NextCure to prioritize NC410 combo, LNCB74 in 2024

NC410: The multi-center, multi-arm, first-in-human Phase 1b combination trial is evaluating the efficacy of NC410 in combination with pembrolizumab. Indications include: ICI Naive and refractory ovarian cancer and immune checkpoint inhibitor Naive and refractory colorectal cancer. The combination has been shown to be well tolerated up to 200 mg of NC410 with Grade 3 or higher Treatment Related Adverse Events of 3.7%. NC410 for Ovarian Cancer: Evidence of early clinical activity and biomarker observations support the proposed mechanism of action for NC410 in relapsed/refractory ICI Naive ovarian cancer, with/without active liver metastasis for subjects in the 100 mg and 200 mg cohorts. Additional observations from the initial 7-patient data set as of February 23, 2024, include: 3 partial responses were observed at the initial 9-week scan. 1 confirmed PR observed in the 200 mg cohort continues on study beyond 6 months. The 2 PRs at the 100 mg cohort are pending confirmatory scans at week 18. Biomarker data on blood samples drawn from patients in both the prior NC410 monotherapy trial and, the current NC410 combo trial support our hypothesis regarding the mechanism of action and activity in PR patients as follows: Decrease in peripheral Granzyme B-expressing CD8+ T cells, which supports our mechanism of action that NC410 remodels the extracellular matrix allowing activated immune cells to infiltrate into the tumor microenvironment. Generation of collagen-derived product 4GZ fragments is mediated by Granzyme B-expressing T cells and provides direct evidence of ECM remodeling and correlates with responses. Decrease in peripheral myeloid-derived suppressor cells reduces suppressive effects and enhances activation of immune cells and anti-tumor activity. Decrease in peripheral CCR7+ DC+ T cells which is consistent with chemokine guided migration of immune cells to the TME. Taken together, the data demonstrate that NC410 mediates activation of immune cells and migration into the TME through remodeling of the ECM. We believe NC410 combo results in anti-tumor activity and clinical responses in patients that have been shown to respond poorly to or are resistant to checkpoint inhibitors. In March 2024, we commenced enrolling an additional 18 patients among the 100 mg and 200 mg cohorts. We plan to present the data from the ovarian cancer patients in the second half of 2024. NC410 Colorectal Cancer: Preliminary evidence of clinical activity in the 100 mg cohort of patients with MSS/ MSI-L ICI naive CRC without active liver metastasis . Additional observations from the 19-patient data set as of February 23, 2024: Both responses were observed at the initial 9-week scan in the 100 mg cohort. Subjects enrolled had a median of 5 lines of prior treatment. The 2 responders remain as PRs, and continue on study for over 10 months and 5 months, respectively. Completed enrollment in January 2024 of an additional 20 patients in the 100 mg cohort. We plan to present the data of the CRC patients at a scientific conference within the second quarter of 2024. LNCB74: Selected our first antibody drug conjugate candidate of a potential of three from our collaboration with LegoChem Biosciences. Under the terms of the Agreement, both parties equally share the costs of developing the molecules and profits on commercialized products. Commenced development of LNCB74 utilizing a NextCure B7-H4 antibody and LegoChem’s ConjuAll ADC technology. Differentiated approach leveraging: B7-H4 specific antibody with an Fc modification that protects immune cells to improve safety; Use of a glucuronidase cleavable linker that offers cancer-selective payload release to minimize toxicity in non-tumor cells, and; Use of a monomethyl auristatin E payload with a drug-to-antibody ratio of 4, that has the advantage of bystander killing of surrounding tumor cells. Pre-clinical experiments in vitro and in vivo demonstrating potent tumor killing and pilot toxicology studies have been completed. Pre-filing feedback from the FDA supports moving forward to planned submission of an IND application by this year-end. Ongoing activities associated with GLP toxicity studies, GMP manufacturing, and clinical development planning are in progress.