NextCure Presents Preclinical and Clinical Data at Immunotherapy Conference

BELTSVILLE, MD, USA | November 05, 2024 | NextCure, Inc. (Nasdaq: NXTC), a cutting-edge biopharmaceutical company dedicated to creating innovative therapies for cancer, has shared pre-clinical findings from LNCB74, a B7-H4-targeting antibody-drug conjugate (ADC) developed alongside LigaChem Biosciences (LCB) (KOSDAQ: 141080), and biomarker data from the NC410 combination study with pembrolizumab for patients with immune checkpoint inhibitor (ICI) naïve and refractory microsatellite stable (MSS)/microsatellite instability-low (MSI-L) colorectal cancer (CRC). These insights were revealed at the Society for Immunotherapy of Cancer (SITC) annual meeting.

Michael Richman, the president and CEO of NextCure, noted the positive outlook for LNCB74, highlighting its potential to become a leading therapeutic due to its unique advantages over other B7-H4 ADCs. The company aims to file an IND application with the FDA by the end of the year to quickly move the program into clinical trials.

LNCB74, a B7-H4 antibody conjugated to the microtubule disrupting agent monomethyl auristatin E (MMAE), features a drug-to-antibody ratio of 4 (DAR4). This ADC uses a glucuronidase-cleavable, site-specific linkage attached to an engineered cysteine in the antibody light chain via LigaChem Biosciences’ ConjuAll technology. This design enhances stability in the bloodstream, ensures payload release specifically in tumor cells, and minimizes release in non-tumor cells. Additionally, LNCB74 includes an Fc mitigating mutation to reduce binding and uptake by Fc receptor-expressing immune cells. These features collectively aim to improve the safety and therapeutic efficacy of LNCB74 compared to other B7-H4-targeted ADCs.

In parallel, NextCure has also shared additional clinical data from the Phase 1b segment of a Phase 1b/2 study evaluating NC410, a LAIR-2 fusion protein, in combination with pembrolizumab. The trial focuses on patients with ovarian cancer and ICI-naïve MSS/MSI-L CRC. The combination therapy has shown promising clinical activity against MSS/MSI-L CRC, a type of cancer typically resistant to immunotherapy. Patients who experienced clinical benefits, such as partial responses or stable disease, showed significant durability in their responses, which is noteworthy in this patient group.

Key findings from the poster presentations include:

1. The details of the LNCB74 presentation, titled “LNCB74 is a B7-H4 antibody-drug conjugate with a β-glucuronide linker-MMAE payload system to enhance therapeutic index in B7-H4 expressing cancers,” will be presented by lead author Shannon M. Kahan (Abstract Number: 1051) on Friday, November 8, 2024, from 5:30 – 7:00 PM.

2. The presentation on NC410, titled “NC410 in combination with pembrolizumab improves anti-tumor responses by promoting collagen remodeling and tumor immunity in advanced ICI naive MSS/MSI-L CRC,” will be delivered by lead author Alina Barbu (Abstract Number: 632) on Saturday, November 9, 2024, from 7:10 – 8:30 PM.

NextCure, Inc. focuses on developing groundbreaking therapies for cancer patients who do not respond to, or have relapsed on, existing treatments. Utilizing a variety of differentiated mechanisms, including antibody-drug conjugates, antibodies, and proteins, NextCure leverages its expertise in understanding biological pathways, biomarkers, cellular interactions, and the tumor microenvironment to advance its therapeutic programs.