DICE Therapeutics, Inc. announced positive topline data from its Phase 1 clinical trial of DC-806, an oral small molecule antagonist of the pro-inflammatory cytokine IL-17. The trial was a first-in-human, randomized, double-blind, placebo-controlled study designed to generate safety and pharmacokinetic (PK) data in healthy volunteers as well as provide early clinical proof-of-concept in psoriasis patients. The trial was conducted in three overlapping parts: Phase 1a single ascending dose (SAD) (n=40); Phase 1b multiple ascending dose (MAD) (n=32); and Phase 1c proof-of-concept in psoriasis patients (n=32).

Proof-of-concept achieved, supporting further development of DC-806 as potential best-in-class oral agent for psoriasis: The Phase 1c, placebo-controlled psoriasis portion enrolled a total of 8 patients in the high dose group (800 mg BID), 13 patients in the low dose group (200 mg BID), and 11 patients in the placebo group. Following 4 weeks of treatment, the mean percentage reduction in Psoriasis Area and Severity Index (PASI) from baseline was 43.7% in the high dose group compared to 13.3% in the placebo group, with an exploratory p-value of 0.0008. Reduction in PASI was an exploratory endpoint with no correction for multiplicity.

Both doses of DC-806 shown to be biologically active via analysis of well-precedented biomarkers: Exploratory biomarker data demonstrated dose-dependent IL-17 target engagement, rapid onset of action, and pharmacodynamic effects consistent with direct inhibition of IL-17 signaling. DC-806 was well tolerated with an excellent safety profile across all dose groups: Data across all three cohorts showed DC-806 was well tolerated with a favorable safety profile in both healthy volunteers and psoriasis patients at all dose levels evaluated with no serious adverse events, no dose-limiting adverse events, no treatment-related discontinuations, and no clinically-significant changes in clinical and safety lab parameters (including liver enzymes). All treatment emergent adverse events (TEAEs) were classified as mild or moderate with no dose-dependent trend in the frequency, severity, or type of TEAEs observed.

Robust PK profile and dose-dependent IL-17 target coverage: DC-806 showed a favorable PK profile with dose-proportional increases in serum concentrations throughout the study. Analysis of the MAD and Phase 1c data showed achievement of IC50 and IC90 coverage at trough with doses of 175 mg QD and 400 mg BID, respectively. DICE plans to advance DC-806 into a dose-ranging Phase 2b clinical trial in patients with moderate-to-severe psoriasis.

The company plans to submit an investigational new drug (IND) application with the U.S. Food and Drug Administration (FDA) in the first half of 2023 and initiate Phase 2b development.