Map the resistance pathway
Tumors resist camptothecins by rapidly degrading their own target, topoisomerase I, through the ubiquitin–proteasome pathway. We identified the proteins that drive it.
Dual-payload ADCs · Oncology
Targeting drug resistance at its source.
D2 Biosciences is developing dual-payload antibody-drug conjugates that pair a topoisomerase I inhibitor with a second payload that shuts down the pathway tumors use to resist it.
2
FDA-approved payloads in our lead candidate
1
FDA-approved antibody, for faster, lower-risk development
P-topoI-Dx
Predictive IHC biomarker, retrospectively validated in gastric and colorectal cancer
The problem
Patients live longer. Tumors still resist on schedule.
Over 50 years of colorectal cancer trials, combination therapy has more than tripled median overall survival. Progression-free survival has barely moved, because new regimens add drugs without overcoming resistance to the backbone therapy.
Read the case for a dual payload →
Our approach
Understand resistance. Predict it. Overcome it.
Predict who will respond
P-topoI-Dx, our IHC assay for topoI-S10 phosphorylation, flags resistant tumors before treatment, with high predictive value in gastric and colorectal cancer.
Overcome it with two payloads
Our ADCs deliver a topoI inhibitor together with a compound that blocks topoI degradation, so the drug keeps working where it used to fail.
Pipeline
Built on approved components.
| Program | Modality | DiscoveryPreclinicalIND-enablingPhase 1 | |||
|---|---|---|---|---|---|
| D2-KiLead candidate | Dual-payload ADC · TopoI inhibitor + kinase inhibitor | Preclinical |
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| Novel payloadSecond lead compound | Non-cytotoxic inhibitor of topoI ubiquitination | Discovery |
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| P-topoI-DxCompanion diagnostic | IHC assay for phosphorylated topoI-S10 | Retrospective clinical validation in GC and CRC | |||
Leadership & board
Decades of oncology firsts.
Ajit Bharti
FounderDeveloped a clinically validated predictive biomarker for topoI inhibitor resistance at Boston University. Founder of Predictus Biosciences, co-founder of Vanas Oncology.
Eric H. Rubin, MD
Board of DirectorsA principal architect of Keytruda at Merck, leading its clinical program and PD-L1 and MSI-H/dMMR biomarkers. Formerly at Dana-Farber and the Cancer Institute of New Jersey.
Ravi J. Chari, PhD
Board of DirectorsThree decades in ADC chemistry. Built ImmunoGen's ADC platform as VP of Chemistry and Biochemistry; 98 patents, including composition of matter for Kadcyla.
Publications
Peer-reviewed science behind P-topoI-Dx and D2-Ki.
2017Shah A et al. Camptothecin resistance is determined by the regulation of topoisomerase I degradation mediated by ubiquitin proteasome pathway. Oncotarget 8:43733–43751
Defined the resistance pathway and its molecular determinants, the foundation of P-topoI-Dx and drug target identification.
2018Ando K et al. Developing a phosphospecific IHC assay as a predictive biomarker for topoisomerase I inhibitors. J Histochem Cytochem 66(8):549–561
Optimization and analytical validation of the phosphospecific antibody in FFPE tissue.
2020Matsuoka H et al. CTDSP1 inhibitor rabeprazole regulates DNA-PKcs–dependent topoisomerase I degradation and irinotecan resistance in CRC. PLoS One 15(8):e0228002
Validates the kinase cascade and identifies a clinically used CTDSP1 inhibitor that modulates resistance.
2020Ando K et al. Multi-cohort retrospective clinical validation of a predictive biomarker for topoisomerase I inhibitors. Clinical Colorectal Cancer
Core clinical validation of P-topoI-Dx: multi-cohort PPV / NPV in CRC and GC.
2021Ando K et al. Efficacy of TopoI-pS10 expression in gastric cancer as a predictive biomarker for irinotecan use. Gan To Kagaku Ryoho 48(3):331–335 [in Japanese]
Review of the clinical utility of P-topoI-Dx by Masaki Mori, a KOL in GC/CRC clinical research.
2026Ebata Y et al. Proteasome inhibitor ixazomib prevents topoisomerase-I degradation and reverses irinotecan resistance in colorectal cancer. Molecular Oncology
Collaboration with Takeda: the proteasome inhibitor enhanced topoI inhibitor sensitivity ~4-fold in mouse xenograft models.