OUR SCIENCE
The Role of Fibroblasts in Fibrosis and Inflammation
Fibrotic and chronic inflammatory diseases are major drivers of morbidity and mortality worldwide, affecting organs such as the lungs, liver, kidneys, and heart. Uncontrolled, persistent inflammation is a key trigger of fibrosis, leading to excessive tissue scarring that disrupts organ function and ultimately results in failure. Despite their widespread impact, current treatments focus on symptom management rather than addressing the underlying mechanisms driving fibrosis. The urgent need for effective, disease-modifying therapies has made targeting fibrosis and inflammation a critical priority in biomedical research.
OUR APPROACH
At INOLYSIS, we are pioneering a fibroblast-targeted approach to treat fibrosis and chronic inflammation by developing small molecules that selectively reverse fibroblast activation.
Our multidisciplinary drug discovery platform is based on the identification and validation of key molecular pathways that drive fibroblast activation, leveraging our extensive expertise in fibroblast biology. We apply structure-based drug design and computational modeling to discover small-molecule hits with strong therapeutic potential. Through medicinal chemistry and lead optimization, we refine these compounds to enhance potency, selectivity, and drug-like properties. We utilise advanced molecular phenotyping and mechanism of action methodologies to confirm that our lead compounds efficacy. To assess therapeutic viability, we conduct in vivo studies in mouse models of fibrosis and chronic inflammation, evaluating efficacy, pharmacokinetics, and safety.
This innovative approach offers several key advantages:
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Precision dual targeting – Directly modulating fibroblasts to both halt fibrosis and inflammation at the source.
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Improved safety – Avoiding broad immunosuppression and the associated infection risks.
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Oral administration – Enhancing patient compliance compared to injectable biologics.
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Scalability and accessibility – Leveraging the efficiency of small-molecule development for cost-effective and widely available treatments.
OUR LEAD
​Our lead compound, VM-313, is a first-in-class small molecule exhibiting potent anti-fibrotic and anti-inflammatory activity across multiple experimental systems. Efficacy has been demonstrated in primary human and mouse fibroblasts (in vitro), in fibrotic precision-cut lung slices (ex vivo), and in murine models of pulmonary fibrosis and systemic inflammation (in vivo).
​VM-313 also demonstrates a favorable safety and ADMET profile, along with a differentiated mechanism of action compared to existing anti-fibrotic agents (eg. Nintedanib).
OUR VISION
By targeting fibroblasts at the core of disease pathology, we aim to transform the treatment landscape for fibrosis and chronic inflammation. Our innovative small-molecule approach has the potential to deliver safer, more effective, and accessible treatments for patients worldwide.
PATENTS
G. Kollias, N. Karagianni, Maria C. Denis, Alexios N. Matralis, Dimitra Papadopoulou, Eleni Karkoulia. Anti-inflammatory carboxamide derivatives.
WO/2022/189636 (PCT/EP2022/056349).
Priority date: 12/9/2021. Published 15/9/2022.
USA: US20240308954 (18/549.986) Published 19.09.2024
EPO: EP4305026 (EP22711080.6) Published 17.01.2024
OUR RELATED PUBLICATIONS
Repurposing antipsychotic drug Amisulpride for targeting synovial fibroblast activation in arthritis
Papadopoulou D, Roumelioti F, Tzaferis C, Chouvardas P, Pedersen AK, Charalampous F, Christodoulou-Vafeiadou E, Ntari L, Karagianni N, Denis MC, Olsen JV, Matralis AN, Kollias G. (2023) JCI insight, 8(9):e165024.
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Discovery of the First-in-Class Inhibitors of Hypoxia Up-Regulated Protein 1 (HYOU1) Suppressing Pathogenic Fibroblast Activation
Papadopoulou D, Mavrikaki V, Charalampous F, Tzaferis C, Samiotaki M, Papavasileiou KD, Afantitis A, Karagianni N, Denis MC, Sanchez J, Lane JR, Brotzakis FZ, Skretas G, Georgiadis D, Matralis AN & Kollias G. (2024) Angew Chem Int Ed Engl., 63(14):e202319157.
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