Pipeline Overview

Molecure, a clinical stage biotechnology company, discovers and develops breakthrough small molecule drugs that modulate unexplored protein targets and novel RNA to treat cancer, fibrotic and inflammatory diseases.

Our exceptional in-house medicinal chemistry and biology capabilities, along with novel target insights gained from leading academic centers, have allowed us to create a broad pipeline of drug candidates targeting unique and unexplored protein targets. Our lead assets, OATD-01 and OATD-02, are in clinical development for the treatment of sarcoidosis and solid tumors respectively.

In addition, we are developing a unique RNA platform, to discover small molecule compounds that interact directly with the mRNA of disease-related proteins, with significant potential across multiple disease areas.

CLINICAL CANDIDATE
SELECTION
Molecular
Target
Indications
Target Validation
Hit-To-Lead
Lead
Optimization
In Vivo Poc
Preclinical
Development
Regulatory Process
Phase I
Phase II
OATD-01 CHIT1/AMCASE
Sarcoidosis, other ILDs
OATD-01 CSR*
2ND GENERATION CHIT1
NASH, ILDs
UNDISCLOSED
Fibrosis
License Agreement with
OATD-02 ARG1/ARG2
ImmunoOncology
OATD-02 CSR*
USP7
ImmunoOncology
USP21
Cancer metabolism
YKL-40
ImmunoOncology
Molecular
Target
Indications
Hit identification
Hit-to-lead
Lead
Optimization
Preclinical
Development
mRNA TARGETS
Undisclosed mRNA
Oncology, other
Current Status
2025 estimate
*Clinical Study Report

Targeting unexplored proteins

Molecule is discovering and developing first-in-class small molecules in oncology, inflammation and fibrosis that target/interact with selected, unexplored proteins.

We have generated a diverse pipeline consisting of seven distinct programs, validating the strength of our discovery and translational capabilities, including:

  • 2 programs in clinical development – one is Phase II ready and one which is currently in a Phase 1 trial
  • 5 programs in preclinical development, spanning 4 unchartered novel target families (arginases, chitinases, deubiquitinases as well as one undisclosed target).

Chitinase Inhibitors

OATD-01, Molecure’s lead candidate, is an oral, once-daily, first-in-class highly selective CHIT1 inhibitor for the treatment of sarcoidosis. CHIT1, or Chitotriosidase, is produced by pathologically activated macrophages, and is the primary active chitinase in the lung.

OATD-01 is potentially a disease modifying therapy that could transform the standard of care.

Multiple published studies, as well as Molecure’s own translational data has shown CHIT1, the target of OATD-01, to be upregulated in sarcoidosis and the level of upregulation to be correlated with disease severity. In sarcoidosis patients, the over-expression of CHIT1, is also a marker of disease progression.

Phase I studies have demonstrated OATD-01 to be safe and to have a novel therapeutic mechanism of action, simultaneously targeting inflammation and fibrosis.

Phase II studies with OATD-01 in sarcoidosis patients are expected to start in the second half of 2023.

Pharmacological Inhibition of Chitotriosidase (CHIT1) as a Novel Therapeutic Approach for Sarcoidosis

OATD-01 has demonstrated potent anti-inflammatory and antifibrotic effects in various disease models and has high therapeutic potential in diverse inflammatory and fibrotic diseases with high unmet medical needs such as sarcoidosis, as well as idiopathic pulmonary fibrosis and NASH where efficacy was demonstrated in preclinical models. Possible further respiratory indications include inflammatory asthma, COPD, other Interstitial Lung Diseases (scleroderma and rheumatoid arthritis-associated fibrosis) or in non-pulmonary diseases, diabetic nephropathy, ALS and Crohn’s disease.

Molecure is focused on developing OATD-01 to realise its significant clinical potential and is looking to advance this asset into a Phase 2 clinical trial in patients with sarcoidosis in 2023.

OATD-01 in Sarcoidosis/The relevance of Chitinase inhibitors in Sarcoidosis

Sarcoidosis is a systemic inflammatory disease that is characterized by the formation of small clumps of inflammatory cells, called granulomas in various organs, mainly the lungs and the lymphatic system. Its cause is unknown.

Sarcoidosis is a global disease, affecting both men and women with a prevalence of about 5–50 in 100 000, with 70% of the patients aged between 25 and 45 years.

The most severe and frequent complication of sarcoidosis is the occurrence of pulmonary fibrosis. This is usually associated with significant impairment of pulmonary function, whereby granulomatous inflammation leads to pulmonary fibrosis. The development of pulmonary fibrosis is associated with significant increase in morbidity and can be fatal.

There is currently no cure for sarcoidosis and existing treatments such as corticosteroids only modify/impede the development of granuloma formation and come with a significant range of side effects. There is also little evidence of extended therapeutic efficacy.

During preclinical development, OATD-01 has been shown to significantly decrease the disease severity, to suppress the development of granulomas and reduce inflammation in the lungs of treated animals.

Our second generation CHIT1 inhibitor program

CHIT1 is also involved in the pathology of various diseases with inflammatory and fibrotic components, including non-alcoholic steatohepatitis (NASH), and potentially a broad spectrum of neurological diseases that are characterized by excessive activation of inflammatory cells in the brain (neuroinflammation).

Molecure is developing other selective CHIT1 inhibitors, structurally different from OATD-01, which have been selected for proof-of-concept validation in models of these diseases.

Arginase Inhibitors

Arginase 1 (ARG1) and Arginase 2 (ARG2) are validated targets that have been found on a variety of tumor types where their increased activity correlates with more advanced disease and worse clinical prognosis due to diminished arginine levels.

Our second proprietary candidate, OATD-02 is the first and only dual acting, highly potent arginase inhibitor in cancer development, involved in both tumor immunity and metabolism. It has been selected as a clinical candidate for the potential treatment of a broad range of tumors in combination with other anti-cancer therapeutics.

In March 2023, Molecure initiated a Phase 1 clinical trial.

Molecure dosed the first patient in 1Q 2023 in a Phase I clinical trial to assess safety, tolerability and preliminary efficacy of OATD-02 in patients with advanced and/or metastatic solid tumors.

Deubiquitinase Platform

At Molecure DUB proteins comprise a potential important group of targets for anticancer therapeutic agents. Ubiquitination, the addition of ubiquitin to a protein, is a post-translational modification affecting the lifespan of proteins and therefore, critical to cell homeostasis. Expression of ubiquitin-specific proteases (USPs), enzymes involved in the cleaving ubiquitin residues froms proteins, can be abnormal in tumors and the tumor microenvironment. This way cancer cells extend the life of specific proteins that allow them for uncontrolled growth.

USP7 Inhibitor Program

Molecure is developing inhibitors of selective and oral inhibitor of ubiquitin specific protease 7(USP7), whose high expression is seen to be aberrant in a number of tumor indications, promoting oncogenesis. In our studies, we have shown that in cancer USP7 regulates the level of many proteins involved in the immune response, hence inhibition of USP7 activity leads to the activation of T cells and the stimulation of the immune system to act against cancer cells.

Molecure has identified a lead molecule OAT-4828, a potent and selective USP7 inhibitor, which demonstrates safety and efficacy in selected models of cancer. Molecure is currently of searching for a lead candidate for pre-clinical development.

USP21 Inhibitors Program

The USP21 inhibitor program is based on the experience built by Molecure and naturally expands the pool of therapeutic targets from the family of enzymes – ubiquitin-specific proteases (USP). The results obtained so far by Molecure’s scientists confirm that the lack of USP21 in cancer cells slows down their proliferation and migration, and also regulates the level of key proteins involved in oncogenesis, which have been considered “undruggable targets” for years. USP21 plays an important role in the modulation of cancer cell metabolism by affecting mitochondrial function. This project is currently at the hit-to-lead stage and focuses on optimizing the identified molecules in terms of their activity, selectivity and pharmacological profile.

A new project targeting an undisclosed signaling pathway crucial to the development of fibrosis

The project aims at the development of new small molecule inhibitors of an undisclosed signaling pathway with potential use in the treatment of fibrotic diseases, in particular idiopathic pulmonary fibrosis. The project is at the stage of lead optimization with an objective to improve lead molecule’s activity and pharmacological profile. The screening of compounds utilizes phenotypic assays and is based on the screening cascade developed by the Molecure team using the know-how from the University of Michigan (provided under a non-exclusive license agreement, including know-how in the area of ​​discovering new molecules targeting an undisclosed signaling pathway crucial for the development lung fibrosis).

YKL-40 Program

YKL-40 which belongs to the chitinase-like proteins (CLPs) family, is a secreted protein with homologies to chitinases but devoid of catalytic function. High levels of YKL-40 are linked to poor prognosis, progression and the severity of various inflammatory disorders and numerous types of cancer. The protein is produced and secreted by immune cells (especially macrophages, neutrophils) and various structural cells like fibroblasts, smooth muscle, epithelial, endothelial and also cancer cells.

The program led to the discovery of the compound OAT-3912, which binds strongly and selectively to YKL-40. In preclinical studies in a colorectal cancer model, OAT-3912 has been shown to slow tumor growth by reactivating the immune system response, offering potential therapeutic benefits in many types of cancer. The compound has also shown efficacy in preclinical models of inflammatory and fibrotic diseases.

Unique RNA platform

Molecure is developing a unique RNA platform to discover small molecule compounds that interact directly with the mRNA of disease-related proteins. By modulating mRNA biological function and affecting its translation we would be able to discover medicines with a novel mechanism of action.

This approach offers access to potentially thousands of new therapeutic targets, which were previously considered ‘undruggable’ to traditional small molecules that interact with proteins.

From the estimated ∼20 000 proteins that comprise the human proteome, only 15% are considered “druggable”. This is because just a fraction of proteins that are potential drug targets i.e. are linked to a disease, have the ability to bind small molecules. As a result, the human transcriptome (RNA molecules) is underexploited as a new source of therapeutic targets and for long considered ‘undruggable’ via conventional approaches.

The development of Molecure’s mRNA platform is being supported by an exclusive research collaboration agreement with the International Institute of Molecular and Cell Biology (IIMCB) in Warsaw. This collaboration provides the company with access to world-leading and unique bioinformatics tools developed by the Laboratory of Bioinformatics and Protein Engineering (LBIB) at IIMCB, headed by Prof. Janusz Bujnicki.

In addition, the platform benefits from the knowledge and experience of experts in the field of RNA research working at renowned academic centers. Our collaborators include:

  • Joanna Sztuba-Solińska, PhD (expert in the field of using experimental methods to determine the 2D structure of RNA molecules),
  • dr Michael T. Wolfinger (professor of bioinformatics at the University of Freiburg, expert in the field of development and utilization of bioinformatics methods for RNA secondary structure prediction, and identification of evolutionarily conserved RNA regions),
  • Chase Weidmann, PhD (assistant professor at the University of Michigan, expert in the field of long-range RNA interactions and RNA-protein interaction investigation).

The RNA platform gives Molecure the opportunity to use unique methods to discover small-molecule drugs targeting mRNA.

Molecure’s workflow consists of:

  • Using algorithms to identify stable and functional fragments of mRNA encoded by genes that are clinically significant, while the proteins they encode are not druggable. The predicted structures of these fragments are then confirmed at single-nucleotide resolution using sequencing and chemical sampling.
  • Using a combination of bioinformatics and experimental methods, allowing rapid and accurate identification of small molecule binding sites.
  • Using a combination of many modern methods to discover new molecules with therapeutic potential that interact directly with mRNA. In the RNA platform, we have successfully applied methods for modeling the structures of biological molecules and their complexes, traditional medicinal chemistry technologies, distinct procedures for screening and optimizing the structures of hits and leading compounds, as well as a wide range of approaches to evaluate the activity of compounds in vitro and in

Molecure’s current goal is to provide the biopharmaceutical industry with a platform for identifying starting compounds, confirming that mRNA can be a therapeutic target for small molecules, which opens up tremendous scientific opportunities providing tangible medical solutions.

 

 

Publications

Inhibition of Macrophage-Specific CHIT1 as an Approach to Treat Airway Remodeling in Severe Asthma

Pharmacological Inhibition of Chitotriosidase (CHIT1) as a Novel Therapeutic Approach for Sarcoidosis

OATD-02 Validates the Benefits of Pharmacological Inhibition of Arginase 1 and 2 in Cancer

Inhibition of CHIT1 as a novel therapeutic approach in idiopathic pulmonary fibrosis

Development of Dual Chitinase Inhibitors as Potential New Treatment for Respiratory System Diseases

Posters

EFMC-ASMC’19 – September 1-5, 2019 | Athens, Greece

ACS National Meeting & Expo – August 25 – 29, 2019 | San Diego, CA

ATS- International Conference – Dallas, 17-22.05.2019

ERS International Congress 2018 – Paris, France 15-19.09.2018

EFMC – YMCS – Young Medicinal Chemist Symposium – Ljubljana 02-06.09.2018

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