Pipeline

AN2 has a pipeline of novel boron-based compounds that have the potential to be best in class therapeutics. The company intends to advance its global health initiatives using non-dilutive funding, which the company obtains from sources such as public and private agencies and foundations.

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About AN2-502998

AN2-502998 (formerly known as AN15368) is a boron-based small molecule therapeutic candidate under development for the treatment of chronic Trypanosoma cruzi (T. cruzi) infection, which causes 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. 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. A Phase 1 clinical study is underway evaluating the safety, tolerability, and pharmacokinetics of oral AN2-502998 in healthy volunteers.

About 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. T. 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, with approximately 300,000 people infected in the U.S. and over 100,000 in Europe.

Chagas disease presents in an acute phase (~2 months after infection) and a chronic phase, where the T. cruzi parasites are hidden in muscle tissue, including the heart and digestive system. For over 50 years, two nitroheterocyclic compounds, benznidazole and nifurtimox, have been available for treatment of the infection and more recently were 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.

About Epetraborole

Epetraborole is a boron-containing, orally-available, 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. Epetraborole forms a complex with a tRNA^Leu molecule, trapping the terminal ribonucleotide of tRNA^Leu in the editing site of the enzyme, which prevents the synthetic site from attaching leucine to tRNA^Leu thus shutting down tRNA leucylation and leading to a block in protein synthesis. This is an example of a completely novel target being enabled by boron chemistry.

We continue to explore epetraborole’s potential in the treatment of non-tuberculous mycobacterial lung disease, or NTM lung disease. While the EBO-301 trial in treatment-refractory MAC lung disease failed to demonstrate adequate efficacy in patients with severe, difficult-to-treat MAC lung disease, we continue to explore epetraborole in M. abscessus lung disease, a highly drug-resistant, rapidly growing non-tuberculous mycobacteria that is a common soil and water contaminant.

About Melioidosis

Melioidosis is an urgent unmet global health infectious disease caused by the bacterium Burkholderia pseudomallei (B. pseudomallei). This bacterium is also designated by the U.S. government as a high priority biothreat pathogen. B. pseudomallei is endemic to tropical regions of the world with the majority of 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. B. pseudomallei can be an intra-cellular pathogen in macrophages, an important element of melioidosis. The disease can manifest as a localized infection causing pain, swelling and ulceration; as a pulmonary infection causing cough, chest pain, high fever, and headache; and as a blood stream infection 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, six 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 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 by AN2, Anacor, the U.S. Army Research Institute of Infectious Diseases, and Colorado State University indicate that epetraborole has potent activity against B. pseudomallei.

M. abscessus (Mycobacterium abscessus)

M. abscessus is a highly drug-resistant, rapidly growing non-tuberculous mycobacteria that is a common soil and water contaminant. We are developing epetraborole as a potential first-line therapy in M. abscessus lung disease. Current treatments for M. abscessus lung disease have poor efficacy (~50%), are often delivered by intravenous infusion, and have significant tolerability and safety issues. We believe that oral epetraborole, in combination with other drugs, has the potential to treat M. abscessus lung disease based on its in vitro and in vivo potency against multiple isolates.

Clinical Trials

AN2 Therapeutics is committed to delivering high-impact drugs to patients that address critical unmet needs and improve health outcomes. Successful clinical trials are required to gain regulatory approval for new medications to advance patient care and may be required to support any approved products.

For information on AN2 Therapeutics clinical trials that may be recruiting, search AN2 Therapeutics at www.clinicaltrials.gov