SG-3-00802 shows single agent activity and has potential to improve responses in immune checkpoint inhibitor-resistant patients
BRISBANE, Calif. – September 16, 2021 – Second Genome, a biotechnology company that leverages its proprietary platform sg-4sight to discover and develop precision therapies and biomarkers from public and proprietary microbiome data, presented preclinical data demonstrating that the Company’s novel microbiome-derived peptide, SG-3-00802, can reverse resistance to anti-programmed death protein-1 (PD-1) therapy, illustrating that the microbiome directly interacts with the immune system to impact antitumor immunity. The data (E-Poster #1023P) were presented at the European Society for Medical Oncology (ESMO) Congress 2021, held virtually September 16-21.
“Despite the clinical success of immune checkpoint inhibitors (ICI) in many cancers, there is still significant unmet need in ICI-resistant patients, but there is encouraging promise for microbiome-derived approaches to turn anti-PD-1 non-responders into responders and ultimately provide innovative new therapies for people living with cancer,” said Helena Kiefel, Ph.D., Head of Immuno-Oncology at Second Genome. “We were pleased to share preclinical data at ESMO demonstrating that the combination of SG-3-00802 with anti-PD-1 antibody was able to achieve complete tumor regression and significant prolongation of survival in an ICI-resistant model. We believe SG-3-00802 has potential to improve responses in immune checkpoint inhibitor-resistant cancer patients. Importantly, based on the mechanism of action, SG-3-00802 has potential for broad clinical development in combination with immunogenic chemotherapies and radiation in earlier lines of therapy. We look forward to advancing SG-3-00802 into the clinic, with an IND submission on track for 2022.”
Using Second Genome’s proprietary algorithms, an ICI responder-specific microbial signature was identified, and biologically active molecules were derived from the ICI-responder microbiome. SG-3-00802’s unique pathway and its use to treat tumors markedly increased CXCL10 and CD8 T cell levels and reduced tumor volumes, increasing overall survival in mouse models. Furthermore, treatment in combination with anti-PD-1 significantly improved overall survival in anti-PD-1-insensitive RENCA mouse model, with many mice showing complete tumor regression, versus anti-PD-1 antibody alone. Surviving mice with fully regressed tumors also rejected newly implanted tumors when rechallenged with RENCA cells, demonstrating long-lasting antitumor memory responses generated by the combination of SG-3-00802 plus anti-PD-1.
The mechanism of action by which SG-3-00802 exerted its anti-tumor effects demonstrated to be CXCR3 dependent. Receptor activation and immune cell recruitment assays demonstrated that SG-3-00802 enhanced the activity of CXCR3 in the presence of its endogenous ligands, resulting in increased lymphocyte migration, validating CXCR3 as the functional target. These observations were confirmed in vivo, as CXCR3 inhibition decreased the anti-tumor activity of SG-3-00802 alone and in combination with anti-PD1.
The poster presentation will be available for on-demand viewing on the ESMO 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.