AN2 Provides Strategic Update for Phase 3 EBO-301 Trial in Treatment Refractory MAC Lung Disease
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
AN2 Therapeutics, Inc. (NASDAQ:ANTX), a biopharmaceutical company focused on discovering and developing novel small molecule therapeutics derived from its boron chemistry platform, today announced its submission of an amended statistical analysis plan to the FDA selecting the Quality of Life – Bronchiectasis (QOL-B) respiratory domain patient reported outcome (PRO) instrument as the primary efficacy endpoint for the Phase 3 part of the EBO-301 trial. The Company will evaluate whether the Phase 3 data supports the Phase 2 findings, where potential clinical proof-of-concept was shown. The Company plans to review both Phase 2 and Phase 3 results with the FDA and discuss potential registrational pathways.
"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 U.S. Securities and Exchange Commission(SEC). These filings, when made, are available on the investor relations section of AN2's website at www.an2therapeutics.com and on the SEC's website at www.sec.gov. Forward-looking statements contained in this press release are made as of this date, and AN2 undertakes no duty to update such information except as required under applicable law.
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COMPANY CONTACT:
Lucy O. Day
Chief Financial Officer
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INVESTOR AND MEDIA CONTACT:
Anne Bowdidge
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