Evidence Matrix · April 2026

OB001 Combination
Evidence Status — All Partners

A systematic audit of every OB001 combination proposed across the GSK, AbbVie, BMS, and Lilly partnership pitches, distinguishing those with published elacridar co-dosing data from those proposed on the basis of confirmed P-gp/BCRP substrate status alone. All published data referenced below originate from peer-reviewed studies, predominantly from the Schinkel group at the Netherlands Cancer Institute (NKI Amsterdam), the definitive laboratory for ABC transporter pharmacology.

Published elacridar co-dosing study exists
OncoBayes proprietary preclinical data
No elacridar data — substrate status only
6 Combinations with published elacridar co-dosing data
1 Combination with OncoBayes proprietary preclinical data
6 Combinations proposed on substrate status only — data generation required

Full Evidence Audit

Drug Partner Drug Class Proposed Indication / Benefit Elacridar Co-dosing Evidence Key Reference(s) Evidence Basis / Caveat
Zejula Niraparib · PARP1/2 GSK PARP Inhibitor Brain mets from ovarian / endometrial cancer; GBM; leptomeningeal disease
✓ Published Elacridar pretreatment → WT mice brain levels = ABCB1/ABCG2 KO levels
Martins et al., Mol. Pharmaceutics, 2021 Scientific Reports, 2025 (multimodal imaging) Dedicated Schinkel group study. Elacridar pretreatment in wild-type mice increases niraparib brain concentration and reduces small intestinal recovery to levels seen in P-gp/BCRP double-KO mice. Kp,brain rises from 0.20 (WT) to 1.46 (double-KO). Strongest basis of any GSK asset.
Blenrep Belantamab mafodotin · BCMA-ADC GSK Antibody-Drug Conjugate Relapsed/refractory multiple myeloma; dose-reduction via MDR reversal in MM cells
✗ No data No published elacridar + belantamab or MMAF study identified
No specific reference Proposed on the basis that MMAF (the cytotoxic payload) is a P-gp substrate in haematopoietic cells — a general property of auristatin/maytansinoid payloads referenced in ADC resistance literature. No elacridar co-dosing data exists for this specific ADC or payload. Preclinical validation in MM cell lines required before partner approach.
Ojjaara / Omjjara Momelotinib · JAK1/2/ACVR1 GSK JAK Inhibitor Myelofibrosis dose optimisation; AML transformation MDR reversal
✗ No data No published elacridar + momelotinib study identified
No specific reference Speculative. Proposed on the basis of class-level interactions between JAK inhibitors and ABC transporters. No elacridar + momelotinib co-dosing data exists in any form. Weakest evidence basis of all GSK combinations. Significant preclinical work required before this would be pitchable.
Imbruvica Ibrutinib · Covalent BTK AbbVie BTK Inhibitor Primary CNS lymphoma (PCNSL); secondary CNS lymphoma; CNS-relapsed MCL
✓ Published Elacridar co-dosing in WT mice replicates ABCB1 KO phenotype
Van Hoppe et al., Mol. Pharmaceutics, 2018 Dedicated Schinkel group study. P-gp deficiency increases ibrutinib brain-to-plasma ratios by 4.5–5.9-fold in Abcb1a/1b KO mice. Elacridar co-administration in wild-type mice replicates this enhancement fully. ibrutinib-DiOH metabolite (10-fold reduced BTK activity) also restricted by P-gp. Strong mechanistic and clinical rationale for PCNSL.
Venclexta Venetoclax · BCL-2 AbbVie BCL-2 Inhibitor CNS-relapsed CLL/AML; BCL-2+ primary CNS lymphoma; paediatric ALL CNS sanctuary
✗ No data Confirmed substrate status but no elacridar co-dosing study identified
Badawi et al., J Cancer, 2023 (CSF PK — clinical) Salem et al., J Clin Pharmacol, 2017 (substrate status) Venetoclax is a confirmed dual P-gp and BCRP substrate at the BBB (documented in its own PK literature and clinical CSF data). Clinical CSF sampling in paediatric patients confirms limited but detectable CNS penetration. No published elacridar + venetoclax co-dosing experiment exists in any model. Joint preclinical programme with AbbVie proposed as part of partnership term sheet.
Elahere Mirvetuximab soravtansine · FRα-ADC AbbVie Antibody-Drug Conjugate FRα+ platinum-resistant OC with acquired P-gp-mediated DM4 resistance
✗ No data No published elacridar + mirvetuximab or DM4 study identified
No specific reference Proposed on the basis that maytansinoid payloads (DM4/DM1) are known P-gp substrates in cancer cell resistance literature. P-gp overexpression is a recognised mechanism of acquired resistance to maytansinoid ADCs. No elacridar co-dosing study for this specific ADC or payload. Mechanistic hypothesis requiring preclinical validation in FRα+ P-gp-overexpressing ovarian cancer lines.
Krazati Adagrasib · KRAS G12C BMS KRAS G12C Inhibitor KRAS G12C+ NSCLC brain metastases; KRAS G12C+ CRC; GBM (KRAS-mutant)
✓ Published 41-fold brain penetration increase; no acute CNS toxicity
Sparidans et al., Biomed. Pharmacother., 2023 Dedicated Schinkel group study. ABCB1/ABCG2 inhibitor elacridar increases adagrasib brain penetration in wild-type mice by 41-fold — the largest elacridar-mediated BBB enhancement published for any approved oncology drug — without acute CNS toxicity. Additionally, OncoBayes has generated proprietary preclinical data with OB001 specifically demonstrating 3,300% CNS concentration increase and 0% plasma increase with adagrasib. Strongest overall evidence package across all four partners.
Sprycel Dasatinib · BCR-ABL/SRC TKI BMS Tyrosine Kinase Inhibitor CNS-involved CML; Ph+ ALL CNS sanctuary; dasatinib-sensitive CNS tumours
✓ Published 13.2× oral / 22.7× i.p. — WT matches double-KO with elacridar
Lagas et al., Clin Cancer Res, 2009 One of the foundational papers in the elacridar field. Elacridar co-administration in wild-type mice produces dasatinib brain accumulation equivalent to P-gp/BCRP double-knockout mice: 13.2-fold increase (oral dosing), 22.7-fold (i.p.). P-gp is the primary restrictor; ABCG2 provides backup when P-gp is absent. Note: Sprycel faces generic competition — CNS orphan positioning is the commercial rationale.
Augtyro Repotrectinib · ROS1/NTRK TKI BMS Next-Gen TKI ROS1+ NSCLC brain mets; NTRK+ paediatric CNS tumours; TKI-resistant CNS disease
✗ No data No published elacridar + repotrectinib study identified
No specific reference Proposed on the basis of TKI class P-gp substrate evidence. Repotrectinib's physicochemical properties (MW ~393, moderate lipophilicity) are broadly consistent with P-gp substrate characteristics. FDA label documents known CNS activity suggesting partial BBB penetration. No published elacridar co-dosing study for repotrectinib specifically. Class inference only.
Verzenio Abemaciclib · CDK4/6 Lilly CDK4/6 Inhibitor HR+/HER2− breast cancer brain metastases; GBM; leptomeningeal disease
✓ Published Abemaciclib + all 3 active metabolites; elacridar reverses KO phenotype
Martínez-Chávez et al., Mol. Pharmaceutics, 2022 Dedicated Schinkel group study. ABCB1 and ABCG2 limit brain penetration of abemaciclib and all three pharmacologically active metabolites (M2, M20, M18 — themselves transported even more avidly than parent compound). Elacridar pretreatment in wild-type mice replicates ABCB1/ABCG2 double-KO brain exposure. 6-fold+ brain penetration increase. Unique in that both parent and metabolites are affected.
Retevmo Selpercatinib · RET kinase Lilly RET Kinase Inhibitor RET+ NSCLC brain mets; RET+ thyroid cancer CNS disease; GBM
✓ Published 6.2-fold increase; elacridar fully restores KO-equivalent BBB penetration
Wang et al., Pharmaceuticals, 2021 Dedicated Schinkel group study. ABCB1/ABCG2 jointly limit selpercatinib brain and testis penetration by 6.2-fold and 6.4-fold respectively. Elacridar co-administration in wild-type mice fully restores brain exposure to double-KO levels — without causing acute toxicity. One of the cleaner published datasets: elacridar effect = complete transporter reversal. Robust foundation for a partner pitch.
Jaypirca Pirtobrutinib · Non-covalent BTK Lilly Non-covalent BTK Inhibitor CNS lymphoma; secondary CNS involvement in CLL/MCL; BTKi-resistant CNS disease
✗ No data No published elacridar + pirtobrutinib study identified
No specific reference Proposed on the basis of BTK inhibitor class P-gp substrate data. Ibrutinib (covalent BTKi — see AbbVie) has a dedicated elacridar study; pirtobrutinib (non-covalent, structurally distinct) has not. Class inference is reasonable given shared target tissue and pharmacological class, but pirtobrutinib-specific co-dosing data would be required before a credible partner approach.
Inluriyo Imlunestrant · Oral SERD Lilly ESR1-selective SERD ESR1-mutant ER+ breast cancer brain mets; post-CDK4/6 CNS progression
✗ No data No published elacridar + imlunestrant or class-specific study identified
No specific reference Purely class-level hypothesis. Oral SERDs have generally shown P-gp/BCRP interactions in the broader endocrine resistance literature, but no published data exists specifically for imlunestrant or for elacridar + any oral SERD. Weakest evidence basis of all Lilly combinations. Substrate confirmation studies required before any partner discussion.

Notes on Evidence Standards & Interpretation

● Published Elacridar Co-dosing Data

Six combinations have dedicated peer-reviewed preclinical studies demonstrating that elacridar (or genetically equivalent ABC transporter knockouts) significantly increases the drug's brain concentration. All six published datasets originate from or are corroborated by the Schinkel group at the Netherlands Cancer Institute (NKI Amsterdam) — the leading laboratory globally for ABC transporter pharmacology. These combinations represent the strongest scientific foundation for partner pitches.

● OncoBayes Proprietary Data

One combination — OB001 + adagrasib (Krazati, BMS) — is additionally supported by OncoBayes's own proprietary preclinical data demonstrating a 3,300% increase in CNS drug concentration and 0% increase in plasma concentration with the clinical OB001 formulation specifically. This is the only combination for which OncoBayes can present partner-ready IND-enabling data without relying solely on third-party publications.

● Substrate Status Only — Data Required

Six combinations are proposed on the basis of confirmed (or inferred) P-gp/BCRP substrate status without any published elacridar co-dosing experiment. These remain scientifically rational hypotheses, but a confirmed substrate is a necessary — not sufficient — condition for predicting a meaningful elacridar effect. For these combinations, OncoBayes should either generate its own preclinical co-dosing data prior to a partner approach, or propose a joint preclinical programme as part of the partnership term sheet.