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

0:03Ben Comer 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, PhD, CEO at AdvanCell, a clinical stage radio pharmaceuticals company developing targeted alpha therapies that uh are targeting prostate cancer, at least the lead indication is.

0:26Ben Comer The company just closed uh an oversubscribed $315 million Series D financing in July. Philina 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.

0:49Ben Comer Before that, she was U.S. brand leader at Algeta, where she worked on the successful launch of Xofigo. Um, 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.

1:11Ben Comer Philina holds a Ph.D. in cell biology from MIT, and I'm thrilled to have her on the show to talk about growing and scaling radio pharmaceutical companies and commercializing therapies, how the recent Series D came together, what Advan Cell is doing to overcome manufacturing and isotope supply issues with radio pharmaceuticals and what the competitive landscape looks like for targeted alpha therapies.

1:37Ben Comer Philina, thank you so much for coming on the show.

1:40Philina Lee, Ph.D. Thanks so much for the opportunity, Ben. I'm really excited to be here.

1:44Ben Comer I'm glad to have you. I wanted to start off uh with some background, uh, Philina. You've worked more or less exclusively in radio pharmaceuticals for the last 15 years, uh, beginning at Algeta. What interested you initially about the radio pharmaceuticals uh space and what has kept you working in it?

2:06Philina Lee, Ph.D. Yeah, thanks for that question. I I feel like that could go back pretty deep to uh the origin of sort of how I started my career as a scientist. Um, and what what drove me to first become a cell biologist is really around finding ways to make um ideally transformative impact on human healthcare. Um so I remember as a kid kind of looking through my first microscope, looking at cells and and uh reading about um you know the biography of Louis Pasteur and and how he unlocked this insight that it's really germs that that cause disease.

2:45Philina Lee, Ph.D. 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 um meaningful impact on human healthcare. So I did, in fact, um, in in the first stage of my training, become a cell biologist and a microbiologist. Um, and I think part of what attracts me to um targeted radiotherapy, kind of fast forwarding, is just this implicit uh intuitive understanding that it should work, right?

3:17Philina Lee, Ph.D. You know, if if you can get a radioisotope targeted to a tumor cell in a quick way and in a specific way, that that radiation can deliver high energy to the tumor cell, cut up the DNA, and it's it's really hard for cells to overcome that. So there is this element of um, as a payload, as a targeted payload for oncology, this really should work.

3:42Philina Lee, Ph.D. And we're only at the very beginning of really unlocking the full potential of what this modality can do for patients.

3:50Ben Comer Yeah, and uh the alpha therapies are a double DNA strand break, right? Like super effective.

3:58Philina Lee, Ph.D. 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, um, there's really an opportunity to improve on that.

4:22Philina Lee, Ph.D. We see upfront resistance from some of these therapies because cells can figure out how to repair single-stranded DNA breaks. It's a lot harder to repair double-stranded DNA breaks, and that's a key, one of the key differentiating features of kind of the next wave of um of payloads that that has come in in uh targeted radiotherapies with the alpha emitters, um, is that in fact they cause double-stranded DNA breaks, um, which are virtually irreparable.

4:51Philina Lee, Ph.D. So there really is potential for greater um anti-tumor activity through these approaches.

4:57Ben Comer Um, so I mentioned you were at Al geta. Um, they were acquired, you joined Blueprint Medicine, uh, Blueprint Medicines uh and were steadily promoted over an 11-year period. I think you ended up as chief commercial officer at Blueprint. Um, it was acquired uh by Sanofi while you were in that role. What were some of the challenges, uh, Philina that you faced um maybe on the commercial side at Blueprint?

5:25Philina Lee, Ph.D. Yeah, I think that um that's a really great question. Um Blueprint was a really formative experience. Um when I joined the company was about 50 people, uh 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.

5:53Philina Lee, Ph.D. Um, and you know, we we went from first in human to registration in four years or less with both of our approved programs. Um, then having the opportunity to be a part of launching and in fact leading the launch of these medicines ultimately across five indications globally. Um it was an incredibly gratifying experience to really be part of that end-to-end drug development and commercialization on a global scale.

6:23Philina Lee, Ph.D. Um, you know, I think some of the challenges that we encountered, um, and you know, Blueprint Medicine started off as a precision therapy uh precision medicine uh company focused on oncology drivers. Um, as we moved forward, the direction of the science, the medical needs that we saw. Um, 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, um, really expanding into mass cell disorders and developing novel treatments to help patients with these mast cell disorders.

7:06Philina Lee, Ph.D. Um, that also was an incredible journey of following all of those breadcrumbs of um, 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 uh, you know, Blueprint was a tyrosine kinase inhibitor platform-based company.

7:30Philina Lee, Ph.D. Um, that was a modality that was kind of um, you know, we you could see that we were reaching the end of the target potential of targeted oncology drivers. Um, I think the number of targets that could be worked on, like, I mean, apart from the phenomenal K RAS, the RAS success with that we've seen recently, you know, um, but but there's a finite number of targets.

7:54Philina Lee, Ph.D. That's that's a space that has really been mined pretty deep. Um, and secondly, um, resistance is a big challenge. Um, 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. Um, and so I think one of the things that um made me so excited to return to the space of targeted radiotherapy and return to oncology is this idea that um, you know, targeted radiotherapy is still really early as a field.

8:29Philina Lee, Ph.D. We have really only unlocked um, you know, two targets. Um there's opportunity to improve on the treatments that deliver against the patients who bear those targets. And there's this incredible green field of opportunity to unlock medicines against additional targets and patients with broader tumor types.

8:54Philina Lee, Ph.D. Um and I would go back a bit to where we started in terms of um the mechanism of this latest generation of payloads in targeted radiotherapy is something that holds incredible promise and that will be very difficult for um for cancer to develop resistance to. And that's what makes me so excited to come back to this space.

9:20Philina Lee, Ph.D. Um there are large number of patients um that uh that can be helped who bear very relevant um targets that we can go after.

9:30Ben Comer And the the two targets that you've identified so far um is it PSMA one, the PSMA receptor, and then what's the other target?

9:40Philina Lee, Ph.D. 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 to low to no expression on healthy tissues.

10:03Philina Lee, Ph.D. And so all of those things start to give you a signature of what makes a really good target for targeted radiopharm approaches. Um I can elaborate more on our lead program, ADVC001, um, which is a novel lead 212 payload. That's a novel alpha emitter that targets PSMA for patients with advanced prostate cancer.

10:27Philina Lee, Ph.D. It's currently in phase two, so I'll I'll plant that there and we can we can go deeper. But um, as far as additional targets, um we we are actively focused on building and diversifying our pipeline. Um we have selected a second target. We haven't disclosed what that is, but what I can say is um it is in a gastrointestinal tumor type with high medical need, very limited treatment options and poor prognosis.

10:56Philina Lee, Ph.D. Um the target bears a lot of those similar qualities of what makes PSMA a great target. Um so we're actively to working towards advancing um this second program towards the clinic while we continue to work on um on additional targets in this space as well.

11:16Ben Comer Yeah, thank you for mentioning that. I I do want to uh pick back up on that in just a second. Um, but I I I wanted to ask, you know, on some of the, you know, kind of the financial aspect. Both both Al geta and Blueprint were uh acquired for for billions of dollars, billions with a B, as was Fusion Pharmaceuticals.

11:35Ben Comer You were on the board when AstraZeneca, I believe, acquired that company for $2.4 billion, I think. Um for company founders and and CEOs out there listening, what what would you say, Philina, is the most important element in attracting those kinds of big pharma deals? And and I know it's not you know a single item uh that that brings in a billion-dollar deal like that, but is there anything that you could say about what makes a company even relevant or or um open to that type of uh transaction?

12:12Philina Lee, Ph.D. I I uh I'm gonna have to lead by just sharing maybe the adage, like great companies are bought, not sold. So I think a common theme across um, you know, these these companies I've I've had the privilege of working in and being a part of um really the teams were laser focused on delivering for for patients, right?

12:36Philina Lee, Ph.D. Sort of playing, working towards that long game of building a fully integrated company. Um, I think that um in fact can also translate into value maximization when MA opportunities um 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.

13:01Philina Lee, Ph.D. Um beyond that, I think um, you know, each of these um, so I think Algeta and Fusion, taking learnings from the radio farm piece, stand out as having both clinical assets as well as the vertical integration on how to manufacture those assets. Um, and that's an important, I think, differentiating feature when you look across the radio pharma space.

13:31Philina Lee, Ph.D. Um, we share that same philosophy at Advan 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. Um, and we've invested in building those capabilities at AdvanCell from day one.

13:57Philina Lee, Ph.D. Um, 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. Um if I go back to the sort of uh the blueprint example in this, again, I would say, you know, from the start, it it was the vision and the goal of the team to take this platform that we had around um tyrosine kinase inhibitors to go after the underlying drivers of disease, follow the science and follow where the medical needs were in the patients.

14:37Philina Lee, Ph.D. Um, you know, we we did that. Um we we were fortunate enough that a couple things worked. Some things didn't work. I also want to make that clear. This is like biotech's a higher risk sport, right? So we had to pivot. Um, we scaled the company in a way that was sustainable. That's a really important point.

14:56Philina Lee, Ph.D. 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. Um, and that's because of how we had scaled um reliably, sustainably. We had hired, we hired team members who are agile, who were able to pivot into different programs and even different modalities, right?

15:19Philina Lee, Ph.D. Or sorry, different therapy areas as we as we move from oncology to allergy and immunology. So I think those learnings around how to build a long-term uh sustainable, scalable company are equally important. And we bring those lenses to Advan Cell as well.

15:38Ben Comer Yeah, I want to bring, I want to dig into that a little bit um in just a second. And I think I maybe misspoke at the beginning. Uh Blueprint Medicines was not a radio pharmaceuticals company. Yeah. So I'll clear that up really quickly. Um, but let let's staying with uh Advan Cell. Um, what what circumstances I guess brought you to the company as a as CEO?

16:01Ben Comer And I it's your first it's your first time as a CEO, I believe, right?

16:05Philina Lee, Ph.D. Yeah, it is, in fact. Yes. Thank you. Thank you for that question. Um it 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. And, you know, I think at this stage in my career, I honestly 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.

16:40Philina Lee, Ph.D. Every piece of what we're doing, whether it's advancing the lead program, unlocking the next target, um, or building out further our US 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.

17:04Philina Lee, Ph.D. Um that's the sort of mission-driven answer to your question. Um, the sort of story answer to your question is um, you know, it it happened really quickly. Um about a year ago, um I I had my last day at Blueprint post-acquisition, you know, I turned in my badge. I think there was a very natural um period of kind of mourning um, that transition, right, after having been invested in a in a company for so long and and showing it as our own.

17:37Philina Lee, Ph.D. Um and uh I was preparing to just really do some very deep soul searching and thinking about what I could possibly do next that would bring me the same degree of meaning um and and gratification. Um, and you know, I thought this was gonna take a while, um, you know, six months, maybe clear my head. Um and uh as luck would have it, I got a phone call one month later from a gentleman named Andrew Kay, who had just joined um Advan Cell as the chairman of our board.

18:13Philina Lee, Ph.D. Now it turns out Andrew Kay was our CEO at Algeta 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 AdvanCell released our very first first in human clinical data, and that came out at ESMO of last year for AD VC001 Phase 1b study.

18:48Philina Lee, Ph.D. And I still remember the feeling that I had when I clicked open that poster and I saw those deep waterfalls, right? Like rapid and deep PSA responses. Um 80% of patients at the recommended phase two dose had a PSA 50 response. And six patients were valuable for radiographic response, and they all responded.

19:13Philina Lee, Ph.D. So 100% ORR. And then on top of that, um, a really compelling safety and tolerability profile. No, no discontinued or dose mods due to adverse events, no dose limiting toxicities. And I I just had this, you know, very visceral reaction um seeing this poster of excitement. And I thought, gosh, um I was privileged to work at my lack company where we saw phase one data that that actually looked like that, right?

19:44Philina Lee, Ph.D. And and launch medicines that benefited patients based on those early phase one signals that were so compelling. And here was another one. Um, but in some ways, all all roads, it felt like all roads led here because that again, that connection to Andrew, the chairman, um, the Al geta, and then the fusion experience and my just core fundamental belief as a cell biologist, like this this has gotta work and we can unlock it.

20:14Philina Lee, Ph.D. So all of that came together. Um, 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. Um, it became a no-brainer, right? Um, so I I didn't think I was going to jump that soon, but I think within a couple of weeks I was signed.

20:42Philina Lee, Ph.D. Um, and it it was, it was, it was, I was compelled to do it, right? Um I was I was going thinking about it. I was waking up thinking about it. Um, 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, you know, you know, there's like the calculus of the mission in the team, but it just becomes a gut feeling at the end of the day on the CEO role.

21:07Ben Comer I guess you're about nine months in as a as a CEO. Um, 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?

21:20Philina Lee, Ph.D. Yeah, it's a great question. Um that's a it's a deep, I mean, that's a deep question. And I'm someone who is just so self-reflective that I'm gonna try to give a quick answer to your question. Um I think that the clearest piece is um truly the joy that I get from working with our team, our leadership team, motivating the team.

21:46Philina Lee, Ph.D. Um that's something I think also that I brought from my last experience at Blueprint. Um, you know, sometimes people have asked me, What was the secret sauce behind your big launch, right? How are you guys so successful? Um, and it started. 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.

22:12Philina Lee, Ph.D. And so I think part of what drove me to want to take this 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.

22:38Philina Lee, Ph.D. 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.

22:56Ben Comer Yeah, those are the key elements, right?

23:00Philina Lee, Ph.D. Stretching the lens. And um, and at some point, um, as I was looking at different opportunities, um I think I realized, you know, some of them just felt too narrow, and maybe I should just go for taking this seat. Um I think in terms of um so you know what what wasn't surprising was the um the the effort, the joy, the gratification of working with the team and seeing it take off, right?

23:31Philina Lee, Ph.D. So like that's that's tangible, I think, to us at at Advan Cell. Um part of that too, there's there's cross-geographic connectivity, right? We've got a uh 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.

23:54Philina Lee, Ph.D. Um and as someone, you know, I'm Canadian, turned American, uh I'm both now. Uh I'm I'm able to connect, I think, with those cultures. Um, I learned some of that also from the Al geta experience, where we had a home base in Oslo and we were building out in the Boston area for U.S. commercialization. Those experiences, I think, um helped prepare me for the work that we have uh ahead here at Advanced Cell.

24:23Philina Lee, Ph.D. I think one of the newer tasks that I took on in this role was our Series D financing. Um, you know, in some ways, nothing could have fully prepared me for that.

24:35Ben Comer Yeah, baptism by fire. That's right.

24:37Philina Lee, Ph.D. Baptism by fire is probably a good way to describe that candidly. Um and uh, you know, I will say um 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. Um so how do you tell a compelling pitch? How do you understand what is what the investors are interested to hear and position um a concise story of our company to highlight how what we're doing is in fact really well in line with what investors are are looking to invest in, right?

25:15Philina Lee, Ph.D. Like they're looking, there's like more less like later stage assets and or de-risked assets and targets. Um, and then how do we talk about sort of the unique um uh scalability of our supply and manufacturing capabilities and what we're trying to build for the long term. Um, so you know that that I think that raise was probably one of the more formative of early experiences.

25:41Philina Lee, Ph.D. I couldn't be more pleased with the outcome. Um we raised $315 million. It was outsized, it was oversubscribed. Um, we brought in a really high-quality investor syndicate who positions us really well for growth going forward.

26:00Ben Comer Yeah, exactly. The investors uh liked what you had to offer. You mentioned uh ADVC001, um, your lead clinical candidate. Do you have a sense of um, I guess maybe what percentage of you know the potential for that lead candidate versus the kind of overall you know integrated manufacturing uh operation that that you've talked about and that I want to ask you about uh a little bit more?

26:27Ben Comer But um, is it do you did you get the sense that investors are are feeling really strongly about the market opportunity for ADVC 001 as a kind of primary value? Or was it, you know, do 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?

26:49Philina Lee, Ph.D. Yeah, that's a really great question. I mean, it it has to start with the clinical data. Um and I think having um that clinical data that that I just described to you is is an incredibly strong hook for investors and to see the strength of that data in a market which already today in prostate cancer is a validated market for targeted radiotherapies.

27:12Philina Lee, Ph.D. The current standard of care um uh you know lutetium-based PSMA um is predicted to have a $5 billion peak potential. Right. Um so I think with the innovative approaches that we're looking at with AD VC001, um, we really see best in class potential and to take a leadership position in terms of the market share of the existing market.

27:40Philina Lee, Ph.D. And importantly, we also see the potential to grow the market and uh and tailor the adoption, the development of these therapies for earlier adoption for patients who are earlier in the prostate cancer treatment and paradigms. So this is a multi-billion dollar opportunity with several indications um within it as well.

28:02Philina Lee, Ph.D. Um in our phase two, we're we're develop we are studying three different patient cohorts, each of which could become a future indication over time. Um, we're studying patients with metastatic castrate-resistant prostate cancer in the frontline setting, which is the largest tranche of it of the RLT market today in prostate cancer, as well as post-lutetium.

28:27Philina Lee, Ph.D. Um, and 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 we're 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.

28:47Philina Lee, Ph.D. So they they have detectable PSA. They're they're easily, you know, sort of um identified by by providers. And what providers have this is a distinct approach from what others um have taken. And what providers tell us is um it's really important because they don't necessarily want to treat all comers.

29:07Philina Lee, Ph.D. They really want to treat this subset where they see the highest urgency to treat. These are patients who are more likely to progress more quickly. Um, so this is another differentiated component. Going back to your question, I think um, you know, truly, I think the big, the big first draw is that we have such differentiated data in a meaningful sized market with multiple potential indications.

29:34Philina Lee, Ph.D. And then the transition to the supply and manufacturing discussion is more about building the confidence that we can really deliver and uh and execute at scale.

29:45Ben Comer Uh ADVC001, it's PB212 or lead uh isotope. You mentioned it's in phase two. Um I think you were you were talking about Pluvicto with the potential of $5 billion in sales. Of course, Xofigo, 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.

30:11Ben Comer But is there anything else that you would say and just in terms of how you're thinking about how this product will be differentiated?

30:20Philina Lee, Ph.D. Yeah, it's such a great question. And I've you know been um sort of working working in prostate cancer since um about 15 years ago was my first launch in prostate cancer. And so um the field has evolved significantly. We've made progress, um, but importantly, there's still some real outstanding unmet medical needs and opportunities for innovation.

30:46Philina Lee, Ph.D. Um and the things that I would underscore are um, you know, first and foremost, um, the need to develop new, you know, additional and new treatment options with um a favorable benefit risk profile. That's important especially important to be able to move earlier uh in the treatment paradigm and preserve patients' quality of life.

31:08Philina Lee, Ph.D. Um I think the second piece that you alluded to is the need to address upfront resistant to current treatment modalities. Um, and 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 are, you know, they validate our hypothesis, right?

31:33Philina Lee, Ph.D. That you know, the potency of a lead 212-based alpha should really be able to overcome these upfront resistance mechanisms. Um, 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 um the duration of treatment benefit for patients.

31:59Philina Lee, Ph.D. And so um, 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. Um importantly, we're so we're leveraging these properties of lead 212. Um, that idea of, you know, get to the tumor, deliver this high potency anti-tumor impact, and then and then you're quickly gone, right?

32:25Philina Lee, Ph.D. 10.6 hour half-life. You're you're minimizing accumulation in healthy surrounding tissues. Um, we are leveraging that to do some truly novel dosing strategies. Um, and I'll break this into two parts. Like, you know, one element of this is giving more doses, right? So, like studying the benefit of extended dosing regimens.

32:47Philina Lee, Ph.D. 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 and um and response. Um, a 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 um we studied uh patients with dosing, you know, four every four or two, one week apart.

33:22Philina Lee, Ph.D. Um and we saw you know the results that have underscored of just you know deep, rapid, deep um responses. The reason why that's so important is um it enables us to get rapidly dividing tumor cells under control. We we see this kind of induction and maintenance approach used with other modalities successfully in on cultures.

33:46Philina Lee, Ph.D. Yeah, right. You know, it hasn't yet been truly tested for targeted radiotherapy and and lead 212 with these properties that I described, like high potency and then quickly, quickly gone, um, is we, you know, we think optimally positioned to look at some of these flexible and extended dosing approaches.

34:06Philina Lee, Ph.D. Um 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.

34:15Ben Comer So that shorter half-life with a lead radioisotope potentially means um 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.

34:32Philina Lee, Ph.D. That's a key part of the hypothesis. And uh, 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. Um, but it's also really important when you just look against um, you know, other emerging modalities.

34:53Philina Lee, Ph.D. Um, you know, there's a lot of innovation happening right now uh in prostate cancer, um, with uh with new modalities like ABCs, T cell engagers, um, novel androgen receptor pathway inhibitors. Um, but importantly, I think there will be an important place for therapies that balance you know strong benefit as well as um like that benefit risk profile that preserves quality of life.

35:23Philina Lee, Ph.D. And we know that um targeted radiotherapies, and particularly what we've seen so far with lead 212, um, 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 feed and paradigm.

35:43Ben Comer Um I want to talk a little bit about manufacturing and supply chain. Um I've covered radio pharmaceutical uh manufacturing and supply chain issues with previous guests. Um radioisotope half-life uh can add complexity to delivery, uh, isotope sourcing can be unpredictable. There are qualified staff shortages, uh, some additional regulatory issues.

36:07Ben Comer I I know you're well aware of all of these, probably others that I didn't mention. Um, but I guess what what would you say about uh uh AdvanCell and scaling up uh for you know this phase two and then Phase 3 to come? How are you how are you thinking about managing those those manufacturing and supply chain issues?

36:31Philina Lee, Ph.D. Yeah, yeah, it's such an important question. Um, because as as we've alluded to, this has been one of the big bottlenecks in the space, right? It's um and it it's hard. It's a hard problem to overcome when you think about how to distribute at scale um in isotope with a finite half-life, um, as well as to feed all of the pieces to manufacture at scale reliably.

36:56Philina Lee, Ph.D. So um this is in fact something we've invested in since the the beginning of the company is developing a novel technology um for how to reliably manufacture lead 212 at scale. Um I will um I'll I'll sort of unpack uh the I think core pieces of our technology, and then I'll talk a little bit about um how we're applying that to really build a US manufacturing network at scale.

37:26Philina Lee, Ph.D. Um so the core um pieces of our technology, I would just start by saying um we've invested in the 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.

37:45Ben Comer So that's what you mean by vertical, vertically integrated, that end-to-end.

37:50Philina Lee, Ph.D. Every case. Exactly, exactly. And uh, you know, the isotope supply part's really important. I'll I'll maybe like I'll draw the analogy to um when you want to bake a cake, we have the ingredients in our pantry.

38:04unknown Right.

38:05Philina Lee, Ph.D. So like if you got to bake that cake really quickly because your customer's coming in in a few hours, um, we've got the flour and sugar and the eggs, right? So like that's the like why it's important that we have um we have um supply agreements in place for strong and secure supply of thorium 228, which is the parent radioisotope for lead 212.

38:27Philina Lee, Ph.D. Um and so part of it is um we've we have the thorium. Um another another differentiating factor I will highlight is the parent radioisotope for actinium is it is much more finite, um, the the amount that's available in, I would say, like in the world. Um 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 of lead T12 uh based companies and um having thorium much more abundant.

39:02Philina Lee, Ph.D. So um we have our pantry stocked. Um and the first step in our process is to um to make these sources where we embed thorium on the sources, um these little sort of disc-shaped material, um, a little bit uh larger than the size of a quarter in diameter that could fit in the palm of your hand. So um so we we deposit thorium onto these um uh disk-like sources that are made of a very strong uh uh radiolytically resistant material.

39:37Philina Lee, Ph.D. And then eight of these sources go into a generator. So just imagine a box about the size of a case of wine. That's that's our generator, which fit in the case.

39:45Ben Comer Yeah, so you guys own a generator, you're doing that yourself.

39:48Philina Lee, Ph.D. Oh, yes. We we so we have we have developed all of this technology in-house. I'll I'll just jump to yeah, to the I'll cut to the chase. So um, all of our clinical doses to date, we have manufactured in-house. Phase one and phase two to date, hundreds of doses. Um, and this has been done through our internal manufacturing site uh in Brisbane in Australia.

40:12Philina Lee, Ph.D. And with that technology in hand, we're now tech transferring that technology over to the US so that we can file our USIND and begin to treat the first US patients on our phase two study and ultimately um scale towards Phase 3 readiness. Um, so so going back to um, you know, what's I think cool about our technology, um, you've got this generator.

40:37Philina Lee, Ph.D. Um, I'll draw the analogy to an espresso machine. So you put eight sources in the generator, and then um the thorium um 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 T12. We draw down that lead and we mix it with the PSMA binding ligand.

41:06Philina Lee, Ph.D. 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 radionuclidic impurities, like no thorium is sort of getting through to that finished drug product.

41:32Philina Lee, Ph.D. Um and so this this full vertical integration of like the capacity to take in high activities of thorium, manufacturing our source technologies, the generators that that we have generated that we have uh we have manufactured in-house, um, all this technology has been done in the hands of the Advan Cell team and really refined over several iterations to maximize the reliability and uh and and the scalability of the process.

42:02Philina Lee, Ph.D. Um, 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 we're constructing this commercial pilot line so that we can validate when you put several generators in a row, the capacity scales accordingly.

42:27Philina Lee, Ph.D. You can then put several manufacturing lines in a manufacturing site, um, and then um you can ultimately have several sites in a manufacturing network. Um, so you know, we often get the question, how are you going to distribute this product given it's 10.6 hour half-life, right? Like you alluded to this as one of the Yeah, that was my next question.

42:49Philina Lee, Ph.D. Yeah. Yeah. So um the how is essentially we are building a network of US manufacturing sites with approximately five sites across the US. Um, and and uh 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 site alone.

43:17Philina Lee, Ph.D. 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 precedents 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 have been very commercially successful with like you know billions of dollars of of sales as well.

43:54Philina Lee, Ph.D. Um so it's it's an eminently doable model. Um I'll go back to the Xofigo. experience. You know, we 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 radio pharmacies, and then ultimately to to customers.

44:20Philina Lee, Ph.D. 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 think could be hard, I would say it's doable with the proper logistics with the proper planning.

44:44Ben Comer So the the doses for the phase one and phase two trials were coming from Brisbane where it was all were all being created in in Australia and and and coming over.

44:54Philina Lee, Ph.D. So yeah just to clarify our phase one to so to date those studies have recruited from Australian sites. I was going to say yeah okay yeah yeah it's a 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 US and start to enroll US patients.

45:15Philina Lee, Ph.D. But I will say we've learned a lot from the initial experience in the phase one and two studies to date when I talk to um the investigators that we're working with and these are these are some of the the world's top experts in in prostate cancer um you know they they've they've told us in in their hands the logistics are no more difficult than the current standard of care.

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

45:51Ben Comer It's uh it's rare in other drug modalities for companies to build out you know all of their own manufacturing it's much more common to work with a C DMO and I'm wondering you know the calculus must be different uh in radio pharmaceuticals when it comes to building your own manufacturing versus versus outsourcing that work.

46:11Ben Comer So why 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?

46:21Philina Lee, Ph.D. Yeah I would say first I'd I would just emphasize um so I think it's really important to have um developed the technology, vetted and learned and refined the technology in-house um but 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 US 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 3 and commercial scale.

47:01Philina Lee, Ph.D. So I would almost say where you have to have the like eureka moments of like, okay, 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 right so actually recently a KOL asked me like when is this going to be like McDonald's right?

47:29Philina Lee, Ph.D. So it's we're not McDonald's yet. Yeah it's a more bespoke you know really nice burger uh but we are working towards um you know a broader scalability. And so I um I I wouldn't say that we're wedded completely to the in-house model because in fact we do have um a you know a great uh we do have a CMO partner.

47:53Philina Lee, Ph.D. 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. And you know a key reason why we've chosen to build out the Greater Boston site that's an Andover is that will be our first sort of true Phase 3 ready and future commercial scale ready internal manufacturing site.

48:24Philina Lee, Ph.D. So it's a really important proof point to do that well, to do that on time with the sort of the validation and porting over the technology and all of the learnings from what we've done in in Brisbane.

48:37Ben Comer We think that's important you know like we control the execution and uh and we think that's that's an important part of um successfully scaling in our last few minutes I I want to um back up a little uh Philina and ask you a kind of a broader question about the the radio pharmaceutical landscape how would you describe the current competitive landscape uh broadly you know not just in prostate cancer and and maybe what it might look like in a couple of years yeah I would I mean 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?

49:16Philina Lee, Ph.D. So there's obviously increasing momentum in the space there are more companies coming in there are more companies working on unlocking um next targets improving on existing targets as well as moving towards um newer radioisotope payloads so all of this is great right so I I uh to me this feels like where the ADC field was several years ago, right?

49:41Philina Lee, Ph.D. Like it's about to it's about to break like it's or in in a good way.

49:44Ben Comer Yeah.

49:46Philina Lee, Ph.D. And so I think in terms of competitive landscape um the I think the simplest way to think about it is about there's like sort of payload innovation um and then there's um sort of product and target innovation. So like with a payload innovation we've already talked about the sealed started with the bigas um you know I would say alphas is kind of where the action is at present.

50:11Philina Lee, Ph.D. There's so many companies that are focusing on actinium. Clearly there's a place for actinium and there's there you know there'll be more targets unlocked as well. That being said from a clinical positioning point of view you you have benefit risk considerations of a longer lived radioisotope you have also the supply and manufacturing considerations of a finite parent radioisotope um so we really think of lead as leading edge.

50:45Philina Lee, Ph.D. I mean that's some of the investors have even told us you know you're on the next wave of um um carbonate 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 um the potential benefit risk advantages as well as scalable supply and uh and manufacturing so I would say there's a very um you know deep area to be mind here like we we haven't even begun to to crack the potential um of of patient benefit both improving on PSMA there are other working on SSTR2 um and then there's there's all of these other new targets um that that we can be working on um so I think that's where my greatest excitement you know

51:39Philina Lee, Ph.D. lies like that's what we're really focused on at um at Advan Cell um I think the other piece we've talked about beyond the clinical innovation is is around supply and manufacturing capabilities and there I would say um you know there are there are companies that have chosen to kind of outsource all of the the manufacturing um and there are companies that have chosen to keep that control um that that vertical integration um we think that's a core strategic and competitive advantage at AdvanCell.

52:15Ben Comer Last question for you Philina uh what are your top priorities for the rest of of 2026?

52:21Philina Lee, Ph.D. Yeah yeah rest of well I I I I think um there's only a couple months left there so maybe no we can take it into the second half of 2026. Yeah yeah I'll I'll sort of think think forward thinking but yeah I mean I think now with the with the raise with the financing in hand our whole team is just laser focused on on execution um we're we're focused on moving forward the lead program AD VC001 um we are excited to present longer term safety follow-up on the phase one data at ESMO next month.

52:54Philina Lee, Ph.D. So that's that's a good literal answer to your end of the year question. We look forward to presenting top line phase two data um but the the real goal that we're focused on is moving this program towards Phase 3 readiness and that the raise will will enable us to do that hand in hand with scaling our supply and manufacturing capabilities to be Phase 3 ready as well and then the third priority is to move a second program into the clinic.

53:24Ben Comer On uh on Phase 3 just a quick follow-up on that um will this series D raise allow you to actually start up Phase 3 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?

53:41Philina Lee, Ph.D. Yeah when we reach Phase 3 readiness um it'll be important for us to evaluate our options for future financing and we'll we'll look at a range of of different options um there that will best position the company um you know as as you know we're we're really building really sort of two companies at the same time a traditional biotech advancing the the programs as well as scaling the supply and manufacturing infrastructure so this is a capital intensive um business that we're building for the long term um 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 um so we look forward to executing

54:29Philina Lee, Ph.D. on those and evaluating our financing options as we reach that Phase 3 readiness.

54:35Ben Comer Philina thank you so much again for for coming on thanks so much for the opportunity Ben I really appreciate it. We've been speaking with Philina Lee, Ph.D., CEO at AdvanCell. I'm Ben Comer and you've just listened to the Business of Biotech. Find us and subscribe anywhere you listen the podcast and be sure to check out our video cast of these conversations every Monday under the Business of Biotech tab at life science leader dot com.

55:02Ben Comer We'll see you next week and thanks as always for listening.