Seres Therapeutics, Inc. · NASDAQ:MCRB
Seres Therapeutics — Investor Presentation (May 2018)
43 slides from Seres Therapeutics's investor presentation, May 9, 2018
Slide 1: Corporate Overview May 2018
Corporate Overview May 2018 Exhibit 99.2
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, statements on the timing and results of our clinical trials, the sufficiency of our financial resources, and dysbiosis as an
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 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 resistan
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 Phase 3 study
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 study C
Slide 11: SER-262: Synthetic, fermented Ecobiotic therapeutic candidate
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, biol
Slide 12: 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 13: Summary of SER-262 Phase 1b preliminary study results
Summary of SER-262 Phase 1b preliminary study results Preliminary unblinded clinical data available from seven of eight patient cohorts No drug related serious adverse events observed No relative differences observed in the risk of relative recurrence rates in SER-262 as compared to placebo Study wa
Slide 14: SER-287 and Ulcerative Colitis
SER-287 and Ulcerative Colitis
Slide 15: 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 16: Modulation of the microbiome is an attractive target for UC
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 17: 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 18: SER-287 Phase 1b Ulcerative Colitis study
SER-287 Phase 1b Ulcerative Colitis study 58 mild-moderate UC patients failing standard of care* * Study designed to enroll 55 patients, with 15 in SER-287 treatment arms and 10 in the placebo / placebo arm Placebo pre-treatment for 6 days Placebo pre-treatment for 6 days Vancomycin pre-treatment fo
Slide 19: 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 20: Clinical efficacy endpoints
Clinical efficacy endpoints Endpoint Protocol Definition Remission Total Modified Mayo Score <=2 and an endoscopic subscore of 0 or 1 Endoscopic Improvement Decrease in endoscopic subscore of >=1 Response Decrease of >=3 points in Total Modified Mayo Score from baseline, along with either a decrease
Slide 21: 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) Endoscopy readings were centrally read by blinded readers. D
Slide 22: 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) Endoscopy readings were centrally read by blinded readers. Data
Slide 23: Illustrative endoscopy improvement findings
Pre-treatment endoscopy showing the sigmoid colon with spontaneous bleeding and ulceration Post-treatment day 64 endoscopy Illustrative endoscopy improvement findings from patient in SER-287 daily treatment arm
Slide 24: Response rate is less reliable endpoint
Response rate is less reliable endpoint; Not recommend by FDA as a primary endpoint for UC Placebo pretreat / Placebo Vancomycin pretreat / SER-287 daily Placebo pretreat / SER-287 weekly Vancomycin pretreat / SER-287 weekly Ulcerative Colitis: Clinical Trial Endpoints Guidance for Industry2 (5/11)
Slide 25: Histological healing
Histological healing RHI score change 8 weeks post SER-287 administration Placebo pretreatment / Placebo Vancomycin pretreatment / SER-287 daily Placebo pretreatment / SER-287 weekly Vancomycin pretreatment / SER-287 weekly Note: Intent to treat population, missing data equal failure Subjects with n
Slide 26: 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 27: 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 28: 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 29: 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 30: 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 31: Specific bacterial species linked with remission
Specific bacterial species linked with remission Remission 7 days 10 days 14 days 56 days 84 days Non-remission 7 days 10 days 14 days 56 days 84 days Identified 27 species ecology statistically significantly correlated with remission Species include both SER-287 bacteria and others augmented by tre
Slide 32: 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 associated with
Slide 33: 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 34: SER-401 and Immuno-oncology
SER-401 and Immuno-oncology
Slide 35: Gut microbiome composition impacts efficacy of checkpoint inhibitors
Gut microbiome composition impacts efficacy of checkpoint inhibitors in oncology patients
Slide 36: Modulation of the microbiome restores anti-PD-1 efficacy
Modulation of the microbiome restores anti tumor efficacy and immune infiltration to anti-PD-1 therapy Immune cell infiltration into tumor following anti-PD-1 administration Dendritic cells CD8+ T cells Seres Research Anti-tumor efficacy following anti-PD-1 administration into colonized mice Tumor G
Slide 37: Collaboration to advance microbiome therapeutic into immuno-oncology
Collaboration to advance microbiome therapeutic into immuno-oncology Planned placebo-controlled 3 arm 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 Sere
Slide 38: Broad IP portfolio and regulatory exclusivity
Broad IP portfolio and regulatory exclusivity Families of Applications Nationalized Pending PCT Pending Provisionals SERES PATENT PORTFOLIO 15 10 1 REGULATORY EXCLUSIVITY years for new biological composition 12 years for new drug 10 ISSUED US PATENTS + LICENSED IP* Demonstrates rationally designed e
Slide 39: Resources to operate for at least the next months
Resources to operate for at least the next 12 months Balance Sheet As of March 31, 2018 Cash, cash equivalents and investments $122 M SER-109: Multiply recurrent C. difficile infection – Phase 3 ongoing SER-287: Ulcerative colitis – Initiate new clinical study (mid-2018) Immuno-oncology clinical stu
Slide 40: Appendix
Appendix
Slide 41: Differentiated microbiome R&D platform
Differentiated microbiome R&D platform Computational discovery using human clinical datasets to allow rational design of microbiome drugs in multiple therapeutic areas Vast microbial strain library and commensal bacteria culturing know-how Disease targeted metabolic, immunological, & efficacy screen
Slide 42: CMC platform enables manufacture of cGMP-compliant candidates
CMC platform enables manufacture of cGMP-compliant, oral, microbiome therapeutic candidates Fermentation of anaerobic and spore-forming microbes Formulation, filling, delivery & packaging enabling active product delivery cGMP Isolation of spores from complex biological materials Synthetic candidates
Slide 43: SER-155: Ecobiotic therapeutic candidate to improve transplantation outcomes
SER-155: Ecobiotic® therapeutic candidate to improve transplantation outcomes 1 Khanna et al, Journal of Infectious Disease 2016 2 Jenq, et al, Biology of Blood and Marrow Transplantation 2015, 3 Taur, et al., Blood 2015. 36% 60% 67% Overall Survival Patient Microbiome Diversity Correlates with Mort
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