OncoBayes Moves Forward with OB-001 to Combat ADC Resistance and Enhance TKI Brain Penetration

OncoBayes Advances OB-001 to Tackle ADC Resistance and Enhance TKI Brain Penetration

OncoBayes, a clinical-stage pharmaceutical company based in London, has announced the successful conclusion of preclinical studies for its product OB-001. This innovative approach aims to address two critical unmet needs in oncology: the resistance to antibody-drug conjugates (ADC) and the brain penetration of tyrosine kinase inhibitors (TKI).

Understanding OB-001

OB-001 functions as a highly selective and efficient inhibitor targeting two key efflux pumps: P-glycoprotein (P-gp) and Breast Cancer Resistance Protein (BCRP). These pumps play a significant role in both the blood-brain barrier and tumor cells, complicating the effectiveness of current therapies.

The drug is being developed as a once-daily oral tablet intended to be used alongside various standard oncology treatments, thereby optimizing their efficacy. In mouse studies utilizing brain perfusion methods, pre-treatment with OB-001 significantly increased cerebral exposure to four standard kinase inhibitors without altering systemic (plasma) exposure. Data shared at the AACR 2026 conference highlighted that OB-001 could enhance brain exposure to osimertinib by nearly 400%, with minimal systemic changes. This increase, according to translational pharmacokinetic-pharmacodynamic-tumor growth inhibition (PK-PD-TGI) models for osimertinib, is anticipated to substantially improve progression-free survival in the central nervous system for patients diagnosed with EGFR-mutant non-small cell lung cancer (EGFRmNSCLC).

The control of brain metastases presents a significant unmet need in both non-small cell lung cancer and breast cancer sectors.

Overcoming Resistance Mechanisms

Research has identified these same efflux pumps as essential resistance mechanisms impacting ADC efficacy. Overexpression of these pumps can reduce the payload concentration within tumors, limiting treatment effectiveness. Preclinical studies utilizing bidirectional transport assays have shown that OB-001 decreases the efflux of several leading payloads, including SN-38 (e.g., sacituzumab govitecan, Tropedvy®), DM4 (e.g., mirvetuximab soravtansine, Elahere®), and DXd (e.g., trastuzumab deruxtecan, Enhertu®).

Clinical Trial Plans

OncoBayes is poised to initiate a clinical trial program to generate proof-of-concept (POC) data, initially in combination with osimertinib, and will evaluate the potential for resensitization to T-DXd. Jim Millen, the CEO of OncoBayes, remarked, "This is a pivotal milestone for our team; we are now optimally positioned to move forward with our clinical plans for OB-001. OB-001 is on track to become a pioneer in its class, with significant potential for use as a simple oral adjunct treatment alongside various commercially successful oncology therapies. It undoubtedly represents a significant product opportunity in development."

With ongoing advancements in the fight against cancer, OncoBayes appears committed to changing the landscape for patients facing tough treatment challenges, making their progress with OB-001 a key development to watch in the future of oncology.