NGM386

NGM386 is an engineered biologic variant of **growth differentiation factor 15 (GDF15)** developed as a potential treatment for obesity. It functions as an **agonist of the GDNF receptor alpha-like (GFRAL)**, which is restricted to brainstem neurons and is a key component of a metabolic “emergency circuit” regulating weight homeostasis. NGM386 binds to GFRAL, activating downstream signaling through the receptor tyrosine kinase **RET** on select neurons, thereby triggering pathways that suppress food intake and promote weight loss. NGM386 was optimized for improved pharmacological properties compared to native GDF15 and designed for once-daily dosing. Despite promising preclinical data, clinical trial results showed that while the drug was well tolerated, it did not achieve significant weight loss versus placebo in Phase 1 studies. Jointly developed by NGM Biopharmaceuticals and Merck, the program was discontinued by Merck in 2019 and returned to NGM for further decisions on development[1][3][4][5][7][9][11][12][14].

Brand names

NGM386NGM-386NGM 386

Other names

NGM386NGM-386NGM 386engineered GDF15 variant