Good morning, everyone, and welcome to day two of Oppenheimer's 34th Annual Healthcare Conference. I'm Jeff Jones, one of the senior analysts here on the biotech team. With that, I'm delighted to welcome John Valliant, CEO of Fusion Pharmaceuticals, to the call to dive into the story here. John, I will let you take it away. Thanks, Jeff, and thanks everyone for joining. If we can jump forward, looking forward to talking to you about Fusion. So Fusion, I mean, the radiopharmaceutical space is incredibly hot at the moment, and we really feel we're well positioned to be a leader in this space. Just some real highlights. So our lead program is an actinium PSMA. We announced that we align with the FDA on a potential registration pathway in a phase 2/3 type design, and it's really designed to position us to be the first actinium PSMA agent to market. And the focus there is to be in the post-lutetium or post-Pluvicto setting with the opportunity to move to earlier lines. So in addition to aligning with the FDA on a potential registration pathway, we also announced that we had opened our manufacturing facility and now are actively shipping doses in support of our actinium PSMA program, which we call 2265. So because Fusion recognized the opportunity in alphas and actinium, we invested not only in the building of a manufacturing facility but also in the supply of actinium itself. Now, one of the things I'll say about the radiopharmaceutical space is that it's largely been focused on prostate and neuroendocrine cancers. We really felt there's no reason whatsoever that alphas and radiopharmaceuticals can't have a major impact in other tumor types, and there's tremendous white space. And so we have built a diversified clinical-stage pipeline, and one of the areas that we've focused on is replacing the toxins in ADCs and creating a next generation of precision medicines. Part of that work that we've done in the antibody-targeted alpha therapy space was through what we feel is a platform-validating partnership with AstraZeneca, and I'll certainly touch on one of the programs there that we've announced. But our goal is to really harness the potency and precision of targeted alpha therapies, leveraging the fact that Fusion's a vertically integrated company with a deep pipeline and manufacturing expertise and capabilities. So focusing on the lead program, which is FPI-2265, it's currently the most advanced actinium-based PSMA-targeted radiotherapy in development. There are more than 400 patients that have been treated with actinium PSMA small molecules globally, including over 100 post-lutetium. And we had seen the literature data on actinium PSMA small molecules. We're really impressed by it, both in terms of the activity that was seen, both in patients who were lutetium naïve but also those who had relapsed or were refractory to lutetium agents. The safety results, in our opinion, were supportive of developability from a heme tox and xerostomia perspective. But one of the big barriers was the actinium supply that was available to drive these programs forward. So we took over a phase 2 IND in the U.S., and the goal here was to really drive this program forward and be first to market. And we think the first opportunity is in the post-Pluvicto setting, which we think is a significant and rapidly growing market that I'll touch on in a moment. But we also see that market growing. So with the data on Pluvicto and the PSMAfore data suggesting that Pluvicto is going to move ahead of taxanes, we think the demand and need for a post-Pluvicto treatment is going to just keep growing. We also see that given in our hands, we continue to see the potency of alphas be greater than that of betas. We also think there's an opportunity to move to earlier lines of therapy. And one of the strategies we're pursuing is looking at combination therapies with drugs like olaparib to achieve that. But the data continues to be exciting. We shared early data on the TATCIST study when we took it over. Sorry, if you could go back one slide. Like this patient shown on the right, where you can see a dramatic reduction in the PSMA PET uptake of patients treated with just a couple of cycles of actinium. This particular patient had a PSA that was over 1,100 and then dropped into single digits after just a couple of cycles of therapy. So we shared data on first 10 patients when we took over this study. They were at different points in their treatment, and now we've been driving that program forward since we took it over. So we announced earlier this year that our target enrollment in the TATCIST study was completed, and we anticipate sharing the data in April. We shared that we will be sharing data on 25-30 patients from this phase 2 study. Our goal when we took over the study and indicated we would share early data on this group of patients was to leverage the data that was already in the literature from investigator-sponsored studies. Our goal was to be able to recapitulate and actually repeat that data, both from an efficacy and safety side. And fortunately, very recently, there was a paper, a meta-analysis published in The Lancet Oncology on about 488 patients treated with actinium PSMA small molecules. We felt the data was very supportive of the literature data that existed previously that we had looked at and was one of the drivers for us taking over this program. So we've guided that our PSA50 response, we expect to be in the 30%-50% range. We'll have a mix of patients who are pre- and post-lutetium, but the majority will be naïve to Pluvicto or lutetium PSMA therapies. When we took over the study, the first 10 patients had already been treated and were Pluvicto naïve, and that was at a time when there were some supply issues. So the study did, we'll have the majority of patients being in the Pluvicto-naïve setting. But when we took it over, we started enrolling those post-Pluvicto patients. The other area was people recognized the potency of alpha emitters, but there were a number of questions about the safety side of it. So our guidance is on xerostomia, which is an on-target toxicity seen with this class of therapeutics. What we'd like to see is it being grade 1 or grade 2 with no grade 3s and, importantly, a low percentage of patients discontinuing as a result of xerostomia and also a low rate of high-grade myelotox with this particular class of molecules. And one of the reasons for the range of PSA 50 responses is this obviously got started as an IST with more broader inclusion criteria than you would see in sort of a typical industry-sponsored study. So there are a number of factors which can impact patient response, not least of which is number of lines of prior therapy, including a lutetium PSMA and the number of cycle of taxanes that the patient had, but also, of course, their general patient characteristics, whether they're superscan patients, whether they have liver mets. And more recently, certainly from publications looking at Pluvicto, is the extent of uptake on PSMA PET can have a tremendous impact on the PSA50 values as well, which makes sense because the amount of drug going in, the more you have in the tumor, the more you would actually expect it to respond. So at this point, we took over the phase 2 TATCIST study. We did amendments to narrow to tighten up the inclusion criteria. In parallel, while we were doing that, we met with the FDA and aligned on the potential registration pathway. And that's what we shared earlier this year, that we've aligned on the phase 2/3 registration pathway. Now, fortunately, based on the literature data and the TASA data, 100 kilobecquerel per kilogram dose administered every 8 weeks for up to 4 cycles we feel is known to be a safe and active dosing regimen. But there's an opportunity to further maximize and improve the benefit-risk ratio, and we took that approach to the FDA. And so if you look at the bottom left of the image, there is data suggesting that some patients can have PSA escape prior to 8 weeks, so between 4 and 6 weeks. So the opportunity to dose patients more frequently could have a potential benefit on the efficacy side. So we approached the FDA about keeping the same total dose but increasing the frequency of dosing. So that results in actually reducing the injected dose per cycle. So you can see in the green boxes, 75 kilobecquerels every 6 weeks, 50 kilobecquerels every 4 weeks. In addition to sort of keeping more frequent pressure on the tumor to give an efficacy advantage by injecting a lower amount of activity in every cycle, there's also the potential to benefit from the safety side if things like xerostomia are a Cmax-driven effect. Nevertheless, 100 kilobecquerels every 8 weeks is known to be an effective dose, but we'd like to see, before we kick off the phase 3, whether or not there's an opportunity to further expand the therapeutic window. From this 60-patient study, which we expect to fully enroll by the end of the year, we'll select a dose to move into the phase 3. Our phase 3 study is based on this 2:1 randomized versus 2265 versus an ARAD switch, a design that people will be familiar with from three other phase 3 studies that are going on in terms of PSMAfore, SPLASH, as well as Eclipse. And so that's a pretty standard design. But we think by aligning with the FDA, we really have an opportunity to push this forward. As I mentioned, the phase 2, we expect to fully enroll by the end of this year and kick off the phase 3 following an FDA meeting in 2025. The opportunity with PSMA and actinium, we think, is quite significant. If you look at the current use of Pluvicto and its approved post-taxane, we think is a blockbuster opportunity unto itself. With the data coming out of PSMAfore, we really do believe that Pluvicto has the potential to move to earlier lines and even larger market opportunities. But a significant number of the patients treated on Pluvicto need to go on to other therapies, and this is where we think there's very high unmet need. So in both settings, we've designed our study to be able to treat both groups of patients and include them in the trial, sort of making sure we understand where the field is going. But we see this as a potential multibillion-dollar opportunity as Pluvicto moves to earlier lines. So in terms of program milestones, we'll report the data from the TATCIST clinical trial on 25-30 patients in April, and we expect to initiate the phase 2/3 registration study in the second quarter. And again, given that we've gotten alignment with the FDA on a potential registration study pathway, this will be the focus of enrollment for us going forward. One thing I didn't mention was that early on, Fusion did some work looking at the potential synergy between actinium agents and PARP inhibitors like olaparib. And the benefit of that combination is that actinium obviously causes single- and double-stranded DNA breaks. The PARP inhibitor inhibits repair, and that gives you synergistic efficacy. And so we felt that there's an opportunity to move to the Pluvicto-naïve and even earlier line settings. So we'll be initiating a trial with 2265 in combination with olaparib this year. We expect to complete the enrollment in the phase 2 in Q4 of this year and then really initiate the phase 3 in the following year. It's a significant market opportunity, and a critical component of that is to have the ability to supply the alpha-emitting PSMA agent to sites and meet what we expect to be growing market demand. Now, Fusion, when it started, recognized the potential of alphas over betas. What we're seeing in the field is that most companies are now shifting from a focus only on betas to really looking at the benefits of alphas, which cause direct double-strand DNA breaks. In preclinical studies, the shorter range and higher energy transfers of alphas really give a lot of benefits, both as monotherapies and potentially in combination therapies because it does cause direct double-strand DNA breaks. It can be active in hypoxic tumors or tumors that have upregulation of single-strand DNA break repair mechanisms. But we liked actinium as one of the key alpha emitters in this case because it has a 10-day half-life, which, like Pluvicto, which is based on lutetium with a 7-day half-life, allows for centralized manufacturing and distribution to clinical sites in a ready-to-use form. But it also emits multiple alphas in relatively rapid succession, creating maximum damage to cancer cells. And we think that's an important part of the efficacy of these targeted alpha therapies, which in the clinic have shown the ability to kill even large-sized tumors. We have great preclinical data showing the superiority of actinium over other isotopes. And I think, importantly now, between the work that was done at Rayze on actinium dotatate as well as the significant literature on actinium PSMA, there's a lot of data showing the safety and efficacy of actinium-based targeted agents in the literature. But a critical barrier to entry in this space is actinium supply, and we recognized this early on. So we've been receiving actinium, like many people, from the Department of Energy, been a tremendous supplier, continued to meet the high clinical demand. We have four clinical programs. But we recognized that for large phase 3s and commercial scale and meeting markets that are large, like in the case of PSMA, we wanted to invest and partner with groups who had actinium production technologies. Two that we've announced are partnerships with BWXT Medical and Niowave. These companies have a tremendous history and experience in developing and producing commercial-scale medical isotopes and high-quality materials. These groups have produced actinium. We've received the actinium, and they continue to scale their technologies. We more recently announced, "Not only can these groups produce actinium and ship it to us," we announced that part of our partnership with BWXT Medical provides the opportunity for us to put on-site generators within our manufacturing facility. This technology is small, convenient, compact. It doesn't require large cyclotron infrastructure if you want to have actinium production on site. It actually involves shipping a parent isotope of radium, which is put on a generator, which you can sort of think is a coffee-maker-sized device with the radium being the coffee grounds. And then, as you pass your hot water through the coffee grounds, you can elute actinium on a regular basis, which can feed into your manufacturing facility. Fusion spun out of a radiopharmaceutical manufacturer, and our experience is having multiple high-quality sources of your key raw material is critical, and that's really what we're set up to have. As I mentioned, we're built on a foundation of radiopharmaceutical manufacturing expertise. We spun out of a radiopharmaceutical manufacturer that I founded and ran for a decade. We have a team with incredible expertise. We felt that the ability to control your manufacturing supply and be able to scale as demand scales was critical, not just in the raw material, actinium, but also in the final drug product. We announced this year that our manufacturing facility is now fully operational. We are shipping doses in support of our lead program, the actinium PSMA. The facility is designed to be able to get to large phase 3 and commercial scales. We have the capacity to produce 100,000 doses annually off a single shift. We're located in an established transportation hub with decades of experience in producing medical isotopes for global distribution. We have a lead program against a target we think there's lots of literature data on and we feel is a de-risk target, and we're excited about pushing forward and being the first to market. But, as I mentioned early on, there is a tremendous white space, in our opinion, in using radiopharmaceuticals to move into other tumor types beyond prostate and neuroendocrine cancers. Fusion has built now a clinical-stage pipeline with the ability to go after targets that are expressed in those other tumor types. The approach that we took was to not lock ourselves into one class of targeting molecules but to actually have a diversified delivery platform. So Fusion has two small molecule programs, including the PSMA one I talked about, as well as antibody-targeted alpha therapies, sort of analogues to ADCs, where you're replacing the toxin with an alpha emitter. Part of the rationale for that is really lessons learned from PSMA. I think lots of excitement around the target, but people forget that actually PSMA was a failed ADC target. Some interesting data is, if you look at this small molecule drug conjugate, which is designed to target tubulysin to PSMA, the PSA change that you're seeing, you can see in this plot that you do see some activity from the drug itself. But if you take the same targeting molecule so if you look at the black portion of the molecule, that's actually what binds to PSMA itself, so identical targeting molecule. But you basically replace the chemical toxin with the isotope. You can see the tremendous impact and benefit you get from delivering radiation to the target. So the idea that you can take a target that has not shown significant activity with a chemical toxin but then replace it with an isotope and see activity is well-founded in the PSMA space, and we think you should build there's an opportunity to build on that looking at other targeted therapies. So one of the first programs that we looked at was targeting a well-known tumor antigen, IGF-1R. And the idea, again, is we have the opportunity to take an antibody which was known to bind a target that had lots of data to say it was expressed on the tumor. But even though it could target the tumor, it did not effectively kill cancer cells in clinical trials. However, we're not trying to block or downregulate the target like they were in those studies. We're simply trying to use it to bring the potent alpha emitter inside the cell. So our approach was to take an IGF-1R antibody that had been in the clinic, showed good safety, good targeting ability, but now convert it into a delivery vehicle for bringing that actinium inside the cells. When we started this study and we started going to increasing radiation doses, we started to see thrombocytopenia and toxicities at the higher doses. What we discovered, however, was that we could pre-administer a small quantity of the naked IGF-1R antibody, which we called the cold antibody, followed by the hot. And what we saw, the results were actually quite exciting for us. We saw both improved safety and improved and more optimal biodistribution. So we started off by testing this. If you go to the next slide, by doing what's called a cold antibody imaging substudy. So this is the same antibody, the same linker technology, but now you're imaging the distribution of your drug. And if you look on the top left panel, the spleen, you can see lots of uptake in the spleen. However, if you administer the cold antibody, you can see the spleen gets decreased so this is the same patient, I should say, and acting as their own control, and you drive more of the drug into the bloodstream. The benefit of that is, in fact, if you look on the bottom panel, you can see increased tumor uptake. We then advanced this into the therapy studies, and we reported data last June that at 15 kilobecquerels per kilogram, not only did we see more optimal biodistribution, but we saw no DLTs, good safety profile, 2 of 3 patients showed stable disease after receiving and 1 patient received up to 5 cycles. We then dose escalated to 25 kilobecquerels per kilogram. We wanted to see if the safety would continue to look good with the cold antibody concept. The cold antibody is administered 30 minutes before the therapy, so it's very convenient to administer. And what we saw, again, we had 2 or 3 patients complete the DLT period. There were no DLTs. Safety continued to look good. But I think what was interesting is we had 1 patient we could deliver 4 cycles of therapy. Again, there have been very few examples of antibody-targeted alpha therapies receiving multiple cycles of therapy. And 1 patient with a Ewing sarcoma shown on the left had a large 4-centimeter lesion, and you can see after a single dose of 1434 that shrunk to below a millimeter or so and demonstrated antitumor activity. What's very interesting about this case was the patient had received the naked IGF-1R antibody plus chemotherapy as a treatment, and really, there was no treatment effect. So going after the same target but now using an alpha emitter, you're now seeing antitumor activity supporting that hypothesis we have in terms of being able to take ADCs or antibodies that don't show the required activity you're looking for and use the potency of alpha to boost that even higher. So in our early-stage pipeline, with the data that we have from the 1434 program, as part of our big partnership with AstraZeneca so they're leaders within the ADC field and antibody fields - we took their EGFR-cMET bispecific antibody using the same linker as in the 1434 program, which is our proprietary Fast-Clear linker, have attached actinium to it. We shared the preclinical data, which looks very exciting. The great thing about this bispecific is not only do you get increased selectivity from targeting both tumor antigens, upon binding, it drives internalization to bring the actinium close to the DNA. So we think there's a real opportunity to drive with this technology in a great collaboration with AZ to bring this forward. The IND is now open, and we're actively looking forward to moving this program forward. I don't want to forget the fact that we do, outside of our antibody programs, have a second small molecule, like in the case of the PSMA programs. Our 2059 goes after a target, NTSR1, neurotensin receptor 1. Like the target of Lutathera, which is SSTR2, this is another class of neuropeptide receptor, but instead of being found on neuroendocrine cancers, it's found on colorectal, pancreatic, and gastric cancers, among a few other tumors. This agent, as a lutetium compound, was taken into the clinic. There's publications showing tumor uptake in a number of different tumor types. We showed that if you replace the lutetium with the actinium, you can get effective tumor kill preclinically at 1,500 times lower dose. This program is also in the clinic, and the IND is open, and we're looking forward to sharing data in the near future. This field has been growing at an incredible rate, and an important part is the depth of expertise you have on your team. At Fusion, we're fortunate that we have people with expertise that range from radiopharmaceutical development, manufacturing, isotope production, clinical development of targeted therapeutics. A tremendous team with expertise that's going to enable us to drive those programs forward. Finally, just a few numbers. So in terms of our unaudited financials and recent report, we have nearly $300 million in cash, which will enable us to fund our operations into Q4 of 2025, which enables us to get to what we feel are some exciting potential value inflection points for the company, including reporting data in April, as I mentioned, on the 2265 program. We'll share an update on the 1434 IGF-1R program around the middle of this year and then initiate the combination trial with our PSMA agent and olaparib, again, in the first half of this year, with the goal of finishing the enrollment in the phase 2 portion of the phase 2/3 study for 2265 by the end of this year. So just quickly to summarize, we have our lead program in a phase 2/3. We've got the manufacturing and a deep pipeline, including looking at sort of those advanced next-generation ADCs. Thank you, John. I've got a whole bunch of questions lined up, but I'll ask you a couple of quick ones before we run out of time here. For the 2265 PSMA targeting program, is the plan for the pivotal study to go for Pluvicto-refractory, or will it be pre- or Pluvicto-naïve patients? For the phase 2/3 registration study, our goal is to be in the post-Pluvicto market. So we're silent on taxane use because right now, obviously, Pluvicto is approved from the VISION study post-taxane, but we see that expanding. But we're going to be post-lutetium to start. The combination study is designed to be in the Pluvicto- or lutetium-naïve space. Okay. Great. That's helpful. And then a question on the actinium from the generators from BWXT. What comes down from the radium-225 generators, does that material include actinium-227, or is it pure actinium-225? Yeah. So we don't look at production methods that have high levels of actinium-227, just I think more broadly for people's background. Actinium-227 has a very long half-life and creates sort of handling and disposal challenges. So the only methods we look at are those that produce the high actinium-225 purity. Okay. Just one quick clarification. On the registrational study, you were talking about holding the total dose delivered steady. Actually, that was the phase 2 portion. The total dose delivered steady over different dosing frequencies. What's the total dose you're going to deliver? You talked. 400 kilobecquerels per kilogram, or 400-450 is sort of the range for that. Got it. And then well, we don't have time for more questions, so I think we'll hold it there. I believe you've got a pretty full schedule of meetings, and certainly happy to facilitate additional discussions. John, thank you very much, and have a great rest of your day and productive meetings. Thanks, Jeff. Appreciate it.