Most cardiovascular trials focus on lowering LDL cholesterol or reducing inflammation to slow disease progression. UDP-003 targets the root cause: toxic 7-ketocholesterol (7KC) inside macrophages and soft plaques. It is designed to convert bloated foam cells back into healthy macrophages that can actively clear the hard plaque.
This clinical trial took place at CMAX, a leading clinical research center in Australia, in partnership with Monash University. It is a two-part Phase 1 study intended to establish safety in human participants. We took the opportunity to catch up with Dr. Matthew O’Connor and talk about how the first part of Cyclarity’s clinical trial went.
Hi Matthew, and thanks for joining us for this third follow-up interview for the new atherosclerosis drug UDP-003. We have covered how UDP-003 works and breaks down plaques in the arteries in previous interviews, so let’s jump right to the big news.
Thank you, Steve. It’s great to talk to you again. We have completed the first in-human study of UDP-003. It was performed in 72 healthy volunteers in Australia under the direction of the Victorian Heart Institute, which is under Dr. Steve Nichols, renowned cardiologist and expert on atherosclerosis, arguably the world’s expert on the subject. It’s super exciting to have finished a safe conclusion of that trial.
So, how did it go?
Amazingly well, everything that we could have hoped for and more was accomplished, and that is divided into three broad categories, two of which are going to be most interesting to your audience.
The first and most important being that UDP-003 is extraordinarily safe. What that means, in slightly technical terms, is that there were no serious adverse events and there were no halts or individuals who had to pull out or who chose to pull out of the trial due to any side effects or suspected side effects. It was as safe as we possibly could have hoped. We got all the way up to the maximum dose with no associated side effects of concern, which allows us to pass freely onto the next stage at the highest dose that we tested: to start testing that dose in patients.
Second, pharmacokinetics, which means what happens to the drug in your body, and that is: nothing happens to the drug. It is not metabolized at all, and you excrete the drug completely in the urine. It happens very quickly, in under three hours, which is exactly what we designed it to do, what we wanted it to do, what we expected it to do. It behaved exactly the way that we wanted it to.
Third and most excitingly is that our drug did exactly what it was designed to do, which was to grab the toxin that it is supposed to be removing from your body. This is the oxidized cholesterol, specifically 7-ketocholesterol (7KC), so that’s tremendously exciting.
I can delve into a bit more detail on that, which is that number one, you’re excreting 7KC into the urine, which has never happened before. Normally, it never goes into your urine, and so we’re causing people to pee out 7KC for the first time.
The data on it is looking really, really nice. It’s a perfect dose response, meaning when we give a little bit of the drug, just a little bit of 7KC comes out in the urine. With every increase in dose, you see more 7KC coming out in the urine, so it’s a beautiful dose-response.
The combination of the safety and the target engagement on the 7KC, I think, means that these healthy volunteers who got our drug came out healthier than they started. That’s not a medical conclusion. That’s an opinion, but it’s an exciting one.
So it works, or it seems to work?
It works to get rid of the toxic 7KC, so if you believe that’s a good in and of itself, like I do, then we’ve already succeeded at exactly what we set out to do. Now to get our drug approved, we need to prove that it has some measurable improvement in people’s health. The way that we want to do that is by showing that it can impact plaque and perhaps inflammation, so that’s what we’re going to be looking at next.
That would be the goal. Speaking of next, what will happen now?
We have already received permission and have already begun a small patient clinical trial in Australia with the same group that ran the healthy volunteer trial. It’s going to be very small, only 12 patients with a placebo group. That is an even smaller number receiving the drug, but they will have a diagnosis of a type of coronary artery disease. We will get to study the safety and the pharmacology, and also the impact on blood biomarkers related to cardiovascular disease. Super excitingly, we’ll get to do imaging on them before and after they receive our drug.
That’s the way to go, isn’t it, soft plaque removal. What about the hard plaques?
Well, we’ll see what we see. We’ll be able to image soft and hard plaque, and our data shows that our drug can penetrate hardened plaque tissue, so we’ll see what impact we have on the characteristics of the plaque, the size of the plaque, the density of the plaque, all of that we’ll get to investigate.
Editor’s note: The researchers are looking for more than just a reduction of plaque size. Because 6 weeks is a very short window for physical remodeling, they are looking for stabilisation and compositional changes of the plaque. These things will signal that UDP-003 has started to remove the 7KC.
That sounds good, so that’s the next step. Then, what about other trials in other jurisdictions like the UK and US, are those on the horizon?
Absolutely, we have already designed our Phase 2 clinical trial, which would only be in patients, so kind of a much larger version of the trial that I just described in the 12 patients, we would do in 150 patients. It will be an international trial, so it will still happen, partially in Australia and partially in the United States, and we are also planning to bring it to the UK and possibly to the EU as well.
Interesting, and you’re on the ILAP pathway, the innovative licensing and access pathway in the UK, so they might even fast-track it based on the promising results of that early data rather than waiting for you to complete a full trial. Speaking of which, last time you gave the most optimistic estimate that “2030 would be the absolute fastest we could be approved and reach the market”. Do you stand by that still?
For a broad, traditional drug release, that’s probably overly optimistic, and going through a complete coronary artery disease approval would probably take until at least 2031-2032. Having different accelerated approval pathways, such as using ILAP or using an accelerated program in the US or elsewhere, are things that we’re constantly exploring, and there’s still an optimistic potential that we could have something released by around 2030.
That would be great. That’s really just around the corner. When will Phase 2 start?
If we can secure funding sooner rather than later, we can start Phase 2 this year and complete it within three years. We would release interim data sooner, but for completely wrapping up and putting a bow on Phase 2, it would be early 2029.
That’s great. Any interest from big pharma?
I can’t say too much about that, but we do have some interesting discussions going with various pharmaceutical companies, and hopefully we will definitely plan to be partnering at least on our first drug. We would like to be partnering around the time of the release in 2029. That said, we do have discussions ongoing, and we could do something much sooner. I think that there could be a lot to gain on both sides. There’s a lot of resources, not just financial, that we could take advantage of with the best partner.
I’d be very surprised if there was no uptake if you demonstrated that it works.
So far, we know that 7KC is coming out, and we just have to wait and see on the plaque regression. If that works and we demonstrate clear and substantial plaque regression in our Phase 2, it’s a slam dunk because it’s never been done before. It is just such an unmet need, and there’s such tremendous impact of plaque in your blood vessels, and the predictions of the reductions in heart attacks and strokes, not to mention all the other health benefits that we think we will eventually be able to demonstrate by removing 7KC. There hasn’t been a pharma company yet that hasn’t said “Yes, if you demonstrate plaque regression, we are very, very interested.”
I think at that point, they would basically buy the license and take it to mass production. You could be on for that 2030 timeline.
Exactly, and the best part of such a partnership would be getting to move as quickly as possible.
Do you think that the price point would be initially very expensive, or do you think that mass production and the large audience for it would effectively make it pennies on the dose?
It’s never going to be pennies on the dose, even at the mass production scale, but we’re working on making it as cheap as possible so that it can be distributed at a worldwide level. We’ve already managed to scale the process so that we can mass-produce it, and we’re working on bringing the cost of production down.
I hope by the time it gets released, we’ll have the manufacturing costs down by something like 90%, which would enable it to be quite affordable on everyone’s insurance plans and to government healthcare agencies.
We will definitely make sure that we do everything we can to convince the authorities that it’s a good use of their funds, because I think we’re going to transform people’s lives with our drug treatment.
What’s next for Cyclarity?
We’re actively working on two broad things, one of which is expanding the uses for UDP-003 into other diseases of aging. We want to look at neurological disease and other chronic diseases, especially dyslipidemic disease.
We don’t have anything new to announce yet but hope to in the coming year. Of course, we’re using our technology platform to invent the next several drugs in the lineup. Again, no big reveals there yet, but we’re hoping to have something that we can bring to the public soon.
To finish, Cyclarity just closed on a bridge funding round for 6 million USD. That will help to keep the lights on for a while longer.
Thanks for taking the time to talk with us today, and we will watch progress eagerly.
View the article at lifespan.io
