Get started. Good morning, everyone, and welcome back to the 2024 RBC Global Healthcare Conference. My name is Greg Renza, one of the biotech equity research analysts here at RBC, and we're pleased now to have Perspective Therapeutics. And joining us from the company is Amos Hedt, the Chief Business Strategy Officer. Amos, it's good to see you.
Thank you. Thanks for having me.
Just for those in the audience, that Perspective with the ticker CATX. Now for those who are new to the story, Amos, maybe you can provide us with an introduction to the company, the technology, and why this is an exciting time for Perspective.
Sure. So, Perspective was actually came about through a merger between two existing companies. One was a brachytherapy company called Isoray, and they were listed on the NYSE for quite a few years, actually. We merged in March last year with a company called Viewpoint Molecular Targeting, which is the radiopharmaceutical development company. Most of the technology and the team that came into that merger came over from the Viewpoint side, and that's now really the focus of the company. So we develop novel radiopharmaceuticals for oncology applications. We're a clinical stage company. We have two products in dose escalation studies at the moment in the U.S., and we have a pipeline of novel molecules coming through from our discovery group based out of Iowa.
Great, and certainly an area of high interest for folks. You know, when it comes to what makes Perspective unique, Amos, just talk to us a bit about how we should be thinking about alpha emitters versus beta emitters from a therapeutic standpoint.
Sure. So when Viewpoint was founded, our Chief Science Officer, Mike Schultz, was a radiopharmaceutical scientist. He sat down and really wanted to look at the best therapeutic isotope available. There were other isotopes available in the space. Lutetium, for example, was a well-established isotope, even at that time. But the move into alphas is really one of the most compelling aspects, I think, of radiopharma at the moment. Alphas just have a much shorter path length, so they can be more precise. They also provide a much larger punch to a cancer cell versus a beta. So for an alpha, you're typically looking at one to two alphas can kill a cancer cell.
For betas, it's typically more than 200 to up to 1,000 being required to actually cause the kind of lethal damage that you'd expect. So Mike selected. You know, actinium was also an isotope that was available at that time. Mike didn't like the biology and the radiobiology of that molecule and the decay chain, et cetera, even though the half-life was quite long and amenable to manufacture, et cetera. He really liked the biology that an isotope like Lead-212 offered, which was a much cleaner decay scheme, a half-life that matches the kinetics of the peptides and peptide-like small molecules that we're developing. And so that was the selection, and we stuck with it, and I think it's now bearing fruit. Yeah.
It's helpful to hear the comparisons. And what other advantages would Lead-212 have over actinium?
So Lead-212 has a 10.5-hour half-life. This is extremely important in radiobiology because it means that you're delivering 80% of the alpha dose within 24 hours of administration. So if you can imagine a peptide molecularly targeted to the cancer, very rapid uptake in the tumor, and then delivering a really rapid high dose of alphas to that tumor within 24 hours. Actinium will only deliver on target 6% of its alphas within 24 hours, and so you've got this long residual radiation sort of in the tumor and the tumor microenvironment. What that does, we think also, is very attractive about Lead, is that it irradiates the tumor, and then it's gone.
That allows the tumor microenvironment to really recover and for things like tumor-infiltrating lymphocytes to move into this into that tumor, and then do the work of educating the immune system about the neoantigens and the destruction that's occurred. So with actinium, with the long half-life and residual radiation, you know, a 10-day half-life, you get the constant irradiation of those tumor-infiltrating lymphocytes. So we think that this is, you know, this is kind of like the killer app, possibly for lead, is to look at combining with standards of care in immuno-oncology, et cetera. So-
And then as far as the platform is concerned, how does the novel chelator technology support lead's value proposition?
So one of the key platforms for the company was actually the development of a novel chelator for lead. So chelating the radiometal is a key fundamental of radiopharmaceutical development. You wanna make sure that the metal is retained on the drug for as long as possible, because that means that you get on-target efficacy, and you don't lose the metal, which can redistribute throughout the body. So Mike and his team designed a lead-specific proprietary chelator that also binds the daughter isotope, which is the actual alpha emitter, which is Bismuth-212. So we can be sure that the radiation that's going to be deposited will be on target, and not released from the drug and circulating.
This is an issue for Actinium, which has a decay chain with three additional alphas and an additional beta, where those radiometals, etc., can redistribute throughout the body, potentially opening up toxicity issues.
Mm-hmm. Great. Well, let's talk clinical programs and maybe with NET, with neuroendocrine tumors, VMT-α-NET. Just talk to us, Amos, a bit about how we should be thinking about this program versus currently approved therapies and care management when it comes to NET, and interestingly, Lutathera as well.
Yeah. So Lutathera is the established, you know, and successful radionuclide therapy in the space. It has a long history, and the patient population is really well educated about Lutathera. Actually, I was having a chat earlier today with someone about, you know, the need for American patients to actually fly to Europe to receive that therapy in the early days. So the patient population is really demanding next generation alpha-type therapies in this space. So the clinicians know about the alphas, and they're really keen to get involved in this. I think Lutathera is a great drug, no doubt about it, but these groups think that we can do better.
Typically, Lutathera will, you know, patients will eventually progress on Lutathera, and so there's a real potential for an alpha to move into that space, and hopefully deliver sort of more a higher objective response rate and more durable responses. So we're excited about that program.
And what are your thoughts on the NETTER study that the foundation for the Lutathera approval? Just talk to us a bit about sort of what you've learned from it, and how you're applying it.
Yeah. So the NETTER, the NETTER study, was really... Actually, it was really groundbreaking in radiopharmaceuticals, because for a long time, radiopharma was not pursued as rigorously as it might have been in terms of randomized controlled trials. NETTER-1 really broke the ground, and AAA and Novartis did the work to deliver a prospective randomized controlled trial, which was great. So I think the level of rigor in the whole industry now actually has come up to that, and it's expected now. But we think that, you know, those larger controlled studies are the way to go.
Mm-hmm.
We'll be looking at that for our programs, in terms of the development paths.
Yeah. And what's the latest on your dose escalation? Talk to us about the phase I/II design.
Yeah. So we're doing a dose escalation in a number of U.S. sites. We are currently in the second cohort, and we may have announced this morning that that's second cohort is full or nearly full. We're certainly very encouraged by the safety profile that we've seen so far. We don't see anything untoward occurring there. And we believe we'll be in the efficacious range with 5 millicuries. That's still obviously to be proven out, and we'll have results probably coming out quarter three or quarter four, depending on if we present at a scientific conference.
Sure, sure. Just as far as the enrollment criteria, just enrolling patients who've never received the PRRT therapy, just walk us through sort of the selection logic.
Yeah. So, the NETTER-2 study that Novartis recently released was quite positive, and that used. That recruited patients earlier in their—after their diagnosis.
Mm-hmm.
So, that's the kind of approach that we'd like to take, is looking at moving further up the treatment chain with all of these products, actually, because they have a-- it appears that they have a relatively benign safety profile. It's also a different safety profile, and I'm talking more broadly now, I guess. It's a different safety profile to a lot of other drugs out there, so the potential to combine with other standards of care is really exciting, really exciting to us.
Great. Great. And a 12-patient data set coming up in June at a conference, what should we be looking for? How should we think about that data?
This is more mature data than was presented at an update at EANM last year.
Mm-hmm
... which was very encouraging data. This is not our data. This is an investigator-initiated study in India. Those patients are particularly sick. They have a large burden of disease, multiple lines of therapy, including some of them receiving both Lutetium dotatate and Actinium dotatate.
Mm-hmm.
And so how should we be thinking about that? I think what we'll really be looking at there is the safety profile. This population has been dosed at a dose only slightly above our initial dose escalation cohort. If we see signs of efficacy there, and it sounds like we will be seeing that, some of that-
Yeah
... then it would be very encouraging for us, I think, particularly because we're dosing at five millicuries in our current dose escalation study, and the average dose in the Indian data was 2.9. So, super encouraging.
Great! And just the context of regulatory discussions around RECIST, around PERCIST.
Yep.
There's always an ongoing debate on the approach to basically assess tumor response. What are your views on using different modalities there?
So ultimately, we'll be driven by the regulator in terms of the tool that we read, and that is typically RECIST. So for all of these studies, RECIST is the standard. PERCIST is actually a really useful clinical tool, but it's not typically used in clinical trials as an endpoint. It's used by clinicians to really get a handle on how the patient is responding in a functional manner, along with additional other sort of functional measurements.
Just keeping with regulatory, and for those not familiar, just to what degree has Perspective engaged FDA just on the use of Lead-212 in conjunction with really what is an interesting decentralized model? Certainly want to talk about that soon as well, but what are some of the key takeaways from those interfaces and maybe some of the next steps?
Yeah. So we've been really encouraged by the FDA feedback on our approach. Particularly, we have an existing isotope generator which we use for our existing clinical trials. So that's a small sort of desktop size generator that can be shipped around. You know, we ship it to India, Germany, across the U.S. And the FDA didn't have any comments on the use of that for our initial clinical studies under the IND. So that was very encouraging. And then we've recently also signed on to the FDA's CMC program, where it's a dialogue in terms of scale up and controls and manufacturing. So this, I think, de-risks that whole isotope supply and manufacturing component of our development, which is really encouraging.
Mm-hmm. Maybe we'll keep with that decentralized manufacturing model and just help break that down for us. What makes it so unique and what makes it actually optimal to conform to essentially the supply and to the clinical delivery?
Sure. So most of the most of the existing radiopharmaceutical products are manufactured more on a central basis, largely because they can do that, it fits Big Pharma's model of, you know, sort of single sites. But, I think, that's a function of the radioisotope half-life. For lutetium, obviously, you have seven days, actinium, 10 days. But we've also seen the fragility that's in that, and I think, you know, with the Pluvicto supply issues last year, I think Novartis started to wake up that actually maybe not putting all your eggs in one basket is a rational approach.
We think that, obviously, with the 10-hour half-life of lead, that limits us in terms of centralized manufacture, because, otherwise we would be shipping very large quantities of lead around the place. With a distributed manufacturing plan that we have in place, you know, we're looking at probably 10-15 type finished product manufacturing centers across the U.S., a network effect, so you're getting some redundancy in the system. So if you have a spill or need to shut down a site, you have other sites that can fill in from around. So we think that this makes a lot of sense. The beauty of Lead-212 is that the decay scheme is such that we don't need to irradiate anything.
We don't need reactors, cyclotrons, linear accelerators, anything like that. So we can store the Thorium-228 parent, which has a two-year half-life centrally, and then the plan would be for us to ship radium out to the facilities, which has a 3.5-day half-life, and then that is purified into lead, and we do a batch process at the local manufacturing facilities. So it also is very flexible. It allows us to scale according to where we are in clinical development, etc. And it's not a. It's not like we're installing cyclotrons, etc. It's a fairly basic sort of hot cell setup.
Sure. The redundancy certainly helps to mitigate the risk.
Yeah.
But also maybe implies some degree of rigor. At this point, what are you in Perspective thinking as far as going it alone versus that of a CMO? How should we be thinking about the investments and the approach?
Sure. I think recently we've seen that manufacturing capability is very attractive.
Yeah
... to Big Pharma, so we're not scared of investing in that space. I think we also, you know, we have a really great pipeline of products coming through, so if we only had one or two products, we might work exclusively with CDMOs.
Mm-hmm.
And that capability is certainly being built out across the U.S. But with additional successful products planned to be in our pipeline, I think, more of an integrated approach makes sense for us.
Mm-hmm.
You know, we're not interested in educating everyone else how to make our products when we're the experts. So I think, you know, we can build that network, and we'll supplement what we're building with CDMO capabilities as we need to.
What do you estimate in terms of cost and time? How are you communicating that for those who understandably ask?
Yeah, yeah, sure. So, this is a, you know, a manufacturing facility will probably take 18 months to two years to fully get up to commercial type capabilities. And in terms of the cost, it's not much more than a cyclotron facility, which, you know, there's 110 of them across the U.S. So, we're probably looking at $10-$20 million, maybe for a finished facility, so.
Okay. I sort of wanna talk pipeline, as you mentioned in talk of VMT-01. But before I do that, I just want to open it up to the audience, and any questions for Amos and Perspective.
Thanks so much for taking my question. Just wanted to ask on the theranostic pair of Lead-203 and Lead-212, how can you leverage Lead-203 over your traditional copper or gallium for imaging and efficacy?
Great, great question. One of the reasons Lead-212 made so much sense was that there was a true paired theranostic. We can use Lead-203 as a SPECT imaging agent. I think we've seen the value of that in the recent human images that we gathered on our third clinical candidate, which targets fibroblast activation protein. We saw a really excellent uptake in those patients with sarcoma and lung adenocarcinoma, etc. It's a real de-risking tool for us. Whether it makes sense to commercialize Lead-203 as an agent is. It probably depends on the indication that we're moving into. It wouldn't make much sense for Alpha-NET, where, you know, there is existing approved, FDA-approved imaging agents.
But as a development tool, it's really invaluable because we can do true dosimetry, and look at the amount of radiation that will be deposited into the tumors and kidney, etc., using Lead-203, because it's a elementally identical drug.
With regard to the third quarter, data updates, I'm just curious, how should we think about, the efficacy profile? I know you're in the dose escalation stage, but should we start thinking about, you know, is it going to give us a signal that, you know, that could potentially be competitive, you know, early, or do you expect that to be from a later doses?
It's a good question. I think from what we've seen in the compassionate use data that's been disclosed, we certainly saw an efficacy signal there. I don't think we can give sort of percentages at this stage. I think it's a little early, but I think we would be, we expect to be deep within the therapeutic window currently at the 5 millicurie dose, 'cause we saw efficacy at 2.9 in the Indian compassionate use data. So, we are very hopeful. I can't sort of guide on any kind of efficacy percentages, but we're hopeful that we'll see the kind of results that we'd expect.
Great. In the remaining time, Amos, let's talk melanoma and VMT-01. Just help set that up for us. What's the value proposition in the target and also in the program?
So, VMT-01 targets MC1R receptor, which is overexpressed in melanoma cells. The exciting data that's emerging there is that whilst we do believe that we'll have some monotherapy efficacy, perhaps combining with standard of care is really the most exciting thing there. Because what we've seen in our preclinical models is this amazing curative effect in checkpoint-resistant melanoma models. So these mice have a tumor type that is particularly resistant to checkpoint inhibitors, but when we combine with VMT-01 labeled with Lead-212, we see this amazing vaccine-like effect, actually, in terms of a curative response. And when we interrogate the immune cells in those mice, we see that we actually generate a T cell memory response.
So, I think this has real potential, and we'd love to open up this idea of using Lead-212 more broadly with combination therapies. I think that's a real potential that we would be looking to exploit in the future.
Great. And just in the closing time, just other assets in the pipeline, other programs you're looking at, you mentioned that FAP alpha, understand that also a PSMA target, very competitive-
Very competitive, yes.
It's tough to differentiate. So how do you see differentiation among some of those earlier programs? How is that informing your prioritization?
Yeah, PSMA is extremely, extremely competitive, even in the lead space. We really wanted to make sure that we bring forward a candidate where there is no salivary uptake, because xerostomia is actually a significant side effect of the alpha particle therapies in this space, and a little bit in the betas too. So, we would really... We're in the process of optimizing that molecule that we licensed from the Mayo, and we really would only advance that if there is significant differentiation. So-
Makes sense. All right. Well, a lot, a lot to cover and, and, and a lot going on. Amos, great, great to see you, and thanks, thanks for the time.
Thanks, everyone.
Thanks, everyone, for joining.
Cheers.
All right. Thanks. Good to see you.