Aslan Pharmaceuticals announced it will develop Aslan003, a potent and highly selective next-generation modulator of the immune system, as a potential therapy for autoimmune diseases such as multiple sclerosis (MS).
Aslan003 is a small molecule blocking the human enzyme dihydroorotate dehydrogenase (DHODH). This enzyme is believed to reduce the activity of B-cells and T-cells — immune cells that drive inflammation that can damage the nervous system in MS.
Existing oral DHODH inhibitors, used in the treatment of autoimmune conditions such as rheumatoid arthritis and MS, have limited effectiveness and associated toxicity, which makes them unsuitable for long-term treatment.
In previous clinical studies, Aslan003 was shown to be specific, potent and safe. That is why Aslan believes it to be a good candidate for development in the treatment of autoimmune diseases.
“We believe Aslan003 has a potential best in class profile as the most potent oral DHODH inhibitor targeting autoimmune indications. There is a current need for a differentiated therapeutic approach to MS that can deliver improved efficacy and addresses the risks of toxicity associated with this and other classes of drug in the field,” Carl Firth, PhD, CEO of Aslan, said in a press release.
In experiments using cells, Aslan003 was 30 times more potent at inhibiting the DHODH enzyme than first-generation MS therapy Aubagio (teriflunomide, marketed by Sanofi Genzyme). Moreover, Aslan003 was shown to be an effective treatment in animal models of MS and other autoimmune conditions.
In previous Phase 1 and Phase 2 clinical trials evaluating the safety, tolerability and how the body affects and processes Aslan003 (pharmacokinetics), the therapy was well-tolerated at doses up to 400 mg per day and suitable for a once-daily oral regimen.
“New and effective treatment approaches with improved safety, efficacy and convenience are highly sought after by the MS community. Aslan003’s potency and favourable safety profile make it a promising next generation DHODH inhibitor,” said Gavin Giovannoni, PhD, chair of neurology at Blizard Institute, Barts and The London School of Medicine and Dentistry.
Aslan has appointed Giovannoni as a scientific advisor to the company to help with the clinical development of Aslan003 for treating autoimmune diseases. The company expects to share further details regarding the development of this therapy in early 2021.
In 2019, a Phase 2 trial (NTC03451084) testing Aslan003 for the treatment of acute myeloid leukemia was completed. At the time, based on an internal strategic review and on the AML treatment market, Aslan decided to focus the strategic plan for Aslan003 on autoimmune diseases.
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