NextCure is going all in on its preclinical B7-H4-directed antibody-drug conjugate (ADC). The biotech has decided to seek partners for its existing clinical candidate and other preclinical programs to free up cash for its new priority.
Before the rethink, NextCure’s pipeline was led by the LAIR-2 Fc fusion protein NC410. The program was built on the hypothesis that collagens promote immune evasion. Betting that LAIR-2 releases immune suppression, NextCure developed a fusion protein to boost T-cell expansion and effector function. The biotech terminated a monotherapy trial of NC410 last year but pushed ahead with a combination study.
NextCure shared an update on the Keytruda combination trial after the market closed Thursday. The biotech saw five partial responses in 20 ovarian cancer patients who were immune checkpoint inhibitor naïve plus three responses in the 36 colorectal cancer patients who received 100 mg of NC410. None of the seven colorectal cancer patients in the 200-mg cohort responded to treatment.
NextCure CEO Michael Richman called the data “encouraging” in a statement. However, Richman’s positivity doesn’t extend to pumping NextCure’s money into the program. The biotech plans to wrap up the current trial and seek a partner for NC410.
The deprioritization of NC410 is part of a broader rethink. NextCure is also seeking external funding for two preclinical programs: Alzheimer’s disease candidate NC181, an antibody that binds to ApoE4; and brittle bone prospect NC605, an anti-Siglec-15 antibody. NextCure said the candidates could be ready for IND filings in 12 to 18 months if funding is secured.
The biotech has opted against taking the programs forward itself to free up cash for B7-H4-directed ADC LNCB74. NextCure is up against some big names that all have assets in the clinic. Pfizer has a candidate that originated at Seagen, while GSK paid $85 million upfront for Hansoh Pharma’s contender. Meanwhile, AstraZeneca’s in-house ADC team is working on another challenger.
NextCure plans to file an IND in the fourth quarter. The biotech will share preclinical data on LNCB74 this month that Richman said will highlight the differentiation between the candidate and other ADCs aimed at B7-H4. NextCure ended the third quarter with $75 million, a sum it expects to fund operations into the second half of 2026.