ADAG News & Events

Adagene (ADAG) announced results from the latest data cut from its Phase 1b/2 study of muzastotug in patients with advanced microsatellite stable colorectal cancer with no liver metastases. FDA has designated muzastotug in combination with Merck's (MRK) anti-PD-1 therapy, Keytruda, as a Fast Track product for adult patients with microsatellite stable metastatic colorectal cancer without current or active liver metastases. Previous results from a data cut on April 22, 2025 were presented at ASCO in June 2025. As of the latest data cut on January 24, a total of 67 MSS CRC patients with no liver metastases, including those with peritoneal involvement, have been treated with muzastotug at a dose of either 10 mg/kg or 20 mg/kg, in combination with pembrolizumab. The 10 mg/kg dose was administered once every three weeks or once every six weeks. The 20 mg/kg dose was administered once as a loading dose, followed by 10 mg/kg every three weeks, or 20 mg/kg every six weeks. Among 65 efficacy-evaluable patients in the dose expansion phase, those in the combined 10 mg/kg cohorts demonstrated an ORR of 13%, which was comprised of an ORR of 0% in the Q6W regimen cohort and an ORR of 17% in the Q3W cohort. The higher response rates in the Q3W cohort and robust safety, to keep patients stable without new lesions, in the Q6W cohort helped inform the decision for the dosing regimens utilized in Arm A of the ongoing randomized Phase 2 trial. The combined 20 mg/kg cohorts demonstrated a confirmed ORR of 31%, including 25% in the Q6W cohort and 36% in the 20 mg/kg loading dose cohort. The higher response rate in the 20 mg/kg cohorts helped inform the 20 mg/kg induction/maintenance dosing regimen utilized in Arm B of the ongoing randomized Phase 2 trial. Median progression-free survival was 4.8 months in the 10 mg/kg cohorts and 6.7 months in the 20 mg/kg cohorts. Notably, median PFS was 15.4 months among the 14 patients in the 20 mg/kg loading dose cohort, compared with 4.9 months among the 12 patients in the 20 mg/kg Q6W cohort, further supporting the induction/maintenance approach now being evaluated in the ongoing randomized Phase 2 study. As of the January 24 data cutoff, across 67 patients in all cohorts, there was a low 4% overall discontinuation rate, no dose limiting toxicities, and no treatment-related Grade 4 or 5 adverse events. Grade 3 TRAEs were 15% in the combined 10 mg/kg cohorts and 38% in the combined 20 mg/kg cohorts, which were generally transient and manageable. The most common treatment-related adverse events were pruritus, fatigue, hypothyroidism, and diarrhea. Regarding GI-related adverse events, the overall incidence of diarrhea, colitis and immune-mediated enterocolitis was relatively low, and such events were generally transient and manageable. The three patients with Grade 3 colitis had all recovered at the time of data cut-off. Infliximab use was low, with approximately 10% of patients requiring its use for management of GI toxicity.

Adagene (ADAG) announced a clinical collaboration with Incyte (INCY) to evaluate the combination of muzastotug and INCA33890, a TGFbetaR2 PD-1 bispecific antibody, in patients with microsatellite stable colorectal cancer with or without liver metastases. Muzastotug in combination with Merck's (MRK) anti-PD-1 therapy, Keytruda has demonstrated encouraging overall response rates and durable responses in a Phase 1b/2 trial in 3L MSS CRC patients. As a monotherapy, INCA33890 has demonstrated promising clinical efficacy and safety in immune checkpoint sensitive and insensitive cancers, including MSS CRC with and without liver metastases. Incyte has recently initiated a Phase 3 study evaluating bevacizumab and Folfox with or without INCA33890 in 700 first-line MSS CRC patients. Muzastotug, a masked anti-CTLA-4 SAFEbody with FDA Fast Track designation, is currently being evaluated in multiple ongoing studies, including: a Phase 1b/2 clinical trial in combination with pembrolizumab in MSS CRC patients without liver metastases. A randomized Phase 2 study in MSS CRC patients without liver metastases designed to determine the optimal dose to advance into a Phase 3 registration trial. A Phase 1b/2 dose escalation and expansion study of muzastotug in combination with Sanofi's SAR445877 in adults with advanced solid tumors. Under terms of the agreement, Incyte will sponsor and conduct the study and Adagene will provide clinical trial supply of muzastotug. The planned dose escalation portion of the study will evaluate safety and tolerability, followed by an efficacy expansion cohort in patients with chemotherapy-refractory MSS CRC patients with and without liver metastases. MSS CRC is well-known to be largely non-responsive to anti-PD-1 / PD-L1 therapy. INCA33890 monotherapy has demonstrated promising initial clinical efficacy and safety in immune checkpoint sensitive/insensitive tumors, including MSS CRC with and without liver metastases.

Reports FY25 revenue $7.7M vs $103,000 last year. "Our clinical data for muzastotug plus pembrolizumab consistently demonstrate potent, dose-dependent efficacy," said Peter Luo, Ph.D., Chairman and President of R&D at Adagene. "The 10 mg/kg data reported at ASCO have now matured into the classic long survival tail of CTLA-4 inhibition. By significantly mitigating severe toxicities, patients remain on therapy longer, allowing CTLA-4-mediated intratumoral Treg depletion, alongside PD-1-mediated reinvigoration and CTLA-4-mediated priming of effector T cells, to drive durable disease control. Importantly, these data provide a clear, de-risked read-through to the 20 mg/kg dose, which already shows an encouraging 29% ORR with median duration of response not yet reached."