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NextCure jettisons monoclonal antibody to focus on ADC aimed at same target

NextCure is dumping a phase 1 monoclonal antibody so it can spend more time on its antibody-drug conjugate (ADC) aimed at the same target.

The Maryland-based biotech jumped into the increasingly crowded ADC space in November 2022 when it signed a pact with LegoChem. The idea was to combine the two companies’ resources to find a new use for NextCure’s anti-B7-H4 antibody NC762 as part of an ADC.

Now, NextCure is halting its work on NC762, which had been undergoing a phase 1b trial in solid tumors, citing “the competitive environment” and “limited activity to date.” Instead, the biotech will shift those resources over to the B7-H4-directed ADC, dubbed LNCB74, that resulted from the LegoChem collaboration.

“Based on a comprehensive preclinical data package, we plan to initiate a dose range-finding toxicology study and GMP manufacturing for LNCB74 in early 2024,” the company explained.

B7-H4 is abnormally expressed by a range of solid tumors and plays a role in key processes such as cell proliferation and metastasis that support the development and spread of cancers. Because of its limited expression in healthy tissues, multiple companies have identified the cell-surface glycoprotein as a good target for ADCs that deliver cytotoxic payloads to cells with certain markers. 

A B7-H4 targeted ADC was at the center of GSK’s $85 million upfront licensing deal with Hansoh Pharma in October. The Big Pharma joined the likes of AstraZeneca, which already has a B7-H4-directed ADC called AZD8205 in a phase 2 trial for solid tumors, and Seagen, which has its own candidate in phase 1.

NextCure has a couple of other clinical-stage assets in the works. A readout from a phase 1b trial of a LAIR-2 fusion protein called NC410 in combination with Keytruda in patients with colorectal cancer is due in the first half of next year. In that same period, the biotech expects data from a phase 1 dose escalation study of its LAIR-1 monoclonal antibody NC525 in acute myeloid leukemia.

In November, the biotech said the $118 million it had on hand should last through to mid-2025.

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