Akero Therapeutics

Akero Therapeutics' Efruxifermin (EFX) demonstrated statistically significant cirrhosis reversal in patients with MASH in a Phase 2b trial.

• Areteia Therapeutics is progressing dexpramipexole, a novel oral therapy, into Phase III clinical trials for severe eosinophilic asthma. • Dexpramipexole aims to reduce eosinophil levels by inhibiting their maturation in the bone marrow, offering a potential alternative to injectable biologics. • Akero Therapeutics will present updates on its MASH treatment, EFX, currently in Phase 3 trials, at the J.P. Morgan Healthcare Conference. • Both Areteia and Akero will present at the J.P. Morgan Healthcare Conference on January 14, 2025, to discuss their clinical-stage programs.

• The non-alcoholic steatohepatitis (NASH) market is poised for substantial growth, projected to expand significantly by 2032 across the United States, EU5 (Germany, Spain, Italy, France, and United Kingdom), and Japan. • This growth is fueled by the introduction of novel therapies targeting NASH, with several drugs in Phase II and Phase III clinical trials showing promise for improving treatment outcomes. • Key players such as Madrigal Pharmaceuticals, Intercept Pharmaceuticals, and Novo Nordisk are actively developing innovative treatments, contributing to a dynamic and competitive market landscape. • The increasing prevalence of NASH and the growing understanding of its pathophysiology are driving the demand for effective therapies, creating opportunities for pharmaceutical companies.

• Boston Pharmaceuticals' efimosfermin alfa demonstrated statistically significant fibrosis improvement in MASH patients, with 45.2% showing at least a one-stage improvement compared to 20.6% in the placebo group. • The Phase II trial also revealed that 67.7% of patients treated with efimosfermin alfa achieved MASH resolution without fibrosis worsening, versus 29.4% in the placebo group, indicating a significant treatment effect. • Efimosfermin alfa, a long-acting FGF21 analog administered monthly, offers a potentially more convenient dosing schedule compared to other FGF21 analogs in development for MASH. • The drug exhibited a good tolerability profile over 24 weeks, with a low incidence of injection-site reactions and gastrointestinal toxicities, supporting its further development.

• Akero Therapeutics' efruxifermin (EFX) demonstrates significant anti-fibrotic effects in patients with F2/F3 MASH, as shown in the Phase 2b HARMONY study. • The Phase 3 SYNCHRONY study, assessing EFX's safety and tolerability, has completed enrollment, with top-line data expected in the first half of 2026. • Analysts maintain a Buy rating for Akero, citing the potential of EFX in treating MASH and MASLD, along with market exclusivity projected through 2037. • Upcoming results from the Phase 2b SYMMETRY study, focusing on EFX’s effects in F4 MASH, are anticipated as a critical catalyst for the company’s future.

• Akero Therapeutics reported a strong cash position of $787.1 million, expected to fund operations into the second half of 2027, supporting the advancement of its MASH treatment program. • The Phase 3 SYNCHRONY program progresses with the first patient dosed in the Outcomes study, evaluating efruxifermin (EFX) in patients with compensated cirrhosis due to MASH. • Results from the Phase 3 SYNCHRONY Real-World study are anticipated in 2026, while the Histology study expects primary endpoint data in the first half of 2027. • Week 96 results from the Phase 2b SYMMETRY study, assessing EFX in compensated cirrhosis patients, are on track for reporting in February 2025.

• Akero Therapeutics has dosed the first patient in its Phase 3 SYNCHRONY Outcomes study, evaluating efruxifermin (EFX) in patients with compensated cirrhosis (F4) due to MASH. • The SYNCHRONY program includes three ongoing, randomized, placebo-controlled trials assessing EFX for both pre-cirrhotic MASH (F2-F3) and compensated cirrhosis (F4). • Week 96 results from the Phase 2b SYMMETRY study, which evaluates EFX in patients with compensated cirrhosis (F4), are expected to be reported in February 2025. • Akero anticipates that its current cash reserves will be sufficient to fund the SYNCHRONY Histology and Real-World studies through the readout of their primary endpoints.

• Novo Nordisk's semaglutide demonstrated statistically significant improvement in liver fibrosis and resolution of steatohepatitis in MASH patients during a Phase 3 trial. • The ESSENCE trial evaluated once-weekly semaglutide 2.4 mg versus placebo in 1,200 adults with MASH and moderate to advanced liver fibrosis over 72 weeks. • Madrigal Pharmaceuticals, recently approved for Rezdiffra, saw a 22% stock increase, while 89Bio and Akero Therapeutics also experienced gains following the announcement. • Semaglutide's potential impact on MASH is significant, as one in three overweight or obese individuals may have the condition, representing a substantial unmet need.

• Sagimet Biosciences' denifanstat has received Breakthrough Therapy Designation from the FDA for treating noncirrhotic MASH with moderate to advanced liver fibrosis. • The designation was supported by Phase 2b FASCINATE-2 study data, which demonstrated statistically significant improvements in MASH resolution and fibrosis reduction. • Denifanstat is an oral, selective fatty acid synthase (FASN) inhibitor that targets fat accumulation, inflammation, and fibrosis, the main drivers of MASH. • Sagimet plans to initiate a Phase 3 clinical program for denifanstat in MASH by the end of 2024, aiming to address the urgent need for new therapies.

• Akero Therapeutics has dosed the first patient in its Phase 3 SYNCHRONY Outcomes trial evaluating Efruxifermin (EFX) for compensated cirrhosis (F4) due to MASH. • The SYNCHRONY program includes two other ongoing trials: SYNCHRONY Histology (pre-cirrhotic MASH, F2-F3) and SYNCHRONY Real-World (non-invasively diagnosed MASLD/MASH, F1-F4). • Efruxifermin (EFX) is a novel Fc-FGF21 fusion protein designed to reduce liver fat and inflammation, reverse fibrosis, and improve insulin sensitivity and lipid metabolism. • Topline results from the Phase 2b SYMMETRY study of EFX in compensated cirrhosis due to MASH (F4) are expected in the first quarter of 2025.