AK006 / Allakos - LARVOL DELTA

Systemic Treatments for Chronic Spontaneous Urticaria: Anti-IgE and Beyond. (PubMed, J Allergy Clin Immunol Pract) - "Current standard of care includes nonsedating H1-antihistamines and omalizumab, which targets peripheral blood IgE and downregulates mast cell and basophil IgE receptors...Dupilumab received FDA approval for H1-antihistamine-refractory CSU, supporting targeting type 2 cytokines, IL-4 and IL-13. Most recently, a Bruton's tyrosine kinase inhibitor (BTKi), remibrutinib, demonstrated significant reductions in Urticaria Activity Score over 7 days in phase 3 trials, leading to FDA approval. Newer c-Kit (cKit or KIT) inhibitors have also shown efficacy in CSU and CIndU, with barzolvolimab showing sustained efficacy post-treatment...Some drugs have been halted in development because of safety concerns, such as fenebrutinib (BTKi), THB001 (Larvol; c-Kit inhibitor), and EP262 (MRGPRX2 antagonist), whereas others, targeting the alarmin thymic stromal lymphopoietin (tezepelumab), the Th2 cytokine IL-5 (mepolizumab) and its receptor IL-5R (benralizumab), as well as lirentelimab..."

Journal • Review • Cardiovascular • Chronic Spontaneous Urticaria • Dermatology • Immunology • Urticaria • IL13 • IL4 • IL5 • SIGLEC8 • TSLP • TYK2

Emerging IgE and non-IgE targeted therapies for chronic urticaria. (PubMed, Ann Allergy Asthma Immunol) - "Dupilumab received FDA approval for antihistamine refractory chronic spontaneous urticaria (CSU) supporting the targeting of type-2 cytokines, IL-4 and IL-13, in this disease. Bruton's tyrosine kinase (BTK) inhibitors show promise, with remibrutinib receiving FDA approval and demonstrating significant reductions in UAS7 in Phase 3 trials. c-Kit (c-Kit or KIT) inhibition with barzolvolimab shows robust efficacy with sustained effects post-treatment...Although some programs have been discontinued due to safety concerns or lack of efficacy such as fenebrutinib (BTK inhibitor), THB001 (c-Kit inhibitor), EP262 (MRGPRX2 antagonist), tezepelumab (anti- TSLP), as well as lirentelimab and AK006 (Siglec-targeting agents), these studies have informed many of the other positive studies. In summary, over the last year, we have seen the CU pipeline mature with multiple Phase 3 programs and new approvals representing diverse mechanisms of action. Nevertheless, significant..."

Journal • Review • Chronic Spontaneous Urticaria • Dermatology • Immunology • Urticaria • IL13 • IL4 • TSLP

Open-Label Extension Study for Subjects With H1 Antihistamine Refractory Chronic Spontaneous Urticaria Completing Study AK006-001 (clinicaltrials.gov) - P1 | N=29 | Completed | Sponsor: Allakos Inc. | Active, not recruiting ➔ Completed

Trial completion • Chronic Spontaneous Urticaria • Dermatology • Immunology • Urticaria

Study to Assess the Safety, Tolerability, Pharmacokinetics and Immunogenicity of AK006 in Healthy Subjects and Subjects With Chronic Spontaneous Urticaria (clinicaltrials.gov) - P1 | N=136 | Completed | Sponsor: Allakos Inc. | Active, not recruiting ➔ Completed

Trial completion • Chronic Spontaneous Urticaria • Dermatology • Immunology • Urticaria

Open-Label Extension Study for Subjects With H1 Antihistamine Refractory Chronic Spontaneous Urticaria Completing Study AK006-001 (clinicaltrials.gov) - P1 | N=29 | Active, not recruiting | Sponsor: Allakos Inc. | Enrolling by invitation ➔ Active, not recruiting | N=60 ➔ 29 | Trial completion date: Apr 2026 ➔ Jun 2025

Enrollment change • Enrollment closed • Trial completion date • Chronic Spontaneous Urticaria • Dermatology • Immunology • Urticaria

Study to Assess the Safety, Tolerability, Pharmacokinetics and Immunogenicity of AK006 in Healthy Subjects and Subjects With Chronic Spontaneous Urticaria (clinicaltrials.gov) - P1 | N=136 | Active, not recruiting | Sponsor: Allakos Inc. | Recruiting ➔ Active, not recruiting | Trial completion date: Dec 2025 ➔ Jun 2025 | Trial primary completion date: Dec 2025 ➔ Jun 2025

Enrollment closed • Trial completion date • Trial primary completion date • Chronic Spontaneous Urticaria • Dermatology • Immunology • Urticaria

Allakos Announces Topline Results from its Phase 1 Trial of AK006 in Patients with Chronic Spontaneous Urticaria and Announces Restructuring (GlobeNewswire) - P1 | N=148 | NCT06072157 | Sponsor: Allakos Inc. | "AK006 did not demonstrate therapeutic activity in CSU...AK006 was well-tolerated with a favorable safety profile. There were no serious adverse events (SAEs) in subjects on AK006. Adverse events occurring in 2 or more subjects on AK006 were headache (2), infusion related reaction (2), and Covid-19 (2) vs. 1, 0, and 0, respectively, on placebo, all of which were mild-to-moderate in severity...The Company plans to discontinue AK006-related activities across clinical, manufacturing, research and administrative functions and reduce its workforce by approximately 75%. The Company plans to retain approximately 15 employees to explore strategic alternatives, maintain compliance with regulatory and financial reporting requirements, and wind-down the phase 1 clinical trial."

Discontinued • P1 data • Chronic Spontaneous Urticaria • Immunology

Open-Label Extension Study for Subjects With H1 Antihistamine Refractory Chronic Spontaneous Urticaria Completing Study AK006-001 (clinicaltrials.gov) - P1 | N=60 | Enrolling by invitation | Sponsor: Allakos Inc.

New P1 trial • Chronic Spontaneous Urticaria • Dermatology • Immunology • Urticaria

AK006 Drives Mast Cell Anergy as a Result of Antibody Binding Location and Distinct Protein Interaction Network (EAACI 2024) - "Conclusion AK006, inherent to native receptor biology of Siglec-6 combined with optimal epitope selection, has significantly stronger and broader MC inhibitory activity compared to AK002. AK006 has the potential to be a best-in-class MC inhibitor for allergic and chronic inflammatory diseases."

Allergy • Immunology • Inflammation • SIGLEC8

Allakos Announces First Patient Dosed in Phase 1 Trial of AK006 in Chronic Spontaneous Urticaria (GlobeNewswire) - "Allakos...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."

P1 data • Trial status • Chronic Spontaneous Urticaria

Study to Assess the Safety, Tolerability, Pharmacokinetics and Immunogenicity of AK006 in Healthy Subjects and Subjects With Chronic Spontaneous Urticaria (clinicaltrials.gov) - P1 | N=124 | Recruiting | Sponsor: Allakos Inc.

New P1 trial • Chronic Spontaneous Urticaria • Dermatology • Immunology • Urticaria

Mast cell silencing: A novel therapeutic approach for urticaria and other mast cell-mediated diseases. (PubMed, Allergy) - "MC silencers, such as agonist monoclonal antibodies that engage inhibitory receptors (e.g., sialic acid-binding immunoglobulin-like lectin8 -[Siglec-8] [lirentelimab/AK002], Siglec-6 [AK006], and CD200R [LY3454738]), have reached preclinical and clinical stages of development. In this review, we (1) describe the role of MCs in the pathogenesis of CU, highlighting similarities with other MC diseases in disease mechanisms and response to treatment; (2) explore current therapeutic strategies, categorized by nonspecific immunosuppression, targeted inhibition of MC activation or mediators, and targeted modulation of MC activity; and (3) introduce the concept of MC silencing as an emerging strategy that could selectively block activation of MCs without eliciting or exacerbating on- or off-target, immunosuppressive adverse effects."

Journal • Review • Dermatology • Immunology • Inflammation • Urticaria • CD200 • CD200R1 • SIGLEC8

Allakos Provides Business Update and Reports Second Quarter 2023 Financial Results (BioSpace) - "Topline data expected from the Phase 2 study of subcutaneous lirentelimab in patients with atopic dermatitis in late Q4 2023 to Q1 2024. Topline data expected from the Phase 2b study of subcutaneous lirentelimab in patients with CSU in late Q4 2023 to Q1 2024. Following the single and multiple ascending dose portions of the Phase 1 AK006 study in healthy volunteers, initiation of the randomized, double-blind, placebo-controlled cohort in patients with CSU is expected in Q2 2024."

New P1 trial • P2 data • P2b data • Atopic Dermatitis • Chronic Spontaneous Urticaria • Dermatology • Immunology • Inflammation • Urticaria

Allakos Presents Preclinical Data at EAACI Hybrid Congress 2023 Highlighting Lirentelimab and AK006 Mechanisms of Mast Cell Inhibition (BioSpace) - "Allakos Inc...today announced an oral presentation at the European Academy of Allergy and Clinical Immunology (EAACI) Hybrid Congress 2023. The presentation highlighted preclinical data detailing lirentelimab and AK006 mechanism of action and inhibitory activity on IgE and non-IgE activated mast cells....Siglec-6 and Siglec-8 interact with numerous activating receptors and signaling molecules in mast cells, including IL-4R⍺, FcεRI, and JAK/STAT, consistent with preclinical data showing that lirentelimab and AK006 inhibit multiple modes of mast cell activation; Siglec-6 interacts with mast cell proteins associated with metabolism and signaling that are not seen with Siglec-8; AK006 inhibits IgE mediated mast cell activation and shows similar IgE inhibitory activity as remibrutinib; AK006 interacts with cell surface KIT and inhibits KIT-mediated mast cell activation..."

Preclinical • Immunology