Clinical

Lirentelimab (AK002) targets Siglec-8, an inhibitory receptor found on the surface of mast cells and eosinophils

We are testing lirentelimab in a number of diseases where mast cells and/or eosinophils have been shown to play a role in the disease pathology.

Lirentelimab has demonstrated clinical activity in diseases believed to be driven by mast cells and eosinophils (e.g., eosinophilic esophagitis, eosinophilic gastritis and/or eosinophilic duodenitis) and diseases believed to be driven by mast cells only (e.g., chronic urticaria, indolent systemic mastocytosis). Clinical and preclinical results demonstrate that lirentelimab broadly inhibits mast cells and rapidly depletes eosinophils. In addition, patients treated with lirentelimab in clinical studies reported improvement in disease symptoms.

Lirentelimab (AK002) Clinical Development

Ongoing and Planned Studies

Status

Atopic Dermatitis

Initiated Q4’21

Chronic Spontaneous Urticaria

Initiation Mid-22

Eosinophilic Duodenitis (EoD)

Results Expected Q3’22

Lirentelimab in Mast Cell and Eosinophil Driven Diseases

To date, lirentelimab has completed a Phase 2 study (ENIGMA 1) and Phase 3 study (ENIGMA 2) in patients with EG and/or EoD, a Phase 2/3 study in patients with EoE (KRYPTOS), as well as proof of concept studies in chronic spontaneous urticaria, severe allergic conjunctivitis, and indolent systemic Mastocytosis.

Eosinophilic Gastritis and/or Eosinophilic Duodenitis

Eosinophilic gastritis (EG) and/or eosinophilic duodenitis (EoD), are conditions characterized by chronic gastrointestinal symptoms with elevated eosinophils and mast cells in the stomach and/or duodenum. Common symptoms of these diseases include abdominal pain, nausea, abdominal cramping, bloating, loss of appetite, early satiety, vomiting and diarrhea. Lirentelimab has been tested in a Phase 2 randomized, double-blind, placebo-controlled study in patients with EG/EoD (ENIGMA) and the results were published in the New England Journal of Medicine. The study met all prespecified primary and secondary endpoints, including eosinophil reduction and symptom improvements compared to placebo (see press release).

Based on these results, Allakos initiated a registrational Phase 3 study in patients with eosinophilic gastritis and/or eosinophilic duodenitis (ENIGMA 2).  During the fourth quarter of 2021 Allakos announced that the ENIGMA 2 study met the histologic co-primary endpoint but failed to meet the symptomatic co-primary endpoint when compared to placebo. The Phase 3 study in patients with EoD (EoDyssey) is expected to have results in the third quarter of 2022.

Eosinophilic Esophagitis

Eosinophilic esophagitis (EoE) is a condition characterized by mast cell and eosinophil driven inflammation of the esophagus. Common symptoms of EoE include difficulty swallowing, food impaction, nausea and vomiting. In the completed Phase 2 ENIGMA study, patients who had concomitant EoE showed esophageal eosinophil reduction and had less difficulty swallowing when treated with lirentelimab (see press release).

Based on these results, Allakos initiated a Phase 2/3 randomized, double-blind, placebo-controlled study of lirentelimab in patients with EoE (KRYPTOS).  During the fourth quarter of 2021 Allakos announced that the KRYPTOS study met the histologic co-primary endpoint but failed to meet the symptomatic co-primary endpoint when compared to placebo. We plan to hold an End-of-Phase 2 meeting with the FDA to discuss the Phase 2/3 KRYPTOS data and the development path with subcutaneous lirentelimab in patients with eosinophilic esophagitis.

Chronic Urticaria

Chronic urticarias are a group of inflammatory skin diseases caused by the inappropriate activation of mast cells in the skin resulting in severe itching, hives, and edema. Allakos has completed an open-label Phase 2a clinical trial evaluating lirentelimab in patients with multiple forms of chronic urticaria (see press release). Patients with chronic spontaneous urticaria (including both Xolair-naïve and Xolair-refractory), cholinergic urticaria or symptomatic dermographism experienced symptomatic improvement after treatment with lirentelimab.

Severe Allergic Conjunctivitis

Severe allergic conjunctivitis is a group of severe ocular disorders resulting from allergic inflammation of the conjunctiva. Patients with severe allergic conjunctivitis suffer from persistent severe ocular pain, itching, photophobia (sensitivity to light), foreign body sensation, watering eyes, redness, swelling and the formation of papillae. Inflammation in these conditions is driven in large part by mast cells and eosinophils and, left untreated, can lead to vision loss. Many patients also suffer from other atopic conditions such as atopic dermatitis, asthma, and rhinitis. Allakos has conducted an open-label Phase 1b clinical trial in patients with three forms of severe allergic conjunctivitis (atopic keratoconjunctivitis, vernal keratoconjunctivitis, and perennial allergic conjunctivitis refractory to topical treatments; see press release). After treatment with lirentelimab in the Phase 1b study, there was a reduction of patient reported ocular symptoms and physician assessed signs and symptoms. Patients also reported improvements in the severity of comorbid atopic dermatitis, asthma and rhinitis symptoms.

Indolent Systemic Mastocytosis

Indolent systemic mastocytosis (ISM) is a disorder where there are increased numbers of active mast cells throughout the body with heterogeneous symptoms related to mast cell inflammatory mediator release. Symptoms include diarrhea, abdominal pain, fatigue, severe itching, difficulty concentrating and headaches. Allakos has conducted an open-label Phase 1 clinical trial in patients with ISM (see press release). In this study, treatment with lirentelimab resulted in clinically meaningful improvements in symptoms and quality of life measures.