zampilimab (UCB7858) / UCB - LARVOL DELTA

Zampilimab, a Novel Monoclonal Antibody Targeting Human Transglutaminase-2 for the Treatment of Idiopathic Pulmonary Fibrosis: Pharmacological Profile in a Humanized Mouse Model (ERS 2026) - P1 | "Pulmonary fibrosis was induced in male hTG2 C57BL/6 mice using bleomycin (BLM) via oropharyngeal aspiration on days 0 and 4. The results obtained from a humanized hTG2 mouse model highlight the central role of TG2 in pulmonary fibrosis, indicating that selective inhibition of transamidation activity of hTG2 by zampilimab can significantly improve lung function and micro-CT–derived functional biomarkers. Its favorable tolerability further support the continued development of zampilimab."

Preclinical • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases • TGM2

Autoradiographic quantification of transglutaminase-2 target occupancy by [¹¹¹In]In-DOTAGA-zampilimab in hTG2-humanized fibrotic mouse lungs and IPF-derived precision cut lung slices (ERS 2026) - "In this study, we quantified zampilimab target occupancy and engagement using a comparable preclinical experimental strategy in lung cryosections from bleomycin (BLM)-induced hTG2-humanized mice and precision cut lung slices (hPCLS) from healthy and IPF patients by autoradiography. Overall, these findings demonstrate that TG2 activity is markedly elevated in fibrotic lung and can be selectively quantified and targeted using a mouse–human experimental approach. Moreover the study supports the clinical translation of zampilimab as promising theragnostic strategy for the diagnosis and treatment of pulmonary fibrosis."

Preclinical • Fibrosis • Idiopathic Pulmonary Fibrosis • TGM2

ZAPPHIRE: A Study to Find an Efficacious and Safe Dose of CHF10067 (Zampilimab) in Participants With Idiopathic Pulmonary Fibrosis (clinicaltrials.gov) - P2 | N=240 | Recruiting | Sponsor: Chiesi Farmaceutici S.p.A. | Trial completion date: Feb 2028 ➔ Jun 2028 | Trial primary completion date: Feb 2028 ➔ Jun 2028

Trial completion date • Trial primary completion date • Idiopathic Pulmonary Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases

ZAPPHIRE: A Study to Find an Efficacious and Safe Dose of CHF10067 (Zampilimab) in Participants With Idiopathic Pulmonary Fibrosis (clinicaltrials.gov) - P2 | N=240 | Recruiting | Sponsor: Chiesi Farmaceutici S.p.A. | Not yet recruiting ➔ Recruiting

Enrollment open • Idiopathic Pulmonary Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases

Randomized Phase 1 Studies Evaluating the Safety, Tolerability, Pharmacokinetics, and Target Occupancy of Zampilimab in Healthy Participants. (PubMed, Clin Pharmacol Drug Dev) - P1 | "Zampilimab safety profile was acceptable after single intravenous and subcutaneous doses ≤1000 mg (UP0029) and intravenous doses ≤3000 mg (UP0105) following optimization of maximum concentration (10 mg/mL) at an infusion rate of 25 mg/min over 120 min. These studies support the ongoing development of zampilimab."

Clinical • Journal • P1 data • PK/PD data • Immunology • Nephrology • TGM2

CLI-10067AA1-02: A study to find an efficacious and safe dose of CHF10067 (zampilimab) in participants with idiopathic pulmonary fibrosis (clinicaltrialsregister.eu) - P1/2 | N=48 | Not yet recruiting | Sponsor: Chiesi Farmaceutici S.p.A.

New P1/2 trial • Idiopathic Pulmonary Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases

ZAPPHIRE: A Study to Find an Efficacious and Safe Dose of CHF10067 (Zampilimab) in Participants With Idiopathic Pulmonary Fibrosis (clinicaltrials.gov) - P2 | N=240 | Not yet recruiting | Sponsor: Chiesi Farmaceutici S.p.A.

New P2 trial • Idiopathic Pulmonary Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases

Pharmacological Evaluation of the TG2-targeting Antibody Zampilimab in Diseased Human Lung Fibroblasts and Ex Vivo Lung Tissue Models (ATS 2026) - No abstract available

Preclinical • Pulmonary Disease • Respiratory Diseases

Spect as a Translational Non-invasive Method to Assess Zampilimab Lung Target Occupancy in a Bleomycin-induced Lung Fibrosis Model in HTg2 Humanized Mice (ATS 2026) - No abstract available

Non-invasive • Preclinical • Fibrosis • Immunology • Respiratory Diseases

Evaluation of the Antifibrotic Effect of Zampilimab, a Monoclonal Antibody Targeting Human Transglutaminase-2, in a Humanized Mouse Model of Pulmonary Fibrosis (ATS 2026) - No abstract available

Preclinical • Immunology • Pulmonary Disease • Respiratory Diseases • TGM2

Cryo-fluorescence Tomography to Assess Zampilimab Lung Target Occupancy in Humanized Fibrotic Mouse Lung (ATS 2026) - No abstract available

Preclinical • Fibrosis

SPECT as a translational non-invasive method to assess occupancy of the tissue transglutaminase-2 by zampilimab in the mouse lung. (PubMed, Respir Res) - No abstract available

Journal • Preclinical • Fibrosis • Immunology • Respiratory Diseases • TGM2

Using skin biopsies to measure target occupancy of anti-fibrotic molecules: assay development and application for zampilimab in a primate model of chronic kidney disease and in healthy human volunteers. (PubMed, BMC Nephrol) - P1 | "Zampilimab inhibited TG2 in cynomolgus monkey kidney and skin. Skin is an accessible surrogate tissue to assess kidney TO and predict TE, and our ex vivo model of skin biopsy has potential for application in the development of other antifibrotic therapeutics. A phase I first-in-human study of zampilimab in healthy volunteers (NCT02879877; 26/08/2016) will provide further proof of concept."

Journal • Chronic Kidney Disease • Fibrosis • Immunology • Nephrology • Renal Disease • TGM2

Safety, Tolerability, and Pharmacokinetics of CHF10067 in Subjects With Idiopathic Pulmonary Fibrosis: A Phase Ib Study (ATS 2025) - P1 | "This abstract is funded by: Chiesi Farmaceutici S.p.A., Parma, Italy RATIONALE: Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive lung disease with limited treatment options. Zampilimab demonstrated a favorable safety and tolerability profile in subjects with IPF at all doses up to 3000 mg. These findings support further clinical development of zampilimab for the treatment of IPF."

Clinical • Late-breaking abstract • P1 data • PK/PD data • Cardiovascular • Fatigue • Hypertension • Idiopathic Pulmonary Fibrosis • Immunology • Infectious Disease • Influenza • Pain • Pulmonary Disease • Respiratory Diseases • TGM2

Spect as a Translational Non-invasive Method to Assess Zampilimab Lung Target Occupancy in Mice (ATS 2025) - "Since hTG2+ cells intratracheally administered are more uniformly distributed within the lung compared to xenograft tumors, where hTG2 is overexpressed in a localized and vascularized area, results from intratracheal model consistently confirmed that Zampilimab can reach the lung and specifically bind the hTG2. Additionally, our study demonstrated that Zampilimab can be effectively radiolabeled for SPECT imaging, allowing for a non-invasive and quantitative assessment of lung TO, paving the way for its clinical application."

Non-invasive • Preclinical • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Oncology • Pulmonary Disease • Respiratory Diseases • TGM2

The effect of TG2-inhibitory monoclonal antibody zampilimab on tissue fibrosis in human in vitro and primate in vivo models of chronic kidney disease. (PubMed, PLoS One) - "Weekly intravenous administration of zampilimab in cynomolgus monkeys with unilateral ureteral obstruction reduced fibrosis at 4 weeks by >50%, with no safety signals. Our data support the clinical investigation of zampilimab for the treatment of kidney fibrosis."

Journal • Preclinical • Chronic Kidney Disease • Fibrosis • Immunology • Nephrology • Renal Disease • TGFB1 • TGM2

A Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Zampilimab in Adult Kidney Transplant Recipients With Chronic Allograft Injury (clinicaltrials.gov) - P1/2 | N=3 | Terminated | Sponsor: UCB Biopharma SRL | N=12 ➔ 3 | Trial completion date: May 2025 ➔ May 2022 | Recruiting ➔ Terminated | Trial primary completion date: May 2025 ➔ May 2022; Recruitment challenges

Enrollment change • Trial completion date • Trial primary completion date • Trial termination • Transplantation

A Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Zampilimab in Adult Kidney Transplant Recipients With Chronic Allograft Injury (clinicaltrials.gov) - P1/2; N=12; Recruiting; Sponsor: UCB Biopharma SRL; N=177 ➔ 12; Trial completion date: Oct 2023 ➔ May 2025; Trial primary completion date: Oct 2023 ➔ May 2025

Clinical • Enrollment change • Trial completion date • Trial primary completion date • Transplantation

A Study to Test Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Single Ascending Intravenous Doses of Zampilimab in Healthy Participants (clinicaltrials.gov) - P1; N=16; Completed; Sponsor: UCB Biopharma SRL; Active, not recruiting ➔ Completed

Trial completion

A Study to Test Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Single Ascending Intravenous Doses of Zampilimab in Healthy Participants (clinicaltrials.gov) - P1; N=16; Active, not recruiting; Sponsor: UCB Biopharma SRL; Recruiting ➔ Active, not recruiting

Enrollment closed

A Study to Test Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Single Ascending Intravenous Doses of Zampilimab in Healthy Participants (clinicaltrials.gov) - P1; N=16; Recruiting; Sponsor: UCB Biopharma SRL; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open

A Study to Test Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Single Ascending Intravenous Doses of Zampilimab in Healthy Participants (clinicaltrials.gov) - P1; N=16; Not yet recruiting; Sponsor: UCB Biopharma SRL

Clinical • New P1 trial

[VIRTUAL] Using Skin Biopsies to Measure Target Occupancy of a Renal Antifibrotic Monoclonal Antibody (mAb) in a Phase 1 Clinical Study (KIDNEY WEEK 2020) - P1, P1/2 | "Our ‘biopsy-on-biopsy’ approach allows early identification of a dose range in Phase 1 studies where the target organ is inaccessible, and is applicable to other therapeutic mAbs intended for treatment of fibrotic kidney disease. A Phase 1/2 study of zampilimab in patients with post-renal transplant fibrosis is ongoing (NCT04335578). Funding: Commercial Support"

Clinical • P1 data • Chronic Kidney Disease • Fibrosis • Immunology • Nephrology • Renal Disease • Transplantation

[VIRTUAL] Development of a CKD Model in Cynomolgus Monkeys and Its Application to Test Zampilimab, a Monoclonal Antibody (mAb) Specific for Human Transglutaminase 2 (TG2) (KIDNEY WEEK 2020) - P1/2 | "Our primate model of CKD demonstrated that zampilimab can effectively block TG2 activity and prevent renal fibrosis. A Phase 1/2 study of zampilimab for the treatment of post-renal transplant fibrosis is ongoing (NCT04335578). Funding: Commercial Support"

Fibrosis • Immunology • Transplantation • TGFB1

A Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Efficacy of UCB7858 in Adult Kidney Transplant Recipients With Chronic Allograft Injury (clinicaltrials.gov) - P1/2; N=177; Recruiting; Sponsor: UCB Biopharma SRL; Trial completion date: Jul 2023 ➔ Nov 2023; Trial primary completion date: Jul 2023 ➔ Nov 2023

Clinical • Trial completion date • Trial primary completion date • Transplantation