Read the Full Video Transcript

Oliver Sartor: Hi, I'm Dr. Oliver Sartor. And coming here from UroToday, we have a very special guest, Alan Taylor, the Executive Chairman of Clarity Pharmaceuticals from Australia, doing some really interesting things. And so first of all, delighted to have you here, Alan.

Alan Taylor: Oliver, thank you. And it's great to be here. Thank you for the invite. And always looking forward, always looking forward to catching up with you. So looking forward to our conversation.

Oliver Sartor: Well, thank you. I'm going to start off with something that is puzzling to some of our viewers. Why do you think that radiopharmaceuticals represent the path forward? We've got antibody-drug conjugates, we've got CAR T cells, we've got bispecifics, chemotherapy, small molecules. Why radiopharmaceuticals?

Alan Taylor: Look, Oliver, it's interesting. Look, I'm just a simple scientist, and so I sit back and I look at this field, and at the moment, we have just a small number of products on the market, right? Really in a big indication, we're just looking at Pluvicto at this point in time. But I truly believe we're on the cusp of something really exciting, purely due to, if you bring it back to first principles, safety and efficacy. And we're seeing with the use of radiopharm and this targeted approach, great efficacy, signals, outcomes. And we're seeing it with a safety profile, but you don't even see this safety profile in first-line therapies. So it represents, I think, a great opportunity to use this very targeted approach. Target the tumors, identify the tumors in the first instance. And the imaging is starting to change the way, firstly in prostate cancer and now in many other areas. But if you're that highly targeted, and you can position radiation close to the tumor, or in the tumor, and have really positive effects, you're going to have good outcomes.

You don't have some of the issues that ADCs necessarily face. There's not no antibodies on the market as far as radiopharmaceuticals are concerned at this point in time. We're focused on peptides. We don't have to be internalized to have a therapeutic benefit. And it's time now to do the clinical trials, to do the work. And importantly, to do some good innovation to make these even better, and work them to first-line therapies, where I think they belong.

Oliver Sartor: I certainly agree with you, Alan, but it was delightful to hear your perspective. Now, in the world of radiopharmaceuticals, we have the lutetium people, we've got the actinium people, we've got the lead people, and you are the copper people. So help us understand your passion for copper, and why that particular choice in isotope?

Alan Taylor: Yeah, great question, and it's a great time. Everyone's talking isotopes. We like to talk products personally. But it's a great question on isotopes because we do have a focus on copper. And the listeners will realize that I have a little bit of a funny accent, and that really drives the history of Clarity.

There was a gentleman called Professor Alan Sargis, and many, many years ago, 70 years ago, who said, there's all these cages that hold all these isotopes, all these different isotopes, lutetium and the like, but there's nothing that holds copper. So he went about building a cage which held copper. And serendipitously, that fell into the hands of Professor Paul Donnelly, a fantastic chemist out at University of Melbourne, who was able to optimize that cage and make it usable in the concept of radiopharm. Importantly, he made it bifunctional; it not only holds the metal, but we can attach everything to it, from a small molecule to a large antibody and everything in between.

So it was a little bit serendipitous, and when I joined, that's all there was really in the company was a couple of provisional patents around that capability. But Copper-67, and I'll focus more on the therapy. Because they were all therapeutic isotopes, Copper-67 as part of this new betas, and the new betas at the moment are radiopharm, the new radiopharm when we look at the two products which are on the market. And we're excited about new betas. We find the betas to be a lot more user-friendly when you're dealing with humans. And this is the goal, isn't it really, to treat humans. And I often give this analogy.

If we were to use nuclear weapons to destroy the earth, we would cure cancer. But the outcome for humans is not so good, right? And the betas relative to the alphas, represent a great opportunity to go and move to first-line therapies that are very safe, and Pluvicto is one of those. Pluvicto with lutetium is very safe.

Now also, and you would've seen just recently, we have moved into the alphas with our bisPSMA agent, and we are utilizing actinium to see what it does. But the alphas are a new beast. They are a lot stronger, a lot more powerful. Everything they hit, they destroy. And you need to be very careful with them when you're looking at side effects, and it'll actually focus then on patients and where they are progressed to, and whether you utilize this level of nuclear weapon. As opposed to the betas, which we're running clinical trials in kids, we've dosed 16, 18 gigabecquerels in a single dose, and you don't have dose-limiting toxicities.

You've seen some of the work we've done in the SECuRE trial, we're having great efficacy without the side effects, without the adverse events that you're seeing with others. So we think the betas have a long way to go. The issue with the betas is, Novartis put the stake in the ground that they're the lutetium player and have taken a lot of that supply, and it's from a very small number of nuclear reactors. And so they dominate that market, and they know the benefits of it. We have Copper-67 because we have proprietary position over a chelator, and are making a number of products. We also have exclusive arrangements on the supply of Copper-67, so no one can get into that. So I think there's been then a jump past the betas into the alphas going, well, we can't get into betas, let's try and get into alphas. But the alpha's a very early stage. The work still needs to be done.

And as I said, we are a radiopharm company, but our focus is strongly on, in particular, Copper-67 bisPSMA in prostate at this point in time. But we do have an alpha strategy to see whether we can actually have some benefits with that. Are we cautious? Yes. And I think there needs to be caution, particularly when you are using antibodies, for instance, and alphas. But when you're working with the betas, much softer, better outcomes for the patients, better opportunity to go to first-line, better opportunity to go to combination therapies. And the data we're seeing, as I was talking about just then with Copper-67 bisPSMA, is outstanding.

Oliver Sartor: You've used this term bisPSMA, and I'll bet you that a lot of our listeners are not familiar with that term. Can you explain what that means?

Alan Taylor: Definitely. Once again, Oliver, I'm just a simple scientist, and we have a number of simple scientists amongst us at Clarity. And what we did many years ago, we made a PSMA agent because the PSMA agents were taking off, right? Diagnostically and therapeutically. So what does a scientist say and do? They say, "I'm going to make one." So we made one. We made one a lot like the others. And there's this urea targeting moiety, which attaches to a cage, which is the basis of Pluvicto Pylarify, the generic product, the Gallium PSMA-11, all of those products are all related to that same structure. So we made one. And ours was as equally as bad as theirs. So as a scientist, and looking at this, once again as a group of scientists, we said, "How do we make it better?"

And so we went back to the drawing board, and we made a product that was bispecific; it has two targeting moieties. Both of them are the urea targeting moiety, and we used some great chemistry to optimize the linker length related to the cage to do two things. We wanted to dramatically increase the amount of product in the lesions, because they only had modest uptake. And we were able to do that, two to three times the amount of product. And you've seen, obviously, the publications on that, where we're getting two to three times the amount of product, even in the same lesion, compared to these agents.

And then we wanted to retain it over time. And what we found when we built this product, we found a lot more product bound to the lesion, but importantly, we found a massive amount being internalized into the lesion. So this bispecific structure, which we have, obviously, a proprietary position over, added all of these benefits which give benefits to imaging, a lot more product in the lesion. So imaging at one hour. But then we can image later, because Copper-64 has a much longer half-life, we can image 24 hours, and there are benefits to that. But importantly, it drives that area under the curve when we're looking at therapies. And that mechanism probably explains why we're getting such exceptional results in the SECuRE trial with single doses. Even though we are dosing even more now, because we're doing a dose escalation, dose expansion, but it probably explains why it works so well.

Oliver Sartor: I'm going to stop calling you a copper company and start calling you a bis company, because that's pretty compelling when you get better uptake and better retention. That's really interesting.

Now, very briefly, PSMA is a fabulous target, but there are other targets. And I'm not trying to get any proprietary information. I wonder if you might be able to speak about some of the other targets that Clarity is focusing on now?

Alan Taylor: Sure. We've got two others, even in the clinic at this point in time. Bombesin has been spoken about for many, many years. Mainly by Andrei Iagaru out of Stanford, and we are close to Andrei. We love Andrei. And so it represents another opportunity.

There is a focus of us at the moment in prostate with that agent. It hits the gastrin-releasing peptide receptor, but that's expressed on many cancers. So it's a pan-cancer target. We did some exciting work with Louise Emmett, who you know and love as much as we do, who's down the road from us here, and we did that in breast cancer, and that was exciting. There's exciting data there to move into other areas even with that agent, and we see that as important. We are in SARTATE in neuroblastoma. We think there's a need to start broadening these applications, and SARTATE can move into NETs, and we can optimize dose and those sorts of things, and compete with those agents like Lutathera at a point in time. But we think kids are important here as well, and they should be benefiting from radiopharmaceuticals, and there's good uptake.

But now, and Oliver, we haven't been so public with our preclinical plan at this point in time, but there's a myriad of targets, and there's great opportunities to target different lesions. We're excited about moving broader. We want to be in difficult-to-treat cancers. More about probably colorectal cancer. We'd love to get into that sort of space, target. We're also keen to look at a broader range of, is ovarian an option? Can we move into different spaces? And we're looking at where we optimize or utilize a beta in the first instance, but we have to tick a few boxes. And the few boxes are exactly what we did with bisPSMA, how do we hit the target in the first instance? How do we maximize uptake and retention into that lesion? And if we tick those boxes, then it's about safety. What is the offsite targeting like?

Even though the betas, as I said, have very good safety profiles, even with offsite targeting. And then, how do we wrap up some intellectual property around that? Even though that doesn't seem to be important these days with a lot of companies just progressing any agents, but we see it as vitally important. And then, how do we progress that into first-in-humans?

Now, we have a number of collaborations around the world at this point in time, looking at different agents, and looking at different opportunities, to really expand out because we are a little bit niche. We actually have a platform opportunity in the copper isotopes, as well as, as you say, a platform opportunity in bisPSMA. But the copper isotopes, diagnostically and therapeutically, we could run out 20, 30, 40, 50 agents, all looking at different cancers, all looking at different opportunities.

The diagnostics, and we are looking at this, moving into other areas. There are high unmet needs in diagnostics more broadly. Breast is an example in oncology, but in other areas. And we've got a few little tricks in the box that should come out over the coming months, and how excited we are with big market opportunities, but really to produce outcomes for patients that might go many, many years without a diagnosis. Maybe be able to fast-track that so they get better treatments earlier.

Oliver Sartor: Yeah. It's a pretty amazing time in the field. Briefly, I'd like to discuss combinations. We could talk about it a long time, but I'm going to keep it kind of short. What type of combinations do you think about? Or at this point, are you thinking about combinations? Just maybe pure betas or alphas?

Alan Taylor: Yeah. I think if I discuss the alphas first, I think alphas are a little harder to go combinations, because they destroy everything. And so, I think the work has to be done on the alphas. There's some alpha PARP work, which is a little bit more difficult to understand and the like, and I find that even PARP's probably hard to go combinations with. But as far as we are in the betas, we are doing, and we spoke about this preclinical work, we're doing a lot of combination work to better understand how our products broadly can work with products like IO. We find that's a good mix, and we're doing some great work in that field to turn cold lesions hot in the concept of IO, and to see whether we can have additive or synergistic benefits. And we're seeing great results preclinically already on that, and we think there's a great opportunity to further expand the IO applications.

But prostate is our major area with bisPSMA. And that's Copper-67 bisPSMA. We're excited about that because of the early data, even in late-stage disease and having, you saw the complete response in the first patient we ever treated twice at what we thought was a therapeutic dose, was amazing. That wasn't a combination. That was after everything. And to have that sort of dramatic response.

But we think the key area is, we think there's a great opportunity to bring Copper-67 bisPSMA even into first-line therapy, even if it's a single dose, in combination with something like an ARPI. We think the ARPI radiopharm combination is fantastic. We think we are best suited for that. We like that ARPIs increase the expression of PSMA. We think that combination therapy actually probably presents the best opportunity for potential curative outcomes in much earlier stage disease.

If you're upregulating the receptor, if you're hitting it as hard as you can with a Copper-67 bisPSMA, I think that represents the best chance. And if you're getting near no side effects, or reducing the side effects of ARPIs, that's a great outcome for the patients. Now, that is a fantastic, I think that's the jewel in the crown. That's what we're aiming for as a company, and we think it's a great opportunity for us, and we'll be looking further into that.

Oliver Sartor: Interesting. Very interesting. A final question. You have a crystal ball. In five years from now, you're going to make a prediction based upon what your crystal ball is showing. Tell me what you envision five years from now as some of the major accomplishments in this field.

Alan Taylor: Yeah, that's a great question. Listen, where we are now, part of it's exciting because big pharma has jumped in, right? But part of it's from a scientific perspective, it's not that exciting. It's not exciting for me that DOTA-TATE is now with BMS, you know? I&T lutetium is with Lilly. I&T actinium is with AstraZeneca. These are not exciting.

What's exciting is, how do we bring new innovation to the space? How do we build new products? Like bisPSMA, we built it from scratch. Why isn't there more of this innovation? And I would love to see in five years' time the innovation now at that grassroots. What's the new receptor we're after? What's the new target, and then what's the new combination? This, and this is going to sound funny, if you're an oncology company now, and if you don't have a radiopharm capability, are you a real oncology company? Because if you've got oncology assets, radiopharm gives the potential to enhance all of those assets with combination, but potentially even with earlier diagnosis.

In diagnostics, we haven't even spoken about our diagnostic platform, much smaller disease. Let's hit it earlier. Let's get there earlier. This will revolutionize the market. But it's a little bit capped at the moment, not just on the innovation side, but the supply side. Lutetium, how do you supply lutetium? How do you supply gallium or fluorine, when there's already the struggles of those assets? We are looking at a whole new game.

Copper-64, 67, don't have the same issues. Centralized manufacture of Copper-64, cyclotron-driven, and Copper-67 rotatron-driven, set up here. When I say here, US-based first, then into Europe, then into Asia, and getting these products broader to everywhere where there's a patient in need.

There's always this discussion of patient-centric medicine, and a lot of people in radiopharm say that. At the moment, it's isotope-centric. If it's a one-hour isotope half-life, you have a one-hour scan. Well, that shouldn't be the case. How do you produce the best outcomes for the patients? Get them products in the first instance. And then, obviously, give them the opportunity to enhance imaging, say with next-day imaging, and then give them the best therapies available, which will require innovation. It's not I&T. It's not octreotide again. It's not anything like that. It is new innovation and broad distribution.

Oliver Sartor: Alan, it's been a pleasure to have you today. I think the UroToday listeners are really going to enjoy your remarks, broad-ranging, futuristic, and fun. Thank you for being here. Thanks for being on UroToday.

Alan Taylor: Thank you so much, Oliver. As I said, always a pleasure, and it was an absolute honor to spend time with you. Thank you so much, and thank you to UroToday.