Seres Therapeutics, Inc. · NASDAQ:MCRB
Seres Therapeutics — Technical Presentation (May 2019)
16 slides from Seres Therapeutics's technical presentation, May 2019
Slide 1: SER-287 induces widespread transcriptional changes related to clinical remission in SERES-101
SER-287, an investigational microbiome therapeutic, induces widespread transcriptional changes related to clinical remission in a placebo-controlled, double- blind randomized trial (SERES-101) in patients with active mild-to-moderate ulcerative colitis Jennifer Russo Wortman VP, Clinical Discovery a
Slide 2: Gastrointestinal microbiota produces metabolites that prevent inflammation and maintain epithelial integrity
Gastrointestinal microbiota produces metabolites that prevent inflammation and maintain epithelial integrity Microbiota can impact innate, adaptive, and regulatory immune systems. • Microbial metabolites such as short chain fatty acids (SCFAs) impact gut epithelial integrity through coordinated regu
Slide 3: SER-287 is an investigational microbiome drug for ulcerative colitis
SER-287 is an investigational microbiome drug for ulcerative colitis • Live biotherapeutic formulated for oral dosing composed of firmicute spores associated with gut health SER-287 Composition & • Bacterial spores are resistant to gastric acid allowing easy Rationale for formulation into capsules f
Slide 4: SERES-101 study design in patients with mild-moderate UC
SERES-101 study design in patients with mild-moderate UC Phase 1b clinical trial 6-day Pre-conditioning 8-week Phase Induction Phase Arm A N=11 PBO PLACEBO Arm B N=15 PBO SER-287 Weekly 58 mild-to-moderate UC subjects Arm C VANCO SER-287 Weekly N=17 Arm D N=15 VANCO SER-287 Daily Total Modified Mayo
Slide 5: Dose-dependent effect of SER-287 on clinical remission
Dose-dependent effect of SER-287 on clinical remission 100% Remission defined as... • Total modified Mayo Score (TMMS) 80% % patients achieving remission ≤2 plus… 60% P = 0.024 • Endoscopic subscore (ESS) of 0/1 40.0% 40% Safety profile: • SER-287 arms had similar safety 20% 17.7% profile to placebo
Slide 6: Defining pharmacokinetics (PK) and pharmacodynamics (PD) of a microbiome therapeutic
Defining pharmacokinetics (PK) and pharmacodynamics (PD) of a microbiome therapeutic Pharmacokinetics (PK) • Kinetics of product engraftment: the presence of spore-forming bacteria from the drug in subjects over time Pharmacodynamics (PD) • Overall changes in the composition of the microbiome (“Who’
Slide 7: SER-287 engraftment (PK) is dose-dependent and facilitated by vancomycin pre-conditioning
SER-287 engraftment (PK) is dose-dependent and facilitated by vancomycin pre-conditioning Days Post Initial Dose of SER-287 ● Significant engraftment observed starting one * p < 0.05 Arm vs Pbo * * week post-dosing Engrafting SER-287 Species * * * * * * * * * * * * Num. High Confidence * p < 0.05 V/
Slide 8: Metabolic pathways modulated by SER-287 can impact host inflammatory and immune state
Metabolic pathways modulated by SER-287 can impact host inflammatory and immune state Gut Lumen Microbiome engraftment Gut Epithelium Microbe-mediated metabolic pathways Lamina Propria Host transcription Blood vessel 8 - © 2019 Seres Therapeutics
Slide 9: Establishing a reference dataset for host transcriptomic analysis (PD)
Establishing a reference dataset for host transcriptomic analysis (PD) • Transcriptomics data from the Integrative Human Microbiome Project (iHMP) IBD Cohort (34 subjects with UC and 24 non-IBD control patients) were used to define human genes upregulated in ulcerative colitis vs non- IBD subjects •
Slide 10: Transcriptomic response in SER-287 subjects compared to reference iHMP data
Transcriptomic response in SER-287 subjects compared to reference iHMP data • Each gene is arrayed on the X-axis I II Increased Increased according to it’s differential expression expression expression of non-IBD in the iHMP reference data at clinical genes at clinical endpoint • The Y-axis displays
Slide 11: Clinical remission is associated with shifts in UC and non-IBD gene expression
Clinical remission is associated with shifts in UC and non-IBD gene expression Shift in expression of disease-related genes among SER-287 treated remitters, not observed in non-remitters SER-287 SER-287 PBO/PBO treated remitters (n=7) treated non-remitters (n=27) subjects (non-remitters, n=8) Log2fo
Slide 12: SERES-101 remitters have decreased gene expression in inflammatory and immune pathways
SERES-101 remitters have decreased gene expression in pathways associated with inflammatory and immune responses We examined the top 40 differentially expressed genes in iHMP data set relevant to UC disease activity Using the iHMP top 40 gene set, we observe expression decreases Gene fold changes ac
Slide 13: Global KEGG analysis shows significant shifts in multiple immune and signaling pathways
Global KEGG analysis shows significant shifts in multiple immune and signaling pathways in SERES-101 remitters Immune Diseases Immune System Expression change: p-value significance at the pathway level 13 - © 2019 Seres Therapeutics
Slide 14: Pathways implicated in IBD are heavily down-regulated in SERES-101 remitters
Inflammatory Bowel Disease (KEGG) Pathways implicated in IBD are heavily down-regulated in SERES-101 remitters B F G A E B C D D A E C E F E G 14 - © 2019 Seres Therapeutics
Slide 15: Conclusion
Conclusion • SER-287-treated remitters exhibited widespread gene expression changes compared to baseline • These changes are characterized by decreased expression of UC-related genes and increased expression of non-IBD genes, using the integrative Human Microbiome Project data as a reference • The i
Slide 16: Acknowledgements
Acknowledgements Liyang Diao, Mauris Nnamani, Asuncion Martinez, Edward O'Brien, Christopher Desjardins, Brian Weiner, Sumon Datta, Sheri Simmons, Kevin Litcofsky, Barbara McGovern, Sherry Weigand, David Cook Patients and Physicians in SER-287 Trials Matthew Henn & Seres R&D Team Kevin Horgan & Sere
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