First patient in the UK is dosed in the OATD-01 Phase 2 KITE study in pulmonary sarcoidosis

- OATD-01 is an innovative, first-in-class chitinase inhibitor for the treatment of sarcoidosis among other diseases where chronic inflammation leads to tissue remodeling and fibrosis

- In the phase II clinical trial (KITE study), patients will take a daily oral dose of 25 mg OATD-01 or placebo (in tablet form) for 12 weeks

- The double-blind, randomised, placebo-controlled study is designed to determine the clinical efficacy, pharmacokinetics, pharmacodynamics and safety of OATD-01

- The Phase II study will be conducted in the UK, US, and the European Union including Norway, and will involve approximately 100 patients

- OATD-01 is a first-in-class chitotriosidase 1 (CHIT1) inhibitor with disease-modifying potential in sarcoidosis and other interstitial lung diseases

Warsaw, March 22, 2024. - Molecure S.A. ("Molecure", WSE ticker: MOC), a biotechnology company that discovers and develops drugs to the clinical stage and uses its globally unique expertise in medicinal chemistry and biology to explore and develop first-in-class small-molecule drugs that directly modulate protein activity and mRNA translation to treat a range of incurable diseases, 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. As part of the trial, patients will take a daily fixed dose of 25 mg OATD-01 or placebo tablets for 12 weeks. Patient safety will be monitored regularly through laboratory tests, neurological examinations and ECG and spirometry.

The Phase II clinical trial for OATD-01 is designed as a randomised, double-blind, placebo-controlled, multi-center study to evaluate the safety and efficacy of the oral CHIT1 inhibitor (OATD-01) in approximately 100 patients with active pulmonary sarcoidosis, including patients both previously receiving other therapies and previously untreated. The study will involve approximately 20-30 centres in the US, the European Union, Norway and the UK. The renowned CRO (Contract Research Organisation) Simbec Orion is responsible for the organization and comprehensive conduct of the study.

„The first administration to a patient with pulmonary sarcoidosis is the realization of our mission focused on helping and transforming the lives of patients with incurable diseases through the development of therapies and the opportunity to offer them new treatment options. Launched in the UK, the Phase II trial involving patients with active disease, the 'proof-of-concept in human' phase, is a significant milestone in the clinical development of our lead program. It is a landmark moment also because it is the first time that a chitotriosidase 1 inhibitor has been offered to patients. Molecure is a pioneer and global leader in the development of therapies based on the inhibition of chitinase activity. The 'PoC in human' study is key to validating this therapeutic approach, as there is a whole spectrum of diseases whose development is associated with similar molecular mechanisms. We will conduct the study in the United States, the United Kingdom, Norway and European Union countries, after obtaining approvals from the relevant EU regulators. 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" - said Dr Marcin Szumowski, Chief Executive Officer and Chairman of the Management Board of Molecure S.A.

Due to the double-blinding requirement of the study, publication of the final unblinded results will follow completion of the study and is anticipated by the end of 2025. For the efficacy trial, an innovative primary endpoint has been agreed with the FDA, namely the response to 12-week administration of OATD-01 as measured by the degree of reduction in granulomatous inflammation in the lung parenchyma, as assessed by PET/CT imaging. After approximately 50 patients have completed their participation in the study, a sub-analysis (intermediate checkpoint) will be scheduled to statistically evaluate the results by an independent committee and decide how to proceed with the study in terms of the number of patients.

„We are very proud of the first patient administration in the KITE study. In a broad spectrum of preclinical studies, we have confirmed the great potential of OATD-01 to become the new standard of care for pulmonary sarcoidosis. In phase 1 clinical trials involving 129 healthy volunteers, we in turn confirmed the good safety profile of OATD-01 and the compound's ability to effectively block chitinases. In a phase 2 study, we aim to demonstrate that blocking chitinases in patients has a therapeutic effect and inhibits inflammatory processes. The primary endpoint of the study is the arrest or reversal of disease progression and lung damage as assessed by the granulomatous inflammation reduction score. The therapy also aims to alleviate the symptoms of the disease understood as an improvement in lung function, as measured by a change in the so-called Forced Vital Capacity (FVC), as well as an improvement in quality of life and a shift away from corticosteroids’’ - said Dr Samson Fung, Chief Medical Officer and Board Member of Molecure S.A.

About OATD-01

OATD-01 is an orally administered once-daily, first-in-class and highly selective CHIT1 inhibitor for potential use in the treatment of sarcoidosis. The CHIT1 enzyme represents a promising molecular target due to its role in converting local anti-inflammatory macrophages into pro-inflammatory and pro-fibrotic types. Blocking CHIT1 activity by OATD-01 resulted in documented anti-inflammatory and anti-fibrotic effects.

The OATD-01 molecule has demonstrated potent anti-inflammatory and anti-fibrotic effects in various disease models and has high therapeutic potential in a variety of inflammatory and fibrotic diseases representing an unmet medical need, such as sarcoidosis, as well as idiopathic pulmonary fibrosis (IPF) and non-alcoholic steatohepatitis (NASH).

Molecure has obtained orphan drug designation (ODD) from the FDA for OATD-01 in the indications of sarcoidosis and idiopathic pulmonary fibrosis.

About sarcoidosis

Sarcoidosis is a multi-organ disease of unknown etiology, characterized by the formation of granulomatous structures in various organs, mainly the lungs and lymphatic system.

Sarcoidosis is a globally prevalent disease, affecting both men and women with an incidence estimated at 5-50 cases per 100,000 population, with 70% of patients being between 25-45 years of age.

The most serious and common complication of sarcoidosis is pulmonary fibrosis. It is usually associated with significant impairment of lung function. Pulmonary fibrosis accounts for the majority of sarcoidosis-related deaths in Western countries.

About Molecure S.A.

Molecure S.A. is a biotechnology company that discovers and develops drugs to the clinical stage, leveraging its own unique expertise in medicinal chemistry and biology to search for and develop first-in-class small-molecule drugs that, through direct modulation of previously unexplored protein and RNA targets, may provide therapies for many incurable diseases.

Molecure has generated a diverse portfolio of seven distinct programmes with support from leading academic research institutions around the world, including Yale University, Rutgers University, the Flemish Institute for Biotechnology (VIB) in Ghent, the University of Michigan and the International Institute of Molecular and Cell Biology in Warsaw, Poland (MIBMiK).

The most advanced drug candidate developed by Molecure is OATD-01, a first-in-class CHIT1 inhibitor for the treatment of interstitial lung diseases such as sarcoidosis and idiopathic pulmonary fibrosis, which is ready to enter Phase 2 clinical trials. The phase 2 trial in sarcoidosis patients started in Q4 2023 in the US and the UK and will also continue in the EU and Norway, after gaining the appropriate regulatory approval.

The second drug candidate is OATD-02, an oral, selective, first-in-class, dual arginase inhibitor (ARG1 and ARG2) for the treatment of cancer, whose Phase I clinical trial has started with first patient administration in Q1 2023.

Molecure's headquarters and laboratories are located in Warsaw and Lodz. The company is listed on the Warsaw Stock Exchange (ticker: MOC).