Clinical

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

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

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

Antolimab (AK002) Clinical Development

Ongoing and Planned Studies

Status

Eosinophilic Gastritis and/or Enteritis (EG/EEn) Phase 3

Planned Q1’20

Eosinophilic Esophagitis (EoE) Phase 2/3

Planned Q1’20

EG/EEn ENIGMA Extension Study

Data H1’20

Mast Cell Gastrointestinal Disease (MGID) Phase 1

Data Q1’20

Subcutaneous Formulation Phase 1

Data H2’20

Antolimab in EGIDs

The lead indications for antolimab (AK002) are eosinophilic gastrointestinal diseases (EGIDs), a group of chronic inflammatory diseases characterized by persistent gastrointestinal symptoms as well as elevated eosinophils and mast cells in the esophagus, stomach, small intestine and/or colon.

Eosinophilic Gastritis and/or Enteritis (EG/EEn)

Eosinophilic Gastritis (EG) and/or Eosinophilic Enteritis (EEn, formerly referred to as EGE), are conditions characterized by chronic gastrointestinal symptoms with elevated eosinophils and mast cells in the stomach and/or small intestine (duodenum). Common symptoms of these diseases include abdominal pain, nausea, vomiting, diarrhea, abdominal cramping, bloating, loss of appetite and early satiety. Antolimab has been tested in a Phase 2 randomized, double-blind, placebo-controlled study in patients with EG/EEn. 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 plans to initiate a registrational Phase 3 study in patients with EG/EEn.

Eosinophilic Esophagitis (EoE)

Eosinophilic Esophagitis (EoE) is a condition characterized by eosinophils and mast cells 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 antolimab (see press release). Allakos plans to initiate a Phase 2/3 randomized, double-blind, placebo-controlled study of antolimab in patients with EoE.

Antolimab in other Mast Cell and Eosinophil Driven Diseases

Antolimab has demonstrated clinical activity in several other mast cell and/or eosinophil driven diseases:

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 antolimab 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 antolimab.

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 antolimab 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 antolimab resulted in clinically meaningful improvements in symptoms and quality of life measures.