Our next session, we've got Perspective Therapeutics represented by Joel, their CFO, and Annie, who's the head of their IR team. Thanks for being here.
Thanks a lot, Leo. Really appreciate the invite to the conference. It's been a great day for us so far.
Oh, excellent. Happy to hear that. maybe to just as a way of a brief introduction, you guys can remind us, you know, on your platform, what's the advantage of the alpha emitter approach? What makes it unique, you guys recently had an R&D Day related somehow differentiating features across, you know, the design of both the payload and the targeting modules themselves, just, you know, sort of remind us what makes Perspective special amongst the different approaches.
Yeah. No, I'm glad you, I'm glad you mentioned that. We put a lot of work into our R&D Day to make sure that we got that message across. You know, we really think the alpha emitter a way to attack cancer is the next generation a next generation approach. It's going to really make a difference for patients. If you look at the continuum over the development of cancer drugs, it's great to have, you know, heard Richard Pazdur kind of talk about the regulatory side at your lunch today. You know, we're way beyond what we started out with chemotherapy and then targeted antibodies and things like that.
If you look at how successful ADCs have been, we think we'll in general we're obviously advocates of the radiotherapeutic area as it is. And we are also not all our drugs are lead based, but that, you know, doesn't mean that that's the only way to go. We think it really works well for us. As you mentioned before, we're not using beta emitters, we're using a alpha emitter. That is what Lead-212 is, and we think there's two levels to it. First, we do in the, at the animal level, as you kind of saw when we at our R&D Day, we can figure out which of the targets are best for our drug to go to the tumor and not to healthy tissue.
That gives you such insight that you would never have with a TKI or even a monoclonal antibody, because you have to wait to get into the clinical trial to figure out whether you're going to have off-target side effects. You know, not to get too far ahead of myself, but I mean, we're super excited about the clinical data that we've shown so far that kind of backs up that hypothesis. Just getting back to the high level again, we do the dosimetry to kind of make sure as best we can prior to going into patients by doing animal work, to figure out where our drugs are going to go, and figure out a way for them to preferentially go to the tumor or get taken up by the tumor, not by the healthy tissue.
If you can do that, you not only set yourself up in ahead of the game in a way, when you do drug development, but you also end up, we hope, with drugs that are much safer for the patients to take. We do that type of thinking throughout our entire portfolio.
Yeah. No, that makes sense. maybe moving on to some of the clinical data especially on the VMT-α-NET program, which is your lead drug. Can you talk about maybe what you've shown to date?
Yeah.
In terms of responses and, you know, maybe we'll stay with the efficacy side. In this, in NETs, and we can talk about this as well, tend to be more indolent, so you know.
Right.
Perhaps, you know, safety plays a bigger role than some other tumors. Maybe just starting with the efficacy side, you know, how should we contextualize the response rate that you've shown so far?
No, that's a good question. I mean, let me start off by just saying we have dosed over 100 patients so far across all of our clinical trials right now. Given the fact that it's you know, we've done this out of effectively two manufacturing facilities and have a plan to have a network of facilities throughout the U.S. I think we've already shown that we can get our drug to patients from a supply standpoint. The fact that we've designed them and have responses for VMT-α-NET kind of gives us credibility that all the heavy lifting we did on the R&D side is paying dividends right now in the clinic. Yeah, we have so far reported on two cohorts from VMT-α-NET.
Cohort one at three millicuries times four, and cohort two, which is five millicuries times four for a total of 20 millicuries of dose. The way we do it is every eight weeks we dose for four cycles. What we've reported at, for example, at AACR, of the first 23 patients of the 46 patients in cohort two is that our response rate was 43%. That's intent to treat over the whole patient population. If you look at just those patients that are SSTR2 expressers, not heterogeneous, but all the target lesions, the response rate's about 50%. Those numbers just in isolation we think are really, really compelling.
If you look at those numbers compared to the on-label response rates for the two other NET Drugs, cabozantinib and LUTATHERA, those response rates range from 5%-18%, depending on the type of subpopulation you're looking at. Just comparing our numbers to those numbers across trials, which I know you're never supposed to do, you know.
I wouldn't have a job if we weren't supposed to.
Exactly, I know how it is. As a former analyst, I think it's what you're paid to do. You know, you draw the conclusion that we have an active drug. The next up would be to look at the rest of cohort two. Also we're doing two other things in cohort three and cohort four for ALPHANET. Even though we don't need to because our, we think our response rate's so strong, we're looking at increasing the dose to 6 millicuries per cycle times four for a total of 24 millicuries. The reason we're doing that, you said, you know, you didn't wanna talk about safety yet, but I'm going to anyway, is that we haven't reached an MTD.
The drug is relatively safe, why not see at six millicuries whether we can do even better for the patients that we're attempting to treat. In cohort four, which we conceived of at the same time as cohort three, it wasn't sequential from cohort three to cohort four. We're going back to the same 20 millicurie cumulative dose that we are delivering in cohort two, but we're doing it in a front-loaded fashion, where we're starting out with six millicuries, then five millicuries, then five millicuries, and then lowering the fourth dose to four millicuries to see if, you know, a theory behind why that could give a better response as well.
Got it. Shown the response data, as you mentioned. Sort of the part of it being an indolent disease is that, you know, maybe some of the longer data time point, endpoints are maybe more meaningful for physicians and patients PFS, duration of response, ultimately OS is always meaningful. How should we think about how your data might translate to some of those, when we might see some of that data?
Yeah. Yeah, no, that's an excellent point, and I would want to stress the fact that we look at our data not as every time we look at it, we're turning over a card to see whether the drug works or not. What we're looking at it, as the data matures, is exactly as you described. We're looking at how the duration of response is evolving. You know, one, you know, thing I will say is if you looked at our presentation at ESMO last fall and compare it to the data that we presented at AACR, nine of the 16, nine of 16 patients, if I have that right, had a deepening of response during that timeframe.
We're not only looking at the actual response rate, but we're also looking at what could be the approvable endpoint, which is PFS. We haven't reached a median. The data's not mature enough for us to quote a number on duration of response, but it's something that our drug, I think, will really look for, VMT-α-NET will really look good when that final data is available.
Leo, you asked about durability of disease control and tumor regression. In addition to seeing all of that, we're seeing deepening of response, which is very important, as Joel was saying.
Yeah, yeah.
Yeah.
On the safety side, you know, there's been some other radiopharma programs that ran into, you know, some toxicity issues. I think one of the key things people watch with radio ligands is, you know, kidney tox, renal tox. You've so far managed to avoid most of these toxicities. I guess, how and is that going to keep going? Is this just inherently a safer, more better, I mean, better designed approach?
That's a good question. I mean, we're certainly looking at all the things that you would want to look at with regard to assessing the safety profile of the drug. We look at it every time. We've been very forthright with regard to giving investors every opportunity to look at our safety profile as it evolves. We do that at virtually every medical meeting. Thanks for the compliment there. Yeah, you're right. It has come out so far to be a lot safer than the competitive drugs in development. As far as why, you know, I would go back to how we conceived of and developed the drug in the first place.
This point of differentiation, probably I would point, if I would have to describe one thing, it would be the chelator that we use. It's proprietary and we use it in all of our compounds, not just VMT-α-NET. Effectively, there's two things about the design that make it differentiated. The first is it's designed with a net neutral charge, and as a net neutral charge particle, it promotes excretion by the kidneys as opposed to reabsorption. If you can imagine in the body, what that means is that's specifically designed to be kind of safe for the kidneys, which is one of the main areas to watch.
That's 1 of the reasons why our kidney data so far has been relatively benign on the safety profile. The other element of it is the chelator holds the daughter isotope, so the lead decays into bismuth, and the bismuth is retained within the chelator. What is important about that is it eliminates the possibility or not eliminates, but it's designed to mostly eliminate or reduce the possibility of unbound metabolites, active metabolite-type things that could end up going to places you don't want them to go to, healthy tissue and causing problems. With those two things in mind, that's what I kinda said at the beginning. The compounds are designed with safety in mind first.
Or I wouldn't say first, but equal to the efficacy, and that's why we're in the enviable position we are right now with a relatively safe safety profile, certainly if you compare us to the competitive drugs in development. Also being able to go into cohort three and cohort four with these higher doses and not having MTD even on our sites right now. While we're in that position with a drug that already has really compelling efficacy data. It's a nice position to be in with VMT-α-NET, and we don't think that that's a one-off. We think that these design benefits will translate also with regard to our other drugs in development that use Lead-212.
Got it. You guys have given a number of presentations on VMT-α-NET this year. What should we think about in terms of data cadence for the rest of the year, I guess?
Yeah.
What will be the major updates we should look forward to? What should we see at each of them? Like, when do we get a more wholesome picture of the program moving forward?
Yeah. We'll probably, I mean, we're gonna have data on VMT-α-NET at ASCO, but given the way that the data cutoffs lie and what we just presented at AACR, it shouldn't be that much more than we presented at AACR, you know, last month. We will have more data by the end of the year. Can't say what conference we'll be presenting at, but it should be one of the larger ones we would hope to present at. At that point we would probably have more data from cohort two. That, remember, there was a total of 46 patients in cohort two, and as well as some of the cohort three and cohort four.
I will just remind you that while we didn't have efficacy data from cohort three at AACR, we did have safety data with 16 patients out of the 20 in that cohort, and we followed them for a median of 16 weeks. That was, you know, kind of important 'cause that shows the higher dose, and we didn't really have any untoward safety results from that, and we'll continue to follow that over the course of the rest of the year.
The other part of this is regulatory.
Yeah
Starting a phase III sign-off with the FDA. I guess how are you thinking about what a design for a phase III or registrational program might look like? I guess where are you with respect to, you know, aligning with the FDA on that? I guess are there any parameters you can tell us in broad strokes as we think about, you know, what could a program look like for the next step?
Yeah. Little bit premature to answer that with any kind of detail, but I know what you're getting at. I would say the most important thing that I would emphasize is our, number one, our relationship with the FDA, and number two, the timing that you just described. You know, we don't look at this as anything other than a complete collaboration. They've been super supportive and collaborative with us so far. When we go into those meetings with the FDA, when we talk about this sort of thing, it's being on the same side of the table looking at all the data we have and all the possibilities in order to come up with the most cost-effective and quickest path to market for our drug for investors and for clearly the patients.
I mean, I think the base case as you build your model should be that we have a registration trial that has a control arm. Probably something along the lines of physician's choice as a control. Anything other than that is speculation. I mean, we'd love to have an accelerated plan of some sort if that's at all possible. You know, that's certainly not our expectation or base. You know, you shouldn't build your model that way. I think that, you know, the other element of it is timing. We haven't given specific guidance on when the phase III trial will start because that depends on, you know, these meetings and how long it takes to sort that out.
We will get the company in a place to be ready to start the phase III, let's say, by the end of the year. We have control over that. We don't necessarily have control over, you know, when the FDA will kinda give us their blessing or whatever. The other thing I would mention, though, is we would like to integrate some of the learnings from the cohort three and cohort four into the phase III trial design if we possibly can. And just to remind everyone, that has to do with this, the higher dosing, the 6 millicurie dosing, whether you do that in a front-loaded fashion or just a higher dose in the 5x4 in the 20 millicuries total.
Don't know how that'll actually pan out, but that's something we're trying to think creatively about to make this a winning registration trial for the patients and for the product.
Got it. Last thing I wanted to touch on here is you guys have done a good job with execution. There's been a lot of enthusiasm for enrollment. I guess can you speak to that and, you know, maybe in terms of, you know, how quickly you could maybe ultimately operationalize a phase III and how ready these sites are, like if you start a trial, maybe expect it to enroll quickly, like how much execution time savings there could be?
I'm really glad you asked that because there was a dramatic change in how easy it was to enroll after our data at ESMO. People were really impressed with the efficacy as people, I mean the investigators, in NETs physicians and things like that. We don't think it will be very difficult for us to enroll rapidly and aggressively based on that. As you saw at Analyst Day, we have a lot of physicians who are very well known in the NETs space who advocate for the drug and want to use it in their patients. I think that's part of it that I think will not be very difficult for us.
The other part, and I'm sure that was your a follow-on question you would ask is, okay, this is a radiopharmaceutical, it's not an off-the-shelf thing that you pill that you swallow. You know, just want to reiterate, we've dosed 100, over 100 patients with our drug out of two sites. A small site in Iowa and a commercial site or what used to be a commercial site in New Jersey. And, you know, we recommissioned that from another company to use for our investigational material. By the time the phase III is fully up and running, We will have built and presumably operational a state-of-the-art production site in Chicago that is centrally located and able to produce more than enough drug for the clinical program.
We're really proud of the work that went into that. It was years in the planning. We'll also be in a position, once that plant is registered, let's say sometime next year, we'll repeat that work and work on another site in another area, where we have land already purchased. One is in L.A. and one is in Houston. If you look at the two major things that would be gating factors to getting to that phase III result, supply and distribution of the drug is a critical one, and getting the patients, finding the patients and getting them onto the trial, and I think both of those things we're super confident that we'll be able to do in a expeditious and efficient manner.
I want to gently push you on that for the commercial setting.
Yeah.
You know, as we think about, you know, in the future, you know, for clinical trials, these centers are still reasonably sophisticated.
Yeah
As you think about NETs and potentially in the community and I guess how broadly applicable is the radiotherapy, can physicians generally use it? Is it going to be restricted to academic sites? What's going to be the manufacturing readiness for, you know, potentially for a commercial launch? We saw even some of the larger pharmas at the time struggle with supply.
Yeah.
I guess how confident are you that you'll be able to, you know, navigate both of those challenges?
Yeah. Well, we're not blind to those challenges that, for example, Novartis had. In fact, we're actively incorporating those experiences into how we're building this out. One of the reasons why we don't use CDMOs is because we don't want to be dependent on their timelines, either for the clinical trial or thinking down to commercial launch. I think we're really confident that we have done the right things to not be blind to those challenges. By the time a couple of years down the road when we have multiple sites, we will have a network that we can use. As far as the part of your question having to do with finding the patients, you know, SSTR2 expression is relatively high.
We found that about 70% of our patients in our clinical trials are SSTR2 positive in all tumors, and the other, the balance are SSTR2 heterogeneous. Those, the incidence there is relatively high. I don't think you're going to be forced to have the patients go to a major academic site. Our drug is delivered ready to go. There's not a lot of work any at all really that the hospital or the physician has to do on the day of administration. We pretty much take care of all the heavy lifting there.
Got it. Got one minute left. You've got three other announced program.
Yeah.
Melanoma, FAP, CCK2R.
Yep.
I guess how are you thinking about, you know, the cadence of catalysts from those over the rest of the year, sort of your relative excitement among those?
Yeah. Well, we're actually excited about all the compounds in our development, in clinical development right now. With only a few seconds left, I will remind everyone that we have posters not only on VMT-α-NET, but on VMT01 for melanoma at ASCO, and FAP as well. I would encourage you to stop by and look at those, and we will have, you know, more data on those and presumably the start of the CCK2R by the end of the year.
Great. Thank you so much for joining us. It's been great.
Awesome. Great questions, Leo. Appreciate it.