The Technology
Fibrosis, or scarring caused by the excessive deposition of extracellular matrix (ECM) is implicated in 45% of deaths in the western world. It is a key pathological feature of diseases like Duchenne Muscular Dystrophy (DMD) and multiple inflammatory and autoimmune conditions. The fibrosis significantly impairs tissue function and in DMD leads to severe outcomes such as immobilization, reduced breathing and cardiac failure. The enzyme LYSYL OXIDASE (LOX) is central to fibrosis due to its role in crosslinking of the ECM, yet it also supports muscle regeneration through its intracellular activities. This dual role presents a therapeutic challenge: inhibiting LOX’s harmful extracellular effects in fibrotic areas without disrupting its beneficial intracellular functions in muscle regeneration.
To address this, a novel Antibody-Drug Conjugate (ADC) has been developed. This ADC targets the extracellular activities of LOX specifically within fibrotic tissues by leveraging an anti-CD206 antibody, which homes in on M2 macrophages prevalent in fibrotic but not healthy tissues. The ADC, by carrying a LOX inhibitor directly to the fibrotic ECM, reduces fibrosis and improves muscle function, potentially also enhancing the efficacy of other treatments by improving drug access to diseased tissues.
ADC weekly administration to mdx mice, the murine model of DMD, over a period of 3 months demonstrated significant improvement of skeletal and cardiac muscle function and a concomitant inhibition of fibrosis. No adverse phenotypes were observed in the treated mice.
Advantages
- Novel drug, a new mechanism of action
- Targeted and specific therapy
- Positive efficacy and safety results (In-Vivo)
- Orphan drug designation
- Multiple potential indications
Applications and Opportunities
- Treatment of Duchenne Muscular Dystrophy
- The ADC can be used to treat all fibrotic processes in which LOX is upregulated, such as muscular dystrophies, Idiopathic pulmonary fibrosis, renal, pancreatic, cardiac, skin, vascular, peritoneal and liver fibrosis, Crohn’s disease and other inflammatory bowel diseases and gastrointestinal cancer
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