Seres Therapeutics, Inc. · NASDAQ:MCRB
Seres Therapeutics — Investor Day (May 2020)
44 slides from Seres Therapeutics's investor day presentation, May 27, 2020
Slide 1: SER-109 Investor Day
SER-109 Investor Day Creating a new wave of medicines powered by the human microbiome May 27, 2020 1 - Seres Therapeutics, Inc. © 2020
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, our development plans, the promise and potential impact of any of our microbiome therapeutics or c
Slide 3: Seres Therapeutics Overview
Seres Therapeutics Overview Leader in microbiome drug development with differentiated drug discovery, Platform manufacturing and clinical capabilities Focus Prioritized pipeline in C. difficile infection, ulcerative colitis, oncology • SER-109 for C. difficile infection; Phase 3 top-line data in mid
Slide 4: Agenda and Speakers
Agenda and Speakers Introductory remarks Clinical burden of Eric Shaff Clostridioides difficile infection President and Chief Executive Officer, Mark Wilcox, M.D. Seres Therapeutics Professor of Medical Microbiology, University of Leeds, and Deputy Chair of the U.K. Department of Health’s Antimicrob
Slide 5: Key Messages for Today
Key Messages for Today • Seres is the leader in microbiome therapeutic development • C. difficile infection is disease area that is in desperate need of a new approach, where the safety AND efficacy of existing choices are suboptimal and poorly understood • We have a differentiated approach, includi
Slide 6: Clinical burden of Clostridioides difficile infection
Clinical burden of Clostridioides difficile infection Mark Wilcox, M.D. Professor of Medical Microbiology University of Leeds & Leeds Teaching Hospitals; National Health Service Antimicrobial Resistance Programme Board; and Lead on C. difficile for Public Health England, UK.
Slide 7: C. difficile infection is a toxin-mediated disease leading to inflammatory colitis
C. difficile infection is a toxin-mediated disease leading to inflammatory colitis Hallmark of this bacterial disease is diarrhea • Can be severe with 10-15 bowel movements in a day C. difficile bacteria Other symptoms: • Nausea, abdominal cramping Severe disease • Low grade fever • Fatigue, weight
Slide 8: CDI is associated with significantly lower quality of life
C. difficile infection is associated with significantly lower quality of life Severe burden on patients 43.2 43.9 Vitality • Poor quality of life and loss of 50.1 productivity due to disabling diarrhea 40.2* 41.7* General Health 49.4 39.6* Physical Functioning 44.5* 50.8 SF-36v2 Health Domain I have
Slide 9: Burden of C. difficile infection on healthcare systems
Burden of C. difficile infection on healthcare systems ESTIMATED BURDEN OF C. DIFF INFECTION CASES: 462,100 (95% CI 428,600 to 495,600) 224,000 20,500 Greater incidence in patients ≥65 years hospitalizations in-hospital deaths than all other age groups combined ADVERSE IMPACT ON SHORT AND LONG-TERM
Slide 10: Current treatment options are suboptimal
Current treatment options are suboptimal Primary C. difficile infection: Vancomycin or fidaxomicin associated with rapid recurrence in 25% within 1 to 3 weeks of antibiotic completion due to original strain Risk factors: age >65 years, female gender, hospitalization Bezlotoxumab for those at high-ri
Slide 11: The pathogenesis of CDI is a two-hit process
The pathogenesis of C. difficile infection is a two-hit process: Disruption and Exposure Leading risk factor for C. difficile infection is exposure to antibiotics, which disrupt the microbiome C. difficile infection Disruption of Exposure to gut microbiome C. difficile spores CDI is the “canary in t
Slide 12: Fecal transplant is a proof-of-concept supporting importance of microbiome recovery
Fecal transplant is a proof-of-concept supporting importance of microbiome recovery Transfer of minimally processed stool from a screened donor to a recipient • Wide range of efficacy reported with lower cure rates in randomized trials (67%) than open-label studies (82%) • Sustained recovery associa
Slide 13: Selection of study subjects: The impact of the diagnostic approach
Selection of study subjects: The impact of the diagnostic approach Two Categories of Diagnostic Assays Why is this important? • +Toxin test strongly correlates with active disease and is recommended by IDSA for suspected recurrence Testing for toxin production (Hallmark of disease) • PCR cannot diff
Slide 14: FMT safety concerns amplified by recent high-profile FDA alerts
FMT safety concerns amplified by recent high-profile FDA alerts Drug-Resistant E. coli Transmission of drug- Bacteremia Transmitted by resistant bacteria Using the Fecal Microbiota Transplant universe of discovered during clinical microbes in stool brings unintended consequences Safety Alert Regardi
Slide 15: Summary
Summary • C. difficile infection causes debilitating toxin-mediated diarrhea with a significant impact on morbidity and mortality and quality of life • The pathogenesis of C. difficile infection requires “two hits”: Disruption of the microbiome and exposure to C. difficile spores • Patients suffer r
Slide 16: In Search of a Sustained Clinical Response: The Role of Advanced Microbiome Therapeutics
In Search of a Sustained Clinical Response: The Role of Advanced Microbiome Therapeutics Lisa von Moltke, M.D. Chief Medical Officer
Slide 17: C. difficile targeted antibiotics are necessary but insufficient for treatment
C. difficile targeted antibiotics are necessary but insufficient for treatment When the microbiome is disrupted, Pseudomembranous Diarrhea C. difficile spores colitis and colitis germinate into toxin-producing bacteria Antibiotics without Antibiotics kill C. difficile and any effect on reduce toxin
Slide 18: SER-109 is an investigational, donor derived, spore-based therapeutic
SER-109 is an investigational, donor derived, spore-based therapeutic designed to break the cycle of recurrent C. difficile infection Strong Scientific Rationale Oral Formulation • Spore-forming Firmicute bacteria prevent • Spores are resistant to gastric C. difficile germination and growth acid, fa
Slide 19: Phase 3 ECOSPOR-III trial design informed by prior clinical studies
Phase 3 ECOSPOR-III trial design informed by prior clinical studies Diagnosis of qualifying episode in Phase 2 likely led to inclusion of subjects without recurrent C. difficile infection • PCR utilized in most patients, which confounded results Dosing matters • Reanalysis of Phase 1 dose-ranging co
Slide 20: Favorable safety profile of SER-109 in Phase 2
Favorable safety profile of SER-109 in Phase 2 • Mainly mild or moderate AEs • Most common AEs were gastrointestinal disorders including diarrhea, abdominal pain, flatulence and nausea • None of the serious adverse events were considered drug-related by the investigators Favorable safety profile may
Slide 21: Phase 3 ECOSPOR-III Trial: Study population
Phase 3 ECOSPOR-III Trial: Study population Adults ≥ 18 years of age Inclusion criteria A qualifying episode of C. difficile infection as defined by: •≥ 3 unformed stools per day for 2 consecutive days plus •Positive C. difficile stool toxin assay •A clinical response to antibiotics (<3 unformed sto
Slide 22: ECOSPOR-III is the model for all C. difficile infection trials
ECOSPOR-III is the model for all C. difficile infection trials Top-line results in mid-2020 Key features that differentiate History Standard- ECOSPOR-III from other trials of ≥2 C. diff. of-care antibiotics recurrences for 10-21 days toxin assay 1 (+) 4 capsules over 3 days All subjects with recent
Slide 23: ECOSPOR-III is the model for all C. difficile infection trials
ECOSPOR-III is the model for all C. difficile infection trials Top-line results in mid-2020 Key features that differentiate ECOSPOR-III from other trials History Standard- 1 of ≥2 C. diff. of-care antibiotics recurrences for 10-21 days All subjects with recent onset of C. difficile infection toxin a
Slide 24: ECOSPOR-III: What does success look like? Clinical viewpoint
ECOSPOR-III: What does success look like? Clinical viewpoint SER-109 efficacy and safety will be demonstrated in patients with true C. difficile infection • Clinically compelling data with statistically significant delta between placebo and SER-109 arms • Safety and tolerability will be consistent w
Slide 25: ECOSPOR-III: What does success look like? Regulatory viewpoint
ECOSPOR-III: What does success look like? Regulatory viewpoint • With favorable ECOSPOR III data, plan to engage with FDA regarding path to approval • ECOSPOR III has potential to be a single pivotal study to support SER-109 product registration, though additional safety data may be required • SER-1
Slide 26: Summary
Summary • C. difficile infection is a two-hit process that requires a two-pronged treatment approach to prevent the vicious cycle of recurrence • SER-109 is an investigational, orally-delivered ecology of Firmicute spores essential for gut health • Our purification and inactivation processes are des
Slide 27: SER-109 Drug Pharmacology
SER-109 Drug Pharmacology Matthew Henn, Ph.D. Chief Scientific Officer
Slide 28: Seres microbiome therapeutics are designed to rapidly restructure the microbiome
Seres microbiome therapeutics are designed to rapidly restructure the microbiome and modulate disease relevant pathways 28 - Seres Therapeutics, Inc. © 2020
Slide 29: SER-109 mechanism targets disrupted microbiota and prevention of C. difficile germination
SER-109 mechanism targets disrupted microbiota and prevention of C. difficile germination and growth Engraft commensal Firmicute spore-forming bacteria that Modulate Bile Acid Metabolism compete with C. difficile • Reduce 1° bile acids that stimulate C. • In human studies show loss of Firmicutes dif
Slide 30: Engraftment of SER-109 bacteria occurs rapidly
Engraftment of SER-109 bacteria occurs rapidly with significantly greater number of drug species observed in treated versus placebo subjects Engraftment of drug species was observed by one-week post treatment & was durable through 8 weeks • Pre-treatment diversity of drug species in subjects was not
Slide 31: Presence of SER-109 bacteria is associated with a metabolite shift
Presence of SER-109 bacteria is associated with a metabolite shift that inhibit C. difficile spore germination and bacterial growth By week 1, positive correlation seen between SER-109 species and concentration of 2° bile acids LCA & DCA LCA = Lithocholic acid DCA = Deoxycholic acid McGovern Clin In
Slide 32: Greater engraftment of SER-109 is associated with reduction of recurrence
Greater engraftment of SER-109 is associated with reduction of C. difficile infection recurrence Significantly greater engraftment of SER-109 species at week-1 (p<0.05) was correlated with reduced rates of C. difficile infection recurrences • Differences between non-recurrent & recurrent not observe
Slide 33: Higher dose of SER-109 can achieve greater engraftment
Higher dose of SER-109 can achieve greater engraftment of drug bacteria in treated patients Re-evaluation of engraftment in the dose ranging cohort of Phase 1b in light of therapeutic window support a higher dose • Prior to treatment, the number of SER-109 species was comparable across dose groups a
Slide 34: Summary
SER-109 treatment targets the proximal cause of C. difficile infection, the GI microbiome • SER-109 mechanisms include the durable engraftment of drug bacteria (PK) and modulation of disease-relevant microbial-associated metabolites (PD) • Rapid engraftment is associated with prevention of C. diffic
Slide 35: SER-109 Production
SER-109 Production John Auniņš, Ph.D. Chief Technology Officer
Slide 36: SER-109: A novel biologically-derived product adapted from proven approaches
SER-109: A novel biologically-derived product adapted from proven approaches Well-established Inactivation Multi-Component, High Potency Active Paradigm, Validated by analogous to other natural biologics: Highly Stable Spore Pathogen Challenge Studies IVIG, Premarin®, Otosporin® Drug Product Donor P
Slide 37: Comprehensive safety approach to product
Comprehensive safety approach to product O R G AN I S M S S T U D I E D F O R P AT H O G E N C L E AR AN C E V AL I D AT I O N • Comprehensive donor program developed for SER-109 product Virus Vegetative Bacteria • Pathogen inactivation and clearance Adenovirus 41 Salmonella enterica steps for veget
Slide 38: GMP manufacturing and quality systems
GMP manufacturing and quality systems • Specialized, dedicated facilities addressing FDA and EMA guidance on manufacturing with spore-forming organisms • Integrated manufacturing capabilities including Quality Control and Quality Assurance for Seres’ products • Overall > 98% success rate in batch re
Slide 39: Fermented products platform (SER-301, SER-155)
Fermented products platform (SER-301, SER-155) Cell Banking & Drug Drug Quality Control Inoculum Substance Product R&D Culture Primary cGMP Secondary cGMP Medium Balancing & Process Optimization Starting Point Media Screen Media Screen Optimization & Scale-up In-house GMP Manufacturing and Quality C
Slide 40: Summary
Summary • SER-109 is unusual to manufacture, yet Seres has mastered the elements of manufacturing the product • SER-109 is a well-characterized and consistent product candidate • We have taken multiple safety precautions to ensure a safe product, which should not be impacted by emerging pathogens su
Slide 41: Closing Remarks
Closing Remarks Eric Shaff Chief Executive Officer
Slide 42: Broad SER-109 commercial potential in the U.S. and globally
Broad SER-109 commercial potential in the U.S. and globally C. difficile infection market (U.S.) 32K 3+ Recurrent Cases Potential SER-109 addressable 38K population of ~170K annual (40% of 1st recurrence cases (U.S.) will recur a 2nd time) 2nd Recurrent Cases 100K (14%-21% of primary recurrence 1st
Slide 43: Commercial readiness activities initiated
Commercial readiness activities initiated C. difficile market opportunity assessment Key stakeholder primary research (physician, patient, and payer) Recurrent C. difficile infection patient segmentation and site-of-care analysis Publication and congress plan Deepening advocacy relationships Brand n
Slide 44: SER-109 Investor Day
SER-109 Investor Day Creating a new wave of medicines powered by the human microbiome May 27, 2020 44 - Seres Therapeutics, Inc. © 2020