Benzinga | Mar 2, 2021 08:22AM EST

NGM Biopharma Reports Initiation Of Its Expansion Of Ongoing Phase 1b Proof-Of-Concept Study Of NGM120 In Patients With Metastatic Pancreatic Cancer

NGM Biopharmaceuticals, Inc. (NASDAQ:NGM), a biotechnology company focused on discovering and developing transformative therapeutics for patients, today announced it has dosed the first patient in an expansion of its ongoing Phase 1b proof-of-concept study of NGM120 in patients with metastatic pancreatic cancer. NGM120 is an antagonistic antibody that binds glial cell-derived neurotrophic factor receptor alpha-like (GFRAL) and inhibits growth differentiation factor 15 (GDF15) signaling. This placebo-controlled study will evaluate the effect of NGM120 on both cancer and cancer-related cachexia. Cachexia is the uncontrolled wasting of both skeletal muscle and fat linked to many cancers. It is estimated to affect 60% to 80% of advanced cancer patients and to be responsible for approximately 30% of all cancer deaths1. This proof-of-concept expansion represents a pre-planned progression of an ongoing Phase 1a/1b dose-finding clinical trial NGM is conducting in patients with select advanced solid tumors and metastatic pancreatic cancer.

NGM is a leader in research elucidating the central role of the GDF15/GFRAL pathway in promoting tumor-associated appetite regulation, metabolic regulation and immune modulation. Through systematic screening of human secreted factors in preclinical models, NGM identified that GDF15 expression has the ability to promote an outsized effect in weight loss. Evidence has also shown that serum levels of GDF15 are elevated in patients with a number of tumor types, including non-small cell lung cancer, melanoma, pancreatic, prostate, colorectal, gastric, esophageal and ovarian cancer, and are associated with a worse prognosis in multiple cancers.

As published in Nature, NGM was the first to identify GDF15's cognate receptor, GFRAL, and the associated signaling pathway2. This discovery enabled the development of NGM120, a proprietary inhibitory antibody binding to GFRAL that is designed to block the effects of elevated GDF15 levels. In preclinical studies, NGM has demonstrated that blocking the interaction between GDF15 and GFRAL both reduces tumor-associated weight loss and slows tumor growth. In a murine pancreatic tumor model, treatment with NGM120s, an anti-GFRAL antibody similar to NGM120, resulted in greater tumor shrinkage as well as improved survival versus the control arm. In a murine cancer cachexia model, NGM120s rapidly reversed tumor-induced weight loss. In addition, in a murine model of chemotherapy-induced weight loss, administration of NGM120s preserved lean mass and muscle function in animals treated with cisplatin, while treatment with cisplatin alone resulted in greater than 20% weight loss.

"We are pleased to advance NGM120 into a placebo-controlled, Phase 1b expansion in patients with metastatic pancreatic cancer. Patients with this aggressive disease are in particularly dire need of therapeutic solutions to fight their disease and enhance their quality of life," said Alex DePaoli, M.D., Senior Vice President, Chief Translational Officer at NGM. "Our approach of targeting the GDF15 receptor, GFRAL, gives NGM120 a novel profile in the GDF15 inhibition space and enables us to evaluate NGM120 as a potential treatment for both cancer-related cachexia and the underlying cancer."