Perspective Therapeutics, Inc. Study update

Thank you, Bill. Good evening, good afternoon. Welcome to the Perspective Therapeutics call to discuss VMT-α-NET clinical data being presented at the European Society for Medical Oncology Congress 2026, ESMO. During the call, we may make forward-looking statements that are subject to risks and uncertainties. Factors that could cause actual results to differ materially from our expectations are detailed in our SEC filings, including in the risk factors section of our most recent annual report on Form 10-K, quarterly report on Form 10-Q, and our other SEC filings, which are available on the investors section of our website. These forward-looking statements apply as of today, and we undertake no obligations to update these statements after the call. Today's call is being webcast and can be accessed on the events page of our website.

The call will be archived and be available for a period of time after the conclusion of the call. Today's call will start with prepared remarks by our Chief Executive Officer, Teys Speir. After the prepared remarks, we will open the call for questions with participation from our Chief Medical Officer, Markus Puhlmann, and members of the clinical development team. With that, I will turn the call over to Teys.

Great. Thanks, Annie, and thank you everyone for tuning into this call. We are here at ESMO. We had a presentation earlier today that Dr. Thor Halfdanarson from Mayo Clinic presented on behalf of the investigators. We really want to talk about why we think this is so important. We think there is an extraordinary ability to help patients with neuroendocrine tumors, especially since the need is for deeper responses and more durable disease control. When we think about what the patients experience, they first experience a somatostatin analog, which really helps manage their symptoms. When we think about their post-somatostatin analog options, it then goes into a broad category, options including Lutathera or everolimus, sunitinib, or cabozantinib, and we believe that we have an ability to develop a medicine here with the potential to really be category-defining.

When we think about how the category was initially created, the NETTER-1 data came out, which actually had a registrable benchmark. In that case, progression-free survival was the primary endpoint. Further on, if people look at the label for Lutathera, you realize that there's a 13% overall response rate in the NETTER-1 patient community. When we look at the data that's now come out from VMT-α-NET, we're extremely pleased because we've got very strong data in GEP-NET patients. We look at really good tumor responses. When we actually look at how patients could perform in a registrational trial, we narrow the aperture a little bit from broader all-comers that are SSTR2 positive to those where we only look at the target lesions, and all target lesions must express SSTR2 positivity.

We look for durable disease responses, and in this case, we're very pleased that we've seen a 72% progression-free survival rate at 18 months across all three cohorts. We've seen a very low-grade incidence of adverse events, and so without having ever seen a grade 4 or 5 adverse event, we have not seen any dose-limiting toxicities. We're really excited about having the ability to bring a very compelling medicine forward and into the clinic. When we look at the overall opportunity space for treating patients with GEP-NETs that are SSTR2 positive, it's a clear medical need. There's approximately 250,000 people living with neuroendocrine tumors in the United States. There's approximately 12,000 patients that are newly diagnosed each year. What's interesting about this particular tumor type is that around 90% of those tumors do express this receptor, SSTR2.

The room for next-generation therapeutic therapy is in the fact we can actually deliver lead-212, which brings an alpha payload to the tumors. We think that our medicines bring a very favorable risk-benefit profile. As we think through the package insert approvals in the space, the 37%-47% ORRs that we're seeing now in GEP-NET patients that are all SSTR2 positive, we think it lends itself very favorably to where we're trying to get to. When we look at the ongoing study that we're performing, we are dosing patients in dose finding. We initially dose patients at 2.5 millicuries times four doses, so 10 millicuries all in. We also escalated quite rapidly to patients at 20 millicuries, and we also went 20% higher, up to a cohort three of patients at 24 millicuries.

Our belief around why we think we can actually move forward is underlined by the conviction of the data. We've developed a medicine that we know has a net neutral charge. We know that the kidneys like picking up charged proteins and charged protein fragments. Our proprietary chelator and targeting entity together have a net zero charge, which means we should have a broader therapeutic window than other attempts in this space. We also think that alpha particles from lead-212 have the ability to give a hard, fast punch and then the ability for the body to recover. We think if we have this unrelenting focus on medicinal chemistry, on opening up the therapeutic window, we then have the ability to explore various doses and always with the goal to try and do this in as safe as way as possible.

Underscoring the fact that safety is critical in these patients, these are patients that are expected to live a long time. Again, that's why the approval endpoint is going to look at disease control. When we look at all these metrics together, we're extremely excited by how this profile looks across all of our doses. If I focus on the center chart initially, if we look at patients who have come in on the waterfall chart, you see that we track these patients through as long as we can. We have not had a long follow-up yet in the patients at cohort 3, 24 millicuries, and we're starting to see follow-up now on the patients across all 46 patients at the 20-millicurie dose.

What's interesting to see as you look at the speed of the responses, we do actually see, with a slightly higher dose, some indications that the responses may be earlier and deeper, and we'll show that in a future graph as well. But if we look at the overall response by cohort on the far left, there's quite a few numbers to pull apart here. We look at the overall response rate, and this is in an ITT, so all comers, everyone that's in the study. In the lower part of the table, we do focus in specifically on what the patients could look like in a registrational study.

In that case, if we just look at patients where all tumors are SSTR2 positive, we're looking at a 37% overall response rate in those patients, and we're also then looking at a 47% response rate in patients at the 24 millicuries. So a lot of patient data here. We're pleased to see that the safety signal that we've seen previously is lasting right now. If we look at safety on the far right-hand side, I want to focus people to the bottom of that graph. Looking at all Grade 3 treatment emergent adverse events, we're looking at numbers that are not disconcerting or unnerving at all for an oncology drug. We still have zero Grade 4 or Grade 5 adverse events. We have not seen any dysphagia whatsoever, and I'll touch upon renal safety shortly as well.

But across the board, this looks a very compelling profile for clinicians. When we actually speak to physicians, they're really excited. Patients are coming into the study. They're usually quite sick. They have a lot of comorbidities. There's lots going on with their health, and the patients are coming in very informed. They want to be able to live longer. They want to be able to have a quality of life that's meaningful and be able to live for as long as they can. While overall response rate is one metric in a slow-growing tumor that we look at, we look to see how these responses emerge over time. The other thing I really want to highlight is that previous overall response rates that we've shown looked at patients that have been on the study the longest.

Since in some cases now in this study, we've seen responses show up as late as 60 weeks, there's naturally going to be what appears to be a perpetual underreporting of the overall response rate as we look through how patients come through. But when we look at the slide here, this looks very compelling for clinicians to really think about what could be best for their patients. When we actually get into what's the approval endpoint, now it gets especially interesting. What we've shown here now is some of the initial Kaplan-Meier estimates of PFS and what that means at a landmark PFS rate. So in cohorts 1 to 3, if we look at the far right-hand curve, three lines down, we're looking at a 72% landmark PFS at the 18-month mark. This is pretty fantastic disease control.

When we actually look at all these other metrics and these curves, we know that we can give a lot of confidence in letting patients be on therapy and have that clinically important and approvable endpoint of disease control. Then actually looking in at specifically what's happening with these patients. When we look at what's happening with cohort 2 and cohort 3, we're really pleased to look at the overall response rates, the PFS as well as disease control rates. This is actually the first time that we've shown the external world, physicians, investors, and patients what happens with the 24-millicurie dose. What's really remarkable about this spider plot is you actually see very, very rapid onset of effect if you're looking at tumor response. We hope this should translate into longer, more durable disease control than we've even seen so far at the lower dose.