Aktis Oncology, Inc. Common stock Morgan Stanley 24th Annual Global Healthcare Conference

Awesome. Thank you, Matthew. Thank you to you and the entire Morgan Stanley team for hosting us here. We are excited to be here. Also thank you to everybody here in the audience for your interest in tracking our story. Aktis Oncology is a clinical stage oncology company focused on developing a novel set of radiopharmaceuticals or radioligand therapies. We are very excited about this space. We think it is a large new category of anticancer medicines, and we are still in the relatively early era of the development of this category. We like radiopharmaceuticals in part because they are validated. We know how they work, we know why they work. We have seen that they have been successful clinically. We see that they have been successful commercially in terms of patient impact and launch ramp.

We also see that the space is, as of today, relatively early in terms of there is only two approved, or I should say, approved products against two targets. The target space for radiopharmaceuticals is wide open. Aktis exists to attempt to bring radiopharmaceuticals to a broad set of patient populations that have no radiopharmaceutical option. The key unlock for that has been our miniprotein radioconjugate platform technology, which enables us to hit a broad array of targets with a clinical or pharmacologic profile that is consistent with what has worked successfully in the radiopharmaceutical space. From that platform, we have advanced two lead programs into the clinic. The first is AKY-1189, which is targeting Nectin-4. Obviously, Nectin-4 is a validated target through PADCEV, which is an approved ADC.

It is now projected to have consensus peak sales numbers of about $7 billion, all in bladder cancer. Our clinical development plan is not only in bladder cancer, with now what is a different payload of a radiopharmaceutical versus an ADC, but also to develop outside of bladder cancers into breast and potentially several other tumor types. We think this is an important and large multi-tumor opportunity for us. Our next program is AKY-2519, which is targeting B7-H3, and that, like Nectin-4, we believe has the potential to be first in class among radiopharmaceuticals, and also has a multi-tumor, large patient impact opportunity and obviously commercial launch opportunity. Beyond that, we have several other programs that are, again, leveraging the miniprotein platform. We haven't disclosed anything beyond the fact that there are multiple programs in various stages of earlier development.

But we have said that we are tracking towards two additional clinical candidate nominations in the first quarter of 2027. The platform continues to produce, and we're excited about the multiproduct, multi-tumor clinical development plans we have. Further from that, based on the platform technology, we do have a strategic collaboration with Eli Lilly that is worth a total value about in excess of $1.2 billion. This was really to explore or generate new miniprotein radioconjugates against targets that Aktis is not working on. It just expands the impact potential of the platform technology. Of course, Aktis retains 100% commercialization ownership of our entire pipeline, including the lead two programs. Beyond that, we've focused on the other critical component of the story is our supply chain. We are principally prioritizing actinium-225 as the effector isotope.

And in order to be in control of our own destiny, we have built a very robust end-to-end supply chain that enables us to, we believe, ramp up to, in the near term, hundreds of patient doses, and then, of course, deliver globally as we advance into later stage development and commercialization. Really it's everything under one roof that you would need to be a leader in the field, all the capabilities and components, and that's what we've been focused on because we're mostly keen to move the needle for patients. At the end of the day, if you can be valuable for patients, then you should be valuable for investors, too. So happy to dig in wherever you'd like.

Yeah, it's a great question. The field of radiopharmaceuticals really started. Well, it started with, of course, iodine for thyroid cancers, but targeted radiopharmaceuticals started in the early days with monoclonal antibodies, like for example Bexxar or Zevalin. Antibodies were a logical choice at the time for delivering radioisotopes, because we know we can generate antibodies against a wide array of targets. We know you can localize antibodies wherever that target is, and so that would be an obvious way to deliver a radioisotope. Unfortunately, one liability of antibodies is that they're long-circulating. That's often an attractive capacity to an antibody because you want it to stick around, you want area under the curve, you want target coverage, et cetera. But for radiopharmaceuticals, the problem is that now what you're doing is you're keeping the radiation payload in the bloodstream for a long period of time.

What has been observed over time with monoclonals is that you have an elevated level, and perhaps unacceptable level, of bone marrow hematotoxicity. The field has largely moved, not entirely, but largely moved to small formats. This is due to the success of, let's say, LUTATHERA and PLUVICTO, both are very small peptides, effectively, that are fast clearing from the bloodstream. In other words, yes, they can hit a target with affinity, but they also are renally cleared through the kidney. They are cleared out relatively quickly in a matter of hours. The field has largely moved to that small format, and we have as well because we think it's a way to maximize the therapeutic index by protecting the bone marrow.

When we were starting the company, we effectively had a whiteboard of every permutation you can imagine of all the component parts you were talking about, and we wanted to optimize for what would be an expected patient outcome. At the same time, we wanted to optimize for, well, how do we hit these other targets, and can we use antibodies or antibody fragments or other sort of antibody-like things? Where we landed was with miniproteins, and we are inspired by the work of David Baker, who subsequently won the Nobel Prize on de novo protein design, specifically around miniproteins. Miniproteins are the smallest polypeptides that can achieve a three-dimensional shape.

That three-dimensional shape, and of course the variability or diversity that comes with the polypeptide, was the enabler to hit a broad array of targets like an antibody could, but to have, because of its super small size, these are typically around 40, 50 amino acids, but then folded up into a very compact shape. They have the pharmacology of these very small formats like PLUVICTO or LUTATHERA. We felt like that was the Goldilocks scenario of having a binder that could be bone marrow sparing, hopefully limit the normal tissue exposure, but also be able to achieve very high affinity and selective binding against a broad array of targets like an antibody could. It was kind of the perfect mix of all the formats. On top of it, one of the really important things that makes this work is the diversity.

We are encoding in our libraries for over 6 billion variants of the miniproteins, and that's across 100 different scaffolds. That's important, and of course, we are also doing generative design, which is now outside of the 6 billion. It's a new search space. It's billions of trillions of variants now that we are looking at through generative AI design. That's been an accelerator to our innovation engine that when we mention we have multiple programs following the lead two, we have multiple programs following the lead two. That's been exciting. The intent here was to deliver something that could really open up the target space but also meet the needs for a patient in terms of maximizing clinical efficacy and safety.

Now, on the part of efficacy, there's a lot of debate about what's the right isotope, and it's our point of view that really any isotope that emits energy should kill tumors. A wide array of isotopes should work with this kind of format, and our technology is isotope agnostic. We have used multiple isotopes in our experimental work, and they all work fine. We did prioritize first, and it's not to say that we won't use other therapeutic payloads, but at least in our first iterations here, our first INDs were with actinium-225. Actinium-225 is a very powerful alpha emitting isotope. It exerts, we think, the maximum amount of energy into the tumor if you can localize it there. The purpose there was to, number one, maximize the efficacy impact on patients, because obviously efficacy is the unmet need in cancer.

Number two, its 10-day half-life enables us to do a central manufacturing process that enables us to be, again, in control of our own destiny and supply chain such that we can deliver at scale globally. Both were important components for us. It's not to say we couldn't use others later, but that's what the priority has been. We think this is the right combination to maximize patient impact. It's not the only combination. We're sure there's other ways, other formats that can be successful. But this is a way for us to repeatedly generate as many different product candidates as we can with this kind of profile.