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AN2 Therapeutics Chief Executive Officer Eric Easom outlined the company’s expanding pipeline strategy at a Stifel investor event, describing AN2 as a boron chemistry platform company with roots in Anacor and more than two decades of experience in boron-based drug discovery.
Easom said AN2 has historically focused on infectious diseases but is increasingly moving into hematology and oncology after following biological signals from its platform. He said the company has three clinical programs and expects three more programs to enter development over the next year.
Epetraborole Moves Toward Polycythemia Vera Study
A major focus of the discussion was epetraborole, or EBO, AN2’s lead infectious disease asset currently in Phase II development for patients with Mycobacterium abscessus. Easom said the company has long observed that the drug has a red cell-specific effect that lowers hematocrit and hemoglobin.
That observation led AN2 to evaluate whether the drug could have utility in polycythemia vera, or PV, a blood disorder characterized by excess red blood cell production. Easom said the signal seen in non-tuberculous mycobacteria patients was predictable but subclinical, meaning patients generally did not notice it.
“Last year we had an aha moment where we were like, ‘This could really benefit patients with PV because it’s red cell specific,’” Easom said.
He said AN2 has evaluated the effect in non-human primates, Phase I volunteers and Phase II studies, and has conducted bone marrow biopsies and toxicology studies. According to Easom, the drug does not appear to affect precursor cells or white cells, with the effect occurring in late-stage erythrocytes.
PV Trial Could Produce Initial Data This Year
Easom said AN2 is in the regulatory process for a Phase II proof-of-concept PV study that will begin in India, which he described as a faster and less expensive way to test the hypothesis. The first part of the open-label trial will enroll a sentinel group of 10 patients at a low dose.
AN2 expects dosing to begin in the third quarter, with data possible as soon as the fourth quarter. A second part of the study is expected to add approximately 54 more patients, bringing the total to about 64, and will evaluate dose ranging and dose finding. Easom said the company hopes the drug may ultimately have a simple dosing profile without extensive titration.
Asked whether epetraborole could reduce the clonal burden of mutant JAK alleles, Easom said the company does not yet know. He said it is possible, but added that AN2 needs clinical data before drawing conclusions.
Potential Role in PV Treatment Landscape
Easom said AN2 sees a broad opportunity for an oral, red cell-specific agent in PV. He cited discussions with key opinion leaders, including Dr. Aaron Gerds of Cleveland Clinic, and said hematocrit control remains poor even with current approaches such as phlebotomy and hydroxyurea.
He said epetraborole could potentially be used early in treatment, added while other therapies such as ropeginterferon are being titrated, or used alongside later-line agents such as Jakafi. He also said frequent phlebotomies are a burden for patients.
On the question of chronic antimicrobial use in a non-infectious indication, Easom said AN2 has not seen issues with C. difficile in long-term NTM treatment and described microbiome-related effects as mild and resolving.
Oncology Pipeline Includes ENPP1 and PI3K Programs
Easom also discussed AN2’s ENPP1 program, which he described as a lead solid tumor oncology asset and an innate immune system stimulator. He said ENPP1 sits on the cell surface and shuts down signaling through the STING pathway, and that inhibition may help restore a natural immune response.
However, Easom acknowledged that ENPP1 remains an unproven target. He said other companies have ENPP1 programs in the clinic, including Riboscience, and that AN2 expects to learn from external clinical data expected next year. He said AN2’s initial clinical approach would likely involve an all-comer Phase I study to evaluate safety and pharmacokinetics before moving into tumor-specific studies, potentially in combination with DNA-damaging agents.
The company is also working on a PI3K alpha program but has not yet nominated a development candidate. Easom described the area as crowded but validated, and said AN2 is pursuing a pan-mutant profile with separation from wild-type PI3K activity. He said the company expects to have a candidate late this year and would likely seek a partner for the program.
Upcoming Catalysts
Easom said AN2 has several near-term development events across its pipeline:
- PV data from the epetraborole Phase II program expected later this year and into next year.
- A Chagas disease program expected to start late this year, with Phase II data next year.
- NTM abscessus Phase II data expected late next year.
- Progress on ENPP1 and PI3K alpha development candidates.
Easom described Chagas disease as a potentially large U.S. market with no FDA-approved drug and said AN2 has observed cures in three non-human primate studies involving natural infections. He also said NTM abscessus affects about 15,000 U.S. patients and that an oral backbone therapy could represent a meaningful market opportunity.
Although the moderator asked about balance sheet runway, Easom did not provide specific cash runway details during the discussion.
About Anthem (NASDAQ:ANTX)
Anthem, Inc, through its subsidiaries, operates as a health benefits company in the United States. It operates through three segments: Commercial & Specialty Business, Government Business, and Other. The company offers a spectrum of network-based managed care health benefit plans to large and small group, individual, Medicaid, and Medicare markets. Its managed care plans include preferred provider organizations; health maintenance organizations; point-of-service plans; traditional indemnity plans and other hybrid plans, such as consumer-driven health plans; and hospital only and limited benefit products.
