Celcuity Inc. ($CELC)

All right. Good afternoon, everyone. I'm Andy Berens, senior biotech analyst at Leerink Partners. Thank you for joining us on day 2 of our Annual Miami Healthcare Conference. We're very excited to have with us Brian Sullivan, CEO of Celcuity. Thank you for joining us.

Your welcome, Pleasure.

You've got a lot going on, Brian. Thank you for making time for us.

We do, no, this is what I need to do.

For those that don't know Celcuity, can you give an overview of the company?

Sure. Well, I started the company a while ago now to initially develop a platform with our Chief Science Officer, to isolate the activity and quantify the activity of live patient tumor cells so that we can help identify patients who might be responsive to particular targeted therapies. We began working the PI3K space and identified what we felt was a fantastic drug, gedatolisib, pan-PI3K/mTOR inhibitor and began developing that drug in '21. Now we have essentially completed 1 Phase III study. We have another 1 we will report out soon in the second-line setting in breast cancer. We also have a first-line study in process. I'm sure we'll talk about that as well in breast cancer. And then we have an early phase study in process in prostate cancer.

Okay. Great. Well, you guys entered a very dynamic space with a lot of moving parts. And since you started your program, a lot has transpired and lot of pieces have fallen into place, others have fallen out of place. How would you say HR-positive breast cancer looks today, first-line, second-line adjuvant? What are you forsee? What's different, I guess, today than it was when you started your program?

Well, I think the most important data set to be reported to be frank is ours because we've validated the importance role this pathway plays, independent irregardless of whether there's a PIK3CA mutation. Our early phase data demonstrated the important role this pathway plays in patients who are treatment-naive, who've never received treatment in the late-line setting. And so I think if I look at the landscape going forward, I think essentially, GEDA will change it. And we hope to have studies that would demonstrate the activity of GEDA in the frontline setting for women who have endocrine-sensitive disease as well as endocrine-resistant disease. We've already shown essentially unprecedented levels of efficacy in the second-line setting in patients who lack mutations. And we hope to kind of close the loop with our data set in the next few months when we report out our mutant setting. I think all the other studies have essentially been trying to optimize existing targets. I think the PAM pathway has really been kind of very, very suboptimally targeted to date, and really have only shown modest efficacy in a subset of patients. And we think our drug has the promise of offering optimal tumor -- antitumor control, irrespective and in both front and -- frontline and second-line settings.

Okay. There certainly seems to be something, I'm going to use the word magical for lack of another term, but when you hit the PAM pathway with both a PI3K drug as well as an mTOR inhibitor versus what you would see with individual, would you agree? I mean, what is causing the better efficacy?

So 1 of the key features -- the 2 key features of this pathway. One is it plays a critical role in regulating glycolic system in a tumor cell, which essentially means it's regulating the uptake of glucose which is the energy source or primary energy source for tumor cells. They're particularly dependent on glucose that consume 100x more of glucose in a healthy cell. And so it's a very relevant pathway. And that's why GEDA has shown its ability to work independent of the mutation. But because it's so important, it seems to have built in these redundancy mechanisms. And so you have multiple targets that are required to be addressed to control it to comprehensively shut it down, the 4 Class 1 isoforms of PI3K, mTORC1 and 2. And that unless you control all of those or inhibit all those targets and shut down this pathway, essentially this pathway can continue to function. Now drugs that hit a single target have shown activity when the tumor has a mutation. But absent that, they really haven't shown as meaningful activity. And so that's been the riddle, how can you essentially address this pathway in light of its complexity and also because of some of the safety challenges associated with this pathway because it does regulate such important physiological activities, depending how you hit it, how often you hit the concentration required to address it. It can induce unacceptable levels of toxicity.

Right. Okay. And then obviously, there's been a lot of attempts for people to improve upon fulvestrant, and that's falling short. We just had the announcement yesterday that another oral SERD was disappointing in the front line this time which I think for you guys, I think it's a double-edged sword in some ways. I think it was good in that it gives some stability to the front line. We have the same stability, I guess, in the second line, meaning the fulvestrant is not going anywhere. It doesn't look like AIs going anywhere, at least in the near term. So I guess how do you view kind of the news about another oral SERD?

Well, look, you never root against another drug, right? To the extent that there's an opportunity to improve outcomes for patients, you want that to work. But the fact it didn't work certainly creates clarity around how to think about improving the outcomes for those patients because you know what the components of a regimen would be, what the components of the control would be. And that makes it very straightforward to take the next step. And again, if you think of breast cancer 3 pathways, you need to close that circuit. And we think GEDA is the only drug under development that we think can effectively close that circuit and create, we hope, based on our early Phase III results, we think we have a very good chance to do that and create a very meaningful treatment benefit in the frontline setting.

Okay. Can you talk a little bit -- look, let's go through the data you showed in the second line, and in the wild types and then the trial that's about to read out in mutants.

Sure. And so we reported out 2 primary endpoints. We reported out data for GEDA plus palbociclib and fulvestrant compared that to fulvestrant, reported 9.3 months median PFS compared to 2. So a 7.3 month delta. That was the biggest delta ever really reported with an endocrine therapy before in the second-line setting. The hazard ratio 0.24 was the most favorable hazard ratio is ever been reported in breast cancer. So it was really unprecedented level of efficacy. And that again, just reflects the importance of the target and how well GEDA does in mitigate or inhibiting that activity. We also saw a very significant activity for GEDA combined with fulvestrant, so a doublet versus fulvestrant. Again, absent the triplet, it would have been the best results reported in the second-line setting. So we think that help validate our hypothesis that it's important to control this pathway comprehensively. And then if you do, it can induce a very, very significant benefit, again, irrespective of the mutational status of PIK3CA.

Okay. And then the data that are coming in the mutant population?

So we haven't -- we expect to report that data end of this quarter, sometime next quarter. We've reported early phase data that is quite promising. Reported in a cohort of patients in a Phase Ib study, about 14.5 months median PFS. And so that would be a great result if we reported that. But to be stat sig in this study, based on the results that have been reported to date for our control, which is alpelisib and fulvestrant. 10 months would be stat sig. And it would also be clinically relevant because the true standard of care today in the mutant -- the patients with PIK3CA mutations is capivasertib and fulvestrant. And in the setting that we in, that drug reported about 5.5 months median PFS. And so even if we just squeak over the line with the stat sig study, we've been nearly double with that drug has been able to offer patients. And so we think it would be very clinically meaningful, given our early phase data, certainly, we think the odds of being positive are high. And we think they're also high of hopefully doing better than that, but we'll see.

Right. Now over 9 though, in the wild types and now you're adding in a tumor that should get an added benefit. So you would think that, that -- plus the data that you've shown. And then I think if I recall in that Ib reanalysis, there was actually a smaller group that actually did even better that was similar to which the way you're seeing it now.

Right. No, I just want to manage expectations. That was great data. It was 19 months median PFS in patients that have mutation. Small sample size, so you have to really caveat that. But I think what it just shows is, GEDA -- all the results we've reported today for GEDA, either the early phase or a later phase setting have shown very, very good results. And again, just demonstrates the relevance of the pathway and capability of GEDA.

Now I mean, obviously, large pharma has spent a tremendous amount of effort to broaden the oral SERDs as broad as they can get them, and they've run into some difficulty beating fulvestrant in the second line, except for an ESR1-mutant patients. And now we haven't seen the data yet, but as I said there was a numerical but not statistical trend in the frontline beating AI. So would it be possible hypothetically to run the trial with GEDA plus an oral SERD and use that to beat fulvestrant or AI?

It would be challenging because you have 2 changes to the study arm. So you would need to control for both. And especially if 1 drug has already failed the comparison and not shown to be active statistically in meaningful way, it would make the trial design very complicated.

Okay. So you have to run like a 3-arm trial?

Right.

I see, but you've done a 3-arm trial?

Yes. Once you've done it once, you want to avoid it if you can.

We've done 2 of them.

Right again. But if you can avoid it, you want to avoid it.

Okay. Let's talk about the front line.

Sure. So we have a Phase III in patients who are HR-positive, treatment-naive, but are considered to be endocrine resistant. And these are patients who didn't really get much benefit from their adjuvant endocrine therapy, essentially at early breast cancer and the disease recurred either while they were receiving a tamoxifen or within 12 months after. So it's a tough group of patients, unfortunately. Current standard of care for the most part that they get only gives them about 7 months median PFS. So in some ways, it feels a little bit like a second-line study in terms of the outcome that they're currently getting. And that population is comparable in size of the second-line population we're treating. It represents about 1/3 of all women who are treatment-naive. And we've been doing a safety run and to evaluate GEDA with ribo, ribociclib, and we expect to report out the results of that and then any updates to the study design in the near term.

And what would be -- so one of the advantages of that subgroup is that it wouldn't be like a 4 or 5-year.

Right. No, exactly. And that's why we prioritize that, a, biggest unmet need and in turn, that also typically corresponds to a relatively short trial, whereas the endocrine-sensitive population, which is roughly 60,000 women who are either well beyond their time of treatment with an adjuvant endocrine therapy or de novo metastatic. They weren't diagnosed with early breast cancer. They just present with metastatic disease. The women treated with current standard of care CDK4/6 plus letrozole get about 25 months. So that's a longer study, right? Your control -- that's your control and then your study arm and hopefully, in our case, be a lot longer than that. But it's an important opportunity, we think, to help these women just stave off progression as long as possible. And earlier, you can do that, we think ultimately, it's better for patients.

And the Ib trial that you cited that had 4 arms. What did you see in the naive that...

So actually, these were really good results. We reported 48 months median PFS, 79% objective response rate. So very, very favorable and encouraging. And that's why we think, ultimately, it will make sense for us to launch a study in that setting.

Okay. What's the gating factor for that now?

Just we have a lot of stuff going on, and we're getting ready to launch a drug. We expect to get an approval decision, PDUFA date is mid-July. And so we're sorting through things, and we'll keep people updated.

Alright. What preparations have you made? How big a sales force do you need?

So we've largely completed the build-out of the organization, except for the sales force. So essentially, you need market access several teams in market access and marketing team, customer operation -- or rather commercial operations team, medical affairs. So all those teams are built, the sales -- head of sales, regional team, regional management team is built. And we'll bring on the sales force beginning in the second quarter. There are a lot of infrastructure systems and process-wise that need to be built, other organizations, other suborganizations within different departments also need to be created, essentially to handle the requirements of being a commercial organization. And so that's well on its way. So we're kind of close to being ready to go and targeting, hopefully, an approval date mid-July.

And what size sales force do you think you need?

So we haven't disclosed that yet, but if you were to benchmark other companies that have drugs in the breast cancer space, you'd see they typically have around 90. So it's a very manageable side -- manageable sales force in terms of how to reach the docs.

Okay. And the fact that it's intravenous would mean you can target a smaller group of...

Well, no. I mean, actually, pretty much every practice because, for instance, breast cancer, the largest drugs, most significant drugs are all IV. So every doc that treats breast cancer patients has to have a connection to an infusion center, just because a good chunk of their patients will be on infused -- will need infused drugs. And as it turns out, that's an important component of, particularly in the community setting, an important part of their practice. So they're well organized and they have the infrastructure to do that. And to be frank, economically, it helps support their practice as well. From a market access standpoint, medical infused drugs are considered to be medical benefit, tends to get less challenging reimbursement pathway than oral drugs. So there are a lot of factors that are to the good for us by having an IV drug. And we think, ultimately, that will actually be a favorable factor for our launch.

Okay. And the feedback, I mean, as you've been doing your commercial assessments has been strong for the IV?

It has. I mean, you do a lot of different testing of messages, of appeal. We present data -- you do a lot of quantitative research, essentially without any prompt just essentially giving information to docs and allowing them to evaluate the data and draw some conclusions from it. And all of that research has been very favorable in terms of what at least we're seeing for preference for use of GEDA versus the current alternatives and the low impact, we think, having the drug administered as an IV will have on that preference.

Okay. Do you want to talk about the prostate program?

Sure. So it's interesting. The biology -- underlying biology of prostate cancer is some parallels to breast cancer, both are hormonally driven tumors. HR positive breast cancer is. And then these hormone pathways in prostate cancer, the androgen receptor pathway has been shown nonclinically and clinically to interact with the PAM pathway. So in a way that essentially could be considered similar to what you see with breast cancer. And so we have a study that's evaluating GEDA combined with very good androgen receptor inhibitor called darolutamide in men whose disease has progressed after they've received frontline or, a, androgen receptor inhibitor. And so we hope to show that we can improve the outcomes for these patients, these men. Early results for 2 different doses were favorable. We think we showed that we can induce a meaningful treatment effect. The safety data actually was very encouraging. It was surprising, it was better than we expected. It seems men have a different safety profile than women that received GEDA and so we thought it was important to evaluate potentially another dose to make sure we haven't ruled out that prematurely. And so we should expect -- we expect those results sometime by the end of this year.

Okay. And the combination partner, you said it is what?

Darolutamide. That's a drug owned by Bayer. And it's the most potent androgen receptor inhibitor, and it's also the best tolerated. Essentially, if you stack these up, it's really the best partner drug for GEDA. And because it's not used as widely as the 2 standards of care enzalutamide or abiraterone, you're going to switch all these patients, say, well, have received this drug. And so it makes it a very good alternative to combine with.

Okay. And are there any other tumor types that do you think?

So there's been interesting work done in endometrial cancer. GEDA actually reported very favorable data in endometrial cancer as monotherapy, and there's been some other -- there have been some other studies that have shown some activity. Hormonally driven roughly 80% or ER-positive endometrial tumors or are HR positive. It's confounded a bit because the PD-1 drugs have become a standard of care for many of these patients in the frontline setting, not 100% clear how that may change the potential responsiveness to targeted therapy because that typically you move on to chemo after PD-1 drugs. So that's an unknown. But there are other tumor types that were other drugs have shown activity, but potentially didn't develop further because of safety issues. And so we think we overcome those safety issues. And so there's some interesting threads to pull on outside of breast or prostate.

Can we talk a little bit about the IP? And then obviously, I know you think the IV formulation is going to be -- it's going to support the commercial launch for the reasons you mentioned. But is there any thoughts about subcutaneous version?

Yes. So I'll talk about the IP. We think we'll have patent term exclusivity through 2042 based on the dosing patent that's critical to optimize outcomes. It's a 3-week on, 1 week off schedule. You have other patents that are shorter duration. And as far as the potential for a subcu, we don't think it's relevant, meaning necessary to optimize penetration in the second line or in the endocrine-resistant population. Certainly in a setting with patients who are endocrine-sensitive where you could potentially be offering 36 months or so of progression-free survival. It would make a lot of sense to think about a subcu form. You could get meaningful penetration. It's a very large market, long duration of treatment. So there's a -- there are independent of whether you have subcu with -- and you only have IV. But you could potentially optimize penetration in a way that you wouldn't really have much impact on these other patient populations.

Okay. Are there any difficulties formulating it?

Well, we haven't really gotten into detail yet on the status of any of those efforts, and we'll update people in the future.

Okay. Outside the U.S., what's your thoughts there? Whether the doctors may not have as much incentive to use IV drugs?

Well, I mean, incentive to try to improve the outcomes of their patients. I think that's usually the primary criteria for selecting a drug for a patient. It's not the convenience. It's really the outcome for them and knowing that the patient is getting a drug. Ex U.S., we won't market ourselves. We're obviously preparing to launch in the U.S. We felt it's important to hold off having any discussions with a potential partner we've had a lot of discussions, but to actually move anything forward until after our data in the mutation cohort is available. But in the meantime, we're laying the groundwork to submit an MAA. That's the equivalent of an NDA in Europe. Soon after, we have our mutant data submission to the FDA or what would be a supplemental, and we would submit that as a joint combined package. And we've also gained alignment with Japanese regulators on what additional data they would expect in addition to what we already have with VIKTORIA-1. And so we're essentially in the major markets, the 5 major EU countries as well as Japan that comprises the bulk of ex U.S. revenue. And so we are marching down the path without delay to get those drugs hopefully approved. And then the partner discussions can fall within that time period, and we think we could wrap that up. And that's Europe, 13-month review cycle. So you're really talking about an approval late '27 at best. Japan will be longer because you're generating additional data. So we have time to optimize our approach there and hopefully find the right partner, right overall approach.

Okay. Let me see if there's any questions from the audience. Any questions?

You asked all the right of questions.

Well, you guys have been very visible. So big news.

Yes, all good, Well, thank you.

Thank you.