STIFEL 2026 HEALTHCARE CONFERENCE - CELCUITY INC

All right, we're going to go ahead and get started. I'm Stephen Willey, one of the senior biotech analysts here at Stifel, and glad to have with us as part of the next session, CEO of CellCuity, Brian Sullivan. Brian, thanks for being here this morning, and I know you guys have a lot going on. Maybe before we jump into Q&A, I'm not sure if there's any, some opening statements that you'd like to make. Well, I think it's helpful maybe just to look back on the past 18 months for us, Because it's been a transformative period. We reported our first phase 3 data, middle of 25, for PIK3CA wild-type patients in the second-line setting of breast cancer. It was very, very positive, unprecedented data. We've subsequently gotten an approval for that indication, so that's a big deal, and launched our first indication, and so we're in the process of that. We also announced positive data for a second phase 3 trial in patients who have PIK2C mutations. Again, very positive. Certain components of that were unprecedented data. And so we've submitted an SND, SND-A there. We did get a producement date, so that'll be end of Q2. And so, we're laying the groundwork. And then, you know, the launch itself is, and I'm sure we'll talk about that in detail, gotten off, in our view, to a good start. In that same period of time, we started two phase three studies in the first line patient population, two different populations. So we're separately evaluating each of those patients in a single study. Market potential for that segment is very, very significant. 90,000 patients would potentially be indicated for Regetta if those trials read out positively. We have very favorable preliminary data in those populations. We think the probability of success is high in those studies. And then we've also reported recently data in the metastatic castration resistant prostate cancer population. Again, very encouraging, not surprising in our view, given the similar biology that underlies prostate cancer and HR-positive breast cancer. So more to come. I mean, we're at an earlier stage, but that data was what we were hoping to see. It certainly then warrants further investigation. So we'll be initiating work and additional work to further prosecute that. Maybe we can kind of start off working through the RevTorpic launch. So I know it's early, you're five weeks in, or you were five weeks in when you reported last week, but it does seem that you have made a meaningful amount of progress within a fairly short period of time. So as you look at some of the early metrics that were provided on that call a week ago, you know, which of those kind of gives you the most confidence that this drug from the outset is really kind of resonating with prescribers? Sure. Well, one of the challenges when you're launching a drug is that there are a lot of gatekeepers that you need to work with to lift the gate. And so, for instance, insurers would be an example of that, right? If they don't incorporate our drug on their policies and patients can't get reimbursed, that would be a huge barrier. So we were successful, and that just reflects the work done prior to launch, not just since launch, but prior to lunch to get incorporated in those policies to get NCCN level one recommendation so that now 90 plus percent of patients have policies that will reimburse them for treatment with RetroPig. That's an important gate to get lifted. Another important gate is with what we label strategic accounts. These are accounts that, when you look at the total population that they collectively treat, represent 50% or treat 50% of breast cancer patients. Now, these accounts have multiple sites. So it's 36 accounts, but ultimately they represent well over 1,000 different treatment locations. And because of the way they're organized, think of them as they have a corporate approach to saying, okay, we want to have this drug on the formulary. We want it to be incorporated in the pathway. we need to have order sets built, we need various committees within our organization to approve usage of this drug, and that's a process. There's a lot of constituents, a lot of infrastructure that needs to get built. And until that's built or those approvals are received, that's a gate. And so if you have an account that has a thousand or rather 400 treating sites, you need to get that gate lifted so that your reps can effectively engage with physicians who treat patients at those sites. And so we were successful there in getting roughly 80% of these key 36 strategic accounts to order, which essentially in order reflects that all of this pre-work was successfully accomplished. So those were very much a focus of the initial launch period. Very, very pleased that a lot of these gates got lifted. Also pleased with the level of engagement that our reps have had at the account level, where we've prioritized accounts based on number of patients they treat. And they've been able to get into roughly 3,400 accounts that comprise or treat roughly 80 plus percent of breast cancer patients. So they're getting access to the doctors who are the accounts that really treat the great bulk of breast cancer patients. And then we've also been pleased with the interest in participating or attending peer-to-peer programs where they can listen to a regional KOL or a national KOL talk about the drug, present the data, get perspective from other physicians who are attending. And that's very powerful because ultimately they'll listen to us, but they'll listen more to someone who's a fellow physician. And so we've been very focused on making sure those programs are scheduled and people show up. And so far, so good. So all of the kind of necessary groundwork that's required, I would say all of it, a lot of the necessary ground work that's acquired has been accomplished as we had hoped. Okay. So I know the distribution channel is a little bit unique here, right? You kind of are functionally the supply chain, right. You're kind of drop shipping vials directly to infusion centers. You don't really need the specialty pharmacies. I know that model limits some of the granularity of the data that you can access. And certainly investors usually try to track, right? So in the absence of having that, you know, what are some of the key metrics that investors should expect to see from you guys on a go forward basis? Well, they'll be fairly basic, right, because we don't see it's not a question of us sharing it. It's just not available to us because the orders come through the distributors and we just get site information. So certainly the revenue and number of vials will be the most important metric. We'll have a lot of internal metrics. We've got a laundry list of metrics that we'll be using primarily to assess momentum at accounts, compare different regions or different territories, assess how certain accounts are doing relative to what we think their potential is. And so a lot of performance metrics to gauge penetration at as granular a level as we can. It's not clear to us that initially how we would translate that into stuff we would report. What we want to make sure is that when we do start reporting, A, we know we'll be obligated to report it consistently going forward, but B, that it's interpretable. If we present information that results in 10 different interpretations, it's not very useful. And so I think as we do our analyses, we will be thoughtful about providing information that will be helpful to investors, but also not be counterproductive either. And so TBD, beyond what I've just described. And I know these infusion centers are generally, and we've talked about this, a bit averse to holding inventory. So maybe, and again, I know it's very early, but are you expecting that these infusion centers are going to be ordering single vials at a time? Are they going to Be ordering three vials, i.e. a cycle of treatment at a Time? And as these infution centers gain more experience on the reimbursement side, certainly get more comfortable with the temporary J code you're going to have in place until April 1. would you expect that pattern to change over time or is it always going to be a single vial drop for each patient at each center you know i think in this day and age when you're able to provide inventory on a just-in-time basis if we receive an order from our distributor for a site before 3 p.m we're shipping that day and they'll receive it the next day and so we've received a kind of a i don't i can't say the percentages but some sites will order one vial some sites order two some will order three. It just depends on their profile. And so that tells you they just started a patient. Over time, they'll have more patients. And, and so then it gets a little more complex for them to order. So they, they may just say it's easier to order a cycle at a time. It's, it's hard to predict. But because they don't have multiple steps of distribution, drug needs to go through, which creates uncertainty about timelines, that gives them the flexibility. And I think a lot of them will use it, you know, to order on a just-in-time basis. So we won't see stocking up really. And I think the maximum stock up would be related to ordering cycles of drug rather than weeks of drug. Okay. I know your field force has been capturing some qualitative feedback. They obviously will on a go-forward basis. Again, it's still early, but what is that feedback telling you with respect to utilization as a function of either line of therapy, i.e., second line or third line plus, and preference for doublet versus triplet. So it's anecdotal, so we have to just caveat it. And we do ask the reps to be diligent in trying to get this information, but there's a lot of steps along the way to get that information. But what we are hearing is that, for the most part, doctors are thinking of this drug and the patients they're going to treat for those who are progressing, whether it's in the second-line setting or potentially the third-line setting. I think there's been this question around, do you have warehousing or do youhave a big bolus of salvage patients? And certainly, I would assume there's some referred, you know, onesie, twosie discussions of that. But I think the bulk of the volume, just based on what we're hearing from reps, is for patients who are presenting with progressive disease, and not just switching therapy from what they're currently receiving, which is what happens in a salivate setting. And then the second versus third line, again, I can't assign a number to it, but I would say it sounds like a good chunk of the volume would be associated with second line patients. As far as the doublet versus the triplet, again anecdotally, we're hearing that there's a preference for the triplets, which is what we have expected. That's what our research has indicated would be the case. We can't assign a number to it, but I guess the most important information was that so far we haven't heard anything from the field force that's anomalous or varies from what our quantitative research did prior to the launch. And so things are essentially so far consistent with what our expectations were. Okay. I know the second line treatment landscape for PIK3CA wild type is pretty fragmented, right? So when you look at all of those available therapies, which of those do you think will be the easiest to displace? And which of Those, if any, do you Think might take a little bit more work to displease? I think they all fall into the same category. They're all kind of second best solutions. And I think the feedback we've received is that the retropig regimen really is the first best alternative. Now, you will always have doctors who are comfortable with what they're doing, and they may take time to switch. But if you have a doctor that's comfortable using an HER2 in the second line setting, which for these patients is probably a fairly, I don't want to say significant, but it's one of the more significant options that physicians select. Well, then, you know, it's a fairly straightforward discussion to explain to the doctor why going to endocrine therapy, because now there's a good endocrinotherapy regimen available to them. And that's very much consistent with the general consensus amongst breast cancer docs, which is if there's a credible opportunity to induce a benefit with an endocrine backbone therapy, that will be preferred prior to inducing, or rather prior to treating patients with chemotherapy or an ADC, which essentially is chemotherapy. And then in the case with NHER2 as an example, and this is typical of chemotherapies, patients will get approximately the same benefit independent of what line of therapy they get them. So there's no reason to move upline with, let's say, NHER 2 as an sample. They'll get the same benefits as a third-line therapy of the patient's will. And so this is information that our reps have been gathering to understand the treatment paradigm they're currently using, and in turn, depending on what that is for a particular physician, help the physician understand how to maybe think through the process or to understand what the data is suggesting and why the revstropic regimen would be a superior alternative for their patients. I know Lilly's, Abema, and Oluminestrin just got approved in second line for ESR1 mutants. I believe Roche's gerodestrin to nebrolimus has a PDUFA date that's coming up maybe before the end of the year. How do you just think about revtorpic kind of competitive profiling against both of those regimens within that ESR1 mutant subset? Sure. As we segment the market, or as we think about how to segment the marketplace, we think there are three practical patient subgroups. The the double mutant patients, patients who are rather double wild-type patients, patients that lack either a PIK3CA or an ESR1 mutation. That represents about 40% of patients. Then there are patients who have a Pik3CA mutation. That represents another 40%of patients. We think the RAF-TurPik regimen has demonstrated superiority that's fairly unequivocal, which would lead to, we think, a high proportion of patients receiving that drug. And then the remaining 20% of patients are ESR1 mutant PIK3CA wild type. And that's where we think that the ABAMA IMLU doublet and the gerodestrin doublet with everolimus will be most competitive. Now, we think our data stacks up very well against those. And we've done meta-analysis, for instance, in the wild type setting that takes into account mutational status of ESR-1 and shown with the study that Sarah Tulaney at Dana-Farber just presented at ESMO, that, you know, get a revtropic regimens of triplet offers two times greater likelihood of a patient surviving without disease progression or death than a BEMA-IMRU. And so it's a fairly very, very compelling efficacy story to be told for revtropic regimen relative to these other regimens. And so we think that'll be a more competitive segment. But at the same time, to the extent that a physician, for whatever reason, decides that they want to use those regimens for that cohort of patients in the second-line setting, then we think it's not unreasonable to expect, potentially, the doctors to use a reptropic regimen in the third-line settings. OK. I know there's been kind of some suggestion that maybe this incidence rate of ESR1 mutations might be higher than what is seen in the literature, right? The literature would suggest, right, as your kind of breakdown explained, is in the 30-ish percent range. 30 to 40 percent, I think, right. But I think there's been some suggestion now where if you were to give folks more sophisticated CT DNA testing, exiting frontline with progression, that maybe that rate would trend up to 50%. Do you agree or disagree with that? I think that's speculative. I mean, I think people are just guessing. I mean I don't think there is any – I don' t know what the study that would say perfect testing yields that result. But I think you do have to take into account the practical real-world practice as far as what is the incidence of ESR1 testing, what are the methods used to detect an ESR2 mutation. And so when these clinical studies are done, there's 100% evaluation of those patients, and they yield about 40-plus percent of ESO1. So, yeah, maybe, but I think it's unlikely that you'd see much greater than that because the clinical trial presents the best case opportunity to detect an ESR1 mutation. They're using the best available technology to evaluate and identify those patients. Okay. So you mentioned the SNDA submission for the mutant data from Study 2 of VIC-1. And I know the PDUFA date now is going to be in late June. You did show some additional subgroup analyses from these patients. And so how does that data that you presented at ESMO kind of further inform your perception regarding the value of the triplet and doublet within each of those patients? Sure. Well, I think the comparison is somewhat confounded by the fact that the triplet was a significant sample size with prescribed alpha assigned to that analysis, whereas the doublet was a third the size. So you'll have natural variation with a smaller population, but you did see in the intensity population a very similar PFS result. But when you dig into some of the additional data, I think you see pretty significant differentiation between the benefit of the triplet versus the doublet. We presented data for patients who lack liver mets, no liver mets. It represents about 70% of all patients, but only 30% have liver mets in the second-line setting based on real-world data. Well, the triplete reported 21.5 months meeting PFS, whereas the doublett, 11.5 month, very consistent with their intent to treat PFS. Well, that's a pretty significant difference. That's a 10-month difference, which provides a very compelling argument that the triplet would be a preferred option for that patient population. The overall survival data has been mature, but again, at this stage, you'd look at the triplete as suggesting a more favorable OS trend. And then if you were to look at The Objective Response Rate, 59% versus 43%. So clearly, there's more activity going on with the triplets than the doublet. And it is not unusual when you have a small sample size that it may not represent the, quote, true effect size, because you just have more potential opportunity for variance. So that's all information that we think provides a pretty compelling rationale to use the triplet, similar to the rationale for using the triplete in the wild-type setting. Okay. How do you think the FDA is going to handle labeling? labeling. I know we've kind of talked about this a little bit before, but both regimens in that trial were clearly superior to control arm therapy, right? That's obviously an important observation. As you said, right, only the triplet regimen was allocated alpha in the analysis, but then the triplete didn't really establish the contribution of palbo relative to the doublet. And I would imagine FDA is maybe a little bit hesitant to approve the triplet with an additional... No, that's not at all the case. The triplet was a primary analysis that demonstrated superiority, so there's no question. The question the regulators are asking, and we'll ask themselves this, and again, this is obvious, is that when you don't have prescribed alpha and you're trying to use that analysis to support an approval, the agencies tend to be very cautious because they're setting precedent and so there's kind of a laundry list of drugs that have attempted to use uh non-alpha supported non-alfa allocated analyses uh to support an approval and uh it's as the agency calls it complex it's a review issue so so really the only question is whether we get the triplet and double it or just the triple okay um and then just with respect to label expansion and of the timeline itself. Can you say if you requested priority review? So they give that to you one way or the other. And we knew going in, we had two options. We could have gone in requesting only a triplet indication. And we think that would have been a very straightforward review, very clear data. We thought it was worth attempting to get a doublet indication. We think there's plausible rationale for that. But then that introduces what the agency refers to as a complex review. And the guidance essentially says priority review is reserved for indications where, you know, there's no complexity involved in reviewing the data. And as soon as you ask them to evaluate an indication that doesn't have an alpha pre-specified analysis, that's complex decision. And so we, you always hope, but from a practical standpoint, we assumed we would just get a regular review because of that. And, you know, that was our decision. We knew that the implication of asking for the doublet would lead most likely to a regular review, but we thought it was worth exploring with the agency. Okay. And so I guess as that is kind of your base case assumption, then has that accelerated um the either the timelines or the urgency with which you've wanted to push that mutant data out into the public domain via a manuscript well i mean we had a timeline independent of uh that was we were in process of uh executing before we got uh the data so you know We kind of have certain steps to take and plans, so we expect that manuscript to come out this quarter. And that manuscript would support submission to NCCN for inclusion in the guidelines. And again, they'll do their review and make their determination, but certainly the data would suggest that this would be a good alternative for the patients and appropriate to include in those guidelines. Okay. I know the KOL feedback that we've received would suggest there's certainly a high amount of enthusiasm to prescribe this regimen in mutants. There are obviously reimbursement mechanisms that are not necessarily tethered to NCCN if prescribers really want to kind of push the issue. You get the sense that there is like that level of enthusiasm here whereby those physicians are willing to jump through some of those hoops and fill out some of that additional paperwork in order to be able to write the script to a patient. Well, we obviously have to be very careful. We can't promote that. And to the extent doctors are taking those kind of steps, we don't want to be in the loop on that discussion. And we're not. there's a lot of enthusiasm for using the regimen in the patients with these mutations. So I wouldn't be surprised if that was the case, but I don't really want to hear about it. But the NCCN guidelines will create, assuming that they recommend the regimens, would create clarity because then it's clear insurance, for the most part, as long as you have a 2A or better recommendation, will reimburse patients for use of that drug. Okay. How do you think about the relevancy of some of the recent launch analogs that we've seen in this space? Every launch is different. I mean, I know the desire is to see if you could use this as a basis for assuming a trajectory or compare it. Depending on the setting, you can legitimately have a lot of salvage patients that are potentially receiving a similar type of drug. Like an ADC that's launched is chemo. So there's a rationale to say, well, just swap out that chemo, right? You're essentially inserting a better chemo and you may have a bolus of salvaged patients, which means that the first quarter revenue in that setting might not be representative of a true trend. In our case, I think the experience will be that patients who are presenting with progressive disease and need a new therapeutic option, that will be the population that we're primarily treating in the first quarter. But again, there's a variety of friction points that still have to be worked through the J-code. For instance, some sites will just decide that they aren't going to make it available until the J code is available. Right. So that's just something you have to work through. It's going to limit the potential population you can treat. And that's nothing specific to us, but it's part of just the environment that we're in. And so you've had other drugs launched in this space that are orals, tends to be a fairly significant load, so it's hard to discern exactly what patient demand is. And we've tried to outline to folks how at least we think about projecting volume. Time to peak is an important metric when you're trying to determine the trajectory of a launch. we think the analogs that are most representative of us are from companies that have launched, or rather, launching their first drug. And if you look at those data points, you'd see it takes about three years, you know, 30 to 42 months, pick 36. And then you look into the number of patients that you have available to treat, how long will they stay on treatment. We've provided those metrics. The price of the drug, obviously, has been made available. And so then the biggest variable that will essentially dictate how big the drug, what the potential revenue is, is related to what your peak penetration assumption is. And so that's where you, analysts, and investors will have to come to some determination. We obviously think that penetration potential is significant, but because of the size of the addressable market, when you use the metrics I've outlined, it's roughly $9 billion. It's a very large potential market for our drug, just given the pricing and the duration of treatment. that you can build a multibillion-dollar drug in this indication with a reasonable level of penetration, which I think just provides a sense of robustness to the opportunity that we have. Okay. I know the original launch date was delayed a little bit just in order to get visibility into the timing of a second supplier coming online. I think you're now guiding to that happening. in the middle part of next year. Is there anything you can say about just kind of what needs to happen at that site between now and then? Right. And so two things. One, our current supplier will be capable of supplying us through 27. We wanted to have visibility at a second supplier who really serves two purposes, one to provide redundancy, one to provided additional capacity. We think that capacity will be required in 28. And so the second component is that, you know, our plan is to get a third manufacturer going. We actually have another manufacturer in process in Europe, but that would be for European supply, eventually European supply. And so it's a case of building a group of manufacturers that, A, provide capacity and then also flexibility in scheduling, and then additionally so you have redundancy. So we'll have multiple things that will be happening in 27 related to capacity. Okay. And maybe just lastly on prostate, we saw the updated data at ESMO. You're certainly seeing a dose-dependent improvement in depth of PSA reduction. You're pushing dose higher, up to 300 mg. What do you need to see from this study to take the next step? And would you expect that next step to be a registrational effort, or would you want to size that out from like a phase two? So we want to complete our phase two study, which will provide more definitive data and also comply with optimist requirements that the FDA has established. And that we expect to happen in 27, and that would tell us two things, A, how to think about the population that we would seek to evaluate, and then secondly, the dose to use. One of the more interesting findings from the study so far is that the 180 dose induces a much different AE profile to the good in these men compared to women, i.e., substantially lower stomatitis, which we hadn't predicted. There was no basis to predict that. And so that's what motivated us to evaluate a higher dose. You know, 240, we think, is the most likely dose that we would take forward beyond the 180 in a subsequent study. And, so, that gives flexibility in the dosing. And So, with those two questions answered, i.e., which population and then dose, then we would expect, assuming the data is consistent with what we've already reported, we would suspect to proceed with a registrational study. Okay. Anything we didn't talk about that you'd like to quickly highlight before we wrap it up? No, I think if you were to assess the addressable market that we're hoping to provide treatments for, it's as large as almost any other opportunity in solid tumors. And the first-line setting is a very, very significant setting. You know, this data that we've provided or that we presented on a preliminary basis, 48 months meeting PFS for first-line patients, which compares to 25 months that's currently available, that's been reported historically for these current standards of care. That provides a wide target zone for us for success. So we think, you know, there's a very—we think a high probability of success. But I say, well, the implications are pretty profound because of the number of patients. 60,000 patients would be eligible. And so that indication alone could be one of the more valuable indications in oncology. So we're very excited about the opportunity to advance, get that study enrolled, hopefully advance soon, not soon, but within the next few years, to submission and hopefully an approval. And then I think as people reflect on the relevance of RevTropin, And I think the data so far indicates that its relevance is a function of the importance of this pathway. And the complexity of the pathway requires a drug like Reftropin, you know, a multi-targeted inhibitor. And so we're in a unique position to really prosecute these indications. And given the data today, we think the probability of getting over the finish line is very high. And that has very significant implications for us as a business, to the good. All right. Great. Thank you, Brian. Great. Thank you everyone. Thank you.