On 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, reported 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 (Press release, Second Genome, SEP 16, 2021, View Source [SID1234587855]). The data (E-Poster #1023P) were presented at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2021, held virtually September 16-21.
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"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 (Free ESMO Whitepaper) 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 (Free ESMO Whitepaper) website and will also be made available on the Company’s website at View Source