Biotheryx Begins Phase 1 Trial of BTX-9341, a Dual CDK4/6 Degrader

SAN DIEGO, CA, USA I July 17, 2024 I Biotheryx, Inc., a pioneering biopharmaceutical company, has announced the dosing of the first patient in a Phase 1 clinical trial of their investigational drug BTX-9341. This novel oral drug is a bifunctional degrader targeting cyclin-dependent kinase 4 (CDK4) and cyclin-dependent kinase 6 (CDK6), aimed at patients with advanced or metastatic hormone receptor-positive (HR+)/human epidermal growth factor receptor 2 negative (HER2-) breast cancer who have undergone prior CDK4/6 inhibitor therapy in either adjuvant or metastatic settings.

Dr. Leah Fung, CEO of Biotheryx, highlighted the significance of this milestone, stating that BTX-9341 has shown potent anti-tumor activity in preclinical models, both in those naïve to and resistant to CDK4/6 inhibitors. The initiation of this trial is a critical step towards addressing an unmet medical need for HR+/HER2- breast cancer patients who have previously received CDK4/6 inhibitors.

The Phase 1 trial will commence with BTX-9341 as a standalone treatment and subsequently combine it with fulvestrant. The trial phases will include dose escalation and dose expansion to evaluate the drug's safety, tolerability, pharmacokinetic, and pharmacodynamic properties. Following determination of the optimal dosage for Phase 2, an efficacy evaluation will be conducted in an expansion cohort.

Dr. Amita Patnaik, Co-Founder and Co-Director of Clinical Research at The START Center for Cancer Research, expressed enthusiasm over the trial’s initiation, noting that BTX-9341 represents an innovative and potent therapeutic approach. She emphasized the drug's potential to revolutionize the treatment landscape for advanced and metastatic HR+/HER2- breast cancer patients, especially those who have already been treated with CDK4/6 inhibitors. This trial aligns with START's mission to accelerate the development of new therapies and provide early access to cutting-edge treatments for cancer patients.

Preclinical studies have demonstrated that BTX-9341, administered orally, effectively reduces CDK4/6 levels and shows enhanced anti-tumor activity compared to standard treatments. The drug also exhibits synergy with selective estrogen receptor degraders like fulvestrant, elacestrant, and camizestrant, in both CDK4/6-naïve and resistant models.

BTX-9341 is characterized by its potent and selective catalytic degradation of CDK4 and CDK6, leading to robust inhibition of Cyclin E and CDK2 transcription, cell cycle arrest, and superior efficacy in breast cancer models. This differentiates it from existing CDK4/6 inhibitor therapies, as it can overcome resistance mechanisms that hinder the effectiveness of these inhibitors in second-line HR+/HER2- breast cancer treatment.

Biotheryx is committed to advancing its clinical-stage portfolio of first-in-class protein degraders. Their proprietary PRODEGY platform leverages their expertise in Cereblon binding, which was instrumental in developing the first FDA-approved modulators of Cereblon. In addition to BTX-9341, Biotheryx’s pipeline includes BTX-10908, targeting SOS1 for pan-KRAS mutant cancers, and PDE4 degraders for treating inflammatory diseases.