Skip to main content

Scorpion Therapeutics Presents Preclinical Data for Potential Best-in-Class PI3Kα Inhibitor at San Antonio Breast Cancer Symposium

— STX-478 shows activity in models harboring kinase or helical domain mutations —

— STX-478 demonstrates mono- and combination activity across multiple breast cancer models —

— Investigational new drug (“IND”) submission on track for Q1 2023; Phase 1 study to include separate cohorts of patients with either kinase or helical domain mutated tumors —

BOSTON, Mass. – December 8, 2022 – Scorpion Therapeutics, Inc. (“Scorpion”), a pioneering oncology company redefining the frontier of precision medicine through its Precision Oncology 2.0 strategy, today announced preclinical data demonstrating that STX-478, the Company’s highly differentiated, allosteric and central nervous-system (“CNS”) penetrant inhibitor of mutant phosphoinositide-3-kinase alpha (“PI3Kα”), has a potentially best-in-class product profile, with the ability to improve outcomes in patients harboring tumors with prevalent PI3Kα kinase or helical domain mutations. The data is being presented for the first time today in a poster session at the San Antonio Breast Cancer Symposium (“SABCS”) in San Antonio, Texas.

“We are delighted to share new preclinical data on STX-478 that further demonstrates its potential best-in-class product profile and supports its advancement into first-in-human clinical trials,” said Axel Hoos, M.D., Ph.D., Chief Executive Officer of Scorpion. “In these studies, STX-478 showed robust anti-tumor activity as both a monotherapy and in combination with standard of care agents in models with kinase or helical domain mutations. Importantly, this activity was coupled with key features that differentiate STX-478 from other PI3Kα inhibitors. STX-478 exhibited high mutant selectivity, without the dose-limiting metabolic dysfunction associated with currently available treatments. It also displayed an ability to reach the CNS, which could address the brain metastases that often occur in patients with solid tumors, but are poorly treated by existing options. We look forward to filing our IND application in the first quarter of 2023 and initiating our Phase 1 study in patients soon thereafter.”

PI3Kα is one of the most highly mutated targets in all of cancer. In the United States, over 166,000 patients per year present with cancers, including breast, gynecological and head and neck, which harbor PI3Kα mutations.[1] Scorpion specifically designed STX-478 to deliver superior safety, tolerability and efficacy compared to currently marketed PI3Kα therapies and certain drug candidates known to be in development, while exhibiting excellent drug-life properties and a favorable therapeutic index.

In the preclinical data presented at SABCS, STX-478 demonstrated exceptional selectivity for PI3Kα, inhibiting the viability of both kinase and helical domain mutated cell lines in vitro. In addition, STX-478 demonstrated robust monotherapy activity in vivo, as well as combination activity with relevant co-treatments, across a variety of cancer types in xenograft studies. This includes a T47D ER+, HER2- breast cancer model, in which STX-478 treatment caused deep tumor regressions alone and in combination with fulvestrant; a panel of ER+ BrCa patient derived xenograft (“PDX”) models, in which STX-478 was highly efficacious alone and in combination with fulvestrant or palbociclib; and an ER+ PDX model carrying a helical domain mutation, in which STX-478 inhibited tumor cell growth.

Importantly, STX-478 also demonstrated promising tolerability. Chronic dosing of STX-478 did not cause metabolic dysfunction in murine models at efficacious doses, nor did it affect blood glucose levels in higher species, even at doses that provide exposure well-above the efficacious exposure in murine models.

“We are particularly encouraged to present data for the first time showcasing STX-478’s activity against PI3Kα helical domain mutations, which could enable our investigational therapy to treat a large number of patients,” said Darrin Stuart, Ph.D., Chief Scientific Officer of Scorpion. “This further showcases the demonstrated ability of our drug development platform to bring together scientific breakthroughs in biology, chemistry and data sciences to create superior product candidates that can extend the reach of precision medicine to many more people battling cancer. We look forward to initiating our first Phase 1 study of STX-478 next year.”

Scorpion has completed IND-enabling studies for STX-478 and expects to file an IND application with the U.S. Food and Drug Administration in the first quarter of 2023. Scorpion anticipates evaluating STX-478 as a monotherapy and in relevant combinations with approved standard-of-care agents in patients harboring PI3Kα mutations in either the kinase or helical domain.

The poster presentation is now available here and under “Media” in the News section of Scorpion’s website: Scorpion previously presented preclinical proof-of-concept data showcasing the exceptional selectivity of STX-478 for PI3Kα against the kinome, as well as pharmacokinetic analyses suggesting that STX-478 demonstrates from outstanding drug-like properties with adequate CNS exposure to treat brain tumors or metastases, at the American Association for Cancer Research (AACR) Annual Meeting in April 2022.

About Scorpion Therapeutics

Scorpion is a pioneering 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

Media Contact:
Ravi Moorthy
Scorpion Therapeutics

Investor Contact:
Hannah Deresiewicz
Stern Investor Relations, Inc.

[1] American Cancer Society, The Cancer Genome Atlas