NextCure (NXTC) investor relations material

Pipeline overview

• Two differentiated antibody-drug conjugates (ADCs), SIM0505 and LNCB74, are in Phase 1 trials targeting multiple solid tumors, including ovarian, lung, renal, breast, and endometrial cancers.

• SIM0505 targets CDH6 with a proprietary topoisomerase 1 inhibitor payload, while LNCB74 targets B7-H4 with a tubulin inhibitor payload and a glucuronidase cleavable linker for improved safety and efficacy.

• Both programs are designed for multi-pronged approaches to overcome resistance, increase durability, and address unmet needs in cancer treatment.

• Strategic partnerships include a global license (ex-China) for SIM0505 from Simcere Zaiming and a 50/50 co-development partnership for LNCB74 with LigaChem Biosciences.

• Additional discovery and preclinical programs target leukemia, osteogenesis imperfecta, and Alzheimer's disease.

Clinical development and data

• SIM0505 Phase 1 trials are ongoing in China and the US, with initial data expected in 2Q 2026; the asset has shown promising safety and early efficacy signals, including a partial response at the lowest dose.

• LNCB74 Phase 1 dose escalation study began in January 2025, targeting breast, ovarian, and endometrial cancers, with trial progress updates expected in 2H 2026.

• SIM0505 demonstrates strong binding affinity, high systemic clearance, and potent cytotoxicity with anticipated safety improvements over competitors.

• LNCB74 utilizes a glucuronidase cleavable linker, providing higher drug concentration in cancer cells and reduced toxicity compared to traditional linkers.

• Both ADCs have shown potent anti-tumor activity in preclinical models, with SIM0505 active in ovarian and renal tumor models and LNCB74 achieving complete responses in breast and ovarian models.

Competitive differentiation

• SIM0505 offers a unique epitope and high-affinity binding, with no dose-limiting toxicities observed to date and a favorable safety profile compared to other CDH6-targeting ADCs.

• LNCB74 stands out with its site-specific conjugation and glucuronidase linker, resulting in improved therapeutic index and lower toxicity versus competitors using protease or val-cit linkers.

• Both ADCs are positioned to address resistance and increase durability through distinct payloads and overlapping target expression.