OncoBayes has developed OB001 — the first orally bioavailable formulation of elacridar, a dual P-gp/BCRP inhibitor. We believe it can reinvigorate multiple BMS 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 BMS marketed oncology portfolio and late-stage pipeline against confirmed P-gp and BCRP substrate profiles. Below is our ranked assessment of every combination opportunity.
Adagrasib presents the most scientifically compelling combination opportunity in the BMS portfolio — and arguably across any partner screened to date. OncoBayes preclinical data demonstrate that OB001 co-administration increases adagrasib CNS concentration by 3,300%, with 0% increase in plasma concentration — illustrating exquisitely selective CNS exposure enhancement through ABCB1/ABCG2 inhibition at the BBB, with no systemic pharmacokinetic amplification. This selectivity is the critical differentiator: it means the systemic safety profile of adagrasib is preserved entirely, while CNS drug levels are transformed. Adagrasib already has demonstrated intracranial ORR of 42% in KRAS G12C+ NSCLC (KRYSTAL-1), but brain penetration is the rate-limiting factor — P-gp efflux is the primary pharmacological brake. OB001 removes that brake entirely. The addressable population in KRAS G12C+ NSCLC with brain metastases is ~20,000 patients per year in the US/EU. Beyond NSCLC, KRAS G12C+ colorectal cancer with hepatic and CNS involvement is a further high-value indication where deeper tissue penetration translates directly to survival benefit.
Target: KRAS G12C+ NSCLC brain mets · KRAS G12C+ CRC · GBM (KRAS-mutant)Dasatinib has some of the most established elacridar BBB enhancement data of any drug in clinical use. Lagas et al. (Clinical Cancer Research, 2009) — one of the foundational papers in the field — demonstrated that elacridar coadministration with dasatinib resulted in brain accumulation equivalent to P-gp/BCRP double-knockout mice: a 13.2-fold increase orally and 22.7-fold intraperitoneally. CNS involvement in CML and Philadelphia chromosome-positive ALL remains a major clinical challenge, with CNS relapse a significant cause of treatment failure. OB001 offers a direct pharmacological solution to the inadequate dasatinib CNS penetration that allows blast crises to emerge in sanctuary sites. While Sprycel faces generic competition, the CNS indication represents a defensible, differentiated repositioning with premium pricing and Orphan Drug eligibility.
Target: CNS-involved CML · Ph+ ALL CNS sanctuary · Dasatinib-sensitive CNS tumoursRepotrectinib is a next-generation ROS1/NTRK TKI with known CNS activity and an FDA label already referencing CNS metastases. However, TKIs of this class are known P-gp substrates, and residual BBB efflux limits full intracranial drug exposure even when partial penetration is observed. OB001 co-administration is expected to push repotrectinib brain concentrations from partial to near-complete transporter saturation, potentially improving intracranial ORR from current observed rates to levels competitive with local CNS therapies. With patent protection to ~2036 and a rapidly expanding ROS1+ and NTRK+ patient population including primary CNS tumours in paediatric patients, this is a commercially attractive second programme with a paediatric rare disease regulatory pathway available.
Target: ROS1+ NSCLC brain mets · NTRK+ paediatric CNS tumours · TKI-resistant CNS diseaseBuilding on the lead programme, KRAS G12C inhibition drives tumour immunogenic cell death and modulates the KRAS-driven immunosuppressive tumour microenvironment — creating a rational mechanistic basis for combining with PD-1 checkpoint blockade. BMS already holds both assets and is actively pursuing adagrasib + nivolumab combinations (CheckMate trials). Adding OB001 to a Krazati + Opdivo backbone ensures adagrasib achieves full CNS exposure, enabling a triple-modality approach (KRAS inhibition + immune checkpoint + BBB penetration enhancement) for KRAS G12C+ NSCLC with brain metastases — potentially the most aggressive CNS cancer regimen available. Opdivo's LOE in 2028 creates additional urgency for BMS to establish a differentiated combination franchise before generic nivolumab erodes the commercial opportunity.
Target: KRAS G12C+ NSCLC brain mets · PD-L1+ KRAS G12C+ NSCLC with CNS diseaseMonoclonal antibodies (Opdivo/nivolumab, Yervoy/ipilimumab, Opdualag combination) are large-MW biologics not subject to P-gp or BCRP-mediated efflux — mechanism does not apply. CAR-T cell therapies (Breyanzi, Abecma) are cellular medicines with entirely distinct PK profiles governed by T-cell expansion and persistence, not ABC transporter efflux. Reblozyl/luspatercept is a fusion protein. These assets are excluded from the OB001 partnership scope.
mAb / Biologic / Cell therapy — mechanism not applicableLead Programme Deep Dive
Adagrasib (Krazati) already has demonstrated intracranial activity — a 42% intracranial ORR in KRYSTAL-1 in KRAS G12C+ NSCLC with untreated CNS metastases. But the fundamental pharmacokinetic problem remains: P-gp at the BBB is actively effluxing adagrasib, limiting how much drug reaches CNS tumour tissue and how durable that exposure is over time.
OncoBayes preclinical data tell a remarkable story. OB001 co-administration increases adagrasib CNS concentration by 3,300% — with 0% increase in plasma concentration. This selective CNS exposure enhancement, achieved through ABCB1/ABCG2 inhibition at the blood-brain barrier, is the defining pharmacological characteristic of OB001: it amplifies drug concentrations precisely where they are needed — in the CNS tumour — without altering systemic exposure or systemic toxicity. This is not a marginal improvement. It is the difference between sub-therapeutic CNS drug levels and concentrations sufficient to drive deep, durable intracranial responses.
KRAS G12C+ NSCLC patients have a 40%+ propensity to develop brain metastases. With ~20,000 new CNS metastasis cases per year in KRAS G12C+ NSCLC in the US and EU, and adagrasib already approved and commercially deployed, OB001 requires no new drug approval — only a combination PK study to define the elacridar dose and a Phase II intracranial efficacy trial to establish the indication. BMS is already closer to a CNS approval for adagrasib than any competitor is for KRAS G12C+. OB001 is the pharmacological amplifier that locks in that advantage.
Opdivo's LOE approaching in 2028 creates strategic urgency. A validated adagrasib + OB001 franchise in CNS metastases provides BMS with a high-margin, patent-protected combination product that extends well beyond Opdivo's generic cliff — anchored by OB001's own patent through 2046.
The adagrasib + OB001 combination in KRAS G12C+ NSCLC brain metastases qualifies for multiple accelerated regulatory designations, with adagrasib's existing IND and safety database substantially de-risking the Phase I package.
At $180,000 per patient-year (consistent with current Krazati pricing) and 35% market penetration across 20,000 KRAS G12C+ NSCLC brain metastasis patients, peak combination sales from the CNS indication alone exceed $1.3bn. Adding KRAS G12C+ CRC CNS disease and the Krazati + Opdivo + OB001 triple combination expands the peak to $3–5bn — a transformational franchise for BMS's targeted therapy business beyond immunotherapy.
OncoBayes has generated its own preclinical data demonstrating that OB001 co-administration with adagrasib produces a 3,300% increase in CNS drug concentration with 0% increase in plasma concentration — confirming exquisitely selective BBB penetration enhancement. This is OncoBayes's own data, generated with the clinical OB001 formulation, and is not reliant on third-party publications. It forms the core of the IND-enabling package that we are prepared to share with BMS under CDA.
OncoBayes holds patents on the bioavailable elacridar formulation. This is independent of and complementary to BMS's adagrasib patents. The OB001 patent extends to 2046, well beyond adagrasib's ~2036 base LOE — and critically, beyond Opdivo's 2028 LOE, giving BMS a new patent-protected franchise just as its largest product faces generic entry.
Partnership Structure
We are proposing a phased co-development and commercialisation partnership, structured to minimise BMS's upfront commitment while aligning long-term incentives. OncoBayes brings the platform, IP, and clinical-stage package. BMS 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 adagrasib + OB001 in KRAS G12C+ NSCLC brain metastases. IND enabling package transferred to BMS.
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 at steady-state. 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.