GUGGENHEIM 3RD ANNUAL HEALTHCARE INNOVATION CONFERENCE - CELLDEX THERAPEUTICS INC

YATIN SUNEJAH, Good morning, everyone. Welcome to Google and IAM Third 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's the Chief Medical Officer. And we have a Terry, where she's the chief commercialization officer. I think Sarah is going to play Anthony for us today. So why don't you do your best? Why don't You make some opening comments? You know, obviously, pretty good results that you announced in September. So congratulations on that. But just frame some of the opening comments on the milestone that we should be watching out for. And then we'll go into some of Q&A. Absolutely. Thank you. We really appreciate you having us here today. So, Jatin, 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 mass cell depletion and mass cell modulation. And you saw top-line Phase III results from our Barzivalumab program in September, which Diane will talk about in much greater detail with you over the course of this. But, you know, we're 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 MBARC studies? You know, what stood out to you? How was the replication from phase two to phase three? talk about maybe some of the nuances on various endpoints, like the angioedemia benefit that your product has, which is very unique than anything out there that is approved. Yes, so 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. You know, we're the first studies that have had a complete response rate in the majority of patients, the first cities 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 and when you take these together these data together with our phase two data where in the 76 week data we showed this you know unprecedented off therapy prolonged response we really have you know, a unique profile and a profile that can really serve a lot of CSU patients. So I don't know if Terry wanted to comment on the competitive profile. Sure. As Diane said, in our interactions with the HCPs indicate barzavolumab can really be a practice-changing therapy. All of our conversations continue to come back to these five big differentiators for HCP's in 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 fourth, 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. And number five, that dosing regimen, right, both the flexibility of Q4 or Q8, but importantly with Q8. The only therapy that offers this view is seven dosing days a year. That's a very compelling package from just the 24-week top-line data. Got it. So 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 Zoller refractory, right, or OMA refractory. So 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, you know, which we have to negotiate with the FDA. But as we said, we designed the study to be able to specifically look at that subgroup. And so, you Know, it's highly statistically significant. So, you Now, it would go in the level, but we expect it. And Terry, it seems like you like both the doses, so you would expect both the doses so that there is flexibility from a physician's standpoint. Optionality is a real advantage. So the intention is to fit seamlessly into HCPs practices and into patients' lives. There are HCP's 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. And 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 on maybe a little bit on the safety side, because that's where we get a lot of questions from investors. 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 that are approved for these big indications. Yeah. So just to take a step back, You know, 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 in grade 3 and 4 adverse events, the rates in placebo and barzavolumab were the same. We had two adjudicated cases of probable anaphylaxis in the Phase III study. They both occurred after the first dose of barzavolumab, and, you know, as we pointed out, these are the only two probable cases adjuditated 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 barzavolumab. The other cases were not adjudicated as anaphlaxis. So 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. And is there a difference between how you would categorize a grade four versus grade three? Are all these anaphalaxis sort of grade four? So it's important there was there was conversation about grade four after our initial call. Grade four was an investigator attribution not the rating of an anaphylaxis adjudication committee. And the scale that we use to evaluate adverse events, if you were seen in the emergency room or hospitalized, you were considered a grade four. So 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. So with regard to the BLA filing is 52 weeks the gating factor for BLA and what is the timing of the BLA so we've guided for B LA submission in 2027 with the full 52 week data okay and then so we're gonna get I don't know if you have said that when do we expect more data or to be presented is it going to be at the quad AI is that and maybe if you can preview anything particular that you know which we should be looking out there. Sure. So at Quad AI, which is in February of 2027, you'll see the 24, the full 24 week experience. So you've already seen 24 weeks of safety. This will really be focused on efficacy and around some of those secondary efficacy measures. Diane, do you want to comment on what specifically you guys are focused on? Yeah. So we're going to go into more depth on the primary and key secondary endpoints through 24 weeks. So, you know, we'll see the 12-week data, the 24-week data, and 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 don't expect to have anything new with regard to safety. And I will just say, I mean, this an amazingly robust data set and so we're already mapping out we're going to have you know many presentations on the other secondary and exploratory endpoints you know coming in the in the coming months got it we did guide with our initial top line results that's consistent with what we've seen in phase two we know that the data continues to deepen um over time so we we're really looking forward to that presentation. Got it, got it. And then the, are the phase three studies set up for an off-label remission sort of data or durability, just like the phase two was, where you followed it, and that really stood out to investigators and physicians. So that was, so as you said, in the phase 2 off-therapy, you know, patients had this amazing prolonged response with, you know, 41% of people still having a complete response seven months after the last dose. So we have to wait a while to see that in the phase three because they have treatment for 52 weeks and then they go into the follow-up period. And we also have a long-term extension study which is going to further follow those patients. So, you Know, we do expect to have that data. You know, we saw clearly in the Phase 2 that those AEs were reversing and we know mechanistically that they will. But, you know, we have to we have to wait a bit for that data from the phase three. Got it. So I'm going to come back to pipeline in a bit, but I want to sort of double click on the on the market and the commercial. Maybe, Terry, for you, maybe tell us how do you think this market evolving? If you look at now or listen to Novartis, I mean, they're saying it's going to be a $4 billion product, like the one that they have. So just like maybe talk about us positioning by the time you come to the market, what patients are ready for you all that stuff. So maybe I'll break that down into two pieces, one, the overall market, and then two, barzavolumab's positioning within that market. This is a market with significant headroom for growth. We've seen this with other INI 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 percent of those patients are diagnosed. And of those who are diagnosed and flew 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 therapist. So we're 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 minority, 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. So with that dynamic occurring for CSU, there are two broad patient populations and growing patient populations where we see barzolfolumab being really distinctive in its competitiveness. The first 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's no syndicated or published data on that. We're leading that assessment. It could be even larger than that. And then for as the therapy of choice for all second line advanced therapy, whether you've initiated with dupirami or OMA, there's a real human behavior driver factor for this as well. You know, once a patient has gone through probably a multi-year diagnosis cycle, and then they've spent months on super high doses of over-the-counter antihistamines, I always tell people, if you haven't, maybe try to take four Claritin and four Zyrtec in a day and see how you feel. Imagine doing that for four months. They've made the big decision to go on an advanced therapy. They're 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's where barzavolumab 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 Rapsido is in the 30% range, right, somewhere in that. So 70% are not even controlled. I mean is that the right way for us to think that, you know, a lot higher number of these patients who are on Rapsidol, maybe the 30 percent that are well controlled might not want another therapy, but you know, 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 is are the attrition rates. And for both omelizumab 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 the 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, you know, if the second- line population is that significant and you don't expect any, I mean 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. In our preliminary discussions with payers, the Barzavolumab profile resonates very clearly. The most expensive therapy for a payer is the one that doesn't work. And 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 differentiations. Our strategy is to pursue a premium value-based price for barzavolumab 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 three results to 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 Pi Exchange in the first half of 2027. So, 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. Do you have a view on Sindhu? How big is that market relative to CSU? First, I should say we can't comment for barzavolumab specifically on off-label use, because we often get asked how much Sindhu uptake will there be once CSU is approved. That said, you know, like many diseases that have been underserved and undertreated, there is enormous unmet need in Sindhu and specifically SDN cold Jew where our phase three 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. Barzavolumab is on track to be the second in this market. And based on our phase two 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 more of a standard timelines? So all we've 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 SINDU phase 3 study, are you able to say anything, how the enrollment is going, any expectations on the data? And do the same for AD, atopic dermatitis, because that's very near term. Hopefully in the next, let's say, few weeks, we're going to get that data. Yeah, so we're very excited about the potential of barzivalumab in SINDУ based on our phase 2 data. The phase three is ongoing, it's enrolling, it is doing well, and we are planning to give additional guidance on this in the next few months. Got it. And 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 think the initial data was interesting, but obviously the translation was not there in phase two. Anything we could read? Are there any overlapping sort of similarities from each perspective in AD versus PN? I think, you know, we've 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're looking forward to the data later this year. Got it. And then in this AD study, are you enrolling, I mean, what type of patients have you enrolled? Are they mostly naive, or is it a blend of naive and exposed patient to biologics? So it's a moderately severe population. We do allow patients who have had any prior therapy, really. and so we will have you know a proportion of those patients will be you know biologically experienced got it and then again like maybe what you're looking for is it just a stat seg there like from an efficacy standpoint and how we define success in ad i think we're um you know we're what we've said is we want to be you Know at least as good as you know if not better than you know currently existing therapies but then you know we would also look for you know particular subsets or particular aspects of biology that might might benefit got it um then maybe um in the interest of time one question on the pipeline the cdx622 the scf and tslp by specific what is that product uh how it is similar or different than barzogolamab i understand the tslb arm where would you go, what are you doing right now with the program? So we're really excited about 622. We think that 622 and barzivalamab are really complementary and synergistic pathways and really show different ways of targeting the stem cell factor kit axis. So barzivolamab is a single antibody. it targets the kit receptor it depletes mass cells 622 preferentially targets soluble stem cell factor which and then it has the effect of you know inhibiting and depleting mass cells but it also but it doesn't necessarily impact some of the other kit targets as much but it it also has the the stem cell the um tslp component so an independent pathway so and we think this is you know the future of um immunoinflammatory diseases is to be able to target more than one pathway so we're we're really excited about you know being able to lead the mass cell science and and discovering all these things about um stem cell factor and and kit got it in In terms of the indication, so I think you're 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? And then what about food allergy? Is that an angle that you can go with this program? Yeah, so the current proof of mechanisms 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, you know, asthma is, you know, a potential indication for this with targeting both mechanisms for the future. But we also are interested in other indications, and food allergy is definitely on our list. And, you Know, we will be, you know, discussing our future indications for Barzal and 622 in the future." Got it. Maybe final question then. How is the financial health? What's the capital position right now and how till when are you funded? Absolutely. So we reported out last week and as of Q3, we have 650 million in cash, which gets us through 2028. And importantly, that brings us up to initial launch. Very good. I think that's all I had for you, ladies. Thank you so much. Thanks for having us. We appreciate it. Thank You.