Exhibit 99.1
Sensei Biotherapeutics Announces New Preclinical Data Demonstrating
Favorable Pharmacokinetic and Immunologic Effects of SNS-101, a pH-selective
VISTA-blocking Antibody
BOSTON, MA – August 31, 2022 – Sensei Biotherapeutics, Inc. (NASDAQ: SNSE), an immuno-oncology company focused on the discovery and development of next-generation therapeutics for cancer, today reported preliminary preclinical data from mouse and non-human primate studies of SNS-101, a monoclonal antibody targeting the immune checkpoint VISTA (V-domain Ig suppressor of T cell activation).
“These preclinical data demonstrate that our conditionally active, pH-selective antibody successfully overcomes pharmacokinetic issues associated with targeting the VISTA immune checkpoint, including target-mediated drug disposition and cytokine release syndrome, in these models. The data also differentiate SNS-101 from non-selective antibodies by showing expansion of naïve and memory T cell phenotypes in vivo, as well as significant enhancement of anti-tumor effects in combination with anti-PD-1 antibodies as compared to anti-PD-1 antibodies alone,” said Robert Pierce, M.D., Chief R&D Officer. “These results represent important progress for our SNS-101 program and a potential breakthrough for the field of VISTA inhibition as a novel therapeutic approach in multiple solid tumor indications. We are thrilled with these preliminary results and the potential of SNS-101 to provide a new standard of care to patients in need of innovative treatment options.”
In a whole-blood assay at neutral pH, a clinical-stage, pH-independent VISTA antibody induced release of pro-inflammatory cytokines, such as IFNy and TNFµ, at substantially higher levels of concentration compared with Sensei’s pH-selective VISTA antibody SNS-101, across doses ranging from 1 mg/mL to 100 mg/mL. These preclinical data support the Company’s hypothesis that pH-driven, conditional binding of SNS-101 could be an effective mechanism for preventing the on-target, off-tumor VISTA binding that has been shown to drive cytokine release syndrome in human patients.
SNS-101 also displayed a favorable pharmacokinetic profile in non-human primates compared with a clinical-stage, pH-independent VISTA antibody. Whereas the pH-independent antibody exhibited target-mediated drug disposition and clearance from the blood within hours of administration due to interaction with VISTA-positive immune cells, the SNS-101 concentration declined linearly with a median half-life of approximately three weeks. These data strongly support the Company’s belief that SNS-101’s selective binding to VISTA at low pH, like that found in the tumor microenvironment, has potential to mitigate the pharmacokinetic and safety issues associated with off-tumor binding and unregulated activity.
Finally, experiments in a mouse tumor model demonstrated a significant increase in the production of anti-tumor CD8+ T cells among animals treated with a combination of SNS-101 and anti-PD-1 antibodies compared with PD-1 alone, which correlated with tumor growth inhibition. Because CD8+ T cells are essential tumor-destroying immune cells, these data provide encouraging evidence that this therapeutic combination has potential to generate a highly effective anti-tumor response in patients.
IND-enabling studies are underway to evaluate the potential of SNS-101 as a novel treatment for solid cancers, both as a monotherapy and in combination with the blockade of other immune checkpoints.
