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Good afternoon, everyone. Welcome back. My name is Yatin Suneja, one of the biotech analysts here at Guggenheim. Welcome to our Inaugural Healthcare Innovation Conference. It is my pleasure to welcome our next presenting company, Celldex. From the company, we have a few executives here with me. We have President and CEO Anthony Marucci. We have Chief Scientific Officer Tibor Keler, and we also have Diane Young, who's a Chief Medical Officer. Anthony, why don't you make some opening comments? A lot of progress, a lot of data were announced this year, longer-term data. Why don't you put that data sort of in context and just talk about some of the upcoming catalysts over the next 12 months?
Sure. So 2024 has been a very busy year for us. We presented data in two phase two studies, one in our CSU study, which is our lead program, and the second was in our CIndU presentation. Both programs ran out statistically significant, very, very high p-values as far as efficacy. The safety in both programs was excellent, so we made all our primary and secondary endpoints. From that, we initiated our global phase three studies in CSU earlier this summer. We presented the CIndU data just last month, and we're looking forward to having our conversation and the phase two meeting with the FDA in 2025, and then initiating our phase three studies in CIndU in 2025 as well. In the closing out 2024, we are going to initiate our phase two study in atopic dermatitis for barzol. We're also putting our second program into the clinic, CDX-622.
We'll be initiating healthy volunteer studies for that drug starting next month, and then looking forward to initiating therapeutic studies for 622 in the second half of 2025. Getting into 2025 with barzol, we'll complete the EOE study in 2025 and present data there, and then also the PN studies will be ongoing as well as AD, so 2025 is going to be just as busy a year as 2024 has been, and we look forward to continuing to show great data.
Got it, so let's start with CSU. Obviously, this year you presented the longer-term data, and I think in a lot of these chronic diseases, longer-term data are very, very meaningful, right, so you show a deepening of an effect, so if you can just review for me, what were the key findings for you for CSU long-term data? How does it stack up relative to current standard of care? What sort of efficacy you are seeing?
Yeah, so the 52-week data was extremely favorable. As you know, we met our primary endpoint in the CSU study with the 12-week endpoint. And then we saw at 52 weeks that we had a deepening of response and having up to 70% of patients with a complete response, which is really unprecedented. We believe that that is the best data out there for CSU. And very importantly, the safety profile was also very favorable for 52 weeks.
Got it. Then on safety, I mean, always has been a focus, but I think continues to mature favorably. What about some of the cosmetic things that you see? Like how do you think patients are going to perceive this and what is the feedback from physicians, whether it's skin pigmentation or hair color changes?
Yeah, so we see hair color changes and skin pigment changes, hypopigmentation, which are KIT-mediated effects. They are reversible. In the case of hair color changes, we've had a few patients who discontinued for hair color changes. Most of those had a complete response of their disease at the time that they discontinued. Nobody discontinued for hypopigmentation. And really the feedback we get from our investigators is that patients really are tolerating these things very well because they are so happy with the efficacy that they're seeing with their urticaria. And so it doesn't really bother them that much.
Got it. With regard to the current standard of care, which is Xolair, right? It does have a black box warning. And I think that has become sort of, I mean, some of the physicians we talked to talk about that, hey, look, because of the black box warning, the uptake might be a little bit limited. So just talk about, do you envision a black box warning for a KIT mechanism, if at all, and what are the considerations around it, commercial considerations around it?
Yeah, so based on our data so far, we're not anticipating having any sort of black box warning.
So that's sort of truly differentiated.
Yeah, I mean, to this point, we've made it public that we have one confirmed anaphylaxis out of 500 plus patients. And that was in the IV study, so.
Got it. So I think you have also generated very consistent efficacy, whether it's naïve patient or Xolair-exposed patient. Could you talk about that? Like how consistent are they? What sort of delta you are seeing?
Yeah, so as you said, consistently across our study, we see the similar response in patients regardless of their prior Xolair treatments. So the Xolair naive, the people that just took Xolair, and Xolair refractory, they all have a similar response. And that's been consistent across all of the studies.
Got it. So regarding the two phase 3 CSU studies that are up and running or the program, what are some of the key features of that study? How is the enrollment? It might be early, but how's the enrollment? What are the data timelines?
Yeah, so the studies have started. We're happy with how they're going so far. It's too early to really project. But in terms of those studies, they're similar in design to the phase 2. We tried to keep everything as similar as possible, except of course they're much larger. And we have sized them so that we can say something statistical about those Xolair refractory patients, which we think is really important. The other change that we've made from the phase 2 is that we've added a loading dose, which we think might even optimize our efficacy further.
Got it. What is the loading dose?
The loading dose is 450 for the 300 group and 300 for the 150 Q4 week group.
Okay. What are some of the scenarios for phase three readout? Like what sort of efficacy you want to show or thinking about replicating?
I think we'd like to see similar efficacy to what we saw in phase two, which is certainly the best efficacy out there. We would like to see the statistically significant impact in the Xolair refractory population as well as the overall population.
Got it. Specifically again on CSU, talk about the commercial positioning, pricing dynamic, given that Xolair is going to be generic or biosimilar, so you're going to go sort of after that.
Yeah, I think, look, Xolair is a great drug. It'll continue to be prescribed, especially now that it's gone off-label. We think we would fit right behind Xolair, especially for the allergists. Where we think that we would have some input or a way in also is with the dermatologists, and the reason why we firmly believe that is that we have dermatologists working with us in our CSU phase three studies, our CIndU phase three, our AD study, our PN study. So by the time barzol gets approved, I think there'll be enough dermatologists here in the US and around the world that would have had a lot of experience with barzol and would feel very, very comfortable, but Xolair is still going to be the drug of choice for the foreseeable future upfront.
The fact that we have seen benefit in all the patient populations, I think that just gives doctors the confidence that, hey, no matter where we dose the barzol patients, they'll do well.
How about the pricing? How are you thinking or what sort of is a good benchmark for us?
You know, certainly we're doing our initial work with payers. Certainly we think that where Galderma is pricing their drug for PN and where Dupy charges for their CSU and other indications, I think it'll be right around there in the 50s.
Okay. Okay. Very good. Now on the CIndU side, again, I think there also you've presented now a lot more data, randomized data now, bigger study. What is the development path? How does the development path look like? And how is that market opportunity different or similar to CSU?
Yeah, so CIndU, we showed the results, our 12-week results from our phase two trial. And we did show that for both cold urticaria and for symptomatic dermographism, we had statistically significant and clinically meaningful results for both doses that we looked at and for both types of CIndU, which, really, we were very happy about. And it's really the first large successful phase two study that has happened in a multicenter global study. And in terms of registration, there is nothing approved for CIndU. So we are going to have to have a discussion with FDA about our data and what are really the appropriate endpoints to look at in CIndU since nobody has successfully gone through that path yet.
Yeah, we'll get there. And as far as the commercial opportunity, historically we have thought, we, the industry, that it's about a third of the CSU population. But I think what we're seeing now with additional work being done by researchers in the field and the work that they're doing, they believe the market for this drug is six times the opportunity we're all thinking about. They think that it is such an underserved market as far as people out there. So Novartis commissioned something that's out there now that the researcher believes it could be anywhere between a million and 1.2 million patients out there.
Just CIndU?
Just CIndU.
Wow.
So again, it's an underappreciated market and something that people haven't focused on, but we think it'll be a big market.
With regard to the phase three program there, would it be as big as the CSU or just like you need two studies, one study?
So we have to work out the details of two studies or one study. We do think, I mean, you have to study each subtype separately, whether it's within a study or within separate studies because they have different tools. But we definitely think it's going to be much, much smaller. A lot of the reason for the size of the CSU phase three is because it's our first indication and we need to establish the safety database. But we'll be able to leverage that for subsequent registrations.
Got it. For the phase three CSU study, what is the timeline that you have established for enrollment?
For the CSU study?
For the CSU study.
We've established two years, and we said that when we put it out, and we think that we're being conservative. We think two years is appropriate, and the reason why we think we're being conservative is that we also, when we did the phase two study, if you remember, we guided towards 18 months and we completed the study in 13. So we think two years is going to be plenty.
Okay. Then moving on to EOE, because that's sort of a newer indication, it opened up the EGIT sort of opportunity for it. Could you maybe put in perspective the scientific rationale where you are? I think the dosing there also is a little bit different. What would you like to see? Just talk about that.
The scientific rationale is based on the fact that there are lots of mast cells within the tissues where this inflammation is occurring. And we think that mast cells have been overlooked as one of the main effector cells for driving the dysphagia, the EOE. Clearly, with a mast cell depleting agent, we think we have a great opportunity to answer that question. The dosing that we are using here, because it's an initial study and we're not sure of whether it's going to require the same amount of barzol in this indication as in urticaria to deplete those mast cells, we just want to make sure we're not underdosing. We went with the 300 milligram every month dosing. And then we can certainly see if that's the appropriate dose going forward.
Okay. I think you narrowed the guidance for data in the second half of next year. How has the enrollment been so far? And is that just because it's going to be only presented at a medical conference?
Medical conference, that's the reason.
Okay.
So Diane and her team strongly feel that presenting things at a medical conference is the way to go. And I couldn't agree more. But we'll have data before then.
Then what is the benchmark? Should we look at the data from Dupixent or some of the?
Yeah, we're looking at the Dupixent data as the benchmark. But I think we've also saw some of the Bristol data that are trying to look at the dysphagia free days. Now, I don't know if we'll do the same thing, but we're looking at the impact that we'll have on dysphagia because we think that's going to be extremely important.
It's extremely important. Okay.
Do you want to answer?
That's fine.
How many doses are there? So it's only 300, one dose?
It's 300 milligrams given every month.
Month.
Yes.
But it's 75 patients total, right? So one is to one?
It's about.
It may be a little bit large. Yeah, it's about 80 patients.
Probably 80 patients.
Yeah.
Okay. Then PN, I think that study is up and running. What is the expectation? How should we think about the PN readout?
Yeah, so we're very encouraged about what we saw in our phase one B for PN in terms of reduction of itch with just a single dose of barzolvolimab. So, we're really; that's where we're anticipating seeing rapid reduction of itch and healing of lesions.
Yeah. I mean, and that's one thing that you can't underestimate, the healing of the lesions. I mean, this is a very, very painful disease and it does have the cosmetic issue with it as far as these lesions go. And I think that what we saw in the phase one and some of the anecdotal stuff in the other phase one studies really gives us a lot of confidence going forward.
Got it. Okay. So I'm going to also discuss a little bit on the competition side because there is a lot going on in the space. So there are similar mechanisms, there are different mechanisms, different modalities. So why don't we sort of talk of just get a perspective on what is your view, how are you viewing whether it's the BTK inhibitor or the oral KIT or the KIT antibodies? How do they stack up?
Certainly everything seems to be targeting the mast cell. Mast cells are the drivers of urticaria and these diseases. We feel that KIT is the best target because it gets at the root cause of the disease in terms of regardless of what mast cell trigger it is, whether that's IgE or other mechanisms. We certainly believe that with the data we have, we have the best in class KIT inhibitor, certainly from an antibody perspective. We think that's the case. We've now demonstrated that. We think our potency, our half-life, our safety profile is very differentiated. We'll see about small molecule KIT inhibitors. They have their unique benefits and also their concerns. We'll just need to wait to see data from those programs to understand how they fit in.
Okay. Any view on the MRGPRX2?
Yeah, so that's another pathway by which mast cells get activated. Again, in certain patients, certain situations, I think that may be a beneficial way. But it's going after one of the triggers, not going after the mast cell, which is really driving the disease regardless of the trigger.
Got it. So with regard, okay, very good, helpful. I missed the AD study. With regard to the atopic dermatitis study, what is the goal? I think you've been very clear that you are positioning for second line, right, right after Dupixent, which I think is a good, that's where it will be. Would you enroll patient population that have been exposed to Dupixent? Just curious how the study set up.
Yeah, so my guess is that Diane, I won't speak to you so you can answer, but my guess it'll be all comers.
Yeah.
We would assume that the vast majority of the patients would be either Dupixent failures or IL-13 failures or any of the other drugs that are competing with Dupixent upfront.
Yeah, that's correct. We're allowing all those prior therapies on the study and we'll certainly look at that.
Is there a particular bar there or what is the bar there, at least on EoE 75? Which drug we should look at or which competition?
I think we'd like to be similar to in efficacy and certainly better than Dupixent in efficacy, but with a good safety profile as well.
Got it. Okay. Other indications that you are thinking, obviously these are a lot of indications already. You're really expanding the aperture. You expanded the aperture. Other indications that you are thinking for barzol?
We're thinking along the lines of the itch component.
I see.
So we would look there. We think those are good enough markets. But as we're going through the rest of our data sets from CSU and CIndU, we'll see what other comorbidities some of these patients had and see if we've had any impact that would lead us down that road as well.
Got it. Then moving on to the pipeline, which I think 622 is a very exciting, I would say, target. There is a lot going on in the TSLP space in general. Yours is unique in the sense that it is SCF bispecific. So could you talk about the biology, where it fits in? It still is on the Th2 pathway. Just love to understand.
Yeah, we're also very excited about this program. It's really to build off the data we have with barzol in terms of mast cells being a really important inflammatory component of many different diseases, but we know in some cases other pathways are also playing a big role. We see the TSLP mediated Th2 inflammation as a sort of complementary non-redundant pathway to what mast cells are doing. This is really evident in certain pulmonary indications like asthma or COPD. We think there's going to be other opportunities as well, but yeah, we're looking forward to taking the first stem cell factor neutralizing antibody approach into the clinic.
Got it. How should we think about the half-life? Because some of these bispecific tend to have shorter half-life. What have you seen in preclinical? What is the expectation in patients?
Yeah, we are very pleased with the pharmacokinetic profile we've seen so far. We have introduced into this molecule, as we have in barzol, half-life extension. And so we expect a very antibody-like pharmacokinetics in people.
Okay. The healthy volunteer study that's going to start, is it like a classic healthy volunteer where you do SAD, MAD?
Correct.
Anything particular you are looking for?
I think with both the SAD and the MAD, we will get a lot of data both on impact on mast cells. We have the tryptase readout that we're all very familiar with. We'll also be looking at all the side effect parameters. We don't anticipate having a great readout for the TSLP component. We might be able to demonstrate target engagement, but that we plan to get once we move into proof of concept studies.
Got it. Very good. Very helpful. Then just final question for me. Anthony, how's the financial health of the company? How are you positioned?
Financial health is good. We finished the quarter with $756 million. We've also guided that that's enough money to get us through 2027 and into 2028. So that means that the CSU studies are complete. That means the CIndU phase three studies are complete. And based on that, we can move forward. So we have plenty of cash to complete everything that we've talked about today and then some.
Got it. I think we have one minute, so I want to sneak in one question. So I think this year you have generated more data and the data have been consistent, right? More safety data. What do you think is the disconnect? Because I think it's a unique dynamic if you see how the stock has performed.
I just think that we need to better describe and communicate the data. So I think one of the things that with the CSU data, it was confusing on the table. The feedback we got was we were counting this plus this plus this. And we were like, no, we had the randomized period, the cumulative period, and then those patients that were placebo that went off to drugs. So it was a little confusing. I think that we've done a decent job in going out and talking about it recently. But I think that we need to make the data as simple and as communicable as we can and have people understand what's going on. Obviously, the KOLs, the PIs, they're extremely excited about the data. They're excited about the efficacy. The safety profile is what we would hope it to be, but there's this disconnect.
We just need to do a better job in communicating it better because at the end of the day, what we're seeing is a drug that has such a high benefit to risk ratio. It's incredible.
Very good. So very good. Thank you so much.
Thank you. Appreciate it as always.
Yep. Thank you.