Cyclarity Unveils Oxidized Cholesterol Excretion Data

Cyclarity Therapeutics, Inc., a clinical stage biopharmaceutical company engineering cyclodextrin molecules into simple, scalable, and affordable therapies that bind and remove toxic targets to address root causes of age-related disease, has just unveiled data from a clinical trial of its lead candidate, UDP-003, at the American Heart Association Vascular Discovery Scientific Sessions.

Data from a study conducted at Monash Victorian Heart Institute (VHI), offers the first clinical evidence that 7-ketocholesterol (7KC), the root cause of atherosclerosis, 7-Ketocholesterol (7KC) can be safely targeted and removed from the human body, marking a pivotal milestone toward moving cardiovascular treatments from managing arterial damage to achieving true plaque reversal. Plaque reversal is significant because research suggests that even a 1% reduction in coronary plaque burden has been associated with up to 25% lower risk of major cardiovascular events, such as heart attack or stroke.

“Cardiovascular disease remains the world’s leading cause of death, yet most treatments focus on slowing its progression rather than removing the underlying damage that drives it,” said Dr. Stephen Nicholls, Director of the Monash Victorian Heart Institute and lead investigator of the trial.“Initial data from this clinical trial of UDP-003, offering the first evidence of safe excretion of oxidized cholesterol in humans, represents a fundamental shift in how we think about treating cardiovascular disease; it’s an early step but suggests we may be able to reverse the course of atherosclerosis and protect against the accumulation of future oxidized cholesterol in the first place.”

Most cardiovascular drugs, including statins, anti-inflammatories, and RNA-based therapies, work systemically throughout the body to alter how cholesterol, inflammation, and gene expression are regulated. In contrast, Cyclarity’s UDP-003 binds directly to 7KC, the root cause of plaque buildup, then facilitates urinary excretion of it. Much like removing rust from metal, this approach directly targets a key source of damage within plaque with the goal of reversing and preventing atherosclerosis, a primary underlying cause of cardiovascular disease, and does so locally within the plaque to reduce risks of unintended systemic effects.

“Maintaining cardiovascular health is one of the most powerful levers for extending both lifespan and healthspan, given its central role in slowing systemic aging and preserving brain, kidney, muscle, and metabolic function. Yet directly targeting 7KC—a key driver of plaque buildup—without disrupting essential biological processes has remained a critical and unsolved challenge in medicine.” said Cyclarity co-CEO and co-founder, Dr. Matthew O’Connor. “By demonstrating it is possible to precisely bind to and safely excrete this toxic byproduct without disrupting the systems the body depends on, we look forward to furthering our work to bring forward treatments that save millions of lives and fundamentally change the trajectory of how we age.”

7KC is considered a biologically active driver of cardiovascular disease, contributing to inflammation, cell death, and plaque instability and has emerged as an important target in emerging therapies aimed at treating the disease at its root. In addition to cardiovascular disease, 7KC is implicated in Alzheimer’s disease, Non-Alcoholic Steatohepatitis (NASH), and other age-related conditions.

UDP-003 is the first clinical-stage therapeutic discovered using Cyclarity’s proprietary drug discovery AI Platform which engineers cyclodextrin molecules to reverse disease and protect against future accumulation of harmful molecules and aging pathologies. These engineered cyclodextrins precisely attract and encapsulate hydrophobic molecules, rendering them dissolvable in water and thus destined to be purged from the bloodstream. This gives them disease-modifying capabilities as well as the potential to prevent the onset of future pathologies by protecting against accumulation of toxins.

About the Trial

Participants in this first-in-human, randomized, double-blind, placebo-controlled trial were randomized to receive UDP-003 or placebo at one of 6 dose levels, for either a single dose or for a series of 6 administrations over 17 days. One cohort of patients had a history of Major Adverse Cardiac Events (MACE).

Results of the phase 1 trial met and exceeded primary, secondary, and exploratory endpoints, evaluating the safety, pharmacokinetics (PK), and pharmacodynamics (PD) of UDP-003. Key findings include:

• Target Neutralization (Exploratory Endpoint: Met): Pharmacodynamic data demonstrated clear, dose-dependent urinary excretion of 7KC in participants receiving active UDP-003. This constitutes the first clinical demonstration that 7KC can be mobilized and excreted from the human body and builds on a preclinical body of evidence.
• Safety & Tolerability (Primary Endpoint: Met): Was well tolerated at all dose levels. No serious adverse events (SAEs) were observed across dose-escalation cohorts. UDP-003 demonstrated a remarkably low half life of just 3 hours and no meaningful bioaccumulation was observed.
• Pharmacokinetics (Secondary Endpoint: Met): A complete PK profile was established in human subjects, demonstrating a linear dose-exposure relationship and a half-life of approximately three hours, consistent with the intended dosing regimen. This robust PK profile supports the feasibility of infrequent dosing schedules that could significantly enhance patient adherence.

Cyclarity is currently enrolling patients with acute coronary syndrome (ACS) into the efficacy cohort of the ongoing Phase 1 trial, which includes pre- and post-treatment coronary CT angiography (CCTA) to assess plaque changes. The Company expects to initiate a Phase 2 trial later in 2026, designed to demonstrate plaque regression as a primary endpoint.

“Most people believe statins shrink plaque, but in reality, even the highest tolerated doses often result in less than 1% reduction,” said Dr. Daniel M. Clemens, Vice President of Biology at Cyclarity. “Our approach is fundamentally different. UDP-003 is a custom-engineered molecule designed to find 7KC, capture it, and safely escort it to the kidneys for urinary excretion. We aren’t just slowing down the fire; we’re sending in the ‘firemen’ to clear out the toxic fuel.”

About UDP-003

UDP-003 is an investigational injectable small molecule (cyclodextrin) designed to shrink plaque by the selective removal of 7-ketocholesterol.

About Atherosclerosis

Atherosclerosis, the buildup of plaque that narrows arteries and can lead to heart attack and stroke, is a primary underlying cause of cardiovascular disease—the world’s leading cause of death.

About Cyclarity

Cyclarity Therapeutics is a biopharma company developing cardiovascular and age-related therapies aimed at disease modification and prevention. The company’s lead candidate is the first clinical asset discovered by Cyclarity’s proprietary AI platform, which leverages the unique chemistry of cyclodextrins to create disease modifying treatments for the world’s deadliest diseases. To learn more, visit https://cyclaritytx.com/.