CIT-013 / Citryll - LARVOL DELTA

Inhibition of EETosis with an anti-citrullinated histone antibody: a novel therapeutic approach for eosinophilic inflammatory disorders. (PubMed, Front Immunol) - "CIT-013 potently inhibits release of EETs (half-maximal inhibitory concentration of 2.5 nM) without inhibiting other eosinophil functions such as degranulation, adhesion, superoxide production and induction of chemokine expression. Together, this study provides new insights into the requirement of protein arginine deiminase 4 (PAD4) for EETosis, differentiates requirements of EETosis from galectin-10 release, and identifies a novel therapeutic approach for EETosis inhibition by targeting citrullinated histones in eosinophil-driven diseases such as ECRS."

Journal • Immunology • Infectious Disease • Inflammation • Nasal Polyps • Otorhinolaryngology • Respiratory Diseases • Sinusitis • LGALS1

Citryll Demonstrates a Broader Therapeutic Potential for CIT-013 in the Treatment of Inflammatory Disorders (GlobeNewswire) - "Citryll...today announces the publication of new research in Frontiers in Immunology. The study demonstrates that CIT-013, originally developed to target NETs, also effectively inhibits the formation of eosinophil extracellular traps (EETs) with the same potency and verifies the presence of CIT-013’s epitope on EETs. These findings further validate Citryll’s approach and highlight the broader therapeutic potential of CIT-013 beyond inflammatory diseases that are neutrophilic in nature.....Citryll is currently investigating CIT-013 in rheumatoid arthritis (RA) and hidradenitis suppurativa (HS)."

Clinical • Hidradenitis Suppurativa • Rheumatoid Arthritis

Citryll Raises EUR 85 Million Series B to Advance Novel NET-Targeting Therapy for Immune-Mediated Inflammatory Disorders (GlobeNewswire) - "Citryll...announces today the successful closing of an oversubscribed EUR 85 million Series B fundraise....The funding will enable next steps for the clinical development of CIT-013, a first-in-class monoclonal antibody which targets Neutrophil Extracellular Traps (NETs), a fundamental component of the inflammatory process that has yet to be addressed therapeutically."

Financing • Hidradenitis Suppurativa • Immunology

Anti-Citrullinated Histone Antibody CIT-013 Targets NETs in Inflamed Joints and Halts NET-mediated Joint Deterioration (ACR Convergence 2024) - "Together, this demonstrates that CIT-013 can target its epitopes in inflamed joints, suppresses the proinflammatory properties of NETs, and thereby has therapeutic potential for IMIDs like RA. This strengthens further the potential of CIT-013 as a unique therapeutic approach for NET-associated diseases with unmet therapeutic needs. CIT-013 is expected to enter phase 2 proof-of-concept clinical trials in RA and Hidradenitis suppurativa during 2024."

Dermatology • Hidradenitis Suppurativa • Immunology • Inflammation • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology

Real-Time, High-Throughput Microscopic Quantification of Human Neutrophil Extracellular Trap Release and Assessing the Pharmacology of Antagonists. (PubMed, J Vis Exp) - "To exemplify the utility of this method to study NETosis antagonists, we used CIT-013, a first-in-class monoclonal antibody inhibitor of NET release...Other anti-histone antibodies tested lacked this NETosis-inhibitory capacity. Altogether, we demonstrate that this protocol enables specific, reliable, and reproducible high-throughput quantification of NETs, enhancing the study of NET release characteristics, kinetics, and pharmacology of NETosis antagonists."

Journal • Immunology

A Study With CIT-013 in RA Patients (clinicaltrials.gov) - P2 | N=150 | Not yet recruiting | Sponsor: Citryll BV

New P2 trial • Immunology • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology

CITRYLL COMPLETES PATIENT DOSING IN THE REPEAT DOSE STAGE OF THE PHASE 1 TRIAL FOR THE NOVEL ANTI-INFLAMMATORY CANDIDATE CIT-013 (GlobeNewswire) - "Citryll...today announces the successful completion of dosing in the repeat dose stage of its Phase 1 trial for its lead drug candidate CIT-013....Part D of the Phase 1 trial is investigating the safety and tolerability of repeat dosing in 9 patient volunteers with rheumatoid arthritis (RA) and 3 healthy volunteers. All trial participants have been enrolled and successfully completed dosing. Results are anticipated in Q4 2024, which, if positive, would lay the groundwork for the initiation of Phase 2a trials. Two Phase 2a studies are planned in patients with RA and hidradenitis suppurativa (HS)..."

P1 data • Trial status • Rheumatoid Arthritis

ANTI-CITRULLINATED HISTONE ANTIBODY CIT-013 TARGETS NETS IN INFLAMED JOINTS AND HALTS NET-MEDIATED JOINT DETERIORATION IN RA (EULAR 2024) - "Together, this demonstrates that CIT-013 can target its epitopes in inflamed joints, suppresses the proinflammatory properties of NETs, and thereby has therapeutic potential for IMIDs like RA. This reinforces the position of CIT-013 as a unique therapeutic approach for NET-associated diseases with unmet therapeutic needs. CIT-013 will enter phase 2 proof-of-concept clinical trials in RA and Hidradenitis suppurativa during 2024."

Dermatology • Hidradenitis Suppurativa • Inflammatory Arthritis • Rheumatoid Arthritis

ANTI-CITRULLINATED HISTONE ANTIBODY CIT-013, A DUAL ACTION THERAPEUTIC FOR NEUTROPHIL EXTRACELLULAR TRAP ASSOCIATED AUTOIMMUNE DISEASES (AUTO 2024) - "This reinforces the position of CIT-013 as unique therapeutic approach for NET-associated diseases with unmet therapeutic needs. CIT-013 will enter phase 2 proof-of-concept trials in RA and HS during 2024."

Dermatology • Hidradenitis Suppurativa • Immunology • Inflammation • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology

Citryll Announces the Appointment of Maarten Kraan as Chief Medical Officer (Businesswire) - "...given its recent start of a first-in-human study in rheumatoid arthritis patients with CIT-013...the Company also anticipates the initiation of Phase 2a proof-of-concept trials later this year in rheumatoid arthritis and hidradenitis suppurativa patients."

New P2 trial • Hidradenitis Suppurativa • Rheumatoid Arthritis

Anti-citrullinated histone antibody CIT-013: Targeting neutrophil extracellular traps as an anti-inflammatory therapy in hidradenitis suppurativa(#60) (EHSF 2024) - "Altogether, this reinforces the position of CIT-013 as a distinctive therapeutic approach for NET-associated diseases with unmet therapeutic needs, such as HS. CIT-013 will enter a phase 2 proof-of-concept trial in HS during 2024."

Dermatology • Hidradenitis Suppurativa • Immunology • Inflammation

Anti-citrullinated histone monoclonal antibody CIT-013, a dual action therapeutic for neutrophil extracellular trap-associated autoimmune diseases. (PubMed, MAbs) - "This is confirmed using a murine neutrophilic airway inflammation model where a mouse variant of CIT-013 reduced tissue NET burden with significant anti-inflammatory consequences. CIT-013's therapeutic activity provides new insights for the development of NET antagonists and indicates the importance of a new emerging therapy for NET-driven diseases with unmet therapeutic needs."

Journal • Immunology • Inflammation • Inflammatory Arthritis • Respiratory Diseases • Rheumatoid Arthritis • Rheumatology

Early Clinical Development of CIT-013, a First in Class NETosis Inhibitor, in a Randomized Phase I Dose Escalation Study in Healthy Volunteers Demonstrating Potent Inhibition of LPS Induced Neutrophil Extracellular Trap Formation (ACR Convergence 2023) - "CIT-013 is well tolerated up to 0.3 mg/kg intravenously and up to 0.9 mg/kg with pre-medication. Dose limiting toxicity was seen when given intravenously, with chest discomfort associated with elevated cytokines, CRP and temperature which was markedly reduced by subcutaneous administration. Near complete inhibition of circulating NET components at 0.3 and 0.9 mg/kg CIT-013 in the LPS challenge study showed effective target engagement."

Clinical • Late-breaking abstract • P1 data • ANCA Vasculitis • Dermatology • Hidradenitis Suppurativa • Immunology • Inflammatory Arthritis • Lupus • Rheumatoid Arthritis • Rheumatology • Systemic Lupus Erythematosus • Vasculitis

Anti-Citrullinated Histone Antibody CIT-013, a Dual Action Therapeutic for Neutrophil Extracellular Trap Associated Autoimmune Disease (ACR Convergence 2023) - "Since NETs contribute to the pathophysiology of many immune mediated inflammatory diseases, including autoimmune diseases such as RA, CIT-013's unique ability to both inhibit NET release and enhance NET clearance indicates the importance of this first in class therapeutic antibody as a new emerging therapy. M. van der Linden: Citryll BV, 3, 12, STOCK APPRECIATION RIGHTS; S. Kumari: Citryll BV, 3, 12, STOCK APPRECIATION RIGHTS; D. Montizaan: Citryll BV, 3, 12, STOCK APPRECIATION RIGHTS; S. van Dalen: Citryll BV, 3, 12, STOCK APPRECIATION RIGHTS; A. Kip: Citryll BV, 3, 12, STOCK APPRECIATION RIGHTS; M. FOSTER: Citryll BV, 2, Ermium Therapeutics, 2;"

Immunology • Inflammation • Inflammatory Arthritis • Pneumonia • Rheumatoid Arthritis • Rheumatology

Anti-Citrullinated Histone Monoclonal Antibody CIT-013, a Dual Action Therapeutic for Neutrophil Extracellular Trap Associated Autoimmune Diseases (EULAR 2023) - "Furthermore, we demonstrate that a mouse variant of CIT-013 reduces tissue NET burden in vivo at least in part through enhanced macrophage phagocytosis. Conclusion Since NETs contribute to the pathophysiology of many immune mediated inflammatory diseases, including autoimmune diseases such as RA, CIT-013‘s unique ability to both inhibit NET release and enhance NET clearance indicates the importance of this first in class therapeutic antibody as a new emerging therapy."

Immunology • Inflammation • Inflammatory Arthritis • Pneumonia • Rheumatoid Arthritis • Rheumatology

Citryll Announces Dosing of the First Healthy Volunteer in a Phase 1 Clinical Trial for CIT-013, a First in Class Antagonist of NET Biology (Businesswire) - "Phase 1 SAD study expected to read-out by the end of 2021. Citryll today announced that the first healthy volunteer has been enrolled and dosed in a Phase 1 clinical trial to evaluate the safety, tolerability, and pharmacokinetics of CIT-013....The first-in-human study is a randomised, double blind, placebo controlled, single ascending dose (SAD) study carried out by the Centre for Human Drug Research (CHDR) in Leiden, The Netherlands, a CRO specialized in early-stage human clinical trials....'The next phase of development is already in full preparation, including expanding to other countries for patient studies.'"

P1 data • Trial status • Idiopathic Pulmonary Fibrosis • Immunology • Systemic Lupus Erythematosus

Citryll completes € 18.5 M fundraise to develop CIT-013, an antibody targeting Neutrophil Extracellular Traps (Businesswire) - "Citryll announced it closed a total fundraise of € 18.5 million...The proceeds will be used to advance the pre-clinical and clinical development of Citryll’s CIT-013 therapeutic antibody, an inhibitor of neutrophil extracellular traps (NETs) and their formation (NETosis). 'We welcome this significant investment by a strong investor syndicate from Europe and China and the substantial support by the Dutch Government.'...The preclinical development and manufacturing process of CIT-013 was accelerated in 2019 through the first closing of the financing round...The program is on track to reach the clinic in 2021."

Clinical • Financing • Idiopathic Pulmonary Fibrosis