CIT-013 / Citryll - LARVOL DELTA

Cityview: PET-Based Imaging of Radiolabeled CIT-013 (clinicaltrialsregister.eu) - P1/2 | N=12 | Recruiting | Sponsor: Citryll B.V.

New P1/2 trial • Immunology • CRP

CITRYLL003: A Phase 2a double blind, randomized, parallel arm, placebo-controlled trial to investigate the effects of two dose levels of CIT-013 on disease activity in patients with Hidradenitis Suppurativa (HS) (clinicaltrialsregister.eu) - P1/2 | N=64 | Recruiting | Sponsor: Citryll B.V.

New P1/2 trial • Dermatology • Hidradenitis Suppurativa • Immunology

Targeting Neutrophil Function as Therapy for Hidradenitis Suppurativa. (PubMed, Int J Mol Sci) - "Strategies advancing through clinical trials include inhibition of chemokine-mediated trafficking, neutrophil serine protease inactivation and suppression of neutrophil extracellular traps (NETs), which amplify inflammatory and autoimmune responses. These emerging therapies mark a significant shift toward targeted neutrophil modulation, offering new opportunities to improve outcomes for patients with HS."

Journal • Review • Dermatology • Hidradenitis Suppurativa • Immunology • Inflammation • Pain • IL17A • TNFA

Citryll...announces that the first patient has been successfully dosed in its imaging study, ‘Cityview’, evaluating the distribution of radiolabeled CIT-013 in participants with rheumatoid arthritis (RA) and hidradenitis suppurativa (HS). (Yahoo Finance) - "Cityview is a Phase IIa, open-label, single-center study planned to enroll 12 participants in two sequential groups starting with participants with active RA, followed by participants with RA in remission and participants with active HS. Following a single dose of radiolabeled CIT-013, participants will undergo PET-CT imaging at intervals over a week follow-up period."

Trial status • Hidradenitis Suppurativa • Rheumatoid Arthritis

Cityview: PET-Based Imaging of Radiolabeled CIT-013 (clinicaltrials.gov) - P2 | N=12 | Recruiting | Sponsor: Citryll BV | Not yet recruiting ➔ Recruiting

Enrollment open • Immunology

Citryll…announces the dosing of the first patient in its Phase IIa hidradenitis suppurativa (HS) clinical trial, 'Citylights' (GlobeNewswire) - "The trial will evaluate its first-in-class monoclonal antibody CIT-013 in patients with moderate to severe HS."

Trial status • Hidradenitis Suppurativa

Neutrophil Extracellular Traps in Hidradenitis Suppurativa Skin and Serum as Target for CIT-013, a Novel NET Inhibiting Therapy (ISDS 2025) - "Collectively, the data support the therapeutic rationale for CIT-013 in HS. A Phase 2 proof-of-concept trial in HS will start this year."

Dermatology • Hidradenitis Suppurativa • Immunology • Inflammation

Citylights: A Study With CIT-013 in HS Patients (clinicaltrials.gov) - P2 | N=96 | Recruiting | Sponsor: Citryll BV | Not yet recruiting ➔ Recruiting

Enrollment open • Dermatology • Hidradenitis Suppurativa • Immunology

Two additional posters provided details from preclinical studies supporting the clinical program. (GlobeNewswire) - "The first outlines the use of radiolabelled CIT-013 as an imaging tool, with data indicating CIT-013 is a targeted therapy which accumulates specifically in inflamed tissue. The second evaluates calprotectin as a biomarker of disease activity, with a correlation seen between treatment response and serum calprotectin levels, supporting its use as a biomarker in RA."

Preclinical • Rheumatoid Arthritis

CIT-013…Additional Phase IIa trial in hidradenitis suppurativa expected to start later this year (GlobeNewswire)

Trial status • Hidradenitis Suppurativa

Citryll Presents Positive Data from Phase I Study of CIT-013 in Rheumatoid Arthritis at ACR Convergence 2025 (GlobeNewswire) - "The featured poster highlights findings from Citryll’s Phase I clinical trial of CIT-013 in participants with RA and healthy volunteers, which demonstrated that CIT-013 was generally well tolerated across all participants, with no serious treatment-related events reported. Importantly, clinically meaningful reductions in disease activity were seen in all active RA participants treated with CIT-013."

P1 data • Rheumatoid Arthritis

Radiolabelled anti-citrullinated histone antibody CIT-013 as a tool to visualize NET rich inflamed joints in a collagen induced arthritic mouse model (ACR Convergence 2025) - "mACHA can be used as a radiotracer to visualize NETs in sites of inflammation. This proof of principle imaging study enables a human whole body PET CT imaging clinical study in RA and hidradenitis suppurativa patients during 2025. This clinical study will lead to further insights in CIT-013's distribution, target engagement and mechanism of action in patients with immune mediated inflammatory diseases."

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

Phase I Trial in Participants with Rheumatoid Arthritis and Healthy Volunteers with CIT-013, a First in Class NETosis Inhibitor (ACR Convergence 2025) - "CIT-013 was well tolerated and a DAS28-CRP reduction was observed in participants with RA and active disease. These findings support further clinical development."

Clinical • P1 data • Immunology • Inflammatory Arthritis • Musculoskeletal Diseases • Orthopedics • Rheumatoid Arthritis • Rheumatology

Calprotectin Serum levels: a potential neutrophil activation biomarker to monitor treatment response in Rheumatoid Arthritis (ACR Convergence 2025) - "Our data obtained from the analyses of two longitudinal RA cohorts demonstrate that serum calprotectin and its change can be used as a biomarker for disease activity and response to treatment. Citryll is developing a novel antibody therapeutic mAb (CIT-013) that targets release of extracellular traps from neutrophils. It is our intention to further probe the utility of calprotectin, along with other conventionally used endpoints, as a marker of response to therapy in an RA phase 2a proof of concept study which will begin in 2025."

Biomarker • Gastrointestinal Disorder • Immunology • Inflammation • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology • KEAP1 • S100A8

FIRST PATIENT DOSED IN CITRYLL’S PHASE IIA TRIAL EVALUATING CIT-013 IN RHEUMATOID ARTHRITIS (GlobeNewswire) - "Citydream is a Phase IIa, randomized, double-blind, placebo-controlled, multi-center study conducted across multiple sites in Europe....The trial will enroll 88 patients who will undergo a 6-week treatment period, followed by an open-label extension phase to further assess safety and efficacy."

Trial status • Rheumatoid Arthritis

A Study With CIT-013 in RA Patients (clinicaltrials.gov) - P2 | N=88 | Recruiting | Sponsor: Citryll BV | Not yet recruiting ➔ Recruiting

Enrollment open • Immunology • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology

Cityview: PET-Based Imaging of Radiolabeled CIT-013 (clinicaltrials.gov) - P2 | N=12 | Not yet recruiting | Sponsor: Citryll BV

New P2 trial • Immunology

A Study With CIT-013 in RA Patients (clinicaltrials.gov) - P2 | N=77 | Not yet recruiting | Sponsor: Citryll BV | N=150 ➔ 77 | Initiation date: Nov 2024 ➔ Aug 2025

Enrollment change • Trial initiation date • Immunology • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology

A Web of Challenges: The Therapeutic Struggle to Target NETs in Disease. (PubMed, Int J Mol Sci) - "The NET inhibitors themselves have several limitations, including off-target effects and bioavailability issues. The challenges facing NET-targeted therapies reported here may explain what is required to go from bench to bedside successfully."

Journal • Review • Immunology • Oncology

Citylights: A Study With CIT-013 in HS Patients (clinicaltrials.gov) - P2 | N=96 | Not yet recruiting | Sponsor: Citryll BV

New P2 trial • Dermatology • Hidradenitis Suppurativa • Immunology

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