Astria Therapeutics, Inc. announced positive initial proof-of-concept results from the ALPHA-STAR Phase 1b/2 clinical trial evaluating STAR-0215, a monoclonal antibody inhibitor of plasma kallikrein, in hereditary angioedema (HAE) patients. Initial results demonstrate a favorable safety and tolerability profile, mean monthly attack rate reduction of 90%-96% for up to 6 months of follow up, and support both three- and six-month dosing regimens. Based on the positive results, Astria plans to advance STAR-0215 to Phase 3 development with trial initiation expected in first quarter of 2025 and top-line results expected by year-end 2026.

ALPHA-STAR is a dose-ranging proof-of-concept trial in adults with HAE Type 1 or 2 designed to assess safety, tolerability, efficacy, pharmacokinetics (PK), pharmacodynamics (PD), and quality of life in patients receiving single and multiple doses of STAR-0215 delivered subcutaneously to prevent attacks in HAE. Target enrollment of 16 patients has been achieved and all doses have been administered. All cohorts began with an eight-week run-in period to measure baseline HAE attacks and safety, efficacy, PK, and PD are assessed through 6-months (Day 168) after the last dose received.

The initial efficacy and safety data-cut was as of March 13, 2024. Cohort 1 evaluated a 450 mg dose and all four patients have completed 6 months of follow-up. Efficacy observations compared to baseline through 6 months of follow-up were as follows: 92% reduction in monthly attack rate; 96% reduction in moderate and severe attacks; 91% reduction in acute rescue medication use; 50% of patients were attack-free through 3 months of follow-up.

Cohort 2 evaluated a 600 mg dose followed by a 300 mg dose three months later, on Day 84. The Company plans to evaluate this dosing regimen in Phase 3. All six patients have completed 3 months of follow up and three patients have completed 6 months of follow-up. Efficacy observations compared to baseline through 6 months of follow-up were as follows: 96% reduction in monthly attack rate; 98% reduction in moderate and severe attacks; 94% reduction in acute rescue medication use; 67% of patients were attack-free and 100% of patients were attack-free in the first month after dosing, demonstrating rapid onset of action.

Cohort 3 received a 600 mg dose followed by a 600 mg dose one month later, on Day 28. Four of six patients have completed 3 months of follow-up. Efficacy observations compared to baseline through 3 months of follow-up were as follows: 90% reduction in monthly attack rate; 100% reduction in moderate and severe attacks; 95% reduction in acute rescue medication use and 50% of patients were attack-free.

Preliminary PK and PD data are consistent with Phase 1a data in healthy subjects and consistent with observed efficacy. STAR-0215 was generally well-tolerated with no serious treatment-emergent adverse events (TEAEs) and no discontinuations. There were two treatment-related TEAEs (both mild), one of which was a case of dizziness and the other a transient injection site reaction (rash).

There were no injection site reactions of pain. After completion of the ALPHA-STAR trial, patients have the opportunity to continue to receive STAR-0215 every three or six months in the long-term open label ALPHA-SOLAR trial. Initial safety and efficacy data from Q3M and Q6M dosing in the ALPHA-SOLAR trial are expected mid-2025.

The observed efficacy, PK, PD, and safety and tolerability profile of STAR-0215 support advancement of STAR-0215 into Phase 3 development. To progress STAR-0215 to market as quickly as possible, the Company plans to focus the Phase 3 program on Q3M dosing initially, immediately followed by a second trial to support label expansion to Q6M. Pending regulatory feedback, the Company expects to start a pivotal Q3M Phase 3 trial in First Quarter 2025, with top-line results expected by year-end 2026.

The Company expects that its current cash, cash equivalents, and short-term investments of $246.5 million as of December 31, 2023, plus $137.1 million from financing activity in the first quarter of 2024, will be sufficient to fund the Company into mid-2027 including all STAR-0215 program activities through the completion of a planned Q3M Phase 3 pivotal trial as well as advancing the Company?s STAR-0310 OX40 program through IND submission and early proof-of-concept results from a Phase 1a trial.