Scorpion Therapeutics Provides Clinical Program Updates for Its Mutant-Selective PI3Kα Inhibitor STX-478

Rhea-AI Summary

Scorpion Therapeutics announced updates for its PI3Kα inhibitor STX-478, including a new collaboration with Pfizer to evaluate a triplet combination therapy for metastatic breast cancer. The collaboration will study STX-478 + atirmociclib + fulvestrant in frontline patients with PI3Kα-mutated HR+/HER2- metastatic breast cancer, with trial initiation planned for 2H25.

Updated Phase 1/2 study results presented at SABCS 2024 showed STX-478 achieved a 23% overall response rate in HR+/HER2- breast cancer and 44% ORR in gynecological tumors. The drug demonstrated favorable safety with minimal dose modifications and no patient discontinuations due to adverse events. The study also revealed a positive dose-response relationship in monotherapy treatment.

Positive

• New collaboration with Pfizer for triplet combination therapy development
• 23% overall response rate in HR+/HER2- breast cancer
• 44% overall response rate in gynecological tumors
• No patient discontinuations due to adverse events
• Positive dose-response relationship demonstrated in monotherapy

Negative

• None.

Insights

Medical Research Analyst

The collaboration between Scorpion Therapeutics and Pfizer represents a significant advancement in targeted cancer therapy development. The key highlight is STX-478's promising 23% overall response rate in HR+/HER2- breast cancer and 44% ORR in gynecological tumors as monotherapy, demonstrating robust efficacy.

The drug's mutant-selective mechanism and favorable safety profile, with no discontinuations due to adverse events, positions it advantageously compared to existing PI3Kα inhibitors. The planned triplet combination study with Pfizer's atirmociclib could potentially establish a new frontline treatment paradigm for PI3Kα-mutated breast cancer patients.

Financial Analyst

The cost-sharing agreement with Pfizer for the triplet combination study represents a strategic financial move for Scorpion Therapeutics. Pfizer's involvement, including supplying atirmociclib, significantly reduces development costs while potentially accelerating the path to market. For Pfizer ($149B market cap), this collaboration provides exposure to a promising next-generation cancer therapy with minimal upfront investment.

The positive clinical data and expanding development program enhance STX-478's commercial potential in the lucrative breast cancer market. The drug's superior safety profile could lead to broader adoption and market penetration compared to existing treatments.

– Entered collaboration with Pfizer to evaluate triplet combination of STX-478 + atirmociclib + fulvestrant in frontline patients with PI3Kα-mutated HR+/HER2- metastatic breast cancer; trial initiation planned for 2H25 –

– Updated analyses from Phase 1/2 study of STX-478 highlighting monotherapy dose response in HR+/HER2- metastatic breast cancer and low dose modification rates presented at the San Antonio Breast Cancer Symposium 2024–

– Scorpion continues enrollment in combination studies with fulvestrant +/- CDK4/6 inhibitors in breast cancer –

BOSTON--(BUSINESS WIRE)-- Scorpion Therapeutics, Inc. (“Scorpion”), a clinical-stage, precision oncology company developing transformational targeted therapies for patients with cancer, today presented updated analyses from its Phase 1/2 study of STX-478 in advanced solid tumor patients in a poster spotlight presentation at the San Antonio Breast Cancer Symposium (“SABCS”) 2024 and provided program updates, including a new collaboration with Pfizer to evaluate the triplet combination of STX-478 + atirmociclib + fulvestrant in frontline patients with PI3Kα-mutated HR+/HER2- metastatic breast cancer.

“Scorpion is dedicated to expanding the reach of precision medicine to as many patients as quickly as possible. Our updated analyses presented at SABCS show STX-478’s low dose modification rates and increased response rate at higher doses, reflecting its high level of pathway inhibition. These studies, along with our new collaboration with Pfizer to advance the triplet study of STX-478 + fulvestrant with their novel, selective investigative CDK4 inhibitor in frontline patients, bring us one step closer to this ambitious goal,” said Adam Friedman, M.D., Ph.D., Chief Executive Officer of Scorpion. “We are committed to being at the forefront of the emerging treatment landscape as we actively enroll our fulvestrant +/- CDK4/6 inhibitors cohorts of STX-478 and explore new triplet combinations with promising next-generation therapies such as atirmociclib.”

Expansion Study Collaboration Updates

Scorpion Therapeutics and Pfizer Inc. (NYSE: PFE) entered into a new clinical trial collaboration and supply agreement to evaluate atirmociclib, Pfizer’s investigative selective-CDK4 inhibitor, in combination with STX-478 and fulvestrant in patients with PI3Kα-mutated, HR+/HER2- metastatic breast cancer in the frontline metastatic setting. Under the terms of the agreement, Scorpion and Pfizer will equally share the development costs of the study. In addition, Pfizer will supply atirmociclib for use in the study and Scorpion will manage the conduct of the study. The STX-478 + atirmociclib + fulvestrant triplet combination is planned to begin in 2H25.

Data from the Phase 1/2 Study of STX-478 in Advanced Solid Tumors at SABCS 2024

Scorpion has shown in Phase 1 monotherapy data that STX-478, an oral, once-daily, mutant-selective, allosteric PI3Kα inhibitor, demonstrated robust PI3Kα pathway inhibition as a monotherapy, with anti-tumor activity observed in multiple cancer types, including a 23% overall response rate (ORR) in HR+/HER2- breast cancer (BC) and a 44% ORR in gynecological tumors, amongst others. STX-478 was well-tolerated, including in pre-diabetic, diabetic and heavily pre-treated patients and showed minimal significant wild-type-mediated toxicities. These results suggest that STX-478 could overcome the limitations of currently available pathway inhibitors and, consequently, meaningfully improve clinical outcomes for patients with PI3Kα kinase or helical domain-mutated solid tumors.

In the poster presented at SABCS 2024, updated analyses for STX-478 demonstrated a favorable safety profile with minimal dose modifications observed, including no patient discontinuations due to an adverse event. Updated efficacy analyses demonstrated a positive dose-response relationship as monotherapy in patients with HR+/HER2- breast cancer, which correlates with a high level of PI3Kα pathway target coverage. Combination cohorts with a STX-478 + fulvestrant doublet and STX-478 + fulvestrant + CDK4/6 inhibitor triplet are actively enrolling in patients with HR+/HER2- breast cancer.

The presentation is available here on Scorpion’s website.

“STX-478 is characterized by a markedly higher therapeutic index, improving clinical outcomes and quality of life for patients during treatment compared to approved non-mutant-selective inhibitors,” said Dejan Juric, M.D., Director of the Termeer Center for Targeted Therapies at the Massachusetts General Hospital and STX-478 trial investigator. “Based on the very promising monotherapy results, I look forward to studying STX-478’s activity in doublet and triplet combination trials, particularly those that capture the known synergy between inhibition of PI3Kα and estrogen receptor antagonism in HR+/HER2-breast cancer, as well as CDK inhibition. Development of higher order combinations of increasingly selective targeted therapeutic agents represents the next frontier in precision oncology, and I believe STX-478 is well-positioned to drive major progress in this area.”

About STX-478

STX-478 is an allosteric, wild-type-sparing, CNS-penetrant, oral small molecule inhibitor of mutant PI3Kα, a well-known, clinically-validated oncogene associated with a variety of solid tumors and one of the most highly mutated targets in all of cancer, which occurs in more than 166,000 patients per year with breast, gynecological and other solid tumors in the United States alone. Based on preclinical data and initial data from the ongoing Phase 1/2 trial, STX-478 has the potential to address significant unmet needs in patients with PI3Kα-mutant cancers left by existing therapies through less toxicity and sustained and deeper responses. STX-478 is in an ongoing Phase 1/2 trial exploring its activity across a range of solid tumors with both kinase and helical domain mutations. The trial includes patients both previously exposed to and naïve to alpelisib and other PI3K pathway inhibitors and includes expansion cohorts in which STX-478 is being evaluated in combination with fulvestrant in second line HR+/HER2- breast cancer and in combination with fulvestrant plus CDK4/6 inhibitors in frontline HR+/HER2- breast cancer. To learn more about the first-in-human trial of STX-478, please visit this page.

About Scorpion Therapeutics

Scorpion is a clinical-stage, precision oncology company developing transformational targeted therapies for patients with cancer. We have built proprietary and fully-integrated discovery capabilities leveraging the most advanced technologies across cancer biology, medicinal chemistry and data sciences. Scorpion’s current pipeline, led by STX-478, our mutant-selective PI3Kα program, consists of three internally discovered clinical product candidates and multiple discovery-stage programs. Our focus is on solving current gaps in therapeutic options for patients with cancer by discovering and developing product candidates selective against well-validated, previously undruggable targets to improve patient outcomes.

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Media Contact:

Genevieve Britton

Precision AQ

genevieve.britton@precisionaq.com

Investor Contact:

Emiley Demick

Precision AQ

emiley.demick@precisionaq.com

Source: Scorpion Therapeutics, Inc.

FAQ

What are the response rates of STX-478 in breast cancer patients?

STX-478 demonstrated a 23% overall response rate (ORR) in HR+/HER2- breast cancer patients and a 44% ORR in gynecological tumors.

When will the Pfizer collaboration trial for STX-478 combination therapy begin?

The triplet combination trial of STX-478 + atirmociclib + fulvestrant is planned to begin in the second half of 2025 (2H25).

What is the safety profile of STX-478 in clinical trials?

STX-478 showed a favorable safety profile with minimal dose modifications and no patient discontinuations due to adverse events, including good tolerability in pre-diabetic, diabetic, and heavily pre-treated patients.

How will Pfizer (PFE) and Scorpion share the development costs?

Under the collaboration agreement, Scorpion and Pfizer will equally share the development costs of the study, with Pfizer supplying atirmociclib while Scorpion manages the study conduct.