Our second BTK inhibitor, PRN2246/SAR442168, is currently being evaluated by our partner, Sanofi, in patients with multiple sclerosis.

PRN2246/SAR442168is an irreversible covalent, oral small molecule with potent and durable action, designed to access the brain and spinal cord by crossing the blood-brain barrier.

Multiple Sclerosis (MS) is a chronic inflammatory degenerative disorder affecting more than 2.3 million people around the world, resulting from the gradual destruction of the myelin sheaths that protect nerve cells, and of the nerve cells themselves. As a result, the nervous system no longer functions properly.  MS patients eventually develop significant morbidity, including difficulty with muscle control, movement, cognition, and vision.

B lymphocytes are widely recognized as a critical driver of the disease process. B cells are essential to a healthy immune system but appear to play a major role in MS by activating the cells that attack nerve sheaths in MS patients. Breakthroughs in MS research supports the theory that disease-causing B-cells may reside in both the periphery and the brain and CNS (central nervous system). Researchers have sought ways to inhibit BTK as a key part of the B cell control mechanism, particularly in the brain to normalize the function of microglia, brain cells that contribute to damaging inflammation.

Specifically targeting BTK in the brain and CNS has the potential to significantly advance the treatment of both progressive and relapsing forms of MS and is why Sanofi, a leader in MS, partnered with us on this BTK inhibitor that we designed specifically to cross into the CNS. It is our shared belief that having a drug that can reach the CNS could significantly improve clinical outcomes in this devastating disease.

Key findings from a Phase 1 trial in healthy volunteers confirmed that PRN2246/SAR442168 was well tolerated in the trial, that BTK occupancy increased in a dose-dependent manner and that cerebral spinal fluid exposure was achieved in all subjects who underwent lumbar puncture. In February 2020, Sanofi announced data for their Phase 2b clinical trial in relapsing MS. Specifically, Sanofi announced that PRN2246/SAR442168 met its primary endpoint, significantly reduced disease activity associated with MS as measured by magnetic resonance imaging, or MRI, and was well tolerated in the Phase 2b trial with no new safety findings. Sanofi also announced that it anticipates initiating four Phase 3 clinical trials in relapsing-remitting (RMS), primary progressive (PPMS) and secondary progressive (SPMS) forms of MS in the middle of 2020.

Ongoing Clinical Studies