IM-3050 (FAP Radioligand Therapy)
Fibroblast activation protein (FAP) is broadly expressed on cancer-associated fibroblasts, the most common tumor stromal cells, and is expressed in 75% of solid tumors. IM-3050 is designed to deliver radioactive 177 Lu directly to FAP-expressing cells, where the beta particles emitted may lead to a “bystander” effect that damages or kills nearby tumor cells. This RLT approach is intended to overcome limitations, such as poor internalization and low expression on tumor cells, that make FAP a challenging target for ADCs.
- IM-3050 incorporates a small molecule FAP-specific ligand, a linker tuned to drive tumor-specific uptake, an albumin-binding domain to improve tumor retention, and a chelator to carry and deliver the radionuclide.
- IM-3050 has been optimized for binding affinity, specificity for FAP, radiostability, in vivo tumor retention, preclinical activity, biodistribution and preclinical tolerability.
- Use of 177Lu-IM-3050 in the U87MG mouse xenograft model demonstrated substantial tumor regression with no significant toxicity signal. In March 2026, Immunome initiated the first clinical trial site for a Phase 1 trial of IM-3050 in patients with FAP-expressing solid tumors.
1. Targeting CAFs
The antibody-drug conjugate (ADC) targets the fibroblast activation protein (FAP) expressed on the surface of cancer-associated fibroblasts (CAFs). The ADC binds specifically to FAP, allowing precise targeting of these cells within the tumor microenvironment.
2. Internalization and Drug Release
Upon binding to FAP, the ADC is internalized by the CAF. Inside the CAF, the ADC breaks down, releasing its cytotoxic drug payload. This release leads to the destruction of the CAF and allows the drug to diffuse into the surrounding area.
3. Bystander Killing
The cytotoxic drug particles, now outside the CAF, diffuse into nearby tumor cells, where the drug disrupts their cellular processes, leading to their death, even though they don’t express FAP directly.
