical trials of our product candidates may not be acceptable or sufficient to support the submission of a BLA or other
submission or to obtain regulatory approval in the United States or elsewhere, and we may be required to conduct additional clinical studies;
the FDA’s or the applicable foreign regulatory agency may disagree regarding the formulation, labeling and/or the specifications of our product
candidates;
the FDA or comparable foreign regulatory authorities may fail to approve the manufacturing processes or facilities of third-party manufacturers
with which we contract for clinical and commercial supplies; and
the approval policies or regulations of the FDA or comparable foreign regulatory authorities may significantly change in a manner rendering our
clinical data insufficient for approval.
Of the large number of drugs in development, only a small percentage successfully complete the FDA or foreign regulatory approval processes and are
commercialized. The lengthy approval process as well as the unpredictability of future clinical trial results may result in our failing to obtain regulatory
approval to market our product candidates, which would significantly harm our business, results of operations and prospects.
In addition, even if we were to obtain approval, regulatory authorities may approve any of our product candidates for fewer or more limited indications than
we request, may not approve the price we intend to charge for our products, may grant approval contingent on the performance of costly post-marketing
clinical trials, including Phase 4 clinical trials, and/or the implementation of a Risk Evaluation and Mitigation Strategy, or REMS, which may be required
to assure safe use of the drug after approval. The FDA or the applicable foreign regulatory agency also may approve a product candidate for a more limited
indication or patient population than we originally requested, 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.
Any breakthrough therapy designation that we may receive from the FDA for our product candidates may not lead to a faster development or
regulatory review or approval process, and it does not increase the likelihood that our product candidates will receive marketing approval.
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We may in the future seek breakthrough therapy designation for some of our product candidates. A breakthrough therapy is defined as a drug that is
intended, alone or in combination with one or more other drugs, to treat a serious or life‑threatening disease or condition, and preliminary clinical evidence
indicates that the drug may demonstrate substantial improvement over existing therapies on one or more clinically significant endpoints. For drugs that
have been designated as breakthrough therapies, interaction and communication between the FDA and the sponsor of the trial can help to identify the most
efficient path for clinical development while minimizing the number of patients placed in ineffective control regimens. Drugs designated as breakthrough
therapies by the FDA are also eligible for accelerated approval.
Designation as a breakthrough therapy is within the discretion of the FDA. Accordingly, even if we believe one of our product candidates meets the criteria
for designation as a breakthrough therapy, the FDA may disagree and instead determine not to make such designation. The availability of breakthrough
therapy designation was established with the passage of the Food and Drug Administration Safety and Innovation Act of 2012. We cannot be sure that any
evaluation we may make of our product candidates as qualifying for breakthrough therapy designation will meet the FDA’s expectations. In any event, the
receipt of a breakthrough therapy designation for a product candidate may not result in a faster development process, review or approval compared to drugs
considered for approval under conventional FDA procedures and does not assure ultimate approval by the FDA. In addition, even if one or more of our
product candidates qualify as breakthrough therapies, the FDA may later decide that such product candidates no longer meet the conditions for qualification
or decide that the time period for FDA review or approval will not be shortened.
Negative public opinion and increased regulatory scrutiny of gene therapy and genetic research may damage public perception of our product
candidates or compromise our ability to conduct our business or obtain regulatory approvals for our product candidates.
Gene therapy remains a novel technology. Public perception may be influenced by claims that gene therapy is unsafe, and gene therapy may not gain the
acceptance of the public or the medical community. In particular, our success will depend upon physicians specializing in the treatment of those diseases
that our product candidates target and prescribing treatments that involve the use of our product candidates in lieu of, or in addition to, existing treatments
they are already familiar with and for which greater clinical data may be available. More restrictive government regulations or negative public opinion
would have a negative effect on our business or financial condition and may delay or impair the development and commercialization of our product
candidates or demand for any products we may develop. Our product candidates, including our products that utilize viral delivery systems, could produce
adverse events. Adverse events in our clinical trials or following approval of any of our product candidates, even if not ultimately attributable to our
product candidates, could result in increased governmental regulation, unfavorable public perception, potential regulatory delays in the testing or approval
of our product candidates, stricter labeling requirements for those product candidates that are approved and a decrease in demand for any such product
candidates.
Our product candidates may cause undesirable side effects or have other properties that could delay or prevent their regulatory approval, limit the
commercial profile of an approved label, or result in significant negative consequences following marketing approval, if any.
Undesirable side effects caused by our product candidates could cause us or regulatory authorities to interrupt, delay or halt clinical trials and could result
in a more restrictive label or the delay or denial of regulatory approval by the FDA or other comparable foreign authorities. Further, therapies such as those
we are developing involve unique side effects that could be exacerbated compared to side effects from other types of therapies with singular components.
Results of our clinical trials could reveal a high and unacceptable severity and prevalence of side effects. In such an event, our trials could be suspended or
terminated, and the FDA or comparable foreign regulatory authorities could order us to cease further development of or deny approval of our product
candidates for any or all targeted indications. For example, a patient in the Phase 1 trial of SEL-403 experienced a Grade 5 SAE (patient death) related to
pneumonitis, which was deemed by the trial investigator to be probably related to ImmTOR and possibly related to the patient’s pleural mesothelioma
condition, and in November 2018, the FDA placed the IND for SEL-403 on full clinical hold due to adverse events observed in the Phase 1 trial. Selecta
has terminated the license of LMB-100 from NCI, effective April 9, 2019 and is no longer pursuing this product candidate.
Further, the SEL-212 multi-year clinical development program requiring multiple clinical trials resulted in the use of different formulations of ImmTOR.
While we do not believe that differences in formulation will affect the safety or the efficacy of SEL-212, we cannot guarantee that any such formulation
changes will not negatively impact the results of any clinical trials related to SEL-212, or result in a significant difference in the safety and efficacy of SEL-
212.
The drug‑related side effects could also affect patient enrollment in our clinical trials or the ability of any enrolled patients to complete such trials or result
in potential product liability claims. Any of these occurrences may harm our business, financial condition and prospects significantly.
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Additionally, if one or more of our product candidates receives marketing approval, and we or others later identify undesirable side effects caused by such
products, a number of potentially significant negative consequences could result, including:
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regulatory authorities may withdraw approvals of such product;
regulatory authorities may require the addition of labeling statements, such as a “black box” warning or a contraindication;
regulatory authorities may impose additional restrictions on the marketing of, or the manufacturing processes for, the particular product;
we may be required to create a medication guide outlining the risks of such side effects for distribution to patients;
we could be sued and held liable for harm caused to patients, or become subject to fines, injunctions or the imposition of civil or criminal penalties;
our reputation may suffer; and
we could be required to develop a risk evaluation and mitigation strategy (REMS) plan to prevent, monitor and/or manage a specific serious risk by
informing, educating and/or reinforcing actions to reduce the frequency and/or severity of the event.
Any of these events could prevent us from achieving or maintaining market acceptance of a particular product candidate, if approved, and could
significantly harm our business, results of operations and prospects.
In addition, if our product candidates are associated with undesirable side effects in certain patient populations, such as pediatric patients or the elderly, we
may need to abandon their development or limit development to more narrow uses or subpopulations in which the undesirable side effects or other
characteristics are less prevalent, less severe or more acceptable from a risk‑benefit perspective, any of which would harm our business.
RISKS RELATED TO OUR DEPENDENCE ON THIRD PARTIES AND MANUFACTURING
We rely on 3SBio in China as our primary supplier of pegadricase and on other third parties for the manufacture of our product candidates for
preclinical and clinical testing, and expect to continue to do so for the foreseeable future. Our reliance on third parties increases the risk that we will
not have sufficient quantities of our product candidates or that such quantities may not be available at an acceptable cost, or in compliance with
regulatory requirements, which could delay, prevent or impair our development or commercialization efforts.
We obtain the biologic pegadricase, a component of SEL‑212, primarily from 3SBio in China. Under our license agreement with 3SBio, we have limited
rights to manufacture pegadricase and, while we have entered into a contract with a back-up supplier located outside of China, we expect to continue to rely
on 3SBio as the primary supplier of pegadricase for the foreseeable future.
Any disruption in production or inability of 3SBio in China to produce adequate quantities of pegadricase to meet our needs, whether as a result of a natural
disaster, public health emergency, such as the novel coronavirus, failure to comply with regulatory requirements or other causes, could impair our ability to
operate our business on a day‑to‑day basis and to continue our research and development of our future product candidates. Furthermore, since 3SBio is
located in China, we are exposed to the possibility of product supply disruption and increased costs in the event of changes in the policies, laws, rules and
regulations of the United States or Chinese governments, political unrest or unstable economic conditions in China. For example, trade tensions between
the United States and China have been escalating in recent years. Most notably, several rounds of U.S. tariffs have been placed on Chinese goods being
exported to the United States. Each of these U.S. tariff impositions against Chinese exports were followed by a round of retaliatory Chinese tariffs on U.S.
exports to China. Pegadricase is subject to, and any other components we purchase from China may be subject to these tariffs, which could increase our
manufacturing costs and could make our products, if successfully developed and approved, less competitive than those of our competitors whose inputs are
not subject to these tariffs.
Any of these matters could materially and adversely affect our business and results of operations. Any issues related to the manufacturing lots or similar
action regarding pegadricase used in preclinical studies or clinical trials could delay the studies or trials or detract from the integrity of the trial data and its
potential use in future regulatory filings. In addition, manufacturing interruptions or failure to comply or maintain compliance with regulatory requirements
by 3SBio could significantly delay our clinical development of potential products and reduce third‑party or clinical researcher interest and support of our
proposed trials. These interruptions or failures could also impede commercialization of our future product candidates and impair our competitive position.
Further, we may be exposed to fluctuations in the value of the local currency in China. Future appreciation of the local currency could increase our costs. In
addition, labor costs could continue to rise as wage rates increase due to increased demand for skilled laborers and the availability of skilled labor declines
in China.
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In addition to 3SBio, we rely, and expect to continue to rely, on other third parties for the manufacture of our product candidates for preclinical and clinical
testing, as well as for commercial manufacture if any of our product candidates receive marketing approval. Our reliance on such third parties increases the
risk that we will not have sufficient quantities of our product candidates on a timely basis or at all, or that such quantities will be available at an acceptable
cost or quality, which could delay, prevent or impair our development or commercialization efforts. For example, we rely on third parties for the
manufacture of our gene therapy preclinical materials. Gene therapy is a relatively new area for commercial biopharmaceutical development and there are a
limited number of CMOs with adequate facilities and expertise in this area. As a result, we may be unable to successfully manufacture our gene therapy
preclinical materials through a third party or scale up the manufacture of our gene therapy product candidates for clinical testing or commercialization, if at
all.
We may be unable to establish any agreements with third‑party manufacturers on acceptable terms or at all. Even if we are able to establish agreements
with third‑party manufacturers, reliance on third‑party manufacturers entails additional risks, including the:
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inability, failure or unwillingness of third‑party manufacturers to comply with regulatory requirements, maintain quality assurance, meet our needs,
specifications or schedules or continue to supply products to us;
reduced control we have over product development, including with respect to our lead product candidate, due to our reliance on such third‑party
manufacturers,
breach of manufacturing agreements by the third‑party manufacturers;
- misappropriation or disclosure of our proprietary information, including our trade secrets and know‑how;
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relationships that the third-party manufacturer may have with others, some of which may be our competitors, and, if it does not successfully carry out
its contractual duties, does not meet expectations, experiences work stoppages, or needs to be replaced, we may need to enter into alternative
arrangements, which may not be available, desirable or cost‑effective; and
termination or nonrenewal of agreements by third‑party manufacturers at times that are costly or inconvenient for us.
The facilities used by our contract manufacturers to manufacture our product candidates must be approved by the FDA pursuant to inspections that will be
conducted after we submit our marketing application to the FDA. We do not control the manufacturing process of, and are completely dependent on, our
contract manufacturing partners for compliance with the regulatory requirements, known as current good manufacturing practices, or cGMPs, for
manufacture of our product candidates. If our contract manufacturers cannot successfully manufacture material that conforms to our specifications and the
strict regulatory requirements of the FDA or others, they will not be able to secure and/or maintain regulatory approval for their manufacturing facilities. In
addition, we have no control over the ability of our contract manufacturers or suppliers to maintain adequate quality control, quality assurance and qualified
personnel. If the FDA or a comparable foreign regulatory authority does not approve these facilities for the manufacture of our product candidates or if it
withdraws any such approval in the future, we may need to find alternative manufacturing facilities, which would significantly impact our ability to
develop, obtain regulatory approval for or market our product candidates, if approved. Our failure, or the failure of our third‑party manufacturers, to
comply with applicable regulations could result in sanctions being imposed on us, including clinical holds, fines, injunctions, civil penalties, delays,
suspension or withdrawal of approvals, license revocations, seizures or recalls of product candidates or products, operating restrictions and criminal
prosecutions, any of which could significantly and adversely affect supplies of our products. In addition, there are a limited number of manufacturers that
operate under cGMP regulations that might be capable of manufacturing our products. Therefore, our product candidates and any future products that we
may develop may compete with other products for access to manufacturing facilities. Any failure to gain access to these limited manufacturing facilities
could severely impact the clinical development, marketing approval and commercialization of our product candidates.
Any performance failure on the part of our existing or future manufacturers could delay clinical development or marketing approval. We do not currently
have arrangements in place for redundant supply or a second source for required raw materials used in the manufacture of our product candidates or for the
manufacture of finished product. Moreover, we often rely on one CMO to produce multiple product components. For instance, one of our CMOs produces
several polymers used in our ImmTOR platform. If our current CMOs cannot perform as agreed, we may be required to replace such manufacturers and we
may be unable to replace them on a timely basis or at all. Our current and expected future dependence upon others for the manufacture of our product
candidates or products could delay, prevent or impair our development and commercialization efforts.
The novel coronavirus outbreak could adversely impact our business, financial condition and results of operations.
In December 2019, a strain of novel coronavirus surfaced in Wuhan, China. In January 2020, the World Health Organization declared the novel coronavirus
outbreak a “Public Health Emergency of International Concern” and the U.S. Department of State instructed travelers to avoid all nonessential travel to
China. The coronavirus has impacted the global economy and may
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impact our operations, including the potential interruption of our clinical trial activities and our supply chain. As a result of the outbreak, certain of our
suppliers and CMOs in China may be affected, which could disrupt their activities. We could therefore face difficulty sourcing key components necessary
to produce supply of SEL-212, which may negatively affect our clinical development activities. While we have a back-up supplier for SEL-037 in the
United States, they may not have capacity in a timely manner for our projects and they may cost more, which could affect our results of operations and
financial position. If the coronavirus further impacts US business operations, including our CMOs and suppliers, we could face additional disruption to our
supply chain that could affect the supply of drug product for the clinical trials. In addition, the coronavirus outbreak could delay enrollment in our clinical
trials due to prioritization of hospital resources toward the outbreak, and some patients may not be able to comply with clinical trial protocols if quarantines
impede patient movement or interrupt healthcare services.
At this point in time, there is significant uncertainty relating to the potential effect of the novel coronavirus on our business. Infections may become more
widespread, including in countries where we are conducting clinical trials, and manufacturing closures and travel restrictions may remain or worsen, all of
which would have a negative impact on our business, financial condition and results of operations.
Our existing collaborations are important to our business, and future licenses may also be important to us. If we are unable to maintain any of these
collaborations, or if these arrangements are not successful, or we are unable to enter into future licenses, our business could be adversely affected.
We have entered into collaborations with other parties, including pharmaceutical companies and universities, to develop products based on our ImmTOR
platform, and such collaborations and licensing arrangements currently represent a significant portion of our product pipeline and are expected to represent
a larger portion of our pipeline in the future. Certain of our collaborations have provided us with important funding for some of our development programs
and we expect to receive additional funding under collaborations in the future although not all of our collaborations may result in funding to the Company,
and certain collaborations, licenses and agreements may result in increased expenditures by the Company. Our existing collaborations, and any future
collaborations we enter into, may pose a number of risks, including the following:
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collaborators have significant discretion in determining the efforts and resources that they will apply to these collaborations;
collaborators may not perform their obligations as expected;
collaborators may not pursue development and commercialization of any product candidates that achieve regulatory approval or may elect not to
continue or renew development or commercialization programs based on preclinical or clinical trial results, changes in the collaborators’ strategic
focus or available funding, or external factors, such as an acquisition, that divert resources or create competing priorities;
collaborators may delay clinical trials, provide insufficient funding for a clinical trial program, stop a clinical trial or abandon a product candidate,
repeat or conduct new clinical trials or require a new formulation of a product candidate for clinical testing;
collaborators could independently develop, or develop with third parties, products that compete directly or indirectly with our product candidates if the
collaborators believe that competitive products are more likely to be successfully developed or can be commercialized under terms that are more
economically attractive than ours, which may cause collaborators to cease to devote resources to the commercialization of our product candidates;
a collaborator with marketing and distribution rights to one or more of our product candidates that achieve regulatory approval may not commit
sufficient resources to the marketing and distribution of such product or products;
disagreements with collaborators, including disagreements over proprietary rights, contract interpretation or the preferred course of development,
might cause delays or termination of the research, development or commercialization of product candidates, might lead to additional responsibilities
for us with respect to product candidates, or might result in litigation or arbitration, any of which would be time‑consuming and expensive;
collaborators may not properly maintain or defend our intellectual property rights or may use our proprietary information in such a way as to invite
litigation that could jeopardize or invalidate our intellectual property or proprietary information or expose us to potential litigation;
collaborators may infringe the intellectual property rights of third parties, which may expose us to litigation and potential liability;
collaborations may be terminated for the convenience of the collaborator or for our failure to comply with our obligations under existing or future
collaborations and, if terminated, we would potentially lose the right to pursue further development or commercialization of the applicable product
candidates;
collaborators may learn about our technology and use this knowledge to compete with us in the future;
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there may be conflicts between different collaborators that could negatively affect those collaborations and potentially others; and
the number and type of our collaborations could adversely affect our attractiveness to future collaborators or acquirers.
If our collaborations do not result in the successful development and commercialization of products or if one of our collaborators terminates its agreement
with us, we may not receive any future research and development funding or milestone or royalty payments under such collaborations. If we do not receive
the funding we expect under these agreements, our continued development of our ImmTOR platform and product candidates could be delayed and we may
need additional resources to develop additional product candidates. All of the risks relating to product development, regulatory approval and
commercialization described in this Annual Report on Form 10-K also apply to the activities of our therapeutic program collaborators and there can be no
assurance that our collaborations will produce positive results or successful products on a timely basis or at all.
Additionally, subject to its contractual obligations to us, if one of our collaborators is involved in a business combination or otherwise changes its business
priorities, the collaborator might deemphasize or terminate the development or commercialization of any product candidate licensed to it by us. If one of
our collaborators terminates its agreement with us, we may find it more difficult to attract new collaborators and the perception of our business in the
business and financial communities, and our stock price, could be adversely affected. In addition, we have a limited number of collaborations and if our
relationship with any one or more of such collaborators were to cease, our business would be harmed as a result. For example, MIT may terminate the MIT
License if we fail to meet a diligence obligation, including the initiation of a Phase 3 clinical trial by a specified date in the fourth quarter of 2019. In
December 2019, we entered into the MIT Amendment. Pursuant to the MIT Amendment, the provision of the MIT License under which we were obligated
to initiate a Phase 3 clinical trial for a licensed product by a specified date in the fourth quarter of 2019 is tolled until the earlier of (i) a specified date in the
second quarter of 2020 or (ii) the effective date of a written amendment to the MIT Agreement. The parties agreed to negotiate in good faith to enter into a
future amendment to the MIT License after we provide MIT with an amended diligence plan. However, if we are unable to reach an agreement with MIT
regarding an acceptable amendment of the MIT License and if we are unable to cure the breach, there could be a material adverse effect on our business.
See “Business - Licenses and Collaborations - Massachusetts Institute of Technology.”
We are actively exploring licenses and other strategic collaborations with additional pharmaceutical and biotechnology companies for development and
potential commercialization of therapeutic products. However, we face significant competition in seeking appropriate collaborators. If we are unable to
reach agreements with suitable collaborators on a timely basis, on acceptable terms, or at all, we may not be able to access specific antigens that would be
suitable to development with our technology, have to curtail the development of a product candidate, reduce or delay its development program or one or
more of our other development programs, delay its potential commercialization or reduce the scope of any sales or marketing activities, or increase our
expenditures and undertake development or commercialization activities at our own expense. If we elect to fund and undertake development or
commercialization activities on our own, we may need to obtain additional expertise and additional capital, which may not be available to us on acceptable
terms or at all. If we fail to enter into collaborations and do not have sufficient funds or expertise to undertake the necessary development and
commercialization activities, we may not be able to further develop our product candidates or bring them to market or continue to develop our programs,
and our business may be materially and adversely affected.
We rely, and expect to continue to rely, on third parties to conduct our clinical trials, and those third parties may not perform satisfactorily, including by
failing to meet deadlines for the completion of such trials.
We expect to continue to rely on third parties, such as CROs, clinical data management organizations, medical institutions and clinical investigators, to
conduct and manage our clinical trials, including our Phase 2 and Phase 3 clinical trials of SEL‑212 and for our other product candidates. We also expect to
rely on other third parties to store and distribute drug supplies for our clinical trials.
Our reliance on these third parties for research and development activities will reduce our control over these activities but does not relieve us of our
responsibilities. For example, we remain responsible for ensuring that each of our clinical trials is conducted in accordance with the general investigational
plan and protocols for the trial. Moreover, the FDA requires us to comply with GCP regulations, for conducting, recording and reporting the results of
clinical trials to assure that data and reported results are credible and accurate and that the rights, safety and welfare of trial participants are protected. Other
countries’ regulatory agencies also have requirements for clinical trials. Regulatory authorities enforce these GCPs through periodic inspections of trial
sponsors, principal investigators and trial sites. If we or any of our CROs or third-party contractors fail to comply with applicable GCPs, the data generated
in our clinical trials may be deemed unreliable and the FDA or comparable foreign regulatory authorities may require us to perform additional clinical trials
before approving our marketing applications. We cannot assure you that upon inspection by a given regulatory authority, such regulatory authority will
determine that any of our clinical trials complies with GCP regulations. In addition, our clinical trials must be conducted with
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product produced under cGMP regulations. Our failure to comply with these regulations may require us to repeat clinical trials, which would delay the
regulatory approval process. We also are required to register ongoing clinical trials and post the results of completed clinical trials on a
government‑sponsored database, ClinicalTrials.gov, within specified timeframes. Failure to do so can result in fines, adverse publicity and civil and
criminal sanctions.
Furthermore, these third parties may also have relationships with other entities, some of which may be our competitors. If these third parties do not
successfully carry out their contractual duties, do not comply with confidentiality obligations, do not meet expected deadlines, experience work stoppages,
terminate their agreements with us or need to be replaced, or do not conduct our clinical trials in accordance with regulatory requirements or our stated
protocols, we may need to enter into new arrangements with alternative third parties, which could be difficult, costly or impossible, and our clinical trials
may be extended, delayed or terminated, or may need to be repeated. If any of the foregoing occur, we may not be able to obtain, or may be delayed in
obtaining, marketing approvals for our product candidates or in commercializing our product candidates.
We have no experience manufacturing our product candidates at commercial scale, and if we decide to establish our own manufacturing facility, we
cannot assure you that we can manufacture our product candidates in compliance with regulations at a cost or in quantities necessary to make them
commercially viable.
We have a pilot manufacturing facility at our Watertown, Massachusetts location where we conduct process development, scale‑up activities and the
manufacture of ImmTOR product candidates for preclinical use. We rely on our scaled equipment installed at our CMOs for the manufacture of the clinical
supply of all of our product candidates. If our facility, or our CMOs’ facilities, were damaged or destroyed, or otherwise subject to disruption, it would
require substantial lead‑time to replace our manufacturing capabilities. In such event, we would be forced to identify and rely entirely on alternative
third‑party contract manufacturers for an indefinite period of time. Any disruptions or delays at our facility or its failure to meet regulatory compliance
would impair our ability to develop and commercialize our product candidates, which would adversely affect our business and results of operations.
In addition, the FDA and other comparable foreign regulatory agencies must, pursuant to inspections that are conducted after submitting a BLA or relevant
foreign marketing submission, confirm that the manufacturing processes for the product candidate meet cGMP regulations. We do not currently have any of
our own manufacturing facilities that meet the FDA’s cGMP requirements for the production of any product candidates used in humans, and rely on our
CMOs for clinical production.
We may choose to establish a manufacturing facility for our product candidates for production at a commercial scale. However, we have no experience in
commercial‑scale manufacturing of our product candidates and this activity will require substantial additional funds and additional qualified employees.
We may not be able to develop commercial‑scale manufacturing facilities that are adequate to produce materials for additional later‑stage clinical trials or
commercial use.
The equipment and facilities employed in the manufacture of pharmaceuticals are subject to stringent qualification requirements by regulatory agencies,
including validation of such facilities, equipment, systems, processes and analytics. We may be subject to lengthy delays and expense in conducting
validation studies, if we can meet the requirements at all.
RISKS RELATED TO COMMERCIALIZATION OF OUR PRODUCT CANDIDATES AND OTHER LEGAL COMPLIANCE MATTERS
Even if any of our product candidates receives marketing approval, it may fail to achieve the degree of market acceptance by physicians, patients,
third‑party payors and others in the medical community necessary for commercial success.
If any of our product candidates receives marketing approval, it may nonetheless fail to gain sufficient market acceptance by physicians, patients,
third‑party payors and others in the medical community. If our product candidates do not achieve an adequate level of acceptance, we may not generate
significant product revenues and we may not become profitable. For example, even if the statistical results from our Phase 2 head-to-head (COMPARE)
trial vs. KRYSTEXXA favor SEL-212 and SEL-212 receives marketing approval, the drug may fail to gain market acceptance from physicians, patients,
third-party payors and others in the medical community who may continue to favor KRYSTEXXA. The degree of market acceptance of our product
candidates, if any, will depend on a number of factors, including:
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their efficacy, safety and other potential advantages compared to alternative treatments;
the clinical indications for which our product candidates are approved;
our ability to offer them for sale at competitive prices;
their convenience and ease of administration compared to alternative treatments;
the willingness of the target patient population to try new therapies and of physicians to prescribe these therapies;
the strength of marketing and distribution support;
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the availability of third‑party coverage and adequate reimbursement for our product candidates;
the prevalence and severity of their side effects and their overall safety profiles;
any restrictions on the use of our product candidates together with other medications;
interactions of our product candidates with other medicines patients are taking;
our ability to create awareness with patients and physicians about the harmful effects of uric acid deposits;
the timing of market introduction of any approved product candidates as well as competitive products and other therapies;
inability of certain types of patients, particularly with respect to certain rare diseases or conditions, to take our product candidates;
their ability to remain attractive in the event of changing treatment guidelines;
adverse publicity about the product or favorable publicity about competitive products; and
potential product liability claims.
We currently have no sales organization. If we are unable to establish effective sales, marketing and distribution capabilities, or enter into agreements
with third parties with such capabilities, we may not be successful in commercializing our product candidates if and when they are approved.
We do not have a sales or marketing infrastructure and have no experience in the sale, marketing or distribution of pharmaceutical products. To achieve
commercial success for any product candidate for which we obtain marketing approval, we will need to establish a sales and marketing organization or
make arrangements with third parties to perform sales and marketing functions and we may not be successful in doing so.
In the future, we expect to build a focused sales and marketing infrastructure to market or co‑promote our product candidates in the United States and
potentially elsewhere, if and when they are approved. There are risks involved with establishing our own sales, marketing and distribution capabilities. For
example, recruiting and training a sales force is expensive and time‑consuming and could delay any product launch. If the commercial launch of a product
candidate for which we recruit a sales force and establish marketing capabilities is delayed or does not occur for any reason, we would have prematurely or
unnecessarily incurred these commercialization expenses. This may be costly, and our investment would be lost if we cannot retain or reposition our sales
and marketing personnel.
Outside the United States, we may rely on third parties to sell, market and distribute our product candidates. We may not be successful in entering into
arrangements with such third parties or may be unable to do so on terms that are favorable to us. In addition, our product revenue and our profitability, if
any, may be lower if we rely on third parties for these functions than if we were to market, sell and distribute any products that we develop ourselves. We
likely will have little control over such third parties, and any of them may fail to devote the necessary resources and attention to sell and market our
products effectively. If we do not establish sales, marketing and distribution capabilities successfully, either on our own or in collaboration with third
parties, we will not be successful in commercializing our product candidates.
We face substantial competition, including from biosimilars, which may result in others discovering, developing or commercializing competing
products before or more successfully than we do.
The development and commercialization of new drug and biologic products and technologies is highly competitive and is characterized by rapid and
substantial technological development and product innovations. We are aware that pharmaceutical and biotechnology companies, including Horizon
Pharma plc, offer or are pursuing the development of pharmaceutical products or technologies that may address one or more indications that our product
candidates target, as well as smaller, early-stage companies, that offer or are pursuing the development of pharmaceutical products or technologies that may
address one or more indications that our product candidates target. We face competition with respect to our current product candidates, and will face
competition with respect to any product candidates that we may seek to develop or commercialize in the future, from major pharmaceutical companies,
specialty pharmaceutical companies and biotechnology companies worldwide.
Many of the companies against which we are competing or against which we may compete in the future have significantly greater financial resources,
established presence in the market and expertise in research and development, manufacturing, preclinical testing, conducting clinical trials, obtaining
regulatory approvals and reimbursement for product candidates and in marketing approved products than we do. Mergers and acquisitions in the
pharmaceutical and biotechnology industries may result in even more resources being concentrated among a smaller number of our competitors.
These third parties compete with us in recruiting and retaining qualified scientific, sales and marketing and management personnel, establishing clinical
trial sites and patient registration for clinical trials, as well as in acquiring technologies complementary to, or necessary for, our programs.
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Our commercial opportunity could be reduced or eliminated if our competitors develop and commercialize products that are more effective, have fewer or
less severe side effects, are more convenient or are less expensive than any products that we may develop. Our competitors also may obtain FDA or other
regulatory approval for their products more rapidly than we may obtain approval for ours, which could result in our competitors establishing a strong
market position before we are able to enter the market, especially for any competitor developing a competing immunomodulating therapeutic that will
likely share our same regulatory approval requirements. In addition, our ability to compete may be affected in many cases by insurers or other third‑party
payors seeking to encourage the use of generic or biosimilar products.
We expect the product candidates we develop will be regulated as biological products, or biologics, and therefore they may be subject to competition
sooner than anticipated.
The Biologics Price Competition and Innovation Act of 2009 (BPCIA) was enacted as part of the Affordable Care Act to establish an abbreviated pathway
for the approval of biosimilar and interchangeable biological products. The regulatory pathway establishes legal authority for the FDA to review and
approve biosimilar biologics, including the possible designation of a biosimilar as “interchangeable” based on its similarity to an approved biologic. Under
the BPCIA, an application for a biosimilar product cannot be approved by the FDA until 12 years after the reference product was approved under a BLA.
The law is complex and is still being interpreted and implemented by the FDA. As a result, its ultimate impact, implementation, and meaning are subject to
uncertainty. While it is uncertain when such processes intended to implement the BPCIA may be fully adopted by the FDA, any such processes could have
a material adverse effect on the future commercial prospects for our biological products.
We believe that any product candidate approved in the United States as a biological product under a BLA should qualify for the 12-year period of
exclusivity. However, there is a risk that this exclusivity could be shortened due to congressional action or otherwise, or that the FDA will not consider the
subject product candidates to be reference products for competing products, potentially creating the opportunity for generic competition sooner than
anticipated. Moreover, the extent to which a biosimilar, once approved, will be substituted for any one of the reference products in a way that is similar to
traditional generic substitution for non-biological products is not yet clear, and will depend on a number of marketplace and regulatory factors that are still
developing.
Even if we are able to commercialize any product candidates, the products may become subject to unfavorable pricing regulations or third‑party
coverage or reimbursement policies, any of which would have a material adverse effect on our business.
Significant uncertainty exists as to the coverage and reimbursement status of any product candidates for which we obtain regulatory approval, especially
novel products like our gene therapy product candidates, and may be particularly difficult because of the higher prices associated with gene therapy product
candidates. Our ability to commercialize any product candidates successfully will depend, in part, on the extent to which coverage and adequate
reimbursement for these products and related treatments will be available from government health administration authorities, private health insurers and
other organizations. Government authorities and third‑party payors, such as private health insurers and health maintenance organizations, decide which
medications they will pay for and establish reimbursement levels.
Obtaining and maintaining adequate reimbursement for our products may be difficult. We cannot be certain if and when we will obtain an adequate level of
reimbursement for our products by third‑party payors. Even if we do obtain adequate levels of reimbursement, third‑party payors, such as government or
private healthcare insurers, carefully review and increasingly question the coverage of, and challenge the prices charged for, products. Government
authorities and third‑party payors have attempted to control costs by limiting coverage and the amount of reimbursement for particular medications.
Increasingly, third‑party payors are requiring that pharmaceutical companies provide them with predetermined discounts from list prices and are
challenging the prices charged for products. We may also be required to conduct expensive pharmacoeconomic studies to justify coverage and
reimbursement or the level of reimbursement relative to other therapies. Some third-party payors may require pre-approval of coverage for new and
innovative therapies, such as our product candidates, before they will provide reimbursement. If coverage and reimbursement are not available or
reimbursement is available only to limited levels, we may not be able to successfully commercialize any product candidate for which we obtain marketing
approval.
There may be significant delays in obtaining reimbursement for newly approved products, and coverage may be more limited than the purposes for which
the product is approved by the FDA or similar regulatory authorities outside of the United States. Moreover, eligibility for reimbursement does not imply
that a product will be paid for in all cases or at a rate that covers our costs, including research, development, manufacture, sale and distribution. Interim
reimbursement levels for new products, if applicable, may also not be sufficient to cover our costs and may not be made permanent. Reimbursement rates
may vary according to the use of the product and the clinical setting in which it is used, may be based on reimbursement levels already set for lower cost
products and may be incorporated into existing payments for other services. Net prices for products may be reduced by mandatory discounts or rebates
required by government healthcare programs or private payors and by any future relaxation of laws that presently restrict imports of products from
countries where they may be sold at lower prices than in the
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United States. Our inability to promptly obtain coverage and adequate reimbursement rates from both government‑funded and private payors for any
approved products that we develop could have a material adverse effect on our operating results, our ability to raise capital needed to commercialize
products and our overall financial condition.
The regulations that govern marketing approvals, pricing, coverage and reimbursement for new products vary widely from country to country. Current and
future legislation may significantly change the approval requirements in ways that could involve additional costs and cause delays in obtaining approvals.
Some countries require approval of the sale price of a product before it can be marketed. In many countries, the pricing review period begins after
marketing or product licensing approval is granted. In some foreign markets, prescription pharmaceutical pricing remains subject to continuing
governmental control, including possible price reductions, even after initial approval is granted. As a result, we might obtain marketing approval for a
product in a particular country, but then be subject to price regulations that delay our commercial launch of the product, possibly for lengthy time periods,
and negatively impact the revenues we are able to generate from the sale of the product in that country. Adverse pricing limitations may hinder our ability
to recoup our investment in one or more product candidates, even if our product candidates obtain marketing approval. There can be no assurance that our
product candidates, if they are approved for sale in the United States or in other countries, will be considered medically necessary for a specific indication
or cost‑effective, or that coverage or an adequate level of reimbursement will be available.
Moreover, there has recently been heightened governmental scrutiny over the manner in which manufacturers set prices for their marketed products, which
has resulted in several Congressional inquiries and proposed bills designed to, among other things, bring more transparency to product pricing, review the
relationship between pricing and manufacturer patient programs, and reform government program reimbursement methodologies for drug products. There
can be no assurance that our product candidates, if approved for sale in the United States or in other countries, will not be subject to heightened
governmental scrutiny, unfavorable regulatory inquiry or action, or congressional inquiry.
Product liability lawsuits against us could cause us to incur substantial liabilities and limit commercialization of any products that we may develop.
We face an inherent risk of product liability exposure related to the testing of our product candidates in clinical trials and will face an even greater risk if we
commercially sell any products that we may develop. If we cannot successfully defend ourselves against claims that our product candidates or products
caused injuries, we will incur substantial liabilities. Regardless of merit or eventual outcome, liability claims may result in:
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regulatory investigations, product recalls or withdrawals, or labeling, marketing or promotional restrictions;
decreased demand for any product candidates or products that we may develop;
injury to our reputation and significant negative media attention;
loss of clinical trial participants or increased difficulty in enrolling future participants;
significant costs to defend the related litigation or to reach a settlement;
substantial payments to trial participants or patients;
loss of revenue;
reduced resources of our management to pursue our business strategy; and
the inability to commercialize any products that we may develop.
distraction of management’s attention from our primary business;
substantial monetary awards to patients or other claimants;
We maintain general liability, product liability and umbrella liability insurance. Our existing insurance coverage may not fully cover potential liabilities that
we may incur. We may need to increase our insurance coverage as we expand our clinical trials or if we commence commercialization of our product
candidates. Insurance coverage is increasingly expensive. We may not be able to maintain insurance coverage at a reasonable cost or in an amount adequate
to satisfy any liability that may arise. A successful product liability claim or series of claims brought against us could cause our share price to decline and,
if judgments exceed our insurance coverage, could adversely affect our results of operations and business, including preventing or limiting the
commercialization of any product candidates we develop.
Failure to obtain marketing approval in international jurisdictions would prevent our product candidates from being marketed abroad.
Although we do not have any current plans to market and sell our products in other jurisdictions outside of the United States, we may decide to do so in the
future and either we or our collaborators would need to obtain separate marketing approvals and comply with numerous and varying regulatory
requirements. The approval procedure varies among countries and can involve
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additional testing. The time required to obtain approval in foreign countries may differ substantially from that required to obtain FDA approval. Clinical
trials conducted in one country may not be accepted by regulatory authorities in other countries. The regulatory approval process outside the United States
generally includes all of the risks associated with obtaining FDA approval. In addition, in many countries outside the United States, it is required that the
product candidate be approved for reimbursement before the product candidate can be approved for sale in that country. We or our collaborators may not
obtain approvals for our product candidates from regulatory authorities outside the United States on a timely basis, if at all. Approval by the FDA does not
ensure approval by regulatory authorities in other countries or jurisdictions, and approval by one regulatory authority outside the United States does not
ensure approval by regulatory authorities in other countries or jurisdictions, or by the FDA. However, a failure or delay in obtaining regulatory approval in
one country may have a negative effect on the regulatory process in others. We may not be able to file for marketing approvals and may not receive
necessary approvals to commercialize our product candidates in any market.
Our relationships with healthcare providers, customers and third‑party payors will be subject to applicable anti‑kickback, fraud and abuse and other
healthcare laws and regulations, which could expose us to criminal sanctions, civil penalties, exclusion from government healthcare programs,
contractual damages, reputational harm and diminished profits and future earnings.
Arrangements with physicians, others who may be in a position to generate business for us, and customers may expose us to broadly applicable fraud and
abuse and other healthcare laws and regulations that constrain the business or financial arrangements and relationships through which we market, sell and
distribute any products for which we obtain marketing approval. Restrictions under applicable federal and state healthcare laws and regulations include the
following:
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the federal Anti‑Kickback Statute, which prohibits, among other things, persons and entities from knowingly and willfully soliciting, offering,
receiving or providing remuneration, directly or indirectly, in cash or in kind, to induce or reward, or in return for, either the referral of an individual
for, or the purchase, order or recommendation of, any good or service for which payment may be made under a federal healthcare program such as
Medicare and Medicaid. A person or entity does not need to have actual knowledge of the statute or specific intent to violate it to have committed a
violation;
the federal False Claims Act, which impose criminal and civil penalties against individuals or entities for knowingly presenting, or causing to be
presented, to the federal government claims for payment that are false or fraudulent. Private individuals (e.g., whistleblowers) can bring these actions
on behalf of the government; in addition, the government may assert that a claim including items or services resulting from a violation of the federal
Anti‑Kickback Statute constitutes a false or fraudulent claim for purposes of the False Claims Act;
the federal Health Insurance Portability and Accountability Act of 1996, or HIPAA, which imposes criminal and civil liability for, among other things,
executing or attempting to execute a scheme to defraud any healthcare benefit program or making false statements relating to healthcare matters. A
person or entity does not need to have actual knowledge of the statute or specific intent to violate it to have committed a violation;
HIPAA, as amended by the Health Information Technology for Economic and Clinical Health Act, or HITECH, and its implementing regulations,
which also imposes obligations, including mandatory contractual terms, on certain types of people and entities with respect to safeguarding the privacy,
security and transmission of individually identifiable health information;
the federal Physician Payments Sunshine Act, which requires applicable manufacturers of certain products for which payment is available under a
federal healthcare program to report annually to the government information related to certain payments or other “transfers of value” made to
physicians (defined to include doctors, dentists, optometrists, podiatrists and chiropractors), certain other health care professionals beginning in 2022,
and teaching hospitals, as well as ownership and investment interests held by the physicians and their immediate family members;
analogous state laws and regulations, such as state anti‑kickback and false claims laws, which may apply to sales or marketing arrangements and
claims involving healthcare items or services reimbursed by third‑party payors, including private insurers; and requirements to comply with federal
and pharmaceutical industry compliance guidelines;
state data privacy and price transparency laws, many of which differ from each other in significant ways and often are broader than and not preempted
by HIPAA or the Sunshine Act, thus complicating compliance efforts; by way of example, the California Consumer Privacy Act, or CCPA, which went
into effect January 1, 2020, among other things, creates new data privacy obligations for covered companies and provides new privacy rights to
California residents, including the right to opt out of certain disclosures of their information. The CCPA also creates a private right of action with
statutory damages for certain data breaches, thereby potentially increasing risks associated with a data breach. Although the law includes limited
exceptions, including for “protected health information” maintained by a covered entity or business associate, it may regulate or impact our processing
of personal information depending on the context; and
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similar healthcare laws and regulations in the European Union and other jurisdictions, including reporting requirements detailing interactions with and
payments to healthcare providers and laws governing the privacy and security of certain protected information, such as the General Data Protection
Regulation, or GDPR, which imposes obligations and restrictions on the collection and use of personal data relating to individuals located in the
European Union (including health data); in addition, the United Kingdom leaving the E.U. could also lead to further legislative and regulatory changes.
It remains unclear how the United Kingdom data protection laws or regulations will develop in the medium to longer term and how data transfer to the
United Kingdom from the E.U. will be regulated, especially following the United Kingdom's departure from the E.U. on January 31, 2020 without a
deal. However, the United Kingdom has transposed the GDPR into domestic law with the Data Protection Act 2018, which remains in force following
the United Kingdom's departure from the E.U.
Efforts to ensure that our business arrangements with third parties comply with applicable healthcare laws and regulations will involve substantial costs. It
is possible that governmental authorities will conclude that our business practices, including our relationships with physicians and other healthcare
providers, some of whom may recommend, purchase and/or prescribe our product candidates, if approved, may not comply with current or future statutes,
regulations or case law involving applicable fraud and abuse or other healthcare laws and regulations. If our operations are found to be in violation of any
of these laws or any other governmental laws and regulations that may apply to us, we may be subject to significant civil, criminal and administrative
penalties, damages, fines, imprisonment, exclusion of products from government funded healthcare programs, such as Medicare and Medicaid,
disgorgement, contractual damages, reputational harm, diminished profits and the curtailment or restructuring of our operations. If any of the physicians or
other healthcare providers or entities with whom we expect to do business is found to be not in compliance with applicable laws, they may be subject to
criminal, civil or administrative sanctions, including exclusions from government funded healthcare programs. The risk of our being found in violation of
these laws is increased by the fact that many of them have not been fully interpreted by the regulatory authorities or the courts, and their provisions are
open to a variety of interpretations.
Recently enacted and future legislation may increase the difficulty and cost for us to obtain marketing approval of and commercialize our product
candidates and affect the prices we may obtain.
In the United States and some foreign jurisdictions, there have been a number of legislative and regulatory changes and proposed changes regarding the
healthcare system that could prevent or delay marketing approval of our product candidates, restrict or regulate post‑approval activities and affect our
ability to profitably sell any product candidates for which we obtain marketing approval.
For example, the Patient Protection and Affordable Care Act, as amended by the Health Care and Education Reconciliation Act, or collectively the ACA, a
sweeping law intended to broaden access to health insurance, reduce or constrain the growth of healthcare spending, enhance remedies against fraud and
abuse, add new transparency requirements for the healthcare and health insurance industries, impose new taxes and fees on the health industry and impose
additional health policy reforms.
Among the provisions of the ACA of importance to our potential product candidates are the following:
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an annual, nondeductible fee payable by any entity that manufactures or imports specified branded prescription drugs and biologic agents;
an increase in the statutory minimum rebates a manufacturer must pay under the Medicaid Drug Rebate Program;
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;
extension of manufacturers’ Medicaid rebate liability to individuals enrolled in Medicaid managed care organizations;
expansion of the entities eligible for discounts under the Public Health Service pharmaceutical pricing program;
a new requirement to annually report drug samples that manufacturers and distributors provide to physicians; and
a new Patient‑Centered Outcomes Research Institute to oversee, identify priorities in, and conduct comparative clinical effectiveness research, along
with funding for such research.
Since its enactment, there have been judicial and Congressional challenges to certain aspects of the ACA. By way of example, the Tax Cuts and Jobs Acts,
or the Tax Act, was enacted, which, among other things, removes penalties for not complying with the individual mandate to carry health insurance. On
December 14, 2018, a U.S. District Court Judge in the Northern District of Texas, ruled that the individual mandate is a critical and inseverable feature of
the ACA, and therefore, because it was repealed as part of the Tax Act, the remaining provisions of the ACA are invalid as well. On December 18, 2019,
the U.S. Court of Appeals for the 5th Circuit ruled that the individual mandate was unconstitutional and remanded the case back to the District Court to
determine whether the remaining provisions of the ACA are invalid as well. It is unclear how these decisions, subsequent appeals, if any, and other efforts
to challenge, repeal or replace the ACA will impact the ACA or our business. We
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cannot predict the ultimate content, timing or effect of any healthcare reform legislation or the impact of potential legislation on us.
We expect that the ACA, as well as other healthcare reform measures that may be adopted in the future, may result in additional reductions in Medicare and
other healthcare funding, more rigorous coverage criteria, new payment methodologies and additional downward pressure on the price that we receive for
any approved product. Any reduction in reimbursement from Medicare or other government programs may result in a similar reduction in payments from
private payors. The implementation of cost containment measures or other healthcare reforms may prevent us from being able to generate revenue, attain
profitability or commercialize our products.
Even if we receive regulatory approval for any of our product candidates, we will be subject to ongoing obligations and continued regulatory review,
which may result in significant additional expense. Additionally, any of our product candidates, if approved, could be subject to post‑marketing
restrictions or withdrawal from the market, and we may be subject to penalties if we fail to comply with regulatory requirements or if we experience
unexpected problems with our products.
Any product candidate for which we obtain marketing approval, along with the manufacturing processes, post‑approval clinical data, labeling, advertising
and promotional activities for such product, will be subject to the continual requirements of and review by the FDA and other regulatory authorities. These
requirements include submissions of safety and other post‑marketing information and reports, registration and listing requirements, cGMP requirements
relating to manufacturing, quality control, quality assurance and corresponding maintenance of records and documents, requirements regarding the
distribution of samples to physicians and recordkeeping. We and our contract manufacturers will also be subject to continual review and periodic
inspections to assess compliance with cGMP. 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.
Even if marketing approval of a product candidate is granted, the approval may be subject to limitations on the indicated uses for which the product may be
marketed or to the conditions of approval, including the requirement to implement a risk evaluation and mitigation strategy, or REMS, which could include
requirements for a medication guide, physician communication plans or additional elements to assure safe use, such as restricted distribution methods,
patient registries and other risk mitigation tools. If any of our product candidates receives marketing approval, the accompanying label may limit the
approved use of our product, which could limit sales of the product.
The FDA may also impose requirements for costly post‑marketing studies or clinical trials and surveillance to monitor the safety or efficacy of our
approved products. The FDA closely regulates the post‑approval marketing and promotion of drugs and biologics to ensure they are marketed only for the
approved indications and in accordance with the provisions of the approved labeling. The FDA imposes stringent restrictions on manufacturers’
communications regarding off‑label use, and if we market our products outside of their approved indications, we may be subject to enforcement action for
off‑label marketing. Violations of the FDA’s restrictions relating to the promotion of prescription products may also lead to investigations alleging
violations of federal and state health care fraud and abuse laws, as well as state consumer protection laws.
In addition, if a regulatory agency or we later discover previously unknown problems with our products, such as adverse events of unexpected severity or
frequency or problems with manufacturers or manufacturing processes, the regulatory agency may impose restrictions on the products or us, including
requiring withdrawal of the product from the market. Any failure to comply with applicable regulatory requirements may yield various results, including:
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litigation involving patients taking our products;
restrictions on such products, manufacturers or manufacturing processes;
restrictions on the labeling or marketing of a product;
restrictions on product distribution or use;
requirements to conduct post‑marketing studies or clinical trials;
warning letters;
withdrawal of products from the market;
suspension or termination of ongoing clinical trials;
refusal to approve pending applications or supplements to approved applications that we submit;
recall of products;
fines, restitution or disgorgement of profits or revenues;
suspension or withdrawal of marketing approvals;
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damage to relationships with existing and potential collaborators;
unfavorable press coverage and damage to our reputation;
refusal to permit the import or export of our products;
product seizure or detention;
injunctions; or
imposition of civil or criminal penalties.
Noncompliance with other requirements in foreign jurisdictions regarding safety monitoring or pharmacovigilance can also result in significant financial
penalties. Similarly, failure to comply with U.S. and foreign regulatory requirements regarding the development of products for pediatric populations and
the protection of personal health information can also lead to significant penalties and sanctions.
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 revenues. If regulatory sanctions are applied or if regulatory approval is withheld or withdrawn, the value of our company and our operating
results will be adversely affected.
The FDA’s and other regulatory authorities’ policies may change, and additional government regulations may be enacted that could prevent, limit or delay
regulatory approval of our product candidates. If we are slow or unable to adapt to changes in existing requirements or the adoption of new requirements or
policies, or if we are not able to maintain regulatory compliance, we may lose any marketing approval that we may have obtained and we may not achieve
or sustain profitability, which would adversely affect our business, prospects, financial condition and results of operations.
We also cannot predict the likelihood, nature or extent of government regulation that may arise from future legislation or administrative or executive action,
either in the United States or abroad. For example, certain policies of the current administration may impact our business and industry. Namely, the Trump
administration has taken several executive actions, including the issuance of a number of Executive Orders, that could impose significant burdens on, or
otherwise materially delay, FDA’s ability to engage in routine regulatory and oversight activities such as implementing statutes through rulemaking,
issuance of guidance, and review and approval of marketing applications. It is difficult to predict how these Executive Orders will be implemented, and the
extent to which they will impact the FDA’s ability to exercise its regulatory authority. If these executive actions impose constraints on FDA’s ability to
engage in oversight and implementation activities in the normal course, our business may be negatively impacted.
Changes in funding for the FDA and other government agencies could hinder their ability to hire and retain key leadership and other personnel, or
otherwise prevent new products and services from being approved, developed or commercialized in a timely manner, which could negatively impact our
business.
The ability of the FDA to review and approve new products can be affected by a variety of factors, including government budget and funding levels, ability
to hire and retain key personnel and accept the payment of user fees, and statutory, regulatory, and policy changes. Average review times at the agency have
fluctuated in recent years as a result. In addition, government funding of other government agencies that fund research and development activities is subject
to the political process, which is inherently fluid and unpredictable.
Disruptions at the FDA and other agencies may also slow the time necessary for new drugs to be reviewed and/or approved by necessary government
agencies, which would adversely affect our business. For example, over the last several years, including for 35 days beginning on December 22, 2018, the
U.S. government has shut down several times and certain regulatory agencies, such as the FDA, have had to furlough critical FDA employees and stop
critical activities. If a prolonged government shutdown occurs, it could significantly impact the ability of the FDA to timely review and process our
regulatory submissions, which could have a material adverse effect on our business
We are subject to U.S. and certain foreign export and import controls, sanctions, embargoes, anti‑corruption laws, and anti‑money laundering laws and
regulations. Compliance with these legal standards could impair our ability to compete in domestic and international markets. We can face criminal
liability and other serious consequences for violations, which can have a material adverse effect on our business.
We are subject to export control and import laws and regulations, including the U.S. Export Administration Regulations administered by the U.S.
Commerce Department’s Bureau of Industry and Security, U.S. Customs regulations, various economic and trade sanctions regulations including those
administered or enforced by relevant government authorities, such as by the U.S. Treasury Department’s Office of Foreign Assets Control or the U.S.
Department of State, the U.S. Foreign Corrupt Practices Act of 1977, as amended, or FCPA, the U.S. domestic bribery statute contained in 18 U.S.C. § 201,
the U.S. Travel Act, the USA PATRIOT Act, and other state and national anti‑bribery and anti‑money laundering laws in the countries in which
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we conduct activities. U.S. sanctions laws and regulations may govern or restrict our business and activities in certain countries and with certain persons.
Anti‑corruption laws are interpreted broadly and prohibit companies and their employees, agents, contractors and other partners from authorizing,
promising, offering or providing, directly or indirectly, improper payments or anything else of value to recipients in the public or private sector. We may
engage third parties for clinical trials outside of the United States, to sell our product candidates abroad once we enter a commercialization phase, and/or to
obtain necessary permits, licenses, patent registrations, and other regulatory approvals. We have direct or indirect interactions with officials and employees
of government agencies or government‑affiliated hospitals, universities and other organizations. We can be held liable for the corrupt or other illegal
activities of our employees, agents, contractors and other partners, even if we do not explicitly authorize or have actual knowledge of such activities. Our
violations of the laws and regulations described above may result in substantial civil and criminal fines and penalties, imprisonment, the loss of export or
import privileges, debarment, tax reassessments, breach of contract and fraud litigation, reputational harm and other consequences.
Governments outside the United States tend to impose strict price controls, which may adversely affect our revenues, if any.
In some 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 candidate. In addition, there can be considerable
pressure by governments and other stakeholders on prices and reimbursement levels, including as part of cost containment measures. Political, economic
and regulatory developments may further complicate pricing negotiations, and pricing negotiations may continue after coverage and reimbursement have
been obtained. Reference pricing used by various countries and parallel distribution or arbitrage between low‑priced and high‑priced countries, can further
reduce prices. To obtain reimbursement or pricing approval in some countries, we may be required to conduct a clinical trial that compares the
cost‑effectiveness of our product candidate to other available therapies, which is time‑consuming and costly. If coverage and reimbursement of our product
candidates are unavailable or limited in scope or amount, or if pricing is set at unsatisfactory levels, our business could be materially adversely affected.
If we or our contract manufacturers or other third parties fail to comply with environmental, health and safety laws and regulations, we could become
subject to fines or penalties or incur costs that could have a material adverse effect on our business.
We and our contract manufacturers and other third parties with whom we do business are subject to numerous environmental, health and safety laws and
regulations, including those governing laboratory procedures and the handling, use, storage, treatment and disposal of hazardous materials and wastes. Our
operations involve the use of hazardous and flammable materials, including biological materials and chemicals. Our operations also produce hazardous
waste products. We generally contract with third parties for the disposal of these materials and wastes. We cannot eliminate the risk of contamination or
injury from these materials. In the event of contamination or injury resulting from our use of hazardous materials, we could be held liable for any resulting
damages, and any liability could exceed our resources. We also could incur significant costs associated with civil or criminal fines and penalties for failure
to comply with such laws and regulations.
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 hazardous materials, this insurance may not provide adequate coverage against potential liabilities. We do not maintain insurance for
environmental liability or toxic tort claims that may be asserted against us in connection with our storage or disposal of biological, hazardous or radioactive
materials.
In addition, we may incur substantial costs in order to comply with current or future environmental, health and safety laws and regulations. These current or
future laws and regulations may impair our research, development or production efforts. The failure to comply with these laws and regulations also may
result in substantial fines, penalties or other sanctions.
RISKS RELATED TO OUR INTELLECTUAL PROPERTY
If we or our licensors are unable to adequately protect our proprietary technology, or obtain and maintain issued patents that are sufficient to protect
our product candidates, others could compete against us more directly, which would negatively impact our business.
Our success depends in large part on our ability to obtain and maintain patent and other intellectual property protection in the United States and other
countries with respect to our proprietary technology and products. We seek to protect our proprietary position by filing patent applications in the United
States and abroad related to our novel technologies and product candidates. We also rely on trade secrets to protect aspects of our business that are not
amenable to, or that we do not consider appropriate for, patent protection.
The patent prosecution process is expensive and time‑consuming, and we may not be able to file and prosecute all necessary or desirable patent
applications at a reasonable cost, in a timely manner or in all jurisdictions. As we reach the statutory deadlines for deciding whether and where to initiate
prosecution in specific foreign jurisdictions by filing national stage applications based on our Patent Cooperation Treaty, or PCT, applications, we will have
to decide whether and where to pursue patent
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protection for the various inventions claimed in our patent portfolio, and we will only have the opportunity to obtain patents in those jurisdictions where we
pursue protection. It is also possible that we will fail to identify patentable aspects of our research and development output before it is too late to obtain
patent protection. It is possible that defects of form in the preparation or filing of our patents or patent applications may exist, or may arise in the future,
such as, with respect to proper priority claims, inventorship, claim scope or patent term adjustments. If there are material defects in the form or preparation
of our patents or patent applications, such patents or applications may be invalid and unenforceable. Moreover, our competitors may independently develop
equivalent knowledge, methods and know‑how. Any of these outcomes could impair our ability to prevent competition from third parties, which may have
an adverse impact on our business. We also cannot guarantee that any of our patent searches or analyses, including but not limited to the identification of
relevant patents, the scope of patent claims or the expiration of relevant patents, are complete and thorough, nor can we be certain that we have identified
each and every patent and pending application in the United States and abroad that is relevant to or necessary for the commercialization of our product
candidates in any jurisdiction.
In some circumstances, we may not have the right to control the preparation, filing and prosecution of patent applications, or to maintain the patents
covering technology that we license from third parties. We may also require the cooperation of our licensors to enforce any licensed patent rights, and such
cooperation may not be provided. Therefore, these patents and applications may not be prosecuted and enforced in a manner consistent with the best
interests of our business. Moreover, we have obligations under our licenses, and any failure to satisfy those obligations could give our licensor the right to
terminate the license. Termination of a necessary license could have a material adverse impact on our business.
We cannot provide any assurances that the issued patents we currently own, or any future patents, include claims with a scope sufficient to protect our
product candidates or otherwise provide any competitive advantage. Further, it is possible that a patent claim may provide coverage for some but not all
parts of a product candidate or third‑party product. These and other factors may provide opportunities for our competitors to design around our patents.
Moreover, other parties may have developed technologies that may be related or competitive to our approach, and may have filed or may file patent
applications, and may have received or may receive patents that may overlap or conflict with our patent applications, either by claiming similar methods or
by claiming subject matter that could dominate our patent position. In addition, it may be some time before we understand how the patent office reacts to
our patent claims and whether they identify prior art of relevance that we have not already considered.
Publications of discoveries in the scientific literature often lag behind the actual discoveries, and patent applications in the United States and other
jurisdictions are typically not published until 18 months after filing, or in some cases not at all. Therefore, we cannot know with certainty whether we were
the first to make the inventions claimed in any owned patents or pending patent applications, or that we were the first to file for patent protection of such
inventions, nor can we know whether those from whom we may license patents were the first to make the inventions claimed or were the first to file. For
these and other reasons, the issuance, scope, validity, enforceability and commercial value of our patent rights are subject to a level of uncertainty. Our
pending and future patent applications may not result in patents being issued that protect our technology or products, in whole or in part, or which
effectively prevent others from commercializing competitive technologies and products. Changes in either the patent laws or interpretation of the patent
laws in the United States and other countries may diminish the value of our patents or narrow the scope of our patent protection.
We may be subject to a third‑party preissuance submission of prior art to the U.S. Patent and Trademark Office, or USPTO, or become involved in
opposition, derivation, reexamination, inter partes review, post‑grant review or interference proceedings challenging our patent rights or the patent rights of
others. An adverse determination in any such submission, proceeding or litigation could reduce the scope of, or invalidate, our patent rights, allow third
parties to commercialize our technology or products and compete directly with us, without payment to us, or result in our inability to manufacture or
commercialize product candidates without infringing third‑party patent rights. In addition, if the breadth or strength of protection provided by our patents
and patent applications is threatened, it could dissuade companies from collaborating with us to license, develop or commercialize current or future product
candidates. Furthermore, an adverse decision in an interference proceeding can result in a third party receiving the patent right sought by us, which in turn
could affect our ability to develop, market or otherwise commercialize our product candidates. The issuance, scope, validity, enforceability and commercial
value of our patents are subject to a level of uncertainty.
The patent position of biotechnology and pharmaceutical companies generally is highly uncertain, involves complex legal and factual questions and has in
recent years been the subject of much litigation. Due to legal standards relating to patentability, validity, enforceability and claim scope of patents covering
biotechnological and pharmaceutical inventions, our ability to obtain, maintain and enforce patents is uncertain and involves complex legal and factual
questions. Even if issued, a patent’s validity, inventorship, ownership or enforceability is not conclusive. Accordingly, rights under any existing patent or
any patents we might obtain or license may not cover our product candidates, or may not provide us with sufficient protection for our product candidates to
afford a commercial advantage against competitive products or processes, including those from branded and generic pharmaceutical companies.
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In addition to the protection afforded by patents, we rely on trade secret protection and confidentiality agreements to protect proprietary know‑how,
information, or technology that is not covered by our patents. Although our agreements require all of our employees to assign their inventions to us, and we
require all of our employees, consultants, advisors and any other third parties who have access to our trade secrets, proprietary know‑how and other
confidential information and technology to enter into appropriate confidentiality agreements, we cannot be certain that our trade secrets, proprietary
know‑how, and other confidential information and technology will not be subject to unauthorized disclosure or that our competitors will not otherwise gain
access to or independently develop substantially equivalent trade secrets, proprietary know‑how, and other information and technology. Furthermore, the
laws of some foreign countries do not protect proprietary rights to the same extent or in the same manner as the laws of the United States. As a result, we
may encounter significant problems in protecting and defending our intellectual property globally. If we are unable to prevent unauthorized disclosure of
our intellectual property related to our product candidates and technology to third parties, we may not be able to establish or maintain a competitive
advantage in our market, which could adversely affect our business and operations.
Any litigation to enforce or defend our patent rights, even if we were to prevail, could be costly and time‑consuming and would divert the attention of our
management and key personnel from our business operations. We may not prevail in any lawsuits that we initiate and the damages or other remedies
awarded if we were to prevail may not be commercially meaningful. 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 potential
collaborators, to prevent misappropriation of our 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 other 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 adversely affected.
If we are unable to protect the confidentiality of our trade secrets and know‑how, our business and competitive position would be harmed.
In addition to seeking patents for some of our technology and product candidates, we also rely on trade secrets, including unpatented know‑how,
technology and other proprietary information, to maintain our competitive position. We seek to protect these trade secrets, in part, by entering into
non‑disclosure and confidentiality agreements with parties who have access to them, such as our employees, corporate collaborators, outside scientific
collaborators, contract manufacturers, consultants, advisors and other third parties. We also seek to enter into confidentiality and invention or patent
assignment agreements with our employees, advisors and consultants. Despite these efforts, any of these parties may breach the agreements and disclose
our proprietary information, including our trade secrets, and we may not be able to obtain adequate remedies for such breaches. Our trade secrets may also
be obtained by third parties by other means, such as breaches of our physical or computer security systems. Enforcing a claim that a party illegally
disclosed or misappropriated a trade secret is difficult, expensive and time‑consuming, and the outcome is unpredictable. In addition, some courts inside
and outside the United States are less willing or unwilling to protect trade secrets. Moreover, if any of our trade secrets were to be lawfully obtained or
independently developed by a competitor, we would have no right to prevent them, or those to whom they communicate it, from using that technology or
information to compete with us. If any of our trade secrets were to be disclosed to, or independently developed by, a competitor, our competitive position
would be harmed.
Changes in U.S. patent law could diminish the value of patents in general, thereby impairing our ability to protect our product candidates.
As is the case with other biotechnology companies, our success is heavily dependent on intellectual property, particularly patents. Obtaining and enforcing
patents in the biotechnology industry involves both technological and legal complexity, and is therefore costly, time‑consuming and inherently uncertain. In
addition, recent patent reform legislation could further increase the uncertainties and costs surrounding the prosecution of our patent applications and the
enforcement or defense of our issued patents. On September 16, 2011, the Leahy‑Smith America Invents Act, or the Leahy‑Smith Act, was signed into law.
The Leahy‑Smith Act includes a number of significant changes to U.S. patent law. These include provisions that affect the way patent applications are
prosecuted and may also affect patent litigation. The USPTO recently developed new regulations and procedures to govern administration of the
Leahy‑Smith Act, and many of the substantive changes to patent law associated with the Leahy‑Smith Act, in particular the first to file provisions, became
effective on March 16, 2013. A third party that files a patent application in the USPTO after that date but 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. This requires us to be cognizant of the time from
invention to filing of a patent application. Thus, for our U.S. patent applications containing a priority claim after March 16, 2013, there is a greater level of
uncertainty in the patent law. Moreover, some of the patent applications in our portfolio will be subject to examination under the pre‑Leahy‑Smith Act law
and regulations, while other patents applications in our portfolio will
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be subject to examination under the law and regulations, as amended by the Leahy‑Smith Act. This introduces additional complexities into the prosecution
and management of our portfolio.
In addition, the Leahy‑Smith Act limits where a patentee may file a patent infringement suit and provides opportunities for third parties to challenge any
issued patent in the USPTO. These provisions apply to all of our U.S. patents, even those issued before March 16, 2013. Because of a lower evidentiary
standard in USPTO proceedings compared to the evidentiary standard in U.S. federal court necessary to invalidate a patent claim, a third party could
potentially provide evidence in a USPTO proceeding sufficient for the USPTO to hold a claim invalid even though the same evidence would be insufficient
to invalidate the claim if first presented in a federal court action.
Accordingly, a third party may attempt to use the USPTO procedures to invalidate our patent claims because it may be easier for them to do so relative to
challenging the patent in a federal court action. It is not 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.
In addition, recent U.S. Supreme Court rulings have narrowed the scope of patent protection available in certain circumstances and weakened the rights of
patent owners in certain situations. From time to time, the U.S. Supreme Court, other federal courts, the U.S. Congress or the USPTO may change the
standards of patentability, and any such changes could have a negative impact on our business.
Depending on these and other decisions by the U.S. Congress, the federal courts and the USPTO, the laws and regulations governing patents could change
or be interpreted in unpredictable ways that would weaken our ability to obtain new patents or to enforce any patents that may issue to us in the future. In
addition, these events may adversely affect our ability to defend any patents that may issue in procedures in the USPTO or in courts.
Third parties may initiate legal proceedings alleging that we are infringing their intellectual property rights, the outcome of which would be uncertain
and could have a material adverse effect on the success of our business.
Our commercial success depends upon our ability, and the ability of our collaborators, to develop, manufacture, market and sell our product candidates and
use our proprietary technologies without infringing the proprietary rights of third parties. There is considerable intellectual property litigation in the
biotechnology and pharmaceutical industries. While no such litigation has been brought against us and we have not been held by any court to have
infringed a third party’s intellectual property rights, we cannot guarantee that our technology, product candidates or use of our product candidates do not
infringe third‑party patents.
We are aware of numerous patents and pending applications owned by third parties, and we monitor patents and patent applications in the fields in which
we are developing product candidates, both in the United States and elsewhere. However, we may have failed to identify relevant third‑party patents or
applications. For example, applications filed before November 29, 2000 and certain applications filed after that date that will not be filed outside the United
States remain confidential until patents issue. Moreover, it is difficult for industry participants, including us, to identify all third‑party patent rights that may
be relevant to our product candidates and technologies because patent searching is imperfect due to differences in terminology among patents, incomplete
databases and the difficulty in assessing the meaning of patent claims. We may fail to identify relevant patents or patent applications or may identify
pending patent applications of potential interest but incorrectly predict the likelihood that such patent applications may issue with claims of relevance to our
technology. In addition, we may be unaware of one or more issued patents that would be infringed by the manufacture, sale or use of a current or future
product candidate, or we may incorrectly conclude that a third‑party patent is invalid, unenforceable or not infringed by our activities. Additionally,
pending patent applications that have been published can, subject to certain limitations, be later amended in a manner that could cover our technologies, our
product candidates or the use of our product candidates.
The biotechnology and pharmaceutical industries are characterized by extensive litigation regarding patents and other intellectual property rights. Other
parties may allege that our product candidates or the use of our technologies infringes patent claims or other intellectual property rights held by them or that
we are employing their proprietary technology without authorization. We may become party to, or threatened with, future adversarial proceedings or
litigation regarding intellectual property rights with respect to our product candidates and technology, including interference or derivation proceedings
before the USPTO and similar bodies in other countries. Third parties may assert infringement claims against us based on existing intellectual property
rights and intellectual property rights that may be granted in the future.
Patent and other types of intellectual property litigation can involve complex factual and legal questions, and their outcome is uncertain. If we are found, or
believe there is a risk we may be found, to infringe a third party’s intellectual property rights, we could be required or may choose to obtain a license from
such third party to continue developing and marketing our product candidates and technology. However, we may not be able to obtain any such license on
commercially reasonable terms or at all. Even if we were able to obtain a license, it could be non‑exclusive, thereby giving our competitors access to the
same technologies licensed to us. We could be forced, including by court order, to cease commercializing the infringing technology
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or product. In addition, we could be found liable for monetary damages, including treble damages and attorneys’ fees if we are found to have willfully
infringed a patent. A finding of infringement could prevent us from commercializing our product candidates or force us to cease some of our business
operations, which could materially harm our business. Claims that we have misappropriated the confidential information or trade secrets of third parties
could have a similar negative impact on our business.
Even if we are successful in such proceedings, we may incur substantial costs and divert management time and attention in pursuing these proceedings,
which could have a material adverse effect on us. Patent litigation is costly and time‑consuming. We may not have sufficient resources to bring these
actions to a successful conclusion. There could be public announcements of the results of hearings, motions or other interim proceedings or developments
and if securities analysts or investors perceive these results to be negative, it could have a substantial adverse effect on the price of our common stock.
Any of these risks coming to fruition could have a material adverse impact on our business.
We may become involved in lawsuits to protect or enforce our patents or other intellectual property, and our issued patents covering our product
candidates could be found invalid or unenforceable or could be interpreted narrowly if challenged in court.
Competitors may infringe our intellectual property, including our patents or the patents of our licensors. As a result, we may be required to file
infringement claims to stop third‑party infringement or unauthorized use. This can be expensive, particularly for a company of our size, and
time‑consuming. If we initiated legal proceedings against a third party to enforce a patent, if and when issued, covering one of our product candidates, the
defendant could counterclaim that the patent covering our product candidate is invalid and/or unenforceable. In patent litigation in the United States,
defendant counterclaims alleging invalidity and/or unenforceability are commonplace. Grounds for a validity challenge include alleged failures to meet any
of several statutory requirements, including lack of novelty, obviousness or non‑enablement, or failure to claim patent‑eligible subject matter. Grounds for
unenforceability assertions include allegations that someone connected with the prosecution of the patent withheld relevant information from the USPTO,
or made a misleading statement, during prosecution. Third parties may also raise similar claims before administrative bodies in the United States or abroad,
even outside the context of litigation. Such mechanisms include re‑examination, post‑grant review, inter partes review, interference proceedings and
equivalent proceedings in foreign jurisdictions, such as opposition proceedings. Such proceedings could result in revocation or amendment of our patents in
such a way that they no longer cover our product candidates or competitive products. The outcome following legal assertions of invalidity and
unenforceability is unpredictable. With respect to validity, for example, we cannot be certain that there is no invalidating prior art, of which we and the
patent examiner were unaware during prosecution. If a defendant were to prevail on a legal assertion of invalidity and/or unenforceability, we would lose at
least part, and perhaps all, of the patent protection on our product candidates. Moreover, even if not found invalid or unenforceable, the claims of our
patents could be construed narrowly or in a manner that does not cover the allegedly infringing technology in question. Such a loss of patent protection
would have a material adverse impact on our business.
The lives of our patents may not be sufficient to effectively protect our products and business.
Patents have a limited lifespan. In the United States, the natural expiration of a patent is generally 20 years after its first effective non-provisional filing
date. Although various extensions may be available, the life of a patent, and the protection it affords, is limited. Even if patents covering our product
candidates, proprietary technologies and their uses are obtained, once the patent life has expired, we may be open to competition. In addition, although
upon issuance in the United States a patent’s life can be increased based on certain delays caused by the USPTO, this increase can be reduced or eliminated
based on certain delays caused by the patent applicant during patent prosecution. Given the amount of time required for the development, testing and
regulatory review of new product candidates, patents protecting such candidates might expire before or shortly after such candidates are commercialized. If
we do not have sufficient patent life to protect our product candidates, proprietary technologies and their uses, our business and results of operations will be
adversely affected.
Obtaining and maintaining our 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 noncompliance with these
requirements.
Periodic maintenance fees on any issued patent are due to be paid to the USPTO and foreign patent agencies in several stages over the lifetime of the patent
and, in some jurisdictions, during the pendency of a patent application. The USPTO and various foreign governmental patent agencies require compliance
with a number of procedural, documentary, fee payment and other similar provisions during the patent application process. While an inadvertent lapse can
in many cases be cured by payment of a late fee or by other means in accordance with the applicable rules, 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.
Noncompliance events that could result in abandonment or lapse of a patent or patent application include, but are not limited to, failure to respond to
official actions within prescribed time limits, non‑payment of fees and failure to properly
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legalize and submit formal documents. In such an event, our competitors might be able to enter the market, which would have an adverse effect on our
business.
If we fail to comply with our obligations in our intellectual property licenses and funding arrangements with third parties, we could lose rights that are
important to our business.
We are party to multiple license agreements that impose, and we may enter into additional licensing and funding arrangements with third parties that may
impose, diligence, development and commercialization timelines, milestone payment, royalty, insurance and other obligations on us. Under our existing
licensing agreements, we are obligated to pay royalties on net product sales of product candidates or related technologies to the extent they are covered by
the agreement. Our results of operations will be affected by the level of royalty payments that we are required to pay to third parties. We cannot precisely
predict the amount, if any, of royalties that we will be required to pay to third parties in the future. Any disagreements with the counterparty over the
amount of royalties owed could lead to litigation, which is costly. In addition, if we fail to comply with our obligations under current or future license
agreements, our counterparties may have the right to terminate these agreements, in which event we might not be able to develop, manufacture or market
any product candidate that is covered by these agreements, or may face other penalties under the agreements. Such an occurrence could materially
adversely affect the value of product candidates being developed using rights licensed to us under any such agreement. Termination of these agreements or
reduction or elimination of our rights under these agreements may result in our having to negotiate new or reinstated agreements with less favorable terms,
or cause us to lose our rights under these agreements, including our rights to important intellectual property or technology. Furthermore, our counterparties
may allege that we are operating outside the scope of the licenses granted and terminate our license or otherwise require us to alter development,
manufacturing or marketing activities.
We may not be successful in obtaining or maintaining necessary rights to our product candidates through acquisitions and in-licenses.
We currently have rights to certain intellectual property, through licenses from third parties and under patents and patent applications that we own, to
develop our product candidates. Because we may find that our programs require the use of proprietary rights held by third parties, the growth of our
business may depend in part on our ability to acquire, in‑license or use these proprietary rights. We may be unable to acquire or in‑license compositions,
methods of use, processes or other third‑party intellectual property rights from third parties that we identify as necessary for our product candidates. The
licensing and acquisition of third‑party intellectual property rights is a competitive area, and a number of more established companies are also pursuing
strategies to license or acquire third‑party intellectual property rights that we may consider attractive. These established companies may have a competitive
advantage over us due to their size, financial resources and greater clinical development and commercialization capabilities. In addition, companies that
perceive us to be a competitor may be unwilling to assign or license rights to us. We also may be unable to license or acquire third‑party intellectual
property rights on terms that would allow us to make an appropriate return on our investment.
We may also be unable to maintain third‑party intellectual property rights. For example, MIT may terminate the MIT License if we fail to meet a diligence
obligation, including the initiation of a Phase 3 clinical trial by a specified date in the fourth quarter of 2019. In December 2019, we entered into the MIT
Amendment. Pursuant to the MIT Amendment, the provision of the MIT License under which we were obligated to initiate a Phase 3 clinical trial for a
licensed product by a specified date in the fourth quarter of 2019 is tolled until the earlier of (i) a specified date in the second quarter of 2020 or (ii) the
effective date of a written amendment to the MIT License. The parties agreed to negotiate in good faith to enter into a future amendment to the MIT
License after we provide MIT with an amended diligence plan. However, if we are unable to reach an agreement with MIT regarding an acceptable
amendment of the MIT License and if we are unable to cure the breach, there could be a material adverse effect on our business. See “Business - Licenses
and Collaborations - Massachusetts Institute of Technology.”
If we are unable to successfully obtain rights to required third‑party intellectual property rights or maintain the existing intellectual property rights we have,
we may have to abandon development of that program and our business and financial condition could suffer.
We may be subject to claims by third parties asserting that our employees or we have misappropriated their intellectual property, or claiming ownership
of what we regard as our own intellectual property.
Many of our employees were previously employed at universities or other biotechnology or pharmaceutical companies, including our competitors or
potential competitors. We may also engage advisors and consultants who are concurrently employed at universities or other organizations or who perform
services for other entities. Although we try to ensure that our employees, advisors 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 our employees, advisors or consultants have used or disclosed intellectual property,
including trade secrets or other proprietary information, of any such party’s former or current employer or in violation of an agreement with another party.
Although we have no knowledge of any such claims being alleged to date, if such claims were to arise, litigation may be necessary to defend against any
such claims.
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In addition, while it is our policy to require our employees, consultants, advisors and contractors who may be involved in the development of intellectual
property to execute agreements assigning such intellectual property to us, we may be unsuccessful in executing such an agreement with each party who in
fact develops intellectual property that we regard as our own. Our and their assignment agreements may not be self‑executing or may be breached, and we
may be forced to bring claims against third parties, or defend claims they may bring against us, to determine the ownership of what we regard as our
intellectual property. Similarly, we may be subject to claims that an employee, advisor or consultant performed work for us that conflicts with that person’s
obligations to a third party, such as an employer, and thus, that the third party has an ownership interest in the intellectual property arising out of work
performed for us. Litigation may be necessary to defend against these claims. Although we have no knowledge of any such claims being alleged to date, if
such claims were to arise, litigation may be necessary to defend against any such claims.
If we fail in prosecuting or 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 prosecuting or defending against such claims, litigation could result in substantial costs and be a distraction to
management.
If our trademarks and trade names are not adequately protected, then we may not be able to build name recognition in our markets of interest and our
business may be adversely affected.
Our registered or unregistered trademarks or trade names may be challenged, infringed, circumvented or declared generic or determined to be infringing on
other marks. We may not be able to protect our rights to these trademarks and trade names, which we need to build name recognition among potential
collaborators or customers in our markets of interest. At times, competitors may adopt trade names or trademarks similar to ours, thereby impeding our
ability to build brand identity and possibly leading to market confusion. In addition, there could be potential trade name or trademark infringement claims
brought by owners of other registered trademarks or trademarks that incorporate variations of our registered or unregistered trademarks or trade names.
Over the long term, if we are unable to establish name recognition based on our trademarks and trade names, then we may not be able to compete
effectively and our business may be adversely affected. Our efforts to enforce or protect our proprietary rights related to trademarks, trade secrets, domain
names, copyrights or other intellectual property may be ineffective and could result in substantial costs and diversion of resources and could adversely
impact our financial condition or results of operations.
We will not seek to protect our intellectual property rights in all jurisdictions throughout the world and we may not be able to adequately enforce our
intellectual property rights even in the jurisdictions where we seek protection.
Filing, prosecuting and defending patents on product candidates in all countries and jurisdictions throughout the world would be prohibitively expensive,
and our intellectual property rights in some countries outside the United States could be less extensive than in the United States, assuming that rights are
obtained in the United States and assuming that rights are pursued outside the United States. In this regard, in addition to the United States, we also seek to
protect our intellectual property rights in other countries. The statutory deadlines for pursuing patent protection in individual foreign jurisdictions are based
on the priority date of each of our patent applications. For all of the patent families in our portfolio, including the families that may provide coverage for
our lead product candidate, the relevant statutory deadlines have not yet expired. Therefore, for each of the patent families that we believe provide coverage
for our lead product candidate, we will need to decide whether and where to pursue additional protection outside 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. Consequently, for our
existing patent rights outside the United States and any foreign patent rights we may decide to pursue in the future, we may not be able to obtain relevant
claims and/or we may not be able to prevent third parties from practicing our inventions in all countries outside the 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 do not pursue and obtain 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 in the United States. These products
may compete with our product candidates and our patents or other intellectual property rights may not be effective or sufficient to prevent them from
competing. Even if we pursue and obtain issued patents in particular jurisdictions, our patent claims or other intellectual property rights may not be
effective or sufficient to prevent third parties from so competing.
If we do not obtain additional protection under the Hatch‑Waxman Act and similar foreign legislation extending the terms of our patents for our
product candidates, our business may be harmed.
Depending upon the timing, duration and specifics of FDA regulatory approval for our product candidates, one or more of our U.S. patents may be eligible
for limited patent term restoration under the Hatch‑Waxman Act. The Hatch‑Waxman Act permits a patent restoration term of up to five years as
compensation for patent term lost during product development and the FDA regulatory review process. Patent term restorations, however, are limited to a
maximum of five years and cannot extend the remaining term of a patent beyond a total of 14 years from the date of product approval by the FDA.
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The application for patent term extension is subject to approval by the USPTO, in conjunction with the FDA. It takes at least six months to obtain approval
of the application for patent term extension. We may not be granted an extension because of, for example, failing to apply within applicable deadlines,
failing to apply prior to expiration of relevant patents or otherwise failing to satisfy applicable requirements. Moreover, the applicable time period or the
scope of patent protection afforded could be less than we request. If we are unable to obtain patent term extension or restoration or the term of any such
extension is less than we request, the period during which we will have the right to exclusively market our product will be shortened, our competitors may
obtain earlier approval of competing products and our ability to generate revenues could be materially adversely affected.
RISKS RELATED TO OUR OPERATIONS
Our new corporate strategy may not be successful.
On January 3, 2019, following a strategic business review, we announced our new strategy to focus on the development of SEL-212 for the treatment of
chronic refractory gout and advancement of our ImmTOR platform in the area of gene therapy, specifically ImmTOR in combination with AAV gene
therapy for the treatment of CN and MMA, as well as the deprioritization of our oncology development program. The success of this strategic shift will
depend on our ability to successfully develop our product candidates, hire and retain senior management or other highly qualified personnel, prioritize
competing projects and efforts and obtain sufficient resources, including additional capital, as well as our ability to enter into collaborations with third
parties. The early stage development of novel product candidates is highly unpredictable due to the lengthy and expensive process of clinical drug
development, potential for safety, efficacy or tolerability problems with such product candidates, unexpected expenses or inaccurate financial assumptions
or forecasts, potential delays or unfavorable decisions of regulatory agencies and competition for targeted indications or within targeted markets.
Accordingly, there are no assurances our change in strategic focus will be successful, which may have an adverse effect on our results of operations or
financial condition.
Our future success depends on our ability to retain key executives and to attract, retain and motivate qualified personnel.
We are highly dependent on Carsten Brunn, Ph.D., our President and Chief Executive Officer, as well as the other principal members of our management,
scientific and clinical team. Although we have entered into employment agreements or offer letters with Dr. Brunn and other executive officers, each of
them may terminate their employment with us at any time. We do not maintain “key person” insurance for any of our executives or other employees.
Recruiting and retaining qualified scientific, clinical, manufacturing, technology and sales and marketing personnel will also be critical to our success. The
loss of the services of our executive officers or other key employees could impede the achievement of our research, development and commercialization
objectives and seriously harm our ability to successfully implement our business strategy. Furthermore, replacing executive officers and key employees
may be difficult and may take an extended period of time because of the limited number of individuals in our industry with the breadth of skills and
experience required to successfully develop, gain regulatory approval of and commercialize product candidates. Competition to hire from this limited pool
is intense, and we may be unable to hire, train, retain or motivate these key personnel on acceptable terms given the competition among numerous
pharmaceutical and biotechnology companies for similar personnel. We also experience competition for the hiring of scientific and clinical personnel from
universities and research institutions. In addition, we rely on consultants and advisors, including scientific and clinical advisors, to assist us in formulating
our research and development and commercialization strategy. Our consultants and advisors may be employed by employers other than us and may have
commitments under consulting or advisory contracts with other entities that may limit their availability to us. If we are unable to continue to attract and
retain high quality personnel, our ability to pursue our growth strategy will be limited.
We expect to expand our development and regulatory capabilities and potentially implement sales, marketing and distribution capabilities, and as a
result, we may encounter difficulties in managing our growth, which could disrupt our operations.
We expect to experience significant growth in the number of our employees and the scope of our operations, particularly in the areas of lead discovery and
product development, regulatory affairs, clinical affairs and manufacturing and, if any of our product candidates receives marketing approval, sales,
marketing and distribution. To manage our expected future growth, we must continue to implement and improve our managerial, operational and financial
systems, expand our facilities and continue to recruit and train additional qualified personnel. Due to our limited financial resources and the limited
experience of our management team in managing a company with such expected growth, we may not be able to effectively manage the expansion of our
operations or recruit and train additional qualified personnel in a timely manner, if at all. The expansion of our operations may lead to significant costs and
may divert our management and business development resources. Any inability to manage or financially support growth could delay the execution of our
business plans or disrupt our operations.
We have incurred increased costs as a result of operating as a public company, and our management will be required to devote substantial time to
compliance initiatives and corporate governance practices.
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As a public company, and particularly after we are no longer an emerging growth company, we have incurred and expect to continue to incur significant
legal, accounting and other expenses that we did not incur as a private company. The Sarbanes‑Oxley Act of 2002, the Dodd‑Frank Wall Street Reform and
Consumer Protection Act, the listing requirements of The Nasdaq Global Market and other applicable securities rules and regulations impose various
requirements on public companies, including establishment and maintenance of effective disclosure and financial controls and corporate governance
practices. Our management and other personnel need to devote a substantial amount of time to these compliance initiatives. Moreover, these rules and
regulations have increased our legal and financial compliance costs and made some activities more time‑consuming and costly.
Pursuant to Section 404 of the Sarbanes-Oxley Act of 2002, or Section 404, we are required to furnish a report by our management on our internal control
over financial reporting. However, while we remain an emerging growth company, we will not be required to include an attestation report on internal
control over financial reporting issued by our independent registered public accounting firm. If we are unable to maintain effective internal control over
financial reporting, we may not have adequate, accurate or timely financial information, and we may be unable to meet our reporting obligations as a public
company or comply with the requirements of the SEC or Section 404. This could result in a restatement of our financial statements, the imposition of
sanctions, including the inability of registered broker dealers to make a market in our common stock, or investigation by regulatory authorities. Any such
action or other negative results caused by our inability to meet our reporting requirements or comply with legal and regulatory requirements or by
disclosure of an accounting, reporting or control issue could adversely affect the trading price of our securities and our business. Material weaknesses in
our internal control over financial reporting could also reduce our ability to obtain financing or could increase the cost of any financing we obtain. This
could result in an adverse reaction in the financial markets due to a loss of confidence in the reliability of our financial statements.
A variety of risks associated with maintaining our subsidiary in Russia or expanding operations internationally could adversely affect our business.
In addition to our U.S. operations, we maintain a wholly owned subsidiary in Russia, Selecta RUS. We may face risks associated with maintaining our
subsidiary in Russia, or with any international operations, including possible unfavorable regulatory, pricing and reimbursement, legal, political, tax and
labor conditions, which could harm our business. We may also rely on collaborators to commercialize any approved product candidates outside of the
United States. Doing business internationally involves a number of risks, including but not limited to:
- multiple, conflicting and changing laws and regulations, such as privacy regulations, tax laws, export and import restrictions, employment laws,
regulatory requirements and other governmental approvals, permits and licenses;
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failure by us to obtain and maintain regulatory approvals for the use of our product candidates in various countries;
additional potentially relevant third‑party patent rights;
complexities and difficulties in obtaining protection of and enforcing our intellectual property rights;
difficulties in staffing and managing foreign operations;
complexities associated with managing multiple‑payor reimbursement regimes, government payors or patient self‑pay systems;
limits on our ability to penetrate international markets;
financial risks, such as longer payment cycles, difficulty collecting accounts receivable, the impact of local and regional financial crises on demand and
payment for our product candidates and exposure to foreign currency exchange rate fluctuations, which could result in increased operating expenses
and reduced revenues;
natural disasters, political and economic instability, including wars, events of terrorism and political unrest, outbreak of disease, including the novel
coronavirus boycotts, curtailment of trade and other business restrictions and economic weakness, including inflation;
changes in diplomatic and trade relationships;
challenges in enforcing our contractual and intellectual property rights, especially in those foreign countries that do not respect and protect intellectual
property rights to the same extent as the United States;
restriction on cross-border investment, including enhanced oversight by the Committee on Foreign Investment in the United States (CFIUS) and
substantial restrictions on investment from China;
certain expenses including, among others, expenses for travel, translation and insurance;
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legal risks, including use of the legal system by the government to benefit itself or affiliated entities at our expense, including expropriation of
property; and
regulatory and compliance risks that relate to maintaining accurate information and control over sales and activities that may fall within the purview of
the FCPA its books and records provisions, or its anti‑bribery provisions.
Any of these factors could significantly harm our future international expansion and operations and, consequently, our results of operations.
Our business and operations would suffer in the event of system failures or unauthorized or inappropriate use of or access to our systems.
Despite the implementation of security measures, our internal computer systems and those of our current and future contractors and consultants are
vulnerable to damage from computer viruses, unauthorized access, natural disasters, terrorism, war and telecommunication and electrical failures. While we
are not aware of any such material system failure, accident or security breach to date, if such an event were to occur and cause interruptions in our
operations, it could result in a material disruption of our development programs and our business operations. For example, the loss of clinical trial data
from completed or future clinical trials could result in delays in our regulatory approval efforts and significantly increase our costs to recover or reproduce
the data. Likewise, we rely on third parties to manufacture our product candidates and conduct clinical trials, and similar events relating to their computer
systems could also have a material adverse effect on our business. To the extent that any disruption or security breach were to result in a loss of, or damage
to, our data or applications, or inappropriate disclosure of confidential or proprietary information, we could incur liability and the further development and
commercialization of our product candidates could be delayed.
Acquisitions or joint ventures could disrupt our business, cause dilution to our stockholders and otherwise harm our business.
We may acquire other businesses, product candidates or technologies as well as pursue strategic alliances, joint ventures, technology licenses or
investments in complementary businesses. We have not made any acquisitions to date, and our ability to do so successfully is unproven. Any of these
transactions could be material to our financial condition and operating results and expose us to many risks, including:
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disruption in our relationships with future customers or with current or future distributors or suppliers as a result of such a transaction;
unexpected liabilities related to acquired companies;
difficulties integrating acquired personnel, technologies and operations into our existing business;
diversion of management time and focus from operating our business to acquisition integration challenges;
increases in our expenses and reductions in our cash available for operations and other uses;
possible write‑offs or impairment charges relating to acquired businesses; and
inability to develop a sales force for any additional product candidates.
Foreign acquisitions involve unique risks in addition to those mentioned above, including those related to integration of operations across different cultures
and languages, currency risks and the particular economic, political and regulatory risks associated with specific countries.
Also, the expected benefit of any acquisition may not materialize. Future acquisitions or dispositions could result in potentially dilutive issuances of our
equity securities, the incurrence of debt, contingent liabilities or amortization expenses or write‑offs of goodwill, any of which could harm our financial
condition. We cannot predict the number, timing or size of future joint ventures or acquisitions, or the effect that any such transactions might have on our
operating results.
RISKS RELATED TO OUR COMMON STOCK
The market price of our common stock may be volatile and fluctuate substantially, which could result in substantial losses for purchasers of our
common stock.
The trading price of our common stock is likely to be volatile and could be subject to wide fluctuations in response to various factors, some of which are
beyond our control. The stock market in general and the market for smaller biopharmaceutical companies in particular have experienced extreme volatility
that has often been unrelated to the operating performance of particular companies. As a result of this volatility, you may not be able to sell your common
stock at or above the price at which you purchased. The market price for our common stock may be influenced by many factors, including:
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the success of competitive products or technologies;
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results or progress, or changes in approach or timelines, of clinical trials of our product candidates or those of our competitors;
failure or discontinuation of any of our development programs;
commencement of, termination of, or any development related to any collaboration or licensing arrangement;
regulatory or legal developments in the United States and other countries;
development of new product candidates that may address our markets and make our product candidates less attractive;
changes in physician, hospital or healthcare provider practices that may make our product candidates less useful;
announcements by us, our partners or our competitors of significant acquisitions, strategic partnerships, joint ventures, collaborations or capital
commitments;
announcement or market expectation of additional financing efforts;
developments or disputes concerning patent applications, issued patents or other proprietary rights;
the recruitment or departure of key personnel;
the level of expenses related to any of our product candidates or clinical development programs;
failure to meet or exceed financial estimates, projections or development timelines of the investment community or that we provide to the public;
the results of our efforts to discover, develop, acquire or in‑license additional product candidates or products;
actual or expected changes in estimates as to financial results, development timelines or recommendations by securities analysts;
variations in our financial results or those of companies that are perceived to be similar to us;
changes in the structure of healthcare payment systems;
sale of common stock by us or our stockholders in the future as well as the overall trading volume of our common stock;
- market conditions in the pharmaceutical and biotechnology sectors;
-
-
general economic, industry and market conditions; and
the other factors described in this “Risk factors” section.
Our executive officers, directors and principal stockholders, if they choose to act together, will continue to have the ability to control or significantly
influence all matters submitted to stockholders for approval.
Our executive officers, directors and stockholders who own more than 5% of our outstanding common stock and their respective affiliates, in the aggregate,
hold shares representing approximately 45.9% of our outstanding voting stock as of December 31, 2019. As a result, if these stockholders choose to act
together, they would be able to control or significantly influence all matters submitted to our stockholders for approval, as well as our management and
affairs. For example, these persons, if they choose to act together, would control or significantly influence the election of directors, the composition of our
management and approval of any merger, consolidation or sale of all or substantially all of our assets.
A significant portion of our total outstanding shares are eligible to be sold into the market, which could cause the market price of our common stock to
drop significantly, even if our business is doing well.
Sales of a substantial number of shares of our common stock in the public market, or the perception in the market that the holders of a large number of
shares intend to sell shares, could reduce the market price of our common stock. Holders of an aggregate of approximately 0.34 million shares of our
common stock as of December 31, 2019 have rights, subject to specified conditions, to require us to file registration statements covering their shares or to
include their shares in registration statements that we may file for ourselves or other stockholders, until such shares can otherwise be sold without
restriction under Rule 144 or until the rights terminate pursuant to the terms of the investors’ rights agreement between us and such holders. We have also
registered and intend to continue to register all shares of common stock that we may issue under our equity compensation plans. Once we register these
shares, they can be freely sold in the public market upon issuance, subject to volume limitations applicable to affiliates.
In addition, on June 27, 2017, we issued and sold in a private placement 3,088,791 shares of our common stock (of which 338,791 shares have continuing
registration rights) and a warrant to purchase 79,130 shares of our common stock, including to certain of our affiliates. Pursuant to a registration rights
agreement entered into with the investors in the private placement, on July 13, 2017, we filed a Registration Statement on Form S-3 to register the shares of
common stock sold in the private
68
placement and the shares of common stock issuable upon exercise of the warrant. Similarly, on December 23, 2019, we issued and sold in a private
placement 37,634,883 shares of our common stock and warrants to purchase 31,330,629 shares of our common stock, including to certain of our affiliates.
Pursuant to a registration rights agreement entered into with the investors in the private placement, on January 29, 2019, we filed a Registration Statement
on Form S-3 to register the shares of common stock sold in the private placement and the shares of common stock issuable upon exercise of the warrant. As
a result, these shares can be freely sold in the public market.
We may not have the funds necessary to fulfill our obligation to repurchase certain warrants.
Under certain circumstances, holders of certain warrants issued in December 2019 may require us to repurchase the remaining unexercised portion of such
warrants for an amount of cash equal to the value of the warrant as determined in accordance with the Black Scholes option pricing model and the terms of
the warrants. Our ability to repurchase the warrants depends on our ability to generate cash flow in the future. To some extent, this is subject to general
economic, financial, competitive, legislative and regulatory factors and other factors that are beyond our control. We cannot be certain that we will maintain
sufficient cash reserves or that our business will generate cash flow from operations at levels sufficient to permit us to repurchase the warrants.
We are an “emerging growth company,” and the reduced disclosure requirements applicable to emerging growth companies may make our common
stock less attractive to investors.
We are an “emerging growth company,” as defined in the Jumpstart Our Business Startups Act of 2012, or the JOBS Act, and may remain an emerging
growth company until the last day of the fiscal year following the fifth anniversary of the closing of the initial public offering of our common stock.
However, if certain events occur prior to the end of such five‑year period, including if we become a “large accelerated filer,” our annual gross revenues
exceed $1.07 billion or we issue more than $1.07 billion of non‑convertible debt in any three‑year period, we will cease to be an emerging growth company
prior to the end of such five‑year period. For so 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:
-
-
-
-
not being required to comply with the auditor attestation requirements in the assessment of our internal control over financial reporting;
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 auditor’s report providing additional information about the audit and the financial statements;
reduced disclosure obligations regarding executive compensation; and
exemptions from the requirements of holding a nonbinding advisory vote on executive compensation and shareholder approval of any golden
parachute payments not previously approved.
We cannot predict whether investors will find our common stock less attractive if we rely on these exemptions. We have, historically, relied on these
exemptions, and we may continue to do so until they are no longer available to us. 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 our stock price may be reduced or more volatile. 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. This allows an
emerging growth company to delay the adoption of these accounting standards until they would otherwise apply to private companies. We have irrevocably
elected not to avail ourselves of this exemption and, therefore, we will be subject to the same new or revised accounting standards as other public
companies that are not emerging growth companies.
If securities or industry analysts do not publish research or reports about our business, or if they issue an adverse or misleading opinion regarding our
stock, our stock price and trading volume could decline.
The trading market for our common stock will be influenced by the research and reports that industry or securities analysts publish about us or our
business. If any of the analysts who cover us issue an adverse or misleading opinion regarding us, our business model, our intellectual property or our stock
performance, or if our preclinical studies, clinical trial programs and operating results fail to meet the expectations of analysts, our stock price would likely
decline. If one or more of these analysts ceases coverage of us or fails to publish reports on us regularly, we could lose visibility in the financial markets,
which in turn could cause our stock price or trading volume to decline.
Provisions in our restated certificate of incorporation and restated bylaws and under Delaware law could make an acquisition of our company, which
may be beneficial to our stockholders, more difficult and may prevent attempts by our stockholders to replace or remove our current management.
Provisions in our restated certificate of incorporation and our restated bylaws, which became effective upon the closing of the initial public offering of our
common stock may discourage, delay or prevent a merger, acquisition or other change in control of
69
our company that stockholders may consider favorable, including transactions in which you might otherwise receive a premium for your shares. These
provisions could also limit the price that investors might be willing to pay in the future for shares of our common stock, thereby depressing the market price
of our common stock. In addition, because our board of directors is responsible for appointing the members of our management team, 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.
Moreover, because we are incorporated in Delaware, we are governed by the provisions of Section 203 of the General Corporation Law of the State of
Delaware, which prohibits a person who owns in excess of 15% of our outstanding voting stock from merging or combining with us for a period of three
years after the date of the transaction in which the person acquired in excess of 15% of our outstanding voting stock, unless the merger or combination is
approved in a prescribed manner.
Furthermore, our restated certificate of incorporation specifies that, unless we consent in writing to the selection of an alternative forum, the Court of
Chancery of the State of Delaware will be the sole and exclusive forum for most legal actions involving claims brought against us by stockholders. We
believe this provision benefits us by providing increased consistency in the application of Delaware law by chancellors particularly experienced in
resolving corporate disputes, efficient administration of cases on a more expedited schedule relative to other forums and protection against the burdens of
multi‑forum litigation. However, the provision may have the effect of discouraging lawsuits against our directors, officers, employees and agents as it may
limit any stockholder’s ability to bring a claim in a judicial forum that such stockholder finds favorable for disputes with us or our directors, officers,
employees or agents. The enforceability of similar choice of forum provisions in other companies’ certificates of incorporation has been challenged in legal
proceedings, and it is possible that, in connection with any applicable action brought against us, a court could find the choice of forum provisions contained
in our restated certificate of incorporation to be applicable or unenforceable in such action.
We could be subject to securities class action litigation.
In the past, securities class action litigation has often been brought against a company following a decline in the market price of its securities. This risk is
especially relevant for us because biopharmaceutical companies have experienced significant stock price volatility in recent years. If we face such
litigation, it could result in substantial costs and a diversion of management’s attention and resources, which could harm our business.
Item 1B. Unresolved Staff Comments
Not applicable.
Item 2. Properties
Our corporate headquarters are currently located at 480 Arsenal Way, Watertown, Massachusetts and consist of 32,933 total square feet of leased office and
laboratory space under a lease that expires in March 2020.
In July 2019, we entered into a lease for 25,078 square feet of laboratory and office space located at 65 Grove Street, Watertown, Massachusetts,
commencing in March 2020, which will serve as our new corporate headquarters.
We also lease approximately 2,500 square feet of office and laboratory space in Moscow, Russia on a month to month basis.
Item 3. Legal Proceedings
We are not party to any material legal proceedings.
Item 4. Mine Safety Disclosures
Not applicable.
Information about our Directors
Carsten Brunn, Ph.D. has served as our President, Chief Executive Officer and member of our board of directors since December 2018. Prior to joining
Selecta Biosciences, Inc., Dr. Brunn was the President of Pharmaceuticals for the Americas Region at Bayer and a member of the Global Pharmaceutical
Executive Committee. Prior to being appointed to that role in 2017, he was the President of Bayer Pharmaceuticals in Japan, a role he held since 2013. He
also served as the Chairman of the European Federation of Pharmaceutical Industries and Associations (EFPIA) Japan, an organization representing
innovative pharmaceutical companies in Japan. Over the last 25 years, Dr. Brunn has held a number of senior leadership positions in Europe, Asia and the
United States at leading companies such as Eli Lilly, Novartis, Basilea and Bausch and Lomb. Dr. Brunn
70
graduated from the University of Freiburg in Germany with a Master of Science in Pharmaceutical Sciences. In addition, he studied at the University of
Washington under a research scholarship. He received his Ph.D. in Chemistry from the University of Hamburg, Germany and completed his executive
education at London Business School. Dr. Brunn's experience as a senior executive of life sciences companies and knowledge of the pharmaceutical and
biotechnology industries contributed to our board of directors' conclusion that he should serve as a director of our company.
Carrie S. Cox has served as a member of our board of directors and as chairman of the board of directors since November 2019. Ms. Cox most recently
served as the Chief Executive Officer of Humacyte, Inc., a regenerative medicine company based in Durham, North Carolina, from 2010 to June 2018, and
has served as a member of its board of directors since 2010, serving as chairman from 2011 to June 2019. Ms. Cox has served on the boards of directors of
Texas Instruments Incorporated since 2004 and Cardinal Health, Inc. since 2009, and as the chairman of the board of directors of electroCore, Inc. since
July 2018. Ms. Cox previously served on the board of directors of Celgene Corporation from 2009 to November 2019 and as chairman of the board of
directors of Array BioPharma, Inc. from August 2018 to July 2019. Ms. Cox received a B.S. from the Massachusetts College of Pharmacy, and was a
registered pharmacist. Ms. Cox’s vast experience as a pharmaceutical executive and member of multiple boards of directors in the biotechnology industry
as well as her knowledge of corporate strategy qualifies her to serve as a director of our company.
Timothy C. Barabe has served as a member of our board of directors since July 2016. Mr. Barabe also serves on the boards of Veeva Systems Inc. and
Vigilant Biosciences, Inc., a private company. From 2001 to January 2020, Mr. Barabe served on the board of ArQule, Inc., and from 2014 to 2017, Mr.
Barabe served on the board of directors of Opexa Therapeutics, Inc. Mr. Barabe retired in June 2013 from his position as Executive Vice President and
Chief Financial Officer of Affymetrix, Inc. Previously, from July 2006 until March 2010, he was Senior Vice President and Chief Financial Officer of
Human Genome Sciences, Inc. From 2004 to 2006, he served as Chief Financial Officer of Regent Medical Limited, a U.K.-based, privately owned,
surgical supply company. Mr. Barabe served with Novartis AG from 1982 through August 2004 in a succession of senior executive positions in finance and
general management, most recently as the Chief Financial Officer of Sandoz GmbH, the generic pharmaceutical subsidiary of Novartis. Mr. Barabe
received his B.B.A. degree from the University of Massachusetts (Amherst) and his M.B.A. degree from the University of Chicago. Mr. Barabe’s
experience as a senior financial executive of life sciences companies and knowledge of the pharmaceutical and biotech industries contributed to our board
of directors’ conclusion that he should serve as a director of our company.
Scott D. Myers has served as a member of our board of directors since June 2019. Mr. Myers most recently served as Chief Executive Officer, President,
and Chairman of the Board of Rainier Therapeutics, a clinical-stage biotechnology company focused on metastatic bladder cancer, from June 2018 to
January 2020. Prior to Rainier Therapeutics, Mr. Myers served as Chief Executive Officer and as a member of the board of directors of Cascadian
Therapeutics, an oncology company, from April 2016 until it was acquired by Seattle Genetics in March 2018. Prior to Cascadian, Mr. Myers served as
Chief Executive Officer of Aerocrine AB, a medical device company, from 2011 through its acquisition by Circassia Pharmaceuticals plc in July 2015. Mr.
Myers held senior commercial operations, general management, and information management positions for UCB SA, a Belgium-based biopharmaceutical
company, and Johnson & Johnson. He currently serves on the board of directors of Harpoon Therapeutics. Mr. Myers earned his B.A. in biology from
Northwestern University and his M.B.A. from the University of Chicago Booth School of Business. Mr. Myers’ experience as a senior executive of life
sciences companies and knowledge of the pharmaceutical and biotech industries contributed to our board of directors’ conclusion that he should serve as a
director of our company.
Amir Nashat, Ph.D. has served as a member of our board of directors since 2008. Dr. Nashat has been a Partner at Polaris Partners, a venture capital firm,
since 2009 and focuses on investments in the life sciences. He currently serves on the board of directors of Fate Therapeutics, Inc., Syros Pharmaceuticals,
Scholar Rock Inc., and several private companies. Dr. Nashat has also served as a director of Receptos, Inc., BIND Therapeutics, Inc., aTyr Pharma, as well
as Adnexus Therapeutics, Inc. (acquired by Bristol-Myers Squibb Company) and other private companies. Dr. Nashat completed his Ph.D. as a Hertz
Fellow in Chemical Engineering at MIT with a minor in biology. Dr. Nashat earned both his M.S. and B.S. in materials science and mechanical engineering
at the University of California, Berkeley. Dr. Nashat’s extensive experience as a venture capitalist and board member to numerous companies in the
biotechnology industry contributed to our board of directors’ conclusion that he should serve as a director of our company.
Aymeric Sallin, M.S. has served as a member of our board of directors since 2008. Mr. Sallin has served as the Chief Executive Officer of NanoDimension,
a venture capital firm, since 2002 and is the founder of that firm. Since 2014, Mr. Sallin has served as a strategic advisory board member of the École
Polytechnique Fédérale de Lausanne, or EPFL. Since 2002, Mr. Sallin has worked to promote nanotechnology around the world, and has received the NSTI
Fellow Award and 2012 EPFL Alumni award for his contribution to the field of nanotechnology. Mr. Sallin has worked to generate and close investments
of hundreds of millions of dollars into several of NanoDimension’s portfolio companies. He currently serves as a board member of H55, Inc., View, Inc.,
CROCUS Technology and Tarveda Therapeutics. Mr. Sallin is also a member of the Swiss Academy of Engineering Science. Mr. Sallin received his
Masters in Physical Engineering from EPFL in Lausanne, Switzerland. Mr. Sallins' extensive
71
knowledge of our business and the nanomedicine field contributed to our board of directors’ conclusion that he should serve as a director of our company.
Timothy A. Springer, Ph.D. has served as a member of our board of directors since June 2016 and as a scientific advisor to us since December 2008. Since
1989, Dr. Springer has served as the Latham Family Professor at Harvard Medical School. He has also served as Senior Investigator in the Program in
Cellular and Molecular Medicine at Boston Children’s Hospital since 2012, and as Professor of Biological Chemistry and Molecular Pharmacology at
Harvard Medical School and Professor of Medicine at Boston Children’s Hospital since 2011. Dr. Springer was the Founder of LeukoSite, a biotechnology
company acquired by Millennium Pharmaceuticals in 1999. Additionally, he is a founder, investor and board member of Scholar Rock and Morphic
Therapeutic. Dr. Springer is a member of the National Academy of Sciences and his honors include the Crafoord Prize, the American Association of
Immunologists Meritorious Career Award, the Stratton Medal from the American Society of Hematology, and the Basic Research Prize from the American
Heart Association. Dr. Springer received a B.A. from the University of California, Berkeley, and a Ph.D. from Harvard University. Dr. Springer’s extensive
knowledge of our business and the nanomedicine field contributed to our board of directors’ conclusion that he should serve as a director of our company.
Patrick Zenner has served as a member of our board of directors since June 2017. Mr. Zenner retired in 2001 from the position of President and Chief
Executive Officer of Hoffmann-La Roche Inc., North America, based in Nutley, N.J. Mr. Zenner held various executive positions during his 32-year career
with the company. Mr. Zenner is currently a member of the board of trustees of Creighton University and is Chairman of the board of trustees of Fairleigh
Dickinson University. In addition, Mr. Zenner is Chairman of the board and a director of West Pharmaceutical Services, Inc. From 2002 until January 2020,
Mr. Zenner served as Chairman of the board and a director of ArQule, Inc. Until its sale in 2012, Mr. Zenner was a director of Par Pharmaceuticals, Inc. In
2010, he resigned from the boards of Geron Corporation, Xoma Ltd. and Exact Sciences, Inc. Until its sale in September 2009, Mr. Zenner was a director
of CuraGen Corporation. Mr. Zenner received a B.S./B.A. from Creighton University and an M.B.A. from Fairleigh Dickinson University. Mr. Zenner’s
extensive experience as a senior pharmaceutical executive and board member to numerous companies in the biotechnology industry contributed to our
board of directors’ conclusion that he should serve as a director of our company.
Information about our Executive Officers
Bradford D. Dahms has served as our Chief Financial Officer since September 2019. Prior to joining Selecta Biosciences, Mr. Dahms was a Senior Vice
President in the Healthcare Group at Cantor Fitzgerald & Co. from April 2014 to August 2019, focused on providing strategic and financial advice to life
sciences companies. Prior to joining Cantor, Mr. Dahms worked as an investment banker at RBC Capital Markets from 2012 to 2014, covering the
healthcare sector. Previously, he worked in the Corporate and Investment Banking Group at J.P. Morgan. Mr. Dahms received his a B.S. in Economics, with
honors, from the Ohio State University.
Lloyd Johnston, Ph.D. has served as our Chief Operating Officer and Senior Vice President, Research and Development since January 2014. Dr. Johnston
served as our Senior Vice President of Pharmaceutical Research, Development and Operations from January 2011 to December 2013 and Vice President of
Pharmaceutical Research from July 2008 to January 2011. Prior to joining Selecta, Dr. Johnston was Vice President of Operations for Alkermes, Inc. from
2004 to 2008, and served in several roles, including Director of Manufacturing, from 1999 to 2004, with responsibility for process development, scale-up,
and clinical manufacturing for pulmonary and sustained release injectable products, as well as leadership of Alkermes’ manufacturing facility in Chelsea,
MA. At Alkermes, Dr. Johnston was also a project leader and member of Steering Committees for numerous products through various stages of
development from Phase 1 through registration. Dr. Johnston was an original member of Advanced Inhalation Research Inc., or AIR, a private company
formed in 1998 and acquired by Alkermes in 1999. Prior to joining AIR, Dr. Johnston was a lecturer in the Department of Chemical Engineering at the
University of New South Wales in Sydney, Australia. He received his B.Sc. in Chemical Engineering from Queen’s University in Ontario, Canada, and his
M.S. and Ph.D. in Chemical Engineering from MIT.
Takashi Kei Kishimoto, Ph.D. has served as our Chief Scientific Officer since June 2011. Prior to joining Selecta, Dr. Kishimoto was Vice President of
Discovery Research at Momenta Pharmaceuticals, Inc., where he served in several leadership positions from March 2006 to June 2011 and led a
multidisciplinary team in advancing both novel and complex generic products for inflammation, oncology, and cardiovascular disease. He served as Senior
Director of Inflammation Research at Millennium Pharmaceuticals, Inc. from 1999 to 2006, where he provided the scientific leadership for four programs
in clinical development, and as an Associate Director of Research at Boehringer Ingelheim Pharmaceuticals. Dr. Kishimoto has published over 60 peer-
reviewed articles in scientific journals, including Nature, Science, Cell and the New England Journal of Medicine. Dr. Kishimoto received his B.A. from
New College of the University of South Florida and his Ph.D. in Immunology from Harvard University.
72
Elona Kogan, J.D. has served as our General Counsel and Secretary since March 2019. Ms. Kogan most recently served as General Counsel and head of
Government Relations at ARIAD Pharmaceuticals, a rare disease oncology company, from July 2016 to April 2017, where she was a key executive through
the acquisition of the company by Takeda Pharmaceuticals Company Ltd. Prior to joining ARIAD, from May 2011 to August 2015, Ms. Kogan led the
legal and government affairs functions of a publicly traded pharmaceutical company dedicated to developing treatments for central nervous system
disorders, where she played a central role in the strategic acquisition of the company by Otsuka Pharmaceutical Co. Ltd. Prior roles included positions of
increasing responsibility at King Pharmaceuticals, Bristol-Myers Squibb, and Bergen Brunswig Corporation. Ms. Kogan is also a member of the board of
directors of Cardax, Inc., a biotechnology company, and serves as the Chairperson of the Compensation Committee, and a member of the Audit Committee.
Ms. Kogan is a graduate of the SCALE program at Southwestern University School of Law. Ms. Kogan graduated cum laude from Columbia University,
Barnard College, with a degree in economics.
Alison D. Schecter, M.D. has served as our Chief Medical Officer since July 2019. Prior to joining Selecta, Dr. Schecter served as Global Project Head
(GPH), Rare Diseases at Sanofi, a pharmaceutical company, from January 2017 to July 2019. She also was the primary BD strategy liaison in Rare Disease.
Prior to Sanofi, Dr. Schecter was GPH at Baxalta, a pharmaceutical company, from September 2016 to December 2017. Prior to Baxalta, she was VP of
Cardiovascular and Metabolism (CVM) at the J&J Innovation Center, a pharmaceutical company, from January 2015 to September 2016. Previously, she
led translational medicine in CVM at Novartis from April 2008 to December 2014. Earlier, Dr. Schecter was Associate Professor in Immunology and
Medicine at Mount Sinai. Her innovative academic translational research led to a successful career in biotechnology. She completed her internal medicine
residency at Johns Hopkins Hospital, cardiology fellowship at Massachusetts General Hospital, and a research fellowship at Mount Sinai. She earned her
M.D. from SUNY Downstate.
Stephen Smolinski has served as our Chief Commercial Officer since October 2017. Mr. Smolinski previously served as the Vice President and Head of the
North American Rheumatology Business Unit of Sanofi/Genzyme, a pharmaceutical company from June 2015 to August 2017, where he led the
development of the company’s commercialization plans for the rheumatoid arthritis medicine KEVZARA®. Prior to this, he served as Group Vice
President of Immunology & Inflammation, Global Strategic Unit at Sanofi a pharmaceutical company, from July 2013 to June 2015. Mr. Smolinski also
previously held senior commercial roles at Roche-Genentech, Bristol-Myers Squibb, Johnson & Johnson and Savient Pharmaceuticals. Mr. Smolinski
received a B.S. in health care administration from Oregon State University.
73
Item 5. Market for Registrant's Common Equity, Related Stockholder Matters and Issuer Purchases of Equity Securities
PART II
Market Information
Our common stock is publicly traded on The Nasdaq Global Market under the symbol “SELB.”
Holders
As of March 6, 2020, there were approximately 86,420,195 shares of our common stock outstanding held by approximately 60 holders of record. The
actual number of stockholders is greater than this number of record holders, and includes stockholders who are beneficial owners, but whose shares are
held in street name by brokers and other nominees.
Dividends
We have never declared or paid any cash dividends on our capital stock. We intend to retain future earnings, if any, to finance the operation and expansion
of our business and do not expect to pay any cash dividends in the foreseeable future. Any future determination related to our dividend policy will be made
at the discretion of our board of directors after considering our financial condition, results of operations, capital requirements, business prospects and other
factors the board of directors deems relevant, and subject to the restrictions contained in any future financing instruments. In addition, our loan and security
agreement with SVB currently prohibits us from paying dividends on our equity securities, and any future debt agreements may likewise preclude us from
paying dividends. See “Management’s Discussion and Analysis of Financial Condition and Results of Operations-Liquidity and Capital Resources.”
Stock Performance Graph
The graph set forth below compares the cumulative total stockholder return on our common stock between June 21, 2016 (the date of our initial public
offering) and December 31, 2019, with the cumulative total return of (a) the Nasdaq Composite Index and (b) the Nasdaq Biotechnology Index, over the
same period. This graph assumes the investment of $100 at the market close on June 21, 2016 in our common stock, the Nasdaq Composite Index and the
Nasdaq Biotechnology Index and assumes the reinvestment of dividends, if any. The stock price performance of the following graph is not necessarily
indicative of future stock price performance.
COMPARISON OF CUMULATIVE TOTAL RETURN SELECTA BIOSCIENCES, INC.,
NASDAQ COMPOSITE INDEX AND NASDAQ BIOTECHNOLOGY INDEX
This performance graph shall not be deemed “soliciting material” or to be “filed” with the SEC for purposes of Section 18 of the Exchange Act, or
otherwise subject to the liabilities under that Section, and shall not be deemed to be incorporated by reference into any of our filings under the Securities
or the Exchange Act.
Purchases of Equity Securities by the Issuer or Affiliated Purchasers
We did not repurchase any of our equity securities during the quarter ended December 31, 2019.
Recent Sales of Unregistered Securities and Use of Proceeds from Registered Securities
74
On December 18, 2019, we entered into a Securities Purchase Agreement (the “2019 Purchase Agreement”) with the purchasers named therein (each, an
“Investor” and, collectively, the “Investors”), including certain members of our board of directors. Pursuant to the 2019 Purchase Agreement, we sold (i) an
aggregate of 37,634,883 shares of our common stock at a purchase price of $1.46 per share, which was equal to the most recent consolidated closing bid
price on the Nasdaq Global Market on December 18, 2019, (ii) warrants to purchase an aggregate of 22,988,501 shares of common stock at a purchase
price equal to $0.125 per share underlying each warrant, and (iii) pre-funded warrants to purchase an aggregate of 8,342,128 shares of common stock at a
purchase price equal to $1.46 per share underlying each pre-funded warrant, for aggregate net proceeds of approximately $65.6 million, after deducting
approximately $4.4 million in placement agent commissions and other transaction costs. Each warrant has an exercise price per share of common stock
equal to $1.46 per share. Each pre-funded warrant has an exercise price per share of common stock equal to $0.0001 per share. The closing of the offering
occurred on December 23, 2019.
This transaction was exempt from registration pursuant to Section 4(a)(2) of the Securities Act and Rule 506 of Regulation D promulgated thereunder, as a
transaction by an issuer not involving a public offering. Each Investor has represented that it is an accredited investor, as defined in Regulation D, and has
acquired the securities for investment only and not with a view to or for sale in connection with any distribution thereof, and appropriate legends have been
affixed to the securities issued in this transaction.
Item 6. Selected Consolidated Financial Data
You should read the following selected consolidated financial data together with our consolidated financial statements and the related notes and with the
“Management’s Discussion and Analysis of Financial Condition and Results of Operations” section of this Annual Report on Form 10-K. The selected
consolidated financial data in this section are not intended to replace the consolidated financial statements and are qualified in their entirety by the
consolidated financial statements and related notes included elsewhere in this Annual Report on Form 10-K.
We have derived the consolidated statement of operations and comprehensive loss data for the years ended December 31, 2019, 2018, and 2017, and the
consolidated balance sheet data as of December 31, 2019, and 2018, from our audited consolidated financial statements included elsewhere in this Annual
Report on Form 10-K. The consolidated statement of operations and comprehensive loss for the years ended December 31, 2016 and 2015 the consolidated
balance sheet data as of December 31, 2017, 2016 and 2015 are derived from our audited consolidated financial statements that are not included in this
Annual Report. Our historical results are not necessarily indicative of the results that should be expected in the future.
(In thousands, except share and per share data)
2019
2018
2017
2016
2015
Year Ended December 31,
Consolidated Statement of Operations Data
Grant and collaboration revenue
Operating expenses
Loss from operations
Loss on extinguishment of debt
Change in fair value of warrant liabilities
Other income (expense), net
Net loss
Net loss per share:
Basic and diluted
Weighted average common shares outstanding:
Basic and diluted
(In thousands)
Consolidated Balance Sheet Data
Cash, cash equivalents, short-term deposits and investments
Total assets
Loans payable
Warrant liabilities
Redeemable convertible preferred stock
Total stockholders' equity (deficit)
$
$
$
$
$
$
$
$
$
6,677
$
903
$
59,132
(52,455)
—
(857)
(2,038)
65,925
(65,022)
—
—
(314)
(55,350)
$
(65,336)
$
207 $
63,991
(63,784)
(673)
—
(864)
(65,321) $
8,083 $
42,753
(34,670)
—
—
(1,540)
(36,210) $
6,011
31,315
(25,304)
—
—
130
(25,174)
(1.22)
$
(2.92)
$
(3.20) $
(3.89) $
(15.13)
45,548,511
22,389,286
20,425,050
10,493,939
2,150,422
2019
2018
2017
2016
2015
As of December 31,
37,403
44,482
21,385
$
$
$
— $
— $
$
(5,418)
96,562 $
101,100 $
21,042 $
— $
— $
51,814 $
84,141 $
89,301 $
12,044 $
— $
— $
54,957 $
36,462
42,824
11,855
—
137,482
(116,493)
89,893
99,569
18,905
41,549
$
$
$
$
— $
$
8,397
75
Item 7. Management’s Discussion and Analysis of Financial Condition and Results of Operations
The following discussion and analysis of our financial condition and results of operations should be read in conjunction with “Item 6. Selected
Consolidated Financial Data” and our consolidated financial statements and related notes appearing elsewhere in this Annual Report on Form 10-K. This
discussion and other parts of this Annual Report on Form 10-K contain forward-looking statements that involve risks and uncertainties, such as statements
regarding our plans, objectives, expectations, intentions and projections. Our actual results could differ materially from those discussed in these forward-
looking statements. Important factors that could cause or contribute to such differences include, but are not limited to, those discussed in Item 1A “Risk
Factors.” A discussion of the year ended December 31, 2018 compared to the year ended December 31, 2017 has been reported previously in our Annual
Report on Form 10-K for the year ended December 31, 2018, filed with the SEC on March 15, 2019, under the heading “Management’s Discussion and
Analysis of Financial Condition and Results of Operations.”
OVERVIEW
We are a clinical-stage biopharmaceutical company using our ImmTOR platform with the goal to effectively and safely treat rare and serious diseases by
enabling the development of novel biologic therapies that would otherwise be limited by their immunogenicity. Many such diseases are treated with
biologic therapies that are foreign to the patient’s immune system and therefore elicit an undesired immune response.
Our proprietary tolerogenic ImmTOR platform encapsulates an immunomodulator in biodegradable nanoparticles and is designed to mitigate the formation
of ADAs by inducing antigen-specific immune tolerance to biologic drugs. We believe ImmTOR has potential to enhance the efficacy without
compromising the safety of existing approved biologic drugs, improve product candidates under development and enable novel therapeutic modalities, such
as re-administration of systemic gene therapy.
Our Current Programs
Chronic Refractory Gout
Our lead product candidate, SEL-212, is designed to be a monthly treatment for chronic refractory gout, a debilitating rare disease with an unmet medical
need. SEL-212 consists of a combination of our ImmTOR platform co-administered with pegadricase. Pegadricase is an investigational recombinant
pegylated uricase (urate oxidase), an enzyme not naturally found in humans, and is therefore highly immunogenic. This enzyme is designed to treat patients
with symptomatic gout, refractory to standard uric acid lowering treatment, by breaking down the excess uric acid to the more soluble allantoin. In
preclinical studies, we observed that ImmTOR, when co-administered with pegadricase, induced antigen-specific immune tolerance to pegadricase and
substantially reduced the formation of associated ADAs. Based on our Phase 1/2 clinical data, we believe that SEL-212 has the potential to control SUA
levels and mitigate the formation of ADAs in response to the therapeutic enzyme.
Our Phase 1 data provided evidence that ImmTOR mitigated the formation of ADAs against pegadricase in a dose-dependent manner after a single dose of
SEL-212. In our Phase 2 trial, ImmTOR inhibited the formation of ADAs in patients with up to five monthly doses, resulting in sustained reduction of SUA
levels. We also observed a lower-than-expected rate of gout flares in the first months after initiation of SEL-212 treatment, with further reductions observed
in months three to five. SEL-212, if successfully developed and approved, has the potential to offer a unique treatment for patients with chronic refractory
gout, including reduced immunogenicity, improved efficacy, and monthly dosing compared to other FDA-approved treatments, and provide clinical
evidence supporting the utility of our ImmTOR platform in providing patients with antigenic specific tolerance.
In March 2019, we initiated a Phase 2 head-to-head clinical trial of SEL-212 (COMPARE), in which SEL-212 is being compared against the current FDA-
approved therapy for chronic refractory gout, KRYSTEXXA, in multiple clinical sites in the United States. We completed enrollment of our Phase 2 head-
to-head (COMPARE) clinical study against KRYSTEXXA in December 2019 and expect to report top-line data in the third quarter of 2020. The two-
armed, open label trial has enrolled approximately 150 patients, randomized 1:1, with one arm receiving KRYSTEXXA (as set forth in the prescribing
information) and the other arm receiving six monthly doses of SEL-212. The primary endpoint in the study is the percentage of patients in each arm that
maintain SUA control below 6.0 mg/dL, for at least 80% of the time during months three and six. We plan to commence the Phase 3 clinical program in
SEL-212 in the second half of 2020. We will require additional resources to complete the planned Phase 3 clinical program for SEL-212.
We expect our clinical and, if approved, marketing strategy for SEL-212 to initially focus on the estimated 160,000 patients in the United States with
chronic refractory gout, and to focus on those patients that are being treated by rheumatologists.
Gene Therapy
76
In August 2019, we entered into a feasibility study and license agreement with AskBio, the AskBio Collaboration Agreement, pursuant to which we and
AskBio will conduct proof of concept studies to potentially validate the use of our ImmTOR platform in conjunction with an AAV gene therapy to mitigate
the formation of neutralizing anti-AAV capsid antibodies, which currently precludes redosing. The initial product candidate being developed under this
collaboration is gene therapy for MMA which can cause severe developmental defects and premature death as a result of an accumulation of toxic
metabolites. We previously conducted preclinical studies for this product candidate based on SEL-302 and will leverage that previous work within the
collaboration. If the proof of concept studies are successful, we will proceed with a collaboration to pursue the development and commercialization of AAV
gene therapy product candidates utilizing ImmTOR for the treatment of certain agreed serious rare and orphan genetic diseases. We plan to enter the clinic
under this collaboration in 2020.
Additionally, in December 2019 we entered into the AskBio License Agreement which provides AskBio with exclusive worldwide rights to our ImmTOR
platform to research, develop and commercialize certain AAV-gene therapy products targeting the GAA gene, or derivatives thereof, to treat Pompe
Disease.
In September 2018, we announced a collaboration with the European consortium, CureCN, for an ImmTOR+AAV gene therapy combination product
candidate in Crigler-Najjar syndrome, a rare genetic disorder characterized by an inability to properly convert and clear bilirubin from the body. We expect
the CureCN consortium to obtain scientific advice from the German drug regulatory authority in 2020.
In December 2016, we entered into the Spark License Agreement which provides Spark with exclusive worldwide rights to our ImmTOR platform to
research, develop and commercialize gene therapies for Factor VIII, an essential blood clotting protein relevant to the treatment of hemophilia A.
Our proprietary gene therapy product candidate, SEL-313, is being developed to treat OTC deficiency and is currently in preclinical development.
FINANCIAL OPERATIONS OVERVIEW
Financial Operations
To date, we have financed our operations primarily through the public offering and private placements of our securities, funding received from research
grants and collaboration arrangements and our credit facility. We do not have any products approved for sale and have not generated any product sales. All
of our revenue to date has been collaboration and grant revenue.
Since inception, we have incurred significant operating losses. We incurred net losses of $55.4 million and $65.3 million for the years ended December 31,
2019 and 2018, respectively. As of December 31, 2019, we had an accumulated deficit of $335.8 million. We expect to continue to incur significant
expenses and operating losses for at least the next several years as we:
-
-
-
-
-
-
conduct additional clinical trials for SEL‑212;
continue the research and development of our other product candidates as well as product candidates that we may be developing jointly with
collaboration partners;
seek to enhance our ImmTOR platform and discover and develop additional product candidates;
seek to enter into collaboration, licensing and other agreements, including, but not limited to research and development, and/or commercialization
agreements;
seek regulatory approvals for any product candidates that successfully complete clinical trials;
potentially establish a sales, marketing and distribution infrastructure and scales‑up external manufacturing capabilities to commercialize any products
for which we may obtain regulatory approval;
- maintain, expand and protect our intellectual property portfolio, including through licensing arrangements; and
-
add clinical, scientific, operational, financial and management information systems and personnel, including personnel to support our product
development and potential future commercialization efforts and to support our operations as a public company.
Until such time, if ever, as we can generate substantial product revenues, we expect to finance our cash needs through a combination of equity offerings,
debt financings, license and collaboration agreements, and research grants. We may be unable to raise capital when needed or on reasonable terms, if at all,
which would force us to delay, limit, reduce or terminate our product development or future commercialization efforts. We will need to generate significant
revenues to achieve profitability, and we may never do so.
77
We will require additional external sources of capital to complete the planned Phase 3 clinical program for SEL-212. Under the terms of our exclusive
patent license agreement with the Massachusetts Institute of Technology, or the MIT License, MIT may terminate the MIT License if we fail to meet a
diligence obligation, including the initiation of a Phase 3 clinical trial by a specified date in the fourth quarter of 2019. On December 13, 2019, we entered
into the Fourth Amendment, which we refer to as the MIT Amendment, to the Exclusive Patent License Agreement by and between us and the
Massachusetts Institute of Technology, or the MIT Agreement. Pursuant to the MIT Amendment, a provision of the MIT Agreement under which we were
obligated to initiate a Phase 3 clinical trial for a licensed product by a specified date in the fourth quarter of 2019 is tolled until the earlier of (i) a specified
date in the second quarter of 2020 or (ii) the effective date of a written amendment to the MIT Agreement. Further, pursuant to the MIT Amendment, the
parties agreed to negotiate in good faith to enter into a future amendment to the MIT Agreement after we provide MIT with an amended diligence plan. If
we are unable to reach an agreement with MIT regarding an acceptable amendment of the MIT License and if we are unable to cure the breach, there could
be a material adverse effect on our business.
We believe that our existing cash, cash equivalents, investments, and restricted cash as of December 31, 2019 will enable us to fund our operating expenses
and capital expenditure requirements into the first quarter of 2021. Because our current operating plan does not contain sufficient resources, we will require
additional external sources of capital to complete the planned Phase 3 clinical program for SEL-212. We have based this estimate on assumptions that may
prove to be wrong, and we could use our capital resources sooner than we currently expect. Because of the uncertainty in securing additional capital, we
have concluded that substantial doubt exists with respect to our ability to continue as a going concern within one year after the date of the filing of this
Annual Report on Form 10-K. For additional information, see “Liquidity and Capital Resources.”
The consolidated financial information presented below includes the accounts of Selecta Biosciences Inc. and our wholly owned subsidiaries, Selecta
(RUS) LLC, a Russian limited liability company, or Selecta RUS, and Selecta Biosciences Security Corporation, a Massachusetts securities corporation.
All intercompany accounts and transactions have been eliminated.
Grant and collaboration revenue
To date, we have not generated any product sales. Our revenue consists of grant and collaboration revenue, which includes amounts recognized related to
upfront and milestone payments for research and development funding under collaboration and license agreements. In addition, we earn revenue under the
terms of government contracts or grants, which require the performance of certain research and development activities. We expect that any revenue we
generate will fluctuate from quarter to quarter because of the timing and amount of fees, research and development reimbursements and other payments
from collaborators. We do not expect to generate revenue from product sales for at least the next several years. If we or our collaborators fail to complete
the development of our product candidates in a timely manner or fail to obtain regulatory approval as needed, our ability to generate future revenue will be
harmed, and will affect the results of our operations and financial position. For a further description of the agreements underlying our collaboration and
grant‑based revenue, see Notes 2 and 12 to our consolidated financial statements included elsewhere in this Annual Report on Form 10-K.
Research and development
Our research and development expenses consist of external research and development costs, which we track on a program‑by‑program basis and primarily
include CMO related costs, fees paid to CROs and internal research and development costs, which are primarily compensation expenses for our research
and development employees, lab supplies, analytical testing, allocated overhead costs and other related expenses. Our internal research and development
costs are often devoted to expanding our programs and are not necessarily allocable to a specific target.
We have incurred a total of $240.8 million in research and development expenses from inception through December 31, 2019, with a majority of the
expenses being spent on the development of SEL‑212 and a prior nicotine vaccine candidate, and the remainder being spent on our various discovery and
preclinical stage product candidate programs and the general expansion of our technology.
In connection with our intention to focus on advancing our ImmTOR platform, as stated in January 2019, we have ceased ongoing work on our immune
stimulation programs SELA-070 and SEL-701, and currently do not have plans to move these programs forward or to perform any additional work on
either of these programs.
As we expand the clinical development of SEL‑212 and our gene therapy programs, we expect our research and development expenses to increase.
We expense research and development costs as incurred. Conducting a significant amount of research and development is central to our business model.
Product candidates in clinical development generally have higher development costs than those in earlier stages of development, primarily due to the size,
duration and cost of clinical trials. We plan to increase our research and development expenses for the foreseeable future as we seek to complete
development of SEL‑212, and to further advance our preclinical and earlier stage research and development projects. The successful development of our
clinical and preclinical product candidates is highly uncertain. At this time, we cannot reasonably estimate the nature, timing or costs of the efforts that
78
will be necessary to complete the development of SEL‑212 or any of our preclinical programs or the period, if any, in which material net cash inflows from
these product candidates may commence. Clinical development timelines, the probability of success and development costs can differ materially from our
expectations. For example, if the FDA or another regulatory authority were to require us to conduct clinical trials beyond those which we currently expect
will be required for the completion of clinical development of a product candidate, or if we experience significant delays in enrollment in any of our
clinical trials, we could be required to expend significant additional financial resources and time to complete any clinical development.
The following table sets forth the components of our research and development expenses during the periods indicated (in thousands):
Research and development expenses (key projects and initiatives):
SEL-212
SELA-070
Discovery and preclinical stage product candidate programs, collectively
Other internal research and development expenses
Total research and development expenses
$
$
General and administrative
Year ended December 31,
2019
2018
2017
25,489 $
46
1,614
15,594
42,743 $
22,770 $
1,602
2,623
20,692
47,687 $
19,593
1,227
6,933
17,412
45,165
General and administrative expenses consist primarily of salaries and related benefits, including stock-based compensation, related to our executive,
finance, business development and support functions. Other general and administrative expenses include facility-related costs not otherwise allocated to
research and development expenses, travel expenses for our general and administrative personnel and professional fees for auditing, tax and corporate legal
services, including intellectual property-related legal services.
Investment income
Investment income consists primarily of interest income earned on our cash and cash equivalents and short-term investments.
Interest expense
Interest expense consists of interest expense on amounts borrowed under our credit facilities.
Other income (expense)
Other income (expense) consists primarily of issuance fees associated with warrant liabilities for the year ended December 31, 2019, and was de minimis
for each of the years ended December 31, 2018 and 2017.
Change in fair value of warrant liabilities
Common warrants classified as liabilities are remeasured at fair value, utilizing a Black-Scholes valuation methodology, quarterly with the change in fair
value recognized as a component of earnings.
Foreign currency transaction gain (loss)
The functional currency of our Russian subsidiary is the Russian ruble. In addition to holding cash denominated in Russian rubles, our Russian bank
accounts also hold cash balances denominated in U.S. dollars to facilitate payments to be settled in U.S. dollars or other currencies. At each of
December 31, 2019 and December 31, 2018, we maintained cash of $0.4 million in Russian banks, all of which was denominated in U.S. dollars. The
amounts denominated in U.S. dollars and used in transacting the day-to-day operations of our Russian subsidiary are subject to transaction gains and losses,
which are reported as incurred.
CRITICAL ACCOUNTING POLICIES AND USE OF ESTIMATES
Our management’s discussion and analysis of financial condition and results of operations is based on our consolidated financial statements, which have
been prepared in accordance with accounting principles generally accepted in the United States, or GAAP. The preparation of these financial statements
requires us to make estimates and judgments that affect the reported amounts of assets and liabilities and the disclosure of contingent assets and liabilities
in our consolidated financial statements, as well as the reported revenues and expenses during the reporting periods. These items are monitored and
analyzed by us for changes in facts and circumstances, and material changes in these estimates could occur in the future. We base our estimates on
historical experience, known trends and events, and on various other factors that we believe are reasonable under
79
the circumstances, the results of which form the basis for making judgments about the carrying value of assets and liabilities that are not readily apparent
from other sources. Changes in estimates are reflected in reported results for the period in which they become known. Actual results may differ materially
from these estimates under different assumptions or conditions.
Clinical Trial Costs
Clinical trial expenses are a significant component of research and development expenses, and we outsource a significant portion of these costs to third
parties. Third party clinical trial expenses include patient costs, clinical research organization costs and costs for data management. The accrual for site and
patient costs includes inputs such as estimates of patient enrollment, patient cycles incurred, clinical site activations, and other pass-through costs.
Payments for these activities are based on the terms of the individual arrangements, which may differ from the pattern of costs incurred, and are reflected
on the consolidated balance sheets as a prepaid asset or accrued clinical trial cost. These third party agreements are generally cancelable, and related costs
are recorded as research and development expenses as incurred. Non-refundable advance clinical payments for goods or services that will be used or
rendered for future R&D activities are recorded as a prepaid asset and recognized as expense as the related goods are delivered or the related services are
performed. We also record accruals for estimated ongoing clinical research and development costs. When evaluating the adequacy of the accrued liabilities,
we analyze progress of the studies, including the phase or completion of events, invoices received and contracted costs. Significant judgments and
estimates may be made in determining the accrued balances at the end of any reporting period. Actual results could differ from the estimates made by the
Company. The historical clinical accrual estimates made by the Company have not been materially different from the actual costs.
Revenue Recognition
Revenue is recognized when a customer obtains control of promised goods or services, in an amount that reflects the consideration which the entity expects
to receive in exchange for those goods or services. Pursuant to ASC 606, Revenue from Contracts with Customers (ASC 606), a customer is a party that has
contracted with an entity to obtain goods or services that are an output of the entity’s ordinary activities in exchange for consideration. To determine
revenue recognition for arrangements that an entity determines are within the scope of ASC 606, we perform the following five steps: (i) identify the
contract(s) with a customer; (ii) identify the performance obligations in the contract, including whether they are distinct in the context of the contract; (iii)
determine the transaction price, including the constraint on variable consideration; (iv) allocate the transaction price to the performance obligations in the
contract; and (v) recognize revenue when (or as) we satisfy each performance obligation. We only apply the five-step model to contracts when it is probable
that the entity will collect the consideration it is entitled to in exchange for the goods or services it transfers to the customer. At contract inception, once the
contract is determined to be within the scope of ASC 606, we assess the goods or services promised within each contract and determines those that are
performance obligations, and assesses whether each promised good or service is distinct. If a promised good or service is not distinct, it is combined with
other performance obligations. We then recognize as revenue the amount of the transaction price that is allocated to the respective performance obligation
when (or as) the performance obligation is satisfied. For example, certain performance obligations associated with Spark (see Note 12 to our consolidated
financial statements included elsewhere in this Annual Report on Form 10-K) will be satisfied over time, and revenue will be recognized using the output
method, based on the proportion of actual deliveries to the total expected deliveries over the initial term.
Collaboration and Grant Revenue: We currently generate our revenue through grants, collaboration and license agreements with strategic collaborators for
the development and commercialization of product candidates. Grants and license agreements with customers are accounted for in accordance with ASC
606. We analyze collaboration arrangements by first assessing whether they are within the scope of ASC Topic 808, Collaborative Arrangements (ASC
808), and evaluate whether such arrangements involve joint operating activities performed by parties that are both active participants in the activities and
exposed to significant risks and rewards that are dependent on the commercial success of such activities. Collaboration agreements with customers that are
not within the scope of ASC 808 are accounted for in accordance with ASC 606. To the extent the collaboration agreement is within the scope of ASC 808,
we also assess whether any aspects of the agreement are within the scope of other accounting literature (specifically ASC 606). We early adopted ASU No.
2018-18, Collaborative Arrangements (Topic 808): Clarifying the Interaction between Topic 808 and Topic 606, which provides guidance on evaluating
certain transactions between collaborative arrangement participants. If we conclude that some or all aspects of the agreement are distinct and represent a
transaction with a customer, we account for those aspects of the arrangement within the scope of ASC 606. We recognize the shared costs incurred that are
not within the scope of other accounting literature as a component of the related expense in the period incurred by analogy to ASC 730, Research and
Development (ASC 730), and record reimbursements from counterparties as an offset to the related costs. In determining the appropriate amount of revenue
to be recognized as it fulfills our obligations under the agreements in accordance with ASC 606, we perform the five steps above. As part of the accounting
for the arrangement, we must develop assumptions that require judgment to determine the stand-alone selling price for each performance obligation
identified in the contract. We use key assumptions to determine the stand-alone
80
selling price, which may include market conditions, reimbursement rates for personnel costs, development timelines and probabilities of regulatory success.
The terms of our arrangements typically include one or more of the following: (i) up-front fees; (ii) milestone payments related to the achievement of
development, regulatory, or commercial goals; (iii) royalties on net sales of licensed products; (iv) reimbursements or cost-sharing of R&D expenses; and
(v) profit/loss sharing arising from co-promotion arrangements.
Licenses of intellectual property: If the license to our intellectual property is determined to be distinct from the other performance obligations identified in
the arrangement, we recognize revenues from non-refundable, up-front fees allocated to the license when the license is transferred to the customer and the
customer is able to use and benefit from the license. If not distinct, the license is combined with other performance obligations in the contract. For licenses
that are combined with other performance obligations, we assess the nature of the combined performance obligation to determine whether the combined
performance obligation is satisfied over time or at a point in time and, if over time, the appropriate method of measuring progress for purposes of
recognizing revenue. We evaluate the measure of progress each reporting period and, if necessary, adjusts the measure of performance and related revenue
recognition. Optional licenses are evaluated to determine if they are issued at a discount, and therefore, represent material rights and accounted for as
separate performance obligations.
Milestone Payments: At the inception of each arrangement that includes developmental and regulatory milestone payments, we evaluate whether the
achievement of each milestone specifically relates to our efforts to satisfy a performance obligation or transfer a distinct good or service within a
performance obligation. If the achievement of a milestone is considered a direct result of our efforts to satisfy a performance obligation or transfer a distinct
good or service and the receipt of the payment is based upon the achievement of the milestone, the associated milestone value is allocated to that distinct
good or service. If the milestone payment is not specifically related to our effort to satisfy a performance obligation or transfer a distinct good or service,
the amount is allocated to all performance obligations using the relative standalone selling price method. We also evaluate the milestones to determine
whether they are considered probable of being reached and estimates the amount to be included in the transaction price using the most likely amount
method. If it is probable that a significant revenue reversal would not occur, the associated milestone value is included in the transaction price to be
allocated, otherwise, such amounts are constrained and excluded from the transaction price. At the end of each subsequent reporting period, we re-evaluate
the probability of achievement of such development milestones and any related constraint, and if necessary, adjusts our estimate of the transaction
price. Any such adjustments to the transaction price are allocated to the performance obligations on the same basis as at contract inception. Amounts
allocated to a satisfied performance obligation shall be recognized as revenue, or as a reduction of revenue, in the period in which the transaction price
changes.
Manufacturing Supply Services: Arrangements that include a promise for future supply of drug substance or drug product for either clinical development or
commercial supply at the customer’s discretion are evaluated to determine if they are distinct and optional. For optional services that are distinct, we assess
if they are priced at a discount, and therefore, provide a material right to the licensee to be accounted for as separate performance obligations.
Royalties: For arrangements that include sales-based royalties, including milestone payments based on the level of sales, and the license is deemed to be the
predominant item to which the royalties relate, we will recognize revenue at the later of (i) when the related sales occur, or (ii) when the performance
obligation to which some or all of the royalty has been allocated has been satisfied (or partially satisfied) in accordance with the royalty recognition
constraint.
Warrant Liabilities
In December 2019, we issued common warrants in connection with the 2019 Purchase Agreement. Pursuant to the terms of these common warrants, we
could be required to settle the common warrants in cash in the event of certain acquisitions of the Company and, as a result, the common warrants are
required to be measured at fair value and reported as a liability on the balance sheet. We recorded the fair value of the common warrants of $40.7 million
upon issuance using the Black-Scholes valuation model, and are required to revalue the common warrants at each reporting date with any changes in fair
value recorded on our statement of operations. Inputs used to determine estimated fair value of the common warrant liabilities include the estimated fair
value of the underlying stock at the valuation date, the estimated term of the warrants, risk-free interest rates, expected dividends and the expected volatility
of the underlying stock. As of December 31, 2019, the fair value of the common warrants of $41.5 million was recorded as a long-term liability on our
balance sheet, which resulted in a change in fair value of $0.9 million for the year ended December 31, 2019. Additionally, we allocated $1.2 million of the
transaction costs associated with the 2019 Purchase Agreement to financing expense on our statement of operations. The remaining $3.2 million of
transaction costs were offset against the proceeds allocated to our common stock and pre-funded warrants.
Stock‑Based Compensation
We account for all stock‑based compensation granted to employees and non‑employees using a fair value method. Stock‑based compensation is measured
at the grant date fair value using the Black‑Scholes option pricing model and is recognized over the requisite service period of the awards, usually the
vesting period, on a straight‑line basis, net of estimated forfeitures. We
81
reduce recorded stock‑based compensation for estimated forfeitures. To the extent that actual forfeitures differ from management’s estimates, the
differences are recorded as a cumulative adjustment in the period the estimates were adjusted. Stock‑based compensation expense recognized in the
consolidated financial statements is based on awards that are ultimately expected to vest.
Emerging Growth Company Status
The Jumpstart Our Business Startups Act of 2012, or the JOBS Act, permits an ‘‘emerging growth company’’ such as us to take advantage of an extended
transition period to comply with new or revised accounting standards applicable to public companies until those standards would otherwise apply to private
companies. We have irrevocably elected not to avail ourselves of this exemption and, therefore, we will be subject to the same new or revised accounting
standards as other public companies that are not emerging growth companies.
Smaller Reporting Company
We qualify as a “smaller reporting company” under the rules of the Securities Act and the Exchange Act. As a result, in addition to the exemptions
available to us as an “emerging growth company,” we may choose to take advantage of certain scaled disclosure requirements available specifically to
smaller reporting companies. Additionally, even if we cease to be an emerging growth company as noted above, as long as we continue to be a smaller
reporting company, we may continue to rely on the reduced executive compensation disclosure obligations available to emerging growth companies. We
will remain a smaller reporting company until the last day of the fiscal year in which the aggregate market value of our common stock held by non-
affiliated persons and entities, or our public float, was less than $250 million as of the last business day of our most recently completed second fiscal
quarter, or the last day of the fiscal year in which we have at least $100 million in revenue and at least $700 million in public float as of the last business
day of our most recently completed second fiscal quarter.
RESULTS OF OPERATIONS
Comparison of the Years Ended December 31, 2019 and 2018
Revenue
The following is a comparison of revenue for the years ended December 31, 2019 and 2018 (in thousands, except percentages):
Grant revenue
Collaboration revenue
Total revenue
Year Ended December 31,
2019
2018
$
$
— $
6,677
6,677
$
903 $
—
903
$
Increase
(decrease)
(903)
6,677
5,774
—%
—%
639%
During the year ended December 31, 2019, we recognized $6.7 million in revenue upon expiration of the term for Spark to exercise additional target
options that represented material rights and less than $0.1 million of revenue for two shipments to Spark under our collaboration agreement. During the
year ended December 31, 2018, we recognized the remaining $0.9 million in grant revenues from NIDA after receiving final approval from NIDA.
Research and development
The following is a comparison of research and development expenses for the years ended December 31, 2019 and 2018 (in thousands, except percentages):
Research and development
$
42,743 $
47,687 $
(4,944)
(10)%
Year Ended December 31,
2019
2018
Increase
(decrease)
During the year ended December 31, 2019, our research and development expenses decreased by $5.0 million, or 10%, as compared to 2018. The decrease
reflects reduced costs in 2019 resulting from the completion of prior programs in 2018 combined with reduced salaries and benefits resulting from the
headcount reduction in early 2019. The cost reductions were offset by an overall increase in costs incurred on our lead product candidate, SEL-212.
General and administrative
82
The following is a comparison of general and administrative expenses for the years ended December 31, 2019 and 2018 (in thousands, except percentages):
General and administrative
$
16,389 $
18,238 $
(1,849)
(10)%
Year Ended December 31,
2019
2018
Increase
(decrease)
During the year ended December 31, 2019, our general and administrative expenses decreased by $1.8 million, or 10%, as compared to 2018. The decrease
is the result of lower salary and stock compensation expense resulting from a reduction in headcount at the end of 2018, and lower patent and professional
fees.
Investment income
Investment income remained relatively unchanged during the years ended December 31, 2019 as compared to 2018.
Foreign currency transaction gain (loss)
We recognized minimal foreign currency losses of less than $0.1 million and gains of $0.1 million during the year ended December 31, 2019 and 2018,
respectively.
Interest expense
Interest expense was $1.5 million for each of the years ended December 31, 2019 and 2018, representing interest expense and amortization of the carrying
costs of our credit facilities.
Change in fair value of warrant liabilities
We recognized $0.9 million as a change in the fair value of warrant liabilities utilizing a Black-Scholes valuation methodology, for the year ended
December 31, 2019, primarily driven by an increase in the share price from issuance (see Note 5).
Other income (expense)
Other (expense) income was $1.3 million and less than $0.1 million for the years ended December 31, 2019 and 2018, respectively. The increase in the
other expense during 2019 was the result of $1.2 million of fees incurred as a result of the issuance of liability classified common warrants in our
December 2019 private placement (see Note 10).
Net Loss
Net loss for the year ended December 31, 2019 was $55.4 million compared to $65.3 million for the year ended December 31, 2018.
LIQUIDITY AND CAPITAL RESOURCES
Since our inception, we have incurred recurring net losses. We expect that we will continue to incur losses and that such losses will increase for the
foreseeable future. We expect that our research and development and general and administrative expenses will continue to increase and, as a result, we will
need additional capital to fund our operations, which we may raise through a combination of equity offerings, debt financings, third‑party funding and other
collaborations and strategic alliances.
From our inception through December 31, 2019, we have raised an aggregate of $416.0 million to fund our operations, which includes $118.5 million from
the sale of preferred stock, $11.1 million in government grant funding, $25.3 million from borrowings under our credit facility, $46.3 million from our
collaborations and license agreements, $64.5 million in combined net proceeds from our initial public offering $118.4 million in combined net proceeds
from private placements of our common stock in June 2017 and August and December 2019, $30.9 million from an underwritten follow-on offering of our
common stock in January 2019, and $1.0 million in aggregate net proceeds from "at-the-market" offerings of our common stock in 2019.
Collaborations
On December 17, 2019, we entered into the AskBio License Agreement. Pursuant to the AskBio License Agreement, AskBio has exercised its option to
exclusively license the Company’s intellectual property rights covering ImmTOR to research, develop, and commercialize certain AAV genetherapy
products utilizing ImmTOR, and targeting the GAA gene, or derivatives thereof, to treat Pompe Disease. As of December 31, 2019, AskBio paid $2.0
million of the aggregate $7.0 million of upfront fees.
Financings
On December 23, 2019, we sold an aggregate of 37,634,883 shares of our common stock at a purchase price of $1.46 per share, warrants to purchase an
aggregate of 22,988,501 shares of common stock at a purchase price of $0.125 per share underlying
83
each common warrant, and pre-funded warrants to purchase an aggregate of 8,342,128 shares of common stock at a purchase price of $1.46 per share for
net proceeds of $65.6 million, after deducting commissions and other transaction costs.
On August 19, 2019, we sold 3,178,174 shares of its common stock pursuant to a Stock Purchase Agreement to individual investors, including certain of
our executive officers and members of our board of directors for aggregate net proceeds of approximately $5.7 million, after deducting transaction costs.
On January 25, 2019, we completed a public offering of 20,000,000 shares of our common stock at a public offering price of $1.50 per share. On
January 29, 2019, an additional 2,188,706 shares were sold at a public offering price of $1.50 per share. The total net proceeds from the offering were $30.9
million, after deducting underwriting discounts and commissions.
In August 2017, we entered into a sales agreement, or the Sales Agreement, with Jefferies LLC, as sales agent, pursuant to which we may, from time to
time, issue and sell common stock with an aggregate value of up to $50 million in an "at-the-market" offering. Sales of common stock, if any, pursuant to
the Sales Agreement, may be made in sales deemed to be an “at the market offering” as defined in Rule 415(a) of the Securities Act, including sales made
directly through the Nasdaq Global Market or on any other existing trading market for our common stock. We intend to use the proceeds from the offering
for working capital and other general corporate purposes. We may suspend or terminate the Sales Agreement at any time. During the year ended
December 31, 2019, we sold 615,453 shares of our common stock pursuant to the Sales Agreement at an average price of approximately $1.84 per share for
aggregate net proceeds of $1.0 million, after deducting commissions and other transaction costs.
As of December 31, 2019, our cash, cash equivalents, and restricted cash were $91.6 million, of which $1.7 million was restricted cash related to lease
commitments and $0.4 million was held by our Russian subsidiary designated solely for use in its operations. Our Russian subsidiary cash is consolidated
for financial reporting purposes.
In addition to our existing cash equivalents, we receive research and development funding pursuant to our research grants and collaboration agreements.
Currently, funding from research grants and payments under our collaboration agreements represent our only source of committed external funds.
Indebtedness
On September 12, 2017, we entered into a term loan facility of up to $21.0 million with Silicon Valley Bank, a California corporation, or SVB, the
proceeds of which were used to repay our previously existing term loan facility with Oxford Finance LLC and Pacific Western Bank, as successor in
interest to Square 1 Bank, and for general corporate and working capital purposes. The term loan facility is governed by a loan and security agreement,
dated September 12, 2017, between us and SVB, which was funded in full on September 13, 2017. The term loan facility with SVB is secured by a lien on
substantially all assets, other than intellectual property, provided that such lien on assets includes any rights to payments and proceeds from the sale,
licensing or disposition of intellectual property. We also granted SVB a negative pledge with respect to our intellectual property.
The term loan facility contains customary covenants and representations, including but not limited to financial reporting obligations and limitations on
dividends, indebtedness, collateral, investments, distributions, transfers, mergers or acquisitions, taxes, corporate changes, deposit accounts, and
subsidiaries. The term loan facility also contains other customary provisions, such as expense reimbursement, non-disclosure obligations as well as
indemnification rights for the benefit of SVB.
The events of default under the term loan facility include, but are not limited to, our failure to make any payments of principal or interest under the term
loan facility or other transaction documents, our breach or default in the performance of any covenant under the term loan facility or other transaction
documents, the occurrence of a material adverse effect, making a false or misleading representation or warranty in any material respect under the term loan
facility, our insolvency or bankruptcy, any attachment or judgment on our assets in excess of approximately $0.3 million, or the occurrence of any default
under any of our agreements or obligations involving indebtedness in excess of approximately $0.3 million. If an event of default occurs, SVB is entitled to
take enforcement action, including acceleration of amounts due under the term loan facility. If we raise any additional debt financing, the terms of such
additional debt could further restrict our operating and financial flexibility.
Plan of operations and future funding requirements
As of the date of this Annual Report on Form 10-K, we have not generated any product sales. We do not know when, or if, we will generate revenue from
product sales. We will not generate significant revenue from product sales unless and until we obtain regulatory approval and commercialize one of our
current or future product candidates. Our primary uses of capital are, and we expect will continue to be, compensation and related expenses, third-party
clinical research and development services, laboratory and related supplies, clinical costs, legal and other regulatory expenses, and general overhead costs.
We expect that we will continue to generate losses for the foreseeable future, and we expect the losses to increase as we continue the development of, and
seek regulatory approvals for, our product candidates, and begin to commercialize any approved products. We are subject to risks in the development of our
products, and we may encounter unforeseen expenses, difficulties,
84
complications, delays and other unknown factors that may adversely affect our business. We expect that we will need substantial additional funding to
support our continuing operations.
As of December 31, 2019 and December 31, 2018, we had an accumulated deficit of $335.8 million and $280.4 million, respectively. We anticipate
operating losses to continue for the foreseeable future due to, among other things, costs related to research, development of our product candidates,
conducting preclinical studies and clinical trials, and our administrative organization. We will require substantial additional financing to fund our operations
and to continue to execute our strategy, and we will pursue a range of options to secure additional capital.
Management is exploring various sources of funding such as strategic collaborations and the issuance of equity to fund our operations. If we raise
additional funds through strategic collaborations and alliances, which may include existing collaboration partners, we may have to relinquish valuable
rights to our technologies or product candidates, or grant licenses on terms that are not favorable to us. To the extent that we raise additional capital through
the sale of equity, the ownership interest of our existing shareholders will be diluted and other preferences may be necessary that adversely affect the rights
of existing shareholders.
We will require additional external sources of capital to complete the planned Phase 3 clinical program for SEL-212. Under the terms of our exclusive
patent license agreement with the Massachusetts Institute of Technology, or the MIT License, MIT may terminate the MIT License if we fail to meet a
diligence obligation, including the initiation of a Phase 3 clinical trial by a specified date in the fourth quarter of 2019. On December 13, 2019, we entered
into the Fourth Amendment, which we refer to as the MIT Amendment, to the Exclusive Patent License Agreement by and between us and the
Massachusetts Institute of Technology, or the MIT Agreement. Pursuant to the MIT Amendment, a provision of the MIT Agreement under which we were
obligated to initiate a Phase 3 clinical trial for a licensed product by a specified date in the fourth quarter of 2019 is tolled until the earlier of (i) a specified
date in the second quarter of 2020 or (ii) the effective date of a written amendment to the MIT Agreement. Further, pursuant to the MIT Amendment, the
parties agreed to negotiate in good faith to enter into a future amendment to the MIT Agreement after we provide MIT with an amended diligence plan. If
we are unable to reach an agreement with MIT regarding an acceptable amendment of the MIT License and if we are unable to cure the breach, there could
be a material adverse effect on our business.
We believe that our existing cash, cash equivalents, investments, and restricted cash as of December 31, 2019 will enable us to fund our operating expenses
and capital expenditure requirements into the first quarter of 2021. We plan to commence our Phase 3 clinical program in SEL-212 in the second half of
2020. Because our current operating plan does not contain sufficient resources, we will require additional external sources of capital to complete the
planned Phase 3 clinical program for SEL-212. We have based this estimate on assumptions that may prove to be wrong, and we could use our capital
resources sooner than we currently expect. Because of the uncertainty in securing additional capital, we have concluded that substantial doubt exists with
respect to our ability to continue as a going concern within one year after the date of the filing of this Annual Report on Form 10-K.
Our future capital requirements will depend on many factors, including:
-
-
-
-
-
-
-
-
-
-
-
the scope, progress, results and costs of our clinical trials of SEL-212;
the number of product candidates that we pursue;
our collaboration agreements remaining in effect, our entering into additional collaboration agreements and our ability to achieve milestones under
these agreements;
the cost of manufacturing clinical supplies of our product candidates;
our headcount growth and associated costs;
the scope, progress, results and costs of preclinical development, laboratory testing and clinical trials for our other product candidates;
the costs, timing and outcome of regulatory review of our product candidates;
the costs and timing of future commercialization activities, including manufacturing, marketing, sales and distribution, for any of our product
candidates for which we receive marketing approval;
the revenue, if any, received from commercial sales of our product candidates for which we receive marketing approval;
the costs and timing of preparing, filing and prosecuting patent applications, maintaining and enforcing our intellectual property rights and defending
any intellectual property-related claims;
the effect of competing technological and market developments; and
85
-
the extent to which we acquire or invest in businesses, products and technologies, including entering into licensing or collaboration arrangements for
product candidates.
Summary of Cash Flows
(In thousands)
Cash provided by (used in):
Operating activities
Investing activities
Financing activities
Effect of exchange rate changes on cash
Net change in cash, cash equivalents, and restricted cash
Operating activities
Year Ended December 31,
2019
2018
2017
$
$
(51,435)
$
229
105,041
34
53,869
$
(59,161) $
25,272
697
(153)
(33,345) $
(52,026)
(2,098)
66,023
78
11,977
Net cash used in operating activities for the year ended December 31, 2019 was $51.4 million compared to $59.2 million in the same period in 2018, a
decrease of $7.8 million. The decrease in net cash used in operating activities was primarily due to a $10.0 million decrease in recorded net loss, a decrease
of $5.8 million in prepaid expenses, and a decrease of $1.4 million resulting from non-cash charges which were offset by an increase of $4.9 million in
accrued expenses and other liabilities, and an increase of $5.0 million in accounts receivable. The change in deferred revenue is due to the receipt of $2.0
million and a receivable of $5.0 million in proceeds from AskBio offset by $6.7 million from the expiration of the term for Spark to exercise additional
target options.
Investing activities
Net cash provided by investing activities for the year ended December 31, 2019 was $0.2 million compared to net cash provided from investing activities
of $25.3 million in the same period in 2018. The net cash provided by investing activities in 2019 was the result of purchases of short-term investments of
$18.2 million, offset by $16.4 million of maturities and $2.0 million of sales of short term investments.
The net cash provided by investing activities in 2018 was primarily due to receipts of $41.7 million from maturities of short-term investments, offset by
$15.6 million of purchases of short-term investments.
Financing activities
Net cash provided by financing activities for the year ended December 31, 2019 was $105.0 million compared to $0.7 million in the same period in 2018.
The net cash provided by financing activities in 2019 was the result of $30.9 million net proceeds from an underwritten follow-on offering of our common
stock in January, $75.7 million net proceeds from private placement offerings in August and December and $1.0 million net proceeds from "at-the-market"
offerings, offset by $2.8 million principal payment on outstanding debt.
The net cash provided by financing activities in 2018 was due to $0.2 million from the issuance of common stock under the ESPP and $0.5 million from
the exercise of employee stock options.
Contractual Obligations
The following summarizes our principal contractual obligations as of December 31, 2019:
Operating leases obligations (1)
Research and development contract obligations (2)
Debt obligations (3)
Total contractual obligations
Total
2020
2021
2022
2023
Later
$
16,169
$
1,566
$
180
20,261
60
9,084
$
36,610
$
10,710
$
1,811 $
60
8,716
10,587 $
1,865 $
60
2,461
4,386 $
1,921 $
—
—
1,921 $
9,006
—
—
9,006
(1) Operating lease obligations represent future minimum lease payments under noncancellable property leases in Watertown, Massachusetts. The minimum lease payments do not include
common area maintenance charges, real estate taxes or any sublease income we may earn.
(2) Research and development contract obligations represent minimum annual license fees payable to universities or partners under our license agreements. Under our license agreement with the
Massachusetts Institute of Technology, or MIT, milestone payments are due upon the occurrence of certain events and
86
royalty payments commence upon our commercialization of a product. For purposes of presenting our contractual obligations under the MIT agreement, we have assumed license payments are
fully offset by royalty payments in 2023.
(3) Debt obligations payments are based on the contractual payment dates.
Recent Accounting Pronouncements
For a discussion of recently adopted or issued accounting pronouncements please refer to Part IV, Note 2 to our consolidated financial statements included
elsewhere in this Annual Report on Form 10-K.
Off-Balance Sheet Arrangements
As of December 31, 2019, we did not have any off-balance sheet arrangements as defined in the rules and regulations of the Securities and Exchange
Commission.
Item 7A. Quantitative and Qualitative Disclosures About Market Risk
The market risk inherent in our financial instruments and in our financial position represents the potential loss arising from adverse changes in interest
rates. As of December 31, 2019 and December 31, 2018, we had cash, cash equivalents, restricted cash and investments of $91.6 million and $37.7 million,
respectively, consisting of non‑interest and interest‑bearing money market accounts. Our primary exposure to market risk is interest rate sensitivity, which
is affected by changes in the general level of U.S. interest rates. Due to the short‑term and the low risk profile of our money market accounts and
investments, and our current plan to hold investments to maturity, an immediate 100 basis point change in interest rates would not have a material effect on
the fair market value of our cash equivalents or short-term investments.
In addition, we are subject to currency risk for balances held in Russian rubles in our foreign subsidiary. We hold portions of our funds in both U.S. dollars
and Russian rubles. The exchange rate between the U.S. dollar and Russian ruble changes from period to period. As of December 31, 2019, we held cash
and cash equivalents totaling $0.4 million in Russian banks to support our Russian subsidiary, all of which were denominated in U.S. dollars. We do not
hedge against foreign currency risks. We do not believe that inflation and changing prices had a significant impact on our results of operations for any
periods presented herein.
Item 8. Financial Statements and Supplementary Data
The consolidated financial statements together with the report of our independent registered public company accounting firm, required to be filed pursuant
to this Item 8 are appended to this Annual Report on Form 10-K. An index of those consolidated financial statements is found in Item 15 of this Annual
Report on Form 10-K.
Item 9. Changes in and Disagreements With Accountants on Accounting and Financial Disclosure
None.
Item 9A. Controls and Procedures
Limitations on effectiveness of controls and procedures
In designing and evaluating our disclosure controls and procedures, management recognizes that any controls and procedures, no matter how well designed
and operated, can provide only reasonable assurance of achieving the desired control objectives. In addition, the design of disclosure controls and
procedures must reflect the fact that there are resource constraints and that management is required to apply judgment in evaluating the benefits of possible
controls and procedures relative to their costs.
Evaluation of disclosure controls and procedures
Our management, with the participation of our Chief Executive Officer and Chief Financial Officer, evaluated, as of the end of the period covered by this
Annual Report on Form 10-K, the effectiveness of our disclosure controls and procedures (as defined in Rules 13a-15(e) and 15d-15(e) under the Securities
Exchange Act of 1934, as amended (the “Exchange Act”)). Based on that evaluation, our Chief Executive Officer and Chief Financial Officer concluded
that our disclosure controls and procedures were effective at the reasonable assurance level as of December 31, 2019.
Management’s annual report on internal control over financial reporting
87
Our management is responsible for establishing and maintaining adequate internal control over our financial reporting, as such term is defined in Rule 13a-
15(f) under the Exchange Act.
Our management conducted an assessment of the effectiveness of our internal control over financial reporting based on the criteria set forth in “Internal
Control - Integrated Framework (2013)” issued by the Committee of Sponsoring Organizations of the Treadway Commission.
Based on this assessment, our management concluded that, as of December 31, 2019, our internal control over financial reporting was effective.
Attestation Report of the Registered Public Accounting Firm
This Annual Report on Form 10-K does not include an attestation report of our registered public accounting firm due to an exemption established by the
JOBS Act for "emerging growth companies."
Changes in internal control over financial reporting
There were no changes in our internal control over financial reporting (as defined in Rules 13a-15(f) and 15d-15(f) under the Exchange Act) during the
three months ended December 31, 2019 that have materially affected, or are reasonably likely to materially affect, our internal control over financial
reporting.
Item 9B. Other Information.
None.
88
Item 10. Directors, Executive Officers and Corporate Governance
PART III
Our board of directors has adopted a written Code of Business Conduct and Ethics applicable to all officers, directors and employees, including our
principal executive officer, principal financial officer, principal accounting officer or controller, or persons performing similar functions. We have posted a
current copy of our Code of Business Conduct and Ethics on our website at www.selectabio.com in the “Investors & Media” section under “Corporate
Governance.” We intend to satisfy the disclosure requirement under Item 5.05 of Form 8-K regarding amendment to, or waiver from, a provision of our
Code of Business Conduct and Ethics, as well as Nasdaq’s requirement to disclose waivers with respect to directors and executive officers, by posting such
information on our website at the address and location specified above. The information contained on our website is not incorporated by reference into this
Annual Report on Form 10-K.
The information required by this Item is contained in part under the caption “Information about our Executive Officers” at the end of Part I of this Annual
Report on Form 10-K. The remainder of the response to this item will be included in our definitive Proxy Statement for the 2020 Annual Meeting of
Stockholders under the headings “Proposal 1-Election of Directors,” “Delinquent Section 16(a) Reports,” and “Committees of the Board” and is
incorporated herein by reference.
Item 11. Executive Compensation
The information required by this Item regarding executive compensation will be included in our definitive Proxy Statement for the 2020 Annual Meeting of
Stockholders under the headings “Executive and Director Compensation” and “Compensation Committee Interlocks and Insider Participation” and is
incorporated herein by reference, as applicable.
Item 12. Security Ownership of Certain Beneficial Owners and Management and Related Stockholder Matters
The information required by this Item will be included in our definitive Proxy Statement for the 2020 Annual Meeting of Stockholders under the headings
“Security Ownership of Certain Beneficial Owners and Management” and “Executive and Director Compensation-Equity Compensation Plan Information”
and is incorporated herein by reference.
Item 13. Certain Relationships and Related Transactions, and Director Independence
The information required by this Item will be included in our definitive Proxy Statement for the 2020 Annual Meeting of
Stockholders under the headings “Corporate Governance,” “Committees of the Board” and “Certain Relationships” and is incorporated herein by reference.
Item 14. Principal Accountant Fees and Services
The information required by this Item regarding principal accountant fees and services will be included in our definitive Proxy Statement for the 2020
Annual Meeting of Stockholders under the heading “Independent Registered Public Accounting Firm Fees and Other Matters” and is incorporated herein
by reference.
89
Item 15. Exhibits, Financial Statement Schedules
PART IV
(a)(1) Financial Statements
The financial statements listed below are filed as part of this Annual Report on Form 10-K.
INDEX TO CONSOLIDATED FINANCIAL STATEMENTS
Report of Independent Registered Public Accounting Firm
Consolidated Balance Sheets at December 31, 2019 and 2018
Consolidated Statements of Operations and Comprehensive Loss for the years ended December 31, 2019, 2018 and 2017
Consolidated Statements of Changes in Stockholders' Equity (Deficit) for the years ended December 31, 2019, 2018 and 2017
Consolidated Statements of Cash Flows for the years ended December 31, 2019, 2018 and 2017
Notes to Consolidated Financial Statements
F-1
F-2
F-3
F-4
F-5
F-7
(a)(2) Financial Statement Schedules
All financial schedules have been omitted because the required information is either presented in the consolidated financial statements filed as part of this
Annual Report on Form 10-K or the notes thereto or is not applicable or required.
(a)(3) Exhibits
The following is a list of exhibits filed as part of this Annual Report on Form 10-K.
Exhibit
Number
3.1
3.2
4.1
4.2
Exhibit Description
Restated Certificate of Incorporation of Selecta
Biosciences, Inc.
Amended and Restated By-laws of Selecta
Biosciences, Inc.
Fifth Amended and Restated Investors' Rights
Agreement, dated as of August 26, 2015, by
and between the Registrant and each of the
stockholders party thereto, as amended by
Amendment No. 1 to Fifth Amended and
Restated Investors Rights Agreement, dated as
of June 7, 2016
Specimen Stock Certificate evidencing the
shares of common stock
Incorporated by Reference
Form
8-K
File No.
001-37798
Exhibit
3.1
8-K
001-37798
S-1/A
333-211555
3.2
4.1
Filing
Date
6/29/2016
6/29/2016
6/8/2016
Filed
Herewith
S-1
333-211555
4.2
5/24/2016
90
4.3
4.4
4.5
4.6
4.7
4.8
4.9
4.10
10.1#
10.2#
10.3#
10.4#
10.5#
10.6#
10.7(a)†
10.7(b)†
10.7(c)†
Form of Warrant to Purchase Shares of Series
D Preferred Stock, dated August 9, 2013 or
July 25, 2014, issued by the Registrant to
Oxford Finance LLC and Square One Bank,
together with a schedule of warrant holders
Form of Warrant to Purchase Shares of Series
E Preferred Stock, dated December 31, 2015,
issued by the Registrant to Oxford Finance
LLC and Square One Bank, together with a
schedule of warrant holders
Common Stock Purchase Warrant, dated June
27, 2017, by and between the Registrant and
Timothy Springer, Ph.D.
Registration Rights Agreement, dated June 27,
2017, by and among the Registrant and the
Investors named therein.
Registration Rights Agreement, dated
December 23, 2019, by and among the
Registrant and the Investors named therein
Form of Common Stock Purchase Warrant,
dated December 23, 2019
Form of Pre-Funded Common Stock Purchase
Warrant, dated December 23, 2019
Description of Securities
2016 Incentive Award Plan and form of award
agreements thereunder
S-1
333-211555
4.5
5/24/2016
S-1
333-211555
4.6
5/24/2016
8-K
001-37798
4.1
6/28/2017
8-K
001-37798
10.3
6/28/2017
8-K
001-37798
10.2
12/26/2019
8-K
8-K
001-37798
001-37798
4.1
4.2
12/26/2019
12/26/2019
S-1/A
333-211555
10.2
6/8/2016
*
2016 Employee Stock Purchase Plan
S-1/A
333-211555
2018 Employment Inducement Incentive
Award Plan, amended and restated, and forms
agreement thereunder
2008 Stock Incentive Plan and form of award
agreements thereunder
Non-Employee Director Compensation
Program
Form of Indemnification Agreement for
Directors and Officers
Exclusive Patent License Agreement, dated as
of November 25, 2008, by and between the
Registrant and the Massachusetts Institute of
Technology
First Amendment to Exclusive Patent License
Agreement, dated as of January 12, 2010, by
and between the Registrant and the
Massachusetts Institute of Technology
Letter Agreement, dated as of November 27,
2012, by and among the Registrant,
Massachusetts Institute of Technology and
Sanofi
S-8
333-230501
S-1/A
333-211555
10-Q
001-37798
333-211555
S-1
S-1
10.3
10.1
6/8/2016
3/25/2019
10.1
10.3
10.5
6/20/2016
8/8/2018
5/24/2016
333-211555
10.7(a)
5/24/2016
S-1
333-211555
10.7(b)
5/24/2016
S-1
333-211555
10.7(c)
5/24/2016
91
10.7(d)†
10.7(e)†
10.7(f)†
10.7(g)†
10.7(h)†
10.7(i)†
10.8†
10.9†
10.10†
10.11†
10.12
10.13#
10.14#
Letter Amendment, dated as of November 27,
2012, by and between the Registrant and the
Massachusetts Institute of Technology
Second Amendment to Exclusive Patent
License Agreement, dated as of August 29,
2013, by and between the Registrant and the
Massachusetts Institute of Technology
Third Amendment to Exclusive Patent License
Agreement, entered into on November 21,
2016 and effective as of November 18, 2016,
by and between the Massachusetts Institute of
Technology and the Registrant
Letter Agreement, dated as of December 2,
2016, by and between the Massachusetts
Institute of Technology and the Registrant
Letter Agreement, dated as of December 2,
2016, by and among Spark Therapeutics, Inc.,
the Massachusetts Institute of Technology and
the Registrant
Fourth Amendment to Exclusive Patent
License Agreement, entered into on December
13, 2019, by and between the Massachusetts
Institute of Technology and the Registrant
Amended and Restated License Agreement,
dated as of May 31, 2017, by and between the
Registrant and Shenyang Sunshine
Pharmaceutical Co., Ltd.
Manufacturing Services Agreement, dated as
of August 1, 2014, by and between the
Registrant and Shenyang Sunshine
Pharmaceutical Co., Ltd.
Lease, dated as of September 30, 2008, as
amended by the First Amendment, dated as of
July 12, 2011, the Second Amendment, dated
as of October 11, 2011 and the Third
Amendment, dated as of April 6, 2015, by and
between the Registrant and ARE-480 Arsenal
Street, LLC
Fourth Amendment to Lease, dated August 21,
2016, by and between ARE-480 Arsenal Street
LLC and Selecta Biosciences, Inc.
Lease Agreement by and between BRE-BMR
Grove LLC and Selecta Biosciences, Inc. dated
July 23, 2019
Employment Agreement, dated as of
September 25, 2018, by and between the
Registrant and Carsten Brunn, Ph.D.
Employment Agreement, dated as of June 6,
2016, by and between the Registrant and
Takashi Kei Kishimoto
S-1
S-1
333-211555
10.7(d)
5/24/2016
333-211555
10.7(e)
5/24/2016
8-K/A
001-37798
10.3(a)
12/14/2016
8-K/A
001-37798
10.3(b)
12/14/2016
8-K/A
001-37798
10.3(c)
12/14/2016
10-Q
001-37798
10.6
8/11/2017
S-1
333-211555
10.10
5/24/2016
S-1
333-211555
10.13
5/24/2016
8-K
001-37798
10.1
9/14/2016
10-Q
001-37798
10.3
11/8/2019
8-K
001-37798
10.2
9/27/2018
S-1/A
333-211555
10.18
6/8/2016
92
*
10.15#
10.16#
10.17#
10.18#
10.19#
10.20†
10.21†
10.22†
10.23†
10.24
10.25
10.26
10.27
21.1
23.1
31.1
Employment Agreement, dated as of June 6,
2016, by and between the Registrant and Lloyd
P. M. Johnston, Ph.D.
Employment Agreement, dated as of August
12, 2019, by and between the Registrant and
Bradford D. Dahms
Employment Agreement, dated as of June 21,
2019, by and between the Registrant and
Alison D. Schecter, M.D
Employment Agreement, dated as of March 19,
2019, by and between the Registrant and Elona
Kogan
Employment Agreement, dated October 26,
2017, by and between the Registrant and
Stephen Smolinski
License and Option Agreement, dated as of
December 2, 2016, by and between Spark
Therapeutics, Inc. and the Registrant
Stock Purchase Agreement, dated as of
December 2, 2016, by and between Spark
Therapeutics, Inc. and the Registrant
Letter Agreement, dated June 6, 2017, by and
between the Registrant and Spark
Therapeutics, Inc.
Feasibility Study and License Agreement by
and between Asklepios BioPharmaceutical,
Inc. and Selecta Biosciences, Inc. dated August
6, 2019
Securities Purchase Agreement, dated June 26,
2017, by and between the Registrant and
Timothy Springer, Ph.D.
Stock Purchase Agreement, dated August 19,
2019, by and among the Registrant and the
Investors named therein
Securities Purchase Agreement, dated
December 18, 2019, by and among the
Registrant and the Investors named therein
Loan and Security Agreement, dated
September 12, 2017, by and between the
Registrant and Silicon Valley Bank
S-1/A
333-211555
10.21
6/8/2016
10-Q
001-37798
10.1
11/8/2019
10-Q
001-37798
10.2
8/8/2019
10-Q
001-37798
10.2
5/8/2019
10-Q
001-37798
10.3
11/7/2017
8-K/A
001-37798
10.1
2/14/2017
8-K/A
001-37798
10.2
12/14/2016
10-Q
001-37798
10.7
8/11/2017
10-Q
001-37798
10.2
11/8/2019
8-K
001-37798
10.2
6/28/2017
8-K
001-37798
10.1
8/20/2019
8-K
001-37798
10.1
12/26/2019
8-K
001-37798
10.1
9/13/2017
Subsidiaries of Selecta Biosciences, Inc.
S-1
333-211555
21.1
5/24/2016
Consent of Ernst & Young LLP, Independent
Registered Public Accounting Firm
Rule 13a-14(a) / 15d-14(a) Certification of
Chief Executive Officer
93
*
*
31.2
32.1
32.2
101.INS
101.SCH
101.CAL
101.DEF
101.LAB
101.PRE
104
Rule 13a-14(a) / 15d-14(a) Certification of
Chief Financial Officer
Section 1350 Certification of Chief Executive
Officer
Section 1350 Certification of Chief Financial
Officer
Inline XBRL Instance Document - the Instance
Document does not appear in the interactive
data file because its XBRL tags are embedded
within the Inline XBRL Document
Inline XBRL Taxonomy Extension Schema
Document
Inline XBRL Taxonomy Extension Calculation
Linkbase Document
Inline XBRL Taxonomy Extension Definition
Linkbase Document
Inline XBRL Taxonomy Extension Label
Linkbase Document
Inline XBRL Taxonomy Extension
Presentation Linkbase Document
Cover Page Interactive Data File (formatted as
Inline XBRL and contained in Exhibit 101)
*
Filed herewith.
**
Furnished herewith.
*** Submitted electronically herewith.
*
**
**
***
***
***
***
***
***
***
#
†
Indicates management contract or compensatory plan.
Portions of this exhibit (indicated by asterisks) have been omitted pursuant to a request for confidential treatment pursuant to Rule 24h-2
under the Securities Exchange Act of 1934.
94
Item 16. Form 10-K Summary
None.
95
Pursuant to the requirements of Section 13 or 15(d) of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its
behalf by the undersigned, thereunto duly authorized.
SIGNATURES
Date: March 12, 2020
SELECTA BIOSCIENCES, INC.
By:
/s/ Carsten Brunn, Ph.D.
Carsten Brunn, Ph.D.
President and Chief Executive Officer
Pursuant to the requirements of the Securities Exchange Act of 1934, this report has been signed by the following persons on behalf of the registrant in the
capacities and on the dates indicated.
Signature
Title
Date
/s/ Carsten Brunn, Ph.D.
President and Chief Executive Officer, and Director
March 12, 2020
Carsten Brunn, Ph.D.
(Principal Executive Officer)
/s/ Bradford D. Dahms
Chief Financial Officer
Bradford D. Dahms
(Principal Financial and Accounting Officer)
/s/ Carrie S. Cox
Carrie S. Cox
Director
/s/ Timothy C. Barabe
Director
Timothy C. Barabe
/s/ Scott D. Myers
Scott D. Myers
Director
/s/ Amir Nashat, Ph.D
Director
Amir Nashat, Ph.D
/s/ Aymeric Sallin
Aymeric Sallin
Director
/s/ Timothy Springer, Ph.D.
Director
Timothy Springer, Ph.D.
/s/ Patrick Zenner
Patrick Zenner
Director
96
March 12, 2020
March 12, 2020
March 12, 2020
March 12, 2020
March 12, 2020
March 12, 2020
March 12, 2020
March 12, 2020
To the Stockholders and the Board of Directors of Selecta Biosciences, Inc.
Report of Independent Registered Public Accounting Firm
Opinion on the Financial Statements
We have audited the accompanying consolidated balance sheets of Selecta Biosciences, Inc. and subsidiaries (the Company) as of December 31, 2019 and
2018, the related consolidated statements of operations and comprehensive loss, changes in stockholders’ equity (deficit), and cash flows for each of the
three years in the period ended December 31, 2019, and the related notes (collectively referred to as the “consolidated financial statements”). In our
opinion, the consolidated financial statements present fairly, in all material respects, the financial position of the Company at December 31, 2019 and 2018,
and the results of its operations and its cash flows for each of the three years in the period ended December 31, 2019, in conformity with U.S. generally
accepted accounting principles.
The Company's Ability to Continue as a Going Concern
The accompanying consolidated financial statements have been prepared assuming that the Company will continue as a going concern. As discussed in
Note 1 to the consolidated financial statements, the Company has recurring losses from operations and insufficient cash resources and has stated that
substantial doubt exists about the Company’s ability to continue as a going concern. Management's evaluation of the events and conditions and
management’s plans regarding these matters are also described in Note 1. The consolidated financial statements do not include any adjustments that might
result from the outcome of this uncertainty.
Adoption of ASU No. 2014-09
As discussed in Note 12 to the consolidated financial statements, the Company changed its method of accounting for revenue in 2018 due to the adoption
of ASU No. 2014-09, Revenue from Contracts with Customers (Topic 606) and the related amendments.
Adoption of ASU No. 2016-02
As discussed in Note 8 to the consolidated financial statements, the Company changed its method of accounting for leases in 2019 due to the adoption of
ASU No. 2016-02, Leases (Topic 842) and the related amendments.
Basis for Opinion
These financial statements are the responsibility of the Company’s management. Our responsibility is to express an opinion on the Company’s financial
statements based on our audits. We are a public accounting firm registered with the Public Company Accounting Oversight Board (United States)
(PCAOB) and are required to be independent with respect to the Company in accordance with the U.S. federal securities laws and the applicable rules and
regulations of the Securities and Exchange Commission and the PCAOB.
We conducted our audits in accordance with the standards of the PCAOB. Those standards require that we plan and perform the audit to obtain reasonable
assurance about whether the financial statements are free of material misstatement, whether due to error or fraud. The Company is not required to have, nor
were we engaged to perform, an audit of its internal control over financial reporting. As part of our audits we are required to obtain an understanding of
internal control over financial reporting but not for the purpose of expressing an opinion on the effectiveness of the Company’s internal control over
financial reporting. Accordingly, we express no such opinion.
Our audits included performing procedures to assess the risks of material misstatement of the financial statements, whether due to error or fraud, and
performing procedures that respond to those risks. Such procedures included examining, on a test basis, evidence regarding the amounts and disclosures in
the financial statements. Our audits also included evaluating the accounting principles used and significant estimates made by management, as well as
evaluating the overall presentation of the financial statements. We believe that our audits provide a reasonable basis for our opinion.
/s/ Ernst & Young LLP
We have served as the Company's auditor since 2009.
Boston, Massachusetts
March 12, 2020
F-1
Selecta Biosciences, Inc. and Subsidiaries
Consolidated Balance Sheets
(Amounts in thousands, except share data and par value)
December 31,
2019
2018
$
89,893
$
37,403
Assets
Current assets:
Cash and cash equivalents
Restricted cash
Accounts receivable
Prepaid expenses and other current assets
Total current assets
Property and equipment, net
Right-of-use asset, net
Long-term restricted cash
Total assets
Liabilities and stockholders’ equity (deficit)
Current liabilities:
Accounts payable
Accrued expenses
Loan payable
Lease liability
Deferred revenue
Total current liabilities
Non‑current liabilities:
Deferred revenue
Warrant liabilities
Other long‑term liabilities
Total liabilities
Commitments and contingencies (Note 17)
Stockholders’ equity (deficit):
Preferred stock, $0.0001 par value; 10,000,000 shares authorized; no shares issued and outstanding at December 31, 2019 and December 31, 2018,
respectively
Common stock, $0.0001 par value; 200,000,000 shares authorized; 86,325,547 and 22,471,776 shares issued and outstanding as of December 31,
2019 and December 31, 2018, respectively
Additional paid-in capital
Accumulated deficit
Accumulated other comprehensive loss
Total stockholders’ equity (deficit)
Total liabilities and stockholders’ equity (deficit)
The accompanying notes are an integral part of these consolidated financial statements.
F-2
$
$
279
5,000
1,495
96,667
1,222
301
1,379
—
—
4,673
42,076
2,127
—
279
99,569
$
44,482
500
$
13,492
18,905
372
1,674
34,943
14,680
41,549
—
91,172
—
9
348,664
(335,753)
(4,523)
8,397
1,100
11,700
21,385
—
959
35,144
13,818
—
938
49,900
—
3
279,539
(280,403)
(4,557)
(5,418)
44,482
$
99,569
$
Selecta Biosciences, Inc. and Subsidiaries
Consolidated Statements of Operations and Comprehensive Loss
(Amounts in thousands, except share and per share data)
Grant and collaboration revenue
Operating expenses:
Research and development
General and administrative
Total operating expenses
Loss from operations
Investment income
Loss on extinguishment of debt
Foreign currency transaction (loss), net
Interest expense
Change in fair value of warrant liabilities
Other (expense), net
Net loss
Other comprehensive loss:
Foreign currency translation adjustment
Unrealized gain on securities
Total comprehensive loss
Net loss per share:
Basic and diluted
Weighted average common shares outstanding:
Basic and diluted
Year Ended December 31,
2019
2018
2017
$
6,677
$
903 $
207
42,743
16,389
59,132
(52,455)
834
—
(47)
(1,519)
(857)
(1,306)
(55,350)
47,687
18,238
65,925
(65,022)
1,050
—
120
(1,494)
—
10
(65,336)
34
—
(55,316)
$
(153)
16
(65,473) $
45,165
18,826
63,991
(63,784)
617
(673)
(123)
(1,206)
—
(152)
(65,321)
78
20
(65,223)
(1.22)
$
(2.92) $
(3.20)
45,548,511
22,389,286
20,425,050
$
$
The accompanying notes are an integral part of these consolidated financial statements.
F-3
Selecta Biosciences, Inc. and Subsidiaries
Consolidated Statements of Changes in Stockholders’ Equity (Deficit)
(Amounts in thousands, except share data)
Common stock
Shares
Amount
Additional
paid‑in
capital
Stock
option
Accumulated
comprehensive
receivable
deficit
loss
18,438,742
$
1
$
211,125
$
(75) $
(151,576) $
(4,518) $
Accumulated
other
Stockholders’
Balance at December 31, 2016
Issuance of common stock under Employee Stock
Purchase Plan
16,263
Issuance of common stock upon exercise of options
269,842
Stock‑based compensation expense
Issuance of common stock, license agreement
Issuance of common stock through private
placement, net of issuance costs
Currency translation adjustment
Unrealized gains on securities
Net loss
—
529,616
3,088,791
—
—
—
Balance at December 31, 2017
22,343,254
$
Adoption of new accounting principle
Issuance of common stock under Employee Stock
Purchase Plan
—
24,738
Issuance of common stock upon exercise of options
103,784
Issuance of common stock upon exercise of options
125,600
Stock‑based compensation expense
Currency translation adjustment
Unrealized gains on securities
Net loss
Balance at December 31, 2018
Issuance of common stock under Employee Stock
Purchase Plan
Issuance of vested restricted stock units
Issuance of common stock, net of issuance costs
Issuance of common stock through at-the-market
offering, net of issuance costs
Issuance of common stock through private
placement, net of issuance costs
Issuance of common stock, pre-funded warrants
and warrants through private placement, net of
issuance costs
Stock‑based compensation expense
Currency translation adjustment
Net loss
Balance at December 31, 2019
—
—
—
—
17,205
93,750
22,188,706
615,453
3,178,174
37,634,883
—
—
—
—
—
—
—
2
—
—
—
180
630
4,080
10,000
47,113
—
—
—
$
3
—
273,128
$
—
—
—
—
—
—
—
196
501
5,714
—
—
—
—
—
—
2
—
—
4
—
—
—
28
150
—
30,940
1,006
5,715
26,125
5,161
—
—
—
75
—
—
—
—
—
—
— $
—
—
—
—
—
—
—
— $
—
—
—
—
—
—
—
—
—
—
— $
—
—
—
—
—
—
—
(65,321)
(216,897) $
1,830
—
—
—
—
—
(65,336)
(280,403) $
—
—
—
—
—
—
—
—
—
(55,350)
(335,753) $
—
—
—
—
—
78
20
—
(4,420) $
—
—
—
—
(153)
16
—
(4,557) $
—
—
—
—
—
—
—
—
34
—
(4,523) $
Equity
(Deficit)
54,957
180
705
4,080
10,000
47,115
78
20
(65,321)
51,814
1,830
196
501
5,714
(153)
16
(65,336)
(5,418)
28
150
—
30,942
1,006
5,715
26,129
5,161
34
(55,350)
8,397
22,471,776
$
3
$
279,539
$
86,325,547
$
9
$
348,664
$
The accompanying notes are an integral part of these consolidated financial statements.
F-4
Selecta Biosciences, Inc. and Subsidiaries
Consolidated Statements of Cash Flows
(Amounts in thousands)
Cash flows from operating activities
Net loss
Adjustments to reconcile net loss to net cash used in operating activities:
Depreciation
Amortization of premiums (accretion of discounts) on investments
Amortization of right-of-use assets
Loss (gain) on disposal of property and equipment
Stock‑based compensation expense
Non‑cash interest expense
Warrant liabilities revaluation
Loss on extinguishment of debt
Net realized losses on investments
Changes in operating assets and liabilities:
Accounts receivable
Prepaid expenses, deposits and other assets
Accounts payable
Deferred revenue
Accrued expenses and other liabilities
Net cash used in operating activities
Cash flows from investing activities
Receipts from the maturity of short-term investments
Purchases of short-term investments
Sale of short term investments
Purchases of property and equipment
Proceeds from the sale of property and equipment
Net cash provided by (used in) investing activities
Cash flows from financing activities
Proceeds from issuance of long-term debt, net of expenses
Repayments of principal on outstanding debt
Net proceeds from issuance of common stock
Net proceeds from issuance of common stock- at-the-market offering
Net proceeds from issuance of common stock- private placement
Net proceeds from issuance of common stock, common warrants, and pre-funded warrants
Proceeds from exercise of stock options
Proceeds from issuance of common stock under Employee Stock Purchase Plan
Net cash provided by financing activities
Effect of exchange rate changes on cash
Net change in cash, cash equivalents, and restricted cash
Cash, cash equivalents, and restricted cash at beginning of period
Cash, cash equivalents, and restricted cash at end of period
Supplement cash flow information
Cash paid for interest
Noncash investing and financing activities
Purchase of property and equipment not yet paid
Issuance costs in connection with common stock, common warrants, and pre-funded warrants in accrued liabilities
Unrealized gain on marketable securities
F-5
Year Ended December 31,
2019
2018
2017
$
(55,350)
$
(65,336) $
(65,321)
726
(154)
1,301
104
5,161
402
857
—
(1)
(5,000)
3,179
(600)
337
(2,397)
(51,435)
16,350
(18,188)
1,992
(47)
122
229
—
(2,800)
30,942
1,006
5,715
70,000
150
28
105,041
34
53,869
37,682
91,551
$
975
(101)
—
(81)
5,714
449
—
—
—
—
(2,631)
(516)
(101)
2,467
(59,161)
41,655
(15,598)
—
(884)
99
25,272
—
—
—
—
—
—
501
196
697
(153)
(33,345)
71,027
37,682 $
1,223
$
1,134 $
4,381
— $
$
— $
145 $
— $
16 $
750
233
—
36
4,081
390
—
673
—
152
1,225
(2,327)
2,432
5,650
(52,026)
60,158
(61,527)
—
(733)
4
(2,098)
20,957
(12,934)
10,000
—
47,114
—
706
180
66,023
78
11,977
59,050
71,027
905
103
—
20
$
$
$
$
$
The accompanying notes are an integral part of these consolidated financial statements.
F-6
Selecta Biosciences, Inc. and Subsidiaries
Notes to Consolidated Financial Statements
1. Nature of the Business and Basis of Presentation
Selecta Biosciences, Inc. (the “Company”) was incorporated in Delaware on December 10, 2007, and is based in Watertown, Massachusetts. The Company
is a clinical-stage biotechnology company focused on unlocking the full potential of biologic therapies based on its immune tolerance technology
(ImmTOR™) platform. The Company plans to combine ImmTOR with a range of biologic therapies for rare and serious diseases that require new
treatment options due to high immunogenicity of existing therapies. Since inception, the Company has devoted its efforts principally to research and
development of its technology and product candidates, recruiting management and technical staff, acquiring operating assets, and raising capital.
The Company is subject to risks common to companies in the biotechnology industry including, but not limited to, new technological innovations,
protection of proprietary technology, dependence on key personnel, compliance with government regulations and the need to obtain additional financing.
Product candidates currently under development will require significant additional research and development efforts, including extensive preclinical and
clinical testing and regulatory approval, prior to commercialization. These efforts require significant amounts of additional capital, adequate personnel
infrastructure and extensive compliance-reporting capabilities.
The Company’s product candidates are in development. There can be no assurance that the Company’s research and development will be successfully
completed, that adequate protection for the Company’s intellectual property will be obtained, or maintained, that any products developed will obtain
necessary government regulatory approval or that any approved products will be commercially viable. Even if the Company’s product development efforts
are successful, it is uncertain when, if ever, the Company will generate significant revenue from product sales. The Company operates in an environment of
rapid change in technology and substantial competition from pharmaceutical and biotechnology companies. In addition, the Company is dependent upon
the services of its employees and consultants.
The accompanying financial statements have been prepared on a basis that assumes the Company is a going concern, and does not include any adjustments
to reflect the possible future effects on the recoverability and classification of assets or the amounts and classifications of liabilities that may result from
any uncertainty related to its ability to continue as a going concern.
Liquidity and Management's Plan
The future success of the Company is dependent on its ability to develop its product candidates and ultimately upon its ability to attain profitable
operations. The Company is subject to a number of risks similar to other early-stage life science companies, including, but not limited to, successful
development of its product candidates, raising additional capital with favorable terms, protection of proprietary technology and market acceptance of any
approved future products. The successful development of product candidates requires substantial working capital which may not be available to the
Company on favorable terms or at all.
To date, the Company has financed its operations primarily through the initial public offering of its common stock, a private placement of its common
stock, issuances of common and preferred stock, debt, research grants and research collaborations. The Company currently has no source of product
revenue, and it does not expect to generate product revenue for the foreseeable future. To date, all of the Company's revenue has been collaboration and
grant revenue. The Company has devoted substantially all of its financial resources and efforts to developing its ImmTOR platform, identifying potential
product candidates and conducting preclinical studies and its clinical trials. The Company is in the early stages of development of its product candidates,
and it has not completed development of any ImmTOR-enabled therapies.
As of December 31, 2019, the Company’s cash, cash equivalents and restricted cash were $91.6 million, of which $1.7 million was restricted cash related
to lease commitments and $0.4 million was held by its Russian subsidiary designated solely for use in its operations. The Company has incurred losses and
negative cash flows from operating activities since inception. As of December 31, 2019 and December 31, 2018, the Company had an accumulated deficit
of $335.8 million and $280.4 million, respectively. The Company anticipates operating losses to continue for the foreseeable future due to, among other
things, costs related to research, development of its product candidates, conducting preclinical studies and clinical trials, and its administrative organization.
The Company will require substantial additional financing to fund its operations and to continue to execute its strategy, and the Company will pursue a
range of options to secure additional capital. These conditions raise
F-7
substantial doubt about the Company's ability to continue as a going concern within one year after the date that the financial statements are issued.
Management is actively exploring licenses and other strategic collaborations that have the potential to provide non-dilutive capital and accelerate the
development of new or existing product candidates incorporating the Company’s ImmTOR platform. Additionally, the Company may seek to fund its
operations through issuances of equity and other securities. If the Company enters into strategic collaborations and alliances, which may include existing
collaboration partners, the Company may have to relinquish valuable rights to its technologies or product candidates, or grant licenses on terms that are not
favorable to the Company. To the extent that the Company raises additional capital through the sale of equity, the ownership interest of its existing
shareholders will be diluted and other preferences may be necessary that adversely affect the rights of existing shareholders. The Company requires
additional external sources of capital to complete the planned Phase 3 clinical program for SEL-212. If the Company is unable to raise sufficient capital
through strategic collaborations and the sale of equity or other securities, it intends to curtail expenses contemplated by the current operating plan, and the
Company may be required to delay, limit, reduce or terminate its product development efforts or grant rights to develop and market product candidates that
it would otherwise prefer to develop and market itself. Because of the uncertainty in securing additional capital and the insufficient amount of capital
resources at December 31, 2019, management has concluded that substantial doubt exists with respect to the Company's ability to continue as a going
concern within one year after the date of the filing of this Annual Report on Form 10-K.
All amounts due under the 2017 Term Loan (see Note 9) have been classified as a current liability as of December 31, 2019 due to the considerations
discussed above and the assessment that the material adverse change clause under the 2017 Term Loan is not within the Company's control. The Company
has not been notified of an event of default by the Lender as of the date of the filing of this Annual Report on Form 10-K.
Guarantees and Indemnifications
As permitted under Delaware law, the Company indemnifies its officers, directors, consultants and employees for certain events or occurrences that happen
by reason of the relationship with, or position held at, the Company. Through December 31, 2019, the Company had not experienced any losses related to
these indemnification obligations, and no claims were outstanding. The Company does not expect significant claims related to these indemnification
obligations and, consequently, concluded that the fair value of these obligations is negligible, and no related reserves were established.
2. Summary of Significant Accounting Policies
Principles of Consolidation
The consolidated financial statements include the accounts of the Company and its wholly owned subsidiaries, Selecta RUS, LLC (“Selecta (RUS)”), a
Russian limited liability corporation, and Selecta Biosciences Security Corporation, a Massachusetts Security Corporation. All significant intercompany
accounts and transactions have been eliminated.
Foreign Currency
The functional currency of Selecta (RUS) is the Russian ruble. Assets and liabilities of Selecta (RUS) are translated at period-end exchange rates, while
revenues and expenses are translated at average exchange rates for the period. Translation gains and losses are reflected in accumulated other
comprehensive loss within stockholders’ equity (deficit). Foreign currency transaction gains or losses are reflected in the consolidated statements of
operations and comprehensive loss.
Use of Estimates
The preparation of consolidated financial statements in conformity with U.S. GAAP requires the Company’s management to make estimates and
assumptions that affect the reported amounts of assets and liabilities, the disclosure of contingent assets and liabilities at the date of the consolidated
financial statements and the reported amounts of revenues and expenses during the reporting period. The Company’s management considers many factors
in selecting appropriate financial accounting policies and controls, and bases its estimates on historical experience and other market-specific or other
relevant assumptions that it believes to be reasonable under the circumstances. In preparing these consolidated financial statements, management used
significant estimates in the following areas, among others: revenue recognition, accounting for stock-based compensation, the valuation of its warrant
liabilities and estimating accrued research and development expenses. The Company assesses the above estimates on an ongoing basis; however, actual
results could materially differ from those estimates.
Segment Information
F-8
Operating segments are identified as components of an enterprise about which separate discrete financial information is available for evaluation by the
chief operating decision maker, the Company’s Chief Executive Officer, in making decisions regarding resource allocation and assessing performance. The
Company views its operations and manages its business in one operating segment, the research and development of nanoparticle immunomodulatory drugs
for the treatment and prevention of human diseases.
Cash Equivalents, Short-term Investments and Restricted Cash
Cash equivalents include all highly liquid investments maturing within 90 days from the date of purchase. Investments consist of securities with remaining
maturities greater than 90 days when purchased. The Company classifies these marketable securities and records them at fair value in the accompanying
consolidated balance sheets. Investments with less than one year until maturity are classified as short term, while investments with maturities greater than
one year are classified as long term. Unrealized gains or losses are included in accumulated other comprehensive income (loss). Premiums or discounts
from par value are amortized to investment income over the life of the underlying investment.
Although available to be sold to meet operating needs or otherwise, securities are generally held through maturity. The cost of securities sold is determined
based on the specific identification method for purposes of recording realized gains and losses. During the year ended December 31, 2019, there were de
minimis realized losses on sales of investments, and no investments were adjusted for other than temporary declines in fair value.
As of December 31, 2019, the Company had restricted cash balances relating to secured letters of credit in connection with its current Headquarters Lease
and New Headquarters Lease (as defined in Note 8). The following table provides a reconciliation of cash, cash equivalents, and restricted cash reported
within the consolidated balance sheet that sum to the total of the same such amounts shown in the consolidated statement of cash flows:
Cash and cash equivalents
Restricted cash
Long-term restricted cash
Total cash, cash equivalents, and restricted cash shown in the consolidated statement of cash flows
Year Ended December 31,
2019
89,893 $
279
1,379
91,551 $
2018
37,403 $
—
279
37,682 $
2017
70,622
76
329
71,027
$
$
Concentrations of Credit Risk and Off‑Balance Sheet Risk
Financial instruments that potentially subject the Company to concentration of credit risk consist primarily of cash, cash equivalents, short-term deposits
and investments, and accounts receivable. Cash and cash equivalents are deposited with federally insured financial institutions in the United States and
may, at times, exceed federally insured limits. Management believes that the financial institutions that hold the Company’s deposits are financially
creditworthy and, accordingly, minimal risk exists with respect to those balances. Generally, these deposits may be redeemed upon demand and therefore
bear minimal interest rate risk. As an integral part of operating its Russian subsidiary, the Company also maintains cash in Russian bank accounts in
denominations of both Russian rubles and U.S. dollars. As of December 31, 2019, the Company maintained approximately $0.4 million in Russian bank
accounts, all of which was held in U.S. dollars.
The Company did not have any off-balance sheet arrangements as of December 31, 2019 and December 31, 2018.
Fair Value of Financial Instruments
The Company’s financial instruments consist mainly of cash equivalents, restricted cash, accounts payable, loans payable, and common warrants. The
carrying amounts of cash equivalents, restricted cash, accounts receivable, and accounts payable approximate their estimated fair value due to their short-
term maturities. At December 31, 2019, the carrying amount of the Company's loan payable approximates its estimated fair value due to the short-term
nature of the instrument.
Accounting standards define fair value as the price that would be received to sell an asset or paid to transfer a liability in an orderly transaction between
market participants at the measurement date. A three‑level hierarchy is used to prioritize the inputs to valuation techniques used to measure fair value. The
hierarchy gives the highest priority to unadjusted quoted prices in active markets for identical assets or liabilities (Level 1 measurements), and the lowest
priority to unobservable inputs (Level 3 measurements). The three levels of the fair value hierarchy are described below:
Level 1—Level 1 inputs are quoted prices in active markets for identical assets or liabilities that the reporting entity has the ability to access at the
measurement date.
F-9
Level 2—Level 2 inputs are inputs other than quoted prices included within Level 1 that are observable for the asset or liability, either directly or
indirectly. If the asset or liability has a specified (contractual) term, a Level 2 input must be observable for substantially the full term of the asset
or liability.
Level 3—Level 3 inputs are unobservable inputs for the asset or liability in which there is little, if any, market activity for the asset or liability at
the measurement date.
To the extent that a valuation is based on models or inputs that are less observable or unobservable in the market, the determination of fair value requires
more judgment. Accordingly, the degree of judgment exercised by the Company in determining fair value is greatest for instruments categorized in Level 3.
A financial instrument’s level within the fair value hierarchy is based on the lowest level of any input that is significant to the fair value measurement. The
fair value of warrant liabilities were determined using Level 3 inputs.
Fair value is a market‑based measure considered from the perspective of a market participant rather than an entity‑specific measure. Therefore, even when
market assumptions are not readily available, the Company’s own assumptions are set to reflect those that market participants would use in pricing the asset
or liability at the measurement date. The Company uses prices and inputs that are current as of the measurement date, including during periods of market
dislocation. In periods of market dislocation, the observability of prices and inputs may change for many instruments. This condition could cause an
instrument to be reclassified within levels in the fair value hierarchy. There were no transfers within the fair value hierarchy during the years ended
December 31, 2019 or December 31, 2018.
Property and Equipment
Property and equipment are recorded at cost and depreciated using the straight‑line method over the estimated useful lives of the respective assets,
generally seven years for furniture and fixtures, five years for laboratory equipment, software and office equipment and three years for computer
equipment. Leasehold improvements are amortized over their useful life or the life of the lease, whichever is shorter. Major additions and betterments are
capitalized. Maintenance and repairs, which do not improve or extend the life of the respective assets, are charged to operations as incurred. Costs incurred
for construction in progress are recorded as assets and are not amortized until the construction is substantially complete and the assets are ready for their
intended use.
Impairment of Long‑Lived Assets
The Company reviews long‑lived assets for impairment whenever events or changes in circumstances indicate that the carrying value of an asset may not
be recoverable. In order to determine if assets have been impaired, assets are tested at the lowest level for which identifiable independent cash flows are
available, which is at the entity level ("asset group"). An impairment loss is recognized when the sum of projected undiscounted cash flows is less than the
carrying value of the asset group. The measurement of the impairment loss to be recognized is based on the difference between the fair value and the
carrying value of the asset group. Based on management's evaluation, the fair value of the asset group, measured as the market capitalization of the
Company exceeds its carrying value, and for this reason the Company did not recognize any material impairment losses during the years ended
December 31, 2019 and 2018.
Debt Issuance Costs
Debt issuance costs and fees paid to lenders are classified as a debt discount and are recorded as a direct deduction from the face amount of the related debt.
Issuance costs paid to third parties that are the direct result of the debt issuance are capitalized as a direct deduction from the face amount of the related
debt. Debt issuance costs are amortized over the term of the related debt using the interest method and recorded as interest expense. Costs and fees paid to
third parties are expensed as incurred.
Accumulated Other Comprehensive Income (Loss)
Comprehensive income (loss) is defined as the change in the equity of a business entity during a period from transactions and other events and
circumstances from non‑owner sources. It includes all changes in equity during a period except those resulting from investments by owners and
distributions to owners. Comprehensive income (loss) consists of: (i) all components of net loss and (ii) all components of comprehensive loss other than
net loss, referred to as other comprehensive loss. Other comprehensive loss is comprised of foreign currency translation adjustments and the unrealized
gains and losses recognized through net income.
F-10
The components of accumulated other comprehensive income (loss), net of tax, were as follows (in thousands):
Balance at December 31, 2016
Other comprehensive income during the year
Balance at December 31, 2017
Other comprehensive income (loss) during the year
Balance at December 31, 2018
Other comprehensive income during the year
Balance at December 31, 2019
Revenue Recognition
Foreign currency translation
adjustment
Unrealized gains (losses)
on marketable securities
Accumulated other
comprehensive income (loss)
$
$
$
$
$
(4,482)
$
78
(4,404)
$
(153)
(4,557)
34
(4,523)
$
$
$
(36) $
20
(16) $
16
— $
— $
— $
(4,518)
98
(4,420)
(137)
(4,557)
34
(4,523)
Revenue is recognized when a customer obtains control of promised goods or services, in an amount that reflects the consideration which the entity expects
to receive in exchange for those goods or services. Pursuant to ASC Topic 606, Revenue from Contracts with Customers (ASC 606), a customer is a party
that has contracted with an entity to obtain goods or services that are an output of the entity’s ordinary activities in exchange for consideration. To
determine revenue recognition for arrangements that an entity determines are within the scope of ASC 606, the Company performs the following five steps:
(i) identify the contract(s) with a customer; (ii) identify the performance obligations in the contract, including whether they are distinct in the context of the
contract; (iii) determine the transaction price, including the constraint on variable consideration; (iv) allocate the transaction price to the performance
obligations in the contract; and (v) recognize revenue when (or as) the Company satisfies each performance obligation. The Company only applies the five-
step model to contracts when it is probable that the entity will collect the consideration it is entitled to in exchange for the goods or services it transfers to
the customer. At contract inception, once the contract is determined to be within the scope of ASC 606, the Company assesses the goods or services
promised within each contract and determines those that are performance obligations, and assesses whether each promised good or service is distinct. If a
promised good or service is not distinct, it is combined with other performance obligations. The Company then recognizes as revenue the amount of the
transaction price that is allocated to the respective performance obligation when (or as) the performance obligation is satisfied. For example, certain
performance obligations associated with Spark and AskBio (see Note 12) will be satisfied over time, and revenue will be recognized using the output
method, based on the proportion of actual deliveries to the total expected deliveries over the initial term.
Collaboration and Grant Revenue: The Company currently generates its revenue through grants, collaboration and license agreements with strategic
collaborators for the development and commercialization of product candidates. Grants and license agreements with customers are accounted for in
accordance with ASC 606. The Company analyzes collaboration arrangements by first assessing whether they are within the scope of ASC Topic 808,
Collaborative Arrangements (ASC 808), and evaluates whether such arrangements involve joint operating activities performed by parties that are both
active participants in the activities and exposed to significant risks and rewards that are dependent on the commercial success of such activities.
Collaboration agreements with customers that are not within the scope of ASC 808 are accounted for in accordance with ASC 606. To the extent the
collaboration agreement is within the scope of ASC 808, the Company also assesses whether any aspects of the agreement are within the scope of other
accounting literature (specifically ASC 606). The Company early adopted ASU No. 2018-18, Collaborative Arrangements (Topic 808): Clarifying the
Interaction between Topic 808 and Topic 606, which provides guidance on evaluating certain transactions between collaborative arrangement participants.
If the Company concludes that some or all aspects of the agreement are distinct and represent a transaction with a customer, the Company accounts for
those aspects of the arrangement within the scope of ASC 606. The Company recognizes the shared costs incurred that are not within the scope of other
accounting literature as a component of the related expense in the period incurred by analogy to ASC Topic 730, Research and Development (ASC 730),
and records reimbursements from counterparties as an offset to the related costs. In determining the appropriate amount of revenue to be recognized as it
fulfills its obligations under the agreements in accordance with ASC 606, the Company performs the five steps above. As part of the accounting for the
arrangement, the Company must develop assumptions that require judgment to determine the stand-alone selling price for each performance obligation
identified in the contract. The Company uses key assumptions to determine the stand-alone selling price, which may include market conditions,
reimbursement rates for personnel costs, development timelines and probabilities of regulatory success.
The terms of the Company’s arrangements typically include one or more of the following: (i) up-front fees; (ii) milestone payments related to the
achievement of development, regulatory, or commercial goals; (iii) royalties on net sales of licensed
F-11
products; (iv) reimbursements or cost-sharing of research and development (R&D) expenses; and (v) profit/loss sharing arising from co-promotion
arrangements.
Licenses of Intellectual Property: If the license to the Company’s intellectual property is determined to be distinct from the other performance obligations
identified in the arrangement, the Company recognizes revenues from non-refundable, up-front fees allocated to the license when the license is transferred
to the customer and the customer is able to use and benefit from the license. If not distinct, the license is combined with other performance obligations in
the contract. For licenses that are combined with other performance obligations, the Company assesses the nature of the combined performance obligation
to determine whether the combined performance obligation is satisfied over time or at a point in time and, if over time, the appropriate method of
measuring progress for purposes of recognizing revenue. The Company evaluates the measure of progress each reporting period and, if necessary, adjusts
the measure of performance and related revenue recognition. Optional licenses are evaluated to determine if they are issued at a discount, and therefore,
represent material rights and accounted for as separate performance obligations.
Milestone Payments: At the inception of each arrangement that includes developmental and regulatory milestone payments, the Company evaluates
whether the achievement of each milestone specifically relates to the Company’s efforts to satisfy a performance obligation or transfer a distinct good or
service within a performance obligation. If the achievement of a milestone is considered a direct result of the Company’s efforts to satisfy a performance
obligation or transfer a distinct good or service and the receipt of the payment is based upon the achievement of the milestone, the associated milestone
value is allocated to that distinct good or service. If the milestone payment is not specifically related to the Company’s effort to satisfy a performance
obligation or transfer a distinct good or service, the amount is allocated to all performance obligations using the relative standalone selling price method.
The Company also evaluates the milestone to determine whether they are considered probable of being reached and estimates the amount to be included in
the transaction price using the most likely amount method. If it is probable that a significant revenue reversal would not occur, the associated milestone
value is included in the transaction price to be allocated, otherwise, such amounts are constrained and excluded from the transaction price. At the end of
each subsequent reporting period, the Company re-evaluates the probability of achievement of such development milestones and any related constraint, and
if necessary, adjusts its estimate of the transaction price. Any such adjustments to the transaction price are allocated to the performance obligations on the
same basis as at contract inception. Amounts allocated to a satisfied performance obligation shall be recognized as revenue, or as a reduction of revenue, in
the period in which the transaction price changes.
Manufacturing Supply Services: Arrangements that include a promise for future supply of drug substance or drug product for either clinical development or
commercial supply at the customer’s discretion are evaluated to determine if they are distinct and optional. For optional services that are distinct, the
Company assesses if they are priced at a discount, and therefore, provide a material right to the licensee to be accounted for as separate performance
obligations.
Royalties: For arrangements that include sales-based royalties, including milestone payments based on the level of sales, and the license is deemed to be the
predominant item to which the royalties relate, the Company will recognize revenue at the later of (i) when the related sales occur, or (ii) when the
performance obligation to which some or all of the royalty has been allocated has been satisfied (or partially satisfied) in accordance with the royalty
recognition constraint.
Research and Development Costs
Costs incurred in the research and development of the Company’s products are expensed as incurred. Research and development expenses include costs
incurred in performing research and development activities, including salaries and benefits, facilities cost, overhead costs, contract services, supplies and
other outside costs. Nonrefundable advance payments for goods and services that will be used in future research and development activities are expensed
when the activity has been performed or when the goods have been received rather than when the payment is made.
Clinical Trial Costs
Clinical trial expenses are a significant component of research and development expenses, and the Company outsources a significant portion of these costs
to third parties. Third party clinical trial expenses include patient costs, clinical research organization costs and costs for data management. The accrual for
site and patient costs includes inputs such as estimates of patient enrollment, patient cycles incurred, clinical site activations, and other pass-through costs.
Payments for these activities are based on the terms of the individual arrangements, which may differ from the pattern of costs incurred, and are reflected
on the consolidated balance sheets as a prepaid asset or accrued clinical trial cost. These third party agreements are generally cancelable, and related costs
are recorded as research and development expenses as incurred. Non-refundable advance clinical payments for goods or services that will be used or
rendered for future R&D activities are recorded as a prepaid asset and recognized as expense as the related goods are delivered or the related services are
performed. The Company also records accruals for estimated ongoing clinical research and development costs. When evaluating the adequacy of the
accrued liabilities, the Company analyzes progress of the studies, including the phase or completion of events, invoices received and contracted costs.
Significant judgments and estimates may be made in determining the accrued balances at the end of any
F-12
reporting period. Actual results could differ from the estimates made by the Company. The historical clinical accrual estimates made by the Company have
not been materially different from the actual costs.
Income Taxes
The Company provides deferred tax assets and liabilities for the expected future tax consequences of temporary differences between the Company’s
financial statement carrying amounts and the tax basis of assets and liabilities using enacted tax rates expected to be in effect in the years in which the
differences are expected to reverse. A valuation allowance is provided to reduce the deferred tax assets to the amount that will more-likely-than-not be
realized.
The Company determines whether it is more likely than not that a tax position will be sustained upon examination. If it is not more-likely-than-not that a
position will be sustained, none of the benefit attributable to the position is recognized. The tax benefit to be recognized for any tax position that meets the
more‑likely‑than‑not recognition threshold is calculated as the largest amount that is more than 50% likely of being realized upon resolution of the
contingency. The Company accounts for interest and penalties related to uncertain tax positions as part of its provision for income taxes. To date, the
Company has not incurred interest and penalties related to uncertain tax positions.
Warrants
The Company determines the accounting classification of warrants that are issued, as either liability or equity, by first assessing whether the warrants meet
liability classification in accordance with ASC 480-10, Accounting for Certain Financial Instruments with Characteristics of both Liabilities and Equity,
and then in accordance with ASC 815-40, Accounting for Derivative Financial Instruments Indexed to, and Potentially Settled in, a Company’s Own Stock.
Under ASC 480, warrants are considered liability classified if the warrants are mandatorily redeemable, obligate the issuer to settle the warrants or the
underlying shares by paying cash or other assets, or must or may require settlement by issuing variable number of shares.
If warrants do not meet liability classification under ASC 480-10, the Company assesses the requirements under ASC 815-40, which states that contracts
that require or may require the issuer to settle the contract for cash are liabilities recorded at fair value, irrespective of the likelihood of the transaction
occurring that triggers the net cash settlement feature. If the warrants do not require liability classification under ASC 815-40, in order to conclude equity
classification, the Company assesses whether the warrants are indexed to its common stock and whether the warrants are classified as equity under ASC
815-40 or other applicable GAAP. After all relevant assessments are made, the Company concludes whether the warrants are classified as liability or
equity. Liability classified warrants are required to be accounted for at fair value both on the date of issuance and on subsequent accounting period ending
dates, with all changes in fair value after the issuance date recorded in the statements of operations as a gain or loss. Equity classified warrants are
accounted for at fair value on the issuance date with no changes in fair value recognized after the issuance date.
Stock‑Based Compensation
The Company accounts for all stock‑based compensation granted to employees and non‑employees using a fair value method. Stock‑based compensation is
measured at the grant date fair value and is recognized over the requisite service period of the awards, usually the vesting period, on a straight‑line basis,
net of estimated forfeitures. The Company reduces recorded stock‑based compensation for estimated forfeitures. To the extent that actual forfeitures differ
from the Company’s estimates, the differences are recorded as a cumulative adjustment in the period the estimates were adjusted. Stock‑based
compensation expense recognized in the consolidated financial statements is based on awards that are ultimately expected to vest.
Net Loss Per Share
The Company has reported losses since inception and has computed basic net loss per share by dividing net loss by the weighted average number of
common shares and pre-funded warrants outstanding for the period. The Company has computed diluted net loss per common share after considering all
potentially dilutive common shares, including stock options, convertible preferred stock, and warrants outstanding during the period except where the effect
of including such securities would be antidilutive. Because the Company has reported net losses since inception, these potential common shares have been
anti‑dilutive and basic and diluted loss per share have been the same.
Contingent Liabilities
The Company accounts for its contingent liabilities in accordance with ASC No. 450, Contingencies. A provision is recorded when it is both probable that
a liability has been incurred and the amount of the loss can be reasonably estimated. With respect to legal matters, provisions are reviewed and adjusted to
reflect the impact of negotiations, estimated settlements, legal rulings, advice of legal counsel and other information and events pertaining to a particular
matter. As of December 31, 2019 and December 31, 2018, the Company was not a party to any litigation that could have a material adverse effect on the
Company’s business, financial position, results of operations or cash flows.
Leases
F-13
Under ASC Topic 842, Leases (ASC 842), which was adopted January 1, 2019, the Company determines whether the arrangement is or contains a lease
based on the unique facts and circumstances present. Most leases with a term greater than one year are recognized on the balance sheet as right-of-use
assets, lease liabilities and, if applicable, long-term lease liabilities. The Company elected not to recognize leases with a term less than one year on its
balance sheet. Operating lease right-of-use (ROU) assets and their corresponding lease liabilities are recorded based on the present value of lease payments
over the expected remaining lease term. The interest rate implicit in lease contracts is typically not readily determinable. As a result, the Company utilizes
its incremental borrowing rates, which are the rates incurred to borrow on a collateralized basis over a similar term, an amount equal to the lease payments
in a similar economic environment.
In accordance with the guidance in ASC 842, components of a lease should be split into three categories: lease components (e.g. land, building, etc.), non-
lease components (e.g. common area maintenance, consumables, etc.), and non-components (e.g. property taxes, insurance, etc.) Then the fixed and in-
substance fixed contract consideration (including any related to non-components) must be allocated based on fair values to the lease components and non-
lease components. Although separation of lease and non-lease components is required, the Company elected the practical expedient to not separate lease
and non-lease components. The lease component results in an operating right-of-use asset being recorded on the balance sheet and amortized on a straight-
line basis as lease expense. Right-of-use assets and operating lease liabilities are remeasured upon certain modifications to leases using the present value of
remaining lease payments and estimated incremental borrowing rate upon lease modification. See Note 8 for details.
Under prior guidance, rent expense and lease incentives from operating leases were recognized on a straight‑line basis over the lease term. The difference
between rent expense recognized and rental payments was recorded as deferred rent in the accompanying consolidated balance sheets.
Recent Accounting Pronouncements
Recently Adopted
In February 2016, the Financial Accounting Standards Board (“FASB”) issued Accounting Standards Update No. (“ASU”) 2016-02, Leases (Topic 842).
ASU 2016-02 requires lessees to recognize most leases on their balance sheet as a right-of-use asset and a lease liability. Leases are classified as either
operating or finance based on criteria similar to current lease accounting, with the classification affecting the pattern and classification of expense
recognition in the statement of operations.
Subsequently, in July 2018, the FASB issued ASU No. 2018-11, Leases (Topic 842): Targeted Improvements (ASU 2018-11), which includes certain
amendments to ASU 2016-02 intended to provide relief in implementing the new standard. Among these amendments is the option to not restate
comparative periods presented in the financial statements. The Company has elected this transition approach, using a cumulative-effect adjustment on the
effective date of the standard, with comparative periods presented in accordance with the existing guidance in ASC 840.
The Company adopted the new standard as of the required effective date of January 1, 2019 resulting in the recognition of a net additional lease liability
and right-of-use asset. The standard did not impact the Company's consolidated net loss. See Note 8 for details.
In November 2018, the FASB issued ASU No. 2018-18, Collaborative Arrangements (Topic 808): Clarifying the Interaction between Topic 808 and Topic
606 (ASU 2018-18), which provides guidance on whether certain transactions between collaborative arrangement participants should be accounted for with
revenue under Topic 606. The new standard is effective for fiscal years beginning after December 15, 2019, including interim periods within those fiscal
years with early adoption permitted. The Company early adopted the new standard effective September 30, 2019, and there was no impact on its
consolidated financial statements. See Note 14 for details.
Not Yet Adopted
In December 2019, the FASB issued ASU 2019-12, Income Taxes (Topic 740) - Simplifying the Accounting for Income Taxes. ASU 2019-12 simplifies the
accounting for income taxes by removing certain exceptions to the general principles in Topic 740. This ASU is effective for public entities for fiscal years
beginning after December 15, 2020. The Company is assessing the impact this standard will have on its consolidated financial statements and disclosures.
In June 2016, the FASB issued ASU 2016-13, Financial Instruments-Credit Losses (Topic 326), Measurement of Credit Losses on Financial Instruments.
Subsequently, in November 2018, the FASB issued ASU 2018-19, Codification Improvements to Topic 326, Financial Instruments-Credit Losses. ASU
2016-13 requires entities to measure all expected credit losses for most financial assets held at the reporting date based on an expected loss model which
includes historical experience, current conditions, and reasonable and supportable forecasts. ASU 2016-13 also requires enhanced disclosures to help
financial statement users better understand significant estimates and judgments used in estimating credit losses. This ASU is effective for smaller reporting
companies for fiscal years beginning after December 15, 2022, with early adoption permitted. The Company is assessing the impact this standard will have
on its consolidated financial statements and disclosures.
F-14
In August 2018, the FASB issued ASU No. 2018-13, Fair Value Measurement (Topic 820): Changes to the Disclosure Requirements for Fair Value
Measurement (ASU 2018-13) which changes the fair value measurement disclosure requirements of ASC 820. Entities will no longer be required to
disclose the amount of, and reasons for, transfers between Level 1 and Level 2 of the fair value hierarchy, the policy of timing of transfers between levels of
the fair value hierarchy and the valuation processes for Level 3 fair value measurements. This ASU is effective for public entities for fiscal years beginning
after December 15, 2019, with early adoption permitted. The Company is assessing the impact this standard will have on its consolidated financial
statements and disclosures.
3. Marketable Securities
As of December 31, 2019, and December 31, 2018, the Company did not have marketable securities.
4. Net Loss Per Share
The Company has reported a net loss for the years ended December 31, 2019, 2018, and 2017. For this reason basic and diluted net loss per share are the
same for all periods presented. Since the shares underlying the 8,342,128 pre-funded warrants are issuable for little or no consideration, they are considered
outstanding for both basic and diluted earnings per share. The following table sets forth the computation of basic and diluted net loss per share (in
thousands, except share and per‑share data):
Numerator:
Net loss attributable to common stockholders
Denominator:
Weighted‑average common shares and pre-funded warrants outstanding—basic and diluted
Net loss per share attributable to common stockholders —basic and diluted
Year Ended December 31,
2019
2018
2017
$
$
(55,350)
$
(65,336)
$
(65,321)
45,548,511
22,389,286
20,425,050
(1.22)
$
(2.92) $
(3.20)
All potential dilutive common shares have been excluded from the computation of the diluted net loss per share for all periods presented, as the effect
would have been anti-dilutive. Potential dilutive common share equivalents consist of the following:
Stock options to purchase common stock
Unvested restricted stock units
Stock warrants to purchase common stock
Total
5. Fair Value Measurements
Year Ended December 31,
2019
2018
2017
6,796,669
181,250
23,084,120
30,062,039
4,093,979
175,000
95,619
4,364,598
2,657,187
—
176,432
2,833,619
Assets and Liabilities Measured at Fair Value on a Recurring Basis
The tables below present information about the Company’s financial assets and liabilities that are measured and carried at fair value as of December 31,
2019 and December 31, 2018, and indicate the level within the fair value hierarchy where each measurement is classified. Below is a summary of assets
and liabilities measured at fair value on a recurring basis (in thousands):
Assets:
Money market funds
Total
Liabilities:
Warrant liabilities
Total
Total
(Level 1)
(Level 2)
(Level 3)
December 31, 2019
50,401
50,401
$
$
50,401 $
50,401 $
41,549
41,549
$
$
— $
— $
— $
— $
— $
— $
—
—
41,549
41,549
$
$
$
$
F-15
Assets:
Money market funds
Total
$
$
10,123 $
10,123 $
$
10,123
10,123
$
— $
— $
—
—
Total
(Level 1)
(Level 2)
(Level 3)
December 31, 2018
At each of December 31, 2019 and December 31, 2018, the money market funds were classified as cash and cash equivalent on the accompanying
consolidated balance sheet as they mature within 90 days from the date of purchase.
Assumptions Used in Determining Fair Value of Common Warrants
In December 2019, we issued common warrants in connection with our private placement of common shares. Pursuant to the terms of the common
warrants, we could be required to settle the common warrants in cash in the event of certain acquisitions of the Company and, as a result, the common
warrants are required to be measured at fair value and reported as a liability on the balance sheet. We recorded the fair value of the common warrants upon
issuance using the Black-Scholes valuation model and are required to revalue the common warrants at each reporting date with any changes in fair value
recorded on our statement of operations. The valuation of the common warrants is considered under Level 3 of the fair value hierarchy due to the need to
use assumptions in the valuation that are both significant to the fair value measurement and unobservable. The significant unobservable inputs used in the
fair value measurement of the warrant liabilities were the volatility rate and the estimated term of the warrants. Generally, increases (decreases) in the fair
value of the underlying stock and estimated term would result in a directionally similar impact to the fair value measurement. The change in the fair value
of the Level 3 warrant liability is reflected in the statement of operations for the year ended December 31, 2019.
The estimated fair value of warrants is determined using Level 3 inputs inherent in the Black Scholes simulation valuation.
Estimated fair value of the underlying stock. The Company estimates the fair value of the common stock based on the closing stock price at the
end of each reporting period.
Risk-free interest rate. The risk-free interest rate is based on the U.S. Treasury at the valuation date commensurate with the expected remaining
life assumption.
Dividend rate. The dividend rate is based on the historical rate, which the Company anticipates will remain at zero.
Expected life. The expected life of the warrants is assumed to be equivalent to their remaining contractual term which expires on December 23,
2024.
Volatility. The Company estimates stock price volatility based on the Company’s historical volatility and the historical volatility of peer companies
for a period of time commensurate with the expected remaining life of the warrants.
A summary of the Black Scholes pricing model assumptions used to record the fair value of the warrants is as follows:
Risk-free interest rate
Dividend yield
Expected life (in years)
Expected volatility
Issued on December 23,
Year Ended December 31,
2019
2019
1.75%
—
5.00
87.29%
1.69%
—
4.98
87.74%
Changes in Level 3 Liabilities Measured at Fair Value on a Recurring Basis
The following table reflects the change in the Company’s Level 3 warrant liabilities, (see Note 10), for the year ended December 31, 2019 (in thousands):
Fair value as of December 31, 2018
Warrants issued in connection with December 2019 private placement
Change in fair value
Fair value as of December 31, 2019
Warrant liabilities
—
40,692
857
41,549
$
$
6. Property and Equipment
F-16
Property and equipment consists of the following (in thousands):
Laboratory equipment
Computer equipment and software
Leasehold improvements
Furniture and fixtures
Office equipment
Construction in process
Total property and equipment
Less accumulated depreciation
Property and equipment, net
December 31,
December 31,
2019
2018
$
4,836
$
5,379
515
278
237
135
2
6,003
(4,781)
$
1,222
$
561
278
247
135
79
6,679
(4,552)
2,127
Depreciation expense was $0.7 million, $1.0 million and $0.8 million for the years ended December 31, 2019, 2018, and 2017, respectively. The Company
recorded accelerated depreciation costs of $0.04 million in the reported property and equipment for the year ended December 31, 2019 relating to the
upcoming new corporate headquarters move in 2020.
7. Accrued Expenses
Accrued expenses consist of the following (in thousands):
Payroll and employee related expenses
Current portion of deferred rent and lease incentive
Collaboration and licensing
Accrued patent fees
Accrued external research and development costs
Accrued professional and consulting services
Accrued grant refund
Accrued interest
Issuance costs, December financing
Other
Accrued expenses
8. Leases
$
December 31,
December 31,
2019
2018
2,235 $
—
1,050
487
4,379
446
—
82
4,381
432
2,497
117
1,222
736
5,344
994
175
106
—
509
$
13,492
$
11,700
On January 1, 2019, the Company adopted ASC 842 using the modified retrospective approach. The Company recorded operating lease assets (right-of-use
assets) of $1.6 million and operating lease liabilities of $1.8 million and reversed a lease liability of $0.2 million related to straight-line rent and incentives.
There was no impact to accumulated deficit upon adoption of ASC 842. The underlying assets of the Company’s leases are primarily office space. The
Company determines if an arrangement qualifies as a lease at its inception.
As a practical expedient permitted under ASC 842, the Company has elected to account for the lease and non-lease components as a single lease
component for all leases of which it is the lessee. Lease payments, which may include lease and non-lease components, are included in the measurement of
the Company’s lease liabilities to the extent that such payments are either fixed amounts or variable amounts that depend on a rate or index as stipulated in
the lease contract.
When the Company cannot readily determine the rate implicit in the lease, the Company determines its incremental borrowing rate by using the rate of
interest that it would have to pay to borrow on a collateralized basis over a similar term, an amount equal to the lease payments in a similar economic
environment. On January 1, 2019, the discount rate used on existing operating leases at adoption, which had remaining lease terms of 15 months, was
10.0%. For new or renewed leases starting in 2020, the discount rate is determined based on the Company’s incremental borrowing rate adjusted for the
lease term including any reasonably certain renewal periods.
The Company enters into lease agreements with terms generally ranging from 2-8 years. Some of the Company’s lease agreements include Company
options to either extend and/or early terminate the lease, the costs of which are included in its operating lease liabilities to the extent that such options are
reasonably certain of being exercised. Leases with renewal options allow the Company to extend the lease term typically between 1 and 5 years. When
determining the lease term, renewal options
F-17
reasonably certain of being exercised are included in the lease term. When determining if a renewal option is reasonably certain of being exercised, the
Company considers several economic factors, including but not limited to, the significance of leasehold improvements incurred on the property, whether
the asset is difficult to replace, underlying contractual obligations, or specific characteristics unique to that particular lease that would make it reasonably
certain that the Company would exercise such option. Renewal and termination options were generally not included in the lease term for the Company’s
existing operating leases.
Leases with an initial term of 12 months or less are not recorded on the balance sheet; the Company recognizes lease expense for these leases on a straight-
line basis over the lease term. For lease agreements entered into or reassessed after the adoption of ASC 842, lease and non-lease components are
combined.
The Company has a non‑cancellable operating lease for its laboratory and office space located at 480 Arsenal Way, Watertown, Massachusetts
("Headquarters Lease"). As part of the Headquarters Lease agreement, the landlord provided the Company a tenant improvement allowance of up to $0.7
million, which the Company fully utilized during 2012. The leasehold improvements are capitalized as a component of property and equipment. In
connection with the Headquarters Lease, the Company secured a letter of credit for $0.3 million which renews automatically each year and is classified in
restricted cash. In August 2016, the Company signed an amendment to the Headquarters Lease, which extends the term through March 31, 2020.
In October 2017, the Company entered into a lease for approximately 5,100 square feet of additional office space located at 75 North Beacon Street,
Watertown, Massachusetts (the “75 North Beacon Lease”). On January 11, 2019, the Company vacated 75 North Beacon Street, Watertown, MA and
consolidated all employees at its corporate headquarters at 480 Arsenal Way, Watertown, MA. The right-of-use asset carrying amount of $0.2 million
attributable to the 75 North Beacon Lease was written down to zero during the first quarter of 2019.
The Company has a month‑to‑month facility agreement for its Moscow, Russia office. Rent expense is recognized as incurred.
As of December 31, 2018 and prior to the adoption of ASC 842, the aggregate future minimum lease payments related to leases are as follows (in
thousands):
Year ending December 31,
2019
2020
Total minimum lease payments
1,482
375
1,857
$
In July 2019, the Company entered into a lease for 25,078 square feet of laboratory and office space located at 65 Grove Street, Watertown, Massachusetts
(the “New Headquarters Lease”). The Company estimates that it will incur $0.8 million in non-reimbursable lessee-paid construction costs for lessor assets.
None of these costs were incurred as of December 31, 2019. The lease begins in March 2020, consistent with when the Company takes control of the office
space and the expected lease term is 8 years, therefore the right-of-use asset and lease liability is not recorded on the balance sheet as of December 31,
2019. Rent payments are expected to occur in May 2020, and the base rent for the first year is $0.2 million per month. The total minimum rental
commitments for the New Headquarters Lease are $15.8 million. In connection with the New Headquarters Lease, the Company secured a letter of credit
from Silicon Valley Bank for $1.4 million which renews automatically each year.
The Company's total minimum rental commitments for the New Headquarters Lease as of December 31, 2019 are as follows (in thousands):
2020
2021
2022
2023
2024
Thereafter
Total New Headquarters Lease commitment
The right-of-use asset and lease liability has not been recorded as of December 31, 2019 as lease commencement will occur in 2020.
F-18
December 31,
2019
1,191
1,811
1,865
1,921
1,979
7,027
15,794
$
$
Rent expense for the years ended December 31, 2019, 2018 and 2017 was $2.1 million, $2.0 million and $1.9 million respectively.
For the year ended December 31, 2019, the components of lease costs were as follows (in thousands):
Operating lease expense
Variable lease expense
Short-term lease expense
Total lease expense
The maturity of the Company's operating lease liabilities as of December 31, 2019 were as follows (in thousands):
Operating leases:
2020
Total future minimum lease payments
Less imputed interest
Total operating lease liabilities
Included in the condensed consolidated balance sheet:
Current operating lease liabilities
Non-current operating lease liabilities
Total operating lease liabilities
The following information represents supplemental disclosure for the statement of cash flows related to operating leases (in thousands):
Operating leases:
Cash paid for amounts included in the measurement of lease liabilities:
Operating cash flows from operating leases
Year Ended
December 31,
2019
1,365
828
16
2,209
December 31,
2019
375
375
3
372
372
—
372
$
$
$
$
$
$
Year Ended
December 31,
2019
$
1,482
The changes in the Company’s right-of-use asset and lease liability for the year ended December 31, 2019 are reflected in the changes in prepaid expenses,
deposits and other assets and accrued expenses and other liabilities, respectively, in the consolidated statements of cash flows.
The following summarizes additional information related to operating leases:
Operating leases:
Weighted-average remaining lease term
Weighted-average discount rate
9. Debt
2017 Term Loan
December 31,
2019
0.3 years
10%
On September 12, 2017, the Company entered into a term loan facility of up to $21.0 million (the “2017 Term Loan”) with Silicon Valley Bank, a
California corporation (“SVB”). The 2017 Term Loan is governed by a loan and security agreement, dated September 12, 2017, between the Company and
SVB (the “Loan Agreement”). The 2017 Term Loan was funded in full on September 13, 2017 (the “Funding Date”).
F-19
On the Funding Date, the Company entered into a payoff letter with SVB, pursuant to which SVB utilized $10.0 million of the 2017 Term Loan to pay off
all outstanding obligations under the 2015 Term Loan. The Company recognized a loss on extinguishment of debt in the amount of $0.7 million during the
three months ended September 30, 2017.
The Company incurred less than $0.1 million in debt issuance costs in connection with the closing of the 2017 Term Loan. Debt issuance costs are
presented in the consolidated balance sheet as a direct deduction from the associated liability and amortized to interest expense over the term of the related
debt.
The 2017 Term Loan will mature on February 1, 2022. Each advance under the 2017 Term Loan accrues interest at a floating per annum rate equal to one-
half of one percent above the prime rate (as published in the money rates section of The Wall Street Journal). The 2017 Term Loan provided for interest-
only payments monthly until August 31, 2019. On September 1, 2019, the Company began making amortization payments on the Term Loan, which will
continue to be payable monthly in equal installments of principal and variable interest to fully amortize the outstanding principal over the remaining term
of the loan. The monthly interest is subject to recalculation upon a change in the prime rate. The Company may prepay the 2017 Term Loan in full but not
in part provided that the Company (i) provides five business days’ prior written notice to SVB, (ii) pays on the date of such prepayment for all outstanding
principal plus accrued and unpaid interest, 1% if prepaid after the second anniversary.
Amounts outstanding during an event of default are payable upon SVB’s demand and shall accrue interest at an additional rate of 4.0% per annum of the
past due amount outstanding. The events of default under the Loan Agreement include, but are not limited to, the Company’s failure to make any payments
of principal or interest under the Loan Agreement or other transaction documents, the Company’s breach or default in the performance of any covenant
under the Loan Agreement or other transaction documents, the occurrence of a material adverse effect, the Company making a false or misleading
representation or warranty in any material respect under the Loan Agreement, the Company’s insolvency or bankruptcy, any attachment or judgment on the
Company’s assets in excess of approximately $0.3 million, or the occurrence of any default under any agreement or obligation of the Company involving
indebtedness in excess of approximately $0.3 million. If an event of default occurs, SVB is entitled to take enforcement action, including acceleration of
amounts due under the Loan Agreement.
The 2017 Term Loan is secured by a lien on substantially all of the assets of the Company, other than intellectual property, provided that such lien on
substantially all assets includes any rights to payments and proceeds from the sale, licensing or disposition of intellectual property. The Company has also
granted SVB a negative pledge with respect to its intellectual property.
The 2017 Term Loan does not include any financial covenants. The 2017 Term Loan requires a final payment fee of 5% on the aggregate principal amounts
borrowed upon repayment at maturity, on a prepayment date, or upon default. The final payment fee totaling $1.1 million is recorded as a loan discount.
Under the 2017 Term Loan, the Company is not required to maintain a minimum cash balance. All deposits in operating, depository and securities accounts
are required to be maintained with SVB in an amount equal to the lessor of (i) 100% of the Company's cash balance or (ii) 105% of the dollar amount of
the then outstanding obligations. In addition, the 2017 Term Loan contains a subjective acceleration clause whereby in an event of default, an immediate
acceleration of repayment occurs if there is a material impairment of the lenders’ lien or the value of the collateral, a material adverse change in the
business condition or operations, or a material uncertainty exists that any portion of the loan may not be repaid.
The Company assessed all terms and features of the 2017 Term Loan in order to identify any potential embedded features that would require bifurcation.
As part of this analysis, the Company assessed the economic characteristics and risks of the 2017 Term Loan, including any put and call features. The
Company determined that all features of the 2017 Term Loan were clearly and closely associated with the debt host and did not require bifurcation as a
derivative liability, or the fair value of the embedded feature was immaterial to the Company's consolidated financial statements. The Company reassesses
the identified features on a quarterly basis to determine if they require bifurcation.
As of December 31, 2019 and December 31, 2018, the outstanding principal balance under the 2017 Term Loan was $18.2 million and $21.0 million,
respectively.
F-20
Future minimum principal and interest payments on the 2017 Term Loan as of December 31, 2019 are as follows (in thousands):
2020
2021
2022
Total minimum debt payments
Less: Amount representing interest
Less: Debt discount and deferred charges
Less: Current portion of loan payable
Loan payable, net of current portion
9,084
8,716
2,461
20,261
(1,011)
(345)
(18,905)
—
$
$
All amounts due under the 2017 Term Loan have been classified as a current liability as of December 31, 2019 due to the considerations discussed in Note
1 and the assessment that the material adverse change clause under the 2017 Term Loan is not within the Company's control. The Company has not been
notified of an event of default by SVB as of the date of the filing of this Annual Report on Form 10-K.
During the years ended December 31, 2019, 2018 and 2017, the Company recognized $1.5 million, $1.5 million and $1.2 million respectively of interest
expense related to the 2017 Term Loan.
10. Equity
December 2019 Financing
On December 18, 2019, the Company entered into a private purchase agreement (the "2019 Purchase Agreement"), and closed the Offering on December
23, 2019. Pursuant to the 2019 Purchase Agreement, the Company sold an aggregate of 37,634,883 shares of its common stock at a purchase price of $1.46
per share, warrants to purchase an aggregate of 22,988,501 shares of common stock at a purchase price of $0.125 per share underlying each common
warrant, and pre-funded warrants to purchase an aggregate of 8,342,128 shares of common stock at a purchase price of $1.46 per share, all with five year
terms. The exercise price of the pre-funded warrants was $0.0001 per share and the exercise price for the common warrants is $1.46 per share. In the event
of a certain sale of the Company, the terms of the common warrants require us to make a payment to such common warrant holders based on a Black-
Scholes valuation (using variables as specified in the warrants). This provision does not apply to the pre-funded warrants. Therefore, we are required to
account for the common warrants as liabilities and record them at fair value, while the pre-funded warrants met the criteria to be classified as permanent
equity. We recorded the fair value of the common warrants of $40.7 million upon issuance using the Black-Scholes valuation model. The common warrants
were revalued as of December 31, 2019 at $41.5 million; the change in fair value of $0.9 million was recorded in our statement of operations for the year
ended December 31, 2019. Issuance costs were allocated between the equity component with an offset to additional paid-in capital and the liability
component recorded as expense on a relative fair value basis. Total net proceeds from the equity offering was $65.6 million, after deducting transaction
costs and commissions of $4.4 million that were accrued at December 31, 2019.
Pursuant to the Registration Rights Agreement, the Company agreed to prepare and file a registration statement with the Securities and Exchange
Commission (the “SEC”) within 45 days after the closing of the Offering for purposes of registering the resale of the Shares, shares of Common Stock
issuable upon exercise of the Warrants, and any shares of Common Stock issued as a dividend or other distribution with respect to the Shares or shares of
Common Stock issuable upon exercise of the Warrants. If the Company did not file such registration statement by the 45-day filing deadline, the Company
would have been required to make pro-rata payments to each investor in an amount equal to 1% of the aggregate amount paid pursuant to the stock
purchase agreement entered into by such investor for each 30-day period or pro-rata portion thereof following the filing deadline. The Company filed a
registration statement on Form S-3 on January 29, 2020, which became effective on February 6, 2020, so no such payments were required.
The Company agreed, among other things, to indemnify the Investors, their officers, directors, members, employees and agents, successors and assigns
under the registration statement from certain liabilities and to pay all fees and expenses (excluding any legal fees of the selling holder(s), and any
underwriting discounts and selling commissions) incident to the Company’s obligations under the Registration Rights Agreement.
August 2019 Financing
On August 19, 2019, the Company sold 3,178,174 shares of its common stock pursuant to a stock purchase agreement (the "2019 Private Placement") to
individual investors, including certain executive officers and members of the board of directors of the Company for aggregate net proceeds of
approximately $5.7 million, after deducting transaction costs, at a purchase price
F-21
equal to $1.81 per share, which was equal to the most recent consolidated closing bid price on the Nasdaq Global Market on August 19, 2019. The shares in
the 2019 Private Placement were issued as “restricted securities” (as defined in Rule 144 of the Securities Act) and carry no registration rights that require
or permit the filing of any registration statement.
January 2019 Financing
On January 25, 2019, the Company completed an underwritten public offering (the “2019 Follow-On”) of 20,000,000 shares of its common stock at a
public offering price of $1.50 per share. On January 29, 2019, an additional 2,188,706 shares were sold at a public offering price of $1.50 per share
pursuant to the underwriters’ exercise of an over allotment option. The total net proceeds from the offering were $30.9 million, after deducting
underwriting discounts, transaction costs and commissions.
2019 “At-the-Market” Offerings
Concurrent with the filing of the shelf registration statement, the Company entered into a sales agreement (the “Sales Agreement”) with Jefferies LLC, as
sales agent, pursuant to which the Company may, from time to time, issue and sell common stock with an aggregate value of up to $50 million in an "at-
the-market" offering.
Sales of common stock, if any, pursuant to the Sales Agreement, may be made in sales deemed to be an “at the market offering” as defined in Rule 415(a)
of the Securities Act, including sales made directly through the Nasdaq Global Market or on any other existing trading market for the Company’s common
stock. The Company intends to use the proceeds from the offering for working capital and other general corporate purposes. The Company may suspend or
terminate the Sales Agreement at any time.
During the year ended December 31, 2019, the Company sold 615,453 shares of its common stock pursuant to the Sales Agreement at an average price of
approximately $1.84 per share for aggregate net proceeds of $1.0 million, after deducting commissions and other transaction costs.
August 2017 Shelf Registration Statement
On August 10, 2017, the Company filed a universal shelf registration statement on Form S-3 with the SEC to sell an aggregate amount of up to $200.0
million of certain of our securities. The shelf registration statement was declared effective by the SEC on August 28, 2017.
June 2017 Financing
On June 26, 2017, the Company entered into a securities purchase agreement (the "Institutional Purchase Agreement") with a select group of institutional
investors (the “Institutional Investors”) and a securities purchase agreement with Timothy A. Springer, Ph.D., a member of the board of directors (the
"Springer Purchase Agreement") for a private placement of the Company's securities (the "2017 PIPE"). The closing of the 2017 PIPE occurred on June 27,
2017.
Pursuant to the Institutional Purchase Agreement, the Company sold an aggregate of 2,750,000 shares of its common stock at a purchase price equal to
$16.00 per share. Pursuant to the Springer Purchase Agreement, the Company sold to Dr. Springer an aggregate of 338,791 shares of common stock at a
purchase price equal to $17.71 per share, which was equal to the most recent consolidated closing bid price on the Nasdaq Global Market on June 23, 2017,
and warrants to purchase up to 79,130 shares of common stock (“Warrant Shares”), exercisable at $17.71 per Warrant Share, and with a term of five years.
The purchase price for each warrant was equal to $0.125 for each Warrant Share, consistent with Nasdaq Global Market requirements for an “at the
market” offering. Under the terms of the Common Stock Purchase Warrant, the warrants can be settled in unregistered shares. The Warrant Shares qualify
for equity classification. The fair value of the allocated proceeds was determined on the relative fair value basis. After deducting for placement agent fees
and offering expenses, the aggregate net proceeds from the 2017 PIPE were approximately $47.1 million.
On June 27, 2017, in connection with the 2017 PIPE, the Company entered into a Registration Rights Agreement (the “Registration Rights Agreement”)
with the Institutional Investors and Dr. Springer. Pursuant to the Registration Rights Agreement, the Company agreed to prepare and file a registration
statement with the SEC within 20 days after the closing of the 2017 PIPE for purposes of registering the resale of the shares of common stock issued and
sold in the 2017 PIPE (the “Shares”), the Warrant Shares, and any shares of common stock issued as a dividend or other distribution with respect to the
Shares or Warrant Shares. The 2017 PIPE registration statement was declared effective by the SEC on July 21, 2017.
The Company agreed to indemnify the Institutional Investors and Dr. Springer, their officers, directors, members, employees and agents, successors and
assigns under the registration statement from certain liabilities and to pay all fees and expenses (excluding any legal fees of the selling holder(s), and any
underwriting discounts and selling commissions) incident to the Company’s obligations under the Registration Rights Agreement.
Warrants
The following table summarizes warrant activity for the years ended December 31, 2019, 2018 and 2017 as follows:
F-22
Outstanding at December 31, 2017
Issuance
Exercises
Expirations/ cancellations
Outstanding at December 31, 2018
Issuance
Exercises
Expirations/ cancellations
Outstanding at December 31, 2019
Common Stock
Number of Warrants
Equity classified
Liability classified
Total
Weighted average
exercise price
176,432
—
—
(80,813)
95,619
—
—
—
—
—
8,342,128
22,988,501
—
—
—
—
8,437,747
22,988,501
176,432 $
—
—
(80,813)
95,619
31,330,629
—
—
31,426,248 $
17.32
—
—
17.55
17.12
1.07
—
—
1.12
As of December 31, 2019, the Company had 200,000,000 shares of common stock authorized for issuance, $0.0001 par value per share, with 86,325,547
shares issued and outstanding. The voting, dividend and liquidation rights of the common stockholders are subject to and qualified by the rights, powers
and preferences of the preferred stock. The common stock has the following characteristics:
Voting
The common stockholders are entitled to one vote for each share of common stock held with respect to all matters voted on by the stockholders of the
Company.
Dividends
The common stockholders are entitled to receive dividends, if and when declared by the Board of Directors. Through December 31, 2019, no dividends
have been declared or paid on common stock.
Liquidation
Upon liquidation of the Company, the common stockholders are entitled to receive all assets of the Company available for distribution to such stockholders.
Reserved Shares
The Company has authorized shares of common stock for future issuance as follows:
Exercise of common and pre-funded warrants
Shares available for future stock incentive awards
Unvested restricted stock units
Outstanding common stock options
Total
11. Stock Incentive Plans
Stock Options
Period ending
December 31, 2019
December 31, 2018
31,426,248
1,765,018
181,250
6,796,669
40,169,185
95,619
1,586,925
175,000
4,093,979
5,951,523
The Company maintains the 2008 Stock Incentive Plan (the “2008 Plan”) for employees, consultants, advisors, and directors. The 2008 Plan provided for
the granting of incentive and non‑qualified stock option and restricted stock awards as determined by the Board. At inception of the 2008 Plan, a total of
2,213,412 shares of common stock were authorized for grants under the 2008 Plan. The Company ceased granting awards under the 2008 Plan upon the
effectiveness of the 2016 Plan (as defined below); however, awards issued under the 2008 Plan remain subject to the terms of the 2008 Plan and the
applicable 2008 Plan agreement. Shares subject to awards that were granted under the 2008 Plan and that expire, lapse or terminate following the
F-23
effectiveness of the 2016 Plan become available under the 2016 Plan as shares available for future grants. All unvested stock options granted under the
2008 Plan may be exercised into restricted stock subject to forfeiture upon termination prior to vesting.
On June 7, 2016, the Company’s stockholders approved the 2016 Incentive Award Plan (the “2016 Plan”), which became effective June 21, 2016. The 2016
Plan provides for the granting of incentive and non‑qualified stock option, restricted stock and other stock and cash-based awards as determined by the
Board. Shares subject to awards that are granted under the 2016 Plan and that expire, lapse or terminate are available for future grants under the 2016 Plan.
At inception of the 2016 Plan, a total of 1,210,256 shares of common stock were authorized for future issuance under the 2016 Plan. The number of shares
of common stock that may be issued under the 2016 Plan automatically increases on the first day of each calendar year, beginning in 2017 and ending in
and including 2026, by an amount equal to the lesser of: (i) 4% of the number of shares of the Company’s common stock outstanding on the last day of the
applicable preceding calendar year and (ii) such smaller number of shares as is determined by the Board. During the year ended December 31, 2019 and
2018, the number of shares of common stock that may be issued under the 2016 Plan was increased by 898,871 shares and 893,730 shares, respectively. As
of December 31, 2019, 267,612 shares remain available for future issuance under the 2016 Plan.
The 2008 Plan and 2016 Plan provide that the exercise price of incentive stock options cannot be less than 100% of the fair market value of the Company's
common stock on the grant date for participants who own 10% or less of the total combined voting power of the Company, and not less than 110% for
participants who own more than 10% of the Company’s voting power. Options and restricted stock awards granted under the 2008 Plan and 2016 Plan vest
over periods as determined by the Board, which are generally four years and, for options, with terms that generally expire ten years from the grant date.
The Company’s 2018 Employment Inducement Incentive Award Plan (the “Inducement Incentive Award Plan”), which was adopted by the Board on
September 25, 2018 without stockholder approval pursuant to Rule 5635(c)(4) of the Nasdaq Stock Market LLC listing rules ("Rule 5635(c)(4)"), provides
for the grant of equity-based awards in the form of non-qualified stock options, stock appreciation rights, restricted stock awards, restricted stock unit
awards and other stock or cash based awards. In accordance with Rule 5635(c)(4), awards under the Inducement Incentive Award Plan may only be made
to a newly hired employee who has not previously been a member of the Board, or an employee who is being rehired following a bona fide period of non-
employment by the Company, as a material inducement to the employee’s entering into employment with the Company. The Company reserved 1,175,000
shares of its common stock for issuance under the Inducement Incentive Award Plan. On March 25, 2019, the Board approved the amendment and
restatement of the Inducement Incentive Award Plan to reserve an additional 2,000,000 shares of the Company’s common stock for issuance thereunder. As
of December 31, 2019, there are 750,000 shares available for future grant under the Inducement Incentive Award Plan.
The fair value of each option award was estimated on the grant date using the Black‑Scholes option pricing model. Expected volatilities are based on
historical volatilities from guideline companies because the Company's common stock has not traded for a period that is at least equal to the expected term
of its stock option awards. The Company uses the “simplified” method to estimate the expected life of options granted and are expected to be outstanding.
The risk‑free interest rate used is the rate for a U.S. Treasury zero coupon issue with a remaining life consistent with the options expected life on the grant
date. The Company has not paid and does not expect to pay in the foreseeable future, any cash dividends. Forfeitures are estimated at the time of grant and
are adjusted, if necessary, in subsequent periods if actual forfeitures differ from those estimates. The Company has estimated a forfeiture rate of 10% based
on historical attrition trends. The Company records stock‑based compensation expense only on awards that are expected to vest.
The estimated grant date fair values of employee stock option awards granted under the 2016 Plan and the 2018 Inducement Incentive Award Plan were
calculated using the Black-Scholes option pricing model, based on the following weighted-average assumptions:
Risk-free interest rate
Dividend yield
Expected term
Expected volatility
Weighted-average fair value of common stock
Year Ended December 31,
2019
2018
2017
1.86%
—
5.94
87.66%
2.85%
—
6.06
85.17%
$
2.01
$
8.45
$
2.03%
—
5.90
84.52%
15.32
The weighted average grant date fair value of stock options granted to employees during the years ended December 31, 2019, 2018 and 2017 was $1.47,
$6.17, and $10.97 respectively. The aggregate intrinsic value of stock options exercised during the years ended December 31, 2019, 2018 and 2017 was
$0.1 million, $0.6 million, and $2.6 million respectively.
F-24
As of December 31, 2019 and December 31, 2018, total unrecognized compensation expense related to unvested employee stock options was $9.8 million
and $9.8 million, respectively, which is expected to be recognized over a weighted average period of 2.5 years and 3.1 years, respectively.
Effective November 20, 2019, the Company amended the terms of the options granted to a non-employee director in connection with his resignation from
the board of directors, whereby he was entitled to receive immediate vesting of his outstanding, unvested stock options (141,328 shares), provided that the
options will become exercisable in accordance with their original vesting schedules irrespective of his termination of service, and an extension of the right
to exercise each of his vested stock options (234,772 shares) until the final expiration date of the applicable option, resulting in a modification. The
subsequent stock-based compensation amount recognized as of December 31, 2019 was $0.1 million.
The estimated grant date fair values of non-employee stock option awards granted under the 2016 Plan were calculated using the Black-Scholes option
pricing model, based on the following weighted-average assumptions:
Risk-free interest rate
Dividend yield
Expected life (in years)
Expected volatility
Year Ended December 31,
2019
2018
2017
1.92%
—
5.33
88.60%
2.77%
—
5.81
85.86%
—%
—
0.00
—%
The weighted average grant date fair value of stock options granted to non-employees during the years ended December 31, 2019 and 2018 was $1.32 and
$6.78, respectively.
As of December 31, 2019 and 2018 total unrecognized compensation expense related to unvested non‑employee stock options was less than $0.1 million
and $1.1 million, respectively, which is expected to be recognized over a weighted average period of 0.4 years and 2.2 years, respectively.
The following table summarizes the activity under the 2008 Plan, 2016 Plan, and 2018 Inducement Incentive Award Plan:
Weighted‑average
remaining
Aggregate
Number of
options
Weighted-average
contractual term
intrinsic value
exercise price ($)
(in years)
(in thousands)
Employee awards
Outstanding at December 31, 2018
Granted
Exercised
Forfeited
Outstanding at December 31, 2019
Vested at December 31, 2019
Vested and expected to vest at December 31, 2019
Non‑employee awards
Outstanding at December 31, 2018
Granted
Exercised
Forfeited
Outstanding at December 31, 2019
Vested at December 31, 2019
Vested and expected to vest at December 31, 2019
Restricted Stock Units
3,681,575
3,876,255
(125,600)
(1,108,634)
6,323,596
1,485,228
5,843,053
$
$
$
$
$
$
$
412,404
73,489
$
$
— $
$
$
(12,820)
473,073
330,528
473,073
$
$
9.49
2.01
1.20
10.38
4.91
10.02
5.10
6.44
1.86
—
0.47
5.89
5.61
5.89
7.77 $
300
8.71 $
6.73 $
8.65 $
6.42 $
6.23 $
5.06 $
6.23 $
1,716
90
1,500
28
38
21
38
During the first quarter of 2019, the Company awarded 100,000 restricted stock units under the Inducement Incentive Award Plan, of which 50,000 were
determined to be granted and 50,000 were reserved for issuance consistent with ASC Topic 718, Compensation-Stock Compensation (ASC 718). The
50,000 granted restricted stock units had a fair value of $2.29 per share based on the closing price of the Company’s common stock on the date of grant.
These restricted stock units were valued at approximately $0.1 million, and will vest on the date an applicable performance condition is achieved on or
prior to December
F-25
31, 2020. If the performance condition is not satisfied on or prior to December 31, 2020, the restricted stock units will be forfeited for no consideration.
The 50,000 reserved restricted stock units did not have defined performance criteria until August 6, 2019, at which time, they were deemed both granted
and vested. These restricted stock units had a fair value of $1.65 per share. These restricted stock units were valued at approximately $0.1 million and fully
expensed as of December 31, 2019.
Unrecognized compensation expense for the restricted stock units was $0.8 million as of December 31, 2019, which is expected to be recognized over a
weighted average period of 2.8 years.
The following table summarizes the status of the Company’s restricted stock units:
Unvested at December 31, 2018
Granted
Vested
Forfeited
Unvested at December 31, 2019
Employee Stock Purchase Plan
Number of shares
Weighted average
fair value ($)
175,000
$
100,000
93,750
—
181,250
$
6.03
1.97
1.65
—
5.00
On June 7, 2016, the Company’s stockholders approved the 2016 Employee Stock Purchase Plan (the “ESPP”), which became effective June 21, 2016. The
ESPP is intended to qualify as an "employee stock purchase plan" under Section 423 of the Internal Revenue Code of 1986 with the purpose of providing
employees with an opportunity to purchase the Company's common stock through accumulated payroll deductions.
Under the ESPP, the Company has set two six-month offering periods during each calendar year, one beginning March 1st and the other beginning
September 1st of each calendar year, during which employees may elect to have up to 25% of their eligible compensation deducted on each payday on an
after-tax basis for use in purchasing the Company's common stock on the last trading day of each offering period, subject to limits imposed by the Internal
Revenue Code. The purchase price of the shares may not be less than 85% of the fair market value on the first or last trading day of the offering period,
whichever is lower. The first ESPP offering period began on March 1, 2017.
At inception of the ESPP, a total of 173,076 shares of common stock were authorized and reserved for future issuance under the ESPP. The number of
shares of common stock that may be issued under the ESPP will automatically increase on the first day of each calendar year, beginning in 2017 and ending
in and including 2026, by an amount equal to the lesser of: (i) 1% of the number of shares of the Company’s common stock outstanding on the last day of
the applicable preceding calendar year and (ii) such smaller number of shares as is determined by the Company’s Board of Directors. During the year ended
December 31, 2019 and 2018, the number of shares of common stock that may be issued under the ESPP was increased by 224,717 shares and 223,432
shares, respectively. During the year ended December 31, 2019, the Company issued 17,205 shares of common stock under the ESPP. As of December 31,
2019, 747,406 shares remain available for future issuance under the ESPP.
For each of the years ended December 31, 2019 and 2018, the Company recognized less than $0.1 million of stock-based compensation expense under the
ESPP.
The Company recorded stock-based compensation expense related to stock option awards, restricted stock units and the ESPP in the following expense
categories of its consolidated statements of operations and comprehensive loss (in thousands):
Research and development
General and administrative
Total stock-based compensation expense
12. Revenue Arrangements
F-26
Year Ended December 31,
2019
2018
2017
$
$
2,079
3,082
5,161
$
$
2,453 $
3,261
5,714 $
1,779
2,302
4,081
The Company adopted ASC 606 on January 1, 2018, using the modified retrospective method for all contracts not completed as of the date of adoption.
The reported results for 2018 reflect the application of ASC 606 guidance while the reported results for 2017 were prepared under the guidance of ASC
605, Revenue Recognition (ASC 605), which is also referred to herein as "legacy GAAP" or the "previous guidance". The adoption of ASC 606 represents
a change in accounting principle that will more closely align revenue recognition with the delivery of the Company's services and will provide financial
statement readers with enhanced disclosures.
Financial Statement Impact of Adopting ASC 606
The cumulative effect of applying the new guidance to all contracts with customers that were not completed as of January 1, 2018, was recorded as an
adjustment to accumulated deficit as of the adoption date. As a result of applying the modified retrospective method to adopt the new revenue guidance, the
Company recorded an adjustment to long term deferred revenue and accumulated deficit totaling $1.8 million. In connection with the adoption of ASC 606,
the Company identified three collaboration/grant arrangements that required analysis to quantify the impact of adoption to its opening accumulated deficit
balance as of January 1, 2018: Spark Therapeutics, Inc., Skolkovo Foundation and National Institutes of Health.
Asklepios Biopharmaceutical, Inc.
License Agreement for Pompe Disease
On December 17, 2019, the Company and AskBio entered into a License Agreement, referred to as the AskBio License Agreement. Pursuant to the AskBio
License Agreement, AskBio has exercised its option to exclusively license the Company’s intellectual property rights covering the Company’s ImmTOR
platform to research, develop, and commercialize certain AAV gene therapy products utilizing ImmTOR, and targeting the GAA gene, or derivatives
thereof, to treat Pompe Disease.
Pursuant to the AskBio License Agreement and ancillary documents, AskBio agreed to pay to the Company upfront fees of an aggregate of $7.0 million.
Assuming successful development and commercialization, the Company could receive up to an additional $237.0 million in development, regulatory, and
sales milestone payments. If commercialized, the Company would be eligible to receive tiered royalties on global net sales at percentages ranging from
mid-to-high single digits. Under the terms of the agreement, the Company will be eligible to receive these royalties commencing on the first commercial
sale of the licensed product until the expiration of the later of (i) ten years after the first commercial sale and (ii) expiration of the last to expire valid claim
on patents covering the licensed product.
Pursuant to the AskBio License Agreement, the Company will supply AskBio with its ImmTOR platform ("Supply Obligation") and AskBio will be
responsible for all preclinical, clinical and commercial manufacture and supply of Licensed Products (other than ImmTOR) and carry out all other activities
related to the research, development, and commercialization of Licensed Products at its sole expense, including all regulatory activities related thereto.
The Company determined that the AskBio License was not capable of being distinct from the Supply Obligation. The Company has concluded that AskBio
cannot derive benefit from the license without the simultaneous transfer of the patent protected ImmTOR supply. Therefore, the License Obligation and
Supply Obligation represent the only promise in the arrangement and are combined as a single performance obligation (the “AskBio License and Supply
Obligation”).
In determining the transaction price, the Company concluded that the future development milestones, regulatory milestones, sales milestones, and sales
royalties all represent variable consideration. Each of these variable consideration items was evaluated under the most likely amount method to determine
whether such amounts were probable of occurrence, or whether such amounts should be constrained until they become probable. As part of its evaluation
of the constraint, the Company considered numerous factors, including that receipt of such milestones is outside the control of the Company. Consideration
related to sales-based milestones as well as royalties on net sales upon commercialization by AskBio, will be recognized when the related sales occur, as
they were determined to relate predominantly to the intellectual property granted to AskBio and, therefore, have also been excluded from the transaction
price in accordance with the royalty recognition constraint. As of December 31, 2019, all milestones were constrained. The Company will re-evaluate the
transaction price in each reporting period, as uncertain events are resolved, or as other changes in circumstances occur.
The total initial transaction price of the contract on the effective date is $7.0 million, which is comprised of the $2.0 million initial up-front payment upon
agreement of terms, and $5.0 million initial up-front execution fee. The $5.0 million execution fee became billable on the effective date and is recorded on
the balance sheet as a receivable and a corresponding contract liability as of December 31, 2019.
As of December 31, 2019, the Company recorded $1.7 million as a short-term contract liability and $5.3 million as a long-term contract liability
representing deferred revenue associated with this agreement.
Spark Therapeutics, Inc.
Spark License Agreement
F-27
In December 2016, the Company entered into a License and Option Agreement (“Spark License Agreement”) with Spark Therapeutics, Inc. (“Spark”)
pursuant to which the Company and Spark agreed to collaborate on the development of gene therapies for certain targets utilizing the ImmTOR platform.
The Spark License Agreement provides Spark with certain exclusive, worldwide, royalty bearing licenses to the Company’s intellectual property, allowing
Spark to develop and commercialize gene therapies in combination with ImmTOR for an initial identified target.
In addition to an upfront cash payment of $10.0 million under the Spark License Agreement, additional payments of an aggregate of $5.0 million in two
payments of $2.5 million each were paid within twelve months of December 2, 2016 (“Contract Date”). The first of the two additional payments was
scheduled to be made on or before May 31, 2017 (the “May 2017 License Payment”) (see “Spark Letter Agreement” below) and the second was made on
October 31, 2017. Spark may also exercise options to research, develop and commercialize gene therapies utilizing the ImmTOR platform for up to four
additional targets. The Company was eligible to receive a variable fee up to $2.0 million for each additional target option elected, dependent on the
incidence of the applicable indication. The election period in which Spark could have exercised additional targets under the Spark License Agreement was
a term of three years from the Contract Date, which expired on December 1, 2019.
Assuming successful development and commercialization, the Company could receive up to an additional $65.0 million in development and regulatory
milestone payments and $365.0 million in commercialization milestone payments for each indication. If commercialized, the Company would be eligible to
receive tiered royalties on global net sales at percentages ranging from mid-single to low-double digits, all of which apply on a target-by-target basis. Under
the terms of the agreement, the Company will be eligible to receive these royalties commencing on the first commercial sale of the licensed product and
terminating upon the later of (i) ten years after the first commercial sale, (ii) expiration of the last to expire valid claim on patents covering the jointly
invented field specific improvements, or (iii) the expiration of regulatory exclusivity in the applicable country for the licensed product.
The Spark License Agreement may be terminated by Spark for convenience upon ninety days’ notice. Either party may terminate the Spark License
Agreement on a target-by-target basis for material breach with respect to such target.
In December 2016, the Company also entered into a Share Purchase Agreement (the “Spark Purchase Agreement”) with Spark. Pursuant to the Spark
Purchase Agreement, the Company sold 197,238 shares of the Company’s common stock to Spark for gross proceeds of $5.0 million, or $25.35 per share
of common stock, at an initial closing (the “Initial Closing”). The purchase price per share represents an amount equal to 115% of the average daily volume
weighted average price (“VWAP”) of the common stock during the thirty consecutive calendar days leading up to and ending on the day prior to the
Contract Date.
Beyond the Initial Closing, the Spark Purchase Agreement contemplated potential future sales of shares by the Company to Spark as follows:
•
•
First Acquisition Right. During the period beginning on May 1, 2017 and ending on June 1, 2017, Spark had the right (the “First Acquisition
Right”) to purchase a number of shares of common stock equal to an aggregate price of $5.0 million. See "Spark Letter Agreement" below.
Second Acquisition Right. During the period beginning on October 1, 2017 and ending on November 1, 2017, Spark had the right (the “Second
Acquisition Right”) to purchase a number of shares of common stock equal to an aggregate price of $5.0 million. On October 31, 2017 Spark
exercised this right and purchased 205,254 shares of common stock from the Company for $5.0 million, or $24.36 per share of common stock.
The purchase price per share represents an amount equal to 115.0% of the average daily VWAP of the common stock during the thirty consecutive
calendar days leading up to and ending on the day prior to the Second Acquisition Right notification date.
The First Acquisition Rights and Second Acquisition Rights are collectively referred to herein as the “Acquisition Rights”.
Under the Spark Purchase Agreement, Spark agreed not to dispose of any of the shares acquired at either the Initial Closing or the from the subsequent
Acquisition Rights that it may acquire until January 1, 2018 and, thereafter, transfers are contractually subject to volume limitations applicable to an
“affiliate” under Rule 144 of the Securities Act.
In connection with the Spark License Agreement and Spark Purchase Agreement, the Company has made contractual payments defined in the MIT license
agreement (see Note 14) totaling $2.2 million for the MIT sub-license provided to Spark, and $0.4 million relative to the calculated premium paid by Spark
for the equity investments made under the Spark Purchase Agreement.
The terms of the Spark Purchase Agreement and the Spark License Agreement were negotiated at the same time between the parties and the terms of the
Spark Purchase Agreement are referenced in the Spark License Agreement in multiple sections. The pricing and terms of the agreements are unique and
must be considered in contemplation with each other. There are provisions within the Spark License Agreement that link to the Spark Purchase Agreement
related to provisions that constitute a material breach of the license agreement. Therefore, the Company concluded that the two agreements must be
combined and evaluated as a single agreement. While the Spark Purchase Agreement and the Spark License agreement are considered to be a single
F-28
agreement, the Company determined that the purchase of common stock and future acquisition rights are not within the scope of ASC 606. The Company
determined that the initial purchase of common stock combined with the embedded future stock Acquisition Rights had a fair value of $2.7 million and this
amount was recorded in equity as of the effective date. The remaining $2.3 million of cash received in exchange for the stock and acquisition rights is
included in allocable consideration, as this represents the premium paid by Spark on the purchase of common stock, and should be allocated to the
remaining performance obligations.
The Company identified the following components of the agreement: (1) certain exclusive, worldwide, royalty bearing licenses to the Company’s
intellectual property and a license to conduct certain research activities under the collaboration, (the "Spark License"), (2) options to research, develop and
commercialize gene therapies utilizing the ImmTOR platform for up to four additional target therapy options, (the "Option Obligation"), (3) manufactured
supply of ImmTOR, (the "Supply Obligation") at a discount. In exchange, the Company received an upfront payment of $15.0 million and is eligible to
receive additional payments of up to $35.0 million based on the achievement by Spark of future specified development milestones, up to $30.0 million
based on the achievement by Spark of future specified regulatory milestones, up to $110.0 million based on the achievement by Spark of future specified
commercial milestones, and up to $255.0 million based on the achievement by Spark of future specified sales milestones. The Company will also be
eligible to receive tiered royalty payments that reach low double-digits based on future net sales for the duration of the royalty term.
The Company determined that the Spark License and Supply Obligation represent a single promise and performance obligation (the “Combined License
and Supply Obligation”). This is because Spark cannot derive benefit from the license without the simultaneous transfer of the patent protected ImmTOR
supply. The Company also determined that the Target Options, which includes the related Supply Obligation, provides the customer with a material right
and is considered a performance obligation in the arrangement since it was priced at an incremental discount. Therefore, the Company determined that the
Spark agreement contains five distinct performance obligations: the Combined License and Supply Obligation, and the four separate Target Options.
In determining the transaction price, the Company considered the future development milestones, regulatory milestones, commercial milestones, sales
milestone, and sales royalties all represent variable consideration. Each of these variable consideration items was evaluated under the most likely amount
method to determine whether such amounts were probable of occurrence, or whether such amounts should be constrained until they become probable. As
part of its evaluation of the constraint, the Company considered numerous factors, including that receipt of such milestones is outside the control of the
Company. Separately, any consideration related to sales-based milestones as well as royalties on net sales upon commercialization by Spark, will be
recognized when the related sales occur as they were determined to relate predominantly to the intellectual property granted to Spark and, therefore, have
also been excluded from the transaction price in accordance with the royalty recognition constraint. As of December 31, 2019, all future milestones are
constrained. The Company will re-evaluate the transaction price in each reporting period, as uncertain events are resolved, or as other changes in
circumstances occur.
The Company determined that the up-front payment of $12.3 million ($15.0 million, less fair value of the equity totaling $2.7 million as discussed above)
was included in the transaction price and was allocated to the performance obligations based on the Company’s best estimate of their relative stand-alone
selling prices. The Company allocated $7.1 million to the Combined License and Supply Obligation and $5.2 million to the discount on the Target Options
($1.3 million for each option) using the relative standalone selling price method to each obligation. The standalone selling price for the Combined License
and Supply Obligation was determined using a discounted cash flow model. The standalone selling price for the Target Options were determined based on
the fair value of the license minus the strike price of the option (the probability of exercise was included in the valuation) as well as the estimated discount
of the Supply Obligation.
The estimated proceeds expected to be received from the sale of the Supply Obligation were also included in the transaction price for the Combined
License and Supply Obligation. The total consideration allocated to the Combined License and Supply Obligation will be recognized using the output
method, based on the proportion of actual deliveries to the total expected deliveries over the initial term which was initially estimated to be approximately
four years.
On December 1, 2019, the term for Spark to exercise additional target options expired; the Company recognized $6.7 million in revenue from deferred
revenue as originally allocated. In addition, during the year ended December 31, 2019, there were two deliveries resulting in less than $0.1 million of
revenue recognized. No revenue related to the Spark License Agreement was recognized during the year ended December 31, 2018.
As of December 31, 2019, there was a contract liability of $9.2 million representing deferred revenue presented as non-current associated with this
agreement. As of December 31, 2018, there was $14.7 million of deferred revenue related to this agreement.
Spark Letter Agreement
F-29
On June 6, 2017, the Company and Spark entered into a letter agreement (the “Letter Agreement”), pursuant to which the parties agreed that Spark would
make the May 2017 License Payment by June 6, 2017. The May 2017 License Payment was received, and recorded as a liability as of June 30, 2017, of
which some or all may potentially constitute the reimbursement described below. The parties also agreed that Spark would be deemed to have delivered
notice on May 31, 2017 exercising its right to purchase the shares pursuant to the First Acquisition Right. The Letter Agreement further outlines a cost
reimbursement arrangement, pursuant to which the Company agreed to reimburse Spark for all costs and expenses, including the cost of materials provided
by the Company, associated with the preclinical research and toxicology studies being performed by Spark for any licensed products for a specified amount
of time (the “Reimbursement Period”), in an amount not to exceed $2.5 million.
Consistent with the First Acquisition Right, Spark purchased 324,362 shares of common stock pursuant to the Spark Purchase Agreement, as amended by
the Letter Agreement, for an aggregate purchase price of $5.0 million, or $15.41 per share of common stock. The purchase price per share represents an
amount equal to 115.0% of the average daily VWAP of the common stock during the thirty consecutive calendar days leading up to and ending on the day
prior to the First Acquisition Right notification date. At the initial contract assessment, the Company allocated $2.7 million to equity (representing the fair
value of the initial purchase of common stock combined with the embedded future stock Acquisition Rights). Upon exercise of the First Acquisition Right,
the Company recorded the purchase amount to stockholders’ equity (deficit).
The Company determined that the Letter Agreement resulted in a modification to the original agreement. The amount received totaling $2.5 million and the
reimbursements pursuant to the Letter Agreement totaling $2.5 million were both included in the transaction price, and a liability was recorded for the
amount expected to be repaid. As repayments were made, the underlying liability was reduced. To the extent that an amount was expected to be applied
towards the clinical supply obligation, the analysis of variable consideration was updated accordingly.
On October 31, 2017, Spark paid the Company a $2.5 million milestone payment pursuant to the Spark License Agreement, which was included in the
transaction price and allocated to the performance obligations using the relative standalone selling price. In addition, Spark exercised the Second
Acquisition Right set forth in Section 2.4 of the Spark Purchase Agreement and purchased 205,254 shares of common stock from the Company for $5.0
million, or $24.36 per share of common stock. The purchase price per share represents an amount equal to 115.0% of the average daily VWAP of the
common stock during the thirty consecutive calendar days leading up to and ending on the day prior to the Second Acquisition Right notification date.
On June 5, 2019, the term of the Reimbursement Period under the Letter Agreement expired. During the year ended December 31, 2019, the Company
updated its estimate of variable consideration included in the transaction price to include $1.2 million of unpaid reimbursements to Spark.
Skolkovo Foundation
The Company has received grant funding from the Russia-based Development Fund of New Technologies Development and Commercialization Center
("Skolkovo"). From grant inception through December 31, 2019, the Company received $2.0 million from Skolkovo.
Based on the guidance in ASC 606, the Company concluded that the entire $2.0 million of grant funds received from Skolkovo is variable consideration.
Although the Company believes it has an enforceable right to the amounts received, there is risk that an audit could result in the Company needing to
refund certain amounts back to Skolkovo, resulting in variability in the transaction price. The Company utilized the “expected value” approach in
determining the amount that can be recognized. The Company estimated that it will be entitled to revenue of $1.8 million from the Skolkovo grant, and
recorded this amount. The remainder of $0.2 million was recorded as a contract liability.
During the year ended December 31, 2018, the Company made a decision to cease work relating to the Skolkovo grant. As a result, Skolkovo performed a
formal review of project expenses incurred by the Company. Skolkovo concluded that the Company should (i) return unused grant funds to Skolkovo in the
amount of less than $0.1 million and (ii) reimburse $0.1 million of costs deemed to have been overspent relative to the cost share requirement stipulated in
the grant.
As of December 31, 2019, a contract liability of $0.1 million remains on the balance sheet and will not be recognized as revenue until the expiration of the
three-year audit period, expected April 2021, or sooner, if resolution is reached with Skolkovo or there is a change in the estimate.
Transaction Price Allocated to Future Performance Obligations
Remaining performance obligations represent the transaction price of contracts for which work has not been performed (or has been partially performed).
As of December 31, 2019, the aggregate amount of the transaction price allocated to remaining performance obligations was $9.2 million. The Company
does not expect to recognize revenue on the remaining performance obligations over the next 12 months.
Contract Balances from Contracts with Customers (AskBio, Spark and Skolkovo Foundation)
F-30
The following table presents changes in the Company’s contract liabilities during the year ended December 31, 2019 (in thousands):
Year Ended December 31, 2019
Contract liabilities:
Deferred revenue
Other liabilities (1)
Total contract liabilities
Balance at
beginning of period
Additions
Deductions
Balance at
end of period
$
$
14,777
$
2,126
16,903
$
8,254 $
—
8,254 $
(6,677) $
(2,126)
(8,803) $
16,354
—
16,354
(1) On June 5, 2019, the term of the Reimbursement Period under the Letter Agreement expired. During the year ended December 31, 2019, the Company updated its estimate of variable
consideration included in the transaction price to include $1.2 million of unpaid reimbursements to Spark.
13. Related‑Party Transactions
Financing
During the year ended December 31, 2019, the Company completed the 2019 Purchase Agreement, 2019 Private Placement, and the 2019 Follow-On. The
following tables set forth the number of shares of common stock, common warrants, and pre-funded warrants purchased by executive officers and members
of the board of directors of the Company (and related parties thereto), as described in Note 10.
Name
TAS Partners, LLC
Carrie S. Cox
Timothy Barabe
Scott D. Myers
Name
Timothy A. Springer, Ph.D.
TAS Partners, LLC (affiliate of Timothy A. Springer, Ph.D.)
Elona Kogan, J.D.
Patrick Zenner
Takashi Kei Kishimoto, Ph.D.
Carsten Brunn, Ph.D.
Scott D. Myers
Stephen Smolinski
Name
Timothy A. Springer, Ph.D.
Entities affiliated with Polaris
Chafen Lu (Timothy A. Springer’s wife)
Jed Springer (Timothy A. Springer’s brother)
Consulting Services
2019 Purchase Agreement
Shares of common
stock purchased
Common warrants
to be purchased
Total
aggregate purchase price
3,940,887
65,681
65,681
39,409
1,970,443 $
32,840 $
32,840 $
19,704 $
6,000,000
99,999
99,999
60,000
2019 Private Placement
Shares of common
stock purchased
Total
purchase price
1,600,000
1,100,000
82,872
55,248
50,000
41,436
41,436
13,812
$
$
$
$
$
$
$
$
2,896,000
1,991,000
149,998
99,999
90,500
74,999
74,999
25,000
2019 Follow-On
Shares of common
stock purchased
Total
purchase price
4,000,000
666,666
66,666
1,000
$
$
$
$
6,000,000
999,999
99,999
1,500
F-31
During 2018, the Company entered into an amended consulting agreement, (the "Consulting Agreement") with Dr. Omid Farokhzad, a member of its Board
of Directors. The term of the amendment to the Consulting Agreement was April 1, 2018 to December 31, 2019, which extended the original consulting
term for an additional nine months from March 31, 2019. Compensation included a $85,000 payment for the period beginning January 1, 2019 and ending
December 31, 2019. The $85,000 was paid quarterly across the contract term in arrears beginning March 31, 2019. Included within this agreement, a stock
option award of 75,000 shares was granted, with a weighted average grant date fair value of $4.35. Effective November 20, 2019, Dr. Farokhzad resigned
as a member of its Board of Directors.
In addition, the Company incurred expenses for consulting services provided by its founders totaling $0.5 million, $0.2 million and $0.2 million during the
years ended December 31, 2019, 2018 and 2017, respectively. The agreements associated with the above consulting services provided by its founders were
terminated effective December 31, 2019. The Company entered into new agreements with its founders to serve roles on its Scientific Advisory Board,
effective January 1, 2020 to December 31, 2021, under which they will be paid quarterly for their services.
14. Collaboration Agreements
Feasibility Study and License Agreement
On August 6, 2019, the Company entered into a Feasibility Study and License Agreement with AskBio, which is referred to as the AskBio Collaboration
Agreement. Pursuant to the AskBio Collaboration Agreement, the Company and AskBio agreed to license intellectual property rights to each other as part
of a collaboration to research, develop, and commercialize certain adeno-associated virus (“AAV”) gene therapy products utilizing the Company’s
ImmTOR platform to enable re-dosing of such AAV gene therapy products to treat serious rare and orphan genetic diseases for which there is a significant
unmet medical need.
Pursuant to the AskBio Collaboration Agreement, the Company and AskBio agreed to conduct proof of concept studies to potentially validate the use of
ImmTOR in conjunction with AAV for the treatment of methylmalonic acidemia (MMA), based on the Company’s product candidate SEL-302, to mitigate
the formation of neutralizing anti-AAV capsid antibodies (the POC Studies). If the POC Studies are successful, or the parties otherwise elect to do so, the
parties will proceed with a collaboration to pursue the development and commercialization of AAV gene therapy product candidates utilizing ImmTOR for
the treatment of certain agreed serious rare and orphan genetic diseases. If the POC Studies fail to demonstrate a proof of concept, and the parties do not
mutually agree in writing to proceed with the collaboration, the AskBio Collaboration Agreement will expire.
The Company and AskBio will share responsibility for the research, development and commercialization of products developed under this collaboration.
The parties will also share research, development and commercialization costs equally for all collaboration products, but with a right of either party to opt
out of certain products, and thereby no longer be required to share costs for such products. Each party will receive a percentage of net profits for each
product sold under the collaboration equal to the percentage of shared costs borne by such party in the development of such product. Pursuant to the
AskBio Collaboration Agreement, AskBio is responsible for manufacturing the AAV capsids and AAV vectors and the Company is responsible for
manufacturing ImmTOR.
The AskBio Collaboration Agreement is considered to be within the scope of ASC 808, as both parties are active participants and exposed to the risks and
rewards of the collaborative activity. The Company evaluated the terms of the AskBio Collaboration Agreement and have identified the following promises
in the arrangement (1) conducting research and development activities to develop and commercialize products under the collaboration, (the “R&D
Services”), (2) granting a non-exclusive, non-transferable, royalty-free, fully paid up, worldwide license to certain intellectual property of the Company,
(the “IP Rights”) for the purpose of performing the POC Studies, (the “Research License”), (3) granting an exclusive, nontransferable, worldwide license to
the IP Rights for use in certain indications (the” Collaboration License”), (4) providing manufactured supply of preclinical and clinical ImmTOR, (the
“Manufactured Supply”), (5) participation on identified steering committees responsible for the oversight of the collaboration, (the “JSC Participation”),
and (6) granting an exclusive option to obtain a license under the IP Rights to research, develop and commercialize Licensed Products. The Company
determined that the R&D Services, Research License, Collaboration License, Manufactured Supply, and JSC Participation were not capable of being
distinct, and therefore must be combined into a single performance obligation. Therefore, promises (1) through (5) identified above were combined into a
single performance obligation. Furthermore, the Company evaluated the Option Agreement and determined that it does not provide AskBio with a material
right under ASC 606 as the option was not priced at a discount (see discussion of the Option exercise in Note 12). The Company noted that AskBio did not
meet the definition of a customer within the scope of ASC 606 for any distinct performance obligations as the Company concluded that such items were not
an output of the Company’s ordinary activities. As such, the Company determined that the entire arrangement would be accounted for within the scope of
ASC 808.
In accordance with ASC 808, collaboration expenses are recognized within R&D expense and selling, general and administrative expense on our
condensed consolidated statements of operations. For the year ended December 31, 2019, the
F-32
Company did not recognize any collaboration expense or record a receivable under the AskBio Collaboration Agreement in which actual costs incurred by
both parties are an approximated 50% cost share.
Under certain collaborative arrangements, the Company is entitled to reimbursement of certain R&D expense. Activities under collaborative arrangements
for which the Company is entitled to reimbursement are considered to be collaborative activities under the scope of ASC 808. For these units of account,
the Company does not analogize to ASC 606 or recognize revenue. Rather, the Company analogizes to the guidance in ASC 730, which requires that
reimbursements from counterparties be recognized as an offset to the related costs. In accordance with ASC 730, the Company records reimbursement
payments received from collaboration partners as reductions to R&D expense.
Massachusetts Institute of Technology
On December 13, 2019, the Company entered into the Fourth Amendment (the MIT Amendment) to the Exclusive Patent License Agreement by and
between the Company and the Massachusetts Institute of Technology (MIT) (the MIT Agreement). Pursuant to the MIT Amendment, a provision of the
MIT Agreement under which the Company was obligated to initiate a Phase 3 clinical trial for a licensed product by a specified date in the fourth quarter of
2019 is tolled until the earlier of (i) a specified date in the second quarter of 2020 or (ii) the effective date of a written amendment to the MIT Agreement.
Further, pursuant to the MIT Amendment, the parties agreed to negotiate in good faith to enter into a future amendment to the MIT Agreement after the
Company provides MIT with an amended diligence plan.
On November 25, 2008, the Company entered into an Exclusive Patent License agreement with MIT, which is referred to as the Exclusive Patent License.
The Company received an exclusive royalty‑bearing license to utilize patents held by MIT in exchange for upfront consideration and annual license
maintenance fees. Such fees are expensed as incurred and have not been material to any period presented.
As of December 31, 2019, and in connection with the execution of the Spark License Agreement, the Company has made contractual payments pursuant to
the Exclusive Patent License totaling $2.2 million for the sublicense granted to Spark, and $0.4 million relative to the calculated premium paid by Spark for
the equity investments made under the Spark Purchase Agreement. The Company made no additional payments during the year ended December 31, 2019.
Shenyang Sunshine Pharmaceutical Co., Ltd
In May 2014, the Company entered into a license agreement with Shenyang Sunshine Pharmaceutical Co., Ltd. (“3SBio”), which is referred to as the
3SBio License. The Company has paid to 3SBio an aggregate of $3.0 million in upfront and milestone-based payments under the 3SBio License as of
December 31, 2019. We are required to make future payments to 3SBio contingent upon the occurrence of events related to the achievement of clinical and
regulatory approval milestones of up to an aggregate of $21.0 million for products containing our ImmTOR platform, and up to an aggregate of $41.5
million for products without our ImmTOR platform.
Massachusetts Eye and Ear Infirmary and The Schepens Eye Research Institute, Inc.
In May 2016, the Company entered into a license agreement with the Massachusetts Eye and Ear Infirmary and The Schepens Eye Research Institute, Inc.
(collectively, “MEE”), which is referred to as the MEE License. On September 16, 2019, in accordance with the terms of the MEE License, the Company
notified MEE of its intention to terminate the MEE License, effective December 15, 2019. In connection with the termination, the Company has accrued
less than $0.1 million for final license fees as of December 31, 2019. Through December 31, 2019, the Company paid a total of $0.4 million in license fees
due under the MEE License.
15. Income Taxes
The Company provides for income taxes under ASC 740. Under ASC 740, the Company provides deferred tax assets and liabilities for the expected future
tax consequences of temporary differences between the Company’s financial statement carrying amounts and the tax bases of assets and liabilities using
enacted tax rates expected to be in effect in the years in which the differences are expected to reverse.
For the years ended December 31, 2019, 2018 and 2017, the Company did not record a current or deferred income tax expense or benefit. The following
table reconciles the federal statutory income rate to the Company's effective income tax rate:
F-33
Statutory U.S. federal rate
State income taxes - net of federal benefit
Permanent items
Research tax credits/other
Change in enacted rates
Valuation allowance, net
Other
Effective income tax rate
Year Ended December 31,
2019
2018
2017
21.0 %
6.3 %
(2.1)%
1.1 %
— %
(26.3)%
— %
— %
21.0 %
7.0 %
(0.5)%
1.6 %
— %
(29.1)%
— %
— %
The tax effects of temporary differences that give rise to the Company's net deferred tax assets are as follows (in thousands):
Deferred Tax Assets
Net operating loss carryforwards
Research and development credits
Stock-based compensations expense
Deferred rent and other expenses
Deferred revenue
Operating lease liability
Patent costs/amortization
Gross deferred tax assets
Deferred Tax Liabilities
Depreciation
Operating lease right-of-use asset
Gross deferred tax liabilities
Net deferred tax assets before valuation allowance
Valuation allowance
Net deferred tax assets
Year Ended December 31,
2019
2018
$
$
$
71,270 $
6,586
2,516
812
4,468
102
5,111
90,865
(57) $
(82)
(139)
90,726
(90,726)
— $
34.0 %
5.8 %
(0.1)%
0.5 %
(35.8)%
(6.7)%
2.3 %
— %
59,126
5,780
1,946
458
4,037
—
4,881
76,228
(66)
—
(66)
76,162
(76,162)
—
The Company has provided a full valuation allowance against its net deferred tax assets, as the Company believes that it is more likely than not that the
deferred tax assets will not be realized.
Realization of future tax benefits is dependent on many factors, including the Company’s ability to generate taxable income within the net operating loss
carryforward period. The Company has evaluated the positive and negative evidence bearing upon the realizability of its deferred tax assets and concluded
that it is more likely than not that the Company will not realize the benefit of its deferred tax assets. The valuation allowance increased by $14.6 million
and $18.5 million for the years ended December 31, 2019 and 2018, respectively, primarily as a result of an increase in net operating loss. In 2014, the
Company's Russian subsidiary was granted a 10 year tax holiday in Russia. The Company's foreign operations continue to benefit from the tax holiday,
which is set to expire on December 31, 2023, however the Company is in the process of closing down operations in Russia and does not expect any tax
liability.
At December 31, 2019, the Company had federal and state net operating loss carryforwards of $262.2 million and $256.5 million, respectively, which will
expire at various times through 2037. Of the federal net operating loss carryforwards, $99.7 million can be carried forward indefinitely. The Company also
has federal and state research and development tax credit carryforwards of $4.2 million and $3.0 million, respectively, available to reduce future tax
liabilities, which will expire at various times through 2039.
Utilization of the net operating loss and research and development credit carryforwards may be subject to a substantial annual limitation under Section 382
and 383 of the Internal Revenue Code due to ownership change limitations that have occurred previously, or that could occur in the future. These
ownership changes may limit the amount of net operating loss and research and development credit carryforwards that can be utilized annually to offset
future taxable income and tax, respectively. As of December 31, 2019, the Company completed a Section 382 study, noting that an ownership change
occurred during 2017. However, the Company has determined that all net operating losses would be available in the future. As a result, the deferred tax
assets related to the federal and Massachusetts net operating losses and credit carryforwards are not currently limited.
The Company applies ASC 740, Income Taxes to uncertain tax positions. As of the adoption date on January 1, 2010 and through December 31, 2019, the
Company had no unrecognized tax benefits or related interest and penalties accrued.
F-34
The Company has not, as of yet, conducted a study of its research and development credit carryforwards. This study may result in an adjustment to the
Company’s research and development credit carryforwards; however, until a study is completed and any adjustment is known, no amounts are being
presented as an uncertain tax position. A full valuation allowance has been provided against the Company’s research and development credits and, if an
adjustment is required, this adjustment would be offset by an adjustment to the valuation allowance. As a result, there would be no impact to the
consolidated balance sheets, statements of operations and comprehensive loss, or cash flows if an adjustment was required.
Interest and penalty charges, if any, related to unrecognized tax benefits would be classified as income tax expense in the accompanying statement of
operations. As of December 31, 2019, the Company had no accrued interest related to uncertain tax positions.
The statute of limitations for assessment by the Internal Revenue Service and Massachusetts tax authorities is open for tax years since inception. The
Company files income tax returns in the United States and Massachusetts. There are currently no federal, state or foreign audits in progress.
16. Defined Contribution Plan
The Company maintains a defined contribution plan under Section 401(k) of the Internal Revenue Code (the “401(k) Plan”). The 401(k) Plan covers all
employees who meet defined minimum age and service requirements, and allows participants to defer a portion of their annual compensation on a pretax
basis. The 401(k) Plan provides for matching contributions on a portion of participant contributions pursuant to the 401(k) Plan’s matching formula. All
matching contributions vest ratably over 4 years and participant contributions vest immediately. Contributions by the Company totaled $0.1 million, $0.2
million and $0.2 million during each of the years ended December 31, 2019, 2018 and 2017.
17. Commitments and Contingencies
As of December 31, 2019, the Company had operating lease agreements for offices in Watertown, MA. See Note 8 for additional information regarding the
Company's leases.
Other
As permitted under Delaware law, the Company indemnifies its directors for certain events or occurrences while the director is, or was, serving at the
Company’s request in such capacity. The term of the indemnification is for the director’s lifetime. The maximum potential amount of future payments the
Company could be required to make is unlimited; however, the Company has directors’ insurance coverage that limits its exposure and enables it to recover
a portion of any future amounts paid. The Company also has indemnification arrangements under certain of its facility leases that require it to indemnify
the landlord against certain costs, expenses, fines, suits, claims, demands, liabilities, and actions directly resulting from certain breaches, violations, or
non‑performance of any covenant or condition of the Company’s lease. The term of the indemnification is for the term of the related lease agreement. The
maximum potential amount of future payments the Company could be required to make under these indemnification agreements is unlimited. To date, the
Company had not experienced any material losses related to any of its indemnification obligations, and no material claims with respect thereto were
outstanding.
The Company is a party in various other contractual disputes and potential claims arising in the ordinary course of business. The Company does not believe
that the resolution of these matters will have a material adverse effect the Company's business, financial position, results of operations or cash flows.
18. Selected Quarterly Financial Data (Unaudited)
The following table summarizes unaudited quarterly financial data for the years ended December 31, 2019 and 2018 (in thousands, except per share data).
F-35
Three Months Ended (unaudited)
March 31,
2019
June 30,
2019
September 30,
December 31,
2019
2019
10
11,866
(12,074)
(12,074)
$
$
$
$
13 $
16,248 $
(16,394) $
(16,394) $
— $
11,794 $
(11,994) $
(11,994) $
6,654
19,224
(14,888)
(14,888)
(0.31)
$
(0.37) $
(0.26) $
(0.28)
Three Months Ended (unaudited)
March 31,
2018
June 30,
2018
September 30,
December 31,
2018
2018
— $
$
$
$
15,813
(15,888)
(15,888)
— $
18,769 $
(18,796) $
(18,796) $
— $
15,941 $
(16,001) $
(16,001) $
903
15,402
(14,651)
(14,651)
(0.71)
$
(0.84) $
(0.71) $
(0.65)
Grant and collaboration revenue
Operating expenses
Net loss
Net loss attributable to common stockholders
Net loss per share attributable to common stockholders, basic and diluted
Grant and collaboration revenue
Operating expenses
Net loss
Net loss attributable to common stockholders
Net loss per share attributable to common stockholders, basic and diluted
$
$
$
$
$
$
$
$
$
$
F-36
DESCRIPTION OF THE REGISTRANT’S SECURITIES
REGISTERED PURSUANT TO SECTION 12 OF THE
SECURITIES EXCHANGE ACT OF 1934, AS AMENDED
Exhibit 4.10
As of December 31, 2019, Selecta Biosciences, Inc. (the “Company,” “we,” “us” and “our”) had one class of securities registered under
Section 12 of the Securities Exchange Act of 1934, as amended: our common stock.
DESCRIPTION OF CAPITAL STOCK
The following description of our capital stock is not complete and may not contain all the information you should consider before
investing in our capital stock. This description is summarized from, and qualified in its entirety by reference to, our restated certificate of
incorporation and our amended and restated bylaws, each of, which has been publicly filed with the Securities and Exchange Commission
(“SEC”).
Our authorized capital stock consists of:
•
•
200,000,000 shares of common stock, par value $0.0001 per share; and
10,000,000 shares of preferred stock, par value $0.0001 per share.
Common Stock
Our common stock is listed on The Nasdaq Global Market under the symbol “SELB.”
Voting Rights. Holders of our common stock are entitled to one vote for each share held on all matters submitted to a vote of
stockholders and do not have cumulative voting rights. An election of directors by our stockholders shall be determined by a plurality of the
votes cast by the stockholders entitled to vote on the election. Subject to the supermajority votes for some matters, other matters shall be
decided by the affirmative vote of our stockholders having a majority in voting power of the votes cast by the stockholders present or
represented and voting on such matter. Our restated certificate of incorporation and amended and restated bylaws also provide that our
directors may be removed only for cause and only by the affirmative vote of the holders of at least two-thirds in voting power of the
outstanding shares of capital stock entitled to vote thereon. In addition, the affirmative vote of the holders of at least two-thirds in voting
power of the outstanding shares of capital stock entitled to vote thereon is required to amend or repeal, or to adopt any provision inconsistent
with, several of the provisions of our restated certificate of incorporation. Holders of common stock are entitled to receive proportionately
any dividends as may be declared by our board of directors, subject to any preferential dividend rights of any series of preferred stock that we
may designate and issue in the future.
Rights upon Liquidation. In the event of our liquidation or dissolution, the holders of common stock are entitled to receive
proportionately our net assets available for distribution to stockholders after the payment of all debts and other liabilities and subject to the
prior rights of any outstanding preferred stock.
Other Rights. Holders of common stock have no preemptive, subscription, redemption or conversion rights. The rights, preferences
and privileges of holders of common stock are subject to and may be adversely affected by the rights of the holders of shares of any series of
preferred stock that we may designate and issue in the future.
Transfer Agent
The transfer agent and registrar for our common stock is American Stock Transfer & Trust Company, LLC.
Dividend
Holders of common stock are entitled to receive proportionately any dividends as may be declared by our board of directors, subject
to any preferential dividend rights of outstanding preferred stock. We have never declared or paid any cash dividends on our capital stock. We
do not intend to pay cash dividends for the foreseeable future. We currently expect to retain all future earnings, if any, for use in the
development, operation and expansion of our business. Any
determination to pay cash dividends in the future will depend upon, among other things, our results of operations, plans for expansion, tax
considerations, available net profits and reserves, limitations under law, financial condition, capital requirements and other factors that our
board of directors considers to be relevant.
Preferred Stock
Under the terms of our restated certificate of incorporation, our board of directors is authorized to direct us to issue shares of
preferred stock in one or more series without stockholder approval. Our board of directors has the discretion to determine the rights,
preferences, privileges and restrictions, including voting rights, dividend rights, conversion rights, redemption privileges and liquidation
preferences, of each series of preferred stock.
The purpose of authorizing our board of directors to issue preferred stock and determine its rights and preferences is to eliminate
delays associated with a stockholder vote on specific issuances. The issuance of preferred stock, while providing flexibility in connection
with possible acquisitions, future financings and other corporate purposes, could have the effect of making it more difficult for a third party
to acquire, or could discourage a third party from seeking to acquire, a majority of our outstanding voting stock. There are no shares of
preferred stock outstanding, and we have no present plans to issue any shares of preferred stock.
Registration Rights
Certain holders our common stock or their transferees are entitled to the following rights with respect to the registration of such
shares for public resale under the Securities Act of 1933, as amended (the “Securities Act”).
These registration rights are granted pursuant to the (i) amended and restated investors’ rights agreement by and among us and
certain of our stockholders, or the investors’ rights agreement, (ii) a registration rights agreement we entered into in connection with the
private placement of 3,088,791 shares of our common stock and a warrant to purchase 79,130 shares of our common stock, or the 2017
Private Placement, which closed on June 27, 2017; and (iii) a registration rights agreement we entered into in connection with the private
placement of 37,634,883 shares of our common stock and warrants to purchase 31,330,629 shares of our common stock, or the 2019 Private
Placement, which closed on December 23, 2019.
Investors’ Rights Agreement
Holders of registrable securities under the investors’ rights agreement have registration rights until such shares can otherwise be sold
without restriction under Rule 144, or until the rights otherwise terminate pursuant to the terms of the investors’ rights agreement. The
registration of shares of common stock as a result of the following rights being exercised would enable holders to trade these shares without
restriction under the Securities Act when the applicable registration statement is declared effective.
Piggyback Registration Rights. Any time we propose to register any shares of our common stock under the Securities Act, subject to
certain exceptions, the holders of registrable securities are entitled to notice of the registration and to include their shares of registrable
securities in the registration. If our proposed registration involves an underwriting, the managing underwriter of such offering will have the
right to limit the number of shares to be underwritten for reasons related to the marketing of the shares.
Form S-3 Registration Rights. If the holders of registrable securities request in writing that we effect a registration with respect to
registrable securities at an aggregate price to the public in the offering of at least $2,000,000, and we are entitled under the Securities Act to
register our shares on a registration statement on Form S-3, we will be required to effect such registration. We will not be required to effect a
registration pursuant to these Form S-3 registration rights if, within a given calendar year, we have already effected two registrations on Form
S-3 for the holders of registrable securities.
Expenses. Ordinarily, other than underwriting discounts and commissions, we will be required to pay all expenses incurred by us
related to any registration effected pursuant to the exercise of these registration rights. These expenses may include all registration and filing
fees, printing expenses, fees and disbursements of our counsel, reasonable fees and disbursements of a counsel for the selling security holders
and blue sky fees and expenses.
Termination of Registration Rights. The registration rights terminate upon the earlier of June 27, 2021, or, with respect to the
registration rights of an individual holder, when the holder can sell all of such holder’s registrable securities in a three-month period without
restriction under Rule 144 under the Securities Act.
2017 Registration Rights Agreement
The shares of common stock underlying the warrants and the shares of common stock issued in connection with our 2017 Private
Placement are currently registered under a registration statement that has been declared effective by the SEC, pursuant to a registration rights
agreement entered into between us and the investors in the private placement. Subject to certain exceptions, pursuant to the related
registration rights agreement, we have agreed to use reasonable best efforts to keep the registration statement registering the resale of these
shares of common effective under the Securities Act until the earlier of (i) such time as all of the securities registered for resale have been
disposed of pursuant to and in accordance with the registration statement, (ii) such time as all of the securities registered for resale have been
sold in accordance with Rule 144 under the Securities Act, (iii) the date on which the shares of common stock registered for resale become
eligible for resale without volume or manner-of-sale restrictions and without current public information pursuant to Rule 144; and (iv) June
27, 2020.
We have also agreed, among other things, to indemnify the investors under the registration statement from certain liabilities and to
pay all fees and expenses (excluding any legal fees of the selling holder(s), and any underwriting discounts and selling commissions) incident
to our obligations under the registration rights agreement.
2019 Registration Rights Agreement
The shares of common stock underlying the warrants and the shares of common stock issued in connection with our 2019 Private
Placement are currently registered under a registration statement that has been declared effective by the SEC, pursuant to a registration rights
agreement entered into between us and the investors in the private placement. Subject to certain exceptions, pursuant to the related
registration rights agreement, we have agreed to use reasonable best efforts to keep the registration statement registering the resale of these
shares of common effective under the Securities Act until the earlier of (i) such time as all of the securities registered for resale have been
disposed of pursuant to and in accordance with the registration statement, (ii) such time as all of the securities registered for resale have been
sold in accordance with Rule 144 under the Securities Act, (iii) the date on which the shares of common stock registered for resale become
eligible for resale without volume or manner-of-sale restrictions and without current public information pursuant to Rule 144; and (iv)
December 23, 2024.
We have also agreed, among other things, to indemnify the investors under the registration statement from certain liabilities and to
pay all fees and expenses (excluding any legal fees of the selling holder(s), and any underwriting discounts and selling commissions) incident
to our obligations under the registration rights agreement.
Anti-Takeover Effects of Delaware Law and Our Certificate of Incorporation and Bylaws
Some provisions of Delaware law, our restated certificate of incorporation and our amended and restated bylaws could make the
following transactions more difficult: an acquisition of us by means of a tender offer; an acquisition of us by means of a proxy contest or
otherwise; or the removal of our incumbent officers and directors. It is possible that these provisions could make it more difficult to
accomplish or could deter transactions that stockholders may otherwise consider to be in their best interest or in our best interest, including
transactions which provide for payment of a premium over the market price for our shares.
These provisions, summarized below, are intended to discourage coercive takeover practices and inadequate takeover bids. These
provisions are also designed to encourage persons seeking to acquire control of us to first negotiate with our board of directors. We believe
that the benefits of the increased protection of our potential ability to negotiate with the proponent of an unfriendly or unsolicited proposal to
acquire or restructure us outweigh the disadvantages of discouraging these proposals because negotiation of these proposals could result in an
improvement of their terms.
Undesignated Preferred Stock. The ability of our board of directors, without action by the stockholders, to issue up to 10,000,000
shares of undesignated preferred stock with voting or other rights or preferences as designated by our board of directors could impede the
success of any attempt to effect a change in control of us. These and other provisions may have the effect of deferring hostile takeovers or
delaying changes in control or management of our company.
Stockholder Meetings. Our amended and restated bylaws provide that a special meeting of stockholders may be called only by our
chairman of the board, chief executive officer or president (in the absence of a chief executive officer), or by a resolution adopted by a
majority of our board of directors.
Requirements for Advance Notification of Stockholder Nominations and Proposals. Our amended and restated bylaws establish
advance notice procedures with respect to stockholder proposals to be brought before a stockholder meeting and the nomination of candidates
for election as directors, other than nominations made by or at the direction of the board of directors or a committee of the board of directors.
Elimination of Stockholder Action by Written Consent. Our restated certificate of incorporation eliminates the right of stockholders to
act by written consent without a meeting.
Staggered Board. Our board of directors is divided into three classes. The directors in each class will serve for a three-year term, one
class being elected each year by our stockholders. This system of electing and removing directors may tend to discourage a third party from
making a tender offer or otherwise attempting to obtain control of us, because it generally makes it more difficult for stockholders to replace
a majority of the directors.
Removal of Directors. Our restated certificate of incorporation provides that no member of our board of directors may be removed
from office by our stockholders except for cause and, in addition to any other vote required by law, upon the approval of the holders of at
least two-thirds in voting power of the outstanding shares of stock entitled to vote in the election of directors.
Stockholders Not Entitled to Cumulative Voting. Our restated certificate of incorporation does not permit stockholders to cumulate
their votes in the election of directors. Accordingly, the holders of a majority of the outstanding shares of our common stock entitled to vote
in any election of directors can elect all of the directors standing for election, if they choose, other than any directors that holders of our
preferred stock may be entitled to elect.
Delaware Anti-Takeover Statute. We are subject to Section 203 of the General Corporation Law of the State of Delaware, which
prohibits persons deemed to be ''interested stockholders" from engaging in a "business combination" with a publicly held Delaware
corporation for three years following the date these persons become interested stockholders unless the business combination is, or the
transaction in which the person became an interested stockholder was, approved in a prescribed manner or another prescribed exception
applies. Generally, an "interested stockholder" is a person who, together with affiliates and associates, owns, or within three years prior to the
determination of interested stockholder status did own, 15% or more of a corporation's voting stock. Generally, a "business combination"
includes a merger, asset or stock sale, or other transaction resulting in a financial benefit to the interested stockholder. The existence of this
law may have an anti-takeover effect with respect to transactions not approved in advance by the board of directors.
Choice of Forum. Our restated certificate of incorporation provides that, unless we consent in writing to the selection of an
alternative form, the Court of Chancery of the State of Delaware will be the sole and exclusive forum for: (1) any derivative action or
proceeding brought on our behalf; (2) any action asserting a claim of breach of a fiduciary duty or other wrongdoing by any of our directors,
officers, employees or agents to us or our stockholders; (3) any action asserting a claim against us arising pursuant to any provision of the
General Corporation Law of the State of Delaware or our restated certificate of incorporation or amended and restated bylaws; or (4) any
action asserting a claim governed by the internal affairs doctrine. Our restated certificate of incorporation also provides that any person or
entity purchasing or otherwise acquiring any interest in shares of our capital stock will be deemed to have notice of and to have consented to
this choice of forum provision. It is possible that a court of law could rule that the choice of forum provision contained in our restated
certificate of incorporation is inapplicable or unenforceable if it is challenged in a proceeding or otherwise.
Amendment of Restated Certificate of Incorporation. The amendment of any of the above provisions in our restated certificate of
incorporation, except for the provision making it possible for our board of directors to issue preferred stock and the provision prohibiting
cumulative voting, would require approval by holders of at least two-thirds in voting power of the outstanding shares of stock entitled to vote
thereon.
The provisions of Delaware law, our restated certificate of incorporation and our amended and restated bylaws could have the effect
of discouraging others from attempting hostile takeovers and, as a consequence, they may also inhibit temporary fluctuations in the market
price of our common stock that often result from actual or rumored hostile takeover attempts. These provisions may also have the effect of
preventing changes in the composition of our board and management. It is possible that these provisions could make it more difficult to
accomplish transactions that stockholders may otherwise deem to be in their best interest.
Exhibit 10.7 (i)
FOURTH AMENDMENT
This Fourth Amendment, effective as of the date set forth above the signatures of the parties below, amends the Exclusive
Patent License Agreement effective November 25, 2008, as amended by a First Amendment dated January 12, 2010, a Second
Amendment dated August 29, 2013, and a Third Amendment dated November 18, 2016 (the "License Agreement") between the
Massachusetts Institute of Technology, a Massachusetts corporation having its principal office at 77 Massachusetts Avenue,
Cambridge, Massachusetts 02139 ("M.I.T."), and Selecta Biosciences, Inc., a Delaware corporation, with a principal place of
business at 480 Arsenal Way, Building One, Watertown, MA 02472 ("COMPANY'').
WHEREAS, COMPANY has represented to M.I.T. that it is continuing to diligently develop LICENSED PRODUCTS, and
has requested that the diligence provisions of the License Agreement be modified.
NOW, THEREFORE, in consideration of the promises and mutual covenants contained herein, the parties hereby agree as
follows:
1.
The parties agree that: (a) the diligence requirement set forth in Section 3.l(j) of the License Agreement shall be
tolled until the earlier of May 15, 2020 or the effective date of a written amendment to the License Agreement pursuant to Section 2
below (the "Future Amendment") and (b) M.I.T. shall not exercise its rights to terminate the License Agreement solely for
COMPANY's failure to fulfill its obligations under Section 3.l(j) unless the parties do not enter into the Future Amendment by May
15, 2020, in which case M.I.T. may elect to terminate the License Agreement based upon COMPANY's failure to fulfill its
obligations under Section 3.1(j). The parties may mutually agree to extend the time by which the Future Amendment must be
executed.
2.
On or before February 15, 2020, COMPANY shall provide M.I.T. with a detailed, written plan for achieving
reasonably extended and/or amended diligence milestones for the development and commercialization of a LICENSED PRODUCT.
Within ninety (90) days of M.I.T.'s receipt of such updated diligence plan, the parties shall negotiate in good faith to enter into the
Future Amendment, which will include any agreed upon changes to the License Agreement.
3.
On or before February 15, 2020, COMPANY shall provide M.I.T. with all of the outstanding information required
to be delivered to M.I.T. pursuant to the License Agreement, including without limitation the Letter Agreement between the parties
dated June 17, 2013.
4.
This License Agreement, as amended hereby, is hereby ratified and confirmed in all respects and except as
expressly amended by this Fourth Amendment, all terms and conditions of the License Agreement shall continue in full force and
effect. All capitalized terms used herein shall have the meanings ascribed to such terms in the License Agreement. The License
Agreement shall, together with this Fourth Amendment, be read and construed as a single instrument. No addition to or modification
of any provision of this Fourth Amendment shall be binding unless made in writing and signed by a duly authorized representative
of each of the parties.
IN WITNESS WHEREOF, the parties have caused this Fourth Amendment to be executed under seal by their duly
authorized representatives.
The Effective Date of this Fourth Amendment is December 13, 2019.
MASSACHUSETTS INSTITUTE OF
TECHNOLOGY
SELECTA BIOSCIENCES, INC.
By:
/s/ Lesley Millar-Nicholson
By:
/s/ Lloyd Johnston
Name:
Lesley Millar-Nicholson
Name:
Lloyd Johnston
Title:
Director, TLO
Title:
COO
Exhibit 23.1
Consent of Independent Registered Public Accounting Firm
We consent to the incorporation by reference in the following Registration Statements:
(1) Registration Statement (Form S-8, File No. 333-212215) pertaining to the 2008 Stock Incentive Plan, as amended, the 2016 Incentive
Award Plan and the 2016 Employee Stock Purchase Plan of Selecta Biosciences, Inc.,
(2) Registration Statement (Form S-8, File No. 333-224109) pertaining to the 2016 Incentive Awards Plan and the 2016 Employee Stock
Purchase Plan,
(3) Registration Statement (Form S-8, File No. 333-228264) pertaining to the 2018 Employment Inducement Incentive Award Plan,
(4) Registration Statement (Form S-8, File No. 333-230501) pertaining to the 2018 Employment Inducement Incentive Award Plan,
(5) Registration Statement (Form S-3, File No. 333-219262),
(6) Registration Statement (Form S-3, File No. 333-219900), and
(7) Registration Statement (Form S-3, File No. 333-236147);
of our report dated March 12, 2020 with respect to the consolidated financial statements of Selecta Biosciences, Inc. included in this Annual
Report (Form 10-K) of Selecta Biosciences, Inc. for the year ended December 31, 2019.
/s/ Ernst & Young LLP
Boston, Massachusetts
March 12, 2020
I, Carsten Brunn, Ph.D. certify that:
CERTIFICATIONS
Exhibit 31.1
1.
I have reviewed this Annual Report on Form 10-K of Selecta Biosciences, Inc.;
2. Based on my knowledge, this report does not contain any untrue statement of a material fact or omit to state a material fact necessary
to make the statements made, in light of the circumstances under which such statements were made, not misleading with respect to
the period covered by this report;
3. Based on my knowledge, the financial statements, and other financial information included in this report, fairly present in all material
respects the financial condition, results of operations and cash flows of the registrant as of, and for, the periods presented in this
report;
4. The registrant’s other certifying officer and I are responsible for establishing and maintaining disclosure controls and procedures (as
defined in Exchange Act Rules 13a-15(e) and 15d-15(e)) and internal control over financial reporting (as defined in Exchange Act
Rules 13a-15(f) and 15d-15(f)) for the registrant and have:
(a) Designed such disclosure controls and procedures, or caused such disclosure controls and procedures to be designed under
our supervision, to ensure that material information relating to the registrant, including its consolidated subsidiaries, is made
known to us by others within those entities, particularly during the period in which this report is being prepared;
(b) Designed such internal control over financial reporting, or caused such internal control over financial reporting to be
designed under our supervision, to provide reasonable assurance regarding the reliability of financial reporting and the
preparation of financial statements for external purposes in accordance with generally accepted accounting principles;
(c) Evaluated the effectiveness of the registrant’s disclosure controls and procedures and presented in this report our conclusions
about the effectiveness of the disclosure controls and procedures, as of the end of the period covered by this report based on
such evaluation; and
(d) Disclosed in this report any change in the registrant’s internal control over financial reporting that occurred during the
registrant’s most recent fiscal quarter (the registrant’s fourth fiscal quarter in the case of an annual report) that has materially
affected, or is reasonably likely to materially affect, the registrant’s internal control over financial reporting; and
5. The registrant’s other certifying officer and I have disclosed, based on our most recent evaluation of internal control over financial
reporting, to the registrant’s auditors and the audit committee of the registrant’s board of directors (or persons performing the
equivalent functions):
(a) All significant deficiencies and material weaknesses in the design or operation of internal control over financial reporting
which are reasonably likely to adversely affect the registrant’s ability to record, process, summarize and report financial
information; and
(b) Any fraud, whether or not material, that involves management or other employees who have a significant role in the
registrant’s internal control over financial reporting.
March 12, 2020
/s/ Carsten Brunn, Ph.D.
Carsten Brunn, Ph.D.
President and Chief Executive Officer, and Director
(Principal Executive Officer)
I, Bradford D. Dahms, certify that:
CERTIFICATIONS
Exhibit 31.2
1.
I have reviewed this Annual Report on Form 10-K of Selecta Biosciences, Inc.;
2. Based on my knowledge, this report does not contain any untrue statement of a material fact or omit to state a material fact necessary
to make the statements made, in light of the circumstances under which such statements were made, not misleading with respect to
the period covered by this report;
3. Based on my knowledge, the financial statements, and other financial information included in this report, fairly present in all material
respects the financial condition, results of operations and cash flows of the registrant as of, and for, the periods presented in this
report;
4. The registrant’s other certifying officer and I are responsible for establishing and maintaining disclosure controls and procedures (as
defined in Exchange Act Rules 13a-15(e) and 15d-15(e)) and internal control over financial reporting (as defined in Exchange Act
Rules 13a-15(f) and 15d-15(f)) for the registrant and have:
(a) Designed such disclosure controls and procedures, or caused such disclosure controls and procedures to be designed under
our supervision, to ensure that material information relating to the registrant, including its consolidated subsidiaries, is made
known to us by others within those entities, particularly during the period in which this report is being prepared;
(b) Designed such internal control over financial reporting, or caused such internal control over financial reporting to be
designed under our supervision, to provide reasonable assurance regarding the reliability of financial reporting and the
preparation of financial statements for external purposes in accordance with generally accepted accounting principles;
(c) Evaluated the effectiveness of the registrant’s disclosure controls and procedures and presented in this report our conclusions
about the effectiveness of the disclosure controls and procedures, as of the end of the period covered by this report based on
such evaluation; and
(d) Disclosed in this report any change in the registrant’s internal control over financial reporting that occurred during the
registrant’s most recent fiscal quarter (the registrant’s fourth fiscal quarter in the case of an annual report) that has materially
affected, or is reasonably likely to materially affect, the registrant’s internal control over financial reporting; and
5. The registrant’s other certifying officer and I have disclosed, based on our most recent evaluation of internal control over financial
reporting, to the registrant’s auditors and the audit committee of the registrant’s board of directors (or persons performing the
equivalent functions):
(a) All significant deficiencies and material weaknesses in the design or operation of internal control over financial reporting
which are reasonably likely to adversely affect the registrant’s ability to record, process, summarize and report financial
information; and
(b) Any fraud, whether or not material, that involves management or other employees who have a significant role in the
registrant’s internal control over financial reporting.
March 12, 2020
/s/ Bradford D. Dahms
Bradford D. Dahms
Chief Financial Officer
(Principal Financial and Accounting Officer)
CERTIFICATION PURSUANT TO
18 U.S.C. SECTION 1350,
AS ADOPTED PURSUANT TO
SECTION 906 OF THE SARBANES-OXLEY ACT OF 2002
Exhibit 32.1
I, Carsten Brunn, Ph.D., President and Chief Executive Officer of Selecta Biosciences, Inc. (the “Company”), hereby certify, pursuant to 18
U.S.C. §1350, as adopted pursuant to §906 of the Sarbanes-Oxley Act of 2002, that, to the best of my knowledge:
1. The Annual Report on Form 10-K of the Company for the period ended December 31, 2019 (the “Report”) fully complies with the
requirements of Section 13(a) or 15(d) of the Securities Exchange Act of 1934, as amended; and
2. The information contained in the Report fairly presents, in all material respects, the financial condition and results of operations of
the Company.
March 12, 2020
/s/ Carsten Brunn, Ph.D.
Carsten Brunn, Ph.D.
President and Chief Executive Officer, and Director
(Principal Executive Officer)
CERTIFICATION PURSUANT TO
18 U.S.C. SECTION 1350,
AS ADOPTED PURSUANT TO
SECTION 906 OF THE SARBANES-OXLEY ACT OF 2002
Exhibit 32.2
I, Bradford D. Dahms, Chief Financial Officer of Selecta Biosciences, Inc. (the “Company”), hereby certify, pursuant to 18 U.S.C. §1350, as
adopted pursuant to §906 of the Sarbanes-Oxley Act of 2002, that, to the best of my knowledge:
1. The Annual Report on Form 10-K of the Company for the period ended December 31, 2019 (the “Report”) fully complies with the
requirements of Section 13(a) or 15(d) of the Securities Exchange Act of 1934, as amended; and
2. The information contained in the Report fairly presents, in all material respects, the financial condition and results of operations of
the Company.
March 12, 2020
/s/ Bradford D. Dahms
Bradford D. Dahms
Chief Financial Officer
(Principal Financial and Accounting Officer)