OATD-01 / Molecure - LARVOL DELTA

Elucidation of the Catalytic Apparatus and Mechanism of Human Chitotriosidase‑1. (PubMed, ACS Catal) - "Finally, we demonstrated that binding of the first-in-class inhibitor OATD-01 induces subtle yet far-reaching dynamical changes within the active site, leading to dissociation of the immunoglobulin-like heterodimer and disruption of interactions with biological partners implicated in disease pathogenesis. These findings not only redefine the mechanistic landscape of hCHIT1 but also provide a robust framework for the rational design of next-generation GH18 inhibitors, for example, targeting multidrug-resistant pathogens."

Journal

KITE: Efficacy and Safety Study of OATD-01 in Patients With Active Pulmonary Sarcoidosis (clinicaltrials.gov) - P2 | N=96 | Recruiting | Sponsor: Molecure S.A. | Trial completion date: Dec 2025 ➔ Apr 2026 | Trial primary completion date: Nov 2025 ➔ Mar 2026

Trial completion date • Trial primary completion date • Immunology • Sarcoidosis

Molecure is preparing to begin patient recruitment at two sites in the Netherlands in early September. [Google translation] (Stockwatch) - "The OATD-01 clinical trial (KITE) is an international Phase II project conducted in the US and Europe, including Denmark, Norway, France, Greece, the UK, and, starting in September, the Netherlands. Its goal is to evaluate the efficacy and safety of OATD-01 in patients with active pulmonary sarcoidosis."

Trial status • Sarcoidosis

Chitinase-1 inhibition attenuates metabolic dysregulation and restores homeostasis in MASH animal models. (PubMed, Front Immunol) - "These results revealed the key role for CHIT1 in regulating metabolism. OATD-01 is a macrophage modulator that can directly restore metabolic balance and consequently inhibit inflammation and fibrosis, supporting its use for MASH treatment."

Journal • Preclinical • Fibrosis • Hepatology • Immunology • Inflammation • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • IL1B

Molecure strengthens recruitment efforts in OATD-01 (KITE) clinical trial and expands study to the Netherlands [Google translation] (Strefa Inwestorów) - "The KITE study is an international multi-center phase II study conducted in the US and Europe (Denmark, Norway, France, Greece, and the UK) to evaluate the efficacy and safety of the innovative clinical candidate OATD-01 in patients with active pulmonary sarcoidosis. In order to increase the reach and speed of recruitment, Molecure decided to extend the clinical trial to the Netherlands - obtaining the above-mentioned consents paved the way for such a further modification of the study, which the company immediately took advantage of by submitting an application to start the study there...The protocol modifications introduced are based on experience gathered during the study, discussions with the principal investigators at the clinical sites and experts in pulmonary sarcoidosis and clinical pharmacology....In the second half of 2025, Molecure plans to conduct an interim analysis of the efficacy and safety by an independent committee (Independent Data Monitoring Committee)."

Clinical protocol • DSMB • Sarcoidosis

Strategic update on the progress and development of Molecure's key clinical projects in 2024 (GlobeNewswire) - "'The KITE trial not only evaluates the efficacy and safety of OATD-01 but also provides crucial data on the CHIT1 protein.'...'This investor support will allow us to execute the next stages of our trials, including accelerating recruitment for the KITE trial and conducting an interim analysis in the second half of 2025.'....'Our priority is to enter into a partnering agreement for OATD-01, which will allow for further research in MASH and strengthen our financial position.'"

Commercial • Trial status • Metabolic Dysfunction-Associated Steatohepatitis • Sarcoidosis

Chitinase 1: a novel therapeutic target in metabolic dysfunction-associated steatohepatitis. (PubMed, Front Immunol) - "A MASH mouse model was constructed to evaluate the effectiveness of OATD-01, a chitinase inhibitor...Our study underscores the pivotal role of CHIT1 in MASH. The observed significant improvement in inflammation and hepatic fibrosis, particularly at higher doses of the CHIT1 inhibitor, strongly suggests the potential of CHIT1 as a therapeutic target in MASH accompanied by progressive liver fibrosis."

Journal • Fibrosis • Hepatology • Immunology • Inflammation • Liver Cirrhosis • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Metabolic Dysfunction-Associated Steatotic Liver Disease • CHIT1 • ITGAM • MERTK

Efficacy and safety of OATD-01, an oral inhibitor of chitinase-1, for treatment of active pulmonary sarcoidosis: study protocol for a randomized, double-blind, placebo-controlled, multicenter, phase 2 trial. (ERS 2024) - "As a secondary objective we quantify the changes of granulomatous inflammation in pulmonary parenchyma, mediastinal/hilar nodes and extra-thoracic locations using PET/CT SUV for secondary endpoint. Other endpoints include assessment of pulmonary function, Qo L, safety and sarcoidosis biomarkers (CHIT1 activity, s IL-2R, CCL18, TNF-α)."

Clinical • P2 data • Immunology • Inflammation • Pneumonia • Sarcoidosis • CCL18 • CHIT1 • IL2RA • TNFA

KITE: Efficacy and Safety Study of OATD-01 in Patients With Active Pulmonary Sarcoidosis (clinicaltrials.gov) - P2 | N=98 | Recruiting | Sponsor: Molecure S.A. | Trial completion date: Mar 2026 ➔ Dec 2025

Trial completion date • Immunology • Sarcoidosis

Examining OATD-01- A First-in-Class Chitnase Inhibitor's MOA in Lung Sarcoidosis to Unveil Potential in Other ILDs (IPF Summit 2024) - "Synopsis • Dive into the mechanism of action a first-in-class chitnase inhibitor • Explore the potential of OATD-01, currently in Phase 2, to address a wider range of ILDs"

Immunology • Sarcoidosis

KITE: Efficacy and Safety Study of OATD-01 in Patients With Active Pulmonary Sarcoidosis (clinicaltrials.gov) - P2 | N=98 | Recruiting | Sponsor: Molecure S.A. | Trial completion date: Oct 2025 ➔ Mar 2026 | Trial primary completion date: Sep 2024 ➔ Dec 2025

Trial completion date • Trial primary completion date • Immunology • Sarcoidosis

Metabolism-driven glycosylation represents therapeutic opportunities in interstitial lung diseases. (PubMed, Front Immunol) - "Examples presented in this review demonstrate that protein glycosylation regulates metabolism-driven immune responses in macrophages, with implications for fibrotic processes and granuloma formation. Targeting proteins that regulate glycosylation, such as fucosyltransferases, neuraminidase 1 and chitinase 1 could effectively block immunometabolic changes driving inflammation and fibrosis, providing novel avenues for therapeutic interventions."

Journal • Review • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Inflammation • Interstitial Lung Disease • Pulmonary Disease • Respiratory Diseases • Sarcoidosis • NEU1

First patient in the UK is dosed in the OATD-01 Phase 2 KITE study in pulmonary sarcoidosis (GlobeNewswire) - "Molecure....has started the clinical trial where OATD-01 is being administered to patients with active pulmonary sarcoidosis as part of a Phase II clinical trial (proof-of-concept in human). The world's first administration of the chitotriosidase 1 (CHIT1) inhibitor (or placebo) to patient took place at the Royal Infirmary in Edinburgh....'The results of this study will be strategically important for further value creation and commercialization of OATD-01, and we look forward to the results of the study in 2025.'"

P2 data • Trial status • Sarcoidosis

KITE: Efficacy and Safety Study of OATD-01 in Patients With Active Pulmonary Sarcoidosis (clinicaltrials.gov) - P2 | N=98 | Recruiting | Sponsor: Molecure S.A. | Not yet recruiting ➔ Recruiting

Enrollment open • Immunology • Sarcoidosis

Molecure hopes to sign a partnering agreement in 2024. OATD-01 has the greatest chance [Google translation] (Bankier) - "Molecure hopes to sign a partnership agreement in 2024 and estimates that the OATD-01 program has the greatest chance of concluding it, company representatives told PAP Biznes....Currently, the company is starting a phase II clinical trial for the OATD-01 molecule, among others, in the United States in patients with active pulmonary sarcoidosis. In the coming weeks, he wants to include the first patient in the study and, after a positive screening result, administer the first dose of the drug."

Licensing / partnership • Trial status • Chronic Obstructive Pulmonary Disease

Efficacy and Safety Study of OATD-01 in Patients With Active Pulmonary Sarcoidosis (clinicaltrials.gov) - P2 | N=96 | Not yet recruiting | Sponsor: Molecure S.A.

New P2 trial • Immunology • Sarcoidosis

POTENTIAL THERAPEUTIC SIGNIFICANCE OF CHIT1 INHIBITION IN NASH-LIVER FIBROSIS (AASLD 2023) - "Combination of Streptozocin (STZ) injection and high fat and high cholesterol diet (HFHC) was used to establish NASH-liver fibrosis model. Our study provides compelling evidence for the significant involvement of CHIT1 in liver fibrosis, supported by elevated CHIT1 expression observed in both human patients and mouse models. Notably, treatment with the CHIT1 inhibitor, OATD-01, exhibited a dose-dependent amelioration of hepatic fibrosis in the STZ-HFHC mouse model. These results strongly indicate that targeting CHIT1 inhibition holds promise as a potential therapeutic approach for addressing NASH-associated liver fibrosis in human patients."

Fibrosis • Hepatology • Immunology • Inflammation • Liver Cirrhosis • Non-alcoholic Steatohepatitis

Multicenter, randomized, double-blind, phase 2 study to assess the efficacy and safety of OATD-01, an oral inhibitor of chitinase-1 for the treatment of active pulmonary sarcoidosis. (ERS 2023) - "Secondary endpoints include evaluation of granulomatous inflammation quantified by PET/CT SUV and volume of the lesions, assessment of pulmonary function, quality of life and safety parameters. Exploratory endpoints include sarcoidosis biomarkers activity namely CHIT1 and ACE.; Imaging; General respiratory patient care; Epidemiology; Pulmonary function testing; Physiology; Pulmonary rehabilitation; Public health"

Clinical • P2 data • Immunology • Inflammation • Interstitial Lung Disease • Pneumonia • Pulmonary Disease • Respiratory Diseases • Sarcoidosis

Molecure Files an Investigational New Drug (IND) application for lead clinical candidate OATD-01 with U.S. FDA ahead of a planned Phase 2 pulmonary sarcoidosis study (GlobeNewswire) - "Molecure S.A...announces that it has filed an Investigational New Drug (IND) application with the U.S. FDA for OATD-01, a first in class and potentially disease modifying Chitotriosidase (CHIT1) inhibitor. Clearance of the IND would allow Molecure to begin an international Phase 2 proof of concept study to evaluate OATD-01 for the treatment of pulmonary sarcoidosis....We anticipate beginning our Phase 2 trial in patients in the US and EU in the fourth quarter of this year....This Phase 2 trial is expected to be a global, multi-center, randomized, double blind and placebo-controlled study to evaluate the safety and efficacy of OATD-01 in approximately 90 patients with active pulmonary sarcoidosis. The results of this double-blinded study will be available once the study is complete, expected in H1 2025."

IND • New P2 trial • P2 data • Pulmonary Disease • Sarcoidosis

Molecure Announces Full Year Financial 2022 Results – A Year of Significant Progress (GlobeNewswire) - "Lead proprietary candidate, OATD-01, a novel chitinase inhibitor in sarcoidosis, expected to advance into a Phase II study with first patient dosed in second half of 2023....OATD-01, a novel chitotriosidase 1 (CHIT1) inhibitor with disease modifying potential in patients with pulmonary sarcoidosis, is nearing the start of Phase II, with the first patient expected to be dosed in the second half of 2023. Positive results of this clinical proof-of-concept study in sarcoidosis may open doors to treatment of other Interstitial Lung Diseases (ILDs), including idiopathic pulmonary fibrosis (IPF) as well as nonalcoholic steatohepatitis (NASH) which represent significantly larger global patient populations. I am looking forward to data from this study which we hope will confirm the key role of CHIT1 inhibition as a new treatment pathway for diseases where chronic inflammation leads to tissue remodeling and fibrosis."

New P2 trial • Idiopathic Pulmonary Fibrosis • Interstitial Lung Disease • Pulmonary Disease • Sarcoidosis

Inhibition of Macrophage-Specific CHIT1 as an Approach to Treat Airway Remodeling in Severe Asthma. (PubMed, Int J Mol Sci) - "OATD-01, a chitinase inhibitor, was tested in a 7-week-long house dust mite (HDM) murine model of chronic asthma characterized by accumulation of CHIT1-expressing macrophages...Both IL-13 expression and TGFβ1 levels in BAL fluid were decreased and a significant reduction in subepithelial airway fibrosis and airway wall thickness was observed. These results suggest that pharmacological chitinase inhibition offers protection against the development of fibrotic airway remodeling in severe asthma."

Journal • Asthma • Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases • IL13 • TGFB1

Molecure Third Quarter 2022 Pipeline Highlights and Financial Results (PRNewswire) - "Molecure's most advanced in-house drug candidate is OATD-01, a first-in-class dual chitinase inhibitor for the treatment of interstitial lung diseases, such as sarcoidosis and idiopathic pulmonary fibrosis, that is Phase II ready. A Phase II trial in patients with sarcoidosis is expected to start in 2023."

New P2 trial • Idiopathic Pulmonary Fibrosis • Sarcoidosis

Pharmacological Inhibition of Chitotriosidase (CHIT1) as a Novel Therapeutic Approach for Sarcoidosis. (PubMed, J Inflamm Res) - "In the chronic model, inhibition of CHIT1 led to a decrease in the number of organized lung granulomas and the expression of sarcoidosis-associated genes. In summary, CHIT1 activity was increased in sarcoidosis patients and OATD-01, a first-in-class CHIT1 inhibitor, demonstrated efficacy in murine models of granulomatous inflammation providing a proof-of-concept for its clinical evaluation in sarcoidosis."

Journal • Immunology • Inflammation • Interstitial Lung Disease • Pulmonary Disease • Respiratory Diseases • Sarcoidosis • IL15

First key steps in pipeline rebuild and strong commercial progress in H1 2022 (GlobeNewswire) - "Galapagos NV...today announced its first half-year 2022 financial results...Pipeline update:...Discontinued development of 4 early-stage programs as part of ongoing scientific and strategic exercise: GLPG3121, a local release formulation JAK1/TYK2 inhibitor with potential in inflammatory diseases; GLPG0555, a JAK1 inhibitor evaluated in osteoarthritis; GLPG4586, a compound with undisclosed mode of action directed toward fibrosis; and GLPG4716, a chitinase inhibitor directed toward idiopathic pulmonary fibrosis"

Discontinued • Idiopathic Pulmonary Fibrosis • Inflammatory Bowel Disease • Osteoarthritis

Drug-drug Interaction Study With GLPG4716 and Nintedanib and Pirfenidone in Healthy Subjects (clinicaltrials.gov) - P1 | N=58 | Completed | Sponsor: Galapagos NV | Recruiting ➔ Completed

Trial completion