All righty, Ben, let's continue here with Ben Hickey, now from Bristol. Welcome. Thanks for joining us today. And so, yeah, before we start with the fireside chat here, yeah, could you just introduce yourself and talk a bit about your role at Bristol? Sure. First of this one, yeah. First of all, good to see you. Can I? No. No, we're on. Good morning. Thanks, Michael, for hosting. Yeah, Ben Hickey, I'm currently the president of RayzeBio. We are going to run RayzeBio as an independent company within the Bristol Myers family, so that'll be a first for Bristol. Prior to that, I was the Chief Commercial Officer and Head of Business Development at Mirati, which was also bought by Bristol Myers Squibb. And then prior to that, a short stint at Halozyme, and before that, I was actually 17 years at Bristol Myers, so I'm a bit of a boomerang. So good to be back with Bristol. Yeah, that was a calling to come back, I guess. Yeah, maybe talk a bit about the acquisition of RayzeBio and, yeah, why does it make sense for Bristol and how is Bristol thinking about the opportunity in general? Sure. Well, the team did an extensive amount of work in the whole radiotherapy space, and RayzeBio was really their top choice, so I'm sure we'll get into some of the reasons around that. But with Bristol being, you know, historically and currently one of the leaders worldwide in on oncology development, it makes a ton of sense to be thinking about what's the next wave. And radiotherapy was top of the list as a modality that Bristol really wanted to get engaged with. So very happy with the outcome. A great deal of excitement around the potential, not only with our current program, but with the pipeline at RayzeBio. And then obviously the potential for combinability in the future with a number of different assets within the pipeline, both within and external to Bristol today. Yeah, so I think you mentioned Bristol's keeping RayzeBio sort of independent, more or less. But can you talk a bit about how this could be integrated into Bristol's existing R&D organization? Yeah, so the structure is what we call a standalone. So there are multiple different archetypes which are similar to this. We plan to have very quick decision-making, just like a biotech, so keep the team in place. I report directly to the CEO of Bristol, Chris Boerner. And the idea is that we move with the agility and speed of a biotech, but at the same time leverage the resources, know-how, and worldwide footprint of Bristol Myers Squibb. So it's worked very well to date. I sit on the leadership team at Bristol, so I bring the updates directly to the team there. The Bristol Myers Squibb board is very supportive of it being a standalone organization. It's a first for Bristol. So very excited about maintaining the speed that the team has already executed against and continue in the future. But having, again, the backbone of Bristol behind us is a massive benefit. And I would say even to date, it's been wonderful just to tap into some of the platforms and expertise within the company. Okay, maybe just one more on the deal. I guess why now? What drove the timing, at this point in time? Well, clearly it's a very hot space, and we really view it as a key modality and next wave of cancer treatment. So, again, RayzeBio was at the top of the list. The team did an extensive review of the market as it heats up. Now was the right time to strike, as it were. I think they're very happy with the outcome of bringing Rayze in-house and super excited about the future. So I think before you got here this morning, we had a little bit of a discussion about actinium-225 as payload, perhaps relative to lutetium-177 or lead. And yeah, maybe talk a bit about how you or how Bristol sees the advantages, perhaps, of actinium-based technology. Sure. Yeah, we see it as the preferred technology at this juncture based upon the data to date. The large particle size and having the, you know, the energy release of something around 400 times lutetium with that degree of increased potency, we really do see the ability of the alpha emitter to create these double DNA strand breaks, which we think over time will lead to more durable responses and hopefully better outcomes for patients over time. So that's one aspect. The second aspect is from a half-life of having it around 10 days. From a logistical standpoint, that really gives us the opportunity to actually source worldwide markets from the US today. Moving forward, that gives us a great deal of comfort that we can actually learn from things like the cell therapy organization and get to just-in-time delivery and make sure the patients in need are able to receive therapy very, very quickly. So those are two of the major reasons. And the third one potentially being that as we've seen from the early data in GEP-NETs, you can also use a different modality, such as actinium post-lutetium treatment, hence after the phase 3 design. So an opportunity to go both, post and maybe in the future even as a, the first option for an actinium-based therapy. Right. And that's a good segue to my next question. So a few clinical questions just about RYZ101 in NETs in GEP-NETs. Just remind us of the opportunity, how do you think about it, and also, sort of what went into the design of the ACTION-1 trial? Yeah, so the phase 3 is designed as a post-lutetium study. So it is a PFS endpoint, which we believe is the right one to look at in this space. And more importantly, the FDA is aligned to that. It's a worldwide study. It's enrolling well currently. And we actually think that the potentially the data that Novartis has rolled out will actually increase the opportunity for an actinium-based therapy in second-line treatment. So we are highly supportive of that data. It looked very positive and looked to build on that for patients who ultimately may progress. So, yeah, enrolling well and excited about what that could look like. Just specific question just as you think about the phase 3 trial. I think the guidance has been sort of the data will be available in the 2026 time frame. Just wondering if there's perhaps an interim analysis built in that could potentially allow for earlier unblinding. Yeah, we haven't disclosed the exact numbers around that, but as you might imagine, we have both a regulatory meaningful as well as a clinically meaningful outcome on that or power the study for the right level of benefit on that front. So we do have an interim built into the study when we're disclosing that, but I feel confident around the 26th timeline that we should be able to see some positive data. Okay. And then, there will be some more phase 1 data here at ASCO from this program. Yeah, any additional learnings here that folks should look forward to? So the presentation at ASCO will be a build upon the data that we've already released earlier. So there will see greater maturity of patients. So really focused on what that looks from a durability standpoint. So that will be the data we're disclosing. We'll also obviously be taking a look at the continued safety of the program, and addressing, you know, some of the earlier concerns, around the accumulation in the kidney. You know, to date, the program has seen very little of that. So we feel, you know, to date very comfortable with the safety profile of the drug as well as the efficacy. Okay. And then, Novartis has already said they'll obviously file for first-line treatment with Lutathera soon, this year. I think they already filed in Europe, which, you know, as you mentioned, obviously may expand the opportunity for post-Lutathera treatment. But yeah, is there a potential path for RYZ101 also into first-line down the road? Is that part of the plan? It's certainly a consideration. We'll obviously look at the therapeutic effect in second-line and make a, you know, a risk-based decision from that. But, you know, the early data, we've certainly seen responses close post-Lutetium. And again, if the hypothesis is true about this alpha particle and just the higher level of energy being released at the tumor, then, it's certainly within the possibility that we could look to move to earlier lines of therapy. And then the drug is also being evaluated in small cell lung cancer. Yeah, in SSTR2-positive small cell lung cancer. Remind us of the percentage of patients that express SSTR2, perhaps relative to things like DLL3. And yeah, what should investors expect here in terms of the data in small cell? Yeah, so we do have a program in small cell. It's actually building on current standard of care, looking at atezolizumab plus chemotherapy. Interestingly enough, when we look at the immunohistochemistry, the tumors, the DLL3 versus the SSTR2 look quite distinct. So probably competing in a bit of a new space and not directly with the DLL3s in the market. The market is significant. Obviously, there is a high unmet need. While response rates have been relatively high in front-line in the 60s range, we're still not seeing great PFS. So we certainly see from a durability standpoint, that progression-free survival is a measurement that we'll be following closely, with the early data in small cell. Yeah, maybe I missed it just now, but yeah, so this first one study is in the first-line small cell setting, right, in combination. So you said, yeah, what is the bar here by standard of care? Yeah, so the response rate's again reasonable in the 60s, but we're just not seeing durability response over time. It's a complex disease. So we're hoping that building on standard of care, which obviously de-derisks, we're not trying to necessarily replace standard of care, gives us an additional opportunity with this modality to hopefully build and could give us proof of concept about how to build on the top of an IO-based therapy as well, which could give us learnings for additional tumor types. Gotcha. Okay. Super helpful. Any sense of, you know, any additional details on that study, sort of in terms of enrollment, how has that been going and, yeah, sort of the extent of the data update? It's enrolling. We have a number of sites open. So we will probably look to, you know, accelerate enrollment this year with probably data coming out next year at this juncture. Okay. Gotcha. All right. Cool. And then, yeah, RayzeBio also had another asset, RYZ801 for, hepatocellular carcinoma, liver cancer. Yeah, can you just tell us about that product, and the opportunity? Sure. We are executing a theranostic approach with the GPC3 program, which means obviously running the diagnostic as well as the therapeutic. HCC is again a high unmet need. We're talking about over 30,000 patients just in the US, and a significant number in Europe and Asia and beyond. So a very large opportunity. It's what we see is GPC3 being expressed in tumor cells and not necessarily healthy cells. So it lends itself to obviously a targeted approach. It's very early days. We hope to be filing the IND in the second part of this year, but excited about the program and the unmet need. I think there have been some imaging studies. So what have the learnings been from the imaging studies? We've done, yeah, a number of imaging studies, and we've been able to see that we've been able to hit the target on a pretty consistent basis. So there's probably about, I think in the, you know, more than 8 out of 10 patients, we're seeing pretty good uptake here, from a diagnostic standpoint. So I'm pretty hopeful that we've found a viable target here. And then I may have just missed it now. The IND is expected, IND second half of this year. Gotcha. All right. Great. And then, yeah, as you think about the pipeline, at this point, how do you think about expanding this into other areas, other targets, from your current, sort of beachhead in this space? Yeah, so we think you'd mentioned that the term beachhead, but I think as leaders in the actinium space in terms of number of patients treated and the size of the programs we have ongoing, we do think there's an opportunity to expand and rapidly invest in the pipeline. That was one of the major reasons that the Bristol purchase RayzeBio was actually just the speed of which the science is moving and have a number of potential targets that we are looking at in-house. And then again, the beauty of this model is being able to look at patient sort of target identification target validation at a very rapid rate. So there are a number of targets we're looking at early on, but probably looking to disclose those over the coming months and maybe into next year. But a lot of activity and rapidly expanding the research team in San Diego, to make sure that we're running these targets down as quickly as possible. Okay. And then on the manufacturing and the CMC side, we just heard actinium is, you know, not the easiest isotope to source just in terms of the general availability in quantity. Sort of talk about how you're tackling that? Sure. We have a site operational in Indy. It is a cutting-edge, brand new build from the ground up, absolutely beautiful facility, which is now operational. In the middle of this year, we'll actually start to conjugate across the actinium-based therapy in our part of our 101 program. We thought it was important to make sure that we actually take our future into our own hands. So having an in-house manufacturing capability is very, very important in this space. As you'd mentioned, we do believe, you know, that over time, the actinium supply issues will just be figured out. We think that the level of demand will ensure that there is the supply on the market. We have a number of agreements in place with organizations, and we'll ensure that we have redundancy through the supply chain. Having your own facility that will be able to get us not only to be able to fulfill clinical need, but also fulfill commercial need was one of the major reasons that we were actually purchased, RayzeBio in the first place. And then from a logistics, you know, down the road and sort of treatment and supply chain, you know, mechanics, you mentioned the sort of the CAR-T analog perhaps where you obviously have Bristol has a lot of experience at this point. But yeah, how do you expect this to play out and how do you plan for managing sort of the supply chain and treatment logistics? Sure. Well, as mentioned, the 10-day half-life is helpful when you think about the worldwide logistics, which needs to go into place. We've spent actually in my, you know, currently now almost two months on the job, but a lot of time in figuring out actually what the systems we need to put in place from GMP through to GCP and ensure that we have a worldwide footprint which can deliver just-in-time and real-time therapy to patients in need. So, very comfortable with how that is going so far. I think like anything else, when you're the, you know, leader in a space, there's going to be bumps on the road in the short term. But we feel confident in the future and having our destiny in our own hands with our own manufacturing facility put us in great shape to serve the market, first of all, in the GEP-NETs where Novartis has already built the infrastructure. But then beyond that, with some of the other novel targets that we've spoken about. And then when folks think about modeling this, yeah, what are expected cost of goods for RYZ101, perhaps relative to Lutathera or other Lutetium-based programs? Yeah, we won't guide exactly to COGS at this juncture, but it's probably within the similar range. We actually use a lot less Actinium is required from a quantity standpoint. And like I said, having to rely on, you know, third-party source suppliers and over time then bringing it in-house in a relatively near future, I think will affect pretty dramatically the COGS. But that will take a little time to get it where we want it to. But we see it certainly a sustainable and profitable business in the future. Okay. Great. And then, so you did mention some in-house work, that's ongoing to look at additional potential targets, new programs. You said you'll probably talk about this in the coming months. But yeah, to what degree does Bristol think about further augmenting the radiotherapeutics pipeline with additional business development versus building in-house based on what you have right now? Yeah, so we're very focused on executing internally at RayzeBio. That's priority number 1. So ensuring that we have secure long-term Actinium supply, which is well underway, make sure that we're accelerating the clinical trial enrollment in the 101 study. And then we do have a lot of discussion and dialogue around. You know we have a dedicated team at Bristol which is looking at the radiotherapy space. So this is not a space which is that, you know, we're at very in the early stages of this. So certainly very active in looking around at potential licensing and collaboration options as we begin to build in this modality. We're very keen to be ultimately the world's leader in this space. We're very excited about the modality, and we know that we can't just do that internally. But we have a lot to digest in the short term. So, with all the acquisitions at Bristol, we have quite a lot to digest. But radiotherapy is certainly a priority as we think about oncology development in the future. Great. Thanks, Ben, is all I had. Let me see if there are any questions on the audience before we wrap up. Yep. So you mentioned a lot of synergy between Rayze and BMS, but what about combination therapies? Is it something you would like to explore with the BMS pipeline? It is. It's a little early to comment on that, but I would say that our my engagement with the CSO, Robert Plenge, and others, they've already done a lot of thinking about what this means. They're very excited about the possibility on this front. So there is a great partnership between my research team at Rayze as well as the Bristol mothership, as it were. We're literally meeting on a weekly basis thinking about what is not just from a novel target standpoint, but what are the rational combinations which make sense moving forward. So yeah, absolutely. Great. Well, thanks, Ben. Really appreciate it. So we speak again at noon at our industry panel. And so next year at 11:30 A.M., we'll have Alpha Tau Medical. So looking forward to that. Thank you. Cheers. Thanks.