Allakos Inc. announced positive results from the single and multiple ascending Phase 1 study of intravenous (IV) AK006 in healthy volunteers. AK006 is a Siglec-6 monoclonal antibody that selectively inhibits mast cells. Inappropriate activation of mast cells has been identified as a pathogenic driver of multiple diseases, including chronic spontaneous urticaria, food allergy and asthma.

Phase 1 Study Results: Single and multiple IV doses of AK006 up to 720 mg were well tolerated with a favorable safety profile. There were no serious adverse events (SAEs). There were no treatment emergent adverse events leading to discontinuation of AK006.

There were no dose limiting toxicities. The most common adverse events occurring in subjects on AK006 were headache and dysmenorrhea, all of which were mild-to-moderate in severity. AK006 showed dose linear exposure and with an estimated half-life of 21 days for the 720 mg IV dose.

AK006 achieved serum concentrations consistent with those showing mast cell inhibition in preclinical experiments. Skin biopsies taken from AK006 treated healthy volunteers showed high levels of receptor occupancy confirming AK006 reaches skin tissue mast cells. Single ascending dose cohorts of AK006 =20mg showed a mean Siglec-6 receptor occupancy of >90% on mast cells at day 29.

Phase 1 AK006 Study in Healthy Volunteers and Patients with Chronic Spontaneous Urticaria: AK006 is being studied in an ongoing Phase 1 single IV and subcutaneous (SC) ascending dose (SAD) and multiple IV ascending dose (MAD) trial that includes a randomized, double-blind, placebo-controlled CSU arm (NCT06072157). The data announced are from Parts A and B of the randomized, double-blind, placebo-controlled SAD and MAD IV cohorts of the study. In these cohorts, healthy volunteers were randomized 6:2 to receive doses of intravenous AK006 or placebo.

AK006 was tested across five single ascending doses (5, 20, 80, 240 and 720 mg) and three MAD (80, 240 and 720 mg monthly) dose cohorts. The primary objective was to evaluate the safety and tolerability of single ascending doses and multiple ascending IV doses of AK006 in healthy volunteers and to explore Siglec-6 receptor occupancy on mast cells in skin biopsy samples. AK006 is also being studied in an ongoing randomized, double-blind, placebo-controlled cohorts of healthy volunteers receiving SC AK006 and also in a cohort of patients with CSU receiving IV AK006.

In the CSU cohort, approximately 60 adult patients with antihistamine refractory CSU (including patients with prior biologics treatment), will be randomized 2:1 to receive 720 mg of IV 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.