On September 30, 2022 Sensei Biotherapeutics, Inc. (Nasdaq: SNSE), an immuno-oncology company focused on the discovery and development of next-generation therapeutics for cancer, reported that presented additional preclinical data on SNS-101, a monoclonal antibody targeting the immune checkpoint VISTA (V-domain Ig suppressor of T cell activation), at the Sixth Annual CRI-ENCI-AACR International Cancer Immunotherapy Conference (CIMT) (Free CIMT Whitepaper): Translating Science into Survival (Press release, Sensei Biotherapeutics, SEP 30, 2022, View Source [SID1234621580]). The presentation contains data from an ongoing collaboration with scientists at Washington University, St. Louis, investigating the mechanism of action of SNS-101.
Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:
Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing
Schedule Your 30 min Free Demo!
"VISTA remains a promising but difficult-to-drug immuno-oncology target due to significant on-target/off-tumor activity. We’re excited to collaborate with Sensei Bio on studies exploring the efficacy and mechanism of action of their conditionally active, pH-dependent VISTA-blocking antibody, SNS-101," said Robert D. Schreiber, Ph.D., Andrew M. and Jane M. Bursky Distinguished Professor, Pathology & Immunology at the Washington University School of Medicine in St. Louis and a member of Sensei’s Immuno-Oncology Advisory Board. "In our PD-1-resistant, immunocompetent 1956 tumor model, we observed strong synergistic anti-tumor activity of SNS-101 in combination with PD-1 inhibition, resulting in five out of eight complete responses versus only one out of eight in the PD-1 monotherapy control group."
"These preclinical data demonstrate that the selectivity of our conditionally active VISTA-blocking antibody has the potential to avoid poor pharmacokinetics from target-mediated drug disposition and lower the risk of cytokine release syndrome, while significantly enhancing the anti-tumor effects of PD-1 blockade selectively within tumors," said Edward van der Horst, Ph.D., Senior Vice President, Biologics Discovery & Early Development. "These findings support the scientific rationale for Sensei’s pH-selective approach, which we believe could offer numerous safety and efficacy advantages over pH-independent antibodies targeting VISTA, including the potential to inhibit tumor growth across a range of indications."
Summary of Key Data:
SNS-101 potently inhibited the critical pH-dependent interaction between VISTA and PSGL-1, as well as interactions with other putative receptors.
In vitro and in vivo cytokine release syndrome (CRS) assays demonstrate that SNS-101 significantly reduced cytokine induction as compared to a pH-independent VISTA antibody, suggesting that SNS-101 has potential to significantly lower the risk of CRS.
Pharmacokinetics studies demonstrate that the pH-sensitive binding of SNS-101 avoided the rapid clearance by target-mediated drug disposition (TMDD) that has been observed with pH-independent VISTA antibodies.
SNS-101 demonstrated significant enhancement of anti-tumor effects in combination with anti-PD-1 antibodies in multiple syngeneic tumor models.