Seres Therapeutics, Inc. · NASDAQ:MCRB
Seres Therapeutics — Investor Presentation (August 2018)
37 slides from Seres Therapeutics's investor presentation, Aug 7, 2018
Slide 1: Corporate Overview August 2018
Corporate Overview August 2018 Exhibit 99.1
Slide 2: Forward looking statements
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 ability of ECOSPOR III to support SER-109 approval, the promise and potential impact of any of our
Slide 3: Seres investor highlights
Seres investor highlights Phase 3 stage company developing microbiome-based therapeutics, a highly promising new area of medicine Leader in microbiome drug development with differentiated capabilities, leading CMC and demonstrated GMP quality, and supportive clinical data Focused R&D efforts in the
Slide 4: The microbiome is essential to human health
The microbiome is essential to human health Human gastrointestinal microbiome is a vast interacting network of organisms Microbial ecology provides essential functions for the host: Modulation of immune system Colonization resistance against potential pathogens Regulation of host metabolism Synthesi
Slide 5: Business strategy
Business strategy Prioritize serious diseases where dysbiosis of the gut microbiome has a causal role Focused R&D on clinical programs Computational biology Basic microbiome research Microbiology Translational science Clinical development Advanced GMP manufacturing World class, differentiated, micro
Slide 6: Robust microbiome therapeutics pipeline
Robust microbiome therapeutics pipeline PRECLINICAL PHASE 1b PHASE 2 Synthetically fermented Infectious Inflammatory SER-401 Inflammatory Bowel Disease (IBD) SER-262 Primary C. difficile SER-301 Immuno-oncology – in combination with anti-PD-(L)1 therapy Biologically sourced SER-287 Ulcerative coliti
Slide 7: Clostridium difficile Infection Overview and R&D Programs
Clostridium difficile Infection Overview and R&D Programs
Slide 8: C. difficile infection overview
C. difficile infection overview Infectious disease caused by toxin-producing anaerobic, spore-forming bacteria, resulting in diarrhea, abdominal pain, fever, and nausea Leading cause of hospital-acquired infection in the US Approximately 29,000 deaths/year ~25% of patients with primary C. difficile
Slide 9: Microbiome therapeutic intervention – Race to Repair
Microbiome therapeutic intervention – Race to Repair Hypothetical patient course Healthy person with intact pathogen resistance High diversity microbiome Use of broad spectrum antibiotics Active C. diff. infection Antibiotic treatment of C. diff. infection Potential for microbiome therapy to reduce
Slide 10: SER-109 ECOSPOR III study – enrollment ongoing
Phase 3 SER-109 ECOSPOR III study – enrollment progress ongoing FDA Breakthrough and Orphan Drug designation Based on FDA feedback, ECOSPOR III designated as a Phase 3 study Phase 3 study incorporates key learnings from prior clinical studies: SER-109 dose is approximately 10-fold higher than dose u
Slide 11: SER-262 Phase 1b dosing study in primary C. difficile infection
SER-262 Phase 1b dosing study in patients with primary C. difficile infection Primary Objective Safety and tolerability at 24 weeks Relative risk of C. difficile recurrence compared to placebo at up to 8 weeks Secondary Objectives Microbiome engraftment Time to C. difficile recurrence Relative risk
Slide 12: Summary of SER-262 Phase 1b preliminary study results
Summary of SER-262 Phase 1b preliminary study results Preliminary clinical results available from eight patient cohorts, full microbiome date are pending No drug related serious adverse events observed No relative differences observed in the risk of relative recurrence rates in SER-262 as compared t
Slide 13: SER-287 and Ulcerative Colitis
SER-287 and Ulcerative Colitis
Slide 14: IBD opportunity for new mechanistic approaches
Inflammatory Bowel Disease (IBD) opportunity for new mechanistic approaches Significant need for improved therapies Large US population: ~700K ulcerative colitis, ~700K Crohn’s Fewer than ~1/3 of patients achieve remission with current therapies Many therapies are immunosuppressive, limiting widespr
Slide 15: Microbiome modulation as a therapeutic target for Ulcerative Colitis
Modulation of the microbiome is an attractive therapeutic target for Ulcerative Colitis 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, t
Slide 16: Microbiota transplantation provides clinical proof of concept
Selected references: Paramsothy et al. Lancet, 2017; Moayyedi et al. Gastroenterology, 2015; Review article: Costello et al. Alimentary Pharmacology & Therapeutics, 2017. Microbiota transplantation provides clinical proof of concept
Slide 17: SER-287 Phase 1b Ulcerative Colitis study
SER-287 Phase 1b Ulcerative Colitis study 58 mild-moderate UC patients failing standard of care* Placebo pre-treatment for 6 days Placebo pre-treatment for 6 days Vancomycin pre-treatment for 6 days Vancomycin pre-treatment for 6 days SER-287 once weekly for 8 weeks Placebo once daily for 8 weeks SE
Slide 18: SER-287 Phase 1b study endpoints
SER-287 Phase 1b study endpoints Primary Objectives Safety and tolerability Change in composition of intestinal microbiome at 8 weeks Secondary Objectives Remission, endoscopic improvement, and response through measure of the total modified Mayo Score Change in serum and fecal biomarkers Pathologic
Slide 19: Significant and dose dependent impact on remission
Significant and dose dependent impact on remission 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) Remission = Total Modified Mayo score ≤ 2 AND endoscopic sub
Slide 20: Dose dependent impact on endoscopic improvement
Dose dependent impact on endoscopic improvement Placebo pretreatment / Placebo Vancomycin pretreatment / SER-287 daily Placebo pretreatment / SER-287 weekly Vancomycin pretreatment / SER-287 weekly p = 0.178 (1/11) (6/15) (5/15) (4/17) Endoscopic Improvement: Decrease in endoscopic subscore ≥ 1 Note
Slide 21: Illustrative endoscopy improvement — SER-287 daily treatment
Pre-treatment endoscopy showing the sigmoid colon with spontaneous bleeding and ulceration Post-treatment day 64 endoscopy Illustrative endoscopy improvement — SER-287 daily treatment
Slide 22: Favorable SER-287 Phase 1b safety profile
Favorable SER-287 Phase 1b safety profile SER-287 daily arm demonstrated a similar safety profile to placebo No serious drug-related adverse events No subject discontinuations in the SER-287 daily treatment arm Reduced gastrointestinal adverse events provide an independent assessment of efficacy wit
Slide 23: Analyses of post SER-287 treatment impact on disease activity
Analyses of post SER-287 treatment impact on disease activity SER-287 Phase 1b patients were followed for up to 26 weeks post treatment: Of the 11 patients treated with SER-287 who achieved clinical remission, no patients experienced a disease flare in the 26 weeks following the end of treatment (0/
Slide 24: Favorable SER-287 efficacy relative to selected UC drugs
Adapted from Leerink Nov. 27 2017 report: Future of IBD: Category should double by 2023 despite GED-0301 disappointment; Note that study-to-study differences limit the ability to directly compare results. Remission Rates for Induction in Active UC SER-287 FDA approved for UC In development for UC Tr
Slide 25: Robust SER-287 species engraftment
Robust SER-287 species engraftment; highest in most efficacious study arm Statistically significant engraftment in vanco pre-treat / SER-287 daily arm, versus placebo pre-treat / placebo arm, beginning at day 7 and maintained throughout the dosing period Statistically significant and dose-dependent
Slide 26: Durable SER-287 engraftment following dosing
Durable SER-287 engraftment following dosing SER-287 species identified SER-287 dosing period Placebo pre-treat / Placebo Vanco pre-treat / SER-287 daily Placebo pre-treat / SER-287 weekly Vanco pre-treat / SER-287 weekly Statistically significant engraftment maintained through at least 4 weeks foll
Slide 27: Bacterial species signature associated with clinical remission
Identified bacterial species signature that associates with clinical remission vs non-remission Predictive species include both SER-287 bacteria and others augmented by treatment Functional characterization of signature species is informing drug mechanism of action Remission 7 days 10 days 14 days 5
Slide 28: SER-287 Phase 1b data demonstrate clinical effect and mechanistic data
SER-287 Phase 1b data demonstrate clinical effect and provide supportive molecular mechanistic data CLINCAL OUTCOME SPECIES SIGNATURES METABOLITES & PATHWAYS Dose dependent clinical remission Engraftment (PK) associated with clinical remission Metabolites and functional pathways (PD) associated with
Slide 29: Planned SER-287 Phase 2b study design
Planned SER-287 Phase 2b study design Mild to moderate UC patients with active disease N= 268 Placebo SER-287 daily high dose followed by step down SER-287 daily high dose followed by step down SER-287 daily high dose 10-week induction period 26-week exploratory maintenance follow-up Study to furthe
Slide 30: SER-301: Synthetic fermented Ecobiotic therapeutic candidate for IBD
SER-301: Synthetic fermented Ecobiotic® therapeutic candidate for inflammatory bowel disease Oral, mechanistically designed follow-on to SER-287 Selection of SER-301 bacterial composition based on: SER-287 study data (clinical and microbiome analysis) Preclinical activity of microbiome compositions
Slide 31: SER-401 and Immuno-oncology
SER-401 and Immuno-oncology
Slide 32: Collaboration to advance microbiome therapeutic into immuno-oncology
Collaboration to advance microbiome therapeutic into immuno-oncology Objective: Modulate the microbiome to increase the response of check-point inhibitor therapy Seres option to license foundational intellectual property from MD Anderson related to the use of bacteria in combination with checkpoint
Slide 33: MD Anderson microbiome signature in melanoma responders
MD Anderson collaborators have identified a microbiome signature in melanoma patients who respond to anti-PD-1 Signature driven by bacteria in the class Clostridia, family Ruminococcaceae, including Ruminoccocus and Faecalibacterium All spore formers that leverage deep Seres expertise in the biology
Slide 34: Microbiome signature restores anti-PD-1 efficacy in mice
Treatment of mice with the microbiome signature composition restores anti-PD-1 efficacy after antibiotics Note: Not all donor-derived bacterial spore compositions result in restoration of anti-PD-1 efficacy Seres research
Slide 35: Planned SER-401 Phase 1b study
Planned SER-401 Phase 1b study Arm A Microbiota transfer from anti- PD-1 complete responders (n=20) All patients = CT scans with RECIST week 12 Patients with metastatic cancer (melanoma) going onto immune checkpoint blockade (anti-PD-1) Arm B SER-401 (n=20) Arm C Placebo (n=20) Primary endpoint = sa
Slide 36: Broad IP portfolio and regulatory exclusivity
Broad IP portfolio and regulatory exclusivity Families of Applications Nationalized Pending Provisionals SERES PATENT PORTFOLIO 16 11 REGULATORY EXCLUSIVITY years for new biological composition 12 years for new drug 10 ISSUED US PATENTS + LICENSED IP* Demonstrates rationally designed ecologies of sp
Slide 37: Resources to operate into the second quarter 2019
Resources to operate into the second quarter 2019* Balance Sheet As of June 30, 2018 Cash, cash equivalents and investments $96.1 M SER-109: Multiply recurrent C. difficile infection – Phase 3 ongoing SER-287: Ulcerative colitis – Initiate Phase 2b study in the coming months Immuno-oncology clinical
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