Akero Therapeutics (AKRO) Jefferies 2024 Global Healthcare Conference summary

Competitive landscape and drug positioning

• Efruxifermin demonstrated a 75% one-stage fibrosis improvement over 96 weeks, with a 51% effect size, outperforming placebo and showing faster action compared to tirzepatide, which had a 21% effect size at 52 weeks.

• Combination with GLP-1s, such as tirzepatide, may benefit advanced patients (F3) by increasing the probability of avoiding cirrhosis, as 80% of patients on GLP-1s alone do not achieve a 1-stage improvement.

• Data show efruxifermin can normalize liver fat in 90% of patients already on GLP-1s within 12 weeks, with added benefits in diabetes and weight loss, and no increase in GI side effects.

• No additive safety or tolerability issues were observed when combining efruxifermin with GLP-1s; in fact, GI adverse events were numerically lower.

F4 cirrhosis study and expectations

• The 36-week F4 study did not meet the primary endpoint (10% effect size), but showed statistical significance for NASH resolution and some patients had two- or three-stage fibrosis improvement.

• The 96-week F4 data is expected in Q1 next year, with anticipation of improved results over the 36-week data, based on prior F2/3 study trends.

• Placebo response in F4 is expected to decrease over time, with historical studies showing 10-11% improvement rates, while efruxifermin could rise from 24% to around 30%.

• A 20% delta in this high-mortality population is considered clinically meaningful, though statistical significance will depend on final sample size and discontinuation rates.

• The F4 study started with 182 patients, with an estimated 25% dropout rate by week 96, still leaving a robust sample size for analysis.

Phase III F2/F3 study and broader market context

• The Phase III F2/F3 study began enrollment in December, targeting 1,000 patients, with strong prior efficacy data supporting rapid enrollment.

• The NASH/MASH market is highly competitive, with multiple agents (GLP-1s, tirzepatide, glucagon agonists) in development or on the market, but efruxifermin's rapid and robust efficacy differentiates it.

• Pharma interest in MASH remains muted from an M&A perspective, but large companies maintain internal programs; Pfizer is a top-10 shareholder and maintains regular contact.

• Upcoming catalysts include the F4 96-week data in Q1 and continued progress in the Phase III F2/F3 trial.