Sienna Biopharmaceuticals, Inc. announced that the results of its recent Phase 2b clinical trial with SNA-120 (pegcantratinib), the Company’s Phase 3 topical, non-steroidal Tropomyosin receptor kinase A (TrkA) inhibitor under investigation for the treatment of psoriasis, will be presented as a late-breaker at the World Congress of Dermatology 2019 Scientific Sessions in Milan. TrkA is the high-affinity receptor for nerve growth factor (NGF). SNA-120 selectively targets the NGF-TrkA signaling pathway, which plays an important role in the pathogenesis of psoriasis and pruritus (itch). SNA-120 was developed using Sienna’s proprietary tissue-targeted technology platform, which yields new chemical entities (NCEs) designed to deliver high local drug concentration in the target tissue with minimal to no systemic exposure for patients. Sienna continues to work towards first patient enrollment in its Phase 3 program with SNA-120 in the second half of 2019. SNA-120 (0.05%) demonstrated in a Phase 2b clinical trial statistically significant improvement compared to vehicle on important pre-specified endpoints of psoriasis disease severity, including the Investigator’s Global Assessment (IGA) 2-grade composite, comprising a 2-grade improvement from baseline and clear (0) or almost clear (1) skin, which has been the Phase 3 primary endpoint for topical psoriasis drugs approved by the U.S. Food and Drug Administration (FDA). Specifically, 29% of patients achieved success on the IGA 2-grade composite, compared to 13% of subjects treated with vehicle. Similarly, 27% of subjects also experienced a 75% reduction from baseline in their Psoriasis Area and Severity Index score (PASI 75), compared to 13% of subjects treated with vehicle. Subjects also experienced an approximately 60% reduction from baseline in the associated pruritus, although the pruritus result did not reach statistical significance compared to vehicle. SNA-120 was well-tolerated with no serious treatment-related adverse events. Treatment-related adverse events were observed in two patients and included dermatitis (0.5% group) and pain and pruritus (vehicle group). SNA-120 has been administered to more than 500 subjects for up to 12 weeks and has been well tolerated across all trials, with minimal to no demonstrated systemic bioavailability. As part of the Phase 2 trial, biopsy analyses were conducted at Rockefeller University on 22 subjects, and included Immunohistochemistry (IHC), MicroArray and quantitative Reverse Transcription Polymerase Chain Reaction (qRT-PCR). These data showed SNA-120 affects key inflammatory cytokines involved in psoriasis, including IL-23, IL-12, IL-17A and IFNg, among others, and continue to support the mechanism of action of SNA-120 and the unique contribution of neurogenic inflammation to psoriasis pathogenesis. Following a positive End-of-Phase 2 (EOP2) meeting with the FDA in April 2019, Sienna is progressing towards enrollment of the first patient in its Phase 3 program with SNA-120 for psoriasis in the second half of 2019.