UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
Washington, DC 20549
FORM 10-K
(Mark One)
☒ ANNUAL REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934
For the fiscal year ended December 31, 2018
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: 001-37465
Seres Therapeutics, Inc.
(Exact Name of Registrant as Specified in Its Charter)
Delaware
(State or Other Jurisdiction of
Incorporation or Organization)
200 Sidney Street – 4th Floor
Cambridge, Massachusetts
(Address of Principal Executive Offices)
27-4326290
(IRS Employer
Identification No.)
02139
(Zip Code)
(617) 945-9626
(Registrant’s Telephone Number, Including Area Code)
Securities registered pursuant to Section 12(b) of the Act
Title of each class
Common stock, par value $0.001 per share
Name of each exchange on which registered
The Nasdaq Global Select 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. Yes ☐ No ☒
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 ☐ 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 ☐
Indicate by check mark whether the registrant has submitted electronically every Interactive Data File required to be submitted 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 such files). Yes ☒ No ☐
Indicate by check mark if disclosure of delinquent filers pursuant to Item 405 of Regulation S-K (§ 229.405 of this chapter) is not contained herein, and will not be
contained, to the best of registrant’s knowledge, in definitive proxy or information statements incorporated by reference in Part III of this Form 10-K or any amendment to this
Form 10-K. ☒
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 the "large accelerated filer," "accelerated filer," "non-accelerated filer," "smaller reporting company" and “emerging growth company”
in Rule 12b-2 of the Exchange Act.
Large accelerated filer
Non-accelerated filer
Emerging growth company
☐
☐
☒
Accelerated filer
Smaller reporting 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 Act). Yes ☐ No ☒
The aggregate market value of common stock held by non-affiliates of the registrant based on the closing price of the registrant’s common stock as reported on the
Nasdaq Global Select Market on June 29, 2018, was $177,045,629.
As of February 28, 2019, there were 41,048,360 shares of the registrant’s common stock, par value $0.001 per share, outstanding.
DOCUMENTS INCORPORATED BY REFERENCE
Portions of the registrant’s definitive Proxy Statement relating to its 2019 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.
TABLE OF CONTENTS
Business
Risk Factors
Unresolved Staff Comments
Properties
Legal Proceedings
Mine Safety Disclosures
Market for Registrant’s Common Equity, Related Stockholder Matters and Issuer Purchases of Equity Securities
Selected 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
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
PART I.
Item 1.
Item 1A.
Item 1B.
Item 2.
Item 3.
Item 4.
PART II.
Item 5.
Item 6.
Item 7.
Item 7A.
Item 8.
Item 9.
Item 9A.
Item 9B.
PART III.
Item 10.
Item 11.
Item 12.
Item 13.
Item 14.
PART IV.
Item 15.
Item 16.
SIGNATURES
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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, and Section 21E of the Securities Exchange
Act of 1934, as amended. All statements other than statements of historical facts contained in this Annual Report on Form 10-K, 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, 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 on Form 10-K 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 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 risks, uncertainties and assumptions described under the
sections in this report titled “Risk Factors” and “Management’s Discussion and Analysis of Financial Condition and Results of Operations” and elsewhere in
this report. These forward-looking statements are subject to numerous risks, including, without limitation, the following:
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our status as a clinical-stage company and our expectation to incur losses in the future;
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 establish our own manufacturing facilities and to receive or manufacture sufficient quantities of our product candidates;
our ability to protect and enforce our intellectual property rights;
federal, state, and foreign regulatory requirements, including U.S. Food and Drug Administration regulation of our product candidates;
our ability to obtain and retain key executives and attract and retain qualified personnel; 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 on Form 10-K and the documents that we reference in this Annual Report on Form 10-K 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.
TRADEMARKS, SERVICE MARKS AND TRADENAMES
We have proprietary rights to trademarks used in this Annual Report on Form 10-K, including Ecobiotic, which are important to our business and
many of which are registered under applicable intellectual property laws. Solely for convenience, the trademarks, service marks, logos and trade names
referred to in this Annual Report on Form 10-K are without the ® and ™ symbols, but such references are not intended to indicate, in any way, that we will
not assert, to the fullest extent under applicable law, our rights to these trademarks, service marks and trade names. This Annual Report on Form 10-K
contains additional trademarks, service marks and trade names of others, which are the property of their respective owners. All trademarks, service marks and
trade names appearing in this Annual Report on Form 10-K are, to our knowledge, the property of their respective owners. We do not intend our use or
display
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of other companies’ trademarks, service marks, copyrights or trade names to imply a relationship with, or endorsement or sponsorship of us by, any other
companies.
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Item 1. Business
PART I
Overview
We are a microbiome therapeutics platform company developing a novel class of biological drugs, which we refer to as Ecobiotic® microbiome
therapeutics. The human microbiome is an ecosystem of microorganisms, including bacteria, fungi and viruses, that, when unhealthy, or dysbiotic, can leave
the body more susceptible to infections, metabolic disorders, allergies, autoimmune disease, inflammation and other serious conditions. Our drug candidates
are designed to restore health by repairing the function of a dysbiotic microbiome. We are initially focused on implementing our microbiome therapeutics
platform to develop Ecobiotic microbiome therapeutics that treat dysbiosis in the colonic microbiome, one of the most diverse microbial ecologies in the
human body.
The human microbiome is one of the richest and most diverse ecosystems on earth, with a population of approximately 30 – 50 trillion
microorganisms that live in our intestines, mouth, skin and elsewhere in or on the body. In a healthy, symbiotic state the colonic microbiome plays an
important role in human health, helping the body digest food, resist pathogens, regulate the metabolic systems, develop and regulate the immune system and
synthesize essential nutrients and vitamins. However, the colonic microbiome may change in composition for a variety of reasons, including in response to
antibiotics or following gastrointestinal infection. These changes in composition may result in the loss of key commensal microbes and/or the gain of
pathogenic microbes, resulting in a state of dysbiosis, and associated loss or gain of metabolic and/or immune function. While the study of the human
microbiome is not new, the scientific community’s understanding of the microbiome, and the colonic microbiome in particular, has been significantly
advanced through metagenomics, which has enabled the broader understanding of the human microbiome at the organismal, functional and community level.
Scientific research has correlated dysbiosis in the colonic microbiome with various conditions, including: infectious diseases, metabolic diseases, and
inflammatory and immune diseases and cancer.
We are developing a new approach to treating disease by modulation of the dysbiotic colonic microbiome by using our Ecobiotic microbiome
therapeutics to improve patient outcomes. Our approach is premised on the hypothesis that the proximal cause of many diseases is a dysbiosis in the natural
state of the colonic microbiome. We believe that the restoration of a dysbiotic colonic microbiome using Ecobiotic microbiome therapeutics represents a
paradigm shift in the approach to treating underlying disease. There are currently no therapeutics approved by the U.S. Food and Drug Administration, or the
FDA, that are designed to restore the microbiome to a healthy state.
Our approach to discovery and design is based on an iterative bedside-to-bench-to-bedside drug discovery strategy, i.e. reverse translation that begins
with data on the human microbiome that we gather from clinical studies. From these clinical data, we identify the microbiological and functional differences
between a healthy and a diseased microbiome, which we then use to design potential Ecobiotic microbiome therapeutics. After further in-lab preclinical
testing, selected Ecobiotic microbiome therapeutic candidates are then studied in clinical trials. We apply a comparative genomic systems biology framework
that leverages proprietary computational, microbiological and screening capabilities to design lead candidates that target the microbiological and functional
deficiencies identified in the setting of human disease. We are able to apply this framework and experience to clinical data sets from published studies and
those generated with our collaborators, as well as to the proprietary clinical data set we have generated through our clinical trials. We believe we can utilize
our knowledge and data to design Ecobiotic microbiome therapeutics to treat various medical conditions. We also have advanced capabilities in
pharmacokinetic and pharmacodynamic analytics, and the production and formulation of colonic bacteria as well as spore forms of bacteria into therapeutics.
We believe that the combination of experience, proprietary data and proprietary know-how that comprise our microbiome therapeutics platform provides us
with a competitive advantage in the design and development of microbiome therapeutics. Further, our approach and platform, which enable the design,
testing, optimization, manufacturing and formulation of Ecobiotic microbiome therapeutic candidates, provide a framework that we believe can significantly
reduce the time typically required to advance therapeutics to the clinic.
Using our microbiome therapeutics platform, we are focusing our resources on obtaining clinical results from our highest-priority, clinical programs in
ulcerative colitis, or UC, a form of inflammatory bowel disease, or IBD, with SER-287, Clostridium difficile infection, or CDI, with SER-109, and our
recently initiated Phase 1b study with SER-401 in patients with metastatic melanoma, as well as our preclinical SER-301 program in UC.
The clinical development of SER-287 to treat UC, is supported by successful clinical and preclinical studies. Preclinical colitis animal models and in
vitro screens provide evidence that SER-287 administration has the potential to result in reduced pathology and modulation of inflammatory and
immunological functional pathways. Published clinical reports also suggest that modulation of the microbiome through repetitive fecal microbiota
transplantation, or FMT may lead to meaningful clinical response in UC patients.
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We completed our Phase 1b clinical study for our UC drug candidate, SER-287, in subjects with active mild to moderate UC who were failing current
therapies. The results of the SER-287 Phase 1b study, a randomized, double-blinded, placebo-controlled, multiple-dose, induction study enrolled patients
with active mild-to-moderate UC, with Total Modified Mayo scores of 4 to 10 were positive. The study enrolled 58 subjects who exhibited pre-study disease
activity despite treatment with standard-of-care therapeutics. SER-287 safety and tolerability was a primary study endpoint. The study showed no imbalance
in adverse events in SER-287-treated patients as compared to patients treated with placebo and no drug-related serious adverse events were observed.
Analyses of microbiome data, a co-primary endpoint of the trial, showed that SER-287 induced regimen-dependent engraftment of SER-287 derived
bacterial species into the colonic microbiome of patients treated with SER-287. Patients administered vancomycin pre-treatment followed by daily
administration of SER-287 had the highest level of SER-287 engraftment, which was statistically significant. This patient cohort corresponded with the study
arm where the most significant clinical benefits were observed, including clinical remission and endoscopic improvement. Differences in the composition of
the microbiome post treatment were also associated with clinical remission. Bacterial engraftment signatures were durable throughout the dosing period of the
trial and were also observed at four weeks post administration of the final SER-287 dose. The pharmacologic impact of the SER-287 engraftment was
supported by metabolomic and transcriptomic data. Analysis of metabolites and gene expression signatures associated with inflammation and immune
modulation, were observed to be correlated with remission in SER-287 treated subjects.
Based on these encouraging data from the Phase 1b trial, in December 2018, we initiated our Phase 2b trial, ECO-RESET, evaluating SER-287 in
patients with active mild-to-moderate UC. Based on feedback obtained from the FDA on the SER-287 Phase 2b study design, we believe the study could
serve as one of two required pivotal trials supporting potential future registration of SER-287. The Phase 2b study is a three-arm placebo-controlled trial of
approximately 200 patients with active mild-to-moderate UC. Two groups of patients will receive different doses of SER-287, both following pretreatment
with a short course of oral vancomycin. A third study arm will receive placebo. The study’s primary endpoint will evaluate clinical remission measured after
10 weeks of SER-287 administration. Endoscopic improvement will be measured as a secondary efficacy measure. We expect to complete trial enrollment by
mid-2020.
Our Phase 3 clinical candidate, SER-109, is designed to rapidly and durably correct dysbiosis in the colonic microbiome in the setting of recurrent
CDI. CDI is most often caused by the use of broad spectrum antibiotics which create a dysbiosis of the microbiome, thus increasing susceptibility to infection
by Clostridium difficile, or C. difficile, a spore forming bacterium. C. difficile expresses toxins leading to debilitating diarrhea in affected individuals, and
which can also cause more severe outcomes, such as inflammation of the colon (colitis), toxic megacolon and death. The U.S. Centers for Disease Control, or
CDC, has identified CDI as one of the top three most urgent antibiotic-resistant bacterial threats in the United States. It is the most common cause of hospital
acquired infection in the United States and has overtaken methicillin-resistant Staphylococcus aureus, or MRSA in incidence of disease. CDI is responsible
for the deaths of approximately 29,000 Americans each year. Based on an epidemiological study conducted by the CDC, the incidence of CDI in the United
States, was estimated to be 453,000 (95% confidence interval, 397,100 to 508,500) (Lessa et. al., Burden of Clostridium difficile Infection in the United
States, New England J. of Medicine, 2015). While the epidemiological data are varied outside the United States due to the widespread use of antibiotics, CDI
is a growing global disease. The standard of care for CDI is to treat with antibiotics. In many cases, antibiotic treatments may resolve the acute infection
caused by C. difficile. However, these antibiotic treatments kill beneficial bacteria indiscriminately, inducing a dysbiosis of the microbiome and potentially
making patients more susceptible to a recurrence of CDI. For those patients who experience a CDI recurrence, it is likely that dysbiosis of the microbiome is
the proximal cause of disease. Published data suggests that the risk of recurrence is approximately 25% after the primary CDI, 40% after a first recurrence and
as high as 60% for those experiencing two or more recurrences.
SER-109 is a donor-derived, purified bacterial spore-based microbiome therapeutic candidate consisting of an average of approximately 50 bacterial
species purified from healthy donor stool. SER-109 is designed to prevent further recurrences of CDI in patients with recurrent CDI by restructuring the
dysbiotic microbiome to a state that resists C. difficile growth and colonization. If approved by the FDA, SER-109 could be a first-in-field oral microbiome
drug. We initiated a Phase 3 clinical study of SER-109 in approximately 320 patients with multiply recurrent CDI. The on-going study is designed to evaluate
patients for 24 weeks with the primary endpoint of comparing the C. difficile recurrence rate in subjects who receive SER-109 verses placebo at up to eight
weeks after dosing.
We continue to enroll the SER-109 Phase 3 study for patients with recurrent CDI despite the widespread use of FMT to treat CDI. As interference
from this uncontrolled, understudied and unapproved product has impacted the enrollment rate of our SER-109 placebo-controlled clinical trial, we are
evaluating modification of the study design to expedite clinical results.
Our SER-301 program is in preclinical discovery and bioprocess development. SER-301 is being rationally designed by utilizing our reverse
translational microbiome therapeutics platform to incorporate learnings from our SER-287 and SER-262 clinical studies. We have identified specific bacterial
species that engraft and are associated with clinical remission, and further we have identified metabolites made by these bacteria that correlate with clinical
efficacy. We also have gene expression data from patient mucosal biopsies showing which genes and pathways are favorably altered by SER-287 treatment.
All of these data are being leveraged in the design of SER-301.
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We are also developing SER-401, for use with checkpoint inhibitors, or CPIs, in patients with solid tumors to enhance efficacy and improve survival.
SER-401 is a microbiome therapeutic candidate sourced from healthy individuals who have been identified to have a microbiome signature that is similar to
that observed in cancer patient responders to CPIs. CPIs block the mechanisms by which cancers evade detection and destruction by the immune
system. Observational studies of humans by a group led by our collaborator, Dr. Jennifer Wargo of MD Anderson Cancer Center, or MD Anderson, suggest
that microbiome composition impacts response to CPIs. This has been supported by mouse model studies conducted by us and at MD Anderson that show
that colonization with human responder microbes affected tumor response to CPI treatment, versus mice colonized with CPI non-responder microbes. These
effects are thought to be a result of a specific microbiome “signature” enriched in certain members of the Firmicutes phylum of bacteria. We are working in
collaboration with MD Anderson and the Parker Institute for Cancer Immunotherapy, or the Parker Institute, to evaluate the potential of SER-401, based upon
this signature, and to modulate the immunological tone of subjects to improve response in patients with metastatic melanoma to CPI treatment. MD Anderson
granted Seres an exclusive option, with pre-defined financial terms, to license intellectual property rights from them related to the use of bacteria in
combination with CPIs. In collaboration with the Parker Institute and MD Anderson, we initiated a Phase 1b study of SER-401 in patients with metastatic
melanoma. Patients will be treated with either CPI alone, or in combination with SER-401, and observed for tumor regression and biomarkers of response to
CPI. We expect to obtain Phase 1b study results in 2020.
On February 7, 2019, we announced corporate changes to focus our resources. We will now concentrate on completing the recently-initiated SER-287
Phase 2b study in mild-to-moderate UC, obtaining results from the ongoing SER-109 Phase 3 study for recurrent CDI and advancing the SER-401 Phase 1b
study, in collaboration with the Parker Institute and MD Anderson, to evaluate augmenting CPI response in patients with metastatic melanoma. We will also
continue to pursue focused preclinical activity on SER-301, a rationally-designed microbiome therapeutic candidate for UC, leveraging learnings obtained
from our prior clinical study results. In connection with the prioritization of these therapeutic candidates, we made changes to our management team and
committed to a workforce reduction plan to reduce headcount by approximately 30 employees.
Other Programs
In July 2016, we initiated a SER-262 Phase 1b dose-escalating study, the first clinical trial conducted using a rationally designed, fermented
consortium of bacteria. SER-262 was rationally designed to be used following antibiotic treatment to prevent an initial recurrence of CDI. We have
established various capabilities to enable the development of rationally designed microbiome therapeutics including metagenomic and metabolomic profiling,
use of curated reference computational databases and proprietary in silico algorithms for drug design, an extensive proprietary bacterial library, advanced
manufacturing processes, and capabilities to conduct pharmacokinetics and pharmacodynamics analyses in clinical studies. SER-262 contains a consortium of
12 bacterial strains derived from a manufacturing process using fermentation and does not require human donor material.
The Phase 1b clinical study was a 24-week, randomized, placebo-controlled, dose-escalation trial. The primary endpoints of the study were safety and
tolerability and a comparison of the CDI recurrence rate in the SER-262 and placebo groups. Key secondary endpoints included analysis of SER-262 bacterial
strain engraftment. Top line clinical and microbiome results from the study are available. No drug-related serious adverse events were observed. No
significant differences were observed in the recurrence rates in patients administered SER-262 as compared to placebo. However, we observed a statistically
significant reduction in CDI recurrence rates in patients pretreated with vancomycin followed by SER-262, as compared to those treated with metronidazole
followed by SER-262. This observation corresponded with an increase in SER-262 microbiome engraftment in patients pretreated with vancomycin. We
believe the analyses of clinical data from both the SER-262 and SER-287 Phase 1b studies suggests that vancomycin pretreatment may augment engraftment
of our microbiome therapeutic candidates.
We are also designing SER-155, a rationally designed, fermented microbiome therapeutic candidate designed to correct dysbiosis in patients following
allogeneic hematopoietic stem cell transplants, or allo-HSCT, or solid organ transplants. This preclinical program is based on published clinical evidence from
our collaborators at Memorial Sloan Kettering Cancer Center showing that allo-HSCT patients with dysbiosis are far more likely to die due to infection and/or
lethal graft versus host disease, or GvHD. In November 2017, we were awarded a highly-competitive grant from Combating Antibiotic-Resistant Bacteria
Accelerator, or CARB-X, to support continued preclinical research and early development work for SER-155. The CARB-X grant provides us with up to $2.5
million of research funding with potential for an additional $3.1 million for manufacture and investigational new drug application, or IND, upon completion
of milestones.
We continue to evaluate microbiome pharmacokinetic and pharmacodynamic data from the SER-262 Phase 1b study, in addition to insights gained
from research efforts with our other rationally designed Ecobiotic microbiome therapeutic candidates, in order to determine next steps in the development of
both SER-262 and SER-155.
We have completed early stages of researching Ecobiotic microbiome therapeutics for the treatment of metabolic diseases, such as non-insulin
dependent diabetes, non-alcoholic steatohepatitis, or NASH, and metabolic syndrome. Research in these indications
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has focused on identifying microbiome signatures associated with various disease states and early discovery efforts to identify Ecobiotic consortia that could
impact specific functional defects in the microbiome.
We have assembled a world class group of scientists, clinicians, directors and investors, who have established our leadership in the field of
microbiome therapeutics. We were co-founded by Drs. Noubar Afeyan, David Berry and Geoffrey von Maltzahn of Flagship Pioneering. Through Flagship
Pioneering’s contribution of foundational scientific concepts and intellectual property, assembly of our management team and critical early-stage support, we
launched as the first company focused on the ecological nature of the microbiome. Led by Eric Shaff, our President and Chief Executive Officer, our
experienced management team possesses core capabilities in microbiome therapeutics, drug development, commercialization, chemistry, manufacturing and
controls, or CMC, public company management and finance. Our management team has extensive experience in microbial ecology, microbiology and live
biological products, with over 25 years of experience studying the microbiome and over 60 published papers on the science of the microbiome. Additionally,
our team has extensive experience in building out commercial capabilities in specialty diseases and has a track record for success in the commercialization of
vaccine products, which have analogous manufacturing processes to that of Ecobiotic microbiome therapeutics.
Our goal is to remain the leading biopharmaceutical company developing and commercializing microbiome therapeutics to address significant unmet
medical needs. We intend to focus in the near term on the highest priority clinical programs which we believe will optimally advance our pipeline: SER-287
for UC; SER-109 for recurrent CDI; and the SER-401 immuno-oncology program. We also intend to continue to strengthen our next generation of rationally
designed, fermented microbiome therapeutic approach with SER-301 for UC being our lead candidate. The critical components of our strategy include:
Our Strategy
Advancing our Programs
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Continuing clinical development of SER-287 for the treatment of UC. The clinical development of SER-287 to treat UC is supported by both
clinical and preclinical studies in multiple animal models of colitis that provide evidence that SER-287 administration may result in reduced
inflammation. Published clinical reports suggest that modulation of the microbiome through repetitive FMT may lead to meaningful clinical
response in certain UC patients. In December 2015, we initiated a Phase 1b clinical trial evaluating SER‐287 in patients with mild‐to‐moderate
UC who were failing current therapies. In October 2017, we announced positive topline results from our Phase 1b clinical trial of SER-287 in
patients with UC. The SER-287 Phase 1b study, a randomized, double-blinded, placebo-controlled, multiple-dose, induction study enrolled
patients with active mild-to-moderate UC, with Total Modified Mayo scores of 4 to 10. The study enrolled 58 patients at 20 sites across the
United States. Study subjects exhibited pre-study disease activity despite use of current therapies in a majority of subjects, which included 5-
amino-salacylic acid, low dose corticosteroids, or immunomodulatory therapy. Based on the encouraging data from the Phase 1b trial, in
December 2018, we initiated our Phase 2b trial, ECO-RESET, evaluating SER-287 in patients with active mild-to-moderate UC. Based on
feedback obtained from the FDA on the SER-287 Phase 2b study design, the study could serve as one of two required pivotal trials supporting
potential future registration of SER-287. The Phase 2b study is a three-arm placebo-controlled trial of approximately 200 patients with active
mild-to-moderate UC. Two groups of patients will receive different doses of SER-287, both following pretreatment with a short course of oral
vancomycin. A third study arm will receive placebo. The study’s primary endpoint will evaluate clinical remission measured after 10 weeks of
SER-287 administration. Endoscopic improvement will be measured as a secondary efficacy measure. SER-287 has been awarded Orphan
Drug Designation designation for pediatric UC.
Advancing the development of our lead product candidate, SER-109, for the prevention of further recurrences of CDI in patients with
recurrent CDI. SER-109 has been granted both Orphan Drug and Breakthrough Therapy designation by the FDA for the treatment of CDI.
Breakthrough Therapy designation provides for intensive guidance from the FDA in an effort to expedite the drug development process. In our
randomized, double-blind, placebo-controlled Phase 2 clinical study, 44% of subjects (26 of 59) who received SER-109 experienced a
recurrence at the 8-week endpoint compared to 53% of subjects (16 of 30) who received placebo, a result that was not statistically significant.
Based on a detailed analysis of clinical, microbiome and CMC factors that may have contributed to the outcome of this study, as well as our
earlier Phase 1b/2 clinical study and following discussions with the FDA, a new SER-109 clinical study in approximately 320 patients with
multiply recurrent CDI was initiated in June 2017. Study participants are being randomized 1:1 between SER-109 and placebo and receiving a
total dose that is approximately 10-fold higher than in the Phase 2 study, administered over three consecutive days.
Developing SER-401 for use with CPIs in patients with solid tumors. We are developing SER-401 for administration in combination with CPI
treatment to increase efficacy in patients with solid tumors. The design is being driven by insights from our collaborators at MD Anderson and
recent published data in a number of high-profile scientific journals from other international research groups that suggest that the microbiome
may impact patients’ response to CPI treatment.
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Together with our collaborators, we have initiated a Phase 1b multicenter study in metastatic melanoma patients as part of our collaboration
with MD Anderson and the Parker Institute.
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Developing SER-301 for the treatment of IBD. We are designing and developing SER-301, a rationally designed, fermented, Ecobiotic
microbiome therapeutic candidate for the treatment of IBD leveraging pharmacokinetic and pharmacodynamic data from our SER-287 clinical
trial, our knowledge of modulation of dysbioses seen in patients with UC, as well as insights from our SER-262 clinical study.
Advancing Our Capabilities
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Leveraging our leading reverse translation microbiome therapeutics platform to develop additional innovative and novel Ecobiotic
microbiome therapeutics across a range of serious medical conditions with high unmet need including infectious and inflammatory disease
and disease associated with modulation of host immunity. We believe that the combination of experience, proprietary data and proprietary
know-how related to the microbiome and of the production of microbial strains provides us a competitive advantage in the design and
development of microbiome therapeutics. Our platform enables us to build upon our existing and growing clinical experience to rationally
design treatments for acute and complex chronic diseases. We intend to leverage this advantage to develop additional innovative Ecobiotic
microbiome therapeutics.
Developing manufacturing capabilities sufficient to support commercialization of any approved Ecobiotic microbiome therapeutic
candidates. Ecobiotic microbiome therapeutic manufacturing will require capabilities that are distinct from other biologic drugs. We have made
strategic investments in manufacturing capabilities to help ensure that we maintain control of our know-how and also because we believe these
capabilities will be necessary and highly advantageous for the development of future Ecobiotic microbiome therapeutic candidates. Our
bioprocess and manufacturing personnel are focused on creating a platform of manufacturing expertise that will set the stage for further
advances in the emerging field of microbiome therapeutics.
Understanding the Microbiome and Its Impact on Disease
Among the various microbial ecosystems in the human body, the colonic microbiome is the most diverse microbial communities with about 100
billion bacterial cells per milliliter. In a healthy, symbiotic state the colonic microbiome enables the body to function normally. However, the colonic
microbiome can change in composition, such as in response to long-term or high-dose exposure to antibiotics or following a gastrointestinal infection. As a
result, there can be a loss of key microbes that results in a state of dysbiosis. Dysbiosis of the microbiome is associated with a wide range of disease and
infections.
Although bacteria are often associated with infection and disease, much of the bacteria that colonize the human body are essential for life. Until
recently, few scientific studies focused on the benefits of the bacteria comprising the microbiome. In 2005, the National Institutes of Health funded the
Human Microbiome Project, or HMP, which had as one of its goals the characterization of the microbiome with enough specificity to enable the study of
variations in the microbiome and their influence on disease.
Historically, researchers studied microbes in patients by isolating pathogens and growing them in culture. This process typically identifies only a
limited diversity of microbial species. The HMP used metagenomic sequencing technologies to analyze 5,000 samples, representing more than 3.5 terabases
of genome sequence data, to identify specific genetic sequences found only in bacteria. The most recent studies estimate that 30-50 trillion bacterial cells
comprising more than 1,000 unique bacterial species occupy the human ecosystem. Importantly, HMP researchers have discovered that different consortia of
microbes may accomplish the same metabolic activity, and the presence of those metabolic activities is more important than the exact species of microbe
providing the function. Results from the HMP have provided a robust baseline microbiome against which disease states can be compared.
Complementing the HMP baseline data, numerous scientific studies are emerging in both animals and humans, suggesting that many human diseases
are correlated with dysbiosis of the microbiome. These include infections, such as CDI or vancomycin-resistant Enterococcus, or VRE; inflammatory
diseases, such as UC, Crohn’s disease and pouchitis; autoimmune disease and cancer, including immune-oncology related applications; and further metabolic
disorders, such as early-stage, non-insulin dependent diabetes, obesity and non-alcoholic fatty liver disease, or NAFLD/NASH. Examples of some studies
include:
•
A study published in PLOS Pathogens in 2012 suggested that a mixture of six different bacteria found naturally in the gastrointestinal system of
mice, when isolated from stool and reintroduced into the infected mice, was effective at suppressing CDI (Lawley et al., PLOS Pathogens,
2012). Researchers in the study found that a single treatment of the bacteria was sufficient and that the suppression lasted for months. We
observed that SER-262, our clinical consortium of human-derived bacterial species formulated as spores, protected mice from disease in a CDI
model.
9
•
•
•
A placebo-controlled, randomized, blinded clinical study published in Gastroenterology in 2015 showed that repetitive FMT delivered via
enema weekly for 6 weeks induced clinical remissions in 24% of patients with active UC compared to 5% receiving placebo (Moayyedi et al.,
Gastroenterology, 2015). This study utilized endoscopy, a direct visualization of the colon, before and after treatment to assess the efficacy of
FMT, thus demonstrating the role of the microbiome in treating active UC. A subsequent randomized, placebo controlled, blinded study of
FMT delivered via enema 5 days per week for 8 weeks demonstrated similar clinical remission rates: 27% receiving FMT and 8% receiving
placebo (Paramsothy et al., Lancet, 2017). Most recently, a study of FMT delivered by a colonoscopy followed by 2 enemas to UC patients
resulted in similar outcomes: 32% receiving donor-FMT and 9% receiving autologous control (Costello et al, JAMA, 2019). We announced
top-line clinical data from our Phase 1b clinical trial for SER-287 in October 2017. In this trial, patients with mild-to-moderate UC, receiving a
vancomycin pre-treatment followed by a daily oral dose of SER-287 for 8 weeks achieved a 40% rate of clinical remission compared to no
clinical remission for treatment with placebo. This analysis followed the intent-to-treat, or ITT, “worst case” analysis used for drug registration
studies in which missing data is counted as failure.
Data from cancer patients undergoing allo-HSCT show the influence of the microbiome on patient survival. An observational study of allo-
HSCT patients following allo-HSCT demonstrated that 3-year survival in patients with a low diversity microbiome was 36% whereas survival
in patients with a medium to high diversity microbiome was ≥60%. Excess mortality in the low diversity subset was driven by deaths due to
infection and GvHD, not the underlying cancer itself (Taur et al, Blood, 2014). A follow up from the same researchers looked at allo-HSCT
patients receiving transplants who are at highest risk of GvHD and showed a greater than 5-fold increase in mortality was correlated with
microbiome composition. (Jenq et al., Biol of Blood and Marrow Transplant, 2015).
Two studies in mouse cancer models, both published in Science in 2015, demonstrated that the anti-tumor response to immune CPIs could be
enhanced by altering the microbiome (Velizou et al., Science 2015; Slvan et al., Science 2015). More recently, independent groups from MD
Anderson, the Institute Gustave Roussy in Paris, France, and the University of Chicago have published data from human studies showing that
cancer patients who successfully respond to immune CPIs tend to have a distinct microbiome from patients who do not respond. Moreover,
when human fecal samples from responding and non-responding patients are transferred into mice, these have been shown to exhibit the same
response to CPIs in tumor model experiments as their human donors (Golpalakrishnan et al, Science, 2017; Routy et al, Science, 2017; Matson
et al, Science, 2018). Taken together, these results suggest that microbiome therapies might improve the efficacy of CPIs in treating cancer.
There are currently no microbiome therapeutics approved by the FDA. We believe that the ability to develop drugs that are able to modulate the
microbiome and return a dysbiotic microbiome to its healthy state presents a significant opportunity to improve human health.
Our Microbiome Therapeutics Platform
We have developed the leading microbiome therapeutics platform, which we believe enables us to significantly reduce the time typically required to
advance therapeutics to the clinic, and ultimately, to the market. We use reverse translation, the practice of driving discovery based on human data sets to
improve the translatability of a preclinical program. Specifically, we start with data sets from both healthy subjects and patients to delineate at high-resolution
the composition of the microbiome and physiological state of subjects and identify specific signatures in the microbiome that associate with disease or the
onset of disease; these in-human insights are leveraged in preclinical drug design and development.
Our discovery process begins with human data derived from clinical trials and cohort studies, which we use as a basis for designing our Ecobiotic
microbiome therapeutic candidates. We compare healthy, normal colonic microbiomes to those in an unhealthy dysbiotic or disease state, revealing the
ecological and functional differences between various states of disease and during the transition from health to disease or vice versa. We then develop our
Ecobiotic microbiome therapeutic candidates to target these differences. Our clinical data from the SER-109, SER-262 and SER-287 programs, and
microbiome data generated with external collaborators, serve to instruct us on how the introduction of certain keystone microbes have the potential to
restructure a dysbiotic colonic microbiome and shift it to a non-disease state.
We have developed a proprietary suite of bioinformatics and computational tools, which facilitate our insights into the human microbiome. Using
whole metagenomic shotgun sequencing, and our proprietary, curated, reference database of novel bacterial genomes, our algorithms enable us to track
changes in the microbiome at the level of bacterial species and individual strains. We have also developed tools integrating gene profiling and metabolomics
data (the small molecules made by the microbiome) with genomic data (the collection of bacteria defined by sequencing) to understand the functions related
groups of organisms contribute to the state of disease or health. Further, we have established de novo analytics for pharmacokinetic and pharmacodynamic
assessments of microbiome therapeutics.
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Our proprietary strain library of over 35,000 bacterial isolates from healthy donors and patients enables us to translate computational insights into
defined compositions. It includes the majority of the HMP’s “most wanted” and many novel species not described in other databases or the scientific
literature. Using proprietary assays and full-genome sequences, we characterize the functional capabilities of the bacteria in our strain library, based on both
metabolomics and how the bacteria interact with human colonic epithelial cells and human immune cells. We also seek to understand how these microbes
improve the health of barrier cells in the gut and how this may impact immune responses.
We select bacteria from our library with specific predicted properties using novel algorithms for functional design and grow the compositions in the
lab to be tested both in vitro and in vivo animal models. Our animal models include conventional mice, germ-free mice, and “humanized” mice that possess
only bacteria derived from humans, which we developed to minimize confounding variables presented by murine microbes. Data from our in vitro and in
vivo screens are analyzed and used to optimize compositional designs; introducing new bacterial strains and optimizing existing strains until we identify a
lead composition suitable for clinical testing.
Finally, we manufacture the bacterial composition under current Good Manufacturing Practices, or cGMP, which are required by FDA and European
regulators. We believe our unique manufacturing capacities position us to exploit the insights of our proprietary human data and the novel biology of species
and strains that have not previously been used for therapeutics. We have optimized fermentation conditions to generate spores and enhance bacterial yields in
anaerobic fermentation and have in-house capabilities to formulate both spores and live non-spore bacteria. Our manufacturing facility in Cambridge,
Massachusetts was designed to be fit-for-purpose and is highly differentiated compared to the offerings of commercial contract research organizations. We
address quality control requirements for our Ecobiotic microbiome therapeutic candidates using proprietary microbiological and sequence-based testing
schemes, including high-throughput quantitative analytics to assess the identity, potency and purity of the final product. These methods have been qualified to
meet regulatory standards for live biotherapeutic products.
Taken together, we believe our platform, spanning drug discovery, preclinical translation, and novel manufacturing and quality control approaches, has
enabled a field leading pipeline across a range of therapeutics areas.
Disease Overview and Our Product Pipeline
We believe our Ecobiotic microbiome therapeutic candidates represent a novel approach with potential application across a broad range of human
diseases. SER-287 is under development for the treatment of active mild-to-moderate UC and has completed a Phase 1b study in the United States. SER-287
has been designated an Orphan Drug for pediatric UC by the FDA. We are designing SER-301, a rationally-designed, fermented Ecobiotic microbiome
therapeutic candidate, for the treatment of IBD. Our most advanced drug development program, SER-109, focuses on recurrent CDI. SER-109 has been
designated as a Breakthrough Therapy and an Orphan Drug by the FDA. Based on feedback received from the FDA, we have initiated a Phase 3 SER-109
clinical study in approximately 320 patients with multiply recurrent CDI. We are designing SER-401 for combination therapy with immune CPIs in cancer.
We have also conducted early stage research on potential Ecobiotic microbiome therapeutic candidates for the treatment of metabolic disorders, such as early-
stage, non-insulin dependent diabetes, NASH, and metabolic syndrome. Research in these indications is focused on developing Ecobiotic drugs that address
specific functional defects in the microbiome, including the specific metabolic products made by the microbes. We believe this approach may enable pursuit
of a range of disorders including various forms of liver disease and rare genetic diseases of metabolism.
Ulcerative Colitis, SER-287 and SER-301
UC is a relapsing-remitting chronic inflammatory disorder affecting the mucosal surface of the colon, leading to episodes of bloody diarrhea, urgency
and mucosal inflammation (Danese and Fiocchi, 2011), which generally begins in young adulthood and endures for life. As the disease mostly affects young
and middle-aged individuals, a time of peak reproductive and economic productivity, the disease leads to decreased quality of life in those affected by the
condition, high morbidity, and significant health economic burden. (Ghosh and Mitchell, 2007; Kappelman et al., 2008; Rubin et al., 2014; Theede et al.,
2015) The incidence of UC is rising worldwide and the prevalence of the disease is highest in the United States, Canada, and Europe. In the United States
alone, the prevalence of UC in adults is estimated to be 263 per 100,000, while in the pediatric population (age <20 years), prevalence of the disease is
estimated to be 33.9 per 100,000. (Kappelman et al., 2013)
UC is characterized by recurring episodes of inflammation limited to the mucosal layer of the colon. The severity of symptoms, diarrhea associated
with blood and abdominal pain, may range from mild disease to severe disease with more than 10 stools per day with severe cramps and continuous bleeding.
The severity, extent, and duration of disease are also risk factors for developing colon cancer, which occurs at a rate as high as 0.5-1.0% per year, an
important complication given the young age at which the disease strikes. Patients with UC also experience increased risk of CDI and primary sclerosing
cholangitis, compared to the general population.
The pathogenesis of UC is unclear but thought to arise from an aberrant immune response to a change in the colonic luminal environment in a
genetically susceptible individual. The key features of UC include diffuse mucosal inflammation in a continuous pattern starting distally in the rectum to more
proximal disease in the left colon to pancolitis.
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Symptoms of UC include rectal bleeding, tenesmus, increased stool frequency, urgency, incontinence, fever, fatigue and malaise, which negatively
impact quality of life, physical and mental health and productivity. A subset of patients has extra-intestinal manifestations ranging from iron deficiency
anemia to primary sclerosing cholangitis with implications for increased morbidity. In pediatric patients, the symptoms of UC have a more damaging impact,
as they affect children’s growth and lead to delayed puberty. These patients also suffer from weight loss, anemia and joint symptoms and current therapy itself
adversely impacts normal growth and development. (Kelsen et al., 2008). Treatment of UC with corticosteroids and immunosuppressive agents adds further
medical complications to these vulnerable patients, including corticosteroid toxicity and increased risk of invasive infections and malignancy. Both
environmental and genetic factors contribute to the etiology of the disease. Environmental factors may induce an ongoing immune response and inflammation
in the genetically predisposed host. Efforts to identify specific environmental factors has implicated commensal bacteria or their products as key determinants
of the inflammatory response in UC patients (Xavier et al., 2007). Thus, we believe SER-287 may target an “underlying cause” of UC rather than its
symptoms.
Current and developing treatment alternatives and their limitations
Currently, patients with UC require life-long therapy. The goals of medical therapy are to induce and maintain clinical and endoscopic remission.
Endoscopic remission is recognized as a key treatment goal since it better predicts short- and long-term clinical outcomes than symptomatic improvement
alone. Attainment of these goals is generally associated with improved quality of life and decreased need for corticosteroids, and lower risk of hospitalization,
colectomy, and colon cancer.
Although the etiology of UC is not fully understood, much progress has been made in the understanding of pathogenesis. Under homeostatic
conditions, there is a balance between pro-inflammatory and anti-inflammatory cytokine signals mediated by epithelial and immune cells in the
gastrointestinal tract. However, UC is characterized by dysregulated mucosal immune responses and translocation of inflammatory mediators of
microbiological origin across a disrupted gastrointestinal barrier that may cause or perpetuate inflammation leading to chronic inflammatory disease.
Migration of innate and adaptive immune cells into gut mucosal tissues is potentiated by locally produced cytokines and chemokines, and by the expression
of integrins that enhance cellular trafficking into the gut lamina propria. Inhibition of the immune response, via antibodies and proteins that sequester pro-
inflammatory cytokines or block the function of integrins, has been an important target of UC drug development over the past decade.
Current management of UC includes medications that decrease general inflammation (e.g., 5-aminosalicylate derivatives, or 5-ASA, corticosteroids)
or dampen specific components of the host immune response (e.g., immunomodulators, inhibitors of tumor necrosis factor, anti-integrin antibodies).
For mild-to-moderate disease, the 5-ASA derivatives are the standard of care for both induction and remission. 5-ASA derivatives achieve clinical
remission in only 25-40% of patients during induction and approximately one-third of responders have disease flares during the first year of maintenance
therapy, necessitating additional treatment interventions such as corticosteroids and immunomodulators (e.g. 6-mercaptopurine, methotrexate, azathioprine).
Corticosteroids are not recommended by guideline panels for chronic therapy since these drugs are ineffective for maintaining remission and are associated
with significant adverse events. Patients taking thiopurines require ongoing monitoring for hepatotoxicity, myelosuppression, and opportunistic infections, as
well as counseling on the potential risk of lymphoma.
Current medical therapies for the treatment of UC suppress the immune system rather than reducing the triggers of immune activation. We believe
there remains an unmet need for safer agents with novel non-immunosuppressive mechanisms of action. Moreover, alternative therapy is needed for patients
with mild-to-moderate UC who experience frequent flares or are intolerant to the aminosalicylate class of medication or where there are safety concerns
relating to the use of immunomodulator or steroid therapy.
SER-287
Given the dysbiosis seen in UC patients, studies have explored the use of FMT to treat UC. (Angelberger et al., 2013; Colman and Rubin, 2014; Kump
et al., 2013; Kunde et al., 2013; Moayyedi et al., 2015; Rossen et al., 2015; Paramsothy et al., 2017). Early reports of enhanced clinical remission and
endoscopic improvement with repetitive FMT compared to placebo motivated the preclinical development and clinical testing of SER-287. SER-287 is a
donor-derived, microbiome therapeutic candidate composed of the spore-forming fraction of the intestinal microbiota that is underrepresented in UC patients.
We initiated our Phase 1b clinical study in December 2015 in subjects with mild-to-moderate UC to evaluate the safety and efficacy of SER-287 added to
standard of care treatment. This SER-287 Phase 1b study, a randomized, double-blinded, placebo-controlled, multiple-dose, induction study enrolled patients
with active mild-to-moderate UC, with Total Modified Mayo scores of 4 to 10. The study enrolled 58 patients at 20 sites across the United States. Study
subjects exhibited pre-study disease activity despite use of current therapies in a majority of subjects, which included 5-ASA, low dose corticosteroids, or
immunomodulatory therapy. Three SER-287 drug product lots, based on human donor material obtained from three separate individuals, were used in the
Phase 1b study.
The primary endpoints of the study were to evaluate the safety and tolerability of SER-287, compare the change in the microbiome composition versus
placebo and determine engraftment of SER-287 bacteria following SER-287 treatment. The study evaluated clinical response, complete remission, and
endoscopic improvement, as well as metabolomic and immunological findings.
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In October 2017, we announced positive topline results from our Phase 1b clinical trial of SER-287 in patients with UC. Study results showed no
imbalance in adverse events in SER-287 treated patients, as compared to patients treated with placebo. No drug related serious adverse events were observed.
Analyses of study patients’ microbiome data, a primary endpoint, indicated that SER-287 induced dose-dependent engraftment of SER-287-derived
bacterial species into the colonic microbiome of the patients treated with SER-287. The cohort of patients that received vancomycin pre-treatment followed
by daily administration of SER-287 showed the highest level of SER-287 engraftment. We also observed the most meaningful clinical benefit in this patient
cohort. Differences in the composition of the microbiome post treatment were also associated with clinical remission. Bacterial engraftment signatures were
durable throughout the dosing period of the trial and were also observed at four weeks post administration of the final SER-287 dose. The pharmacologic
impact of the SER-287 engraftment was supported by metabolomic and transcriptomic data. Analysis of metabolites and gene expression signatures
associated with inflammation and immune modulation, were observed to be correlated with remission in SER-287 treated subjects.
Microbiome results showed engraftment of SER-287-derived bacterial species in patients pre-treated with vancomycin who received SER-287, with
daily dosing providing the most rapid and robust change in patients’ microbiome. Engraftment observed in these patients was maintained during the entire
dosing period and was observed four weeks after the last dose of SER-287 was administered. Thus, engraftment was durable. Vancomycin pre-treatment, as
compared to placebo pre-treatment, led to an immediate reduction of microbiome diversity followed by rapid and robust engraftment of SER-287-derived
bacterial species. We believe these data suggest that vancomycin pre-treatment may open ecological niches for SER-287 engraftment in the human
microbiome of patients with UC.
In December 2017, the FDA granted Orphan Drug Designation to SER-287 for treatment of UC in pediatric patients.
Further Details of Phase 1b clinical study design.
The Phase 1b clinical study was a multicenter, randomized, double-blind, placebo-controlled multiple dose study utilizing weekly or daily dosing with
SER-287. We enrolled eligible subjects at approximately 20 sites in the United States. The Phase 1b clinical study was designed to enroll adults 18 years of
age and older who had mild-to-moderate UC as defined by a Total Modified Mayo score between 4 and 10, inclusive, with a modified Mayo endoscopic
subscore ≥ 1, who were failing current therapies.
Patients were randomized to one of four study arms:
•
•
•
•
Pre-treatment with placebo for 6 days, followed by weekly dosing of SER-287 for 8 weeks
Pre-treatment with placebo for 6 days, followed by daily dosing with placebo for 8 weeks
Pre-treatment with vancomycin for 6 days, followed by daily dosing of SER-287 for 8 weeks
Pre-treatment with vancomycin for 6 days, followed by weekly dosing of SER-287 for 8 weeks
The primary objectives of the study were to evaluate the safety and tolerability of SER-287 compared to placebo; to compare the baseline composition
of the intestinal microbiome to the composition at 8 weeks post-initiation of SER-287 or placebo; and to determine the engraftment of SER-287 bacteria into
the intestinal microbial community in each of the SER-287 arms compared to the placebo arm.
The secondary objectives of the study were to determine the proportion of subjects in each of the treatment arms who at eight weeks post-initiation of
treatment achieve a clinical response, complete remission, and endoscopic improvement; to assess changes in serum and fecal biomarkers from baseline
throughout treatment; to determine the complement of metabolic pathways; and to compare the changes in exploratory biomarkers from mucosal biopsies and
stool in each of the treatment arms from baseline through eight weeks.
This study was designed to provide evidence of safety of SER-287 compared to placebo for the UC population, describe the changes in the
microbiome as a result of treatment with SER-287 and provide potential predictive biomarkers for future studies. UC is characterized by a decrease in
microbial diversity and richness, with a lower prevalence of spore-forming organisms within the phylum Firmicutes. Preliminary data using FMT suggest that
microbial interventions can affect clinical outcomes in UC, and this study evaluated whether the ecology of bacterial spores in SER-287 could correct the
dysbiosis in UC, increase microbial diversity and safely lead to a clinical response in UC patients with mild-to-moderate disease.
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Phase 1b clinical study results
Results were analyzed using the ITT “missing equals failure” analysis and the ITT “observed case” analysis methods. The ITT “missing equals
failure” analysis, included all 58 randomized subjects. For this analysis, incalculable clinical endpoints due to missing data, UC medication added due to UC
flare during the treatment period and discontinuation from the trial prior to Day 48 were considered as not achieving the clinical endpoints (worst
outcome). However, if the end-of-trial endoscopy at Day 48, or later, was available, and the subject did not take additional UC medication due to UC flare,
then the observed data was used to define success or failure for the subject. A period of 48 days of microbiome therapy was considered sufficient treatment to
estimate the outcome of clinical endpoints and was prespecified. The ITT “observed case” analysis included 53 of 58 subjects randomized, excluding those
who were missing their end-of-treatment endoscopies and used the observed data to define success or failure for each subject in the analysis.
Clinical Efficacy Results
In the “missing equals failure” analysis, remission showed a statistically significant improvement in the vancomycin pre-treatment / SER-287 once-
daily dosing arm as compared to the placebo/placebo daily arm: 40% (6 of 15 in SER-287) vs 0% (0 of 11 in placebo); change from placebo of 40.0% (95%
confidence interval: 15.2%, 64.8%), (p-value, 0.0237). (See Figure 1).
The SER-287 weekly treatment arms also showed an improvement over placebo in both remission and endoscopic improvement but the effect was less
than with the daily dosing regimen, showing a dose-response to SER-287 in these efficacy endpoints. Addition of vancomycin to the SER-287 weekly dosing
regimen did not clearly alter efficacy results, although we believe this may be due to the small size of the study.
Clinical response (data not shown), showed a numeric increase in the vancomycin/SER287 daily treatment arm compared to placebo but did not reach
statistical significance.
Figure 1:
SER-287 Phase 1b Clinical Study Efficacy Data – Missing Equals Failure
Legend: Δ = change from placebo; Remission was defined as a Total Modified Mayo score of less than or equal to 2, and an endoscopic sub-score of 0 or 1;
Endoscopic improvement was defined as a decrease in endoscopic sub score of greater than or equal to 1. Endoscopy measures were analyzed by a Central
Reader.
Clinical Safety Results
The primary safety objective (short-term safety) was to evaluate the safety and tolerability of SER-287 in adults with active mild-to-moderate UC up
to 92 days after randomization as determined by clinical and laboratory safety assessments.
The treatment-emergent adverse events, or TEAEs, were balanced across all the treatment arms. No drug-related serious adverse events, or SAEs,
were reported. All adverse events, or AEs, were considered mild to moderate in intensity. Gastrointestinal, or GI, disorders had the greatest number of AEs
compared to other system organ classes, with the most efficacious treatment arm (vancomycin/SER-287 daily) experiencing the lowest percentage of GI AEs.
SER-287 was observed to be well-tolerated in all treatment arms, showing a safety profile consistent with the placebo arm. The safety profile, when
evaluating GI AEs, showed an improvement in the vancoymycin/SER-287 treatment arm compared to vancomycin/placebo and the vancomycin/SER-287
weekly treatment arms.
14
Diverse analyses of microbiome data of patients in this trial, a primary endpoint, was completed after completion of the trial. Analyses of study
patients’ microbiome data, a co-primary study endpoint of the trial, indicate that SER-287 induced dose-dependent engraftment of SER-287-derived bacterial
species into the colonic microbiome of the patients treated with SER-287. Patients administered vancomycin pre-treatment followed by daily administration
of SER-287 had the highest level of SER-287 engraftment, which was statistically significant. This patient cohort corresponded with the study arm where the
most significant clinical benefits were observed, including clinical remission and endoscopic improvement. Differences in the composition of the microbiome
post treatment were also associated with clinical remission. Bacterial engraftment signatures were durable throughout the dosing period of the trial and were
also observed at four weeks post administration of the final SER-287 dose. The SER-287 Phase 1b study microbiome data support the previously reported
clinical results.
Microbiome results showed engraftment of SER-287-derived bacterial species in patients pre-treated with vancomycin who received SER-287. The
degree of SER-287 engraftment, as measured by the number of detectable SER-287-derived bacterial species, increased in a dose-dependent manner, with
daily dosing providing the most rapid and robust change in patients’ microbiome. Engraftment was maintained during the entire dosing period and was
observed four weeks after the last dose of SER-287 was administered. Thus, engraftment was durable. Changes in the composition of the GI microbiome
were associated with clinical remission and further associated with changes in metabolite and gene expression signatures associated with inflammation and
immune modulation. Vancomycin pre-treatment, as compared to placebo pre-treatment, led to an immediate reduction of microbiome diversity followed by
rapid and robust engraftment of SER-287-derived bacterial species. These data suggest that vancomycin pre-treatment opens ecological niches for SER-287
engraftment in the human microbiome of patients with UC.
Phase 2b Clinical Study Design
Based on feedback from the FDA, we believe that the results from the SER-287 Phase 2b ECO-RESET study in conjunction with data from a second
pivotal study, could enable submission of a SER-287 Biologics License Application.
The Phase 2b study, initiated in December 2018, is a three-arm placebo-controlled trial of approximately 200 patients with active mild-to-moderate
UC. Two groups of patients will receive different doses of SER-287, both following pretreatment with a short course of oral vancomycin. A third study arm
will receive placebo. The study’s primary endpoint will evaluate clinical remission measured after 10 weeks of SER-287 administration. Endoscopic
improvement will be measured as a secondary efficacy measure.
SER-301
Our SER-301 program is in preclinical discovery and bioprocess development. SER-301 is being rationally designed by utilizing our reverse
translational platforms to incorporate learnings from our SER-287 clinical study, as well as our SER-262 clinical study. We have identified specific bacterial
species that engraft and are associated with clinical remission, and further we have identified metabolic products made by these bacteria that have correlated
with clinical efficacy. We also have gene expression data from patient mucosal biopsies showing which genes and pathways are favorably altered by SER-
287 treatment. All of these data are being leveraged in the design of SER-301.
CDI Overview and SER-109
Clostridium difficile Infection
C. difficile is a Gram-positive, toxin-producing, spore forming bacterium that may cause debilitating diarrhea in infected individuals, but can also lead
to more severe outcomes, such as inflammation of the colon, or colitis, toxic megacolon and death. C. difficile bacteria express toxins that disrupt the
structural architecture of cells causing leakage of fluids through the GI epithelium. The cells disrupted by these toxins eventually undergo apoptosis and die,
releasing their contents into the colon, resulting in inflammation of the colon, severe and persistent diarrhea and, in the most serious cases, death.
CDI is most often associated with the prior use of antibiotics, although age and poor immune status are important risk factors as well. Antibiotics are
thought to decrease resistance to CDI by causing dysbiosis in the microbiome. Since C. difficile spores are able to survive for long periods of time outside the
body, and because healthcare settings are often sites of significant antibiotic use, CDI transmission rates in hospitals, long-term acute care facilities and
nursing homes have been increasing. CDI is also a cause of morbidity and mortality among hospitalized cancer patients and bone marrow transplant patients
as their immune systems are suppressed by cytotoxic drugs, which are drugs that inhibit or prevent the function of cells including cells of the immune system,
and they may be heavily treated with antibiotics to prevent or treat infections. More recently, the rise of community-acquired CDI has been recognized as a
growing problem.
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The CDC has identified C. difficile as one of the top three most urgent antibiotic-resistant bacterial threats in the United States. It is the most common
cause of hospital acquired infection in the United States, having overtaken MRSA. CDI is responsible for the deaths of approximately 29,000 Americans each
year. CDI is also costly to the healthcare system. According to a study published in Clinical Infectious Diseases, the economic burden of CDI in 2008 in U.S.
acute care facilities alone was estimated to be as much as $4.8 billion. In addition, a summary of studies published in 2009 in The Journal of Hospital
Infection, calculated that the treatment cost per episode of primary CDI was as much as $5,000 and as much as $18,000 per recurrence of CDI (Ghantoji et al.,
2010). Further, according to a 2014 article in the American Journal of Infection Control, from 2001 to 2010, incidence of CDI per 1,000 patients discharged
increased from 4.5 to 8.2 with an average hospital stay of eight days. Research suggests that the risk of recurrence is approximately 25% after primary CDI,
40% after a first recurrence and greater than 60% for those experiencing two or more recurrences (Higa & Kelly, New Drugs and Strategies for Management
of Clostridium difficile Colitis, J. of Intensive Care Medicine, 2013). Based on an epidemiological study conducted by the CDC, the incidence of CDI in the
United States, based on a positive toxin or molecular assay in patients who did not have a positive result in the previous 8 weeks, was estimated to be 453,000
(95% confidence interval, 397,100 to 508,500) (Lessa et. al., Burden of Clostridium difficile Infection in the United States, New England J. of Medicine,
2015).
Current and developing treatment alternatives and their limitations
Patients with CDI utilize antibiotics, FMT, unapproved over-the-counter probiotics, and antibodies. Several therapeutic vaccines are also being
developed.
Antibiotics. According to the Infectious Disease Society of America, or IDSA, guidelines, the current standard of care for primary CDI is to
treat with antibiotics, such as fidaxomicin or vancomycin. Metronidazole is only recommended for mild disease or where access to other drugs is
limited. In addition, while fidaxomicin is recommended to treat primary CDI, it does not have a label claim to reduce or prevent CDI recurrence. No
antibiotic therapeutics are currently approved for treatment of recurrent CDI.
Recurrent CDI, defined as the presence of diarrhea and a positive C. difficile stool assay within two to eight weeks following the initial episode,
is not well addressed by any of the available antibiotics. When a patient has recurred two or more times after the initial occurrence, CDI recurrence
rates are greater than 60% and the probability of additional recurrences increases with successive cycles. In extreme cases, patients are treated
continuously for years with vancomycin, even while they continue to experience gastrointestinal symptoms including diarrhea and abdominal
discomfort.
The primary limitation of antibiotics is that their use appears to exacerbate dysbiosis, resulting in increased risk of future CDI. Research in
animal models has shown that antibiotic use not only eliminates many healthy bacteria in the GI tract, but also leads to the release of nutrients that
facilitate the growth of C. difficile. Antibiotics have also been shown to change the ratio of primary versus secondary bile acids in the colon by killing
bacteria required to metabolize bile acids. This shift to a predominance of primary bile acids further facilitates the growth of C. difficile, as it requires
primary bile acids for germination of its spores. As a result, antibiotic use may induce a lasting dysbiosis that makes it possible for C. difficile to
colonize a person and then cause, or further perpetuate, disease.
Fecal microbiota transplantation. FMT, also known as a stool transplantation, is a procedure during which donated stool, including fecal
microbes, is typically instilled via colonoscopy into a patient with CDI. We believe that the efficacy of FMT, which has resulted in cure rates for
recurrent CDI of 81% in a randomized controlled study reported in 2013 in the New England Journal of Medicine, supports the role of dysbiosis as a
cause of CDI recurrence. However, FMT presents several challenges for effective treatment of the disease. FMT has the potential to transmit infectious
or allergenic agents between hosts, involves the transmission of potentially hundreds of unknown strains of bacteria, fungi and viruses from donor to
subject, and is difficult to perform on a mass scale. Additionally, FMT is inherently non-standardized so that different desired and/or undesired
material may be transmitted in any given donation. FMT is not approved by the FDA and we believe that, as currently practiced by clinical centers in
the United States, it may be unable to gain such approval since the product, to our knowledge, cannot be characterized according to current regulatory
requirements for identity, potency, purity and safety and has not been tested in rigorous, placebo controlled, randomized and blinded clinical studies.
Commercial providers of FMT must meet FDA regulatory requirements for a biologics license and must produce FMT material using cGMP.
Probiotic therapies. Probiotics represent a group of products typically available over the counter in supplements and in some foods, which
contain a small number of species of bacteria. However, to date there have been no clinical studies that have established the ability of probiotics to
repair a dysbiosis of the microbiome. Further, there is neither a legally recognized definition of, nor a standard of identity for, the term probiotic in the
United States or Europe. The European Food Safety Authority has rejected many of the claims of health benefits associated with probiotics because
the microbes had not been sufficiently characterized, the claimed effect was not considered beneficial and human studies in support of the claims had
not been made available. As a result, after December 14, 2012, food and nutritional supplements companies were no longer allowed to communicate
health benefits for their products on account of probiotic content in the EU.
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Antibodies. Bezlotoxumab a fully human monoclonal antibody directed against C. difficile toxin B was approved in the United States in October
2016 and in Europe in 2017 for the treatment of CDI. The antibody demonstrated 10% absolute risk reduction in preventing recurrence of CDI.
Antibodies bind toxins to alleviate the symptoms of CDI, but they do not address the underlying dysbiosis of the microbiome, which we believe is the
cause of recurrent CDI. Bezlotoxumab requires intravenous infusion.
Vaccines. The efficacy of vaccines in treating CDI in humans currently remains under investigation. In addition, it is difficult to define and
access a target population for a CDI vaccine, given that the at-risk patient population is largely elderly individuals who typically respond less robustly
to vaccination therapies.
SER-109
SER-109 is an investigational, donor-derived ecology of bacteria in spore form purified from fecal donations obtained from healthy screened donors.
SER-109 consists of an average of approximately 50 bacterial species and is designed to reduce recurrences of CDI in patients suffering from recurrent CDI
by restoring a dysbiotic microbiome to a state of health. In our open label Phase 1b/2 clinical study of SER-109, we evaluated the effect of treatment with
SER-109 in patients with three or more occurrences of CDI in a 12-month period. Of the 30 patients enrolled in the trial, 87% of patients (26 of 30) met the
predefined endpoint and 97% (29 of 30), achieved a clinical cure, which we defined as the absence of CDI requiring antibiotic treatment during the eight-
week period after SER-109 dosing. A subsequent randomized, double-blind, placebo-controlled Phase 2 clinical study was conducted in 89 subjects to
evaluate the safety, tolerability and efficacy of SER-109 in adults with recurrent CDI. In that study, 44% of subjects (26 out of 59) who received SER-109
experienced a recurrence at the 8-week endpoint compared to 53% of subjects (16 out of 30) who received placebo, a result that did not show a statistically
significant difference between the two treatment arms. SER-109 was generally safe and well tolerated in both the Phase 1b/2 and Phase 2 clinical studies. In
each study we also performed an analysis of the microbiome using next-generation sequencing technology and microbiological analysis. These studies
demonstrated a re-establishment of keystone organisms and a rapid increase in bacterial diversity, which enable the restoration of the microbiome to a healthy
state.
SER-109 is formulated as oral capsules for administration after completion of antibiotics. Four capsules of SER-109 is comprised of about 30 million
SCFU that are delivered in four oral capsules. The spores in SER-109 are intended to germinate in the GI tract and compete for the same nutrients required
by C. difficile.
Phase 1b/2 clinical study design. The Phase 1b/2 clinical study was a two-part trial designed to evaluate the safety and efficacy of SER-109 in
30 patients with recurrent CDI. Part 1 of the study evaluated a single dose of SER-109 administered orally in 30 capsules over two days, with a dose
that varied between 3 x 107 and 2 x 1010. Part 2 of the study evaluated a single dose of SER-109 administered orally in a range of one to 7 capsules
over one day. The target dose in Part 2 was 1x108 spores per dose, which was approximately 17-fold lower than the mean dose in Part 1.
Phase 1b/2 clinical study results. The primary efficacy measure was the absence of CDI (defined in this study as more than three unformed
bowel movements in a 24-hour period with laboratory confirmation of a positive C. difficile stool test) during the eight weeks after initiating therapy.
Twenty-six of 30 patients, or 87% of patients, in the Phase 1b/2 clinical study achieved the primary efficacy endpoint, consisting of 13 patients in each
of Part 1 and Part 2 of the study. Among the 26 patients was one patient who experienced an initial recurrence on Day 26 and was re-treated, per
protocol, with a dose from the same donor. Following re-treatment, this patient also achieved the primary efficacy endpoint. Of the patients who did
not meet the primary efficacy endpoint, one had a recurrence of CDI on Day 5 and did not receive a second treatment with SER-109 and the three
other patients were determined by their attending investigator to be recovering from their diarrheal episode by the time they submitted their stool
sample for CDI testing. The three patients were determined to be clinically CDI free at eight weeks. As a result, the clinical cure rate for the study,
which we defined as the absence of CDI requiring antibiotic treatment during the eight-week period after SER-109 dosing, was 97%, or 29 of 30
patients. SER-109 was observed to be well tolerated in this study. The most common AEs were diarrhea, nausea, and abdominal pain. The majority of
TEAEs were mild in severity and consistent with post-antibiotic recovery from CDI.
Phase 2 clinical study design. The Phase 2 clinical study was a randomized, double-blinded, placebo-controlled, parallel-group two arm trial
that enrolled a total of 89 patients with a history of multiply-recurrent CDI, defined as 3 or more CDI episodes within 9 months. Subjects were
randomized at a 2:1 ratio with 59 subjects receiving SER-109 and 30 subjects receiving placebo. SER-109 was administered orally as a single dose of
1x108 bacterial spores, following the completion of antibiotic treatment for CDI. The study was conducted at 36 centers across the United States. The
primary endpoint was the absence of recurrence of C. difficile positive diarrhea requiring antibiotic treatment up to 8 weeks following treatment with
SER-109 or placebo.
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Phase 2 clinical study results. The predefined study primary efficacy endpoint was the relative risk of CDI recurrence up to 8 weeks after
treatment with SER-109 compared to treatment with placebo. CDI recurrence was defined as diarrhea for 2 or more consecutive days, a positive CDI
test, and the requirement for antibiotic treatment. Based on 8-week data, CDI recurrence occurred in 44% of subjects (26 of 59) who received SER-
109, compared to 53% of subjects (16 of 30) who received placebo. The relative risk of CDI recurrence for the placebo population compared to the
SER-109 population was not statistically significant.
The most commonly reported AEs in both the SER-109 and placebo arms were in the GI category, and were diarrhea (25% vs 14%), abdominal
pain (22% vs 14%), flatulence (12% vs 3%), and nausea (10% vs 10%), for SER-109 and placebo, respectively. No drug-related SAEs were observed.
The SER-109 analyses were shared with the FDA. Based on feedback received from the FDA, a new Phase 3 SER-109 clinical study in approximately
320 patients with multiply recurrent CDI was initiated. Study participants are randomized 1:1 between SER-109 and placebo and receive a total dose
that is approximately 10-fold higher than in the Phase 2 study, administered over three consecutive days. Diagnosis of CDI for both study entry and for
endpoint analysis is confirmed by C. difficile cytotoxin assay, compared to the first Phase 2, where most patients were diagnosed by polymerase chain
reaction, or PCR. The primary endpoint will compare the C. difficile recurrence rate in subjects who receive SER-109 verses placebo at up to eight
weeks after dosing. The FDA has agreed that this new trial may qualify as a pivotal study with achievement of a persuasive clinical effect and
addressing FDA requirements, including clinical and statistical factors, an adequately sized safety database, and certain CMC parameters.
Analysis of Phase 1b/2 and Phase 2 clinical study results. In our Phase 2 clinical study, the study’s primary endpoint of reducing the relative
risk of CDI recurrence at up to 8 weeks after treatment was not achieved. In order to understand the difference in outcome between Phase 1b/2 and
Phase 2 clinical studies, we conducted an analysis of the available clinical, microbiome and CMC data. This root-cause investigation looked at the
clinical trial population, study conduct, and diagnostic testing used for study inclusion and endpoint analysis, assessed clinical specimens for genomic
and metabolomic biomarkers that might give insight into SER-109 efficacy and potency, reviewed manufacturing procedures and processes, performed
retrospective analysis using high-resolution whole metagenomics sequencing of Phase 1b/2 clinical study stool samples, and reviewed analytical
methods, that may have differed between the Phase 1b/2 and Phase 2 clinical studies. We identified key factors that potentially explain the Phase 2
clinical study results, including issues related to both the accurate diagnosis of C. difficile recurrent infection, and potential suboptimal dosing of
subjects in the trial.
The key factors include:
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•
•
•
•
The diagnostic test for entry may not have differentiated subjects with active CDI disease from those with other disease but who had C. difficile
carriage (e.g., irritable bowel syndrome)
The diagnostic test for CDI recurrence during the study (the primary endpoint) overestimated recurrences, as PCR was the most common test
performed.
The difference in recurrence rates by age in the placebo arm was confounded by the small number of placebo subjects (30) and the likely
inclusion of subjects with irritable bowel syndrome rather than recurrent CDI, or RCDI
The safety profile of SER-109, which may include diarrhea in the first week following dosing, led to SER-109 subjects presenting for
evaluation of recurrence at a time when they were likely to be colonized with C. difficile leading to mistaken diagnosis of RCDI
The dose and dosing regimen used in the study may not have been optimal in the Phase 2 clinical study based upon an assessment of the
microbiome response using whole metagenomics shotgun sequencing.
We performed an analysis of the microbiome of our Phase 2 clinical study and a reanalysis of our Phase 1b/2 clinical study using whole
metagenomics shotgun sequencing and microbiological analysis to evaluate long-term changes in the microbiome, including the restoration of
bacterial diversity in the colon of patients. This demonstrated a rapid increase in bacterial diversity and a restructuring of the microbiome towards a
healthy state. Upon introduction, SER-109 appears to engraft its bacterial species into the microbiome, with some of these species persisting in the
patient’s GI tract for at least 24 weeks after dosing. In addition, in some patients we noted the repopulation of organisms that were not in SER-109 and
had not been detected in the patient prior to treatment. We believe this phenomenon, which we refer to as augmentation, is an important element for
restoration of bacterial diversity and repair of dysbiosis. We did not observe any dose-dependent effect on engraftment, augmentation, or the clinical
resolution of CDI in the Phase 1b/2 clinical study.
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Phase 3 clinical study design. In June 2017 we initiated a Phase 3 clinical study of SER-109 in approximately 320 patients with multiply
recurrent CDI. Study participants are being randomized 1:1 between SER-109 and placebo. Diagnosis of CDI for both study entry and for endpoint
analysis utilizes a C. difficile cytotoxin assay, compared to the Phase 2 clinical study, where most patients were diagnosed by PCR. Patients in the
SER-109 arm receive a total SER-109 dose, administered over three days, approximately 10-fold higher than the dose used in the Phase 2 clinical
study. The study evaluates patients for 24 weeks and the primary endpoint is to compare the C. difficile recurrence rate in subjects who receive SER-
109 verses placebo at up to eight weeks after dosing. CDI recurrence is defined as diarrhea (>3 unformed bowel movements/day for 2 or more
consecutive days), a positive CDI toxin test, and the decision by the primary investigator that antibiotic treatment is warranted. The study is being
conducted at approximately 100 sites in the United States and Canada.
Manufacturing. SER-109 is a purified ecology of spores produced through a process of extraction from a natural human stool source, obtained
from qualified, highly screened donors. The donor raw material is collected in a controlled setting, under a protocol that ensures that donors meet
appropriate qualification criteria.
Donors are required to be in good health, and to possess a medical history that minimizes the risk of exposure to and transmission of an
infectious disease. Donors are tested for infectious agents and screened for GI and other health factors. Donors are monitored for health status changes
during the donation period. At the end of the donation period, the qualification assessment is repeated to help ensure the donor has maintained their
health status. After successful completion of an exit screening, donations are released for use in manufacturing.
We initially process the donor material in a Cambridge manufacturing facility, and then transfer the process intermediate to a contract
manufacturing organization, or CMO, to isolate and concentrate SER-109 for finishing to the oral capsule dosage form. The purified drug substance is
tested for identity, potency and purity, and subsequently formulated into drug product where it is again tested for identity, potency, purity, and
pharmaceutical properties in our Cambridge facility. The final drug product dosage form is four hard capsules for oral administration. Steps are
specifically built into the process to remove and kill non-spore microbes. We have conducted validation studies demonstrating the ability of the
process to inactivate and clear hypothetical extraneous pathogens of concern, and we believe we have sufficient data from these studies to support
ongoing and proposed clinical trials.
Raw materials, intermediates, drug substance and drug product are tested using cGMP assays developed with our know-how to assess the key
quality attributes of identity, potency and purity of the product. Identity testing has been developed to assure the presence of specific live spore forms
in the product. Potency assays assure the intended dose of spores and assess stability of the spores during storage. Stability of the dosage form is also
confirmed. Proprietary microbiological purity assays have been developed to enable testing for microbial contaminants in the presence of the live
spore product.
We believe we can address market demand with a relatively small-scale manufacturing process. If approved, we anticipate that we will be able
to produce a sufficient commercial supply of SER-109 to meet estimated demand in the United States using donations from a modest number of
donors.
Other Programs
SER-401
We are also developing SER-401, for use with CPIs in patients with solid tumors to enhance efficacy and improve survival. SER-401 is a microbiome
therapeutic candidate sourced from healthy individuals who have been identified to have a microbiome signature that is similar to that observed in cancer
patient responders to CPIs. CPIs block the mechanisms by which cancers evade detection and destruction by the immune system. Observational studies of
humans by a group led by our collaborator Dr. Jennifer Wargo of MD Anderson suggest that microbiome composition impacts response to CPIs. This has
been supported by mouse model studies conducted by us and at MD Anderson that show that colonization with human responder microbes affected tumor
response to CPI treatment, versus mice colonized with CPI non-responder microbes. These effects are thought to be a result of a specific microbiome
‘signature’ that is enriched with certain members of the Firmicutes phylum of bacteria. We are working in collaboration with MD Anderson and the Parker
Institute to evaluate the potential of SER-401, based upon this signature, to modulate the immunological tone of subjects to improve response in patients with
metastatic melanoma to CPI treatment. MD Anderson granted us an exclusive option, with pre-defined financial terms, to license intellectual property rights
from them related to the use of bacteria in combination with CPIs. In collaboration with the Parker Institute and MD Anderson, we have initiated a study of
SER-401 in patients with metastatic melanoma. Patients will be treated with either CPI alone, or in combination with SER-401, and observed for tumor
regression and immunological markers of response to CPI.
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SER-262
In July 2016, we initiated a SER-262 Phase 1b dose-escalating study, the first clinical trial conducted using a rationally designed, fermented ecology of
bacteria. SER-262 was designed to be used following CDI antibiotic treatment to prevent an initial recurrence of CDI. We have established various
capabilities to enable the development of rationally designed microbiome therapeutics including metagenomic and metabolomic profiling, use of curated
reference computational databases and proprietary in silico algorithms for drug design, an extensive proprietary bacterial library, advanced manufacturing
processes, and capabilities to conduct pharmacokinetics and pharmacodynamics analyses in clinical studies. SER-262 contains a consortium of 12 bacterial
strains derived from a manufacturing process that utilizes in vitro fermentation and does not require human donor material.
The Phase 1b clinical study was a 24-week, randomized, placebo-controlled, dose-escalation trial. The primary endpoints of the study were safety and
tolerability and a comparison of the CDI recurrence rate in the SER-262 and placebo groups. Key secondary endpoints included analysis of SER-262 bacterial
strain engraftment. Top-line clinical and microbiome results from the study are available. No drug-related SAEs were observed. No significant differences
were observed in the recurrence rates in patients administered SER-262 as compared to placebo. However, we observed a statistically significant reduction in
CDI recurrence rates in patients pretreated with vancomycin followed by SER-262, as compared to those treated with metronidazole followed by SER-262.
This observation corresponded with an increase in SER-262 microbiome engraftment in patients pretreated with vancomycin. Clinical data from both the
SER-262 and SER-287 studies suggest that vancomycin pretreatment supports robust engraftment of our microbiome therapeutic candidates.
SER-155
We are also designing SER-155, a rationally designed product candidate to prevent infections and improve GI barrier function (including the
consequences of GvHD) in patients following allo-HSCT liver transplants. This preclinical program is based on published clinical evidence from our
collaborators at Memorial Sloan Kettering Cancer Center showing that allo-HSCT patients with reduced microbiome diversity are far more likely to die due
to infection and/or lethal GvHD (Taur et al., Blood, 2014; Jenq et al, Biology of Blood and Marrow Transplantation, 2015). The selection of the patient
population will be based on preclinical data, and the assessment of our clinical development plan, regulatory path and market opportunities. We plan to
conduct studies in animal models as well as conduct further in vitro characterization of individual strains, in order to define and nominate a composition for
clinical development In November 2017, we announced that we were awarded a grant from CARB-X (Combating Antibiotic-Resistant Bacteria Accelerator)
to support continued preclinical research and early development work for SER-155. The CARB-X grant provides us with up to $2.5 million of research
funding with potential for an additional $3.1 million for manufacture and IND upon completion of milestones.
We continue to evaluate microbiome pharmacokinetic and pharmacodynamic data from the SER-262 Phase 1b study, in addition to insights gained
from research efforts with our other rationally designed Ecobiotic microbiome therapeutic candidates, in order to determine future steps in the development of
both SER-262 and SER-155.
Sales and Marketing
If SER-109 is approved in the United States and Canada, we believe it can be commercialized with a focused specialty sales force of 100 or fewer
sales representatives that will target gastrointestinal and infectious disease physicians, which are the two primary groups of physicians who treat multiply
recurrent CDI patients.
In January 2016, we entered into an agreement with Nestec Ltd., or NHS, for the development and commercialization outside of the United States and
Canada of our product candidates in development for CDI and IBD, including UC and Crohn’s disease. The agreement will support the development of our
portfolio of products for CDI and IBD in markets outside of the United States and Canada and provide financial support for our ongoing research and
development.
Manufacturing
The production of live bacterial products is highly specialized. Owing to their hardiness and environmental persistence, production of spore-forming
organisms poses unique considerations for product, personnel, and facility protection. Manufacturing activities with spores are subject to specialized
regulations. We expect that a typical commercial fermentation will yield on the order of hundreds or thousands of doses per liter depending on the product and
its composition. Additionally, because a given total dose is split between several strains, the per-strain requirements for production may be even lower. As a
result, we believe the high productivity relative to the dose level will enable production scales for both clinical and commercial supply to be modest.
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We have developed supply chains for producing and testing materials to ensure the availability of future clinical trial supplies. Our development
processes are designed to ensure that the raw materials, process technologies and analytical tests we use are scalable and transferable to a cGMP
manufacturing environment. These include the following core elements:
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•
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•
Fermentation. We are using microscale screening to optimize culture of the bacterial strains of interest in our current and foreseeable product
candidates. These screens are designed to identify the fermentation platform that is best-suited for optimization and scale-up of the strains.
Small-scale fermentation systems (0.1 L to 50 L) enable the optimization of a wide variety of culture conditions and have been demonstrated to
be scalable to larger fermentation processes and enable technology transfer to clinical and final manufacturing sites. We employ platform
fermentation processes as starting points for cGMP production processes and develop strain specific processes as required. To develop master
cell banks, working cell banks, and bulk drug substance for commercial product, we are using bacterial strains originating from a unique
research cell bank precursor, so we expect the research cell banks and final drug product should be genetically and physiologically similar.
Purification. Similar to fermentation, we believe small-scale purification operations are available for assessing large-scale cGMP
manufacturing of live cells, and to quickly assess downstream process yield, quality and robustness. For our oral products, purification is
typically less complex than for parenteral biologics such as monoclonal antibodies that must purify away very similar components from the
culturing process. Separation of viable microbes from soluble fermentation broth components is typically much simpler.
Formulation. Our Ecobiotic microbiome therapeutic candidates are combinations of live bacteria and can be administered by a number of
methods and by different routes. The primary goal in developing a formulation is to deliver live bacteria to the intended location in a condition
where they are able to replicate and correct dysbiosis. Formulation development generally uses approved excipients and preservatives, and will
include screening of liquid, solid, and suspension formulations to maximize the opportunity for extended stability with minimal cold-chain
requirements. Dosage forms for oral products may be capsules, tablets, sachets, or liquid containers.
Analytical. We are addressing quality control requirements for our Ecobiotic microbiome therapeutic candidates using proprietary
microbiological, chemical, biochemical, and molecular sequence-based testing schemes. We have available and are further developing quality
control and in-process analytical tools that can quantitatively measure the composition of spore, vegetative microbe and spore/vegetative
combinations, which we believe enable a wide variety of drug products to be manufactured. Throughout the bioprocess and formulation
development platform we use and will expand on high- throughput quantitative analytics to assess the identity, potency and purity of the final
product.
We currently have two internal manufacturing facilities; a small-scale 7,000 ft2 unit at our Kendall Square location in Cambridge, Massachusetts,
where we conduct cGMP manufacture of Ecobiotic therapeutic candidates to support drug substance and drug product for early phase and small-scale clinical
supplies, and a larger 10,000 ft2 cGMP manufacturing facility at our headquarters, with the ability to perform both drug substance and drug product
manufacturing for early and late-phase clinical development and at larger scales of operation. We may establish further manufacturing facilities that will serve
late-phase clinical and commercial supply for our product candidates. We may do this by expanding our current facilities, or by purchasing or building
additional facilities. We also use contract manufacturing and testing organizations to supplement our internal capacity.
Material Agreements
In January 2016, we entered into the Collaboration and License Agreement, or the License Agreement, with NHS, an affiliate of Nestlé Health Science
US Holdings, Inc., a significant stockholder of ours, for the development and commercialization of certain product candidates in development for the
treatment and management of CDI and IBD, including UC and Crohn’s disease. The License Agreement will support the development of our portfolio of
products for CDI and IBD in markets outside of the United States and Canada, or the Licensed Territory. We have retained full commercial rights to our entire
portfolio of product candidates with respect to the United States and Canada.
Under the License Agreement, we granted to NHS an exclusive, royalty-bearing license to develop and commercialize, in the Licensed Territory,
certain products based on our microbiome technology that are being developed for the treatment of CDI and IBD, including SER-109, SER-262, SER-287
and SER-301, or collectively, the NHS Collaboration Products. The License Agreement sets forth our and NHS’ respective obligations for development,
commercialization, regulatory and manufacturing and supply activities for the NHS Collaboration Products with respect to the licensed fields and the
Licensed Territory.
In exchange for the license, NHS made an upfront cash payment to us of $120.0 million. NHS also agreed to pay us tiered royalties, at percentages
ranging from the high single digits to high teens, of net sales of NHS Collaboration Products in the Licensed Territory. Under the License Agreement we are
eligible to receive up to $285.0 million in development milestone payments, $375.0 million in regulatory payments and up to an aggregate of $1,125.0 million
for the achievement of certain commercial milestones related to the sales of NHS Collaboration Products.
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In November 2018, we executed a letter agreement with NHS, or the Letter Agreement, modifying certain terms of the License Agreement. Under the
Letter Agreement, NHS agreed to accelerate the payment of the $20.0 million Phase 3 commencement milestone to be payable upon the commencement of
the Phase 2b study for SER-287. Further, based on the results of the Phase 2b study, the Letter Agreement modifies certain terms and conditions related to the
extent and timing of expense reimbursement associated with the ongoing SER-287 clinical trials. The Phase 2b study was initiated and the $40.0 million of
milestone payments were received in December 2018.
To date, we have received $70.0 million in development milestones under the License Agreement and the Letter Agreement.
Intellectual Property
We strive to protect the proprietary technology that is important to our business, including seeking and, if granted, maintaining patents intended to
cover our product candidates and compositions, their methods of use and processes for their manufacture and any other aspects of inventions that are
commercially important to the development of our business. We also utilize regulatory exclusivity as well as trade secrets to protect aspects of our business.
We plan to continue to expand our intellectual property estate by filing patent applications directed to compositions, methods of treatment, methods of
manufacture and methods for patient selection created or identified from our ongoing development of our product candidates. Our success will depend on our
ability to obtain and maintain patent and other proprietary protection for commercially important technology, inventions and know-how related to our
business, defend and enforce any patents that we may obtain, preserve the confidentiality of our trade secrets and operate without infringing the valid and
enforceable patents and proprietary rights of third parties. We also rely on know-how and continuing technological innovation to develop and maintain our
proprietary position and, in the future, may rely on or leverage in-licensing opportunities. We seek to obtain domestic and international patent protection, and
endeavor to promptly file patent applications for new commercially valuable inventions.
The patent positions of biopharmaceutical companies like us are generally uncertain and involve complex legal, scientific and factual questions. In
addition, the coverage claimed in a patent may be challenged in courts after issuance. Moreover, many jurisdictions permit third parties to challenge issued
patents in administrative proceedings, which may result in further narrowing or even cancellation of patent claims. We cannot predict whether the patent
applications we are currently pursuing will issue as patents in any particular jurisdiction or at all, whether the claims of any patent applications, should they
issue, will cover our product candidates, or whether the claims of any issued patents will provide sufficient protection from competitors or otherwise provide
any competitive advantage.
Because patent applications in the United States and certain other jurisdictions are maintained in secrecy for 18 months or potentially even longer, and
because publication of discoveries in the scientific or patent literature often lags behind actual discoveries and patent application filings, we cannot be certain
of the priority of inventions covered by pending patent applications. Accordingly, we may not have been the first to invent the subject matter disclosed in
some of our patent applications or the first to file patent applications covering such subject matter, and we may have to participate in interference proceedings
or derivation proceedings declared by the United States Patent and Trademark Office, or USPTO, to determine priority of invention.
Our patent portfolio includes issued U.S. patents and patent applications in various stages of prosecution, including ex-U.S. international counterparts.
We believe that issued claims will provide protection for our microbiome therapeutic candidates.
Patent term
The base term of a U.S. patent is 20 years from the filing date of the earliest-filed non-provisional, patent application from which the patent claims
priority. The term of a U.S. patent can be lengthened by patent term adjustment, which compensates the owner of the patent for administrative delays at the
USPTO. In some cases, the term of a U.S. patent is shortened by terminal disclaimer that reduces its term to that of an earlier-expiring patent.
The term of a U.S. patent may be eligible for patent term extension under the Drug Price Competition and Patent Term Restoration Act of 1984,
referred to as the Hatch-Waxman Act, to account for at least some of the time the drug is under development and regulatory review after the patent is granted.
With regard to a drug for which FDA approval is the first permitted marketing of the active ingredient, the Hatch-Waxman Act allows for extension of the
term of one U.S. patent that includes at least one claim covering the composition of matter of such an FDA-approved drug, an FDA- approved method of
treatment using the drug and/or a method of manufacturing the FDA-approved drug. The extended patent term cannot exceed the shorter of five years beyond
the non-extended expiration of the patent or fourteen years from the date of the FDA approval of the drug, and a patent cannot be extended more than once or
for more than a single product. During the period of extension, if granted, the scope of exclusivity is limited to the approved product for approved uses. Some
foreign jurisdictions, including Europe and Japan, have analogous patent term extension provisions, which allow for extension of the term of a patent that
covers a drug approved by the applicable foreign regulatory agency. In the
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future, if and when our product candidates receive FDA approval, we expect to apply, if appropriate, for patent term extension on patents covering those
product candidates, their methods of use and/or methods of manufacture.
Trade secrets
In addition to patents, we rely on trade secrets and know-how to develop and maintain our competitive position. We typically utilize trade secrets to
protect aspects of our business. We protect trade secrets and know-how by establishing confidentiality agreements and invention assignment agreements with
our employees, consultants, scientific advisors, contractors and collaborators. These agreements provide that all confidential information developed or made
known during the course of an individual or entities’ relationship with us must be kept confidential during and after the relationship. These agreements also
provide that all inventions resulting from work performed for us or relating to our business and conceived or completed during the period of employment or
assignment, as applicable, shall be our exclusive property. In addition, we take other appropriate precautions, such as physical and technological security
measures, to guard against misappropriation of our proprietary information by third parties.
Competition
The development and commercialization of new drug and biologic products is highly competitive and is characterized by rapid and substantial
technological development and product innovations. 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. We are aware of a number of large pharmaceutical and biotechnology companies, as well as smaller,
early-stage companies, that are pursuing the development of products, including microbiome therapeutics, and disease indications we are targeting. Potential
competitors also include academic institutions, government agencies and other public and private research organizations that conduct research, seek patent
protection and establish collaborative arrangements for research, development, manufacturing and commercialization.
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 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, clinical, manufacturing 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.
The key competitive factors affecting the success of the product candidates that we develop, if approved, are likely to be their efficacy, safety,
convenience, price, the level of 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, 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 microbiome therapeutic which 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 lower cost products.
Government Regulation
The FDA and other regulatory authorities at federal, state and local levels, as well as in foreign countries, extensively regulate, among other things, the
research, development, testing, manufacture, quality control, import, export, safety, effectiveness, labeling, packaging, storage, distribution, record keeping,
approval, advertising, promotion, marketing, post-approval monitoring and post-approval reporting of drugs and biologics such as those we are developing.
We, along with our contract manufacturers, will be required to navigate the various preclinical, clinical and commercial approval requirements of the
governing regulatory agencies of the countries in which we wish to conduct studies or seek approval for our product candidates. The process of obtaining
regulatory approvals and ensuring subsequent compliance with appropriate federal, state, local and foreign statutes and regulations requires the expenditure of
substantial time and financial resources.
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In the United States, the FDA regulates drug and biologic products under the Federal Food, Drug and Cosmetic Act, its implementing regulations and
other laws, including, in the case of biologics, the Public Health Service Act. Our product candidates are subject to regulation by the FDA as biologics.
Biologics require the submission of a biologics license application, or BLA, and approval by the FDA before being marketed in the United States. None of
our product candidates has been approved by the FDA for marketing in the United States, and we currently have no BLAs pending. If we fail to comply with
applicable FDA or other requirements at any time during product development, clinical testing, the approval process or after approval, we may become
subject to administrative or judicial sanctions. These sanctions could include the FDA’s refusal to approve pending applications, suspension or revocation of
approved applications, warning letters, product recalls, product seizures, total or partial suspensions of manufacturing or distribution, injunctions, fines, civil
penalties or criminal prosecution. Any FDA enforcement action could have a material adverse effect on us.
The process required by the FDA before our biologic product candidates may be marketed in the United States generally involves the following:
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completion of preclinical laboratory tests and animal studies performed in accordance with the FDA’s good laboratory practice, or GLP,
regulations;
submission to the FDA of an IND, which must become effective before clinical trials in the United States may begin;
performance of adequate and well-controlled human clinical trials to establish the safety and efficacy of the product candidate for each
proposed indication, conducted in accordance with the FDA’s good clinical practice, or GCP, regulations;
submission to the FDA of a BLA;
satisfactory completion of an FDA inspection of the manufacturing facility or facilities at which the product is produced to assess compliance
with cGMP regulations; and
FDA review and approval of the BLA prior to any commercial marketing, sale or shipment of the product.
The testing and approval process requires substantial time, effort and financial resources, and we cannot be certain that any approvals for our product
candidates will be granted on a timely basis, if at all.
Preclinical and Clinical Trials
Once a product candidate is identified for development, it enters the preclinical testing stage. Preclinical studies include laboratory evaluations of drug
chemistry, formulation and stability, as well as studies to evaluate toxicity in animals, which must be conducted in accordance with GLP requirements. The
results of the preclinical studies, together with manufacturing information and analytical data, are submitted to the FDA as part of an IND. The IND
automatically becomes effective 30 days after receipt by the FDA, unless the FDA, within the 30-day time period, raises concerns or questions about the
conduct of the clinical trial, including concerns that human research subjects will be exposed to unreasonable health risks. In such a case, the IND sponsor
and the FDA must resolve any outstanding concerns before the clinical trial can begin. Submission of an IND may result in the FDA not allowing clinical
trials to commence or not allowing clinical trials to commence on the terms originally specified in the IND. A separate submission to an existing IND must
also be made for each successive clinical trial conducted during product development, and the FDA must grant permission, either explicitly or implicitly by
not objecting, before each clinical trial can begin.
Clinical trials involve the administration of the product candidate to human subjects under the supervision of qualified investigators. Clinical trials are
conducted under protocols detailing, among other things, the objectives of the clinical trial and the parameters and criteria to be used in monitoring safety and
evaluating effectiveness. Each protocol must be submitted to the FDA as part of the IND. An independent institutional review board, or IRB, for each
investigator site proposing to participate in a clinical trial must also review and approve the clinical trial before it can begin at that site, and the IRB must
monitor the clinical trial until it is completed. The FDA, the IRB, or the sponsor may suspend or discontinue a clinical trial at any time on various grounds,
including a finding that the subjects are being exposed to an unacceptable health risk. Clinical testing also must satisfy extensive GCP requirements, including
requirements for informed consent.
For purposes of BLA approval, clinical trials are typically conducted in three sequential phases, which may overlap or be combined.
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Phase 1 — Phase 1 clinical trials involve initial introduction of the investigational product into healthy human subjects or patients with the
target disease or condition. These studies are typically designed to test the safety, dosage tolerance, absorption, metabolism and distribution of
the investigational product in humans, the side effects associated with increasing doses, and, if possible, to gain early evidence on effectiveness.
Phase 2 — Phase 2 clinical trials typically involve administration of the investigational product to a limited patient population with a specified
disease or condition to evaluate the preliminary efficacy, optimal dosages and dosing schedule and to identify possible adverse side effects and
safety risks.
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Phase 3 — Phase 3 clinical trials typically involve administration of the investigational product to an expanded patient population to further
evaluate dosage, to provide statistically significant evidence of clinical efficacy and to further test for safety, generally at multiple
geographically dispersed clinical trial sites. These clinical trials are intended to establish the overall risk/benefit ratio of the investigational
product and to provide an adequate basis for product approval.
In some cases, the FDA may condition approval of a BLA on the sponsor’s agreement to conduct additional clinical trials to further assess the
biologic’s safety and effectiveness after BLA approval. Such post-approval clinical trials are typically referred to as Phase 4 clinical trials.
Although most clinical research performed in the United States in support of a BLA must be authorized in advance by the FDA, under the IND
regulations and procedures described above, there are certain circumstances under which clinical trials can be conducted without submission of an IND. For
example, a sponsor who wishes to conduct a clinical trial outside the United States may, but need not, obtain FDA authorization to conduct the clinical trial
under an IND. Similarly, the FDA may exercise enforcement discretion to permit sponsors to conduct certain types of clinical investigations without an IND.
Pursuant to the FDA guidance document “Enforcement Policy Regarding Investigational New Drug Requirements for Use of Fecal Microbiota for
Transplantation to Treat Clostridium difficile Infection Not Responsive to Standard Therapies” (July 2013), the FDA announced its intention to exercise
enforcement discretion and not apply the IND requirements for the use of FMT to treat CDI not responsive to standard therapies, provided that the treating
physician obtains adequate informed consent from the patient or his or her legally authorized representative for the use of FMT products. In March 2014, the
FDA issued a draft guidance document to clarify its Enforcement Policy in the July 2013 guidance. In the March 2014 draft guidance, the FDA noted that
since the issuance of its Enforcement Policy in July 2013, it has continued to review its policies in this area and it intends to continue to exercise enforcement
discretion in more narrow circumstances than previously identified. Specifically, the March 2014 draft guidance indicated the FDA’s intent to limit
enforcement discretion in circumstances where the licensed health care professional treating the patient obtains adequate informed consent from the patient or
his or her legally authorized representative for the use of FMT products; the FMT product is obtained from a donor known to either the patient or the licensed
health care provider; and the stool donor and stool are qualified by screening and testing performed under the discretion of the licensed health care provider
for the purposes of providing the FMT product. Following receipt of public comments on the March 2014 draft guidance proposing to modify the July 2013
Enforcement Policy, the FDA issued a new draft guidance in March 2016 announcing its intention to further modify its approach to enforcement discretion
for INDs for the use of FMT products. In this draft guidance, the FDA indicated that it intends to continue to exercise enforcement discretion, provided that
the licensed health care professional treating the patient obtains adequate informed consent for use of the FMT product; the FMT product is not obtained from
a stool bank; and the stool donor and stool are qualified by screening and testing performed under the direction of the licensed health care provider for
purposes of providing the FMT product to treat his or her patient. The FDA further clarified in the March 2016 that, when finalized, the policy would
supersede the final Enforcement Policy espoused in the July 2013 Guidance. However, to date, the FDA has not finalized the March 2016 draft
guidance. The FDA provided confirmation to us that it intended to exercise enforcement discretion with respect to our Phase 1b/2 clinical study of SER-109,
and accordingly, we did not conduct this trial under an IND. However, we have conducted and will continue to conduct all subsequent clinical studies of SER-
109 under an IND.
Concurrent with clinical trials, companies usually complete additional animal studies and must also develop additional information about the
chemistry and physical characteristics of the biologic and finalize a process for manufacturing the biologic in commercial quantities in accordance with
cGMP requirements. The manufacturing process must be capable of consistently producing quality batches of the product candidate and manufacturers must
develop, among other things, methods for testing the identity, strength, quality and purity of the final biological product. Additionally, appropriate packaging
must be selected and tested, and stability studies must be conducted to demonstrate that the product candidate does not undergo unacceptable deterioration
over its shelf life.
BLA Submission and FDA Review
The results of preclinical studies and clinical trials, together with other detailed information, including extensive manufacturing information and
information on the composition of the biologic, are submitted to the FDA in the form of a BLA requesting approval to market the biologic for one or more
specified indications. The submission of a BLA requires payment of a substantial user fee unless a waiver is granted. However, an orphan-designated product,
such as our SER-109, is not subject to an application user fee unless the human drug application includes an indication for other than a rare disease or
condition. Each BLA submitted to the FDA is reviewed for administrative completeness and reviewability within 60 days of the FDA’s receipt of the
application. If the BLA is found to be complete, the FDA will file the BLA, triggering a full review of the application. The FDA may refuse to file any BLA
that it deems incomplete or not properly reviewable at the time of submission.
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Once a BLA has been accepted for filing, by law the FDA has 180 days to review the application and respond to the applicant. However, the review
process is often significantly extended by FDA requests for additional information or clarification. Under the Prescription Drug User Fee Act, the FDA has a
goal of reviewing BLAs within ten months of the 60-day filing date for standard review or six months for priority review, but the overall timeframe is often
extended by FDA requests for additional information or clarification. The FDA reviews a BLA to determine, among other things, whether the biological
product is safe, pure and potent and whether the facility or facilities in which it is manufactured meet standards designed to assure the product’s continued
safety, purity and potency. The FDA may refer the application to an advisory committee for review, evaluation and recommendation as to whether the
application should be approved. The FDA is not bound by the recommendation of an advisory committee, but it generally follows such recommendations.
Before approving a BLA, the FDA will inspect the facility or the facilities at which the biologic product is manufactured and will not approve the product
unless cGMP compliance is satisfactory. The FDA may also inspect the sites at which the clinical trials were conducted to assess their compliance with GCP
requirements and will not approve the biologic unless compliance with such requirements is satisfactory.
The FDA may deny approval of a BLA if the applicable statutory and regulatory criteria are not satisfied, or it may require additional preclinical or
clinical data. Even if such data are submitted, the FDA may ultimately decide that the BLA does not satisfy the criteria for approval. Data from clinical trials
are not always conclusive and the FDA may interpret data differently than sponsors. Once the FDA approves a BLA, such approval defines the indicated uses
for which the biologic may be marketed. The FDA may also require implementation of a Risk Evaluation and Mitigation Strategy, or REMS, which can
include a medication guide, communication plan, or elements to assure safe use, such as restricted distribution methods, physician training, patient registries
and other risk minimization tools. The FDA also may condition approval on, among other things, changes to proposed labeling claims or the development of
adequate controls and specifications. Once approved, the FDA may withdraw the product approval if compliance with pre- and post-marketing regulatory
standards is not maintained or if problems occur after the product reaches the market. The FDA may require one or more Phase 4 post-market studies and
surveillance to further assess and monitor the product’s safety and effectiveness after commercialization and may limit further marketing based on the results
of these post-marketing studies.
The biologic testing and approval processes encompasses significant risk, and requires substantial time, effort and financial resources, and each may
take several years to complete. The FDA may not grant approval on a timely basis, or at all. Even if we believe a clinical trial has demonstrated safety and
efficacy of one of our product candidates for the treatment of a disease or condition, the results may not be satisfactory to the FDA. Preclinical and clinical
data may be interpreted by the FDA in different ways, which could delay, limit or prevent regulatory approval. We may encounter difficulties or unanticipated
costs in our efforts to secure necessary governmental approvals which could delay or preclude us from marketing our product candidates. The FDA may limit
the indications for use or place other conditions on any approvals that could restrict the commercial application of our products. After approval, certain
changes to the approved biologic, such as adding new indications, manufacturing changes or additional labeling claims, are subject to further FDA review and
approval. Depending on the nature of the change proposed, a BLA supplement must be filed and approved before the change may be implemented. For many
proposed post-approval changes to a BLA, the FDA has up to 180 days to review the application. As with new BLAs, the review process is often significantly
extended by the FDA requests for additional information or clarification.
Expedited Development and Review Programs
The FDA maintains several programs intended to facilitate and expedite development and review of new drugs and biologics to address unmet medical
needs in the treatment of serious or life- threatening diseases or conditions. These programs include Fast Track designation, Breakthrough Therapy
designation, Priority Review designation and Accelerated Approval, and the purpose of these programs is to provide important new drugs to patients earlier
than under standard FDA review procedures.
A new drug or biologic is eligible for fast track designation if it is intended to treat a serious or life- threatening disease or condition and demonstrates
the potential to address unmet medical needs for such disease or condition. Fast Track designation provides increased opportunities for sponsor meetings with
the FDA during preclinical and clinical development, in addition to the potential for rolling review once a marketing application is filed, meaning that the
agency may review portions of the marketing application before the sponsor submits the complete application, as well as Priority Review, discussed below. In
addition, a new drug or biologic may be eligible for breakthrough therapy designation if it is intended 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. Breakthrough Therapy designation provides all the features
of Fast Track designation in addition to intensive guidance on an efficient drug development program beginning as early as Phase 1, and FDA organizational
commitment to expedited development, including involvement of senior managers and experienced review staff in a cross-disciplinary review, where
appropriate.
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Any product submitted to the FDA for approval, including a product with Fast Track or Breakthrough Therapy designation, may also be eligible for
additional FDA programs intended to expedite the review process, including Priority Review designation and accelerated approval. A product is eligible for
Priority Review if it has the potential to provide a significant improvement in safety or effectiveness in the treatment, diagnosis or prevention of a serious
disease or condition. Additionally, products are eligible for accelerated approval if they can be shown to have an effect on a surrogate endpoint that is
reasonably likely to predict clinical benefit, or an effect on a clinical endpoint that can be measured earlier than an effect on irreversible morbidity or
mortality which is reasonably likely to predict an effect on 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. Accelerated approval is usually contingent on a sponsor’s agreement to
conduct additional post-approval studies to verify and describe the product’s clinical benefit. In addition, unless otherwise informed by the FDA, the FDA
currently requires, as a condition for accelerated approval that all advertising and promotional materials that are intended for dissemination or publication
within 120 days following marketing approval be submitted to the agency for review during the pre-approval review period, and that after 120 days following
marketing approval, all advertising and promotional materials must be submitted at least 30 days prior to the intended time of initial dissemination or
publication.
Fast Track designation, Breakthrough Therapy designation, Priority Review designation and Accelerated Approval do not change the standards for
approval but may expedite the development or review process. We have received Breakthrough Therapy designation for SER-109, and we may apply for one
or more of the FDA’s expedited programs for our other product candidates. The FDA may find that our product candidates no longer satisfy the criteria for
such programs for which we have already obtained the relevant designation or approval, such programs may fail to result in expedited development or review
timelines, or the FDA may ultimately refuse to approve our product candidates despite their inclusion in any expedited programs. In addition, if the
Breakthrough Therapy designation for SER-109 is no longer supported by subsequent data, FDA may rescind the designation.
Post-Approval Requirements
Approved biologics that are manufactured or distributed in the United States are subject to pervasive and continuing regulation by the FDA, including,
among other things, requirements relating to recordkeeping, periodic reporting, product distribution, advertising and promotion and reporting of adverse
experiences with the product. There also are continuing, annual user fee requirements for products marketed pursuant to approved applications.
Any biologics manufactured or distributed by us or our contract manufactures pursuant to FDA approvals would be subject to continuing regulation by
the FDA, including recordkeeping requirements and reporting of adverse experiences associated with the product. Manufacturers and their subcontractors 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 ongoing regulatory requirements, including cGMP, which impose certain procedural and documentation requirements upon
us and our contract manufacturers. Failure to comply with statutory and regulatory requirements can subject a manufacturer to possible legal or regulatory
action, such as warning letters, suspension of manufacturing, product seizures, injunctions, civil penalties or criminal prosecution. We cannot be certain that
we or our present or future third-party manufacturers or suppliers will be able to comply with the cGMP regulations and other ongoing FDA regulatory
requirements. If we or our present or future third-party manufacturers or suppliers are not able to comply with these requirements, the FDA may halt our
clinical trials, require us to recall a product from distribution or withdraw approval of the BLA for that product.
Later discovery of previously unknown problems with a product, including adverse events of unanticipated severity or frequency, or with
manufacturing processes, or failure to comply with regulatory requirements, may result in revisions to the approved labeling to add new safety information,
requirements for post-market studies or clinical trials to assess new safety risks, or imposition of distribution or other restrictions under a REMS. Other
potential consequences include, among other things:
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restrictions on the marketing or manufacturing of the product, complete withdrawal of the product from the market or product recalls;
fines, warning letters or holds on post-approval clinical trials;
refusal of the FDA to approve applications or supplements to approved applications, or suspension or revocation of product approvals;
product seizure or detention, or refusal to permit the import or export of products; or
injunctions or the imposition of civil or criminal penalties.
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The FDA closely regulates the post-approval marketing and promotion of biologics, including standards and regulations for direct-to-consumer
advertising, off-label promotion, industry-sponsored scientific and educational activities, and promotional activities involving the internet and social media. A
company can make only those claims relating to safety and efficacy that are approved by the FDA. Physicians may prescribe legally available biologics for
uses that are not described in the product’s labeling and that differ from those tested by us and approved by the FDA. The FDA does not regulate the behavior
of physicians in their choice of treatments. The FDA does, however, impose stringent restrictions on manufacturers’ communications regarding off-label use.
Failure to comply with these requirements can result in adverse publicity, warning letters, corrective advertising and potential civil and criminal penalties.
Biosimilars and Regulatory Exclusivity
We believe that any of our product candidates approved under a BLA should qualify for a 12-year period of exclusivity against biosimilar competition
currently permitted by the Biologics Price Competition and Innovation Act, or BPCIA. Specifically, as part of the Patient Protection and Affordable Care Act
enacted in 2010, as amended by the Health Care and Education Affordability Reconciliation Act, collectively the ACA, the BPCIA established an abbreviated
pathway for the approval of biosimilar and interchangeable biological products. The abbreviated regulatory pathway provides legal authority for the FDA to
review and approve biosimilar biologics based on their similarity to an existing brand product, referred to as a reference product, including the possible
designation of a biosimilar as interchangeable with a brand product. Under the BPCIA 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. Moreover, the extent to which a biosimilar, once approved, will be
substituted for any one of our reference products in a way that is similar to traditional generic substitution for non-biological drug products is not yet clear,
and will depend on a number of marketplace and regulatory factors that are still developing. The BPCIA is complex and continues to be interpreted and
implemented by the FDA. As a result, its ultimate impact, implementation and meaning is subject to uncertainty. While it is uncertain when any such
processes may be fully adopted by the FDA, any such processes that operate to limit the scope or length of exclusivity afforded by the BPCIA could have a
material adverse effect on the future commercial prospects for our biological products. In addition, the period of exclusivity provided by the BPCIA only
operates against third parties seeking approval via the abbreviated pathway but would not prevent third parties from pursuing approval via the traditional
approval pathway. In addition, foreign regulatory authorities may also provide for exclusivity periods for approved biological products. For example,
biological products in the EU may be eligible for at least a ten-year period of exclusivity.
Orphan Drug Designation
Under the Orphan Drug Act, the FDA may grant orphan designation to a drug or biologic intended to treat a rare disease or condition, which is a
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 making the product available in the United States for the disease or condition will be recovered
from sales of the product. Orphan designation must be requested before submitting a BLA. Orphan designation does not convey any advantage in or shorten
the duration of the regulatory review and approval process, though companies developing orphan products are eligible for certain incentives, including tax
credits for qualified clinical testing and waiver of application fees.
If a product that has orphan designation subsequently receives the first FDA approval for the disease or condition for which it has such designation, the
product is entitled to a seven-year period of marketing exclusivity during which the FDA may not approve any other applications to market the same
therapeutic agent for the same indication, except in limited circumstances, such as a subsequent product’s showing of clinical superiority over the product
with orphan exclusivity or where the original applicant cannot produce sufficient quantities of product. Competitors, however, may receive approval of
different therapeutic agents for the indication for which the orphan product has exclusivity or obtain approval for the same therapeutic agent for a different
indication than that for which the orphan product has exclusivity. Orphan product exclusivity could block the approval of one of our products for seven years
if a competitor obtains approval for the same therapeutic agent for the same indication before we do, unless we are able to demonstrate that our product is
clinically superior. Further, if a designated orphan product receives marketing approval for an indication broader than the rare disease or condition for which
it received orphan designation, it may not be entitled to orphan exclusivity.
In August 2015, the FDA granted orphan drug designation to SER-109 for the treatment of recurrent CDI. In December 2017, the FDA granted
Orphan Drug Designation to SER-287 for treatment of UC in pediatric patients.
We may seek additional orphan designation for one or more of our product candidates, but the FDA may disagree with our analysis of the prevalence
of a disease or condition or other criteria for designation and refuse to grant orphan status. We cannot guarantee that we will obtain designation or approval
for any product candidate, or that we will be able to secure orphan product exclusivity if we do obtain approval.
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Government Regulation Outside of the United States
To market any product outside of the United States, we would need to comply with numerous and varying regulatory requirements of other countries
regarding safety and efficacy and governing, among other things, clinical trials, marketing authorization, manufacturing, commercial sales and distribution of
our products.
For instance, in the EEA (comprised of the 28 EU Member States plus Iceland, Liechtenstein and Norway) medicinal products must be authorized for
marketing by using either the centralized authorization procedure or national authorization procedures.
Centralized procedure—Under the centralized procedure, following the opining of the EMA’s Committee for Medicinal Products for Human Use, or,
CHMP, the European Commission issues a single marketing authorization valid across the EEA. The centralized procedure is compulsory for human
medicines derived from biotechnology processes, advanced therapy medicinal products (such as gene therapy, somatic cell therapy and tissue engineered
products), products that contain a new active substance indicated for the treatment of certain diseases, such as HIV/AIDS, cancer, neurodegenerative
disorders, diabetes, autoimmune diseases and other immune dysfunctions, viral diseases, and officially designated orphan medicines. For medicines that do
not fall within these categories, an applicant has the option of submitting an application for a centralized marketing authorization to the EMA, as long as the
medicine concerned contains a new active substance not yet authorized in the EEA, is a significant therapeutic, scientific or technical innovation, or if its
authorization would be in the interest of public health in the EEA. Under the centralized procedure the maximum timeframe for the evaluation of an MAA by
the EMA 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 assessment might be granted by the CHMP in exceptional cases, when a medicinal product is expected to be of a major public health
interest, particularly from the point of view of therapeutic innovation. The timeframe for the evaluation of an MAA under the accelerated assessment
procedure is 150 days, excluding clock stops.
National authorization procedures—There are also two other possible routes to authorize medicinal products in several countries, which are available
for products that fall outside the scope of the centralized procedure:
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Decentralized procedure. Using the decentralized procedure, an applicant may apply for simultaneous authorization in more than one EU
country of medicinal products that have not yet been authorized in any EU country and that do not fall within the mandatory scope of the
centralized procedure.
Mutual recognition procedure. In the mutual recognition procedure, a medicine is first authorized in one EU Member State, in accordance with
the national procedures of that country. Following this, further marketing authorizations can be sought from other EU countries in a procedure
whereby the countries concerned recognize the validity of the original, national marketing authorization.
In the EEA, new products authorized for marketing (i.e., reference products) qualify for eight years of data exclusivity and an additional two years of
market exclusivity upon marketing authorization. The data exclusivity period prevents generic or biosimilar applicants from relying on the preclinical and
clinical trial data contained in the dossier of the reference product when applying for a generic or biosimilar marketing authorization in the EU during a period
of eight years from the date on which the reference product was first authorized in the EU. The market exclusivity period prevents a successful generic or
biosimilar applicant from commercializing its product in the EU until ten years have elapsed from the initial authorization of the reference product in the EU.
The ten-year market exclusivity period can be extended to a maximum of eleven years if, during the first eight years of those ten years, the marketing
authorization holder obtains an authorization for one or more new therapeutic indications which, during the scientific evaluation prior to their authorization,
are held to bring a significant clinical benefit in comparison with existing therapies.
The criteria for designating an “orphan medicinal product” in the EEA are similar in principle to those in the United States. In the EEA 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 EU when the application is made, or (b) the product, without the benefits
derived from orphan status, would not generate sufficient return in the EU to justify investment; and (3) there exists no satisfactory method of diagnosis,
prevention or treatment of such condition authorized for marketing in the EU, or if such a method exists, the product will be of significant benefit to those
affected by the condition. 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. During this ten-year orphan market exclusivity
period, 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 EU for pediatric studies. The ten-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 (i) the second applicant can establish that its product, although similar, is safer, more effective or otherwise
clinically superior; (ii) the applicant consents to a second orphan medicinal product application; or (iii) the applicant cannot supply enough orphan medicinal
product.
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Other Healthcare Laws
In addition to FDA restrictions on marketing of pharmaceutical and biological products, other healthcare regulatory laws restrict business practices in
the biotechnology industry, which include, but are not limited to, anti-kickback, false claims, physician payment and pricing transparency and data privacy
and security laws. The federal Anti-Kickback Statute prohibits the offer, receipt, or payment of remuneration in exchange for or to induce the referral of
patients or the use of products or services that would be paid for in whole or part by Medicare, Medicaid or other federal healthcare programs. Remuneration
has been broadly interpreted to include anything of value, including cash, improper discounts and free or reduced-price items and services. The government
has enforced the Anti-Kickback Statute to reach large settlements with healthcare companies based on sham research or consulting and other financial
arrangements with physicians. Further, 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. In addition, the government may assert that a claim including items or services resulting from a violation of the Anti-Kickback Statute
constitutes a false or fraudulent claim for purposes of the False Claims Act (discussed below). Many states have similar laws that apply to their state
healthcare programs as well as private payors.
The federal false claims and civil monetary penalties laws, including the False Claims Act, or FCA, impose liability on persons who, among other
things, knowingly present or cause to be presented, a false, fictitious or fraudulent claim for payment to, or approval by, the federal government, knowingly
make, use, or cause to be made or used a false record or statement material to a false or fraudulent claim to the federal government, or knowingly make a false
statement to avoid, decrease or conceal an obligation to pay money to the U.S. federal government. The FCA has been used to prosecute persons submitting
claims for payment that are inaccurate or fraudulent, that are for services not provided as claimed, or for services that are not medically necessary. Actions
under the FCA may be brought by the Attorney General or as a qui tam action by a private individual in the name of the government. Violations of the FCA
can result in significant monetary penalties and treble damages. The federal government is using the FCA, and the accompanying threat of significant liability,
in its investigation and prosecution of pharmaceutical and biotechnology companies throughout the country, for example, in connection with the promotion of
products for unapproved uses and other sales and marketing practices. The government has obtained multi-million and multi–billion-dollar settlements under
the FCA in addition to individual criminal convictions under applicable criminal statutes. In addition, companies have been forced to implement extensive
corrective action plans and have often become subject to consent decrees or corporate integrity agreements, severely restricting the manner in which they
conduct their business. Given the significant size of actual and potential settlements, it is expected that the government 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, created additional federal criminal statutes that prohibit, 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. Similar to the federal Anti-Kickback Statute, 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.
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, which impose specified requirements relating to the privacy, security and transmission of individually identifiable health information. Among
other things, HITECH makes HIPAA’s privacy and security standards directly applicable to “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. In addition, 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.
In addition, there has been a recent trend of increased federal and state regulation of payments made to physicians and other healthcare providers. The
ACA, among other things, imposed new reporting requirements through the Physician Payments Sunshine Act on certain manufacturers of drugs covered by a
federal healthcare program for payments made by them to physicians and teaching hospitals, as well as ownership and investment interests held by
physicians, certain other healthcare professionals and their immediate family members. Failure to submit required information may result in civil monetary
penalties for all payments, transfers of value or ownership or investment interests that are not timely, accurately and completely reported in an annual
submission. Manufacturers must submit reports by the 90th day of each calendar year. Certain states also mandate implementation of compliance programs,
impose restrictions on drug manufacturer marketing practices and/or require the tracking and reporting of gifts, compensation and other remuneration to
physicians, and pricing information and marketing expenditures.
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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.
The shifting commercial compliance environment and the need to build and maintain robust systems to comply with different compliance and/or
reporting requirements in multiple jurisdictions increase the possibility that a healthcare company may violate one or more of the requirements. If our
operations are found to be in violation of any of such laws or any other governmental regulations that apply to us, we may be subject to penalties, including,
without limitation, civil and criminal penalties, damages, fines, the curtailment or restructuring of our operations, exclusion from participation in federal and
state healthcare programs, reporting obligations and oversight if we become subject to a corporate integrity agreement or other agreement, and imprisonment,
any of which could adversely affect our ability to operate our business and our financial results.
Coverage and Reimbursement
Significant uncertainty exists as to the coverage and reimbursement status of any product candidates for which we obtain regulatory approval. In both
domestic and foreign markets, sales and reimbursement of any approved products will depend, in part, on the extent to which third-party payors, such as
government health programs, commercial insurance and managed healthcare organizations provide coverage, and establish adequate reimbursement levels
for, such products. Third-party payors are increasingly challenging the prices charged for medical products and services and imposing controls to manage
costs. Third-party payors may limit, or hinder, 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. Additionally, we may need to conduct expensive pharmacoeconomic studies in order to demonstrate
the cost-effectiveness of our products, as well as provide rebates and discounts which may impact the net selling price of our products. If third-party payors
do not consider our products to be cost-effective compared to other therapies, the payors may not cover our products as a benefit under their plans or, if they
do, the level of reimbursement may not be sufficient to allow us to sell our products on a profitable basis.
The containment of healthcare costs also has become a priority of federal and state governments and the prices of pharmaceutical and biological
products have been a focus in this effort. Governments have shown significant interest in implementing cost-containment programs, including price controls,
restrictions on reimbursement and requirements for substitution of generic products. Adoption of price controls and cost-containment measures, and adoption
of more restrictive policies in jurisdictions with existing controls and measures, could further limit our net revenue and results.
Outside the United States, ensuring adequate coverage and payment for our products will face challenges. Pricing of prescription pharmaceuticals is
subject to governmental control in many countries. Pricing negotiations with governmental authorities can extend well beyond the receipt of regulatory
marketing approval for a product and may require us to conduct a clinical trial that compares the cost effectiveness of our product candidates or products to
other available therapies. Conducting such a clinical trial could be expensive and result in delays in our commercialization efforts. Third-party payors are
challenging the prices charged for medical products and services, and many third-party payors limit reimbursement for newly approved healthcare products.
Recent budgetary pressures in many countries are also causing governments to consider or implement various cost-containment measures, such as price
freezes, increased price cuts and rebates. If budget pressures continue, governments may implement additional cost-containment measures. Cost-control
initiatives could decrease the price we might establish for products that we may develop or sell, which would result in lower product revenues or royalties
payable to us. There can be no assurance that any country that has price controls or reimbursement limitations for pharmaceutical products will allow
favorable reimbursement and pricing arrangements for any of our products.
Healthcare Reform
In the United States, there have been a number of federal and state proposals during the last few years regarding the pricing of pharmaceutical and
biological products, government control and other changes to the healthcare system. It is uncertain what legislative proposals will be adopted or what actions
federal, state or private payors for medical goods and services may take in response to any healthcare reform proposals or legislation. We cannot predict the
effect medical or healthcare reforms may have on our business, and no assurance can be given that any such reforms will not have a material adverse effect.
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By way of example, in March 2010, the ACA was signed into law, which, among other things, includes changes to the coverage and payment for
pharmaceutical and biological products under government health care programs. Among other things, the ACA:
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expanded manufacturers’ rebate liability under the Medicaid Drug Rebate Program by increasing the minimum rebate for both branded and
generic drugs and revising the definition of ‘‘average manufacturer price,’’ or AMP, for calculating and reporting Medicaid drug rebates on
outpatient prescription drug prices;
extended Medicaid drug rebates, previously due only on fee-for-service utilization, to Medicaid managed care utilization, and created an
alternate rebate formula for new formulations of certain existing products that is intended to increase the amount of rebates due on those drugs;
expanded the types of entities eligible for the 340B drug discount program that mandates discounts to certain hospitals, community centers and
other qualifying providers. With the exception of children’s hospitals, these newly eligible entities will not be eligible to receive discounted
340B pricing on orphan drugs. In addition, because 340B pricing is determined based on AMP and Medicaid drug rebate data, the revisions to
the Medicaid rebate formula and AMP definition described above could cause the required 340B discounts to increase; and
established the Medicare Part D coverage gap discount program by requiring manufacturers to provide a 70% point-of-sale-discount off the
negotiated price of applicable brand drugs to eligible beneficiaries during their coverage gap period as a condition for the manufacturers’
outpatient drugs to be covered under Medicare Part D.
There have been judicial and Congressional challenges to certain aspects of the ACA, as well as efforts to repeal or replace certain aspects of the ACA.
For example, the Tax Cuts and Jobs Act was enacted, which, among other things, removes the penalties for not complying with the ACA’s 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 Cuts and Jobs Act, the remaining provisions of the ACA are
invalid as well. While the current Presidential administration and the Centers for Medicare & Medicaid Services, or CMS, have both stated that the ruling will
have no immediate effect, it is unclear how this decision, subsequent appeals, if any, and other efforts to repeal and replace the ACA will impact the ACA and
our business. Similarly, we expect there will be additional challenges and amendments to the ACA in the future, particularly in light of the current
Presidential administration and U.S. Congress.
Other legislative changes have been proposed and adopted in the United States since the ACA was enacted. In For example, the Budget Control Act of
2011, enacted in August 2011, among other things, included reductions of Medicare payments to providers of 2% per fiscal year, which went into effect in
April 2013 and, due to subsequent legislative amendments, will remain in effect through 2027 unless additional Congressional action is taken. In January
2013, the American Taxpayer Relief Act of 2012 was signed into law, which, among other things, further reduced Medicare payments to several types of
providers, including hospitals, and increased the statute of limitations period for the government to recover overpayments to providers from three to five
years. More recently, there has been heightened governmental scrutiny over the manner in which manufacturers set prices for their marketed products, which
have 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 for
pharmaceutical and biological products. Individual states in the United States have also become increasingly active in passing legislation and implementing
regulations designed to control pharmaceutical product pricing, including price or patient reimbursement constraints, discounts, restrictions on certain product
access and marketing cost disclosure and transparency measures, and, in some cases, designed to encourage importation from other countries and bulk
purchasing. Adoption of other new legislation at the federal or state level could further limit reimbursement for pharmaceuticals, including our product
candidates if approved.
As of December 31, 2018, we had 145 full-time permanent employees. Twenty-three employees work in administration and operations and 122 work
in research and development.
Employees
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Our Corporate Information
We were incorporated in the State of Delaware in 2010 under the name Newco LS21, Inc. In October 2011, we changed our name to Seres Health,
Inc., and in May 2015, we changed our name to Seres Therapeutics, Inc. Our principal executive offices are located at 200 Sidney Street, Cambridge,
Massachusetts 02139 and our telephone number is (617) 945-9626. Our website address is www.serestherapeutics.com. The information contained in, or
accessible through, our website does not constitute a part of this annual report on Form 10-K.
We are subject to the informational requirements of the Securities Exchange Act of 1934, as amended, or the Exchange Act, and, accordingly, file
reports, proxy statements and other information with the Securities and Exchange Commission. The Securities and Exchange Commission maintains a web
site (http://www.sec.gov) that contains material regarding issuers that file electronically, such as ourselves, with the Securities and Exchange Commission.
We make available free of charge on our website our Annual Reports on Form 10-K, Quarterly Reports on Form 10-Q, Current Reports on Form 8-K
and amendments to those reports filed or furnished pursuant to Section 13(a) or 15(d) of the Exchange Act, as soon as reasonably practicable after we
electronically file such material with, or furnish it to, the Securities and Exchange Commission.
Item 1A. Risk Factors
Our business faces significant risks and uncertainties. Accordingly, in evaluating our business, you should carefully consider the risk factors discussed
below, as well as the other information in this Annual Report on Form 10-K, including our consolidated financial statements and the related notes and
“Management’s Discussion and Analysis of Results of Operations and Financial Condition.” The occurrence of any of the events or developments described
below or elsewhere in this report could harm our business, financial condition, results of operations or growth prospects.
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. As a result, there is substantial doubt about our ability to continue as a going concern.
Since inception, we have incurred significant operating losses. Our net loss was $98.9 million for the year ended December 31, 2018, $89.4 million for
the year ended December 31, 2017, and $91.6 million for the year ended December 31, 2016. As of December 31, 2018, we had an accumulated deficit of
$389.4 million. To date, we have financed our operations through the initial public offering of our common stock, private placements of our preferred stock,
milestone payments under the licensing agreement with Nestec, Ltd., or NHS, and loan financing. We have devoted substantially all of our financial resources
and efforts to developing our microbiome therapeutics platform, identifying potential product candidates and conducting preclinical studies and clinical trials.
We have not completed development of any of our product candidates, which we call Ecobiotic microbiome therapeutics, or other drugs or biologics. We
expect to continue to incur significant expenses and operating losses for the foreseeable future. We anticipate that our expenses may increase substantially as
we:
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continue the clinical development of SER-109, our lead product candidate, in the Phase 3 clinical study;
continue the clinical development of SER-287 for the treatment of UC in adults and children and potential other studies of IBD;
continue the clinical development of SER-401 in a Phase 1b clinical trial in patients with metastatic melanoma;
conduct research and continue preclinical development of additional Ecobiotic microbiome therapeutic candidates, including SER-301;
make strategic investments in manufacturing capabilities;
maintain and augment our intellectual property portfolio and opportunistically acquire complementary intellectual property;
scale-up manufacturing capabilities to commercialize any products for which we may obtain regulatory approval;
perform our obligations under the collaboration agreement with NHS;
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seek to obtain regulatory approvals for our product candidates; 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 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 for these product candidates and manufacturing, marketing and selling any products
for which we may obtain regulatory approval. We are in the preliminary stages of many of these activities. We may never succeed in these activities and, even
if we do, may never generate revenue that is significant enough to achieve profitability.
Because of the numerous risks and uncertainties associated with pharmaceutical product and biological 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.
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 even continue our operations.
As discussed in Note 1 of the consolidated financial statements included in this Annual Report under Accounting Standards Update, or ASU, 2014-
15, Presentation of Financial Statements-Going Concern (Subtopic 205-40), or, ASC 205-40, we have the responsibility to evaluate whether conditions
and/or events raise substantial doubt about our ability to meet our future financial obligations as they become due within one year after the date the financial
statements are issued. Under ASC 205-40, this evaluation initially cannot take into consideration the potential mitigating effects of plans that have not been
fully implemented as of the date the financial statements are issued. Since we currently anticipate that our existing financial resources will enable us to meet
forecasted operating plans into the fourth quarter of 2019, we have determined that our cash runway of less than 12 months along with our accumulated
deficit, history of losses, and future expected losses meet the ASC 205-40 standard for raising substantial doubt about our ability to continue as a going
concern within one year of the issuance date of our consolidated financial statements. We may not be successful in our mitigation efforts, which primarily
consist of raising additional capital through some combination of equity or debt financings, and/or potential new collaborations and reducing cash
expenditures. Lack of necessary funds may require us, among other things, to delay, scale back, or eliminate some or all of our planned clinical trials.
We will need 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.
Our expenses may increase in connection with our ongoing activities, particularly as we continue the clinical development of SER-109, including
conducting the Phase 3 clinical study, continue the clinical development of SER-287, including conducting the Phase 2b clinical study, initiate clinical studies
of SER-401, and continue to research, develop and initiate clinical trials of SER-301 and 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. Furthermore, we have incurred and expect to continue to incur additional costs associated with operating as a public company. Accordingly, we
will need to obtain substantial additional funding in connection with our continuing operations. If we are unable to raise capital when needed or on attractive
terms, we could be forced to delay, reduce or eliminate our research and development programs or any future commercialization efforts.
We do not expect that our existing cash, cash equivalents and investments will be sufficient to fund our operating expenses and capital expenditure
requirements for a one-year period from the issuance of the consolidated financial statements included in this Annual Report. This estimate excludes net cash
flows from future business development activities. In addition, the specifics of existing and future clinical trial activities could impact capital requirements
and cash projections. 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. Our future capital requirements will depend on many factors, including:
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the progress and results of our Phase 3 clinical study of SER-109;
the progress and results of future clinical studies of SER-287;
the progress and results of our studies in immuno-oncology;
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the cost of manufacturing clinical supplies for our product candidates;
the scope, progress, results and costs of preclinical development, laboratory testing and clinical trials for our other product candidates, including
SER-301;
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 and may decrease our stock price. 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 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 or the commercialization of any product candidates, or be unable to 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 limited operating history may make it difficult to evaluate the success of our business to date and to assess our future viability.
Since our inception in October 2010, we have devoted substantially all of our resources to developing our clinical and preclinical program, building
our intellectual property portfolio, developing our supply chain, planning our business, raising capital and providing general and administrative support for
these operations. We have completed our Phase 1b and a Phase 2 clinical study of SER-109, our lead product candidate, and have reported top-line data in our
Phase 1b studies of SER-287 and SER-262. We have not yet demonstrated our ability to successfully complete any Phase 3 clinical study 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 made about our future success or viability may not be as accurate as they could be if we had a longer operating history.
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Risks Related to the Discovery, Development and Regulatory Approval of Our Product Candidates
Other than SER-109, we are early in our development efforts and may not be successful in our efforts to use our microbiome therapeutics platform to
build a pipeline of product candidates and develop marketable drugs.
We are using our microbiome therapeutics platform to develop Ecobiotic microbiome therapeutics. We are at an early stage of development and our
platform has not yet, and may never, lead to approvable or marketable drugs. We are developing additional product candidates that we intend to be used to
prevent infection and treat diseases where the microbiome is implicated. We may have problems applying our technologies to these areas, and our product
candidates may not be effective in preventing infection and disease. Our product candidates may not be suitable for clinical development, including as a result
of their 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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completion of preclinical studies and clinical trials with positive results;
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 our own, commercial manufacturing capabilities;
launching commercial sales of our products, if and when approved, whether alone or in collaboration with others;
entering 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, the medical community and third-party payors;
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 a continued 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 products and technology.
If we do not successfully develop and commercialize product candidates we will not be able to obtain product revenue in future periods, which likely
would result in significant harm to our financial position and adversely affect our stock price.
Our product candidates are based on microbiome therapeutics, which is an unproven approach to therapeutic intervention.
All of our product candidates are based on microbiome therapeutics, a therapeutic approach that is designed to prevent infection and treat disease by
restoring the function of a dysbiotic microbiome. We have not, nor to our knowledge has any other company, received regulatory approval for, or
manufactured on a commercial scale, a therapeutic based on this approach. We cannot be certain that our approach will lead to the development of approvable
or marketable products or that we will be able to manufacture at commercial scale, if approved. In addition, our Ecobiotic microbiome therapeutics may have
different effectiveness rates in various indications and in different geographical areas. Finally, the FDA or other regulatory agencies may lack experience in
evaluating the safety and efficacy of products based on microbiome therapeutics, which could result in a longer than expected regulatory review process,
increase our expected development costs and delay or prevent commercialization of our product candidates.
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Our microbiome therapeutics platform relies on third parties for biological materials, including human stool. Some biological materials have not
always met our expectations or requirements, and any disruption in the supply of these biological materials could materially adversely affect our business. For
example, if any supplied biological materials are contaminated with disease organisms, we would not be able to use such biological materials. Although we
have control processes and screening procedures, biological materials are susceptible to damage and contamination and may contain active pathogens.
Improper storage of these materials, by us or any third-party suppliers, may require us to destroy some of our materials or products, which could delay the
development or commercialization of our product candidates.
Clinical drug development involves a risky, 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.
It is difficult 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. Clinical testing is expensive, difficult to design and implement, can take many years to complete and is uncertain as to outcome. A failed clinical
trial can occur at any stage of testing. The outcome of preclinical testing and early clinical trials may not be predictive of the success of later clinical trials,
and interim or preliminary results of a clinical trial, that we may from time to time announce, do not necessarily predict final results. A number of companies
in the pharmaceutical and biotechnology industries have suffered significant setbacks in advanced clinical trials due to lack of efficacy or adverse safety
profiles, notwithstanding promising results in earlier studies, and we cannot be certain that we will not face similar setbacks. 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. Preliminary or topline data remain subject to audit and verification procedures that may result in the final data being materially
different from the preliminary or interim data we previously published. As a result, these data should be viewed with caution until the final data are available.
Adverse changes between preliminary or interim data and final data could significantly harm our business prospects.
In addition, we cannot be certain as to what type and how many clinical trials the FDA, or other regulators, will require us to conduct before we may
successfully gain approval to market any of our other product candidates. 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. In some situations, evidence from a Phase 2 trial and a Phase 3 trial or from a
single Phase 3 trial can be sufficient for FDA approval, such as in cases where the trial or trials provide highly reliable and statistically strong evidence of an
important clinical benefit. In 2014, the FDA had indicated that we may be required to conduct more than one Phase 3 clinical trial of SER-109 in order to gain
approval. More recently, the FDA has indicated that a single Phase 3 study for SER-109 will be sufficient for approval provided that we show a persuasive
clinical effect and certain chemistry, manufacturing and controls parameters.
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 or commercialize our product candidates, including:
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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;
failures or delays in reaching agreement on acceptable clinical trial contracts or clinical trial protocols with prospective trial sites;
clinical trials of our product candidates may demonstrate undesirable side effects or produce negative or inconclusive results, and we may
decide, or regulators may require us, to conduct additional clinical trials or abandon product development programs;
the number of patients required for clinical trials of our product candidates may be larger than we anticipate, enrollment in these clinical trials
may be slower than we anticipate or participants may drop out of these clinical trials at a higher rate than we anticipate;
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;
regulators or institutional review boards may require that we or our investigators suspend or terminate clinical research for various reasons,
including noncompliance with regulatory requirements or a finding that the participants are being exposed to unacceptable health risks;
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the cost of clinical trials of our product candidates may be greater than we anticipate;
the supply or quality of our product candidates or other materials necessary to conduct clinical trials of our product candidates may be
insufficient or inadequate;
regulators may revise the requirements for approving our product candidates, or such requirements may not be as we anticipate; and
regarding trials managed by 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, we may:
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be delayed in obtaining marketing approval for our product candidates;
lose the support of current or any future collaborators, requiring us to bear more of the burden of development of certain compounds;
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 we intend or desire;
obtain approval with labeling that includes significant use or distribution restrictions or safety warnings;
be subject to additional post-marketing testing requirements;
be subject to increased pricing pressure; or
have the product removed from the market after obtaining marketing approval.
In June 2017, we initiated a Phase 3 clinical study of SER-109 (ECOSPOR III) in patients with multiply recurrent CDI. Additional clinical trials or
changes in our development plans could cause us to incur significant development costs, delay or prevent the commercialization of SER-109 or otherwise
adversely affect our business.
Our product development costs will increase if we experience delays in clinical testing or 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. We are developing our lead product
candidate, SER-109, to reduce recurrence of CDI in patients suffering from recurrent CDI. There is a limited number of patients from which to draw for
clinical studies.
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, including the use of unapproved fecal microbiota transplant, or FMT, for
CDI;
the existence of competing clinical trials;
the efforts to facilitate timely enrollment in clinical trials;
our payments for conducting clinical trials;
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the patient referral practices of physicians;
the burden, or perceived burden, of the clinical study;
the ability to monitor patients adequately during and after treatment; and
the proximity and availability of clinical trial sites for prospective patients.
Our inability to enroll a sufficient number of patients for our clinical trials or a delayed rate of enrollment would result in significant delays and could
require us to abandon one or more clinical trials altogether. We continue to enroll the SER-109 Phase 3 study for patients with recurrent CDI despite the
widespread use of unapproved, FMT to treat CDI. As interference from this uncontrolled procedure has impacted the enrollment rate of our placebo-
controlled clinical trial, we are evaluating modification of the study design to expedite clinical results. Enrollment delays in our clinical trials would result in
increased development costs for our product candidates, which would cause the value of our company to decline and limit our ability to obtain additional
financing.
If we are not able to obtain, or if there are delays in obtaining, required regulatory approvals, we will not be able to commercialize our product candidates
or will not be able to do so as soon as anticipated, and our ability to generate revenue will be materially impaired.
Our product candidates and the activities associated with their development and commercialization, including their design, testing, manufacture,
safety, efficacy, recordkeeping, labeling, storage, approval, advertising, promotion, sale and distribution, are subject to comprehensive regulation by the FDA
and other regulatory agencies in the United States and by the EMA and similar regulatory authorities outside the United States. Failure to obtain marketing
approval for a product candidate in any jurisdiction will prevent us from commercializing the product candidate in that jurisdiction and may affect our plans
for commercialization in other jurisdictions as well. We have not received approval to market any of our product candidates from regulatory authorities in any
jurisdiction. We have only limited experience in filing and supporting the applications necessary to gain marketing approvals and expect to rely on third
parties to assist us in this process. Securing marketing approval requires the submission of extensive preclinical and clinical data and supporting information
to regulatory authorities for each therapeutic indication to establish the product candidate’s safety and efficacy. Securing marketing approval also requires the
submission of information about the product manufacturing process to, and inspection of manufacturing facilities by, the regulatory authorities. Our product
candidates may not be effective, may be only moderately effective or may prove to have undesirable or unintended side effects, toxicities or other
characteristics that may preclude our obtaining marketing approval or prevent or limit commercial use.
The process of obtaining marketing approvals, both in the United States and abroad, is expensive, risky and may take many years. The scope and
amount of clinical data required to obtain marketing approvals can vary substantially from jurisdiction to jurisdiction, and it may be difficult to predict
whether a particular regulatory body will require additional or different studies than those conducted by a sponsor, especially for novel product candidates
such as our Ecobiotic microbiome therapeutics. The FDA or foreign regulatory authorities may delay, limit, or deny approval to market our product
candidates for many reasons, including: our inability to demonstrate that the clinical benefits of our product candidates outweigh any safety or other perceived
risks; the regulatory authority’s disagreement with the interpretation of data from nonclinical or clinical studies; the regulatory agency’s requirement that we
conduct additional preclinical studies and clinical trials; changes in marketing approval policies during the development period; changes in or the enactment
of additional statutes or regulations, or changes in regulatory review process for each submitted product application; or the regulatory authority’s failure to
approve the manufacturing processes or third-party manufacturers with which we contract. Regulatory authorities have substantial discretion in the approval
process and may refuse to accept a marketing application if deficient. In addition, varying interpretations of the data obtained from preclinical and clinical
testing could delay, limit or prevent marketing approval of a product candidate. Any marketing approval we ultimately obtain may be limited or subject to
restrictions or post-approval commitments that render the approved product not commercially viable. Of the large number of drugs in development, only a
small percentage successfully complete the FDA or other regulatory approval processes and are commercialized.
Furthermore, our product candidates may not receive marketing approval even if they achieve their specified endpoints in clinical trials. Clinical data
is often susceptible to varying interpretations and many companies that have believed that their products performed satisfactorily in clinical trials have
nonetheless failed to obtain regulatory agency approval for their products. The FDA or foreign regulatory authorities may disagree with our trial design and
our interpretation of data from nonclinical and clinical studies. Upon the FDA’s review of data from any pivotal trial, it may request that the sponsor conduct
additional analyses of the data and, if it believes the data are not satisfactory, could advise the sponsor to delay filing a marketing application.
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Even if we eventually complete clinical testing and receive approval of a biologics license application, or BLA, or foreign marketing authorization for
one of our product candidates, the FDA or the applicable foreign regulatory agency may grant approval contingent on the performance of costly additional
clinical trials, which may be required after approval. The FDA or the applicable foreign regulatory agency may also approve our product candidates for a
more limited indication and/or a narrower patient population than we originally request, and the FDA, or applicable foreign regulatory agency, may not
approve the labeling that we believe is necessary or desirable for the successful commercialization of our product candidates. Any delay in obtaining, or
inability to obtain, applicable regulatory approval would delay or prevent commercialization of our product candidates and would materially adversely impact
our business and prospects.
The development of therapeutic products targeting the underlying biology of the human microbiome is an emerging field, and it is possible that the
FDA and other regulatory authorities could issue regulations or new policies in the future affecting our Ecobiotic microbiome therapeutics that could
adversely affect our product candidates.
If we experience delays in obtaining approval or if we fail to obtain approval of our product candidates, the commercial prospects for our product
candidates may be harmed and our ability to generate revenues will be materially impaired.
A Fast Track designation by the FDA may not actually lead to a faster development or regulatory review or approval process.
We may seek Fast Track designation for some of our product candidates. If a drug or biologic is intended for the treatment of a serious or life-
threatening condition and nonclinical or clinical data demonstrate the potential to address unmet medical needs for this condition, the drug or biologic sponsor
may apply for FDA Fast Track designation. Fast Track designation provides increased opportunities for sponsor meetings with the FDA during preclinical
and clinical development, in addition to the potential for rolling review once a marketing application is filed. The FDA has broad discretion whether or not to
grant this designation, and even if we believe a particular product candidate is eligible for this designation, we cannot be certain that the FDA would decide to
grant it. Even if we do receive Fast Track designation, we may not experience a faster development process, review or approval compared to conventional
FDA procedures. Fast Track designation does not assure ultimate approval by the FDA. The FDA may withdraw Fast Track designation if it believes that the
designation is no longer supported by data from our clinical development program.
A Breakthrough Therapy designation by the FDA for our product candidates may not lead to a faster development, regulatory review or approval process,
and it does not increase the likelihood that our product candidates will receive marketing approval.
We have received Breakthrough Therapy designation for SER-109, and we may seek a Breakthrough Therapy designation for our other product
candidates. A Breakthrough Therapy is defined as a drug or biologic that is intended to treat a serious or life-threatening disease or condition, and preliminary
clinical evidence indicates that the drug or biologic may demonstrate substantial improvement over existing therapies on one or more clinically significant
endpoints, such as substantial treatment effects observed in early clinical development. For drugs that have been designated as breakthrough therapies,
interaction and communication between the FDA and the sponsor can help to identify the most efficient path for clinical development. Drugs designated as
breakthrough therapies by the FDA are also eligible for rolling review of the associated marketing application, meaning that the agency may review portions
of the marketing application before the sponsor submits the complete application, as well as priority review, where the agency aims to act on the application
within eight months.
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 receipt of a Breakthrough
Therapy designation for a product candidate may not result in a faster development process, review or approval compared to conventional FDA procedures
and does not assure ultimate approval by the FDA. In addition, not all products designated as breakthrough therapies ultimately will be shown to have the
substantial improvement over available therapies suggested by the preliminary clinical evidence at the time of designation. As a result, if the Breakthrough
Therapy designation for SER-109 or any future designation we receive is no longer supported by subsequent data, the FDA may rescind the designation.
We may seek orphan drug designation for some of our product candidates but may not be able to obtain it.
We have obtained orphan drug designation from the FDA for SER-109 for recurrent CDI and SER-287 for pediatric ulcerative colitis and may seek
orphan drug designation and exclusivity for some of our future product candidates. Regulatory authorities in some jurisdictions, including the United States
and Europe, may designate drugs and biologics for relatively small patient populations as orphan drugs. In the United States, the FDA may designate a drug
or biologic as an orphan drug if it is intended to treat a rare disease or condition, which is defined as a disease or condition that affects fewer than 200,000
individuals in the United States.
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Generally, if a product with an orphan drug designation subsequently receives the first marketing approval for the indication for which it has such
designation, the product is entitled to a period of marketing exclusivity, which precludes the EMA or the FDA from approving another marketing application
for the same drug or biologic for that time period. The applicable period is seven years in the United States and ten years in Europe. The European exclusivity
period can be reduced to six years if a product no longer meets the criteria for orphan drug designation or if the product is sufficiently profitable so that
market exclusivity is no longer justified. Orphan drug exclusivity may be lost if the FDA or EMA determines that the request for designation was materially
defective or if the manufacturer is unable to assure a sufficient quantity of the drug or biologic to meet the needs of patients with the rare disease or condition.
Orphan drug exclusivity for a product 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 in that it is shown to be safer, more effective or makes a major contribution to patient care.
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 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 and biologics 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.
Risks Related to our Dependence on Third Parties and Manufacturing
The Collaboration and License Agreement, or the License Agreement, with NHS is important to our business. If we or NHS fail to adequately perform
under the License Agreement, or if we or NHS terminate the License Agreement, the development and commercialization of our CDI and IBD product
candidates, including SER-109, SER-262, SER-287, and SER-301, would be delayed or terminated and our business would be adversely affected.
The License Agreement may be terminated:
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by NHS in the event of serious safety issues related to SER-109, SER-262, SER-287, SER-301 or other specific products added under the
License Agreement, or, collectively, the NHS Collaboration Products;
by us if NHS challenges the validity or enforceability of any of our licensed patents; and
by either NHS or us in the event of the other party’s uncured material breach or insolvency.
Upon termination of the License Agreement, all licenses granted to NHS by us will terminate, and all rights in and to the NHS Collaboration Products
held by NHS will revert to us. If we commit a material breach of the License Agreement, NHS may elect not to terminate the License Agreement but instead
apply specified adjustments to its payment obligations and other terms and conditions of the License Agreement. If NHS were to make such adjustments, the
funding from and benefits of the License Agreement could be diminished, which could adversely affect our financial condition. Unless the License
Agreement is terminated by us for NHS’ uncured material breach, upon termination of the License Agreement, NHS will be eligible to receive post-
termination royalties from us until NHS has recouped certain development costs related to the NHS Collaboration Products and specified percentages of any
milestone payments paid to us under the License Agreement prior to termination, which could have a material adverse effect on our business.
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Termination of the License Agreement could cause significant delays in our product development and commercialization efforts that could prevent us
from commercializing our CDI and IBD product candidates, outside of the United States and Canada, without first expanding our internal capabilities or
entering into another agreement with a third party. Any alternative collaboration or license could also be on less favorable terms to us. In addition, under the
License Agreement, NHS agreed to provide funding for certain clinical development activities. If the License Agreement were terminated, we may need to
refund those payments and seek additional financing to support the research and development of any terminated products or discontinue any terminated
products, which could have a material adverse effect on our business.
Under the License Agreement, we are dependent upon NHS to successfully commercialize any NHS Collaboration Products outside of the United
States and Canada. We cannot directly control NHS’ commercialization activities or the resources it allocates to our product candidates. Our interests and
NHS’ interests may differ or conflict from time to time, or we may disagree with NHS’ level of effort or resource allocation. NHS may internally prioritize
our product candidates differently than we do or it may not allocate sufficient resources to effectively or optimally commercialize them. If these events were
to occur, our business would be 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
failing to meet deadlines for the completion of such trials.
We expect to continue to rely on third parties, such as contract research organizations, or CROs, clinical data management organizations, medical
institutions and clinical investigators, to conduct and manage 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 regulatory standards, commonly referred to as good clinical practices, 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 with which we must comply. 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 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 and
may not be able to, or may be delayed in our efforts to, successfully commercialize our product candidates.
We also expect to rely on other third parties to store and distribute drug supplies for our clinical trials. Any performance failure on the part of our
distributors could delay clinical development or marketing approval of our product candidates or commercialization of our products, producing additional
losses and depriving us of potential product revenue.
We rely on third parties for certain aspects of the manufacture of our product candidates for preclinical and clinical testing and expect to continue to do
so for the foreseeable future. This 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, which could delay, prevent or impair our development or commercialization efforts.
We rely, and expect to continue to rely, on third parties for certain aspects of materials supply for our product candidates in preclinical and clinical
testing, as well as for commercial manufacture if any of our product candidates receive marketing approval. This reliance on 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.
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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:
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failure of third-party manufacturers to comply with regulatory requirements and maintain quality assurance;
breach of supply agreements by the third-party manufacturers;
failure to supply components, intermediates, services, or product according to our specifications;
failure to supply components, intermediates, services, or product according to our schedule or at all;
misappropriation or disclosure of our proprietary information, including our trade secrets and know-how; and
termination or nonrenewal of agreements by third-party manufacturers at times that are costly or inconvenient for us.
Third-party manufacturers may not be able to comply with current good manufacturing processes, or cGMP, regulations or similar regulatory
requirements inside or outside the United States. Our failure, or the failure of our third-party manufacturers, to comply with applicable regulations could
result in sanctions being imposed on us, including 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. The contract manufacturers we rely on to produce our product candidates have never produced an FDA-approved
therapeutic. If our manufacturers are unable to comply with cGMP regulation or if the FDA or other regulators do not approve their facility upon a pre-
approval inspection, our therapeutic candidates may not be approved or may be delayed in obtaining approval. In addition, there are a limited number of
manufacturers that operate under cGMP regulations and 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. Except for our
clinical production facility in Massachusetts, we do not currently have arrangements in place for redundant supply of product. We do not currently have a
second source for required materials used for the manufacture of finished product. If our current manufacturers 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 anticipated future dependence upon others for
the manufacture of our product candidates or products could delay, prevent or impair our development and commercialization efforts.
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 manufacturing facilities at our Cambridge, Massachusetts locations where we conduct process development, scale-up activities and a portion
of the manufacture of Ecobiotic microbiome therapeutics. 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 meet cGMP. We have
not yet had any of our manufacturing facilities inspected.
We may establish a manufacturing facility for our product candidates for production at a commercial scale. We have no experience in commercial-
scale manufacturing of our product candidates. We currently intend to develop our manufacturing capacity in part by expanding our current facility or
building additional facilities. This activity will require substantial additional funds and we would need to hire and train significant numbers of qualified
employees to staff these facilities. 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 facility, 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.
In addition, some of our product candidates require donor material, of which we may not be able to collect sufficient quantities for commercial-scale
or other manufacturing.
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Risks Related to Commercialization of Our Product Candidates and
Other Legal Matters
Even if any of our product candidates receives marketing approval, it may fail to achieve the degree of market acceptance by physicians, patients,
hospitals, 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. For example, current CDI treatment involves the use of antibiotics that are well established in the
medical community or the use of FMT and physicians may continue to rely on these treatments and our competitors and physicians may continue to seek to
standardize and implement this procedure. If our product candidates receive approval but do not achieve an adequate level of acceptance, we may not
generate significant product revenue and we may not become profitable. The degree of market acceptance of our approved 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 products 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;
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 products together with other medications;
interactions of our products with other medicines patients are taking; and
the ability of patients to take our products.
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 have employees with experience in sales and marketing, but we have limited sales or marketing infrastructure and, as a company, have no
experience in the sale, marketing, or distribution of pharmaceutical products. To achieve commercial success for any product 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.
Factors that may inhibit our efforts to commercialize our products on our own include:
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our inability to recruit, train and retain adequate numbers of effective sales and marketing personnel;
the inability of sales personnel to obtain access to or educate physicians on the benefits of our products;
the lack of complementary products to be offered by sales personnel, which may put us at a competitive disadvantage relative to companies
with more extensive product lines;
unforeseen costs and expenses associated with creating an independent sales and marketing organization; and
inability to obtain sufficient coverage and reimbursement from third-party payors and governmental agencies.
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Outside the United States, we rely and may increasingly rely on third parties, including NHS, 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, 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 is highly competitive and is characterized by rapid and substantial
technological development and product innovations. 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. We are aware of a number of large pharmaceutical and biotechnology companies, as
well as smaller, early-stage companies, that are pursuing the development of products, including microbiome therapeutics, for reducing CDI and other disease
indications we are targeting. Some of these competitive products and therapies are based on scientific approaches that are the same as or similar to our
approach, and others may be based on entirely different approaches. For example, FMT is a procedure that has resulted in reports of high cure rates for
recurrent CDI and our competitors and physicians may continue to seek to standardize and implement this procedure. Potential competitors also include
academic institutions, government agencies, not-for-profits, and other public and private research organizations that conduct research, seek patent protection
and establish collaborative arrangements for research, development, manufacturing and commercialization.
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 and 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.
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 microbiome therapeutic which 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.
Even if we are able to commercialize any product candidates, the products may become subject to unfavorable pricing regulations or third-party coverage
and reimbursement policies, any of which would harm our business.
Our ability to commercialize any product candidates successfully will depend, in part, on the extent to which coverage and 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 impact 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, drugs. Reimbursement rates
from private health insurance companies vary depending on the company, the insurance plan and other factors. A primary trend in the U.S. healthcare industry
and elsewhere is cost containment. 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 drug companies provide them with predetermined discounts from
list prices and are challenging the prices charged for drugs. We may also be required to conduct expensive pharmacoeconomic studies to justify coverage and
reimbursement or the level of reimbursement relative to other therapies. 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, and the royalties resulting
from the sales of those products may also be adversely impacted.
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There may be significant delays in obtaining reimbursement for newly approved drugs, and coverage may be more limited than the purposes for which
the drug is approved by the FDA or similar regulatory authorities outside the United States. Moreover, eligibility for reimbursement does not imply that a
drug 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 drugs, 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 drug and the clinical setting in which it is used, may be based on reimbursement levels already set for lower cost treatment approaches and may
be incorporated into existing payments for other services. Net prices for drugs may be reduced by mandatory discounts or rebates required by government
healthcare programs or private payors and by any future relaxation of laws that presently restrict imports of drugs from countries where they may be sold at
lower prices than in the United States. 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 drug 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 drug before it can be reimbursed. 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.
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;
withdrawal of clinical trial participants;
significant costs to defend the related litigation;
substantial monetary awards 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.
We currently hold $5.0 million in product liability insurance coverage in the aggregate, with a per occurrence limit of $5.0 million, which may not be
adequate to cover all 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.
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We may face competition from biosimilars, which may have a material adverse impact on the future commercial prospects of our product candidates.
Even if we are successful in achieving regulatory approval to commercialize a product candidate faster than our competitors, we may face competition
from biosimilars. In the United States, the Biologics Price Competition and Innovation Act, or BPCIA, enacted in 2010 as part of the ACA, created an
abbreviated approval pathway for biological products that are demonstrated to be “highly similar,” or biosimilar, to or “interchangeable” with an FDA-
approved biological product. 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. This pathway could allow competitors to
reference data from innovative biological products 12 years after the time of approval of the innovative biological product. This data exclusivity does not
prevent another company from developing a product that is highly similar to the innovative product, generating its own data and seeking approval. Data
exclusivity only assures that another company cannot rely upon the data within the innovator’s application to support the biosimilar product’s approval.
We believe that any of our product candidates approved 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 our product
candidates to be reference products for competing products, potentially creating the opportunity for generic competition sooner than anticipated. It is possible
that Congress or the FDA may take these or other measures to reduce or eliminate periods of exclusivity. The BPCIA is complex and continues to be
interpreted and implemented by the FDA. As a result, its ultimate impact is subject to uncertainty. The FDA has issued several guidance documents to date
discussing the biosimilar pathway, and the FDA approved the first biosimilar under the BPCIA in March 2015. However, the FDA continues to implement the
BPCIA, and such FDA implementation could have a material adverse effect on the future commercial prospects for our product candidates.
In Europe, the European Commission has granted marketing authorizations for several biosimilars pursuant to a set of general and product class-
specific guidelines for biosimilar approvals issued over the past few years. In Europe, a competitor may reference data supporting approval of an innovative
biological product but will not be able to get on the market until 10 years after the time of approval of the innovative product. This 10-year marketing
exclusivity period will be extended to 11 years if, during the first eight of those 10 years, the marketing authorization holder obtains an approval for one or
more new therapeutic indications that bring significant clinical benefits compared with existing therapies. In addition, companies may be developing
biosimilars in other countries that could compete with our products. If competitors are able to obtain marketing approval for biosimilars referencing our
products, our products may become subject to competition from such biosimilars, with the attendant competitive pressure and consequences.
Failure to obtain marketing approval in international jurisdictions would prevent our product candidates from being marketed abroad.
In order to market and sell our products in the European Union, or EU, and many other jurisdictions, we or our collaborators must obtain separate
marketing approvals and comply with numerous and varying regulatory requirements. The approval procedure varies among countries and can involve
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 be approved for reimbursement before the product 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 products in any market.
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Any product candidate for which we obtain marketing approval 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 unanticipated problems with our products, when and if
any of them are approved.
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 specific conditions of approval, including a requirement to implement a risk evaluation and mitigation strategy, which could include
requirements for a medication guide, communication plan, or restricted distribution system. If any of our product candidates receives marketing approval, the
accompanying label may limit the approved use of our drug, 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 or promotion. Violations of the FDA’s restrictions relating to the promotion of prescription drugs 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 unanticipated
severity or frequency, problems with manufacturers or manufacturing processes, or failure to comply with regulatory requirements, 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;
damage to relationships with 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.
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Noncompliance with similar EU requirements 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. In addition, the FDA’s regulations, policies or guidance may change and new or additional statutes or government regulations may be
enacted that could prevent or delay regulatory approval of our product candidates or further restrict or regulate post-approval activities. For example, in
December 2016, the 21st Century Cures Act was signed into law, which is intended, among other things, to modernize the regulation of biologics and to spur
innovation, though its ultimate implementation remains unclear. 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. We also cannot predict the likelihood, nature, or extent of adverse government regulation that may arise
from pending or future legislation or administrative action, either in the United States or abroad. For example, certain policies of the current Presidential
administration may impact our business and industry. Namely, the current Presidential 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, the FDA’s ability to engage in routine
regulatory and oversight activities such as implementing statutes through rulemaking, issuance of guidance, and review and approval or marketing
applications. It is difficult to predict how these requirements 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 the FDA’s ability to engage in oversight and implementation activities in the normal
course, our business may be negatively impacted. 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.
Our relationships with customers, physicians and third-party payors are and 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 governmental healthcare programs,
contractual damages, reputational harm and diminished profits and future earnings.
Healthcare providers, physicians and third-party payors will play a primary role in the recommendation and prescription of any product candidates for
which we obtain marketing approval. Our current and future arrangements with third-party payors, physicians and customers expose us to broadly applicable
fraud and abuse and other healthcare laws and regulations that may restrict 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 prohibits, among other things, persons 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. 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 federal False Claims Act (described below);
the false claims and civil monetary penalties laws, including the federal False Claims Act, which, among other things, impose criminal and civil
penalties, including through civil whistleblower or qui tam actions, against individuals or entities for knowingly presenting, or causing to be
presented, to the federal government, claims for payment that are false or fraudulent, knowingly making, using or causing to be made or used, a
false record or statement material to a false or fraudulent claim or from knowingly making a false statement to avoid, decrease or conceal an
obligation to pay money to the federal government;
the federal Health Insurance Portability and Accountability Act of 1996, or HIPAA, imposes criminal and civil liability for executing a scheme
to defraud any healthcare benefit program or making false statements relating to healthcare matters; similar to the federal Anti-Kickback
Statute, a person or entity does not need to have actual knowledge of these statutes or specific intent to violate them to have committed a
violation;
HIPAA, as amended by the Health Information Technology for Economic and Clinical Health Act and its implementing regulations, also
imposes obligations, including mandatory contractual terms, with respect to safeguarding the privacy, security and transmission of individually
identifiable health information;
the federal Physician Payment Sunshine Act requires applicable manufacturers of covered drugs to report payments and other transfers of value
to physicians, certain other healthcare professionals, and teaching hospitals, and ownership and investment interests held by physicians and
their immediate family members; manufacturers are required to submit reports to the government by the 90th day of each calendar year;
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analogous state and foreign laws and regulations, such as state anti-kickback and false claims laws, may apply to our business practices,
including but not limited to, research, distribution, sales or marketing arrangements and claims involving healthcare items or services
reimbursed by non-governmental third-party payors, including private insurers; state laws that require pharmaceutical companies to comply
with the pharmaceutical industry’s voluntary compliance guidelines and the relevant compliance guidance promulgated by the federal
government and may require drug manufacturers to report information related to payments and other transfers of value to physicians and other
healthcare providers, pricing information or marketing expenditures; and
state and foreign laws that govern the privacy and security of health information in some circumstances, many of which differ from each other
in significant ways and often are not preempted by HIPAA, thus complicating compliance efforts.
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. Any action against us for violation of these laws, even if we successfully
defend against it, could cause us to incur significant legal expenses and divert our management’s attention from the operation of our business. The shifting
compliance environment and the need to build and maintain a robust system to comply with multiple jurisdictions with different compliance and reporting
requirements increases the possibility that we may violate one or more of the requirements.
Efforts to ensure that our business arrangements with third parties will comply with applicable healthcare laws and regulations will involve substantial
costs. It is possible that governmental authorities will conclude that our business practices 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 from government funded healthcare programs, such as Medicare and Medicaid, reporting obligations and oversight if we become
subject to a corporate integrity agreement or other agreement, and the curtailment or restructuring of our operations.
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.
In the United States, the Patient Protection and Affordable Care Act, as amended by the Health Care and Education Affordability Reconciliation Act,
or collectively the ACA, is 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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establishment of a new pathway for approval of lower-cost biosimilars to compete with biologic products, such as those we are developing;
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 Medicare Part D coverage gap discount program, in which manufacturers must agree to offer point-of-sale discounts off negotiated
prices;
extension of manufacturers’ Medicaid rebate liability;
expansion of eligibility criteria for Medicaid programs;
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.
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There have been judicial and Congressional challenges to certain aspects of the ACA, and we expect there will be additional challenges and
amendments to the ACA in the future, particularly in light of the current Presidential administration and Congress. Some of the provisions of the ACA have
yet to be implemented, and there have been judicial and Congressional challenges to certain aspects of the ACA as well as recent efforts by the current
Presidential administration to repeal or replace certain aspects of the ACA. For example, President Trump has signed Executive Orders and other directives
designed to delay the implementation of certain provisions of the ACA or otherwise circumvent some of the requirements for health insurance mandated by
the ACA. Concurrently, Congress has considered legislation that would repeal or repeal and replace all or part of the ACA. While Congress has not passed
comprehensive repeal legislation, bills affecting the implementation of certain taxes under the ACA have been signed into law. The Tax Cuts and Jobs Act of
2017 includes a provision repealing, effective January 1, 2019, the tax-based shared responsibility payment imposed by the ACA on certain individuals who
fail to maintain qualifying health coverage for all or part of a year that is commonly referred to as the “individual mandate.” On December 14, 2018, a U.S.
District Court Judge in the Northern District of Texas, or the Texas District Court Judge, 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 Act of 2017, the remaining provisions of the ACA are invalid as well.
While the current Presidential administration and CMS have both stated that the ruling will have no immediate effect, and on December 30, 2018 the Texas
District Court Judge issued an order staying the judgment pending appeal, it is unclear how this decision, subsequent appeals and other efforts to repeal and
replace the ACA will impact the ACA and our business. In addition, other legislative changes have been proposed and adopted since the ACA was enacted.
For example, the Budget Control Act of 2011, enacted in August 2011, included aggregate reductions of Medicare payments to providers of 2% per fiscal
year, which went into effect on April 1, 2013 and, due to subsequent legislative amendments, will remain in effect through 2027 unless additional
Congressional action is taken. On January 2, 2013, the American Taxpayer Relief Act of 2012 was signed into law, which, among other things, reduced
Medicare payments to several providers, including hospitals, and an increase in the statute of limitations period for the government to recover overpayments
to providers from three to five years. These laws may result in additional reductions in Medicare and other healthcare funding and otherwise affect the prices
we may obtain.
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 in 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 product candidates, if approved.
Moreover, there has recently been heightened governmental scrutiny over the manner in which manufacturers set prices for their marketed products.
Individual states in the United States have become increasingly active in implementing regulations designed to contain pharmaceutical and biological product
pricing, including price or patient reimbursement constraints, discounts, restrictions on certain product access and marketing cost disclosure and transparency
measures. Legally mandated price controls on payment amounts by third-party payors or other restrictions could harm our business, results of operations,
financial condition and prospects. In addition, regional healthcare authorities and individual hospitals are increasingly using bidding procedures to determine
what pharmaceutical products and which suppliers will be included in their prescription drug and other healthcare programs. This could reduce the ultimate
demand for our product candidates, if approved, or put pressure on our product pricing, which could negatively affect our business, results of operations,
financial condition and prospects.
Legislative and regulatory proposals have been made to expand post-approval requirements and restrict sales and promotional activities for
pharmaceutical products. We cannot be sure whether additional legislative changes will be enacted, or whether the FDA regulations, guidance or
interpretations will be changed, or what the impact of such changes on the marketing approvals of our product candidates, if any, may be. In addition,
increased scrutiny by Congress of the FDA’s approval process may significantly delay or prevent marketing approval, as well as subject us to more stringent
product labeling and post-marketing testing and other requirements.
Governments outside the United States tend to impose strict price controls, which may adversely affect our revenues, if any.
In some countries, particularly the countries of the EU, 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. 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 EU member states and parallel distribution or arbitrage between low-priced and
high-priced member states, 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. If coverage and reimbursement of our products are
unavailable or limited in scope or amount, or if pricing is set at unsatisfactory levels, our business could be harmed, possibly materially.
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Risks Related to Our Intellectual Property
If we 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 have a material adverse impact on our business, results of operations, financial
condition and prospects.
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. Prosecution of our patent portfolio is at a very early stage. For some patent
applications in our portfolio, we have filed national stage applications based on our Patent Cooperation Treaty, or PCT, applications, thereby limiting the
jurisdictions in which we can pursue patent protection for the various inventions claimed in those applications. 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, financial condition and operating
results.
We have obtained licenses and options to obtain licenses from third parties and may obtain additional licenses and options in the future. 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, if we do obtain necessary licenses, we will likely have obligations under those 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.
Our patent portfolio is in the early stages of prosecution. Although we have numerous patent applications pending, substantive prosecution has begun
in only a small number of those applications. We cannot provide any assurances that any of our pending patent applications will mature into issued patents
and, if they do, that such patents or our current patents will include claims with a scope sufficient to protect our product candidates or otherwise provide any
competitive advantage. For example, we are pursuing claims to therapeutic, binary compositions of certain bacterial populations. Any claims that may issue
may provide coverage for such binary compositions and/or their use. However, such claims would not prevent a third party from commercializing alternative
compositions that do not include both of the bacterial populations claimed in pending applications, potential applications or patents that have or may issue.
There can be no assurance that any such alternative composition will not be equally effective. Further, given that our SER-109 product candidate is a complex
composition with some variation from lot-to-lot and that, likewise, third-party compositions may have similar complexity and variability, it is possible that a
patent claim may provide coverage for some but not all lots of a product candidate or third-party product. These and other factors may provide opportunities
for our competitors to design around our patents, should they issue.
Moreover, other parties 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 or cover one or more of our products. In addition, given the early stage of prosecution of our
portfolio, it may be some time before we understand how patent offices react 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 which 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.
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We may be subject to third-party preissuance submissions of prior art to the United States Patent and Trademark Office, or USPTO, or in a foreign
jurisdiction in which our applications are filed, 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. For example, on April 25, 2017, we filed a notice of opposition in the
European Patent Office challenging the validity of a patent issued to The University of Tokyo. See “—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.” 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 products 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.
The degree of future protection for our proprietary rights is uncertain, and we cannot ensure that:
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any of our pending patent applications, if issued, will include claims having a scope sufficient to protect our product candidates or any other
products or product candidates;
any of our pending patent applications will issue as patents at all;
we will be able to successfully commercialize our product candidates, if approved, before our relevant patents expire;
we were the first to make the inventions covered by any existing patent and pending patent applications;
we were the first to file patent applications for these inventions;
others will not develop similar or alternative technologies that do not infringe or design around our patents;
others will not use pre-existing technology to effectively compete against us;
any of our patents, if issued, will be found to ultimately be valid and enforceable;
third parties will not compete with us in jurisdictions where we do not pursue and obtain patent protection;
we will be able to obtain and/or maintain necessary or useful licenses on reasonable terms or at all;
any patents issued to us will provide a basis for an exclusive market for our commercially viable products, will provide us with any competitive
advantages or will not be challenged by third parties;
we will develop additional proprietary technologies or product candidates that are separately patentable; or
our commercial activities or products will not infringe upon the patents or proprietary rights of others.
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 significantly harmed.
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If we are unable to protect the confidentiality of our trade secrets and know-how, our business and competitive position may be harmed.
In addition to seeking patents for some of our technology and product candidates, we also utilize our 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 products.
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, 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 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, only 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 will require us to be cognizant going forward 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 patent applications in our portfolio will 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, 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 Supreme Court, other federal courts, Congress, or the USPTO, may change the standards of patentability
and any such changes could have a negative impact on our business.
A number of cases decided by the Supreme Court have involved questions of when claims reciting abstract ideas, laws of nature, natural phenomena
and/or natural products are eligible for a patent, regardless of whether the claimed subject matter is otherwise novel and inventive. These cases include
Association for Molecular Pathology v. Myriad Genetics, Inc., 569 U.S. 12-398 (2013); Alice Corp. v. CLS Bank International, 573 U.S. 13-298 (2014); and
Mayo Collaborative Services v. Prometheus Laboratories, Inc., 566 U.S. 10-1150 (2012). In response to these cases, the USPTO has issued guidance to the
examining corps.
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The full impact of these decisions is not yet known. For example, in view of these and subsequent court decisions, the USPTO has issued various
materials to patent examiners providing guidance for determining the patent eligibility of claims reciting laws of nature, natural phenomena or natural
products. Our current product candidates include natural products, therefore, this decision and its interpretation by the courts and the USPTO may impact
prosecution, defense and enforcement of our patent portfolio. On March 4, 2014, the USPTO issued a memorandum reflecting the USPTO’s interpretation of
the cases related to patent eligibility of natural products. The March 4, 2014 memorandum was superseded by interim guidance published on December 15,
2014. Additional guidance was published in July 2015 (July 2015 Update: Subject Matter Eligibility) and May 2016 (May 2016 Subject Matter Eligibility
Update). The USPTO’s interpretation of the case law and new guidelines for examination may influence, possibly adversely, prosecution and defense of
certain types of claims in our portfolio.
In addition to increasing uncertainty with regard to our ability to obtain future patents, this combination of events has created uncertainty with respect
to the value of patents, once obtained. Depending on these and other decisions by 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, products or use of our products do not infringe third-party patents.
We are aware of numerous patents and pending applications owned by third parties 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 products or the use of our products. We are aware of several
pending patent applications containing one or more claims that could be construed to cover some of our product candidates or technology, should those claims
issue in their original form or in the form presently being pursued. In addition, we are aware of third-party patent families that include issued and allowed
patents, including claims that, if valid and enforceable, could be construed to cover some of our product candidates or their methods of use. On April 25,
2017, we filed a notice of opposition in the European Patent Office challenging the validity of a patent issued to The University of Tokyo and requesting that
it be revoked in its entirety for the reasons set forth in our opposition. The oral proceedings were held at the European Patent Office on February 18, 2019
and the Opposition Division required The University of Tokyo to narrow the scope of the claims of the patent. We expect The University of Tokyo to appeal.
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 products 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. If we were to challenge the validity of an issued U.S. patent in court, such as an issued U.S.
patent of potential relevance to some of our product candidates or methods of use, we would need to overcome a statutory presumption of validity that
attaches to every U.S. patent. This means that in order to prevail, we would have to present clear and convincing evidence as to the invalidity of the patent’s
claims. There is no assurance that a court would find in our favor on questions of infringement or validity.
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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 products 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 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 these 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. If we are unable to avoid infringing the patent rights of others, we may be required to seek a
license, defend an infringement action or challenge the validity of the patents in court, or redesign our products. Patent litigation is costly and time-
consuming. We may not have sufficient resources to bring these actions to a successful conclusion. In addition, intellectual property litigation or claims could
force us to do one or more of the following:
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cease developing, selling or otherwise commercializing our product candidates;
pay substantial damages for past use of the asserted intellectual property;
obtain a license from the holder of the asserted intellectual property, which license may not be available on reasonable terms, if at all; and
in the case of trademark claims, redesign, or rename, some or all of our product candidates or other brands to avoid infringing the intellectual
property rights of third parties, which may not be possible and, even if possible, could be costly and time-consuming.
Any of these risks coming to fruition could have a material adverse effect on our business, results of operations, financial condition and prospects.
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 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 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.
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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 legalize and submit formal documents. In such an event,
our competitors might be able to enter the market, which would have a material adverse effect on our business.
We may be subject to claims challenging the inventorship or ownership of our patents and other intellectual property.
It is our policy to enter into confidentiality and intellectual property assignment agreements with our employees, consultants, contractors and advisors.
These agreements generally provide that inventions conceived by the party in the course of rendering services to us will be our exclusive property. However,
these agreements may not be honored and may not effectively assign intellectual property rights to us. For example, even if we have a consulting agreement
in place with an academic advisor pursuant to which such academic advisor is required to assign any inventions developed in connection with providing
services to us, such academic advisor may not have the right to assign such inventions to us, as it may conflict with his or her obligations to assign all such
intellectual property to his or her employing institution.
Litigation may be necessary to defend against these and other claims challenging inventorship or ownership. If we fail in defending any such claims, in
addition to paying monetary damages, we may lose valuable intellectual property rights, such as exclusive ownership of, or right to use, valuable intellectual
property. Such an outcome could have a material adverse effect on our business. Even if we are successful in defending against such claims, litigation could
result in substantial costs and be a distraction to management and other employees.
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.
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.
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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. The statutory deadlines for pursuing patent protection
in individual foreign jurisdictions are based on the priority date of each of our patent applications. For each of the patent families that we believe provide
coverage for our product candidates, we decide whether and where to pursue 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, even if we do elect to
pursue patent rights outside the United States, 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 that in the United States. These
products may compete with our products and our patents or other intellectual property rights may not be effective or sufficient to prevent them from
competing. 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.
The laws of some foreign countries do not protect intellectual property rights to the same extent as the laws of the United States. Many companies
have encountered significant problems in protecting and defending intellectual property rights in certain foreign jurisdictions. The legal systems of some
countries, particularly developing countries, do not favor the enforcement of patents and other intellectual property protection, especially those relating to
biotechnology. This could make it difficult for us to stop the infringement of our patents, if obtained, or the misappropriation of our other intellectual property
rights. For example, many foreign countries have compulsory licensing laws under which a patent owner must grant licenses to third parties. In addition,
many countries limit the enforceability of patents against third parties, including government agencies or government contractors. In these countries, patents
may provide limited or no benefit. Patent protection must ultimately be sought on a country-by-country basis, which is an expensive and time-consuming
process with uncertain outcomes. Accordingly, we may choose not to seek patent protection in certain countries, and we will not have the benefit of patent
protection in such countries.
If our ability to obtain and, if obtained, enforce our patents to stop infringing activities is inadequate, third parties may compete with our products, and
our patents or other intellectual property rights may not be effective or sufficient to prevent them from competing. Accordingly, our intellectual property
rights around the world may be inadequate to obtain a significant commercial advantage from the intellectual property we develop or license.
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Our new corporate strategy and restructuring may not be successful.
Risks Related to Our Operations
On February 7, 2019, following a strategic business review, we announced our new strategy to focus our resources on advancing our highest-
priority, clinical-stage microbiome therapeutic candidates. As a result, we plan to concentrate on completing the SER-287 Phase 2b study in mild-to-moderate
UC, obtaining results from the ongoing SER-109 Phase 3 study for recurrent CDI and advancing the SER-401 Phase 1b study, in collaboration with the
Parker Institute for Cancer Immunotherapy and MD Anderson Cancer Center, to evaluate augmenting checkpoint inhibitor response in patients with
metastatic melanoma. The success of this strategic shift will depend on our ability to successfully advance our therapeutics candidates, complete our ongoing
studies, retain senior management or other highly qualified personnel, prioritize competing projects and efforts and obtain sufficient resources, including
additional capital. Accordingly, there are no assurances our change in strategic focus will be successful, which may have an adverse effect on our results of
operations and financial condition.
Also, on February 7, 2019, we announced the restructuring of our executive team and a reduction in our workforce by approximately 30 employees
and contractors, which in total represented approximately 30% of our workforce. The positions eliminated are primarily related to research, manufacturing,
and general and administrative services. Following the reduction in workforce, we expect to have approximately 100 full-time employees, and we believe we
will be appropriately resourced to continue executing on our current strategy. However, our workforce may not be sufficient to fully execute our strategic
shift, and we may not be able to effectively retain the management or personnel needed to fully implement our strategy. We estimate that we will incur one-
time costs related primarily to employee termination benefits between $1.5 million and $2.0 million. Our restructuring and reduction in workforce activities
may also result in unexpected risks or costs, such as employee claims and contractual disputes, and the risk that the actual financial and other impacts of the
reductions could vary materially from the outcomes anticipated, which may have a material 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 Eric Shaff, 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 with our 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 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 products. 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.
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We may expand our operational capabilities, and as a result, we may encounter difficulties in managing our growth, which could disrupt our operations.
We may 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 potential 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 potential growth, we may not be able to effectively manage the expansion of our operations or recruit
and train additional qualified personnel. The expansion of our operations may lead to significant costs and may divert our management and business
development resources. Any inability to manage growth could delay the execution of our business plans or disrupt our operations.
We will continue to incur increased costs as a result of being a public company, and our management will continue to devote substantial time to
compliance initiatives and corporate governance practices.
As a public company, we have incurred and will continue to incur significant legal, accounting and other expenses, particularly after we are no longer
an emerging growth company. The Sarbanes-Oxley Act of 2002, the Dodd-Frank Wall Street Reform and Consumer Protection Act, the listing requirements
of The Nasdaq Global Select 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 devote
and will need to continue to devote a substantial amount of time to these compliance initiatives. Moreover, these rules and regulations have increased and will
continue to increase our legal and financial compliance costs and make some activities more time-consuming and costly. For example, we expect that these
rules and regulations may make it more difficult and more expensive for us to maintain director and officer liability insurance, which in turn could make it
more difficult for us to attract and retain qualified members of our board of directors.
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 Securities and Exchange Commission 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 operating internationally could materially adversely affect our business.
We currently have limited international operations, but our business strategy incorporates potentially expanding internationally if any of our product
candidates receive regulatory approval. We currently plan to rely on collaborators, including NHS, to commercialize any approved products outside of the
United States. Doing business internationally involves a number of risks, including but not limited to:
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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;
failure by us to obtain and maintain regulatory approvals for the use of our products in various countries;
additional potentially relevant third-party patent rights;
complexities and difficulties in obtaining protection and enforcing our intellectual property;
difficulties in staffing and managing foreign operations;
complexities associated with managing multiple payor reimbursement regimes, government payors or patient self-pay systems;
limits in 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 products and exposure to foreign currency exchange rate fluctuations;
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natural disasters, political and economic instability, including wars, terrorism and political unrest, outbreak of disease, boycotts, curtailment of
trade and other business restrictions;
certain expenses including, among others, expenses for travel, translation and insurance; 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 U.S. Foreign Corrupt Practices Act, 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 information technology and other system failures.
Despite the implementation of security measures, our internal computer systems and data and those of our current and future contractors and
consultants are vulnerable to damage or compromise from computer viruses, unauthorized access, human error, loss of data privacy, 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 reputational damage 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, products 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;
unanticipated liabilities related to acquired companies;
additional exposure to cybersecurity risks and vulnerabilities from any newly acquired information technology infrastructure;
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.
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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 anticipated 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.
We have in the past been subject to securities class action litigation and may be subject to similar or other litigation in the future, which may harm our
business.
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. On September 28, 2016, a
purported stockholder filed a putative class action lawsuit in the U.S. District Court for the District of Massachusetts against us entitled Mariusz Mazurek v.
Seres Therapeutics, Inc., et.al. alleging false and misleading statements and omissions about our clinical trials for our product candidate SER-109 in our
public disclosures between June 25, 2015 and July 29, 2016. Although this lawsuit has been dismissed by the court, should we face similar or other litigation
again, it could result in substantial costs and a diversion of management’s attention and resources, which could harm our business. In addition, the uncertainty
of a pending lawsuit or potential filing of additional lawsuits could lead to more volatility and a reduction in our stock price.
If we fail to comply with environmental, health and safety laws and regulations, we could become subject to fines or penalties or incur costs that could
harm our business.
We 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
chemicals and biological materials such as human stool. 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. Our failure to comply with these laws and regulations also
may result in substantial fines, penalties or other sanctions.
Comprehensive tax reform bills could adversely affect our business and financial condition.
The U.S. government recently enacted comprehensive federal income tax legislation that includes significant changes to the taxation of business
entities. These changes include, among others, (i) a permanent reduction to the corporate income tax rate, (ii) a partial limitation on the deductibility of
business interest expense, (iii) a shift of the U.S. taxation of multinational corporations from a tax on worldwide income to a territorial system (along with
certain rules designed to prevent erosion of the U.S. income tax base) and (iv) a one-time tax on accumulated offshore earnings held in cash and illiquid
assets, with the latter taxed at a lower rate. Notwithstanding the reduction in the corporate income tax rate, the overall impact of this tax reform is uncertain,
and our business and financial condition could be adversely affected. We urge our stockholders to consult with their legal and tax advisors with respect to any
such legislation and the potential tax consequences of investing in our common stock.
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Risks Related to Our Common Stock
The price of our common stock may be volatile and fluctuate substantially, which could result in substantial losses for purchasers of our common stock.
Our stock price is likely to be volatile. Furthermore, 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, our
stockholders may not be able to sell their common stock at or above the price they paid for their common stock. 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;
actual or anticipated changes in our growth rate relative to our competitors;
results of clinical trials of our product candidates or those of our competitors;
developments related to any future collaborations;
regulatory or legal developments in the United States and other countries;
development of new product candidates that may address our markets and may 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 collaborators or our competitors of significant acquisitions, strategic partnerships, joint ventures, collaborations or
capital commitments;
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 and projections 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 anticipated 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;
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, have the ability to control or significantly influence all matters
submitted to stockholders for approval.
Our executive officers, directors and stockholders who owned more than 5% of our outstanding common stock and their respective affiliates, in the
aggregate, hold shares representing approximately 65% of our outstanding voting stock. As a result, if these stockholders were to 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 and approval of any merger, consolidation or
sale of all or substantially all of our assets. This concentration of ownership control may:
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delay, defer or prevent a change in control;
entrench our management and the board of directors; or
impede a merger, consolidation, takeover or other business combination involving us that other stockholders may desire.
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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. Moreover, holders of an aggregate of approximately 18.3 million shares of
our common stock 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
promulgated under the Securities Act of 1933, as amended, or the Securities Act, 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.
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 that term is used 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 $1.0 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:
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not being required to include audited financial statements in our selected financial data and in any future registration statements under the
Securities Act for any period prior to the earliest audited financial statements presented in our registration statement on Form S-1 for the initial
public offering of our common stock;
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 and from having to disclose the ratio of compensation of our chief executive officer to the median
compensation of our employees.
We cannot predict whether investors will find our common stock less attractive if we rely on these exemptions. If some investors find our common
stock less attractive as a result, there may be a less active trading market for our common stock and 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 issue an adverse or misleading opinion regarding our business, our common stock price and trading volume could
decline.
The trading market for our common stock is 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 clinical studies and operating results fail to meet the expectations of analysts, our stock price would likely decline. If one or more of
these analysts cease coverage of us or fail 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.
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Provisions in our restated certificate of incorporation and amended 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 amended and restated bylaws may discourage, delay or prevent a merger, acquisition or
other change in control of our company that stockholders may consider favorable, including transactions in which stockholders might otherwise receive a
premium for their 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. Among other things, these provisions include those establishing:
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a classified board of directors with three-year staggered terms, which may delay the ability of stockholders to change the membership of a
majority of our board of directors;
no cumulative voting in the election of directors, which limits the ability of minority stockholders to elect director candidates;
the exclusive right of our board of directors to elect a director to fill a vacancy created by the expansion of the board of directors or the
resignation, death or removal of a director, which prevents stockholders from filling vacancies on our board of directors;
the ability of our board of directors to authorize the issuance of shares of preferred stock and to determine the terms of those shares, including
preferences and voting rights, without stockholder approval, which could be used to significantly dilute the ownership of a hostile acquirer;
the ability of our board of directors to alter our bylaws without obtaining stockholder approval;
the required approval of the holders of at least two-thirds of the shares entitled to vote at an election of directors to adopt, amend or repeal our
bylaws or repeal the provisions of our restated certificate of incorporation regarding the election and removal of directors;
a prohibition on stockholder action by written consent, which forces stockholder action to be taken at an annual or special meeting of our
stockholders;
the requirement that a special meeting of stockholders may be called only by the chairman of the board of directors, the chief executive officer,
the president or the board of directors, which may delay the ability of our stockholders to force consideration of a proposal or to take action,
including the removal of directors; and
advance notice procedures that stockholders must comply with in order to nominate candidates to our board of directors or to propose matters
to be acted upon at a stockholders’ meeting, which may discourage or deter a potential acquirer from conducting a solicitation of proxies to
elect the acquirer’s own slate of directors or otherwise attempting to obtain control of us.
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 actions 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 and officers. 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 inapplicable or unenforceable in such action.
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Because we do not anticipate paying any cash dividends on our capital stock in the foreseeable future, capital appreciation, if any, will be the sole source
of gain for our stockholders.
We have never declared or paid cash dividends on our capital stock. We currently intend to retain all of our future earnings, if any, to finance the
growth and development of our business. As a result, capital appreciation, if any, of our common stock will be our stockholders’ sole source of gain for the
foreseeable future.
Item 1B. Unresolved Staff Comments
None.
Item 2. Properties
Research and Offices
Our corporate headquarters is located in Cambridge, Massachusetts, where we lease approximately 83,396 square feet of office, laboratory, and pilot
manufacturing space under a lease that expires in November 2023. We also maintain a research and development facility in Cambridge, Massachusetts, where
we lease approximately 7,484 square feet of office and laboratory facilities under a lease that expires in April 2020.
Clinical Manufacturing
We currently conduct part of our manufacturing operations in our leased facilities in Cambridge, Massachusetts, which contain manufacturing facilities
for clinical products. We believe our current laboratory facilities and contract relationships are sufficient to meet our current bioprocess development and
manufacturing needs. Product candidates may be brought into the facilities for economies of operation, or may remain external with contract manufacturing
organizations, depending on business dynamics and development needs.
We plan to control the production of all products under current good manufacturing practices by making strategic investments in manufacturing, which
may include collaborations with third parties, the design and renovation of existing facilities and the construction of additional new facilities for commercial
supply.
Item 3. Legal Proceedings
Opposition Proceeding
On October 19, 2016, the European Patent Office granted European Patent No. 2 575 835 B1 to The University of Tokyo. On April 25, 2017, we filed
a notice of opposition to this patent in the European Patent Office, requesting that it be revoked in its entirety for the reasons set forth in our opposition. The
oral proceedings were held at the European Patent Office on February 18, 2019 and the Opposition Division required The University of Tokyo to narrow the
scope of the claims of the patent. We expect The University of Tokyo to appeal.
Item 4. Mine Safety Disclosures
Not applicable.
Directors of the Registrant
Noubar B. Afeyan, Ph.D., has served as a member of our board of directors since October 2010. Since 1999, Dr. Afeyan has served as the Senior
Managing Partner and Chief Executive Officer of Flagship Pioneering, formerly known as Flagship Ventures, an early-stage venture capital firm that he co-
founded, which conceives, creates, resources and develops first-in-category life sciences companies. Dr. Afeyan serves on the boards of numerous privately
and publicly held companies, including Moderna, Inc., Rubius Therapeutics, Inc. Kaleido Biosciences, Inc. and Evelo Biosciences, Inc. and has previously
served on the board of directors of several public companies including, BG Medicine, Inc., BIND Therapeutics, Inc., and Sensen Bio (formerly Eleven
Biotherapeutics, Inc.). Dr. Afeyan received a B.S. in chemical engineering from McGill University and a Ph.D. in Biochemical Engineering from the
Massachusetts Institute of Technology. He is currently a visiting lecturer of business administration at Harvard Business School and was previously a senior
lecturer at the Massachusetts Institute of Technology’s Sloan School of Management where he taught courses on technology-entrepreneurship, innovation and
leadership.
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Dennis A. Ausiello, M.D., has served as a member of our board of directors since April 2015. Dr. Ausiello serves as the Director of the Center for
Assessment Technology and Continuous Health (CATCH), Jackson Distinguished Professor of Clinical Medicine at Harvard Medical School and Physician-
in-Chief Emeritus at Massachusetts General Hospital. From 1996 to April 2013, Dr. Ausiello served as the Chief of Medicine at Massachusetts General
Hospital. Dr. Ausiello is a member of the Institute of Medicine of the National Academy of Sciences and a fellow of the American Academy of Arts and
Sciences. Dr. Ausiello has also served on the board of directors of Pfizer Inc. since December 2006 and Alnylam Pharmaceuticals since April 2012. Dr.
Ausiello received his undergraduate degree from Harvard College and an M.D. from the University of Pennsylvania.
Grégory Behar has served as a member of our board of directors since December 2014. Mr. Behar has served as Chief Executive Officer of Nestlé
Health Science S.A., a health sciences company, since October 2014. From July 2011 to July 2014, Mr. Behar was President and Chief Executive Officer of
Boehringer Ingelheim Pharmaceuticals Inc. (USA), a pharmaceutical company. From 2010 to July 2011, Mr. Behar was Corporate Vice President Region
NECAR (North European Union, Canada and Australasia) for Boehringer-Ingelheim GmbH, a pharmaceutical company. Mr. Behar has also served on the
board of directors of Aimmune Therapeutics, Inc. since November 2016. Mr. Behar received his B.S. from the University of California, Los Angeles, an
M.S. in Mechanical Engineering and Manufacturing from EPFL in Switzerland and an MBA from INSEAD in France.
Willard Dere, M.D., has served on our board of directors since July 2017. Since November 2014, Dr. Dere has been Professor of Internal Medicine, B.
Lue and Hope S. Bettilyon Presidential Endowed Chair in Internal Medicine for Diabetes Research, Executive Director of Personalized Health, and Co-
Principal Investigator of the Center for Clinical and Translational Science at the University of Utah Health Sciences Center. Prior to his professorship, from
2003 until his retirement in October 2014, Dr. Dere held multiple roles at Amgen, including head of global development, and both corporate and international
chief medical officer, and led development of programs in various therapeutic areas. Dr. Dere has served on the boards of directors of BioMarin
Pharmaceutical since 2016, Radius Health since 2015, Mersana Therapeutics, Inc. since 2018 and Ocera Therapeutics between 2016 and 2017. Dr. Dere
received his undergraduate and medical degrees from the University of California, Davis, completed his internal medicine residency training at the University
of Utah, and his postdoctoral training in endocrinology and metabolism at the University of California, San Francisco.
Richard N. Kender has served as a member of our board of directors since October 2014. From October 1978 to September 2013, Mr. Kender held
positions in a variety of corporate areas at Merck & Co., Inc., or Merck, a pharmaceutical company, most recently serving as Senior Vice President of
Business Development and Corporate Licensing. Mr. Kender has served on the board of directors of Poxel S.A. since 2015 and Abide Therapeutics, Inc. since
2015, and previously served on the boards of director of INC Research Holdings, Inc. between 2014 and 2017. Mr. Kender received a B.S. from Villanova
University and an M.B.A. from Fairleigh Dickinson University.
Lorence H. Kim, M.D., has served as a member of our board of directors since October2014. Since April 2014, Dr. Kim has been the Chief Financial
Officer of Moderna Therapeutics, a biotechnology company. From July 2000 to April 2014, Dr. Kim held a number of positions at Goldman, Sachs & Co., an
investment bank, most recently as Managing Director and Co-Head of Biotechnology Investment Banking. Dr. Kim received an A.B. from Harvard
University, an MBA in Healthcare Management from the Wharton School of the University of Pennsylvania, and an M.D. from the University of
Pennsylvania’s School of Medicine.
Kurt C. Graves has served as a member of our board of directors since November 2015. Mr. Graves has been the Chairman, President and Chief
Executive Officer of Intarcia Therapeutics, a biotechnology company, since April 2012. Mr. Graves served as Executive Chairman of Biolex Therapeutics, a
biotechnology company, from November 2010 to March 2012, and served as Executive Chairman of Intarcia Therapeutics from August 2010 to April 2012.
Previously, he served as Executive Vice President, Chief Commercial Officer and Head of Strategic Development at Vertex Pharmaceuticals Inc. from July
2007 to October 2009. Prior to joining Vertex, Mr. Graves held various leadership positions at Novartis pharmaceuticals from 1999 to June 2007. He was also
the first Chief Marketing Officer for the Pharmaceuticals division from September 2003 to June 2007. He has served as a director of Intarcia Therapeutics,
Inc. since 2012, Radius Health, Inc. since 2011, and Achillion Pharmaceuticals, Inc. since 2012. Mr. Graves received a B.S. in Biology from Hillsdale
College.
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Roger J. Pomerantz, M.D., has served as Chairman of our board of directors since November 2013. Previously, he served as our President and Chief
Executive Officer from June 2014 to January 2019. Since July 2014, Dr. Pomerantz has been a Senior Partner at Flagship Pioneering, formerly known as
Flagship Ventures, an early-stage venture capital firm. From January 2011 to September 2013, Dr. Pomerantz was Worldwide Head of Licensing and
Acquisitions and Senior Vice President at Merck, where he oversaw licensing and acquisitions for Merck Research Laboratories, the research and
development division of Merck. From February 2010 to February 2013, Dr. Pomerantz served as Global Head of Infectious Diseases and Senior Vice
President at Merck, where he oversaw pharmaceutical development and discovery of antibiotics, antivirals, antifungals and antiparasitic agents. Prior to
Merck, Dr. Pomerantz was Global Head of Infectious Diseases for the pharmaceutical division of Johnson & Johnson, Inc., a multinational medical device,
consumer goods and pharmaceutical corporation, where he was responsible for anti-infective agents worldwide. He joined Johnson & Johnson, Inc. in August
2005 as President of Tibotec Pharmaceuticals, Inc., now Janssen Therapeutics and a subsidiary of Johnson & Johnson, Inc., a pharmaceutical company
focused on the treatment of infectious diseases. Dr. Pomerantz has developed ten approved infectious disease drugs for diseases including HIV, HCV and
tuberculosis. He has served on the boards of director of Contrafect Corporation, since 2014, Rubius Therapeutics, Inc., since 2014, and Intec Therapeutics,
Inc since 2018. Dr. Pomerantz received his B.A. in Biochemistry from The Johns Hopkins University and his M.D. from The Johns Hopkins School of
Medicine.
Eric D. Shaff has served as our Chief Executive Officer and a member of our board of directors since January 2019. Previously, he served as our Chief
Operating and Financial Officer and Executive Vice President from January 2018 until January 2019 and as our Chief Financial Officer from November 2014
to January 2019. Mr. Shaff has also served on the board of directors of Sigilon Therapeutics, Inc. since November 2017. From January 2012 to November
2014, Mr. Shaff was Vice President of Corporate Finance for Momenta Pharmaceuticals, a biotechnology company, where he helped manage Momenta’s
accounting, finance, planning, and procurement functions, as well as contributing to Momenta’s investor relations efforts. From June 2004 to December 2011,
Mr. Shaff held a number of corporate development and finance positions with Genzyme Corporation, a biotechnology company, most recently as Vice
President of Finance/Controller for the Personalized Genetic Health division. Mr. Shaff received his B.A. from the University of Pennsylvania and his MBA
from Cornell University.
Meryl Zausner has served as a member of our board of directors since August 2018. From April 2012 to November 2014, Ms. Zausner served as chief
financial and administrative officer of Novartis Pharmaceuticals Inc. in the United States and served as a member of the Pharmaceutical Executive Committee
and Global Finance Leadership Team. At Novartis, she helped launch the Oncology Business Unit, as well as the company’s shared services organization.
Prior to serving as chief financial and administrative officer, Ms. Zausner was a member of the Novartis Global Oncology leadership team and chief financial
officer, where she contributed to the development and commercialization of therapies, including Gleevec® (imatinib). Ms. Zausner also serves on the boards
of directors of Neon Therapeutics, Inc. and the Multiple Myeloma Research Foundation. Ms. Zausner received a B.S. in accounting and economics from the
University at Albany, SUNY.
Executive Officers of the Registrant
John G. Aunins, Ph.D., has served as our Chief Technology Officer and Executive Vice President of Bioprocess Development since December 2012.
Prior to joining our company, Dr. Aunins served on our Scientific Advisory Board from February 2012 to December 2012. From April 1989 to November
2011, Dr. Aunins served in various roles at Merck, most recently as Executive Science Director. At Merck, Dr. Aunins led process and product development
teams for six licensed vaccines and multiple vaccine candidates. He is a Fellow of the American Institute for Medical and Biological Engineering and an
adjunct Full Professor at the Instituto de Tecnologia Quimica e Biologica in Oeiras, Portugal. Dr. Aunins received his B.S. from the University of Kansas and
his Ph.D. in Chemical Engineering from the Massachusetts Institute of Technology.
Thomas J. DesRosier has served as our Chief Legal Officer, Executive Vice President, and Secretary since May 2016. Previously, he served as
Executive Vice President, Chief Legal and Administrative Officer and Secretary of ARIAD Pharmaceuticals, Inc., a biopharmaceutical company, from 2015
to 2016, as Executive Vice President, Chief Legal and Administrative Officer and Secretary of Cubist Pharmaceuticals, Inc., or Cubist, a biopharmaceutical
company, from 2014 to 2015 and as Senior Vice President, Chief Legal Officer and Secretary of Cubist from 2013 to 2014. Before that, Mr. DesRosier served
as Senior Vice President, General Counsel North America of Sanofi, a global biopharmaceutical company, from 2011 to 2013. From 1999 to 2011,
Mr. DesRosier held several increasing leadership roles within the legal group of Genzyme Corporation, a biotechnology company, culminating in his role as
Senior Vice President, Chief Legal Officer. Mr. DesRosier serves as a director on the board of Avanir Pharmaceuticals, a Delaware corporation and wholly-
owned subsidiary of Otsuka Pharmaceutical Company, Ltd. Mr. DesRosier earned a B.A. in chemistry from the University of Vermont and a J.D. from Wake
Forest University School of Law.
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Matthew Henn, Ph.D., has served as our Executive Vice President and Chief Scientific Officer since February 2019. Since joining at the launch of our
company in June 2012, he has held positions of increasing seniority, most recently prior to his current position he served as our Executive Vice President,
Head of Discovery and Microbiome R&D. Prior to Seres, he was the Director of Viral Genomics and Assistant Director of the Genome Sequencing Center
for Infectious Diseases at the Broad Institute of MIT and Harvard. He currently serves on the scientific advisory boards of the Forsyth Institute
and Growcentia, Inc, an agricultural microbiome company. Dr. Henn earned his B.S. in ecology and evolutionary sciences from the University of New
Hampshire and his Ph.D. in ecosystem sciences from the University of California at Berkeley, were he was a NASA Earth Systems Sciences Fellow, and
trained as a NSF Postdoctoral Fellow in Microbiology at Duke University.
Kevin Horgan, M.D., has served as our Chief Medical Officer and Executive Vice President since October 2018. Dr. Horgan has contributed to the
development and approval of multiple therapeutics across immunological and oncology indications. Most recently, from April 2015 to October 2018, Dr.
Horgan was Vice President of Clinical Development at Astra Zeneca, where he led the development of combination immune-oncology programs. Prior to
Tucana, Dr. Hogan held Chief Medical Officer roles at Soligenix from January 2011 to October 2013 and Coronado from October 2013 to January 2014. Prior
to those roles, he was Vice President of Clinical Immunology at Centocor during the development and approval of Remicade, Stelara and Simponi. Dr. Hogan
began his industry career at Merck, following positions in academic medicine at the University of California, Los Angeles. Dr. Horgan earned his
undergraduate and medical degrees from University College Cork in Ireland. He did his medical residency on the Osler Service, at The Johns Hopkins
Medical School and Medical Center in Baltimore, MD.
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Item 5. Market for Registrant’s Common Equity, Related Stockholder Matters and Issuer Purchases of Equity Securities
Our common stock is been traded on The Nasdaq Global Select Market under the symbol “MCRB.”
PART II
Stock Performance Graph
The graph set forth below compares the cumulative total stockholder return on our common stock between June 26, 2015 (the date of our initial public
offering) and December 31, 2018, with the cumulative total return of (a) the Nasdaq Biotechnology Index and (b) the Nasdaq Composite Index, over the same
period. This graph assumes the investment of $100 on June 26, 2015 in our common stock, the Nasdaq Biotechnology Index and the Nasdaq Composite Index
and assumes the reinvestment of dividends, if any. The graph assumes our closing sales price on June 26, 2015 of $51.40 per share as the initial value of our
common stock and not the initial offering price to the public of $18.00 per share.
Holders
As of February 28, 2019, there were approximately 20 holders of record of our common stock. 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. The
number of holders of record also does not include stockholders whose shares may be held in trust by other entities.
We have not paid any cash dividends on our common stock since inception and do not anticipate paying cash dividends in the foreseeable future.
Dividends
We did not make any sales of unregistered securities during the quarter ended December 31, 2018.
Recent Sales of Unregistered Securities
Purchases of Equity Securities by the Issuer or Affiliated Purchasers
There were no repurchases of shares of common stock made during the quarter ended December 31, 2018.
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Item 6. Selected Consolidated Financial Data
The following selected consolidated financial data should be read in conjunction with “Management’s Discussion and Analysis of Financial Condition
and Results of Operations,” our consolidated financial statements and related notes, and other financial information included in this Annual Report on
Form 10-K. We have derived the consolidated statement of operations data for the years ended December 31, 2018, 2017, and 2016 and the consolidated
balance sheet data as of December 31, 2018 and 2017 from our audited consolidated financial statements, which are included elsewhere in this Annual Report
on Form 10-K. The consolidated statement of operations and consolidated balance sheet data as of December 31, 2015 and 2014 are derived from our audited
consolidated financial statements that are not included in this Annual Report on Form 10-K. Our historical results are not necessarily indicative of the results
that should be expected in the future.
Consolidated Statement of Operations Data:
Collaboration revenue - related party(1)
Grant revenue
Total revenue
Operating expenses:
Research and development
General and administrative
Total operating expenses
Loss from operations
Other income (expense):
Interest income (expense), net
Other income
Revaluation of preferred stock warrant
liability
Total other income (expense), net
Net loss
Accretion of convertible preferred stock to
redemption value
Net loss attributable to common stockholders
Net loss per share attributable to common
stockholders, basic and diluted(2)
2018
Year Ended December 31,
2017
2015
2016
(in thousands, except per share data)
2014
$
26,917 $
1,350
28,267
32,100 $
—
32,100
21,766 $
—
21,766
— $
—
—
—
95,955
32,596
128,551
(100,284)
89,455
34,040
123,495
(91,395)
81,989
32,616
114,605
(92,839)
38,095
16,761
54,856
(54,856)
10,718
4,364
15,082
(15,082)
1,172
170
1,590
425
1,260
—
83
—
(209)
—
—
1,342
(98,942)
—
2,015
(89,380)
—
1,260
(91,579)
(7)
76
(54,780)
(1,418)
(1,627)
(16,709)
—
(1,291)
$ (98,942) $ (89,380) $ (91,579) $ (54,780) $ (18,000)
—
—
—
$
(2.43) $
(2.21) $
(2.30) $
(2.33) $
(2.67)
(1) We adopted ASC 606 on January 1, 2018, using the modified retrospective method for all contracts not completed as of the date of adoption. Our
reported results for 2018 reflect the application of ASC 606 guidance while our reported results for 2017 and 2016 were prepared under the guidance
outlined in ASC 605. See Note 9 to our consolidated financial statements appearing at the end of this Annual Report on Form 10-K for further details.
See Note 11 to our consolidated financial statements appearing at the end of this Annual Report on Form 10-K for further details on the calculation of
basic and diluted net loss per share attributable to common stockholders.
(2)
Consolidated Balance Sheet Data:
Cash and cash equivalents
Investments
Working capital(1)
Total assets
Preferred stock warrant liability
Long-term debt, net of discount,
including current portion
Convertible preferred stock(2)
Total stockholders’ equity (deficit)
2018
2017
As of December 31,
2016
(in thousands)
2015
2014
$
85,820 $
—
50,624
120,472
—
36,088 $
113,895
123,453
189,522
—
54,539 $
175,456
167,912
272,646
—
73,933 $ 114,185
—
109,140
117,345
1,582
131,149
196,690
216,900
—
—
—
(48,045)
—
—
60,699
—
—
132,631
—
—
205,394
2,504
136,077
(26,721)
(1) We define working capital as current assets less current liabilities.
(2)
Convertible preferred stock was converted into our common stock upon the listing of our common stock on The Nasdaq Global Select Market on
June 26, 2015. See Note 8 to our consolidated financial statements appearing at the end of this Annual Report on Form 10-K for further details.
71
Item 7. Management’s Discussion and Analysis of Financial Condition and Results of Operations
You should read the following discussion and analysis of financial condition and results of operations together with Item 6 “Selected Consolidated
Financial Data” and our consolidated financial statements and related notes included 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. Factors that could cause or contribute to such differences include, but are not limited to, those discussed in Item 1A. Risk Factors.
Overview
We are a microbiome therapeutics platform company developing a novel class of biological drugs, which are designed to treat disease by restoring the
function of a dysbiotic microbiome. SER-287 is being developed to treat ulcerative colitis, or UC. Our lead product candidate, SER-109, is designed to reduce
recurrences of Clostridium difficile, or C. difficile infection, or CDI, a debilitating infection of the colon, in patients who have received antibiotic therapy for
recurrent CDI by treating the dysbiosis of the colonic microbiome and, if approved by the U.S. Food and Drug Administration, or FDA, could be a first-in-
field oral microbiome drug. In addition, using our microbiome therapeutics platform, we are developing product candidates to treat diseases where the
microbiome is implicated, including SER-301, a rationally designed, fermented inflammatory bowel disease, or IBD, candidate, and SER-401, a microbiome
therapeutic candidate for use with checkpoint inhibitors, or CPIs, in patients with metastatic melanoma. We continue to evaluate microbiome pharmacokinetic
and pharmacodynamic data from the SER-262 Phase 1b study and other completed clinical trials, in addition to insights gained from research efforts with our
other rationally designed Ecobiotic microbiome therapeutic candidates, in order to determine next steps in the development of both SER-262 to treat an initial
recurrence of CDI, and SER-155 to modulate the microbiome and dysbioses in patients following allogeneic hematopoietic stem cell transplants. We are also
using our microbiome therapeutics platform to conduct research on various indications, including: infectious diseases, metabolic diseases, and inflammatory
and immune diseases, including immuno-oncology.
Since our inception in October 2010, we have devoted substantially all of our resources to developing our programs, building our intellectual property
portfolio, developing our supply chain, business planning, raising capital and providing general and administrative support for these operations.
All of our product candidates other than SER-287, SER-109, SER-262 and SER-401 are still in preclinical development or early stage discovery. Our
ability to generate product revenue sufficient to achieve profitability will depend heavily on the successful development and eventual commercialization of
one or more of our product candidates. Since our inception, we have incurred significant operating losses. Our net loss was $98.9 million for the twelve
months ended December 31, 2018. As of December 31, 2018, we had an accumulated deficit of $389.4 million and cash and cash equivalents totaling $85.8
million. Based on our current plans and forecasted expenses, we believe that our existing cash and cash equivalents as of December 31, 2018, will enable us
to fund our operating expenses and capital expenditure requirements into the fourth quarter of 2019, raising a substantial doubt regarding our ability to
continue as a going concern. 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. As further discussed in “—Liquidity and Capital Resources” below, these factors raise substantial doubt about our ability to continue as a
going concern.
On October 2, 2017, we announced positive topline results from our Phase 1b clinical trial of SER-287 in patients with UC who were failing current
therapies. The SER-287 Phase 1b study, a randomized, double-blinded, placebo-controlled, multiple-dose, induction study enrolled 58 patients at 20 sites
across the United States with active mild-to-moderate UC, with Total Modified Mayo scores of 4 to 10. Study subjects exhibited pre-study disease activity
despite use of current therapies in a majority of subjects, which included 5-amino-salacylic acid, low dose corticosteroids, or immunomodulatory
therapy. Evaluation of SER-287 safety and tolerability was a primary study endpoint and study results showed no drug-related serious adverse events and no
imbalance in adverse events in SER-287-treated patients as compared to patients treated with placebo.
Analyses of study patients’ microbiome data, a co-primary study endpoint of the trial, demonstrated that SER-287 induced dose-dependent
engraftment of SER-287-derived bacterial species into the colonic microbiome of the patients treated with SER-287. Patients administered vancomycin pre-
treatment followed by daily administration of SER-287 had the highest level of SER-287 engraftment, which was statistically significant. This patient cohort
corresponded with the study arm where the most significant clinical benefits were observed, including clinical remission and endoscopic improvement.
Differences in the composition of the microbiome post treatment were also associated with clinical remission. Bacterial engraftment signatures were durable
throughout the dosing period of the trial and were also observed at four weeks post administration of the final SER-287 dose. The pharmacologic impact of
the SER-287 engraftment was supported by metabolomic and transcriptomic data. Analysis of metabolites and gene expression signatures associated with
inflammation and immune modulation, were observed to be correlated with remission in SER-287 treated subjects.
72
In December 2018, we initiated our Phase 2b trial, ECO-RESET, evaluating SER-287 in patients with active mild-to-moderate ulcerative colitis. Based
on feedback obtained from the FDA on the SER-287 Phase 2b study design, we believe that the study could serve as one of two required pivotal trials
supporting potential future registration of SER-287. The Phase 2b study is a three-arm placebo-controlled trial of approximately 200 patients with active
mild-to-moderate UC. Two groups of patients will receive different doses of SER-287, both following pretreatment with a short course of oral vancomycin. A
third study arm will receive placebo. The study’s primary endpoint will evaluate clinical remission measured after 10 weeks of SER-287 administration.
Endoscopic improvement will be measured as a secondary efficacy measure. We expect to complete study enrollment by mid-2020.
In June 2017 we initiated a Phase 3 clinical study of SER-109, termed ECOSPOR III, in approximately 320 patients with multiply recurrent CDI.
Based on analysis of the available clinical, microbiome, and chemistry, manufacturing and control data from our Phase 1b and Phase 2 clinical studies of
SER-109, diagnosis of CDI for both study entry and for endpoint analysis will be confirmed by C. difficile cytotoxin assay, rather than polymerase chain
reaction, or PCR, which was used in the prior studies. Patients in the SER-109 arm will receive a total SER-109 dose, administered over three days,
approximately 10-fold higher than the dose used in the Phase 2 clinical study. The study will evaluate patients for 24 weeks and the primary endpoint will
compare the CDI recurrence rate in subjects who receive SER-109 verses placebo at up to eight weeks after dosing. ECOSPOR III enrolment continues to
progress, with over 100 sites open across the United States and Canada. Several factors have impacted study enrollment, including the C. difficile cytotoxin
test required for diagnosis, which has screened out some individuals who might otherwise have been included had we used PCR-based testing, and the
widespread availability of unapproved and unregulated fecal microbiota transplantation. We continue to add and implement various operational measures to
expedite study enrollment. Additionally, we are considering alternatives, including study design modification, to expedite the availability of clinical results.
We have initiated a Phase 1b clinical study with our collaborators at MD Anderson Cancer Center, or MD Anderson, and the Parker Institute for
Cancer Immunotherapy, or the Parker Institute, of SER-401, a donor derived microbiome therapy designed to replicate the bacterial signature found in the
approximately one third of patients who have a robust response to anti-PD-1 therapy. SER-401 is designed to modify the cancer immune set point and
meaningfully improve patients’ response to checkpoint inhibitor therapy. The scientific basis for SER-401 is supported by published findings from our
collaborator, Dr. Jennifer Wargo of MD Anderson, indicating that a specific set of bacteria in the gastrointestinal microbiome can have an important role in
determining the immunological response to checkpoint inhibitor therapy. Our own preclinical research has extended these findings and continues to ascertain
how specific bacterial species impact the response to checkpoint inhibitors. These data demonstrate the strong role of specific bacterial species in anti-tumor
response to anti-PD-1 therapy and on the impact of the microbiome the immune system and on specific T cell classes, including CD8 and T regulatory cells.
We continue to evaluate microbiome pharmacokinetic and pharmacodynamic data from the SER-262 Phase 1b study and other completed clinical
trials, in addition to insights gained from preclinical research efforts with our other rationally designed Ecobiotic microbiome therapeutic candidates, in order
to determine future steps in the development of both SER-262 and SER-155.
While we plan to focus our investment on our highest priority clinical programs in the near-term, our expenses may increase substantially in
connection with our ongoing and planned activities, particularly as we:
•
•
•
•
•
•
•
•
•
•
continue the clinical development of SER-109, our lead product candidate, in the Phase 3 clinical study;
continue the clinical development of SER-287 for the treatment of UC;
continue the clinical development of SER-401, a microbiome therapeutic candidate for use with CPIs in a Phase 1b clinical trial in patients with
metastatic melanoma;
conduct research and continue preclinical development of SER-301, our rationally designed IBD product candidate;
make strategic investments in manufacturing capabilities;
maintain and augment our intellectual property portfolio and opportunistically acquire complementary intellectual property;
potentially establish a sales and distribution infrastructure and scale-up manufacturing capabilities to commercialize any products for which we
may obtain regulatory approval;
perform our obligations under the license and collaboration agreement with Nestec Ltd., or NHS;
seek to obtain regulatory approvals for our product candidates; 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 challenges.
73
In addition, if we obtain marketing approval for any of our product candidates, we expect to incur significant commercialization expenses related to
product manufacturing, marketing, sales and distribution. Furthermore, we expect to continue to incur additional costs associated with operating as a public
company.
As a result, we will need additional financing to support our continuing operations. Until such time as we can generate significant revenue from
product sales, if ever, we expect to finance our operations through a combination of public or private equity or debt financings or other sources, which may
include collaborations with third parties. Adequate additional financing may not be available to us on acceptable terms, or at all. Our inability to raise capital
as and when needed would have a negative impact on our financial condition and our ability to pursue our business strategy. We will need to generate
significant revenue to achieve profitability, and we may never do so. If we are unable to raise sufficient capital to fund our current operating plans in the next
twelve months, we may need to reduce our expenditures, potentially requiring us, among other things, to delay, scale back, or eliminate some or all of our
planned clinical trials and other research and development programs.
In January 2016, we entered into a Collaboration and License Agreement, or the License Agreement, with NHS, for the development and
commercialization of certain of our product candidates in development for the treatment and management of CDI and IBD, including UC and Crohn’s
disease. The License Agreement supports the development of our portfolio of products for CDI and IBD in markets outside of the United States and Canada,
or the Licensed Territory, and is expected to provide financial support for our ongoing research and development. We have retained full commercial rights to
our entire portfolio of product candidates with respect to the United States and Canada, where we plan to build our own commercial organization.
Under the License Agreement, we granted to NHS an exclusive, royalty-bearing license to develop and commercialize, in the Licensed Territory,
certain products based on our microbiome technology that are being developed for the treatment of CDI and IBD, including SER-109, SER-262, SER-287
and SER-301, or, collectively, the NHS Collaboration Products. We also granted to NHS a non-exclusive license to export, develop and make NHS
Collaboration Products in the licensed fields worldwide solely for commercialization in the licensed fields and in the Licensed Territory.
In exchange for the license, NHS made an upfront cash payment of $120.0 million to us in February 2016. NHS has also agreed to pay us tiered
royalties, at percentages ranging from the high single digits to high teens, of net sales of NHS Collaboration Products in the Licensed Territory. Additionally,
NHS has agreed to pay us up to $285.0 million in development milestone payments, $375.0 million in regulatory payments and up to an aggregate of $1.125
billion for the achievement of certain commercial milestones related to the sales of NHS Collaboration Products. We received a $10.0 million milestone
payment in 2016 associated with the initiation of a Phase 1b study for SER-262 in CDI. In June 2017, we initiated a Phase 3 clinical study of SER-109
(ECOSPOR III) in patients with multiply recurrent CDI. In July 2017, we recorded revenue of $20.0 million based on the achievement of this milestone under
the License Agreement.
In November 2018, we executed a letter agreement with NHS, or the Letter Agreement, modifying certain terms of the License Agreement. Under the
Letter Agreement, NHS agreed to pay us the $20.0 million Phase 3 milestone payment upon commencement of the Phase 2b study for SER-287. In December
2018, we received $40.0 million in milestone payments in connection with the commencement of the Phase 2b study for SER-287. The full potential value of
the upfront payment and milestone payments payable by NHS is over $1.9 billion, assuming all products receive regulatory approval and are successfully
commercialized. NHS is also obligated to pay some of the costs related to our clinical trials. See “—Liquidity and Capital Resources.”
Revenue
To date we have not generated any revenues from the sale of products. Our revenues have primarily been derived from the License Agreement with
Financial Operations Overview
NHS.
Operating Expenses
Our operating expenses since inception have consisted primarily of research and development activities and general and administrative costs.
74
Research and Development Expenses
Research and development expenses consist primarily of costs incurred for our research activities, including our discovery efforts, and the
development of our product candidates, which include:
•
•
•
•
•
•
expenses incurred under agreements with third parties, including contract research organizations, or CROs, that conduct research, preclinical
activities and clinical trials on our behalf as well as contract manufacturing organizations that manufacture drug products for use in our
preclinical and clinical trials;
salaries, benefits and other related costs, including stock-based compensation expense, for personnel in our research and development
functions;
costs of outside consultants, including their fees, stock-based compensation and related travel expenses;
the cost of laboratory supplies and acquiring, developing and manufacturing preclinical study and clinical trial materials;
costs related to compliance with regulatory requirements; and
facility-related expenses, which include direct depreciation costs and allocated expenses for rent and maintenance of facilities and other
operating costs.
We expense research and development costs as incurred. We recognize external development costs based on an evaluation of the progress to
completion of specific tasks using information provided to us by our vendors and our clinical investigative sites. Payments for these activities are based on the
terms of the individual agreements, which may differ from the pattern of costs incurred, and are reflected in our financial statements as prepaid or accrued
research and development expenses. Costs incurred under our license agreement with NHS are included in the costs listed above. All costs associated with
the License Agreement are recorded in research and development expense in the consolidated statements of operations and comprehensive loss.
Our primary focus of research and development since inception has been on our microbiome therapeutics platform and the subsequent development of
our programs. Our direct research and development expenses are tracked on a program-by-program basis and consist primarily of external costs, such as fees
paid to investigators, consultants, CROs in connection with our preclinical studies and clinical trials, lab supplies and consumables, and regulatory fees. We
do not allocate employee-related costs and other indirect costs to specific research and development programs because these costs are deployed across
multiple product programs under development and, as such, are classified as costs of our microbiome therapeutics platform research, along with external costs
directly related to our microbiome therapeutics platform.
The table below summarizes our research and development expenses incurred on our platform and by product development program for those that
have begun clinical development.
Microbiome therapeutics platform
SER-109
SER-262
SER-287
Total research and development expenses
2018
Year Ended December 31,
2017
(in thousands)
2016
$
$
62,804 $
18,482
3,090
11,579
95,955 $
63,695 $
16,306
4,971
4,483
89,455 $
46,611
25,386
5,269
4,723
81,989
Research and development activities are central to our business model. Product candidates in later stages of clinical development generally have higher
development costs than those in earlier stages of clinical development, primarily due to the increased size and duration of later-stage clinical trials. We expect
that our research and development expenses will continue to increase in the foreseeable future as we advance the clinical development of SER-287, complete
our ECOSPOR III Phase 3 clinical study of SER-109, continue to discover and develop additional product candidates, including SER-401, SER-155 and
SER-301 and pursue later stages of clinical development of our product candidates.
Research and development expenses of $96.0 million for the year ended December 31, 2018 were comprised of $7.8 million in external services, $28.1
million in clinical and manufacturing costs, and $60.1 million in other costs.
75
General and Administrative Expenses
General and administrative expenses consist primarily of salaries and other related costs, including stock-based compensation, for personnel in our
executive, finance, corporate and business development and administrative functions. General and administrative expenses also include legal fees relating to
patent and corporate matters; professional fees for accounting, auditing, tax and consulting services; insurance costs; travel expenses; and facility-related
expenses, which include direct depreciation costs and allocated expenses for rent and maintenance of facilities and other operating costs.
Our general and administrative expenses may increase in the future if we increase our headcount to support the potential growth in our research and
development activities and the potential commercialization of our product candidates. We also may continue to incur increased expenses associated with
being a public company, including increased costs of accounting, audit, legal, regulatory and tax-related services associated with maintaining compliance with
exchange listing and the requirements of the Securities and Exchange Commission, director and officer insurance costs and investor and public relations
costs.
Other Income (Expense), Net
Interest Income (Expense), Net
Interest income consists of interest earned on our cash, cash equivalents and investments.
Other Income
Other income consists of an award from the Massachusetts Life Sciences Center that we earned in 2017 when we met the required employment
thresholds.
Income Taxes
Since our inception in 2010, we have not recorded any U.S. federal or state income tax benefits for the net losses we have incurred in each year or our
earned research and development tax credits, due to our uncertainty of realizing a benefit from those items. As of December 31, 2018, we had federal and
state net operating loss carryforwards of $185.6 million and $185.9 million, respectively, both of which begin to expire in 2035. As of December 31, 2018, we
also had federal and state research and development tax credit carryforwards of $28.6 million and $4.9 million, respectively, which begin to expire in 2031
and 2028, respectively. The federal research and development tax credits include an orphan drug credit carryforward of $17.5 million.
Critical Accounting Policies and Significant Judgments and Estimates
Our consolidated financial statements are prepared in accordance with generally accepted accounting principles, or GAAP, in the United States. The
preparation of our consolidated financial statements and related disclosures requires us to make estimates and assumptions that affect the reported amount of
assets, liabilities, revenue, costs and expenses and related disclosures. We believe that the estimates and assumptions involved in the accounting policies
described below may have the greatest potential impact on our consolidated financial statements and, therefore, consider these to be our critical accounting
policies. We evaluate our estimates and assumptions on an ongoing basis. Our actual results may differ from these estimates under different assumptions and
conditions.
Revenue Recognition
We recognize revenue in accordance with the guidance under ASC 606, Revenue from Contracts with Customers. ASC 606 applies to all contracts
with customers, except those contracts that are within the scope of other guidance, such as leases, insurance, and financial instruments. We enter into
agreements that are within the scope of ASC 606, under which we license certain of our product candidates and perform research and development services in
connection with such arrangements. The terms of these arrangements typically include payment of one or more of the following: nonrefundable up-front fees,
reimbursement of research and development costs, development, clinical, regulatory and commercial sales milestone payments, and royalties on net sales of
licensed products. Under ASC 606, we recognize revenue when our customer obtains control of promised goods or services, in an amount that reflects the
consideration which we expect to receive in exchange for those goods or services. When determining the timing and extent of revenue recognition for
arrangements that we determine are within the scope of ASC 606, we perform the following five steps:
(i)
(ii)
(iii)
(iv)
(v)
identify the contract(s) with a customer;
identify the performance obligations in the contract;
determine the transaction price;
allocate the transaction price to the performance obligations in the contract; and
recognize revenue when (or as) the entity satisfies a performance obligation.
76
We only apply the five-step model to contracts when it is probable that we will collect the consideration to which we are entitled in exchange for the
goods or services transferred to our 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 the contract
to determine whether each promised good or service is a performance obligation. The promised goods or services in our arrangements typically consist of a
license to our intellectual property and/or research and development services. We may provide options to additional items in such arrangements, which are
accounted for as separate contracts when our customer elects to exercise such options, unless the option provides a material right to our
customer. Performance obligations are promises in a contract to transfer a distinct good or service to our customer that (i) our customer can benefit from on
its own or together with other readily available resources, and (ii) is separately identifiable from other promises in the contract. Goods or services that are not
individually distinct performance obligations are combined with other promised goods or services until such combined group of promises meet the
requirements of a performance obligation.
We determine transaction price based on the amount of consideration we expect to receive for transferring the promised goods or services in the
contract. Consideration may be fixed, variable, or a combination of both. At contract inception for arrangements that include variable consideration, we
estimate the probability and extent of consideration we expect to receive under the contract utilizing either the most likely amount method or expected amount
method, whichever best estimates the amount expected to be received. We then consider any constraints on the variable consideration and include in the
transaction price variable consideration to the extent it is deemed probable that a significant reversal in the amount of cumulative revenue recognized will not
occur when the uncertainty associated with the variable consideration is subsequently resolved.
We then allocate the transaction price to each performance obligation based on the relative standalone selling price and recognize as revenue the
amount of the transaction price that is allocated to the respective performance obligation when (or as) control is transferred to our customer and the
performance obligation is satisfied. For performance obligations which consist of licenses and other promises, we utilize judgment to 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. We evaluate the measure of progress each reporting period and, if necessary, adjust the measure of performance
and related revenue recognition.
We record amounts as accounts receivable when the right to consideration is deemed unconditional. When consideration is received, or such
consideration is unconditionally due, from our customer prior to transferring goods or services to our customer under the terms of a contract, a contract
liability is recorded for deferred revenue.
We do not assess whether a contract has a significant financing component if the expectation at contract inception is that the period between payment
by our customer and the transfer of the promised goods or services to our customer will be one year or less. Incremental costs of obtaining a contract are
expensed as and when incurred if the expected period over which we would have amortized the asset is one year or less, or the amount is immaterial.
Adoption of ASC 606
We adopted ASC 606 on January 1, 2018, using the modified retrospective method for all contracts not completed as of the date of adoption. Our
reported results for 2018 reflect the application of ASC 606 guidance while our reported results for 2017 and 2016 were prepared under the guidance outlined
in ASC 605, Revenue Recognition (“ASC 605”). The adoption of ASC 606 is considered a change in accounting policy which impacts the pattern and timing
of revenue recognition under our license and collaboration agreement with NHS. Under ASC 605, the upfront fee of $120,000 received by the Company in
the first quarter of 2016 was deferred and recognized on a straight-line basis over the estimated performance period of ten years. In addition, the Company
recognized revenue associated with substantive development milestones not considered probable at the inception of the License Agreement with NHS in their
entirety in the period in which the milestone was achieved, in accordance with ASC 605-28, Revenue Recognition-Milestone Method.
77
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 the opening balance of accumulated deficit for 2018, with an associated impact to deferred revenue, as of the adoption date as follows:
Deferred revenue - related party
Deferred revenue, net of current portion - related party
Accumulated deficit
As Reported at
December 31, 2017
12,079
84,847
(263,571)
Adjustments Due to
ASC 606
Balance at
January 1, 2018
17,418
106,365
(290,428)
5,339
21,518
(26,857)
Further, the impact of adoption to our current year results in the Consolidated Statements of Operations and Comprehensive Loss is as follows:
Collaboration revenue - related party
Loss from operations
Net loss
Net loss per share attributable to common stockholders,
basic and diluted
Year Ended December 31, 2018
As Reported under
ASC 606
Pro forma as if
accounted for
under ASC 605
$
$
$
$
26,917 $
(100,284)
(98,942)
52,197
(75,004)
(73,662)
(2.43)
$
(1.81)
Finally, the impact of the adoption to our current year Consolidated Statements of Cash Flows is as follows:
Net loss
Deferred revenue
Collaboration revenue
Year Ended December 31, 2018
As Reported under
ASC 606
$
$
(98,942) $
13,476
Pro forma as if
accounted for
under ASC 605
(73,662)
(11,804)
Arrangements with collaborators may include licenses to intellectual property, research and development services, manufacturing services for clinical
and commercial supply, and participation on joint steering committees. We evaluate the promised goods or services to determine which promises, or group of
promises, represent performance obligations. In contemplation of whether a promised good or service meets the criteria required of a performance obligation,
we consider the stage of development of the underlying intellectual property, the capabilities and expertise of our customer relative to the underlying
intellectual property, and whether the promised goods or services are integral to or dependent on other promises in the contract. When accounting for an
arrangement that contains multiple performance obligations, we must develop judgmental assumptions, which may include market conditions, reimbursement
rates for personnel costs, development timelines and probabilities of regulatory success to determine the stand-alone selling price for each performance
obligation identified in the contract.
When we conclude that a contract should be accounted for as a combined performance obligation and recognized over-time, we must then determine
the period over which revenue should be recognized and the method by which to measure revenue. We generally recognize revenue using a cost-based input
method.
Licenses of intellectual property
If a license to our intellectual property is determined to be distinct from the other performance obligations identified in the arrangement, we recognize
revenue allocated to the license when the license is transferred to our customer and our customer is able to use and benefit from the license. For licenses that
are bundled with other promises, we utilize judgment to 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 associated with the bundled performance obligation. We evaluate the measure of progress each reporting period and, if necessary, adjust the measure
of progress and related revenue recognition.
78
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, otherwise it will be
allocated to all performance obligations of the arrangement based on the initial allocation.
We evaluate each milestone to determine when and how much of the milestone to include in the transaction price. We first estimate the amount of the
milestone payment that we could receive using either the expected value or the most likely amount approach. We primarily use the most likely amount
approach as that approach is generally most predictive for milestone payments with a binary outcome. Then, we consider whether any portion of that
estimated amount is subject to the variable consideration constraint (that is, whether it is probable that a significant reversal of cumulative revenue would not
occur upon resolution of the uncertainty.) We update the estimate of variable consideration included in the transaction price at each reporting date which
includes updating the assessment of the likely amount of consideration and the application of the constraint to reflect current facts and circumstances.
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 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). To date, we have not recognized any revenue related to sales-
based royalties or milestone payments based on the level of sales.
Manufacturing supply services
For arrangements that include a promise of supply of clinical or commercial product, we determine if the supply is a promise in the contract or a future
obligation at our customer’s option. If determined to be a promise at inception of the contract, we evaluate the promise to determine whether it is a separate
performance obligation or a component of a bundled performance obligation. If determined to be an option, we determine if the option provides a material
right to our customer and if so, account for the option as a separate performance obligation. If determined to be an option but not a material right, we account
for the option as a separate contract when our customer elects to exercise the option.
Application of the above guidance requires significant judgment and requires us to make determinations based on the facts and circumstances under
each arrangement.
Accrued Research and Development Expenses
As part of the process of preparing our consolidated financial statements, we are required to estimate our accrued research and development expenses.
This process involves reviewing open contracts and purchase orders, communicating with our personnel to identify services that have been performed on our
behalf and estimating the level of service performed and the associated costs incurred for the services when we have not yet been invoiced or otherwise
notified of the actual costs. The majority of our service providers invoice us in arrears for services performed, on a pre-determined schedule or when
contractual milestones are met; however, some require advanced payments. We make estimates of our accrued expenses as of each balance sheet date in our
financial statements based on facts and circumstances known to us at that time. Examples of estimated accrued research and development expenses include
fees paid to:
•
•
•
•
CROs in connection with performing research services on our behalf and clinical trials;
investigative sites or other providers in connection with clinical trials;
vendors in connection with preclinical and clinical development activities; and
vendors related to product manufacturing, development and distribution of preclinical and clinical supplies.
79
We base our expenses related to preclinical studies and clinical trials on our estimates of the services received and efforts expended pursuant to quotes
and contracts with multiple CROs that conduct and manage clinical trials on our behalf. The financial terms of these agreements are subject to negotiation,
vary from contract to contract and may result in uneven payment flows. There may be instances in which payments made to our vendors will exceed the level
of services provided and result in a prepayment of the clinical expense. Payments under some of these contracts depend on factors such as the successful
enrollment of patients and the completion of clinical trial milestones. In accruing service fees, we estimate the time period over which services will be
performed, enrollment of patients, number of sites activated and the level of effort to be expended in each period. If the actual timing of the performance of
services or the level of effort varies from our estimate, we adjust the accrual or amount of prepaid expense accordingly. Although we do not expect our
estimates to be materially different from amounts actually incurred, our understanding of the status and timing of services performed relative to the actual
status and timing of services performed may vary and may result in us reporting amounts that are too high or too low in any particular period. To date, we
have not made any material adjustments to our prior estimates of accrued research and development expenses.
Stock-Based Compensation
We measure stock options and other stock-based awards granted to employees and directors based on the fair value on the date of grant and recognize
the corresponding compensation expense of those awards over the requisite service period, which is generally the vesting period of the respective award.
Generally, we issue stock options and restricted stock awards with only service-based vesting conditions and record the expense for these awards using the
straight-line method. We recognize adjustments to stock compensation expense for forfeitures as they occur.
We measure stock-based awards granted to consultants and non-employees based on the fair value of the award on the date at which the related service
is complete. Compensation expense is recognized over the period during which services are rendered by such consultants and non-employees until completed.
At the end of each financial reporting period prior to completion of the service, the fair value of these awards is remeasured using the then-current fair value
of our common stock and updated assumption inputs in the Black-Scholes option-pricing model.
We estimate the fair value of each stock option grant using the Black-Scholes option-pricing model. Use of this model requires that we make
assumptions as to the volatility of our common stock, the expected term of our stock options, the risk-free interest rate for a period that approximates the
expected term of our stock options and our expected dividend yield. Because we lack company-specific historical and implied volatility information, we
estimate our expected volatility based on the historical volatility of a group of publicly traded peer companies. We expect to continue to do so until such time
as we have adequate historical data regarding the volatility of our traded stock price. We use the simplified method prescribed by Securities and Exchange
Commission Staff Accounting Bulletin No. 107, Share-Based Payment, to calculate the expected term of options granted to employees and directors. We base
the expected term of options granted to consultants and non-employees on the contractual term of the options. We determine the risk-free interest rate by
reference to the U.S. Treasury yield curve in effect at the time of grant of the award for time periods approximately equal to the expected term of the award.
Expected dividend yield is based on the fact that we have never paid cash dividends and do not expect to pay any cash dividends in the foreseeable future. We
adjust stock-based compensation expense for forfeitures as they occur.
The assumptions we used to determine the fair value of stock options granted to employees and directors are as follows, presented on a weighted
average basis:
Risk-free interest rate
Expected term (in years)
Expected volatility
Expected dividend yield
2018
Year Ended December 31,
2017
2016
2.39%
6.0
76.0%
0%
2.20%
6.0
80.9%
0%
1.54%
6.0
84.2%
0%
These assumptions represented our best estimates, but the estimates involve inherent uncertainties and the application of our judgment.
The following table summarizes the classification of our stock-based compensation expenses recognized in our Consolidated Statements of
Operations:
Research and development
General and administrative
2018
Year Ended December 31,
2017
(in thousands)
2016
$
$
8,388
8,253
16,641
$
$
8,115
9,247
17,362
$
$
8,310
8,547
16,857
80
Emerging Growth Company Status
The Jumpstart Our Business Startups Act of 2012 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 to ‘‘opt out’’ of this provision and, as a result, we will comply with new or revised accounting standards when they are required
to be adopted by public companies that are not emerging growth companies.
Comparison of the Years Ended December 31, 2018 and 2017
The following table summarizes our results of operations for the years ended December 31, 2018 and 2017:
Results of Operations
Revenue:
Collaboration revenue - related party
Grant revenue
Total revenue
Operating expenses:
Research and development
General and administrative
Total operating expenses
Loss from operations
Other income (expense):
Interest income (expense), net
Other income
Total other income (expense), net
Net loss
Revenue
Year Ended
December 31,
2018
2017
(in thousands)
Change
$
$
$
26,917 $
1,350
28,267
95,955 $
32,596
128,551
(100,284)
1,172
170
1,342
(98,942) $
32,100 $
—
32,100
89,455 $
34,040
123,495
(91,395)
1,590
425
2,015
(89,380) $
(5,183)
1,350
(3,833)
6,500
(1,444)
5,056
(8,889)
(418)
(255)
(673)
(9,562)
Total revenue was $28.3 million and $32.1 million for the years ended December 31, 2018 and 2017, respectively. The revenue for both periods
principally relates to the recognition of amounts received under the License Agreement. The decrease is mainly due to the adoption of ASC 606, described in
detail in Note 9. Additionally, we recognized a $20.0 million substantive milestone under the License Agreement during the twelve months ended December
31, 2017.
Research and Development Expenses
Microbiome therapeutics platform
SER-109
SER-262
SER-287
Total research and development expenses
Year Ended
December 31,
2018
2017
(in thousands)
Change
$
$
62,804 $
18,482
3,090
11,579
95,955 $
63,695 $
16,306
4,971
4,483
89,455 $
(891)
2,176
(1,881)
7,096
6,500
81
Research and development expenses were $96.0 million for the year ended December 31, 2018, compared to $89.5 million for the year ended
December 31, 2017. The increase of $6.5 million was due primarily to the following:
•
•
•
•
a decrease of $0.9 million in research expenses related to our microbiome therapeutics platform, due primarily to a decrease in research
consulting expenses of $2.0 million and IT expenses of $0.4 million and is partially offset by an increase in salary and consulting costs of $1.4
million and facilities and supplies costs of $0.1 million;
an increase of $2.2 million in expenses related to our SER-109 program, due primarily to an increase in contract manufacturing costs of $2.7
million, an increase in clinical trial consulting expenses of $0.6 million and an increase of $0.2 million in sequencing costs. This is partially offset
by a decrease of $1.3 million in other consulting costs;
a decrease of $1.9 million in expenses of our SER-262 program primarily driven by a decrease in clinical trial costs of $1.2 million, and
decrease in lab supplies and consumables of $0.7 million; and
an increase of $7.1 million in expenses of our SER-287 program primarily driven by an increase in clinical trials costs of $4.3 million, an
increase in other consulting costs of $1.4 million and increase in lab supplies and consumables of $1.4 million.
We expect that our research and development expenses may increase in the foreseeable future as we advance the clinical development of SER-109,
SER-287 and SER-262, and continue to discover and develop additional product candidates, including SER-401, SER-301 and SER-155, and pursue later
stages of clinical development of our product candidates.
General and Administrative Expenses
Personnel related (including stock-based compensation)
Professional fees
Facility-related and other
Total general and administrative expenses
Year Ended
December 31,
2018
2017
(in thousands)
Change
$
$
15,765 $
7,609
9,222
32,596 $
17,233 $
8,265
8,542
34,040 $
(1,468)
(656)
680
(1,444)
General and administrative expenses were $32.6 million for the year ended December 31, 2018, compared to $34.0 million for the year ended
December 31, 2017. The decrease of $1.4 million was primarily due to the following:
•
•
•
a decrease in personnel related costs of $1.5 million primarily due to the decrease in stock-based compensation expense;
a decrease in professional fees of $0.7 million due primarily to a decrease in legal fees of $0.8 million and a decrease in consulting fees of $0.3
million, partially offset by an increase in recruiting fees of $0.4 million; and
an increase in facility-related and other costs of $0.7 million primarily due to an increase in information technology expenses of $1.4 million,
partially offset by a decrease in office-related expenses of $0.7 million.
Other Income (Expense), Net
Other income (expense), net for the year ended December 31, 2018 was $1.3 million, compared to $2.0 million for the year ended December 31, 2017.
The $0.7 million decrease in other income (expense), net was primarily due to a decrease in interest income from lower cash and investment balances in 2018
versus 2017.
82
Comparison of Years Ended December 31, 2017 and 2016
The following table summarizes our results of operations for the years ended December 31, 2017 and 2016:
Revenue
Operating expenses:
Research and development
General and administrative
Total operating expenses
Loss from operations
Other income (expense):
Interest income (expense), net
Other income
Total other income (expense), net
Net loss
Revenue
Year Ended
December 31,
2017
2016
(in thousands)
Change
$
32,100 $
21,766 $
10,334
89,455
34,040
123,495
(91,395)
1,590
425
2,015
(89,380) $
81,989
32,616
114,605
(92,839)
1,260
—
1,260
(91,579) $
$
7,466
1,424
8,890
1,444
330
425
755
2,199
Total revenue was $32.1 million and $21.8 million for the year ended December 31, 2017 and 2016, respectively. Of the $32.1 million of revenue
recognized for the year ended December 31, 2017, $20.0 million was received from NHS associated with the initiation of the Phase 3 study for SER-109 in
patients with multiply recurrent CDI, which is a substantive milestone under the License Agreement. Of the $21.8 million of revenue recognized for the year
ended December 31, 2016, $10.0 million was received from NHS associated with the initiation of the Phase 1b study for SER-262 in CDI, which was a
substantive development milestone under the License Agreement. Prior to the adoption of ASC 606 we recognize revenue associated with substantive
milestones in accordance with FASB ASC Topic 605-28, Revenue Recognition-Milestone Method, or ASC 605-28. The $20.0 million and $10.0 million
payments were recognized in full as related party collaboration revenue during the years ended December 31, 2017 and 2016, respectively. The remaining
revenue for both periods principally relates to the recognition of the $120.0 million upfront payment under the License Agreement over the estimated
performance period of 10 years.
Research and Development Expenses
Microbiome therapeutics platform
SER-109
SER-262
SER-287
Total research and development expenses
Year Ended
December 31,
2017
2016
(in thousands)
Change
$
$
63,695 $
16,306
4,971
4,483
89,455 $
46,611 $
25,386 $
5,269 $
4,723
81,989 $
17,084
(9,080)
(298)
(240)
7,466
Research and development expenses were $89.5 million for the year ended December 31, 2017, compared to $82.0 million for the year ended
December 31, 2016. The increase of $7.5 million was due primarily to the following:
•
•
an increase of $17.1 million in research expenses related to our microbiome therapeutics platform, due primarily to higher payroll and
consultant costs of $6.1 million, an increase in facilities and depreciation costs of $5.3 million, an increase in sponsorship and license costs of
$2.7 million, an increase in laboratory consumables and supplies of $1.6 million, an increase in IT expenses of $0.6 million, and an increase in
office expenses of $0.7 million;
a decrease of $9.1 million in expenses related to our SER-109 program, due primarily to a decrease in clinical trial costs of $1.7 million, a
decrease in other consulting costs of $1.2 million, a decrease in laboratory consumables and supplies of $3.5 million, a decrease in sequencing
costs of $1.3 million, a decrease in animal studies of $0.6 million, a decrease in conference costs of $0.5 million, a decrease in office expenses
of $0.3 million, and a decrease in IT expenses of $0.2 million, partially offset by an increase in contract manufacturing costs of $0.3 million;
83
•
•
a decrease of $0.3 million in expenses of our SER-262 program primarily driven by a decrease in contract manufacturing costs of $1.0 million,
a decrease in animal studies costs of $0.2 million, and a decrease in other consulting costs of $0.2 million, partially offset by an increase in
clinical trial costs of $0.9 million and an increase in sequencing costs of $0.3 million; and
a decrease of $0.2 million in expenses of our SER-287 program primarily driven by a decrease in contract manufacturing costs of $0.3 million a
decrease in other consulting costs of $0.2 million, and a decrease in lab consumables and supplies of $0.6 million, partially offset by an increase
in clinical trial costs of $0.3 million and an increase in sequencing costs of $0.6 million.
General and Administrative Expenses
Personnel related (including stock-based compensation)
Professional fees
Facility-related and other
Total general and administrative expenses
Year Ended
December 31,
2017
2016
(in thousands)
Change
$
$
17,233
8,265
8,542
34,040
$
$
16,623 $
9,090
6,903
32,616 $
610
(825)
1,639
1,424
General and administrative expenses were $34.0 million for the year ended December 31, 2017, compared to $32.6 million for the year ended
December 31, 2016. The increase of $1.4 million was primarily due to the following:
•
•
•
an increase in personnel related costs of $0.6 million primarily due to the increase in stock-based compensation expense;
a decrease in professional fees of $0.8 million due to a decrease in consulting costs of $0.9 million, partially offset by an increase in legal,
accounting, and audit fees of $0.1 million; and
an increase in facility-related and other costs of $1.6 million primarily due to an increase in information technology expenses of $2.5 million,
partially offset by a decrease in office-related expenses of $1.0 million.
Other Income (Expense), Net
Other income (expense), net for the year ended December 31, 2017 was $2.0 million, compared to $1.3 million for the year ended December 31, 2016.
The $0.8 million increase in other income (expense), net was primarily due to an increase of $0.3 million in interest income and the recognition of $0.3 million of
non-operating income related to the Massachusetts Life Sciences Center tax incentive received in 2016.
Liquidity and Capital Resources
Since our inception, we have generated revenue primarily from collaborations and have incurred recurring net losses. We anticipate that we will
continue to incur losses for at least the next several years. Our research and development and general and administrative expenses may continue to increase
and, as a result, we will need additional capital to fund our operations, which we may obtain from additional financings, public offerings, research funding,
additional collaborations, contract and grant revenue or other sources.
In January 2016, we entered into the License Agreement with NHS, for the development and commercialization of certain of our product candidates in
development for the treatment and management of CDI and IBD, including UC and Crohn’s disease. In exchange for the license, NHS agreed to pay us an
upfront cash payment of $120 million, which we received in February 2016. NHS has also agreed to pay us tiered royalties, at percentages ranging from the
high single digits to high teens, of net sales of NHS Collaboration Products in the Licensed Territory. We are eligible to receive up to $285.0 million in
development milestone payments, $375.0 million in regulatory payments and up to an aggregate of $1.125 billion for the achievement of certain commercial
milestones related to the sales of NHS Collaboration Products. The full potential value of the up-front payment and milestone payments payable by NHS is
over $1.9 billion, assuming all products receive regulatory approval and are successfully commercialized. In September 2016, we received a $10.0 million
milestone payment associated with the initiation of the Phase 1b clinical study for SER-262 in CDI. In June 2017, we initiated a Phase 3 clinical study of
SER-109 (ECOSPOR III) in patients with multiply recurrent CDI. In July 2017, we recorded revenue of $20.0 million based on the achievement of this
milestone under the License Agreement. In November 2018, we executed the Letter Agreement modifying certain terms of the License Agreement. Under the
Letter Agreement, NHS agreed to pay us the $20.0 million Phase 3 milestone payment upon commencement of the Phase 2b study for SER-287. In December
2018, we received $40.0 million in milestone payments in connection with the commencement of the Phase 2b study for SER-287.
84
For the development of NHS Collaboration Products for IBD under a global development plan, we agreed to pay the costs of clinical trials of such
products up to and including Phase 2 clinical trials, and 67% of the costs for Phase 3 and other clinical trials of such products, with NHS bearing the
remaining 33% of such costs. The Letter Agreement also provides scenarios under which NHS’ reimbursement to us for certain Phase 3 development costs
would be reduced or delayed depending on the outcomes of the SER-287 Phase 2b study. For other clinical development of NHS Collaboration Products for
IBD, we agreed to pay the costs of such activities to support approval in the United States and Canada, and NHS agreed to bear the cost of such activities to
support approval of NHS Collaboration Products in the Licensed Territory.
With respect to development of NHS Collaboration Products for CDI under a global development plan, we agreed to pay all costs of Phase 2 clinical
trials for SER-109 and for Phase 3 clinical trials for SER-109. We agreed to bear all costs of conducting any Phase 1 or Phase 2 clinical trials under a global
development plan for NHS Collaboration Products other than SER-109 for CDI. We agreed to pay 67% and NHS agreed to pay 33% of other costs of Phase 3
clinical trials conducted for NHS Collaboration Products other than SER-109 for CDI under a global development plan. For other clinical development of
NHS Collaboration Products for CDI, we agreed to pay costs of such development activities to support approval in the United States and Canada, and NHS
agreed to bear the cost of such activities to support approval of NHS Collaboration Products in the Licensed Territory.
As of December 31, 2018, we had cash and cash equivalents totaling $85.8 million and an accumulated deficit of $389.4 million. Based on our current
plans and forecasted expenses, we believe that our existing cash and cash equivalents as of December 31, 2018, will enable us to fund our operating expenses
and capital expenditure requirements into the fourth quarter of 2019. 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. These factors raise substantial doubt about our ability to continue as a going concern.
Cash Flows
The following table summarizes our sources and uses of cash for each of the periods presented:
Cash provided by (used in) operating activities
Cash provided by (used in) investing activities
Cash provided by financing activities
Net decrease in cash and cash equivalents and restricted cash
Operating Activities
2018
Year Ended December 31,
2017
(in thousands)
2016
$
$
$
$
(62,854) $
112,318
268
49,732 $
(75,523) $
55,702
83
(19,738) $
43,921
(65,592)
2,138
(19,533)
During the year ended December 31, 2018, operating activities used $62.9 million of cash, primarily due to a net loss of $98.9 million and partially
offset by cash provided by changes in our operating assets and liabilities of $11.8 million and non-cash charges of $24.3 million. Net cash provided by
changes in our operating assets and liabilities during the year ended December 31, 2018 consisted of a $13.5 million increase in deferred revenue, a $0.8
million increase in accrued expenses and other liabilities, offset in part by a $2.1 million decrease in prepaid expenses and other current assets. The increase
in deferred revenue is due to the receipt of the $40 million milestone payments under the License Agreement offset by recognition of collaboration revenue
during the year. The increase in accrued expenses was due to the timing of payments.
During the year ended December 31, 2017, operating activities used $75.5 million of cash, primarily due to a net loss of $89.4 million and cash used
from changes in our operating assets and liabilities of $10.6 million, partially offset by non-cash charges of $24.4 million. Net cash used by changes in our
operating assets and liabilities during the year ended December 31, 2017 consisted of a $0.9 million decrease in accounts payable and a $11.9 million
decrease in deferred revenue, offset in part by a $2.2 million increase in accrued expenses and other liabilities. The decrease in our accounts payable and
increase in accrued expenses were due to the timing of payments, an increase in payroll related costs, and an increase in amounts accrued for clinical trial
expenses. The decrease in deferred revenue was due to the recognition of revenue related to the $120.0 million upfront payment under the License Agreement
over the estimated performance period of 10 years.
During the year ended December 31, 2016, operating activities provided $43.9 million of cash, primarily due to the upfront cash payment of $120.0
million and a milestone payment of $10.0 million received in connection with the License Agreement, and cash provided by changes in our operating assets
and liabilities of $6.0 million. This increase was partially offset by a net loss of $91.6 million, less non-cash charges of $20.7 million. Net cash provided by
changes in our operating assets and liabilities during the year ended December 31, 2016 consisted of a $3.6 million increase in accounts payable and a $5.0
million increase in accrued expenses and other current liabilities, offset in part by $2.6 million increase in prepaid expenses and other current assets. The
increases in our accounts payable and accrued expenses were due to the timing of payments, an increase in payroll related costs, and an increase in amounts
accrued for clinical trial and contracted manufacturing expenses. The increase in prepaid expenses and other current assets was due primarily to prepayments
made for clinical trial activities.
85
Investing Activities
During the year ended December 31, 2018, investing activities provided $112.3 million of cash, consisting of sales and maturities of investments of
$136.1 million; these amounts were partially offset by purchases of investments of $21.8 million, and purchases of property and equipment of $1.9 million.
During the year ended December 31, 2017, investing activities provided $55.7 million of cash in investing activities, consisting of sales and maturities
of investments of $158.3 million; these amounts were partially offset by purchases of investments of $97.9 million and purchases of property and equipment
of $4.7 million.
During the year ended December 31, 2016, we used $65.6 million of cash in investing activities, consisting of sales and maturities of investments of
$246.5 million; these amounts were partially offset by purchases of investments of $290.6 million, and purchases of property and equipment of $21.5 million.
Financing Activities
During the year ended December 31, 2018, net cash provided by financing activities was $0.3 million in connection with $0.3 million received from
the issuance of common stock under our employee stock purchase plan and $0.2 million from the issuance of common stock and exercise of stock options.
These were partially offset by payments for employee tax obligations relating to vesting of restricted stock units of $0.2 million.
During the year ended December 31, 2017, net cash provided by financing activities was $0.1 million in connection with the exercise of options to
purchase our common stock, partially offset by payments for the repurchase of common stock.
During the year ended December 31, 2016, net cash provided by financing activities was $2.1 million in connection with the exercise of options to
purchase our common stock.
Funding Requirements
Our expenses may increase substantially in connection with our ongoing and planned activities related to our pipeline products, which are in clinical
development, and our follow-on therapeutic candidates and other programs. In addition, we expect to continue to incur additional costs associated with
operating as a public company. We anticipate that our expenses will increase substantially if and as we:
•
•
•
•
•
•
•
•
•
•
continue the clinical development of SER-109, our lead product candidate, in the Phase 3 clinical study;
continue the clinical development of SER-287 for the treatment of UC;
continue the clinical development of SER-401, a microbiome therapeutic candidate for use with CPIs in a Phase 1b clinical trial in patients with
metastatic melanoma;
conduct research and continue preclinical development of SER-301, our rationally designed IBD product candidate;
make strategic investments in manufacturing capabilities;
maintain and augment our intellectual property portfolio and opportunistically acquire complementary intellectual property;
potentially establish a sales and distribution infrastructure and scale-up manufacturing capabilities to commercialize any products for which we
may obtain regulatory approval;
perform our obligations under the collaboration agreement with NHS;
seek to obtain regulatory approvals for our product candidates; 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 challenges.
86
Because of the numerous risks and uncertainties associated with the development of our programs, we are unable to estimate the amounts of increased
capital outlays and operating expenses associated with completing the research and development of our product candidates. Our future capital requirements
will depend on many factors, including:
•
•
•
•
•
•
•
•
•
the progress and results of our Phase 3 clinical study of SER-109;
the progress and results of any future clinical studies of SER-287;
the cost of manufacturing clinical supplies of our product candidates;
the costs, timing and outcome of regulatory review of our product candidates and research activities;
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.
We continue to evaluate microbiome pharmacokinetic and pharmacodynamic data from the SER-262 Phase 1b study and other completed clinical
trials, in addition to insights gained from preclinical research efforts with our other rationally designed Ecobiotic microbiome therapeutic candidates, in order
to determine future steps in the development of both SER-262 and SER-155.
Identifying potential product candidates and conducting preclinical testing and clinical trials is a time-consuming, expensive and uncertain process that
takes years to complete, and we may never generate the necessary data or results required to obtain marketing approval and achieve product sales. In addition,
our product candidates, if approved, may not achieve commercial success. Our commercial revenues, if any, will be derived from sales of products that we do
not expect to be commercially available for many years, if ever. Accordingly, we will need to obtain substantial additional funds to achieve our business
objectives.
Adequate additional funds may not be available to us on acceptable terms, or at all. We do not currently have any committed external source of funds.
To the extent that we raise additional capital through the sale of equity or convertible debt securities, our shareholders’ ownership interest will be diluted, and
the terms of these securities may include liquidation or other preferences that adversely affect our shareholders’ rights as common stockholders. Additional
debt financing and preferred equity financing, if available, may involve agreements that include covenants limiting or restricting our ability to take specific
actions, such as incurring additional debt, making capital expenditures or declaring dividends and may require the issuance of warrants, which could
potentially dilute our shareholders’ ownership interest.
If we raise additional funds through collaborations, strategic alliances or licensing arrangements with third parties, in addition to the License
Agreement, we may have to relinquish valuable rights to our technologies, future revenue streams, research programs, or product candidates or grant licenses
on terms that may not be favorable to us. If we are unable to raise additional funds through equity or debt financings when needed, we may be required to
delay, limit, reduce or terminate our product development programs or any future commercialization efforts or grant rights to develop and market product
candidates that we would otherwise prefer to develop and market ourselves.
As discussed in Note 1 of the consolidated financial statements included in this Annual Report we have the responsibility to evaluate whether
conditions or events raise substantial doubt about our ability to meet our future financial obligations as they become due within one year after the date the
financial statements are issued. This evaluation initially cannot take into consideration the potential mitigating effects of plans that have not been fully
implemented as of the date the financial statements are issued or potential contingent milestone payments under the License Agreement that we have not
earned. As such, we have determined that our cash runway of less than 12 months along with our accumulated deficit, history of losses, and future expected
losses raise substantial doubt about our ability to continue as a going concern within one year of the issuance date of the consolidated financial statements
included in this Annual Report on Form 10-K. While we have plans in place to mitigate this risk, which primarily consist of raising additional capital through
a combination of equity or debt financings, and, depending on the availability and level of additional financings, potentially new collaborations and reducing
cash expenditures, there is no guarantee that we will be successful in these mitigation efforts. Lack of necessary funds may require us, among other things, to
delay, scale back, or eliminate some or all of our planned clinical trials.
87
The following table summarizes our contractual obligations at December 31, 2018 and the effect such obligations are expected to have on our liquidity
and cash flows in future periods:
Contractual Obligations and Commitments
Operating lease commitments(1)
MD Anderson/Parker Institution collaboration(2)
Total
Total
1 Year
Less Than
Payments Due by Period
1 - 3 Years
(in thousands)
4 - 5 Years
More Than
5 Years
$
$
30,213 $
789
$
31,002
6,342 $
789
$
7,131
12,341 $
—
$
12,341
11,530 $
—
$
11,530
—
—
—
(1)
(2)
Amounts in the table reflect payments due for (i) our laboratory and office space in Cambridge, Massachusetts under an operating lease agreement that
expires in November 2023 and (ii) our lease for office and laboratory space in Cambridge, Massachusetts with a term expiring April 2020.
Amounts in the table reflect payment obligations under an agreement with MD Anderson Cancer Center and Parker Institute for Cancer
Immunotherapy.
We enter into contracts in the normal course of business with CROs for clinical trials, preclinical research studies and testing, manufacturing and other
services and products for operating purposes. These contracts generally provide for termination upon notice, and therefore we believe that our non-cancelable
obligations under these agreements are not material.
We did not have during the periods presented, and we do not currently have, any off-balance sheet arrangements, as defined in the rules and
regulations of the Securities and Exchange Commission.
Off-Balance Sheet Arrangements
For a discussion of recent accounting standards see Note 2, Summary of Significant Accounting Policies, to our consolidated financial statements
included in this report.
Recently Issued and Adopted Accounting Pronouncements
Item 7A. Quantitative and Qualitative Disclosures about Market Risks
Interest Rate Fluctuation Risk
We are exposed to market risk related to changes in interest rates. As of December 31, 2018, our cash and cash equivalents consisted of cash and
money market accounts. Our primary exposure to market risk is interest income sensitivity, which is affected by changes in the general level of U.S. interest
rates. However, because of the short-term nature of the instruments in our portfolio, an immediate 10% change in market interest rates would not have a
material impact on the fair market value of our investment portfolio or on our financial position or results of operations.
Item 8. Financial Statements and Supplementary Data
The financial statements required to be filed pursuant to this Item 8 are appended to this report. An index of those financial statements is found in
Item 15.
Item 9. Changes in and Disagreements with Accountants on Accounting and Financial Disclosure
None.
88
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 principal executive officer and principal financial officer, has evaluated 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), as of the end of
the period covered by this Annual Report on Form 10-K. Based on such evaluation, our principal executive officer and principal financial officer has
concluded that as of such date, our disclosure controls and procedures were effective at the reasonable assurance level.
Management’s Annual Report on Internal Control Over Financial Reporting
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 Securities Exchange Act of 1934, as amended.
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, 2018, our internal control over financial reporting was effective.
There were no changes in our internal control over financial reporting during our most recent fiscal quarter that have materially affected, or are
reasonably likely to materially affect, our internal control over financial reporting.
Changes in Internal Control over Financial Reporting
Item 9B. Other Information
None.
89
Item 10. Directors, Executive Officers, and Corporate Governance
PART III
Our board of directors has adopted a Code of Business Conduct and Ethics applicable to all officers, directors and employees, which is available on
our website at www.serestherapeutics.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 in the preceding sentence.
The information in response to this item is contained in part under the captions, “Directors of the Registrant” and “Executive Officers of the
Registrant” at the end of Part I of this Annual Report on Form 10-K. The remainder of the response to this item is contained in the Proxy Statement for our
Annual Meeting of Stockholders scheduled to be held on June 13, 2019 and is incorporated herein by reference.
Item 11. Executive Compensation
The information required to be disclosed by this item will be contained in the Proxy Statement for our Annual Meeting of Stockholders scheduled to
be held on June 13, 2019 and is incorporated herein by reference.
Item 12. Security Ownership of Certain Beneficial Owners and Management and Related Stockholder Matters
The information required to be disclosed by this item will be contained in the Proxy Statement for our Annual Meeting of Stockholders scheduled to
be held on June 13, 2019 and is incorporated herein by reference.
Item 13. Certain Relationships and Related Transactions and Director Independence
The information required to be disclosed by this item will be contained in the Proxy Statement for our Annual Meeting of Stockholders scheduled to
be held on June 13, 2019 and is incorporated herein by reference.
Item 14. Principal Accountant Fees and Services
The information required to be disclosed by this item will be contained in the Proxy Statement for our Annual Meeting of Stockholders scheduled to
be held on June 13, 2019 and is incorporated herein by reference.
90
Item 15. Exhibits, Financial Statements and Schedules
(a)(1) Financial Statements.
PART IV
See the “Index to Consolidated Financial Statements” on page F-1 below for the list of financial statements filed as part of this report.
(a)(2) Financial Statement Schedules.
All schedules have been omitted because they are not required or because the required information is given in the Consolidated Financial Statements
or Notes thereto set forth below beginning on page F-1.
(a)(3) Exhibits.
Exhibit
Number
3.1
3.2
4.1
4.2
10.1#
10.2#
10.3#
10.4#
10.5
10.6
10.7#
10.8#
10.9#
10.10#
10.11#
10.12#
10.13#
10.14#
Exhibit Description
Form
File No.
Exhibit
Incorporated by Reference
Restated Certificate of Incorporation, filed on July 1, 2015
Amended and Restated By-Laws
Amended and Restated Investors’ Rights Agreement, dated
December 19, 2014, by and among the Registrant and each of the
investors listed on Schedule A thereto
Specimen Stock Certificate evidencing the shares of common
stock
2015 Incentive Award Plan and forms of award agreements
thereunder
2015 Employee Stock Purchase Plan
2012 Stock Incentive Plan, as amended and form of option
agreement thereunder
8-K
8-K
S-1
001-37465
001-37465
333-204484
S-1/A
S-1/A
333-204484
333-204484
S-1/A
S-1
333-204484
333-204484
3.1
3.2
4.1
4.2
10.2
10.3
10.1
Non-Employee Director Compensation Program
S-1/A
333-204484
333-204484
10.4
10.13
Filed/
Furnished
Herewith
Filing
Date
7/1/15
7/1/15
5/27/15
6/16/15
6/16/15
6/16/15
5/27/15
6/16/15
5/27/15
Lease Agreement, dated April 1, 2015, by and between the
Registrant and ARE-MA Region No. 38, LLC
Lease, dated November 11, 2015, by and between the Registrant
and BMR-Sidney Research Campus, LLC
Employment Agreement, dated June 14, 2015, by and between
the Registrant and Roger J. Pomerantz
First Amendment to Employment Agreement, dated February 3,
2016, by and between the Registrant and Roger J. Pomerantz
Second Amendment to Employment Agreement, dated March 7,
2018, by and between the Registrant and Roger J. Pomerantz
Separation Agreement and Release, dated January 14, 2019 by
and between the Registrant and Roger J. Pomerantz.
Amended and Restated Employment Agreement, dated January
14, 2019, by and between the Registrant and Eric D. Shaff
Employment Agreement, dated August 10, 2015, by and between
the Registrant and John G. Aunins
Amendment to Employment Agreement, dated February 8, 2017
by and between the Registrant and John G. Aunins
Employment Agreement, dated June 13, 2015, by and between
the Registrant and Michele Trucksis
91
S-1
10-K
8-K
10-K
8-K
8-K
10-Q
10-K
001-37465
10.13
3/14/16
S-1/A
333-204484
001-37465
10.6
10.1
6/16/15
2/4/16
001-37465
10.18
3/8/18
001-37465
001-37465
10.1
10.2
1/15/19
1/15/19
001-37465
10.10
8/10/15
001-37465
10.13
3/16/17
S-1/A
333-204484
10.10
6/16/15
Exhibit
Number
10.15#
10.16#
10.17#
10.18#
10.19#
10.20#
10.21^
10.22
10.23^^
21.1
23.1
31.1
32.1
101.INS
101.SCH
101.CAL
101.LAB
101.PRE
101.DEF
Exhibit Description
Form
File No.
Exhibit
Incorporated by Reference
Filing
Date
Filed/
Furnished
Herewith
10-Q
001-37465
10.12
8/10/15
10-K
001-37465
10.19
3/8/18
8-K
8-K
10-Q
10-Q
10-Q
001-37465
001-37465
001-37465
001-37465
001-37465
10.1
10.2
10.1
10.1
10.1
11/21/18
11/21/18
8/11/16
11/08/18
5/16/16
Amendment to Employment Agreement, dated August 7, 2015 by
and between the Registrant and Michele
Trucksis
Amendment to Employment Agreement, dated March 7, 2018 by
and between the Registrant and Michele Trucksis
Separation Agreement and Release, dated November 16, 2018, by
and between the Registrant and Michele Trucksis
Consulting Agreement, dated November 16, 2018, by and
between the Registrant and Michele Trucksis
Employment Agreement, dated April 26, 2016 by and between
the Registrant and Thomas J. DesRosier
Employment Agreement, dated October 5, 2018, by and between
the Registrant and Kevin Horgan
Collaboration and License Agreement, dated January 9, 2016, by
and between the Registrant and Nestec Ltd.
Amendment No 1 to the Collaboration and License Agreement,
dated August 10, 2016, by and between the Registrant and Nestec
Ltd.
Letter Agreement dated October 30, 2018, by and between the
Registrant and Nestec Ltd.
Subsidiaries of Seres Therapeutics, Inc.
Consent of PricewaterhouseCoopers LLP, Independent
Registered Public Accounting Firm
Rule 13a-14(a)/15d-14(a) Certification of Chief Executive
Officer
Section 1350 Certification of Chief Executive Officer
XBRL Instance Document
XBRL Taxonomy Extension Schema Document
XBRL Taxonomy Extension Calculation Linkbase Document
XBRL Taxonomy Extension Label Linkbase Document
XBRL Taxonomy Extension Presentation Linkbase Document
XBRL Taxonomy Extension Definition Linkbase Document
*
*
*
*
*
**
*
*
*
*
*
*
*
**
#
^
^^
Filed herewith.
Furnished herewith.
Indicates management contract or compensatory plan.
Confidential treatment has been granted with respect to redacted portions of this exhibit. Redacted portions of this exhibit have been filed separately
with the SEC.
Confidential treatment has been requested with respect to redacted portions of this exhibit. Redacted portions of this exhibit have been filed separately
with the SEC.
Item 16. Form 10-K Summary
None.
92
INDEX TO CONSOLIDATED FINANCIAL STATEMENTS
Report of Independent Registered Public Accounting Firm
Consolidated Balance Sheets as of December 31, 2018 and 2017
Consolidated Statements of Operations and Comprehensive Loss for the years ended December 31, 2018, 2017 and 2016
Consolidated Statements of Stockholders’ Equity (Deficit) as of December 31, 2018, 2017 and 2016
Consolidated Statements of Cash Flows for the years ended December 31, 2018, 2017 and 2016
Notes to Consolidated Financial Statements
Page
F-2
F-3
F-4
F-5
F-6
F-7
F-1
REPORT OF INDEPENDENT REGISTERED PUBLIC ACCOUNTING FIRM
To the Board of Directors and Stockholders of Seres Therapeutics, Inc.
Opinion on the Financial Statements
We have audited the accompanying consolidated balance sheets of Seres Therapeutics, Inc. and its subsidiaries (the “Company”) as of December 31, 2018
and 2017, and the related consolidated statements of operations and comprehensive loss, of stockholders’ equity (deficit) and of cash flows for each of the
three years in the period ended December 31, 2018, including 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 as of December 31, 2018 and
2017, and the results of its operations and its cash flows for each of the three years in the period ended December 31, 2018 in conformity with accounting
principles generally accepted in the United States of America.
Substantial Doubt About 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 incurred losses and negative cash flows from operations since its inception, that raise substantial
doubt about its ability to continue as a going concern. Management's plans in regard to 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.
Change in Accounting Principle
As discussed in Note 2 to the consolidated financial statements, the Company changed the manner in which it accounts for revenues from contracts with
customers in 2018.
Basis for Opinion
These consolidated financial statements are the responsibility of the Company’s management. Our responsibility is to express an opinion on the Company’s
consolidated 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 of these consolidated financial statements 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 consolidated 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 consolidated 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 consolidated 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 consolidated financial statements. We believe that our audits provide a reasonable basis for our opinion.
/s/ PricewaterhouseCoopers LLP
Boston, Massachusetts
March 6, 2019
We have served as the Company's auditor since 2014.
F-2
SERES THERAPEUTICS, INC.
CONSOLIDATED BALANCE SHEETS
(In thousands, except share and per share data)
Assets
Current assets:
Cash and cash equivalents
Investments
Prepaid expenses and other current assets
Total current assets
Property and equipment, net
Restricted investments
Restricted cash
Total assets
Liabilities and Stockholder's Equity (Deficit)
Current liabilities:
Accounts payable
Accrued expenses and other current liabilities
Deferred revenue - related party
Total current liabilities
Lease incentive obligation, net of current portion
Deferred rent
Deferred revenue, net of current portion - related party
Other long-term liabilities
Total liabilities
Commitments and contingencies (Note 11)
Stockholders’ equity (deficit):
Preferred stock, $0.001 par value; 10,000,000 shares authorized at December 31, 2018
and 2017; no shares issued and outstanding at December 31, 2018 and 2017
Common stock, $0.001 par value; 200,000,000 shares authorized at December 31, 2018
and 2017; 40,936,735 and 40,571,015 shares issued and outstanding
at December 31, 2018 and 2017
Additional paid-in capital
Accumulated other comprehensive income (loss)
Accumulated deficit
Total stockholders’ equity (deficit)
Total liabilities and stockholders’ equity (deficit)
December 31,
2018
2017
85,820 $
—
6,845
92,665
26,294
1,400
113
120,472 $
6,415 $
15,207
20,419
42,041
7,250
2,216
116,840
170
168,517
36,088
113,895
5,095
155,078
32,931
1,400
113
189,522
7,033
12,513
12,079
31,625
8,989
2,233
84,847
1,129
128,823
—
—
41
341,284
—
(389,370)
(48,045)
120,472 $
40
324,376
(146)
(263,571)
60,699
189,522
$
$
$
$
The accompanying notes are an integral part of these consolidated financial statements.
F-3
SERES THERAPEUTICS, INC.
CONSOLIDATED STATEMENTS OF OPERATIONS AND COMPREHENSIVE LOSS
(In thousands, except share and per share data)
Revenue:
Collaboration revenue - related party
Grant revenue
Total revenue
Operating expenses:
Research and development expenses
General and administrative expenses
Total operating expenses
Loss from operations
Other income (expense):
Interest income (expense), net
Other income
Total other income (expense), net
Net loss
Net loss per share attributable to common stockholders, basic and diluted
Weighted average common shares outstanding, basic and diluted
Other comprehensive income (loss):
Unrealized gain (loss) on investments, net of tax of $0
Total other comprehensive income (loss)
Comprehensive loss
2018
Year Ended December 31,
2017
2016
26,917 $
1,350
28,267
32,100 $
—
32,100
95,955
32,596
128,551
(100,284)
1,172
170
1,342
(98,942)
89,455
34,040
123,495
(91,395)
1,590
425
2,015
(89,380)
(2.43) $
(2.21) $
21,766
—
21,766
81,989
32,616
114,605
(92,839)
1,260
—
1,260
(91,579)
(2.30)
40,743,492
40,449,410
39,846,928
146
146
(98,796) $
3
3
(89,377) $
(179)
(179)
(91,758)
$
$
$
$
$
The accompanying notes are an integral part of these consolidated financial statements.
F-4
SERES THERAPEUTICS, INC.
CONSOLIDATED STATEMENTS OF STOCKHOLDERS’ EQUITY (DEFICIT)
(In thousands, except share data)
Additional
Paid-in
Capital
Accumulated
Other
Comprehensive
Income (Loss)
Accumulated
Deficit
Total
Stockholders
Equity
(Deficit)
Balance at December 31, 2015
Issuance of common stock upon exercise of stock options
Stock-based compensation expense
Unrealized loss on investments
Net loss
Balance at December 31, 2016
Issuance of common stock upon exercise of stock options
Issuance of common stock upon vesting of RSUs, net of
tax
withholdings
Stock-based compensation expense
Unrealized gain on investments
Net loss
Balance at December 31, 2017
Issuance of common stock upon exercise of stock options
Issuance of common stock upon vesting of RSUs, net of
tax
withholdings
Repurchase of common stock for employee tax
withholdings
Issuance of common stock under ESPP plan
Stock-based compensation expense
Unrealized gain on investments
Adoption of new revenue standard (ASC 606)
Net loss
Balance at December 31, 2018
Common Stock
Shares
39,082,017
1,273,736
—
—
—
40,355,753
174,386
40,876
—
—
—
40,571,015
$
212,240
Par
Value
39
1
—
—
—
40
—
—
—
—
—
40 $
1
287,937
2,137
16,857
—
—
306,931
116
(33)
17,362
—
—
324,376
$
146
61
138,048
—
(17,900)
33,332
—
—
—
—
40,936,735
$
—
—
—
—
—
—
41 $
(197)
257
16,641
—
—
—
341,284
$
30
—
—
(179)
—
(149)
—
(82,612)
—
—
—
(91,579)
(174,191)
—
—
—
3
—
(146) $
—
—
—
(89,380)
(263,571) $
—
—
—
—
—
—
—
146
—
—
0 $
—
—
—
—
(26,857)
(98,942)
(389,370) $
205,394
2,138
16,857
(179)
(91,579)
132,631
116
(33)
17,362
3
(89,380)
60,699
147
61
(197)
257
16,641
146
(26,857)
(98,942)
(48,045)
The accompanying notes are an integral part of these consolidated financial statements.
F-5
SERES THERAPEUTICS, INC.
CONSOLIDATED STATEMENTS OF CASH FLOWS
(In thousands)
Cash flows from operating activities:
Net loss
Adjustments to reconcile net loss to net cash provided by (used in)
operating activities:
Stock-based compensation expense
Depreciation and amortization expense
Non-cash interest expense
Accretion of discount on investments
Changes in operating assets and liabilities:
Prepaid expenses and other current assets
Deferred revenue
Accounts payable
Accrued expenses and other liabilities
Net cash provided by (used in) operating activities
Cash flows from investing activities:
Purchases of property and equipment
Purchases of investments
Sales and maturities of investments
Net cash provided by (used in) investing activities
Cash flows from financing activities:
Proceeds from exercise of stock options
Proceeds from issuance of common stock and restricted common stock
Payments for repurchase of common stock for employee tax withholdings
Issuance of common stock under ESPP plan
Net cash provided by financing activities
Net increase (decrease) in cash, cash equivalents and restricted cash
Cash, cash equivalents and restricted cash at beginning of year
Cash, cash equivalents and restricted cash at end of year
Supplemental disclosure of cash flow information:
Cash paid for interest
Supplemental disclosure of non-cash investing and financing
activities:
Property and equipment purchases included in accounts payable and
accrued expenses
2018
Year Ended December 31,
2017
2016
$
(98,942) $
(89,380) $
(91,579)
16,641
7,862
—
(214)
(2,056)
13,476
(353)
732
(62,854)
(1,937)
(21,832)
136,087
112,318
147
61
(197)
257
268
49,732
36,201
85,933 $
17,362
7,259
3
(216)
31
(11,888)
(856)
2,162
(75,523)
(4,676)
(97,934)
158,312
55,702
116
—
(33)
—
83
(19,738)
55,939
36,201 $
16,857
4,205
—
(386)
(2,598)
108,814
3,581
5,027
43,921
(21,492)
(290,594)
246,494
(65,592)
2,138
—
—
—
2,138
(19,533)
75,472
55,939
— $
1 $
109
157 $
877
$
1,650
$
$
$
The accompanying notes are an integral part of these consolidated financial statements.
F-6
SERES THERAPEUTICS, INC.
NOTES TO CONSOLIDATED FINANCIAL STATEMENTS
(amounts in thousands, except share and per share data)
1.
Nature of the Business and Basis of Presentation
Seres Therapeutics, Inc. (the “Company”) was incorporated under the laws of the State of Delaware in October 2010 under the name Newco LS21,
Inc. In October 2011, the Company changed its name to Seres Health, Inc., and in May 2015, the Company changed its name to Seres Therapeutics, Inc. The
Company is a microbiome therapeutics platform company developing a novel class of biological drugs, which are designed to restore health by repairing the
function of a dysbiotic microbiome. SER-287 is being developed by the Company to treat ulcerative colitis (“UC”). The Company’s lead product candidate,
SER-109, is designed to prevent further recurrences of Clostridium difficile infection (“CDI”), a debilitating infection of the colon, and, if approved by the
U.S. Food and Drug Administration (“FDA”), could be a first-in-field oral microbiome drug. The Company is also developing product candidates to treat
diseases where the microbiome is implicated, including SER-301, a rationally designed, fermented inflammatory bowel disease (“IBD”), candidate, and SER-
401, a microbiome therapeutic candidate for use with checkpoint inhibitors (“CPI’s”) in patients with metastatic melanoma. The Company continues to
evaluate microbiome pharmacokinetic and pharmacodynamic data from their SER-262 Phase 1b study and other completed clinical trials, in addition to
insights gained from research efforts with their other rationally designed Ecobiotic microbiome therapeutic candidates, in order to determine next steps in the
development of both SER-262 to treat an initial recurrence of CDI and SER-155 to modulate the microbiome and dysbiosis in patients following allogeneic
hematopoietic stem cell transplants. The Company is also using its microbiome therapeutics platform to conduct research on various indications, including:
infectious diseases, metabolic diseases, and inflammatory and immune diseases and cancer.
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, 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.
Under Accounting Standards Update (“ASU”) 2014-15, Presentation of Financial Statements—Going Concern (Subtopic 205-40) (“ASC 205-40”),
the Company has the responsibility to evaluate whether conditions and/or events raise substantial doubt about its ability to meet its future financial obligations
as they become due within one year after the date that the financial statements are issued. As required by ASC 205-40, this evaluation shall initially not take
into consideration the potential mitigating effects of plans that have not been fully implemented as of the date the financial statements are issued.
As of December 31, 2018, the Company had an accumulated deficit of $389.4 million and cash and cash equivalents of $85.8 million. For the year
ended December 31, 2018, the Company incurred a loss of $98.9 million and used $62.9 million of cash in operations. Management has assessed the
Company’s ability to continue as a going concern in accordance with the requirements of ASC 205-40 and determined that the Company’s accumulated
deficit, history of losses, and future expected losses meet the ASC 205-40 standard for raising substantial doubt about the Company’s ability to continue as a
going concern within one year of the issuance date of these consolidated financial statements.
The Company’s current financial resources and currently forecasted operating plan would allow the Company to operate into the fourth quarter of
2019 which is within one year from the issuance of these consolidated financial statements. The Company has developed plans to mitigate this risk, which
primarily consist of raising additional capital through some combination of equity or debt financings, and/or potentially new collaborations and reducing cash
expenditures.
F-7
SERES THERAPEUTICS, INC.
NOTES TO CONSOLIDATED FINANCIAL STATEMENTS
(amounts in thousands, except share and per share data)
If the Company is not able to secure adequate additional funding, the Company plans to make reductions in spending. In that event, the Company may
have to delay, scale back, or eliminate some or all of the Company’s planned clinical trials and research stage programs. The actions necessary to reduce
spending under this plan at a level that mitigates the factors described above is not considered probable, as defined in the accounting standards; as such, under
the requirements of ASC 205-40, the full extent to which management may extend the Company’s funds through these actions may not be considered in
management’s assessment of the Company’s ability to continue as a going concern for the next 12 months as defined by ASC-205-40.
As a result, in accordance with the requirements of ASC 205-40, management has concluded that it is required to disclose that substantial doubt exists
about the Company’s ability to continue as a going concern for one year from the date these financial statements are issued.
The Company is eligible to receive contingent milestone payments under its license and collaboration agreement with Nestec Ltd. (“NHS”), an
affiliate of Nestlé Health Science US Holdings, Inc. (“Nestlé Health Science”), a significant stockholder of the Company, if certain development milestones
are achieved. However, these milestones are uncertain and there is no assurance that the Company will receive any of them. Until such time, if ever, as the
Company can generate substantial product revenue, the Company will finance its cash needs through a combination of public or private equity offerings, debt
financings, governmental funding, collaborations, strategic partnerships or marketing, distribution or licensing arrangements with third parties. The Company
may not be able to obtain funding on acceptable terms, or at all. If the Company is unable to raise additional funds as and when needed, it would have a
negative impact on the Company’s financial condition, which may require the Company to delay, reduce or eliminate certain research and development
activities and reduce or eliminate discretionary operating expenses, which could constrain the Company’s ability to pursue its business strategies.
The accompanying financial statements have been prepared in conformity with accounting principles generally accepted in the United States of
America (“GAAP”) and include the accounts of the Company and its wholly owned subsidiaries after elimination of all intercompany accounts and
transactions.
2.
Summary of Significant Accounting Policies
Use of Estimates
The preparation of financial statements in conformity with GAAP requires 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 expenses during the reporting periods. Significant estimates and assumptions reflected in these consolidated financial statements include, but are not
limited to, revenue recognition, the accrual of research and development expenses and the valuation of stock-based awards. Estimates are periodically
reviewed in light of changes in circumstances, facts and experience. Actual results could differ from the Company’s estimates.
Cash Equivalents
The Company considers all short-term, highly liquid investments with original maturities of 90 days or less at acquisition date to be cash equivalents.
Cash equivalents, which consist of money market accounts and corporate bonds purchased with original maturities of less than 90 days from the date of
purchase, are stated at fair value.
Restricted Cash
The Company held cash of $113 as of December 31, 2018 and December 31, 2017 in a separate restricted bank account as a security deposit for the
lease of the Company’s facilities. The Company has classified these deposits as long-term restricted cash on its balance sheet.
Investments
The Company classifies its available-for-sale marketable debt securities as current assets on the consolidated balance sheet if they mature within one
year from the balance sheet date.
F-8
SERES THERAPEUTICS, INC.
NOTES TO CONSOLIDATED FINANCIAL STATEMENTS
(amounts in thousands, except share and per share data)
The Company classifies all of its marketable debt securities as available-for-sale securities. Accordingly, these marketable debt securities are recorded
at fair value and unrealized gains and losses are reported as a separate component of accumulated other comprehensive income (loss) in stockholders’ equity
(deficit). The cost of securities sold is determined on a specific identification basis, and realized gains and losses are included in other income (expense)
within the consolidated statement of operations and comprehensive loss. If any adjustment to fair value reflects a decline in the value of the investment that
the Company considers to be “other than temporary”, the Company reduces the investment to fair value through a charge to the consolidated statement of
operations and comprehensive loss. No such adjustments were necessary during the periods presented.
Restricted Investments
The Company held investments of $1,400 as of December 31, 2018 and December 31, 2017 in a separate restricted bank account as a security deposit
for the lease of the Company’s facilities. The Company has classified these deposits as long-term restricted investments on its balance sheet.
Concentration of Credit Risk and of Significant Suppliers
Financial instruments that potentially expose the Company to concentrations of credit risk consist primarily of cash, cash equivalents and investments.
The Company has all cash, cash equivalents and investments balances at accredited financial institutions, in amounts that exceed federally insured limits. The
Company does not believe that it is subject to unusual credit risk beyond the normal credit risk associated with commercial banking relationships.
The Company is dependent on third-party manufacturers to supply products for research and development activities of its programs, including
preclinical and clinical testing. These programs could be adversely affected by a significant interruption in the supply of such drug substance products.
Fair Value Measurements
Certain assets and liabilities are carried at fair value under GAAP. Fair value is defined as the exchange price that would be received for an asset or
paid to transfer a liability (an exit price) in the principal or most advantageous market for the asset or liability in an orderly transaction between market
participants on the measurement date. Valuation techniques used to measure fair value must maximize the use of observable inputs and minimize the use of
unobservable inputs. Financial assets and liabilities carried at fair value are to be classified and disclosed in one of the following three levels of the fair value
hierarchy, of which the first two are considered observable and the last is considered unobservable:
•
•
•
Level 1—Quoted prices in active markets for identical assets or liabilities.
Level 2—Observable inputs (other than Level 1 quoted prices), such as quoted prices in active markets for similar assets or liabilities, quoted
prices in markets that are not active for identical or similar assets or liabilities, or other inputs that are observable or can be corroborated by
observable market data.
Level 3—Unobservable inputs that are supported by little or no market activity and that are significant to determining the fair value of the
assets or liabilities, including pricing models, discounted cash flow methodologies and similar techniques.
The Company’s cash equivalents and investments are carried at fair value, determined according to the fair value hierarchy described above. The
Company’s investments in certificates of deposit are carried at amortized cost, which approximates fair value. Certain cash equivalents or investments that are
measured at fair value using the net asset value per share (or its equivalent) practical expedient have not been classified in the fair value hierarchy. The
carrying values of the Company’s accounts payable and accrued expenses approximate their fair value due to the short-term nature of these liabilities.
Property and Equipment
Property and equipment are stated at cost less accumulated depreciation. Depreciation expense is recognized using the straight-line method over the
useful life of the asset. Laboratory equipment is depreciated over five years. Computer equipment and furniture and office equipment are depreciated over
three years. Leasehold improvements are amortized over the shorter of the lease term or the estimated useful life of the related asset. Expenditures for repairs
and maintenance of assets are charged to expense as incurred. Upon retirement or sale, the cost and related accumulated depreciation of assets disposed of are
removed from the accounts and any resulting gain or loss is included in loss from operations.
F-9
SERES THERAPEUTICS, INC.
NOTES TO CONSOLIDATED FINANCIAL STATEMENTS
(amounts in thousands, except share and per share data)
Impairment of Long-Lived Assets
Long-lived assets consist of property and equipment. Long-lived assets to be held and used are tested for recoverability whenever events or changes in
business circumstances indicate that the carrying amount of the assets may not be fully recoverable. Factors that the Company considers in deciding when to
perform an impairment review include significant underperformance of the business in relation to expectations, significant negative industry or economic
trends and significant changes or planned changes in the use of the assets. If an impairment review is performed to evaluate a long-lived asset for
recoverability, the Company compares forecasts of undiscounted cash flows expected to result from the use and eventual disposition of the long-lived asset to
its carrying value. An impairment loss would be recognized when estimated undiscounted future cash flows expected to result from the use of an asset are less
than its carrying amount. The impairment loss would be based on the excess of the carrying value of the impaired asset over its fair value, determined based
on discounted cash flows. To date, the Company has not recorded any impairment losses on long-lived assets.
Research and Development Costs
Research and development costs are expensed as incurred. Research and development expenses include salaries, stock-based compensation and
benefits of employees, third-party license fees and other operational costs related to the Company’s research and development activities, including allocated
facility-related expenses and external costs of outside vendors engaged to conduct both preclinical studies and clinical trials.
Research Contract Costs and Accruals
The Company has entered into various research and development contracts with research institutions and other companies. These agreements are
generally cancelable, and related payments are recorded as research and development expenses as incurred. The Company records accruals for estimated
ongoing research 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 are made in determining the accrued balances at the end of
any reporting period. Actual results could differ from the Company’s estimates. The Company’s historical accrual estimates have not been materially different
from the actual costs.
Patent Costs
All patent-related costs incurred in connection with filing and prosecuting patent applications are expensed as incurred due to the uncertainty about the
recovery of the expenditure. Amounts incurred are classified as general and administrative expenses.
Accounting for Stock-Based Compensation
The Company measures all stock options and other stock-based awards granted to employees and directors based on the fair value on the date of the
grant and recognizes compensation expense of those awards over the requisite service period, which is generally the vesting period of the respective award.
Generally, the Company issues stock options, restricted stock units and restricted stock awards with only service-based vesting conditions and records the
expense for these awards using the straight-line method. For stock options or restricted stock units issued with performance-based vesting conditions, the
stock compensation expense related to these awards is recognized based on the grant date fair value when achievement of the performance condition is
deemed probable.
The Company measures stock-based awards granted to consultants and non-employees based on the fair value of the award on the date on which the
related service is complete. Compensation expense is recognized over the period during which services are rendered by such consultants and non-employees
until completed. At the end of each financial reporting period prior to completion of the service, the fair value of these awards is remeasured using the then-
current fair value of the Company’s common stock and updated assumption inputs in the Black-Scholes option-pricing model.
The Company classifies stock-based compensation expense in its consolidated statement of operations and comprehensive loss in the same manner in
which the award recipient’s payroll costs are classified or in which the award recipients’ service payments are classified.
F-10
SERES THERAPEUTICS, INC.
NOTES TO CONSOLIDATED FINANCIAL STATEMENTS
(amounts in thousands, except share and per share data)
The Company recognizes adjustments to stock compensation expense for forfeitures as they occur.
The fair value of each stock option grant is estimated on the date of grant using the Black- Scholes option-pricing model. The Company lacks
sufficient company-specific historical and implied volatility information. Therefore, it estimates its expected stock volatility based on the historical volatility
of a publicly traded set of peer companies and expects to continue to do so until such time as it has adequate historical data regarding the volatility of its own
traded stock price. We use the simplified method prescribed by Securities and Exchange Commission Staff Accounting Bulletin No. 107, Share-Based
Payment, to calculate the expected term of options granted to employees and directors. The expected term of stock options granted to non-employees is equal
to the contractual term of the option award. The risk-free interest rate is determined by reference to the U.S. Treasury yield curve in effect at the time of grant
of the award for time periods approximately equal to the expected term of the award. Expected dividend yield is based on the fact that the Company has never
paid cash dividends and does not expect to pay any cash dividends in the foreseeable future.
Revenue Recognition
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 while the reported results for 2017 and 2016 were prepared under ASC 605,
Revenue Recognition (“ASC 605”).
The Company recognizes revenue in accordance with the guidance under ASC 606, Revenue from Contracts with Customers. ASC 606 applies to all
contracts with customers, except those contracts that are within the scope of other guidance, such as leases, insurance, and financial instruments. The
Company enters into agreements that are within the scope of ASC 606, under which the Company licenses certain of the Company’s product candidates and
performs research and development services in connection with such arrangements. The terms of these arrangements typically include payment of one or
more of the following: nonrefundable up-front fees, reimbursement of research and development costs, development, clinical, regulatory and commercial
sales milestone payments, and royalties on net sales of licensed products. Under ASC 606, an entity recognizes revenue when its 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. When
determining the timing and extent of revenue recognition for arrangements that the Company determines are within the scope of ASC 606, the Company
performs the following five steps:
(vi)
identify the contract(s) with a customer;
(vii)
identify the performance obligations in the contract;
(viii) determine the transaction price;
(ix)
allocate the transaction price to the performance obligations in the contract; and
(x)
recognize revenue when (or as) the entity satisfies a performance obligation.
The Company only applies the five-step model to contracts when it is probable that the entity will collect the consideration to which it is entitled in
exchange for the goods or services transferred 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
the contract to determine whether each promised good or service is a performance obligation. The promised goods or services in the Company’s arrangements
typically consist of a license to the Company’s intellectual property and/or research and development services. The Company may provide options to
additional items in such arrangements, which are accounted for as separate contracts when the customer elects to exercise such options, unless the option
provides a material right to the customer. Performance obligations are promises in a contract to transfer a distinct good or service to the customer that (i) the
customer can benefit from on its own or together with other readily available resources, and (ii) is separately identifiable from other promises in the contract.
Goods or services that are not individually distinct performance obligations are combined with other promised goods or services until such combined group of
promises meet the requirements of a performance obligation.
F-11
SERES THERAPEUTICS, INC.
NOTES TO CONSOLIDATED FINANCIAL STATEMENTS
(amounts in thousands, except share and per share data)
The Company determines transaction price based on the amount of consideration the Company expects to receive for transferring the promised goods
or services in the contract. Consideration may be fixed, variable, or a combination of both. At contract inception for arrangements that include variable
consideration, the Company estimates the probability and extent of consideration it expects to receive under the contract utilizing either the most likely
amount method or expected amount method, whichever best estimates the amount expected to be received. The Company then considers any constraints on
the variable consideration and includes in the transaction price variable consideration to the extent it is deemed probable that a significant reversal in the
amount of cumulative revenue recognized will not occur when the uncertainty associated with the variable consideration is subsequently resolved.
The Company then allocates the transaction price to each performance obligation based on the relative standalone selling price and recognizes as
revenue the amount of the transaction price that is allocated to the respective performance obligation when (or as) control is transferred to the customer and
the performance obligation is satisfied. For performance obligations which consist of licenses and other promises, the Company utilizes judgment to 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. The Company evaluates the measure of progress each reporting period and, if necessary, adjusts
the measure of performance and related revenue recognition.
The Company records amounts as accounts receivable when the right to consideration is deemed unconditional. When consideration is received, or
such consideration is unconditionally due, from a customer prior to transferring goods or services to the customer under the terms of a contract, a contract
liability is recorded for deferred revenue.
The Company does not assess whether a contract has a significant financing component if the expectation at contract inception is that the period
between payment by the customer and the transfer of the promised goods or services to the customer will be one year or less. Incremental costs of obtaining a
contract are expensed as and when incurred if the expected period over which the Company would have amortized the asset is one year or less, or the amount
is immaterial.
Collaboration Revenue
Arrangements with collaborators may include licenses to intellectual property, research and development services, manufacturing services for clinical
and commercial supply, and participation on joint steering committees. The Company evaluates the promised goods or services to determine which promises,
or group of promises, represent performance obligations. In contemplation of whether a promised good or service meets the criteria required of a performance
obligation, the Company considers the stage of development of the underlying intellectual property, the capabilities and expertise of the customer relative to
the underlying intellectual property, and whether the promised goods or services are integral to or dependent on other promises in the contract. When
accounting for an arrangement that contains multiple performance obligations, the Company must develop judgmental assumptions, which may include
market conditions, reimbursement rates for personnel costs, development timelines and probabilities of regulatory success to determine the stand-alone selling
price for each performance obligation identified in the contract.
When the Company concludes that a contract should be accounted for as a combined performance obligation and recognized over-time, the Company
must then determine the period over which revenue should be recognized and the method by which to measure revenue. The Company generally recognizes
revenue using a cost-based input method.
Licenses of intellectual property
If a license to the Company’s intellectual property is determined to be distinct from the other performance obligations identified in the arrangement,
the Company recognizes revenue allocated to the license when the license is transferred to the customer and the customer is able to use and benefit from the
license. For licenses that are bundled with other promises, the Company utilizes judgment to 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 associated with the bundled performance obligation. The Company evaluates the measure of progress each
reporting period and, if necessary, adjusts the measure of progress and related revenue recognition.
F-12
SERES THERAPEUTICS, INC.
NOTES TO CONSOLIDATED FINANCIAL STATEMENTS
(amounts in thousands, except share and per share data)
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, otherwise it will be allocated to all performance obligations of the arrangement based on the initial allocation.
The Company evaluates each milestone to determine when and how much of the milestone to include in the transaction price. The Company first
estimates the amount of the milestone payment that the Company could receive using either the expected value or the most likely amount approach. The
Company primarily uses the most likely amount approach as that approach is generally most predictive for milestone payments with a binary outcome. Then,
the Company considers whether any portion of that estimated amount is subject to the variable consideration constraint (that is, whether it is probable that a
significant reversal of cumulative revenue would not occur upon resolution of the uncertainty). The Company updates the estimate of variable consideration
included in the transaction price at each reporting date which includes updating the assessment of the likely amount of consideration and the application of the
constraint to reflect current facts and circumstances.
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). To date, the Company has not
recognized any revenue related to sales-based royalties or milestone payments based on the level of sales.
Manufacturing supply services
For arrangements that include a promise of supply of clinical or commercial product, the Company determines if the supply is a promise in the
contract or a future obligation at the customer’s option. If determined to be a promise at inception of the contract, the Company evaluates the promise to
determine whether it is a separate performance obligation or a component of a bundled performance obligation. If determined to be an option, the Company
determines if the option provides a material right to the customer and if so, accounts for the option as a separate performance obligation. If determined to be
an option but not a material right, the Company accounts for the option as a separate contract when the customer elects to exercise the option.
Grant Revenue
The Company generates revenue from government contracts that reimburse the Company for certain allowable costs for funded projects. For contracts
with government agencies, when the Company has concluded that it is the principal in conducting the research and development expenses and where the
funding arrangement is considered central to the Company’s ongoing operations, the Company classifies the recognized funding received as revenue.
The Company has concluded to recognize funding received as revenue, rather than as a reduction of research and development expenses, because the
Company is the principal in conducting the research and development activities and these contracts are central to its ongoing operations. Revenue is
recognized as the qualifying expenses related to the contracts are incurred. Revenue recognized upon incurring qualifying expenses in advance of receipt of
funding is recorded in the Company’s consolidated balance sheet as prepaid expenses and other current assets. The related costs incurred by the Company are
included in research and development expense in the Company’s consolidated statements of operations and comprehensive loss.
F-13
SERES THERAPEUTICS, INC.
NOTES TO CONSOLIDATED FINANCIAL STATEMENTS
(amounts in thousands, except share and per share data)
Income Taxes
The Company accounts for income taxes using the asset and liability method, which requires the recognition of deferred tax assets and liabilities for
the expected future tax consequences of events that have been recognized in the consolidated financial statements or in the Company’s tax returns. Deferred
taxes are determined based on the difference between the financial statement and tax basis of assets and liabilities using enacted tax rates in effect in the years
in which the differences are expected to reverse. Changes in deferred tax assets and liabilities are recorded in the provision for income taxes. The Company
assesses the likelihood that its deferred tax assets will be recovered from future taxable income and, to the extent it believes, based upon the weight of
available evidence, that it is more likely than not that all or a portion of the deferred tax assets will not be realized, a valuation allowance is established
through a charge to income tax expense.
The Company accounts for uncertainty in income taxes recognized in the financial statements by applying a two-step process to determine the amount
of tax benefit to be recognized. First, the tax position must be evaluated to determine the likelihood that it will be sustained upon external examination by the
taxing authorities. If the tax position is deemed more-likely-than-not to be sustained, the tax position is then assessed to determine the amount of benefit to
recognize in the financial statements. The amount of the benefit that may be recognized is the largest amount that has a greater than 50% likelihood of being
realized upon ultimate settlement. The provision for income taxes includes the effects of any resulting tax reserves, or unrecognized tax benefits, that are
considered appropriate as well as the related net interest and penalties.
Segment Data
The Company manages its operations as a single segment for the purposes of assessing performance and making operating decisions. The Company’s
singular focus is on developing Ecobiotic microbiome therapeutics to treat dysbiosis in the colonic microbiome. Revenue to date has been generated solely
through the Company's collaboration with NHS, all of which has been earned in the United States. All tangible assets are held in the United States.
Comprehensive Loss
Comprehensive loss includes net loss as well as other changes in stockholders’ equity (deficit) that result from transactions and economic events other
than those with stockholders. For the years ended December 31, 2018, 2017 and 2016, other comprehensive income (loss) consisted of changes in unrealized
gains (losses) from available-for-sale investments.
Net Loss per Share
Basic net loss per share is computed using the weighted average number of common shares outstanding during the period. Diluted net loss per share is
computed using the sum of the weighted average number of common shares outstanding during the period and, if dilutive, the weighted average number of
potential shares of common stock, including the assumed exercise of stock options and unvested restricted stock. The Company applies the two-class method
to calculate its basic and diluted net loss per share attributable to common stockholders, as its convertible preferred stock was, and common stock is a
participating security. The two-class method is an earnings allocation formula that treats a participating security as having rights to earnings that otherwise
would have been available to common stockholders. However, the two-class method does not impact the net loss per share of common stock as the Company
was in a net loss position for each of the periods presented and preferred stockholders did not participate in losses.
The Company’s convertible preferred stock contractually entitled the holders of such shares to participate in dividends but did not contractually require
the holders of such shares to participate in losses of the Company. Similarly, restricted stock awards granted by the Company entitle the holder of such awards
to dividends declared or paid by the board of directors, regardless of whether such awards are unvested, as if such shares were outstanding common shares at
the time of the dividend. However, the unvested restricted stock awards are not entitled to share in the residual net assets (deficit) of the Company.
Accordingly, in periods in which the Company reports a net loss attributable to common stockholders, diluted net loss per share attributable to common
stockholders is the same as basic net loss per share attributable to common stockholders, since dilutive common shares are not assumed to have been issued if
their effect is anti-dilutive.
F-14
SERES THERAPEUTICS, INC.
NOTES TO CONSOLIDATED FINANCIAL STATEMENTS
(amounts in thousands, except share and per share data)
Recently Issued and Adopted Accounting Pronouncements
In May 2014, the Financial Accounting Standards Board (the “FASB”) issued ASU 2014-09, Revenue from Contracts with Customers (Topic 606),
which supersedes all existing revenue recognition requirements, including most industry-specific guidance. The new standard requires a company to
recognize revenue when it transfers goods or services to customers in an amount that reflects the consideration that the company expects to receive for those
goods or services. The FASB subsequently issued additional ASUs related to the new standard delaying the effective date and clarifying several aspects of the
new revenue guidance, all of which collectively are herein referred to as “ASC 606.” The Company has adopted this standard as of the required effective date
of January 1, 2018, using the modified retrospective transition method. See Note 9, “Revenue,” for discussion of the impact of adoption of this standard.
In August 2016, the FASB issued ASU No. 2016-15, Statement of Cash Flows: Classification of Certain Cash Receipts and Cash Payments. This
standard addresses specific cash flow issues with the objective of reducing existing diversity in practice in how certain cash receipts and cash payments are
presented in the statement of cash flows. The standard was effective for the Company on January 1, 2018. The Company adopted this standard as of the
required effective date of January 1, 2018. The adoption of this standard did not have any impact on the Company’s financial statements.
In November 2016, the FASB issued ASU 2016-18, Restricted Cash. The new standard requires restricted cash and restricted cash equivalents be
included with cash and cash equivalents when reconciling the total beginning and ending amounts for the periods shown on the statement of cash flows. The
new standard was effective for the Company on January 1, 2018. The Company adopted the new standard as of the required effective date of January 1, 2018
and will reflect the adoption retrospectively to all periods presented. The Company’s statements of cash flows includes restricted cash with cash and cash
equivalents when reconciling the beginning-of-period and end-of-period total amounts shown on such statements. A reconciliation of the cash, cash
equivalents, and restricted cash reported within the balance sheet that sum to the total of the same amounts shown in the statement of cash flows is as follows:
Cash and cash equivalents
Restricted cash
Total cash, cash equivalents and restricted cash as shown
in the statement of cash flows
December 31
December 31,
December 31,
December 31,
2018
2017
2016
2015
$
85,820 $
113
36,088 $
113
54,539 $
1,400
73,933
1,539
$
85,933 $
36,201 $
55,939 $
75,472
In February 2016 the FASB issued ASU No. 2016-02, Leases (Topic 842). This standard established a right-of-use model that requires all lessees to
recognize right-of-use assets and liabilities on their balance sheet that arise from leases with terms longer than 12 months as well as provide disclosures with
respect to certain qualitative and quantitative information related to their leasing arrangements. This standard became effective for the Company on January 1,
2019.
The FASB has subsequently issued the following amendments to ASU 2016-02, which have the same effective date and transition date of January 1,
2019, and which the Company collectively refers to as the new leasing standards:
•
•
•
•
ASU No. 2018-01, Leases (Topic 842): Land Easement Practical Expedient for Transition to Topic 842, which permits an entity to elect an
optional transition practical expedient to not evaluate under Topic 842 land easements that exist or expired prior to adoption of Topic 842 and
that were not previously accounted for as leases under the prior standard, ASC 840, Leases
ASU No. 2018-10, Codification Improvements to Topic 842, Leases, which amends certain narrow aspects of the guidance issued in ASU 2016-
02
ASU No. 2018-11, Leases (Topic 842): Targeted Improvements, which allows for a transition approach to initially apply ASU 2016-02 at the
adoption date and recognize a cumulative-effect adjustment to the opening balance of retained earnings in the period of adoption as well as an
additional practical expedient for lessors to not separate non-lease components from the associated lease component
ASU No. 2018-20, Narrow-Scope Improvements for Lessors, which contains certain narrow scope improvements to the guidance issued in ASU
2016-02
F-15
SERES THERAPEUTICS, INC.
NOTES TO CONSOLIDATED FINANCIAL STATEMENTS
(amounts in thousands, except share and per share data)
The Company adopted the new leasing standards on January 1, 2019, using a modified retrospective transition approach to be applied to leases
existing as of, or entered into after, January 1, 2019. The Company elected to apply the package of practical expedients which allows entities not to reassess
whether contracts are or contain leases, lease classification, and whether initial direct costs qualify for capitalization. Additionally, the Company elected not to
separate lease and non-lease components. The Company’s primary operating leases represent the lease of its corporate headquarters at 200 Sidney Street and a
lease for additional research space at 215 First Street, both in Cambridge, Massachusetts. Upon adoption of the new leasing standards, the Company expects
to recognize a lease liability of approximately $25,000 and a related right-of-use asset of approximately $14,000 on its consolidated balance sheet with the
difference being due to the elimination of previously reported lease incentive obligations and deferred rent. The impact of adoption of the new leasing
standards will have an immaterial impact to the Company’s consolidated statements of operations and comprehensive loss and cash flows.
In June 2018, the FASB issued ASU 2018-07, Compensation – Stock Compensation (Topic 718). ASU 2018-07 simplifies the accounting for
nonemployee share-based payment t awards and aligns the accounting for share-based payment awards issued to employees and non-employees. The ASU
expands the scope of Topic 718 to apply to non-employee awards under which non-employee awards will be measured on the grant date and the associated
compensation cost will be recognized over the vesting period.. This ASU is effective for public entities for interim and annual reporting periods beginning
after December 15, 2018. The adoption of ASU 2018-17 is not expected to have a material impact on the Company’s financial statements.
In August 2018, the FASB issued ASU No. 2018-13, Disclosure Framework - Changes to the Disclosure Requirements for Fair Value Measurement
(“ASU 2018-13”). This standard eliminates, adds and modifies certain disclosure requirements for fair value measurements as part of its disclosure
framework project. ASU 2018-13 is effective for annual reporting periods beginning after December 15, 2019 and interim periods within those annual periods
and early adoption is permitted. The Company is currently in the process of evaluating the impact of the adoption of ASU 2018-13 on its consolidated
financial statements.
3.
Fair Value of Financial Assets and Liabilities
The following tables present information about the Company’s assets and liabilities as of December 31, 2018 and 2017 that are measured at fair value
on a recurring basis and indicate the level of the fair value hierarchy utilized to determine such fair values:
Assets:
Cash Equivalents
Fair Value Measurements as of December 31, 2018 Using:
Level 1
Level 2
Level 3
Not Subject to
Leveling (1)
Total
$
$
— $
— $
— $
— $
— $
— $
39,982 $
39,982 $
39,982
39,982
(1)
Certain cash equivalents and investments that are valued using the net asset value per share (or its equivalent) practical expedient have not been
classified in the fair value hierarchy.
F-16
SERES THERAPEUTICS, INC.
NOTES TO CONSOLIDATED FINANCIAL STATEMENTS
(amounts in thousands, except share and per share data)
Assets:
Cash Equivalents
Investments:
Commercial Paper
Certificates of Deposit
Corporate Bonds
Government Securities
Treasury Bonds
Fair Value Measurements as of December 31, 2017 Using:
Level 1
Level 2
Level 3
Not Subject to
Leveling (1)
Total
$
—
$
— $
— $
25,964 $
25,964
—
—
—
—
—
—
$
6,198
8,916
58,865
22,954
16,961
113,894 $
—
—
—
—
—
— $
—
—
—
—
—
25,964 $
6,198
8,916
58,865
22,954
16,961
139,858
$
(1)
Certain cash equivalents and investments that are valued using the net asset value per share (or its equivalent) practical expedient have not been
classified in the fair value hierarchy.
As of December 31, 2018 and 2017, the Company’s cash equivalents consisted of money market funds with original maturities of less than 90 days
from the date of purchase.
Excluded from the tables above are restricted cash and restricted investments as the cost approximates current fair value. The Company has a money
market fund and certificate of deposit as security deposits on its two facility leases. As of both December 31, 2018 and 2017 the restricted cash and restricted
investment balances were $113 and $1,400, respectively.
The fair value of the Company’s investments, which consisted of corporate bonds, commercial paper, certificates of deposit, government securities,
and treasury bonds as of December 31, 2017 were determined using Level 2 inputs.
4.
Investments
As of December 31, 2018 the Company had no investments. As of December 31, 2017, the fair value of available-for-sale investments by type of
security was as follows:
Investments:
Commercial Paper
Certificates of Deposit
Corporate Bonds
Government Securities
Treasury Bonds
Amortized
Cost
Gross
Unrealized Gain
Gross
Unrealized Loss
Fair
Value
December 31, 2017
$
$
6,198 $
8,916
58,937
22,997
16,992
114,040 $
— $
—
—
—
—
— $
— $
—
(72)
(43)
(31)
(146) $
6,198
8,916
58,865
22,954
16,961
113,894
Investments with original maturities of less than 90 days are included in cash and cash equivalents on the consolidated balance sheets and are not
included in the table above. Investments with maturities of less than 12 months are considered current and those investments with maturities greater than 12
months are considered non-current.
Excluded from the table above are restricted investments of $1,400 as the cost approximates current fair value.
F-17
SERES THERAPEUTICS, INC.
NOTES TO CONSOLIDATED FINANCIAL STATEMENTS
(amounts in thousands, except share and per share data)
5.
Property and Equipment, Net
Property and equipment, net consisted of the following:
Laboratory equipment
Computer equipment
Furniture and office equipment
Leasehold improvements
Construction in progress
Less: Accumulated depreciation and amortization
December 31,
2018
December 31,
2017
$
$
14,695 $
2,864
1,033
27,977
26
46,595
(20,301)
26,294 $
13,181
2,832
1,033
27,963
361
45,370
(12,439)
32,931
Depreciation and amortization expense was $7,862, $7,259 and $4,205 for the years ended December 31, 2018, 2017 and 2016, respectively.
6.
Accrued Expenses and Other Current Liabilities
Accrued expenses and other current liabilities consisted of the following:
Development and clinical manufacturing costs
Payroll and payroll-related costs
Facility and other
December 31,
2018
December 31,
2017
$
$
7,046 $
5,020
3,141
15,207 $
3,910
4,962
3,641
12,513
7.
Convertible Preferred Stock
On July 1, 2015, in connection with the closing of the initial public offering of the Company’s common stock (“IPO”), the Company effected its
Restated Certificate of Incorporation, which authorizes the Company to issue 10,000,000 shares of preferred stock, $0.001 par value per share.
8.
Stockholders’ Equity Common Stock
On July 1, 2015, in connection with the closing of the IPO, the Company effected its Restated Certificate of Incorporation, which authorizes the
Company to issue 200,000,000 shares of common stock, $0.001 par value per share.
2012 Stock Incentive Plan
The Company’s 2012 Stock Incentive Plan, as amended, (the “2012 Plan”) provided for the Company to sell or issue common stock or restricted
common stock, or to grant incentive stock options or nonqualified stock options for the purchase of common stock, to employees, members of the board of
directors and consultants of the Company. The 2012 Plan is administered by the board of directors, or at the discretion of the board of directors, by a
committee of the board of directors. The exercise prices, vesting and other restrictions are determined at the discretion of the board of directors, or their
committee if so delegated, except that the exercise price per share of stock options may not be less than 100% of the fair market value of the share of common
stock on the date of grant and the term of stock option may not be greater than ten years. The Company generally granted stock-based awards with service
conditions only (“service-based” awards).
F-18
SERES THERAPEUTICS, INC.
NOTES TO CONSOLIDATED FINANCIAL STATEMENTS
(amounts in thousands, except share and per share data)
Stock options granted under the 2012 Plan generally vest over four years and expire after ten years, although options have been granted with vesting
terms less than four years. As of December 31, 2018, there were no shares available for future grant under the 2012 Plan.
2015 Incentive Award Plan
On June 16, 2015, the Company’s stockholders approved the 2015 Incentive Award Plan (the “2015 Plan”), which became effective on June 25, 2015.
The 2015 Plan provides for the grant of incentive stock options, nonqualified stock options, stock appreciation rights, restricted stock awards, restricted stock
units and other stock-based awards. The number of shares initially reserved for issuance under the 2015 Plan was the sum of (i) 2,200,000 shares of common
stock and (ii) the number of shares subject to awards outstanding under the 2012 Plan that expire, terminate or are otherwise surrendered, cancelled, forfeited
or repurchased by the Company on or after the effective date of the 2015 Plan. In addition, the number of shares of common stock that may be issued under
the 2015 Plan is subject to increase on the first day of each calendar year, beginning in 2016 and ending in 2025, 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 preceding applicable calendar year and (ii) an amount determined by the
Company’s board of directors.
Stock options granted under the 2015 Plan generally vest over four years and expire after ten years, although options have been granted with vesting
terms less than four years. As of December 31, 2018, there were 1,353,580 shares available for future grant under the 2015 Plan.
2015 Employee Stock Purchase Plan
On June 16, 2015, the Company’s stockholders approved the 2015 Employee Stock Purchase Plan (the “ESPP”), which became effective on June 25,
2015. A total of 365,000 shares of common stock were reserved for issuance under the ESPP. In addition, the number of shares of common stock that may be
issued under the ESPP automatically increase on the first day of each calendar year, beginning in 2016 and ending in 2025, by an amount equal to the least of
(i) 400,000 shares, (ii) 1% of the number of shares of the Company’s common stock outstanding on the last day of the applicable preceding calendar year and
(iii) an amount determined by the Company’s board of directors. Offering periods under the ESPP will commence when determined by the plan administrator.
As of December 31, 2018, there were 33,332 shares issued under the ESPP and 1,522,488 shares were reserved and available for issuance under the ESPP.
The ESPP provides that eligible employees may contribute up to 15% of their eligible earnings toward the semi-annual purchase of the Company's
common stock. The ESPP is qualified under Section 423 of the Internal Revenue Code. The employee's purchase price is derived from a formula based on the
closing price of the common stock on the first day of the offering period versus the closing price on the date of purchase (or, if not a trading day, on the
immediately preceding trading day). The offering period under the ESPP has a duration of six months, and the purchase price with respect to each offering
period beginning on or after such date is, until otherwise amended, equal to 85% of the lesser of (i) the fair market value of the Company's common stock at
the commencement of the applicable six-month offering period or (ii) the fair market value of the Company's common stock on the purchase date. The
Company estimates the fair value of common stock under the ESPP using a Black-Scholes valuation model. The fair value was estimated on the date of grant
using the Black-Scholes option valuation model and the straight-line attribution approach with the following weighted-average assumptions: risk-free interest
rate (2.30%); expected term (0.5 years); expected volatility (60.2%); and an expected dividend yield (0%). The Company recorded $145 of stock-based
compensation expense under the ESPP for the twelve months ended December 31, 2018. There was no stock-based compensation expense under the ESPP
for the twelve months ended December 31, 2017, and 2016 respectively.
F-19
SERES THERAPEUTICS, INC.
NOTES TO CONSOLIDATED FINANCIAL STATEMENTS
(amounts in thousands, except share and per share data)
Stock Option Valuation
The assumptions that the Company used to determine the fair value of the stock options granted to employees and directors were as follows, presented
on a weighted average basis:
Risk-free interest rate
Expected term (in years)
Expected volatility
Expected dividend yield
Stock Options
2018
Year Ended December 31,
2017
2016
2.39%
6.0
76.0%
0%
2.20%
6.0
80.9%
0%
1.54%
6.0
84.2%
0%
The following table summarizes the Company’s stock option activity for the twelve months ended December 31, 2018:
Outstanding as of December 31, 2017
Granted
Exercised
Forfeited
Outstanding as of December 31, 2018
Options vested and expected to vest as of December 31, 2018
Options exercisable as of December 31, 2018
Weighted
Average
Exercise
Price
Weighted
Average
Remaining
Contractual
Term
(in years)
Aggregate
Intrinsic
Value
13.00
9.67
0.69
15.99
12.26
12.26
12.56
7.70
$
15,808
7.23
7.23
6.21
$
$
$
4,958
4,958
4,958
Number of
Shares
6,125,692 $
2,074,776
(212,240)
(426,509)
7,561,719 $
7,561,719 $
4,386,848 $
The weighted average grant-date fair value of stock options granted during the years ended December 31, 2018, 2017 and 2016 was $6.53, $7.07, and
$18.45 per share, respectively. The total intrinsic value of stock options exercised during the years ended December 31, 2018, 2017, and 2016 was $1,801,
$1,912, and $34,871.
The aggregate intrinsic value of stock options is calculated as the difference between the exercise price of the stock options and the fair value of the
Company’s common stock for those stock options that had exercise prices lower than the fair value of the Company’s common stock.
The Company granted performance-based stock options to certain employees. These stock options were exercisable only upon achievement of
specified performance targets. During the year ended December 31, 2016, the Company determined that the achievement of specified performance targets
occurred. Upon achievement of the performance targets, 60,000 options became immediately vested. The Company recorded stock-based compensation
expense of $235 during the year ended December 31, 2016 related to these awards. The grant date fair value of these awards was $3.92 per share.
As of December 31, 2018 and 2017, there were outstanding unvested service-based stock options held by non-employees for the purchase of 193,282
and 45,000 shares, respectively, of common stock.
F-20
SERES THERAPEUTICS, INC.
NOTES TO CONSOLIDATED FINANCIAL STATEMENTS
(amounts in thousands, except share and per share data)
Restricted Stock Units
The Company has granted restricted stock units with time-based vesting conditions. The table below summarizes the Company’s restricted stock
activity for the twelve months ended December 31, 2018:
Unvested restricted stock units as of December 31, 2017
Granted
Forfeited
Vested
Unvested restricted stock units as of December 31, 2018
Number
of Shares
Weighted
Average Grant
Date Fair Value
356,778 $
30,900 $
(22,730) $
(138,048) $
226,900 $
10.01
7.50
9.87
10.09
9.64
The aggregate intrinsic value of restricted stock units that vested during the years ended December 31, 2018, 2017 and 2016 was $1,206, $445, and $0,
respectively.
Stock-based Compensation
The Company recorded stock-based compensation expense related to stock options and restricted stock units in the following expense categories of its
consolidated statements of operations and comprehensive loss:
Research and development expenses
General and administrative expenses
2018
Year Ended December 31,
2017
2016
$
$
8,388 $
8,253
16,641 $
8,115 $
9,247
17,362 $
8,310
8,547
16,857
As of December 31, 2018, the Company had an aggregate of $21,554 of unrecognized stock-based compensation cost, which is expected to be
recognized over a weighted average period of 2.19 years.
9.
Collaboration Revenue
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 while the reported results for 2017 and 2016 were prepared under ASC 605.
Adoption of ASC Topic 606, Revenue from Contracts with Customers
The adoption of ASC 606 changed the pattern and timing of revenue recognition under the Collaboration and License Agreement (“License
Agreement”) with NHS. Under ASC 605, the upfront fee of $120,000 received by the Company in the first quarter of 2016 was deferred and recognized on a
straight-line basis over the estimated performance period of ten years. In addition, the Company recognized revenue associated with substantive development
milestones not considered probable at the inception of the License Agreement with NHS in their entirety in the period in which the milestone was achieved, in
accordance with ASC 605-28, Revenue Recognition-Milestone Method.
Under ASC 606, the Company recognizes revenue using the cost-to-cost method which best depicts the transfer of control to the customer. Under the
cost-to-cost method, the extent of progress towards completion is measured based on the ratio of actual costs incurred to the total estimated costs expected
upon satisfying the identified performance obligation. Under this method, revenue will be recorded as a percentage of the estimated transaction price based on
the extent of progress towards completion. The estimate of the Company’s measure of progress and estimate of transaction price will be updated at each
reporting date, as a change in estimate, and will require judgement. The amount of consideration allocated to satisfied performance obligations, based on the
Company’s measure of progress will be recognized immediately on a cumulative catch-up basis, resulting in an adjustment to revenue in the period of change.
The amount related to the unsatisfied portion will be recognized as that portion is satisfied over time. In addition, substantive
F-21
SERES THERAPEUTICS, INC.
NOTES TO CONSOLIDATED FINANCIAL STATEMENTS
(amounts in thousands, except share and per share data)
development milestones, which were previously recognized in the period when the milestone was achieved, will be recognized over the remaining
performance period under ASC 606.
The cumulative effect of applying ASC 606 as of the adoption date of January 1, 2018, was recorded as an adjustment to accumulated deficit in the
statement of stockholders’ equity (deficit). As a result of applying the modified retrospective method to adopt ASC 606, the following adjustments were made
to the consolidated balance sheet on January 1, 2018:
Deferred revenue - related party
Deferred revenue, net of current portion - related party
Accumulated deficit
As Reported at
December 31, 2017
12,079
84,847
(263,571)
Adjustments Due to
ASC 606
Balance at
January 1, 2018
17,418
106,365
(290,428)
5,339
21,518
(26,857)
The following table compares the reported consolidated balance sheet as of December 31, 2018 to the pro-forma amounts had ASC 605 been in effect:
Deferred revenue - related party
Deferred revenue, net of current portion - related party
Accumulated deficit
As of December 31, 2018
As Reported under
ASC 606
Pro forma as if
accounted for
under ASC 605
20,419
116,840
(389,370)
12,118
73,004
(337,233)
Total reported liabilities were $52,137 greater as reported under ASC 606 than would have been reported under ASC 605 as of December 31, 2018.
This change consists of a $43,836 increase in deferred revenue, net of current portion, related party, and a $8,301 increase in deferred revenue - related
parties.
The following table compares the reported consolidated statements of operations and comprehensive loss for the year ended December 31, 2018 to the
pro forma amounts had ASC 605 been in effect:
Collaboration revenue - related party
Loss from operations
Net loss
Net loss per share attributable to common stockholders,
basic and diluted
Year Ended
December 31, 2018
As Reported under
ASC 606
Pro forma as if
accounted for
under ASC 605
$
$
$
$
26,917 $
(100,284)
(98,942)
52,197
(75,004)
(73,662)
(2.43)
$
(1.81)
Collaboration revenue – related party decreased by approximately $25,280 as reported under ASC 606 when compared to what would have been
reported under ASC 605 for the year ended December 31, 2018.
The following table compares the reported consolidated statements of cash flows for the year ended December 31, 2018 to the pro forma amounts had
ASC 605 been in effect:
Net loss
Deferred revenue
Year Ended December 31, 2018
As Reported under
ASC 606
Pro forma as if
accounted for
under ASC 605
$
$
(98,942) $
13,476
(73,662)
(11,804)
F-22
SERES THERAPEUTICS, INC.
NOTES TO CONSOLIDATED FINANCIAL STATEMENTS
(amounts in thousands, except share and per share data)
The adoption of ASC 606 resulted in a $25,280 increase in net loss, due to a corresponding decrease in revenue and an increase of $25,280 in the
change in deferred revenue for the year ended December 31, 2018. The adoption of ASC 606 did not change net cash used in operating activities.
NHS Collaboration Agreement
Summary of Agreement
In January 2016, the Company entered into the License Agreement for the development and commercialization of certain product candidates in
development for the treatment and management of CDI and IBD, including UC and Crohn’s disease. The License Agreement supports the development of the
Company’s portfolio of products for CDI and IBD in markets outside of the United States and Canada (the “Licensed Territory”). The Company has retained
full commercial rights to its entire portfolio of product candidates with respect to the United States and Canada.
Under the License Agreement, the Company granted to NHS an exclusive, royalty-bearing license to develop and commercialize, in the Licensed
Territory, certain products based on its microbiome technology that are being developed for the treatment of CDI and IBD, including SER-109, SER-262,
SER-287 and SER-301 (collectively, the “NHS Collaboration Products”). The License Agreement sets forth the Company’s and NHS’ respective obligations
for development, commercialization, regulatory and manufacturing and supply activities for the NHS Collaboration Products with respect to the licensed
fields and the Licensed Territory.
Under the License Agreement, NHS agreed to pay the Company an upfront cash payment of $120,000, which the Company received in February
2016. The Company is eligible to receive up to $285,000 in development milestone payments, $375,000 in regulatory payments and up to an aggregate of
$1,125,000 for the achievement of certain commercial milestones related to the sales of NHS Collaboration Products. NHS also agreed to pay the Company
tiered royalties, at percentages ranging from the high single digits to high teens, of net sales of NHS Collaboration Products in the Licensed Territory.
Under the License Agreement, the Company is entitled to receive a $20,000 milestone payment from NHS following initiation of a SER-287 Phase 2
study and a $20,000 milestone payment from NHS following the initiation of a SER-287 Phase 3 study. In November 2018, the Company entered into a letter
agreement with NHS which modified the License Agreement to address the current clinical plans for SER-287. Through the letter agreement, the Company
and NHS agreed that following initiation of the SER-287 Phase 2b study, the Company will receive $40,000 in milestone payments from NHS which
represents the milestone due to the Company for the initiation of the SER-287 Phase 2 and Phase 3 studies. The SER-287 Phase 2b study was initiated and the
$40,000 of milestone payments were received in December 2018. The letter agreement also provides scenarios under which NHS’ reimbursement to the
Company for certain Phase 3 development costs would be reduced or delayed depending on the outcomes of the SER-287 Phase 2b study.
Accounting Analysis
The Company assessed the License Agreement in accordance with ASC 606 and concluded that NHS is a customer. The Company identified the
following promises under the contract: (i) a license to develop and commercialize the NHS Collaboration Products in the Licensed Territory, (ii) obligation to
perform research and development services, (iii) participation on a joint steering committee, and (iv) manufacturing services to provide clinical supply to
complete future clinical trials. In addition, the Company identified a contingent obligation to perform manufacturing services to provide commercial supply if
commercialization occurs, which is contingent upon regulatory approval. This contingent obligation is not a performance obligation at inception and has been
excluded from the initial allocation as it represents a separate buying decision at market rates, rather than a material right in the contract. The Company
assessed the promised goods and services to determine if they are distinct. Based on this assessment, the Company determined that NHS cannot benefit from
the promised goods and services separately from the others as they are highly interrelated and therefore not distinct. Accordingly, the promised goods and
services represent one combined performance obligation and the entire transaction price will be allocated to that single combined performance obligation.
At contract inception, the Company determined that the $120,000 non-refundable upfront amount constituted the entirety of the consideration to be
included in the transaction price as the development, regulatory, and commercial milestones were fully
F-23
SERES THERAPEUTICS, INC.
NOTES TO CONSOLIDATED FINANCIAL STATEMENTS
(amounts in thousands, except share and per share data)
constrained. During the year ended December 31, 2016, the Company received $10,000 from NHS in connection with the initiation of the Phase 1b study for
SER-262 in CDI. During the year ended December 31, 2017, the Company received $20,000 from NHS in connection with the initiation of the Phase 3 study
for SER-109. Therefore, as of January 1, 2018, the aggregate amount of the transaction price allocated to the remaining performance obligation of the
License Agreement was approximately $150,000.
During the year ended December 31, 2018, the Company received $40,000 from NHS in connection with the initiation of the Phase 2b study for SER-
287. In the third quarter of 2018, the Company increased the transaction price by $20,000 associated with the Phase 2 milestone for SER-287. The Company
estimated the $20,000 of variable consideration by using the most likely amount method which best predicts the amount of consideration to which the
Company will be entitled. The Company included the $20,000 in the transaction price because it is probable that a significant reversal in the amount of
cumulative revenue recognized will not occur when the uncertainty associated with the variable consideration is subsequently resolved.
In the fourth quarter of 2018, the Company entered into a letter agreement with NHS which modified the License Agreement to address the current
clinical plans for SER-287. As a result of this modification, the Company and NHS agreed that the $20,000 milestone payment due to the Company from
NHS following the initiation of a Phase 3 study for SER-287 would now be due to the Company upon initiation of the SER-287 Phase 2b study. The Letter
Agreement constituted a contract modification under ASC 606. The Company accounted for the contract modification through a cumulative catch-up
adjustment because the contract modification did not add any additional goods or services and the remaining goods and services are not distinct. The SER-
287 Phase 2b study was initiated in December 2018 and the Company included the $20,000 in the transaction price as of December 31, 2018. The transaction
price as of December 31, 2018 was approximately $190,000.
During the twelve months ended December 31, 2018, using the cost-to-cost method, which best depicts the transfer of control to the customer, the
Company recognized $26,917 of Collaboration revenue – related party. Included in the revenue recognized during the twelve months ended December 31,
2018 were cumulative catch-up adjustments of approximately $5,020 and $5,517, related to including the $20,000 Phase 2 milestone for SER-287 in the
transaction in the third quarter of 2018 and the $20,000 Phase 3 milestone for SER-287 in the transaction price in the fourth quarter of 2018.
For the twelve months ended December 31, 2017, the Company recognized $32,100 of Collaboration revenue – related party under ASC 605 which
comprised (i) a $20,000 milestone for the initiation of the Phase 3 study for SER-109, recognized in accordance with the milestone method of revenue
recognition (ASC 605-28) and (ii) $12,100 of revenue from the upfront license fee. For the twelve months ended December 31, 2016, the Company
recognized $21,766 of Collaboration revenue – related party under ASC 605 which comprised (i) a $10,000 milestone for the initiation of the Phase 3 study
for SER-109, recorded in accordance with the milestone method of revenue recognition (ASC 605-28) and (ii) $11,766 of revenue from the upfront license
fee.
As of December 31, 2018 and 2017, there was $137,259, and $96,926 of deferred revenue related to the unsatisfied portion of the performance
obligation under the License Agreement. As of December 31, 2018, the deferred revenue is classified as current or non-current in the consolidated balance
sheets based on the Company’s estimate of revenue that will be recognized within the next twelve months which is determined by the cost-to-cost method
which measures the extent of progress towards completion based on the ratio of actual costs incurred to the total estimated costs expected upon satisfying the
performance obligation. All costs associated with the License Agreement are recorded in research and development expense in the consolidated statements of
operations and comprehensive loss.
F-24
SERES THERAPEUTICS, INC.
NOTES TO CONSOLIDATED FINANCIAL STATEMENTS
(amounts in thousands, except share and per share data)
Income Taxes
The adoption of ASC 606 resulted in an increase to deferred revenue, which in turn generated an additional deferred tax asset that increased the
Company’s net deferred tax asset position. As the Company fully reserves its net deferred tax assets, the impact was offset by the valuation allowance.
Contract Balances from Contracts with Customers
The following table presents changes in the Company’s contract liabilities during the twelve months ended December 31, 2018:
Year ended December 31, 2018
Contract liabilities:
Deferred revenue
Balance as of
January 1, 2018
Additions
Deductions
Balance as of
December
31, 2018
123,783
40,393
(26,917)
137,259
During the twelve months ended December 31, 2018 we recognized the following revenues as a result of changes in the contract liability balances in
the respective periods:
Revenue recognized in the period from:
Amounts included in the contract liability at the beginning
of the period
Year Ended December 31,
2018
15,774
When consideration is received, or such consideration is unconditionally due, from a customer prior to transferring goods or services to the customer
under the terms of a contract, a contract liability is recorded. Revenue is recognized from the contract liability over time using the cost-to-cost method.
10.
Net Loss per Share
Basic and diluted net loss per share attributable to common stockholders was calculated as follows:
Numerator:
Net loss attributable to common stockholders
$
(98,942) $
(89,380) $
(91,579)
2018
Year Ended December 31,
2017
2016
Denominator:
Weighted average common shares outstanding,
basic and diluted
Net loss per share attributable to common
stockholders, basic and diluted
40,743,492
40,449,410
39,846,928
$
(2.43) $
(2.21) $
(2.30)
F-25
SERES THERAPEUTICS, INC.
NOTES TO CONSOLIDATED FINANCIAL STATEMENTS
(amounts in thousands, except share and per share data)
The Company’s potential dilutive securities, which include stock options, unvested restricted common stock and shares issuable under the ESPP, have
been excluded from the computation of diluted net loss per share as the effect would be to reduce the net loss per share. Therefore, the weighted average
number of common shares outstanding used to calculate both basic and diluted net loss per share attributable to common stockholders is the same. The
following potential common shares, presented based on amounts outstanding at each period end, were excluded from the calculation of diluted net loss per
share attributable to common stockholders for the periods indicated because including them would have had an anti-dilutive effect:
Stock options to purchase common stock
Unvested restricted stock units
Shares issuable under ESPP
11.
Commitments and Contingencies
Leases
Year Ended December 31,
2017
6,125,692
356,778
—
2018
7,561,719
226,900
49,495
7,838,114
6,482,470
2016
5,069,133
115,500
—
5,184,633
The Company previously leased office and laboratory space with a lease term expiring in January 2018 and no extension periods. In May 2016, upon
mutual agreement with the landlord, the Company accelerated the termination of the operating lease to June 30, 2016. Upon termination of the lease, the
Company recorded a benefit to rent expense of $136 to write off amounts previously recorded as deferred rent. The outstanding security deposit of $119,
which was secured by a cash collateralized letter of credit, was released in September 2016.
On April 1, 2015, the Company entered into a lease for additional office and laboratory space with a term expiring in April 2020.
On November 11, 2015, the Company entered into a non-cancelable property lease with BMR-Sidney Research Campus LLC (“BMR”) for 83,396
square feet of office, laboratory and pilot manufacturing space at 200 Sidney Street, Cambridge, Massachusetts. The lease term commenced in March 2016
and ends in November 2023. The Company has the option to extend the lease twice, each for a five-year period. The Company moved its corporate
headquarters to this location in April 2016. BMR has contributed a total of $12,509 toward the cost of tenant improvements. BMR’s contributions toward the
cost of tenant improvements is recorded as a lease incentive obligation on the Company’s consolidated balance sheet. The lease incentive obligation is
amortized to the Company’s consolidated statement of operations as reductions to rent expense over the lease term. As of December 31, 2018, the Company
recorded a lease incentive obligation of $8,544. During the year ended December 31, 2018, the Company amortized $1,768 of this lease incentive obligation
as a reduction to rent expense.
During the years ended December 31, 2018, 2017 and 2016, the Company recognized $4,377, $4,458, and $3,826, respectively, of rental expense
related to office and laboratory space.
Future minimum lease payments for these operating leases as of December 31, 2018 are as follows:
Year Ending December 31,
2019
2020
2021
2022
2023
2024 and thereafter
Total
F-26
$
$
6,342
6,120
6,221
6,372
5,158
—
30,213
SERES THERAPEUTICS, INC.
NOTES TO CONSOLIDATED FINANCIAL STATEMENTS
(amounts in thousands, except share and per share data)
Indemnification Agreements
In the ordinary course of business, the Company may provide indemnification of varying scope and terms to vendors, lessors, business partners and
other parties with respect to certain matters including, but not limited to, losses arising out of breach of such agreements or from intellectual property
infringement claims made by third parties. In addition, the Company has entered into indemnification agreements with members of its board of directors and
its officers that will require the Company, among other things, to indemnify them against certain liabilities that may arise by reason of their status or service
as directors or officers. The maximum potential amount of future payments the Company could be required to make under these indemnification agreements
is, in many cases, unlimited. To date, the Company has not incurred any material costs as a result of such indemnifications. The Company does not believe
that the outcome of any claims under indemnification arrangements will have a material effect on its financial position, results of operations or cash flows,
and it has not accrued any liabilities related to such obligations in its consolidated financial statements as of December 31, 2018 or 2017.
12.
Income Taxes
During the years ended December 31, 2018, 2017 and 2016, the Company recorded no income tax benefits for the net operating losses incurred in each
year or interim period, due to its uncertainty of realizing a benefit from those items.
A reconciliation of the U.S. federal statutory income tax rate to the Company’s effective income tax rate is as follows:
Federal statutory income tax rate
Research and development tax credits
State taxes, net of federal benefit
Stock-based compensation
Revaluation of preferred stock warrant liability
Other
Change in deferred tax asset valuation allowance
Effective income tax rate
F-27
2018
Year Ended December 31,
2017
2016
(21.0)%
(7.2)
(7.2)
2.0
—
0.8
32.6
—%
(34.0)%
(7.7)
(4.8)
1.2
33.1
(0.3)
12.5
—%
(34.0)%
(8.8)
(5.8)
(6.3)
—
0.1
54.8
—%
SERES THERAPEUTICS, INC.
NOTES TO CONSOLIDATED FINANCIAL STATEMENTS
(amounts in thousands, except share and per share data)
As permitted by SEC Staff Accounting Bulletin 118, Income Tax Accounting Implications of the Tax Cuts and Jobs Act (“TCJA”), the Company
recorded provisional estimates during the year ended December 31, 2017 and have subsequently finalized its accounting analysis based on the guidance,
interpretations, and data available as of December 31, 2018. The Company finalized its accounting for the income tax effects of the TCJA during 2018, with
no adjustment to the provisional amounts previously recorded.
Net deferred tax assets as of December 31, 2018 and 2017 consisted of the following:
Deferred tax assets:
Net operating loss carryforwards
Research and development tax credit carryforwards
Capitalized organization costs
Stock-based compensation expense
Charitable Contributions
Deferred Revenue
Accrued expenses
Capitalized research and development expenses
Total deferred tax assets
Deferred tax liabilities:
Depreciation and amortization
Total deferred tax liabilities
Valuation allowance
Net deferred tax assets
F-28
December 31,
2018
2017
$
$
$
$
50,723 $
32,522
275
9,178
11
37,499
4,279
66
134,553 $
(2,544)
(2,544)
(132,009) $
— $
32,997
25,405
306
7,714
8
26,480
4,613
73
97,596
(3,470)
(3,470)
(94,126)
—
SERES THERAPEUTICS, INC.
NOTES TO CONSOLIDATED FINANCIAL STATEMENTS
(amounts in thousands, except share and per share data)
As of December 31, 2018, the Company had net operating loss carryforwards (“NOLs”) for federal and state income tax purposes of $185,583 and
$185,927, respectively. Federal NOLs of $119,781, generated before 2018, will begin expiring in varying amounts in 2035 unless utilized. The remaining
federal NOLs of $65,801, generated after 2017, will be carried forward indefinitely and could be used to offset up to 80% of taxable income of each future tax
year. Massachusetts does not follow federal time periods for NOLs and as such the Company’s Massachusetts NOLs of $185,927 will expire in at various
times starting in 2035. As of December 31, 2018, the Company also had available research and development tax credit carryforwards for federal and state
income tax purposes of $28,638 and $4,916, respectively, which begin to expire in 2031 and 2028, respectively. The federal research and development tax
credits include an orphan drug credit carryforward of $17,552. Utilization of the NOLs and research and development tax credit carryforwards may be subject
to a substantial annual limitation under Section 382 of the Internal Revenue Code of 1986 due to ownership changes that have occurred previously or that
could occur in the future. These ownership changes may limit the amount of carryforwards that can be utilized annually to offset future taxable income. In
general, an ownership change, as defined by Section 382, results from transactions increasing the ownership of certain shareholders or public groups in the
stock of a corporation by more than 50% over a three-year period. Since our formation, the Company has raised capital through the issuance of capital stock
on several occasions. These financings, combined with the purchasing shareholders' subsequent disposition of those shares, may have resulted in a change of
control as defined by Section 382 or could result in a change of control in the future upon subsequent disposition. The Company conducted an analysis under
Section 382 to determine if historical changes in ownership through August 31, 2015 would limit or otherwise restrict its ability to utilize these NOLs and
research and development credit carryforwards. As a result of this analysis, the Company does not believe there are any significant limitations on its ability to
utilize these carryforwards. However, future changes in ownership after August 31, 2015 could affect the limitation in future years. Any limitation may result
in expiration of a portion of the NOLs or research and development credit carryforwards before utilization.
The Company has evaluated the positive and negative evidence bearing upon its ability to realize the deferred tax assets. Management has considered
the Company’s history of cumulative net losses incurred since inception and its lack of commercialization of any products or generation of any revenue from
product sales since inception and has concluded that it is more likely than not that the Company will not realize the benefits of the deferred tax assets.
Accordingly, a full valuation allowance has been established against the deferred tax assets as of December 31, 2018 and 2017. Management reevaluates the
positive and negative evidence at each reporting period.
Changes in the valuation allowance for deferred tax assets during the years ended December 31, 2018, 2017 and 2016 related primarily to the increases
in NOLs, research and development tax credit carryforwards, stock-based compensation and decrease of the deferred rate due to tax reform were as follows:
Valuation allowance at beginning of year
Decreases recorded as benefit to income tax provision
Increases recorded to income tax provision
Valuation allowance as of end of year
2018
Year Ended December 31,
2017
2016
$
$
(94,126) $
—
(37,883)
(132,009) $
(82,994) $
29,546
(40,678)
(94,126) $
(32,777)
—
(50,217)
(82,994)
As of December 31, 2018, 2017, and 2016, the Company had no unrecognized tax benefits. Interest and penalty charges, if any, related to
unrecognized tax benefits would be classified as income tax expense. The Company does not expect any significant change in its uncertain tax positions in the
next 12 months.
During the year ended December 31, 2016, the Company was awarded a tax incentive for job creation from the Massachusetts Life Sciences Center.
The program was established in 2008 in order to incentivize life sciences companies to create new sustained jobs in Massachusetts. Jobs must be maintained
for at least five years, during which time the grant proceeds can be recovered by the Massachusetts Department of Revenue if the Company does not meet and
maintain its job creation commitments. The award was received in 2016 and recorded in other current liabilities as of December 31, 2016 as the Company did
not meet the job creation commitments. During the year ended December 31, 2018, the Company met the job creation commitments and recorded $170 as
other income in the consolidated statement of operations for the portion of the award earned through the year ended December 31, 2018. The balance of the
incentive award has been recorded in the Company’s consolidated balance sheet as a liability until such time that the award is fully earned.
F-29
SERES THERAPEUTICS, INC.
NOTES TO CONSOLIDATED FINANCIAL STATEMENTS
(amounts in thousands, except share and per share data)
13.
Selected Quarterly Financial Data (Unaudited)
The following table contains quarterly financial information for 2018 and 2017. The Company believes that the following information reflects all
normal recurring adjustments necessary for a fair statement of the information for the periods presented. The operating results for any quarter are not
necessarily indicative of results for any future period.
Collaboration revenue - related party (1)
Grant revenue
Total operating expenses
Loss from operations
Net loss
Net loss per share applicable to common
stockholders - basic and diluted
Collaboration revenue - related party (1)
Total operating expenses
Loss from operations
Net loss
Net loss per share applicable to common
stockholders - basic and diluted
First
Quarter
Second
Quarter
2018
Third
Quarter
Fourth
Quarter
$
3,766 $
205
32,237
(28,266)
(27,919)
4,271 $
341
32,748
(28,136)
(27,787)
8,684 $
371
31,266
(22,211)
(21,949)
10,196 $
433
32,300
(21,671)
(21,287)
Total
26,917
1,350
128,551
(100,284)
(98,942)
$
(0.69) $
(0.68) $
(0.54) $
(0.52) $
(2.43)
First
Quarter
Second
Quarter
2017
Third
Quarter
Fourth
Quarter
$
3,015 $
28,905
(25,890)
(25,474)
3,014 $
31,430
(28,416)
(28,018)
23,015 $
30,329
(7,314)
(6,935)
3,056 $
32,831
(29,775)
(28,953)
Total
32,100
123,495
(91,395)
(89,380)
$
(0.63) $
(0.69) $
(0.17) $
(0.72) $
(2.21)
(1)
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 Company’s reported results for 2018 reflect the application of ASC 606 guidance while its reported results for 2017 and 2016 were
prepared under the guidance outlined in ASC 605. Refer to Note 9 for further details.
14.
Related Party Transactions
In October 2010, the Company entered into a services agreement with Flagship Ventures Management, Inc., an affiliate of one of its stockholders (and
now known as Flagship Pioneering), Flagship Venture Funds, to provide general and administrative services to the Company, including the employer portions
of employee health and dental benefit plans for the Company’s employees and consulting services. The Company made payments under the agreement of $17
during the year ended December 31, 2016. There were no payments made during the year ended December 31, 2018 and 2017. There were no amounts due to
Flagship Pioneering related to the services agreement as of December 31, 2018 and 2017.
As described in Note 9, in January 2016 the Company entered into a License Agreement and, in November 2018, a letter agreement with NHS for the
development and commercialization of certain product candidates in development for the treatment and management of CDI and IBD, including UC and
Crohn’s disease. NHS is a related party since NHS is an affiliate of Nestlé Health Science, one of the Company’s significant stockholders. During the year
ended December 31, 2018, 2017, and 2016, the Company recognized $26,917, $32,100, and $21,766, respectively, of related party revenue associated with
the License Agreement. As of December 31, 2018 and 2017, there was $137,259 and $96,926, respectively, of deferred revenue related to the License
Agreement, which is classified as current or non-current in the consolidated balance sheets. The Company has made no payments to NHS during the year
ended December 31, 2018. There is no amount due from NHS as of December 31, 2018.
F-30
SERES THERAPEUTICS, INC.
NOTES TO CONSOLIDATED FINANCIAL STATEMENTS
(amounts in thousands, except share and per share data)
15.
401(k) Savings Plan
The Company has a defined contribution savings plan under Section 401(k) of the Internal Revenue Code. This plan covers substantially all employees
who meet minimum age and service requirements and allows participants to defer a portion of their annual compensation on a pre-tax basis. Effective January
1, 2016, the Company elected to match 50% of the first 6% of an employee’s deferral. Company contributions are expensed in the year for which they are
declared. During the year ended December 31, 2018, 2017, and 2016 the Company recorded expense of $604, $484, and $457, respectively for 401(k) match
contributions.
16.
Subsequent Events
On January 14, 2019, Roger J. Pomerantz, M.D. notified the Company of his resignation from his position as President and Chief Executive Officer of
the Company effective immediately. In connection with his resignation, Dr. Pomerantz entered into a separation agreement and release (the “Separation
Agreement”) with the Company pursuant to which Dr. Pomerantz will receive the severance payments and benefits described in his existing employment
agreement with the Company upon his involuntary or constructive termination, subject to and in accordance with the previously disclosed terms of his
employment agreement. Dr. Pomerantz will continue to serve as a director and as Chairman of the Board of Directors (the “Board”) of the Company. The
Company expects to record a liability in the first quarter of 2019 to reflect its obligations to Dr. Pomerantz under the Separation Agreement.
On January 15, 2019, the Company announced that the Board had appointed Eric D. Shaff, as the Company’s President and Chief Executive Officer
and as a member of the Board.
On February 7, 2019, the Company announced corporate changes to focus its resources on advancing its clinical-stage therapeutics candidates. As a
result, the Company will now concentrate on completing the recently-initiated SER-287 Phase 2b study in mild-to-moderate UC, obtaining results from the
ongoing SER-109 Phase 3 study for recurrent CDI and advancing the SER-401 Phase 1b study, in collaboration with the Parker Institute for Cancer
Immunotherapy and MD Anderson Cancer Center, to evaluate augmenting checkpoint inhibitor response in patients with metastatic melanoma. In connection
with the prioritization of these therapeutics candidates, the Company made changes to its management team and committed to a workforce reduction plan to
reduce headcount by approximately 30 employees. Accordingly, the Company expects to incur one-time costs related primarily to employee termination
benefits between $1,500 and $2,000.
F-31
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 6, 2019
SERES THERAPEUTICS, INC.
By: /s/ Eric D. Shaff
Eric D. Shaff
President, Chief Executive Officer and Director
Pursuant to the requirements of the Securities Exchange Act of 1934, this report has been signed below by the following persons on behalf of the
registrant and in the capacities and on the dates indicated.
/s/ Eric D. Shaff
Signature
Eric D. Shaff
Title
Date
President, Chief Executive Officer
and Director
(Principal Executive Officer and Principal Financial
and Accounting Officer)
/s/ Roger J. Pomerantz
Chairman of the Board
Roger J. Pomerantz, M.D.
/s/ Noubar B. Afeyan
Noubar B. Afeyan, Ph.D.
/s/ Dennis Ausiello
Dennis Ausiello, M.D.
/s/ Willard Dere
/s/ Grégory Behar
/s/ Kurt C. Graves
Willard Dere
Grégory Behar
Kurt C. Graves
/s/ Richard N. Kender
Richard N. Kender
/s/ Lorence H. Kim
Lorence H. Kim, M.D.
/s/ Meryl Zausner
Meryl Zausner
Director
Director
Director
Director
Director
Director
Director
Director
March 6, 2019
March 6, 2019
March 6, 2019
March 6, 2019
March 6, 2019
March 6, 2019
March 6, 2019
March 6, 2019
March 6, 2019
March 6, 2019
EXHIBIT 10.22
AMENDMENT #1 TO THE COLLABORATION AND LICENSE AGREEMENT
This AMENDMENT #1 TO THE COLLABORATION AND LICENSE AGREEMENT (the "Amendment") is entered into
this tenth day of August, 2016 by and between NESTEC LTD., a limited company organized and existing under the laws of
Switzerland, having an office located at Avenue Nestle 55, 1800 Vevey, Switzerland ("NHSc"), and Seres Therapeutics, Inc., a
corporation incorporated and existing under the laws of the State of Delaware, having an office located at 200 Sydney Street,
Cambridge MA 02139, USA ("Seres"). NHSc and Seres are sometimes referred to herein as the "Parties".
WHEREAS, the Parties entered into a COLLABORATION AND LICENSE AGREEMENT dated January 9, 2016 (the
"Agreement") whereby Seres granted to NHSc certain licenses under intellectual property controlled by Seres relating to a new
class of medicinal microbiome products to treat and manage inflammatory bowel disease, and treat and prevent the recurrence of C.
difficile infections (the "Products"), outside the US and Canada;
WHEREAS, in the course of the collaboration under the Agreement, Seres conducted a Phase 2 study for the initial C.
difficile product SER-109, and recently determined that the primary endpoint of such study was not achieved;
WHEREAS, Seres has begun to gather and analyze data relating to the Phase 2 study in order to make appropriate
adjustments to the SER-109 development plan, and NHSc would like to assist Seres therewith;
WHEREAS, in order to facilitate NHSc so-assisting Seres, Seres will share with NHSc highly confidential information which
the Parties agree will require a higher level of confidential treatment by NHSc than is currently provided for in ARTICLE 11 of the
Agreement, and hence the Parties wish to provide for such higher level of confidential treatment in accordance with this
Amendment, for this currently contemplated exchange of highly confidential information, and for potential future exchanges of
other highly confidential information.
NOW, THEREFORE in consideration of the foregoing and the terms below, the Parties agree to amend the Agreement by
adding the following new section 11.7 (capitalized terms below not defined herein shall have the meanings set forth in the
Agreement):
11.7Special Treatment of Highly Confidential Information. A Party may from time to time be in possession of information
which such party desires to disclose to the other Party under more restrictive terms than otherwise provided for in this
ARTICLE 11 ("Highly Confidential Information"). In such case, the party desiring to make such disclosure ("Disclosing
Party") shall notify the other Party ("Receiving Party") in writing of the general category of information proposed to be
so disclosed in order to allow the Receiving Party the opportunity to agree to receive the Highly Confidential Information
from the Receiving Party under the terms of this section 11.7. If the Receiving Party elects not to receive such Highly
Confidential Information on such terms, the Disclosing Party may elect to either not disclose the information at all, or to
disclose the information under the terms of sections 11.1 through 11.6 of this ARTICLE 11. If the Receiving Party elects
to receive such Highly Confidential Information under the terms of this section 11.7, then each Party shall select no more
than four (4) people agreeable to the other Party to be participants in the exchange of, and discussions concerning, Highly
Confidential Information ("Section 11.7 Participants") unless, on a case by case basis, the Parties agree in writing to a
number greater than four (4). The Section 11.7 Participants shall agree upon a process to exchange and discuss Highly
Confidential Information, and the Parties shall arrange for the recording of minutes of such exchanges and discussions.
All such minutes, and other materials such as agendas, slide presentations, Webex content, handouts, etc. used as part of
such exchanges and discussions, shall be clearly marked as "Highly Confidential Information", and all such materials
including the information contained therein shall be held in strict confidence by the Section 11.7 Participants, including
to the exclusion of other employees, agents and Affiliates of their respective Party. Each Section 11.7 Participant will
promptly notify the other Party upon becoming aware of any use or disclosure of Highly Confidential Information not
permitted pursuant to this section 11.7. Sections 11.1.1 and 11.2 shall not apply to Highly Confidential Information, and
sections 11.4, 11.5 and 11.6 shall apply to Highly Confidential Information.
IN WITNESS WHEREOF, the Parties have caused this Amendment to be executed by their respective duly authorized
officers.
SERES THERAPEUTICS, INC.
By:
/s/ Roger J. Pomerantz, M.D.
Name:
/s/ Roger J. Pomerantz, M.D., F.A.C.P.
Title
President, CEO and Chairman
NESTEC LTD.
By:
/s/ Claudio Vuoni
Name:
/s/ Claudio Vuoni
Title
General Counsel NHSc
CONFIDENTIAL
EXHIBIT 10.23
*** INDICATES MATERIAL THAT WAS OMITTED AND FOR WHICH CONFIDENTIAL TREATMENT WAS
REQUESTED. ALL SUCH OMITTED MATERIAL WAS FILED SEPARATELY WITH THE SECURITIES AND
EXCHANGE COMMISION PURUSANT TO RULE 24b-2 PROMULGATED UNDER THE SECURITIES ECHANGE
ACT OF 1934, AS AMENDED.
NESTEC LTD.
Attention: General Counsel, Nestlè Health Science
Avenue Nestle 55
1800 Vevey
Switzerland
October 30, 2018
This letter agreement (“Letter Agreement”) sets forth the agreement between NESTEC LTD. (“NHSc”) and Seres Therapeutics,
Inc. (“Seres”) (each of NHSc and Seres, a “Party”, and together, the “Parties”), pursuant to which certain terms of the
Collaboration and License Agreement between Seres and NHSc dated January 9, 2016 (the “Agreement”) will be amended and
clarified with respect to the conduct of a particular clinical study of the product designated as SER‑287.
Capitalized terms used but not defined herein shall have the meanings ascribed to them in the Agreement.
Notwithstanding anything to the contrary in the Agreement (including without limitation all Development Plans thereunder), the
Parties hereby agree as follows, effective as of the date of this Letter Agreement (the “Letter Agreement Effective Date”):
a)
Seres recognizes that its obligation under Section 4.1 to use Diligent Efforts to Develop Collaboration Products and
obtain approval of a BLA thereon in the European Union includes an obligation to Develop Products that are
commercially viable, i.e., that such obligation should take into consideration the “profit potential” of Collaboration
Products per the definition of Diligent Efforts in the Agreement. [***]
b)
Upon commencement of the 3‑Arm SER‑287 Clinical Trial (as defined below), NHSc shall pay to Seres an amount equal
to forty million US dollars ($40,000,000) (the “Total Phase II/III SER‑287 Milestone Payment”) in connection with
the following two milestone payments set forth in the Agreement as listed as the first and second milestone payments in
the table in Section 8.2.1 of the Agreement (respectively, the “Applicable Milestone Payments”, and the “Applicable
Milestone Events”):
Applicable Milestone Event
Applicable Milestone Payment
Commencement of a Phase II Clinical Trial, as contemplated in
the Global Development Plan, in respect of the First IBD
Product for UC (Induction).
$20,000,000
Commencement of a Phase III Clinical Trial, as contemplated
in the Global Development Plan, in respect of the First IBD
Product for UC (Induction).
$20,000,000
In the event the 3‑Arm SER‑287 Clinical Trial commences before December 15, 2018, NHSc will pay the Total Phase
II/III SER‑287 Milestone Payment before December 31, 2018. In the event the 3‑Arm SER‑287 Clinical Trial
commences between December 16, 2018 and December 27, NHSc will use commercially reasonable efforts to pay the
Total Phase II/III SER‑287 Milestone Payment before December 31, 2018. In order to facilitate logistics of such a
payment, Seres will regularly inform NHSc about the expected commencement of the 3‑Arm SER‑287 Clinical
Trial. For clarity, the Applicable Milestone Payments for the achievement of the Applicable Milestone Events set forth in
this paragraph b) shall replace the first and second milestone payments that are set forth in Section 8.2.1 of the
Agreement, upon Seres’s receipt of the Total Phase II/III SER‑287 Milestone Payment.
c)
Seres shall conduct a Clinical Trial with respect to the First IBD Product for the treatment of UC, which Clinical Trial
will consist of three (3) arms, 67 patients per arm for a total of 201 subjects, the arms being P/P, [***] in accordance with
the protocol therefor as to be approved by the JSC (the “Protocol Amendment”) (the “3‑Arm SER‑287 Clinical
Trial”). The JSC shall update the applicable Development Plan to account for the conduct of the 3‑Arm SER‑287
Clinical Trial by Seres promptly after the Letter Agreement Effective Date. For purposes of this Letter Agreement, the
treatment arm of the 3‑Arm SER‑287 Clinical Trial designed to include a [***] of the First IBD Product shall be referred
to herein as the “Lower Dose”.
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REQUESTED. ALL SUCH OMITTED MATERIAL WAS FILED SEPARATELY WITH THE SECURITIES AND
EXCHANGE COMMISSION PURSUANT TO RULE 24b-2 PROMULGATED UNDER THE SECURITIES EXCHANGE
ACT OF 1934, AS AMENDED.
2
d)
e)
f)
If after submission by or on behalf of Seres of the Protocol Amendment for the 3‑Arm SER‑287 Clinical Trial to the
FDA, (i) FDA provides feedback indicating that the 3‑Arm SER‑287 Clinical Trial could not be used as one of the two
necessary Phase III Clinical Trials for the First IBD Product for the treatment of UC (i.e., the data from the 3‑Arm
SER‑287 Clinical Trial, even if it shows statistically compelling efficacy, could not be used in a BLA submission as one
of two such Phase III Clinical Trials) and (ii) the results of the 3‑Arm SER‑287 Clinical Trial are sufficient to allow Seres
to proceed to conduct the first of the two Phase III Clinical Trials in respect of the Lower Dose, then (X) [***] and (Y)
Section 4.8 and Section 4.8.1(b) of the Agreement shall continue to apply with respect to the sharing of Development
Costs for both the first and second Phase III Clinical Trials to be conducted by Seres for the First IBD Product for the
treatment of UC.
If after submission by or on behalf of Seres of the Protocol Amendment for the 3‑Arm SER‑287 Clinical Trial to the
FDA, (i) the FDA provides feedback indicating that the 3‑Arm SER‑287 Clinical Trial could not be used as one of the
two necessary Phase III Clinical Trials for the First IBD Product for the treatment of UC (i.e., the data from the 3‑Arm
SER‑287 Trial, even if it shows statistically compelling efficacy, could not be used in a BLA submission as one of two
such Phase III Clinical Trials) and (ii) the results of the 3‑Arm SER‑287 Trial do not demonstrate statistically significant
efficacy of the Lower Dose, then (X) [***] and (Y) all future Development Costs to be shared by the Parties pursuant to
Section 4.8 of the Agreement will be shared as between Seres and NHSc pursuant to Sections 4.8.1(b) (IBD Products)
and 4.8.2(c) (C Difficile Products) of the Agreement provided that, [***]
If after submission by or on behalf of Seres of the Protocol Amendment for the 3‑Arm SER‑287 Clinical Trial to the
FDA, (i) the FDA provides feedback indicating that the 3‑Arm SER‑287 Clinical Trial could be used as one of the two
necessary Phase III Clinical Trials for the First IBD Product for the treatment of UC (i.e. the data from the 3‑Arm
SER‑287 Trial, if statistically compelling, could be used in a BLA submission as one of two such Phase III Clinical
Trials) and (ii) the results of the 3‑Arm SER‑287 Clinical Trial demonstrate statistically significant efficacy to allow for
Seres to conduct the second of the two Phase III Clinical Trials required for Regulatory Approval of the First IBD
Product for the treatment of UC, then the Development Costs of the 3‑Arm SER‑287 Clinical Trial and the second of the
two Phase III Clinical Trials required for Regulatory Approval shall be shared by Seres and NHSc pursuant to Section
4.8.1(b) of the Agreement, provided that [***]
*** INDICATES MATERIAL THAT WAS OMITTED AND FOR WHICH CONFIDENTIAL TREATMENT WAS
REQUESTED. ALL SUCH OMITTED MATERIAL WAS FILED SEPARATELY WITH THE SECURITIES AND
EXCHANGE COMMISSION PURSUANT TO RULE 24b-2 PROMULGATED UNDER THE SECURITIES EXCHANGE
ACT OF 1934, AS AMENDED.
3
g)
h)
i)
j)
k)
l)
m)
If after submission by or on behalf of Seres of the Protocol Amendment for the 3‑Arm SER‑287 Clinical Trial to the
FDA, (i) the FDA provides feedback indicating that the 3‑Arm SER‑287 Clinical Trial could be used as one of the two
necessary Phase III Clinical Trials for the First IBD Product for the treatment of UC (i.e. the data from the 3‑Arm
SER‑287 Trial, if statistically compelling, could be used in a BLA submission as one of two such Phase III Clinical
Trials) and (ii) the results of the 3‑Arm SER‑287 Clinical Trial demonstrate statistically significant efficacy with respect
to the Lower Dose only to the extent that such results would make such 3‑Arm SER‑287 Clinical Trial constitute only a
Phase II Clinical Trial (i.e. two additional Phase III Clinical Trials for the First IBD Product for the treatment of UC are
still required to be conducted for a BLA submission therefor), then [***] and the Development Costs of both of the Phase
III Clinical Trials which are additionally required to be conducted shall be shared by Seres and NHSc pursuant to Section
4.8.1(b) of the Agreement.
If after submission by or on behalf of Seres of the Protocol Amendment for the 3‑Arm SER‑287 Clinical Trial to the
FDA, (i) FDA provides feedback indicating that the 3‑Arm SER‑287 Clinical Trial could be used as one of the two
necessary Phase III Clinical Trials for the First IBD Product for the treatment of UC (i.e. the data from the 3‑Arm
SER‑287 Trial, if statistically compelling, could be used in a BLA submission as one of two such Phase III Clinical
Trials) and (ii) the results of the 3‑Arm SER‑287 Trial do not demonstrate statistically significant efficacy of the Lower
Dose, then (X) [***] and (Y) [***]
[***]
Notwithstanding the foregoing provisions of this Letter Agreement, if NHSc after a commercial viability assessment
decides in its sole discretion to launch in the EU a First IBD Product for the treatment of UC comprised of a higher
dosage strength than the Lower Dose (“Commercial Viability Determination”), then within thirty (30) days after the
Commercial Viability Determination, NHSc will pay to Seres the amount calculated by determining the amount NHSc
would have paid under Section 4.8 of the Agreement to support Development Costs for Clinical Trials for the First IBD
Product for the treatment of UC, without taking into account the terms and conditions of this Letter Agreement, and
subtracting from such amount the amount of Development Costs previously paid by NHSc for the First IBD Product for
UC by operation of the terms of this Letter Agreement.
The Parties acknowledge that the terms and conditions of this Letter Agreement shall be treated as the Confidential
Information of both Parties, subject to Article 11 of the Agreement.
Except as expressly provided in this Letter Agreement, the Agreement shall continue in full force and effect. This Letter
Agreement, and the other terms and conditions of the Agreement, constitute the entire agreement of the Parties with
respect to the subject matter hereof.
This Letter Agreement may be executed in counterparts, each of which shall constitute an original and all of which shall
together constitute a single agreement. This Letter Agreement may be executed and delivered electronically, including
via PDF format, and upon such delivery such electronic signature will be deemed to have the same effect as if the original
signature had been delivered to the other Parties.
[Signature Page Follows]
4
*** INDICATES MATERIAL THAT WAS OMITTED AND FOR WHICH CONFIDENTIAL TREATMENT WAS
REQUESTED. ALL SUCH OMITTED MATERIAL WAS FILED SEPARATELY WITH THE SECURITIES AND
EXCHANGE COMMISSION PURSUANT TO RULE 24b-2 PROMULGATED UNDER THE SECURITIES EXCHANGE
ACT OF 1934, AS AMENDED.
To agree that this Letter Agreement accurately reflects our mutual agreement, please execute and return to me a copy of this Letter
Agreement.
By:
/s/ Roger J. Pomerantz
Roger J. Pomerantz, MD, FACP
President, CEO and Chairman
Seres Therapeutics, Inc.
Agreed to this 1 day of November, 2018
By:
/s/ Claudio Kuoni
Printed Name:
Claudio Kuoni
Title:
NESTEC LTD.
General Counsel Nestlé Health Science
*** INDICATES MATERIAL THAT WAS OMITTED AND FOR WHICH CONFIDENTIAL TREATMENT WAS
REQUESTED. ALL SUCH OMITTED MATERIAL WAS FILED SEPARATELY WITH THE SECURITIES AND
EXCHANGE COMMISSION PURSUANT TO RULE 24b-2 PROMULGATED UNDER THE SECURITIES EXCHANGE
ACT OF 1934, AS AMENDED.
5
SUBSIDIARIES OF SERES THERAPEUTICS, INC.
EXHIBIT 21.1
Legal Name of Subsidiary
Seres Therapeutics Securities Corporation
Seres Therapeutics UK Limited
Seres Therapeutics Netherlands B.V.
Jurisdiction of Organization
Massachusetts
United Kingdom
The Netherlands
CONSENT OF INDEPENDENT REGISTERED PUBLIC ACCOUNTING FIRM
EXHIBIT 23.1
We hereby consent to the incorporation by reference in the Registration Statements on Forms S-8 (No. 333-223514, 333-210171 and 333-205253) and Form
S-3 (No. 333-216735) of Seres Therapeutics, Inc. of our report dated March 6, 2019 relating to the financial statements, which appears in this Form 10-K.
/s/ PricewaterhouseCoopers LLP
Boston, Massachusetts
March 6, 2019
1
Exhibit 31.1
I, Eric D. Shaff, certify that:
1. I have reviewed this Annual Report on Form 10-K of Seres Therapeutics, Inc.;
CERTIFICATIONS
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. I am 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. 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.
Date: March 6, 2019
By:
/s/ Eric D. Shaff
Eric D. Shaff
President, Chief Executive Officer and Director
(Principal Executive Officer and 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, Eric D. Shaff, President and Chief Executive Officer of Seres Therapeutics, 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)
(2)
March 6, 2019
The Annual Report on Form 10-K of the Company for the period ended December 31, 2018 (the “Report”) fully complies with the
requirements of Section 13(a) or 15(d) of the Securities Exchange Act of 1934, as amended; and
The information contained in the Report fairly presents, in all material respects, the financial condition and results of operations of the
Company.
/s/ Eric D. Shaff
Eric D. Shaff
President, Chief Executive Officer and Director
(Principal Executive Officer and Principal Financial and Accounting Officer)