–As previously reported, the ALPINE 4 study met its primary endpoint, with aldafermin 3 mg demonstrating a statistically significant reduction in Enhanced Liver Fibrosis (ELF) score compared to placebo after 48 weeks of treatment–

–ELF, an FDA-approved non-invasive blood test, can be used to predict liver-related events in patients with nonalcoholic steatohepatitis (NASH) and compensated cirrhosis–

–Dose-dependent improvements reported across histologic and multiple non-invasive secondary endpoints in ALPINE 4–

–In the trial, aldafermin treatment up to one year was generally well tolerated with no treatment-related serious adverse events–

SOUTH SAN FRANCISCO, CA, USA I November 13, 2023 I NGM Biopharmaceuticals, Inc. (NGM Bio) (Nasdaq: NGM), a biotechnology company focused on discovering and developing transformative therapeutics for patients, today shared positive, comprehensive results from its Phase 2b ALPINE 4 trial of aldafermin, an engineered FGF19 analog product candidate, in patients with compensated cirrhosis (liver fibrosis stage 4 or F4) due to NASH in an oral plenary presentation at the American Association for the Study of Liver Diseases (AASLD) The Liver Meeting®.

The presentation titled “Positive Results from the ALPINE 4 Study: a Randomized, Double-blind, Placebo-controlled, Multicenter, Phase 2b Trial Evaluating Multiple Doses of the FGF19 Analogue Aldafermin in Patients with Compensated Cirrhosis Due to Nonalcoholic Steatohepatitis,” is available to conference attendees for the duration of AASLD The Liver Meeting and will be archived on the ‘Publications’ page of NGM Bio’s website here following the meeting. The ALPINE 4 data shared at AASLD The Liver Meeting follow positive topline results on the primary endpoint reported by NGM Bio in May 2023.

Mary E. Rinella, M.D., Professor of Medicine and Director, Metabolic and Steatotic Liver Disease Program at the University of Chicago Pritzker School of Medicine, who gave the oral presentation, commented, “We are pleased to see that the ALPINE 4 study is the first Phase 2b in NASH cirrhosis to reach its primary endpoint. In addition to demonstrating statistically significant reductions in ELF score, the trial primary endpoint, aldafermin also signaled dose-dependent improvements in liver fibrosis and multiple non-invasive secondary endpoints. Compensated cirrhosis due to NASH is a notoriously difficult-to-treat disease with no approved treatment options. It’s very encouraging to see multiple key clinical measurements moving in the right direction in the ALPINE 4 study, a promising achievement in the quest to bring forward safe, effective therapeutics for patients suffering with F4 NASH.”

“We are excited to share the comprehensive positive data set from the ALPINE 4 study with the hepatology community at AASLD. It’s gratifying to see the potential impact aldafermin is having on NASH progression and liver health in patients with F4 NASH. This Phase 2b data set furthers our belief in aldafermin’s therapeutic potential,” said Hsiao D. Lieu, M.D., Chief Medical Officer at NGM Bio.

The ALPINE 4 trial evaluated the efficacy, safety and tolerability of 1 mg and 3 mg doses of aldafermin compared to placebo in 160 patients with compensated cirrhosis (F4) due to NASH. (A 0.3 mg aldafermin cohort was part of the original design of the trial and enrolled seven patients prior to being discontinued in favor of enrolling more patients in the 1 mg and 3 mg arms of the trial. Patients in the 0.3 mg arm were primarily evaluated for safety.) The study showed that the primary endpoint was achieved; patients treated with aldafermin 3 mg showed a statistically significant reduction in ELF score compared to the placebo arm after 48 weeks of treatment. ELF is the first and only FDA-approved non-invasive test reflecting NASH prognosis. ELF measures direct markers of liver fibrosis and can be used to predict liver-related events in patients with NASH and compensated cirrhosis.

Although ALPINE 4 was not statistically powered for the secondary endpoint of histological fibrosis improvement of ≥ 1-stage (NASH Clinical Research Network, or CRN, criteria), a dose-dependent trend in fibrosis improvement was observed. Aldafermin demonstrated significant, dose-dependent improvements across all of the study’s non-invasive secondary endpoints, including neoepitope-specific N-terminal propeptide of type III collagen (Pro-C3), alanine aminotransferase (ALT), aspartate aminotransferase (AST), 7alpha-hydroxy-4-cholesten-3-one (C4), bile acids and liver stiffness measurement (LSM) by FibroScan® at week 48. These non-invasive tests are correlated with liver fibrogenesis, liver inflammation and injury, and NASH progression.

Aldafermin was generally well tolerated in the ALPINE 4 study with no treatment-related serious adverse events and a safety and tolerability profile generally consistent with prior trials of aldafermin, including higher levels of gastrointestinal events in patients treated with aldafermin as compared to patients treated with placebo. Aldafermin-associated increase in low-density lipoprotein cholesterol, consistent with on-target inhibition of bile acid synthesis, was mitigated by co-administration of rosuvastatin. There was no observed signal for adverse cardiovascular events in this trial related to aldafermin.

A manuscript on the ALPINE 4 study has been accepted and published online ahead-of-print in Hepatology (Hepatology 2023; doi: 10.1097/HEP.0000000000000607).

About NGM Bio
NGM Bio is focused on discovering and developing novel, life-changing medicines for people whose health and lives have been disrupted by disease. The company’s biology-centric drug discovery approach aims to seamlessly integrate interrogation of complex disease-associated biology and protein engineering expertise to unlock proprietary insights that are leveraged to generate promising product candidates and enable their rapid advancement into proof-of-concept studies. As explorers on the frontier of life-changing science, NGM Bio aspires to operate one of the most productive research and development engines in the biopharmaceutical industry. All therapeutic candidates in the NGM Bio pipeline have been generated by its in-house discovery engine, always led by biology and motivated by unmet patient need. Visit us at www.ngmbio.com for more information.