Hi, everyone. Thank you for coming to the Jeffreys Healthcare Conference. My name is Nora. I work in the investment banking team at Jeffreys. I'm in the healthcare group. And here we have Matthew Rodin, the CEO of Atkis Oncology. And I'll leave it to him now.
Thanks, Nora. And thanks to the entire Jeffreys team. It's a pleasure to be here and to present the story of Atkis Oncology. We are a targeted radiopharmaceutical company looking to transform the space by opening up the field of radiopharmaceuticals for patients who have no access to radiopharmaceuticals as of yet. Obviously, I'll be making forward-looking statements, and I invite you to our website to read our filings on potential risks and uncertainties. So to start off, Actis Oncology is an organization, as I mentioned, that, you know, the vision here and the goal is to really extend the benefit, the clinical benefit of radiopharmaceuticals to new targets that are expressed in patient subsets where there's no radiopharmaceutical treatment option. And so in order to do that, we as a team have systematically created all of the capabilities that we think you need to be a leader in the field. And so you can see here around the circle on the slide, multiple things that we've worked on and advanced and evolved over time that we think are all important to that goal of moving the needle for patients. And it starts, obviously, on the portfolio side. It started with our very different platform approach. We felt that in order to maximize the benefit of radiopharmaceuticals, we felt that it was needed to optimize the formats that are being used, the molecular architectures, to deliver radioisotopes safely to various different tumor types. And so we created a novel mini-protein radioconjugate platform, which we'll talk about a bit. And from that platform, we have thus far advanced two assets to the clinic. We'll talk about those today. Both of them have the potential to address multiple large market opportunities, different tumor types, which we'll talk about. I think it's certainly exciting to me to see really where we feel like we're at the foot of the mountain here with respect to an inflection point of radiopharmaceuticals becoming a large new category of anti-cancer medicines. With the initial two programs, we do have clinical imaging, proof of concept in patients, which provides a lot of excitement moving through dose escalation into expansion cohorts. We'll talk about the next steps with that as we go on. But in addition to the portfolio side, we felt from the beginning that it would be really important to be able to build the infrastructure required to deliver for patients. And so what am I referring to? We're talking about the manufacturing, the end-to-end supply chain. And, of course, with that, one component of that is access to the isotopes, the payloads that you want to deliver. And so we feel that we have built an extraordinary end-to-end supply chain. It has redundancies at multiple points of the end-to-end process and really a strong position on isotope supply, particularly in actinium-225, where we have announced some time ago three commercial supply agreements that varied across geographies and across production methodology. But importantly, since that time, we've signed several additional supply agreements that we believe is the industry-leading portfolio of isotope supply. On top of that, we're very well capitalized. We have, as of the last quarter, $538 million on the balance sheet, which gives us a capital runway into 2029 and through multiple inflection points, which I think is really important because it just gives you the flexibility to continue investing in what could we believe has the potential to emerge as the leader in the field. And so to illustrate the opportunity that we see and that we're working against, this slide shows really the opportunity and where our positioning is different than others in the field of radiopharmaceuticals. On the left-hand side, what you see is a representation of the total incidence of solid tumors in the U.S., and it's broken out by tumor type. And so it just gives you a sense of the size and the proportions. On the right-hand side, on the top, what you look at is, hey, how does radiopharmaceutical, how does the modality map onto the broader oncology market? And what you can see is it's really quite targeted. It's focused on PSMA, which obviously is expressed only in prostate cancers. And as of yet, SSTR2-targeted agents are only approved in that small little sliver at the five o'clock position of the wheel. It is being developed in other indications, but as of yet, it's still had relatively, let's call it, defined patient impact. Our approach has been to work in new targets where there's no radiopharmaceutical option. We are potentially, well, we're currently first in class position, potentially first in class at launch for a Nectin-4 targeted radiopharmaceutical and a B7H3 targeted radiopharmaceutical. These two are just the tip of the iceberg. We have several other assets in development. But as you can see here, these targets are expressed in multiple other tumor types where there is no radiopharmaceutical option. This just illustrates the differentiated positioning we have vis-a-vis others in the field. And so this is really core to our story. So how do we do that? We employed what we call a mini-protein radioconjugate platform technology. We built it from scratch ourselves. And so on the left-hand side is kind of why did we do this or, you know, what was our goal here? So obviously with radiopharmaceuticals, you're interested in RLT because you want to drive that efficacy that is, let's say, different than other modalities of cell kill. So what we're talking about is targeting radiation in the tumors. There's multiple other therapeutic modalities one can reach for in anti-cancer therapy. but there are very few radiopharmaceuticals as we mentioned that can deliver the kind of that can deliver the efficacy that we're looking for at the same time we want to do it safely right so you want to expand the the therapeutic index to the maximum chance you have and unlike other radiopharmaceutical approaches the goal here is to open up the tar the adjustable targets okay and so if we can do that we think that we're at the foot of the curve sort of like where adcs These were five to seven years ago, where format optimizations led to an inflection point in that modality. And so on the right-hand side, this leads us to why we picked and why we designed the mini-protein radio conjugates. You can see here a space-filling, sorry, a surface representation of a mini-protein, a real mini-protein radio conjugate. And you can see the red is the linker, and the black is the isotope payload. And what you can see here is that this is actually a very small binder. These are typically four to six amino acids, but they fold into a very compact little structure. And that very small diameter allows it to be, number one, very highly tumor-penetrant, number two, fast clearing from the plasma. And so those two things we think are important for efficacy and safety, respectively. But unlike other small-format binders like peptides, like, for example, Lutatherap, Plavicto or small peptide binders, this type of platform can be used to hit with high affinity and selectivity against a broad array of targets. Small peptide binders are very difficult to adapt to non-native peptide binding targets. And so this would enable us, we believed, in the beginning when we stood up this company, to really just broaden the impact of radiopharmaceuticals. So it's kind of a Goldilocks profile of the small peptide-like pharmacology, fast in, fast out, but also with the ability like an antibody to hit a broad array of targets with very high affinity. And so that was the game. What we've done is we've built our own proprietary screening libraries that are encoding for over 6 billion variants of these things, right? And so that obviously lends itself to high probability success. But on top of that, we're using the latest and greatest tools in generative AI where we're screening effectively billions of trillions of new sequences beyond that, and so this is a very powerful way of advancing new options for patients. So this page summarizes where we are from a pipeline perspective. Our platform technology has given rise to a whole portfolio. Our lead program is AKY 1189. It's targeting Nectin-4, expressing solid tumors. Our second program is AKY 2519. This is a B7H3 targeting radio conjugate. Both of these are in phase 1B dose escalation programs in patients that are expressing the target. And beyond that, as I mentioned, these two are just the start. We have multiple undisclosed preclinical stage assets that are on the come, and we do expect to name two clinical candidates early next year in addition to the first two that we have. We also have separately a discovery collaboration with Eli Lilly in which we're using our platform technology, that is the mini protein radio conjugate platform, to discover novel mini protein radio conjugates against targets that are outside of our target space, our focused target space, and at a certain stage of development we would hand it back to Lilly for them to fully develop and commercialize. And so far, you know, we've worked very hard to be a very good partner to Lilly. And in our S1 earlier this year, we did disclose that we have hit the first milestone of that So clearly, there's been progress, and that's trending in a very nice direction. We're pleased to work with them. In terms of the opportunity that we see here, just with the lead two programs, if successful, we believe that these have very significant patient impact opportunities. On the top right, you can see Plavicto and PADCEV are two benchmarks that we think about. These are single disease area drugs, but are approved in multiple indications. And when you have a multiple indication drug like Plavicto, PADCEV, you can get to mega blockbuster statuses. They are expected to do. What you see here are consensus peak sales numbers. If you look at our opportunities on the left-hand side, Nectin-4, B7H3 targeted agents, you can see that these are expressed not only in single disease areas but multiple disease areas and so now we have the opportunity to have not only multi-indication opportunities but multiple disease area indication opportunities and we expect to fully develop these assets to their maximum extent to maximize the patient impact and certainly commercial opportunity. As I mentioned earlier, it's been equally important for us since the beginning of our company build to be in control of our own destiny in terms of being able to have the infrastructure to deliver for patients. So it's one thing to have a portfolio of assets, but it's another thing to be able to actually get the drug product into patients on time. And with radiopharmaceuticals, there's obviously an on-time delivery piece of that, which is important. And there's very few organizations on the planet that have the operational capabilities that we have built. On the left-hand side, what you can see is we've built really an end-to-end supply chain that starts with the mini-protein, the cold conjugate manufacturing. I mentioned earlier the robust portfolio of isotope supply that we have. You put those together in a manufacturing process, which is the middle box. This is actually one of the key unlocks, is having the drug product manufacturing capacity that is not only through multiple contract manufacturing relationships, but also we have our own suite, GMP suite, that's up and coming and expects to be open later this year. And so this combination of capabilities, we have multiple points of redundancy at every single node of this supply chain from start to finish so that we have not only the backups to the main, but we have backups to the backups to ensure that at any given time that we can fully deliver for patients. So that's been important to us, not only, you know, operationally. Obviously, it's our goal to deliver these products on time and to enroll studies on time and to eventually commercialize on time, but it's also a key strategic capability that we have. As I mentioned, there's very few organizations that have the capacity or capability to do this. Okay. So let's turn to the programs. The first program is targeting Nectin-4s, AKY 1189, and what you see here is some clinical imaging data in patients, and I'll just walk you through a couple highlights. But first I'm just going to summarize and say the evidence that we have so far supports the idea that this radioconjugate in this format, mini-protein radioconjugate, can get into tumors, is retained in tumors, and is rapidly cleared from normal tissues, exactly the way one would hope. And so on the top row, what you can see on the top left, first is the bolded numbers, is the absorbed dose that's kind of an area under the curve of our drug, AKY-1189, in the kidney and the bone marrow. Why kidney and bone marrow? Because we're renally cleared, and so it's important to measure how much activity you're leaving in the kidney. In the bone marrow, because bone marrow has historically been dose-limiting for radiopharmaceuticals. And what you see is the numbers, you know, one way to contextualize the numbers is, first of all, it's in gray per gigabec administered activity, but that's done in that format in order to compare to what's been published for approved products like Pluvicto and Lutathera. And you can see that for the normal tissue exposure, obviously, you want lower is better. You don't want to impart radiation exposure to normal tissues. What you can see here is it's below the numbers, or I would better say not higher than the values that you've seen with approved products like Pluvictone and Ludothera, which are judged by the FDA, is having a favorable benefit-risk profile. So that was a really good starting point, and we felt that those values and the key normal tissues would enable us to dose up to active levels in order to really push the therapeutic index. On the right-hand side on the top is just the time activity curves that led to the numbers on the left. On the bottom, it's more about the tumors. So, on the left-hand side, what you can see here is a PET-CT image of AKY 1189 conjugated to gallium. With that, you can measure standard uptake value, or SUV max, in various different tumor lesions. What we're able to measure here across five different tumor types is very robust levels of uptake. These values, if you look in the literature, are consistent with responses to other products like Pluvicto, as an example. Generally speaking, the published thresholds that people talk about are high single digits or better. You can see here that we're anywhere from high single digits up to about 100 with central tendency in the 20s to 40s. And so these were numbers that we felt very much supported. This is initial tumor uptake, very much supported moving into real efficacy, safety-based studies. On the right-hand side, this is a SPECT-CT time course looking out to two days post-injection with AKY 1189 conjugated lutetium, and what you basically see here is very limited normal tissue uptake and some washout of the kidney. But what you also see is very sort of flat retention in the tumors. In fact, there's even more in the tumor at 48 hours than there is at three hours, according to these images, which are scaled to the first time point. And so we're excited by that finding because it really was visual evidence anyway that even though the initial uptake is high, that the retention is long and that that would correspond, in theory that should correspond to a heavy impact on the tumor. So all of these things taken together really supported the notion that the mini-protein conjugate is doing exactly what it was designed to do, which is land the isotope into the tumor to import that anti-cancer activity, but also clear out of the normal tissues without causing undue harm. So in addition to bladder cancers, which is what we were just looking at, we also looked at tumor uptake across a number of different tumor types, and you can see here patients with various subsets of breast cancer and colorectal cancer, and we have other data beyond these as well, just showing relatively robust uptake. All of the lesions you can see in the breast cancer patients in the thorax and around the thorax and in other metastatic sites, really bright uptake, SUV max values typically in the 20s and 40s, certainly what you would want to see, and similarly with colorectal cancer patients and others. This was very, very much supportive, the concept that this should be developed not only in bladder cancers where Nectin-4 is well known, but also in other tumor types where no Nectin-4 product is yet approved. And so to prosecute that opportunity, we have an ongoing Phase I-B study. This is called the Nectinium II trial, and we're currently in Part I, which is dose escalation. You can see here that we started a 4-megabequerel dose. We're dose escalating up to 12. This started later in 2025, so we're moving through the dose escalation curve. What we've said about this is that we're very much on track, very happy with the progress of this study so far, and that we expect to present data on this in the first quarter of 2027. So we're excited about this opportunity. The patients are in dose escalation, not only post-pads of bladder initially, but also patients who are Nectin-4 uptake positive across different tumor types, including triple negative breast, HR positive breast, lung cancers, and other tumor types as well. There is a Part 2 plan for this study, which is on the right-hand side, so once we backfill two doses in Part 1, we'll have a dose that we can then move forward into a dose expansion in specific tumor types, which would support, we believe, various registration paths where in which will be as aggressive as the FDA and the data allow us to be. So we're excited about that program. Everything is on track, and we look forward to sharing more information as those data SHIFTING GEARS NOW TO OUR SECOND PROGRAM IN THE CLINIC, THIS IS AKY2519, AND IT'S TARGETING B7H3, WHICH IS TO US AND OTHERS, OUR ADVISORS AND CLINICIANS, A VERY EXCITING TARGET, AGAIN A FIRST IN CLASS OPPORTUNITY FOR A RADIO CONJUGATE HERE. WE JUST SHARED DATA THIS PAST WEEK AT THE ASCO ANNUAL MEETING AND LOOK FORWARD TO SHARING A FEW UPDATES HERE. So again, what you're looking for in a radioconjugate is the ability to put drug in a tumor and have as little normal tissue exposure as possible. And so these are data that were in the poster presentation presented by Prof. Mike Satayi from Numeri, South Africa. What you can see here is one patient case study that really illustrates very nicely what this molecule is doing. On the next page, I'll have more aggregate data across a number of patients. But just to start, on the upper left, you can see a PET CT image. This is just a snapshot shortly after administration, and what you see here is already immediate uptake in tumors along the clavicle and certainly throughout the abdomen and down to the prostate bed. That's all tumor activity that you're seeing. As you would expect, and you see this with any radiopharmaceutical, in the first couple hours you do see some as it's perfusing through the body in a couple passes you do see some normal tissue exposures including in the salivary glands the liver spleen and some kidney and so that's informative thus far but what you really want to do is look at the time course get the time activity curves and understand what the area under the curve is and so that's section b the spec ct images, where this time we use AKY2519 conjugated to low-dose lutetium 177, and this enables you to image patients over a six-day period, okay? So you inject the dose, and then you do the first scan three hours later, second scan a day later, third scan six days later. And what you can see is immediately the normal tissues, including the salivary glands in the liver, are immediately retreating, okay? And so we believe this is due to perfusion, not target-related activity, because the target-related activity is in the tumor, and what you can see is the long retention out to six days. And so in particular, if you look at the 144-hour time point, six days post-injection, really all that's left is the tumor, and that was something that was exciting for us. So the machines have the capability of quantitating this. This is a standard methodologies being used by the Numeri team. You can see in C and D below, these are axial images of those tumors that were identified. There's four tumors in particular that are identified for measurement. And then on the top right-hand side, what you can see is a histogram. So what the histogram is asking is, for any given dose, what proportion is going to various normal tissues and what proportion are going to the four tumor lesions that you looked at. And you can see very clearly that the normal tissues, very little of the dose is actually going to the normal tissues. You can see a great number of normal tissues were assessed in this. There's probably 15 or 20 lines in there. You can see, and all of them were more or less along the Y axis, which is exciting to us. In contrast, you can see much more of the proportion of the activity was over on the right-hand side on the tumors, and each of those lines refer to or correspond to the four tumor lesions that were tracked in C and D. So then this gets quantified under F, and what you see here was very exciting to us again because not only was the dose coefficients calculated in gray per megaback of actinium-225 activity was anywhere from 0.1 to 0.3 gray per gigaback administered to the normal tissues, but whereas it was anywhere from 2.4 to 4.8 gray per megaback in the tumors. There's also the opportunity to look at something called partial volume correction for tumors. This is special for tumors because there's not a pre-existing phantom that enables you to quantify in tumors because tumors are inherently, you know, they don't have a uniform shape. And so they do effectively like a 2D measurement, and then there's a partial volume correction that looks at a way of assigning three-dimensional activity. And so it's a bit of a sensitivity analysis. You can see that for the tumors, that means that the activity could be anywhere from 2.4 of 4.5 for the bony disease, and the periodic lymph nodes anywhere from 3.8 to 7.5 gray per megaback administered activity absorbed in the tumor. And so we're excited about this because obviously to us and our advisors and clinical experts with whom we're working, this suggests really a wide therapeutic index to step into as you think about dose escalating, which we'll come back to in a moment. These data here summarize the aggregate data across the patients that were assessed in this dosimetry analysis. You can see in the top left, again, the dose coefficients are similar to the individual patient I just shared. In the kidneys, as not surprising as the organ of clearance, is the one that, again, we would look at as the expected highest activity, and yet that's right in line with what you see with approved products like Pluvicto. And so this, we felt, very strongly supports moving into dose escalation. On the right-hand side, this is, again, not just a single patient anymore. This is multiple patients where there's activity in tumors, and you can, again, see the amount of activity being deposited in the tumor is dramatically higher than the amount of activity that we're seeing in normal tissues. So this is all, again, very exciting for us as we move into the next step. So moving beyond prostate, we asked the question, and this is in collaboration with Prof. Ken Herman in Essen, Germany. We asked the question, how many other tumor types are we going to see uptake with AKY2519? And you can see here that he was indeed able to recapitulate a lot of the prostate cancer data that we saw elsewhere. But we also saw a really nice uptake in patients' lesions with newly diagnosed adenocarcinoma of the lung, which is the second patient you see here, clearly across lesions, relatively high uptake with 17 to 22 or so SUVs. with small cell lung cancer, which is typically a target for B7H3 targeted agents, but also in rectal cancer and other patients with CRC as well. And so these are a couple of patient examples. There's more in the posters that are now on our website. But long story short, the punchline here is that in aggregate, these data with the PET-CT uptake supports the development not only in prostate but in multiple other tumor types. And so to that end, we have two trials, one ongoing and one planned, for exploring AKY-2519 in clinical development. You can see here the Bactinium-1 study, which is in metastatic castration-resistant prostate cancer. This study is now open and enrolling. And you can see here, it's really broken into two cohorts, so it's almost like two studies in one. At the behest of the prostate cancer experts on our advisory board, we did open not only the Plavicto experienced cohort, which is what you would expect, but also they really urged us to open the Plavicto Naive cohort as well because they were very excited about the dosimetry findings that we had, and so this is the plan here. We have here only three dose escalation cohorts or three dose levels, I should say, and that That should enable us to identify a dose relatively quickly because two of the three-dose cohorts can be backfilled up to 30 patients each. And so we're excited about this because the prostate community has given us terrific feedback. And just to go back two pages, I just want to highlight one additional thing that really underpins some of their excitement. I talked about the limited exposure to normal tissues, but one of the things that really stood out to the experts in the field was actually the salivary gland dose. And so what you can see here is that the dose coefficient was 0.13 gray per megabect. And if you were to give like a, you know, a full, illustratively a full course of therapy at eight megabects times four cycles, that turns out to about four gray total, right? And so that is very ‑‑ I invite you to look up the dosimetry data for Plavicto. You'll see that this is dramatically lower than the salivary gland dose that is administered or I should say delivered to patients receiving Plavicto and other PSMA targeted agents. So we think that this is ‑‑ or the feedback we've gotten from the experts is that this is a really key point of differentiation. So the second study that we have now cleared regulatory review on, this study is in startup mode, is expected to start enrolling the second half, is the Bactinium-2 study, and this is a non-prostate basket study. It is going to focus to some extent on patients with lung cancers, not only non-small cell but also small cell, and will also enroll other B7H3 positive tumor types, and you can see here, starting at 6, going to 9, some more dose escalation schema with backfill that will enable us to inform a dose moving forward. In terms of upcoming milestones, we've talked about this I think already, but the Nectin 4 program, we expect to deliver the first of the data in the first quarter of 2027, but of course there's going to be several following presentations henceforth from there. For the B7H3 program, we've already hit a number of key points already this year. The next one is to start the second study, and we have committed to delivering data in 2027 for the prostate study. We also talked about the manufacturing site. The manufacturing site for Actis is expected to be open later this year. Again, a key corporate goal for us, as well as advancing two additional clinical candidates early next year. So, with that, I want to thank you for your time and attention, and I'm happy to take questions offline. Thanks very much.