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Item 1. Business

2026-03-17 compared with 2025-03-25 · 130 added, 172 removed, 356 unchanged (46% of the section changed)

AN2 Therapeutics, Inc.

(also referred to in this document as “AN2,” “we,” the “Company” or the “Registrant”) is a biopharmaceutical company focused on discovering and developing novel small molecule therapeutics derived from our boron chemistry platform.

AN2 has a pipeline of boron-based compounds in development for Chagas disease, non-tuberculous mycobacterial (“NTM”) and melioidosis, along with early-stage programs focused on targets in infectious diseases and oncology.

Our initial candidate is epetraborole, which we are studying as a potential once-daily, oral treatment with a novel mechanism of action for patients with non-tuberculous mycobacterial (“NTM”) lung disease, a rare, chronic and progressive infectious disease caused by bacteria known as mycobacteria, which leads to irreversible lung damage and can be fatal.

Epetraborole is designed to produce broad-spectrum antimycobacterial activity through inhibition of an essential and universal step in bacterial protein synthesis.

Its novel mechanism of action is enabled by boron chemistry, our core technology approach.

We in-licensed the exclusive worldwide development and commercialization rights for epetraborole from Pfizer Inc.

The FDA granted us Fast Track designation to investigate epetraborole for treatment-refractory MAC lung disease, Qualified Infectious Disease Product (“QIDP”) designation for treatment-refractory MAC lung disease, and orphan drug designation for the treatment of infections caused by NTM.

We have also received orphan medicinal product designation from the European Commission for the treatment of NTM lung disease using epetraborole.

Based on clinical and preclinical data generated with epetraborole, its novel mechanism of action, and the convenience associated with once-daily, oral dosing, we believe that epetraborole, if approved, has the potential to become an important component of a multi-drug treatment regimen for patients suffering from NTM lung disease.

Epetraborole in NTM

Our lead development target in NTM is treatment-refractory MAC lung disease, a condition with high unmet need where the mycobacterial infection persists despite standard front-line therapies.

These patients represent complex cases for treatment, often presenting with structural lung damage, high levels of resistance to background therapies, and persistent symptoms that can significantly degrade quality of life.

In 2023, the FDA issued a Guidance for Industry entitled, “ Nontuberculous Mycobacterial Pulmonary Disease Caused by Mycobacterium Avium Complex:

Developing Drugs for Treatment Guidance for Industry ,” which among other things, recommended that new potential therapies intended for the treatment of NTM caused by MAC utilize clinical outcome assessments, such as patient-reported outcome ("PRO") measures that assess symptomatic improvement, as primary efficacy endpoints in registrational trials intended to support applications for traditional approval.

To date, no drugs have been approved by FDA based on achievement of an endpoint demonstrating symptom improvement in a treatment refractory population.

The only FDA-approved therapy for treatment-refractory MAC lung disease received accelerated approval based on the surrogate endpoint of sputum culture conversion without having demonstrated symptom improvement.

On August 8, 2024, we announced topline results from the Phase 2 part of EBO-301, a Phase 2/3 study evaluating epetraborole on top of optimized background regimen (“OBR”) in treatment-refractory MAC lung disease ("TR-MAC"), and terminated the Phase 3 portion of the trial early with 97 patients enrolled.

The Phase 2 part of the study met its primary objective of demonstrating the potential validation of a novel PRO tool and a numerically higher PRO-based clinical response rate in the epetraborole + OBR arm (39.5%) vs.

placebo + OBR (25.0%;

treatment difference 13.9%, p=0.19).

However, sputum culture conversion at Month 6, a key secondary endpoint, was similar between treatment arms (13.2% in epetraborole + OBR vs.

10.0% placebo + OBR;

treatment difference 3.4%, p=0.64).

Epetraborole was generally well tolerated in the Phase 2 portion of the trial.

The primary purpose of the Phase 2 part of the EBO-301 study was to test the validity of multiple patient-reported outcome tools in a treatment refractory population, with the goal of identifying a PRO-based primary endpoint for the Phase 3 portion of the trial.

To that end, we recently submitted an amended statistical analysis plan to the FDA selecting the Quality of Life – Bronchiectasis ("QOL-B") respiratory domain patient reported outcome instrument as the primary efficacy endpoint for the Phase 3 part of the EBO-301 trial.

Using QOL-B as a continuous measure of clinical improvement, epetraborole showed nominal statistical superiority versus placebo in change from baseline to month 6 in the Phase 2 portion of the trial (prespecified secondary endpoint, difference in least squares mean change from baseline:

6.90, p=0.0365).

Furthermore, a post-hoc analysis of the MACrO 2 PRO using a 100-point continuous scale similar to QOL-B showed a comparable nominally statistically superior result for the epetraborole arm versus the placebo arm (difference in least squares mean change from baseline:

5.81, p=0.0433).

Blinded psychometric analyses incorporating the data from both treatment arms of the Phase 2 study demonstrated strong evidence for the reliability, validity, ability to detect change (responsiveness), and clinically meaningful within-patient changes in both the QOL-B respiratory domain score and the post-hoc MACrO 2 total scaled score, suggesting that the scores measured from either PRO may be fit-for-purpose in evaluating response to treatment in patients with treatment-refractory NTM lung disease.

Based on the Phase 2 results and subsequent analyses, we believe epetraborole is the first drug candidate to show statistically favorable patient reported outcome-based improvement in a treatment-refractory MAC lung disease population.

We anticipate releasing top-line Phase 3 data from the 97 Phase 3 patients in the second quarter of 2025.

If the Phase 3 data are consistent with [LD1] [JP2] the Phase 2 findings, we plan to meet with FDA to discuss potential registrational pathways in TR-MAC lung disease.

Pipeline Programs

We are also studying epetraborole for the treatment of acute melioidosis.

We completed enrollment in a 200-patient observational trial (non-epetraborole treatment) in October 2024 and expect to announce topline data in the second half of 2025.

These data will inform a potential Phase 2 proof of concept study that is planned to initiate start up activites in the second half of 2025.

Melioidosis is a deadly bacterial infection and global bioterrorism threat with a 90-day mortality rate of approximately 50% using standard of care ("SOC") drugs ceftazidime or meropenem.

The aim of the program is to meaningfully lower the expected mortality rate by dosing epetraborole on top of SOC.

Beyond epetraborole, we are conducting Investigational New Drug Application (“IND") enabling studies with AN2-502998 (formerly known as AN15368), an investigational, boron-based small molecule in development for the treatment of chronic Chagas disease, and have several research programs targeting the development of novel compounds in oncology and infectious disease based on our boron chemistry platform.

In October 2023, we announced an exclusive license agreement with the University of Georgia Research Foundation to advance the development of AN2-502998, originally discovered by researchers at Anacor, in close collaboration with the University of Georgia.

AN2-502998 is the only compound of which we are aware to have demonstrated curative activity in preclinical studies across multiple species, including in non-human primates with long-term, naturally acquired chronic infections of diverse T.

cruzi genetic types.

We anticipate initiating a Phase 1 study in 2025.

We also anticipate nominating 1 to 2 new development candidates in oncology in 2025.

AN2 is committed to using our boron chemistry platform to address areas of high unmet need in global health, primarily using non-dilutive funding from sources such as public and private agencies and foundations.

In September 2023 we received a research grant from the Bill and Melinda Gates Foundation to discover novel, boron containing small molecules for the treatment of tuberculosis and malaria which was renewed in September 2024.

In 2022 we received a cost-reimbursement contract award from the National Institute of Allergy and Infectious Diseases (“NIAID”), part of the National Institutes of Health (“NIH”), under which we are able to receive up to $17.8 million in cost reimbursements to advance the development of epetraborole for acute systemic melioidosis and other biothreat pathogens.

Epetraborole Mechanism of Action

Epetraborole is an investigational, boron-containing, orally bioavailable, small molecule inhibitor of bacterial leucyl-tRNA synthetase, or LeuRS, an enzyme that catalyzes the attachment of leucine to transfer RNA, or tRNA, molecules, an essential step in protein synthesis.

As shown in Figure A below, epetraborole forms a complex with a tRNA Leu molecule, trapping the terminal ribonucleotide of tRNA Leu in the editing site of the enzyme, to prevent the synthetic site from attaching leucine to tRNA Leu thus shutting down tRNA leucylation and leading to a block in protein synthesis.

Epetraborole is designed to inhibit the protein synthesis enzyme leucyl-tRNA synthetase, or LeuRS, by binding to the terminal adenosine ribose of tRNALeu in the editing site.

As shown in Table 1 below, epetraborole has demonstrated antimicrobial activity against a broad panel of 161 isolates of MAC, with minimum inhibitory concentrations, or MICs, of 0.25 mg/ml to 16 mg/ml.

Epetraborole also maintained activity against MAC isolates that are resistant to clarithromycin, a current therapy for NTM treatment regimens.

Clarithromycin

Antimicrobial activity of epetraborole, clarithromycin and amikacin against 161 isolates of MAC including M.

intracellulare isolates, M.

avium isolate, M.

avium complex isolates, M.

hominissuis isolates, and M.

chimaera isolates.

Unmet Need in NTM and Market Opportunity for Epetraborole

NTM lung disease is a rare, chronic, and progressive infectious disease caused by bacteria known as mycobacteria that leads to irreversible lung damage and can be fatal.

Unlike most bacteria, which replicate quickly and spread outside of cells, mycobacteria replicate slowly and mostly infect alveolar (lung) macrophages and survive within them.

Due to the slow growth and survival within macrophages of mycobacteria, the current standard of care for NTM lung infections requires prolonged treatments, often for 18 months or longer, with a combination of three or more antibiotics.

Initially, we are focused on developing epetraborole to treat the most common type of NTM, MAC, which accounts for approximately 80% of NTM lung disease in the United States.

There are an estimated 200,000 patients with NTM lung disease in the United States.

We believe that many remain underdiagnosed due to lack of clinical suspicion, nonspecific respiratory symptoms, and underlying lung diseases that are frequent in patients with this infection.

The prevalence of NTM lung disease is increasing in the United States by an estimated 8% per year.

Among the approximately 55,000 patients diagnosed with NTM lung disease in the United States, approximately 44,000 patients have MAC lung disease, and approximately 35% of these patients have treatment-refractory MAC lung disease.

In addition, Japan has some of the highest rates of NTM lung disease in the world.

It is estimated that there are 220,000 patients with NTM lung disease and 21,000 patients with treatment-refractory MAC lung disease in Japan.

There is only one FDA-approved therapy for treatment-refractory MAC lung disease:

Arikayce, an inhaled liposomal formulation of amikacin.

Arikayce is also approved in Japan and certain other countries around the world.

Insmed Incorporated reported net sales of Arikayce of approximately $363.7 million in 2024 ($254.8 million in the United States, $87.7 million in Japan, and $21.2 million in Europe and the rest of the world), a 19% increase over 2023.

We believe there is significant unmet need for new treatments, particularly in an oral dosage form with differentiated tolerability and mechanism of action.

In a clinical trial, the addition of Arikayce to standard of care (SOC) combination antibiotic therapy resulted in the resolution of MAC infection in 29% of patients as compared to 9% for SOC alone (based on an intent to treat population).

Arikayce has boxed warnings for risk of increased respiratory adverse reactions, and warnings and precautions including ototoxicity, a known class effect with aminoglycosides, and other safety findings.

In its clinical trial, between 20.3% and 33.5% of patients treated with Arikayce discontinued treatment.

Other drugs used in combination with Arikayce as a part of a standard-of-care regimen are not approved to treat MAC lung disease and carry numerous safety and tolerability liabilities of their own.

Prior Clinical Experience with Epetraborole

Prior to our clinical development program in NTM lung disease, epetraborole had been administered intravenously or orally as a monotherapy agent to over 200 subjects at a wide range of clinical doses across six Phase 1 and two truncated Phase 2 clinical trials conducted by Anacor and GSK with a focus on gram-negative infections that were unrelated to NTM lung disease, some of which were terminated prior to completion due to clinical resistance observed in a small number of patients in one of the two Phase 2 clinical trials.

Epetraborole was not tested by Anacor or GSK in patients with NTM lung disease or in combination with other antimicrobial agents.

Epetraborole Regulatory Exclusivity

As an orphan and QIDP-designated product, if approved in the United States for use in patients with treatment-refractory MAC lung disease, it is possible we could obtain up to 12 years of regulatory exclusivity, independent of any applicable patent protection.

If approved in Japan, we believe we could obtain at least eight years of exclusivity, independent of any applicable patent protection that we may acquire.

AN2-502998 Chagas Disease

Chagas disease is caused by the parasite Trypanosoma cruzi , which spreads via triatomine bugs (vector), a subspecies of blood-feeding insects more commonly known as “kissing bugs” because they tend to bite people on the face and lips.

cruzi is also transmitted congenitally from infected mothers to their babies, through consumption of contaminated food or beverages, and via blood transfusions and organ transplants.

While the disease can progress slowly, chronic infection almost inevitably results in irreparable damage to heart and digestive system tissues.

If untreated, infection is lifelong and can be life threatening.

Chagas disease kills more people in Latin America than any other infectious disease–including malaria, tuberculosis, and HIV—and is one of the major causes of infection-induced myocarditis or cardiomyopathy worldwide.

An estimated 30% of Chagas patients develop chronic and often severe heart disease that leads to premature death.

According to the World Health Organization, approximately 6-7 million people worldwide are estimated to be infected with the parasite T.

cruzi , mostly in Latin America.

An increasing number of cases of Chagas are also being documented in the United States of America and Europe.

In the United States, the CDC estimates that there more than 300,000 people infected with T.

cruzi , most of whom were infected in Chagas-endemic regions in Latin America.

Chagas disease presents in an acute phase (~2 months after infection) and a chronic phase, where the T.

cruzi parasites are hidden mainly in the heart and digestive muscles.

For over 50 years, two nitroheterocyclic compounds, benznidazole and nifurtimox, have been available for treatment of the infection and are FDA approved for use in children, but are rarely used due to their inconsistent efficacy and high frequency of side effects.

There are currently no approved therapies to cure the disease once it reaches the chronic phase;

however, benznidazole and nifurtimox may be offered to people younger than age 50 because they may help slow the progression of the disease and its most serious complications.

In October 2023, we announced that we signed an exclusive license agreement with the University of Georgia Research Foundation to advance development of AN2-502998 (formerly known as AN15368), a boron-based small molecule therapeutic candidate under development for the treatment of Chagas disease.

AN2-502998 was originally discovered by researchers at Anacor, in close collaboration with the University of Georgia, and with grant funding from Wellcome.

IND-enabling studies are well underway for this compound.

AN2-502998, previously published under AN15368, is the only compound of which we are aware to have demonstrated curative activity in preclinical studies across multiple species, including in non-human primates with long-term, naturally acquired chronic infections of diverse T.

All brand names or trademarks appearing in this report are the property of their respective owners.

Unless the context requires otherwise, references in this report to “ AN2,” “we,” “our,” the “Company” or the “Registrant” refer to AN2 Therapeutics.

We are a clinical stage biopharmaceutical company focused on the discovery and development of novel small-molecule therapeutics derived from our boron chemistry platform.

Our development pipeline spans hematologic diseases, infectious diseases, and oncology with three Phase 2 studies expected to initiate in 2026, two preclinical candidates, as well as advanced research programs focused on targets in oncology, bone disorders, and infectious diseases.

We are committed to delivering high-impact drugs to patients that address critical unmet needs and improve health outcomes.

Our pipeline is represented in the diagram below:

Company Pipeline

Polycythemia vera

In March 2026, we announced our plan to expand the development of oral epetraborole into a Phase 2 proof-of-concept clinical study in adults with phlebotomy-dependent polycythemia vera ( “PV”).

PV is a blood cancer characterized by overproduction of red blood cells in the bone marrow.

This overproduction increases hematocrit, which can lead to serious medical complications including arterial and venous thromboembolic events.

If untreated, PV can be life-threatening.

Despite available therapies, many patients experience uncontrolled hematocrit levels and persistent symptom burden, requiring long-term management to maintain adequate disease control.

PV is estimated to affect approximately 155,000 people in the U.S.

We are proceeding through the regulatory process and anticipate initiating the Phase 2 trial in India in the third quarter of 2026.

We expect to provide periodic data readouts beginning as early as the fourth quarter of 2026 and throughout 2027, subject to regulatory clearance and enrollment progress.

The Phase 2 study is expected to consist of an open-label epetraborole sentinel cohort, an open-label dose optimization cohort for dose selection (Part 1), followed by a double-blind, randomized, placebo-controlled cohort (Part 2), and an optional open-label extension cohort (Part 3).

The study is designed to assess the efficacy of oral epetraborole in phlebotomy-dependent adults with PV and its effect on key hematological variables, to optimize a dose regimen on a by-patient level, to assess safety and tolerability, to assess patient-reported outcomes (“PROs”) using validated PRO instruments, and to assess other key hematological parameters.

We expect to enroll approximately 40-50 patients across 3-5 or more sites.

Mycobacterium abscessus complex lung disease

In December 2025, the U.S.

Food and Drug Administration (“FDA”) cleared an Investigational New Drug Application (“IND”) to proceed with a Phase 2 investigator-initiated study (“IIT”) in collaboration with Oregon Health and Sciences University (“OHSU”) evaluating epetraborole for the treatment of Mycobacterium abscessus ( “ M.

abscessus ” ) complex lung disease.

This 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 conjunction with other investigators across an estimated 10-15 sites in the U.S.

abscessus lung disease is a serious and difficult-to-treat non-tuberculous mycobacterial infection requiring prolonged therapy including IV-only antibiotics and characterized by limited treatment options and high rates of morbidity, and 5-year mortality.

No FDA-approved drugs currently exist for its treatment.

We expect to initiate enrollment in the first quarter of 2026 and to report topline results in late 2027.

Chagas disease

In August 2025, as part of our Chagas disease clinical development program, we commenced our Phase 1 first-in-human trial of oral AN2-502998 in healthy volunteers.

Chagas disease (American trypanosomiasis), is an infectious disease caused by Trypanosoma cruzi , which affects an estimated 6-10 million people worldwide, including approximately 300,000 people in the U.S.

and over 100,000 in Europe.

Chagas disease can remain asymptomatic for years before progressing to chronic disease.

In approximately 20–30% of infected individuals, chronic infection leads to serious cardiac and gastrointestinal complications, including cardiomyopathy, heart failure, arrhythmias, stroke, and megacolon or megaesophagus, which can result in significant morbidity and premature death.

AN2-502998 is the only compound of which we are aware to have demonstrated curative activity in preclinical studies across multiple species, including in nonhuman primates (“NHPs”) with long-term, naturally acquired chronic infections caused by diverse T.

cruzi genetic types.

Melioidosis is an urgent unmet global health infectious disease caused by the bacterium Burkholderia pseudomallei ( B.

pseudomallei ).

This bacterium is also documented as a high priority biothreat pathogen by the U.S.

pseudomallei is endemic to tropical regions of the world with the majority of reported melioidosis cases occurring in South Asia.

Melioidosis is contracted from direct contact with B.

pseudomallei contaminated soil and water and is not transmitted person-to-person.

Similar to NTM, B.

pseudomallei can be an intra-cellular pathogen in host cells including macrophages and other cellular components, an important element in melioidosis disease.

The disease can manifest as localized infections causing pain, swelling and ulceration;

as pulmonary infections causing cough, chest pain, high fever, and headache;

and as blood stream infections causing fever, headache, respiratory distress, and abdominal discomfort.

Current treatment generally starts with an intense phase of intravenous antibiotic treatment for a minimum of two weeks.

Even with antibiotic treatment, the mortality rate is between 20% and 40%.

Without treatment, it is estimated that six to nine out of ten people die.

There are an estimated 165,000 cases of melioidosis diagnosed globally each year, mostly outside the United States, although small outbreaks due to bacterial exposure have occurred in the United States and the pathogen was recently discovered in soil and water sampling from the Gulf Coast region of Mississippi.

Nonclinical studies conducted by us, Anacor, the U.S.

Army Medical Research Institute of Infectious Diseases and Colorado State University indicate that epetraborole has potent activity against B.

pseudomallei.

In September 2022, we received a cost-reimbursement contract award to receive up to $17.8 million from the NIAID to advance the development of epetraborole for acute systemic melioidosis and additional bacterial biothreat pathogens.

The base period contract award is $4.3 million with additional options that, if exercised, would enable us to receive up to $17.8 million in total to support preclinical, Phase 1 studies, and other activities to enable advancement of epetraborole into advanced clinical trials for acute systemic melioidosis.

In July 2023, the NIAID exercised one of seven available options under the NIAID contract (No:

75N93022C00059), resulting in an increase in committed contract funding of $0.7 million, for a total of $5.0 million.

In May 2024, the NIAID exercised a second contract option, resulting in an increase in committed contract funding of $3.8M, for a total of $8.8M.

The project has been funded in whole with nondilutive federal funds from the NIAID, NIH, and the Department of Health and Human Services.

Our work with the NIAID on our melioidosis program has resulted in our partnering with the University of Oxford’s Mahidol Oxford Tropical Medicine Research Unit to conduct a prospective observational study in Thailand and Laos.

This trial completed enrollment of 200 patients in October 2024 (NCTC 06089668), and topline data is expected to be available in the second quarter of 2025.

We plan to initiate a Phase 2 study in mellioidosis in the second half of 2025.

We have also partnered with Colorado State University on preclinical research for our melioidosis program.

We believe these partners provide substantial technical and capital resources to advance the mellioidosis program and provide scientific, technical, and material benefits to our NTM lung disease program.

Because NHP infections are naturally acquired in the environment, these efficacy data may be more predictive of efficacy in human clinical trials than other animal models.

There are no FDA-approved treatments for adults with Chagas disease.

Our Phase 1 first-in-human trial with oral AN2-502998 is nearing completion, with initial clinical data expected in the first quarter of 2026 and initiation of the proof-of-concept Phase 2 trial in patients with chronic Chagas disease in 2026, depending on the outcome and timing of completion of the Phase 1 study.

FDA approval of a treatment for Chagas disease, which is designated as a tropical disease under Section 524 of the Federal Food, Drug, and Cosmetic Act (“FDCA”), would qualify us to receive a priority review voucher intended to incentivize the development of therapies for neglected infectious diseases.

Our Research and Development Initiatives

We are pursuing a number of oncology targets where we believe our boron chemistry may offer a competitive advantage in terms of binding-site differentiation, pharmacodynamics, drug-like properties and intellectual property.

Our lead oncology programs target PI3Kα and ENPP1.

We plan to advance two oncology candidates into development in 2026 targeting PI3Kα and ENPP1.

We are advancing a preclinical oncology program focused on the development of a selective, pan-mutant PI3Kα inhibitor.

Activating mutations in PIK3Cα are among the most common oncogenic drivers across solid tumors and occur in both kinase-domain and helical-domain forms, with substantial prevalence in breast, endometrial, colorectal, and other cancers.

Clinical experience with existing PI3Kα inhibitors, while highly effective, have a high rate of side effects, particularly treatment-limiting hyperglycemia.

Second generation molecules target mutants with selectivity over wild-type that has been shown to cause hyperglycemia, however preclinical and clinical date show activity that is biased toward kinase-domain mutations, leaving over half of patients with helical domain mutations with lower efficacy potential and greater exposure to toxicities.

Our PI3Kα program is designed to address these limitations by targeting true pan-mutant coverage across both kinase and helical mutations while maintaining selectivity over wild-type PI3Kα.

Preclinical studies of lead compounds derived from our boron chemistry platform have demonstrated potent activity against multiple clinically relevant PIK3Cα mutations, in vivo antitumor activity in murine models, and tumor regression without evidence of hyperglycemia or hyperinsulinemia in these models.

We believe these results, if replicated in future studies, could support a differentiated therapeutic approach aimed at improving tolerability and enabling more durable disease control in patients with PIK3CA-mutant cancers.

We are also advancing a preclinical oncology program focused on inhibition of ectonucleotide pyrophosphatase/phosphodiesterase 1 (“ENPP1”), an enzyme implicated in tumor immune evasion.

ENPP1 is expressed on the surface of certain tumor cells, where it degrades cyclic GMP–AMP (“cGAMP”), a key signaling molecule in the cGAS–STING pathway that mediates innate immune activation in response to tumor-derived DNA.

Elevated ENPP1 expression has been observed across multiple solid tumor types, including colorectal, lung, pancreatic, and breast cancers, and may contribute to immune suppression within the tumor microenvironment.

In contrast to direct STING agonists, which can produce rapid and systemic inflammatory responses, ENPP1 inhibition is designed to preserve endogenous cGAMP signaling and enable more localized and sustained immune activation.

Preclinical studies of ENPP1 inhibitors derived from our boron chemistry platform have demonstrated antitumor activity in murine models, including tumor growth inhibition and durable responses when used in combination with the immune checkpoint blockade.

We believe this approach, if successfully translated into the clinic, could support a differentiated immuno-oncology strategy with the potential to enhance antitumor immunity while maintaining a favorable therapeutic window.

Global Health Programs

Our global health strategy focuses on leveraging our proprietary boron chemistry platform to develop treatments for infectious diseases that disproportionately affect underserved populations.

These programs are funded primarily through non-dilutive grant funding, including sources such as public and private agencies and foundations.

Our global health programs include melioidosis, a severe bacterial infection associated with high death rates in endemic regions (funded by the U.S.

government), and tuberculosis, a leading cause of death from infectious disease worldwide that affects millions of people each year in partnership with the Gates Foundation and GSK.

Our strategy is to be a leader in the discovery and development of novel boron-based, small-molecule therapeutics across multiple disease areas.

Key elements of our strategy include:

• Advance our boron-based product candidates through clinical development.

Progress our lead assets through Phase 2 and into later-stage studies, with a focus on demonstrating safety, efficacy, and a clear development path through potential registration.

• Advance and expand research pipeline.

Apply our boron chemistry platform to discover and optimize new molecules targeting high-value pathways in oncology, bone disorders, and infectious disease, ensuring a sustainable flow of future product candidates.

• Leverage non-dilutive funding to support global health programs .

Continue to secure and utilize non-dilutive capital, such as grants, government contracts and partnerships to advance global health programs.

Manufacturing

67 unchanged sentences

For any individual patent, the term depends on the applicable law in the country in which the patent is issued.

In most countries where we have in-licensed patents and patent applications, including the United States, patents have a term of 20 years from the application filing date or earliest claimed nonprovisional priority date.

In the United States, the patent term may be shortened if a patent is terminally disclaimed over another patent that expires earlier.

In most countries where we have in-licensed patents and patent applications, including the U.S., patents have a term of 20 years from the application filing date or earliest claimed nonprovisional priority date.

In the U.S., the patent term may be shortened if a patent is terminally disclaimed over another patent that expires earlier.

The term of a U.S.

1 unchanged sentence

Patent and Trademark Office (“USPTO”) in examining and granting a patent.

In the United States, the term of a patent that covers an FDA-approved drug or biologic may be eligible for patent term extension in order to restore the period of a patent term lost during the premarket FDA regulatory review process.

In the U.S., the term of a patent that covers an FDA-approved drug or biologic may be eligible for patent term extension in order to restore the period of a patent term lost during the premarket FDA regulatory review process.

Specifically, the Drug Price Competition and Patent Term Restoration Act of 1984 (the “Hatch-Waxman Act”) permits a patent term extension of up to five years beyond the natural expiration of the patent (but the total patent term, including the extension period, must not exceed 14 years following FDA approval).

6 unchanged sentences

patents, along with patents and pending patents in various foreign jurisdictions.

We own three pending patent applications for epetraborole.

We have filed additional patent applications for epetraborole in MAB and PV.

Patents and patent applications, if granted, are expected to expire between 2028 and 2046, without taking potential patent term extensions or patent term adjustments into account.

18 unchanged sentences

Finally, the development of new treatment methods for the diseases we are targeting could render our product candidates non-competitive or obsolete.

We believe the competitive factors that will affect the development and commercial success of our initial product candidate, epetraborole, if approved, will be convenience of oral dosing, efficacy, safety, and tolerability profile, coverage of drug-resistant bacteria strains, lack of cross-resistance, price, and availability of reimbursement from governmental and other third-party payors.

If approved, epetraborole would compete with Insmed’s Arikayce, which is the only currently approved therapy for patients with treatment refractory MAC lung disease.

Other drugs used to treat these patients include generic drugs such as macrolides (clarithromycin and azithromycin), ethambutol, rifabutin, and fluoroquinolones such as levofloxacin, bedaquiline, linezolid, and clofazimine.

PV is typically managed with phlebotomy and low-dose aspirin, with cytoreductive therapy such as hydroxyurea commonly used in patients requiring additional disease control.

Two drugs are approved by the U.S.

Food and Drug Administration for the treatment of PV:

ruxolitinib, a JAK1/2 inhibitor approved for patients who are intolerant of or have an inadequate response to hydroxyurea, and ropeginterferon alfa-2b (Besremi®), an interferon therapy.

Despite these treatment options, many patients require ongoing phlebotomy to maintain hematocrit control, and existing therapies may be associated with limitations related to efficacy, tolerability, and route of administration.

If approved, epetraborole would be positioned as the first oral, red-cell targeting therapy for hematocrit control.

We believe that its potential targeted effects, tolerability profile, and oral dose administration could offer significant competitive advantages, if approved.

There are currently no FDA-approved therapies specifically indicated for the treatment of M.

abscessus lung disease.

Current treatment regimens rely on off-label use of IV antibiotics selected based on susceptibility testing and clinical judgment, frequently including intravenous agents associated with significant treatment burden and toxicity.

Epetraborole, if successfully developed and approved, would be positioned as the first FDA-approved drug for M.

There are currently no FDA-approved therapies specifically indicated for the treatment of Chagas disease in adults.

Available off-label therapies are typically administered for extended durations and may be associated with adverse effects that limit patient adherence or suitability, particularly in chronic infection.

In addition, treatment efficacy in established chronic disease remains variable, and access to therapy may be constrained in certain settings.

Within this landscape, we believe AN-502998 has the potential to address persistent unmet needs relating to safety, efficacy, tolerability and treatment burden, and if successfully developed and approved, could be positioned as a differentiated therapeutic option for Chagas disease.

Government Regulation and Product Approval

Government authorities in the United States, at the federal, state, and local level, and other countries extensively regulate, among other things, the research, development, testing, manufacture, quality control, approval, labeling, packaging, storage, record-keeping, promotion, advertising, distribution, marketing, and export and import of drug products.

A new drug must be approved by the FDA through the NDA process before it may be legally marketed in the United States.

Government authorities in the U.S., at the federal, state, and local level, and other countries extensively regulate, among other things, the research, development, testing, manufacture, quality control, approval, labeling, packaging, storage, record-keeping, promotion, advertising, distribution, marketing, and export and import of drug products.

A new drug must be approved by the FDA through the NDA process before it may be legally marketed in the U.S.

We, along with any third-party contractors, will be required to navigate the various preclinical, clinical and commercial approval requirements of the governing regulatory agencies of the countries in which we wish to conduct studies or seek approval of our product candidates.

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Drug Development Process

In the United States, the FDA regulates drugs under the federal Food, Drug, and Cosmetic Act (“FDCA”) and its implementing regulations.

In the U.S., the FDA regulates drugs under the federal Food, Drug, and Cosmetic Act (“FDCA”) and its implementing regulations.

The process of obtaining regulatory approvals and the subsequent compliance with appropriate federal, state and local statutes and regulations require the expenditure of substantial time and financial resources.

The process required by the FDA before a drug may be marketed in the United States generally involves the following:

The process required by the FDA before a drug may be marketed in the U.S.

generally involves the following:

• completion of certain preclinical laboratory tests, animal studies and formulation studies in accordance with Good Laboratory Practice regulations and other applicable regulations;

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• satisfactory completion of potential inspection of selected clinical investigation sites to assess compliance with GCPs;

• the FDA review and approval of the NDA to permit commercial marketing of the product for particular indications for use in the United States.

• the FDA review and approval of the NDA to permit commercial marketing of the product for particular indications for use in the U.S.

Once a product candidate is identified for development, it enters the preclinical testing stage.

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Orphan Drug Designation

Under the Orphan Drug Act, the FDA may grant orphan designation to a drug intended to treat a rare disease or condition, which is a disease or condition that affects fewer than 200,000 individuals in the United States or, if it affects more than 200,000 individuals in the United States, there is no reasonable expectation that the cost of developing and making a drug product available in the United States for this type of disease or condition will be recovered from sales of the product.

or, if it affects more than 200,000 individuals in the U.S., there is no reasonable expectation that the cost of developing and making a drug product available in the U.S.

for this type of disease or condition will be recovered from sales of the product.

Orphan designation must be requested before submitting an NDA.

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Orphan designation does not convey any advantage in or shorten the duration of the regulatory review and approval process.

If a product that has orphan designation subsequently receives the first FDA approval for the disease or condition for which it has such designation, the product is entitled to orphan product exclusivity, which means that the FDA may not approve any other applications to market the same drug for the same disease or condition for seven years, except in limited circumstances, such as a showing of clinical superiority to the product with orphan exclusivity or inability to manufacture the product in sufficient quantities.

If a product that has orphan designation subsequently receives the first FDA approval for the same approved use or indication within such rare disease or condition for which it has such designation, the product is entitled to orphan product exclusivity, which means that the FDA may not approve any other applications to market the same drug for the same approved use or indication within the applicable rare disease or condition for seven years, except in limited circumstances, such as a showing of clinical superiority to the product with orphan exclusivity or inability to manufacture the product in sufficient quantities.

The designation of such drug also entitles a party to financial incentives such as opportunities for grant funding towards clinical trial costs, tax advantages and user-fee waivers.

However, competitors, may receive approval of different products for the disease or condition for which the orphan product has exclusivity or obtain approval for the same product but for a different disease or condition for which the orphan product has exclusivity.

Orphan exclusivity also could block the approval of a competing product for seven years if a competitor obtains approval of the “same drug,” as defined by the FDA, or if the active moiety of the product candidate is determined to be contained within the competitor’s product for the same disease or condition.

However, competitors, may receive approval of different products for the same use or indication within the rare disease or condition for which the orphan product has exclusivity or obtain approval for the same product but for a different use or indication within the rare disease or condition for which the orphan product has exclusivity.

In addition, if an orphan designated product receives regulatory approval for a disease or condition broader than what is designated, it may not be entitled to orphan exclusivity.

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Regulatory exclusivity provisions under the FDCA can delay the submission or the approval of certain marketing applications.

The FDCA provides a five-year period of non-patent data exclusivity within the United States to the first applicant to obtain approval of an NDA for a new chemical entity.

The FDCA provides a five-year period of non-patent data exclusivity within the U.S.

to the first applicant to obtain approval of an NDA for a new chemical entity.

A drug is a new chemical entity if the FDA has not previously approved any other new drug containing the same active moiety, which is the molecule or ion responsible for the action of the drug substance.

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However, an applicant submitting a full NDA would be required to conduct, or obtain a right of reference to, all of the preclinical studies and adequate and well-controlled clinical trials necessary to demonstrate safety and effectiveness.

Pediatric exclusivity is another type of marketing exclusivity available in the United States.

Pediatric exclusivity is another type of marketing exclusivity available in the U.S.

Pediatric exclusivity provides for an additional six months of marketing exclusivity attached to another period of existing exclusivity or an available patent term if a sponsor conducts clinical trials in children in response to a “written request” from the FDA.

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Other Healthcare Laws

In the United States, we are subject to a number of federal and state healthcare regulatory laws that restrict business practices in the healthcare industry.

In the U.S., we are subject to a number of federal and state healthcare regulatory laws that restrict business practices in the healthcare industry.

These laws include, but are not limited to, federal and state anti-kickback, false claims, and other healthcare fraud and abuse laws, as follows:

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HIPAA, as amended by the Health Information Technology for Economic and Clinical Health Act of 2009 (“HITECH”), and their respective implementing regulations, which impose obligations on “covered entities,” including certain healthcare providers, health plans, and healthcare clearinghouses, as well as their respective “business associates” and their respective subcontractors that create, receive, maintain, or transmit individually identifiable health information for or on behalf of a covered entity, with respect to safeguarding the privacy, security, and transmission of individually identifiable health information.

The federal Physician Payments Sunshine Act requires certain manufacturers of drugs, devices, biologics, and medical supplies for which payment is available under Medicare, Medicaid, or the Children’s Health Insurance Program, with specific exceptions, to report annually to the Centers for Medicare & Medicaid Services (“CMMS”), information related to payments or other transfers of value made to physicians (defined to include doctors, dentists, optometrists, podiatrists, and chiropractors), certain other healthcare professionals including physician assistants and nurse practitioners, and teaching hospitals, and applicable manufacturers and applicable group purchasing organizations to report annually to CMMS ownership and investment interests held by physicians and their immediate family members.

The federal Physician Payments Sunshine Act requires certain manufacturers of drugs, devices, biologics, and medical supplies for which payment is available under Medicare, Medicaid, or the Children’s Health Insurance Program, with specific exceptions, to report annually to the Centers for Medicare & Medicaid Services (“CMS”), information related to payments or other transfers of value made to physicians (defined to include doctors, dentists, optometrists, podiatrists, and chiropractors), certain other healthcare professionals including physician assistants and nurse practitioners, and teaching hospitals, and applicable manufacturers and applicable group purchasing organizations to report annually to CMS ownership and investment interests held by physicians and their immediate family members.

Similar state and local laws and regulations may also restrict business practices in the pharmaceutical industry, such as state anti-kickback and false claims laws, which may apply to business practices, including but not limited to, research, distribution, sales, and marketing arrangements and claims involving healthcare items or services reimbursed by non-governmental third-party payors, including private insurers, or by patients themselves;

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Sales of any pharmaceutical product depend, in part, on the extent to which such product will be covered by third-party payors, such as federal, state, and foreign government healthcare programs, commercial insurance and managed healthcare organizations, and the level of reimbursement for such product by third-party payors.

In the United States, no uniform policy exists for coverage and reimbursement for pharmaceutical products among third-party payors.

In the U.S., no uniform policy exists for coverage and reimbursement for pharmaceutical products among third-party payors.

Therefore, decisions regarding the extent of coverage and amount of reimbursement to be provided are made on a plan-by-plan basis.

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Healthcare Reform

In the United States and certain foreign jurisdictions, there have been, and we expect there will continue to be, a number of legislative and regulatory changes to the healthcare system.

In the United States, by way of example, in March 2010, the Affordable Care Act (“ACA”) was signed into law, which substantially changed the way healthcare is financed by both governmental and private insurers in the United States and significantly affected the pharmaceutical industry.

and certain foreign jurisdictions, there have been, and we expect there will continue to be, a number of legislative and regulatory changes to the healthcare system.

In the U.S., by way of example, in March 2010, the Affordable Care Act (“ACA”) was signed into law, which substantially changed the way healthcare is financed by both governmental and private insurers in the U.S.

and significantly affected the pharmaceutical industry.

The ACA, among other things, increased the minimum level of Medicaid rebates payable by manufacturers of brand name drugs;

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Moreover, there has recently been heightened governmental scrutiny over the manner in which manufacturers set prices for their marketed products, which has resulted in several Congressional inquiries and proposed and enacted legislation designed, among other things, to bring more transparency to product pricing, review the relationship between pricing and manufacturer patient programs and reform government program reimbursement methodologies for pharmaceutical products.

Most significantly, in August 2022, the Inflation Reduction Act of 2022 (IRA) was signed into law.

Among other things, the IRA requires manufacturers of certain drugs to engage in price negotiations with Medicare (beginning in 2026), with prices that can be negotiated subject to a cap;

imposes rebates under Medicare Part B and Medicare Part D to penalize price increases that outpace inflation (first due in 2023);

and replaces the Part D coverage gap discount program with a new manufacturer discounting program (which began in 2025).

In August 2022, the Inflation Reduction Act of 2022 (“IRA”) was signed into law.

Among other things, the IRA requires manufacturers of certain drugs to engage in price negotiations with Medicare, with prices that can be negotiated subject to a cap, imposes rebates under Medicare Part B and Medicare Part D to penalize price increases that outpace inflation (first due in 2023), and replaces the Part D coverage gap discount program with a new manufacturer discounting program (which began in 2025).

The IRA permits the Secretary of the Department of Health and Human Services (“HHS”) to implement many of these provisions through guidance, as opposed to regulation, for the initial years.

HHS has issued and will continue to issue guidance implementing the IRA.

CMS published the negotiated prices for the initial ten drugs, which will first be effective in 2026, and the list of the subsequent 15 drugs that will be subject to negotiation, although the Medicare drug price negotiation program is currently subject to legal challenges.

CMS published the negotiated prices for the initial ten drugs, which went into effect in 2026, and the subsequent 15 drugs, which will first be effective in 2027, as well the next set of 15 drugs that will be subject to negotiation, although the Medicare drug price negotiation program is currently subject to legal challenges.

While the impact of the IRA on our business and the pharmaceutical industry cannot yet be fully determined, it is likely to be significant.

Individual states in the United States have also become increasingly active in implementing regulations designed to control pharmaceutical product pricing, including price or patient reimbursement constraints, discounts, restrictions on certain product access and marketing cost disclosure, drug price reporting and other transparency measures and, in some cases, mechanisms to encourage importation from other countries and bulk purchasing.

The One Big Beautiful Bill Act, which was enacted in July 2025, imposes significant reductions in the funding of the Medicaid program.

Such reductions are expected to decrease the number of persons enrolled in Medicaid and reduce the services covered by Medicaid, which could adversely affect our sales of any product candidate that we commercialize.

The Trump administration is pursuing a two-fold strategy to reduce drug costs in the U.S.

While it is unclear whether and how the Trump proposals will be implemented, the Trump policies are likely to have a negative impact on the pharmaceutical industry and on our ability to receive adequate revenues for any product candidate that we commercialize.

On the one hand, President Trump has threatened to impose significant tariffs on pharmaceutical manufacturers that do not adopt pricing policies such as most favored nation pricing, which would tie the price for drugs in the U.S.

to the lowest price in a group of other countries.

In response, multiple manufacturers have reportedly entered into confidential pricing agreements with the federal government.

On the other hand, the Trump administration is pursuing traditional regulatory pathways to impose drug pricing policies, and published two proposed regulations in December 2025, referred to as Globe and Guard.

If finalized, these regulations would implement mandatory payment models under which manufacturers of eligible drugs would be required to pay rebates to the federal government on a portion of the units of their drugs that are reimbursed by Medicare, with the rebate amount based on most favored nation pricing.

While the impact of the Globe and Guard proposed regulations, if finalized, cannot yet be determined, it is likely to be significant.

Even regulatory proposals or executive actions that are ultimately deemed unlawful could negatively impact the U.S.

pharmaceutical sector and our business.

Individual states in the U.S.

have also become increasingly active in implementing regulations designed to control pharmaceutical product pricing, including price or patient reimbursement constraints, discounts, restrictions on certain product access and marketing cost disclosure, drug price reporting and other transparency measures and, in some cases, mechanisms to encourage importation from other countries and bulk purchasing.

Some states have enacted legislation creating so-called prescription drug affordability boards, which ultimately may attempt to impose price limits on certain drugs in these states.

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As a pharmaceutical company, we are subject to state, federal and foreign laws, including consumer protection laws and regulations, governing the collection, dissemination, use, access to, confidentiality, and security of personal information, including health-related information.

For example, in the United States, numerous federal and state laws and regulations, including data breach notification laws, health information privacy and security laws (e.g., the Health Insurance Portability and Accountability Act (“HIPAA”)), and federal and state consumer protection laws and regulations (e.g., Section 5 of the Federal Trade Commission Act) that govern the collection, dissemination, use, protection and other processing of health-related and other personal information currently or could in the future apply to our operations or the operations of our partners.

For example, in the U.S., numerous federal and state laws and regulations, including data breach notification laws, health information privacy and security laws (e.g., the Health Insurance Portability and Accountability Act (“HIPAA”)), and federal and state consumer protection laws and regulations (e.g., Section 5 of the Federal Trade Commission Act) that govern the collection, dissemination, use, protection and other processing of health-related and other personal information currently or could in the future apply to our operations or the operations of our partners.

In addition, certain state and non-U.S.

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Japanese Drug Regulation

Being a member of the ICH, Japan has pharmaceutical regulations fundamentally similar to those of the United States and the EU.

Being a member of the ICH, Japan has pharmaceutical regulations fundamentally similar to those of the U.S.

Clinical trials of medicinal products in Japan must be conducted in accordance with Japanese regulations based on ICH guidelines governing GCP.

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Employees and Human Capital Resources

As of February 28, 2025, we had 22 full-time employees, consisting of research, manufacturing, clinical operations, regulatory, quality, finance, and operational personnel.

As of March 17, 2026, we had 21 full-time employees, consisting of research, manufacturing, clinical operations, quality, finance, and operational personnel.

None of our employees are subject to a collective bargaining agreement.

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We incorporated in Delaware on February 24, 2017 and launched operations in November 2019.

We completed the initial public offering (the “IPO”) of our common stock in March 2022, and our common stock is listed on the Nasdaq Global Select Market under the symbol “ANTX.” Our principal executive offices are located at 1800 El Camino Real, Suite D, Menlo Park, California, 94027, and our telephone number is (650) 331-9090.

We completed the initial public offering (the “IPO”) of our common stock in March 2022, and our common stock is listed on the Nasdaq Global Select Market under the symbol “ANTX.” Our principal executive offices are located at 1300 El Camino Real, Suite A, Menlo Park, California, 94025, and our telephone number is (650) 331-9090.

Securities Exchange Act Reports

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Compared sentence by sentence after normalising whitespace, quotation marks, case and digits, so re-formatting and restated figures do not read as changed language. Wording changes appear as one removal and one addition. The current filing and the prior one are authoritative.

What changed 10-K

Item 1. Business