Cyclarity aims to deliver simple and affordable therapies for cardiovascular disease and other chronic diseases of aging.
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.
Cyclarity’s Novel Approach:
Atherosclerosis is the world’s leading cause of death, responsible for 44 out of every 100 deaths.
Risk Adjusted Mortality, All Cause
Data from WHO and US Dept of HHS, 2017.
Why haven’t we fixed the world’s most lethal disease?
The Current Standard of Care is Inadequate
The Root Cause of Atherosclerosis
Showing the formation of arterial plaques when macrophages become foam cells due to oxidized cholesterol.
- Monocytes adhere to arterial wall
- Monocytes differentiate into macrophages
- Macrophages become foam cells (due to 7KC accumulation)
- 7KC-laden foam cells trigger:
- further inflammation
- damage to arterial infrastructure, and
- accumulation of more oxidized cholesterol
Proposed Mechanism of Action
Our 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.
UDP-003: Enabling cyclodextrin as API
“A transformational and revolutionary approach”
- Lajos Szente, Leading World Expert on Cyclodextrins
The Cyclarity Platform™
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.
The Cyclarity Platform allows for the testing of thousands of cyclodextrin candidates against thousands of both targeted and non-targeted molecules.
With an iterative process of improvement, the platform provides exceptional opportunities in a broad spectrum of molecular dynamics, including:
- Improved specificity for predetermined targets
- Potential discovery of off-target effects
- Improved bioavailability
- Ability to test any CD/target combination
- Customizable output
- An iterative learning process
In developing The Cyclarity Platform, we are creating the possibilities to unlock the full potential of cyclodextrins. Our Head of Scientific Computing is also in the process of integrating AI into an iterative cyclodextrin construction program that will further accelerate our pipeline.
Reversing Disease by Rehabilitating the Self-Repair System
We’ve known since the 1990’s that heart disease is fundamentally driven by toxic oxidized cholesterol derivatives.
Showing how our cyclodextrins will remove oxidized cholesterol, thereby restoring the functionality of macrophages to clear plaques from arteries.
- Delivery of drug candidate
- Cyclodextrin enters arterial plaques
- Foam cells rehabilitated into healthy, functional macrophages
- 7KC is extracted and excreted
Cyclodextrins have a hydrophilic shell (attracted to and soluble in water), but a hydrophobic core (repels water and is non-polar). This means that our engineered cyclodextrins can attract and encapsulate hydrophobic molecules, and then contain them in a manner that can be dissolved in water, and thus purged from the bloodstream.
Soluble Inclusion Complex
A New, Superior Class of CVD Drug
Unlike current drugs on the market and in development, our engineered cyclodextrins will be disease modifying – that is have the potential to reverse the course of cardiovascular disease. They will additionally server to prevent the onset of future pathologies, and will protect against the accumulation of oxidized cholesterol in the first place.
Traditional drugs & animal models typically apply interventions far “upstream” (e.g., reduce the number of harmless circulating LDL particles, most of which will never be oxidized and contribute to atherosclerosis).
Hydroxypropyl Beta Cyclodextrin (HPβCD )
Cyclodextrins have countless industrial and pharmaceutical applications. Hydroxypropyl Beta Cyclodextrin is currently in clinical trials.
Cyclarity cyclodextrin derivatives have been designed to target only 7-ketocholesterol, the damaged cholesterol that actually drives atherosclerotic disease.
Our iterative process combines bench chemistry and computational modeling to design, test, and evaluate the potential efficacy of engineered cyclodextrins as candidate active pharmaceutical ingredients. We use molecular dynamics simulations to provide clear visuals demonstrating how various cyclodextrins form complexes with 7KC.
These simulations are then put to the test in the lab setting.
The potential for cyclodextrins to encapsulate molecules
An Engineered Iterative Process
We developed a platform that allows us to computationally reduce potential candidates to identify cyclodextrins that most conform to our desired goals. We can then physically synthesize these select engineered molecules for laboratory testing thereby significantly reducing the costs of discovery. Empirical data is then fed back into the platform to further optimize its ability to computationally predict molecular interactions, and with additional simulations, we are able to further optimize the end product, thus increasing efficacy while reducing any undesirable off-target effects.
Our Groundbreaking Platform Creates Enormous Opportunities
Because of the hydrophilic / hydrophobic nature of our engineered cyclodextrins, they have the potential to be used for countless health, environmental, and industrial purposes to achieve molecular transport mechanisms previously unavailable.
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.
We expect phase 1 trials to begin in 2024. Phase 2 readout should be complete in 2026. All our early stage trials will include imaging components to measure plaque impact.