BOSTON, MA, USA I August 31, 2022 I 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 TNF, at substantially higher levels of concentration compared with Sensei’s pH-selective VISTA antibody SNS-101, across doses ranging from 1 g/mL to 100 g/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. The Company plans to file an IND during the first half of 2023. Additional information from these studies can be found in the Company’s corporate presentation, available on the Company’s website, and in its SEC filings. More detailed findings will be published at upcoming scientific conferences.
About Sensei Biotherapeutics
Sensei Biotherapeutics (NASDAQ: SNSE) is an immuno-oncology company focused on the discovery and development of next generation therapeutics for cancer. Sensei has designed two unique approaches to develop highly selective therapeutics – its TMAb™ (Tumor Microenvironment Activated biologics) platform, which disables checkpoints and other immunosuppressive signals in the tumor microenvironment to unleash existing T cells against tumors, and the ImmunoPhage™ platform, which trains new T cells to recognize and kill malignant cells. Using its TMAb platform, the company is developing SNS-101, a fully human antibody designed to block the V-domain Ig suppressor of T cell activation (VISTA) checkpoint selectively only within the low pH tumor microenvironment, where VISTA acts as a suppressor of T cells by binding the receptor PSGL-1. The company is also using its platforms to develop other preclinical programs targeting multiple solid tumor indications. For more information, please visit www.senseibio.com, and follow the company on Twitter @SenseiBio and LinkedIn.
SOURCE: Sensei Biotherapeutics
Post Views: 119
BOSTON, MA, USA I August 31, 2022 I 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 TNF, at substantially higher levels of concentration compared with Sensei’s pH-selective VISTA antibody SNS-101, across doses ranging from 1 g/mL to 100 g/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. The Company plans to file an IND during the first half of 2023. Additional information from these studies can be found in the Company’s corporate presentation, available on the Company’s website, and in its SEC filings. More detailed findings will be published at upcoming scientific conferences.
About Sensei Biotherapeutics
Sensei Biotherapeutics (NASDAQ: SNSE) is an immuno-oncology company focused on the discovery and development of next generation therapeutics for cancer. Sensei has designed two unique approaches to develop highly selective therapeutics – its TMAb™ (Tumor Microenvironment Activated biologics) platform, which disables checkpoints and other immunosuppressive signals in the tumor microenvironment to unleash existing T cells against tumors, and the ImmunoPhage™ platform, which trains new T cells to recognize and kill malignant cells. Using its TMAb platform, the company is developing SNS-101, a fully human antibody designed to block the V-domain Ig suppressor of T cell activation (VISTA) checkpoint selectively only within the low pH tumor microenvironment, where VISTA acts as a suppressor of T cells by binding the receptor PSGL-1. The company is also using its platforms to develop other preclinical programs targeting multiple solid tumor indications. For more information, please visit www.senseibio.com, and follow the company on Twitter @SenseiBio and LinkedIn.
SOURCE: Sensei Biotherapeutics
Post Views: 119
