NextCure, Inc. announced the presentation of new preclinical data on LNCB74, a B7-H4-targeting antibody drug conjugate (ADC) developed in partnership with LigaChem Biosciences, Inc. (LCB), formerly LegoChem Biosciences, Inc., at the 2024 American Association for Cancer Research (AACR) Annual Meeting in San Diego, CA. The poster presentation highlights LNBC74?s promising preclinical safety and anti-tumor activity. LNCB74 is an ADC utilizing LigaChem Biosciences?

proprietary site-specific conjugation and plasma-stable, cancer selectively activating linker technology to link monomethyl auristatin E (MMAE) to a B7-H4 targeting antibody in a drug-to-antibody ratio of 4 (DAR4). The presentation includes data demonstrating LNCB74?s high affinity and specificity for human B7-H4, a protein highly expressed on a range of solid tumors including breast, ovarian and endometrial cancers. LNCB74 was shown to specifically bind to B7-H4 expressing tumor cells and was rapidly internalized in a target-dependent manner.

In addition, data showed that LNCB74 mediated potent cytotoxicity in B7-H4-positive cancer cells in vitro and demonstrated serum stability with a favorable pharmacokinetic (PK) activity in rodents. LNCB74 demonstrated significant tolerability in cynomolgus monkeys and showed strong anti-tumor activity in multiple cell-line derived (CDX) and patient-derived xenograft (PDX) tumor models in vivo. The increase in tolerability and strong efficacy is expected to translate into clinical activity of LNCB74.

Key Findings: LNCB74 was engineered for an improved safety profile and therapeutic index with increased stability in circulation, tumor selective payload release, and a reduction in off-target release of active payload, mitigating toxicity compared to traditional vedotin ADCs. A single 3 mg/kg dose of LNCB74 resulted in durable tumor regression in multiple CDX and PDX tumor models, suggesting activity comparable or superior to competitor B7-H4 targeting ADCs. LNCB74 was well tolerated in cynomolgus monkeys following 2 doses of up to 10 mg/kg, showing a superior safety profile compared to traditional MMAE bearing ADCs.

LNCB74 demonstrates favorable pharmacokinetics and stability in rodents, consistent with the molecule?s preclinical safety profile. LNCB74 mediates potent cytotoxicity, with sub-nanomolar to low nanomolar EC50 values on multiple B7-H4-positive cancer cell lines.