Allakos Shares Phase 1 Results for Subcutaneous AK006 in Healthy Volunteers

Allakos Inc., a biotechnology enterprise listed on Nasdaq under ALLK, has released the outcomes from its Phase 1 research of subcutaneous AK006 conducted on healthy individuals. AK006 is a monoclonal antibody targeting Siglec-6, which plays a role in inhibiting mast cells. These cells are implicated in numerous disorders, such as chronic spontaneous urticaria, food allergies, and asthma, due to their inappropriate activation.

The initial Phase 1 study revealed that subcutaneously administered AK006 had a bioavailability of approximately 77%. The estimated half-life of this formulation ranges between 12 to 22 days. Notably, skin biopsy results from the study indicated high receptor occupancy of AK006 on mast cells, confirming its effective reach to skin tissue. Particularly, the highest dose of 720 mg showed a receptor occupancy rate of 98% at day 113, pointing to the potential for less frequent dosing.

In terms of safety, both single and multiple doses of intravenous AK006, as well as a single subcutaneous dose up to 720 mg, were generally well-tolerated by the subjects. There were no serious adverse events, no discontinuations due to adverse events, and no dose-limiting toxicities. The most common side effects, occurring in 10% or more of the participants, were headaches and dysmenorrhea, all of which were mild to moderate in severity.

The ongoing Phase 1 study of AK006 comprises a single ascending dose (SAD) and multiple ascending dose (MAD) trial, which includes a randomized, double-blind, placebo-controlled arm for chronic spontaneous urticaria (CSU). The results discussed in this announcement pertain to the SAD subcutaneous cohorts. In these cohorts, healthy volunteers were randomized in a 6:2 ratio to receive either subcutaneous AK006 or a placebo. The primary focus was to assess the safety and tolerability of single doses of subcutaneous AK006, determine its bioavailability and pharmacokinetics, and evaluate Siglec-6 receptor occupancy on mast cells through skin biopsies.

For the CSU arm of the Phase 1 study, up to 60 adult patients with antihistamine-refractory CSU, including those previously treated with biologics, are being randomized in a 2:1 ratio to receive 720 mg of intravenous AK006 or a placebo every four weeks. The primary efficacy measure will be the change in the urticaria activity score (UAS7) over 14 weeks, with data from approximately 30 patients expected to be available in early Q1 of 2025.

AK006 is a humanized IgG1 monoclonal antibody that activates the inhibitory receptor Siglec-6, found on mature mast cells. Through preclinical studies, AK006 has been observed to inhibit both IgE-dependent and IgE-independent mast cell activations, including those via IgE, MRGPRX2, and KIT receptors. Additionally, AK006 not only inhibits mast cell activity but also reduces their numbers through antibody-dependent cellular phagocytosis when macrophages are activated.

Allakos Inc. is focused on developing therapies targeting immunomodulatory receptors on immune effector cells involved in allergic, inflammatory, and proliferative diseases. The most advanced antibody in their pipeline is AK006, which targets the Siglec-6 receptor on mast cells. This receptor plays a crucial role in the inflammatory response and is implicated in several severe diseases affecting various organs. Preclinical studies suggest that AK006 can provide substantial inhibition of mast cells and reduce their numbers.

Allakos continues to advance its clinical program with AK006, aiming to offer new therapeutic options for mast cell-driven diseases, with significant milestones expected in the near future.