Scorpion Therapeutics Announces First Patient Dosed in Phase 1/2 Clinical Trial of STX-478, Its Mutant-Selective PI3Kα Inhibitor for the Treatment of Breast Cancer and Other Solid Tumors

BOSTON--(BUSINESS WIRE)-- Scorpion Therapeutics, Inc. (“Scorpion”), a pioneering clinical-stage oncology company redefining the frontier of precision medicine through its Precision Oncology 2.0 strategy, today announced that the first patient has been dosed in a Phase 1/2 first-in-human dose escalation and expansion clinical trial evaluating STX-478, Scorpion's highly differentiated, allosteric and central nervous-system (“CNS”) penetrant inhibitor of mutant phosphoinositide-3-kinase alpha (“PI3Kα”), for the treatment of HR+/HER2- breast cancer and other solid tumors. The Phase 1/2 clinical trial will evaluate STX-478 as a monotherapy in a variety of solid tumors including breast and gynecological cancers, head and neck squamous cell carcinoma ("HNSCC") and others, as well as a monotherapy and in combination with approved agents in patients with HR+/HER2- breast cancer.

STX-478 is designed to improve outcomes in patients harboring prevalent PI3Kα mutations in their tumors and has shown activity in both kinase and helical domain mutated tumors in preclinical models. PI3Kα mutations are among the most prevalent drivers of cancer, occurring in over 166,000 patients per year with breast, gynecological and head and neck cancers in the United States alone. The frequency of PI3Kα mutations and the scarcity of available treatment options has made the target a high priority for drug discovery.

“We are excited to begin clinical evaluation of STX-478, our mutant-selective PI3Kα inhibitor with a potentially best-in-class profile, for the treatment of HR+/HER2- breast cancer and a wide array of other solid tumors,” said Axel Hoos, M.D., Ph.D, Chief Executive Officer of Scorpion. “The initiation of this clinical trial in just three years after our company was founded is an important validation of our Precision Oncology 2.0 strategy. The quality of the compound and the rapid progression of this program from target selection to clinical development demonstrate the expertise of our scientific team, the technical capabilities of our discovery platform, and their combined ability to create potentially transformational therapies.”

Currently available treatments for PI3Kα-mutated cancers are limited by their inhibition of the normal, or wild-type, version of PI3Kα in healthy tissues, that can lead to significant side effects such as hyperglycemia and rash, which hinder the ability of patients to tolerate these therapies on a long-term basis. Further, these treatments also have little to no CNS penetrance, despite the fact that up to 50% of all solid tumor patients develop significant morbidity and mortality from brain metastases.

“STX-478 is a wild-type-sparing, CNS-penetrant, oral inhibitor of mutant PI3Kα with excellent pre-clinical pharmacokinetic properties,” said Michael Streit, M.D., Chief Medical Officer of Scorpion. “In this Phase 1/2 trial, we will aim to demonstrate how these important traits translate into a potentially superior product profile that offers a wider therapeutic window and greater efficacy. We anticipate presenting initial safety, pharmacokinetic, and pharmacodynamic results in 2024, including data on STX-478’s impact on potential biomarkers suggestive of anti-tumor activity. We believe these initial data could differentiate STX-478 from existing agents currently on the market or in development, and support its profile as a safe and highly differentiated therapeutic for the treatment of solid tumors, especially HR+/HER2- breast cancer. We look forward to partnering with study investigators to evaluate STX-478 in patients with PI3Kα-mutated cancers.”

About STX-478 Phase 1/2 Trial
Scorpion’s Phase 1/2 clinical trial is a multi-center, open-label study designed to evaluate the safety and tolerability of STX-478 in multiple ascending doses for patients with locally advanced or metastatic HR+/HER2- breast cancer driven by PI3Kα-mutations. The goal of the trial is to characterize the safety profile of STX-478 and establish a maximum tolerated dose (“MTD”) or a lower optimal-biologically active dose, if appropriate, as the recommended Phase 2 dose (“RP2D”) as a monotherapy for breast cancer and other solid tumor types, and as a combination agent in PI3Kα-mutant HR+/HER-2- breast cancer. Once the MTD is reached, or a RP2D is established, Scorpion intends to open expansion cohorts evaluating STX-478 as monotherapy for several indications such as breast cancer, gynecological cancers, HNSCC, gastrointestinal cancers and other solid tumors, all harboring PI3Kα-mutations. In addition, the combination of STX-478 and fulvestrant, as well as other standard of care agents, will be investigated in breast cancer patients harboring PI3Kα mutations. Secondary objectives for this Phase 1/2 trial include assessing the pharmacokinetic profile, pharmacodynamic effects and clinical response as measured by Response Evaluation Criteria In Solid Tumors (“RECIST”) version 1.1. To learn more about the first-in-human trial of STX-478, please visit this page.

About Scorpion Therapeutics
Scorpion is a pioneering clinical-stage oncology company redefining the frontier of precision medicine to deliver optimized and transformational therapies for larger populations of patients with cancer, a strategy Scorpion refers to as Precision Oncology 2.0. Scorpion has built a proprietary and fully integrated platform of the most advanced technologies across cancer biology, medicinal chemistry, and data sciences, with the goal of consistently and rapidly creating exquisitely selective small molecule compounds against an unprecedented spectrum of targets. Scorpion aims to leverage its platform to advance a broad pipeline of wholly owned, optimized compounds across three target categories: best-in-class molecules targeting validated oncogene targets; first-in-class molecules for previously undruggable targets; and first-in-class molecules for novel cancer targets. For more information, visit www.scorpiontx.com.

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