On February 21, 2023 Sensei Biotherapeutics, Inc. (Nasdaq: SNSE), an immuno-oncology company focused on the discovery and development of next-generation therapeutics for cancer patients, reported its preclinical data on SNS-101, a conditionally active, pH-selective VISTA-blocking antibody, in an oral presentation at Next Generation Antibody Therapeutics: From Discovery to Patient, organized by Keystone Symposia (Press release, Sensei Biotherapeutics, FEB 21, 2023, View Source [SID1234627454]).
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"Preclinical studies to date have demonstrated SNS-101’s potential to significantly enhance the anti-tumor effects of PD-1 blockade while abrogating target-mediated drug disposition (TMDD) and with lower risk of cytokine release syndrome (CRS). New crystal structure analysis further elucidates the antibody’s mechanism of action, showing that SNS-101 directly blocks the pH-dependent interaction between VISTA and PSGL-1," said Edward van der Horst, Ph.D., Chief Scientific Officer of Sensei Biotherapeutics. "Together, these preclinical data support the biological rationale for our pH-dependent approach, which we believe is key to targeting active protonated VISTA with exquisite selectivity."
Presentation highlights:
The epitope of SNS-101 was determined by co-crystallization of VISTA with the fragment antigen-binding domain of SNS-101. Crystal structure analysis suggests SNS-101 directly blocks the pH-dependent interaction between VISTA and PSGL-1, as well as interactions with other putative receptors.
In vitro and in vivo assays demonstrated that treatment with SNS-101 potentially has a significantly lower risk of inducing CRS than a non-pH-dependent VISTA antibody.
SNS-101 exhibited linear elimination kinetics in non-human primates, overcoming TMDD-induced pharmacokinetic limitations observed with other anti-VISTA antibodies.
SNS-101 induced expansion of naïve and memory T-cell phenotypes in vivo without activation or depletion of monocytes, differentiating it from non-pH-selective antibodies.
SNS-101 demonstrated significant enhancement of anti-tumor effects in combination with anti-PD-1 antibodies in syngeneic tumor models.
Sensei expects to submit an Investigational New Drug (IND) application for SNS-101 in or before April 2023, with a Phase 1/2 clinical trial expected to commence in 2023, pending regulatory clearance.
A poster summarizing content from Dr. van der Horst’s oral presentation will be on display at the conference during Poster Session 2, being held today, February 21, 2023, at 7:30 p.m. MST. The poster will be available on the Sensei website following the poster session.