Results from a first-in-human study assessing the safety and early activity of PRN2246 confirmed that the oral compound can reach into the brain and spinal cord.
This finding adds new evidence that PRN2246 has the potential to target the immune cells that drive the inflammatory process involved in multiple sclerosis (MS) and other diseases of the central nervous system (CNS).
PRN2246 is being developed by Principia Biopharma, in collaboration with Sanofi Genzyme, to specifically target cells involved in autoimmunity and inflammatory processes in the CNS. It was designed to cross the blood-brain-barrier and inhibit the activity of the Bruton’s tyrosine kinase (BTK), a key mediator of B-cell receptor signaling. As such, it aims to modulate the activity of CNS-resident immune B-cells without depleting them.
The toxicity, tolerability, and stability of the investigational agent, in a liquid formulation, is being tested in a placebo-controlled Phase 1 trial (ACTRN12617001457336) conducted in Australia. The study included more than 70 healthy volunteers, who were treated with increasing doses of PRN2246 that ranged from 7.5 mg up to 120 mg. Based on trial data, the researchers will select an optimal dose to be used in future clinical studies.
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Preliminary results revealed that PRN2246 is well-tolerated, with no reports of serious treatment-related adverse events. The agent was also shown to effectively inhibit BTK at clinically relevant dose levels.
In a dedicated arm of the trial, the researchers confirmed that PRN2246 was present in the cerebral spinal fluid of the volunteers, meaning that it can achieve its goal of passing the blood-brain-barrier, which protects the brain from disease-causing pathogens and toxins that may be present in the blood.
This important finding indicates that PRN2246 holds the ability to overcome this shield and have a positive impact on immune cells that reside in the CNS and drive damaging mechanisms in the brain and spinal cord of MS and other patients.
“Confirmation that PRN2246 crosses the blood-brain barrier in humans and achieves therapeutic levels in the CSF [cerebral spinal fluid] is an important milestone for this program,” Martin Babler, CEO of Principia Biopharma, said in a press release. “We now look forward to evaluating the potential additional benefit of modulating B-cells directly in both the periphery and the CNS in MS patients.”
After this study fully concludes — final data collection is expected in August — Sanofi is planning to test the potential of PRN2246 to treat MS and possibly for other CNS diseases associated with inflammation and autoantibodies.