Getting To A First Product Approval With Celcuity's Brian Sullivan

0:04Brian Sullivan: 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 Brian Sullivan, co-founder, chairman and CEO at Circuity, a biotech company that received FDA approval on July 14th for RevTorpec. generic name, get a tolisib, which was indicated in combination with fulvestrant for HR positive and HR2 negative locally advanced or metastatic breast cancer patients without a PIC3CA mutation. It's the company's first product approval, but hopefully not the last. RevTorPic is also in active development for other breast cancer types, including use as a first line therapy, as well as a metastatic castration-resistant prostate cancer candidate.

0:52Brian Sullivan: Brian is a serial entrepreneur. He worked previously as chairman and CEO at SterileMed, a medical device company sold to J &J for$330 million in 2011. And before that, he co-founded and led Recovery Engineering, a filtration company that he took public and sold to Procter & Gamble for$265 million in 1999. I'm thrilled to have Brian on the show today to talk about RevTorPix approval and what it means for breast cancer patients, how he identified and licensed get a tolasib from Pfizer, his engagement with the FDA up through approval, commercialization plans and how to balance ongoing pipeline development with a new drug launch.

1:36Brian Sullivan: Brian, thank you so much for being here. Oh, it's my pleasure. Thanks for having me. I want to start off with a couple of questions on your background. I just mentioned that you've led and sold two companies, a water filtration company, a medical device company that reprocessed single use devices prior to self-cuity. What did you learn from those experiences and what made you want to take a swing at cancer therapeutics? Well, I started my first company out of college, right? And so, one of the benefits of that is that you don't know what you don't know. And so, you're somewhat fearless because your downside is almost nothing, right?

2:18If I failed, I go to business school, you can take the keys to my car. That was really it. I didn't have a family. I was a young guy, 23 years old. And so I really respect, this is, by the way, the entrepreneurs who are in their mid-40s. They've had a career. They have a family. They have a mortgage. They have tuition. And then they take a risk and go off to start a company. In my case, it was pretty straightforward. But when you build a business, you're ultimately focused on how to solve problems. You realize, wow, you need to get fantastic people who have a lot of experience in particular areas.

2:57And then you need to always be thinking about objectively whether what you're developing will make a difference and allow you to win. And so, you know, kind of the underlying philosophy I've had about starting a business or thinking about the products to develop is whether or not we're creating what I term a definitive solution. If we step back and are objective about the problem that we're trying to solve and then think about what is the ultimate solution, i.e. what's the solution that just takes any other alternative off the table, that's what we want to create. And so when we were developing our first products, that was our goal.

3:35So this is ultimately what the consumer is essentially needing to solve the problem that they have. And so similar type of analysis when we were thinking about in our medical device space. And then coming to cancer, well, there's a zillion problems to solving cancer, unfortunately, right? It's an intractable disease. So, there's a huge canvas, but then that just creates its own complexity because you can't treat cancer, right? You're digging in and tumor types and subtypes. but there's a certain discipline that's required that you learn when you're developing products of how to assess you aware that you might have something to add right it's not enough just to say oh i'd like to treat cancer i'd like to help these patients of course but so do a lot of other people and so you need to compete for dollars you need to compete for team uh teams and individuals and you need to have a prospect of success and that requires this discipline of really carefully isolating, you know, the problem and whether you could come up with something that's differentiated, that deserves to win, in effect, if you're successful in executing the plan.

4:48Brian Sullivan: Did you have, and I wanted to ask you about, you know, the circumstances that led to the co-founding of CellCuity in 2012. At that point, did you have that locked-in focus of, this is a specific cancer type I want to target, this is how I want to target it? Or did that by necessity come later? Yeah. So I was kind of in the middle of negotiations with J &J and my co-founder, Lance Lang, our CSO, called me up on the way back from this negotiation. And he had an idea about developing an instrument that could do the cellular analysis. And I said, well, I don't really want to develop an instrument, but I would be interested in being able to isolate potential disease activity in ways, you know, molecular tests can.

5:35And so we went back and forth and basically collectively defined the mission. And because of what we were trying to do, we basically both agreed that breast cancer was potentially the right opportunity to focus on because there were some biomarkers that were already being used to stratify patients. HER2, as an example, ER. But those biomarkers weren't very specific or specific enough to, you know, yield very, very high response rates. And so we thought, wow, there's some undiagnosed activity here that's going on. And then there's some other pathways involved. So, you know, I guess early on we knew breast cancer was the area we wanted to focus on and then dug in there.

6:16And one, you know, one thing, and I'm sure we'll talk about this, one thing led to another as we, you know, dug deeper and deeper.

6:22Brian Sullivan: Yeah, you a lot has changed in breast cancer therapeutics since 2012. And, you know, you mentioned several of the biomarkers. There's also the BRCA gene that really came into play during that period. I'm curious if your clinical strategy had to adapt or pivot in response to new treatments coming into the market. I mean, I think get a tolisib or get a tolisib was licensed from Pfizer, I think, in 2021. Is that right? Yes. Yes. So here's how we got to get a tolisib. So, you know, we were digging into breast cancer and one pathway, you know, cell signaling pathway that was clearly important and understood to be a driver of breast cancer.

7:11But at the time we began looking at it, there were no approved therapies to treat it. And so this was clearly a huge unmet need. How do you treat this pathway? When it was discovered 20 years ago, every major pharmaceutical company had a program to develop a PAN-PI3K-MTORC 1-2 inhibitor because it was clearly important. very hard to do though hard to hit six targets in one hard to do that in a way that could be tolerable to patients and so all those programs failed and over time you had this migration towards just hitting a single component of this pathway i.e pi3k alpha mtorque 1 akt but that was suboptimal because this pathway is so complex it has all these workarounds redundancies that hitting one target doesn't do enough to prevent this pathway from continuing to serve as a disease driver.

7:58So we zeroed in on this pathway just because of that conundrum. Untreated mechanism that's clearly important. Nobody else has something that really looks optimal or definitive. And so even though there's all this other work going on, in a disease setting, if there's clear evidence that a particular pathway is relevant and it's not being treated, it's going to continue to be a disease driver. And so, you know, given what we viewed as the lack of good alternatives, addressing this pathway, we felt there was a bit of an open goal for us to go. And so, but that came from a lot of analysis. You know, we set up a program to specifically assess using the cellular analysis program, a platform that we developed to look at all the drugs out there that had been developed and really isolate.

8:45Why did they fail or their attributes, et cetera, from a cellular activity functional perspective? And that's when we came across Gatitalisa. Essentially, we're looking at 100 candidates to think about trying to sort out what would be the right approach to address this pathway. And then Getup popped up. It's clearly, in our view, the winner. We happened to be working with Pfizer already on a collaboration. Pfizer was the owner of that drug. And we didn't know its status. We assumed they were continuing to develop it because it had several trials in process. Okay, so it had clinical data. It had some clinical data.

9:21And so that's when we approached Pfizer and said, hey, you guys, you have this, what looks like a great drug. We didn't have any clinical data. They hadn't published much. We'd love to collaborate with you. Maybe we can help you using our cellular analysis platform to optimize patient selection. We didn't know really enough to say much more than that. And that's when we found out that Pfizer had decided to stop developing the drug. It essentially put it on the shelf. And that was the turning point really for Cellcuity. You know, we were saying, you know, I basically said, I can remember sitting in my office thinking, well, we've thought about developing our own drugs.

9:57And then I said, well, if there was ever a pathway to focus on, it's the PAM pathway. And if there was ever a drug to target the PAM pathway, it's this drug. So let's let it rip. And so, yeah, started having conversations with Pfizer. And, you know, thankfully, it all, you know, all worked out where we were able to get the drug in 2021 and then take over development of the drug.

10:21Brian Sullivan: Was that the first in licensing agreement that you had negotiated? Yes. Yes. It was anything. Was there anything surprising about that process or particularly difficult? Yeah. Well, so what was interesting was that we were constrained. I mean, we had you know, we were funded like a biotech at that point. You know, we had maybe 20 million of cash in the bank. So, you know, it limited negotiating parameters, right? And sometimes that's good, right? Right. Because ultimately, the person on the other side of the table knows, you know, you can't go any higher, right? Yeah. Well, you can't take 100 million.

10:53I don't have 100 million to give you. And so basically negotiated a deal that just very back end weighted so that if the drug was successful, it would be a very fair deal to Pfizer. But if it wasn't, well, you know, we weren't going to go out of business. because of it. And so, we were able to reach an agreement with Pfizer. I think because we had some relationship with them, they had a sense of how we thought our capabilities and thought that, okay, this drug will be in good hands and it'll be responsibly developed, aggressively developed. And that's, I think, part of what we, you know, a lot of what we brought to the table.

11:32And obviously, Geta is the star of the show. I mean, it's a great drug. And so, So, yeah, we we were fortunate because we could develop with our platform these very proprietary insights about this drug and in ways that, you know, maybe we weren't just weren't possible to develop with other tools that people use to evaluate evaluate drugs.

11:54Brian Sullivan: So you you brought you brought the drug in. Cellcuity, you know, was was already formed as a company, although you didn't have a lot of cash. I'm sure you had to then start fundraising for clinical development. Did you encounter any were there any investors out there who were sort of put off by the idea of, you know, this was a Pfizer drug? They just they they chose not to develop. You know, was that a serve as a kind of black mark for for some investors? Well, it was kind of it worked both ways. But the first question I would get from people when I would describe the attributes of this drug and early phase data, because it was very promising.

12:36You know, the approach, i.e., this multi-target inhibitor, early phase data was very promising. So they're going, well, wait a sec, what did we miss? I mean, this looks great. Why would Pfizer kick this to the curb? And my response was, look, they, you know, Pfizer has as big a company as there is. They had the revenue from COVID. They had a zillion potential ways they could go. And so, they were looking for – they had other criteria that they were applying for their pipeline. And that's life and times. A lot of drugs get outlicensed because of other priorities that rise to the top. But that was very much of a question like, what are we missing here?

13:14Is this too good to be true? And if it's so good, why isn't Pfizer doing it? The flip side, though, is that Pfizer has outlicensed drugs that ended up being very successful. Yeah. And so, essentially, it worked both ways. Say, well, look, you know, Pfizer, you know, they develop good drugs. Sometimes they don't fit into their portfolio. But when they've been out-licensed, they've turned into big wins. And so, ultimately, you know, I had to answer a lot of questions, just as you asked. And we raised about$60 million a couple months after we closed the deal. And that was important for us because, you know, basically, the day was good enough, in our view.

13:54to warrant going to phase three. We'd initially thought we might go to phase two, do a small randomized study, just confirm the phase 1b data. But if you really dug into the data and kind of did statistical analysis and kind of develop a view on the probability of success, so I concluded that the probability of success was high enough that it would really be detrimental to pause development by three years, essentially to get confirmation in a phase two setting. I felt So, you know, you're paying one way or the other. And I felt that, you know, it's more important to optimize and accelerate development as much as possible.

14:34Take the risk. Right.

14:37Brian Sullivan: I wanted to ask about, you know, we've talked a little bit about the mTOR pathway, you know, what was intriguing and compelling about the pathway itself and the target for you. But what about the unmet medical need, I guess, from a patient perspective? You saw this market opportunity. Can you describe the unmet need in breast cancer that you're planning to address with this product? So there are some great drugs that were developed for the first-line setting, CDK4-6 inhibitors. But unfortunately, after patients progressed on those drugs, the alternatives offered, in some cases, just two to four months of median progression-free survival.

15:15So a very short period of time. There had been a drug Novartis developed called alpalypsid, which was an alpha inhibitor. It had just been approved in 2019. It was a tough drug. Very toxic, high, high levels of hypoglycemia. Didn't, you know, offer, you know, kind of only modest, you know, you could say, but not as much benefit as people were hoping. So this second line setting for HR positive breast cancer was considered to be very tough, i.e. not a lot of good alternatives. Doctors would like to delay giving chemo to patients at that stage because you start getting into irreversible side effects on patients.

15:55So there was a hole in the treatment paradigm. And that's where we felt, A, that would be the first place we'd go, right? First, second line. But we also had some first line data from the early phase study that was very promising. I mean, great data. And so we thought, okay, we can see the development path. We're going to get, you know, focus on getting an approval in the second line setting. and then quickly go, which we've done, and to the first line setting with additional phase three trials. But basically the second line setting just had enough significant unmet need that we felt the probability of success was high and that we could elevate, if we're successful, the standard of care as a result and really make a profound difference for the patients.

16:41And the data suggests that we've done that. You know, we really, we think the data, and I think the feedback we've gotten from oncologists is that we'll establish a new standard of care for these patients.

16:53Brian Sullivan: How large is the patient with this first indication? How large is the patient population? So about 37 ,000 women in the U.S. each year kind of get to the second line setting. They've progressed on their first line treatment. And so, you know, that's in the tumor landscape, that's a huge patient population. Yeah. And then roughly 60 % of them lack a PIC3-CM mutation, 40 % have a PIC3-CM mutation. Because these patients have different alternatives for treatment, we designed our phase three study to separately analyze patients with and without a mutation. And that proved to be very advantageous for us and for patients because we really isolated the treatment effect in these two populations.

17:39Most people didn't think our drug would work in the patients who lacked mutations because the paradigm has been, well, C mutation, hip mutation. You know, targeted therapies. But this pathway is different. It plays a key role in driving metabolism of cells. It regulates the energy source that cells rely on to glucose, to hyperproliferate. And so our hypothesis was, well, this pathway is intrinsically involved, independent of whether there's a mutation.

18:12Brian Sullivan: I wanted to ask, you know, about that decision for, you know, to include the mutation and not include the mutation. Like how you were able to, you know, make what sounds like a really critical decision about the trial protocol. Right. So it's interesting. When you're thinking about a phase three study design, you're balancing a lot of considerations, right? The cost, global study. So your inclination is to do something that will minimize your patient population. And in our case, we were solving for what we felt the right information would be to demonstrate that this was the right drug for all patients, irregardless of their mutation.

18:54And we felt the only way to do that was to separately power and analyze those populations. You also had different standards of care for control. And again, I think sometimes we're very frugal, but at the same time, if you're going to do something, you have to do it right. Just because you're small doesn't mean you can get away with doing it kind of halfway. You're either in or you're out. And so we were in. And the frugality helps you because you're not wasting money on this other stuff. I mean, so if people look at what our expense run rate was, I always get a lot of comments of, guys, you guys are spending a lot less than a lot of biotechs.

19:31I said, well, you know, that's probably because of my entrepreneurial background where you're starting something from scratch and you're cheap. So we weren't spending a lot of money in what I would call non-working dollars, which meant you had more dollars to go directly into, in this case, a phase three trial. uh and uh and and that was uh that was key uh but you had you know the end result is you also have a lot of skeptics right because wait you're you're going against the grain these drugs are only supposed to work when there's a mutation present why is this drug going to work without a mutation and and so then you're getting to the fundamental nature of the pathway and again it's a science story but and we we we took it on all the other drug developers in this space were focused on just patients with mutations.

20:16And so here you have all these major pharma, Lilly and Novartis. Other companies have these targeted therapies only focused on patients with mutations, you know, PICTC mutations. And here's this, who are these guys and why are they tacking left when everybody was tacking right? You know, what do you guys know? I mean, so there's, And that's part of life. And if you're confident, though, you say, well, that's fine. You know, you guys are wrong and we'll prove you right. And thankfully, you know, we were found to be correct.

20:52Brian Sullivan: And the indication is for patients without the mutation, this initial indication, right? Yeah. Because that's the larger population. And it just turned out that we were able to get the data faster because these patients really have a crummy prognosis. There aren't very good alternatives for patients lacking mutations. So it just so happens, and that was one of the other benefits. We get the data would essentially be available independently, and we could proceed with an approval as soon as the first data set was available, which happened to be the wild site. And that worked out for us. Now we have an approval.

21:24We have our data from mutant. We'll be submitting a supplemental NDA for the mutant population, but we're able to launch. And so that's obviously the whole goal is to make a drug available for these patients as quickly as you can. And so we were also solving for that, too.

21:42Brian Sullivan: Getatelisib received FDA's breakthrough therapy and fast track designations. It's also included in the FDA's real time oncology review or RTOR. Can you talk me through that RTOR process? You start submitting clinical data prior to the full NDA. Is that how it works? Correct. No, exactly. So, you know, the FDA, one, I guess, confirmation of the unmet need is that FDA only grants breakthrough designation when they believe there's a significant unmet need. Right. So, you know, we were addressing one. And that if our data held, that there's prospect of establishing a new standard of care. So that, in turn, supported the RTOR.

22:23And the benefit of RTOR is that you're submitting on a rolling basis. And we submitted initially the first submission. You had three submissions or sub-submissions. Three submissions. And the first one was essentially our database, you know, the clinical database. So they can start to do their own analyses and determine, you know, or begin that assessment. And then your CMC package. So, you know, things that require the longest lead time. And then you fill in the blanks with other modules. But the FDA is essentially taking a risk and saying, okay, even though we don't have the full package, we believe, A, the data, which we provided them a top line, it warrants taking a risk of beginning an FDA review because the probability of it leading to a positive approval decision is high.

23:20And so they have to feel very good about the data, all the other work that we had done to say, hey, we're willing to take this risk that it won't be a waste of our time. And good for the FDA. I mean, I would say we've had a fantastic relationship with the FDA. I mean, very collaborative. I mean, they're obviously very tough. But at the same time, we've learned from them. And to the extent, in many cases, they have very good suggestions. And we developed a better clinical trial design as a result of that collaboration, developed a better package just for our modules and our NDA because of the feedback we got.

23:58So we really leveraged the breakthrough status to get, you know, kind of as much feedback as we could along the way to make sure we were aligned with them and then took advantage of their expertise. I mean, they've obviously seen a lot of different things. So, you know, all hands on deck. We want as much help as we can get.

24:16Brian Sullivan: Uh, biotech companies work, uh, really hard to get to Indian, uh, to get to NDA submission and then have to wait typically, you know, months for a PDUFA date and approval decision to arrive. Uh, you've just gone through that, that waiting period. Can you describe the company's activities, uh, during that NDA to PDUFA date period? You know, what you were focused on, what your top priorities were at that time? Well, when you submit data to the FDA in an NDA, they're reviewing it and they're asking questions. They're called information requests. So there's an iterative process involved. It's not like they just send you an approval letter six months later.

24:58I wish. So they're doing a review. But at the same time, we were finishing up enrollment of our other phase three study and the mutant population. and then while we were waiting for the PDUFMA date, we read out that data, we presented that at ASCO. So we quickly, while we were working on our NDA or rather waiting for the PDUFMA date, we actually were preparing our SNDA for the next submission. You can't submit while you have another, when you have an active NDA. But so essentially we were already collaborating with the FDA. We had a pre-SNDA meeting with the FDA for our next indication while they were reviewing our NDA.

25:44And we had other meetings with the FDA to talk about our first-line studies and getting their advice on design. So, we have a lot of initiatives in process, you know, two phase three first-line studies, our SNDA, you know, mute population, you know, the castration-resistant prostate cancer, etc. So a lot to keep us busy.

26:06Brian Sullivan: Is there a risk though in continuing other clinical programs, particularly with get a tolisib, for example, you know, if there's, let's say, an adverse event had popped up and you'd have to all of a sudden report this negative thing during an NDA review process, you know, even if it's a different indication, how'd you think about that? Well, it's a good question. And so, you know, the big part of an entrepreneur's responsibility is assessing risk, you know, upside, downside. And that includes assessing what the probability is of the downside. Now, if the downside is horrific, right, you want to avoid it at all costs.

26:48Sure. But we felt that we had enough data. Before we started our phase three study, I think we had data from over 500 patients in a variety of different settings. And so we felt that the safety signal and the safety profile was well characterized. We did not believe that we were likely to get surprised. In fact, we felt that it would be very, very unlikely. And any event that occurred would be viewed as anomalous. So, it was a consideration, but we felt that it was too low a risk to really stop us because ultimately, time is your enemy. If patients are in need today of better therapies, as a business, you want to try to accelerate as much as you can.

27:38So, we made some calculated bets. I mean, we started our phase three study on the first line population before we had our first data. And I had some investors say, well, what if it doesn't work out? I said, well, again, that's a possibility. I think it's a low probability event. And so when I'm factoring in the benefit upside of accelerating the development here, I said, just taking a year out of the development process for this phase three indication could yield a billion dollars of incremental net present value to the business. So it's a big decision or rather big opportunity, i.e. consequential.

28:12And I felt the downside was nominal. I mean, in terms of, okay, I'll have spent maybe$20 million to get that phase three going. And if I shut it down because the data is unfavorable, so be it. So I'm betting 20 million to potentially have a billion dollar upside. And that's a big part of how you manage. And if you're an entrepreneur or any business person, you have to estimate your upside downside, have a good ability to characterize those so that you can just focus on the downside. but if the upside is huge, it's a good bet, right? A 50 to one bet. Well, that's good. And low probability of the downside occurring is say, man, you don't get many bets like that in life.

28:55So that's ultimately what you're doing is you're managing a risk and you are proceeding apace. And so, you know, those are all considerations. And then in retrospect, they can say, you know, well, it all worked out, but of course, you never know. I mean, you know, stuff does happen,

29:14Brian Sullivan: in this space, right? Absolutely. Right. Tell me about your commercialization plans. I read in the press release that you plan to launch in late Q3, which is right around the corner. What have you got cooking on the commercial front? So another aspect of the drug development business that is daunting is that while you're developing, or rather you're running your phase three trials, you kind of have to assume success because the time required to build out a commercial organization is several years. Yeah. And develop the capabilities and do the research needed. So we began our commercialization process several years ago, two and a half years ago, and then slowly built out the team in 24 and then 25 kicked it into gear where by the end of 25, we had for the most part, our commercial organization, except for the Salesforce built.

30:09And so you essentially have to go to where you think the puck will be, assume success. And so then in late Q1, Q2, we brought on our Salesforce, fantastic group of individuals, really, really great. And then you train them and get them ready to go. So we've essentially built out our commercial team and all the capabilities, market access, working with the payers, the insurance companies, working with strategic accounts, So all that capability that's required, having a patient hub. So you're able to essentially handle medical inquiries or patient inquiries, having patient support services in place so that, you know, for some patients, they won't be able to afford the drug or the copay.

30:53Well, we've made it as a policy that, you know, essentially we're not, we want to do everything we can to make sure any patient, regardless of their insurance status, will have access to our drug. And so that's all, you know, infrastructure that needs to be built. You want to develop insights, right? How do doctors think about this or that? What about, you know, if you think about this adverse event, how do we present that? And so you want to gather as much information as you can to optimize, you know, how you go to market. Make sure you're training your sales force accordingly. And then, you know, release the hounds.

31:29Brian Sullivan: Yeah. Every time. Right. Can you give me a sense of how large the sales force is for a drug like this? So we have oncology cell specialists, and they'll be targeting the oncologists. And there's 90 of them. Then that's split into 10 regions. So you have 10 regional directors managing those specialists. And then you have a separate team that's focused on the insurance companies, the payers, national accounts. So that's a separate group of individuals. And then you have another group of individuals focusing on the strategic accounts. like the U.S. Oncologies of the world or Dana-Farber's or City of Hope, these very large systems.

32:11They also have other impact on the whole decision-making process for other accounts. And so you have essentially folks working from the top down, folks working from the bottom up. And then you do the math and figure out what you need. And, you know, the math says to cover all the oncologists that are really treating the most patients, you know, you need this many reps. And so it's possible to kind of make a very considered decision about the sizing of that force.

32:43Brian Sullivan: And then as far as the commercial folks that you hired prior to the sales force, like the early people that you brought starting two years ago that you brought in, who were those individuals? You know, who were those first kind of commercial people? Yeah, the first people were the senior people. So, Chief Commercial Officer, Eldon Meyer, launched a number of drugs, a lot of experience in big pharma, small pharma, had successfully launched the Blockbuster before. And then our Head of Marketing, VP of Marketing, Head of Commercial Operations, Head of Market Access, Medical Affairs, which kind of is a dotted line to commercial, but key for commercial launch and obviously supports clinical development.

33:22So, those individuals are the next people. So, we had to build that senior team and they in turn would build a team underneath them. And this would be people who are focusing on communications or managing MSLs, medical science liaisons. And so you build that, you know, those kind of couple layers of individuals who can really get the projects going, managing these initial efforts. And then as you get closer, you know, then it's a lot of execution. Okay, the people who are going to be responding to inquiries that we might be getting from the field. For instance, and other elements or components of the organization, we need to expand our safety team quite a bit, the pharmacovigilance, because we're going to be dealing with thousands of oncologists potentially.

34:07We need to build on IT systems that you don't need when you're in clinical development. So there's probably 30 different systems we needed to develop. And it affects every part of your organization, our finance team. You have to have separate accountants or a group managing revenue recognition, managing the coordination for reimbursement, etc. And so it's a very complex undertaking to transform from clinical development stage company to a commercial organization. And it's not just getting a sales force in place. It's really a holistic shift and expansion of your organization, all these other requirements.

34:43Brian Sullivan: Did you ever consider a commercial partner? Are you still considering a commercial partner? How do you think about that versus, you know, setting up, building up your own commercial function, which is not easy, as you've just described? Well, because I started a couple of businesses from scratch and built out commercial organizations and launched successfully in tough markets. In my first company, we were working with all the major retailers in the country, in the world really. And so, we had by the time we ended up kind of selling to Product and Gamble, we had 40 ,000 retail outlets, which is complex undertaking.

35:20Yeah. My second company, we had 2000 hospitals we were working with where we had people embedded in those hospitals that were supporting our work. And so, you know, I kind of thought through how to and executed, you know, what were essentially fairly sophisticated and complex commercial or field support organizations before. and so it's just a matter of breaking it down into its pieces and and identifying you know what you need and then executing and for right or wrong i've always felt that you know i could figure out execute it accordingly uh and uh and then you go from there and and uh so had no doubt that or uh that we were gonna launch this ourselves now ex-us you know globally it's a much different story in our view.

36:10We're starting the global regulatory submission process. We will have an MAA submitted to Europe, the European Medicines Agency, by the end of this year. We're submitting to other key countries or begin the regulatory process with them. So we will have a global footprint. We'll most likely have partners to execute the launch in those countries.

36:34Brian Sullivan: You have just described what happens to an organization when the product is approved and you now have to commercialize it. It's fundamentally changing the company from an R &D-focused organization exclusively to a company that's now doing both things at once. I'm curious how you manage that balance and focus, you know, between ensuring a successful commercial launch, which is no small task in 2026 and continuing your pipeline development efficiently. How do you how do you think about that? How do you avoid overextending the company? Right. Well, again, I mean, everything starts with making sure you have the right people.

37:14And so we have very good leadership at all of these critical positions from our chief commercial officer, chief medical officer. We have a chief strategy officer, our head of pharmaceutical development. And so that's the starting point. You can't do anything without the right people. But then we spend a lot of time thinking through plans and the budgets to carry out those plans, how to manage those plans, how to see whether we're executing against them. and and so then if you do that uh and you have a good way of of uh focusing on them you can execute you know broadly but it has to be very deliberate um and you can't overextend yourself either because you don't have the right people or you don't have enough money uh or uh you you haven't set yourself up to review your status so so i think that's that's something that I've learned with my other businesses how to maintain momentum, right?

38:09And when people ask me, oh, Brian, it must be great. You've got this drug approval. Do you take time to reflect? I said, well, to be frank, about a minute. Because there's the momentum that comes from an approval, obviously the launch, but then the implications in terms of what else you can do, or you have a lot of other things in process. And so, you know, a key to really developing a high growth company that really delivers on its promise is to learn how to manage both not only today, but the future. And so you need to have the ability to focus on short and long term to ensure that. You can't get too just focused on the short term.

38:51And that's why you have great people leading these functions that carry it, keep the momentum. You know, I'm very involved, but, you know, very quickly and have always, you know, made sure our clinical development plan is robust, even at a pre-commercial stage. You know, having two phase three first line studies is not typical. And but given the potential, it just was warranted and we capitalize ourselves accordingly. And so now there's more stuff we can do. Right. Execute.

39:20Brian Sullivan: Well, on finding good people, was your network large enough by this point that, you know, you could go to kind of friends or friends of friends or, you know, cancer is such a specific and complex area. You really need, you know, the best specialists in some ways to bring into the company. How did you how'd you go about staffing those roles? Well, at the start, I had to rely on search firms. Right. I didn't have a network. come from the industry. So you get the senior people, had to use search firms and very lucky and very happy that we were able to build the team we did. But they, because of their experience, had networks.

39:59And so one thing we're all quite proud of is that the Salesforce we hired was all through internal referrals. So that we started off with people that essentially people could vouch for and that new would fit into our culture. And so we minimized, we felt the risk of either having a culture misfit or somebody wasn't quite at the caliber that we were hoping for. But that was because we had over time built a great network. We had hired the kind of people that had all those relationships. And as we've advanced, then for the most part, if possible, Well, not every position makes that possible. If we can find an internal candidate or rather a candidate that's internal reference, it's great because they know what we're looking for.

40:46They're top-notch people. They're not going to recommend a subpar individual. They're going to look for a top-notch person that they've worked with. And again, because the opportunity we're pursuing is very significant. It's a very attractive setting to be in. Breast cancer is important. This drug has the potential to be a very, very important drug. And so we're able, I think, to really plausibly go after as good of people as are out there. And I think we've done a great job of getting really grade A people throughout the organization.

41:28Brian Sullivan: On your pipeline, you've got this approval now, obviously. And I believe you mentioned a phase three in the first line setting, but give me a sense of what's coming next, maybe in breast cancer and then outside of breast cancer. Well, the pathway that our drug is treating, this PAM pathway, is intrinsically involved in this disease. And it's not a result of an adaptive mutation or evolution based on prior treatment. And so patients who are treatment naive. These are women who may have had early breast cancer and 10 years later, it comes back, it recurs. Or a woman who had early breast cancer, but it comes back right away.

42:05Those are kind of two different populations. And so, our early phase data was very promising in that setting with these women. We reported 48 months meeting PFS for a woman who had treatment naive, which is an unbelievably favorable preliminary small sample size 40 patients but that's about as good as it gets and so felt that that was more than support more than sufficient to justify phase three in that first line population and and it's also a large population unfortunately you know 60 either 90 roughly between the two groups of women who are treatment naive that we're targeting separate clinical trials.

42:47There's over 90 ,000 women a year in the U.S. who are diagnosed and require that first treatment for metastatic disease. So, you know, that's as large a population as exists in cancer for a first-line study. So, it's an appropriate place to try to develop a good solution for it. And we do believe this is the next, this is what's required, a drug like get to create a step function improvement in the outcomes for these patients. It's an untreated disease mechanism. Many studies or many drugs, and that's great, are improving on an existing therapy or drug class. And so, they're replacing maybe a drug.

43:32In our case, and this is usually areas where you have the highest probability of success, we're treating an untreated disease mechanism, i.e. hyperactive PAM signaling. And so, you will have, again, it depends on the drug, et cetera, but if you have a great drug, and now we've demonstrated we do, and you have an untreated disease mechanism, you can assign a pretty high probability of success to those future studies. And so, we think it's reasonable for us to be very confident that we'll have positive readouts in those studies. I mean, obviously, we have to show off with the goods, but we think it's a high probability event.

44:11Brian Sullivan: This is not very important in the grand scheme of things, but I'm going to ask just because I'm curious, Rev Torpik, do you anticipate that that name will stay the same with new indication approvals or will you have, you know, you'll just sort of add the indications or will you have a new product name? No, that'll be our name. I mean, that'll be the drug. And so it's, that's the common practice. I mean, I think you might only change the name of the drug if you go into a different disease setting. For instance, on oncology, you'll have the same name. But Avastin, right? The VEGF antibody from Roche.

44:46You know, that was Avastin for cancer and forget the name. It was a separate name, but went AMD. And they basically got to rebrand it because you're really talking to a whole different community. And that's saying it's a whole different dosing, a whole different set of circumstances.

45:03Brian Sullivan: So, but yeah, and the same is true with like Humira and Embraer and those drugs. But then you have I was I've seen other instances where companies will change the name for one reason or another. The GLP ones, I guess, are the kind of front and center example there. But yeah, in cancer, you're going to even if it's prostate cancer, you would start. Yeah, oftentimes what you'll do if you if you change the molecule, like with this GLPs, they're kind of they're changing the molecule. They're still hitting the target, but they might be hitting it, you know, multiple targets like literally sampling three different targets.

45:40Well, it's different molecule, different name. And that's typically the driver of either it's a new setting or it's a new molecule, even though you're already got one molecule that's that's going after that.

45:52Brian Sullivan: That's got it. OK, we're getting to the end of our time here, Brian. And before I let you go, I wanted to ask about your top goals for the rest of 2026. I imagine successful launch is probably pretty high up there. But what do you yeah. What do you hope to achieve for the rest of this year? So getting have a fantastic launch is top of the list. Having our SNDA submitted for the mutation cohort that we evaluated in this second line setting. reporting additional data for our prostate cancer study and then proceeding based on that data, we hope, to the phase two setting where we'll do some additional work to characterize the activity in these men with castration-resistant prostate cancer.

46:44And then to continue to think through our lifecycle development plan. This pathway, the PAM pathway, is implicated in a lot of different cancers as well as a lot of other disease areas outside of cancer. And so we want to make sure we are properly evaluating other areas where we could potentially develop this drug. And then one other project I should mention is that we're developing a new formulation of GEDA. GEDA is now infused. It's a 30-minute infusion. We're developing a subcutaneous formulation that

47:19Brian Sullivan: Oh, you are. Okay. It'll allow you to inject it as a shot, essentially. Does that be – yeah. No, I'm sorry. Go ahead. Yeah, no. And so that's an important project for us. That would be most important really for the population that we're treating, this first-line population where their current standard of care gives them 24, 25 months. If our trial is successful, we probably would be giving them at least 33 months as an example. Well, that's a long time to be coming in three times a month for an infusion. We would get, we think, a good share of those patients because the benefit would warrant that.

47:55But to the extent we can improve that experience, that would be important. And so, sub-Q, in our view, would help expand penetration potential. We don't think it'll change much the penetration potential in the current settings we're focused on. Certainly won't hurt, but not necessary. But in the first line endocrine sensitive setting, sub-Q would be good. So we're moving that through the pipeline as well, evaluating and optimizing a variety of different candidates. There's a lot of variables to optimize when you're developing a new formulation. And so that work is ongoing, and we want to kind of continue to make progress on that front as well.

48:33Brian Sullivan: With the subcutaneous formulation, would patients potentially be able to use that at home, or would it be still administered in the doctor's office? Yeah, it's too early to commit. That would be the goal, right? We have a profile that we're shooting for, functional requirements for this formulation. We'd like to be able to achieve that. But if we're able to only develop a drug that would require going into just a doctor's office, we still think that would be a win. Sure. It would just, you know, create much more flexibility for the patient. But so, you know, you shoot for what would be optimal.

49:08And that's what we're shooting for. But if you get something that's still very good and accomplishes and delivers an improvement for the patient, we proceed with that too.

49:19Brian Sullivan: Yeah, I mean, a quick shot over a 30-minute infusion. No, exactly, exactly. So, you know, you want to be careful not to rule out what could be a very good alternative if you're not able to optimize or achieve what you think is the optimal, in this case, formulation. Brian, thanks again for being here. I really enjoyed speaking with you. Oh, you're welcome. That was my pleasure. We've been speaking with Brian Sullivan, co-founder, chairman, and CEO at Cellcuity. 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 weekly video cast of these conversations every Monday under the Business of Biotech tab at LifeScienceLeader.com.

50:00Brian Sullivan: We'll see you next week. And thanks, as always, for listening.