Maybe we can get started. I think we're at the top of the hour. Thanks for joining this session with Aktis Oncology. My name is Alec Stranahan. I cover Aktis and Small Biotech at Bank of America, very pleased to be joined by Matthew Roden, Chief Executive Officer of Aktis, and Akos Czibere, Chief Medical Officer. I think I was in the ballpark. Thanks guys, Akos and Matthew for being here. Yeah. Thanks for having us. We're excited to be here, and thank you Alec for the invitation, and to the entire Bank of America team. Great. Yeah, looking forward to the conversation and we'll have follow-ups at our dinner later as well today, which I'm looking forward to as well. Maybe just to start off, Matt, recent IPO, great to see the interest in that offering, given the sector backdrop. I guess this gives you cash runway into 2029. I think just at a high level, the core thesis that you guys have built the company on is the miniprotein radioconjugates. These are antibody like targeting affinity, small molecule pharmacology, but with a radiopharmaceutical payload. I guess maybe could you talk to how this opens up the opportunity set within radiopharmaceuticals broadly? We've seen success from, I guess, the beta emitters, PLUVICTO, LUTATHERA. What are maybe the one or two things that you think you're building upon here and sort of what you hope to prove out in the clinic? Yeah, great. No, that's a great setup, and really the way it starts is with us at Aktis, we had the vision along with others in the field, that radiopharmaceuticals, targeted radiopharmaceuticals could be a large new category of anticancer medicines, right? It started with the new renaissance in the field, with the emergence a few years ago of what is now PLUVICTO and LUTATHERA. What the field learned from that, in our opinion, is that fast clearing molecules, fast clearing radiopharmaceuticals can widen the therapeutic index for radiopharmaceuticals because it's bone marrow sparing. Previously, the field was looking at monoclonal antibodies as delivering radioisotopes, which of course are long lived enough in the body that it's sharing its radioactive payload for the entirety of its circulation time. If you could shorten the circulation time by having molecules that leave the body quickly, you should be able to expand that therapeutic index, provided that you're able to get the drug into the tumor and exert a hit at the tumor level. We're excited to see the emergence of PLUVICTO and LUTATHERA because those are small peptides, they're fast clearing, but they are effective binders to their targets, and they're able to exert that payload to create an anti-tumor effect. What we were interested in doing, to your point, with the miniprotein radioconjugate platform that we've built, is to figure out a way of how do you replicate that success that you saw with PLUVICTO across a broad new array of targets that are expressed in tumor types where there's no radiopharmaceutical option. In other words, if you think of it this way, we think of the initial movers in this field as the pioneers or the ones who did the experiments that show in a certain instance that it can work, and we are sort of the optimizers that are looking to take over a much bigger position across the field by opening up these white space opportunities as first in class molecules, bringing radiopharmaceuticals into these large patient populations where unmet need exists and there's no radiopharmaceutical option. To accomplish that, we built this miniprotein radioconjugate platform. Miniproteins were selected intentionally because they have the properties that we felt would lend itself to that fast clearing, you know, bone marrow sparing profile. Also by virtue of their very small size and three-dimensional structure that we felt that it was likely or was designed to, I should say, really deeply penetrate tumors and get internalized into tumors. Also by virtue of its diversity in the three-dimensional structure, that it would be able to hit effectively with high affinity and selectivity, a broad array of targets. In other words, you would just be able to hit a broader array of targets. Small peptides are great when they work. Unfortunately, they are not really effective binders against many different targets in the target universe that we care about biologically. This is a way for us to sort of say, "All right, let's do small peptide pharmacology, but with an antibody-like ability to hit a broad array of targets with high affinity and selectivity." That's what we felt the miniproteins were likely to deliver. We built the platform. Now we're screening. You know, we have libraries that we built ourselves that are very highly curated and selected for the properties that we want, and even those are expanding in diversity. We're now screening north of 6 billion variants across about 100 different scaffolds or protein folds. On top of that, we've really added on a significant effort on generative AI, binder approaches, where now Our head of computational chemistry is saying that we're now effectively sampling billions of trillions of different variants in silico as we seek to expand the search space to find very high affinity, very highly selective, target binders that can enable us to broaden the impact of radiopharmaceuticals to a broader array of patients. The data that we've generated and have presented really are principally very broad, deep, preclinical data sets, as well as imaging and dosimetry work in patients of various different tumor types, both for the Nectin-4 program and now the B7-H3 program. Those data for the B7-H3 program will be presented in a couple weeks at ASCO. We previewed that to some extent in our S-1 earlier this year. These are the bases with which we've moved forward into really broad phase I-B development plans that we are looking to convert the data that we have now, which we think are very encouraging to a more formal clinical proof of concept to come. Great. Great. Maybe one more high level question then I wanna get into the different pipeline assets you have in the clinic. You know, you framed in the past that the radiopharmaceutical space is kind of at a similar inflection point to where ADCs were roughly five years ago. What are the analogs here? You've got a few approved drugs, and then there's a format optimization, such as your miniproteins, that unlocked a much larger opportunity. I guess what kind of format optimizations with your design do you think are most analogous to the payload and linker improvements that have sort of expanded the ADC field? Yeah. It's a fascinating topic to look across the different modalities and see where the analogies are. It wasn't just us that felt that we're approaching an inflection point in the field of radiopharmaceuticals. There was actually, what we cited in the S-1, was a presentation by Boston Consulting Group at a fall conference last year, where they pointed out multiple parallels between the ADC field pre, let's call it pre Daiichi Sankyo. Now the inflection point that occurred, now there's multiple ADCs now approved by the FDA, and with a total TAM of about $35 billion by 2030. That has really expanded, right? ADCs are very well known and understood in terms of the opportunities that exist there. Radiopharmaceuticals, I would say, are in a similar position as ADCs five years ago, where, as you mentioned, a couple approved products, a clear clinical validation. You also have clear commercial validation with PLUVICTO being the best launching oncology drug since Ibrance, so that's about 10 years that passed. That's how far back you have to go to see a oncology drug launch as strong as PLUVICTO was. So there's the commercial validation. Obviously, there's strategic validation, lots of deal value generated along the way in the field of radiopharmaceuticals. Now the question is, how do you make it just bigger? How do you open up those white space opportunities? That's what Aktis is intended to do, and that's where we're excited about the positioning that we've created, where we have two, we believe first in class or potential first in class, targeted radiopharmaceuticals, the first one targeting Nectin-4, and the second targeting B7-H3. These targets are expressed in very important patient groups, and we look forward to moving them forward. I would further add that, you know, this is just the start, right? Nectin-4, B7-H3, these two programs for us, are really just the tip of the iceberg of what Aktis is working on. Below the surface, we have many additional projects ongoing. I alluded already to the discovery platform, but we have various programs in different stages of early development, and that was also something that we've been working on in our collaboration with Eli Lilly. To leverage our platform capabilities to generate even more radioconjugates against targets outside of our scope. Great. Obviously, Lilly stepped up in large for the IPO as well as an equity holder. Maybe we can talk about that towards the end, but maybe we can just, you know, go stepwise down the pipeline. AKY-1189, this is your Nectin-4 targeting radioligand therapy. This is in phase I-B. We've seen fairly de-risking tissue localization data, which is kind of the first step, and maybe one of the distinct benefits of radioligand therapy generally is you can actually see where it's going and making sure that it's getting excreted in the way that you want before you actually dose patients with the active compound. A basket of tumor types here of a few very high, Nectin-4 expressing tumors, lung cancer, CRC, cervical, urothelial cancer, which is probably the most de-risked. Maybe you could just walk us through sort of the backfill design and, you know, the dose expansion, escalation, and sort of, you know, the number of patients and just the design broadly of the study. Sure. I'm gonna make some opening comments. Sure Akos will add on the clinical strategy here. You're right. The Nectin-4 AKY-1189 opportunity is an important one for us. Obviously, Nectin-4 is a clinically and commercially validated target. The thinking is if you can hit it effectively, that you should be able to see anticancer activity. We are mindful of the fact that the leading compound here, which is Padcev, commercialized now by Pfizer and others, is really focused on urothelial carcinomas or bladder cancers. In addition to those opportunities in bladder cancer, we also see the opportunity for several other high-expressing Nectin-4 tumor types, including breast cancers, lung cancers, and several others. The approach that we've taken, first, as you mentioned, we have tumor uptake data, so we can show uptake of our drug in tumors of various different histologies, including bladder, breast, cervical, colorectal, and lung. We've shown that in our previous presentations. The clinical development plan that we've set forth is, A, focused on bladder. Obviously, as you mentioned, clear proof of concept exists for the target in bladder cancer, but also enables us to really pursue opportunities outside of that. Akos, you wanna talk about the trial designs that we have there and what we expect to see? Yeah, happy to. That study, the NECTINIUM-2 trial, has been under IND for about onw year now, right? We cleared the IND last year around this time. It follows a Bayesian backfill design, so it's dose escalation under the Bayesian principle, where we tend to do three to four patients per dose level as we move up through escalating doses. Once we have identified a dose level of interest, and it could be safety, it could be some early efficacy, we're able to expand that dose level out to 30 patients, right? We can do that in two dose levels. That helps us really find the right dose to move into the more targeted expansion phase of the study, where we'll be looking at a cohort, as it's currently planned, of triple negative breast cancer patients, post-Padcev pembro bladder cancer patients, obviously, and then there's a large 50-patient basket for the other non-TNBC, non-UC tumor types as well. Great. You know, obviously you've guided to a 1Q27 update from sort of the phase I-B or Part 1 of the phase I-B. That tends to be the data card flip that I get the most questions about from investors. You know, from the sound of it's gonna be a pretty substantive update, kind of to the scale that we saw with RayzeBio prior to their acquisition. I guess, how do you sort of frame this in your conversations in terms of, you know, the endpoints that are most important, the number of patients that you're gonna have in sort of that metastatic UC indication and, you know, what sort of good would look like to advance the program? Yeah. Maybe just to add a nuanced point on the RayzeBio data set, since that data was less dose escalation, more expansion at a given dose, right? That was that waterfall plot at the go forward dose. We're obviously starting a step behind that, finding the dose first that we then wanna carry into that. That data set will be built around the dose escalation, clinical safety efficacy, right? All dose levels, all five dose levels that are planned, once they're completed, will be included and then potentially some backfill patients with varying degrees of follow-up. Double-digit numbers. Mm-hmm. Do you wanna comment on the endpoints as well? In terms of endpoints, if you just look at the technicality of the protocol, those escalation Part 1 endpoints are all around safety, right? It will be safety focused, but we'll obviously also present the efficacy that we observed in that. There's no formal hypothesis testing going on in this part of the study where we have to hit a certain response rate target or anything like that. That will be following in the expansion phase- Okay of the study. Okay. Obviously there will be efficacy data included, right? Yeah. You're not gonna push it forward just based on safety. No. You know, TRODELVY is kind of the de-risking asset for the target, in the Padcev- is what I meant. In the, I guess, post-Padcev failure, is that kind of the target indication, and what are sort of the outcomes for those patients typically? We view the post-Padcev pembrolizumab space as sort of the low-hanging fruit, quick-to-patient opportunity, right? Because there's no established standard of care, with TRODELVY, as you mentioned, having to do another lap, right? With that study not reading out until like mid 2029. I think this continues to be an opportunity to be the first new therapy in a post-Padcev pembrolizumab setting. I think the real question to the field and the agency is gonna be what is post-Padcev pembrolizumab, right? Is it post-Padcev pembrolizumab in a metastatic setting? Does it include the perioperative setting? I think there's a lot of work that can be done to really have a meaningful impact for patients. Right now the expectation, I think or the bar is very low. Expectations are always high, but the bar is low. Yeah. Is response a clinically meaningful endpoint for those patients, or is it more around survival- So- duration? I mean, the gold standard for any regulatory approval is overall survival, right? A response is, of course, meaningful to a patient if it lasts, if it has durability, right? I do think that a response rate can be very useful to guide the next study, right? How do you have to size it? How does it correlate with PFS, OS? Response rate is great to get Breakthrough Therapy designation from the agency, right? Which can further expedite the development, but we've seen it in the past, but it's unclear at this point if response rate will be a regulatory endpoint going forward, right? If you need PFS with some OS read. I think that's all in the question. All will need to be discussed with the agency. Yeah. Okay. That makes sense. I alluded to it before that we have the tissue localization imaging data for the non-therapeutic isotope for AKY-1189. I guess how does this normal tissue localization kind of compare to other RLTs in the space? I know we've seen some, you know, salivary gland accumulation for some of the beta emitters. Any expectations with the therapeutic compound now around, you know, renal accumulation, salivary glands, et cetera? Maybe I'll start on that one. The way we view the imaging dosimetry analyses is effectively something that we can use as a stage gate for development. The way we've described the imaging dosimetry is as supportive of the clinical plans that we've brought forward, right? There are instances where a certain biodistribution pattern or absorbed dose profile may give you pause in terms of moving ahead. Or it may inform like a starting dose, for example, it may require you to start at a very low dose, in dose escalation. But in the cases of our AKY-1189 and in 2519, the data that were generated were informative. They were in our opinions, clear go signals to phase I-B. They did inform our dose escalation schema that we've described now for both of the lead programs. We think that this is, you know, what we're seeing here is certainly something that's supportive and consistent of the go-forward approach. What we described recently, when we kicked off the initial AKY-2519 B7-H3 targeted radioconjugate program in the clinic, we now have sites open and enrolling. What we described there was an approach where the initial protocol is gonna be in metastatic castrate-resistant prostate cancer patients broadly, and then there's gonna be a second protocol that we expect to open in the second half of this year that's gonna address lung, colorectal, pancreatic, several other tumor types. And this is all supported by the imaging and dosimetry data that we have and that we're gonna present at ASCO, and that were previewed in S-1 in January. There's a lot to be that we're excited about in terms of the protocols that we have set up, and the intent of those protocols is to give us a clear go signal to the next stage of development as well. Obviously we're thinking about various accelerating paths to registration, and ultimately that'll be data dependent, but we're trying to create as many options as possible to reach patients as quickly as possible. I guess on the accelerated path, is there maybe precedence you can point to there, like is that kind of the post-Padcev pembro line of therapy that we've been talking about? We'll be exploring multiple options to accelerate these programs to patients once we have the data supporting that. Akos, do you wanna comment? I think more on the acceleration rather than accelerated approval pathways, which may or may not go away, right? Depending on who's in charge. We shall see. I do think if you have great data, there's always a path to patients that is accelerated with the agency. They have been, over the years, extremely collaborative across multiple modalities, right, and sponsors. They share that interest in bringing the breakthroughs to the patients, so I'm less worried about that. I think just to pick up on your point on where does dosimetry help us, right? Specifically, it helps us bring that first therapeutic study into the clinic in a more efficient way, right? You can see that with the AKY-2519 program where we did this close to three dose levels that we're going through in dose escalation, starting at 6 megabecquerel. Which is a fairly high dose for actinium targeted therapy, and that's supported by the data that we're presenting in a couple weeks. Yeah. Weeks at ASCO. There, I think dosimetry is really strong. After that, really clinical safety and efficacy I think will be driving the future prospects and future studies. Yeah. I imagine the learnings from AKY-1189 sort of helped you, plus the dosimetry you're seeing for. Yeah. AKY-2519 It's a rapidly evolving field, right? When we set out to collaborate on the AKY-1189 dosimetry experience, the main question we were asking is, are we staying out of the bone marrow? Because that's so important, right? What is the kidney exposure? We were able to answer that. Now, two years later, we have different questions, right? What about the glands? What about tumor? Can we look at that? With evolving technologies, methodologies, we're now able to look at that, right, today. Who knows what we'll be able to look at two years from now? I don't think we'll ever be in a position where dosimetry will replace any type of safety efficacy evaluation. Okay. Maybe we can switch gears to AKY-2519. Yeah. I think that's a pretty good segue. Maybe just to start, looking forward to the presence at ASCO. We'll obviously be there for the presentation. You know, what does this data sort of need to show to confirm, you know, sort of the early localization that you've seen in a handful of patients? You know, how de-risking do you think this will be ultimately for pushing the therapeutic compound into the clinic? I think the data is exciting to the KOLs investigators and to us to go into a broad development program. We were very focused two trial in one prostate study that's now open for a couple weeks. ClinicalTrials went up yesterday on that one. That study is enrolling, PLUVICTO-exposed and PLUVICTO -naive patients in parallel dose escalations, and then leading also into backfill expansions, 30 patients each in two dose levels, and then there's gonna be a basket lung-focused study starting in the second half of next year. But to answer your question, we'll need the clinical data to then look back, right? How de-risking was it? How much of the thesis translated? Yeah, I hope you stop by. Yeah, maybe just to build on that. Yeah. At ASCO we're gonna be presenting two posters, and very conveniently they're side by side. Yeah. It's one-stop shopping. One of the posters is looking at tumor uptake with AKY-2519 imaging agents principally gallium labeled AKY-2519 in a number of different tumor types Yeah -kind of asking the question, would the tumor uptake support development in various different tumor types? That will in a way link to or support it in our mind, the basket trial approach that we're describing, that second protocol. That we expect to open the second half of the year. The other poster that is gonna be presented is looking at 16 patients with metastatic castrate-resistant prostate cancer patients, so this is prostate focused. That is not only the PET CT based analysis like the first, but is also gonna have SPECT CT lutetium labeled AKY-2519, that's looking at exposure of the drug over a longer timeframe, up through six days. That is underpinning a dosimetry analysis. In other words, what is the absorbed dose in various normal tissues, and what is the absorbed dose in the selected tumors. In that population. That's, they're due to some technical advancements, even over the last two years that Akos referred to. We're able to provide a more expansive analysis than even we could do two years ago with the AKY-1189 program. What that did is that helped us inform specifically for the prostate cancer population, what the parameters for dose escalation would be as Akos Czibere described. You know, that was really the part of the basis for the excitement for us to move this into phase I-B in that specific population, as well as the feedback we got from the key opinion leaders that focus principally on prostate cancer treatment. We invite you to the poster to have that discussion. Yep. Great. Yeah, looking forward to it. Maybe in the last few minutes here, I do wanna double-click on the Lilly collaboration that you alluded to earlier. Lilly seems fairly vested in the company in several ways. It sounds like the partnership is actually advancing even ahead of schedule in terms of target ID, et cetera. I guess maybe you can just outline sort of the structure of that collaboration with Lilly and sort of the cadence that we should expect for milestones out of the collaboration. Sure. The Lilly collaboration started in 2024, where at that time our platform technology and capabilities to generate these miniprotein radioconjugates were now available to us and to Lilly, and to others. Right. Based on what was broad interest, we selected Lilly as a partner for a platform deal. What this is, it's a discovery collaboration where we are using our platform capabilities to generate novel miniprotein radioconjugates against targets that they pick that are outside of our target space. What this does is this is a win-win all around because this just expands the number of patients that can potentially benefit from our technology. That collaboration, as you said, we think it's going well. We disclosed in our S-1 that we've already hit the first milestone in that collaboration. We're gratified to see the participation from Lilly in our IPO. You know, there's been a good mojo all around in that, in that collaboration. That is in the end an up to $1.2 billion collaboration deal for us. We're working very hard to serve the collaboration well. We've worked very hard to be good partners to Lilly. Lilly's been very good partners to us. That said, you know, again, this is restricted to the molecules that we are working to deliver for Lilly for their development in the clinic and commercialization. To underscore the point, all the programs that we're working on, including AKY-1189, AKY-2519, and the others that are still to come are wholly owned by Aktis, right? Where there's no option rights or other rights to, by any other party, to those programs. We have the opportunity to work both for patients through our wholly owned programs, as well as expand that through the collaboration with Lilly. Okay. Obviously nice to get the non-dilutive milestones through that partnership. I guess, how do you reinvest those then back into the company, whether it's on the manufacturing? Maybe if you could just touch on that quickly at the end here. Yeah. We are well capitalized, not only through the non-dilutive sources, but also through the very strong interest that we've seen in our capital raises to date. We're able by virtue of the strong cash position, we just reported $538 million on the balance sheet, cash equivalents as of March 31st. That puts us in a position to where we can invest not only in these broad multi-tumor clinical development programs for two assets with multi-tumor potential, but also invest in our own pipeline to come. As I mentioned, tip of the iceberg. There's a lot going on beneath the surface that we haven't really described, as well as to service the Lilly collaboration. You mentioned manufacturing. That's something we haven't talked about. I know we're running up against time. I'll just say that this has been a really, really important effort for us to ensure that we are in control of our own destiny by building our own manufacturing capabilities inclusive of isotope supply, final drug substance, drug product manufacturing, delivery to patients. All those things are areas of focus and priorities for us because we think these are the things are gonna enable us to have that, you know, significant patient impact that we're working to have. Yeah. Very good. Well, I think that's a great note to end on. I know we're at time here, but Matt, Akos, thank you so much for the conversation and thanks everyone for attending and your interest in Aktis. Thank you. Thank you.