Seres Therapeutics (MCRB) Presents Research from its Early-Stage Microbiome Therapeutic Oncology Programs at ASCO – StreetInsider.com

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Seres Therapeutics, Inc. (Nasdaq: MCRB), a leading microbiome therapeutics company, today announced data from their collaboration with the University of Cologne (Kln, Germany) demonstrating that decreased microbiome diversity in allogeneic hematopoietic stem cell transplantation (HSCT) recipients is associated with poor clinical outcomes including mortality and increased incidence of intestinal graft-versus-host disease (GvHD). The data are being presented in an oral presentation at the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting, taking place virtually. A separate poster presentation, including data from a collaboration with Memorial Sloan Kettering Cancer Center (New York, NY), established a significant association between microbiome composition and response to immune checkpoint inhibitor (ICI) treatment in patients who have metastatic melanoma, metastatic lung (NSCLC), urothelial, or renal cancer.

Seres is advancing development programs in oncology to evaluate the potential of microbiome therapeutics to modulate host immunity or inflammation to improve response and tolerability of cancer treatments. This includes SER-155, an investigational, oral, rationally-designed, cultivated microbiome therapeutic, which is advancing into a Phase 1b clinical trial to reduce the incidence of antibiotic-resistant bacterial infections and GvHD in patients following transplant procedures.

Disruption of microbiome-modulated functions can impact clinical outcomes for patients being treated for cancer, including those who are undergoing allogeneic hematopoietic stem cell transplantation and those treated with cancer immunotherapy, said Lisa von Moltke, M.D., Chief Medical Officer at Seres. The findings we are presenting at ASCO provide further evidence that our SER-155 program, as well as our earlier stage oncology programs, will help to advance our understanding of the potential of microbiome therapeutics to work with the bodys immune system to improve cancer treatment outcomes.

Clinical Evidence of Impact of Microbial Diversity on Mortality and GvHD in HSCT Patients

In collaboration with the University of Cologne, a prospective observational study was conducted to evaluate changes in microbial diversity over time in acute myeloid leukemia (AML) and acute lymphocytic leukemia (ALL) patients undergoing allogeneic HSCT and the impact on clinical outcomes. Patients were administered antibiotics as empiric treatment for febrile neutropenia or as targeted treatment and were monitored for incidence of GvHD. Stool was collected on a weekly basis prior to an HSCT procedure and up to 28 days post HSCT, with additional samples collected at days 56, 90, and 365, as well as upon diagnosis of intestinal GvHD. Gut microbiome profiles were generated from 381 stool samples (representing 65 subjects) to evaluate the relationship between gastrointestinal microbial diversity over time and clinical outcome.

Frequent complications associated with stem cell transplantation include antibiotic-resistant infection and GvHD. Current treatments for the prevention of GvHD rely on increased immunosuppression, leaving the patient susceptible to a host of bacterial infections and offer limited efficacy. The findings from this prospective study demonstrate a need for continued investigation into the use of microbiome therapeutics to reduce morbidity and mortality among transplant recipients, said Christopher Ford, Ph.D., Senior Director, Computational Microbiome Sciences at Seres Therapeutics and co-author of the presentation.

Twenty-eight patients (42%) developed intestinal GvHD and 16 (25%) died prior to study completion. Across all subjects, a decline in microbiome diversity was observed immediately following HSCT. Decreased diversity and intestinal domination by two bacterial groups Enterococcus and Enterobacteriaceae - was significantly associated with mortality across the study time course (p

Evaluation of Microbiome Composition in Correlation to Cancer-Specific Immune Checkpoint Inhibitor (ICI) Response

A study conducted with Memorial Sloan Kettering explored the relationship between microbiome composition and ICI response in patients with metastatic melanoma, metastatic lung (NSCLC), urothelial, or renal cancer. Fecal microbiome samples were collected from 94 patients (metastatic melanoma, n=17, NSCLC, n=44, urothelial, n=23, renal cancer, n=10) immediately before ICI therapy. Bacterial genomic DNA was isolated and profiled by whole metagenomic sequencing to evaluate bacterial signatures associated with response (R) and nonresponse (NR).

Treatment included anti-PD(L)1 monotherapy (n=51), anti-PD1 + anti-CTLA4 combination therapy (n=17), or a combination of anti-PD1 and chemotherapy (n=26). Clinical response was observed in 58% of patients, including partial or complete response (45%) and on treatment for more than 6 months (55%, with 31% on treatment for more than 1 year). Ordination of microbiome data from all four cancers reveals a small cluster of patients that were NR regardless of cancer type. Although the variance in the composition of pretreatment microbiome samples did not explain response alone (R vs. NR, PERMANOVA, p=0.273), a significant portion of the variance in microbiome composition was explained by the interaction of cancer type and outcome (PERMANOVA, p=0.014), suggesting a cancer-specific microbiome relationship. Notably, there was some similarity in the signature of NR across three of the four cancer types. The relationship observed in this study was also identified and corroborated in pre-clinical models of ICI response. In these models, NR was characterized by active tumor growth in mice and a lack of induction of cytotoxic CD8+ T cells after ICI treatment.

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Seres Therapeutics (MCRB) Presents Research from its Early-Stage Microbiome Therapeutic Oncology Programs at ASCO - StreetInsider.com