Seres Therapeutics, Inc. · NASDAQ:MCRB
Seres Therapeutics — J.P. Morgan Healthcare Conference 2018
44 slides from Seres Therapeutics's conference presentation, Jan 11, 2018
Slide 1: J.P. Morgan Healthcare Conference
J.P. Morgan Healthcare Conference Roger J. Pomerantz, M.D. President, Chief Executive Officer and Chairman January 11, 2018 L e ad i n g t h e M i c ro b i o me R e vo l u t i o n
Slide 2: Forward looking statements
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, statements on the timing and results of our clinical trials, the sufficiency of our financial reso
Slide 3: Seres investor highlights
Seres investor highlights Phase 3 stage company developing microbiome-based Opportunity therapeutics, a highly promising new area of medicine Leader in microbiome drug development Platform with differentiated capabilities, leading CMC and demonstrated GMP quality, and supportive clinical data Broad
Slide 4: The microbiome is essential to human health
The microbiome is essential to human health Infectious Disease • A diverse microbiome resists colonization by exogenous pathogens • Exposure to broad spectrum antibiotics, and resulting gut microbiome dysbiosis, increase risk for C. difficile infection and colonization / infection by multi-drug resi
Slide 5: Business strategy
Business strategy World class, Research in new Focused R&D differentiated, therapeutic areas microbiome expertise • Prioritize serious • Computational • Collaborate with diseases where biology leading academic dysbiosis of the gut • Basic microbiome centers to advance microbiome has a research resea
Slide 6: Robust microbiome therapeutics pipeline
Robust microbiome therapeutics pipeline PRECLINICAL PHASE 1b PHASE 2 PHASE 3 SER-109 Recurrent C. difficile Pivotal study Positive SER-287 Ulcerative colitis Phase 1b results SER-262 Primary C. difficile SER-301 Inflammatory Bowel Disease (IBD) Immuno-oncology – in combination with anti- Collaborati
Slide 7: Clostridium difficile Infection
Clostridium difficile Infection Overview and R&D Programs Leading the Microbiome Revolution 7
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. diff.
Slide 9: Microbiome therapeutic intervention – Race to Repair
Microbiome therapeutic intervention – Race to Repair Hypothetical patient course High diversity microbiome Antibiotic Potential for mediated microbiome therapy microbiome diversity dysbiosis C. diff. bacterial & to increase cytotoxin levels Gastrointestinal bacterial diversity in the GI tract Antibi
Slide 10: Phase 3 SER-109 ECOSPOR III study ongoing
Phase 3 SER-109 ECOSPOR III study 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 efforts: • SER-109 dose is approximately 10-fold higher than dose used in Phase 2
Slide 11: SER-262: Synthetic, fermented Ecobiotic therapeutic candidate for primary C. difficile infection
SER-262: Synthetic, fermented Ecobiotic® therapeutic candidate for primary C. difficile infection • Oral, microbiome therapeutic candidate comprising twelve strains of fermented, rationally-selected bacterial spores • Bacterial species selected based on analysis of SER-109 Phase 1b microbiome data,
Slide 12: SER-262 Phase 1b dosing study in patients with primary C. difficile infection
SER-262 Phase 1b dosing study in patients with primary C. difficile infection Cohort A: Tx with 104 spores (n=10); placebo (n=2); single dose Primary Objective Safety and tolerability at 24 weeks Cohort B: Tx with 105 spores (n=10); placebo (n=2); single dose Relative risk of C. difficile recurrence
Slide 13: SER-287 and Ulcerative Colitis
SER-287 and Ulcerative Colitis Leading the Microbiome Revolution 13
Slide 14: Inflammatory Bowel Disease (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 w
Slide 15: Modulation of the microbiome is an attractive therapeutic target for Ulcerative Colitis
Modulation of the microbiome is an attractive therapeutic target for Ulcerative Colitis • May address drivers of Gut Lumen Microbiome inflammation, barrier integrity, innate immune activation, and adaptive immune education and Gut Epithelium cell trafficking • Effector molecules may include short ch
Slide 16: Microbiota transplantation provides clinical proof of concept
Microbiota transplantation provides clinical proof of concept Subject A, Subject A, Baseline 8-wk post FMT Selected references: Paramsothy et al. Lancet, 2017; Moayyedi et al. Gastroenterology, 2015; 16 Review article: Costello et al. Alimentary Pharmacology & Therapeutics, 2017.
Slide 17: SER-287 Phase 1b Ulcerative Colitis study
SER-287 Phase 1b Ulcerative Colitis study Placebo pre- Placebo once daily for treatment for 6 days 8 weeks (n=11) Vancomycin pre- SER-287 once daily for 58 mild- treatment for 6 days 8 weeks (n=15) moderate UC patients failing standard Placebo pre- SER-287 once weekly of care* treatment for 6 days f
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 New data Secondary Objectives • Remission, endoscopic improvement, and response through measure of the total modified Mayo Score • Change in serum and fecal bioma
Slide 19: Clinical efficacy endpoints
Clinical efficacy endpoints Endpoint Protocol Definition Total Modified Mayo Score <=2 and Remission an endoscopic subscore of 0 or 1 Modified Mayo score components 1. Mucosal Appearance by Endoscopic Decrease in endoscopic endoscopy (Most objective) Improvement subscore of >=1 2. Stool Frequency 3.
Slide 20: Significant and dose dependent impact on remission
Significant and dose dependent impact on remission 40.0% (6/15) 40% achieving remission 30% p = 0.0237 % patients 17.7% 20% 13.3% (3/17) (2/15) 10% 0.0% (0/11) 0% Placebo Vancomycin Placebo Vancomycin pretreatment / pretreatment / pretreatment / pretreatment / Placebo SER-287 daily SER-287 weekly SE
Slide 21: Dose dependent impact on endoscopic improvement
Dose dependent impact on endoscopic improvement 40.0% (6/15) 40% 33.3% endoscopic improvement (5/15) % patients with 30% p = 0.178 23.5% (4/17) 20% 9.1% (1/11) 10% 0% Placebo Vancomycin Placebo Vancomycin pretreatment / pretreatment / pretreatment / pretreatment / Placebo SER-287 daily SER-287 weekl
Slide 22: Illustrative endoscopy improvement findings from patient in SER-287 daily treatment arm
Illustrative endoscopy improvement findings from patient in SER-287 daily treatment arm Pre-treatment endoscopy showing the Post-treatment day 64 sigmoid colon with spontaneous endoscopy bleeding and ulceration 22
Slide 23: Response rate is less reliable endpoint
Response rate is less reliable endpoint; Not recommend by FDA as a primary endpoint for UC 80% High placebo response rate 70% 60.0% reported in other UC achieving response (9/15) clinical studies using drugs % patients with 60% 45.5% with diverse mechanisms1 50% (5/11) 40.0% (6/15) 40% 23.5% Ulcerat
Slide 24: Histological healing RHI score change
Histological healing RHI score change 8 weeks post SER-287 administration 0.0 RHI score – mean reduction from -1.0 -2.0 -1.5 -3.0 -4.0 baseline -3.6 -5.0 -4.7 -6.0 -7.0 -8.0 -9.0 -8.5 -10.0 Placebo Vancomycin Placebo Vancomycin pretreatment pretreatment / pretreatment / pretreatment / / Placebo SER-
Slide 25: 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 effi
Slide 26: 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 (
Slide 27: Favorable SER-287 efficacy relative to selected approved and development stage UC drugs
Favorable SER-287 efficacy relative to selected approved and development stage UC drugs Remission Rates for Induction in Active UC FDA approved for UC In development for UC SER-287 39.0% 40.0% 40.0% 34.0% 28.0% 24.0% 18.5% 17.0% 18.5% 16.5% 15.0% 16.6% 16.0% 12.0% 13.0% 14.0% 9.3% 10.3% 10.0% 9.3% 8
Slide 28: 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 New data Secondary Objectives • Remission, endoscopic improvement, and response through measure of the total modified Mayo Score • Change in serum and fecal bioma
Slide 29: Robust SER-287 species engraftment
Robust SER-287 species engraftment; highest in most efficacious study arm Placebo pre-treat / Placebo Vanco pre-treat / SER-287 daily Placebo pre-treat / SER-287 weekly Vanco pre-treat / SER-287 weekly 20 SER-287 species identified 15 10 5 0 Day 3 Day 7 Day 10 Day 14 Day 56 Day 84 SER-287 dosing per
Slide 30: Durable SER-287 engraftment following dosing
Durable SER-287 engraftment following dosing Placebo pre-treat / Placebo Vanco pre-treat / SER-287 daily Placebo pre-treat / SER-287 weekly Vanco pre-treat / SER-287 weekly 20 SER-287 species identified 15 10 5 0 Day 3 Day 7 Day 10 Day 14 Day 56 Day 84 SER-287 dosing period ● Statistically significa
Slide 31: Microbiome composition is distinct in patients achieving remission
Microbiome composition is distinct in patients achieving remission Ordination plot for vancomycin pre-treatment / SER-287 daily patients (day 10 through 4 weeks post-dosing) Days Post Initial SER-287 Dose NMDS Coordinate 2 10 days 14 days 56 days 84 days Clinical Outcome Remission Non-remission NMDS
Slide 32: Specific bacterial species linked with remission
Specific bacterial species linked with remission ● Identified 27 species ecology statistically significantly correlated with remission ● Species include both SER-287 bacteria and others augmented by treatment Remission Non-remission Relative species 7 days 10 days 14 days 56 days 84 days 7 days 10 d
Slide 33: Advancing SER-287 clinical development
Advancing SER-287 clinical development • Compelling Phase 1b results: • Beneficial impact on remission and endoscopic improvement • Favorable safety and tolerability profile • Microbiome data provide mechanistic support for clinical results and demonstrate species-level bacterial signatures associat
Slide 34: SER-301: Synthetic fermented Ecobiotic therapeutic candidate for inflammatory bowel disease
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 compo
Slide 35: SER-401 and Immuno-oncology
SER-401 and Immuno-oncology Leading the Microbiome Revolution 35
Slide 36: Gut microbiome composition impacts efficacy of checkpoint inhibitors in oncology patients
Gut microbiome composition impacts efficacy of checkpoint inhibitors in oncology patients November 2017 Collaboration 36
Slide 37: Modulation of the microbiome restores anti tumor efficacy to anti-PD-1 therapy
Seres Research Modulation of the microbiome restores anti tumor efficacy and immune infiltration to anti-PD-1 therapy Tumor Growth Curves - Tumor Growth Curves – Germ free Colonized Control 1 0 0 0 1 0 0 0 C Control o n t r o l C o n t r o l tumor volume (mm3) tumor volume (mm3) Anti-PD-1 Anti-PD-1
Slide 38: Collaboration to advance microbiome therapeutic into immuno-oncology
Collaboration to advance microbiome therapeutic into immuno-oncology • Planned clinical study to evaluate impact of checkpoint inhibitors plus adjunctive microbiome therapeutics on clinical outcomes in patients with advanced metastatic melanoma • Planned start study in 2018 • Seres option to license
Slide 39: Broad IP portfolio and regulatory exclusivity
Broad IP portfolio and regulatory exclusivity 8 ISSUED US PATENTS + LICENSED IP* • Demonstrates rationally designed ecologies of spores and microbes are patentable • Composition of matter and method claims, including option to license foundational IP from MD Anderson related to the use of bacteria i
Slide 40: Well positioned for success
Well positioned for success SER-109: Multiply recurrent C. difficile infection – Phase 3 ongoing SER-287: Ulcerative colitis – Initiate new clinical study (mid-2018) SER-262: Primary C. difficile infection - Phase 1b read-out (early 2018) Immuno-oncology clinical study start (2018) Advancing pipelin
Slide 41: Appendix
Appendix Leading the Microbiome Revolution 41
Slide 42: Differentiated microbiome R&D platform
Differentiated microbiome R&D platform Computational discovery In silico using human clinical derivation of datasets to allow “backbone” rational design of functional microbiome drugs in microbial multiple therapeutic ecologies Microbial Functional areas networks pathways Vast microbial strain libra
Slide 43: CMC platform enables manufacture of cGMP-compliant, oral, microbiome therapeutic candidates
CMC platform enables manufacture of cGMP-compliant, oral, microbiome therapeutic candidates Fermentation of anaerobic and cGMP Isolation of spores from complex biological spore-forming microbes materials Synthetic Biologically candidates a sourced a Novel germination, cultivation, and sporulation Fo
Slide 44: SER-155: Ecobiotic therapeutic candidate to improve transplantation outcomes
SER-155: Ecobiotic® therapeutic candidate to improve transplantation outcomes Patient Microbiome Diversity • Ecobiotic® therapeutic candidate Correlates with Mortality Risk3 to improve outcomes in patients receiving allogeneic Overall Survival hematopoietic stem cell 67% transplantation (HSCT) or so
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