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
Target
Hit-To-Lead
Optimization
Development
CHIT1
(Incl. 2ND GENERATION CHIT1 **)
Target
Optimization
Development
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 six distinct programs, validating the strength of our discovery and translational capabilities, including:
- 2 programs in clinical development – currently one is in Phase II trial (OATD-01) and one is in a Phase I trial (OATD-02)
- 4 programs in preclinical development (discovery phase).
Chitinase Inhibitors
Molecure has developed a unique series of chitinase inhibitors that modulate macrophage function, reducing the severity of inflammation and thus offering a novel therapeutic approach in inflammatory and fibrotic diseases. Elevated levels of one of the chitinases, chitotriosidase (CHIT1), are associated with inflammatory and fibrotic diseases, leading to excessive macrophage activation.
OATD-01
OATD-01, the lead drug candidate developed by Molecure, is a first-in-class dual chitinase inhibitor for the treatment of fibrotic and inflammatory diseases, including interstitial lung diseases such as sarcoidosis and idiopathic pulmonary fibrosis (IPF). OATD-01 is an innovative, effective and safe non-steroidal new chemical entity (NCE) dual inhibitor of AMCase and CHIT1 with a mechanism of action that targets inflammation and fibrosis simultaneously.
Numerous clinical studies and Molecure’s own translational data have shown that CHIT1 is upregulated in many inflammatory and fibrotic diseases, where its activity correlates with disease stage, progression and clinical prognosis. CHIT1 is most highly expressed in pathologically activated macrophages located in lesional areas.
Molecure studies showed that CHIT1 activity was significantly elevated in the serum of sarcoidosis patients and that CHIT1 expression was restricted to granulomas and localised in macrophages. Ex vivo OATD-01 inhibited the production of pro-inflammatory mediators in lung macrophages.
OATD-01 has demonstrated potent anti-inflammatory and anti-fibrotic effects in preclinical studies in various disease models, including sarcoidosis, MASH (metabolic dysfunction-associated steatohepatitis) and pulmonary fibrosis. In acute models of granulomatous inflammation in mice, OATD-01 showed anti-inflammatory effects. Furthermore, in a chronic model, inhibition of CHIT1 by OATD-01 led to a reduction in the number of organised granulomas in the lung and a decrease in sarcoidosis-related gene expression.
The Phase I clinical trials of OATD-01, which assessed the safety, tolerability, and pharmacokinetics of OATD-01 in healthy volunteers, were successfully completed in 2022. In March 2024, a Phase II clinical trial (KITE) was launched. It is a randomized, double-blind, placebo-controlled, multicenter study aimed at evaluating the efficacy, safety, pharmacokinetics, and pharmacodynamics of OATD-01 in patients with active pulmonary sarcoidosis (more information available at https://thekitestudy.com/ and in Patients section.
Our second generation CHIT1 inhibitor program
Molecure has developed other selective CHIT1 inhibitors, structurally different from OATD-01, whose further development depends on the progress of OATD-01 clinical trials.
Arginase Inhibitors
Our proprietary candidate, OATD-02 is the first and only dual acting, highly potent arginase 1 and 2 (ARG1/2) inhibitor in cancer development, involved in tumor immunity via tumor metabolism regulation. 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. OATD-02 is currently in Phase I clinical trials.
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 and intracellular metabolic changes.
OATD-02 restores effective antitumor immune responses by inhibition of arginases ARG1 and ARG2 subsequently increasing levels of arginine to promote the antitumor response. The ongoing Phase I clinical trial of OATD-02 is an open-label, multi-center, dose-escalation study aimed at evaluating the safety, tolerability, preliminary anti-cancer activity, and determining the maximum tolerated dose in patients with advanced or metastatic solid tumors. More information can be found in the Patients section.
Unique RNA platform
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.
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.
Molecure is one of the few biotech companies in the world developing small-molecule drugs that directly interact with mRNA.
In December 2023, for one of the developed mRNA targets a Proof-of-Concept (PoC) was achieved, i.e., in an in vitro cell-based test, the inhibition of protein translation by compounds targeting the mRNA encoding this protein was confirmed. Six months later, in June 2024, the ability of another molecule, developed within the mRNA platform, to effectively bind to the intended mRNA fragment and block the translation process of the pathogenic protein was confirmed. Currently, the platform is focused on three therapeutic targets, validating the effectiveness of previous efforts in the development of research methods and building know-how, with one early-stage program in the Hit-to-Lead phase.
The beginnings of the platform’s development are linked to a scientific collaboration between Molecure and Professor Janusz Bujnicki from the Bioinformatics and Protein Engineering Laboratory at the International Institute of Molecular and Cell Biology (IIMCB), that was focused on the discovery of small molecules that modulate RNA function and the development of bioinformatics methods for modeling and predicting the binding of small molecules to RNA fragments.
In addition, the platform benefits also from the knowledge and experience of experts in the field of RNA research working at other renowned academic centers. Our collaborators include:
- 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),
- Prof. Eric Westhof, (Emeritus professor, University of Strasbourg, France, expert in the field of RNA structural biology, specializing in studying the structure and dynamics of RNA, with particular emphasis on its functional and evolutionary aspects, as well as its interactions with other molecules).
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, followed by the experiments aiming at the demonstration of the functionality of the identified stable mRNA region in regulating the protein translation process.
- Using a combination of bioinformatics and experimental methods, allowing rapid and accurate identification of small molecule binding sites.
- Using a combination of 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 vivo.
The team’s experience in drug discovery, including the development of advanced research methods and unique know-how, provides a solid foundation for creating a competitive service offering that supports the process of discovering new RNA-targeting drugs. Thanks to practical knowledge and proven solutions, the team is able to effectively assist business partners at various stages of drug discovery — from identifying RNA regions with small ligand binding potential to validating and developing active compounds. More about our services can be found in the Solutions & Services section.
Deubiquitinase Platform
At Molecure DUB proteins (deubiquitinating enzymes) 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 (ubiquitine-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 – suspended
Molecure is developing inhibitors of selective inhibitors 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 not only the level of proteins crucial for cancer cell proliferation, but also the 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 an advanced lead molecule, a selective USP7 inhibitor, that demonstrates safety and efficacy in several preclinical cancer models, including solid tumor models and hematologic malignancies. The USP7 inhibitor program has been suspended at the stage of characterization of the preclinical candidate.
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.
YKL-40 Program – suspended
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 program led to the discovery of the compound OAT-3912 – advanced lead, 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.