I don't know if that was me. Hello, everyone, well, I'm Nick Varghese, I'm a Vice President on Tyler Van Buren's team. Welcome to TD Cowen's 46th Annual Healthcare Conference, if you guys haven't heard that enough already.
For the work that we've done together, looking forward to more of that, excited to share an update with you all as to what's going on with the company and what our opportunities are. I invite you to our website to explore our disclaimers. To start off, Aktis Oncology is a targeted radiopharmaceutical company working in the category that we're really very excited about as a large new potential category of anticancer medicines.
We believe that this is a category or modality that is approaching an inflection point, meaning that we have clear validation of the clinical benefit of radiopharmaceuticals as a category. We have clear commercial validation, a really strong uptake. Pluvicto is actually the best-launching oncology drug in 10 years since Ibrance. Strategic validation in terms of all the strategic activity and the robust deal flow that's occurred through advancement of these medicines for patients. That said, we believe that there is still a massive opportunity to inflect this category into something that's much broader than it is today. Of course, the entire category right now is based on programs targeting two targets, PSMA and SSTR2.
Aktis Oncology was founded initially and built to expand the benefit of radiopharmaceuticals to additional targets and therefore patients who are, as of today, not getting any benefit from radiopharmaceuticals. In order to accomplish that, we created and developed a novel platform technology around the use of miniprotein binders as the format for radioconjugates. We deliberately picked these because we felt that they had the right characteristics to deliver the right clinical benefit for patients, but also we felt had the ability that unlike other small binder types that would be have the potential to just hit a much broader universe of targets and therefore expand into these white space opportunities.
From my perspective, you know, the target space is wide open in radiopharmaceuticals, and we seek to deliver for patients benefit of this modality. From our capabilities, we've been able to bring forward now two lead programs. The first is AKY-1189, which is targeting Nectin-4. The second is AKY-2519, which is targeting B7-H3. Through these two targets, we believe we're gonna have really multi-indication, but also multi-disease area opportunities to intervene and really change standards of care. If you look at, you know, prior examples in oncology where you have that kind of profile and that kind of footprint, these turn out to be very large multi-blockbuster opportunities. If successful, we believe that that's the opportunity, at least for these two.
Again, this is just the tip of the iceberg for what we're bringing to the table, because we have an entire pipeline of agents behind these two as well. As we look ahead, we're focused on a couple things over the next one to two years. You can see, we're excited about the data that we've generated already for the lead two programs. We're looking to generate additional clinical data that would support further advancement of these molecules in the form of dose finding, safety, preliminary response data over the next one to two years for both of those programs.
In addition to that, in the background, our platform technology, our discovery team, and lead optimization teams continue to crank away and further expand and refine our platform capabilities. From that, we are looking to bring forward to give some visibility on two additional programs over the next couple years here as well. Then on top of that, of course, we're building the company, we're building a leadership position in the field. In order to do that, there's many other enterprise-wide activities that we're involved in, including, as you see here, building our own manufacturing facility. We already have a very high-functioning end-to-end supply chain for radiopharmaceuticals. It's working very, very well and as designed for a Phase I-B study, which is ongoing.
We're looking to further verticalize that by increasing our ownership of that end-to-end supply chain through our own facility. Of course, there would be more to come as we generate more data as well. In addition to that, we're also working over the next one to two years on an further expansion of our clinical trial footprint, which is a precursor to what we see as a large and broad global phase III trials to come. We're excited about a number of things and looking forward to continue to build this leadership position in the field.
This slide is designed to illustrate the opportunity we have and the ambition we have to extend the benefit of radiopharmaceuticals from what is today a relatively defined set of patients benefiting to a much broader universe of patients that can take advantage of the benefit of radiopharmaceuticals. You can see on the left-hand side, this is just a representation of the entire solid tumor market from our perspective. This is incident cases of solid tumors in the US, and it's broken up by tumor type. The, if you ask the question, where do radiopharmaceuticals map onto the broader solid tumor universe? You can see on the upper right-hand side, the approved products are really hitting some very defined patient populations.
Obviously, PSMA is expressed only in prostate, and SSTR2 is approved, only in a small indication in these GI tumors and neuroendocrine origin. It is being developed in other categories, but as of today, it's relatively narrow. I should also parenthetically add, of course, everybody knows, there's really quite a number of assets targeting these two spaces, and so the level of competition is really quite intense. Aktis is positioned entirely different. You can see in the lower right-hand corner here that where we're going after with first-in-class agents, where there's much less competitive intensity, we're first in class for Nectin-4, we believe first in class for B7-H3.
You can see that the footprint or the patients that we seek to serve, really fill out the wheel if you will, that the number of categories of patients who can benefit from this, really fundamentally is different than where the field is today. How do we do it, and what is the focus of what we're doing? We focus, as I mentioned, on miniprotein radioconjugates. This is a new and different architecture of a radioconjugate. You can see a figure that on the left-hand side that's a surface representation of an actual miniprotein radioconjugate. What you can see from this hopefully is that the size is actually really small.
You can actually see in the space-filling part of the representation that these are very small binders, right? You can see that the diameter here is something tantamount to a very small peptide. That gives it very nice properties like, for example, a very high tumor penetrance, which is important, we think, for being able to localize the isotope into tumors. Also on the safety side that by virtue of the size, these are very rapidly cleared through the kidney and out through the urine. What that does is the design feature is such that we can really spare the bone marrow and other unwanted radiation exposure to the periphery outside the tumor.
On the other hand, you can see hopefully from the, the shape of the, of the binder that these things have distinct three-dimensional shape. What that does, that enables like a proper, you know, protein-protein interaction, if you will, to a target and gives you very high affinity, where routinely in the picomolar and low picomolar binding affinity range, but also very importantly for radiopharmaceuticals, selectivity for the target. In addition to that, these are you can vary these, you know, in a very significant way. We have tremendous diversity in our, in our screening libraries, now more than 5 billion variants that we're able to bring to bear against every single target.
In addition to that, over the last one to two years, we've added a further capability beyond the 5 billion variants, and that is we're doing generative AI design, that enables us to get into a search space that's even beyond the 5 billion that we're screening with traditional methods. This is a really very powerful way to be able to prosecute multiple targets, you know, with a single effectively format of a radiopharmaceutical.
If we're successful, as so far the data we have is translating, as we would have hoped and designed, but if we're able to do that is the key unlock or enabler, to be able to really extend the benefit to not only broader patient populations, but also to be able to bring it earlier in disease, and expand the engagement from what has traditionally been a nuclear medicine space into a much more broader and deeper, and more commercially relevant, solid tumor oncology space. From that pipeline, you can see here, or from that technology, we have the lead two programs. I just wanna make a comment on AKY-1189, which is Nectin-4 targeted. That is in, ongoing Phase I-B, study called NECTINIUM-2.
Last week, we announced that we have received FDA Fast Track designation for that. It just illustrates that we're doing everything we can to maximize the speed and quality and depth and breadth of the programs that we have. You can expect us to pull every lever we can find to benefit patients and the programs and bringing them forward. We are enrolling the NECTINIUM-2 study. We have nine sites open at present and more to come very shortly. These are some of the top Phase I-B investigative trial sites in the U.S. We will continue to be enrolling this over, you know, throughout 2026 and accumulating data at various different dose levels.
We are also employing a Bayesian backfill design that would enable us to expand any dose cohorts of interest out to 30 patients each so that we can accelerate our dose finding and optimization. With that, we would expect to submit for presentation the initial cut of these data for a medical conference in early 2027. The second program, which has really narrowed the gap between the two, we've moved very quickly with this program, B7-H3 targeted AKY-2519. We described in S-1 the initial clinical imaging data we have in patients. Those data suggest that like the Nectin-4 program, we're able to get into tumors with relatively high uptake, and yet at the same time, have low in relatively brief exposure to normal tissues.
Those imaging data, we are preparing for presentation at a medical conference this year in the middle part of this year. We're excited to share not only the imaging data in various different tumor types, but also the quantitative dosimetry data that really informs us on the absorbed dose profile, both in tumors and in normal tissues, which is something we haven't been able to do before because of technical advancements. With that program, we are submitting our IND in the first half of this year for the Phase 1b dose escalation. We would expect that phase I-B dose escalation to start in the second half of the year.
If we're successful here with the clinical development, we think that there's a very significant patient impact opportunity here. What we're showing here with permission is an analysis from Boston Consulting Group that they presented last year at a conference saying that their point of view is that the therapeutic segment of radiopharmaceuticals they believe will be $6 billion-$9 billion by the end of this decade, but really significantly expanding beyond that into a base case, $25 billion-$35 billion market with upside to $60 billion depending on how many big tumor types that you can get into. This is a very significant opportunity in our point of view.
The field is wide open with respect to targets, and the key enabler, again, is being able to have the technology that widens the therapeutic index while hitting those targets that have not been able to be hit yet. We're excited about that opportunity and more specifically to us. You can see on this page, really the patient populations that we're pursuing are really very significant. You can see on the left-hand side, if I get you to the third and the fourth columns there, you can see the proportion of patients in each of those segments on the rows that are expression positive for these targets.
You can see that this is an enabler of moving radiopharmaceuticals from just prostate and a rare GI tumor to patients with bladder cancers, breast cancers, lung cancers of various different subsets, head and neck, colorectal, cervical, et cetera. Very significant multi-tumor opportunities here. Of course, if you look at the comps on the right-hand side of the page, you can see both Nectin-4 targeted agent like Padcev and a PSMA RLT like Pluvicto. These are multi-indication agents that have really very significant peak sales estimates from covering analysts. What we see on the left-hand side of the page for us is if we're successful, these are not only multi-indication drugs, but these are also multi-disease area drugs, unlike the ones on the right.
This is exciting for us to think of what the patient impact could be. It's not sufficient alone to just have portfolio in our view. We think it's really important to have the capability to deliver for patients. We have established a very high functioning end-to-end supply chain to be able to deliver our agents to patients. This, thus far, as I mentioned, is working as designed in our Phase I-B ongoing study. It starts with the upper left, this is like the CMC development, right? We own the CMC development portion of these molecules.
We have not only a chief technical officer who's been there and done that before, we've also built out a very robust team of seasoned radiochemists, radiopharmacologists, et cetera. We own the formulation, the product development, the process development. All that work is done in-house. We own the IP to it and the process and the trade secrets, et cetera. The miniprotein manufacturing, so this is the precursor, if you will, the cold conjugate. This can be outsourced. This is solid-phase peptide synthesis. This can be made in large grand batches, which really gives us years worth of material because we're in a microdosing paradigm here. That we can effectively stockpile the precursor.
You have the isotope, which is often a topic of discussion. The technology that we have is isotope-agnostic. We can really use any number of isotopes, and we have experimentally used many different isotopes. For clinical development, as you've seen already, our priority has been with Actinium-225 for the effector isotope. We have, we think, potentially industry-leading portfolio of actinium supply. We announced a couple years back, three commercial actinium supply agreements, since that time, we've signed multiple more in addition to that.
We've calculated the amount of actinium that we have access to through those that are already producing material, and what proportion we have access to, and it is well beyond what is already a very healthy demand on our side, as you can see in the upper right-hand side. Then lastly, we're working with a number of contract manufacturers for the last step. This is the chelation fill-finish step. We have a number of partners that are qualified in our IND. In addition to that, we are building our own site to do the final step manufacture as well. This has been the really the most important part is that you have multiple points of redundancy at every node of the supply chain.
That's what we've built, and the idea is that this is a scalable and capital-efficient way of reaching patients. Lastly, it's the team. Really, I think this is perhaps the most important part, is that the people that we have are really accomplished in their respective fields. They're resilient, they're problem solvers, they're leaders. Every one of us on the senior level have held leadership roles in big commercial companies in the past. But all of us are excited and engaged around the opportunity we have here for patient impact. You know, I mentioned the accomplishment. You can see here that the team combined has 14 FDA approvals previously, right? It just gives you a sense of the gravitas and capability of this team, and it's something I'm very excited about.
Further, we have some of the world's experts working with us. This is a subset of those that are on our scientific advisory board. You can see it's the who's who in nuclear medicine and molecular design and radiopharmaceutical development. We're privileged to work with these folks as we work for patients. To wrap up, this is really to me one of the most important points that really we find resonates with both our employees and those external, which is effectively under one roof, we have built an organization that has all the ingredients necessary to extend and build and grow our leadership position. Obviously starts with a very different platform technology that we believe is repeatable to generate multiple potential assets here.
From that, we have already lead programs that have the potential to really address very significant, large market opportunities. From those, we have imaging data supporting a reason to believe for each of them. We have a pipeline beyond that. We have a cornerstone partnership. We haven't mentioned it here yet, but we have a $1.2 billion discovery collaboration with Eli Lilly, which is something that we've disclosed in S-1 has already hit the first milestones. Going very well. As we talked about end-to-end manufacturing made only stronger now with our internal suite that we're building. We talked about the isotope supply and the other parts of the corporate structure that we think are paramount for building leadership position in the field.
I'll leave it here and maybe, turn it over to Nick for some Q&A.
Yeah. That's great. Thank you very much for the detailed presentation. If anyone in the audience has any questions, feel free to raise your hand and we can ask them. Let's get started. I wanted to start first with the actinium isotope supply because that's, I think pretty underappreciated. Can you explain how you were able to get out to this many suppliers and how you were able to secure all this? That's really not been seen across the field. Is this also sufficient for commercial supply? Like, as the suppliers build up product, would that work?
Yeah. No, this is an important question. You're right that, you know, isotope supply, particularly actinium, tends to be one of the questions that people who are newer to the field need to get comfortable with. I wanna start first with why actinium.
Mm-hmm.
First of all, I would add just taking a step back that like you see in imaging, you can use many different isotopes effectively for imaging, and we believe that in the treatment, at the end of the day, there will likely be multiple different isotopes you can use for treatment as well. It'll depend on the specific asset and the patient population, things like that. The reason that we prioritize for development initially, Actinium-225, is that we had two real goals. One was to maximize the efficacy benefit for patients, and with Actinium's four alpha emissions, it just expends the most energy in the tumor.
With that, it was also there's some clinical validation of the efficacy potential of actinium-containing compounds, like, for example, the clinical investigation work that was done initially with PSMA actinium.
Mm-hmm.
Very profound efficacy for patients. Secondly is we felt that, you know, given our sort of background in large commercial organizations in the past, we felt it important to be able to control, to the maximum extent possible, the supply chain distribution, and to be able to go global with that, right? We felt that Actinium-225 with the central manufacturing and distribution profile would enable us to scale and reach the most. That was really the purpose. Very early on, we had the foresight to go out to Actinium-225 suppliers early. It was even 2022, I believe, we announced the first three of those deals, and we weren't in the clinic yet, right?
We were actually still effectively two years away from the clinic at that point, yet we already signed those first two deals. We continued on from them, you know, engaging with others. You know, of course, there's the experimental work, there's the CMC development work. You have to get in front of it. Nevertheless, this is something that we've studied very closely, and what we've seen is that across the different production methods, whether it's generator-based production or linear accelerator or cyclotron-based production methods, that really all the methods so far are working. The generator-based material is the sort of gold standard up until now, right? The accelerator-based approaches are working, right? That's gonna be something that's gonna be important for the scaling.
Mm-hmm.
We have line of sight by virtue of our, you know, partnerships with a large number of these players. We have line of sight into exactly where they are with their process development, in some cases, their proof of concept and their early scaling. We're very confident that the material is gonna be there. You know, I'll give you an example. There's 1 supplier alone that if they're successful with their projections, and we don't see a reason to not believe them yet, then they alone, as a single actinium producer, we believe will be able to meet the demand of the entire industry. There's, you know, multiple suppliers here and multiple different methods, different geographies. We're contracted with pretty much everybody.
This is something that we are comfortable with.
Yeah.
Yeah.
That's great.
Yeah.
That's really great. Moving into the programs, since we have about five minutes left, we have to get to the programs.
Sure.
Starting with 1189 Nectin-4 targeting with Actinium. With the Phase I-B data coming early next year, what are your expectations for that? What are you looking for, to support, like, continued progression of this, and what did you see in the dosimetry data that's de-risking?
Yeah. Thank you for that. In the Nectin-4 program, again, we're super excited. We're by far and away first in class among radioconjugates for Nectin-4. We're the only Nectin-4 program under IND that's a radioconjugate. Let's take a step back. The dosimetry data we generated outside the U.S. in patients with multiple different tumor types, those data were initially presented in an oral plenary session of the EORTC-NCI-AACR Symposium about a year and a half ago. What those data showed was that we had high initial uptake in the tumors across all the five tumor types that we looked at. They weren't, you know, they were selected for Nectin-4 positivity. We had high initial uptake.
The time course data that we had only went through 48 hours 'cause that's what the capabilities were at the time. Even at the 48-hour mark, we had just as much drug in the tumor, from the, you know, visual inspections we had, even more so at three hours. We had evidence, preliminary evidence also for what we call hang time in the tumor, right? But at the same time, maybe the most critical part of the analysis was what's your absorbed dose in normal tissues because that's obviously patient safety is paramount, and that will speak also to your therapeutic index.
We're very gratified to see that in the key normal tissues, where the only place where you saw any uptake was in the kidney, as you would expect, it's renally cleared, but also in the bone marrow, which has historically been dose limiting for radiopharmaceuticals. For those data, what we're able to see is that the level of absorbed dose, so that's like the, think of it as, like, the area under the curve.
Mm-hmm
exposure to normal tissues was not higher than what's been reported and published for approved drugs like Pluvicto and Lutathera. That was very reassuring to us that we had likely a therapeutic index to work with, but at the same time, we had evidence that we're nailing the tumors, right? That was something that was exciting to us and exciting to our investigators, exciting to our investors, et cetera. With that, we've gone into this NECTINIUM-2 study. It's on ClinicalTrials.gov. You can see the full details there. This is really in Nectin-4 positive patients. Yes, there's a component of it that's bladder-focused, but we're also in parallel enrolling Nectin-4 positive patients from breast cancers, lung, colorectal, head and neck, and cervical.
There, we're excited to bring this forward. What we shared is that the first dose cohort of that had cleared at the time of the S-1 filing, and we continue to progress that through. We now have nine sites open. As I mentioned, we'll be enrolling those patients throughout this year as we climb that dose escalation curve. The part one of the study is what I'm describing, you know, really the goal there is to establish safety in a dose, right? As I mentioned, there's a Bayesian backfill design which enables us to, you know, pick at least two of those dose levels and expand the number of patients at those dose levels, which kind of accelerates our time to dose optimization and also signal seeking.
Mm-hmm.
Right? Obviously, initial preliminary response will be also important there. Also there's a part two, which is the expansion cohorts, which is when you more traditionally.
Mm-hmm
W ould look for the more definitive efficacy signal. Nevertheless, this is an important ongoing work, and we're excited to share the data when we're able.
We have a minute, but I need to ask you more questions. First, maybe you can answer these relatively quickly, first, what have you heard from your advisory board about the registration path, the accelerator approval? I know you've mentioned that a bunch of times, so if you can just speak a little bit to that would be great.
For the Nectin-4 program, as well as with the B7-H3 program, we've done several key ad boards, and these are the names that everyone I think would recognize from the podiums of ASCO and ESMO and the like. We've also had preliminary discussions with, you know, others, regulatory agencies, et cetera.
Mm-hmm.
The most logical thing is to initially to extend the patient populations we're in now, which is essentially the, like, second and third line setting.
Mm-hmm.
One of the things that we've heard repeatedly from the ad boards is that they aren't so keen to follow chemo with chemo or chemo and ADC or ADC and ADC.
Mm-hmm.
We've heard that many of the investigators wanna have us kinda jump the line, if you will, into earlier lines, in front of other ADC or the like. As a result, we believe that the, it's obviously everything is data dependent, but provided that there's the right signal there, it would be in the initial labels that we would seek and have. Obviously, we need to have the regulatory discussions, but the logical first step would be in the patients that we're studying in the phase I-B. Of course, you can imagine we're very ambitious. We've talked about patient impact multiple times. Really the maximum patient impact is in early disease settings-
Mm-hmm
W here you can really bend the cure curves, if you will. As you think about it longer term, that's clearly on our radar screen, and we are currently investigating opportunities to move into early-stage disease as well.
Mm-hmm. Yeah. Interesting. Since we're over, we like to end these with one main question. What do you view as the most underappreciated aspect by investors of the Aktis story?
The field of radiopharmaceuticals, as I mentioned earlier, is kind of approaching this inflection point, and not everybody is seeing it like ADCs from five years ago.
Mm-hmm
W hich is kind of where we are, right? There's multiple hallmarks of the RLT space that eerily resemble what was happening in ADCs, you know, five years ago. As I mentioned, ADCs are projected now to do $35 billion in sales, in just, you know, four years out from now as a category. You know, we see that as a large new category opportunity. I think one of the things where people think, "Well, if ADCs are there, then why do I need an RLT?" This is another piece of the underappreciated puzzle, which are these are completely orthogonal and unrelated means of cell kill.
Mm-hmm.
Meaning that the acquired resistance mechanisms are not shared. Therefore, regardless of what response rate that you deliver, that's gonna be incremental to what you can get, in additive to the patient journey. That's the most important thing from our perspective.
Great. Thank you very much for joining me, man. Thank you everyone for coming to listen to this presentation.
Thanks, everybody.