AN2's stock craters as phase 3 lung disease trial for lead antibiotic paused over efficacy

Just five months after launching the phase 3 part of a lung disease trial for its sole clinical asset, AN2 Therapeutics is pressing pause.

The California biotech has voluntarily halted a late-stage study of an antibiotic called epetraborole in treatment-refractory mycobacterium avium complex (MAC) lung disease after an analysis of a phase 2 portion of the trial “showed potentially lower than expected efficacy.”

The decision was not due to safety concerns, the company pointed out, adding that it still expects to announce top-line data from the phase 2 portion of the trial in the summer.

As the biotech’s only clinical-stage asset, epetraborole was at the center of AN2’s pitch to prospective investors when the company went public in a March 2022 IPO that reeled in $69 million. The biotech’s stock has fluctuated in the subsequent two years but looks set for its biggest crash yet on Monday in the wake of the trial’s pause. Shares dropped over 70% in premarket trading to $5.63 from a Friday closing price of $20.

“Developing new therapies for patients suffering with treatment-refractory MAC lung disease, a disease with limited treatment options and low response rates to existing therapies, is a complex undertaking,” AN2’s CEO Eric Easom explained in this morning’s release.

“In light of recently available blinded aggregate data, we believe our voluntary decision to pause enrollment in the phase 3 part of the study will provide us the opportunity to further evaluate study data, and determine the best path forward,” Easom added.

Epetraborole, a small-molecule inhibitor of bacterial leucyl-tRNA synthetase, had been put through clinical trials by Anacor Pharmaceuticals and GSK over a decade earlier, before GSK scrapped the partnership after seeing microbiological resistance in some patients who received the drug in a phase 2 study. Anacor was then bought by Pfizer in 2016, and, three years later, AN2 secured the rights to epetraborole from the Big Pharma.

AN2 had big plans for the antibiotic and completed enrollment of 80 patients in the phase 2 portion of the EBO-301 trial by September 2023. The aim was to seamlessly move into a phase 3 segment of the study, which as of this morning had enrolled 100 patients out of a planned 230 across the U.S., Japan, South Korea and Australia.

Back in September, Easom pointed out that there remains no approved oral therapies for MAC lung disease. “Given epetraborole’s novel mechanism of action, encouraging clinical and non-clinical data to date, and convenient once daily oral dosing, we believe that if approved, epetraborole has the potential to become the backbone of therapy for patients suffering with often debilitating treatment-refractory MAC lung disease,” the CEO said at the time.

AN2 ended September with $150.2 million in cash and investments, which was expected to cover operations through summer 2025.