SER-155 Phase 1b Readout

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SER-155 is designed to reduce life-threatening complications of

allo-HSCT Investigational live oral biotherapeutic cultivated from clonal master cell banks SER-155 Designed to prevent GI-derived bacterial bloodstream infections (BSIs) and other pathogen-associated complications Allo-HSCT

treatment regimen and SER-155 Only ~60% survival 3 years post- transplant Chemotherapy Allo-HSCT Increased risk of infection, GvHD Anti-infectives ~10% transplant mortality in first infusion Additional SER-155 dosing 1st SER-155

dosing 100 days post-transplant ~80% of adult deaths in first 100 -14 0 +100 Days days caused by complications of Conditioning Immunosuppression procedure; half of these due to infections and GvHD Extensive GI microbiome disruption

Complications have substantial impact: mortality, cost, hospital stay Sources: CIBMTR 2023 US summary slides; Penack et al, Blood Adv 2020; Khan et al, Blood 2021; Peled et al, Seres Therapeutics, Inc. 2024 4 NEJM 2020; Stein-Thoeringer et

al, Science 2019; Bleakley & Riddell, Nat Rev Cancer 2004

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 Received US FDA Fast Track Designation in December 2023; Intend to pursue Breakthrough Therapy designation Seres Therapeutics, Inc. 2024 5

Cohort 2 patient disposition ITT Safety mITT-1 SER-155 n = 23 n = 21 n =

20 -2 randomized untreated -1 consent withdrawal mITT-1 population studied for efficacy Safety mITT-1 ITT Placebo n = 19 n = 14 n = 22 -3 randomized untreated -3 disease progression -1 transplant delay -1 consent withdrawal ITT (intent-to-treat):

all enrolled subjects Seres Therapeutics, Inc. 2024 6 Safety: all subjects receiving any amount of drug st m-ITT1 (modified intent-to-treat 1): all subjects who received study drug in 1 course and underwent HSCT

Cohort 2 demographics: Representative of the allo-HSCT population

Median age: 63 years Demographics Gender: 50% male, 50% female Ethnicity: 88% white Most common diagnosis: acute myeloid leukemia (AML): 38% Cancer Diagnosis Other common diagnoses: acute lymphocytic leukemia

(ALL), myelodysplastic syndrome, myeloproliferative neoplasia 91% received peripheral blood 62% received stem cells from a non-relative Transplant 59% HLA-matched unrelated donor 79% underwent a reduced intensity

conditioning (RIC) regimen 79% received post-transplant cyclophosphamide (PTCy) for GvHD prophylaxis in Cohort 2 vs. 18% in Cohort 1 GvHD Prophylaxis o SER-155 arm: 70% (14/20) o Placebo arm: 93% (13/14) Seres Therapeutics, Inc. 2024

7 mITT-1 (n=34) Safety (n=40)

Patient Safety: Cohort 2 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. 2024 8

Efficacy: SER-155 administration favorable with significant* reduction

in both bacterial BSIs and systemic antibiotic exposure; lower febrile neutropenia Significant decrease in bacterial bloodstream infections in SER-155-treated Bloodstream infections subjects vs. placebo Numerically lower incidence rate of febrile

neutropenia in SER-155-treated Febrile neutropenia subjects vs. placebo All GI infections were CDI**; 4 subjects in SER-155-treated (20%) and 2 GI infections subjects in placebo (14.3%) developed GI infections from HSCT Day 0-100 No subjects in

either arm developed Grade 3 acute GvHD; Acute GvHD 2 subjects in each arm developed Grade 2 acute GvHD Significantly lower mean cumulative exposure (days) to systemic antibacterials / antimycotics for SER-155-treated subjects vs. placebo

Antibacterial / antimycotic exposure Significantly lower cumulative exposure rate to systemic antibacterials / antimycotics for SER-155-treated subjects vs. placebo * no multiplicity adjustments were applied Seres Therapeutics, Inc. 2024 9 **

CDI: C. difficile infection Exploratory Secondary Efficacy Efficacy

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 Seres Therapeutics, Inc. 2024 10 Odds ratio: for incidence between treatment groups (SER-155 and

placebo) with 95% 2-sided confidence interval and the corresponding p-value calculated based on the Fisher's Exact test

Febrile neutropenia from HSCT Day 0 to Day 100: Lower incidence in

SER-155 treated subjects vs. placebo Febrile neutropenia from Day 0 to SER-155 Placebo Day 100 n=20 n=14 (# patients) n (%) n (%) Subjects with FN 13 (65.0) 11 (78.6) 95% confidence interval (40.8, 84.6) (49.2, 95.3) mITT-1 population Odds ratio

0.51 95% confidence interval (0.07, 2.99) p-value 0.4674 CI: 95% 2-sided Clopper-Pearson confidence interval of incidence is applied Seres Therapeutics, Inc. 2024 11 Odds ratio: for the incidence between treatment groups

(SER-155 vs. placebo) with 95% 2-sided confidence interval and the corresponding p-value are 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 (%) n (%) 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. 2024 12 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 (% of days) n (%) n (%) 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 Seres Therapeutics, Inc. 2024 13 100 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 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 Strain Engraftment: Primary objective achieved - drug bacteria

strain engraftment was robust and as expected The majority of SER-155 strains were present at start of HSCT conditioning and durable through chemotherapy exposure Engraftment decreased but was detectable post- neutrophil recovery,

suggesting sustained engraftment, even under unfavorable GI conditions (e.g., antibiotic exposure), and through period of greatest BSI susceptibility The second course of SER-155 was effective at increasing strain engraftment following

transplant & neutrophil recovery, with engraftment durable out to day 100 following transplant Cohort 1 and Cohort 2 engraftment magnitude and kinetics had high congruence Seres Therapeutics, Inc. 2024 14

Pathogen Domination: Prevalence in SER-155 Cohort 2 was substantially

lower relative to Historical Control Cohort SER-155 was designed to reduce pathogen domination that has been associated with risk of BSIs and other negative 1 clinical outcomes 2 In Cohort 2, the ability to detect pathogen domination

(i.e., relative abundance in the GI 30%) in the placebo arm, and differences between the study arms, was constrained due to the limited number of placebo stool samples and an imbalance in the number of available stool samples between the arms

Observed pathogen domination events were low in the placebo and SER-155 arms with no significant differences observed 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. 2024 15 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

Summary and Next Steps Seres to engage with FDA on advancement Phase 1

results support Seres' strategy to of SER-155 allo-HSCT program pursue SER-155 and other live biotherapeutics for prevention of serious bacterial infections Intend to evaluate SER-155 in additional patient Seek Breakthrough

Therapy designation given populations with high risk of serious bacterial high unmet medical need associated with infections bloodstream infections Opportunities to address multiple medically Pursue additional designations (Orphan

Drug vulnerable patient groups with SER-155 and designation, Qualified Infectious Disease Product) additional pipeline programs Seres Therapeutics, Inc. 2024 16