Biotheryx Completes Enrollment in Phase 1a Trial of First-in-Class CDK4/6 Degrader BTX-9341 for HR+/HER2- Breast Cancer
Key Insights
Biotheryx (search) has completed enrollment in its Phase 1a clinical trial of BTX-9341, a first-in-class oral CDK4/6 (search) degrader for advanced HR+/HER2- breast cancer (search) patients who previously received CDK4/6 inhibitor therapy.
The trial evaluates BTX-9341 as monotherapy and in combination with fulvestrant, with topline data expected in Q1 2026.
Preclinical studies demonstrated BTX-9341's superiority over CDK4/6 (search) inhibitors through selective protein degradation and ability to overcome resistance mechanisms.
Biotheryx (search), Inc. announced the completion of enrollment in its Phase 1a clinical trial of BTX-9341, a first-in-class oral CDK4/6 (search) degrader, for treating advanced and/or metastatic HR+/HER2- breast cancer (search) in patients who have previously received CDK4/6 inhibitor therapy. The San Diego-based biopharmaceutical company expects topline data readout from the Phase 1a trial in Q1 2026.
Novel Protein Degradation Approach
BTX-9341 represents a significant departure from conventional CDK4/6 (search) inhibitors through its protein degradation mechanism. The drug functions as a bifunctional degrader that achieves potent and highly selective catalytic degradation of CDK4 and CDK6 proteins, while also providing robust inhibition of Cyclin E (search) and CDK2 (search) transcription.
In preclinical breast cancer models, BTX-9341 demonstrated superior efficacy compared to CDK4/6 (search) inhibitors in breast cancer xenografts. The drug's differentiated mechanism enables it to overcome key resistance mechanisms that limit the effectiveness of inhibitors in second-line HR+/HER2- breast cancer (search) treatment.
Trial Design and Objectives
The Phase 1a clinical trial follows a structured approach, beginning with dose escalation of BTX-9341 as monotherapy, followed by combination treatment with fulvestrant. The primary objective focuses on assessing safety, tolerability, pharmacokinetic and pharmacodynamic activity of BTX-9341 both as monotherapy and in combination with fulvestrant.
Based on the recommended dose determined from Phase 1a results, the study will proceed to a dose expansion phase that will formally evaluate efficacy outcomes.
Clinical Significance for Resistant Disease
The trial specifically targets patients with advanced and/or metastatic HR+/HER2- breast cancer (search) who have previously received CDK4/6 (search) inhibitor therapy in either the adjuvant or metastatic setting. This patient population represents a significant unmet medical need, as resistance to CDK4/6 inhibitors remains a major clinical challenge.
"Completing enrollment in the Phase 1a trial for BTX-9341 marks a significant step forward in advancing a very promising first-in-class treatment option for patients with HR+/HER2- breast cancer (search) who have received prior CDK4/6 (search) inhibitor therapy," said Dr. Leah Fung, Chief Executive Officer of Biotheryx (search).
PRODEGY Platform Technology
Biotheryx (search) has developed BTX-9341 through its proprietary PRODEGY platform, which focuses on protein degraders for oncology and inflammatory diseases. The company's approach deploys molecular glues to target undruggable proteins and bifunctional degraders to target validated proteins that conventional protein inhibition strategies have insufficiently addressed.
The founding and scientific teams at Biotheryx (search) previously developed the first FDA-approved modulators of Cereblon (search), the most widely validated E3 ligase involved in protein degradation. This expertise in Cereblon modulation has been applied to build the company's protein degrader pipeline.
Pipeline Development
Beyond BTX-9341, Biotheryx (search)'s preclinical pipeline advances undisclosed bifunctional degraders and molecular glues, including degraders designed as payloads for antibody drug conjugation. The company's portfolio represents a comprehensive approach to first-in-class protein degraders across multiple therapeutic areas.