AN2 Therapeutics Announces Strategic Update on Phase 3 EBO-301 Trial for Treatment-Refractory MAC Lung Disease
AN2 Therapeutics, Inc. (Nasdaq: ANTX), a biopharmaceutical company dedicated to discovering and developing innovative small-molecule therapeutics leveraging its proprietary boron chemistry platform, has announced a significant update regarding the Phase 3 portion of its ongoing EBO-301 clinical trial. The company has submitted an amended statistical analysis plan (SAP) to the U.S. Food and Drug Administration (FDA), incorporating the Quality of Life – Bronchiectasis (QOL-B) respiratory domain patient-reported outcome (PRO) instrument as the primary efficacy endpoint. This decision underscores AN2 Therapeutics’ commitment to aligning with FDA guidance on non-tuberculous mycobacterial (NTM) lung disease drug development while building on promising findings from the Phase 2 study.
The Phase 3 segment of the EBO-301 trial is a critical component in evaluating the efficacy of AN2’s novel therapy for patients suffering from treatment-refractory Mycobacterium avium complex (MAC) lung disease, a serious and often debilitating condition characterized by persistent infection, chronic respiratory symptoms, and significant reductions in quality of life. AN2 Therapeutics aims to assess whether the Phase 3 data reinforces the clinical proof-of-concept established in Phase 2 and intends to engage with the FDA to discuss potential regulatory pathways should the trial yield positive results.
Advancing Clinical Development in a Critical Unmet Need
NTM lung disease, particularly MAC lung infections, remains a substantial unmet medical need. Current treatment regimens often consist of long, complex antibiotic courses with limited efficacy, especially for patients with treatment-refractory disease. AN2 Therapeutics recognizes the urgent demand for novel therapeutic options that improve clinical outcomes and patient-reported symptoms in this highly refractory population with minimal or no viable treatment alternatives.
“In Phase 2, we observed potentially meaningful clinical improvement in a highly refractory population,” stated Eric Easom, Co-Founder, President, and Chief Executive Officer of AN2 Therapeutics. “The FDA has made it clear that the primary benchmark for NTM drug approval is patient-reported improvement in symptoms. Our recent statistical analysis plan submission provides an opportunity to seek FDA input on our selection of QOL-B as the new primary efficacy endpoint before unblinding the Phase 3 data and requesting a formal regulatory meeting. Should the Phase 3 data confirm the Phase 2 findings, we plan to meet with the FDA to discuss potential registrational pathways in this population with minimal to no treatment options.”
The FDA’s emphasis on patient-reported outcomes as a critical determinant for regulatory approval in NTM lung disease is shaping the design of new clinical trials. By incorporating the QOL-B respiratory domain PRO score as the primary efficacy endpoint, AN2 Therapeutics is adopting a patient-centric approach that aligns with the evolving regulatory landscape. This strategic decision enhances the potential for EBO-301 to demonstrate meaningful clinical benefit in a manner consistent with prior FDA-approved treatments.
Significance of the QOL-B Respiratory Domain PRO as the Primary Endpoint
The updated statistical analysis plan for the Phase 3 portion of the EBO-301 trial designates the QOL-B respiratory domain PRO score change from baseline to treatment at month 6 (least squares mean analysis) as the primary endpoint. The selection of this outcome measure follows regulatory precedent and scientific rationale.
AN2 Therapeutics has drawn insights from the FDA’s guidance on NTM drug development, which emphasizes the importance of clinical outcome measures that reflect symptom improvement from the patient’s perspective. The use of the QOL-B respiratory domain PRO score as the primary endpoint is supported by its validation in previous studies, including Insmed’s confirmatory ENCORE study of Arikayce (amikacin liposome inhalation suspension) in treatment-naïve MAC patients, where the same instrument served as the primary efficacy measure.
By aligning with prior regulatory approvals and clinical development strategies, AN2 Therapeutics is positioning EBO-301 for a streamlined and well-supported regulatory review process. The QOL-B respiratory domain PRO is specifically designed to capture changes in key respiratory symptoms experienced by MAC lung disease patients, including cough, sputum production, breathlessness, and overall functional impairment. This metric ensures that efficacy assessments are directly relevant to patient experiences and treatment expectations.
Regulatory and Commercial Implications
The decision to modify the primary efficacy endpoint has broader implications for AN2 Therapeutics’ regulatory and commercial strategy. The FDA’s growing emphasis on patient-reported outcomes in NTM lung disease suggests that therapies demonstrating meaningful symptom relief could have a clear pathway toward approval. If the Phase 3 data corroborates the Phase 2 findings, AN2 Therapeutics intends to engage in discussions with the FDA to determine the most efficient pathway to potential regulatory submission.
The commercial landscape for NTM lung disease treatments is evolving, with increasing recognition of the need for new therapies that improve patients’ quality of life. AN2 Therapeutics’ boron-based small molecule approach offers a novel mechanism of action distinct from conventional antibiotic regimens, potentially providing a differentiated therapeutic option for patients with refractory MAC lung disease. Should EBO-301 gain FDA approval, it could offer a much-needed alternative to existing treatments, which often have limited efficacy and significant toxicity concerns.
Future Steps and Expected Milestones
AN2 Therapeutics remains committed to executing a rigorous clinical development program for EBO-301. The company has outlined key milestones for the coming year, including the anticipated release of topline Phase 3 results in the second quarter of 2025. The timing of FDA feedback on the amended statistical analysis plan may impact this timeline, but AN2 is proactively preparing for regulatory discussions and potential next steps.
Looking ahead, the company will focus on:
- Engaging with the FDA to finalize discussions on the updated primary efficacy endpoint and seek alignment on the regulatory pathway.
- Analyzing Phase 3 data to determine whether the results confirm the findings observed in the Phase 2 trial.
- Exploring commercialization strategies in anticipation of a potential future product launch, should the trial outcomes support regulatory approval.
- Collaborating with the medical community to ensure that healthcare providers and patients are informed about EBO-301’s potential role in addressing treatment-refractory MAC lung disease.
