All-cause mortality risk-adjusted to account for atherosclerosis as the underlying cause of death.
Data from WHO and US Dept of HHS, 2017.
OUR SCIENCE
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:
- A true disease-modifying drug, and
- An efficient regimen to measure clinical modification of the disease
Curing Atherosclerosis
The Standard of Care for Cardiovascular Disease is Inadequate
Current Standard of Care
- Drugs to slow rate of disease progression
- Drugs to reduce CVD events resulting from atherosclerosis
- Surgery and major CVD event recovery
The Mechanism of Atherogenesis
- 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
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.
- Delivery of drug candidate
- Cyclodextrin enters arterial plaques
- Foam cells rehabilitated into healthy, functional macrophages
- 7KC is extracted and excreted
Our Process
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.
Native beta cyclodextrin complexes well with 7KC, but it is relatively toxic to cells.
Hydroxypropyl beta cyclodextrin is extremely inert, but it needs a higher affinity for 7KC to be effective.
These simulations are then put to the test in the lab setting.
The potential for cyclodextrins to encapsulate molecules
Hydroxypropyl beta cyclodextrin is extremely inert, but it needs a higher affinity for 7KC to be effective.
Hydroxypropyl beta cyclodextrin is extremely inert, but it needs a higher affinity for 7KC to be effective.
The Cyclarity Therapeutics Vision:
Our Company: Cyclarity aims to deliver simple and affordable therapies for cardiovascular disease and other chronic diseases of aging.
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.
Disease Impact: Contributing to stroke, COPD, and heart disease, atherosclerosis causes more than 40% of all deaths worldwide. We are designing our first clinical trials to reverse diagnosed cardiovascular disease; we will simultaneously drive towards its use as a broad preventive long-term medication. Our intent is to create an effective, genuinely disease-modifying drug for atherosclerosis, radically reducing the trillion-dollar burden of this condition and saving countless lives.
Healthspan Impact: Cyclarity will address age-related diseases by repairing an underlying cause common to many of them: the accumulation of toxic biomolecules inside of cells. A single cure for atherosclerosis will of course have a significant impact on healthspan; our programs will also offer the opportunity to develop new disease biomarkers and new clinical paradigms for the evaluation of therapies.
Development Status: 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.
Our diligence data package includes strong safety and efficacy data, and demonstrates our ability to rehabilitate sick foam cells into healthy, functional macrophages. We have commenced cGMP drug product manufacture and GLP toxicity testing; both will complete in early 2023. We have successfully completed our MHRA Scientific Advice Meeting and FDA pre-IND (as well as our ILAP Application and Kick-Off Meetings).
Corporate Status: Launched from a research program begun in 2016, since founding in 2019 we have raised $14 million in two private equity seed rounds. Our IP assets include strong patent groups with composition coverage. Our proprietary computational modeling platform will allow the design of synthetic molecules targeting a variety of age-related diseases.
Team: Cyclarity’s principals, Michael Kope and Dr. Matthew O’Connor, are leaders in the development of rejuvenation technologies. Our Board includes the principals and Frank Schüler of Kizoo Technology Capital GmbH, our current lead, a part of the Forever Healthy Group in Germany with a $360 million commitment to accelerating rejuvenation biotechnology therapies. We have a team of biology, synthetic chemistry, CMC, and computational experts; and we are supported by critical external partnerships with the premier engineers of custom cyclodextrins, CarboHyde Zrt, in Hungary; and the world’s leading specialists in the development of cyclodextrin-specific simulations, MD.USE, SA, in Spain. Cyclarity owns all intellectual property from these collaborations.
The Standard of Care for Cardiovascular Disease is Inadequate
Risk Adjusted Mortality, All Cause
Diseased Artery
Current Standard of Care
- Drugs to slow rate of disease progression
- Drugs to reduce CVD events resulting from atherosclerosis
- Surgery and major CVD event recovery
A New Drug to Reverse Atherosclerosis
The root cause of atherosclerosis
- Macrophages recruited to injury
- Macrophages become foam cells
- Foam cells build plaque
Reversing disease by rehabilitating the self-repair system
- Drug extracts oxidized cholesterol
- Foam cells reversed
- Plaque repair and reduction
The root cause of atherosclerosis
- Macrophages recruited to injury
- Macrophages become foam cells
- Foam cells build plaque
Reversing disease by rehabilitating the self-repair system
- Drug extracts oxidized cholesterol
- Foam cells reversed
- Plaque repair and reduction
Atherosclerosis-Reversing UDP-003
Cyclodextrins history:
- Well known and very safe
- Built to be great carrier molecules
- Surprisingly little API engineering
UDP-003: Enabling cyclodextrin as API
- Tailored precisely to the oxidized target
- Maximized affinity
- Effective dosing in safe ranges
“A transformational and revolutionary approach”
- Lajos Szente, Leading World Expert on Cyclodextrins
Underdog Platform™
Docking Calculations
1
Molecular Dynamics
2
PMF
3
The result: pre-screened candidates for new targets
A New Drug to Reverse Atherosclerosis
The root cause of atherosclerosis
- Macrophages recruited to injury
- Macrophages become foam cells
- Foam cells build plaque
Reversing disease by rehabilitating the self-repair system
- Drug extracts oxidized cholesterol
- Foam cells reversed
- Plaque repair and reduction
Cyclodextrins
Soluble Inclusion Complex
Groundbreaking Platform Design with Enormous Opportunity
A New, Superior Class of CVD Drug
| Protective | Preventative | Disease Modifying | |
|---|---|---|---|
| Statins | |||
| PCSK9 Inhibitors | |||
| ACE Inhibitors | |||
| Blood thinners | |||
| Fibrates | |||
| CETP Inhibitors | |||
| Generic Cyclodextrins |  | | |
 |
Market
Cholesterol and Triglyceride Mediation Market (current non-disease modifying drugs)
Drug Class
Indication
- Hypercholesterolemia
- Coronay Artery Disease
- Higher Triglycerides
Market Projection (Global)
$60.9 B
2030
CAGR 4.5%
42%
Adults without heart disease that have measurable plaque load
| CVD annual costs (US) | Current | 2035 |
|---|---|---|
| Medical costs up 135% | $318 billion | $749 billion |
| Indirect costs up 55% (Lost productivity) | $237billion | $368 billion |
| TOTAL COSTS | $555 billion | $1.1 trillion |
| CVD annual costs (US) | Current | 2035 |
|---|---|---|
| Medical costs up 135% | $318 billion | $749 billion |
| Indirect costs up 55% (Lost productivity) | $237billion | $368 billion |
| TOTAL COSTS | $555 billion | $1.1 trillion |
“By 2035, across all conditions, total CVD costs will more than triple among those age 80+ and more than double among those age 65-79.”
Platform and Pipeline
| Product | Target | Indication | Stage | |
|---|---|---|---|---|
| UDP-003 | 7-Ketocholesterol | CAD, PAD, Carotid Stenosis | Late Preclinical | Lead |
| UDP-003 UDP-003 UDP-003 | 7-Ketocholesterol 7-Ketocholesterol 7-Ketocholesterol | Stroke Recovery Alzheimer’s Niemann Pick Type C | Early Preclinical Early Preclinical Early Preclinical | New Indications |
| UDP-200 UDP-300 | Undisclosed Undisclosed | Macular Degeneration Reversal of Drug Overdoses | Discovery Discovery | New Targets in Discovery |
| Oral UDP-003 | 7-Ketocholesterol | Discovery | Formulation |
| Product | Target | Indication | Stage | |
|---|---|---|---|---|
| UDP-003 | 7-Ketocholesterol | CAD, PAD, Carotid Stenosis | Late Preclinical | Lead |
| UDP-003 UDP-003 UDP-003 | 7-Ketocholesterol 7-Ketocholesterol 7-Ketocholesterol | Stroke Recovery Alzheimer’s Niemann Pick Type C | Early Preclinical Early Preclinical Early Preclinical | New Indications |
| UDP-200 UDP-300 | Undisclosed Undisclosed | Macular Degeneration Reversal of Drug Overdoses | Discovery Discovery | New Targets in Discovery |
| Oral UDP-003 | 7-Ketocholesterol | Discovery | Formulation |
