AN2 Therapeutics Partners with DNDi to Advance Oral Chagas Disease Treatment AN2-502998
Key Insights
AN2 Therapeutics and DNDi announced a collaboration to advance clinical development of AN2-502998, an oral drug candidate with curative potential for chronic Chagas disease (search) affecting 6-7 million people worldwide.
The boron-based benzoxaborole compound targets CPSF3 (search) in T. cruzi parasites, utilizing the same mechanism as acoziborole which achieved ~95% cure rates in African sleeping sickness (search) trials.
Phase 1 first-in-human studies are underway with completion expected in the second half of 2025, followed by Phase 2 proof-of-concept trials planned for 2026.
AN2 Therapeutics, Inc. (Nasdaq: ANTX) and the Drugs for Neglected Diseases initiative (DNDi) have announced a strategic collaboration to advance clinical development of AN2-502998, an oral drug candidate targeting chronic Chagas disease (search). The partnership leverages DNDi's extensive clinical trial network and expertise to rapidly advance development of the compound, which demonstrates curative potential for a disease affecting 6 to 7 million people worldwide, including an estimated 300,000 in the United States.
Novel Mechanism Targets Critical Parasite Pathway
AN2-502998 is a boron-based small molecule therapeutic candidate from the benzoxaborole class, functioning as an orally active CPSF3 (search) inhibitor in Trypanosoma cruzi (search) parasites. CPSF3 represents a key factor involved in messenger RNA processing and serves as the same target as acoziborole, a benzoxaborole drug candidate that demonstrated approximately 95% cure rates after a single oral dose in Phase 2/3 studies for human African trypanosomiasis (search).
The benzoxaborole class has established clinical precedent, with two FDA-approved drugs (crisaborole and tavaborole) already demonstrating the therapeutic potential of this chemical scaffold. This foundation provides confidence in the safety and efficacy profile of AN2-502998 as it advances through clinical development.
Addressing Critical Unmet Medical Need
Chagas disease (search), also known as American trypanosomiasis (search), is caused by the parasite Trypanosoma cruzi (search) and represents a significant global health challenge. The T. cruzi parasite invades the body and establishes long-term residence in various tissues, including the heart and gastrointestinal system. Patients with chronic Chagas disease (search) often remain asymptomatic for years while the infection silently causes irreversible damage to vital systems, analogous to the chronic liver damage experienced by patients with hepatitis C.
Approximately 30% of patients with chronic T. cruzi infection develop serious manifestations that can lead to heart failure (search), arrhythmias, aortic aneurism, megacolon, megaesophagus, and other life-threatening conditions. The disease follows a chronic, progressive course, making timely diagnosis and access to treatment critical. Currently, there are no FDA-approved treatments for adults with Chagas disease (search), highlighting the urgent need for effective therapeutic options.
Strategic Partnership Accelerates Development
"By drawing upon DNDi's deep expertise in Chagas disease (search) clinical trials, our collaboration optimizes resources, supports rigorous scientific execution, and accelerates access to a potential breakthrough therapy across multiple geographies, all while allowing AN2 to maintain full investment in our other high-potential pipeline programs," said Eric Easom, Co-Founder, Chairman, President, and CEO of AN2 Therapeutics.
DNDi brings substantial experience to the collaboration, having led and participated in multiple clinical trials for Chagas disease (search) through an established network of clinical trial sites throughout Latin America and Spain. In 2009, DNDi and its partners created the Chagas Clinical Research Platform, which advances pharmaceutical research and development for Chagas disease through stakeholder partnerships.
Dr. Laurent Fraisse, R&D Director at DNDi, emphasized the organization's commitment to the collaboration: "We are committed to sharing DNDi's deep expertise to accelerate the development of candidates with strong potential to fulfill the Chagas disease (search) target product profile, as is the case for AN2-502998. Having worked with members of the AN2 team for nearly 20 years, we successfully discovered and developed several drug candidates from the oxaborole class, including acoziborole, a single oral dose cure for African sleeping sickness (search) and DNDI-6148, which emerged as a promising clinical candidate for leishmaniasis (search) and Chagas disease working through the same novel mechanism of action as AN2-502998."
Clinical Development Timeline
AN2 Therapeutics has initiated startup activities for its Phase 1 first-in-human clinical study of oral AN2-502998, with completion expected in the second half of 2025. The company anticipates initiation of a Phase 2 proof-of-concept study in 2026, supported by DNDi's clinical infrastructure and expertise.
One of DNDi's core priorities is developing an oral, age-adapted, shorter-course treatment for Chagas that is safer, better tolerated, and more effective than current options while remaining accessible to patients in all affected regions. Dr. María Jesús Pinazo, Head of Chagas disease (search) at DNDi, noted that "this collaboration with AN2 complements DNDi's broader early-stage pipeline of novel candidates for Chagas disease. In parallel to the development of therapeutics, we are also investing in biomarker research and implementation studies to ensure that effective diagnostics and treatments can reach the people who need them most."
Global Health Impact Potential
The collaboration represents a significant opportunity to address a neglected tropical disease that disproportionately affects underserved populations. An estimated 6-7 million people worldwide are infected with T. cruzi, mostly in endemic regions in Latin America, with approximately 300,000 people infected in the U.S. and over 100,000 in Europe. Left untreated, chronic Chagas infection is lifelong and silently damages the heart and digestive system, potentially resulting in heart failure (search), stroke, or sudden death.
The partnership between AN2 Therapeutics and DNDi exemplifies the potential for public-private collaborations to accelerate development of treatments for neglected diseases. Since its creation in 2003, DNDi has collaborated with public and private partners worldwide to deliver twelve new treatments for six deadly diseases, saving millions of lives. The organization was founded by Doctors Without Borders/Médecins Sans Frontières (MSF) using their Nobel Prize money and continues to focus on discovering, developing, and delivering safe, effective, and affordable treatments for neglected populations.