Antisense Therapeutics is currently developing ATL1102 as a therapeutic candidate for relapsing-remitting forms of multiple sclerosis (MS). ATL1102 is a second generation antisense inhibitor of CD49d, a subunit of the VLA-4 (Very Late Antigen-4) receptor on the surface of lymphocytes. Antisense drugs (therapies containing the non-coding strand of messenger RNA, or mRNA, a molecule central to the translation of DNA into protein) are used over the years to treat different types of cancers, amyotropic lateral sclerosis, diabetes, and diseases with an inflammatory component like asthma and arthritis.
How ATL1102 Works
The mode of action of ATL1102 is thought to involve inhibition of the VLA-4 receptor on lymphocytes, preventing these immune cells from attaching to sites of damage and inflammation, so as to reduce disease progression. VLA-4 is a clinically validated target for an MS treatment, and antisense inhibition of the receptor has demonstrated effectiveness in published preclinical studies in MS animal models of the disease.
History of ATL1102
Preclinical trials in MS-treated monkeys showed positive results at doses ranging from 1.5 to 3 mg/kg over six months. Likewise, Phase 1 clinical trials successfully tested the drug’s safety and tolerance in healthy human hosts. A Phase 2a trial was then conducted in 77 patients with the relapsing and remitting MS, and met its primary endpoint by demonstrating a significant reduction in disease progression (54.4 percent), compared to placebo, after two months of treatment. This trial, whose results were reported in the journal Neurology in November 2014, was said by its principal investigator to provide “evidence for the first time that antisense oligonucleotides may be used as a therapeutic approach in neuroimmunologic disorders such as MS.”
Next Steps For ATL1102
A Phase 2b clinical trial is planned and, according to Multiple Sclerosis Society UK, the company announced in February 2016 its intent to submit an Investigational New Drug application to the U.S. Food and Drug Administration (FDA) to begin the trial. But no date has been set.
Currently, Antisense Therapeutics is looking for a pharmaceutical partner to advance its clinical trial program for ATL1102.
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