UNITED STATES
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CURRENT REPORT
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| Item 7.01. | Regulation FD Disclosure. |
On January 13, 2025, Seres Therapeutics, Inc. (the “Company”) posted an updated corporate presentation in the “Investors and News” portion of its website at www.serestherapeutics.com. A copy of the slide presentation is attached as Exhibit 99.1 to this Current Report on Form 8-K (this “Current Report”) and incorporated herein by reference.
The information in Item 7.01 of this Current Report, including Exhibit 99.1 attached hereto, is intended to be furnished and shall not be deemed “filed” for purposes of the Securities Exchange Act of 1934, as amended (the “Exchange Act”), or otherwise subject to the liabilities of that section, nor shall it be deemed incorporated by reference in any filing under the Securities Act of 1933, as amended, or the Exchange Act, except as expressly set forth by specific reference in such filing. The Company undertakes no obligation to update, supplement or amend the materials attached hereto as Exhibit 99.1.
| Item 9.01. | Financial Statements and Exhibits. |
(d) Exhibits.
The following Exhibit 99.1 relates to Item 7.01 and shall be deemed to be furnished, and not filed:
| Exhibit No. |
Description | |
| 99.1 | Seres Therapeutics, Inc. Corporate Presentation as of January 2025 | |
| 104 | Cover Page Interactive Data File - the cover page XBRL tags are embedded within the Inline XBRL document. | |
SIGNATURES
Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.
| Date: January 13, 2025 | SERES THERAPEUTICS, INC. | |||||
| By: | /s/ Thomas J. DesRosier | |||||
| Name: | Thomas J. DesRosier | |||||
| Title: | Chief Legal Officer and Executive Vice President | |||||
Exhibit 99.1 J.P. Morgan Conference Seres Therapeutics Investor 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: Société des Produits Nestlé 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, Inc. © 2025 6
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 7
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; Bolaños-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; Bolaños-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 Δ ≥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 Day 0 (counting once per day, regardless of number of antibacterial/antimycotic medications taken in a day) through HSCT Day 100 over the total number of days a subject was on the study from HSCT Day 0 to the earliest of EOS, or HSCT Day 100 Seres Therapeutics, Inc. © 2025 20 • 95% confidence interval and p-value are based on independent samples t-test of the difference in mean days or mean rate of cumulative exposure between SER-155 and Placebo
SER-155 Pharmacokinetics: Primary objective achieved - drug bacteria strain engraftment was robust and as expected • The majority of SER-155 strains engrafted and were durable through chemotherapy exposure • Engraftment decreased but was detectable post- neutrophil recovery, suggesting sustained engraftment through period of greatest BSI susceptibility • The second course of SER-155 was effective at increasing strain engraftment following neutrophil recovery • Engraftment durable out to day 100 following transplant Seres Therapeutics, Inc. © 2025 21
SER-155 Pharmacodynamics: the Ph1b study included multiple measures of drug pharmacodynamics SER-155 Mechanism of Action Preclinical Measurements on Ph1b clinical study Optimization Targets Genomic measurements of pathogen abundance in Inhibit Pathogens or gastrointestinal tract, including domination by pathogenic “Undesirable” Microbes bacteria Repair & Protect Mucosal Concentration of fecal albumin in subject stool, reflecting barrier Epithelial Barrier Integrity damage and leakage of serum albumin into the GI tract New Data Concentrations of plasma cytokines, chemokines and signaling Modulate Immune function molecules reflecting GI inflammation, systemic inflammation, and immune homeostasis New Data Seres Therapeutics, Inc. © 2025 22
SER-155 Pharmacodynamics (pathogen domination): prevalence in SER-155 Cohort 2 was substantially lower relative to Historical Control Cohort • Pathogen domination (i.e., relative abundance in the GI ≥30%) has been associated with risk of BSIs and other 1, 2 negative clinical outcomes • Observed pathogen domination events were low in both the placebo and SER-155 arms with no significant differences observed • The ability to detect pathogen domination in the placebo arm was constrained due to the imbalance in the number of available stool samples between the arms. • Pathogen domination was substantially lower in SER-155 3 Cohort 2 compared to Historical Control Cohort 1 - Peled et al, NEJM 2020; Stein-Thoeringer et al, Science 2019; Kusakabe et al, BBMT 2020 2 - Bacteria in the families: ESKAPE (Enterococcaceae, Enterobacteriaceae & Staphylococcaceae) & Streptococcaceae; domination defined as ≥30% relative abundance in the GI Seres Therapeutics, Inc. © 2025 23 3 - Subjects that are sampled at similar time points as SER-155 Phase 1b subjects; microbiome data produced using same protocols as SER-155 Phase 1b subjects
US HCPs seek significant reduction of infection risk without compromising patient safety and would incorporate such a therapeutic into standard of care • Reduce incidence of bloodstream infections: target 20% BSI rate vs. current 40% rate • Reduce systemic antibiotic use that is contributing to rising resistance Efficacy • Reduce incidence of febrile neutropenia: target 60% FN rate vs. current 80% rate • No major adverse event signals Safety • Expect translation to fewer deaths in the active study arm Health economics • Shorten hospital stay, reduce readmissions & reduce ICU utilization SER-155 Phase 1b data suggest potential to deliver this profile in a pivotal study Seres Therapeutics, Inc. © 2025 Source: Seres primary market research 2024 24 Profile of SER-155
HCPs see SER-155 as a potentially transformative means to eliminate complications that get in the way of achieving transplant success Reducing the risk of HSCT-related complications, thus ensuring successful engraftment Primary Value Driver for and long-term health of the patient SER-155 A relative risk reduction of 50% in BSIs is seen as “transformative” and would support broad inclusion in standard protocols for allo-HSCT patients The benefit would be massive because Health Care Providers people die from these infections and so “ preventing them, the biggest benefit is Streamlines the transplant process so they can spend more time treating mortality. The rest of the stuff with ICU the patient’s underlying conditions and less time dealing with potential admits and sepsis protocols and all…I morbidities think some of that also gets averted. That would be huge.” Patients One less thing to worry about for patients already dealing with a lot; additional financial and QoL benefits due to shortened hospital stays “This would probably be standard of “ “ care. It would be all eligible patients minus those who cannot tolerate it or are allergic.” Healthcare System Reduced healthcare costs due to shorter hospital stays, fewer ICU visits, fewer antibiotic days and lower incidence of severe negative outcomes Seres Therapeutics, Inc. © 2025 Source: Seres primary market research 2024 25
New Data US payers confirm high unmet clinical need for infection prophylaxis in allo- HSCT recipients and robust profile of SER-155 Clinical Burden Rating • High perceived clinical burden of BSIs within the allo-HSCT patient population is driven by high frequency of occurrences and poor associated outcomes HIGH • Lack of an efficacious prophylactic therapy that successfully limits incidence of High clinical burden BSIs is considered a key unmet need and current driver of clinical burden and unmet need • Top unaided clinical concerns raised by payers include risk of febrile neutropenia, sepsis, and antibiotic-resistant infection LOW • Proposed risk reduction of BSIs and related endpoints were seen as clinically meaningful and supportive of value proposition Profile of SER-155 • “The reductions in primary and secondary endpoints are encouraging and brings positively received hope that you are going to escape this risky scary complication of cancer therapy.” Site of dispensing • Oral administration is viewed as convenient by payers, with most expecting coverage under outpatient pharmacy benefit given oral administration likely outside of the drives reimbursement hospital setting pathway Seres Therapeutics, Inc. © 2025 Source: Q4 2024 US market research with sample including national and regional health plans + PBMs representing ~128M covered lives 26
Viral prophylaxis provides precedent in medically vulnerable patients Prevymis - increasingly used for viral infection prophylaxis (e.g., allo-HSCT and • Overall cost of allo-HSCT is high solid organ transplant populations) (~$400K US year 1 allo-HSCT costs) • Transplant-related complications (e.g., $605M ‘23 infections) raise cost by ~$180K WW sales • Infections result in longer hospital stays, readmissions, increased ICU utilization • Reduces CMV infection in allo-HSCT recipients • Lowers mortality rate Sources: CMS.gov; Broder et al, Am Drug Health Benefits 2017; Perales et al, Biol Seres Therapeutics, Inc. © 2025 27 Blood Marrow Transplant 2017; Merck SEC filings
SER-155 has blockbuster commercial potential, driven by a robust SER-155 profile and substantial unmet needs in allo-HSCT and additional groups ✓ High unmet need to prevent frequent and serious infections ✓ ~40K annual transplants worldwide; 3% annual growth from aging population and transplant success rates ✓ Costly procedure (~$400K US year 1 allo-HSCT per patient cost) with high incremental costs of infections (incremental ~$180K/patient) ✓ SER-155 has potentially transformational profile with robust efficacy and safety ✓ Highly concentrated universe of transplant centers conducting stem ell transplant procedures allows for an efficient commercial model with rapid education on new standard of care Sources: CIBMTR; HRSA; Passweg et al, BMT 2021; IQVIA; Broder et al, Am Drug Health Benefits 2017; Seres Therapeutics, Inc. © 2025 28 Perales et al, Biol Blood Marrow Transplant 2017 CMS.gov; Merck SEC filings
Indication expansion: potential 10x addressable population Broader leukemia & Allo-HSCT Autologous HSCT lymphoma population* WW annual ~40,000 ~60,000 ~500,000 diagnoses or transplants US annual ~9,300 ~13,500 ~87,000 diagnoses or initial focus transplants Unmet needs Prevent mortality and Prevent mortality and Reduce morbidity, addressed by cost of post- costs of post- mortality, and cost of SER-155 transaction infections transplant infections infections and febrile neutropenia from chemotherapy *Includes acute myeloid leukemia, multiple myeloma, and aggressive B cell non-Hodgkin lymphomas (diffuse large B-cell lymphoma, mantle cell, Burkitt’s lymphoma) Seres Therapeutics, Inc. © 2025 29 Sources: CIBMTR, US NCI SEER, Thandra et al 2021 report of WHO data, Niederwieser et al Haematologica 2022; WHO Global Cancer Observatory; American Cancer Society
Accelerating SER-155 clinical development with positive Ph1b outcomes Aim to accelerate SER-155 development in allo-HSCT • Potential to follow successful precedent from VOWST development with single registrational study for efficacy Seeking SER-155 Engage with FDA on advancement of SER-155 allo- strategic partnership to HSCT program accelerate next study in • Received Breakthrough Therapy designation in December 2024 allo-HSCT • Applied for Orphan Drug designation and expand to multiple target populations Intend to evaluate SER-155 in additional patient populations with high risk of serious bacterial infections Seres Therapeutics, Inc. © 2025 30
Advancing SER-147 to prevent infections in chronic liver disease patients Substantial unmet need Promising preclinical data SER-147 is an investigational live oral biotherapeutic designed to reduce pathogens 0.5M 2.1M causing gut-seeded SBP and BSIs in liver disease patients Declining E. coli titers experience bacterial Example: 1-3 log ~50% infections in a 6 month period reduction of E. coli in in vitro models, of infections are spontaneous plus reduction of bacterial peritonitis (SBP) and ~20-25% other pathogens bloodstream infections likely to be gut-seeded Sources: GBD 2017 Cirrhosis Collaborators, Lancet Gastroenterology & Hepatology 2020; United Nations world population data; Seres Therapeutics, Inc. © 2025 31 Trebicka et al, J Hepatol 2020; Seres preclinical data from 2023 IDWeek
Manufacturing platform delivers defined consortia in oral formulation using cost-effective production Strain isolation and characterization pipeline to rapidly identify cGMP- suitable medium components Highly intensive strain bioprocessing leveraging flexible, single-use manufacturing technology for cost-effective production Novel formulations enabling consistent drug product composition, drug stability for distribution, and targeted drug delivery Quality systems to ensure product quality and stability, extending prior regulatory successes, including developing product release specifications with the FDA Seres Therapeutics, Inc. © 2025 32
Maximizing opportunity of live biotherapeutics going forward • Prevent life-threatening bacterial infections, including antimicrobial resistant infections in additional populations Additional • Treat immune-related diseases (e.g., IBD, GvHD, checkpoint Opportunities colitis) • Infections in Chronic liver disease: Progressing towards IND readiness SER-147 • Indication expansion (e.g., radiation enteritis, ICU and long-term care patients, organ transplant) • Bloodstream infections in Allo-HSCT: Engaging with FDA to accelerate; received Breakthrough Therapy designation and filed for Orphan Drug designation SER-155 • Evaluate in additional cancer treatment populations with high risk of serious bacterial infections VOWST • rCDI: Proven clinical and regulatory success; asset sale to Nestlé; Seres to participate in future milestones Seres Therapeutics, Inc. © 2025 33
Summary and path forward SER-155 Phase 1b placebo-controlled clinical efficacy data further support Seres’ strategy • Developing a pipeline of Pipeline aims to bring transformative medicines to a wider set of patients, led by SER-155 while • novel live biotherapeutics in advancing SER-147 areas of high unmet need VOWST approval validates using live biotherapeutics to prevent life-threatening infections • Administration associated with 77% relative risk reduction for BSIs, significant reduction in • systemic antibiotic exposure and lower incidence of febrile neutropenia vs placebo; Exploratory biomarker data support epithelial barrier integrity and the potential role for Seres’ platform to SER-155 Phase 1b provide clinical benefit to patients with inflammatory and immune diseases, such as IBD, including ulcerative colitis and Crohns disease placebo-controlled clinical results promising FDA Breakthrough Designation obtained • Company pursuing SER-155 strategic partnership to accelerate next study in allo-HSCT and • expand to multiple target populations • ~$31M in cash/cash equivalents at Dec 31, 2024; cash runway projected into Q1 2026 VOWST asset sale • Fully retired debt strengthens financial • VOWST asset sale closed in Sept 2024; $50M expected to be received in January 2025 and position $25M (less ~$1.5M in employment-related payments) due in July 2025 + $275M potential future milestones Seres Therapeutics, Inc. © 2025 34