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New Research Published in Toxicology in Vitro Provides Insight Into the Hepatotoxicity of DHODH Inhibitors Suggesting ASLAN003 Has the Potential to Be Best-In-Class
— New research shows ASLAN003 to have the lowest potential for hepatotoxicity of the compounds tested despite being one of the most potent DHODH inhibitors
— Data differentiates ASLAN003 from first generation DHODH inhibitors and other drugs in the class, supporting its potential to be best-in-class DHODH inhibitor for the treatment of autoimmune diseases
SINGAPORE, Jan. 26, 2021 (GLOBE NEWSWIRE) -- ASLAN Pharmaceuticals (Nasdaq:ASLN), a clinical-stage immunology focused biopharmaceutical company developing innovative treatments to transform the lives of patients, today announced that new data from a study conducted by University of Liverpool, UK, published in the Toxicology in Vitro Journal, demonstrates that, out of a panel of six dihydroorotate dehydrogenase (DHODH) inhibitors tested, ASLAN003 has the lowest potential for hepatotoxicity despite being one of the most potent inhibitors of DHODH.
Drug-induced liver injury (DILI) is a major driver of both pre- and post-market drug attrition, often hampering the development of therapeutically applicable compounds. Safety concerns around the use of first generation DHODH inhibitors (leflunomide and teriflunomide) have arisen in recent years and the US Food and Drug Administration has issued black-box warnings for hepatotoxicity.
Scientists at the University of Liverpool, a world leading centre for hepatotoxicity, undertook a study to evaluate the hepatotoxic potential of a panel of six DHODH inhibitors in two readily available hepatic in vitro models. In one model, ASLAN003 was shown to be the least toxic compound tested despite being one of the most potent DHODH inhibitors, while teriflunomide and leflunomide were equally the most toxic compounds tested. The data further demonstrate that the activity of ASLAN003 is mechanistically distinct from the hepatotoxicity associated with leflunomide and teriflunomide, and is consistent with the observation that ASLAN003 has been well tolerated in clinical trials to date. Taken together these data suggest that the toxicities observed in the study may not be related to the potency of the compound against DHODH and confirm that ASLAN003 has the potential to be best-in-class for the treatment of autoimmune diseases.
In preclinical studies, ASLAN003 has been shown to be efficacious in various animal models of autoimmune diseases. ASLAN is finalising its clinical development plan for ASLAN003 in autoimmune disease and the company expects to share further details in early 2021.
The publication, titled ‘Investigating Dihydroorotate Dehydrogenase Inhibitor Mediated Mitochondrial Dysfunction in Hepatic in vitro Models’, is available to view at: https://doi.org/10.1016/j.tiv.2021.105096
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