DEFA14A: Seres Therapeutics' SER-155 Shows Positive Phase 1b Results in Allo-HSCT Patients, Company to Seek Breakthrough Therapy Designation

Seres Therapeutics announces positive topline results from its SER-155 Phase 1b study, demonstrating a significant reduction in bloodstream infections and antibiotic use in patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT).

Summary

• Seres Therapeutics announced topline clinical data from Cohort 2 of its SER-155 Phase 1b placebo-controlled study in patients undergoing allo-HSCT.
• The study demonstrated that SER-155 was associated with a significant reduction in bloodstream infections (BSIs) and systemic antibiotic exposure compared to placebo through day 100 post-HSCT.
• SER-155 was generally well-tolerated, with no treatment-related serious adverse events observed.
• The incidence of BSIs was significantly lower in the SER-155 arm (10%) compared to the placebo arm (42.9%).
• Patients administered SER-155 were treated with antibiotics for a significantly shorter duration (9.2 days) compared to those in the placebo arm (21.1 days).
• The incidence of febrile neutropenia was lower in patients administered SER-155 (65%) compared to placebo (78.6%).
• The company intends to seek Breakthrough Therapy designation from the FDA and discuss advancing the development of SER-155 for allo-HSCT.
• Seres also plans to evaluate SER-155 in additional patient populations at high risk of serious bacterial infections.
• Seres expects the VOWST asset sale to close shortly after the September 26 shareholder meeting, with $175M due at closing less an ~$20M settlement of net obligations, and $75M (less ~$1.5M in employment-related payments) in installment payments due in 2025 + $275M potential future VOWST asset sale milestones.
• The asset sale is expected to extend the company's cash runway into Q4 2025.

Sentiment

Score: 8

Explanation: The document presents positive clinical trial results and a strategic asset sale, indicating a favorable outlook for the company. The successful Phase 1b trial results for SER-155 and the anticipated financial boost from the VOWST asset sale contribute to a positive sentiment.

Positives

• SER-155 showed a significant reduction in BSIs and antibiotic use.
• SER-155 was generally well-tolerated.
• The company intends to seek Breakthrough Therapy designation.
• The VOWST asset sale will strengthen the company's financial position and extend its cash runway.
• SER-155 bacterial strains engrafted into the gastrointestinal tract of patients following administration.

Negatives

• Six cases of gastrointestinal infections (C. difficile infections) were observed in the study, with four cases (20%) in the SER-155 arm and two cases (14.3%) in the placebo arm.
• The ability to detect pathogen domination in the placebo arm was constrained due to the limited number of placebo stool samples and an imbalance in the number of available stool samples between the arms.

Risks

• The company has incurred significant losses and may never become profitable.
• The company needs additional funding.
• The company relies on third parties to conduct clinical trials and manufacture product candidates.
• There are risks associated with clinical trials and the possibility that the FDA may not grant Breakthrough Therapy Designation.
• The company faces competition and risks related to protecting its intellectual property and retaining key personnel.

Future Outlook

Seres plans to engage with the FDA to advance the SER-155 allo-HSCT program, seek Breakthrough Therapy designation, and evaluate SER-155 in additional patient populations. The company also aims to expand its pipeline and address other therapeutic areas.

Management Comments

• Lisa von Moltke, M.D., Chief Medical Officer of Seres Therapeutics, stated that the Phase 1b study results provide further evidence supporting the potential of SER-155 to reduce the risk of bacterial bloodstream infections.
• Eric Shaff, Chief Executive Officer of Seres Therapeutics, believes that SER-155 could provide meaningful value for patients and the healthcare system, given the high unmet need.
• Mr. Shaff is particularly encouraged by the consistency of related efficacy outcomes in this study, especially the significantly lower rates of bloodstream infections and systemic antibiotic exposure as well as fewer instances of febrile neutropenia, as compared to placebo.

Industry Context

The announcement highlights the significant unmet need for preventing bacterial infections in vulnerable patient populations, particularly those undergoing allo-HSCT. The potential of live biotherapeutics like SER-155 to address this need could represent a novel approach compared to traditional antibiotic treatments.

Comparison to Industry Standards

• The document mentions that approximately 40,000 patients worldwide undergo allogeneic stem cell transplantation each year.
• The potential to contract a bloodstream infection during the allogeneic transplant process is significant, with incidence reports in the literature reaching up to 45%.
• Allogeneic transplant-related complications, including infections, increase already significant treatment costs by approximately $180,000 per patient.
• The document references CIBMTR 2023 US summary slides; Penack et al, Blood Adv 2020; Khan et al, Blood 2021; Peled et al, NEJM 2020; Stein-Thoeringer et al, Science 2019; Bleakley & Riddell, Nat Rev Cancer 2004.

Stakeholder Impact

• Shareholders may benefit from the positive clinical trial results and strengthened financial position.
• Patients undergoing allo-HSCT may benefit from SER-155's potential to reduce bloodstream infections and antibiotic use.
• Healthcare providers may have a new tool to combat infections in vulnerable patient populations.
• The healthcare system may benefit from reduced treatment costs associated with infections.

Next Steps

• Seres intends to seek Breakthrough Therapy designation from the FDA for SER-155.
• Seres plans to discuss advancing the development of SER-155 for allo-HSCT with the FDA.
• Seres intends to evaluate SER-155 in additional patient populations at high risk of serious bacterial infections.
• The company anticipates the VOWST asset sale to close shortly after the September 26 shareholder meeting.
• Seres anticipates SER-147 will be IND ready in H2 '25.

Key Dates

Keywords

SER-155, allo-HSCT, bloodstream infections, antibiotic exposure, febrile neutropenia, live biotherapeutics, VOWST, FDA, Breakthrough Therapy designation, microbiome