IRL1117, Potential Improvement on Levodopa, May Enter Clinical Trial
IRLAB planning for 2024 trial of longer-lasting oral therapy with fewer side effects
IRLAB Therapeutics has selected a dopamine receptor agonist candidate called IRL1117 to advance as a Parkinson’s disease treatment, potentially as a longer-lasting alternative to levodopa with lesser side effects.
IRL1117 is designed to be a once-daily oral therapy for the hallmark symptoms of Parkinson’s — tremors, rigidity, and slowness of movements — and the company plans to bring it into a Phase 1 clinical trial in 2024.
In preclinical studies, IRLAB reported that IRL1117 showed long-lasting efficacy without causing dyskinesia, the uncontrolled and involuntary movements that are a complication of long-term levodopa use.
It is the first therapy to advance in development from the company’s P003 research project looking into potential and oral dopamine receptor agonist compounds without levodopa’s limitations, which include short-duration effectiveness and dyskinesia.
Company has two other Parkinson’s therapies in Phase 2 clinical trials
“We are looking forward to learning more about the efficacy and safety profile of IRL1117 as it develops toward clinical studies,” Nicholas Waters, IRLAB’s executive vice president and head of research and development, said in a company press release.
Parkinson’s is marked by the progressive dysfunction and death of nerve cells in the brain responsible for producing the chemical messenger dopamine.
Levodopa is the mainstay therapy for the disease’s hallmark motor symptoms, and it works to provide a patient’s brain with the raw materials used to make dopamine. Its effectiveness, however, is known to diminish over time, causing patients to experience “off” periods, or times between levodopa doses marked by a return of dyskinesia and other disease-related motor complications.
Specifically, IRL1117 works as an agonist, or activator, of dopamine receptor proteins called D1 and D2.
“IRL1117 is an orally available and potent dopamine D1 and D2 receptor agonist that has demonstrated rapid onset and more than 10 hours of sustained efficacy in preclinical studies,” Waters said.“This is a sharp contrast to the short duration of today’s Parkinson’s treatment alternatives, thus indicating that IRL1117 could become a significant improvement in the treatment of Parkinson’s.”
Overall, “we are very excited about the P003 project,” added Richard Godfrey, IRLAB’s chief executive officer. “A drug candidate from the project could, after successful clinical development, come to be an important drug for the mainstay treatment of the hallmark symptoms of Parkinson’s.”
Two other potential Parkinson’s treatments by the company are in or recently completed clinical testing.
A Phase 2b trial (NCT04435431) of oral mesdopetam (formerly, IRL790) in easing dyskinesia in adults patients finished in December and results are expected soon.
A separate Phase 2b trial (NCT05258071) is testing pirepemat (formerly, IRL752), at a low and high dose against a placebo, as an oral add-on therapy to improve balance and prevent falls in up to 165 adults, ages 55 to 85, with Parkinson’s and at least a three-month history of frequent falls, including at least two falls within the month before study entry.
The study’s main goal is the change in the number of falls through 12 weeks of treatment. It is currently recruiting eligible patients at sites across Europe.
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