AN2 Therapeutics (ANTX) Leerink’s Global Healthcare Conference 2025 summary

Development program overview

• Lead compound epetraborole targets nontuberculous mycobacteria (NTM) lung disease caused by MAC, studied in a seamless phase II/III pivotal trial with 80 patients in phase II and 97 in phase III.

• Phase II showed clinical efficacy on primary PRO endpoint (MACrO2), with nominal statistical significance, but culture conversion rates were similar to placebo.

• Patient population was highly refractory: average disease duration nine years, over 50% with severe cavitary disease, and two-thirds resistant to amikacin.

• Phase III was paused to analyze data; primary endpoint shifted to QOL-B respiratory demand, aligning with FDA and precedent from Insmed.

• Phase III data from 97 patients expected to read out in Q2, with database locked and ready for unblinding.

Clinical endpoints and efficacy

• QOL-B respiratory domain chosen as primary endpoint due to relevance and regulatory alignment; both QOL-B and MACrO2 showed nominal statistical significance in phase II.

• At six months, QOL-B improvement was 7.2 points for epetraborole vs 0.2 for placebo (p=0.03), with greater benefit in more severe patients.

• Culture conversion rates were low due to refractory population, but clinical endpoints are prioritized for FDA approval.

• Phase III is powered for the QOL-B endpoint with a 2:1 randomization; baseline characteristics are equal or worse than phase II, favoring potential for improvement.

• No significant emergence of resistance observed during the study, supporting combination therapy approach.

Safety and tolerability

• Epetraborole was generally well tolerated; most adverse events were mild, primarily transient GI effects.

• Mild, slow hemoglobin reduction observed, stabilizing over time and reversible upon discontinuation.

• No significant safety concerns identified, supporting long-term use.