AN2 Provides Strategic Update for Phase 3 EBO-301 Trial in Treatment Refractory MAC Lung Disease
AN2 Therapeutics (NASDAQ: ANTX) has announced a strategic update for its Phase 3 EBO-301 trial in treatment-refractory MAC lung disease. The company has submitted an amended statistical analysis plan to the FDA, selecting the Quality of Life – Bronchiectasis (QOL-B) respiratory domain patient reported outcome as the primary efficacy endpoint.
In the Phase 2 study, epetraborole showed nominal statistical superiority versus placebo, with a difference in least squares mean change from baseline of 6.90 (p=0.0365). The company plans to unblind Phase 3 data in Q2 2025, which includes 97 completed subjects. If Phase 3 data confirms Phase 2 findings, AN2 will discuss potential registrational pathways with the FDA for this highly refractory population.
This approach aligns with FDA's 2023 Guidance for Industry on NTM drug development and follows the precedent of Insmed's confirmatory Arikayce study in treatment-naïve MAC patients.
AN2 Therapeutics (NASDAQ: ANTX) ha annunciato un aggiornamento strategico per il suo studio di fase 3 EBO-301 nel trattamento della malattia polmonare MAC refrattaria ai trattamenti. L'azienda ha presentato un piano di analisi statistica modificato alla FDA, selezionando il Quality of Life – Bronchiectasis (QOL-B) come principale endpoint di efficacia, basato sui risultati riportati dai pazienti.
Nello studio di fase 2, epetraborole ha mostrato una superiorità statistica nominale rispetto al placebo, con una differenza nel cambiamento medio dei minimi quadrati rispetto al basale di 6,90 (p=0,0365). L'azienda prevede di rendere noti i dati della fase 3 nel secondo trimestre del 2025, che includono 97 soggetti completati. Se i dati della fase 3 confermeranno i risultati della fase 2, AN2 discuterà le potenziali vie di registrazione con la FDA per questa popolazione altamente refrattaria.
Questo approccio è in linea con le linee guida della FDA del 2023 per l'industria sullo sviluppo di farmaci contro il NTM e segue il precedente studio di conferma di Insmed su Arikayce in pazienti MAC naïve al trattamento.
AN2 Therapeutics (NASDAQ: ANTX) ha anunciado una actualización estratégica para su ensayo de fase 3 EBO-301 en la enfermedad pulmonar MAC refractaria al tratamiento. La empresa ha presentado un plan de análisis estadístico modificado a la FDA, seleccionando el Quality of Life – Bronchiectasis (QOL-B) como el principal criterio de eficacia basado en los resultados reportados por los pacientes.
En el estudio de fase 2, epetraborole mostró una superioridad estadística nominal frente al placebo, con una diferencia en el cambio medio de mínimos cuadrados desde la línea base de 6.90 (p=0.0365). La empresa planea hacer públicos los datos de la fase 3 en el segundo trimestre de 2025, que incluye 97 sujetos completados. Si los datos de la fase 3 confirman los hallazgos de la fase 2, AN2 discutirá posibles vías de registro con la FDA para esta población altamente refractaria.
Este enfoque está alineado con la Guía de la FDA de 2023 para la industria sobre el desarrollo de medicamentos contra NTM y sigue el precedente del estudio de confirmación de Insmed sobre Arikayce en pacientes MAC naïve al tratamiento.
AN2 Therapeutics (NASDAQ: ANTX)는 치료에 저항성이 있는 MAC 폐 질환에 대한 3상 EBO-301 시험의 전략적 업데이트를 발표했습니다. 이 회사는 FDA에 수정된 통계 분석 계획을 제출했으며, Quality of Life – Bronchiectasis (QOL-B) 호흡기 영역 환자 보고 결과를 주요 유효성 평가 지표로 선택했습니다.
2상 연구에서 epetraborole는 위약에 비해 명목상 통계적 우위를 보였으며, 기준선에서 최소 제곱 평균 변화의 차이는 6.90(p=0.0365)로 나타났습니다. 이 회사는 2025년 2분기에 97명의 완료된 피험자를 포함한 3상 데이터의 결과를 공개할 계획입니다. 3상 데이터가 2상 결과를 확인하면, AN2는 이 고도로 저항성인 인구에 대해 FDA와의 잠재적인 등록 경로에 대해 논의할 것입니다.
이 접근 방식은 NTM 약물 개발에 대한 FDA의 2023년 산업 지침과 일치하며, 치료 경험이 없는 MAC 환자에 대한 Insmed의 확인 연구인 Arikayce의 선례를 따릅니다.
AN2 Therapeutics (NASDAQ: ANTX) a annoncé une mise à jour stratégique pour son essai de phase 3 EBO-301 dans le traitement de la maladie pulmonaire MAC réfractaire aux traitements. L'entreprise a soumis un plan d'analyse statistique modifié à la FDA, sélectionnant le Quality of Life – Bronchiectasis (QOL-B) comme critère principal d'efficacité basé sur les résultats rapportés par les patients.
Dans l'étude de phase 2, l'epetraborole a montré une supériorité statistique nominale par rapport au placebo, avec une différence dans le changement moyen des moindres carrés par rapport à la ligne de base de 6,90 (p=0,0365). L'entreprise prévoit de rendre publics les données de la phase 3 au deuxième trimestre 2025, qui incluent 97 sujets complétés. Si les données de la phase 3 confirment les résultats de la phase 2, AN2 discutera des voies d'enregistrement potentielles avec la FDA pour cette population hautement réfractaire.
Cette approche est conforme aux directives de la FDA de 2023 pour l'industrie sur le développement de médicaments contre le NTM et suit le précédent de l'étude de confirmation d'Insmed sur l'Arikayce chez les patients MAC naïfs de traitement.
AN2 Therapeutics (NASDAQ: ANTX) hat ein strategisches Update für seine Phase-3-Studie EBO-301 zur Behandlung von therapieresistenten MAC-Lungenkrankheiten bekannt gegeben. Das Unternehmen hat einen geänderten statistischen Analyseplan bei der FDA eingereicht und den Quality of Life – Bronchiectasis (QOL-B) Atemweg-Domänen-Patientenbericht als primäres Wirksamkeitsziel ausgewählt.
In der Phase-2-Studie zeigte epetraborole eine nominelle statistische Überlegenheit gegenüber dem Placebo, mit einer Differenz im kleinsten quadratischen Mittelwertsänderung von 6,90 (p=0,0365). Das Unternehmen plant, die Daten der Phase 3 im 2. Quartal 2025 zu veröffentlichen, die 97 abgeschlossene Probanden umfassen. Wenn die Daten der Phase 3 die Ergebnisse der Phase 2 bestätigen, wird AN2 potenzielle Zulassungswege mit der FDA für diese hochgradig refraktäre Population diskutieren.
Dieser Ansatz steht im Einklang mit den Leitlinien der FDA von 2023 für die Industrie zur Entwicklung von NTM-Arzneimitteln und folgt dem Präzedenzfall der bestätigenden Arikayce-Studie von Insmed bei behandlungsnaiven MAC-Patienten.
- Phase 2 showed statistical superiority vs placebo (p=0.0365)
- 97 subjects completed Phase 3 treatment
- Alignment with FDA guidance on NTM drug development
- Strong evidence for reliability and validity in PRO measurements
- Phase 3 trial was previously terminated
- Change in primary endpoint mid-trial
- Delayed results timeline to Q2 2025
- Regulatory uncertainty pending FDA review
Insights
The strategic modification of AN2 Therapeutics' Phase 3 trial endpoint represents a calculated pivot that could significantly accelerate their path to market. The selection of QOL-B as the primary endpoint is particularly noteworthy for three key reasons:
First, this change aligns perfectly with the FDA's 2023 guidance emphasizing patient-reported outcomes in NTM drug development. The nominal statistical superiority demonstrated in Phase 2 (6.90-point improvement, p=0.0365) provides a strong foundation for the Phase 3 evaluation. This statistical significance, while modest, suggests meaningful clinical improvement in a highly challenging treatment-refractory population.
Second, by following Insmed's Arikayce precedent, AN2 is taking a well-validated regulatory approach. This strategic alignment with an approved therapy's confirmatory study significantly reduces regulatory risk and could streamline the approval process. The fact that 97 subjects completed the Phase 3 treatment provides a robust dataset for analysis.
Third, the timing of this modification is crucial. With Phase 3 data unblinding planned for Q2 2025, AN2 is positioning itself for potentially expedited discussions with the FDA regarding registrational pathways. This is particularly significant given the treatment options available for refractory MAC lung disease patients.
However, investors should note several critical factors: The change in endpoint, while strategically sound, indicates a careful recalibration of expectations. The focus on patient-reported outcomes rather than traditional microbiological endpoints suggests a more nuanced approach to demonstrating clinical benefit. The market opportunity remains substantial, but success will depend on the Phase 3 data confirming the Phase 2 findings and subsequent FDA discussions.
AN2 Selects QOL-B as New Phase 3 Primary Efficacy Endpoint
Goal to Accelerate Unblinding Phase 3 Data in Q2 2025 Ahead of Potential FDA Meeting
“In Phase 2, we observed potentially meaningful clinical improvement in a highly refractory population. The FDA has made it clear that the primary bar for NTM drug approval is patient-reported improvement in NTM symptoms. Our recent statistical analysis plan submission provides the opportunity to seek FDA input on our selection of QOL-B as the new primary efficacy endpoint prior to unblinding the Phase 3 data and requesting a formal meeting,” said Eric Easom, Co-Founder, President and Chief Executive Officer. “Should the Phase 3 data confirm the Phase 2 findings, we plan to meet with the FDA to discuss potential registrational pathways in this highly refractory population with minimal to no treatment options.”
QOL-B Respiratory Domain PRO as Revised Primary Endpoint Follows Recent Precedent of Arikayce Confirmatory ENCORE Study
Based on the results of the Phase 2 study, the Company has updated the Phase 3 portion of the statistical analysis plan to designate the QOL-B respiratory domain PRO score change from baseline to treatment at month 6 (least squares mean analysis) as the primary Phase 3 endpoint. The Company believes that this approach aligns with current FDA Guidance for Industry on NTM drug development regarding the use of a clinical outcome measure as the sole primary endpoint and, it also follows the precedent established by Insmed’s confirmatory study of Arikayce in treatment-naïve MAC patients, where the same QOL-B instrument has been reported as the primary efficacy measure. The Company intends to release topline Phase 3 results in the second quarter of 2025, subject to the timing of any potential FDA response.
About the QOL-B Respiratory Domain PRO Endpoint
FDA’s 2023 Guidance for Industry on NTM drug development recommends PRO-based clinical outcome measures as the primary efficacy endpoint in registrational trials. The primary purpose of the Phase 2 part of the EBO-301 study was to test the validity of multiple patient-reported outcome tools in a treatment refractory population, with the goal of identifying a PRO-based primary endpoint for the Phase 3 portion of the trial.
Using QOL-B as a continuous measure of clinical improvement, epetraborole showed nominal statistical superiority versus placebo in change from baseline to month 6 in the Phase 2 portion of the trial (prespecified secondary endpoint, difference in least squares mean change from baseline: 6.90, p=0.0365). Furthermore, a post-hoc analysis of the MACrO2 PRO using a 100-point continuous scale similar to QOL-B, showed a comparable nominally statistically superior result for the epetraborole arm versus the placebo arm (difference in least squares mean change from baseline: 5.81, p=0.0433). Blinded psychometric analyses incorporating the data from both treatment arms of the Phase 2 study demonstrated strong evidence for the reliability, validity, ability to detect change (responsiveness), and clinically meaningful within-patient changes in both the QOL-B respiratory domain score and the post hoc MACrO2 total scaled score, suggesting that the scores measured from either PRO may be fit-for-purpose in evaluating response to treatment in patients with treatment-refractory NTM lung disease.
The Company reported Phase 2 topline results in August 2024, where it also announced termination of the ongoing Phase 3 portion of the trial. The Company also initiated a full review of the Phase 2 data and an assessment of pathways for continued development in TR-MAC. Ninety-seven subjects completed treatment in Phase 3, the data for which remains blinded and available for analysis as a Phase 3 dataset.
For more information about the EBO-301 study, please visit: www.clinicaltrials.gov (NCT05327803).
About AN2 Therapeutics, Inc.
AN2 Therapeutics, Inc. is a biopharmaceutical company focused on discovering and developing novel small molecule therapeutics derived from its boron chemistry platform. AN2 has a pipeline of boron-based compounds in development for Chagas disease, NTM, and melioidosis, along with early-stage programs focused on targets in infectious diseases and oncology. For more information, please visit our website at www.an2therapeutics.com.
Forward-Looking Statements
This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Forward-looking statements expressed or implied in this press release include, but are not limited to, statements regarding: changes to the primary efficacy endpoint for the Phase 3 part of the EBO-301 trial; regulatory meetings and pathways and alignment with and interpretations of FDA guidance; the Company’s plans to unblind and release top-line results from the Phase 3 data in the second quarter of 2025; the potential of the Company’s boron chemistry platform and early-stage pipeline programs; and other statements that are not historical fact. These statements are based on AN2’s current estimates, expectations, plans, objectives and intentions, are not guarantees of future performance and inherently involve significant risks and uncertainties. Actual results and the timing of events could differ materially from those anticipated in such forward-looking statements as a result of these risks and uncertainties, which include, but are not limited to, risks and uncertainties related to: future trials and data readouts of epetraborole in NTM-MAC and the ability to show clinical efficacy consistent with PRO-based data observed in prospective and post-hoc analyses to date; potential disruptions related to AN2’s ability to implement its plans for its internal boron chemistry platform and early-stage pipeline programs; timely enrollment of patients in AN2’s existing and future clinical trials; disruptions at the FDA and other government agencies caused by funding shortages, staff reductions and statutory, regulatory and policy changes; AN2’s ability to procure sufficient supply of its product candidates for its existing and future clinical trials; the potential for results from clinical trials to differ from preclinical, early clinical, preliminary or expected results; significant adverse events, toxicities or other undesirable side effects associated with AN2’s product candidates; the significant uncertainty associated with AN2’s product candidates ever receiving any regulatory approvals; continued funding by the National Institute of Allergy and Infectious Disease (NIAID) of AN2’s development program for melioidosis; AN2’s ability to obtain, maintain or protect intellectual property rights related to its current and future product candidates; implementation of AN2’s strategic plans for its business and product candidates; the sufficiency of AN2’s capital resources and need for additional capital to achieve its goals; global macroeconomic conditions and global conflicts and other risks, including those described under the heading “Risk Factors” in AN2’s Annual Reports on Form 10-K and Quarterly Reports on Form 10-Q, and AN2’s other reports filed with the
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COMPANY CONTACT:
Lucy O. Day
Chief Financial Officer
l.day@an2therapeutics.com
INVESTOR AND MEDIA CONTACT:
Anne Bowdidge
ir@an2therapeutics.com
Source: AN2 Therapeutics, Inc.
FAQ
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