Totus Medicines Announces Presentations at the Upcoming American Association for Cancer Research (AACR) Annual Meeting

10 Apr 2023
www.prnewswire.com
EMERYVILLE, Calif., April 10, 2023 /PRNewswire/ -- Totus Medicines, a clinical stage biotechnology company fueled by its breakthrough Accel™ platform, announced it will be presenting four posters at the American Association for Cancer Research (AACR) Annual Meeting, regarding its lead program, TOS-358, the first highly specific, covalent PI3Kα inhibitor. Totus has created the Accel™ Platform that, for the first time ever, can search, map, and decode billions of drug molecules across multiple cellular targets in a single experiment. This has allowed Totus to identify candidate molecules in months, not years, and rapidly advance these molecules toward the clinic. Notably, the Accel™ Platform enabled discovery of TOS-358 at an unprecedented pace. TOS-358 was discovered in under 4 months and received IND approval in ~2 years from original screening.
TOS-358 represents the first highly specific covalent inhibitor of PI3Kα, which is mutated in ~15% of all cancers (Breast, Colorectal, Lung, Bladder, etc.).  However, the therapeutic benefit of current molecules is limited by two key problems. Firstly, current non-covalent PI3Kα inhibitors cannot achieve continuous >95% target pathway inhibition, which is required for anti-tumor efficacy. Secondly, high doses of current non-covalent PI3Kα inhibitors are non-specific and inhibit other PI3K isoforms at effective doses. This leads to toxicity such as hyperglycemia and GI toxicity. TOS-358 represents the first ever highly specific covalent molecule targeting PI3Kα that can achieve durable, near 100% inhibition of PI3Kα activity and avoid these safety issues in preclinical studies.
Totus will outline three key points at AACR to support TOS-358 as the best-in-class PI3Kα inhibitor:
Despite claims indicating 80% inhibition is sufficient, PI3Kα-mutant tumorsPI3Kα-mutant tumors consistently require >95% inhibition to induce significant anti-tumor effects, and TOS-358 can uniquely achieve this level of inhibition.
Common pathway feedback mechanisms re-activate PI3Kα in most cell lines and render non-covalent approaches ineffective. TOS-358 can uniquely block these feedback mechanisms and retain >95% inhibition over time.
PI3Kα-WT inhibition alone does not induce significant hyperglycemia or metabolic dysfunction. Previous non-covalent molecules (Alpelisib) inhibit both PI3Kα and other off-target (PI3Kβ) leading to significant toxicities. TOS-358 does not cause significant metabolic dysfunction due to its highly specific ability to target PI3Kα.
Based on these studies, we outline the best-in-class status of TOS-358 due to its unique ability to achieve >95% inhibition of PI3Kα with limited side effects leading to unprecedented monotherapy efficacy in preclinical models.
"We're thrilled to be presenting several posters at AACR that demonstrate the preclinical efficacy, safety, and differentiation of TOS-358, the world's first covalent inhibitor of PI3Kα in clinical development," said Neil Dhawan, CEO and co-founder of Totus Medicines. "We've come a long way, fast, and are looking forward to sharing our findings with the broader cancer research community, which we believe will redefine the cancer community's understanding of PI3Kα targeting."
The poster presentations are listed below and the full abstracts will be available on the AACR and Totus Website.
A study to evaluate the safety and tolerability of the covalent phosphoinositide-3-kinase (PI3K)-alpha Inhibitorphosphoinositide-3-kinase (PI3K)-alpha Inhibitor, TOS-358, in adult subjects with select solid tumors
Abstract number: CT249
Date and Time: Tuesday April 18 at 1:30 PM - 5:00 PM ET
Development and validation of a pharmacodynamic (PD) assay for TOS-358, the first covalent inhibitor of PI3Kα in clinical development
Abstract number: 2249
Date and Time: Monday, April 17 at 9:00 AM - 12:30 PM ET
Inhibition of wild-type PI3Kα signaling is required for durable efficacy in PI3Kα mutant cancer cells due to robust re-activation of wild-type PI3Kα signaling
Abstract number: 4946
Date and Time: Tuesday, April 18 at 1:30 PM - 5:00 PM ET
TOS-358, a first-in-class covalent PI3Kα inhibitor, demonstrates superior efficacy and does not induce significant hyperglycemia at efficacious doses in multiple animal models
Abstract number: 4945
Date and Time: Tuesday, April 18 at 1:30 PM - 5:00 PM ET
Founded in 2019, Totus Medicines has developed the next generation of cellular analysis to create life-changing therapies to treat previously untreatable diseases. Totus' platform uses proprietary molecular tags that track drug binding in individual cells to enable the screening of billions of molecules across any drug target. Totus is based in the Bay Area.
For more information, please visit totusmedicines.com and follow Totus on LinkedIn and Twitter.
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