OncoBayes has developed OB001 — the first orally bioavailable formulation of elacridar, a dual P-gp/BCRP inhibitor. We believe it can reinvigorate multiple Lilly assets, open entirely new indications, and generate billions in combination sales that no other partner can unlock.
Our Platform
OB001 simultaneously inhibits both P-glycoprotein (ABCB1) and Breast Cancer Resistance Protein (ABCG2) — the two major efflux transporters limiting oral bioavailability and CNS penetration of most small-molecule oncology and antiviral drugs.
Elacridar's clinical potential has been known for 30 years but was blocked by its own poor oral bioavailability (<5% in standard formulation). Our patented ASD formulation achieves 100% bioavailability with consistent plasma exposure.
By blocking P-gp and BCRP at the BBB, OB001 increases CNS drug concentration of co-administered substrate drugs by 12-fold — making previously ineffective CNS treatment strategies clinically viable.
The original form of Elacridar has extensive phase I data. OncoBayes has built on this and is now poised to enter the clinic.
Portfolio Analysis
We have systematically screened the Lilly marketed oncology portfolio and late-stage pipeline against confirmed P-gp and BCRP substrate profiles. Below is our ranked assessment of every combination opportunity.
Abemaciclib is the single most compelling combination partner in the Lilly portfolio. It is a confirmed dual P-gp/BCRP substrate — as are its three active metabolites (M2, M20, M18) which are transported even more avidly than the parent compound (Martínez-Chávez et al., 2022). While abemaciclib has better baseline CNS penetration than palbociclib, ABCB1 and ABCG2 remain the primary brake on its brain distribution. OB001 co-administration is expected to significantly amplify brain concentrations. This unlocks brain metastases from HR+/HER2− breast cancer — affecting ~30% of metastatic breast cancer patients — as a new indication with no approved CDK4/6-directed standard of care, plus glioblastoma (GBM) potential where CDK4/6 pathway activation is common. Verzenio's monarchE OS benefit in early breast cancer is already established; OB001 opens an entirely new patient population.
Target: HR+/HER2− breast cancer brain mets · GBM · Leptomeningeal diseaseSelpercatinib has one of the strongest transporter-specific evidence bases in the Lilly portfolio. The Schinkel group (Wang et al., Pharmaceuticals, 2021) demonstrated that ABCB1/ABCG2 jointly limit selpercatinib brain penetration by 6.2-fold, and that elacridar co-administration fully restores brain exposure to knockout-equivalent levels in wild-type mice — without acute toxicity. RET fusions are enriched in CNS tumours and occur in approximately 15% of non-small cell lung cancers with brain metastases. Despite selpercatinib's known intracranial activity, penetration remains suboptimal in intact BBB settings. OB001 amplifies this directly and without altering systemic plasma exposure. A RET+ CNS metastases indication with OB001 is mechanistically and clinically well-supported.
Target: RET+ NSCLC brain mets · RET+ thyroid cancer CNS disease · GBMPirtobrutinib is a non-covalent BTK inhibitor active in covalent BTK inhibitor-resistant CLL and MCL. BTK inhibitors as a class are known P-gp substrates with restricted CNS penetration, and CNS lymphoma (primary and secondary) represents a setting of profound unmet need where systemic BTK inhibition often fails due to inadequate BBB penetration. OB001 co-administration is expected to enhance pirtobrutinib brain concentrations meaningfully, given its small-molecule profile and the class-wide evidence of P-gp efflux. Additionally, MDR reversal in P-gp-overexpressing resistant CLL/MCL cells may re-sensitise tumour cells in patients progressing on pirtobrutinib monotherapy — extending the commercial lifecycle of a product with a growing but uncertain durability profile.
Target: CNS lymphoma · Secondary CNS involvement in CLL/MCL · BTKi-resistant diseaseImlunestrant is Lilly's next-generation oral SERD targeting ESR1-mutant ER+ breast cancer, recently approved and positioned as a potential backbone agent. Oral SERDs as a drug class have generally shown P-gp and BCRP interactions, and CNS penetration of oestrogen receptor antagonists is highly relevant given that ESR1 mutations are enriched in brain metastases from ER+ breast cancer. OB001 co-administration with imlunestrant could both improve oral bioavailability consistency and enhance CNS exposure, particularly valuable in ESR1-mutant brain metastases — where imlunestrant's selectivity profile is most advantageous. Preclinical substrate validation is required, but the scientific rationale and patient population logic are strong. A combination product with Verzenio (abemaciclib + imlunestrant + OB001) represents a future triple-combination franchise.
Target: ESR1-mutant ER+ breast cancer brain mets · Post-CDK4/6 progression with CNS diseaseMonoclonal antibodies (Cyramza/ramucirumab, Erbitux/cetuximab, Portrazza/necitumumab) are large-MW biologics not subject to P-gp or BCRP-mediated efflux — mechanism does not apply. Radiopharmaceutical assets from POINT Biopharma involve radiolabelled small molecules or peptides targeting PSMA; their pharmacokinetics are governed by renal clearance and binding kinetics rather than ABC transporter efflux. These assets are excluded from the OB001 partnership scope.
mAb / Radiopharmaceutical routes — mechanism not applicableLead Programme Deep Dive
Verzenio is growing strongly, but the CDK4/6 inhibitor class faces a looming challenge: brain metastases from HR+/HER2− breast cancer occur in up to 30% of metastatic patients and represent an indication where CDK4/6 inhibitors have been largely excluded from efficacy trials — because of inadequate CNS penetration.
The CNS metastasis opportunity is real, urgent, and scientifically validated. Brain metastases from HR+ breast cancer affect ~40,000 patients per year in the US and EU. Median survival is under 12 months on current best supportive care. There is no approved CDK4/6-directed therapy for this setting. The pharmacological problem is well defined: ABCB1 and ABCG2 at the BBB are the primary barriers to abemaciclib CNS efficacy.
Abemaciclib and all three of its pharmacologically active metabolites (M2, M20, M18) are confirmed P-gp/BCRP substrates. Published data (Martínez-Chávez et al., 2022, Mol. Pharmaceutics) demonstrate that combined ABCB1/ABCG2 deficiency increases abemaciclib brain penetration significantly in mouse models, and that elacridar is the validated tool to replicate this pharmacologically in wild-type animals. OB001 provides the selective CNS amplification that makes abemaciclib viable in the intracranial setting without increasing systemic exposure or systemic toxicity.
Orphan Drug Designation eligibility applies to the brain metastases indication, extending exclusivity by 7 years. The OB001 patent extends to 2046, providing a combination exclusivity horizon that more than doubles the remaining window on abemaciclib's base LOE.
The combination qualifies for multiple regulatory incentives that extend the commercial horizon well beyond the base abemaciclib LOE and provide significant development cost recovery.
At $120,000 per patient-year pricing (consistent with CDK4/6 inhibitor pricing) and 25% market penetration across 40,000 addressable HR+ breast cancer brain metastasis patients, peak combination sales exceed $1.2bn. With GBM and leptomeningeal disease expansion, and a future triple combination with imlunestrant, the ceiling is $3–4bn. This is incremental to Verzenio's already large base business.
Martínez-Chávez et al. (Molecular Pharmaceutics, 2022) — a dedicated published study of abemaciclib and its three active metabolites in ABCB1/ABCG2 knockout and elacridar-pretreated mice — provides the mechanistic foundation. The Schinkel group data directly validates the OB001 combination hypothesis. Multiple clinical trials are already evaluating abemaciclib in brain metastases (NCT02308020), confirming Lilly's own interest in this setting.
OncoBayes holds patents on the bioavailable elacridar formulation. This is independent of and complementary to Lilly's abemaciclib patents. The OB001 patent extends to 2046, creating a joint defensible position that materially outlasts abemaciclib's 2031 base LOE — adding 15 years of protected combination exclusivity post-approval.
Partnership Structure
We are proposing a phased co-development and commercialisation partnership, structured to minimise Lilly's upfront commitment while aligning long-term incentives. OncoBayes brings the platform, IP, and clinical-stage package. Lilly brings the partner asset, development infrastructure, and global commercial reach.
Development Roadmap
Partnership Signed
Term sheet executed. Joint steering committee established. IP licences and co-development agreement signed. Orphan Drug Designation filing submitted for abemaciclib + OB001 in HR+ breast cancer brain metastases. IND enabling package transferred to Lilly.
Phase I Initiation
Phase I PK/safety study opens in HR+/HER2− breast cancer patients with brain metastases. Dose escalation to determine optimal OB001 exposure for ≥80% P-gp/BCRP inhibition. Adaptive design allows seamless expansion into Phase II intracranial efficacy cohort.
Phase II Efficacy
Pivotal Phase II opens in HR+/HER2− breast cancer patients with brain metastases, stratified by ESR1 mutation status and prior CDK4/6 inhibitor exposure. Primary endpoint: intracranial objective response rate. BTD application submitted on Phase I PK data.
NDA Filing & Approval
Phase II data package supports NDA/MAA filing. Priority Review designation targets 6-month FDA review. Approval anticipated Q4 2031 / Q1 2032. OB001 patent protection to 2046 provides ~15 years of post-approval exclusivity — exceptional commercial runway for the combination franchise.
Next Steps
OncoBayes is proposing a meeting to continue existing discussions and discuss next steps.