Adagene and Incyte form alliance to target treatment-resistant colorectal cancer

Adagene (NASDAQ:ADAG) and Incyte (NASDAQ:INCY) have entered into a clinical trial collaboration to evaluate a potent combination of immunotherapy agents in patients with microsatellite stable colorectal cancer (MSS CRC), a disease state notoriously resistant to standard immune checkpoint inhibitors.

The partnership will focus on a Phase 1 study, expected to commence in 2026, evaluating Adagene’s muzastotug (ADG126) in combination with Incyte’s INCA33890.

The trial will enroll third-line (3L) chemotherapy-refractory patients, including those with and without liver metastases—a subgroup that typically faces the poorest prognoses in the MSS CRC landscape.

Muzastotug is a masked anti-CTLA-4 "SAFEbody" designed to activate selectively within the tumor microenvironment to reduce systemic toxicities.

The candidate recently received FDA Fast Track designation based on encouraging Phase 1b/2 data, which showed durable responses in MSS CRC patients when combined with other anti-PD-1 therapies.

Incyte’s contribution to the duo, INCA33890, is a bispecific antibody targeting both the TGFβ receptor 2 (TGFβR2) and PD-1.

By simultaneously blocking the TGFβ pathway—a known driver of immune exclusion and resistance—and the PD-1 checkpoint, the therapy aims to "prime" the tumor for the immune-stimulating effects of Adagene’s CTLA-4 inhibitor.

Under the terms of the agreement, Incyte will be responsible for sponsoring and conducting the Phase 1 trial, while Adagene will supply muzastotug for the study.

The collaboration marks a strategic attempt to solve the "cold tumor" problem in colorectal cancer.

While approximately 5% of CRC patients with high microsatellite instability (MSI-H) respond well to existing immunotherapies, the vast majority (MSS) do not.

By combining a masked CTLA-4 with a dual-targeting TGFβ/PD-1 bispecific, the two companies are betting on a multi-pronged attack to overcome the immunosuppressive barriers that define the MSS subtype.