Pathos AI announced today that the first patient has been dosed in its Phase 1b/2a clinical trial evaluating pocenbrodib, a CBP/p300 inhibitor, for the treatment of metastatic castration-resistant prostate cancer (mCRPC). The trial will assess pocenbrodib both as monotherapy and in combination with established treatments including abiraterone acetate, olaparib, or 177Lu-PSMA-617.
The Chicago-based biotechnology company, which specializes in AI-driven drug development, is advancing pocenbrodib as its first clinical-stage asset. The compound targets the CREBBP/EP300 proteins that activate genes promoting cancer cell growth and proliferation.
"The clinical promise of pocenbrodib, our potential best-in-class CBP/p300 inhibitor, lies not only in its remarkable efficacy in resistant prostate cancer models, but also in our sophisticated biomarker strategy that identifies patients most likely to benefit," said Dr. Jens Renstrup, Chief Medical Officer at Pathos AI.
Trial Design and Patient Population
The multicenter, open-label, dose-finding study (P300-02-001, NCT06785636) aims to enroll approximately 203 patients with mCRPC who have progressed despite prior therapy and have received at least one anti-androgen therapy, such as enzalutamide, apalutamide, abiraterone acetate, or darolutamide.
Primary objectives include:
- Assessing safety and tolerability
- Measuring objective response rates
- Evaluating PSA decline
- Determining the recommended Phase 2 dose of pocenbrodib in combination with other therapies
The trial builds upon previously reported data from the COURAGE study (NCT04575766) in metastatic castration-resistant prostate cancer, which provided initial evidence of pocenbrodib's potential efficacy.
Addressing Unmet Needs in Advanced Prostate Cancer
Metastatic castration-resistant prostate cancer represents a significant clinical challenge, as patients often develop resistance to existing therapies. According to the American Cancer Society, prostate cancer is the second leading cause of cancer death in American men, with more aggressive forms like mCRPC having limited treatment options once resistance develops.
Dr. Renstrup emphasized the significance of their approach: "Our precision medicine approach allows us to target the underlying resistance mechanisms to AR-targeted therapy through CBP/p300 inhibition, addressing a significant area of high unmet need for patients with advanced prostate cancer."
AI-Driven Patient Selection
A distinguishing feature of Pathos AI's development strategy is its use of artificial intelligence to optimize patient selection. The company's PathOS™ platform integrates multiomic data with real-world outcomes to identify specific molecular signatures that may predict response to treatment.
"By integrating multiomic data tied to real-world outcomes to identify specific molecular signatures, our PathOS™ platform enables us to select the right patients for treatment, potentially improving outcomes in a disease with limited therapeutic options as resistance develops," Dr. Renstrup explained.
Mechanism of Action
Pocenbrodib is an oral, small molecule inhibitor designed to block the activity of CREBBP/EP300 (CBP/p300) proteins. These proteins play a crucial role in activating genes that drive cancer cell growth and proliferation. By inhibiting these proteins, pocenbrodib impacts the expression of key cancer drivers, including the androgen receptor (AR) and its variants.
This mechanism makes pocenbrodib potentially relevant not only for advanced prostate cancer but also for other cancer indications, either as monotherapy or in combination with other treatments.
About Pathos AI
Pathos AI is a clinical-stage biotechnology company that leverages advanced artificial intelligence to re-engineer drug development, with a particular focus on optimizing patient selection strategies in phase 2 clinical trials. The company partners with pharmaceutical companies to accelerate precision medicine development through AI-driven computational approaches across multimodal real-world data and patient-derived biological models.
The company has raised over $100 million to expand its AI platform and accelerate the development of targeted treatments. This funding supports Pathos AI's mission to bring innovative therapies to patients faster through more efficient clinical development pathways.
As the trial progresses, Pathos AI will continue to leverage its AI capabilities to refine patient selection and potentially improve outcomes for patients with metastatic castration-resistant prostate cancer, a disease with significant unmet medical needs.
