Seres Therapeutics, Inc. · NASDAQ:MCRB
Seres Therapeutics — Technical Presentation (January 2017)
24 slides from Seres Therapeutics's technical presentation, Jan 31, 2017
Slide 1: Key Findings from SER-109 Phase 2 Study Analyses
Key Findings from SER-109 Phase 2 Study Analyses January 31, 2017 Exhibit 99.1
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. Such statements are subject to factors, risks and uncertainties (such as those detailed in the Company’s periodic filings with th
Slide 3: Microbiome dysbiosis and potential for therapeutic intervention
Microbiome dysbiosis and potential for therapeutic intervention 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 risk of C. diff.
Slide 4: SER-109 overview
SER-109 overview Lead product candidate, completed Phase 2 study in patients with recurrent C. difficile infection Oral, biologically sourced, spore based therapeutic candidate Intended to catalyze an increase in the diversity of commensal microbes to repair a dysbiotic, disease state microbiome The
Slide 5: Phase 2 ECOSPOR study overview
SER-109 Phase 2 ECOSPOR study overview Screening Treatment Safety Follow-up Randomization SER-109 Arm n = 59 (Dose: 1 × 108 spore equivalents) 1 dose on Day 1 Placebo Arm n=30 1 dose on Day 1 Screening In Clinic Visit c c c c c c c End of Treatment Period -21 to Day -1 Day 1 Week 4 Week 8 Week 12 We
Slide 6: Phase 1b and Phase 2 (8-week) study results
SER-109 Phase 1b and Phase 2 (8-week) study results n=59 n=30 n=28 n=15 n=31 n=15 Phase 1b Open Label, Single-Arm (n=30; 4 sites) Phase 2 – Interim results Randomized, Placebo-Controlled (n=89; randomized 2:1; 28 sites) Primary Endpoint CDI recurrence up to 8 weeks defined by: >3 unformed stools ove
Slide 7: Comparison of SER-109 Phase 1b and Phase 2 studies
Comparison of SER-109 Phase 1b and Phase 2 studies Parameter Phase 1b Phase 2 Study Design Overview Open label; investigator sponsored; 4 sites; n=30 Placebo controlled randomized 2:1 SER-109:placebo; 28 sites enrolled subjects, n=89 Endpoint CDI recurrence at up to 8 weeks defined by: ≥ 3 unformed
Slide 8: Phase 2 24-week study results
SER-109 Phase 2 24-week study results Phase 2 efficacy results 5 additional patients recurred after the 8 week primary endpoint in the SER-109 arm but 3/5 (60%) were patients who terminated the trial early (i.e., lost to follow-up - imputed recurrences) 1 additional patient recurred in the placebo a
Slide 9: Phase 2 open label extension study results
SER-109 Phase 2 open label extension study results Open label extension (OLE) study (SERES-005) design: Phase 2 subjects who experienced a C. difficile recurrence in the first 8 weeks following drug administration had the option to enroll in the 24-week OLE study to assess safety and efficacy Same S
Slide 10: Clinical Analyses & Findings
SER-109 Analyses & Findings Leading the Microbiome Revolution
Slide 11: Organization of SER-109 study analyses
Organization of SER-109 study analyses Analysis component Key issues addressed Clinical Detailed analyses of clinical data Investigation of C. difficile diagnostics Pharmacodynamics / microbiome analyses Investigation of drug activity Chemistry, Manufacturing and Controls (CMC) Drug product distribu
Slide 12: Comparison of common C. difficile diagnostic tests
Comparison of common C. difficile diagnostic tests Test Basis of test Comments PCR Detects genes encoding cytotoxins Most sensitive test Does not distinguish C. difficile carriage from active infection Most common test in U.S. Used for 80.9% of entry tests and 74% of exit tests in Phase 2 study EIA
Slide 13: Analysis of C. difficile diagnostic test: Qualifying episode
Analysis of C. difficile diagnostic test: Qualifying episode PCR was the most common method used to qualify patients for enrollment into Phase 2 study: 72 of 89 (80.9%) subjects were diagnosed by PCR Qualifying Phase 2 stool samples were not available for re-testing by Cytotoxin EIA Available stool
Slide 14: Analysis of C. difficile diagnostic test: Phase 2 recurrence endpoint results
Analysis of C. difficile diagnostic test: Phase 2 recurrence endpoint results 32 of 42 (76%) of Phase 2 stool samples associated with a presumed recurrence were available to be analyzed by re-testing for cytotoxin by an independent laboratory Use of PCR to measure C. difficile recurrences may have o
Slide 15: Microbiome Response & CMC Analyses
SER-109 Microbiome Response & CMC Analyses Leading the Microbiome Revolution
Slide 16: Seres microbiome platforms
Seres microbiome platforms Taxonomic Resolution Engraftment Confidence 16S - Genera/Clades WMS- Species WMS- Strains Lower-resolution Higher-resolution WMS- Functional Profile Microbiome dynamics interrogated using genomic, metabolomic, and microbiology platforms Genomic tools leverage 16S ribosomal
Slide 17: SER-109 treatment demonstrates increased microbiome diversity
SER-109 treatment demonstrates increased microbiome diversity Ph2 Pbo Ph2 109 Ph1b 109 Ph2 Pbo Ph2 109 Ph1b 109 Ph2 Pbo Ph2 109 Ph1b 109 PRE-TREATMENT WEEK 1 WEEK 8 Average Spore-Former Species Richness 30 20 10 0 Note: Data reported as mean ± standard deviation Demonstrated in Ph2 an increase in di
Slide 18: Increased prevalence of SER-109 associated bacterial species in Phase 2 patients
Increased prevalence of SER-109 associated bacterial species observed in Phase 2 patients treated with SER-109 More prevalent placebo Differential Species Prevalence Phase 2 data, week 1 timepoint Differential prevalence plot; non-transparent, colored points represent species that are significantly
Slide 19: Microbiome signatures specific to SER-109 treatment may lead to positive clinical outcome
Microbiome signatures specific to SER-109 treatment may lead to positive clinical outcome Clinical outcome More prev. Non-Recur. More prev. HC Recur. Differential prevalence plot; 1-week data; colored points represent species that are significantly more prevalent in arm:outcome category HC-R indicat
Slide 20: Dose impacts Phase 1b vs. Phase 2 microbiome dynamics
Dose impacts Phase 1b vs. Phase 2 microbiome dynamics Analyses suggest that suboptimal dosing in some patients may have contributed to the previously reported SER-109 Phase 2 study outcome Phase 1b subjects who received a higher dose (dark purple) achieved a significantly greater increase in diversi
Slide 21: Phase 2 CMC Analyses
SER-109 Phase 2 CMC Analyses Leading the Microbiome Revolution
Slide 22: CMC: Detailed analyses did not reveal any detectable causative issues
CMC: Detailed analyses did not reveal any detectable causative issues Several steps in the manufacturing and formulation SER-109 process were different between the Phase 1b and the Phase 2 studies Changes in manufacturing to increase the purity of the SER-109 spores Changes in formulation (capsule d
Slide 23: Next Steps for SER-109 development
Next Steps for SER-109 development Leading the Microbiome Revolution
Slide 24: Strong rationale for further SER-109 clinical development
Strong rationale for further SER-109 clinical development Phase 2 analysis data suggest parameters for future clinical development of SER-109 Diagnosis - Utilization of C. difficile cytotoxin assay for both patient study inclusion and assessment of recurrence endpoint Dose - Increased SER-109 dosage
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