# Clinical proof of concept for small molecule mediated inhibition of IL-17 in psoriasis

**Authors:** Richard B. Warren, Hamish J. A. Hunter, Kim A. Papp, Kenneth B. Gordon, Meina T. Tang, Jeffrey V. Enejosa, Kuan-Chieh Huang, Debasish Raha, Hashini M. Batugedara, Craig Skinner, Philip A. Kobel, Peter M. Rademacher, Nico Ghilardi, Paul Fatheree, John R. Jacobsen, Timothy T. Lu

PMC · DOI: 10.1371/journal.pone.0341049 · PLOS One · 2026-01-23

## TL;DR

A new oral treatment for psoriasis, DC-806, shows promise in early trials with good safety and some effectiveness.

## Contribution

DC-806 is a novel small molecule inhibitor of IL-17 with demonstrated preclinical and early clinical efficacy.

## Key findings

- DC-806 showed secukinumab-like therapeutic efficacy in preclinical models.
- The 800 mg BID dose of DC-806 significantly reduced PASI scores compared to placebo.
- DC-806 was well tolerated with no serious adverse events reported.

## Abstract

Efficacious and well-tolerated systemic, oral treatments for psoriasis are needed. We report preclinical and phase 1c (NCT06808815) results for DC-806, a small molecule interleukin (IL)-17 inhibitor, for the treatment of mild-to-moderate psoriasis. Preclinical results demonstrated DC-806 targets IL-17AA and IL-17AF with secukinumab-like therapeutic efficacy. In the phase 1c trial, 32 patients consented to receive twice daily (BID) doses of placebo or DC-806 (200 mg or 800 mg) for 28 days. No serious adverse events (SAEs) or discontinuations due to treatment-related adverse events (TRAEs) occurred. In an exploratory analysis, adjusted mean percentage reductions from baseline in psoriasis area and severity indices (PASI) at Day 29 were 43.7%, 15.1%, and 13.3% for 800 mg BID, 200 mg BID, and placebo arms, respectively (800 mg BID vs placebo, P value = 0.0008). DC-806 was found to be well tolerated with an acceptable safety profile and preliminary signals of clinical efficacy in mild-to-moderate psoriasis. EudraCT Identifier: 2021-002888-21.

## Linked entities

- **Proteins:** IL17A (interleukin 17A)
- **Diseases:** psoriasis (MONDO:0005083)

## Full-text entities

- **Genes:** IL19 (interleukin 19) [NCBI Gene 29949] {aka IL-10C, MDA1, NG.1, ZMDA1}, Il17a (interleukin 17A) [NCBI Gene 301289] {aka CTLA-8, IL-17, IL-17A, Il17}, Il6 (interleukin 6) [NCBI Gene 16193] {aka Il-6}, IL17RA (interleukin 17 receptor A) [NCBI Gene 23765] {aka CANDF5, CD217, CDw217, IL-17RA, IL17R, IMD51}, IL17A (interleukin 17A) [NCBI Gene 3605] {aka CTLA-8, CTLA8, IL-17, IL-17A, IL17, ILA17}, DEFB4A (defensin beta 4A) [NCBI Gene 1673] {aka BD-2, DEFB-2, DEFB102, DEFB2, DEFB4, HBD-2}, IL17F (interleukin 17F) [NCBI Gene 112744] {aka CANDF6, IL-17F, ML-1, ML1}
- **Diseases:** arthritis (MESH:D001168), congenital anomaly (MESH:D000013), inflammatory disease of the skin (MESH:D012871), suicidal ideation (MESH:D001072), inflammation (MESH:D007249), hidradenitis suppurativa (MESH:D017497), ankylosing spondylitis (MESH:D013167), CIA (MESH:D001169), headache (MESH:D006261), cellulitis (MESH:D002481), COVID-19 (MESH:D000086382), Psoriasis (MESH:D011565), PASI (MESH:D045169), IMP (MESH:D007787), nausea (MESH:D009325), birth defect (MESH:D000014), immunological diseases (MESH:D007154), uveitis (MESH:D014605), psoriatic (MESH:D015535), death (MESH:D003643), ulcerative colitis (MESH:D003093), IBD (MESH:D015212), toxicity (MESH:D064420), Crohn's disease (MESH:D003424), psychiatric condition (MESH:D001523), abdominal discomfort (MESH:D000007)
- **Chemicals:** bimekizumab (MESH:C000625981), methotrexate (MESH:D008727), DMSO (MESH:D004121), cyclosporine (MESH:D016572), ixekizumab (MESH:C549079), BID (-), apremilast (MESH:C505730), sodium citrate (MESH:D000077559), vitamin E TPGS (MESH:C014225), dexamethasone (MESH:D003907), deucravacitinib (MESH:C000628674), PG (MESH:D019946), brodalumab (MESH:C571216), Dex (MESH:D003915), secukinumab (MESH:C555450)
- **Species:** Homo sapiens (human, species) [taxon 9606], Rattus norvegicus (brown rat, species) [taxon 10116], Mus musculus (house mouse, species) [taxon 10090]
- **Cell lines:** -Blue — Homo sapiens (Human), Burkitt lymphoma, Cancer cell line (CVCL_1967), HEK — Homo sapiens (Human), Human papillomavirus-related endocervical adenocarcinoma, Cancer cell line (CVCL_M624), NIH-3T3 fibroblasts — Mus musculus (Mouse), Transformed cell line (CVCL_L992), HaCaT — Homo sapiens (Human), Spontaneously immortalized cell line (CVCL_0038)

## Full text

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## Figures

6 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12829784/full.md

## References

45 references — full list in the complete paper: https://tomesphere.com/paper/PMC12829784/full.md

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Source: https://tomesphere.com/paper/PMC12829784