Target
Our most advanced program, NGM282 is an engineered variant of the human hormone fibroblast growth factor 19, or FGF19, which we are developing as a once-daily injection for the treatment of NASH. FGF19 is a highly specific and potent regulator of liver fat metabolism and bile acid synthesis that we believe is responsible for some of the beneficial effects of gastric bypass surgery on NASH.

Data
Preliminary results from Phase 2 clinical trials have provided clinical proof of concept of NGM282 by demonstrating statistically significant reductions in liver fat, liver transaminases and biomarkers of fibrosis, which has translated to improvements in liver histology and fibrosis at 12 weeks.

Anticipated Upcoming Milestone
We plan to begin Phase 2b dose range-finding clinical trials of NGM282 for the treatment of NASH patients with F2 or F3 liver fibrosis in mid 2019 and NASH patients with F4 liver fibrosis in the second half of 2019.

Target
NGM313 is an agonistic antibody binding to fibroblast growth factor receptor 1c-beta-klotho, or FGFR1c/KLB, which regulates insulin sensitivity, blood glucose and liver fat. NGM313, being developed as a once-monthly injection, has the potential to be a best-in-class insulin sensitizer for the treatment of type 2 diabetes (T2D) and NASH. NGM313 works by selectively activating the FGFR1c/KLB co-receptor complex, which regulates energy expenditure and glucose uptake in fat cells and other tissues.

Data
In November 2018, NGM presented preliminary data at AASLD’s The Liver Meeting® in San Francisco from a Phase 1b proof-of-concept clinical trial of NGM313 in obese, insulin resistant subjects with nonalcoholic fatty liver disease, or NAFLD. The data demonstrated that a single dose of NGM313 resulted in a statistically significant reduction in liver fat content and improvements in multiple metabolic parameters.

Program Status and Upcoming Milestone
In January 2019, Merck exercised its option to license NGM313 (now renamed MK-3655). This one-time option to license NGM313, part of the original agreement announced by NGM and Merck in 2015, was triggered by NGM’s completion of the Phase 1b clinical study of NGM313. Based on the findings of this study, Merck intends to advance MK-3655 into a Phase 2b study to evaluate the effect of MK-3655 on liver histology and glucose control in NASH patients with or without diabetes.

Target
NGM120 is a long-acting antagonistic antibody binding glial cell-derived neurotrophic factor receptor alpha-like, or GFRAL, that is designed to inhibit the effects of elevated GDF15 levels on cancer anorexia/cachexia syndrome, or CACS, and possibly, cancer. NGM120 works by selectively inhibiting the interaction between GDF15 and its cognate receptor GFRAL, through which the autonomic nervous system and, possibly, the neuroendocrine axis influence the body’s fuel flux to propel uncontrolled weight loss associated with many types of cancer and, possibly, cancer itself, in cancer patients who have high serum levels of GDF15.

Upcoming Anticipated Milestone
We are currently testing NGM120 in healthy volunteers in a Phase 1 clinical trial to assess its safety, tolerability and pharmacokinetic profile. We expect to initiate a Phase 1b clinical trial of NGM120 in cancer patients with CACS in the second half of 2019.

NGM217 is a long-acting antibody binding an undisclosed target, designed to restore pancreatic islet function and increase insulin production in patients with diabetes. NGM217 is in a Phase 1 clinical trial where we are assessing its safety and tolerability profile in adults with diabetes.

NGM621 is a long-acting antibody binding an undisclosed target, designed to decrease levels of a protein implicated in the dry form of age-related macular degeneration, or dry AMD. NGM621 is in IND-enabling studies, and we expect to begin a Phase 1 safety, tolerability and pharmacokinetics clinical trial in patients with geographic atrophy, or GA, an advanced form of dry AMD, in the second half of 2019.

Target

NGM386 is an engineered variant of the human hormone known as growth differentiation factor 15, or GDF15, which was being developed by Merck for the treatment of obesity. GDF15 drives profound metabolic activity by regulating fuel flux and has been considered a challenging therapeutic target. NGM discovered that metabolic activity of GDF15 is mediated by glial cell-derived neurotrophic factor receptor alpha-like, or GFRAL, which is located in a region of the brain stem outside of the blood-brain barrier. NGM386 is designed to stimulate a pathway that modulates the autonomic nervous system and, possibly, the neuroendocrine axis to modify body weight and fat levels in the body.

Program Status

As part of the original collaboration agreement, Merck received an exclusive worldwide license to NGM’s GDF15 analogs, including NGM386 and NGM395, protein variants of GDF15 with potential for once-daily and once-weekly or less frequent dosing, respectively. In 2018, Merck completed dosing of a Phase 1 multiple ascending dose clinical trial evaluating NGM386 in otherwise healthy overweight/obese subjects. Preliminary data from this study indicate that while NGM386 was generally well tolerated, treatment with the drug for 28 days did not result in body weight loss relative to placebo.

As announced in March 2019, Merck has decided to terminate its license to the GDF15 receptor agonist program and return the program, including NGM386 and NGM395, to NGM, effective May 31, 2019. NGM continues to believe that the biology of GDF15 and GFRAL can play an important role in human disease. Upon transition of NGM386 and NGM395 back to NGM, we will conduct an analysis of the clinical data and make a decision about whether to pursue further development of these programs.

Target

NGM395 is an engineered long-acting variant of the human hormone known as growth differentiation factor 15, or GDF15. GDF15 drives profound metabolic activity by regulating fuel flux and has been considered a challenging therapeutic target. NGM discovered that metabolic activity of GDF15 is mediated by glial cell-derived neurotrophic factor receptor alpha-like, or GFRAL, which is located in a region of the brain stem outside of the blood-brain barrier. NGM395 is designed to stimulate a pathway that modulates the autonomic nervous system and, possibly, the neuroendocrine axis to modify body weight and fat levels in the body.

Program Status

As part of the original collaboration agreement, Merck received an exclusive worldwide license to NGM’s GDF15 analogs, including NGM386 and NGM395, protein variants of GDF15 with potential for once-daily and once-weekly or less frequent dosing, respectively.

As announced in March 2019, Merck has decided to terminate its license to the GDF15 receptor agonist program and return the program, including NGM386 and NGM395, to NGM, effective May 31, 2019. NGM continues to believe that the biology of GDF15 and GFRAL can play an important role in human disease. Upon transition of NGM386 and NGM395 back to NGM, we will conduct an analysis of the clinical data and make a decision about whether to pursue further development of these programs.