Hello, everyone. Thanks for joining us. My name is Jonathan Chang. I'm part of the Leerink Partners Equity Research Team. It's my pleasure to host the team of Aktis Oncology. We have with us today President and CEO, Matt Roden. Thank you very much for joining us.
Thank you, Jonathan. It's exciting to be here. Thank you for the invite and for the work we're doing together.
Great. Would you like to first briefly introduce the company?
Sure. Thanks. Aktis Oncology is focused on targeted radiopharmaceuticals and really transforming the category to a large new category of anti-cancer medicines. We recognize the clinical benefit that's accrued to patients who have been treated with existing approved radiopharmaceuticals like Pluvicto and Lutathera. We're excited by the profiles and the patient impact of the modality, but we're keen to figure out a way to extend that clinical benefit to patients that have no radiopharmaceutical option as part of their armamentarium. In order to do that, we felt that we had to reinvent how radiopharmaceuticals are made.
We think of it in this way, sort of like where ADCs were about five years ago, where you had a couple approved products, but there was some format optimizations led by like, for example, Daiichi Sankyo and others, that really expanded the therapeutic index of ADCs and led to an explosion of the number of assets and the number of opportunities for patient impact. We see the radiopharmaceutical space kind of coming into a similar inflection point, where from our perspective, it's a total white space opportunity where there's only a couple approved medicines and the target space is just wide open. What we did is we went about reformatting radiopharmaceuticals. We used a novel way of targeting tumors for radioisotope delivery.
We're using mini-proteins, which are a small folded polypeptide binder, that we think has all the right characteristics to be able to deliver a high dose of radiation to tumors, but also at the same time, clear out of the periphery so that you minimize unwanted long circulating radiation exposure in normal tissues. Where it differs from other small formats like peptides, macrocycles, things like that, is that ours is the smallest binder that has actual three-dimensional shape. What that enables us to do is just expand the number of targets that one can prosecute with a binder format like this.
In other words, what we're seeking is sort of like an antibody-like ability to hit a broad array of targets with high affinity and high selectivity, but with the pharmacology of a small peptide that would get into the tumor, it would hopefully internalize into the tumor, which is what we've observed. If it's not in the tumor, then you basically clear it out through the kidney and into the bladder, and you pee it out in a couple of hours' time. That just minimizes the systemic exposure, and in particular, was designed to be bone marrow protective. As we all know, the bone marrow has been dose-limiting for radiopharmaceuticals to date. That was the profile that we're seeking.
We then set about using this miniprotein capability to screen against several targets where, that are expressed in large tumor types where there's no radiopharmaceutical option. For example, our first program is targeting Nectin-4, our second program is targeting B7-H3. Each of these targets are expressed in these relatively broad, large patient populations that are being treated with other modalities, but There's no radiopharmaceutical option for these patients. We felt that being able to bring forward a molecule can deliver an isotope like Actinium-225, which is what our highest priority is for clinical development. To be able to do that safely and effectively for patients would be an important addition to the armamentarium for fighting against cancer.
Obviously, there's other options, things like chemo, ADCs, even emerging TCEs and some other modalities. We felt that this would be clearly at minimum additive because the mode of cell kill is non-overlapping or the resistance mechanisms are non-overlapping with these other mechanisms of intervention. At minimum, it would be additive. If we do it really well, and if the profile translates really well, it could become a central part of the armamentarium, not only in metastatic disease, but potentially in early disease, where there's the opportunity to really bend the cure curve. We felt that this is a really important positioning. We are very uniquely positioned among radiopharmaceuticals in that we have this, you know, addressable target space, which is bigger, wider, than others.
Also alongside that, a very important part, which is the portfolio of what we're bringing forward. We've also built a second leg of the company, which is the infrastructure, right? This is an end-to-end supply chain. It's really our ability to reach patients, you know, in, you know, with a modality that's going after large patient populations globally. We wanted to be in control of our own destiny, and so we've built our own end-to-end supply chain capabilities. It starts with the CMC piece, which we're entirely in control of. We do all of the work in-house. We own the entire process of, you know, formulation, process development, product development. Have an entire team of seasoned radiochemists and radiopharmacologists that are doing the work there.
Once we land on the, on the right process, we can then tech transfer that out to a contract manufacturer, that follows our instructions, follows our documentation, our SOPs, et cetera. We can then qualify them and then validate them under INDs. That's the process, you know, there. We are also to add to that and to further strengthen, which is already a highly a resilient supply chain. We are now currently working to open our own GMP manufacturing facility that should be open by the end of this year. That would further verticalize our ownership of the end-to-end supply chain together with our partners. We're never gonna give up our partners. They're a critical piece of the puzzle because as Novartis has taught us, you can't just live with a single site of manufacture.
You have to have multiple sites of manufacture, even for central manufacturing as we do. We intend to use not only our own sites of manufacture, but complemented with those contract manufacturers that are qualified under our INDs. We're excited about that. Next up, we also have a very important discovery collaboration with Eli Lilly, that was a deal struck in 2024. They were able to see our entire preclinical data package for, at that time, the Nectin-4 program, which got them excited about the potential for miniproteins.
We, they wanted to get access to our discovery capabilities and development capabilities, so we struck a deal whereby we do the work to create molecules, novel miniprotein radioconjugates that are focused on target areas outside of our own wholly owned pipeline, and where they are, they have the rights to then take over clinical development and commercialization. Of course, there's all the downstream economics that come with that. That's been a very productive collaboration thus far. We disclosed in our S-1 recently that we had already hit the first milestone in that collaboration, and that occurred ahead of schedule, well ahead of the jointly agreed research plan. That's been an important part of the story as well.
Lilly has no rights outside of the discovery collaboration. They don't have any rights to our lead programs like Nectin-4 or B7-H3 or the other wholly owned pipeline programs that we have. They have been, you know, a terrific partner and to the point that they were big participants in our IPO as well. We're excited about that. Lastly, I'll just mention, one of the things that's, you know, most important to us is, and I kind of alluded to this particularly in the, in the infrastructure supply chain piece, is that we're somewhat uniquely positioned in that we're sort of, we have all the ingredients we think we need to lead in the field of radiopharmaceuticals. We have novel platform technology.
From that platform technology, we have lead programs that have achieved imaging proof of concept. Those are you know, addressing large segments of the solid tumor market. We have this cornerstone relationship with Lilly. We have end-to-end supply chain that's being made even stronger with our ongoing manufacturing build. We have industry-leading actinium supply. It's one thing I didn't mention earlier is that we do have, we've announced publicly three actinium supply deals, but in reality, we've also disclosed that we've signed several additional actinium supply deals. We think that this gives us a really strong position and portfolio to deliver for patients.
Lastly, we have a really strong balance sheet, really strong investor base, and a leadership team, last but probably most importantly, we have a leadership team that is very accomplished, all with big pharma experience in the background, but people who wanted to build something special, something different, operate in a different way, really with the patient in mind, that's what's been so exciting about this opportunity.
Great. Thank you for the intro. I was gonna ask you about your secret sauce, but I feel like you guys have touched on that in multiple levels already. Maybe we'll skip to your lead program, 1189. This targets Nectin-4. First, why is Nectin-4 a great target for your platform?
We think that Nectin-4 is a great first target for us. We're very excited about the patient impact opportunity here. The first thing is that it aligns to our vision. We're trying to open up the field for radiopharmaceuticals in patients that don't have access. Nectin-4 is expressed not only in bladder cancer, which everybody knows, but it's also expressed at relatively high levels in a very high proportion of patients with breast cancers, lung cancers, cervical, head and neck, even colorectal cancer in a significant chunk of those patients as well. None of those patient populations have a radiopharmaceutical option. We think this is a great first place to go because it is expressed broadly and with high specificity in the tumor versus normal tissues in really all of those histologies.
Secondly, Nectin-4 is a clinically validated target by Padcev. There's already this sense that if you can hit the target, then you should see an effect, right? We're excited by that, and it certainly we felt as we were developing it, even as an early company, that we were avoiding stacked risks in the company, that we were deliberately trying to isolate what risks we were handling. That was format risk initially. Now we have data that really supports the format as being a validated way to deliver a radioisotope. We just can't wait to get through the dose escalation and be able to deliver some updates on that.
Great. How do you see 1189 positioned in the competitive landscape? I mean, you mentioned Padcev.
Yeah.
Probably the notable player there.
Padcev is obviously approved in multiple indications in bladder cancers, both in metastatic setting and now in earlier disease settings. Really important intervention for patients, and yet, as you see with any anticancer drug, not everybody's responding. Initially, our approach is gonna be in the post-pembrolizumab Padcev setting. You can see on ClinicalTrials.gov that our Actinium-two study, which is our phase I-B dose escalation and expansion cohort study, is focusing among others on that second line urothelial setting. In this case, there's really no standard of care following the failure of Trodelvy in the later line setting. There is this kinda gap in the treatment paradigm that the KOL ad boards have suggested that we should step into.
We're very excited about that. I would also add that, vis-a-vis, you know, we're not the only Nectin-4-targeted agent in the world outside of Padcev. There are other ADCs and other modalities that are looking at that target. What we've heard from clinical investigators is that based on the different mechanism of action that they're interested in slotting us in relatively early in that mix, because of the different mode of cell kill and the non-overlapping, you know, chemo-based intervention.
We think it's a really important, as I mentioned, and minimal, additive piece to the armamentarium, but we do think that, as we further develop, and obviously the first indications are going to be in that sort of second line setting, that, there will be other, and broader, treatment opportunities in earlier lines as well.
Got it. You've previously disclosed some imaging data for this program, what would you say are the key highlights from those data?
Yeah. In the 2024 Triple Meeting, we had an oral plenary session where our initial human imaging and dosimetry analysis was presented by Professor Mike Sathekge. He's a global, internationally known key opinion leader in the field of nuclear medicine. What those data showed. He did imaging analyses in patients with 5 different tumor types. In those tumor types, we saw uniformly high initial uptake in tumors as measured by standard uptake value max, SUVmax, which is a normal way of looking at tumor uptake initially.
Those numbers generally range from about 10-100, which is relatively high in terms of uptake relative to what, for example, what we know about Pluvicto as an example. It screens well against that, and it also screens well versus what's been published by, for example, Michael Hofman and others around the minimum requirements for activity for radiopharmaceuticals. We're excited about that. Most importantly, though, from a patient safety perspective is we did the normal tissue dosimetry to try to get a handle on how much dose could we give and give safely for patients. The dosimetry analysis is a way of measuring what is the total absorbed dose, you know, that you hit a normal tissue with. It's kind of like an area under the curve analysis.
With that, what we saw are numbers that were published and presented there that showed that the impact to normal tissues was not higher than what has been published or in the product inserts for approved radiopharmaceuticals like Pluvicto or Lutathera. What that suggested to us and our investigators is that we would have a therapeutic index that we felt that we could step into. In other words, it suggested evidence that we would have the opportunity to dose to relatively high activity levels for patients safely. Given that we are renally cleared, it's important to look at the kidney exposure. Those numbers were, you know, certainly exciting to us and exciting to the investigators.
At the same time, the bone marrow. Remember, this is designed to be bone marrow sparing. We saw a very, very low uptake in the bone marrow, so in the blood and bone marrow. That was also, I think, important because that, more so than anything else, that's what gives you the therapeutic index. If you look across the space of targeted radiopharmaceuticals, it tends to be the bone marrow that is dose limiting. That was exciting for us. The summary of what we learned was, hey, the suggestion that we could dose to relatively high activity levels, and if we did, there's evidence of uptake and some retention in those tumors that we could measure at least through 48 hours.
If you compare that or combine that, I should say, with what we know from our non-clinical data, we have evidence in animals that the retention level or the retention time is really very long for assets in tumor models. We're pretty excited about all the pieces are kind of in place as a reason to proceed with this very aggressive phase I-B dose escalation that we have ongoing now.
Got it. When could we get the next data update for this program? What could we learn at that update?
Throughout this year, we'll be in dose escalation. There is a component of the dose escalation study that's a BOIN backfill design. What that means is that when there's a reason to want to explore further two dose levels, then you can expand those dose levels out to 30 patients each. It's a way of really getting at this question of how do you optimize dose as soon as possible, and how do you get to a signal detection as soon as possible? That's built in now, so we should be able to start to get in this year into that BOIN backfill segment of the dose escalation.
We intend to then be in a position to be able to present those data for publication or presentation, I should say, at a medical conference in the first quarter of next year. That should be as we've described, a relatively substantive update of the dose escalation data that we have to date. As with any first disclosure of dose escalation, there's gonna be some variance between the level of follow-up, right, from low dose to high dose, et cetera. We are looking forward to being able to show those data at that time.
Got it. Maybe switching over to your second program, 2519, which targets B7-H3. Why is B7-H3 a great target for your platform? How do you see this program positioned in the competitive landscape also dominated by ADCs?
Yeah. B7-H3 we're equally excited about. This is a really, I think, awesome target for radiopharmaceuticals as well. Like Nectin-4, I should say Nectin-4 or 1189 is the only Nectin-4 targeted radiopharmaceutical under IND, and it's been so for now several months. We have a really sizable lead with respect to any other Nectin-4 radioconjugates. With B7-H3, there's a little bit more competitive intensity, but we still believe we're the first ever to do a human image with a B7-H3 targeted radiopharmaceutical. We feel that we're in really strong position to have potential to emerge as first in class there as well.
B7-H3 is expressed at relatively high copy number in a number of important tumor types, including lung cancers, including some underserved patient populations like squamous cell, non-small cell lung, as well as several other tumor types, including prostate cancers. Prostate, obviously, it's hard to say that there aren't RLT options in prostate cancer with Pluvicto being approved there and doing very, very well. This is a totally different target, and we intend to bring a different isotope to bear with Actinium-225. Further, we think that there's room to further expand the RLT benefit in prostate cancer patients by having a non-overlapping toxicity profile.
In particular, we're keen to see whether or not we can bring across with B7-H3 an RLT that can safely deliver actinium, but also spares the salivary glands, which is very debilitating to some of the patients who take Pluvicto. This is kind of a wide-open space, high patient impact potential. What we shared in our S-1 was that we had preliminary human imaging data that showed, like Nectin-4, we're able to get good tumor uptake initially in the various different tumor types that we looked at that were B7-H3 expressing. Also that there was relatively quick washout from normal tissues. That again suggested to us that there would be a nice profile to take forward into a dose escalation.
We intend to file that, even though we have the imaging data now, we intend to file for IND in the first half of this year, and that would put us in a position to start the dose escalation. Again, a big, robust dose escalation study in the second half of this year. Also, we intend to present those imaging and dosimetry data from the B7-H3 program at a medical conference in the middle part of this year. That I think will be an important maybe milestone to just see how we're doing with the B7-H3 program and what that profile looks like and how that translates. We're excited about that.
Got it. What could investors learn with the imaging data that we can expect this year?
The B7-H3 program, again, it's expressed in prostate, lung, and other tumor types. We have said that we're gonna show the tumor uptake, general biodistribution in various different tumor types. Specifically within the prostate population, we're gonna look for a couple things. Number one, concordance with uptake versus PSMA. Number two, just the dosimetry, you know, in other words, how is it doing in the normal tissues? How much of that therapeutic index can one infer from normal tissue uptake? For the first time, the sites now have the sites that we're working with now have the capability to do tumor dosimetry. We expect to get a read on the tumor dosimetry for the first time in our platform.
Those are the various things we're looking for. I think overall, we're looking for a robust discussion around how the imaging by distribution dosimetry data can translate as we get our phase I-B up and running.
Got it. What could the development strategy for this program look like?
Because B7-H3 is expressed in a number of different important tumor types, we're keen to, again, maximize the clinical benefit and patient impact of this program. You can imagine we're thinking about a clinical development program that captures the size of that opportunity. B7-H3, as I mentioned, is expressed in lung and various other solid tumors. Prostate, I'm gonna hold off on the side for a second. There's a, you know, clearly a path forward for selecting patients that are uptake positive for B7-H3 in various different tumor types, and that's one of the angles we're going after. Separately for prostate, obviously prostate is an important segment. There tends to be a non-overlapping group of physicians that are managing prostate cancer patients.
We are thinking carefully about how to ensure that we can prioritize development not only in prostate, but also in lung and other tumor types. It's a big, ambitious, broad program, but it's meant, like the Nectin-4 program, to have the expansion cohorts that would enable us, and BOIN backfill design, that would enable us to move quickly into potentially accelerated approval pathways in various different settings. In other words, the phase I-B is meant to shoot off or to give rise to several parallel accelerated approval opportunities.
Understood. Let me check with the audience, see if there are any questions. How should we be thinking about targets, and programs beyond 1189 and 2519?
Again, with the sort of vision and goal of opening up the space, like I said in the beginning, this is a white space opportunity. The target space is wide open for radiopharmaceuticals. You can imagine we're thinking across all of the various different tumor types that have no radiopharmaceutical option and looking for all the targets that could, you know, help us locate the radioisotopes in those tumors. We've used a blend of like what you saw, you mentioned the ADC presence for both Nectin-4 and B7-H3. That's a target-rich environment to think about where there's other clinically validated targets, but that's not the only thing that Aktis is doing.
We also have work streams looking at various other tumor targets that we think will emerge as the, you know, the next important next wave of targets for direct tumor killing approaches. It's really a blend of, let's say, clinically validated and known targets and some that are less known, but we think have at least as big of a patient impact opportunity. What you see with Nectin-4 and B7-H3 is really the tip of the iceberg because we have a whole, you know, wave 2 and wave 3 of assets behind. We're very keenly looking forward to sharing more information as it's available.
Understood. You mentioned the Lilly partnership, in your intro remarks. How are you thinking about the business development opportunities, from here?
Business development is part of our fabric. We've done innumerable deals to really build the business to what you see it today, and we will continue to do so. Business development is gonna be an important part of any biotech growth cycle, right? There's multiple different ways to go about it, whether we're talking about sharing of capabilities, whether or not we're talking about technology access, whether we're talking about specific assets. One thing I would mention is that with our lead programs, you know, AKY-1189, AKY-2519, it's really important to keep the key economic rights to these, right?
What we won't do is do like a major partnership where we'd give up the lion's share of economic rights without some sort of more meaningful, sort of payback to the shareholders. We are very focused on shareholder value creation, and so we're looking for ways to maximize the long-term growth opportunity for the company, while also maximizing the patient impact of these of these medicines. Lastly, I would just add that, look, all of us have Big Pharma backgrounds. I used to run corporate development at a big company, so we're not naive to the opportunities here. We also are very respectful of the clinical development and commercialization capabilities of the big companies out there.
There's certainly ways of hitting win-wins when it comes down to it, to really maximize the speed and the impact of the that these medicines can have for patients.
Understood. Maybe just last question from me. How should we be thinking about your cash position and runway, and where is that, you know, relative to the development plans that we've discussed?
Yeah, this is a really important point. Earlier this year, we were able to complete our initial public offering of stock. We raised, well, $240 million in net proceeds. $340 million. Sorry, I misspoke. $340 million in net proceeds. That was on top of, you know, the last quarter that we reported was the third quarter of 2025, and there we had almost $250 million on the balance sheet. Pro forma, you know, there's a significant number there, and that would give us cash runway, we're currently projecting into 2029.
If you think about the clinical development plans that we've talked about for Nectin-4, B7-H3, that would give us runway through multiple, various data points for each of those programs, not to mention additional pipeline programs to come. We have a lot of flexibility with when and how we raise additional capital. We certainly are interested in continuing to work with investors to continue to grow what is really, we think, a very significant opportunity.
Understood. Thank you very much for taking the time. We appreciate it.
Thanks a lot. Thanks for having us.