NGM Bio Announces New Histology Data from Phase 2 Trial of NGM282 in Patients with NASH

SOUTH SAN FRANCISCO, Calif., Nov. 9, 2018 /PRNewswire/ -- NGM Biopharmaceuticals, Inc., a clinical stage biotechnology company focused on harnessing powerful biology to develop transformative therapeutics for patients, today announced preliminary histology data from open-label, single-blind, dose-finding expansion cohorts of its Phase 2 study evaluating its lead product candidate, NGM282, in patients with nonalcoholic steatohepatitis (NASH). This ongoing, adaptive Phase 2 trial is evaluating the efficacy, safety and tolerability of daily subcutaneous injections of 0.3 mg, 1 mg, 3 mg and 6 mg of NGM282, an investigational engineered version of the human hormone known as fibroblast growth factor 19 (FGF19), in patients with biopsy-confirmed NASH. The new data reveal that treatment with 1 mg doses of NGM282 resulted in a rapid and robust impact on both fibrosis stage and disease activity as measured by the non-alcoholic fatty liver disease (NAFLD) activity score (NAS) at 12 weeks.

These findings are consistent with data from the NGM282 3 mg biopsy cohort presented earlier this year at EASL's The International Liver Congress in Paris. The new 1 mg biopsy cohort data will be presented during an oral session at 2:15 p.m. PST on Sunday, November 11 at AASLD's The Liver Meeting, which is taking place November 9-13, 2018 in San Francisco.

"These new data augment a growing body of scientific evidence demonstrating the potential of NGM282 to have a profound impact on the underlying pathophysiological drivers of NASH," said Stephen A. Harrison, M.D., Medical Director at Pinnacle Clinical Research, Visiting Professor of Hepatology at University of Oxford, UK and principal investigator on the NGM282 Phase 2 study. "The significant histological improvements observed after just 12 weeks of treatment with NGM282 point to an agent that, if ultimately approved, could provide an important and much needed medicine for physicians to reverse fibrosis in NASH patients with well-established disease."

NGM Bio also will present data on Monday, November 12, 2018 during a poster presentation at The Liver Meeting demonstrating that NGM282 maintained a durable off-treatment response at 18 weeks (i.e., six weeks following cessation of treatment in the 12-week Phase 2 NASH study) on hepatic steatosis, inflammation and fibrosis in biopsy-confirmed NASH patients as measured by MRI-PDFF, ALT and PRO-C3 levels, respectively.

About the Phase 2 NGM282 1 mg and 3 mg Biopsy Cohort Design

Biopsy-confirmed NASH patients were enrolled into two sequential open-label cohorts and dosed with either NGM282 1 mg or 3 mg daily for 12 weeks. Key inclusion criteria included biopsy-proven NASH within three months of screening, NAS ?4 (at least 1 point in each component), Stage 1-3 fibrosis and absolute liver fat content (LFC) of ?8% as assessed by MRI-PDFF. The primary endpoint was a reduction in absolute LFC at 12 weeks, with ?5% identified as clinically significant. Imaging parameters, key biomarkers and histologic response were assessed in all subjects completing 12 weeks of treatment. MRI-PDFF and LiverMultiScantm (LMS) were performed at baseline, six (6) weeks and 12 weeks. Liver biopsies were performed at screening and 12 weeks and centrally read using the NASH CRN criteria by an independent hepatopathologist that was blinded to patient and sequence. Analysis of these two biopsy cohorts, NGM282 1 mg and 3 mg, included only patients that completed 12 weeks of treatment with paired biopsies, n=24 and n=19, respectively.

Baseline patient characteristics were comparable between the two biopsy cohorts and consistent with a general NASH population. Over 80% of subjects across both cohorts had Stage 2 or more advanced fibrosis and the mean NAS at baseline was ?5 for both cohorts.

About the Phase 2 NGM282 1 mg and 3 mg Biopsy Cohort Findings

Improvements seen in the non-invasive and histologic endpoints of NASH were comparable between the two doses. 92% and 100% of subjects treated with NGM282 1 mg and 3 mg, respectively, experienced both a ?5% absolute decrease in LFC and a ?30% relative decrease in LFC at 12 weeks. Statistically significant reductions in ALT, AST, PRO-C3 and ELF were demonstrated by both biopsy cohorts at 12 weeks. Fibrosis improved by ?1 stage in 25% and 42% of subjects treated with NGM282 1 mg and 3 mg, respectively, with four subjects across both doses improving by two stages. A similar proportion of patients in both dose groups demonstrated an improvement in each of the NAS components of steatosis, lobular inflammation and hepatocellular ballooning, and 75% and 84% of NGM282 1 mg and 3 mg patients experienced an improvement in the total NAS.

"We are pleased to continue to share detailed data from our Phase 2 clinical program of NGM282 and are highly encouraged by the consistency seen in the 1 mg and 3 mg dose levels, as well as the durable off-treatment response we have observed," said Alex DePaoli, M.D., Senior Vice President and Chief Medical Officer. "We believe that the breadth and magnitude of the beneficial effect demonstrated by NGM282 across the histological parameters of NASH at 12 weeks will further increase with longer treatment duration."

** p<0.01; *** p<0.001

¹ Analysis included only subjects completing 12W of treatment with paired biopsies in each cohort

NGM282 1 mg and 3 mg demonstrated a favorable safety and tolerability profile consistent with prior clinical studies. Consistent with the drug's mechanism of action and potent inhibition of CYP7A1, LDL-C increased by a similar magnitude above baseline with both study groups but was reduced below baseline levels within two to four weeks by administration of a statin. The most common adverse events were mild gastrointestinal symptoms (nausea, loose/frequent stools) and injection site erythema that resolved during the treatment phase. In the two biopsy study cohorts, there were five serious adverse events, none of which was deemed to be related to treatment by the investigator.

An additional Phase 2 expansion cohort is ongoing to assess the histological effect of NGM282 1 mg in NASH patients at 24 weeks as compared to placebo. In addition, NGM Bio plans to evaluate NGM282 0.3 and 3 mg doses in a 24-week double-blind, placebo-controlled Phase 2b study of NGM282 in NASH patients with F2/F3 fibrosis commencing in the first quarter of 2019.

About NGM Bio

NGM Bio is a clinical-stage biopharmaceutical company focused on developing novel therapeutics based on scientific understanding of key biological pathways underlying cardio-metabolic, liver, oncologic and ophthalmic diseases. The company leverages its biology-centric drug discovery approach to uncover novel mechanisms of action and generate proprietary insights that enable it to move rapidly into proof-of-concept studies and deliver potential first-in-class medicines to patients. NGM Bio aspires to operate one of the most productive research and development engines in the biopharmaceutical industry, with multiple programs in clinical development. Visit www.ngmbio.com for more information.

SOURCE NGM Biopharmaceuticals, Inc.