NGM Bio Provides Update On NGM282 In NASH

SOUTH SAN FRANCISCO, Calif., Oct. 19, 2017 /PRNewswire/ -- NGM Bio, a research-driven biotechnology company that translates powerful biology into transformative medicines, today provided an update on the development of NGM282, a compound in Phase 2 clinical testing for the treatment of nonalcoholic steatohepatitis (NASH), and the presentation of new NGM282 data at The Liver Meeting® 2017 hosted by the American Association for the Study of Liver Diseases (AASLD).

As previously reported, NGM282 demonstrated profound and highly significant reductions in MRI measures of liver fat content (LFC) and serum biomarkers associated with the resolution of NASH and improvement in fibrosis in the company's randomized, double-blind, placebo-controlled Phase 2 trial in 82 patients with biopsy-confirmed NASH. Seventy-nine percent of the NASH patients in that study met the primary endpoint of greater than 5% absolute LFC reduction, with 34% of patients achieving normal LFC after 12 weeks of therapy.

"The unprecedented, rapid reduction in steatosis seen in the double-blind Phase 2 trial supported the initiation of a Phase 2 expansion trial to further explore NGM282's broad activity in NASH, including a cohort of patients in which we will assess the compound's impact on liver histology after 12 weeks of treatment," said Alex M. DePaoli, M.D., Chief Medical Officer of NGM Bio. "We look forward to reporting those biopsy data in the first quarter of 2018 and commencing the next phase of clinical development for NGM282 as soon thereafter as possible."

The NGM282 expansion trial in patients with biopsy-confirmed NASH replicates the original Phase 2 NASH trial in duration and eligible patient population. The expansion study includes the evaluation of lower dose levels of NGM282, as well as a histological assessment after 12 weeks of treatment in a subset of patients receiving a 3 milligram daily dose. Certain of these data will be presented at The Liver Meeting, with the remainder to be presented at future medical meetings.

The powerful anti-steatotic effects of NGM282 will be reinforced by data to be presented at The Liver Meeting demonstrating that NGM282 reduces LFC across a broad cross-section of NASH patients, independent of disease stage and with varied baseline predictors of disease progression. Significant positive correlations between LFC and liver transaminases, lipids, 7-alpha-hydroxy-4-cholesten-3-one (C4) and metabolic markers will be shown, demonstrating a strong association between NGM282's target engagement and patient response to treatment. (Publication 2178)

Drug-induced increases in LDL are a marker of drug potency in modulating the FGF19 pathway, and clinical data to be presented at The Liver Meeting will describe the rapid reversal of NGM282-induced changes in the cholesterol profile following the co-administration of rosuvastatin. Further, the study demonstrates an alteration of lipoparticle characteristics that is consistent with the beneficial features of improved insulin sensitivity. (Publication 2143)

NGM's scientists will also present non-clinical data showing that treatment with NGM282 leads to NASH resolution and improvement in fibrosis through a multifactorial mechanism. NGM282 demonstrates the ability to ameliorate the two primary drivers of hepatoxicity in NASH, lipotoxicity and bile acid toxicity.  The drug's inhibition of de novo lipogenesis, bile acid synthesis and ceramide synthesis likely contribute to the compound's anti-steatotic, anti-inflammatory and anti-fibrotic effects. (Publication 2008)

Details for the three poster presentations at The Liver Meeting are as follows. First authors will host their respective poster between 12:30 p.m. and 2:00 p.m. ET:

Title:  NGM282 Significantly Reduces Hepatic Steatosis Independent of Baseline Patient Characteristics and Highly Correlates with Markers of FGFR4 Target Engagement:  Results from a Phase 2 Trial in Biopsy-Confirmed NASH Patients (Publication 2178)
Authors:  Rohit Loomba, Manal F. Abdelmalek, James F. Trotter, Angelo H. Paredes, Mark Jaros, Lei Ling, Stephen J. Rossi, Alex M. DePaoli, Mary E. Rinella, Stephen A. Harrison
Date:  Monday, October 23, 2017
Time:  8:00 a.m. to 5:30 p.m. ET
Session:  Steatosis and Steatohepatitis

Title:  NGM282 Induces Low Density Lipoprotein Cholesterol (LDLc) Changes, Consistent with Potent FGFR4 Signaling, which are Rapidly Mitigated with Statin Therapy in Patients with Biopsy-Confirmed Nonalcoholic Steatohepatitis (NASH) (Publication 2143)
Authors:  Mary E. Rinella, James F. Trotter, Guy Neff, Grisell Ortiz LaSanta, Manal F. Abdelmalek, Marcelo Kugelmas, Angelo H. Paredes, Margery A. Connelly, Lei Ling, Stephen J. Rossi, Alex M. DePaoli, Rohit Loomba, Stephen A. Harrison
Date:  Monday, October 23, 2017 
Time:  8:00 a.m. to 5:30 p.m. ET
Session:  Steatosis and Steatohepatitis

Title:  NGM282 Ameliorates Hepatic Lipotoxicity as Measured by Lipidomics and Gene Expression in a Diet-Induced Mouse Model of Nonalcoholic Steatohepatitis (NASH) (Publication 2008)
Authors:  Lei Ling, Mei Zhou, Marc Learned, Stephen J. Rossi, Alex M. DePaoli, Hui Tian
Date:  Monday, October 23, 2017
Time:  8:00 a.m. to 5:30 p.m. ET
Session:  Steatohepatitis Experimental
Presidential Poster of Distinction
Eposter presentation:  Monday, October 23, 2017 from 9:00 a.m. to 9:30 a.m. ET

Abstracts and additional information can be found on The Liver Meeting website.

About NGM282 in NASH
NGM282 is an analog of the human hormone FGF19 that dramatically reduces LFC and improves liver function by targeting multiple pathogenic pathways of nonalcoholic steatohepatitis (NASH). NGM Bio has generated robust preclinical and clinical evidence supporting NGM282's ability to significantly improve steatosis, inflammation and fibrosis. This single-agent therapeutic has the potential to resolve NASH and reverse fibrosis rapidly, completely and across a broad spectrum of patients.

About NGM Biopharmaceuticals, Inc.
NGM Bio is a research-driven biotechnology company committed to discovering and developing novel biologics for the treatment of life-threatening diseases. NGM Bio's portfolio consists of multiple programs in clinical testing and more than a dozen additional programs in various stages of preclinical development. The company's most advanced compound, NGM282, is a wholly-owned asset that has completed a Phase 2 trial in NASH. NGM Bio has established a broad strategic collaboration with Merck. NGM Bio is backed by The Column Group, Merck, Prospect Ventures, Topspin Partners, Rho Ventures, Tichenor Ventures and other leading investors around the world. For more information, please visit www.ngmbio.com.

SOURCE NGM Bio