MC2 Therapeutics announces breakthrough discovery with the potential to help millions of people suffering from urea associated skin diseases

• Breakthrough discovery of a novel biological paradigm for treatment of several urea associated skin diseases
• MC2 Therapeutics has patented and initiated development of drug candidates for chronic kidney disease associated pruritus (stages 3-5) and lichen sclerosus
• Urea associated diseases affect more than 50 million people in US and EU alone and represent major unmet medical needs in areas with limited or no approved therapies

COPENHAGEN, Denmark, Sept. 1, 2022 /PRNewswire/ -- MC2 Therapeutics A/S, a commercial stage pharmaceutical company, engaged in research and development of novel treatment paradigms for autoimmune and chronic inflammatory skin conditions, announces breakthrough discovery of a novel biological paradigm applicable for treatment of a number of urea associated skin diseases affecting millions of people globally.

MC2 Therapeutics has discovered that carbamylation of proteins, peptides and amino acids in the skin, caused by isocyanate, may be the root cause of several poorly understood skin diseases such as chronic kidney disease associated pruritus (CKD-aP also known as uremic pruritus) and genital lichen sclerosus.

Results from an in vitro reconstructed human uremic skin model have shown that the selected lead drug candidate is an effective isocyanate scavenger demonstrating >90 % inhibition of protein carbamylation and counteracting the morphological skin changes induced by carbamylation.

Jesper J. Lange, LLM, CEO of MC2 Therapeutics said: "This is an important breakthrough discovery in a field that has eluded researchers for decades and it is a validation of our research into skin biology. It gives hope to many people and paves the way for novel treatment paradigms in a number of poorly understood skin diseases." Mr. Lange continues: "MC2 Therapeutics has ongoing programs in CKD-aP stages 3-5 and genital lichen sclerosus and is committed to further expanding our pipeline of new treatments in indications with limited or no approved therapies."

"People suffering from CKD have severe dry skin and evidence of damaged skin nerve fibers. CKD-associated itch is a severe condition, which leads to an overall increased mortality risk, as well as higher frequency of depression and reduced quality of life. Despite decades of research, we have yet to fully identify the root cause of itch in CKD, and the millions of people affected by this condition currently have very limited treatment options. MC2 Therapeutics has really set the stage for solving this evidence gap, offering patients an innovative treatment potentially providing relief from skin dryness and itch for patients with CKD," said Kieran McCafferty, MD, at Barts Health NHS Trust and Senior Lecturer at Queen Mary University London.

MC2 Therapeutics' breakthrough discovery also targets people with genital lichen sclerosus who suffer from debilitating itch and pain due to skin erosions and fissures. Recent studies suggest that the pathogenesis of genital lichen sclerosus is driven by chronic urine exposure due to incontinence leading nerve changes and skin damage caused by carbamylation.

About carbamylation

Urea, a by-product of protein metabolism, is produced in the liver and enters the blood stream, until it is finally excreted in urine. Urea is also deposited in high concentrations on the skin via the sweat glands. Accordingly, skin is exposed to urea both from the inside via the blood, and from the outside via either sweat or, in the genital area, via urine spilling.

With age, urea blood levels increase due to gradually declining kidney function. The same process occurs, at an accelerated rate, in people with chronic kidney disease (CKD). Even people with moderate reduction in kidney function may suffer from debilitating itch and dry skin which severely impact their quality of life. The origin of itch in CKD has so far been unknown, but the main theories have evolved around the existence of a 'uremic toxin', the identity of which has eluded researchers for decades.

Urea is remarkably non-toxic in acute animal models for which reason it historically has been disregarded as the uremic toxin. However, urea is in equilibrium with isocyanate, a very reactive molecule known both to be neurotoxic and to readily react with proteins, peptides and amino acids present in the body. This chemical reaction is often referred to as "carbamylation", and although this is a natural process which slowly increases with age, excessive carbamylation is toxic. Although systemic carbamylation is known, there has until now been no focus on the potential causal role of carbamylation in the skin of people with CKD and lichen sclerosus.

About MC2 Therapeutics A/S

MC2 Therapeutics A/S is a privately held commercial stage pharmaceutical company committed to research and development of novel treatment paradigms for people with autoimmune and chronic inflammatory skin conditions.

Its innovative approach to address complex challenges more effectively is anchored in deep understanding of the skin biology combined with learnings from the pathophysiology across disease segments. Fuelled by an entrepreneurial mindset and creativity, MC2 Therapeutics aims for breakthrough discoveries and innovative technologies leading to novel treatment paradigms in areas with a high unmet medical need.

For additional information on MC2 Therapeutics Group, please visit www.mc2therapeutics.com

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