Allakos Inc. announced that the first patient with chronic spontaneous urticaria (CSU) has been dosed in a randomized, double-blind, placebo-controlled Phase 1 trial of AK006. The Phase 1 trial is designed to assess the safety, tolerability and pharmacokinetics of AK006, and to explore the therapeutic effects of AK006 in patients with CSU using the urticaria activity score (UAS7) at 14 weeks. Top-line results from the trial are expected at year end 2024.

CSU symptoms are caused by the inappropriate activation of mast cells in the skin. IgE-dependent mast cell activation has been identified as a pathogenic driver of CSU, and agents which target this pathway have demonstrated therapeutic activity. More recently, IgE-independent pathways, such activation through the MRGPRX2 receptor, have been implicated in CSU disease pathogenesis.

Agents that target both IgE-dependent and IgE-independent modes of mast cell activation have the potential to work in a broader patient population or show greater symptom improvement. AK006 is a humanized IgG1 monoclonal antibody which activates the inhibitory receptor Siglec-6. Siglec-6 is found on the surface of mature mast cells and offers a way to selectively target mast cells. In preclinical experiments, AK006 inhibits IgE-dependent and IgE-independent mast cell activation including activation through IgE, MRGPRX2 and KIT receptors.

In these experiments, AK006 drives deep mast cell inhibition and, in addition to its inhibitory activity, can reduce mast cell numbers via antibody-dependent cellular phagocytosis in the presence of activated macrophages. AK006 is being studied in a Phase 1 randomized, double-blind, placebo-controlled single and multiple ascending dose trial that includes a randomized, double-blind, placebo-controlled CSU arm (NCT06072157). The CSU arm will enroll up to 60 adult patients with antihistamine refractory CSU (including patients with prior biologics treatment).

Patients will be randomized 2:1 to receive intravenous AK006 or placebo once every four weeks (Q4W). The primary efficacy analysis will be the change in the urticaria activity score (UAS7) at week 14. Data from approximately 30 patients is expected at year end 2024.