epetraborole (AN3365) / AN2 Therap, Brii Biosci - LARVOL DELTA

Boron-Based Bioisosteres in Medicinal Chemistry: Advances in Heterocycles and Therapeutic. (PubMed, ChemMedChem) - "Benzoxaboroles have reached clinical relevance, including antifungal drugs such as tavaborole and crisaborole, as well as late-stage candidates like epetraborole and acoziborole. Benzoxaborinines and olaparib isosteres exhibit activity against carbonic anhydrases and PARP enzymes, while boronic acid drugs such as bortezomib and ixazomib are established proteasome inhibitors used in cancer therapy...Despite these advances, challenges remain regarding potency, pharmacokinetics, and mechanistic understanding of boron-target interactions. Overall, boron-based bioisosteres represent a versatile platform for developing new therapeutics across diverse disease areas."

Journal • Review • Oncology • PARP1

Discovery of repurposed drugs that disrupt intracellular replication of Burkholderia pseudomallei and Burkholderia mallei and protect against lethal aerosol infection. (PubMed, PLoS Pathog) - "Of these hits, 23 were found to disrupt the intracellular replication of both organisms including 8 compounds targeting dihydrofolate reductase, 3 tetracycline-class antibiotics, an inhibitor of bacterial leucyl-tRNA synthetase (epetraborole), and 2 host-directed compounds targeting receptors on the surface of mammalian cells. Selected compounds were evaluated in vivo using a BALB/c mouse model of aerosol infection and we discovered that daily treatment with epetraborole (20 mg/kg) and the fluoroquinolone levofloxacin (5 mg/kg) completely protected mice against exposure to lethal doses of Bm and Bp, reducing bacterial burdens in the lungs and spleen to undetectable levels in all animals by day 14 post-challenge."

Journal • Infectious Disease • DHFR

Epetraborole Demonstrates an Exposure-Dependent Effect on Erythropoiesis in Healthy Subjects (SOHO 2026) - "EBO exhibited well-behaved PK, was generally well tolerated, and showed dose-dependent decreases in hemoglobin without clinically meaningful elevations in platelets or WBCs. These data support further evaluation of EBO for the treatment of PV. AE: adverse event, GI: gastrointestinal, PK: pharmacokinetics, PV: polycythemia vera, TSAT: transferrin saturation, WBC: white blood cell, WNL: within normal limits."

Clinical • Oncology • Polycythemia Vera

Hematological Profile in Nonhuman Primates of Epetraborole, a Novel Boron-Containing Candidate for Oral Treatment of Polycythemia Vera (SOHO 2026) - "Repeated EBO administration to NHPs at doses exceeding those used clinically produced dose-dependent decreases in Hct, with no evidence of toxicity preventing reversibility. These data provide support for the planned clinical development of EBO as a potential therapy for PV."

Oncology • Polycythemia Vera

Exposure-Response Analyses of Hemoglobin Changes During Epetraborole Administration to Nonhuman Primates Predict Human Exposure-Response Relationships (SOHO 2026) - "Exposure-response analyses of hemoglobin changes during drug administration to NHPs were informative for predicting hemoglobin changes in humans during epetraborole treatment. AUC: area under the curve, AUC0-24: area under the curve over 24 hours, AUCss: area under the curve at steady-state, LLN: lower limit of normal."

Oncology • Polycythemia Vera

Hematologic and Safety Profile of Epetraborole in a Non-Polycythemia Vera Patient Population (SOHO 2026) - "These data from a severely ill population further inform the hematologic effect and overall safety and tolerability profile of EBO. The hepatic and renal safety profile of EBO supports its use in PV. COVID-19: coronavirus disease 2019, GI: gastrointestinal, Fe: iron, Hct: hematocrit, Hgb: hemoglobin, MCV: mean corpuscular volume, MCH: mean corpuscular hemoglobin, MCHC: mean corpuscular hemoglobin concentration, PBO: placebo, PV: polycythemia vera, TEAE: treatment-emergent adverse event, TSAT: transferrin saturation, WBC: white blood cell."

Clinical • Oncology • Polycythemia Vera

AN2 Therapeutics…announced that four abstracts highlighting clinical and nonclinical data supporting the development of epetraborole, a novel boron-containing oral candidate for the treatment of polycythemia vera (PV), will be presented at the Society of Hematologic Oncology (SOHO) 2026 Annual Meeting (Businesswire) - "Clinical and nonclinical studies demonstrated potential beneficial effects of epetraborole on erythropoiesis and hemoglobin-related parameters. Data further characterized the hematological and safety profile of epetraborole across healthy volunteers, non-PV patients, and nonhuman primate models. Exposure-response relationships observed in nonhuman primates were predictive of effects subsequently observed in humans, supporting the translational relevance of these models. Collectively, the findings support the ongoing clinical development of epetraborole as a potential oral treatment for PV."

Clinical data • Preclinical • Polycythemia Vera

Activity of MMV Pandemic Response Box compounds against Mycobacterium ulcerans viability and mycolactone production. (PubMed, Microbiol Spectr) - "By combining this mycolactone-detecting assay with the routinely used resazurin microplate assay, we identified hits (such as pradigastat) that are potential starting points for further development of antivirulence drugs for BU...In addition, we reliably reidentified drugs known to be active against M. ulcerans (such as bedaquiline, Q203, clofazimine, sutezolid, and epetraborole), thus validating our screening approach.IMPORTANCEMycolactone is a key requirement in the pathogenesis of Buruli ulcer (BU)...Here, we used our screening platform, which comprises a simple mycolactone-detecting ELISA combined with a standard resazurin microplate assay, to identify a set of hits from the Medicines for Malaria Venture Pandemic Response Box that could reduce mycolactone expression even without affecting M. ulcerans viability. This screening methodology will contribute to further development of antivirulence drugs for BU."

Journal • Infectious Disease • Malaria

Second Quarter & Recent Business Updates: Polycythemia vera (Businesswire) - "The Company recently held a pre-IND meeting with the FDA and now plans to expand the Phase 2 study (EBO-PV-201) to add sites in the U.S. and Australia, with an IND filing expected in the third quarter of 2026. As a result of this expansion, Phase 2 enrollment is anticipated to commence in the fourth quarter of 2026, beginning with an open-label sentinel cohort at a sub-therapeutic dose aimed at assessing pharmacokinetics and safety in PV patients. Following successful conclusion of the sentinel group, the safety monitoring committee will advise on dose selections for Part 1, an open-label, single arm, 28-week evaluation of epetraborole’s ability to maintain hematocrit control and reduce the frequency of phlebotomy in phlebotomy-dependent PV patients. The Company anticipates releasing Part 1 data periodically throughout 2027."

FDA event • IND • New P2 trial • P2 data • Polycythemia Vera

Boron-Containing Drug Candidates in Clinical Trials. (PubMed, Handb Exp Pharmacol) - "The agents reviewed include borofalan, delanzomib, flovagatran, dutogliptin, talabostat, numidargistat, OATD-02, AN0128, epetraborole, ganfeborole, acoziborole, taniborbactam, xeruborbactam, and sodium borocaptate, as well as the five FDA-approved boroncontaining drugs (bortezomib, ixazomib, crisaborole, tavaborole, vaborbactam). The review also highlights how clinical success depends on matching pharmacology with unmet need, feasible administration, competitive differentiation, and durable development partnerships. Ongoing advances in scaffold design, delivery, combination therapy, and indication selection are expected to broaden the therapeutic impact of boron-containing medicines."

Journal • Cardiovascular • Head and Neck Cancer • Hematological Disorders • Infectious Disease • Oncology • Pulmonary Disease • Respiratory Diseases • Solid Tumor • Thrombosis • Tuberculosis

Advancing oral epetraborole into a Phase 2 trial for polycythemia vera (Businesswire) - "In March 2026, the Company outlined plans to expand the development of oral epetraborole into a Phase 2 proof-of-concept clinical study in adults with phlebotomy-dependent polycythemia vera (PV)....The Company is proceeding through the regulatory process and plans to initiate the Phase 2 clinical trial in the third quarter of 2026. Subject to regulatory clearance and enrollment progress, the Company expects to provide periodic data readouts beginning as early as the fourth quarter of 2026 and throughout 2027."

New P2 trial • Polycythemia Vera

REBOUND: Epetraborole in Patients With Mycobacterium Abscessus Lung Disease (clinicaltrials.gov) - P2 | N=84 | Recruiting | Sponsor: Kevin Winthrop | Not yet recruiting ➔ Recruiting | Trial completion date: Dec 2027 ➔ May 2028 | Trial primary completion date: Jul 2027 ➔ Dec 2027

Enrollment open • Trial completion date • Trial primary completion date • Infectious Disease • Pulmonary Disease • Respiratory Diseases

Systematic and quantitative analyses of hollow fiber model of Mycobacterium abscessus lung disease studies and new dosing recommendations. (PubMed, Microbiol Spectr) - "The highest-ranked drugs were sulbactam-durlobactam-ceftriaxone (177-fold), epetraborole (15-fold), and omadacycline (7-fold) better than guideline-based therapy...The optimal inhalational dose of imipenem was 250 mg/day, for tigecycline 4 mg/day, for cefoxitin 50 mg/day, and for amikacin liposome inhalation suspension 590 mg once weekly...The inhaled doses were multiple-fold lower than intravenous ones, which could be less toxic. The hollow fiber system model is an easily managed system from drug development and dose finding for M. abscessus lung disease."

Journal • Pulmonary Disease • Respiratory Diseases

Novel regimens for treatment of Mycobacterium avium lung disease based on advanced in vitro systems and the mathematics of basis functions. (PubMed, bioRxiv) - "Azithromycin-minocycline-ethambutol, azithromycin-omadacycline-ethambutol, epetraborole-omadacycline-ethambutol, ceftriaxone-omadacycline-rifabutin, and the SOC were compared in the intracellular hollow fiber system model of M. avium lung disease (HFS-MAC). BF 2 described rebound growth and drug-resistant subpopulation growth, and demonstrated that contrary to popular belief, SOC rebound was best explained by ethambutol-resistance (r 2 >0.99, p =0.01) and not by azithromycin-resistance (r 2 =0.27, p=0.32), questioning ethambutol's role in the SOC. The BF framework is potentially easy to adapt for modeling other anti-infective agents across many infectious diseases."

Journal • Preclinical • Infectious Disease • Pulmonary Disease • Respiratory Diseases

Sulbactam-durlobactam plus ceftriaxone dosing and novel treatment regimens for Mycobacterium abscessus lung disease. (PubMed, Antimicrob Agents Chemother) - "Next, the sulbactam-durlobactam target exposure plus ceftriaxone was administered in the HFS-MAB inoculated with three different MAB isolates, as was the sulbactam-durlobactam-ceftriaxone combination with epetraborole and omadacycline (SDCEO). Sulbactam-durlobactam-ceftriaxone achieved the highest microbial kill encountered so far in the HFS-MAB. Sulbactam-durlobactam-ceftriaxone should be tested as the backbone for novel treatment shortening regimens."

Journal • Pulmonary Disease • Respiratory Diseases

Public contributions to the development of antibiotics: two successful and two failed investments. (PubMed, J Pharm Policy Pract) - "The aim is to showcase a detailed analysis of the contribution of public funding to two successful (gepotidacin and zoliflodacin) and two failed (epetraborole and ridnilazole) public sector investments in antibiotic development, using a previously developed and refined framework...Whilst the two unsuccessful antibiotics received considerably smaller sums from public or philanthropic sources ($85 million for ridinilazole and $18 million for epetraborole)...However, there is a significant amount of missing funds-related information. The work we have done on identifying sources for funding can be referenced in support pharmaceutical price negotiations to better reflect the level of public contribution to product development."

Journal

AN2 Therapeutics Announces Plans to Advance Oral Epetraborole into Phase 2 Study for Polycythemia Vera (PV) (Businesswire) - "The Company’s decision to pursue PV is supported by data from multiple clinical trials of oral epetraborole in healthy volunteers and non-PV patients in which the drug consistently demonstrated early, controlled, sustained, and dose-dependent reductions in hematocrit at potentially clinically meaningful levels for PV...'This program creates additional, near-term value inflection points within our current runway and broadens our pipeline, which now includes three Phase 2 studies initiating in 2026, and two preclinical oncology compounds that are expected to move into development this year.'...The Company is currently proceeding through the regulatory clearance process and anticipates initiating the Phase 2 trial in the third quarter of 2026. The Company expects to provide periodic public data updates as early as the fourth quarter of 2026..."

New P2 trial • Pipeline update • Polycythemia Vera

AN2 Therapeutics Announces FDA Clearance to Proceed with 90-Patient Investigator-Initiated Trial (IIT) of Epetraborole in Patients with M. abscessus Lung Disease (Businesswire) - "Patient enrollment expected to be initiated in 1Q 2026....The multicenter, randomized, double-blind, placebo-controlled, prospective clinical study will be led by Dr. Kevin Winthrop, Professor of Public Health and Infectious Diseases at OHSU, in collaboration with other investigators across an estimated 10-15 sites in the U.S."

IND • Trial status • Infectious Disease

REBOUND: Epetraborole in Patients With Mycobacterium Abscessus Lung Disease (clinicaltrials.gov) - P2 | N=84 | Not yet recruiting | Sponsor: Kevin Winthrop

New P2 trial • Infectious Disease • Pulmonary Disease • Respiratory Diseases

Mycobacteria susceptibility to epetraborole: how far can it go? (PubMed, Int J Tuberc Lung Dis) - "For MTB (n = 21), MIC50 and MIC90 were 2 and 8 mg/L respectively.CONCLUSIONEpetraborole MICs and EC50s were lowest for MAB while the best kill was with MAC. Systematic pharmacokinetic/pharmacodynamic studies are warranted for non-tuberculous mycobacteria and MTB.."

Journal • Infectious Disease • Nontuberculous Mycobacterial Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis

Repurposing epetraborole to combat Neisseria gonorrhoeae and Chlamydia trachomatis infections. (PubMed, Antimicrob Agents Chemother) - "Ceftriaxone (CRO) is the only recommended treatment for gonococcal infections but has no activity against C. trachomatis. Azithromycin (AZM) or doxycycline (DOX) is recommended for C. trachomatis infections; however, N. gonorrhoeae has developed resistance to both agents...Finally, in an in vivo mouse model of CRO-resistant N. gonorrhoeae genital tract infection, EBO exhibited a 99.95% reduction in bacterial burden after 2 days of treatment. Collectively, our findings highlight EBO as a promising candidate for the treatment of sexually transmitted infections that warrants further investigation."

Journal • Infectious Disease • Nontuberculous Mycobacterial Disease • Respiratory Diseases

Preclinical evaluation of epetraborole in the hollow fibre system model of Mycobacterium abscessus lung disease. (PubMed, J Antimicrob Chemother) - "Epetraborole microbial kill is the best, thus far, achieved in the HFS-MAB, more than two times omadacycline's 123 cfu/mL below B0. We propose to test a novel combination regimen of epetraborole plus omadacycline plus a β-lactam versus GBT first in the HFS-MAB, followed by clinical trials."

Journal • Preclinical • Pulmonary Disease • Respiratory Diseases

Pharmacokinetics and in vivo efficacy of epetraborole against Burkholderia pseudomallei. (PubMed, Sci Rep) - "Notably, this study represents the first demonstration of in vivo efficacy against a panel of ten genetically and geographically diverse B. pseudomallei strains in a murine model. This unprecedented breadth of strain coverage provides strong evidence of EBO's robust and strain-independent therapeutic potential."

Journal • PK/PD data • Preclinical • Infectious Disease • Respiratory Diseases

Epetraborole pharmacokinetics/pharmacodynamics in the hollow fiber system model of Mycobacterium tuberculosis. (PubMed, Antimicrob Agents Chemother) - "In the hollow fiber system model of tuberculosis (TB), the ratio of area under the concentration-time curve to MIC (AUC0-24/MIC) of 327.1 was identified as the epetraborole optimal exposure target for Mycobacterium tuberculosis kill. Monte Carlo simulation experiments showed that even the intravenous dose of 1,500 mg/twice daily would fail in the majority of patients, and the dose needed for good efficacy for TB may likely not be safe for patients."

Journal • PK/PD data • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis

Sulbactam-Durlobactam Plus Ceftriaxone Dosing and Novel Treatment Regimens for Mycobacterium abscessus Lung Disease. (PubMed, bioRxiv) - "Next, the sulbactam-durlobactam target exposure plus ceftriaxone was administered in the HFS-MAB inoculated with three different MAB isolates, as was the sulbactam-durlobactam-ceftriaxone combination with epetraborole and omadacycline (SDCEO). Sulbactam-durlobactam-ceftriaxone achieved the highest microbial kill encountered so far in the HFS-MAB. Sulbactam-durlobactam-ceftriaxone should be tested as the backbone for novel treatment shortening regimens."

Journal • Pulmonary Disease • Respiratory Diseases