8-K: Seres Therapeutics Announces Positive Phase 1b Results for SER-155 in Stem Cell Transplant Patients

Seres Therapeutics reports that its SER-155 therapy significantly reduced bloodstream infections and antibiotic use in patients undergoing stem cell transplants.

Summary

• Seres Therapeutics announced positive topline results from the Phase 1b study of SER-155 in patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT).
• The study showed a significant reduction in bloodstream infections (BSIs) in the SER-155 arm compared to the placebo arm, with 10% of patients in the SER-155 group experiencing BSIs versus 42.9% in the placebo group.
• Patients receiving SER-155 also had a significantly shorter duration of antibiotic treatment, averaging 9.2 days compared to 21.1 days in the placebo group.
• The incidence of febrile neutropenia was lower in the SER-155 group (65%) compared to the placebo group (78.6%), although this difference was not statistically significant.
• SER-155 was generally well-tolerated, with no treatment-related serious adverse events observed.
• The study included 45 patients in Cohort 2, with 20 receiving SER-155 and 14 receiving placebo, and the median age of participants was 63 years.
• The company intends to seek Breakthrough Therapy designation from the FDA and discuss further development of SER-155 for allo-HSCT.

Sentiment

Score: 8

Explanation: The document presents very positive clinical trial results for SER-155, showing significant reductions in bloodstream infections and antibiotic use, which are major advancements. The company's plan to seek Breakthrough Therapy designation and expand to other patient populations further enhances the positive outlook. The VOWST asset sale also strengthens the company's financial position. However, the company still faces risks related to funding and competition.

Positives

• The study demonstrated a significant reduction in bloodstream infections with SER-155.
• SER-155 significantly reduced the duration of antibiotic use.
• The treatment showed a lower incidence of febrile neutropenia.
• SER-155 was well-tolerated with no treatment-related serious adverse events.
• The drug showed successful engraftment of bacterial strains in the gastrointestinal tract.
• The company has a clear plan to seek Breakthrough Therapy designation and expand the use of SER-155 to other patient populations.

Negatives

• The difference in febrile neutropenia incidence between the SER-155 and placebo groups was not statistically significant.
• There were six cases of gastrointestinal infections (C. difficile) observed in the study, with four in the SER-155 arm and two in the placebo arm.
• The ability to detect pathogen domination in the placebo arm was constrained due to limited stool samples.

Risks

• The company has a history of operating losses and may never become profitable.
• There is a need for additional funding to support ongoing operations and development.
• The company relies on third parties to conduct clinical trials and manufacture product candidates.
• There are risks associated with clinical trials, including the possibility of unfavorable results.
• The company faces competition in the development of live biotherapeutics.
• There is no guarantee that the FDA will grant Breakthrough Therapy designation.
• The company needs to protect its intellectual property and retain key personnel.
• The proposed transaction with SPN for the sale of the VOWST business carries risks.

Future Outlook

Seres plans to engage with the FDA to seek Breakthrough Therapy designation for SER-155 and discuss advancing its development in allo-HSCT. The company also intends to evaluate SER-155 in additional patient populations with high risk of serious bacterial infections. They anticipate SER-147 will be IND ready in the second half of 2025. The VOWST asset sale is expected to close shortly after the September 26 shareholder meeting, extending the company's operational runway into Q4 2025.

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.
• David Fredricks, M.D., Professor at the Fred Hutchinson Cancer Center, noted that live oral biotherapeutics like SER-155 hold promise as a novel approach to protect patients against serious bacterial infections.
• Eric Shaff, Chief Executive Officer of Seres Therapeutics, expressed encouragement by the consistency of efficacy outcomes, especially the lower rates of bloodstream infections and antibiotic exposure.

Industry Context

This announcement is significant in the context of the broader industry trend of developing novel therapies to combat infections, particularly in vulnerable patient populations. The use of live biotherapeutics represents a cutting-edge approach to addressing the challenges of antibiotic resistance and the high mortality rates associated with infections in transplant patients. The results position Seres as a leader in the microbiome therapeutics space.

Comparison to Industry Standards

• The reported 10% incidence of bloodstream infections in the SER-155 arm is significantly lower than the 42.9% in the placebo arm, and also lower than the reported incidence of up to 45% in the literature for allo-HSCT patients, suggesting a potential improvement over current standards of care.
• The reduction in antibiotic exposure, with a mean difference of -11.9 days, is a notable improvement compared to standard treatment protocols, which often involve prolonged antibiotic use.
• While the reduction in febrile neutropenia was not statistically significant, the trend towards lower incidence is still clinically relevant, as this condition is a major complication in transplant patients.
• The successful engraftment of SER-155 bacterial strains is consistent with the goals of microbiome-based therapies, which aim to restore a healthy gut microbiome.
• The safety profile of SER-155 is comparable to other live biotherapeutics, with no treatment-related serious adverse events reported, which is a positive sign for its potential clinical use.
• The company's plan to seek Breakthrough Therapy designation is similar to other companies developing novel therapies for unmet medical needs, such as Prevymis for viral infection prophylaxis in transplant patients.

Stakeholder Impact

• Shareholders will benefit from the positive clinical results and the strengthened financial position of the company.
• Patients undergoing allo-HSCT may benefit from a new treatment option that reduces the risk of serious infections and antibiotic use.
• Healthcare providers may have a new tool to manage infections in transplant patients.
• The healthcare system may benefit from reduced costs associated with infections and hospital stays.

Next Steps

• Seres will engage with the FDA to discuss advancing the development of SER-155 for allo-HSCT.
• The company will seek Breakthrough Therapy designation for SER-155.
• Seres plans to evaluate SER-155 in additional patient populations with high risk of serious bacterial infections.
• The company anticipates SER-147 will be IND ready in the second half of 2025.
• The VOWST asset sale is expected to close shortly after the September 26 shareholder meeting.

Key Dates

Keywords

SER-155, allo-HSCT, bloodstream infections, live biotherapeutics, antibiotic exposure, febrile neutropenia, stem cell transplant, FDA, Breakthrough Therapy, microbiome