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 Moderate to Severe Rheumatoid Arthritis (RA)

The goal of this clinical trial is to learn if CIT-013 works to treat rheumatoid arthritis in adults. It will also learn about the safety of CIT-013. The main questions it aims to answer are:
Does CIT-013 lower the disease activity of RA patients? What medical problems do participants have when receiving CIT-013? Researchers will compare CIT-013 to a placebo (a look-alike substance that contains no drug) to see if CIT-013 works to treat the symptoms of RA.
Participants will:
Take receive CIT-013 or placebo every other week for 12 weeks Visit the clinic once every 2 weeks for checkups and tests Keep monitor their symptoms during this period

Start Date01 Nov 2024

Sponsor / Collaborator

Citryll BVStartup

NL-OMON24009

/ RecruitingNot Applicable

A first-in-human, randomized, double-blind, placebo-controlled, single ascending dose study to evaluate CIT-013 in healthy volunteers with and without an intravenous lipopolysaccharide challenge

Start Date26 Jul 2021

Sponsor / Collaborator

Citryll BVStartup

100 Clinical Results associated with CIT-013

100 Translational Medicine associated with CIT-013

100 Patents (Medical) associated with CIT-013

Literatures (Medical) associated with CIT-013

31 Dec 2023·mAbs

Anti-citrullinated histone monoclonal antibody CIT-013, a dual action therapeutic for neutrophil extracellular trap-associated autoimmune diseases

Article

Author: Bruurmijn, Tirza ; Erpenbeck, Luise ; Neubert, Elsa ; Foster, Martyn ; Reinieren-Beeren, Inge ; van Es, Helmuth ; Kip, Annemarie ; Te Poele, Rezie ; Meldrum, Eric ; Kumari, Sangeeta ; Chirivi, Renato G S ; van der Linden, Maarten ; Montizaan, Daphne ; van Zandvoort, Peter ; Vink, Paul ; Waaijenberg, Kelsy ; van Dalen, Stephanie

Neutrophil extracellular traps (NETs) contribute to the pathophysiology of multiple inflammatory and autoimmune diseases. Targeting the NETosis pathway has demonstrated significant therapeutic potency in various disease models. Here, we describe a first-in-class monoclonal antibody (CIT-013) with high affinity for citrullinated histones H2A and H4, which inhibits NETosis and reduces tissue NET burden in vivo with significant anti-inflammatory consequences. We provide a detailed understanding of the epitope selectivity of CIT-013. Detection of CIT-013 epitopes in rheumatoid arthritis (RA) synovium provides evidence that RA is an autoimmune disease with excessive citrullinated NETs that can be targeted by CIT-013. We show that CIT-013 acts upon the final stage of NETosis, binding to its chromatin epitopes when plasma membrane integrity is compromised to prevent NET release. Bivalency of CIT-013 is necessary for NETosis inhibition. In addition, we show that CIT-013 binding to NETs and netting neutrophils enhance their phagocytosis by macrophages in an Fc-dependent manner. 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.

13 Jan 2020·Angewandte Chemie International EditionQ1 · CHEMISTRY

3D Electron Diffraction Unravels the New Zeolite ECNU‐23 from the “Pure” Powder Sample of ECNU‐21

Q1 · CHEMISTRY

Article

Author: Han, Lu ; Jiang, Jingang ; Luo, Yi ; Sun, Junliang ; Wu, Peng ; Xu, Hao ; Mao, Wenting ; Liu, Xue

AbstractA novel crystalline high‐silica zeolite with 12×8‐membered ring (R) channel system is prepared with the aid of the 3D electron diffraction (3D ED) technique. A crystal with the same topology as one of the predicted daughter structures of CIT‐13 germanosilicate, named ECNU‐23 (East China Normal University 23) was coincidentally detected by the 3D ED investigation during the structure characterization of the “pure” powder sample of existing one‐dimension (1D) 10‐R ECNU‐21. By controlling the alkaline‐assisted hydrolysis under moderate conditions, we purified the phase of ECNU‐23 by selectively breaking and removing the chemically weak Ge(Si)‐O‐Ge and metastable Si‐O‐Si bonds. Its structure was determined based on the 3D ED data, and confirmed by high‐resolution TEM images and powder X‐ray diffraction (PXRD) data. The aluminosilicate Al‐ECNU‐23 shows unique catalytic properties in the isomerization/ disproportionation of m‐xylene as solid‐acid catalyst.

21 Mar 2019·Chemistry – A European JournalQ2 · CHEMISTRY

Topotactic Conversion of Alkali‐Treated Intergrown Germanosilicate CIT‐13 into Single‐Crystalline ECNU‐21 Zeolite as Shape‐Selective Catalyst for Ethylene Oxide Hydration

Q2 · CHEMISTRY

Article

Author: Peng, Mingming ; Liu, Xue ; Jiang, Jingang ; Xu, Hao ; Wu, Peng ; Lu, Xinqing ; Che, Shun‐ai ; Han, Lu ; Mao, Wenting

AbstractThe conversion of the alkali‐treated intergrowth germanosilicate CIT‐13 into the single‐crystalline high‐silica ECNU‐21 (named after East China Normal University) zeolite, with a novel topology and a highly crystalline zeolite framework, has been realized through a creative top‐down strategy involving a mild alkaline‐induced multistep process consisting of structural degradation and reconstruction. Instead of acid treatment, hydrolysis in aqueous ammonia solution not only readily cleaved the chemically weak Ge(Si)−O−Ge bonds located within the interlayer double four ring (D4R) units of CIT‐13, but also cleaved the metastable Si−O−Si bonds therein. This led to extensive removal of the D4R units, and also generated silanol groups on adjacent silica‐rich layers, which then condensed to form a novel daughter structure upon calcination. Individual oxygen bridges in the reassembled ECNU‐21 replaced the germanium‐rich D4R units in CIT‐13, thereby eliminating the original intergrowth phenomenon along the b axis. With an ordered crystalline structure of 10‐ring (R) channels as well as suitable germanium‐related Lewis acid sites, ECNU‐21 serves as a stable solid Lewis acid catalyst for the shape‐selective hydration of ethylene oxide (EO) to ethylene glycol (EG) at greatly reduced H2O/EO ratios and reaction temperature in comparison with the noncatalytic industrial process.

News (Medical) associated with CIT-013

09 Dec 2024

·www.globenewswire.com

Citryll Raises EUR 85 Million Series B to Advance Novel NET-Targeting Therapy for Immune-Mediated Inflammatory Disorders

CITRYLL RAISES EUR 85 MILLION SERIES B TO ADVANCE NOVEL NET-TARGETING THERAPY FOR IMMUNE-MEDIATED INFLAMMATORY DISORDERS Financing co-led by Johnson & Johnson Innovation – JJDC, Inc., Forbion and Novartis Venture Fund Lead first-in-class product candidate, monoclonal antibody CIT-013, to be advanced into two Phase 2a studies Oss, Netherlands – 09 December 2024 – Citryll, a biotech company pioneering a transformative approach to treating immune-mediated inflammatory diseases by targeting Neutrophil Extracellular Traps (NETs), announces today the successful closing of an oversubscribed EUR 85 million Series B fundraise. The funding round was co-led by Johnson & Johnson (through its corporate venture capital organization, Johnson & Johnson Innovation – JJDC, Inc.), Forbion and Novartis Venture Fund, with the participation of Pureos Bioventures, alongside existing investors BioGeneration Ventures, Seventure Partners, BOM, Curie Capital, and Citryll’s founders. 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. NETs are web-like structures composed of DNA, histones, and antimicrobial proteins, released by neutrophils to trap and degrade pathogens. Excessive NET formation can contribute to tissue damage and chronic inflammation in various immune-mediated inflammatory disorders. Citryll recently completed its first-in-human Phase 1 trials including successful repeat dosing of rheumatoid arthritis (RA) patients. Phase 2a trials are planned in both RA and hidradenitis suppurativa (HS), intended to establish CIT-013’s unique dual mechanism of action, which enhances the clearance of existing NETs and inhibits the formation of new NETs. CIT-013 is highly selective for its epitope, minimizing off-target effects, and does not enter cells, preserving normal intracellular functions. While initially focusing on RA and HS, Citryll's NET-targeting approach has potential applications across a wide range of immune-mediated inflammatory diseases. Following this Series B round, Geert-Jan Mulder, Managing Partner at Forbion, Florian Muellershausen, Managing Director at Novartis Venture Fund, and a representative of JJDC, will join Citryll’s Board as non-executive directors. Geert-Jan Mulder, Managing Partner at Forbion, said: “Citryll’s progress highlights the potential of a novel NET-targeting therapy to address significant unmet needs in inflammatory disorders, offering hope for conditions like rheumatoid arthritis and hidradenitis suppurativa, where many patients lack adequate disease control. Together with new and existing investors we are proud to support the outstanding team to further advance this truly differentiated program into clinical development for inflammatory disorders.” Eduardo Bravo, Chief Executive Officer of Citryll, commented: “Securing funding from such a fantastic range of global life sciences investors, who share our excitement for the potential of CIT-013, strengthens the next steps for our clinical development program. We believe our NET-targeting approach, developed by the company founders Renato Chirivi, Helmuth van Es, and the late Jos Raats, has the potential to be beneficial in conditions where current therapies fall short. As we move forward with our clinical trials, we're excited about the possibility of providing a more effective treatment option for patients who have long struggled with inadequate disease control.” -ENDS- About Citryll Citryll is pioneering a transformative approach to treating inflammatory diseases by targeting Neutrophil Extracellular Traps (NETs), a fundamental component of the inflammatory process that has yet to be addressed therapeutically. Citryll is developing the first NET-targeting therapy, and potentially creating a new class of therapeutics with broad applications across immune-mediated inflammatory diseases. Our lead asset, CIT-013, is a first-in-class monoclonal antibody with a unique dual mechanism of action: it enhances the clearance of existing NETs and inhibits the formation of new NETs. By addressing this key driver of inflammation, CIT-013 has the potential to offer a differentiated and comprehensive treatment option for conditions such as rheumatoid arthritis and hidradenitis suppurativa, where current therapies often fall short of providing adequate disease control. Contacts CitryllSjoerd van Gorp, COOEmail: info@citryll.com Citryll Media ContactsICR HealthcareAmber Fennell, Sukaina Virji, Lucy FeatherstoneEmail: citryll@icrinc.com

Phase 1Phase 2

09 Dec 2024

·endpts.com

Dutch biotech nabs €85M to position inflammatory antibody for a pharma buyer

Citryll, a Dutch biotech that has largely flown under the radar for most of its nearly 10-year history, has patched together an €85 million Series B to test a monoclonal antibody in two inflammatory conditions. The financing will help the Oss, Netherlands-based startup collect data by late 2026 or early 2027 in rheumatoid arthritis and hidradenitis suppurativa, CEO Eduardo Bravo told Endpoints News . The capital will keep the engine running at the 20-employee biotech until almost 2028, he said. The data in these two inflammatory conditions, in which many patients still don’t get complete disease resolution with current medicines, will serve as the backbone for a potential M&A exit, Bravo said. “The problem is that we have one compound today, so licensing is less of an option,” he said. “The idea and the main goal, if everything goes well and the data is as strong as it could be, would probably be exiting just through a sale of the company to a big pharma.” Citryll already has the peripheral support of two pharma giants. Both Novartis and Johnson & Johnson’s corporate VC arms co-led the Series B alongside Dutch biotech investor Forbion , who has had a strong track record this year of portfolio drug developers getting snapped up by pharma companies . J&J’s conviction on Citryll’s monoclonal antibody, dubbed CIT-013, helped catalyze other investors to come off the sidelines and support the company, Bravo said. The other new backer is Pureos Bioventures. Existing investors also took part, including BioGeneration Ventures, Seventure Partners, BOM, Curie Capital and Citryll’s founders. Citryll hopes to be the first to target neutrophil extracellular traps, or NETs. The web-like structures have been found to be implicated in a variety of immune-mediated diseases. DNA, histones and antimicrobial proteins comprise the structures, the company said. Too much of the web and tissue can become damaged, chronic inflammation can flare up and other immune-mediated issues can go haywire. “We’ve met companies that were very interested in the pathway, but never found a way of targeting it. And as always, there’s some skeptical that are not convinced that this is the right target to go against,” Bravo said. “But when you’re first-in-class with a new mechanism of action, you’re always going to find the believers and the skeptics.” Bravo’s startup will move into a Europe-only Phase 2a trial in rheumatoid arthritis next year, testing whether CIT-013 is better than placebo on a primary endpoint known as DAS28, or a 28-joint disease activity score, the CEO said. A few months later, the biotech will then open a Phase 2a in hidradenitis suppurativa, with that trial being global in nature and including US sites, he added. “A few years ago, HS was a complete unknown space,” Bravo said. “With the arrivals of the IL-17s, now suddenly there are many compounds that are being developed.” Novartis’ Cosentyx snagged the HS approval from the FDA last year, and UCB’s Bimzelx also recently secured the US green light. “But they’re all IL-17s, which seems to be a very logical choice as well,” Bravo said, “but the same as with the RA compounds, that’s a single pathway, a single cytokine, and we believe that by targeting NETs, we have a wider mechanism of action.” A slew of biopharmas are catching up in HS, too, including AbbVie, Incyte, Sanofi and others . Acelyrin’s work in the field is in limbo . After RA and HS, and with the help of a pharma parent, Citryll could expand into multiple other disease areas, like respiratory, cardiovascular, gastrointestinal and others, Bravo said. If the initial data are clean, “this will become a certainly multibillion product,” the Citryll CEO said. “With a monoclonal antibody, [it is] very low CMC risk, very low risk in general, safety-wise, as well.” Citryll is a spinout of ModiQuest, which itself was acquired by ImmunoPrecise Antibodies in 2018.

Phase 2IND

09 Dec 2024

·www.pharmaceutical-technology.com

Citryll gains Series B funds to develop NET-targeting antibody

Phase IIa trials are set to focus on both rheumatoid arthritis and hidradenitis suppurativa, aiming to establish the antibody’s dual mechanism of action. Credit: CrizzyStudio/Shutterstock. Citryll has secured an oversubscribed Series B funding round, raising €85m ($89.8m) to advance the clinical development of the first-in-class monoclonal antibody, CIT-013, designed to target neutrophil extracellular traps (NETs), which play a key role in inflammation and have not been previously therapeutically targeted. Novartis Venture Fund, Johnson & Johnson Innovation – JJDC and Forbion co-led the funding round. It also saw participation from Pureos Bioventures and existing investors Seventure Partners, BioGeneration Ventures, BOM, Curie Capital and the founders of Citryll. With the completion of the Series B round, a representative from JJDC along with Geert-Jan Mulder, managing partner at Forbion, and Florian Muellershausen, managing director at Novartis Venture Fund, are set to join Citryll’s board as non-executive directors. Citryll CEO Eduardo Bravo stated: “Securing funding from such a fantastic range of global life sciences investors, who share our excitement for the potential of CIT-013, strengthens the next steps for our clinical development programme. “We believe our NET-targeting approach, developed by the company founders Renato Chirivi, Helmuth van Es and the late Jos Raats, has the potential to be beneficial in conditions where current therapies fall short. “As we move forward with our clinical trials, we’re excited about the possibility of providing a more effective treatment option for patients who have long struggled with inadequate disease control.” NETs can be characterised as the web-like structures that neutrophils release to trap and degrade pathogens. However, their excessive formation can lead to tissue damage and chronic inflammation in immune-mediated inflammatory disorders. The company has recently completed Phase I trials, along with repeat dosing in rheumatoid arthritis subjects. Phase IIa trials are set to focus on both rheumatoid arthritis and hidradenitis suppurativa, aiming to establish the antibody’s dual mechanism of action, which clears existing NETs and prevents the formation of new ones. The antibody is designed to be highly selective for its epitope, reducing the risk of off-target effects. It does not enter cells, which helps to preserve normal intracellular functions.

Phase 2Phase 1ADC

100 Deals associated with CIT-013

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Rheumatoid Arthritis	Phase 2	NL	Citryll BVStartup	01 Nov 2024
Rheumatoid Arthritis	Phase 2	DE	Citryll BVStartup	01 Nov 2024
Rheumatoid Arthritis	Phase 2	HU	Citryll BVStartup	01 Nov 2024
Rheumatoid Arthritis	Phase 2	PL	Citryll BVStartup	01 Nov 2024
Rheumatoid Arthritis	Phase 2	BE	Citryll BVStartup	01 Nov 2024
Rheumatoid Arthritis	Phase 2	ES	Citryll BVStartup	01 Nov 2024
Idiopathic Pulmonary Fibrosis	Preclinical	-	Citryll BVStartup	-
Systemic Lupus Erythematosus	Preclinical	-	Citryll BVStartup	-
Vasculitis	Preclinical	-	Citryll BVStartup	-

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