Fighting arterial plaques

Atherosclerosis is the world’s leading cause of death, responsible for 44 out of every 100 deaths.

Why haven’t we fixed the world’s most lethal disease? The Current Standard of Care is Inadequate as:

• Drugs to slow rate of disease progression
• Drugs to reduce CVD events resulting from atherosclerosis
• Surgery and major CVD event recovery

7-Ketocholesterol (7-KC), an oxidation product of cholesterol, plays a pivotal role in atherosclerosis. It contributes to plaque formation by promoting inflammation and oxidative stress. Elevated 7-KC levels are associated with increased cardiovascular risk and adverse outcomes. Additionally, 7-KC is implicated in vascular calcification, further impacting plaque stability. Understanding its role is crucial for managing cardiovascular disease.

Cyclarity Therapeutics (https://cyclaritytx.com/) has developed a new class of cyclodextrin (CD) dimers as a potential new treatment for atherosclerosis. These CD therapies work by forming strong, soluble inclusion complexes with oxysterols, allowing the body to reduce and heal arterial plaques. Cyclarity's research has combined computational and synthetic chemistry programs to create custom-engineered cyclodextrins (polysaccharides with known industrial and pharmaceutical excipient uses) to capture, and remove from cells, oxidized cholesterol derivatives such as 7-ketocholesterol, which are broadly toxic molecules with no known biological function.

Their Lead Product: UDP-003 is a first-in-class drug; a specially engineered cyclodextrin which will target and remove toxic oxidized cholesterol, a key driver of atherosclerosis, neurodegenerative diseases, and other chronic diseases. UDP-003 is designed to restore the cardiovascular self-repair function and reduce arterial plaque.

Cyclarity was awarded one of the first ‘Innovation Passports’ under the United Kingdom’s Innovative Licensing and Access Pathway (ILAP) in 2021. The program provides enhanced early development input, accelerated assessment, rolling clinical reviews, and adaptive authorization.

They expect phase 1 trials to begin shortly in 2024. Phase 2 readout should be complete in 2026. All early stage trials will include imaging components to measure plaque impact.

Cyclarity Therapeutics, Inc., is pursuing a mission to treat the underlying causes of age-related disease. The company develops simple and direct interventions targeting oxidized cholesterol using rationally designed molecules, to provide the first true disease-modifying treatments for common age-related conditions such as atherosclerosis, heart attack and stroke. Its products are based on novel derivatives of a well-known, safe compound and a new way of looking at cardiovascular disease.

Synthetic chemistry for cyclodextrins is very promising but also both extremely expensive and time consuming. So we built a proprietary discovery tool – The Cyclarity Platform. With it, we are able to model cyclodextrins and run virtual experiments, performing complex measurements of molecular-dynamic combinations between potential cyclodextrin forms and potential targets. Our tools can also run very broad-based docking analyses with these to test a variety of candidates against hundreds of possible on-target (and potential off-target) effects.

I would be delighted to hear suggestions for upcoming topics and engage in Q&A, so please feel free to add your impressions in the comments or via email at [email protected]. Thank you.

In the coming weeks, we will continue focusing on using cyclodextrins as active ingredients, disease by disease. Stay tuned!

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