NEOK Bio, a Burlingame, California-based oncology company, has dosed the first patients in Phase I clinical trials of its two lead bispecific antibody-drug conjugates, NEOK001 and NEOK002, marking the company's transition to clinical stage. As per a company press release, each study is evaluating safety, tolerability, and early efficacy in patients with advanced solid tumors that co-express the relevant target pairs, with initial data readouts anticipated in 2027. Specific enrollment numbers, dosing schedules, and primary endpoint definitions were not disclosed.

NEOK001 is described as a potential first-in-class bispecific ADC targeting B7-H3 and ROR1, two surface proteins with broad expression across solid tumors and limited presence in normal adult tissue. NEOK002 targets EGFR and MUC1, a pairing designed to address known limitations of monospecific approaches to each antigen. Both candidates are backed by preclinical data the company says demonstrated superior in vivo efficacy relative to conventional monovalent ADCs, though those data have not been published in peer-reviewed form. NEOK Bio is supported by ABL Bio, a South Korean antibody engineering company.

Scientific and clinical context

B7-H3 is a co-inhibitory immune checkpoint protein overexpressed across a wide range of solid tumor types — including lung, breast, colorectal, and pancreatic cancers — while expression in normal adult tissue remains restricted. That differential creates a therapeutic window relevant to ADC design, where selective payload delivery depends on antigen enrichment at the tumor site. ROR1 is an oncofetal receptor tyrosine kinase, active during embryogenesis and re-expressed in multiple cancers including triple-negative breast cancer and lung adenocarcinoma, but largely absent from mature adult tissues. Zilovertamab vedotin, a ROR1-directed ADC developed by Merck and Vincera Pharma, has established clinical proof of concept for this target in hematologic malignancies, and CStone Pharmaceuticals is advancing CS5001, a ROR1 ADC with a PBD dimer payload, in Phase I across solid tumors and lymphomas.

In the B7-H3 space, GSK and Hansoh Pharma are co-developing GSK5764227 in Phase I/II trials across multiple solid tumor types, and CSPC Pharmaceutical's YL201, a B7-H3-directed ADC with a topoisomerase I inhibitor payload, has completed Phase I/Ib evaluation with results published in Nature Medicine. NEOK001's bispecific format — simultaneously engaging both targets — is designed to reduce the probability of antigen escape and improve ADC internalization efficiency relative to agents targeting either antigen alone.

For NEOK002, the EGFR/MUC1 pairing addresses a well-characterized problem in monospecific ADC development: EGFR-directed agents carry on-target toxicity in normal epithelial tissue, while MUC1-directed agents are undermined by ectodomain shedding, which releases soluble MUC1 into circulation and sequesters the ADC away from tumor cells. By requiring co-expression of both antigens for full activity, the bispecific format restricts payload delivery predominantly to tumor cells. Merck KGaA and Sutro Biopharma are developing M1231, a MUC1×EGFR bispecific ADC using a hemiasterlin payload, currently in Phase I — the most clinically advanced comparator to NEOK002.

Both NEOK001 and NEOK002 employ topoisomerase I inhibitor payloads, a class validated by the clinical success of trastuzumab deruxtecan (Enhertu, AstraZeneca/Daiichi Sankyo) and datopotamab deruxtecan (Datroway, AstraZeneca/Daiichi Sankyo), the latter approved in 2025 for EGFR-mutated NSCLC. The payload class offers both high potency and a bystander effect, enabling cytotoxicity in neighboring antigen-negative cells within heterogeneous tumors.

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