Growing And Scaling A Radiopharmaceuticals Company With AdvanCell's Philina Lee, Ph.D.

0:03Philina Lee, Ph.D.: Welcome back to the Business of Biotech. I'm your host, Ben Comer, Chief Editor at Life Science Leader. And today I'm speaking with Philina Lee, Ph.D., CEO at Advanced Cell, a clinical stage radiopharmaceuticals company developing targeted alpha therapies that are targeting prostate cancer. or at least the lead indication is. The company just closed an oversubscribed$350 million Series D financing in July. Felina joined the company as CEO at the beginning of this year. She was previously chief commercial officer following other senior level roles at Blueprint Medicines, which Sanofi acquired for over$9 billion in 2025.

0:49Philina Lee, Ph.D.: Before that, she was U.S. brand leader at Algeta, where she worked on the successful launch of Zofigo. Algeta was acquired by Bayer for$2.9 million in 2014. She also worked as a global product manager at Sanofi and has served as a board member at Fusion Pharmaceuticals and is a current board member at DBV Technologies. Phelena holds a PhD in cell biology from MIT, and I'm thrilled to have her on the show to talk about growing and scaling radiopharmaceutical companies and commercializing therapies, how the recent Series D came together, what Advanced Cell is doing to overcome manufacturing and isotope supply issues with radiopharmaceuticals, and what the competitive landscape looks like for targeted alpha therapies.

1:37Philina Lee, Ph.D.: Phelena, thank you so much for coming on the show. Thanks so much for the opportunity, Ben. I'm really excited to be here. I'm glad to have you. I wanted to start off with some background, Felina. You've worked more or less exclusively in radiopharmaceuticals for the last 15 years, beginning at Algata. What interested you initially about the radiopharmaceuticals space and what has kept you working in it? Yeah, thanks for that question. I feel like that could go back pretty deep to the origin of sort of how I started my career as a scientist. And what drove me to first become a cell biologist is really around finding ways to make ideally transformative impact on human healthcare.

2:28So I remember as a kid kind of looking through my first microscope, looking at cells, and reading about the biography of Louis Pasteur and how he unlocked this insight that it's really germs that cause disease. So somewhat naively as a seven-year-old, I thought, well, gosh, I want to do things like that when I grow up. I want to have meaningful impact on human health care. So I did, in fact, in the first stage of my training, become a cell biologist and a microbiologist. And I think part of what attracts me to targeted radiotherapy kind of fast forwarding is just this implicit intuitive understanding that it should work, right?

3:17If you can get a radioizotope targeted to a tumor cell in a quick way and in a specific way, that radiation can deliver high energy to the tumor cell, cut up the DNA, and it's really hard for cells to overcome that. So there is this element of as a payload, as a targeted payload for oncology, this really should work. And we're only at the very beginning of really unlocking the full potential of what this modality can do for patients. Yeah.

3:50Philina Lee, Ph.D.: And the alpha therapies are a double DNA strand break, right? Like super effective to get into the right cell. Exactly. That's a really important point. As we've seen the field evolve, some of the first therapies that came to approval were focused on a different mechanism, the so-called beta emitters, and those work by causing single-stranded DNA breaks. So while clearly those therapies have shown there is a degree of efficacy, there's really an opportunity to improve on that. We see upfront resistance from some of these therapies because cells can figure out how to repair single-stranded DNA breaks.

4:30it's a lot harder to repair double-stranded DNA breaks. And that's one of the key differentiating features of kind of the next wave of payloads that has come in targeted radiotherapies with the alpha emitters, is that, in fact, they cause double-stranded DNA breaks, which are virtually irreparable. So there really is potential for greater anti-tumor activity through these approaches.

4:58Philina Lee, Ph.D.: So I mentioned you were at Algeta. They were acquired. You joined Blueprint Medicines and were steadily promoted over an 11-year period. I think you ended up as chief commercial officer at Blueprint. It was acquired by Sanofi while you were in that role. What were some of the challenges, Felina, that you faced maybe on the commercial side at Blueprint? Yeah, I think that that's a really great question. Blueprint was a really formative experience. When I joined the company, it was about 50 people, research phase, private company. And so I really had the opportunity to be part of bringing the company public, sitting embedded in all of the programs as we moved rapidly into the clinic, reaching proof of concept.

5:52And, you know, we went from first in human to registration in four years or less with both of our approved programs. then having the opportunity to be a part of launching and, in fact, leading the launch of these medicines ultimately across five indications globally. It was an incredibly gratifying experience to really be part of that end-to-end drug development and commercialization on a global scale. You know, I think some of the challenges that we encountered and, you know, Blueprint Medicine started off as a precision therapy, precision medicine company focused on oncology drivers. as we moved forward, the direction of the science, the medical needs that we saw, and I would say to some degree like the market appetite, led us to evolve from precision oncology into a different therapeutic space, into INI, really expanding into mast cell disorders and developing novel treatments to help patients with these mast cell disorders.

7:06That also was an incredible journey of following all of those breadcrumbs of, you know, the direction of the science, the need that we were hearing from patients, and then evolving as an organization to meet that need. I think, honestly, one of the things that became clear over that journey is, you know, Blueprint was a tyrosine kinase inhibitor platform-based company. That was a modality that was kind of, you know, you could see that we were reaching the end of the target potential of targeted oncology drivers. I think the number of targets that could be worked on, like, I mean, apart from the phenomenal KRA, the RAS success that we've seen recently, you know, but there's a finite number of targets.

7:54That's a space that has really been mined pretty deep. And secondly, resistance is a big challenge. I think when you have this kind of lock and key type of modality, there are different ways that cells can overcome the binding of a tyrosine kinase inhibitor. And so I think one of the things that made me so excited to return to the space of targeted radiotherapy and return to oncology is this idea that, you know, targeted radiotherapy is still really early as a field. We have really only unlocked, you know, two targets. There's opportunity to improve on the treatments that deliver against the patients who bear those targets.

8:43And there's this incredible greenfield of opportunity to unlock medicines against additional targets and patients with broader tumor types. And I would go back a bit to where we started in terms of the mechanism of this latest generation of payloads in targeted radiotherapy is something that holds incredible promise and that will be very difficult for cancer to develop resistance to. And that's what makes me so excited to come back to this space. There are a large number of patients that can be helped who bear very relevant targets that we can go after.

9:30Philina Lee, Ph.D.: And the two targets that you've identified so far, is it PSMA1, the PSMA receptor? And then what's the other target? Yeah, the first target that we're focused on is PSMA, which is important in prostate cancer. 90 % of patients bear this target. They keep it for the majority of their course of their disease. It's something that's highly expressed on the surface of tumor cells with minimal low to no expression on healthy tissues. And so all of those things start to give you a signature of what makes a really good target for targeted radiopharm approaches. I can elaborate more on our lead program ADVC001, which is a novel lead 212 payload.

10:20That's a novel alpha emitter that targets PSMA for patients with advanced prostate cancer. It's currently in phase two. So I'll plant that there and we can go deeper. But as far as additional targets, we are actively focused on building and diversifying our pipeline. We have selected a second target. We haven't disclosed what that is. But what I can say is it is in a gastrointestinal tumor type with high medical need, very limited treatment options and poor prognosis. The target bears a lot of those similar qualities of what makes PSMA a great target. And so we're actively working towards advancing this second program towards the clinic while we continue to work on additional targets in this space as well.

11:16Philina Lee, Ph.D.: Yeah, thank you for mentioning that. I do want to pick back up on that in just a second. But I wanted to ask, you know, on some of the, you know, kind of the financial aspect, both Algetta and Blueprint were acquired for billions of dollars, billions with a B, as was Fusion Pharmaceuticals. You were on the board when AstraZeneca, I believe, acquired that company for$2.4 billion, I think. For company founders and CEOs out there listening, what would you say, Felina, is the most important element in attracting those kinds of big pharma deals? And I know it's not, you know, a single item that brings in a billion dollar deal like that.

12:01Philina Lee, Ph.D.: But is there anything that you could say about what makes a company, you know, even relevant or open, you know, to that type of transaction? I'm going to have to lead by just sharing maybe the adage, like great companies are bought, not sold. So I think a common theme across these companies I've had the privilege of working in and being a part of, really, the teams were laser focused on delivering for patients, right? Sort of playing, working towards that long game of building a fully integrated company. I think that, in fact, can also translate into value maximization when M &A opportunities do come up is the fact that you've got a strong and solid business plan and you've got a team who's really motivated on executing the strategy and achieving those value driving milestones.

13:00Um, beyond that, I think, um, you know, each of these, um, so I think Algetta and Fusion, taking learnings from the radiopharm piece, stand out as having both clinical assets as well as the vertical integration, um, on how to manufacture those assets. And that's an important, I think, differentiating feature when you look across the radiopharma space. We share that same philosophy at Advance Cell that it's not enough to be advancing innovative science and have differentiated clinical assets as we do with ADVC001 and working on more to come. But equally important is the ability to ensure scalable supply and manufacturing.

13:52And we've invested in building those capabilities at AdvanceL from day one. I think I can't underscore enough why that's so important because scaling supply and manufacturing has really been one of the key bottlenecks to the progress of this targeted radiotherapy field. if I go back to the sort of the blueprint example in this again I would say you know from the start it was the vision and the goal of the team to take this platform that we had around tyrosine kinase inhibitors to go after the underlying drivers of disease follow the science and follow where the medical needs were in the patients and you know we we did that we we were fortunate enough that a couple things worked.

14:41Some things didn't work. I also want to make that clear. This is like biotech is a high risk sport, right? So we had to pivot. We scaled the company in a way that was sustainable. That's a really important point. Because when we hit the bumps that every biotech company will, right, we had a pivotal trial fail and read out. We actually didn't have to lay off our staff, any staff. And that's because of how we had scaled reliably, sustainably. We hired team members who are agile, who are able to pivot into different programs and even different therapy areas as we move from oncology to allergy and immunology.

15:25So I think those learnings around how to build a long-term, sustainable, scalable company are equally important, and we bring those lenses to advanced cell as well.

15:38Philina Lee, Ph.D.: Yeah, I want to bring I want to dig into that a little bit. And just a second, I think I maybe misspoke at the beginning. Blueprint Medicines was not a radio pharmaceuticals company. So I'll clear that up really quickly. But let's staying with advanced cell. What what circumstances I guess brought you to the company as a as CEO? And it's your first it's your first time as a CEO, I believe, right? Yeah, it is. In fact, yes. Thank you. Thank you for that question. I think at its core, the answer to that, it's a very mission-driven cause, and it goes back to a core belief that targeted radiotherapy is a modality that's just really early on.

16:25And I think at this stage in my career, I honestly, I can't think of anything better to work on than really helping to be a part of leading in this space and unlocking the potential of this modality to deliver for patients. Every piece of what we're doing, whether it's advancing the lead program, unlocking the next target, or building out further our U.S. manufacturing network to manufacture lead-based therapies at scale, like all of those things are contributing to this momentum that we're seeing to deliver patient impact at the end of the day based on these approaches. That's the sort of mission-driven answer to your question.

17:09The sort of story answer to your question is, you know, it happened really quickly. About a year ago, I had my last day at blueprint post acquisition, you know, I turned in my badge. I think there was a very natural period of kind of mourning that transition right after having been invested in a company for so long and knowing it as our own. And I was preparing to just really do some very deep soul searching and thinking about what could I possibly do next that would bring me the same degree of meaning and gratification. And, you know, I thought this was going to take a while, you know, six months, maybe clear my head.

18:00And as luck would have it, I got a phone call one month later from a gentleman named Andrew Kay, who had just joined Advanced Cell as the chairman of our board. Now, it turns out Andrew Kay was our CEO at Algetta and just a longtime mentor, leader, highly respected. I always thought when I'm ready to be a CEO on my on my dream list of board chairs would be would be Andrew Kay. So so that was a phone call I had to take. And then very shortly after that, advanced cell released our very first first in human clinical data. And that came out at ESMO of last year for ADVC001 phase one B study. And I still remember the feeling that I had when I clicked open that poster and I saw those deep waterfalls, right?

18:55Like rapid and deep PSA responses. 80 % of patients at the recommended phase 2 dose had a PSA 50 response. And six patients were valuable for radiographic response, and they all responded. So 100 % ORR. Wow. And then on top of that, a really compelling safety and tolerability profile. No discontinuation or dose mods due to adverse events. No dose-limiting toxicities. And I just had this very visceral reaction seeing this poster of excitement. And I thought, gosh, I was privileged to work at my last company where we saw phase one data that actually looked like that, right? and launch medicines that benefited patients based on those early phase one signals that were so compelling.

19:52And here was another one. But in some ways, it felt like all roads led here because, again, that connection to Andrew, the chairman, the Algeta, and then the fusion experience. And my just core fundamental belief as a cell biologist, like this has got to work and we can unlock it. So all of that came together. And as I got to meet more of the team and really understand, in addition to that, how we had invested in building our manufacturing platform and that we had really focused on developing technology that's innately scalable, it became a no-brainer, right? so I didn't think I was going to jump that soon but I think within a couple weeks I was signed and it was I was compelled to do it I was going thinking about it, I was waking up thinking about it and so it became a really easy choice, all my career I've made decisions at the end of the day based on my gut as long as there's the calculus of the mission and the team but it just becomes a gut feeling at the end of the day

21:06Philina Lee, Ph.D.: On the CEO role, I guess you're about nine months in as a CEO. Is it about what you expected it to be? Were there any parts of the job that, you know, kind of came as a surprise? Yeah, it's a great question.

21:25That's a deep, I mean, that's a deep question. And I'm someone who is so self-reflective that I'm going to try to give a quick answer to your question. And I think that the clearest piece is truly the joy that I get from working with our team, our leadership team, motivating the team. That's something I think also that I brought from my last experience at Blueprint. You know, sometimes people have asked me, what was the secret sauce behind your big launch, right? How are you guys so successful? And it starts with the team, right? It was the work that we did as a commercial leadership team at the time, elevating each person as an individual, elevating the team as a high-functioning team.

22:12And so I think part of what drove me to want to take the CEO chair was that element of, I love working with high-performing leadership teams. I want to foster them. I want to cultivate them. I want to attract talent. We have been incredibly fortunate in the strength of executive leaders that we have recruited to the organization over the past nine months. I think another component of it has to do with just my background as a cell biologist, commercial leader who became involved in high growth company building. It's a broad lens. lens.

22:56Philina Lee, Ph.D.: And I know those are the key elements, right? It's stretching the lens. And and at some point, as I was looking at different opportunities, I think I realized, you know, some of them just felt too narrow and maybe I should just go for taking this seat. I think in terms of so, you know, what what wasn't surprising was

23:24the effort, the joy, the gratification of working with the team and seeing it take off, right? So like that's tangible, I think, to us at Advanced Cell. Part of that too, there's cross geographic connectivity, right? We've got a team based in Brisbane, Australia, where the company was founded. We've got a team that's growing in the United States, where we recently moved our headquarters to earlier this year. And as someone, you know, I'm Canadian turned American. I'm both now. I'm able to connect, I think, with those cultures. I learned some of that also from the Algeta experience where we had a home base in Oslo and we were building out in the Boston area for U.S.

24:14commercialization. Those experiences, I think, helped prepare me for the work that we have ahead here at AdvanceSell. I think one of the newer tasks that I took on in this role was our Series D financing. So, you know, in some ways, nothing could have fully prepared me for that.

24:35Philina Lee, Ph.D.: Yeah, baptism by fire, that's right. Baptism by fire is probably a good way to describe that candidly. And, you know, I will say, I what I took to that exercise was my core I leveraged my core strengths in storytelling right I've been in commercial the majority of my career so how do you tell a compelling pitch how do you understand what is what the investors are interested to hear and position a concise story of our company to highlight how what we're doing is in fact really well in line with what investors are looking to invest in, right? Like they're looking, there's like more, less, like later stage assets and or de-risked assets and targets.

25:22And then how do we talk about sort of the unique scalability of our supply and manufacturing capabilities and what we're trying to build for the longterm. So, you know, that, I think that raise was probably one of the more formative early experiences. I couldn't be more pleased with the outcome. We raised$315 million. It was outsized. It was oversubscribed. We brought in a really high quality investor syndicate who positions us really well for growth going forward.

26:00Philina Lee, Ph.D.: Yeah, exactly. The investors liked what you had to offer. You mentioned ADVC001, your lead clinical candidate. Do you have a sense of, I guess, maybe what percentage of the potential for that lead candidate versus the kind of overall integrated manufacturing operation that you've talked about and that I want to ask you about a little bit more? But is it, do you get the sense that investors are feeling really strongly about the market opportunity for ADVC 001 as a kind of primary value? Or was it, you know, is it your sense that it's more of like what, you know, what's yet to come and your manufacturing and supply chain structure?

26:49Yeah, that's a really great question. I mean, it has to start with the clinical data. And I think having that clinical data that I just described to you is an incredibly strong hook for investors. And the strength of that data in a market which already today in prostate cancer is a validated market for targeted radiotherapies. The current standard of care, you know, metetium-based PSMA is predicted to have a$5 billion peak potential. Right. So I think with the innovative approaches that we're looking at with ADVC001, we really see best-in-class potential and to take a leadership position in terms of the market share of the existing market.

27:39And importantly, we also see the potential to grow the market and tailor the adoption, the development of these therapies for earlier adoption for patients who are earlier in the prostate cancer treatment paradigm. So this is a multibillion-dollar opportunity with several indications within it as well. In our phase two, we are studying three different patient cohorts, each of which could become a future indication over time. We're studying patients with metastatic castrate-resistant prostate cancer in the frontline setting, which is the largest tranche of the RLT market today in prostate cancer, as well as post-lutetium.

28:27And importantly, we're also studying metastatic hormone-sensitive prostate cancer patients. But we're taking a really unique approach in this earlier stage cohort where it's like a precision approach where we're targeting about a third of patients who are not well controlled by current standard of care. So they have detectable PSA. They're easily, you know, sort of identified by providers. And what providers, this is a distinct approach from what others have taken. And what providers tell us is it's really important because they don't necessarily want to treat all comers. They really want to treat this subset where they see the highest urgency to treat.

29:13These are patients who are more likely to progress more quickly. So this is another differentiated component. Going back to your question, I think, you know, truly, I think the big first draw is that we have such differentiated data in a meaningful sized market with multiple potential indications. And then the transition to the supply and manufacturing discussion is more about building the confidence that we can really deliver and execute at scale.

29:44Philina Lee, Ph.D.: uh 880 vc 001 it's pb 212 or lead isotope you mentioned it's in phase two um yeah i think you were you were talking about pluvicto with the potential of five billion dollars in sales of course dofigo which you're very familiar with is also uh prescribed to treat prostate cancer um and you mentioned differentiation and maybe patient response is a key one but is there anything else that you would say just in terms of how you're thinking about how this product will be differentiated? Yeah, it's such a great question. And I've been sort of working in prostate cancer since about 15 years ago was my first launch in prostate cancer.

30:30And so the field has evolved significantly. We've made progress. But importantly, there's still some you know, real outstanding unmet medical needs and opportunities for innovation. And the things that I would underscore are, you know, first and foremost, the need to develop new, you know, additional and new treatment options with a favorable benefit risk profile. That's especially important to be able to move earlier in the treatment paradigm and preserve patients' quality of life. I think the second piece that you alluded to is the need to address upfront resistant to current treatment modalities.

31:16And again, like the lutetium-based approaches, about 30 % of patients have upfront resistance. I think the degree of response that we're seeing in our phase one data to date, they validate our hypothesis, right? That the potency of a lead 212-based alpha should really be able to overcome these upfront resistance mechanisms. A third piece that we haven't really talked about much yet that I think is really important to our clinical differentiation is around maximizing the duration of treatment benefit for patients. And so, you know, if you look at targeted radiotherapies to date, most of them are given up to a maximum of four or maybe six doses, and then they stop.

32:11Importantly, so we're leveraging these properties of lead T12, that idea of, you know, get to the tumor, deliver this high potency anti-tumor impact, and then you're quickly gone, right? 10.6-hour half-life, you're minimizing accumulation in healthy surrounding tissues. We are leveraging that to do some truly novel dosing strategies. And I'll break this into two parts. One element of this is giving more doses, right? So studying the benefit of extended dosing regimens. In our phase two, we're studying up to 12 doses of ADVC001 to test the hypothesis that giving more doses should extend the benefit of treatment duration and response.

33:05A second important component of this is the ability to give doses closer together. And that's actually part of what we studied in the phase one trial where we studied patients with dosing, you know, for every four to one week apart. And we saw, you know, the results that I've underscored of just, you know, deep, rapid, deep responses. The reason why that's so important is it enables us to get rapidly dividing tumor cells under control. We see this kind of induction and maintenance approach used with other modalities successfully in oncology. Yeah, right. You know, it hasn't yet been truly tested for targeted radiotherapy and led to 12 with these properties that I described, like high potency and then quickly gone, is we think optimally positioned to look at some of these flexible and extended dosing approaches.

34:06And so that's a key area of focus in our phase two study as well. And we believe that that will further extend the clinical differentiation that we're seeing.

34:15Philina Lee, Ph.D.: So that shorter half-life with a lead radioisotope potentially means less off-target effects, less toxicities potentially than, you know, some of the other medications that you mentioned that are only being dosed four to six times? That's a key part of the hypothesis. And, you know, importantly, we see the potential for differentiation not only against other radiotherapy approaches, sort of, I would say, like longer dwelling radioisotope approaches, but it's also really important when you just look against, you know, other emerging modalities. You know, there's a lot of innovation happening right now in prostate cancer with new modalities like ADCs, T-cell engagers, novel androgen receptor pathway inhibitors.

35:07But importantly, I think there will be an important place for therapies that balance strong benefit as well as that benefit-risk profile that preserves quality of life. And we know that targeted radiotherapies, and particularly what we've seen so far with lead-212, we believe is really amenable to a great benefit-risk profile. So that's important to enable that potential for broad adoption across the prostate cancer fetin paradigm.

35:43Philina Lee, Ph.D.: I want to talk a little bit about manufacturing and supply chain. I've covered radiopharmaceutical manufacturing and supply chain issues with previous guests. Radioisotope half-life can add complexity to delivery. Isotope sourcing can be unpredictable. There are qualified staff shortages, some additional regulatory issues. I know you're well aware of all of these, probably others that I didn't mention. But I guess what would you say about advanced cell and scaling up for, you know, this phase two and then phase three to come? How are you how are you thinking about managing those those manufacturing and supply chain issues?

36:30Yeah, it's such an important question because, as we've alluded to, this has been one of the big bottlenecks in the space, right? And it's hard. It's a hard problem to overcome when you think about how to distribute at scale an isotope with a finite half-life, as well as to feed all of the pieces to manufacture at scale reliably. So this is, in fact, something we've invested in since the beginning of the company is developing a novel technology for how to reliably manufacture lead 212 at scale. I'll sort of unpack the, I think, core pieces of our technology, and then I'll talk a little bit about how we're applying that to really build a U.S.

37:24manufacturing network at scale. So the core pieces of our technology, I would just start by saying we've invested in the vertical integration, right? So end-to-end control of this process from isotope supply through to finished drug product manufacturing from the beginning of the company.

37:45Philina Lee, Ph.D.: Okay, so that's what you mean by vertically integrated, that end-to-end. Yeah, exactly. Exactly, exactly. And, you know, the isotope supply part's really important. And maybe I'll draw the analogy to when you want to bake a cake, we have the ingredients in our pantry, right? So if you got to bake that cake really quickly because your customer's coming in a few hours, we've got the flour and sugar and the eggs, right? So that's why it's important that we have supply remints in place for strong and secure supply of thorium-228, which is the parent radioizotope for lead-212. And so part of it is we have the thorium.

38:32Another differentiating factor I will highlight is the parent radioizotope for actinium is much more finite. the amount that's available in, I would say, like in the world.

38:45Philina Lee, Ph.D.: Yeah, it's more scarce. Innately, it's much more scarce. And you have hundreds of companies, I think, competing for access to a scarce resource in contrast to a handful of lead T12-based companies and having thorium much more abundant. So we have our pantry stocked. And the first step in our process is to make these sources where we embed thorium on the sources. These little sort of disc-shaped material, a little bit larger than the size of a quarter in diameter that could fit in the palm of your hand. So we deposit thorium onto these disk-like sources that are made of a very strong, radiolytically resistant material.

39:37And then eight of these sources go into a generator. So just imagine a box about the size of a case of wine. That's our generator, which fits. Yeah, so you guys own a generator.

39:46Philina Lee, Ph.D.: You're doing that yourself. Oh, yes. So we have developed all of this technology in-house. I'll just jump to, yeah, I'll cut to the chase. So all of our clinical doses to date, we have manufactured in-house. Phase one and phase two to date, hundreds of doses. And this has been done through internal manufacturing site in Brisbane, in Australia. And with that technology in hand, we're now transferring that technology over to the U.S. so that we can file our U.S. IND and begin to treat the first U.S. patients on our Phase II study and ultimately scale towards Phase III readiness. So going back to what's, I think, cool about our technology, you've got this generator.

40:37I'll draw the analogy to an espresso machine. So you put eight sources in the generator and then the thorium emanates to radon gas, which ultimately collects as solid lead 212 in the bottom of some collection cups. The whole process takes about a day to make one batch of lead 212. We draw down that lead and we mix it with the PSMA binding ligand. that's a fast room temperature reaction and that's that's how we get to our finished drug product we have extensive purification and quality control testing processes in place to ensure that this process has occurred with high fidelity and that we have had no radionucleic impurities like no thorium is sort of getting through to that finished drug product And so this full vertical integration of the capacity to take in high activities of thorium, manufacturing our source technologies, the generators that we have manufactured in-house, all this technology has been done in the hands of the advanced cell team and really refined over several iterations to maximize the reliability.

41:58and the scalability of the process, I'll emphasize because it works as this fully automated modular generator, all you have to do to scale is put several generators in a manufacturing line. That's what we're building now in Brisbane. We're constructing this commercial pilot line so that we can validate when you put several generators in a row, the capacity scales accordingly. You can then put several manufacturing lines in a manufacturing site. And then you can ultimately have several sites in the manufacturing network. So, you know, we often get the question, how are you going to distribute this product given its 10.6 hour half-life, right?

42:46Like you alluded to this as one of the - Yeah, that was my next question. Yeah. So the how is essentially we are building a network of U.S. manufacturing sites with approximately five sites across the U.S. And we've already mapped out the ideal location of these sites so that we'll be able to serve over 95 % of metastatic prostate cancer patients. um so so the answer is you can't do it with one side alone you need to take this more regional approach um this is eminently doable right other other companies are building towards manufacturing networks um we've seen precedence with um i would say um prostate cancer imaging agents that have only a few hours of of uh of shelf life um and they they go to an even more regionalized model that, you know, clearly some of these imaging agents, like they too have been very commercially successful with like, you know, billions of dollars of sales as well.

43:54So it's an eminently doable model. I'll go back to the Zofigo experience. You know, we learned from that experience how to successfully distribute a product that had to leave the dock in Oslo, fly into the United States, move to regionalized radiopharmacies, and then ultimately to customers. And we were able to execute on that very successfully in our launch process and with very high rates of patients successfully receiving their doses on time. So all of the things that, you know, you think could be hard, I would say it's doable with the proper logistics, with the proper planning.

44:44Philina Lee, Ph.D.: So the doses for the phase one and phase two trials were coming from Brisbane, where it was all, were all being created in Australia and coming over. So yeah, just to clarify, so to date, those studies have recruited from Australian sites. I was going to say, yeah. Yeah, yeah. It's an important clarification. And so currently, we are building out the infrastructure and transferring our technology so that we can begin the manufacturing in the U.S. and start to enroll U.S. patients. But I will say we've learned a lot from the initial experience in the phase one and two studies to date. When I talked to the investigators that we're working with, and these are some of the world's top experts in prostate cancer, they've told us in their hands the logistics are no more difficult than the current standard of care.

45:39The way that they're bringing in patients, the way that they're scheduling is very similar. So we just have to do the hard work of getting it there on time.

45:51Philina Lee, Ph.D.: It's rare in other drug modalities for companies to build out all of their own manufacturing. It's much more common to work with a CDMO. And I'm wondering, you know, the calculus must be different in radio pharmaceuticals when it comes to building your own manufacturing versus versus outsourcing that work. So, you know, why is it important to have your own facilities? Are there partners available that that could do it? Or what would you say to that? Yeah, I would say first I would just emphasize. So I think it's really important to have developed the technology, vetted and learned and refined the technology in-house.

46:38But even where we stand, like we do take a blended model. We're partnered with the CDMO who will manufacture our first doses in the U.S. But hand in hand with that, we're also building a flagship manufacturing facility in the greater Boston area. That's going to contribute to future phase three and commercial scale. So I would almost say where you have to have the like eureka moments of like, OK, we figured out how to make lead. We figured out how to make sources like reliably. We figured out how to make generators that are automated and modular. Now we can port that like, you know, how do you get that technology to a stage where it's validated and you can hand that to a partner and it can scale.

47:25Right. So actually recently a KOL asked me, like, when is this going to be like McDonald's? Right. So it's we're not McDonald's yet. Yeah, it's a more bespoke, you know, really nice burger. But we are working towards, you know, a broader scalability. And so I wouldn't say that we're wedded completely to the in-house model, because in fact, we do have, you know, a great, we do have a CMO partner. um but going back to the why is it so important to build your own and those eureka moments um we if we've taken the time to understand and really hone and improve and continually improve our technology um and you know a key reason why we've chosen to build out the greater boston site that's in andover is that will be our first sort of true phase three ready and future commercial scale ready internal manufacturing site.

48:24So it's a really important proof point to do that well, to do that on time with the sort of the validation and porking over the technology and all of the learnings from what we've done in Brisbane. We think that's important. You know, like we control the execution and we think that's an important part of successfully scaling.

48:48Philina Lee, Ph.D.: In our last few minutes, I want to back up a little, Felina, and ask you a kind of a broader question about the radiopharmaceutical landscape. How would you describe the current competitive landscape broadly, you know, not just in prostate cancer and maybe what it might look like in a couple of years? Yeah, I would first start by going back to that sort of inflection point or tipping point, which I think is ultimately that's really great for patients, right? So there's obviously increasing momentum in the space. There are more companies coming in. There are more companies working on unlocking next targets, improving on existing targets, as well as moving towards newer radioizotope payloads.

49:33So all of this is great, right? To me, this feels like where the ADC field was several years ago, right? Like it's about to break, like it's in a good way. And so I think in terms of competitive landscape, I think the simplest way to think about it is about there's like sort of payload innovation and then there's sort of product and target innovation. So like the payload innovation we've already talked about, the SEAL started with the Bayes. You know, I would say Alphas is kind of where the action is at present. There's so many companies that are focusing on Actinium. Clearly, there's a place for Actinium.

50:19And there's, you know, there'll be more targets unlocked as well. That being said, from a clinical positioning point of view, you have benefit-risk considerations of a longer-lived radioisotope. You have also the supply and manufacturing considerations of a finite parent radioisotope. So we really think of lead as leading edge. I mean, some of the investors have even told us, you know, you're on the next wave of carbon ed radiotherapy and at the front. There's only a handful of companies that are focused on lead 212-based targeted alpha therapies. We've already spoken to the potential benefit risk advantages as well as scalable supply and manufacturing.

51:09So I would say there's a very, you know, deep area to be mined here. Like we haven't even begun to crack the potential of patient benefit, both improving on PSMA, there are others working on SSTR2. And then there's all of these other new targets that we can be working on. And so I think that's where my greatest excitement lies. That's what we're really focused on at Advanced Cell. I think the other piece we've talked about beyond the clinical innovation is around supply and manufacturing capabilities. And there, I would say, there are companies that have chosen to kind of outsource all of the manufacturing.

52:01And there are companies that have chosen to keep that control, that vertical integration. We think that's a core strategic and competitive advantage at Advanceall.

52:15Philina Lee, Ph.D.: Last question for you, Felina. What are your top priorities for the rest of 2026? Yeah, yeah. Rest of 2026. Well, I think there's only a couple months left there. So maybe we can take it into the second half. Yeah, yeah. Yeah, I'll sort of think forward thinking. But yeah, I mean, I think now with the raising, with the financing in hand, our whole team is just laser focused on execution. We're focused on moving forward the lead program, ADVC 001. We are excited to present longer term safety follow-up on the phase one data at ESMO next month. So that's a good literal answer to your end of the year question.

52:57And we look forward to presenting top line phase two data. But the real goal that we're focused on is moving this program towards phase three readiness. And the RAISE will enable us to do that hand in hand with scaling our supply and manufacturing capabilities to be phase three ready as well. And then the third priority is to move a second program into the clinic.

53:24Philina Lee, Ph.D.: On phase three, just a quick follow up on that. Will this Series D raise allow you to actually start up phase three or will you need to do do you expect to do some additional fundraising at that point or or seek a deal? How are you thinking about that? Yeah, when we reach phase three readiness, it'll be important for us to evaluate our options for future financing. And we'll look at a range of different options there that will best position the company. You know, as you know, we're really building really sort of two companies at the same time, a traditional biotech advancing the programs as well as scaling the supply and manufacturing infrastructure.

54:08So this is a capital intensive business that we're building for the long term. And I think we have a number of milestones ahead of us that we are excited about and will de-risk the progress of the program along with supply and manufacturing. So we look forward to executing on those and evaluating our financing options as we reach that phase three readiness.

54:35Philina Lee, Ph.D.: Felina, thank you so much again for coming on. Thanks so much for the opportunity, Ben. I really appreciate it. We've been speaking with Felina Lee, PhD, CEO at Advancel. I'm Ben Comer, and you've just listened to the Business of Biotech. Find us and subscribe anywhere you listen to podcasts, and be sure to check out our video cast of these conversations every Monday under the Business of Biotech tab at lifescienceleader.com. We'll see you next week, and thanks, as always, for listening.

55:15We'll see you next time.