Good morning, everyone. Welcome to Guggenheim's 3rd Annual Healthcare Innovation Conference. My name is Yatin Suneja, one of the biotech analysts here at the firm. It is my pleasure to welcome our next presenting company, Celldex. From the company, we have a few executives here who I will be chatting with. We have Sarah Cavanaugh. She is the SVP Corporate Affairs. We have Diane Young. She is the Chief Medical Officer. And we have Teri Lawver . She is the Chief Commercialization Officer. I think Sarah is going to play Anthony for us today. Sarah, why don't you
I will do my best.
Do your best. Why don't you make some opening comments? Obviously, pretty good results that you announced in September, so congratulations on that. Just frame some of the opening comments, some of the milestones that we should be watching out for, and then we will go into some of the Q&A.
Absolutely. Thank you. We really appreciate you having us here today. Yatin, as you know, Celldex has this deep heritage in the antibody space, and we have applied that over the last several years to drive new science around mast cell depletion and mast cell modulation. You saw top-line phase III results from our barzolvolimab program in September, which Diane will talk about in much greater detail with you over the course of this. We are very excited about that, and we are moving forward to probably the biggest milestone for us, BLA submission in 2027.
Got it. Very, very good. Diane, why don't you maybe then talk about some of the highlights from the EMBARQ studies. What stood out to you? How was the replication from phase II to phase III? Talk about maybe some of the nuances on various endpoints, like the angioedema benefit that your product has, which is very unique than anything out there that is approved.
Yeah. We are thrilled with our phase III data, and we have been sharing it with outside experts who are also giving us very positive feedback and are really just as excited about what they call best in disease efficacy as we are. When I think about it, we have shown in these trials a number of things that nobody else has demonstrated to date. We're the first studies that have had a complete response rate in the majority of patients, the first studies that have prospectively set out to show angioedema clearing at 12 weeks. We've shown that omalizumab refractory patients respond as well as the overall population, and we have one of our regimens with all these improvements only requires seven doses in a year.
When you take these data together with our phase II data, where in the 76-week data, we showed this unprecedented off-therapy prolonged response, we really have a unique profile and a profile that can really serve a lot of CSU patients. I don't know if Teri wanted to comment on the competitive profile.
Sure. As Diane said, in our interactions with the HCPs indicate barzolvolimab can really be a practice-changing therapy. All of our conversations continue to come back to these five big differentiators for HCPs and patients. Number one, that complete response number. Up till this point, patients and HCPs have settled for some improvement in symptoms, but what they really want is complete clearance of symptoms, and that's the difference with that complete response in a majority of patients. Second, the effect is rapid, durable, and actually deepens over time. Third and four, the ability to address patient populations that none of the other therapies currently can, that first-line patient with severe disease and angioedema, and then the biologic refractory patients. Number five, that dosing regimen, right?
Both the flexibility of Q4 or Q8, but importantly with Q8, the only therapy that offers as few as seven dosing days a year. That's a very compelling package from just the 24-week top-line data.
Got it. With regard to the study, again, it was unique in the sense that, number one, it was one of the largest, let's say, CSU program, but you also went after a defined subset, which is XOLAIR refractory, right, or omalizumab refractory. When it comes to, let's say, the labeling discussion and all, will that be on the label?
We do expect to have that in the label in some form, which we have to negotiate with the FDA. As we said, we designed the study to be able to specifically look at that subgroup, and so it's highly statistically significant. It's a matter of where it would go in the label, but we expect it to.
Got it. Teri, it seems like you like both the doses, so you would expect both the doses so that there is flexibility from a physician standpoint?
Mm-hmm. Optionality is a real advantage. The intention is to fit seamlessly into HCPs' practices and into patients' lives. There are HCPs who prefer that monthly interaction with the patient, and that fits into their practice, and there are patients who prefer to not think about their disease when they don't have to, so the fewer dosing days per year is a real advantage. Because after the loading dose, it's the same amount of drug over the course of a year, payers will be supportive of this optionality. It really reflects real-world treatment paradigms.
Got it. Let's focus a little bit on the safety side, because that's where we get a lot of questions from investor. I think there is still confusion or lack of understanding on what exactly you have shown on the anaphylaxis side, because when the data became available, we put out a note saying that there's actually more anaphylaxis on the placebo arm than the drug arm, right? Just put that in perspective. Also, maybe talk about what we see with other drugs, like, that are approved for these big indications.
Yeah. Just to take a step back, we were very pleased with the overall safety profile that we saw in the studies. The most common adverse events were the KIT-mediated events that are mostly mild to moderate and expected to be reversible. In terms of serious adverse events and grade 3 and 4 adverse events, the rates in placebo and barzolvolimab were the same. We had two adjudicated cases of probable anaphylaxis in the phase III study. They both occurred after the first dose of barzolvolimab, and as we pointed out, these are the only two probable cases adjudicated in the entire subcutaneous program, which is 2,400 patients. There was another case that was adjudicated as anaphylaxis, but occurred with a dose of placebo, not with barzolvolimab. The other cases were not adjudicated as anaphylaxis.
We really feel that our data are supportive of a label similar to other biologics, which is in the warnings and precautions section, there's language about hypersensitivity, including anaphylaxis has been observed.
Got it. Is there a difference between how you would categorize a grade 4 versus grade 3? Are all these anaphylaxis sort of grade 4?
So it's important, there was conversation about grade 4 after our initial call. Grade 4 was an investigator attribution, not the rating of an anaphylaxis adjudication committee. The scale that we use to evaluate adverse events, if you were seen in the emergency room or hospitalized, you were considered a grade 4. There's many other different scales that could be used, but this was a very conservative scale that the investigators used.
Got it. Sarah, maybe a question for you. With regard to the BLA filing, is 52 weeks the gating factor for BLA, and what is the timing of the BLA?
We've guided for BLA submission in 2027 with the full 52-week data.
Full 52. Okay. We are going to get, I do not know if you have said it, when do we expect more data to be presented? Is it going to be at the AAAAI? And maybe if you can preview anything particular that we should be looking out there?
Sure. At AAAAI, which is in February of 2027, you will see the full 24-week experience. You have already seen 24 weeks of safety. This will really be focused on efficacy and around some of those secondary efficacy measures. Diane Young, do you want to comment on what specifically you guys are focused on?
Yeah. We are going to go into more depth on the primary and key secondary endpoints through 24 weeks. We will see the 12-week data, the 24-week data, the time course. Very importantly, we presented the full safety picture for the 24 weeks on our call, and we have no new findings, so we really do not expect to have anything new with regard to safety. I will just say, this is an amazingly robust data set, and so we are already mapping out. We are going to have many presentations on the other secondary and exploratory endpoints coming in the coming months.
Got it.
We did guide with our initial top-line results that is consistent with what we have seen in phase II. We know that the data continues to deepen over time, so we are really looking forward to that presentation.
Got it. Got it. Are the phase III studies set up for an off-therapy remission sort of data or durability, just like the phase II was, where you followed it, and that really stood out to investigators and physicians?
As you said, in the phase II, off therapy, patients had this amazing prolonged response with 41% of people still having a complete response seven months after the last dose. We have to wait a while to see that in the phase III, because they have treatment for 52 weeks, and then they go into the follow-up period. We also have a long-term extension study, which is going to further follow those patients. We do expect to have that data. We saw clearly in the phase II that those AEs were reversing, and we know mechanistically that they will, but we have to wait a bit for that data from the phase III.
Got it. I am going to come back to pipeline in a bit, but I want to sort of double-click on the market and the commercial. Maybe Teri, for you, maybe tell us, how do you think this market evolving? If you look at Novartis, listen to Novartis, they are saying it is going to be a $4 billion product, right? The one that they have. Just maybe talk about us, positioning, by the time you come to the market, what patients are ready for you, all that stuff.
Mm-hmm. I will break that down into two pieces. One, the overall market, and then two, barzolvolimab's positioning within that market. This is a market with significant headroom for growth. We have seen this with other I&I diseases in the era before there were multiple biologics available. The market size was well underestimated, and we think the same dynamic is occurring right now in CSU. Today, only 30% of estimated prevalence in the U.S., only 30% of those patients are diagnosed. And of those who are diagnosed and flow through antihistamine therapy, less than 20% of those who are clinically eligible for advanced therapy are seeing even one advanced therapy.
And if we keep in mind, up until last year, there was only one advanced therapy, so we are in the very early days of this treatment paradigm evolving, and we think psoriasis is a nice potential analog for how it might evolve, where when we saw the IL-23 therapies come on board, and they were the first to demonstrate complete clearance in a majority of patients, analogous to our complete response in a majority, they also demonstrated strong efficacy in patients and disease that was refractory to current standard of care. And when those IL-23s entered the market, we saw both a significant growth in penetration among biological eligible, as well as second-line therapy began to eclipse first-line therapy because of the dynamic in lines of therapy.
With that dynamic occurring for CSU, there are two broad patient populations and growing patient populations where we see barzolvolimab being really distinctive in its competitiveness. The first-line therapy for patients presenting with severe disease or severe angioedema, and we estimate the size of that population to be at least 25% of the first line. There is no syndicated or published data on that. We are leading that assessment. It could be even larger than that. And then, as the therapy of choice for all second-line
Yeah
advanced therapy, whether you have initiated with DUPIXENT or OMA. There is a real human behavior driver factor for this as well. Once a patient has gone through probably a multi-year diagnosis cycle, and then they have spent months on super high doses of over-the-counter antihistamines, I always tell people, "If you have not, maybe try to take four Claritin and four Zyrtec in a day and see how you feel." Imagine doing that for four months. They have made the big decision to go on an advanced therapy. They have gotten coverage from their payer. They go on to this advanced therapy, and they are still suffering with their symptoms. At that point, they are going to turn to the therapy with the highest likelihood to deliver rapid, profound, deep, and durable response, and that is where barzolvolimab stands out.
Got it. With regard to the second-line market, I mean, that market should be substantial, right? Because if you look at the remission rate for even XOLAIR is in the 30% range, right? Somewhere in there. So 70% are not even controlled. I mean, is that the right way for us to think that a lot higher number of these patients who are on XOLAIR, or maybe the 30% that are well-controlled might not want another therapy, but the 60%, 70% would want to?
That's right. I think there are two dimensions we look at. First is the complete response rate-
for the currently available therapies, and as you said, that hovers between 30% and 38% for the other therapies. So the remainder are eligible for a further therapy with continued symptoms. The other real-world evidence we look at are the attrition rates, and for both omalizumab and dupilumab, the real-world attrition rate at one year is 50% for patients who initiate on CSU. So that combination of factors tells us this second-line advanced therapy opportunity is extremely large and would be likely to follow a pattern that we've seen in RA, in psoriasis, in Crohn's, in ulcerative colitis, where second-line therapy eclipses first-line within a few years of a novel biologic.
Got it. How should we think about pricing here? I mean, again, if the second-line population is that significant and you don't expect any, I don't know if you expect any step edit because you've already taken the one that is approved. So number one, step edits and pricing.
Mm-hmm. In our preliminary discussions with payers, the barzolvolimab profile resonates very clearly. The most expensive therapy for a payer is the one that doesn't work. Complete response, and payers are accustomed to the analogy with the psoriasis market on complete clearance, so the complete response numbers and the high efficacy in these large first and second-line populations of unmet need, payers easily see that translating, that clinical differentiation translating into economic differentiation. Our strategy is to pursue a premium value-based-
price for barzolvolimab that reflects the value it delivers for the health system.
Got it. How should we think about a commercial infrastructure when you launch it?
First, I should say, our approach to building our commercial infrastructure is disciplined, data-based, and milestone-driven. We have done the foundational work. We are very clear on how and where we will build out. We're currently focused on expanding our MSL team-
in light of the phase III results to continue to share these results with not only the KOL community, but a broader set of leaders in CSU treatment. We're also currently building out our market analytics team, our brand team, and of course, our payer team, as we anticipate being in front of payers through PIE exchange in the first half of 2027. We'll continue to be disciplined, high ROI and competitive. We know precisely who the CSU advanced therapy prescribers are. We know who they are by decile, and we will be building to be effective and competitive in the right accounts.
Got it. Do you have a view on CIndU? How big is that market relative to CSU?
Mm-hmm. First, I should say, we can't comment for barzolvolimab specifically on off-label use, because we often get asked how much CIndU uptake will there be once CSU is approved. That said, like many diseases that have been underserved and undertreated, there is enormous unmet need in CIndU, and specifically SD and ColdU, where our phase III trials are ongoing. Novartis put out a release earlier this year where they indicated that the global prevalence could be in the tens of millions, with a high percentage of those having extreme disease, high disease burden. Right now, there is only one approved therapy. Barzolvolimab is on track to be the second in this market, and based on our phase II results, we believe we can have a highly differentiated profile and be part of shaping and driving the growth in this marketplace.
Got it. Very good. Very good. A question for Sarah again. With regard to the BLA, this is going to be a priority review, or do you think it's going to be more of a standard timelines?
All we have guided is that we will be submitting in 2027, and our goal is to get this in the hands of patients as quickly as possible.
Got it. Then, maybe for Diane, with regard to the CIndU phase III study, are you able to say anything, how the enrollment is going, any expectations on the data? Do the same for AD, atopic dermatitis, because that is very near term. Hopefully, in the next, let us say, few weeks, we are going to get that data.
Yeah. We are very excited about the potential of barzolvolimab in CIndU based on our phase II data. The phase III is ongoing, it is enrolling, it is doing well, and we are planning to give additional guidance on this in the next few months.
Got it.
In terms of AD, we have said we are going to have data by the end of the year.
Got it. Any learnings from the PN study? I mean, there, I think the initial data was interesting, but obviously, the translation was not there in phase II. Anything we could read? Are there any overlapping similarities from the itch perspective in AD versus PN?
I think we have said we were certainly very optimistic about the outcome potentially in PN, particularly given the experience that we saw in our phase I study. Seeing a positive outcome in PN would have given us even greater enthusiasm going into the atopic dermatitis readout, but each study stands on its own, and we are looking forward to the data later this year.
Got it. In this AD study, are you enrolling, I mean, what type of patients have you enrolled? Are they mostly naive, or there is a blend of naive and exposed patient to biologics?
It is a moderately severe population.
We do allow patients who have had any prior therapy, really, and so we will have a proportion of those patients will be biologically experienced.
Got it. Then, again, maybe what you are looking for, is it just a stat sig there? From an efficacy standpoint, how would you define success in AD?
I think what we have said is we want to be at least as good as, if not better than, currently existing therapies. But then we would also look for particular subsets or particular aspects of biology that might benefit.
Got it. Then maybe, in the interest of time, one question on the pipeline, the CDX-622, the SCF and TSLP bispecific. What is that product? How it is similar or different than barzolvolimab? I understand the TSLP arm. Where would you go? What are you doing right now with the program?
We are really excited about 622. We think that 622 and barzolvolimab are really complementary and synergistic pathways and really show different ways of targeting the stem cell factor KIT axis. Barzolvolimab is a single antibody. It targets the KIT receptor. It depletes mast cells. 622 preferentially targets soluble stem cell factor,
which, and then it has the effect of inhibiting and depleting mast cells, but it does not necessarily impact some of the other KIT targets as much. But it also has the TSLP component, so an independent pathway. We think this is the future of immuno-inflammatory diseases, is to be able to target more than one pathway. We are really excited about being able to lead the mast cell science and discovering all these things about stem cell factor and KIT.
Got it. In terms of the indications, I think you are running a proof of mechanism in asthma. Maybe talk about that. Is that of an interest, or is this just to establish the TSLP angle? What about food allergy? I mean, is that an angle that you can go with this program?
Yeah. The current proof of mechanism study, the primary objective of it is to make sure that the TSLP part is working and to learn something about this molecule itself in asthma. We think asthma is a potential indication for this with targeting both mechanisms for the future. We also are interested in other indications, and food allergy is definitely on our list. We will be discussing our future indications for Barzol and CDX-622 in the future.
Got it. Maybe final question then, how is the financial health? What is the capital position right now, and till when are you funded?
Absolutely. We reported out last week, and as of Q3, we have $650 million in cash, which gets us through 2028. Importantly, that brings us up to initial launch.
Very good. I think that is all I had for you ladies. Thank you so much.