STX-478 is Scorpion’s highly differentiated, allosteric and central nervous system (CNS) penetrant inhibitor of mutant phosphoinositide-3-kinase alpha (PI3Kα).
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 US alone.
The frequency of PI3Kα mutations and the scarcity of available treatment options has made the target a ‘high priority’ for drug discovery.
The current 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 including hyperglycemia and rash.
Such side effects may hinder the ability of patients to tolerate these therapies on a long-term basis.
These treatments also have little to no CNS penetrance, despite 50% of all solid tumor patients developing significant morbidity and mortality from brain metastases.
“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, chief executive officer at 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,” he added.
“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.”
Upon completion of the phase 1/2 trial, Scorpion expects to present initial safety, pharmacokinetic, and pharmacodynamic results in 2024, including data on STX-478’s impact on potential biomarkers suggestive of anti-tumor activity, said Michael Streit, chief medical officer at Scorpion.