NGM Bio Initiates Expansion of Ongoing Phase 1b Proof-of-Concept Study of NGM120 in Patients with Metastatic Pancreatic Cancer - Seite 2

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.”

About the Design of the NGM120 Phase 1b Expansion

In February 2020, NGM initiated a Phase 1a/1b multi-site, open-label, dose-escalation clinical study to evaluate the safety, tolerability and pharmacokinetics of NGM120 as a monotherapy in patients with select advanced solid tumors (Cohort 1) and in combination with gemcitabine and Abraxane (paclitaxel protein bound) in patients with metastatic pancreatic cancer (Cohort 2). Entry criteria included elevated serum levels of GDF15. Cohorts 1 and 2 are fully enrolled.

The Phase 1b expansion portion of the study will evaluate the safety, tolerability and efficacy of NGM120 as a first-line treatment in 60 patients with metastatic pancreatic cancer. Entry criteria includes elevated serum GDF15 levels. The study is a randomized, single-blind (sponsor unblinded), placebo-controlled, multi-center trial. Patients will be randomized 1:1 to receive either NGM120 or placebo monthly in combination with the first-line standard of care, gemcitabine and Abraxane. The study will have both cancer and cachexia endpoints, including overall response rate (ORR), progression-free survival (PFS), overall survival (OS), body weight change, lean body mass change, patient reported outcomes and functional status changes.