Aktis Oncology, Inc. (AKTS) May 13, 2026 Conference Transcript

All right, great. Maybe we can get started, I think we're at the top of the hour. Thanks for joining this session with Actis Oncology. My name is Alex Stranahan. I cover Actis and SMID Biotech at Bank of America. And very pleased to be joined by Matt Rodin, Chief Executive Officer of Actis. And Akos, I'm going to try the last name, Zibri, Chief Medical Officer. I think I was in the ballpark. Thanks, guys, Akos and Matt, for being here.

Yeah, thanks for having us, and 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. But 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 mini protein 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, Plavicto, 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 Actis, we had the vision, along with others in the field, that radiopharmaceuticals, targeted radiopharmaceuticals, could be a large new category of anti-cancer medicines, right? And so it started with the new renaissance in the field with the emergence a few years ago of what is now Pluvicto and Lutathera. And 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. And so if you could shorten the circulation time by having molecules that leave the body quickly, that 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. So we're excited to see the emergence of Clavicto 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 antitumor effect. What we were interested in doing, to your point, with the mini-protein 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. So to accomplish that, we built this mini-protein radio-conjugate platform. Mini-proteins were selected intentionally because they have the properties that we felt would lend itself to that fast-clearing, bone marrow sparing profile. but 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, but 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, but unfortunately, they are not really effective binders against many different targets in the target universe that we care about biologically. And so 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 effinine selectivity. And so that's what we felt the mini proteins were likely to deliver. We built the platform. And now we're screening, you know, we have libraries that we've 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 now 6 billion variants across about 100 different scaffolds or protein folds. And 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. And so 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 B7H3 program. Those data for the B7H3 program will be presented in a couple weeks at ASCO. We previewed that to some extent in our S1 earlier this year. But 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. And maybe one more high-level question, and then I want to 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 mini proteins, that unlocked a much larger opportunity. So 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 S1 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, and 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. And so that has really expanded, right, and ADCs are very well known and understood in terms of the opportunities that exist there. So, radio pharmaceuticals, I would say, are in a similar position as ADC's five years ago, where, as you mentioned, a couple approved products, clear clinical validation. You also have clear commercial validation with Pluvicto being the best launching oncology drugs since iBrand. So, that's about a decade that passed. That's how far back you have to go to see an 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. So now the question is, how do you make it just bigger? How do you open up those white space opportunities? And that's what Actis 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 neptin-4 and the second targeting B7H3. 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? So Nectin-4, B7H3, these two programs for us are really just the tip of the iceberg of what Actis 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 radio conjugates against targets outside of our scope.

Great. And 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 1189 this is your nectin 4 targeting radioligand therapy this is in phase 1b 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, a few very high nectin-4-expressing tumors, lung cancer, CRC, cervical, urethral cancer, which is probably the most de-risk. Maybe you could just walk us through sort of the backfill design and the dose expansion, and escalation in sort of, you know, the number of patients and just the design probably of the study.

Sure. I'm going to make some opening comments, and Akash will add on the clinical strategy here. So 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. So the thinking is, if you can hit it effectively, that you should be able to see anti-cancer activity. And so we are mindful of the fact that the leading compound here, which is PADSEV, commercialized now by Pfizer and others, is really focused on urothelial carcinomas or bladder cancers. But 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. So 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. So we've shown that in our previous presentations and so the the clinical development plan that we've set forth is a focused on on bladder obviously as you mentioned uh clear uh proof of concept exists for the target in bladder cancer but also enables us to uh really pursue opportunities outside of that so uh question you want to talk about the the trial designs that we have there and what we expect to see yeah happy to and that study the nectinium 2 trial has been um under ind for about about a year now right We cleared the IND last year around this time.

And it follows a Boyne backfill design. So it's dose escalation under the Boyne principle where we tend to do three to four patients per dose level as we move up through escalating doses. And then 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? And we can do that in two-dose levels. And 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-PAT-SF-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 and you know obviously you've guided to a 1q 27 update from um sort of the phase 1b or part one of the phase 1b uh that tends to be the the data card flip that i get the most questions about from investors um and you know from the sound of it it's going to be a pretty substantive update kind of to the scale that we saw with ray's bio 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 going to 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 RACE-Bio data set, since that data was less dose escalation, more expansion at a given dose, right, so 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 want to carry into that. So 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. So double-digit numbers.

Do you want to comment on the endpoints as well?

In terms of endpoints, if you just look at the technicality of the protocol, right, those escalation part one endpoints are all around safety, right, and it will be safety-focused and will obviously also present the efficacy that we observed in that. But 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 of the study.

Okay.

But obviously there will be efficacy data included, right?

Yeah, you're not going to push it forward just based on safety. And, you know, Tridel V is kind of the de-risking asset for the target in the post-Pembro or sorry, PADSIV is what I meant in the I guess post-PADSIV failure is that kind of the target indication and what are sort of the outcomes for those patients typically?

So we view the post-PADSIV PEMBRO space as sort of the low hanging fruit quick to patient opportunity because there's no established standard of care and with Trodelvi, as you mentioned, having to do another lab, with that study not reading out until like mid-29, I think there continues to be an opportunity to be the first new therapy in a post-PAT-CF-Pembro setting. I think the real question to the field and the agency is going to be, what is post-PAT-CF-Pembro, right? Is it post-PAT-CF-Pembro in a metastatic setting? Does it include the perioperative setting? so i think there's a lot of work that can be done to to really have a meaningful impact for patients but right now the expectation i think or the bar is very low expectation is always high but the bar is low yeah is his response um 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? And a response is, of course, meaningful to a patient if it lasts, if it has durability, right? And 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, whether if you need PFS with some OS read.

I think that's all in the question.

We'll all need to be discussed with the agency.

That makes sense.

And I alluded to it before that we have the tissue localization imaging data for the non-therapeutic isotope for 1189. i guess how does this normal tissue localization kind of compare to other rlt's in the space i know we've seen some you know salivary gland accumulation for some of the beta emitters so you know any expectations with the therapeutic compound now around you know renal accumulation salivary glands etc yeah maybe i'll start on that one so the way we we view the imaging dosimetry analyses is it's effectively something that we can use as a stage gate for development.

And so the way we've described the imaging dosimetry is as supportive of the clinical plans that we've brought forward. And so 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, may require you to start at a very low dose in dose escalation. But in the cases of our AQI 1189 and in 2519, the data that were generated were informative. They were, in our opinions, clear go signals to phase 1B, and they did inform our dose escalation schema that we've described now for both of the lead programs. So 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 AKY2519 B7H3 targeted radio-conjugate program in the clinic, we now have sites open and enrolling. What we described there was an approach where the initial protocol is going to be in metastatic estrate-resistant prostate cancer patients broadly, and then there's going to be a second protocol that we expect to open in the second half of this year that's going to 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 going to present at ASCO and that were previewed in RS1 in January. So there's a lot 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. And obviously, we're thinking about various accelerated 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 um is there maybe precedence you can point to there like is that kind of the post passive pembro um uh line of therapy that we've been talking about so we'll be exploring multiple uh options to accelerate these programs to patients once we have the data supporting that but uh i guess you want to comment on next 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.

But 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've been, over the years, extremely collaborative across multiple modalities, right, and sponsors. So 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? And you can see that with the 2519 program where we did disclose the three dose levels that we're going through in dose escalation starting at 6 megabecquerel, which is a fairly high dose for nectinium targeted therapy. And that's supported by the data that we're presenting in a couple of weeks. So 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.

And I imagine the learnings from 1189 sort of helped you, plus the dosimetry you're seeing for 25 minutes.

It's a rapidly evolving field, right? And when we set out to collaborate on the 1189 dosimetry experience, the main question we were asking is, are we staying out of the bone marrow? Because that's so important, right? And what is the kidney exposure? And 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? And with evolving technologies, methodologies, we're not able to look at that, right, today. And who knows what we'll be able to look at two years from now. but I don't think we'll ever be in a position where the symmetry will replace any type of safety efficacy evaluation.

Okay, maybe we can switch gears to 2519. I think that's a pretty good segue. And maybe just to start, looking forward to the presence at ASCO will obviously be there for the presentation. What does this data sort of need to show to confirm sort of the early localization that you've seen in a handful of patients and, 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 have a very focused two-trial-in-one prostate study that's now open for a couple weeks ago. Clean trials 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 going to 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? And, yeah, I hope you stop by.

Yeah, maybe just to build on that. So at ASCO, we're going to be presenting two posters, and very conveniently, they're side by side. So it's one-stop shopping. One of the posters is looking at tumor uptake with AKY2519 imaging agents, principally gallium labeled AKY-2519 in a number of different tumor types and so that's kind of asking the question would the tumor uptake support development in various different tumor types and so that will in a way link to or support it in our mind the the basket trial approach that we're just that we're describing that second protocol that we expect to open in the second half of the year. The other poster that is going to be presented is looking at 16 patients with metastatic castrate-resistant prostate cancer patients. So this is prostate-focused. And that is not only the PET-CT-based analysis like the first, but it's also going to have SPECT-CT lutetium labeled, AKY2519, just looking at exposure of the drug over a longer time frame, up through six days. And so 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? Due to some technical advancements, even over the last two years that Akash referred to, we're able to provide a more expansive analysis than even we could do two years ago with the AQI 1189 program. So what that did is that helped us inform specifically for the prostate cancer population what the parameters for dose escalation would be as Akash described. And so that was really part of the basis for the excitement for us to move this into phase 1B in that specific population, as well as the feedback we got from the key opinion leaders that focus principally on prostate cancer treatment. So we invite you to the poster to have that discussion. Yeah, looking forward to it.

Maybe in the last few minutes here, I do want to 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. So the Lilly collaboration started in 2024, where at that time our platform technology and capabilities to generate these mini protein radioconjugates were now available to us and to Lilly and to others. And based on what was broad interest, we selected Lilly as a partner for a platform deal. So what this is, is it's a discovery collaboration where we are using our platform capabilities to generate novel mini protein-rated conjugates against targets that they pick that are outside of our target space. And so 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. And so that collaboration, as you said, we think it's going well. We disclosed in our S1 that we've already hit the first milestone in that collaboration. And we're gratified to see the participation from Lilly in our IPO. and there's been a good mojo all around in that collaboration. So that is, in the end, an up to $1.2 billion collaboration deal for us, and 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. And so but that said, you know, again, this is restricted to the molecules that we are working to deliver for Lilly for their further development in the clinic and commercialization. But to underscore the point, all the programs that we're working on, including 1189, 2519 and the others that are still to come are wholly owned by Actis. Right. And so where there's no option rights or other rights to by any other party. to those programs. So 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 just touch on that quickly at the end here.

Yeah, so we are well capitalized not only through the non-dilutive sources, but also through the very strong interests that we've seen in our capital raises to date. And so we're able, by virtue of the strong cash position, we just reported $538 million on the balance sheet cash-cash equivalents as of March 31st. And so 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 the lily collaboration and you mentioned manufacturing is 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 and delivery to patients. So all of those things are areas of focus and priorities for us, because we think these are the things that are going to enable us to have that significant patient impact that we're working to have.

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 And thanks, everyone, for attending and your interest in Actis.

Thanks, Ali.