Treatment with RGRN-305, a novel HSP90 inhibitor, demonstrated an acceptable safety, particularly in the low-dose (250 mg) group, and was linked with substantial improvement in a subset of people suffering from plaque psoriasis.

A study was carried out to determine the safety and efficacy of RGRN-305 for the management of plaque psoriasis.

This phase 1b, open-label, single-center, single-arm, dose-selection, proof-of-concept study recruited people suffering from plaque psoriasis. The enrolled participants were given either 250 mg or 500 mg RGRN-305 daily for twelve weeks. Evaluation of effectiveness was done with the aid of Dermatology Life Quality Index (DLQI), Physician Global Assessment scores, Psoriasis Area and Severity Index (PASI), and body surface area.

Collection of skin biopsies was done at baseline and at four, eight, and twelve weeks after treatment start and were utilized for immunohistochemical staining and for gene expression assessment. With the aid of vital signs, physical examinations, laboratory tests, and ECG, monitoring of safety was done.

In total, 6/11 participants who finished this assessment responded to HSP90 inhibitor with a PASI improvement between 71% and 94%. Overall, 5 participants were considered non-responders with a PASI response < 50%. No serious noxious events were noted. A mild to moderate exanthematous drug-elicited eruption due to study therapy was reported in 4/7 participants treated with 500 mg RGRN-305 daily.

Due to this exanthematous eruption, 2 participants preferred to discontinue this phase 1b study. RGRN-305 therapy led to considerable suppression of interleukin-23, tumor necrosis factor-alpha, and interleukin-17A signalling pathways and normalization of both histological alterations and psoriatic lesion gene expression profiles in participants responding to therapy.

The HSP90 inhibitor RGRN-305 was found to be safe and resulted in clinically meaningful improvements in people with plaque psoriasis. HSP90 can serve as a new future target for the  management of psoriasis.