P3, N=300, Not yet recruiting, Vanda Pharmaceuticals

The PK of mocravimod and mocravimod-phosphate were bioequivalent with or without co-administration of multiple doses of itraconazole and a moderate interaction is observed when co-administered with cyclosporin. The most commonly-reported treatment-emergent adverse events were bradycardia and decreased lymphocyte count, which are expected side effects for S1PR modulators.

P3, N=366, Recruiting, Priothera SAS | Trial primary completion date: Nov 2028 --> May 2027

P3, N=366, Recruiting, Priothera SAS | Active, not recruiting --> Recruiting | N=249 --> 366 | Trial completion date: Nov 2028 --> Nov 2029 | Trial primary completion date: Nov 2027 --> Nov 2028

P3, N=249, Active, not recruiting, Priothera SAS | Trial completion date: Nov 2025 --> Nov 2028 | Trial primary completion date: Nov 2025 --> Nov 2027

P3, N=249, Active, not recruiting, Priothera SAS | Recruiting --> Active, not recruiting

These results suggest a model that noncanonical spatial reorganization of phosphoinositides by KRP203 alters the endosomal maturation process, leading to vacuolization. Taken together, this study reveals a previously unrecognized bioactivity of KRP203 as a vacuole-inducing agent and its unique mechanism of phosphoinositide modulation, providing a new insight of phosphoinositide regulation into vacuolization-associated diseases and their molecular pathologies.

P3, N=877, Completed, Actelion | Active, not recruiting --> Completed

Moreover, treatment with ponesimod alone or in combination with A971432, an S1P5 monoselective modulator, significantly increased primary mouse OPC differentiation based on O4 immunocytochemistry. In conclusion, S1P1 functional antagonism by ponesimod increases remyelination in the cuprizone model of demyelination and significantly increases OPC differentiation in vitro.

Small molecules under development include tumor necrosis factor inhibitors, IL-23 inhibitors, IL-17 inhibitors, phosphodiesterase-4 inhibitors, Janus kinase inhibitors, A3 adenosine receptor agonists, and sphingosine-1-phosphate receptor 1 agonists, several of which are entering phase III trials. Oral microbials have also demonstrated success in early phase studies. As new oral therapies emerge for the treatment of psoriasis, real-world data and comparative trials are needed to better inform their use among patients.

P2, N=353, Completed, Actelion | Active, not recruiting --> Completed

At cellular levels, 3 h of KRP203 treatment induces a prominent increase of PI(3)P and moderate increase of PI(5)P, PI(3,5)P and PI(3,4,5)P levels in U87MG cells. Collectively, the finding of multimodal activity of KRP203 towards multi-phosphoinositide kinases may open a novel basis to modulate cellular processes, potentially leading to more effective treatments for diseases associated with phosphoinositide signaling pathways.