Progress Towards Clinical Trials for Atherosclerosis at Cyclarity

Cyclarity is taking a fast path to the clinic for clearance of 7-ketocholesterol, a toxic altered form of cholesterol that contributes to the dysfunction of macrophage cells that lies at the root of atherosclerosis. To the degree that macrophage cells can be rescued from the local excess of cholesterol and altered cholesterol present in an atherosclerotic plaque, they will work to dismantle that plaque. The question is whether removing only 7-ketocholesterol will produce a bigger effect on established atherosclerotic plaque than the presently established approach of lowering LDL-cholesterol in the bloodstream. This is a low bar, as even greatly lowered LDL-cholesterol, while slowing the progression of the condition, actually does very little to reverse existing plaque.

Our lead drug candidate is a cyclodextrin that targets an oxidized cholesterol called 7-ketocholesterol that accumulates in various cells and tissues with age, and the main type of tissue that we are looking at is in the artery where, as I'm sure everyone knows, cholesterol is considered the bad guy that accumulates and causes plaque, the buildup inside of your arteries. What a lot of people don't know is that the most toxic and the most atherogenic is the oxidized cholesterol form. Atherosclerosis is the buildup of plaque inside of your arteries, which is formed by the accumulation of this oxidized cholesterol form. Additionally, unlike cholesterol, which you absolutely need to survive, you don't need any of this oxidized form. And so that's our target. Our lead drug candidate can go into cells and tissues and even penetrate plaque and grab onto that oxidized cholesterol, pull it out and then float away with it, so you can safely excrete it.

We studied all the cyclodextrins in the chemical catalog, and then we did all this computational modeling, and we figured out that the best way to grab onto our target was to dimerize it to basically take two cyclodextrin molecules, stick them together in the right configuration, and then modify it chemically in particular ways to give it the right shape in the binding cavity. Then what it does is, it grabs it and then it eats a single molecule of its target, a bit like Pac-Man, then wraps around it, and the inside cavity forms a shape around the target that fits it. It can then bind it with extremely high affinity and specificity and float away with the 7-ketocholesterol.

We're well into the process of preparing for clinical trials. We've brought on board a noted expert in developing cardiovascular drugs, and are building a team to plan, initiate, and run the clinical trials. Importantly, this is going to start in months, not years. We're going to start clinical trials in 2023, and.we're well along the path of getting ready for that. There's a certain number of things that you need to do with a drug candidate to be ready for that, and you can put them into two basic categories. First is safety testing your drug and the other is in the manufacturing process, and so we're in the final stages of doing the safety testing. Then we need to manufacture the actual version of the drug that will go into people. We're making several kilograms of the final drug product right now, and that's already begun. Then, all the data on both the manufacturing of the drug and the safety testing will be submitted to the regulatory body, at which point we ask for permission to initiate clinical trials.



Maybe this will be the 1st anti-aging therapy developped from SENS which will reach the market. I always thought it would be Oisin. Now we just need to wait until the early 2030s to use it. Others therapies developped from SENS will reach phase 1 trials within the next 2 or 3 years. LEV is on track for 2035.

Posted by: Weaver Jonathan at March 9th, 2023 8:27 AM

i started a statin and was pleased with the results. now i have what seems to be a safe level of ldl and total cholesterol. this is atorvastatin 10mg daily. so i thought how about try 20mg. lower is better right? then i read about the possibility of brain bleeds. i'm 49 with already a few white matter lesions on the mri. so... I put it back to 10mg.

Posted by: matt at March 9th, 2023 9:33 AM

No profit and therefore interest in raw apple cider vinegar.

Posted by: Thomas Schaefer at March 10th, 2023 8:28 AM

Probably why garlic consumption is associated with reduced CVD.

"The effect of onion and garlic on the formation of two cholesterol oxidation products (COPs): 7-ketocholesterol and 7-hydroxycholesterol was evaluated by comparing their concentrations in meat and gravy samples obtained from three pork dishes prepared in the presence and absence of these flavourings. The concentration of these compounds in meat samples was between 82.4 and 1331.6 ng/g of cooked meat. Gravies contained lower amounts: from 18.3 to 45.6 ng/g of cooked meat. The addition of onion (30 g/100g of meat) caused a decrease in 7-ketocholesterol and 7-hydroxycholesterol concentrations in all of the investigated pork dishes by 9.5-79%, whilst the addition of 15 g of garlic to 100g of meat lowered the concentration by 17 to 88%. The greatest decrease was found in grilled minced chops. "

Posted by: Lee at March 11th, 2023 6:26 AM
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