Good day, and thank you for standing by. Welcome to the Aktis Oncology AKY-2519 Clinical Development Strategy conference call. At this time, all participants are in a listen-only mode. After the speaker's presentation, there will be a question-and-answer session. To ask a question during the session you will need to press star one one on your telephone, you will then hear an automated message advising your hand is raised. To withdraw you question please press star one one again. Please be advised that today's conference is being recorded. I would now like to hand the conference over to your speaker today, Matthew Roden, President and CEO. Please go ahead.
Thank you, Dee Dee, and thank you all for joining us this morning. Before we begin, I'd like to remind you that today's remarks will include forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. We ask that you refer to our filings on sec.gov, including our most recent annual report on Form 10-K, filed with the SEC on March 31st, 2026 for a full list of risks and uncertainties. Actual results may differ material from those indicated by these statements. Unless required by law, Aktis does not undertake any obligation to update these statements regarding the future or to confirm these statements in relation to actual events. Joining me on the call today with prepared remarks is Akos Czibere, our Chief Medical Officer.
Also joining the call on the question and answer session in alphabetical order is Tyler Benedum, our Chief Technical Officer, Paul Feldman, our Chief Scientific Officer, Kyle Kuvalanka, our Chief Financial Officer, and Shulamit Ron-Bigger, our Chief Operating Officer. We're excited to discuss the announcements we made yesterday related to our second program to enter the clinic, AKY-2519, a B7-H3 targeted miniprotein radioconjugate. We see an opportunity to advance a broad clinical development plan for AKY-2519, given the high expression of B7-H3 across multiple solid tumor types and given the poor prognosis associated with B7-H3 overexpression. First, we announced the initiation of a dedicated phase I-B clinical trial of AKY-2519 in metastatic castration-resistant prostate cancer.
Second, we highlighted our clinical development strategy to evaluate AKY-2519 more broadly in various B7-H3 expressing tumors, including plans to initiate a second phase I-B basket trial in lung, colorectal, and other solid tumors in the second half of 2026. During today's call, we will highlight the following. The unique opportunity for B7-H3 as a differentiated radiopharmaceutical target in metastatic castrate-resistant prostate cancer and in other indications. The rationale underpinning our strategy, which we believe is significantly enhanced from what we described in our S-1 and has been informed by insights from our clinical advisory boards in the distinct treatment patterns and clinical needs of patients with castrate-resistant prostate cancer compared to other solid tumor patient groups. As well as discuss the phase I-B trial design for a dedicated prostate cancer protocol.
Before we dive into the AKY-2519 updates, I'm gonna take a moment to remind you of our mission and the progress we've made as a company. Aktis Oncology is focused on extending the benefit of targeted radiopharmaceuticals to large patient populations that have no radiopharmaceutical option or where unmet needs persist. At present, approved radiopharmaceuticals such as Pluvicto and Lutathera have demonstrated clinical benefit in patients. There remains a significant opportunity to address molecular targets expressed in several other tumor types. We're keen to extend this clinical benefit of radiopharmaceuticals to many more patients who have no radiopharmaceutical option.
Starting at the top of this page, you can see our novel and differentiated platform is designed to produce miniprotein radioconjugates that selectively deliver the tumor-killing properties of radioisotopes by maximizing tumor penetration, internalization into the tumor, and retention in the tumor, while rapidly clearing from normal tissues to limit unwanted exposure. From this platform, we have now advanced two distinct lead programs to the clinic, both of which are intended to address several important solid tumor patient populations, including those where unmet needs persist, such as bladder, prostate, lung, breast, colorectal, head and neck cancers, and various other tumor types. Aside from our two lead programs, we're further developing a pipeline of wholly-owned programs in earlier development and supporting a discovery collaboration with Eli Lilly that leverages our platform for the discovery and development of additional novel miniprotein radioconjugates for the treatment of cancers.
Another major pillar of Aktis Oncology is our unique infrastructure, which includes a resilient and scalable end-to-end supply chain that we believe is paramount for us to maximize our patient impact potential. Taken together with a strong balance sheet and accomplished leadership team, we are well-positioned to prosecute our mission to expand the reach of radiopharmaceuticals to patients in need. Slide 5 depicts how our miniprotein radioconjugate platform allows us to explore a portfolio of assets. Our most advanced clinical stage program is our Nectin-4 targeted radioconjugate, AKY-1189, which is currently enrolling a phase I-B clinical trial. AKY-1189 has FDA Fast Track designation, and we expect to present preliminary dose escalation data from this program in the first quarter of 2027.
Next, AKY-2519, the topic of today's call, and this miniprotein radioconjugate we have advanced to the clinic in the past 12 months. On March 30th, we announced that the FDA had cleared our IND applications for this program. We're delighted to have now achieved the critical milestone of opening the first sites for the AKY-2519 clinical program. Our two-trial strategy includes leading with a dedicated phase I-B study in patients with metastatic castration-resistant prostate cancer, as announced in yesterday's press release. This trial has been initiated and will evaluate AKY2519 in both Pluvicto naïve and Pluvicto -experienced patients. This prostate-focused protocol will be followed by a basket phase I-B protocol, which will evaluate AKY2519 in B7-H3-expressing cancers, including lung, colorectal, and other cancer types.
This study protocol is under regulatory review. We expect to initiate the basket trial in the second half of this year. In summary, we're working diligently to advance a portfolio of novel programs for patients in need of new and potentially transformative anti-cancer treatment options. With that context, I'll turn the call over to Akos to provide an overview of B7-H3 biology and the foundation that has informed our clinical development strategy for AKY-2519.
Good morning, everyone, and thank you, Matt. As Matt just explained, our clinical development strategy for AKY-2519 aligns closely with our vision to bring radiopharmaceuticals to large tumor types where we continue to see high unmet need. Specifically, the two-trial strategy here enables us the evaluation of AKY-2519 in a way that really allows us to efficiently generate indication-relevant data for actionable data-driven decision-making as we already, at the beginning of AKY-2519's clinical journey, start to think about the next set of potentially pivotal studies. Our now-initiated phase I-B trial in mCRPC will be, to that end, enroll patients who have not been exposed or treated with Pluvicto and those who have and received perhaps Pluvicto therapy across two separate cohorts. The study is conducted under IND in the U.S., of course, and will utilize a mix of prostate-specific radioligand therapy centers and academics.
Our upcoming phase I-B basket trial, the second study for the AKY-2519 program, will of course also be conducted in the U.S. under IND at multiple, more academically focused centers. That study will focus on lung cancers as a whole, colorectal cancers, and other solid tumors where we see high expression levels of B7-H3. The protocol for the basket trial has been finalized and is currently under regulatory review, and we anticipate to initiate that second study in the second half of 2026. This two-trial approach was informed by insights from our expert clinical advisory boards and steering committees and really takes into account the distinct clinical trial landscape that is in existence for the prostate cancer, for prostate cancers versus other solid tumors where we just haven't seen that deep penetration of radioligand therapies like we are seeing in prostate cancer.
We believe that this will enable us to more efficiently generate relevant data to inform the future studies, as mentioned before. Like Nectin-4, we do see B7-H3 as an ideal target for radiopharmaceuticals, given its high expression across multiple tumor types and low expression across normal tissues. Clinically, it's also interesting, and that speaks to the high unmet need for B7-H3-expressing tumors, that it's been shown to be associated with poor prognosis and lack of response to certain therapies in non-small cell lung cancer, for example. We do think B7-H3, like Nectin-4, has the potential to be a true first-in-class opportunity across multiple major tumor types spanning multiple lines of therapy. Let's take a brief look at the development data to date, focusing of course on a few preclinical highlights.
AKY-2519 is a high-affinity and selective binder for B7-H3 that was generated using our proprietary miniprotein platform with some promising preclinical data. Important for radiopharmaceuticals, we observed internalization of AKY-2519 in vitro, leading to durable tumor retention in vivo with limited normal tissue biodistribution and exposure, as you can see here in these data slides and the imagery. This translated to robust anti-tumor effects and a dose-dependent survival benefit after single administration of AKY-2519 in a cell line-derived xenograft model of non-small cell lung cancer. Of high interest, of course, as we think about metastatic castration-resistant prostate cancer, AKY-3212, which is a sister molecule to AKY-2519, a classic tool molecule, when chelated to actinium-225, demonstrated superior efficacy compared to PSMA-617 chelated to lutetium-177 in a patient-derived xenograft model of mCRPC.
This model was engineered to be resistant to PSMA-617 lutetium-177. While resistant to that particular medicine, these tumors remained sensitive to AKY-3212 chelated to actinium-225 when equivalent levels of drug were delivered or dose were delivered to tumors, as you can see in the lower right panel. Pivoting our focus now to clinical data that we're not gonna be speaking about today, but will be presenting at that Lakeside [inaudibe] conference , which of course is ASCO, as we talked about previously. We're really gratified and excited to be able to share with you clinical imaging and dosimetry data, looking at normal tissues and tumors across two posters at the upcoming meeting.
These two posters will have a strict focus, where one poster will focus on mCRPC, describing normal tissue biodistribution dosimetry and tumor dosimetry, and then a second poster that will be evaluating tumor uptake and normal tissue biodistribution across multiple tumor types, including non-small cell lung cancer and CRC. We do see a significant opportunity for B7-H3 as differentiated radiopharmaceutical target in prostate cancer specifically, and of course, expanding that to other indications as well. Let's talk a little bit more about prostate cancer here. First, as you all know very well, Pluvicto has been very successful since launch, but we do think there's a significant opportunity with a differentiated target like B7-H3 and a differentiated payload like actinium-225.
Despite the success that we've seen with Pluvicto , there continues to be an unmet need in prostate cancer for novel therapies with differentiated targets. Partly, this is because while PSMA works as a target, there are varying degrees of PSMA expression with a lot of heterogeneity across patients, and some patients just lack any response to PSMA-directed therapies. Second, there's also expression, as it has been shown, of PSMA on the salivary glands, which can be specifically challenging when administering high energy, radioligand therapies or radiopharmaceuticals that utilize alpha emitters. This normal tissue expression liability is not expected to be present with B7-H3, since there's no expression of B7-H3 on the salivary glands.
Adding to that, in metastatic cancers and prostate cancer, it's been shown that B7-H3 is expressed very consistently in about 90% of all patients with low expression in normal tissues, as mentioned earlier, and most critically here again, not present in the salivary glands. Of course, we do think that even beyond prostate cancer, B7-H3 has the potential to unlock wide space opportunities, as we call them, true first-in-class opportunities in additional large tumor types such as lung cancers. That really goes beyond just the small cell lung cancer indications. Why did we end up splitting the program into two trials? As we just reviewed, radiopharmaceuticals are already well-established and rapidly evolving treatment modality in prostate cancer.
As a result of that, here in the U.S., we have a robust network of prostate cancer-specific RLT centers with deep expertise and experience in both patient selection and trial execution with this modality. By splitting the prostate cancer indication out of the overall phase I-B basket study, we now have access to these centers, and that will enable us to really optimize the build selection process for this population, and also enable us to look in parallel at Pluvicto naive and Pluvicto experienced patients, which we think is gonna be key as you think about the future positioning and development of this drug in prostate cancer. It also really helps us to leverage the enthusiasm among those physicians working at those centers and the prostate cancer community at large, as we can offer many treatment opportunities for their patients in this study.
All together, this dedicated prostate cancer protocol really gives us a unique opportunity to more efficiently generate indication-relevant data in this key tumor type. Let's take a look at the design of this study. This study will enroll in parallel in a BOIN dose escalation, as Noah mentioned a few times, Pluvicto naive and exposed patients across cohort A and B. We only have three dose levels in this study, starting already at a starting dose of 6 MBq, and then going 3 MBq increments to 9 MBq and then 12 MBq at the top dose. Very efficient. There's obviously in between dose levels if we need to go to dose, but the plan as outlined right now and active in the clinic, calls for three dose levels.
These dose levels, two of these three can and will be expanded for further dose optimization work across these two cohorts, giving us a very robust data set to inform future studies once the study has data available. I would now like to turn the call back over to Matt.
Great. Thanks, Akos Czibere. As you've heard today, we've designed a clinical strategy to position AKY-2519 to demonstrate broad potential across multiple tumor types in patient populations with distinct needs. This includes prostate cancer, where radiopharmaceuticals are well established. With AKY-2519, we're delivering a new option with a differentiated target and payload, and with a protocol that focuses on indication-relevant signals generated in a timely fashion.
The plan also includes addressing multiple other large patient populations such as lung and colorectal cancers, which represent wide space opportunities for delivering the clinical benefits of radiopharmaceuticals. Lastly, looking ahead, company-wide over the next 12 months, we're working to deliver several important milestones, including for AKY-2519, as you've heard at the upcoming ASCO Annual Meeting later this month, we will present results from the clinical imaging and dosimetry analysis in patients with prostate cancers and other various solid tumors. In the second half of this year, as we've described, we expect to commence the phase I-B basket trial in lung colorectal and other PSMA expressing solid tumors. In 2027, we expect preliminary data from the phase I-B prostate study to be reported.
For AKY-1189, in the first quarter of 2027, we expect preliminary data from part one of the ongoing phase I-B clinical trial. Moving to the early pipeline, we have two programs tracking towards development candidate nomination as well as commencement of IND-enabling activities in the first quarter of 2027. On the corporate side, we expect our in-house GMP manufacturing facility to be operational in the second half of this year as part of the company's hybrid manufacturing strategy to expand capabilities and scale and to support the ramping demands of our ongoing clinical trials. In closing, we believe AKY-2519 has the potential to be a highly differentiated and targeted radiopharmaceutical, and I want to thank all Aktis employees for your unwavering commitment to patients in bringing this forward.
The strategy we outlined today reflects thoughtful positioning, of the program to create value for patients and investors alike. This concludes the prepared remarks, and I'd like to open up the call for questions. Dee Dee, feel free to, proceed from here. Thank you.
Thank you. As a reminder to ask a question, please press star one one on your telephone and wait for your name to be announced. To withdraw your question, please press star one one again. Please stand by while we compile the Q&A roster. Our first question comes from Jessica Fye of JP Morgan. Your line is open.
Hi, everyone. This is Sylvia in for Jess Fye. Thanks for taking our question. You're going into both Pluvicto -naïve and experienced patients here. For the patients who are Pluvicto -naïve, can you speak with a bit more detail to the profile of patient you anticipate enrolling? Would they likely have low PSMA target expression? Then also, can you touch on what you expect the market to come away from ASCO, having learned about AKY-2519? Thanks.
Sylvia, thanks for the question. This is Matt. I'm gonna take the last part first, and then I'm gonna ask Akos to comment on the development in PSMA, or I should say Pluvicto -naïve patients. First, at ASCO, we're excited to bring forward the imaging and dosimetry data that we've generated. We're gonna have to wait until then to go through in more detail, but in short, we believe that the imaging and dosimetry data that we have support for the development of the program, as well as help to inform the clinical trial design that you saw here today. With that, I'm gonna ask Akos to comment on the Pluvicto -naïve population.
Yeah, thank you for that question. The protocol does not dictate or query PSMA expression levels via imaging, for example. From an eligibility perspective, these patients could come onto our study in lieu of receiving Pluvicto right? This will all be on clinicaltrials.gov when the posting goes up. They do not need to have received prior chemotherapy. They just need to have metastatic castration-resistant prostate cancer and documented disease progression at least two ARPIs.
Great. Thank you.
Thank you. Our next question comes from Tyler Van Buren of TD Cowen. Your line is open.
Hey, guys. Good morning. Thank you very much for the presentation. I have a couple. First, kind of a two-parter. What number of castration-resistant prostate cancer patients are ineligible for PSMA-targeted therapy due to low target expression specifically? How many would you say have a suboptimal response to a PSMA-targeted therapy? The second is related to ASCO. Understanding you're waiting till the conference to discuss the data, but perhaps you can review the measurements of focus that will be most important as we think about the potential to reduce tumor burden in patients.
Yeah. I can start with the PSMA-related question. When we look at the outcomes for patients who receive Pluvicto , I loosely bucket them a third, a third, a third, right? A third has excellent outcomes, a third has okay outcomes, and a third has no response to Pluvicto In terms of PSMA level expression, I think we're seeing many patients who have robust uptake of the imaging agent for PSMA and still not respond. The label's requirements to receive Pluvicto are fairly broad, right? I think it's only the presence of a lesion larger than the centimeter that's uptake negative that precludes from prescribing Pluvicto . I think the biology is a little more complex than just present/absent when it comes to PSMA and potential response to PSMA-617 or other PSMA-directed therapies.
We're very interested in learning more about the relationship also of PSMA expression and B7-H3 expression, and how that may drive differential responses for the two agents. Tyler, would you mind repeating the second part of the question related to ASCO?
Just understand that you're waiting for the conference to discuss the data, but I just thought it would be helpful for you to kind of review the measurements that will be in focus when you report the data as we think about the p otential for AKY-2519 to reduce tumor burden.
Yeah
-in patients.
What we are going to have in the prostate-specific poster will be an imaging and dosimetry assessment done in 16 patients that will share or show normal tissue predicted absorbed doses to key organs, including salivary glands, kidney, et cetera. There's going to be dosimetry assessments done on tumor as well across a number of patients. For the second study, it's going to be SUV-centric measurements for tumor uptake, like SUVmean, SUVmax, across multiple tumor types and normal tissues without dosimetry.
That's perfect. Thank you.
Thank you. Our next question comes from Jonathan Chang of Leerink Partners. Your line is open.
Hi, guys. Good morning, and thanks for taking my questions. First question, how did you decide on the three dose levels being evaluated in the prostate cohorts? Second question, for the phase I-B basket study, for other B7-H3 high-expressing solid tumors, given the broad expression profile of the target, what tumor types do you anticipate will be evaluated and represented in the study? Thank you.
Thank you, Jonathan. This is Matt. I'll start actually with the second one. As you heard, the basket study is intended to look broadly across B7-H3 expressing tumor types. We do see a particular concentration in high expression level in various subsets of lung cancers, and so those will be broadly included in that trial, as well as other patient populations such as colorectal cancers and others. If you look at the expression levels of B7-H3, what's in the literature, we have some of our own data as well, you can see that there's really quite a broad opportunity to really do a signal-seeking analysis here.
Of course, the key goal of the dose escalation is safety and dose finding. In regard to the dose, I'll start and Akos may add, clearly, both the preclinical work that we've done as well as the dosimetry work in patients informs what a starting dose would be. All of that was worked into our discussions with our advisors as well as with the regulatory agencies to land on this current dose escalation. Akos , is there anything further to add to that?
No. You covered it.
Okay. Thank you, Jonathan.
Thank you.
Thank you. Our next question comes from Alec Stranahan of Bank of America. Your line is open.
Hey, guys. Good morning. Thanks for taking our questions and walking through the latest data here. One question on B7-H3 expression pre/post Pluvicto . We've heard that target expression decline has been observed with other RLTs. Curious if this is something you've also seen with PSMA expression in prostate. I imagine B7-H3 expression in this context wouldn't be affected, but any thoughts there would be great. I guess as a follow-up to that, is the reason to include both Pluvicto naive and experienced cohorts more of a standard of care staging consideration, or does this target expression piece maybe feed into that as well?
Yeah. I'll start at the back end of your question. Alec , I think the splitting of the cohorts is one key There's one key reason to it, That is patients who have already received radioligand therapy may tolerate a different dose than patients who are naive to it, right. Because we do have to think about the cumulative radiation that we deposit to whatever normal tissue we're depositing to, right. Even though, you'll appreciate the normal tissue or normal tissue dosimetry at ASCO, since we're gonna be sharing it there's still cumulative radiation deposited, right. Just starting off, with patients receiving six doses of Pluvicto , sometimes more.
Just to be able to really dial the right dose in for the two naive and it's more the radiation exposed rather than Pluvicto -exposed patients, we think, and our advisors think it makes the most sense to split the two. We think the bigger opportunities are going to be not after Pluvicto , right? That's something we want to do and we have to do and we're interested in, we think this could be much more impactful in earlier disease settings.
Okay.
And it seems-
Yeah, just on the expression.
That's a bit of an open question. At this point, we have a data set that we'll continue to analyze where we do have matched PSMA and B7-H3 PET CT imaging. And we'll share when that is available. We do not expect B7-H3 expression to be lost, though, following PSMA directed therapy. If anything, we expect it to be more pronounced. There's very limited data to this end at this point. I actually think we're going to be the first B7-H3 imaging presentation in a large number of prostate cancer patients at ASCO.
Okay. That's very helpful. Maybe just one quick one for Matt on actinium supply. Great that you guys are launching, you know, the studies for AKY-2519, then you've got AKY-1189 as well ongoing. I guess, are you comfortable with sort of your current capacity, and, you know, how does the GMP suite coming online later this year kind of feed into your study plans for the future? Thanks.
Yep. Thanks, Alec, for the question. We have been very focused on ensuring that our supply chain can scale up to what is really increasing demand from our clinical trial enrollment for this year. I think what you see today is somewhat of an acceleration of the enrollment plan vis-a-vis what we had talked about in S-1 in the context of the IPO. That did require us to really focus on being able to scale up our needs here. Tyler and the team have done a really nice job to ensure that we're in good position to serve the needs of patients.
As we've discussed, both on the actinium supply side and on the manufacturing capacity side, final drug manufacturing capacity side, what we have set ourselves up to be able to ramp up to that increasing patient need.
Got it. Thank you.
Thanks, Alec.
Thank you. Our next question comes from Alex Ramsey of William Blair. Your line is open.
Hi. Thanks so much for taking our question, congrats on all the progress on this program. Maybe first a bit of a theoretical question. You have the upcoming data at ASCO, and say you have great SUV, great biodistribution, long-term retention. In that case, what's your confidence in that kind of translating to the phase I-B clinical data? How is the platform designed to mitigate risk when translating from dosimetry and imaging data to efficacy data? The second question, in the post- Pluvicto setting, we're just curious how you think about cumulative dose exposure in these patients, given that they'll be exposed to radiation across multiple lines of therapy. How has the FDA kind of viewed this based on your conversations, especially in terms of renal tox and that 23 gray limit that has been set?
Thank you, Alex, for the question, and I'll ask Akos to comment on that one.
It was two questions really, right. On the confidence in translating the imaging and dosimetry data to the clinic, I'd say we're obviously excited in putting a broad clinical development program into the clinic supported by the imaging and dosimetry data and also, of course, supported by strong preclinical data. How that will translate, we'll have to wait for the clinical data to read out, right. I don't think there's a lot of really prospective correlative analysis that's been done on that end, but we're excited with what we're seeing to this point. What was your point on the EBRT limit?
Just for the post Pluvicto setting, for the patients that were exposed to Pluvicto and then will be exposed to AKY-2519, just in terms of the cumulative tox, especially on renal tox, given that the FDA has pretty strict limits for the cumulative exposure.
Yeah. I think this will be more driven by clinical AEs toxicity than cumulative radiation doses. Obviously, we're collecting the administered doses as a prior therapy for patients in the Pluvicto -exposed cohort, so we can include that in all subsequent analysis. You may have noticed that the dose levels are the same for the two populations, right? There's no limitation in place when starting dose escalation. We'll let the clinical data drive what dose we end up with.
Awesome. Thank you for all the insight.
Thank you. I'm showing no further questions at this time. I'd like to turn it back to Matthew Roden for closing remarks.
Thank you, Dee Dee, and thank you all for joining today. We're excited about the progress we've made and appreciate your continued support, and we look forward to keeping you updated as the program advances. Have a great rest of the day.
This concludes today's conference call. Thank you for participating, and you may now disconnect.