Allakos announces first phase 3 data from the ENIGMA 2 study and phase 2/3 data from the KRYPTOS study in patients with eosinophilic gastrointestinal disease

REDWOOD CITY, Calif., December 21, 2021 (GLOBE NEWSWIRE) – Allakos, Inc. (the “Company” or “Allakos”) (Nasdaq: ALLK), a biotechnology company developing lirentelimab (AK002) for the treatment of eosinophils and mast cell disease, today published data from ENIGMA 2, a 24-week, randomized, double-blind, placebo-controlled phase 3 study of lIREelimab in patients with confirmed eosinophilic gastritis (EG) biopsy and / or eosinophilic duodenitis (EoD) and KRYPTOS, a phase 2/3 randomized, double-blind, placebo-controlled study of lIREelimab in patients with biopsy-confirmed eosinophilic esophagitis (EoE). The ENIGMA 2 and KRYPTOS studies both met their histologic co-primary endpoints, but did not achieve statistical significance on the symptomatic co-primary endpoints reported by patients.

“We are deeply disappointed that the studies did not reach their symptomatic results,” said Robert Alexander, PhD, CEO of Allakos. “The company is grateful to the patients with gastrointestinal eosinophilic disease (EGID) and to the researchers who participated in the ENIGMA and KRYPTOS trials. “

Dr. Craig Paterson, MD, Medical Director of Allakos, added: “Although the EGID results are surprising and disappointing, we will continue to analyze the data to understand the results and determine the way forward for lireelimab. in EGIDs. At this time, we intend to continue our development efforts with lirentelimab subcutaneously in atopic dermatitis, spontaneous chronic urticaria and asthma. The Atopic Dermatitis study is ongoing and we plan to launch Chronic Spontaneous Urticaria and Asthma studies in 2022 and will continue to advance other programs in our preclinical pipeline.

Main results of phase 3 of ENIGMA 2

The co-primary endpoints for the phase 3 study were (1) the proportion of patients achieving histologic resolution (defined as ≤4 eosinophils (eos) / high power field (hpf) in 5 hpfs in the stomach and / or ≤15 eos / hpf in 3 hpfs in duodenum) and (2) symptomatic improvement as measured by the absolute change in total symptom score (TSS) at six symptoms.

Primary endpoints Lireelimab (n = 91) Placebo (n = 89)
Histological endpoint: proportion of responders
determined by the number of eosinophils in gastric or duodenal tissue1
84.6%
(p
4.5%
Symptom end point: absolute mean change in
patient reported total symptom score (TSS-6)2
Basic TSS: 29.5 Baseline TSS: 27.7
-10.0
(p = 0.343)
-11.5

1 = A responder is a patient achieving the following peaks of eosinophils: number of eosinophils ≤4 cells per hpf in 5 gastric hpf and / or number of eosinophils ≤15 cells per hpf in 3 duodenal hpf. Criterion assessed at the end of week 24.
2 = TSS-6 is a daily patient-reported symptom questionnaire rating 6 symptoms (abdominal pain, nausea, bloating, early satiety, abdominal cramps and loss of appetite) on a scale of 0 to 10. The criterion of valuation is assessed as an average change from baseline at weeks 23-24.

The safety results of the trial were generally consistent with those of previously reported studies with lireelimab. No new safety signals were observed. Mild to moderate infusion-related reactions (including flushing, feeling hot, headache, nausea and / or dizziness) occurred in 34% of patients treated with lireelimab and 14% of patients on placebo.

Main results of phase 2/3 of KRYPTOS

The co-primary endpoints for the phase 2/3 study were (1) the proportion of patients achieving histologic resolution (defined as ≤ 6 eosinophils (eos) / high power field (hpf) in the esophagus ) and (2) symptomatic improvement as measured by the absolute change in the Dysphagia Symptom Questionnaire (DSQ).

Primary endpoints Liretelimab
High dose (n = 91)
Liretelimab
Low dose (n = 93)
Placebo (n = 92)
Histological endpoint: proportion of
responders (eos ≤6 / hpf) as determined
by the number of eosinophils in the esophageal tissue 1
87.9%
(p
92.5%
(p
10.9%
Primary endpoint of symptoms: absolute
mean change in patients reported
Dysphagia Symptom Questionnaire (DSQ)2
DSQ reference:
34.2
DSQ reference:
36.4
DSQ reference:
35.2
-17.4
(p = 0.237)
-11.9
(p = 0.247)
-14.6

1 = A responder is a patient who reaches the following maximum number of eosinophils: ≤6 eosinophils (eos) / high power field (hpf) in 1 hpf in the esophagus. Criterion assessed at the end of week 24.
2 = DSQ is a questionnaire on the symptoms reported by patients assessing difficulty in swallowing. The endpoint was assessed as the absolute mean change from baseline at weeks 23 to 24.

The safety results of the trial were generally consistent with those of previously reported studies with lireelimab. No new safety signals were observed. Mild to moderate infusion-related reactions (including flushing, feeling hot, headache, nausea and / or dizziness) occurred in 39% of patients treated with high dose lIREelimab, 26% of patients treated with lireelimab at low dose and 12% of patients on placebo -treated patients.

Phase 3 Design of the ENIGMA 2 study

The randomized, double-blind, placebo-controlled phase 3 trial of intravenous lireelimab enrolled 180 patients with EG and / or EoD. Patients were expected to have moderate to severe symptoms based on a patient-reported symptom questionnaire and had stomach eosinophilia confirmed by biopsy (≥30 eosinophils / hpf in 5 hpfs) and / or duodenum (≥30 eosinophils / hpf in 3 hpfs). Patients were randomized 1: 1 to receive: 1.0 mg / kg of lirentelimab for the first month followed by five doses of 3.0 mg / kg given monthly or (b) monthly placebo. Symptoms of the disease were measured daily using a Patient-Reported Symptom Questionnaire that assessed 6 symptoms (abdominal pain, nausea, bloating, early satiety, abdominal cramps, loss of appetite) each on a scale from 0 to 10 (TSS). The main co-endpoints were (1) the proportion of responders with ≤4 eos / hpf in 5 hpfs in the stomach and / or ≤15 eos / hpf in 3 hpfs in the duodenum at the end of week 24 and (2 ) the absolute change from baseline in the TSS at weeks 23-24.

Design of the KRYPTOS phase 2/3 study

The randomized, double-blind, placebo-controlled phase 2/3 trial of intravenous lireelimab enrolled 276 patients with EoE. Patients were expected to have moderate to severe symptoms according to the Dysphagia Symptom Questionnaire (DSQ) and have biopsy-confirmed esophageal eosinophilia (≥15 eosinophils in 1 hpf). Patients were randomized 1: 1: 1 to receive: 1.0 mg / kg lireelimab for the first month followed by five doses of 3.0 mg / kg given monthly (b) monthly 1.0 mg / kg lirentelimab (c) a monthly placebo. Symptoms of the disease were measured daily using a Patient-Reported Symptom Questionnaire that assessed difficulty swallowing. The co-primary endpoints were (1) the proportion of responders with ≤ 6 eosinophils in 1 hpf in the esophagus and (2) the absolute change in the dysphagia symptom questionnaire from baseline.

About Allakos

Allakos is a clinical-stage biotechnology company that develops antibodies that target immunomodulatory receptors present on immune effector cells involved in allergic, inflammatory and proliferative diseases. The Company’s main antibody, lirentelimab (AK002), is an investigational drug currently being evaluated in clinical studies, particularly in EGIDs and a phase 2 study in atopic dermatitis. The Company plans to initiate a Phase 2/3 study in chronic spontaneous urticaria and a Phase 2 study in asthma in mid-2022 and Q4 2022, respectively. Lireelimab targets Siglec-8, an inhibitory receptor selectively expressed on eosinophils and human mast cells. Eosinophils and inappropriately activated mast cells have been identified as key factors in a number of serious diseases affecting the gastrointestinal tract, eyes, skin, lungs and other organs. For more information, please visit the company’s website at www.allakos.com.

Forward-looking statements

This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, as contained in Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act. of 1934, as amended. These forward-looking statements include, without limitation, Allakos’ progress and business plans, the expected timing of anticipated study results, and plans for its future clinical trials. Such statements are subject to many important factors, risks and uncertainties that may cause actual events or results to differ materially from current expectations and beliefs, including, but not limited to: stages of clinical development of ‘a medicine from Allakos; the ability of Allakos to complete clinical trials on time and, if approved, to market lireelimab (AK002), its lead compound; Allakos’ ability to obtain the required regulatory approvals for its product candidates; uncertainties related to the recruitment of patients in its clinical trials; Allakos’ ability to demonstrate sufficient safety and efficacy of its product candidates in its clinical trials; uncertainties associated with the success of late stage clinical trials, regardless of the results of preclinical trials and early stage trials; market acceptance of Allakos product candidates; uncertainties related to projections of the size of patient populations suffering from the diseases targeted by Allakos; Allakos’ ability to advance other product candidates beyond lirentelimab; Allakos’ ability to raise additional capital to finance its operations; and other significant risk factors set out in Allakos’ most recent annual report on Form 10-K filed with the SEC on March 1, 2021, the quarterly report on Form 10-Q filed with the SEC on November 8, 2021, and future reports to be filed with the SEC. These documents contain and identify important factors that could cause Allakos ‘actual results to differ materially from those contained in Allakos’ forward-looking statements. All forward-looking statements contained in this press release speak only as of the date hereof, and Allakos specifically disclaims any obligation to update any forward-looking statement, except as required by law. These forward-looking statements should not be taken as representing the views of Allakos as of any date subsequent to the date of this press release.

Investor contact:
Adam Tomasi, President and Chief Operating Officer
Alex Schwartz, Vice President of Strategic Finance and Investor Relations
[email protected]

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