Seres Therapeutics, Inc. · NASDAQ:MCRB
Seres Therapeutics — Investor Day (January 2022)
50 slides from Seres Therapeutics's investor day presentation, Jan 31, 2022
Slide 1: Infection Protection Investor Event
Infection Protection Investor Event January 31, 2022
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, inc
Slide 3: Pioneering the Development of Microbiome Therapeutics
Pioneering the Development of Microbiome Therapeutics Seres’ mission: To transform the lives of patients worldwide with revolutionary microbiome therapeutics Orally formulated bacterial consortia Encapsulated consortia of commensal bacteria designed to target multiple disease- relevant pathways simu
Slide 4: NEJM Publication Highlights Value of SER-109 and Microbiome Therapeutics
New England Journal of Medicine Publication Highlights Potentially Practice- Changing Value of SER-109 and Microbiome Therapeutics Approximately 88% sustained clinical response rate Response rate far exceeded FDA predefined threshold for single pivotal trial January 20, 2022 issue 4 Seres Therapeuti
Slide 5: On Track for SER-109 BLA Submission in Mid 2022
On Track for SER-109 BLA Submission in Mid 2022 Potential SER-109 Open-label safety study BLA submission FDA review approval and launch • Enrollment completed in • BLA submission mid-2022 • Expect timely review in September after study completion light of Breakthrough Therapy and Orphan • Study has
Slide 6: Expanding Microbiome Leadership Position in 2022 and Beyond
Expanding Microbiome Leadership Position in 2022 and Beyond Bring first-in-class Maximize Optimize plans for microbiome opportunities in continued therapeutic to patients infection protection, development in UC with potential SER-109 building off of SER-109 based on SER-287 BLA approval and mechanis
Slide 7: Seres is Maximizing the Opportunity in Infection Protection and AMR
Seres is Maximizing the Opportunity in Infection Protection and AMR Broadly Target Additional Opportunities Antimicrobial Resistant Infections Autologous HSCT Pre-clinical Portfolio Cancer Neutropenia Solid Organ Transplant Cirrhosis Programs designed to protect medically SER-155 compromised Active
Slide 8: Novel Approach to Infection Protection Delivers Remarkable Clinical Results
Novel Approach to Infection Protection Delivers Remarkable Clinical Results with Potentially Broad Applicability SER-109 data • Clinical outcomes can result from pathogen decolonization validates approach with a microbiome therapeutic • Pathogen overgrowth in the gut microbiome leads to poor Broad p
Slide 9: Agenda & Speakers
Agenda & Speakers Introductory remarks Role of GI microbiome in allogeneic HSCT transplantation Eric Shaff Marcel van den Brink, M.D., Ph.D. President and Chief Executive Officer, Head, Division of Hematologic Malignancies; Seres Therapeutics Alan N. Houghton Professor in Immunology; Member, Memoria
Slide 10: Role of GI microbiome in allogeneic HSCT
Role of GI microbiome in allogeneic HSCT transplantation Marcel van den Brink, M.D., Ph.D. Head, Division of Hematologic Malignancies; Alan N. Houghton Professor in Immunology; Member, Memorial Sloan-Kettering Cancer Center 10 Seres Therapeutics, Inc. © 2022
Slide 11: The gut microbiome has a significant role in human health
The gut microbiome has a significant role in human health 1014 microbes / person 104 species across human hosts 3% human body mass 150 species /person microbes : human cells Associations With = 1:1 • Infection • IBD • Obesity • Atherosclerosis 10x microbial : human • Diabetes genes • Malnutrition •
Slide 12: Current allogeneic HSCT regimen associated with significant risks
Current allogeneic hematopoietic stem cell regimen associated with significant risks to positive outcome ~50% 3-year Conditioning Regimen Allogeneic HSCT Risks ! survival rates Total body irradiation Chemotherapy Causes of mortality at 1 year Antibodies Organ Second failure Malignancy 1% 7-9% Infect
Slide 13: Evidence showing impact of gut microbiome diversity on transplant outcomes
Substantial body of evidence showing impact of gut microbiome diversity on outcomes of bone marrow transplantation Overall Survival, Infection, GVHD, Organ Toxicity, Relapse 13 Adapted from Taur 2016
Slide 14: Microbiome diversity declines after both allogeneic and autologous HSCT
Microbiome diversity declines after both allogeneic and autologous HSCT Allogeneic HSCT Autologous HSCT 32 Simpson reciprocal index 16 8 Duke Duke 4 MSK MSK 2 -10 0 10 20 -10 0 10 20 Simpson reciprocal index measures biodiversity based on number of species and evenness of abundance 14 Allogeneic HCT
Slide 15: Microbiome diversity is a predictor of mortality in allogeneic HCT
International observational study demonstrates gut microbiome diversity is a predictor of mortality in allogeneic hematopoietic cell transplantation 15
Slide 16: Lower microbiome diversity associated with decreased overall survival
Lower microbiome diversity post allogeneic HSCT is associated with decreased overall survival Initial cohort (MSK) Validation cohort Association seen across 4 international transplant centers Similar kinetics of reduced diversity across centers Peled et al, NEJM 2020 Effect also observed post autolo
Slide 17: Frequent enterococcal microbiome domination after allogeneic HSCT
Frequent enterococcal microbiome domination after allogeneic HSCT Domination events are prevalent Enterococcus frequently dominant HSCT Day Day relative to HSCT 17 Stein-Thoeringer et al, Science 2019
Slide 18: Microbiome domination precedes bacteremia after allogeneic HSCT
Microbiome domination precedes bacteremia after allogeneic HSCT Organ Second failure Malignancy 1% 7-9% Infection 17-21% Primary GVHD disease 19-23% 46-60% Enterococcal domination associated with VRE bacteremia 18 Taur et al., Clin Inf Dis 2012; Harris, et al., AJRCCM 2016
Slide 19: Enterococcal domination increases acute GvHD risk and decreases survival
Enterococcal domination increases acute GvHD risk and decreases survival Enterococcal domination associated with MSK (n=520) Overall survival Acute GvHD (grade 2-4) Validation (n=160) GvHD-related mortality Stein-Thoeringer et al, Science 2019 Increased fecal Enterococcal abundance associated with i
Slide 20: Broad-spectrum antibiotic exposure associated with lower GI microbiome diversity
Broad-spectrum antibiotic exposure associated with lower GI microbiome diversity 20 n=976 patients (5936 samples) with allo HCT; p = 0.008 at Day 15 post-HCT (greatest difference) Gray shading is 95% confidence interval (Loess smoothing)
Slide 21: Anaerobe-targeting antibiotic exposure associated with increased GvHD mortality
GVHD-related mort 20 Incidence Anaerobe-targeting antibiotic exposure associated with increased GvHD mortality 10 p=0.007 Piperacillin-tazobactam 0 Imipenem-cilastin 0 12 24 36 48 60 Months after HCT piperacillin-tazobactam imipenem-cilastatin 30 30 GVHD-related mortality (%) GVHD-related mortality
Slide 22: Treatments reducing microbiome diversity after autologous HSCT linked to decreased survival
Treatments reducing microbiome diversity after autologous HSCT associated with decreased overall survival MSK + Penn ALL/NHL: Overall Survival P-I-M • Data collected from patients with B cell malignancies treated with CAR T cell therapies • Treatment with anaerobe-targeting antibiotics (piperacillin
Slide 23: Conclusions
Conclusions • Loss of gut microbiome diversity is associated with decreased survival and increased GVHD/bacteremia in allogeneic and autologous HSCT patients • Antibiotics and other medicines that modulate microbiome diversity and enterococcal abundance significantly change overall survival • Therap
Slide 24: Microbiome therapeutic pharmacology
Microbiome therapeutic pharmacology Matthew Henn, Ph.D. Chief Scientific Officer, Seres Therapeutics 24 Seres Therapeutics, Inc. © 2022
Slide 25: GI Tract is a Reservoir of Potential Bacterial Invaders
GI Tract is a Reservoir of Potential Bacterial Invaders A healthy, diverse microbiome is essential to preventing colonization and infection with pathogens Beneficial microbes outcompete pathogens and can enhance epithelial barrier integrity and Therapeutics Microbiome modulate immune responses Antib
Slide 26: Seres' Investigational Microbiome Therapeutics are Encapsulated Microbial Consortia
Seres’ Investigational Microbiome Therapeutics are Encapsulated Microbial Consortia Designed to Target Multiple Disease-Relevant Pathways Pharmacokinetics Pharmacodynamics Building upon SER-109, Seres is developing novel microbiome therapeutics, such as SER-155, to specifically target infections and
Slide 27: SER-109 Restructures the Microbiome and Changes its Function
SER-109 Restructures the Microbiome and Changes its Function SER-109 bacteria engraft durably SER-109 bacteria shift gut metabolic & rapidly to restructure microbiome landscape following engraftment SER-109 Dose Species Engraftment Bile Acid Metabolism 10,000 Engrafting Dose Species (#) 2° Bile Acid
Slide 28: SER-109 Data Support Reducing Pathogens that Harbor Antimicrobial Resistance
SER-109 Data Support that Microbiome Therapeutics can Reduce Pathogens that can Harbor Antimicrobial Resistance Reduce Proteobacteria* associated Reduced antimicrobial resistance with antimicrobial resistance genes gene carriage 10,000 gene abundance (RPKM) Antimicrobial resistance 150 -log10(p-valu
Slide 29: Seres Integrated Rational Design Platform
Seres Integrated Rational Design Platform Provides End-to-End Capabilities and Increases Value Over Time as Data are Compounded GMP Disease Target Hit-to-Lead Lead Candidate Manufacturing Identification Identification Optimization & Quality Systems Advanced Biorepository Strain Library Fermentation
Slide 30: Scalable GMP Manufacturing Provides Access to Broad Microbial Diversity
GMP Manufacturing Scalable GMP Manufacturing Provides Access to Broad & Quality Systems Spectrum of Microbial Diversity and Biological Function • Established capabilities to produce both donor-derived and cultivated bacterial LBP consortia • Drug product formulation capabilities for both spore-formi
Slide 31: Rationally-Designed Microbiome Therapeutics to Combat Infections and AMR
Rationally-Designed Microbiome Therapeutics to Combat Infections, Antimicrobial Resistance, Bacteremia, and Associated Complications Disrupted Gastrointestinal Microbiome Microbiome Therapeutics 1 Restore colonization resistance and Antibiotic resistant decrease patient-to-patient transmission Intes
Slide 32: Seres Has Differentiated Consortium Design with Proprietary Data Access
Disease Hit-to-Lead Seres Has Differentiated Consortium Design with Proprietary Target ID ID Data Access and Advanced Experimental & Data Sciences Seres proprietary clinical data sets combined Seres strain library and microbiome-optimized with advanced data sciences & microbiome preclinical experime
Slide 33: SER-155 Leads to a Reduction in VRE and CRE Colonization In Vivo
Hit-to-Lead Lead Candidate SER-155 Leads to a Reduction in VRE and CRE ID Optimization Colonization In Vivo • SER-155 reduces CRE (carbapenem-resistant Enterobacteriaceae) and VRE (vancomycin-resistant Enterococci) in in vivo specific pathogen-free mouse models • Enterococcus species and Enterobacte
Slide 34: SER-155 Designed to Prevent Bacterial Translocation and Reduce GvHD
Hit-to-Lead Lead Candidate SER-155 Designed to Prevent Translocation of Bacteria to ID Optimization Bloodstream and Reduce GvHD Consortia strains optimized for production of metabolites that: • Prevent Translocation: Enhance epithelial barrier integrity, mucosal homeostasis & tight junction gene exp
Slide 35: SER-155 Data Supports Potential to Impact Multiple Disease-Relevant Pathways
SER-155 Data Supports Potential to Impact Multiple Disease-Relevant Pathways ✓ 1 Restore colonization resistance to decrease patient-to-patient transmission potential by preventing pathogen growth via nutrient competition and other functional mechanisms ✓ 2 Enhance epithelial barrier integrity and r
Slide 36: Seres is Maximizing the Opportunity in Infection Protection and AMR
Seres is Maximizing the Opportunity in Infection Protection and AMR Broadly Target Antimicrobial • Broad preclinical Resistant portfolio Additional Opportunities Infections • Driving to an additional clinical development Autologous HSCT program in 2023 Cancer Neutropenia • Potentially up to 3 Pre-cl
Slide 37: SER-155 clinical development
SER-155 clinical development Lisa von Moltke, M.D. Chief Medical Officer, Seres Therapeutics 37 Seres Therapeutics, Inc. © 2022
Slide 38: SER-155 is Designed for Maximum Clinical Impact
SER-155 is Designed for Maximum Clinical Impact SER-155 is a cultivated consortium SER-155 designed to address multiple of the leading designed using proprietary data causes of mortality following allogeneic HSCT Second Organ Malignancy 1% failure 7-9% Infection 17-21% Primary disease GVHD 46-60% 19
Slide 39: SER-155 Phase 1b Trial Design
SER-155 Phase 1b Trial Designed to Assess Its Safety and Efficacy in Treating Allo HSCT Patients; First Patient Enrolled in November 2021 Cohort 1 Cohort 2 • Open-label study with 10 subjects • Randomized, placebo-controlled study with 60 subjects • Evaluate SER-155 safety for 52 • Evaluate SER-155
Slide 40: SER-155 Phase 1b: Defining Successful Outcomes
SER-155 Phase 1b: Defining Successful Outcomes Safety profile (primary endpoint) Safe profile would validate path forward with other compromised Favorable safety profile populations Engraftment (primary endpoint) Engraftment results would confirm species selection and inform Confirm SER-155 strains
Slide 41: Infection protection commercial opportunities
Infection protection commercial opportunities Terri Young, Ph.D. Chief Commercial and Strategy Officer, Seres Therapeutics 41 Seres Therapeutics, Inc. © 2022
Slide 42: SER-109 Provides Example of Value of Infection Protection
SER-109 Provides a Robust Example of the Potential Value of Infection Protection with a Microbiome Therapeutic Approach High HCP Likelihood to A potentially novel solution for patients with rCDI Prescribe (% of MDs) • SER-109 works differently from traditional antibiotic 25% Definitely or probably w
Slide 43: Protecting Patients from Antimicrobial Resistant Infections Meets Unmet Need
Protecting Patients from Antimicrobial Resistant Infections Meets a Substantial and Growing Unmet Need Antimicrobial resistant infections are a major threat • WHO has declared a “top ten” global public health threat • ARI results in ~35,000 deaths in US/year*, with $4.6 billion in direct treatment c
Slide 44: GvHD and Bloodstream Infections are Common Life-Threatening Complications
GvHD and Bloodstream Infections are Common Life-Threatening Complications for Allogeneic HSCT Patients Despite Preventative Options • GvHD and severe infections are two of the most frequently GvHD and Infections in HSCT occurring complications and drive significant mortality • Both result in signifi
Slide 45: SER-155 Could Become Core Part of Allogeneic HSCT Armamentarium
SER-155 Could Become Core Part of the Allogeneic HSCT Armamentarium, Increasing Successful Outcomes for Vulnerable Cancer Patients Potential to provide substantial clinical value for the ~9,800 allogeneic HCST patients/year (US) ✓ Meaningful Risk Reduction – compared to Number of Treatments SOC alon
Slide 46: Sizable Pool of Patients May Benefit From Infection Protection
Sizable Pool of Patients May Benefit From Infection Protection • Focus on medically compromised populations with high infection rates Patient Potential in Infection Protection • Potentially attractive Patient Pool Potential # Patients Example Indications pricing corridor with high patient management
Slide 47: Microbiome Therapeutics for Cancer Patients with Neutropenia
Microbiome Therapeutics may be Uniquely Well Suited to Improve Outcomes of Cancer Patients with Neutropenia • Neutropenia followed by subsequent infections is common among cancer patients • 2.8 million annual cancer-related hospitalizations in the US • Half of patients undergoing chemotherapy experi
Slide 48: Microbiome Therapeutics to Address Antibiotic Resistance in Cirrhosis
Microbiome Therapeutics have Potential to Address Antibiotic Resistance Driving Mortality in Patients with Cirrhosis • Cirrhosis is a chronic, progressive and final common pathway for a multitude of hepatic diseases (e.g., NASH, viral hepatitis) • 630,000 patients in US • 10-15% hospitalized per yea
Slide 49: Seres' mission: Maximizing opportunities in infection protection
Seres’ mission: To transform the lives of Maximizing patients worldwide with revolutionary opportunities in microbiome therapeutics infection protection SER-109 data validates Broad portfolio Industry-leading franchise approach applicability potential • NEJM publication • Modality can target • Full
Slide 50: Q&A
Q&A 50 Seres Therapeutics, Inc. © 2022