AN2 Therapeutics, Inc. Announces Plans to Advance Oral Epetraborole into Phase 2 Study for Polycythemia Vera
AN2 Therapeutics, Inc., a clinical-stage biopharmaceutical company focused on developing innovative small molecule therapeutics derived from its proprietary boron chemistry platform, today announced plans to expand the clinical development of its investigational oral therapy, epetraborole, into a Phase 2 proof-of-concept study in adults with phlebotomy-dependent polycythemia vera (PV). The company expects to initiate the Phase 2 trial in the third quarter of 2026, subject to regulatory clearance, with potential initial data readouts anticipated as early as the fourth quarter of 2026 and continuing throughout 2027.
The decision to advance epetraborole into PV is supported by a growing body of clinical evidence demonstrating consistent and potentially clinically meaningful reductions in hematocrit levels across multiple patient populations studied to date. These findings, observed in healthy volunteers as well as in patients treated in prior clinical programs, provide a strong scientific rationale for further investigation of the therapy in PV, a chronic blood cancer characterized by excessive red blood cell production.
Clinical Rationale for Advancing Epetraborole in PV
Polycythemia vera is driven by the overproduction of red blood cells in the bone marrow, leading to elevated hematocrit levels. Persistently high hematocrit increases blood viscosity and significantly raises the risk of serious complications, including arterial and venous thromboembolic events such as stroke, deep vein thrombosis, and pulmonary embolism. Without adequate management, PV can be life-threatening.
Data from multiple clinical studies of epetraborole demonstrated early, controlled, sustained, and dose-dependent reductions in hematocrit levels—effects that may be clinically meaningful in patients with PV. Importantly, these reductions were observed across diverse clinical populations, including healthy volunteers and patients with nontuberculous mycobacterial (NTM) lung disease, and were maintained for up to six months of treatment in certain studies.
The pharmacodynamic and clinical profile of epetraborole has been characterized by several key observations:
- Consistent hematocrit reductions across multiple clinical populations.
- Early onset of hematocrit reduction following initiation of therapy.
- Durable and stable hematocrit control during treatment.
- Reversibility of effect upon discontinuation of therapy.
- No clinically relevant changes in white blood cell counts.
- Minimal changes in platelet counts.
- Sustained hematocrit reductions in nine-month chronic non-human primate studies.
- A potentially differentiated mechanism of action that likely acts on globin synthesis rather than directly targeting heme synthesis.
Collectively, these findings suggest that epetraborole may offer red-cell selectivity and hematologic control without broad suppression of other blood cell lineages, an important consideration in PV management.
Epetraborole has been generally well tolerated in clinical trials conducted to date, including at dose levels anticipated for potential use in PV. The overall safety profile further supports continued clinical development in this new indication.
Potential Differentiation in PV Treatment Landscape
Current management strategies for PV focus primarily on maintaining hematocrit levels below established thresholds to reduce the risk of thrombotic complications. Standard approaches include periodic phlebotomy, cytoreductive therapies, and injectable treatments. However, despite available therapies, many patients continue to experience suboptimal hematocrit control and persistent symptom burden.
“We believe epetraborole may offer a differentiated hematological profile that combines hematocrit control via red-cell selectivity, early onset, titratability and oral delivery,” said Eric Easom, Co-Founder, Chairman, President and Chief Executive Officer of AN2 Therapeutics. “These attributes could address key treatment objectives in polycythemia vera and offer patients a new therapeutic option where current approaches fall short.”
Easom added that the advancement of epetraborole into a Phase 2 study in PV represents an important strategic milestone for the company. The PV program introduces additional near-term value inflection points within AN2’s existing financial runway and broadens its development pipeline. With three Phase 2 studies expected to initiate in 2026 and two preclinical oncology programs anticipated to enter development this year, the company is positioning itself for a period of significant clinical and operational progress.
Unmet Need in Polycythemia Vera
Although therapeutic advances have improved outcomes for some patients, PV remains a chronic and incurable condition that requires lifelong disease management. Many patients must undergo repeated phlebotomy procedures to maintain acceptable hematocrit levels, which can be burdensome and impact quality of life. Injectable treatments may also carry tolerability concerns or logistical challenges associated with administration.
“While current therapies are effective for some patients, many continue to have inadequately controlled hematocrit levels and rely on repeated phlebotomy or injectable treatments,” said Dr. Stan Gerson, hematologist and oncologist at University Hospitals Cleveland Medical Center and Dean and Professor of Medicine at Case Western Reserve University School of Medicine. “As a chronic illness with no cure, PV carries a persistent risk of thrombosis and a substantial symptom burden. There remains a clear need for additional oral treatment options, including those with novel mechanisms of action, that can help manage hematocrit while minimizing treatment burden and long-term tolerability concerns.”
The potential for an oral therapy with a differentiated mechanism of action could represent an important advancement in the treatment paradigm, particularly for patients seeking alternatives to injectable therapies or frequent phlebotomy.
PV is estimated to affect approximately 155,000 individuals in the United States. Despite its classification as a rare disease, its chronic nature and long-term complications create significant medical and economic burdens for patients and healthcare systems.
Phase 2 Development Plans and Timeline
AN2 Therapeutics is currently proceeding through the regulatory clearance process required to initiate the Phase 2 proof-of-concept trial in adults with phlebotomy-dependent PV. The company anticipates commencing the study in the third quarter of 2026.
Pending regulatory clearance and enrollment progress, AN2 expects to provide periodic public updates on the program, with the potential for initial data disclosures as early as the fourth quarter of 2026 and additional readouts throughout 2027.
The Phase 2 study will be designed to further evaluate the safety, tolerability, and efficacy of epetraborole in controlling hematocrit levels in PV patients, while also assessing dosing flexibility and durability of response.
Polycythemia vera is a myeloproliferative neoplasm characterized by clonal proliferation of hematopoietic stem cells, leading to excessive red blood cell production. The resulting elevation in hematocrit increases blood viscosity and predisposes patients to serious thrombotic events. In addition to thrombosis risk, patients may experience symptoms such as fatigue, pruritus, headache, and splenomegaly.
If left untreated, PV can progress to myelofibrosis or acute leukemia in a subset of patients. While available treatments aim to reduce hematocrit and mitigate complications, long-term disease control remains a clinical challenge for many individuals.
Webcast and Investor Update
AN2 Therapeutics will host a live webcast presentation on Wednesday, March 4, 2026, at 9:30 a.m. Eastern Time to provide an overview of the PV development program and discuss the scientific rationale supporting the Phase 2 study.
The event will feature Dr. Aaron Gerds, Associate Professor of Medicine at the Cleveland Clinic Lerner College of Medicine of Case Western Reserve University and Deputy Director for Clinical Research at the Cleveland Clinic Taussig Cancer Institute, alongside members of the AN2 management team.
The live webcast will be accessible through the “Events” section of the company’s investor relations website. Registered participants will receive confirmation details and calendar integration options. An archived replay of the webcast will remain available for 30 days following the presentation, beginning approximately two hours after the live event concludes.
Through this strategic expansion into polycythemia vera, AN2 Therapeutics aims to leverage its boron-based chemistry platform to address a significant unmet medical need. If successful, epetraborole could emerge as a novel oral therapy offering meaningful hematocrit control and improved treatment flexibility for patients living with this chronic and potentially life-threatening blood cancer.
About Epetraborole
Epetraborole is a boron-containing, orally available, small molecule that has shown dose and exposure-dependent decreases in hematocrit. Evidence suggests that it operates by reducing production of early-stage erythrocytes (red blood cells) while sparing other cell lineages in the marrow, including white blood cells and platelets. Epetraborole’s clinical data package supporting evaluation in PV is comprehensive, including 10 Phase 1 studies, two Phase 2 studies, and a Phase 2/3 study in NTM lung disease. The drug has been generally well tolerated in prior trials at doses anticipated for PV and, to date, no tolerability barriers to long-term use have been identified. Epetraborole, if approved, would represent a distinct chemical class in both PV and anti-infectives.
