Full Press Release Details
Presentation January 16, 2025
Disclaimers Forward Looking Statements This communication contains
forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. All statements contained in this communication that do not relate to matters of historical fact should be considered forward-looking statements,
including statements about: our anticipated financial performance, including cash and cash equivalents, for any period of time, including for the year ended December 31, 2024; the timing and results of our clinical studies and data readouts; our
clinical development plans; the anticipated timing of communications with or feedback from the FDA; the impact, value or potential benefits of Breakthrough Therapy designation, Fast Track designation or any other regulatory designations; our ability
to secure a partnership and/or generate additional capital; the potential market and commercial opportunity for SER-155 and other product candidates, if approved; projected cash runway; and other statements which are not historical fact. These
forward-looking statements are based on management's current expectations. These statements are neither promises nor guarantees, but involve known and unknown risks, uncertainties and other important factors that may cause our actual results,
performance or achievements to be materially different from any future results, performance or achievements expressed or implied by the forward-looking statements, including, but not limited to, the following: (1) we have incurred significant
losses, are not currently profitable and may never become profitable; (2) our need for additional funding; (3) our history of operating losses; (4) our novel approach to therapeutic intervention; (5) our reliance on third parties to conduct our
clinical trials and manufacture our product candidates; (6) the competition we will face; (7) our ability to protect our intellectual property; (8) our ability to retain key personnel and to manage our growth; (9) the effect of the VOWST sale on our
ability to retain and hire key personnel and maintain relationships with our customers, suppliers, advertisers, partners and others with whom we do business, or on our operating results and businesses generally (10) the risks associated with
the disruption of management's attention from ongoing business operations due to the obligation to provide transition services (11) our failure to receive the installment payments or the milestone payments in the future (12) the
uncertainty of impact of the 50/50 profit and loss sharing arrangement on our reported results and liquidity; and (13) we may not be able to realize the anticipated benefits of the VOWST sale. These and other important factors discussed under the
caption "Risk Factors" in our Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission (SEC), on November 13, 2024, and our other reports filed with the SEC could cause actual results to differ materially from
those indicated by the forward- looking statements made in this communication. Any such forward-looking statements represent management's estimates as of the date of this communication. While we may elect to update such forward-looking
statements at some point in the future, we disclaim any obligation to do so, even if subsequent events cause our views to change. These forward-looking statements should not be relied upon as representing our views as of any date subsequent to the
date of this communication. 2 Seres Therapeutics, Inc. 2025 2
Transforming patient outcomes using proprietary consortia of live
biotherapeutics Strong Foundation Positive SER-155 Phase Blockbuster SER-155 Expansive Platform 1b Data in Allo-HSCT Opportunity Potential Validated platform highlighted by VOWST 77% relative risk reduction Accelerate
SER-155 Systemic inflammation and FDA approval as first ever for bloodstream infections development in allo-HSCT immune homeostasis oral microbiome therapy biomarker data support the Well tolerated safety profile; Potential
to initiate multiple with outstanding clinical potential in inflammatory no treatment-related SAEs clinical trials in next 12-18 results and immune diseases, such and engraftment months for additional as IBD (e.g., ulcerative VOWST asset
sale indications colitis and Crohn's disease) Biomarker data supports strengthened balance impact on epithelial barrier SER-155 represents multi- sheet and streamlined SER-147 designed to integrity billion net sales
opportunity organization prevent infections in chronic across indications (e.g., liver disease FDA Breakthrough Cash into Q1 2026 autologous-HSCT, blood Designation cancers, CAR-T recipients) Pursuing SER-155 strategic partnership to
accelerate next study in allo-HSCT and expand to multiple target populations Seres Therapeutics, Inc. 2025 3
Validated therapeutic modality and platform: Seres pioneered the
development and FDA approval of VOWST as the first-ever oral live microbiome therapeutic DRAMATIC CLINICAL BENEFIT - Preventing infection recurrence Approximately 88% FDA approved (April 2023) to prevent the recurrence of sustained clinical
response rate (C. diff. recurrence, at up to 8 weeks) C. difficile infection in adults VOWST asset sale (completed September 2024) provided capital to support pipeline advancement and resulted in a more streamlined, focused organization Source:
Feuerstadt P et al. N Engl J Med. 2022;386(3):220-229 Seres Therapeutics, Inc. 2025 4
VOWST asset sale completed September 30, 2024: transformational for
Seres - provides resources to support SER-155 advancement KEY FINANCIAL TERMS $100M upfront payment to Seres, less ~$20M in net obligations due to an affiliate of SPN* VOWST asset purchase agreement $15M equity investment by SPN at
closing provided infusion of capital and $60M prepaid sales-based milestone at closing supports SER-155 development $75M in deferred payments due in 2025 (less ~$1.5M in employment-related payments) Asset sale extended operational runway
into Q4 25; now into Q1 26 $275M in potential future sales-based milestone payments (subject to reductions for interest on prepaid Retires debt and other obligations milestone payment) Transaction results in a more streamlined,
focused Seres organization and lower cash burn rate *SPN: Soci t des Produits Nestl S.A. Seres Therapeutics, Inc. 2025 5
The gut microbiome has substantial untapped therapeutic potential to
both prevent and treat diseases The genetic content of the microbes living within and on your body is at least 100-fold greater than that contained in the human genome Sources: Ley et al. (2006) Cell; Qin et al. (2010) Nature Seres Therapeutics,
Disrupted gastrointestinal microbiome is mechanistically linked to
infections and disease Disrupted & Disease Susceptible Not Disrupted Impacted Biology & Disease Relevance Pathogen or "undesirable" microbe abundance Increased pathogen abundance, in combination with impaired barrier integrity
Lost epithelial barrier & and decreased immune mucosal integrity function enables bacterial and antigen translocation leading Unfavorable immune to infections & inflammation responses Seres Therapeutics, Inc. 2025
Consortia of live commensal bacteria can be used as therapeutics Live
Biotherapeutics Consortia of PD PK bacterial strains Optimized to target Engraftment Restructure Change in Change Disrupted Microbiome multiple of drug microbiome microbiome in host with functional disease-relevant strains composition function
function deficiencies pathways (Disease susceptible) Other Bile acids Tryptophan metabolites Short-chain fatty acids Seres Therapeutics, Inc. 2025 8
Seres' biotherapeutics and pipeline candidates are expected to
have well tolerated safety profile, reducing development risk Based on GI bacteria naturally found in healthy humans, and not associated with disease VOWST product profile includes well tolerated safety without drug-related serious
adverse events Well tolerated safety profile in multiple clinical trials and patient populations, including medically vulnerable allo-HSCT recipients Safety profile has potential to mitigate a primary cause of drug development failure
Sources: Nanayakkara et al, CA Cancer J Clin 2021; Penack et al, Blood Adv 2020; Seres Therapeutics, Inc. 2025 9 Zheng et al, Infect Dis Ther 2021
Seres' initial focus is preventing infections in allo-HSCT;
potential is broad Allo-HSCT Autologous HSCT Chronic Liver Disease Survival by microbiome diversity Survival by microbiome diversity Survival by microbiome diversity Lower microbiome diversity post allo- Lower microbiome diversity post Microbiome
diversity decreases with HSCT is associated with increased auto-HSCT is associated with worse disease severity and is associated with blood stream infections and overall and progression-free survival increased risk of infection & death decreased
overall survival Common biology across vulnerable populations: pathogen domination in the GI microbiome, loss of epithelial barrier integrity, impacted immune function Sources: Peled, et al, NEJM 2020; Khan et al, Blood 2021; Bajaj et al, Clin
Gastroenterol Seres Therapeutics, Inc. 2025 10 Hepatol 2019; Odenwald, et al. Nature Micro. 2023
Near-term focus on SER-155 as anchor biotherapeutic program; achieved
Breakthrough and Fast Track designations Lead Indication & Therapeutic Potential Additional Program Development Stage Objectives Indications Allogeneic HSCT: provides clinical Phase 1b Reduce incidence of Autologous HSCT proof of concept
Cohort 2 (placebo serious bacterial infections Reduces risk of SER-155 Blood cancers controlled) data announced (e.g., BSIs), febrile recurrent C. diff CAR-T Sept. 24 and exploratory neutropenia, and GvHD infections
biomarker data in Jan 25 Well tolerated safety profile Solid organ Reduce incidence of transplant Chronic liver disease: serious bacterial infections SER-147 ICU patients IND-enabling activities (e.g., SBP, BSIs) and
Long-term care related complications patients Briefing Book Submitted - engaging with FDA in Q1 25 to explore potential for SER-155 to have single registrational study for efficacy, following successful precedent from VOWST BSI:
bloodstream infection; SBP: spontaneous bacterial peritonitis Seres Therapeutics, Inc. 2025 11
Allo-HSCT regimen can result in life-threatening complications
Allo-HSCT treatment regimen Only ~60% survival 3 years post- Chemotherapy Allo-HSCT Increased risk of infection, GvHD Anti-infectives infusion transplant Significant immune compromise ~10% transplant mortality for adults in
first 100 days post- -14 0 +100 Days transplant Conditioning Immunosuppression Infections are leading cause of death in first 100 days post- transplant for adults Extensive GI microbiome disruption Other leading causes of death are
disease relapse and organ failure Sources: CIBMTR 2023 US summary slides; Penack et al, Blood Adv 2020; Khan et al, Blood 2021; Peled et al, NEJM 2020; Seres Therapeutics, Inc. 2025 12 Stein-Thoeringer et al, Science 2019; Bleakley &
Riddell, Nat Rev Cancer 2004
Bloodstream infections (BSIs) are a leading cause of death
post-transplant and are increasing in incidence Bacterial BSI in first 30 days BSI risk increasing due to recent adoption post-HSCT Incidence of post-transplant cyclophosphamide (PTCy) 50% for GvHD prophylaxis 40% ~50% of infections
are gut-seeded 30% 50-80% febrile neutropenia incidence 43% 20% 10% 14% 0% Non-PTCy PTCy Salas et al 2024 Infection is leading cause of death in first 100 days post-HSCT for adults Impact ~7.5% mortality rate from bloodstream
infections Complications including infection associated with longer hospital stay and ICU utilization, driving substantial cost increase Sources: Gill et al, Microorganisms 2023; Sava et al, Bone Marrow Transplantation 2022; Carreira et al,
Transplant Cell Ther 2022; Youssef et al, Pediatric Transplantation 2020; Song et al, Infect Drug Resist 2023; Bola os-Meade J et al, NEJM 2023; Salas et al, Transplant Cell Ther 2024; Rearigh et al, Annals Seres Therapeutics, Inc. 2025
13 of Hematology 2020; CIBMTR 2023 US summary slides; Perales et al Biol Blood Marrow Transplant 2017; 2024 Seres physician market research
Standards of care to prevent bloodstream infections in allo-HSCT
patients are poor and decreasing in efficacy Joint ASCO* and IDSA EBMT guidelines and Infectious Disease recommendation Working Party recommendations Fluoroquinolones (FQ) recommended 2022 Workshop recommends move to for
antibacterial prophylaxis targeted antibacterial prophylaxis Prophylaxis recommended during Multiple analyses suggest reduced infections window of expected neutropenia from antibacterial prophylaxis but no overall survival benefit
High BSI rate happening despite broad FQ prophylaxis in the US Prophylaxis efficacy decreasing as bacteria become resistant to antibiotics Trends PTCy adoption for GvHD prophylaxis is increasing BSI rates * ASCO: American
Society of Clinical Oncology; IDSA; Infectious Diseases Society of America; EBMT: formerly known as the European Society for Blood and Marrow Transplantation; PTCy: post-transplant cyclophosphamide Seres Therapeutics, Inc. 2025 14 Sources:
Taplitz et al, J Clin Oncol 2018; EBMT 2022 report; Neuerberg et al Transplant Cell Ther 2024; Bola os-Meade et al, NEJM 2023
SER-155 Phase 1b study evaluated safety, pharmacology, and efficacy in
adult allo- HSCT recipients COHORT 1 COHORT 2 Open-label (n=15 enrolled) Placebo-controlled 1:1 (n=45 enrolled) SER-155 SER-155 Placebo results reported May 2023 results announced Sept. 2024 Primary Endpoints: Key Secondary Endpoints through HSCT
Day 100: Safety and tolerability Incidence of bloodstream infections (BSI), GI infections, and acute GvHD Grade 2 SER-155 bacterial strain engraftment Incidence and duration of febrile neutropenia
Bacterial pathogen abundance Seres Therapeutics, Inc. 2025 15
SER-155 Safety: SER-155 was generally well tolerated with no
treatment-related SAEs All but one subject in the placebo arm experienced at least 1 TEAE Most common for SER-155 treated subjects ( 50% and with 5% greater than placebo): Treatment-emergent diarrhea (86% vs. 74%
placebo), nausea (62% vs. 53% placebo) adverse events 1/40 (3%) subject experienced a TEAE leading to treatment discontinuation (active = 0; placebo = 1) (TEAEs) 3/40 (8%) subjects experienced a TEAE leading to study discontinuation
(active = 1; placebo = 2) 19/40 (48%) subjects experienced an SAE: 11/21 (52%) SER-155-treated subjects vs. 8/19 (42%) placebo-treated subjects; none considered related to SER-155 (no SUSARs) Serious adverse events o Most common SAE SOC:
infections & infestations (24% active vs. 37% placebo) (SAEs) o 3 deaths prior to Day 100 (active = 1; placebo = 2), 1 death after Day 100 (active), none considered related to SER-155 Adverse events of AESIs (bloodstream infections, GI
infection, invasive infection): 14/40 (35%) subjects special interest Rates of AESIs were lower in SER-155 arm vs placebo arm (29% vs 42% respectively) (AESIs) No SER-155 species were identified in culture from any subject Seres
Therapeutics, Inc. 2025 16
SER-155 Efficacy: SER-155 associated with 77% relative risk reduction
in bacterial BSIs and reduction in systemic antibiotic exposure Significant decrease in bacterial bloodstream infections in SER-155-treated subjects vs. Bloodstream infections placebo with 77% relative risk reduction Significantly lower mean
cumulative exposure (days) and exposure rate to systemic Antibiotic exposures antibacterials / antimycotics for SER-155-treated subjects vs. placebo Numerically lower incidence rate of febrile neutropenia in SER-155-treated subjects vs. Febrile
neutropenia placebo * CDI: C. difficile infection Seres Therapeutics, Inc. 2025 17
Bloodstream infections from HSCT Day 0 to Day 100: Lower incidence in
SER-155 treated subjects vs. placebo Bloodstream infections from Day 0 SER-155 Placebo to Day 100 n=20 n=14 (# patients) n (%) n (%) Subjects with confirmed BSI 2 (10.0%) 6 (42.9%) 95% confidence interval (1.2, 31.7) (17.7, 71.1) mITT-1 population
Odds ratio 0.15 95% confidence interval (0.01, 1.13) p-value 0.0423 Organisms in SER-155 patients: Finegoldia magna; E. coli/Strep mitis Organisms in placebo patients: E.coli; Enterococcus faecium/staph haemolyticus/Candida krusei; Staph aureus;
Staph haemolyticus; Pseudomonas aeruginosa; E coli CI: 95% 2-sided Clopper-Pearson confidence interval of incidence is applied Odds ratio: for incidence between treatment groups (SER-155 and placebo) with 95% 2-sided confidence Seres
Therapeutics, Inc. 2025 18 interval and the corresponding p-value calculated based on the Fisher's Exact test
Cumulative exposure to systemic antibacterials / antimycotics through
HSCT Day 100: Lower incidence in SER-155 treated subjects vs. placebo Cumulative Antibacterial or SER-155 Placebo Antimycotic Exposure n=20 n=14 (HSCT Days) n (SD) n (SD) Mean (SD) 9.2 (5.44) 21.1 (20.31) Median 9.0 14.0 Min, Max 0, 19 0, 74 mITT-1
population Mean Difference (95% CI) -11.9 (-23.85, -0.04) p-value 0.0494 Cumulative exposure is the sum of all days a subject received systemic antibacterials and/or antimycotics between HSCT Day 0 through Day 100; counting once per day
regardless of number of agents taken Seres Therapeutics, Inc. 2025 19 95% confidence interval and p-value based on independent samples t-test of the difference in mean days between SER- 155 and placebo
Cumulative exposure rate to systemic antibacterials / antimycotics
through HSCT Day 100: Lower incidence in SER-155 treated subjects vs. placebo Cumulative Antibacterial or SER-155 Placebo Antimycotic Exposure Rate n=20 n=14 Rate (SD) Rate (SD) Mean (SD) 0.090 (0.0530) 0.305 (0.2898) Median 0.089 0.244 Min, Max
0.00, 0.18 0.00, 0.90 mITT-1 population Mean Difference (95% CI) -0.2 (-0.38, -0.05) p-value 0.0163 Cumulative exposure rate is calculated as the sum of all days a subject received systemic antibacterials and/or antimycotics on or after HSCT