Celldex Therapeutics, Inc. (CLDX) Earnings Call Transcript & Summary

Ladies and gentlemen, thank you for standing by, and welcome to the Celldex Interim Data Update Call. [Operator Instructions] Please be advised that today's conference is being recorded. [Operator Instructions] I would now like to hand the conference over to your speaker today, Sarah Cavanaugh, Senior Vice President of Corporate Affairs. Thank you. Please go ahead, ma'am.

Thank you. Good morning, and thank you all for joining us to discuss the exciting interim data set we reported earlier today from our Phase IB study of CDX-0159 in chronic inducible urticaria. With me on the call today from Celldex are Anthony Marucci, Co-Founder, President and CEO; Dr. Margo Heath-Chiozzi, Senior Vice President of Regulatory Affairs and Medical Lead on the study; Dr. Diane Young, Senior Vice President and Chief Medical Officer; Dr. Tibor Keler, Co-Founder, Executive Vice President and Chief Scientific Officer; and Dr. Diego Alvarado, Senior Director of Research and the Research Lead on the study. We are also very pleased to welcome Dr. Marcus Maurer in Berlin. He is conducting the study, and Margo will introduce him more formally after our opening remarks. In the Investors section of the celldex.com website, you will find today's press release and the slides we refer to on this call, which are located on the Events and Presentations page. Before we begin our discussion, I would like to direct your attention to Slide 2 with respect to important information regarding the forward-looking statements that today's speakers will be making. Please be advised that a question-and-answer period will be held later on this call. I would now like to turn the call over to Anthony. Anthony?

Thank you, Sarah. Good morning, and thank you for joining us on this early call. Earlier this morning, we issued our press release on interim data from our Phase Ib CIndU study that includes cold contact urticaria and symptomatic dermographism. As part of the call this morning, we want to take advantage of the window of time that Dr. Maurer was able to make available in his busy schedule to be with us today, which we greatly appreciate. The interim results we shared this morning continues to add to our enthusiasm about the prospects of CDX-0159. As you all remember, it was Dr. Maurer who presented the impressive results from a healthy volunteer study of 0159 in a late-breaking session at the EAACI meeting last June. In that study, 0159 demonstrated profound and durable reductions in plasma tryptase, which is to believe to reflect the symptomatic reduction in mast cell burden. The Phase-I study we are discussing today is evaluating 0159 in the most common forms of chronic inducible urticaria, where mast cell activation is the key pathogenic driver of the disease. We are very pleased to see what we believe is the translational of the results of the healthy volunteer study now reached through to patients with chronic urticaria. I will now turn the call over to Margo to take you through the interim results. Margo?

Thanks, Anthony. The Phase Ib study, as outlined on Slide 3, is an open-label clinical trial evaluating the safety and pharmacodynamics of a single dose of CDX-0159 in up to 10 patients with cold contact urticaria and 10 patients with symptomatic dermographism who are refractory to antihistamines. Patient symptoms are induced via provocation testing that resembles real-life triggering situation. CDX-0159 is administered as an add-on to antihistamine and patients were followed for 12 weeks after treatment. On Slide 4, you will see that at the interim data cut, 15 out of 20 patients have received a single intravenous infusion of CDX-0159 at 3 milligrams per kilogram including 9 patients with cold contact urticaria and 6 patients with symptomatic dermographism. Safety results were reported for all 15 of these patients. Activity results were reported for the 10 patients who were assessed for up to at least 15 days. Seven with cold urticaria is shown on the graph in the left and 3 with symptomatic dermographism shown on the graph on the right. Given the weather in Germany, recruitment of the cold urticaria patients was prioritized over the last few months, and the cold average follow-up is 6 weeks with a range of 2 to 12 weeks. With that cohort close to enrollment completion, the focus has recently shifted to patients with symptomatic dermographism. There were fewer patients on the symptomatic dermographism cohort eligible for activity assessment at this time. So the data here is emerging with an average follow-up of only 2 weeks in a range of 2 to 4 weeks. The patient population in this study clearly has high disease activity. The cold urticaria patients had a mean baseline critical temperature threshold test of 18.7 Celsius with a range of 5 to 27 degree Celsius, and the symptomatic dermographism patients baseline Fric thresholds were 3 or 4 pins. To put the term cold into perspective, this means that half of our patients develop hives on their baseline temp test between 65 and 80 degrees Fahrenheit, which highlights the extreme sensitivity to temperatures below their normal body temperature. The baseline disease severity makes the results that we've seen to date even more impressive. So far, 8 of the 10 patients have experienced a complete response as assessed by provocation threshold testing through their latest assessment. Again, this includes all 7 patients with cold urticaria and 1 with symptomatic dermatographism. Please note that the graph for cold urticaria only shows 6 lines because 2 of the cold urticaria patients had the same baseline temperature of 21 degrees and their lines directly overlap. Please, let's talk about cold urticaria first. Every single cold urticaria patients assessed for clinical activity to date experienced a complete response, and these responses occurred quickly, 5 by 2 weeks. Importantly, we are seeing strong signs of durability, as you can see, based on the last observation time, which is included to the right for each patient in the cold urticaria data on the slide, with 1 patient out to 12 weeks and 3 out to 6 weeks. We were also seeing promising signs in the symptomatic dermatographism cohort based on early data. The complete response observed here occurred at 4 weeks. The remaining 2 patients were just recently treated and have only been followed for 2 weeks. One patient experienced a partial response thus far, and the other has reported decreased itching during the Fric test. We are hopeful these patients will continue to improve over time and look forward to observing their progress. As a reminder, all patients will continue to be assessed for response through 12 weeks. Other measurements used to assess activity reinforce the response data. Both the patient and physician global assessment results are consistent with the provocation testing results, and measurements of serum tryptase also tell the same story. While serum tryptase levels are available for only the first 6 patients, all of them cold urticaria, the mean level was 3.3 plus or minus 0.2 nanograms per milliliter baseline and then dropped to below the limit of detection by the day 15 treatment. All 6 of these patients experienced complete responses on provocation testing. While Dr. Maurer can certainly speak to this in more detail, patients with inducible urticaria spend a significant amount of time and energy avoiding their triggers. An anecdotal data from the site tells us that patients are feeling better and are able to participate in activities they had once avoided. From an efficacy perspective, we believe this data tells us that we have an active drug, and we are truly excited to explore CDX-0159 to the fullest extent possible. As shown on Slide 5, we believe that the growing safety experience we have observed to date also supports broad development opportunities for CDX-0159. CDX-0159 continues to be generally well tolerated. Six of the 15 patients that have been treated had mild infusion reactions, generally areas of localized redness and itching, which were similar to the events that we saw in our previous normal volunteer study and they resolved quickly. We did observe a single severe infusion reaction. The patient developed a single hive followed by brief loss of consciousness. He awoke with a few shaking followed by profuse sweating that rapidly recovered. He was treated with antihistamines and steroids. No epinephrine was administered. The patient was hospitalized for overnight observation with no further manifestations of this event. Importantly, there was no wheezing, shortness of breath or generalized cutaneous or mucous membrane involvement or hypotension. Therefore, this event is not considered anaphylaxis. In addition, there was no evidence of mast cell activation as assessed by serum tryptase measurements. Serum tryptase levels were measured shortly after the infusion and at a later time point, and both were below the pre-infusion baseline tryptase level and demonstrated a progressive decline. We have seen no other events of this nature across any of our studies, but we'll continue to monitor closely. As we have said in the past, we believe subcutaneous presentation is optimal for CDX-0159, both for ease of administration and to offset potential infusion reactions. We have made excellent progress here and expect to introduce the subcutaneous formulation into clinical studies in the third quarter. The bottom of this slide outlines the laboratory data. Through day 15, no patients had meaningful declines in their white blood cell count. Three female patients had transient mild decreases in hemoglobin. We believe that the early hematology observations are consistent with the data from our normal volunteer study, and we will continue to monitor in larger patient numbers with longer observation. In closing, we were excited about the data emerging from this study, which further supports the potential of CDX-0159 to be a field changing product. We look forward to completing enrollment in both the cold urticaria and symptomatic dermographism cohorts in the coming weeks and following all patients out to 12 weeks. We plan to provide updated data cohorts at a medical meeting this summer. In addition, the results observed thus far compelled us to add a third cohort of 10 cholinergic urticaria patients which we expect to open for a moment in May. With that, I'd now like to introduce Dr. Maurer, who is one of the world's leading experts in urticaria, and his research focuses on the physiologic and pathologic functions of mast cells. He is Professor of Dermatology and Allergy at Charité in Berlin. Dr. Maurer, thank you again for joining us. May I ask you to please share some perspectives on the interim data we announced today and your experience thus far in treating patients in the study before we open for questions?

Sure. I'll be happy to do that. Thank you very much. Good morning. Margo, you said a lot already, so let me just provide some color on some of the things you said. So first of all, these are exciting days for urticaria patients -- chronic inducible urticaria patients, but they are very exciting to us as their treating physicians. Look, this is a group of diseases that doesn't make us look good, and it certainly has a huge impact on our patients. As you said, the life of CIndU patients centers around the avoidance of triggers. And just take the 2 diseases that we have treated so far, cold utricaria and symptomatic dermographism, as much as you try to avoid cold when cold means 18 degrees, room temperature, this is unavoidable. When the trigger, scratching is -- a T-shirt that rubs on your skin and induces whealing. This is unavoidable. So patients go to great length to minimize the exposure to trigger, which impairs all parts of their lives, their work, their concentration, their sleep, their social behavior. And yet, they do have a lot of problems with this disease in their lives. It is a disease for which we now only have antihistamines, which we know don't work well in the majority of cases. So we really need better treatment options for patients with chronic inducible urticaria. And patients with chronic inducible urticaria are excited about this new treatment options. It was no problem at all to fill these slots. We could have doubled and tripled the number of patients. Patients in the chronic urticaria community, they see this as a light at the end of the tunnel. And the results that you shared certainty support that. Look at the complete responder rate. What does complete responder mean? It means that in a patient who has cold urticaria, where contact with cold produces robustly -- every time you are exposed to the cold, an itchy wheal that lasts for hours, and now this no longer happens. Now you can go out. Now you can drink things from the fridge. Now you can wash your face with lukewarm water. It translates to real benefit in real-life. And well, our patients are very happy with this. We're also very happy that you have decided to include cholinergic urticaria patients now. Cholinergic urticaria is a devastating disease where sweating, either active or passive, heat causes you to break out in hives, mainly affects younger adults, severely impairs their ability to work and their social life. Look, most of these patients cannot walk up a flight of stairs without breaking out in hives. And to be able to offer these patients within the study now a treatment that has, well, a breakthrough effect in the cold urticaria and symptomatic dermographism patients, that's just -- it's phenomenal. Look, many of these patients included in the trial are treatment-resistants. Certainly to the only licensed treatment option, antihistamines, they all failed that. So what is there for them? Some of the patients in this clinical trial even failed omalizumab, which is licensed for chronic spontaneous urticaria but not licensed for chronic inducible utricaria, and yet is sometimes used off-label, simply because we need to do something to help these patients get on with their lives. I'll be happy to answer any questions on the tolerability of the drug, how patients view this. Patients who come back after 2 weeks and report to us that they no longer need to avoid the trigger in real life and who see when we do the provocation test that no wheal developed, no itch comes are very happy and consider this to be a game-changing treatment. Safety. Yes, let's talk about this. This is perceived as safe by myself and our study physicians. And we haven't seen anything that would make us think that this is not a treatment option for patients with chronic inducible urticaria moving forward or chronic urticaria or mast cell-driven disease. Look, what we're doing here is we're going to the root problem of a mast cell-driven disease, and chronic urticaria is not the only one. So there really is a lot of hope riding on these initial results, and we'll be very happy to monitor our patients moving forward to include new patients and to help to develop this to become a chronic inducible urticaria treatment.

Great. Thank you, Dr. Maurer. I realize your time with us is short today, and we have about 15 minutes for questions. So I'd like to now open the call to questions for you and for any of us on the Celldex team. Operator, if you could, can you open the session?

[Operator Instructions]. Our first question comes from Sam Slutsky with LifeSci Capital.

I guess to start, as you mentioned, prior Xolair was allowed in the study as long as there's a washout period. So for these patients, is it known how they responded to Xolair versus CDX-0159?

Sam, yes, it is. Look, we have very few patients in this trial, and even fewer patients were treated with Xolair. But we know of 2 people who were treated with Xolair before. One of them is a cold urticaria patient, one of them is a symptomatic dermographism patient. And both had only partial response with their Xolair, then switched into the trial and were complete responders on 0159. Now you and I, we know that 2 swallows don't make a summer, but 2 out of 2 is 2 out of 2. So this is certainly something that we will have an eye on. And patients who have partial response to omalizumab and complete response on 159, well, that's certainly very encouraging.

Got it. Okay. Dr. Maurer, can you just walk us through the background of the patients who had these severe adverse event and your thoughts around this event in general?

Yes, sure. I mean we were surprised by this. Margo already shared some of the details on this. I can tell you a little bit more. This is a young patient who mid through infusions started to feel a little dizzy then lost consciousness for a short amount of time. Procedures were put in place. Antihistamine was given. Patient came to very soon after. And our ER physicians were called, as protocol requires. Patient was feeling well after that. Patient and we, as the study team, did not share the ER's physician to transfer the patient to the ER facility. But this is protocol. So it was done, and this is why this transient event was then classified as a severe reaction. Because it happened midway through the infusion, we have to consider there that it is [ costly ] related. And Margo already shared that there's no sign for this to support that it was an anaphylactic reaction or a mast cell-driven reaction, not a single wheal, but no changes in tryptase, no signs and symptoms of anaphylaxis, especially no hypotension. So the one thing that may be important to share here is that this patient had a history -- childhood history of repeated loss of consciousness, which was then followed up in childhood by EEG that showed pathology. Without further follow-up, so this was sort of lost and the patient didn't have these episodes moving forward. And it certainly didn't preclude him from being included in the study. But in talking to the neurologist who is now involved, this seems to be the most likely explanation for the event that happened. Patient is doing well, and we are monitoring this patient. So I think at this point, what we can say is not anaphylaxis, not a mast cell-driven response, possibly based on neurological precondition, idiosyncratic in nature.

Okay. That's super helpful. And then I guess for the Celldex team, I think you mentioned it, but just anything you're able to say on the ongoing CIndU study and IRRs there and whether severe adverse events happened?

So Sam, it's Margo. I mean as I said in the script, we've not seen anything like this in any other studies in the program.

Okay. And then just lastly, any patients in the study have any overlapping like allergic conditions? I know urticaria patients often do. And if so, any anecdotal evidence or response on those symptoms?

Sam, is this for me?

Sure.

I'll be happy to answer. Of course, as you can imagine, being a mast cell-an and allergist and urticariologist, we have a very close eye on any comorbidities that may benefit from this treatment. And indeed, we do have 1 patient in this trial who reported not only response of urticaria but also of a comorbid allergy, in fact, complete response of the allergic disease.

Got it. And what other condition was that, that was overlapping?

Well, allergic rhinoconjunctivitis, hay fever.

Next question comes from the Joseph Pantginis with H.C. Wainwright.

This is Emanuela on for Joe Pantginis. A few of my questions have been answered already, but can you discuss a little bit more the kinetic of the response you observe? Does a patient have the chance to evolve their -- to a response over time? And if not, what is the hypothesis for their resistance?

I can take it. Margo, please chime in if you have additional...

Go ahead, Marcus. Yes, go ahead.

Okay. So look, we were very, very happy to see how fast the response happens in most patients. And so by day 15, you have response in 5 of 10 -- complete response in 5 of 10 patients. And those patients who show partial response or even nonresponse at this time have a high chance of experiencing complete or partial response later on with 80% complete responders later on. What this means is that the most likely explanation for what happens is impact of this treatment on mast cells. Well, this is an anti kit -- an antibody kit is needed for mast cells to survive. And the most likely explanation is that we are deleting mast cells here, that they go into apoptosis because of the action of the antibody. And you cannot have a mast cell-driven disease if you don't have any mast cells, and the kinetics in most patients certainly speak to that. Why there are some patients who have maybe initial partial response and then come -- to become complete responders a little bit later on, we don't know. We need to match the clinical response with the monitoring of tryptase levels, also with the mast cell numbers in the skin that we are monitoring in these patients before and after treatment. And that will give us clarity on the exact MOA. It could be that we are doing something to the susceptibility of mast cells in the skin to get activated in addition to depriving them of a key survival factor. So those are the options that are on the table. Certainly, the deletion MOA makes a lot more sense based on the preclinical data based on the tryptase levels that we saw in the healthy volunteers and also those that we see here in the first group of patients analyzed for tryptase.

Got it. That's very helpful. And just -- could you tell a little bit more about the cholinergic urticaria? Is the pathogenic mechanism similar to chronic inducible urticaria? What is the rationale behind choosing that indication as well?

That's a very good question. Look, we think that all urticarias are must cell driven. mast cells are the key of the pathogenesis of all forms of urticaria, chronic spontaneous as well as chronic inducible. Cold urticaria, symptomatic dermographism and cholinergic urticaria are the most common ones. So that's one of the reasons why it makes sense to include them in a clinical trial. They're also very debilitating. cholinergic urticaria, you can imagine -- well, some of our patients even described it as sports allergy. When they get hot, when they start to sweat, and that could be, as I said, walking to the bus, climbing a flight of stairs, that will trigger whole body essentially whealing, hundreds, hundreds of wheals that appear within minutes and that remain there for minutes to a few hours, super, super itchy. This also happens when patients take a warm bath, go to the sauna, go to a warm room. When they go step on public transportation in the winter, it's cold outside, they have their coats on, they walk into a warm subway and this is the trigger for them to break out and have their hives. It's a horrible disease to have. And as you can imagine, it interferes with a lot of activities, certainly sports. These patients cannot do physical exercise but also many other activities, and they always need to be aware to not start to sweat. So to provide these patients with something that protects them from this is key. And so far, we don't have anything. Antihistamines in these patients even given higher than standard doses don't help most of them. And that's why the treatment needs is very high in these patients. In addition to this being one of the more common forms of chronic inducible urticaria, that makes for a very strong rationale. And we're happy that these patients will now benefit from inclusion in this trial.

Our next question comes from Kristen Kluska with Cantor Fitzgerald.

Congrats on these results. The first one, I wanted to ask about the cold U patients. Sounds like a lot of them reached a complete response quite early. So while this is just an interim update, how are you thinking about durability considering some of these patients have been observed past 6 weeks as well? And I know it's a single dose trial. So what are your initial thoughts there?

I'll be happy to go first. Company strategy is not mine, but from a mast cell and urticariologist point of view, this is very exciting. You have an early response that is most likely based on the lesion of mast cells. Now for mast cells to come back, it takes quite a while. They come from stem cells and progenitors that need to find their way to the skin and go from very immature progenitor cells to mature mast cells in order for them to then be ready to produce urticarial reactions again. And this, from a biological point of view, will take weeks to months. What this translates to is that this may be a therapy where interval treatment could help patients. This is what we've learned from this trial. We see early response, and we're monitoring patients for time to relapse. And if this is 3 months, well, what this will translate to is that patients can be with one treatment free of signs and symptoms for 3 months. So to have something in a very chronic disease -- don't forget, chronic inducible urticaria is of longer duration than chronic spontaneous out carrier and in the chronic spontaneous urticaria. And in chronic spontaneous urticaria, we're talking 5 to 7 years on average. And many patients have this for 10 years or longer. So we need treatment that can be given for a long time, and yet can be adapted to the need of the patients. So treatment that with its effect come soon and has a durable response is ideal for chronic inducible urticaria patients.

Great. And then as a follow-up, I know that Xolair isn't approved for these subset of patients, but there have been a few studies looking to collect the data. So could you share from a real-world setting with you and your colleagues, what you believe is the true complete response rate? And then again, I know you emphasized the onset of effect with CDX-0159. So how should we be thinking about those comparisons?

Thank you. That's a very good question. And in fact, there are very few randomized controlled trials with Xolair in chronic inducible urticaria. Two of them are from our team, one on cold urticaria and one on symptomatic dermographism and they're published. And at the time, we saw a marked reduction in thresholds, so that's good, 10-degree Celsius, for example, for the cold coal urticaria patients treated with 150 or 300 mg of Xolair. But we saw something that points to a mixed response, maybe a 2 distribution response where patients either had tremendous benefit and became complete responders or they had no benefit at all. Pointing to the fact -- or pointing to the possibility, I should say, that IgE, the IgE receptor and this pathway of mast cell activation is relevant in some but not relevant in others. Now here, we're going one step further. We're going to the mast cell. And if you delete the mast cells or silence it, then it doesn't really matter if you target one pathway, you target them all. It doesn't matter what activating pathway is relevant in these patients. And I think this is what explains the higher rate of responders that we saw here. Now mind you, these are early days. This is not a placebo-controlled trial. We'll be looking forward to seeing what 159 can do in a placebo-controlled setting. But certainly, this complete response in all patients treated says 2 things: First of all, we are right in saying that this is a mast cell-driven disease because we target mast cells. And second of all, we're not using an approach where we inhibit one pathway of activation. We're using an approach that inhibits all pathways of activation because we take away the responder cells of these different activating pathways.

Our next question comes from Yatin Suneja with Guggenheim Partners.

Great. Congrats on the results. Dr. Maurer, question for you. Can you maybe talk about the applicability of this drug across other indications? Based on the proof of concept and mechanism, what are some indications that could be pursued outside urticaria with this compound? And then I have a follow-up.

Yes. Yes, sure. That's an excellent question. Look, we think of mast cells and their role in disease as different groups of diseases. The true bona fide in mast cell-dependent diseases are urticaria, mastocytosis and, by definition, mast cell activation syndrome, with the type-1 allergies, food allergy, anaphylaxis coming close to being 100% mass cell dependent. So these diseases must respond to a treatment that targets mast cells. There's a second group, a very big group of diseases where mast cells are held to play a role. Now don't forget that mast cells are the most prone inflammatory cells of the human body. They are experts at producing inflammation. And virtually every form of chronic inflammation -- chronic inflammatory disease is linked to a mast cell signature, be it more numbers of mast, higher numbers of mast cells, elevated levels of mast cell mediators, sometimes linked to disease activity. So there's a lot of circumstantial evidence that mast cells are also involved in chronic inflammatory bowel disorders, in inflammatory disorders of the joint, of the airways. This needs to be explored after someone has looked at the true mast cell-driven diseases, which can be assumed to respond in a mast cell-targeted treatment.

Got it. The other question I have is on the safety and tolerability side. Can you maybe talk about your experience with other drugs that target the components of mast cell? How does the safety and tolerability profile change with repeat dosing? Because I understand in this study, it was just one dose. So maybe put in context what happens with Xolair. Does the safety and tolerability profile improves as patient gets familiar -- or the body gets familiarized with those agents? And what would you envision with the repeat dosing with this compound? Could the signals get amplified or maybe improved?

Those are very good questions, but we're -- the answer to those questions lies in the future. We know that Xolair is a very safe drug in asthma and probably even more so in urticaria. We know that this is also true for other -- well, for the few other mast cell-targeted treatments that have been looked at [indiscernible], no major signal here. So what we have to say is that right now, in this trial, we're treating patients once. We will need to treat them more than once in order for them to have the benefit with their chronic disease. Do we expect that the safety profile will change? No. If something were to happen because you're deleting mast cells or because you're using this approach, it would happen when you first do this. And this wasn't seen in the healthy adults. This wasn't seen in any of the patients that are in this clinical trial. So I don't expect that there will be long-term consequences, but I cannot tell you that for sure because we simply don't have the data yet.

Our next question is a follow-up from Sam Slutsky with LifeSci Capital.

In terms of the patients in CR, as noted on the slide, 5 of 8 were present at day 15, I guess, anything we can say on durability in terms of once they had CR, they maintained follow-up visits?

Sam, you were hard to understand on this one. You're asking about the durability of the response?

Of the CRs, yes. In terms of when they first had a CR since 5 of the 8 were present at day 15. I guess was it they maintained CR at subsequent visits?

Yes, they do.

Okay. And then in terms of the 2 patients not in CR, they're only at week 2. So I guess is there a reason to believe that we could see continued benefit there?

That's the reason, Sam, why we think they are not yet CRs. It's just too short. And we do see, in the other patients who have been on treatment longer or had been treated earlier that this can occur and does occur. So the expectation is, yes, that we're looking at them to become complete responders, too. But let's not speculate. In 4 weeks, we'll know more. And certainly at EAACI, we will bring an updated set on these patients as well.

Okay. And then just talking to safety report. I guess, anything to note on the transient decrease in hemoglobin or anything on white blood cell count?

Mast cells are not the only cells that express kit. So you kind of have to be ready for other kit expressing cells to also show a response. Personally, I think -- well, personally, I don't have -- I need to think. I know that this is not something that would have me worried to give this drug. I think it is interesting to see that there is something there, but it's mild and transient. So it's not a concern. I think this drug, in addition to helping us help patients with mast cell-driven diseases, will also show us something about other kit-positive populations. And so far, it seems to be mast cells that when you go for kit show the strongest effect, shown here as no more mast cell-driven signs and symptoms in these patients with chronic inducible urticaria.

Got it. And then just lastly, too, as you noted, the IRR for most patients is slight redness, itching, I guess on subsequent doses, patients probably won't have mast cells, so I guess the reason for that to go down hypothetically.

Yes, that's an excellent point, except for even in the patient who had this response, we don't think it was mast cell mediated. But in principle, you're absolutely right. If you time it right, then you're going into a system where mast cells are still gone or, let's say, not fully functional, so that would reduce any risk, if there were any, even further.

And I'm showing no further questions at this time. I'd like to turn the call back over to Anthony Marucci for any closing remarks.

Thank you, operator. We are highly encouraged by the initial data from the study, including the 80% complete response rate in patients with substantial disease burden, refractory to antihistamines. As Margo said, we are still enrolling the following patients out to 12 weeks and to plan to report a complete data set this summer. In the meantime, we are pleased to be expanding this study to include a cohort of cholinergic urticaria patients. And in parallel, our Phase I study in chronic spontaneous urticaria is actively enrolling patients and is on track for results by year-end. We also plan to initiate a third clinical study in prurigo nodularis during the fourth quarter. And as Margo mentioned, we expect to introduce the subcu formulation into clinical studies in the third quarter. 2021 is shaping up to be a big year for CDX-0159, and we appreciate your continued interest and support of Celldex. We look forward to updating you further in the coming months. Thank you all for joining us this morning. And operator, you may now close the call.

Ladies and gentlemen, this concludes today's conference call. Thank you for participating. You may now disconnect.