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Zach Klaassen: Hi, my name is Zach Klaassen. I'm a urologic oncologist at the Georgia Cancer Center in Augusta, Georgia. I'm delighted to be joined today by Dr. Geoffrey Johnson, a nuclear medicine physician at the Mayo Clinic in Rochester, Minnesota. Jeff, thanks very much for joining us today.

Geoffrey Johnson: Hey, thanks, Zach.

Zach Klaassen: So we're going to talk today about the SECuRE trial. We had a trial in progress presented at ASCO, and so let's pull up some slides and you can walk us through some of the background info and the trial design for this trial.

Geoffrey Johnson: Yeah, happy to do so. The SECuRE trial is a dose escalation expansion phase 1-2 trial. It's a PSMA targeted radiopharmaceutical for prostate cancer, and we accept patients both before and after chemotherapy in the trial. It's a beta emitter, like Lutetium, but it's a copper 67 beta emitter. So, it is slightly different in the radionuclide we've chosen. And given the design of the radiopharmaceutical, that actually has some advantages. So, the background SAR-bisPSMA is what it's called. It has two binding sites of PSMA, and it has a unique chelator called SAR, which gives it major advantages over other chelators used for copper in imaging and therapy. So the company has good experience and has published quite a bit on the imaging agent. I think you guys have talked to some of the authors on that in the past, and it’s quite exciting. Trial design and summary we'll get into.

So if we look here on the left, you can see the design of the molecule. And I'll highlight a couple of things. One, the SAR chelators' proprietary chelator coming out of Australia is designed to have really good binding of copper, copper 64 for PET imaging and copper 67 for beta emitting therapeutic. Unlike DOTA, which is commonly used in say, copper dotatate, which is FDA approved for imaging, the copper doesn't leak out when it's in the body. So you get much better radiation to target and less leakage of the radionuclide into the systemic blood and going where you don't want it to go. The other advantage here is that you've got two PSMA binding sites, and for this particular molecule developed out of Melbourne, that has a really nice benefit. It increases the amount of drug we're getting to cancer compared to how much of the medicine you inject.

So that was shown in the COBRA and the PROpel trials. And the longer you go after injection, the more radiopharmaceutical you're getting on your cancer. So you see more on the imaging and in theory get more in actual therapy. And so you can look here, there's some head-to-head comparison just on the imaging side in the prostate. And obviously, you're seeing a lot more signal in prostate cancer there in a patient compared to gallium PSMA-11. Now clearly what we really want to do is show the efficacy of the therapy in this trial. So that's an imaging. You can see that it really works in the preclinical models with delayed tumor growth and it's dose-dependent. And if you split the dose, it works beautifully. And so that's some good preclinical data on the bottom there. Now it's a trial in progress, so we have certain restrictions on what we can say about the actual results in the trial.

So here I'm showing a patient on the left, their patient journey in more detail on the right, but the imaging is profound. So if you look at the patient at the time of screening, this is a patient who had metastatic castrate-resistant prostate cancer, and you can see it lighting up where the arrow is, a very high amount of activity with the imaging version of this drug. The therapy here is chemically identical. It's a bioidentical pair, so that's different than gallium PSMA-11 or DCFPyL with F18 matched with lutetium PSMA-617 that we currently have on the market. Here you can actually predict exactly how much and where the medicine, the therapeutic, is going to go based on the imaging. Because they're chemically identical. You're swapping out one version of copper for the other. So you see this beautiful high uptake on the left. On the right, you can see that this patient has gone through two cycles and had a complete response based on imaging and a complete response based on PSA.

And you can see that on the right, the PSA went undetectable. The reason I can show this is this patient went on to a second dose off trial on expanded access. So it's outside of the trial. Having said that, we've seen this kind of response in not just one, but a number of patients. And so quite excited that we have a beta therapy with a very strong response. And so basically you get the drug to the target faster, you hit it with more radiation quicker, the radiation is actually shorter-lived, but because you're hitting it faster, harder in the beginning and it trails off later. Maybe that is part of why this looks to be so effective. In the trial, we're moving up through dose escalation. So obviously it's phase one, its safety is the first primary goal here. And we haven't seen any significant toxicities, and we've moved all the way up to 12 GBq.

So we're injecting more than lutetium PSMA, and getting a lot more of the drug we inject to the target in theory. So now we're expanding out into a cohort four where we're giving multiple doses within the study, and looking forward to enrolling in that coming up this summer. And the patients are being pre-vetted right now. So that's where we're headed. It looks very promising. Summary, again, it's a unique design. We are getting more drug to the tumor target, maybe two to threefold more.

It depends on how you do your comparison. Again, we don't have direct head-to-head comparison of the actual therapeutics, but we can image the copper 67 therapeutic on SPECT, just like we can image lutetium PSMA on SPECT. And so we can confirm the drug hit the target and we can confirm how much with each cycle if you wish. The preliminary data looks great, encouraging that we have a good safety profile so far and we do hope to expand out. And so far we think there's no obvious red flag that would block us from moving on to phase three, but that I'll stop and say thank you. All right, Jack.

Zach Klaassen: Geoff, that's some excellent data there. Those pictures are phenomenal, especially after a dose or two. We're seeing complete resolution and PSA response as well. So tell us more, the early part of this trial, some of the tolerability of the therapeutic, how is it being tolerated?

Geoffrey Johnson: About as expected? One of the exciting things about this field, and we've treated over 900 patients with lutetium PSMA here at our institution, is the low toxicity, where the patients really feel actually better on that therapy than they did in the therapies beforehand. So we have a high target of really low toxicity to be comparable and so far I think we're hitting right where we want to be.

Zach Klaassen: That's great. So you mentioned a little bit in your presentation that you're working on the expanded cohort four over the summer. When do you expect that to be accrued to? And then the expanded cohort as well on the right side of the screen that you presented?

Geoffrey Johnson: Literally in the coming months. So this is opening up in the summer. We're waiting for completion of the follow-up period of the prior cohort, presuming, knock on wood, everything goes well, we'll be moving forward within weeks to months.

Zach Klaassen: That's great. And the beauty of these conversations is we can be a little bit hypothetical. We've got a patient, they're getting two, maybe up to four doses. From a clinical perspective, a patient sitting in your office, what does that potentially mean to them versus having to go up to six doses with some of the other radioligand therapies that we have currently?

Geoffrey Johnson: Well, it depends where your practice is. Our practice is in a small town where 80% of our very large population of patients getting these therapies are not even from Minnesota. So it really is destination medical care for many of these patients. And so travel, which is not reimbursed, hotel rooms, which once you're clinically approved, you might be reimbursed for a trial, but it's not reimbursed in practice. So any ability to shorten that and all the other assistance that these poor patients need from their families, etc., is a tremendous benefit. So being able to hit the tumor hard, get a response quickly with fewer doses has a significant impact on the quality of life of our patients.

About 20% of them say just the financial hardship of travel and hotel is the significant barrier. So if you're in a community, quite frankly the same thing. If you're in a large city, it can be very difficult to get to the hospital and travel around, especially when you're frail. So no surprise there. At some point, these will expand out and become more community therapy accessible. But right now, despite the fact that there are hundreds of centers that are open to giving these kinds of therapies, very few of them have significant access or experience yet. And so right now the overwhelming majority of patients are treated at major academic centers and major leading private practices.

Zach Klaassen: Yeah, that's a great answer. You touched a little bit on the potential of a phase three. Obviously, we have to get through this trial and the data is exciting. What's the hope and what's the goal of a phase three down the road if it's feasible?

Geoffrey Johnson: Well, the goal is FDA approval. It's pivotal, but you have to prove it. So as a scientist, as a leader of the trial, you have to have your hat on saying the data could go either way and you have to take it that way. But obviously for our patients, we hope to get more therapies available for them and prove they're safe and efficacious. So I will admit that there's some excitement building that this could give us a new tool. When you look at the patients we currently treat, maybe 30% of them have a very good response, very few have a response like the one I just showed you. That was at eight GBq, that's not even at the 12 GBq dose we're at right now. So you get hopeful that you're going to be more effective than in the current therapy that we're giving, but you need the data to prove that out.

But that kind of hope really builds momentum in the field. And beta emitting therapies in general are probably not going to be curative. Having said that, really, we don't have any medications that are curative for metastatic prostate cancer, so no surprise there. But in terms of being able to put patients on this and maybe even repeatedly when the cancer comes back, hit them again, hit them again with low toxicity, fewer stays, and fewer visits would be phenomenal. What I really hope for, if you talk to the patients, what they want is they don't want to be on chemo ever. They don't want to be on hormonal therapy, because it's like going through menopause for months and months on end or even years. Anything we can do to get them a therapy and remove the need for those therapies, maybe by doing combinations with less toxic levels of these medications, I think would be thrilling for our patients.

Zach Klaassen: Yeah, that's well said. Great discussion. This is exciting data and thanks so much for your time. Maybe a couple of take-home messages for our listeners today.

Geoffrey Johnson: Yeah, this therapy has the potential to really go head to head with what's out there right now. We get more drug to target because of the double PSMA binding design of the drug. With the new chelator, it carries the radioactive payload without leakage with much higher drug on target. And so far we haven't really seen any toxicity. So there really isn't a red flag here where you're saying, well, it might work, but there's this thing we're worried about. All of the things are there, and even the supply chain for copper 64 and copper 67 are quite scalable. It's just a question of investment and machinery. It's not a question of limited resources that we don't have access to.

Zach Klaassen: Excellent. Very exciting. Geoff, thanks so much for your time and expertise and sharing this with our listeners today.

Geoffrey Johnson: Hey, thanks, Zach. Happy to do it.