On November 13, 2024 AN2 Therapeutics, Inc. (Nasdaq: ANTX), a biopharmaceutical company focused on discovering and developing novel small molecule therapeutics derived from its boron chemistry platform reported financial results for the quarter ended September 30, 2024 and provided an update from its ongoing analysis of data from the Phase 2 portion of the EBO-301 trial (Press release, AN2 Therapeutics, NOV 13, 2024, View Source [SID1234648261]).

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"Treatment options for patients with refractory MAC lung disease are extremely limited. Many of these patients are significantly more challenging to convert microbiologically due to the microbial complexity of their infections as well as their very complex lung anatomy, and often experience severe clinical symptoms at this advanced stage of disease. The fact that epetraborole appears to have demonstrated improvements based on two patient reported outcome measures is highly encouraging," said Stephen J. Ruoss, M.D., Professor of Medicine, Pulmonary and Critical Care Medicine at Stanford University School of Medicine. "By potentially improving both their quality of life and clinical outcomes, epetraborole represents a potentially significant advancement in treatment possibilities."

"We are encouraged by this recent data analysis, which indicate that epetraborole may provide clinical improvement in patients with treatment-refractory MAC lung disease, as measured by two patient-reported outcome instruments, including the same instrument recently selected for the primary endpoint in the Arikayce TN-MAC pivotal trial," stated Eric Easom, Co-Founder, Chairman, President, and Chief Executive Officer of AN2 Therapeutics. "We look forward to engaging with the FDA in the near-term to discuss next steps for the epetraborole program, including the potential reinitiation of a pivotal Phase 3 trial for treatment-refractory MAC lung disease."

Easom continued, "With a strong cash runway and optimized operating plan, we continue to advance our diverse pipeline of boron-based compounds to address unmet patient needs. This includes the recent strategic expansion into oncology, underscoring our dedication to innovating and improving patient outcomes across multiple therapeutic areas."

Third Quarter & Recent Updates:

Ongoing Analysis from Epetraborole Phase 2/3 Clinical Study in TR-MAC Lung Disease

The Company has provided an update from its ongoing analysis of the Phase 2 portion of the EBO-301 Phase 2/3 study. Two PROs evaluated in the trial indicated statistically significant clinical response, the QOL-B Respiratory Domain (Table 1) and MACrO2 (post-hoc analysis, Table 2), using continuous response measures instead of the binary responder methodology previously reported. Patients treated with epetraborole indicated clinical response using the same PRO instrument (QOL-B respiratory domain) and analysis method (least squares mean change from Baseline to Month 6) that was recently reported as the primary endpoint in the Arikayce ENCORE trial, after alignment with FDA. These EBO-301 PRO findings appear to align with FDA’s current recommendation for PRO-based primary endpoints in NTM-MAC trials.

Table 1: Quality of Life – Bronchiectasis (QOL-B respiratory domain) (least squares mean change from Baseline to Month 6)*

EBO-301 prespecified secondary endpoint

Epetraborole + OBR

(n=34)

Placebo + OBR

(n=35)

LS Mean Difference

p-value

Change from Baseline to Month 6

7.20

0.30

6.90

0.0365

*Measures of patient improvement for QOL-B are shown by positive changes in the score measured from baseline.

•
Epetraborole treated patients showed nominally statistically significant improvements in the QOL-B respiratory domain measured from baseline to month 6.
•
The p-value is termed "nominal" because this was not the prespecified primary endpoint in the Phase 2 part of the trial.

Table 2: MACrO2 PRO (least squares mean)*

Post-hoc analysis

Epetraborole + OBR (n=34)

Placebo + OBR

(n=35)

LS Mean Difference

p-value

Change from Baseline to Month 6

-12.91

-7.10

-5.81

0.0433

*Measures of patient improvement for MACrO2 are shown by negative changes in the score measured from baseline. The least squares mean calculation for MACrO2 utilized the same approach as the prespecified QOL-B LSM in the EBO-301 statistical analysis plan.

•
Epetraborole treated patients showed nominally statistically significant improvements in MACrO2 measured from baseline to month 6 in post-hoc analysis.

There was a high rate of MAC resistance to background antimycobacterial therapies at baseline, including approximately one-third of the patients with macrolide resistance and 60% with amikacin resistance, indicators of the complexity of the patient population. Notably, there was no evidence of induced epetraborole resistance in isolates from patients treated with epetraborole.

Further analysis showed no change in the previously reported safety profile; epetraborole was generally well-tolerated, with 2 (5%) discontinuations due to TEAEs in the epetraborole arm.

Epetraborole:Next Steps

The Company believes these findings are particularly noteworthy given the severe refractory status of the patients studied, and that improvements in QOL-B and MACrO2 appear to align with FDA’s current guidance for the primary efficacy endpoint in NTM-MAC studies. The Company will seek an End-of-Phase 2 meeting with FDA in the first half of 2025, with the goal of leveraging insights from the Phase 2 results to evaluate potential reinitiation of a pivotal Phase 3 TR-MAC study. In addition, the Company also plans to seek alignment with the FDA on a statistical analysis plan for the 97 patients who completed six months of treatment in the Phase 3 portion of EBO-301 at the time the Company halted the trial in August 2024. The Company anticipates releasing top-line Phase 3 data from these patients in mid-2025, subject to the timing of discussions with the FDA.

Other AN2 Boron Chemistry Pipeline Programs

Chagas Disease

During the quarter, the Company advanced preclinical activities aimed to initiate clinical studies in chronic Chagas disease, a disease that affects an estimated 6-7 million people worldwide, including approximately 300,000 in the U.S., and causes severe cardiac disease and death. The Company plans to initiate Phase 1 clinical development with AN2-502998 in mid-2025.

Melioidosis

The Company completed enrollment in a 200-patient observational trial for epetraborole in acute melioidosis in October 2024 and these data will inform a Phase 2 proof of concept study that is planned to initiate enrollment in the second half of 2025. Melioidosis is a deadly bacterial infection and global bioterrorism threat with a 90-day mortality rate of approximately 50% using standard of care (SOC) drugs ceftazidime or meropenem. The aim of the program is to meaningfully lower the expected mortality rate by dosing epetraborole on top of SOC.

Boron Chemistry Pipeline

Additional development programs are underway and focused on targets in infectious diseases and oncology with high unmet needs. The Company anticipates delivering up to three development compounds in 2025.

Global Health

In October, the Company announced that it received a second-year continuation of a research grant from the Bill & Melinda Gates Foundation to discover novel boron containing small molecules for the treatment of tuberculosis and malaria. The Company will continue its efforts to tackle global health disease through non-dilutive funding.

Selected Third Quarter Financial Results

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Research and Development (R&D) Expenses: R&D expenses for the third quarter of 2024 were $8.3 million compared to $14.4 million for the same period during 2023 due to decreased clinical trial costs, personnel-related expenses, preclinical and research study expenses, consulting and outside services, and other costs, partially offset by an increase in chemistry manufacturing and controls activity.
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General and Administrative (G&A) Expenses: G&A expenses for the third quarter of 2024 were $3.5 million compared to $3.8 million for the same period during 2023 due to a decrease in professional services.
•
Restructuring Charges: Restructuring charges for the third quarter of 2024 were $2.2 million due to severance payments and other employee termination-related expenses, partially offset by a reduction in stock-based compensation expense as a result of applying modification accounting for consulting agreements entered into with certain terminated employees.
•
Other Income, Net: Other income, net for the third quarter of 2024 was $1.3 million compared to $1.5 million for the same period during 2023 due to lower cash, cash equivalents and investment balances.
•
Net loss: Net loss for the third quarter of 2024 was $12.7 million, compared to $16.7 million for the same period during 2023.