UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
WASHINGTON, D.C. 20549
FORM
CURRENT REPORT
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| Item 7.01. | Regulation FD Disclosure. |
On November 20, 2020, Seres Therapeutics, Inc. (the “Company”) posted an updated corporate slide presentation in the “Investors and News” portion of its website at www.serestherapeutics.com. A copy of the slide presentation is attached as Exhibit 99.1 to this Current Report on Form 8-K (the “Current Report”). The slide presentation includes the following business updates: The Company is actively enrolling patients in its SER-109 open-label study to expand the safety database to meet the U.S. Food and Drug Administration (“FDA”) guidance of at least 300 subjects to enable a planned filing of the biologics license application (“BLA”). The BLA filing will also be supported by the positive SER-109 Phase 3 study results, announced in August 2020. In November 2020, the FDA indicated to the Company that the SER-109 safety database should include at least 300 treated subjects with 24 weeks of follow-up. The FDA indicated that the safety database should be provided no later than 30 days subsequent to the filing of the biologics license application for SER-109. In addition, in November 2020, the Company dosed the first patient in its Phase 1b clinical trial of SER-301 in adults with mild-to-moderate ulcerative colitis. The Phase 1b study of SER-301, an oral, rationally-designed microbiome therapeutic, is designed to include approximately 65 patients and is being conducted in Australia and New Zealand.
The information in Item 7.01 of this Current Report, including Exhibit 99.1 attached hereto, is intended to be furnished and shall not be deemed “filed” for purposes of Section 18 of the Securities Exchange Act of 1934, as amended (the “Exchange Act”), or otherwise subject to the liabilities of that section, nor shall it be deemed incorporated by reference in any filing under the Securities Act of 1933, as amended, or the Exchange Act, except as expressly set forth by specific reference in such filing. The Company undertakes no obligation to update, supplement or amend the materials attached hereto as Exhibit 99.1.
Forward-Looking Statements
This Current Report on Form 8-K (the “Current Report”) contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. All statements contained in this Current Report that do not relate to matters of historical fact should be considered forward-looking statements, including the timing and overall safety database requirements for SER-109, initiation of additional clinical sites in the open-label study of SER-109 and acceleration of enrollment in the open-label study, the timing, content and outcome of any meetings with the FDA, and the timing of submission of a BLA for SER-109.
These forward-looking statements are based on management’s current expectations. These statements are neither promises nor guarantees, but involve known and unknown risks, uncertainties and other important factors that may cause the Company’s actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or implied by the forward-looking statements, including, but not limited to, the following: the Company has incurred significant losses, is not currently profitable and may never become profitable; the Company’s need for additional funding; the Company’s limited operating history; the Company’s unproven approach to therapeutic intervention; the lengthy, expensive, and uncertain process of clinical drug development; the Company’s reliance on third parties to manufacture, develop, and commercialize its product candidates, if approved; the Company’s ability to develop and commercialize its product candidates, if approved; the potential impact of the COVID-19 pandemic; the Company’s ability to retain key personnel and to manage its growth; and that the Company’s management and principal stockholders have the ability to control or significantly influence its business. These and other important factors discussed under the caption “Risk Factors” in the Company’s Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission, or SEC, on November 9, 2020 and its other reports filed with the SEC could cause actual results to differ materially from those indicated by the forward-looking statements made in this Current Report. Any such forward-looking statements represent management’s estimates as of the date of this Current Report. While the Company may elect to update such forward-looking statements at some point in the future, the Company disclaims any obligation to do so, even if subsequent events cause its views to change. These forward-looking statements should not be relied upon as representing the Company’s views as of any date subsequent to the date of this Current Report.
| Item 9.01. | Financial Statements and Exhibits. |
(d) Exhibits
The following Exhibit 99.1 relates to Item 7.01, and shall be deemed to be furnished, and not filed:
| Exhibit No. |
Description | |
| 99.1 | Seres Therapeutics, Inc. Corporate Slide Presentation as of November 20, 2020 | |
| 104 | Cover Page Interactive Data File (embedded within the Inline XBRL document) | |
SIGNATURES
Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.
| SERES THERAPEUTICS, INC. | ||||||
| Date: November 20, 2020 | By: | /s/ Thomas J. DesRosier | ||||
| Name: | Thomas J. DesRosier | |||||
| Title: | Chief Legal Officer and Executive Vice President | |||||
Seres Therapeutics Overview November 2020 Exhibit 99.1
Some of the statements in this presentation constitute “forward looking statements” under the Private Securities Litigation Reform Act of 1995, including, but not limited to, our development plans, the promise and potential impact of any of our microbiome therapeutics, the ability of our clinical trials to support approval, the timing of clinical studies, the timing and ultimate results of the SER-109 safety data, the size of the market for SER-109, the sufficiency of cash to fund operations, and the potential benefits of Seres’ collaborations. Such statements are subject to important factors, risks and uncertainties, such as those discussed under the caption "Risk Factors" in the Company’s Quarterly Report on Form 10-Q filed on November 9, 2020, and its other filings with the SEC, that may cause actual results to differ materially from those expressed or implied by such forward looking statements. Any forward looking statements included herein represent our views as of today only. We may update these statements, but we disclaim any obligation to do so. Forward looking statements
SER-109 Phase 3 success highlights that the time for microbiome therapeutics is now
Formulated for oral delivery using current Good Manufacturing Practices (cGMP) Consortia capture breadth of biological & functional diversity Mechanisms includes microbial engraftment in GI tract to restructure the microbiome Designed to target inflammatory & immunological disease pathways simultaneously Ecobiotic® microbiome therapeutics are encapsulated consortia of commensal bacteria with specific pharmacologic properties Seres is developing a novel drug modality that modulates the gut microbiome
End-to-End GMP Manufacturing Lead Optimization & Bioprocess Hit-to-Lead Identification Clinical sample biorepository Microbiome Biomarker Discovery Consortia Design Pharmacological Properties Validation Oral formulation Proprietary genomic & metabolomic analytics World-class collaborations Broad strain library & culturing know-how Genomic & host function screening In-silico drug design for functional targets Ex vivo & in vivo disease modeling Fermentation & formulation optimization platforms Donor-derived & multi-strain fermentation Anaerobic, spore & lyophilized technologies Late clinical stage drug release assays Disease Target Identification Industry-leading, in-house research engine for drug discovery, development & manufacturing
1. Collaboration with Nestlé Health Science, announced Jan. 11, 2016, regarding C. difficile and IBD programs for markets outside of North America 2. Collaboration with University of Texas MD Anderson Cancer Center and the Parker Institute for Cancer Immunotherapy, announced Nov. 14, 2017, regarding evaluation of microbiome therapies to improve the outcomes of cancer patients treated with immunotherapy. The Parker Institute is the IND application holder for SER-401. 3. Collaboration with AstraZeneca, announced Mar. 11, 2019, regarding advancing mechanistic understanding of the microbiome in augmenting the efficacy of cancer immunotherapy, including potential synergy with AstraZeneca compounds. Broad opportunities for microbiome therapeutics Collaborators Preclinical Phase 1b Phase 2b Phase 3 SER-109 Recurrent C. difficile Phase 3 SER-287 Ulcerative colitis Phase 2b SER-401 Metastatic melanoma in combination with anti-PD-1 MAb Phase 1b SER-301 Ulcerative colitis (Rationally-designed, fermented) Improve response to check-point therapies; potential synergies with AZ pipeline Immuno-Oncology Infectious Disease Inflammatory Oncology SER-155 Infection, Bacteremia & GvHD in HSCT for cancer (Rationally-designed, fermented)
C. difficile Infection Overview and SER-109 Phase 3 study
August 2020: Positive ECOSPOR III Phase 3 study read-out Primary endpoint: C. diff. recurrence, at up to 8 weeks SER-109 (n = 90) Multiply recurrent C. difficile patients (n=182) All subjects treated with standard of care antibiotics Placebo (n = 92) 0 weeks 8 weeks 24 weeks Safety follow-up to 24 weeks Toxin testing to ensure inclusion of subjects with active rCDI, and for accuracy of endpoint Substantially higher dose vs. Phase 2 designed to result in greater and earlier microbiome restoration Placebo arm to provide invaluable safety and efficacy data that cannot be obtained in open-label trials
Topline SER-109 Phase 3 study efficacy results Time point SER-109 (N =90) Placebo (N =92) RR (95%CI) p-Value (p1/p2) n (%) n (%) Week 8 10 (11.1) 38 (41.3) 0.27 (0.15, 0.51) <0.001 / <0.001 Highly statistically significant 30.2% absolute reduction in the rate of CDI recurrence compared to placebo Number needed to treat = approximately 3 Primary efficacy endpoint results: Sustained clinical response rate (i.e., percentage of patients who remain free of CDI at 8 weeks): SER-109 was effective in 88.9% of SER-109 subjects vs. 58.7% of subjects in the placebo arm Results were statistically significant in both age stratified subgroups: 18-64 years old, or 65 and over
Favorable safety profile observed in Phase 3 SER-109 was well tolerated, with no treatment-related serious adverse events (SAEs) observed in the active arm, and an adverse event profile similar to placebo Overall incidence of patients who experienced AEs during the eight-week study period was similar between SER-109 and placebo arms Most commonly observed treatment-related AEs were flatulence, abdominal distention and abdominal pain, which were generally mild to moderate in nature, and these were observed at a similar rate in both the SER-109 and placebo arms
Substantial recurrent C. difficile infection market opportunity Infectious disease caused by toxin-producing bacteria, resulting in diarrhea, abdominal pain, fever and nausea Leading cause of hospital-acquired infection in the U.S. ~ 453K cases of primary CDI within the U.S. each year ~ 170K episodes per year (100K episodes of first recurrence; ~ 73K episodes of 2+ recurrences) Estimated ~ $5B in healthcare burden each year Source: * Desai et al., Epidemiological and economic burden of Clostridium difficile in the United States: estimates from a modeling approach, BMC Infectious Diseases (2016) 16:303; Guh AY et al. NEJM 2020 25% of primary C. difficile recur Over 20,000 deaths per year Potential broad FDA label covering rCDI patients
FMT safety concerns highlight the need for improved, FDA-approved treatment options for C. difficile infection In contrast to FMT, SER-109 is comprised of a highly purified consortia of spore-based bacteria manufactured under GMP conditions to ensure product quality and consistency Unique manufacturing process to inactivate potential pathogens Process inactivates many emerging potential pathogens where diagnostic assays may not yet be widely available, such as SARS-CoV-2 Since July 2020, the largest U.S. provider of FMT has quarantined supply and halted shipments
SER-109 open label study enrollment ongoing to support expanded safety database Seres is currently enrolling recurrent CDI patients in an open label study to expand the SER-109 safety database, supporting a Biologics License Application (BLA) to the U.S. Food and Drug Administration (FDA) In November 2020, FDA indicated that the SER-109 safety database should include at least 300 treated subjects with 24 weeks of follow-up, 30 days subsequent to the BLA filing With support from the FDA, Seres is including patients with a first recurrence of CDI, in addition to those with multiple recurrent CDI, in the open label study Seres is working toward activating approximately 130 clinical sites in the U.S. and Canada to fulfill the safety database obligation, and to enable a BLA filing, as rapidly as possible
Amplifying efforts for market preparation and launch Medical communications strategy KOL mapping Develop and deploy payer value proposition Scaling Market Education Efforts Enhancing Understanding of Commercial Opportunity Deeper patient journey analysis Pricing analysis Customer segmentation Identify options for go-to-market model Building Infrastructure to Launch Scale Medical Affairs organization and deploy MSL team Hire key commercial leadership roles Key external strategic partners on board
Strong clinical & scientific data Dramatic reduction in CDI recurrence rate Spore-forming Firmicute bacteria prevent C. difficile germination and growth SER-109: Investigational, spore-based therapeutic designed to break the cycle of recurrent C. difficile infection Oral formulation Spores are resistant to gastric acid, facilitating oral delivery to gastrointestinal tract Favorable safety profile Favorable tolerability & safety profile with no imbalance in adverse event Spore purification mitigates risk of transmission of known and unknown infectious agents SER-109 Oral formulation of Firmicute bacteria spores FDA regulatory designations Breakthrough designation Orphan drug status
SER-287 and Ulcerative Colitis
Serious chronic condition characterized by inflammation of the colon and rectum resulting in abdominal pain, bowel urgency and diarrhea Significant need for improved therapies - Many drugs are immunosuppressive, limiting use to more severe patients ~700K in the United States Only ~1/3 achieve remission Ulcerative colitis overview
Steroids Thiopurines / MTX Anti-TNFs JAK Inhibitors Anti IL12/23 Microbiome Anti-Integrins S1P1 Agonists Gut Lumen Lamina Propria Blood vessel Gut Epithelium Microbiome therapeutics may drive therapeutic benefit May address drivers of inflammation, barrier integrity, innate immune activation, and adaptive immune education and cell trafficking Effector molecules may include short chain fatty acids, secondary bile acids, tryptophan metabolites, and TLR ligands Microbial consortia can likely target multiple pathways simultaneously Opportunity to develop both first-line and combination therapies The dysbiotic microbiome may be a trigger of inflammation in ulcerative colitis
Published study regarding microbiota transplantation provided clinical proof-of-concept in ulcerative colitis Note: SER-287 was not involved in this study
DAILY Primary Objectives Safety and tolerability Change in composition of intestinal microbiome at 8 weeks (n=11) (n=15) (n=15) (n=17) Placebo pre-treatment for 6 days 58 mild-to-moderate ulcerative colitis patients Placebo once daily for 8 weeks Vancomycin pre-treatment for 6 days SER-287 once daily for 8 weeks Placebo pre-treatment for 6 days SER-287 once weekly for 8 weeks Vancomycin pre-treatment for 6 days SER-287 once weekly for 8 weeks WEEKLY SER-287 Phase 1b ulcerative colitis study
Remission = Total Modified Mayo score ≤ 2 AND endoscopic subscore ≤ 1 Note: Missing data treated as failure; statistical significance not found in SER-287 weekly arms Phase 1b study results – Statistically significant clinical remission improvement observed in Vanco/SER-287 daily treatment arm Placebo pretreatment / Placebo Vancomycin pretreatment / SER-287 daily Placebo pretreatment / SER-287 weekly Vancomycin pretreatment / SER-287 weekly p = 0.0237 (0/11) (6/15) (2/15) (3/17)
Illustrative endoscopy improvement — Vanco/SER-287 daily treatment Pre-treatment endoscopy showing the sigmoid colon with spontaneous bleeding and ulceration Post-treatment day 64 endoscopy
SER-287 Phase 1b safety results show safety profile comparable to placebo SER-287 daily arm demonstrated a similar safety profile to placebo No serious drug-related adverse events Reduced gastrointestinal adverse events provide an independent assessment of efficacy as the GI adverse events likely reflect ulcerative colitis disease activity SER-287 daily arm GI AEs: 2/15 (13.3%) vs. placebo arm: 5/11 (45.5%)
Phase 1b study results – SER-287 bacteria engrafted in subjects and was durable to four weeks after dosing Significant engraftment observed starting one week post-dosing Engraftment is significantly higher in arms with vancomycin pre-conditioning Engraftment in vancomycin arms is dose-dependent; significantly greater in daily dosing arm (arm with greatest efficacy) Henn et al. (in review)
SER-287 Phase 1b study results published
Ongoing SER-287 ECO-RESET Phase 2b study in patients with mild-to-moderate active ulcerative colitis 10-week induction period Pbo pre-treat Mild to moderate UC patients with active disease N=201 Vanco pre-treat Vanco pre-treat Placebo SER-287 daily high dose SER-287 daily high dose followed by step down dose 26-week exploratory maintenance follow-up FDA Fast Track designation FDA feedback: Phase 2b study results, in conjunction with data from a second pivotal study, could support BLA submission Over 75% enrolled (as of Nov. 9, 2020) Primary endpoint: Clinical remission
Earlier stage development programs: SER-401, SER-301, SER-155
SER-301: Next-generation, rationally designed fermented microbiome therapeutic candidate for ulcerative colitis Reduces induction of pro-inflammatory activity Improves epithelial barrier integrity & TNF-α driven inflammation in IECs Modulates UC-relevant anti-inflammatory, innate & adaptive immune pathways
SER-301: Ongoing Phase 1b in adults with mild-to-moderate ulcerative colitis Screening Induction Treatment (daily dosing) Safety Period Pre- Cond. 10 weeks 16 weeks * * endoscopy, pre- and post-treatment 6d Cohort 1, Open Label (15 subjects, SER-301) SER-301 after pre-conditioning Cohort 2, Placebo-controlled (50 subjects, 2:3 Placebo to SER-301) Placebo after placebo SER-301 after pre-conditioning Study Objectives Primary endpoint = safety and tolerability Assess drug activity via changes in biomarkers of clinical remission in patients treated with SER-301 Secondary endpoints = engraftment and measures of clinical remission First patient dosed in November 2020
Gopalakrishnan et al, Science 2017 SER-401 composition driven by bacteria consistent with responder profile All spore formers that leverage deep Seres expertise in the biology and manufacturing of these organisms SER-401: Immuno-oncology - Microbiome signature in melanoma patient responder to anti-PD-1
Patients with metastatic melanoma treated with anti-PD-1 (nivolumab) SER-401; biologically sourced product to match microbiome signature of anti-PD-1 responders (n=20) Placebo (n=10) Day -14 Day -7 Day +7 Day 0 Day +14 Day +28 Day +56 Biospecimens: SER-401 / Placebo Day +84 Blood Stool Biopsy SER-401: Ongoing Phase 1b study Study Objectives Primary endpoint = safety and tolerability Assess drug activity via microbiome engraftment and its association with biomarkers of clinical response in tumor biopsies in patients treated with SER-401 in combination with nivolumab, an approved anti-PD-1 checkpoint inhibitor therapy Secondary Endpoints = engraftment, response, and clinical biomarkers) Additional study arm may be added including fecal microbiota obtained from responders Daily dosing
Decreases infection by antibiotic resistant bacteria in the gastrointestinal tract that lead to bacteremia Enhances epithelial barrier integrity to prevent bacterial translocation to the blood stream Modulates local and systemic immunomodulatory responses to decrease graft versus host disease Collaboration with: Antibiotic resistant pathogens can dominate the GI microbiome Compromised epithelial layer with thin mucus layer Basal TLRs SER-155: Rationally-designed, fermented microbiome therapeutic candidate for infection, bacteremia & GvHD Catalyzes changes in the microbiome & microbe-derived metabolites to prevent bacteremia Lead candidate nominated U.S. regulatory submission preparation in process
SER-109 success validates our microbiome therapeutic approach, presenting opportunity in multiple additional areas Deep understanding of the broad role of the microbiome in health: Resistance to pathogens Gut & systemic inflammation Innate & adaptive immunity Regulation of metabolism Novel drug discovery and development platform Option to pursue multiple diseases with high unmet need Highly productive R&D engine pursing multiple promising potential opportunities Infectious (e.g. Antibiotic resistant infections) Inflammatory (e.g. Crohn’s, RA) Oncology (e.g. tumor progression & bacteremia) Immune modulation & autoimmune disease Neurologic & CNS disease Metabolic & Cardiovascular (e.g. NASH)
Differentiated CMC capabilities producing rationally designed fermented products Potential best-in-class clinical profile based on species specific properties Fermented approach enables efficient and highly scalable manufacturing process to serve large markets Cell banking & inoculum Drug substance Drug product Quality control Seres in-house GMP manufacturing and quality control capabilities
Broad IP portfolio and regulatory exclusivity PROJECTED BIOSIMILAR REGULATORY EXCLUSIVITY years for new biological composition 12 Have obtained issued patents in the US, demonstrating that rationally designed ecologies of spores and microbes are patentable Portfolio includes composition of matter and method claims, including option to license foundational IP from MD Anderson related to the use of bacteria in combination with checkpoint inhibitors. Portfolio also includes exclusive licenses to Memorial Sloan Kettering Cancer Center IP related to use of bacteria to treat gastrointestinal disorders and cancer relapse. Issued claims related to SER-109/ C. difficile & SER-287 / ulcerative colitis lead candidates extend through 2033 13 Issued US Patents obtained Families of Applications 21 Nationalized 15 Pending Provisionals 1 years for new drug 10 PATENT PORTFOLIO OF OWNED & LICENSED PATENTS AND APPLICATIONS*
Seres is well positioned to harness core microbiome capabilities to advance its pipeline Positive ECOSPOR III Phase 3 study results expected to serve as single study to support BLA Metastatic melanoma – Phase 1b ongoing SER-287 SER-109 SER-401 Ulcerative colitis – Phase 2b ongoing Antibiotic resistant bacterial infections, bacteremia, & GvHD –Initiated clinical development activities Rationally-designed, fermented consortia SER-155 SER-301 Ulcerative colitis – Phase 1b ongoing Rationally-designed, fermented consortia Multiple earlier stage programs under consideration as new development opportunities Additional R&D opportunities As of Sept. 30, 2020: $320M in cash, cash equivalents and short and long-term investments