AN2 Therapeutics Reports Phase 3 Data from EBO-301 Trial and Details Strategic Pipeline Advancements Across Boron Chemistry Platform
AN2 Therapeutics, Inc. (Nasdaq: ANTX), a clinical-stage biopharmaceutical company pioneering boron-based small molecule therapeutics, has announced topline results from the truncated Phase 3 portion of its EBO-301 study evaluating epetraborole in combination with an optimized background regimen (EBO+OBR) in patients with treatment-refractory Mycobacterium avium complex (MAC) lung disease. In parallel, the company outlined significant milestones and forward-looking strategies across its broader boron chemistry pipeline, encompassing programs in infectious diseases, oncology, and global health.
The EBO-301 study aimed to assess the efficacy of epetraborole in improving the quality of life for patients suffering from advanced, treatment-resistant MAC lung infections. Despite encouraging early signals, the Phase 3 segment of the study did not meet its primary endpoint: an improvement from baseline to month six in the respiratory domain of the Quality of Life – Bronchiectasis (QOL-B) patient-reported outcome instrument.
Understanding the EBO-301 Results
The patient cohort enrolled in EBO-301 represented a particularly challenging population, consisting of individuals with severe, chronic MAC lung disease. These patients exhibited prolonged disease duration, widespread cavitary and fibrocavitary involvement, and high levels of resistance to multiple standard-of-care antibiotics. The severity of their conditions contributed to the complexity of achieving meaningful quality-of-life improvements within the study’s timeframe.
“While we’re disappointed in these results, it’s important to contextualize them within the high disease burden and multi-drug resistance of the enrolled patients,” said Eric Easom, Co-founder, Chairman, President, and CEO of AN2 Therapeutics. “That said, we believe epetraborole still holds promise—especially in other non-tuberculous mycobacteria (NTM) indications such as M. abscessus lung disease, where there is a critical unmet need for more tolerable and effective oral therapies.”
Easom emphasized that the setback has not derailed the company’s momentum. Instead, it has sharpened AN2’s focus on leveraging its proprietary boron chemistry platform to pursue high-impact clinical opportunities in infectious diseases and oncology. “With multiple first-in-class candidates and strong intellectual property protections, our pipeline provides us with several viable paths to success within our existing cash runway,” he noted.
Pipeline Highlights and Upcoming Milestones
Despite the EBO-301 trial outcome, AN2 Therapeutics is rapidly advancing several pipeline programs built upon its boron chemistry foundation. The company’s lead candidates target major unmet needs in global health, biodefense, and oncology, and offer the potential for significant commercial and clinical value.
Chagas Disease: AN2-502998 in Phase 1 Preparation
AN2 is preparing to launch a Phase 1 clinical trial of AN2-502998, its investigational candidate for chronic Chagas disease. Trial startup activities are underway, and the company expects completion of the first-in-human study in the second half of 2025.
Chagas disease, caused by the parasite Trypanosoma cruzi, affects an estimated 6 to 7 million people globally, including approximately 300,000 in the United States. Left untreated, it can lead to severe cardiac complications and death. Current treatments are limited and often poorly tolerated.
AN2-502998 operates via the same mechanism of action as acoziborole, a related compound that has shown remarkable success in treating human African trypanosomiasis (HAT), also known as sleeping sickness. Acoziborole, developed by DNDi and Sanofi, demonstrated up to a 95% cure rate in a Phase 3 trial and is currently undergoing regulatory review in Europe.
Preclinical studies of AN2-502998 have demonstrated a 100% cure rate in nonhuman primates chronically infected with Chagas disease—an encouraging result in a model considered highly predictive of human disease outcomes. AN2 estimates the peak annual sales potential for this candidate could reach $1 billion. If approved, AN2-502998 would be eligible for a U.S. FDA priority review voucher (PRV), a valuable regulatory incentive.
Melioidosis: Targeting a Lethal and Neglected Infection
AN2 also plans to initiate a Phase 2 clinical study evaluating epetraborole for the treatment of melioidosis, a life-threatening bacterial infection caused by Burkholderia pseudomallei. The disease has a global mortality rate nearing 40% within three months of infection and is considered a potential bioterrorism agent by U.S. health authorities.
The company aims to demonstrate a significant reduction in the observed mortality rate with its novel therapy. If successful, the program could be eligible for another FDA priority review voucher and would serve both government stockpiling initiatives and treatment markets in endemic regions, including parts of the U.S., Southeast Asia, and northern Australia.
NTM Lung Disease Caused by M. abscessus: A New Avenue for Epetraborole
Following its extensive work on MAC, AN2 intends to pursue non-dilutive funding sources to advance epetraborole for M. abscessus lung disease, a rapidly growing, highly drug-resistant NTM infection. Unlike MAC, current treatment regimens for M. abscessus rely heavily on prolonged and toxic intravenous therapies.
Epetraborole’s oral bioavailability and novel mechanism of action position it as a compelling candidate to help fill this gap. In preclinical testing, the compound showed a 256-fold greater in vitro potency against M. abscessus compared to MAC, based on findings from the TR-MAC Phase 3 trial. The company has also been invited to participate in an international initiative aimed at developing an all-oral regimen for M. abscessus lung disease—further validating interest in the compound’s potential.
Oncology Pipeline: Boron Chemistry Enables First-in-Class Targets
Beyond infectious disease, AN2 is rapidly building a portfolio of preclinical oncology candidates designed to tackle targets previously considered undruggable. The company’s boron chemistry approach allows for unique binding interactions that result in high ligand efficiency, selectivity, and favorable drug-like properties.
AN2 has developed potent, highly selective inhibitors for key cancer-related enzymes, including ENPP1 and PI3Kα, both of which are implicated in tumor progression and immune evasion. These candidates exhibit sub-nanomolar potency and excellent oral pharmacokinetics in preclinical models.
The first oncology programs are expected to enter formal development later this year, with AN2 aiming to reach clinical proof-of-concept within its current cash reserves. This expansion into oncology reflects the broad applicability of the company’s platform and its ability to generate best-in-class therapeutics across disease areas.
Commitment to Global Health and Non-Dilutive Partnerships
AN2 continues to prioritize global health challenges such as tuberculosis and malaria through strategic collaborations and grant-based funding mechanisms. These programs, supported by organizations like the Bill & Melinda Gates Foundation, enable AN2 to extend its impact without drawing on shareholder capital.
“Our strategy is clear: we are harnessing the versatility of boron chemistry to develop transformative medicines across multiple fronts, from neglected tropical diseases to precision oncology,” said Easom. “With a strong foundation, protected intellectual property, and multiple potential sources of non-dilutive funding, we are well-positioned to deliver long-term value.”
Despite the setback in the Phase 3 EBO-301 study, AN2 Therapeutics is progressing with a robust and diversified pipeline. The company’s leadership remains confident that its innovative boron chemistry platform will unlock new therapeutic avenues in both infectious disease and oncology, and that multiple near-term catalysts—including clinical trial initiations, data readouts, and regulatory submissions—will drive continued momentum.
As the biopharmaceutical industry turns increasingly toward first-in-class solutions for challenging diseases, AN2’s strategic positioning and scientific innovation offer a compelling vision for future success.
