Novartis: An Early-Stage Study for Chagas Disease Treatment
Chagas disease remains one of the most neglected parasitic infections in the Americas, affecting approximately six million people and often progressing from an acute infection to potentially life-threatening chronic disease.
Current treatments can require prolonged dosing and are associated with adverse effects that can lead patients to discontinue therapy, while less than 1% of affected individuals receive appropriate treatment.
Researchers at Novartis have identified IID432, an optimised small molecule that achieved sterile cure of chronic Trypanosoma cruzi infection in mice after a single oral dose.
The findings, published in the study titled: IID432, a parasite-selective topoisomerase II inhibitor, achieves rapid single-dose parasite clearance in a murine chronic Chagas model, point towards a potential new approach for shortening Chagas disease treatment.
Targeting the parasitic infection
IID432 is a cyanotriazole designed to act on T. cruzi through a mechanism that distinguishes the parasite from its human host.
The compound targets the parasiteās topoisomerase II, an enzyme involved in managing DNA during the parasiteās lifecycle and forms a covalent bond with a parasite-specific cysteine known as Cys477.
This interaction stabilises the topoisomerase II-DNA cleavage complex, triggering parasite-specific DNA damage and ultimately killing the parasite.
Importantly, the researchers reported that IID432 showed no off-target activity against human topoisomerases, supporting its potential selectivity.
āI'm proud to share this work from our Novartis Global Health researchers showing potential for our experimental drug candidate for chronic chagas disease in an early-stage study,ā says Fiona H.Marshall, President of Biomedical Research at Novartis, on LinkedIn.
āIn their preclinical investigation, which theyāve published in PNAS, the compound achieved rapid parasite clearance in a murine Chagas model in a single dose.
āOur researchers discovered a novel way to selectively target the parasite while potentially sparing human cells, opening the possibility of dramatically shorter treatment regimens.
āWhile additional work lies ahead, this is the kind of breakthrough science that has the potential to change what is possible for patients.ā
- Annually, the disease causes 12,000 deaths.
- Approximately 1% of patients receive adequate treatment.
- Globally, six million people are affected.
- To date, 21 Latin American countries are endemic.
- The acute phase for Chagas disease can last up to two months, often remaining asymptomatic or unrecognised.
The study also found that brief exposure to the compound rapidly produced sterilising activity in laboratory and animal models, with no evidence of parasite recrudescence.
A potential shift towards shorter treatment
The findings are particularly significant because existing nitroheterocyclic therapies for Chagas disease face challenges linked to treatment duration and safety-related discontinuation.
In a murine model of chronic T. cruzi infection, IID432 achieved sterile cure after a single oral dose, while also demonstrating favourable oral pharmacokinetics.
The researchers describe the compound as a fast-acting, parasite-selective topoisomerase poison, distinguishing it from approaches that require extended exposure to treatment.
Although the results are currently based on preclinical research, the findings provide evidence for further development of IID432 as a potential Chagas disease therapy.
Millions of people are affected by Chagas disease, yet current treatments for this life-threatening infection can require weeks of therapy, which is often abandoned due to side effects.
A shorter treatment approach could address an important unmet need if the compound can ultimately demonstrate comparable safety and efficacy in humans.
An integrated approach to Chagas disease
Novartis’ work on Chagas disease extends beyond drug discovery, encompassing clinical research, healthcare-system strengthening and partnerships across Latin America.
The company says its Biomedical Research teams focused on Global Health are investigating parasite-specific growth inhibitors for Chagas disease and other kinetoplastid diseases, while it has also supported research into chronic Chagas cardiomyopathy.
Since 2019, Novartis has collaborated with the Brazilian Clinical Research Institute on a Phase IV study involving people with heart failure caused by chronic Chagas cardiomyopathy, including sub-studies examining biomarkers, arrhythmia burden and cardiac structure.
The company has also worked with partners including ISGlobal, the Global Chagas Disease Coalition, the World Heart Federation and the Federal University of Minas Gerais on healthcare capability and understanding the disease burden.
The IID432 research was supported by Novartis Biomedical Research and in part by the Wellcome Trust, while the authors disclosed that multiple researchers are Novartis employees and some own Novartis shares.
Acquisitions and partners
Chinook Therapeutics
Novartis acquired Chinook Therapeutics to strengthen its renal portfolio and expand its presence in kidney disease. The acquisition brought two late-stage IgA nephropathy programmes, atrasentan and zigakibart, alongside earlier-stage research programmes. Chinook’s precision-medicine approach complements Novartis’ focus on innovative treatments for patients with serious chronic kidney conditions.
Tourmaline Bio
Novartis acquired Tourmaline Bio to strengthen its cardiovascular pipeline with pacibekitug, an investigational anti-IL-6 monoclonal antibody for atherosclerotic cardiovascular disease. The therapy targets systemic inflammation, an important driver of cardiovascular risk. The acquisition added a Phase 3-ready asset, supporting Novartis’ efforts to develop new approaches to cardiovascular care.
DTx Pharma
Novartis acquired DTx Pharma to expand its RNA-based therapeutic capabilities and neuroscience pipeline. DTx’s proprietary FALCON platform enables the development of siRNA therapies, including DTx-1252 for Charcot-Marie-Tooth disease type 1A. The acquisition also included two additional preclinical neuroscience programmes, broadening Novartis’ capabilities in targeted RNA delivery.
Regulus Therapeutics
Novartis acquired Regulus Therapeutics to advance treatments for autosomal dominant polycystic kidney disease, the most common genetic cause of renal failure. Its lead programme, farabursen, is an investigational next-generation oligonucleotide targeting miR-17, with preferential kidney exposure. The acquisition strengthens Novartis’ renal pipeline and its focus on diseases with significant unmet needs.
Avidity Biosciences
Novartis acquired Avidity Biosciences to strengthen its neuroscience pipeline and advance its xRNA strategy. Avidity’s Antibody Oligonucleotide Conjugates platform enables targeted RNA delivery to muscle, supporting programmes for genetic neuromuscular diseases. The acquisition brought three late-stage programmes and a differentiated delivery platform into Novartis’ portfolio, expanding its RNA therapeutic capabilities.
Anthos Therapeutics
Novartis acquired Anthos Therapeutics to strengthen its cardiovascular pipeline with abelacimab, a late-stage monoclonal antibody targeting the FXI pathway. Abelacimab is being developed for the prevention of stroke and systemic embolism in patients with atrial fibrillation. The acquisition added a Phase 3 asset to Novartis’ cardiovascular portfolio and supports its focus on innovative cardiovascular medicines.
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Executives
Fiona H. Marshall
President, Biomedical Research
