On February 24, 2025 Synnovation Therapeutics, a precision medicine company focused on the discovery and development of best-in-class targeted medicines, reported that the first patient has been dosed in a Phase I trial evaluating SNV4818 as a monotherapy and in combination with fulvestrant, in patients with breast cancer and other solid tumors (Press release, Synnovation Therapeutics, FEB 24, 2025, View Source [SID1234650499]). SNV4818 is a potentially best-in-class pan-mutant-selective PI3Kα inhibitor that may effectively cover kinase (H), helical domain (E), and other PI3Kα mutations clinically. This marks the second Synnovation program to enter the clinic in just over three years since company formation. Synnovation’s lead candidate and potentially best-in-class PARP1 selective program, SNV1521, entered a Phase I trial in January of 2024.
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The SNV4818 Phase I trial, which is being led by Timothy Yap, M.D., Ph.D., Professor of Investigational Cancer Therapeutics at the University of Texas MD Anderson Cancer Center, is designed to evaluate the safety, tolerability and preliminary efficacy of SNV4818 as a monotherapy in tumor agnostic patients with PI3Kα activating mutations as well as in combination with fulvestrant in HR+/HER2- advanced breast cancer patients.
"We are excited to initiate the clinical development of our second potential best-in-class program, both of which were discovered at Synnovation," said Kevin O’Hayer, M.D., Ph.D., Senior Vice President, Head of Clinical Development at Synnovation. "SNV4818 has the potential to address a significant unmet need for a large population of patients with breast cancer and multiple other tumor types."
The potential of the PI3Kα inhibitor class has been limited by a lack of selectivity against wild type PI3Kα. First generation PI3Kα-isoform specific inhibitors are limited by significant toxicities due to wild type PI3Kα inhibition, including stomatitis, hyperglycemia and rash. A pan-mutant selective, wild-type-sparing, inhibitor enables a wider therapeutic index leading to greater target inhibition which may improve clinical efficacy while decreasing toxicity, unlocking significant potential for this therapeutic class.
SNV4818 is a potentially best-in-class, highly potent pan-mutant PI3Kα inhibitor with excellent selectivity against wild type PI3Kα. This selectivity may allow for broad spectrum PI3Kα mutation coverage including targeting both H1047X and E545/542X classes of driver mutations in breast cancer and other solid tumor indications.