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Scorpion Therapeutics Presents Preclinical Proof-of-Concept Data Supporting the Development of Its Potentially Best-in-Class Mutant-Selective PI3Kα Inhibitor for the Treatment of Solid Tumors at the AACR Annual Meeting 2022

— STX-478 named as Company’s first development candidate in March 2022 —
— STX-478 was rapidly discovered using Scorpion’s proprietary, fully integrated drug hunting platform —
— Investigational new drug (“IND”) application submission expected in 1H 2023 —

BOSTON, Mass. – April 8, 2022 – Scorpion Therapeutics, Inc. (“Scorpion Therapeutics” or the “Company”), a pioneering oncology company redefining the frontier of precision medicine through its Precision Oncology 2.0 strategy, today announced preclinical proof-of-concept data for STX-478, the Company’s first development candidate from its STX-H1047-PI3Kα program. STX-478, formerly ST-814, is a highly differentiated, allosteric and central nervous system (“CNS”)-penetrant small molecule specifically designed to inhibit the H1047X-mutant form of phosphoinositide 3-kinase alpha (“PI3Kα”), one of the most frequent variations in PI3Kα and a validated oncogenic disease driver across a variety of solid tumors. The data will be presented on Wednesday, April 13 in a late-breaking poster presentation at the American Association for Cancer Research (“AACR”) Annual Meeting 2022 in New Orleans, Louisiana.

“We are pleased to announce preclinical proof-of-concept data for STX-478, a potential best-in-class mutant-selective PI3Kα inhibitor and our first development candidate,” said Axel Hoos, M.D., Ph.D., chief executive officer of Scorpion Therapeutics. “These data are a perfect exemplar of our approach to deliver potential best-in-class molecules against validated targets through our Precision Oncology 2.0 strategy, which aims to optimize drug design to achieve target product profiles that directly address unmet patient needs. In only 18 months since program initiation, we believe we have developed a highly differentiated inhibitor of PI3Kα that overcomes the two major limitations of currently available agents – lack of selectivity for mutant PI3Kα and limited CNS penetrance – to potentially deliver superior efficacy across an array of tumor types. We are now focused on progressing STX-478 through IND-enabling studies and look forward to submitting our first IND application in the first half of 2023.”

PI3Kα is one of the most highly mutated targets in cancer and mutations at the H1047X residue represent the highest frequency variants in PI3Kα. More than 55,000 people in the United States annually are diagnosed with cancers driven by mutations at this residue. The frequency of PI3Kα mutations in driving tumor progression has made the target a high priority for drug discovery. However, currently available treatments are limited by their inhibition of the normal, or wild-type, version of PI3Kα in healthy tissues, which can lead to significant metabolic side effects, including hyperglycemia, that hinder the ability of patients to tolerate these therapies. In addition, despite the fact that up to 50% of all solid tumor patients will develop significant morbidity and mortality from brain metastases, existing options have little to no CNS penetrance, and are therefore unable to treat tumors that have progressed into the brain.

In the preclinical data presented at AACR, STX-478 demonstrated exceptional selectivity for PI3Kα against the kinome, with activity against PI3Kα kinase domain mutants, including the most commonly occurring variant, H1047R. Additionally, STX-478 demonstrated activity across a spectrum of PI3KαH1047X cell line-derived xenograft models and tumor types, while avoiding the metabolic dysfunction induced by currently marketed therapies and achieving superior tumor growth inhibition. Pharmacokinetic analyses suggest that STX-478 benefits from outstanding drug-like properties, with adequate CNS exposure to treat brain tumors or metastases. The predicted long half-life and minimum peak-to-trough plasma concentrations support once-daily dosing and a favorable therapeutic index in patients.

“Through our proprietary drug-hunting platform, we have developed an atomic-level understanding of the activating mutations in PI3Kα and successfully designed STX-478 to selectively target mutant PI3Kα, while avoiding the normal, or wild-type, form in healthy tissues,” said Darrin Stuart, Ph.D., chief scientific officer of Scorpion Therapeutics. “Despite widespread recognition of PI3Kα as a clinically validated oncogene, currently marketed agents are not wild-type sparing and therefore can be associated with significant dose-limiting toxicities. The new data to be presented at AACR demonstrate the potential of STX-478 to deliver superior safety, tolerability and efficacy, and we look forward to advancing our small molecule to deliver better solutions to patients with cancer.”

Based on these data, Scorpion Therapeutics named STX-478 as the lead development candidate from its STX-H1047-PI3Kα program in March 2022. STX-478 is currently advancing through preclinical development with an investigational new drug application submission expected in the first half of 2023.

The poster presentation is now available here under “Media” in the News section of Scorpion Therapeutics’ website:

1Source: The Cancer Genome Atlas (TCGA), Surveillance, Epidemiology, and End Results Program (SEER), and internal research

About Scorpion Therapeutics
Scorpion Therapeutics 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 Therapeutics refers to as Precision Oncology 2.0. Scorpion Therapeutics 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 Therapeutics 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

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Ravi Moorthy
Scorpion Therapeutics

Investor Contact:
Hannah Deresiewicz
Stern Investor Relations, Inc.