Dalazatide

Venom-Derived / Autoimmune

Also known as: ShK-186, Dalazatide

Sea Anemone Venom Peptides (Engineered)Research phase: Phase 1bRegulatory: Not approved. Investigational for autoimmune diseases.

Mechanism

Dalazatide is an engineered version of the sea anemone ShK toxin designed to selectively block Kv1.3 channels on autoimmune T cells. It completed Phase 1b trials in psoriasis.

Technical detail

Dalazatide (ShK-186) is an engineered analog of ShK toxin with an N-terminal phosphotyrosine extension providing >100-fold selectivity for Kv1.3 over Kv1.1. Phase 1b trials in plaque psoriasis demonstrated reduced skin lesion severity and decreased TEM cell numbers. Subcutaneous dosing showed acceptable safety and pharmacokinetics.

Evidence

  • Safety and pharmacodynamics of dalazatide, a Kv1.3 channel inhibitor, in the treatment of plaque psoriasis: A randomized phase 1b trial.

    Tarcha EJ, Olsen CM, Probst P, Peckham D, Muñoz-Elías EJ, Kruger JG, Iadonato SP (2017) — PLoS One — PMID: 28723914

    In a randomized phase 1b study, 24 adults with mild-to-moderate plaque psoriasis received dalazatide 30 mcg, dalazatide 60 mcg, or placebo twice weekly for 9 subcutaneous doses over 4 weeks. Dalazatide was generally well tolerated, most adverse events were transient mild paresthesia or hypoesthesia, 9 of 10 patients in the 60 mcg group improved PASI from baseline, mean PASI reduction in that group was significant, and treatment reduced inflammatory plasma markers plus activation markers on peripheral memory T cells.

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