Our findings that SG-3-0020 enhanced PD-1 expression and IFNg secretion by anti-CD3 activated human T cells in vitro provide a strong rationale for SG-3-0020’s potential future use in cancer therapies. Additionally, we are pleased to see these results provided additional validation of the advanced capabilities of sg-4sight, Second Genome’s proprietary platform, to identify targets for microbial peptides and proteins with potential therapeutic relevance in immuno-oncology,” said Helena Kiefel, Ph.D., Head of Immuno-Oncology at Second Genome.
BRISBANE, Calif. – October 7, 2021 – Second Genome, a biotechnology company that leverages its proprietary platform sg-4sight to discover and develop precision therapies and biomarkers, presented preclinical data demonstrating that the Company’s novel microbiome-derived peptide, SG-3-0020, can upregulate key co-stimulatory and checkpoint molecules on T cells. The data (poster P260) were presented at the 2021 AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics, held virtually on October 7-10, 2021.
“Our findings that SG-3-0020 enhanced PD-1 expression and IFNg secretion by anti-CD3 activated human T cells in vitro provide a strong rationale for SG-3-0020’s potential future use in cancer therapies. Additionally, we are pleased to see these results provided additional validation of the advanced capabilities of sg-4sight, Second Genome’s proprietary platform, to identify targets for microbial peptides and proteins with potential therapeutic relevance in immuno-oncology,” said Helena Kiefel, Ph.D., Head of Immuno-Oncology at Second Genome. “Given these promising preclinical data, we are looking to further develop SG-3-0020 with an experienced partner, as we continue to advance SG-3-00802, our lead immuno-oncology program for which we anticipate an IND submission in 2022 for SG-3-00802.”
Using Second Genome’s large and curated microbiome database coupled with its proprietary bioinformatics and machine learning tools, the Company analyzed the genome of Bifidobacterium (B.) breve and B. longum for proteins which were potentially secreted and had unknown functions. 50 peptides were chemically synthesized and then screened in cell-based assays for T cell activation and cytokine secretion.
SG-3-0020, a novel B. breve-derived 42-aa peptide, stimulated secretion of effector cytokines by in vitro-cultured T cells (IFNg, TNF-a, IL-10 and IL-2) and increased the expression of PD-1 on both CD4+ and CD8+ T cells when stimulated with low-dose anti-CD3 antibody. Mass spec analysis showed that SG-3-05308, a variant of SG-3-0020, binds to a transmembrane glycoprotein of the immunoglobulin superfamily. Silencing this gene via CRISPR-Cas significantly decreased PD-1 levels, cell proliferation and IFNg production in human pan T cells.
The potency of SG-3-0020 was further optimized for binding to activated T cells through protein engineering. The peptide with the highest potency, SG-3-05429, was selected for further investigation of the mechanism by which binding of its glycoprotein target results in activation of downstream T cell signaling pathways.
The poster presentation will be available for on-demand viewing on the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics website and will also be made available on the Company’s website at https://www.secondgenome.com/events/.
About Second Genome
Second Genome is a biotechnology company that leverages its proprietary tech platform sg-4sight to discover and develop transformational precision therapies and biomarkers through clinical development and commercialization based on novel microbial genetic insights. We built a proprietary microbiome-based drug discovery and development platform with machine-learning analytics, customized protein engineering techniques, phage library screening, mass spec analysis and CRISPR, that we couple with traditional drug development approaches to progress the development of therapies and diagnostics for wide-ranging diseases. Second Genome is advancing a deep drug discovery and biomarker pipeline with precision therapeutics and biomarker programs in inflammatory bowel disease (IBD) and cancer, with the lead programs IBD and cancer expected to enter clinical development in 2022. We also collaborate with industry, academic and governmental partners to leverage our microbiome platform and data science. We hold a strategic collaboration with Gilead Sciences, Inc., utilizing our proprietary platform and comprehensive data sets to identify novel biomarkers associated with clinical response to Gilead’s investigational medicines. We also hold a strategic collaboration with Arena Pharmaceuticals to identify microbiome biomarkers associated with clinical response for their lead program in gastroenterology, etrasimod. For more information, please visit www.secondgenome.com.