CALY-002 / Calypso Biotech - LARVOL DELTA

CALY-002, AN ANTI-IL-15 ANTIBODY, RESULTS IN HISTOLOGICAL AND CLINICAL IMPROVEMENT IN PATIENTS WITH EOSINOPHILIC ESOPHAGITIS IN A PHASE 1A/B STUDY (DDW 2024) - P1 | "Conclusion Preliminary data reveal that CALY-002 can reverse esophageal inflammation – eosinophilia and morphological tissue damage, as well as ameliorate symptoms in EoE patients who previously failed on corticosteroids, while showing a good safety profile. This first demonstration of preliminary efficacy in patients with EoE by blocking IL-15 warrants further studies."

Clinical • P1 data • Celiac Disease • Eosinophilia • Eosinophilic Esophagitis • Gastrointestinal Disorder • Immunology • Inflammation • Mucositis • IL15

CALY-002, AN ANTI-IL-15 ANTIBODY, PREVENTS GLUTEN CHALLENGE-INDUCED MUCOSAL DAMAGE AND INFLAMMATION: RESULTS FROM A PHASE 1A/B STUDY (DDW 2024) - P1 | "Conclusion This Phase 1a/b trial is the first to demonstrate that blocking IL-15 using a potent antibody can attenuate mucosal injury induced by gluten challenge in well-controlled CeD patients. These encouraging results warrant further investigations of CALY-002 in CeD."

P1 data • Celiac Disease • Hematological Disorders • Inflammation • IL15

Dose Escalation Study to Evaluate an Experimental New Treatment (CALY-002) in Healthy Subjects and Subjects With Celiac Disease and Eosinophilic Esophagitis (clinicaltrials.gov) - P1 | N=73 | Completed | Sponsor: Calypso Biotech BV | Active, not recruiting ➔ Completed

Trial completion • Celiac Disease • Eosinophilic Esophagitis • Gastrointestinal Disorder • Immunology

Dose Escalation Study to Evaluate an Experimental New Treatment (CALY-002) in Healthy Subjects and Subjects With Celiac Disease and Eosinophilic Esophagitis (clinicaltrials.gov) - P1 | N=73 | Active, not recruiting | Sponsor: Calypso Biotech BV | Recruiting ➔ Active, not recruiting | Trial completion date: Sep 2023 ➔ Apr 2024 | Trial primary completion date: Sep 2023 ➔ Apr 2024

Enrollment closed • Trial completion date • Trial primary completion date • Celiac Disease • Eosinophilic Esophagitis • Gastrointestinal Disorder • Immunology

Exploring the role of interleukin 15 in atopic dermatitis: Lesson from a humanized mouse model (ISDS 2023) - "To investigate the role of IL-15 in AD and compare the blockade of this pathway with IL-4/IL-13 signaling inhibition, mice were treated prophylactically or therapeutically either with a monoclonal antibody against IL-15 (CALY-002), the monoclonal antibody blocking IL-4Rα (Dupilumab), or IgG controls. Enrichment for GO BP terms related to regulation of cytokine production, B cell, antimicrobial immunity, T-cell activation was detected for both treatments, while among others, those associated to TNF and IFNg responses were linked only to CALY-002 administration. Thus, our data further confirm that IL-15 signaling is involved in AD pathogenesis, and invites therapeutic targeting of IL-15 for AD management."

Preclinical • Atopic Dermatitis • Dermatitis • Dermatology • Immunology • Transplantation • FLG • IFNG • IL13 • IL15 • IL17A • IL2 • IL22 • IL4

INTERIM RESULTS FROM A FIRST-IN-HUMAN STUDY OF THE ANTI-IL-15 ANTIBODY CALY-002 FOR TREATING CELIAC DISEASE AND EOSINOPHILIC ESOPHAGITIS (DDW 2023) - P1 | "The observed pharmacological activity at and above 0.3 mg/kg is consistent with the neutralization of the known homeostatic and anti-apoptotic effects of IL-15 on NK cells as also reported for JAK inhibitors. Multiple dosing for 8 weeks in gluten-challenged subjects with CeD and for 12 weeks in subjects with EoE is ongoing."

P1 data • Celiac Disease • Eosinophilic Esophagitis • Gastrointestinal Disorder • Immunology • Inflammation • Inflammatory Bowel Disease • IL15

IL-15 contributes to atopic dermatitis pathogenesis: Lessons from a novel humanized mouse disease model (ISID 2023) - "Monoclonal antibodies against IL-15 (CALY-002), or IL-4Rα (Dupilumab, DUPI), or IgG controls were administered to these mice i.v. either prophylactically or therapeutically. Nanostring-based transcriptomics revealed that IL-15 inhibition downregulates AD-relevant genes including alarmins, defensins, Th2 cytokine receptors and Th1 transcription factors, and may promote T-cell exhaustion and regulate B-cell activity. Thus, IL-15 signaling functionally contributes to AD pathogenesis, and deserves further exploration as a therapeutic target to reduce inflammation in AD."

Preclinical • Atopic Dermatitis • Dermatitis • Dermatology • Immunology • Transplantation • FLG • IFNG • IL15 • IL17A • IL2 • IL22 • IL4

Experimentally induced atopic dermatitis lesions in xenotransplanted skin are ameliorated by interleukin 15 (IL-15) inhibition (AAD 2023) - "Thereafter, mice were treated prophylactically or therapeutically either with a monoclonal antibody against IL-15 (CALY-002), a monoclonal antibody blocking IL-4Rα (Dupilumab), or IgG controls. However, increased in NK (tendential), IL-4+ (tendential), and IFNg+ (significant) cell numbers were prevented by IL-15 blockade similarly to Dupilumap. Our data support involvement of IL-15 signaling in AD development, and suggest, that inhibition of IL-15 signaling might have therapeutic potential in AD management."

Atopic Dermatitis • Dermatitis • Dermatology • Immunology • Transplantation • FLG • IFNG • IL15 • IL17A • IL2 • IL22 • IL4

Dose Escalation Study to Evaluate an Experimental New Treatment (CALY-002) in Healthy Subjects and Subjects With Celiac Disease and Eosinophilic Esophagitis (clinicaltrials.gov) - P1 | N=95 | Recruiting | Sponsor: Calypso Biotech BV | Trial completion date: Sep 2022 ➔ Sep 2023 | Trial primary completion date: Sep 2022 ➔ Sep 2023

Trial completion date • Trial primary completion date • Celiac Disease • Eosinophilic Esophagitis • Gastrointestinal Disorder • Immunology

Dose Escalation Study to Evaluate an Experimental New Treatment (CALY-002) in Healthy Subjects and Subjects With Celiac Disease and Eosinophilic Esophagitis (clinicaltrials.gov) - P1; N=95; Recruiting; Sponsor: Calypso Biotech BV

Clinical • New P1 trial • Celiac Disease • Eosinophilic Esophagitis • Gastrointestinal Disorder • Immunology