Hi, everyone. My name is Dr Andy Blauvelt. I’m a dermatologist and I’m a consultant, for a company that I own, Blauvelt Consulting, LLC. I’ve retired from clinical trials, as of last year, but the work I’m going to be discussing today is part of work that I’ve done over the last several years.

Q. What are the main challenges that remain in psoriasis treatment, despite the success of existing biologics? (0:30)

The EVERLAST-A study is a phase 2 study that’s being sponsored by the company Oruka. It’s looking at a novel IL-23 blocker, or IL-23 inhibitor, called ORKA-001. This drug aims to take the best of the best drug that we have now, or one of the best, risankizumab, and make it even better.

ORKA-001, was designed to have a similar antigen binding epitope as risankizumab. It was tested against risankizumab in the laboratory. The main difference, however, is that it was modified to add what we call a YTE substitution in the antibody that allows for the antibody to have a long half-life. Again, the goal is to have a risankizumab like drug, but that is dosed for very long.

What are our needs in psoriasis, to get back to your question? We have great drugs right now. We have great drugs in the IL-17, IL-23 class. This is trying to take a great drug and make it even better. The goal is not only to have fewer shots, but to push the PASI 100 numbers even higher with ORKA-001.

Q. How does ORKA-001 differ from currently available IL-23 targeting therapies for psoriasis? (2:13)

It’s very similar to risankizumab. The main difference comparing ORKA-001 and risankizumab is the YTE substitution that allows for a long half-life. We estimate for risankizumab that the half-life is in the range of 28 days, where we estimate the ORKA-001 antibody will actually have a half-life in the 100 day range. So a much longer half-life. We actually think that it’s going to be good for patients and that the drug will stay around longer, allowing for fewer shots. But we also think it’s going to be safe because the IL-23 class has been associated with a great safety profile. We don’t anticipate any problems by having the drug around for a long time.

Then, as I mentioned, we’re planning on dosing it higher than risankizumab. This is similar to a study that I did called the KNOCKOUT study. The KNOCKOUT study took risankizumab and dosed it in patients at 300mg or 600mg, which was two-times or four-times the normal dose of risankizumab. There are two things that are novel in my view. The knockout dosing, with ORKA-001, similar to what I used in the KNOCKOUT study, and that this antibody has a very long half-life, in the range of 100 days.

Q. Could you outline the aims, design, and eligibility criteria of the EVERLAST-A Phase 2a study? (4:15)

EVERLAST-A, which I’ll be discussing and revealing at the EADV, is a phase 2a study. It’s the first study of ORKA-001 in psoriasis patients. This drug has actually been studied already earlier this year in phase 1, and that was done in healthy volunteers. This is the very first study in psoriasis.

The entry criteria are typical for what we see with any biologic trial. So greater than or equal to 10% body surface area, a PASI of 12 or greater, a global score of 3 or 4. So very, very typical criteria. Patients with “moderate-to severe-psoriasis” will be in this trial. The design is 3:1. For every three patients on drug, there’s one patient on placebo. Three patients will receive ORKA-001 600mg at week 0 and 4. Again, we call that knockout dosing, because it’s much higher than the 150mg dose of risankizumab. It’s four-times as much drug as risankizumab, but it’s also given at the same time points, week 0 and week 4, as risankizumab.

We think that those two doses are going to knock out psoriasis and lead to high levels of PASI 100. Then the patients who were on initially on placebo after 16 weeks will go over to ORKA-001, and they’ll receive 600mg at week 16 and at week 20. So they’re guaranteed the drug. Now the other interesting point is that at week 28, there’s a decision. It’s not the primary endpoint, but there’s a decision. If patients are completely clear, we’re keeping some of them on no drug to see how long we can see the clearance for, how long is the remission for.

Then for other patients who are not completely clear, we will put them on 300mg of drug every 6 months. We think that twice-a-year dosing 300mg every 6 months may be the future maintenance dose for those patients who need more drug. But we definitely think there’s going to be subsets of patients who after these first two will stay clear for a long time. That’s one of the main purposes of the EVERLAST-A study; to determine how long we can see people stay clear.

We think that a a subset of patients are going to go for a whole year before they actually need another dose. So we’ll figure that out in EVERLAST-A. We’ll figure out how many patients can go after two shots, how many can go a whole year before they need another shot. Some really interesting things going on. Not only trying to push the PASI 100 number really high, but also looking to see how long we can induce remissions with this long half-life antibody.

Q. What are the primary and secondary endpoints being assessed in this trial? (7:56)

The goal in recent years for psoriasis therapies has been PASI 100, which means complete clearance, absolutely no disease left. That’s where we’ve seen the really great drugs shine, if you will. So risankizumab, bimekizumab, ixekizumab, guselkumab.

Those drugs have really shined in terms of PASI 100. Any new drug we think has to have PASI 100 as the primary endpoint, and we’re looking at the standard endpoint of week 16. So, what is the percentage of patients who are 100% clear at week 16?

Q. When do you anticipate the results will be available? (8:44)

Probably sometime mid next year, second quarter maybe, third quarter, maybe in time for the EADV in 2026.

Q. How might ORKA-001 potentially change the way psoriasis is managed in clinical practice? (9:00)

Well, it’s a really important question. I think it leads to the importance of this work and what we’re envisioning as an ideal would be to treat patients two times, knock out their disease, and then have them require either a once-a-year dose – you go in for your flu shot, you go in for your psoriasis shot once a year, and you’re taken care of for the whole year – or possibly, patients staying clear and only having shots as needed. I think that would completely shake up things.

Right now we have drugs that are used at the minimum four times per year. We have quarterly drugs. You imagine if it was only once a year or every now and then as needed. We think it would change things a lot. I just want to say thank you to everyone for their interest in the EVERLAST-A study and thank you to the investigators and the patients who are participating in the study.