SER-401 / Seres Therap - LARVOL DELTA

Precision Targeting of the Gut Microbiome for Cancer Immunotherapy. (PubMed, Cancer Discov) - "Glitza and colleagues propose selective manipulation of the gut microbiome with SER401 following antibiotic preconditioning and highlight multiple challenges in delivering microbiome manipulation to the clinic. See related article by Glitza et al., p. 1161 (8)."

Journal • Oncology

MCGRAW: Melanoma Checkpoint and Gut Microbiome Alteration With Microbiome Intervention (clinicaltrials.gov) - P1 | N=14 | Completed | Sponsor: Parker Institute for Cancer Immunotherapy | Phase classification: P1b ➔ P1

Combination therapy • Metastases • Phase classification • Cutaneous Melanoma • Melanoma • Mucosal Melanoma • Oncology • Solid Tumor

Randomized Placebo-Controlled, Biomarker-Stratified Phase Ib Microbiome Modulation in Melanoma: Impact of Antibiotic Preconditioning on Microbiome and Immunity. (PubMed, Cancer Discov) - P1b | "Fecal microbiota signatures were characterized at baseline; patients were stratified by high versus low Ruminococcaceae abundance prior to randomization to the SER-401 arm (oral vancomycin-preconditioning/SER-401 alone/nivolumab + SER-401), versus the placebo arm [placebo antibiotic/placebo microbiome modulation (PMM)/nivolumab + PMM (NCT03817125)]. This first-of-its-kind, placebo-controlled, randomized biomarker-driven microbiome modulation trial demonstrated that vancomycin + SER-401 and anti-PD-1 are safe in melanoma patients. Although limited by poor accrual during the pandemic, important insights were gained via translational analyses, suggesting that antibiotic preconditioning and interventional drug dosing regimens should be carefully considered when designing such trials."

Biomarker • IO biomarker • Journal • P1 data • Infectious Disease • Melanoma • Novel Coronavirus Disease • Oncology • Solid Tumor

Randomized placebo-controlled, biomarker-stratified phase 1b microbiome modulation trial for metastatic melanoma demonstrates impact of antibiotic pre-conditioning regimen on the microbiome and immunity (AACR 2024) - P1b | "Patients received an oral vancomycin (vanco) preparative regimen+SER-401 (vanco+SER-401 arm), versus placebo antibiotic+placebo (Placebo arm), followed by nivolumab. This first-of-its-kind, placebo-controlled, randomized biomarker-driven microbiome modulation trial demonstrated that SER-401 and anti-PD1 are a safe combination in melanoma patients. The study was limited by poor accrual during the COVID-19 pandemic. Nonetheless, important insights were gained via translational analyses, suggesting that antibiotic preconditioning and interventional drug dosing regimens should be carefully considered when designing such trials."

Biomarker • Clinical • IO biomarker • Metastases • P1 data • Melanoma • Oncology • Solid Tumor

Identification of novel umami peptides from yeast extract and the mechanism against T1R1/T1R3. (PubMed, Food Chem) - "Molecular docking studies revealed that specific amino acid residues in the T1R1 subunit, including Arg316, Ser401, and Asp315, played a critical role in the umami perception with these peptides. Overall, the study highlights the potential of natural flavor enhancers and provides insights into the mechanism of umami taste perception."

Journal

MCGRAW Trial: Evaluation of the safety and efficacy of an oral microbiome intervention (SER-401) in combination with nivolumab in first line metastatic melanoma patients (SITC 2022) - "Enrollment challenges and sub-optimal SER-401 engraftment resulted in early termination of the study. Despite these limitations, our integrative clinical and biomarker analysis provides information regarding the link between the gut microbiome, peripheral immune cell populations, and the tumor microenvironment during nivolumab therapy with or without SER-401."

Clinical • Combination therapy • IO biomarker • Melanoma • Oncology • Solid Tumor • CD8

Melanoma Checkpoint and Gut Microbiome Alteration With Microbiome Intervention (clinicaltrials.gov) - P1b | N=14 | Completed | Sponsor: Parker Institute for Cancer Immunotherapy | Active, not recruiting ➔ Completed | Trial completion date: Sep 2022 ➔ Mar 2022

Combination therapy • Trial completion • Trial completion date • Cutaneous Melanoma • Melanoma • Mucosal Melanoma • Oncology • Solid Tumor

Melanoma Checkpoint and Gut Microbiome Alteration With Microbiome Intervention (clinicaltrials.gov) - P1b | N=14 | Active, not recruiting | Sponsor: Parker Institute for Cancer Immunotherapy | Trial completion date: Mar 2023 ➔ Sep 2022

Combination therapy • Trial completion date • Cutaneous Melanoma • Melanoma • Mucosal Melanoma • Oncology • Solid Tumor

Seres Therapeutics Announces Discontinuation of Enrollment in SER-401 Study in Metastatic Melanoma (Businesswire) - "Seres Therapeutics...has voluntarily discontinued further enrollment in the Melanoma Checkpoint and Gut Microbiome Alteration With Microbiome Intervention (MCGRAW) study evaluating the safety and drug activity of SER-401 or fecal microbiota transplant (FMT) in combination with nivolumab in patients with metastatic melanoma...Subjects currently enrolled in the study will complete the study protocol...The Company will continue to advance its research and development efforts in cancer, applying learnings from the SER-401 trial....Seres' immuno-oncology patent portfolio includes the option to exclusively license foundational intellectual property from MD Anderson, based upon the work of Jennifer Wargo, M.D...."

Enrollment closed • Melanoma • Oncology

In a new setback, Seres cites Covid impact after deciding to shelve its lead microbiome cancer program (Endpoints News) - "The biotech $MCRB says that its partnered program with the Parker Institute for Cancer Immunotherapy in metastatic melanoma is being shelved, citing 'challenges' presented by running the study during the pandemic. Word is that they came to the decision to sideline the effort after 10 patients received a combination of SER-401 with Opdivo, Bristol Myers' big PD-1....And the biotech insists that it's hyped up over its potential in oncology, where it's working with Memorial Sloan Kettering Cancer Center and considering an option IP for Jennifer Wargo at MD Anderson."

Melanoma Checkpoint and Gut Microbiome Alteration With Microbiome Intervention (clinicaltrials.gov) - P1b; N=14; Active, not recruiting; Sponsor: Parker Institute for Cancer Immunotherapy; Trial primary completion date: Feb 2021 ➔ Jan 2022; Trial completion date: Feb 2022 ➔ Jan 2023

Clinical • Combination therapy • Trial completion date • Trial primary completion date • Cutaneous Melanoma • Melanoma • Mucosal Melanoma • Oncology • Solid Tumor

The C-terminal of the α1b-adreneroceptor is a key determinant for its structure integrity and biological functions. (PubMed, Biosci Biotechnol Biochem) - "This is particularly true in the case of the ∆C-90, ∆C-70, or ∆C-50 which retained the potential phosphorylation sites (Ser401, Ser404, Ser408 or Ser410). The ∆C-90 showed an increase in agonist-induced FRET signal changes and ERK1/2 phosphorylation in PKC- or endocytosis-dependent and EGFR-, src- or β-arrestin 2-independent."

Journal

"$MCRB Announces Discontinuation of Enrollment in SER-401 Study in Metastatic Melanoma" (@BioStocks)

Melanoma • Oncology • Solid Tumor

Melanoma Checkpoint and Gut Microbiome Alteration With Microbiome Intervention (clinicaltrials.gov) - P1b; N=14; Active, not recruiting; Sponsor: Parker Institute for Cancer Immunotherapy; Recruiting ➔ Active, not recruiting; N=30 ➔ 14

Clinical • Combination therapy • Enrollment change • Enrollment closed • Cutaneous Melanoma • Melanoma • Mucosal Melanoma • Oncology • Solid Tumor

The CNS-specific proteoglycan, brevican, and its ADAMTS4-cleaved fragment show differential serological levels in Alzheimer's disease, other types of dementia and non-demented controls: A cross-sectional study. (PubMed, PLoS One) - "We aimed to develop two assays capable of detecting the brevican N-terminal (N-Brev) and the ADAMTS4-generated fragment (Brev-A), cleaved at Ser401, in serum and to perform a preliminary assessment of their diagnostic potential in dementias...In conclusion, we developed the first assays detecting the N-terminal of brevican as well as an ADAMTS4-cleaved fragment of brevican in blood. Differential levels of N-Brev and Brev-A between AD and OD allow for these biomarkers to possibly distinguish between different forms of dementias."

Journal • Observational data • Alzheimer's Disease • CNS Disorders • Dementia