Welcome to the DBV Technologies three-year results from the Open-Label Extension to EPITOPE Phase III trial conference call. All participants will be in a listen-only mode. Should you need assistance, please signal a conference specialist by pressing the star key followed by zero. After today's presentation, there will be an opportunity to ask questions. To ask a question, you may press star, then one on your telephone keypad. To withdraw your question, please press star, then two. Please note this event is being recorded. I would now like to turn the conference over to Katie Matthews, Investor Relations. Please go ahead.
Thank you. This afternoon, DBV Technologies issued a press release announcing year three results from our ongoing Open-Label Extension to the EPITOPE Phase III trial, DBV's prior Phase III efficacy study which evaluated Viaskin Peanut in toddlers ages one to three years old, as well as data from EPITOPE supporting a potential labeling approach for Viaskin Peanut. This press release is available in the press releases section of the DBV Technologies website.
Before we begin, please note that today's call may include a number of forward-looking statements, including but not limited to comments regarding our clinical and regulatory development plans, the design of our anticipated clinical trials, the timing and results of interactions with regulatory agencies, our plans and expectations with respect to our clinical trials, plans with respect to submission of BLAs to FDA, expectations with respect to any action or regulatory pathways, including an accelerated approval pathway, and the ability of any of our product candidates, if approved, to improve the lives of patients with food allergies. These forward-looking statements are based on assumptions that are subject to risks and uncertainties that could cause the company's actual results to differ significantly from those suggested by these statements. Given these risks and uncertainties, you should not place undue reliance on these forward-looking statements.
Please refer to the company's filings with the SEC and the French AMF for information concerning risk factors that could cause a company's actual results to differ materially from expectations, including any forward-looking statements made on this call. Except as required by law, the company disclaims any obligation to publicly update or revise any forward-looking statements to account for or reflect events or circumstances that occur after this call. Joining me on the call today are Daniel Tassé, Chief Executive Officer of DBV, and Dr. Pharis Mohideen, our Chief Medical Officer. I will now pass the call over to Daniel. Daniel?
Katie, thank you, and thank you all for joining us on this call this evening. Before diving into the details of today's press release, let's provide a quick recap on the clinical development pathway for Viaskin Peanut in toddlers and in children. Recall that we have two Viaskin Peanut patches: the original square patch for toddlers, ages one to three years old, and the modified, larger circular patch for children, ages four to seven years old. Each patch is regarded as a separate product candidate by the FDA and hence follows its own regulatory pathway, meaning that we plan to submit two BLAs, one for each age group. You will recall from our last conference call last month that we believe we have clear and straightforward regulatory pathways for Viaskin Peanut patch with the FDA.
To recap, for our toddlers program using the original square patch, we plan to submit a BLA under the accelerated approval pathway, which we anticipate taking place in the second half of 2026. At that time, we will have completed two Phase III studies: EPITOPE, the Phase III efficacy and safety study, which has already been completed, reported, and the results were published last year, I think in 2023, in the New England Journal of Medicine, and the COMFORT Toddlers Six-Month Supplemental Safety Study, which is on track to be initiated in Q2 of 2025. A post-market and confirmatory study will be initiated at the time of BLA submission, as agreed to with the agency.
Now, similarly, for a children program using the modified circular patch, the BLA will consist of two core Phase III studies: the ongoing and fully enrolled VITESSE trial in children with top-line data expected in Q4 of this year. That data will be coupled with a six-month supplemental safety study, which is called or will be called COMFORT Children, which is also on track to be initiated in Q2 of this year. Like toddlers, we anticipate a BLA for our children program in the second half of 2026. Now, we will focus on our toddlers program for today's update call. Now, I'd like to take a moment to remind everyone on the call that Viaskin Peanut is a novel technology that has no analogues on the market or in development. And remember also that Viaskin Peanut has Breakthrough Designation .
Over the last year, we have worked closely with the FDA to build a mutual understanding of EPIT and the Viaskin platform that we hope will benefit all our future Viaskin programs and, most importantly, benefit patients. As you know, unlike other immunotherapies approved or in development, the Viaskin platform, Viaskin Peanut as a product, targets the upper layer of the skin and relies on specialized antigen-presenting cells within the epidermis. These cells are known as Langerhans cells. Langerhans cells pick up and process allergens and migrate to local lymph nodes to progressively induce tolerance and thus a benefit for the child.
Not surprisingly, due to the novelty of the Viaskin platform, we have had to work together with the agency to pave the way, not just for the potential approval of Viaskin Peanut, but also for our other Viaskin programs in development beyond food allergy and other immunological disorders. This also bodes well then for other novel therapies in development. And again, because of the novelty of our product, there are some valid questions from caregivers and physicians that we will need to answer in preparation for the launch of Viaskin Peanut if approved. For instance, how is Viaskin Peanut going to be used if approved? And two key questions. What are we going to tell prescribers? What will the label say to prescribers and caregivers on how to use the product? And what will the label look like? Again, it's a unique product that has no analog.
And secondly, and importantly, what is the likely duration of treatment of Viaskin Peanut? What are the benefits that accrue with a longer treatment? Hence, trying to further understand the everyday use of a novel product like Viaskin Peanut is essential. And today, I am, we are delighted to announce that we have two additional data sets which we strongly believe will help address these questions. So yes, we have several positive highlights to share with you today. First, I'm delighted to announce positive results from the ongoing Open-Label Extension of the EPITOPE Phase III trial, DBV's prior efficacy study which evaluated Viaskin Peanut in toddlers ages one to three. As you saw in today's press release, these data would show continued improvement in treatment benefit of Viaskin Peanut after 36 months of total treatment.
We're accepted as a poster at this year's Eastern Allergy Conference, which kicks off tomorrow, January 9th, and runs through Sunday the 12th in Palm Beach, Florida, and it will be presented by Dr. Matthew Greenhawt of Children's Hospital Colorado. It is well understood in the allergy community that the benefits of the immunotherapy can be achieved with long-term treatment, which is why we are very committed to these open-label extensions. They're critical, and they're important for us to best capture and understand the use in real life in the long term of our product. The data help further characterize clinical response and help us form hypotheses on achieving the best long-term outcome for patients.
I'm absolutely thrilled to share with you the results of our open-label extension study in toddlers for Viaskin Peanut, which shows further continued improvement through 36 months of treatment across all efficacy parameters. I'll let Pharis share the detailed data, but suffice it to say that they are consistent with the efficacy and safety seen after long treatment periods in our prior studies. More patients respond, and overall, they respond better. We also recall that we have observed statistically significant improvements in efficacy measures after two years of therapy, and that was presented last year, or at least in November of 2023, at the College.
There are several highlights of this new data set in toddlers, but what's particularly striking to me is that among subjects on active treatment EPITOPE who continued this Open-Label Extension study after three years of total treatment of Viaskin Peanut, almost 70%, seven in 10, of subjects completed the Oral Food Challenge at a cumulative equivalent of 12-14 peanut kernels without triggering stopping symptoms. Way beyond what could be anticipated during accidental exposure, which is often as little as a fraction of a peanut kernel. In fact, the median dose for patients coming onto our studies is exactly that, a fraction of a peanut kernel, and something that has the potential to be rather transformative to the life of these families. Another key finding from our Open-Label Extension study was a consistent safety and tolerability profile in the toddlers age group, as Pharis will elaborate on shortly.
But in a nutshell, no new safety findings were observed, and local treatment-related events such as skin reactions, which are the most commonly reported adverse events with Viaskin Peanut, further improved after three years of total treatment with Viaskin Peanut. So efficacy improves, tolerability improves. The second part of our call today will focus on daily patch wear time data from EPITOPE that is supportive of our proposed labeling strategy that we've offered FDA. You may recall that we proposed the strategy to the FDA in June of last year, and this was a pivotal catalyst in our discussions with the agency to gain accelerated approval status of the Viaskin Peanut program in toddlers.
As I have articulated previously, providing prescribers and parents with clear data-driven instructions in the Viaskin Peanut patch label on how to manage the unavoidable, and you'll see the data from Pharis, the unavoidable variability in daily patch wear time and its potential impact on treatment effectiveness is of paramount interest to us here at DBV. If Viaskin Peanut is approved, a valid question will of course be asked by some parents. Can my child benefit from Viaskin Peanut therapy if he or she cannot wear the patch for 24 hours every day? Now, because Viaskin Peanut is a novel therapy, it understandably took some time to come to alignment with the agency regarding how to collect the wear time data from patients to help answer that question, to agree on how to analyze those data, and how to translate those results into meaningful guidance for both allergists and families.
Today, we will share with you those data that form the basis of our labeling approach that was proposed to the FDA. These informed data will be shared also at the Eastern Allergy Conference as part of a poster presentation by Dr. Edwin Kim. As will become even more evident to you when I hand over to Pharis momentarily, we have made significant strides in our Viaskin Peanut toddler development program for the last year. We are excited about its potential to help toddlers with peanut allergies, and I am inviting Pharis to provide you even more granularity. Pharis?
Thank you, Daniel. Let's start with the two-year results from our EPITOPE Open-Label Extension, or OLE, study, which provides data on 36 months of treatment for the subjects initially randomized to Viaskin Peanut in EPITOPE.
But first, let me take a moment to revisit the Viaskin Peanut results from the initial 12 months of treatment in EPITOPE. This was the Phase III pivotal efficacy and safety study conducted in toddlers ages one to three years that used the original square patch. This will help to put the 36-month results into better context. The initial 12-month study design is shown on the left-hand side of the slide, with the primary endpoint shown on the right. As we previously announced, the FDA confirmed that the EPITOPE study met the pre-specified criteria for success for the primary endpoint, with the lower bound of the 95% confidence interval being well above the 15% mark at 22.4%. 67% of subjects in the Viaskin Peanut treatment arm met the responder criteria. Here we see the study design schematic for the Open-Label Extension.
Subjects randomized to Viaskin Peanut at the start of EPITOPE could receive an additional 24 months of treatment for a total of 36 months of treatment. That's the data that I'll be presenting in the next few slides. Subjects originally randomized to placebo were eligible to cross over to Viaskin Peanut in the Open-Label Extension and receive treatment for 36 months as well. Those subjects will complete 36 months of treatment later this year, so we won't be presenting that data today. It's important to note that caregivers, as well as the study investigators, remained blinded to the subjects' randomized treatment prior to deciding to enter the Open-Label Extension. So there was minimal bias in terms of which subjects decided to enter the extension. As a reminder, 175 out of 244 subjects treated with Viaskin Peanut for one year in EPITOPE opted to enter the Open-Label Extension.
Out of those 175 subjects, 166, or 95%, underwent the double-blind placebo-controlled food challenge at month 24, and 149, or 85%, underwent the double-blind placebo-controlled food challenge at month 36. That's a remarkably high percentage of subjects retained in a study for three years. Most of the dropouts were due to withdrawal of consent, unrelated to any safety issues. We believe this underscores the simplicity, ease of use, and overall tolerability of Viaskin Peanut. These are the efficacy data at 12, 24, and 36 months for the group originally randomized to Viaskin Peanut in the EPITOPE study. Let's start with the percentage able to achieve an eliciting dose of at least 1,000 milligrams. After a relatively short 12-month treatment period, about two-thirds of subjects achieved this level. The percentage increased to about 80% in the second year and was sustained in the third year.
If we move to a more robust endpoint, an ED of greater than or equal to 2,000 milligrams, we see a really nice stepwise increase in years two and three, with more than 70% of subjects achieving that efficacy level. What's most impressive to me is the data set on the far right. About 70% of subjects were able to consume the entire food challenge material, equivalent to about 12-14 peanut kernels without meeting stopping criteria. Recall that the median eliciting dose at baseline was 100 milligrams, or about one-third of a peanut kernel. This change represents a tremendous amount of protection against accidental peanut consumption.
These year-on-year improvements in efficacy are not at all surprising, as this is entirely consistent with allergen immunotherapy, and it only reinforces the safety profile and tolerability of Viaskin Peanut to maintain subjects on treatment for this long, which leads me to the next slide: safety and tolerability. No new safety signals were observed, and findings were generally similar to what was reported during the second year of treatment with Viaskin Peanut. Overall, safety and tolerability with Viaskin Peanut continues to be consistent in our toddler data as it was relative to our subjects four years and older. As you can see, the most commonly reported adverse events, mild local application site reactions, continued to decrease in frequency during the third year of treatment. No treatment-related anaphylaxis or treatment-related epinephrine use was reported in either the second or third years of treatment. Overall, Viaskin Peanut represents a very well-tolerated product.
To summarize, the results demonstrate continued improvements in treatment benefit out to three years with no new or worsening safety findings and actually a decrease in the frequency of local application site skin reactions. There was also a very high retention rate during the course of three years. We have always placed tremendous value in generating longer-term treatment data, and we strongly believe these data provide further evidence of how Viaskin Peanut will perform if approved. Let's continue with our toddler one to three-year-old data, but in the context of how prescribers might optimize Viaskin Peanut use in their practice if approved. Last year, in our July press release, we discussed the labeling proposal that we submitted to the FDA in June 2024.
This focused on patch wear time experience and how average daily wear time during the first 90 days on treatment could be used to inform the label if approved. Specifically, this approach was used to answer the FDA's question: What should prescribers tell caregivers if they have variability in day-to-day wear time? We believe the post-hoc analysis submitted to the FDA was a significant turning point in their understanding of the difference between average daily wear time, which is highly correlated with treatment response, versus patch detachments, which does not correlate well with treatment response. Recall that the intersection of patch adhesion and efficacy was at the heart of the 2020 Complete Response Letter, so it was imperative that we gain clarity and alignment with the FDA on this critical aspect of the Viaskin platform. Let me share this data with you now.
These are data from the 244 subjects randomized to Viaskin Peanut in the EPITOPE one- to three-year-old toddler study. You can clearly see two distinct lines: a blue line and a red line. The solid lines are the means of the average daily wear times. The dashed lines, which are a bit more difficult to see, are the medians of the average daily wear times. The wider shaded blue and pink areas are the interquartile ranges for each group of low and high average daily wear times. Patch wear time was recorded daily by caregivers and was averaged over the 12-month study for each participant, with a protocol-specified targeted daily wear time of 24 plus or minus 4 hours. Let me highlight the main points of these data.
First, the group in blue with very low day-to-day variability in wear time has most days being greater than 20 hours and represents about 70% of subjects, while the group in red has high day-to-day variability in wear time. However, both subgroups have essentially identical baseline characteristics as far as markers of atopic disease severity, such as peanut-specific IgE, SCORAD scores which are used to score atopic dermatitis, skin prick test, and baseline eliciting dose. All these subjects appear to be similar from an atopic disease standpoint. I'll get to why this is really important in the next few slides. Secondly, the average daily wear time observed during the first 90 days is highly predictive of the average daily wear time over the 12-month treatment period, with a correlation coefficient or R-value of 0.81.
So what is observed in the first 90 days is highly likely to be what will be observed for the rest of the year. Now, this is where it gets really interesting. This graph has the same assessment parameters as the previous slide. In light blue, you see the 167 subjects with low day-to-day variability in wear time, the same data I presented in the previous slide. But this time, we have the subjects randomized to placebo in the black data points. The two groups, Viaskin Peanut low day-to-day variability in wear time and placebo, have virtually identical average daily wear time experiences. So what do these data tell us? Well, they demonstrate that the Viaskin Peanut subjects with low day-to-day variability in wear time have a patch wear time experience that is nearly identical to wearing a placebo patch.
That is, they have seemingly little to no issues with the application of the antigen peanut protein, leading to local immune-mediated reactions that may have a negative impact on daily wear time. Another way to look at this is that any differences in patch wear time experience are driven by individual subject immune-mediated physiology. Simply put, the data shows that it's not the mechanical characteristics of the patch. It's the intersubject variability that drives differences in patch wear time experience. As I mentioned previously, the baseline characteristics of the low day-to-day variability group and the high day-to-day variability group were similar, as presented in this table. However, there's one very critical parameter where there are differences, and that's in the occurrence of scratching leading to patch detachments.
The high day-to-day variability group had more than doubled the rate of scratching leading to detachments, even though the frequency and the severity of local application site reactions was the same between the two groups, as was the use of topical corticosteroids. Thus, we conclude that subjects with high day-to-day variability in wear time just have a more intensive itchiness response to the locally applied antigen. Again, this has absolutely nothing to do with the mechanics of the patch. There's no way to predict this using biomarkers or other parameters at baseline. But that's why the average daily wear time during the first 90 days on treatment becomes such a powerful tool in the hands of prescribers of Viaskin Peanut if approved. Let me now pivot to the efficacy data, which is largely why all of this really matters.
In the first 12 months of treatment, subjects with low day-to-day variability and higher average daily wear times have a more robust efficacy response. The percentage of subjects meeting the EPITOPE primary endpoint jumps to nearly 76% relative to 67% for the overall Viaskin treatment group and much higher relative to the high day-to-day variability group. There's also a striking difference between the groups when assessing on ED greater than or equal to 1,000 milligrams. There's less of a difference when assessing on ED of greater than or equal to 2,000 milligrams. But remember, this is only 12-month data, and we have observed more robust responses in years two and three. Thus, the average daily wear time during the first 90 days on treatment correlates with a more robust treatment response and may serve as a marker to identify or optimize best responders to Viaskin Peanut if approved.
To put this into further context, most other allergen immunotherapies require multiple years on treatment to be able to know whether the treatment is really effective, but no way to predict eventual response. This is significant. Shared decision-making between the doctor, the child, and the parents is the norm in allergen immunotherapy. Treatment goals, impact on daily life, and treatment benefit expectations are at the very core of allergen immunotherapy decision-making. The data we present here fits perfectly with the very dialogue that we expect will take place for every child in every office. We have presented the overall safety during the first year of treatment in the New England Journal of Medicine for both Viaskin and placebo subjects. What we see on this slide is that there are some slight numerical imbalances between the low day-to-day variability group and the high day-to-day variability group for a few safety parameters.
These are very low occurrence rates to begin with. The largest differences appear to be in the discontinuations, which again suggests a tolerability difference between the two groups. Okay, let me summarize. The post-hoc data we presented here shows that if Viaskin Peanut is approved, prescribers can use the average daily wear time during the first 90 days to help guide the shared decision-making process with caregivers and decide whether their child is likely to be one of the roughly 70% of subjects with an optimal response to Viaskin Peanut. We believe this approach is very pragmatic and entirely consistent with the simplicity and ease of use that has always been a hallmark of Viaskin Peanut. At this point, I'll pass the call back to Daniel. Daniel.
Thanks, thank you. Nice job. Before opening the floor to your questions, I would like to take a moment to first express our excitement by the compelling data from our open label extension study, which we believe nicely complement the FDA results from EPITOPE and the first year of the open label extension study results, which were presented at American College of Allergy, Asthma, and Immunology meeting in November of 2023, and will soon be published as a manuscript. Simply put, we believe that these additional data show that Viaskin Peanut, if approved, offers a real treatment solution for this population with extremely high unmet need and, importantly, that multi-year treatment Viaskin Peanut has the potential to be transformative to the lives of peanut allergic toddlers if approved.
We also believe that the labeling approach that we've previously proposed is an effective way to quickly and efficiently identify those subjects who may have a more variable wear time experience, may not always get the full benefit of Viaskin Peanut, and this labeling strategy essentially opens the door to a conversation that always takes place anyway with the physician and caregiver and identifies ways to improve their daily wear time experience, get to or closer to an average daily wear time of 20 hours or more, consider this as a potentially unique advantage of Viaskin Peanut in something that has not been described before for other immunotherapies.
As Pharis has said, by a relatively short time, just three months in fact, patients and their families will be informed as to whether they are most likely to benefit fully from the treatment versus those that may need some intervention at least for the first year of treatment. We remain confident that Viaskin Peanut, if approved, has the potential to be a game changer, not only for children with peanut allergies but also for the broader food allergy community, which faces the daily challenges of living with peanut allergy. While the landscape has evolved with the approval of new treatments providing families with much-needed approved options, it's clear that more progress is still needed, especially in toddlers, where approved treatments may be more burdensome and not fit into the daily busy lifestyles of families or simply not preferred.
2025 will be a pivotal year for us here at DBV, marking the initiation of our two COMFORT studies in Q2, followed by anticipated top-line data from VITESSE for Phase III trial in four- to seven-year-olds in Q4 of this year. We are in full execution mode with exciting developments ahead as we work to bring Viaskin Peanut to patients and their families as swiftly as possible. I want to thank everyone on the phone and webcast for joining us today. Now, I ask Pharis and Virginie to join me for the Q&A.
First question comes from Jonathan Wolleben of JMP Securities.
Hey, good afternoon and congrats on the data. Pretty compelling stuff.
Thanks.
Questions? Wondering if you have any sense from data in older children or whether mechanistically when responses would plateau? Three years now is quite a long time, but I can't imagine that things will get better forever. But do you guys have any inkling what that could look like?
Yeah, I'll have Pharis answer that one. But you're right. Eventually, we start running out of headroom for improvement. That's sort of the beauty of it. But Pharis, from perspective here?
Yeah, I think this is more or less aligned with what we see with other allergen immunotherapies. The analog we use most often is Venom therapy, where you need three to five years to see maximum effect. Obviously, we stopped at three years. For some of the parameters, John, you can see it sort of plateaus a bit between year two and three, depending on which efficacy parameter you're looking at. The interesting one to me was the nearly 70% that completed the food challenge without meeting stopping criteria, because that one had the biggest jumps between first year, second year, and third year. So had there been a fourth year or fifth year, it would be interesting to see if that gets even closer to 100%.
Obviously, we don't have that data, but if we follow other allergen immunotherapies, there would be an expected plateau somewhere out there, exactly where, whether it's three, four, five, or six years, we don't really know yet. We don't have the data.
Got it. And safety looks to be improving. But I noticed you guys gave treatment-related anaphylaxis. Wondering if you could comment at all on unrelated anaphylaxis and unrelated epinephrine use in the context of an accidental exposure?
Yeah, for those, we strictly look at peanut accidental exposures. Obviously, we collect all of that data, whether it's peanut or milk, or, as you know, these children have multiple food allergies. The non-treatment-related looks like it's been in the past also. We don't see huge jumps or risk-taking behavior or anything like that. It's very consistent with the longer-term data that we've seen in the older patients also.
Okay, and then maybe last one from me, and I'll jump back in the queue. I noticed in the release that the Label In, Label Out , which I think will be tremendously helpful in the real world, you started that 90-day counter after the first month, and I was wondering if you could walk through a little bit about the rationale for that and what that actually will look like.
Oh, okay.
Important question, Sir. Yeah, so in the first 28 days, we have the up-titration where they don't have the full days' use. And so it didn't make a lot of sense to pull that in where you're doing two, four, six, or I'm sorry, two, four, eight, 12 hours. You would not get an accurate presentation of the average daily wear time once they get up to four days' wear time. That was all, John. So it's really the last 60 days and the first 90 days.
Makes perfect sense. All right. Thanks, guys.
Yep.
Again, if you have a question, please press star, then one. And our next question comes from Jonathan Wolleben, JMP Securities.
I'll take advantage of the time. How did you determine 20 hours for the cutoff? And did you look at that as a continuous parameter as well?
Yeah, we did a number actually, John, with 20.3. So we rounded it down to 20 as we did the optimization function of clinical response and wear time. Obviously, there's a number of places we could pull the cursor, but the optimization function doesn't look at 20.3 hours to be quite specific about it. So 20 hours became the commonsensical translation of that and what would be an eventual label. Am I correct? First was 20.3, right?
Yeah, that's correct. That's correct. Yeah.
Does that answer your question, Jonathan?
Yes. And then the last one for me, if you could just provide an update on kind of activities necessary to get a couple of trials up and running on schedule?
Yeah. So basically, we're at the point where we're looking at serial selections, site selections. Most of that is already done. We have a really good feel for our sites and who wants to participate, and obviously, there's always some new sites coming in, things like that. It's nothing unusual. Typical study startup activities. We're in a good place, and we'll just pull the trigger as the timelines have been laid out.
All right. Thanks again.
Sure.
Okay, John.
This concludes our question-and-answer session. I would like to turn the conference back over to Mr. Daniel Tassé for any closing remarks.
Thank you, Operator. So in closing, the year two results for our ongoing open label extension study that we announced earlier today and we presented at the upcoming Eastern Allergy Conference give us great optimism that the potential of this treatment is approved to potentially improve the lives of peanut allergy toddlers and their families and their caregivers. We look forward to bringing this open label extension study to its conclusion later this year while in parallel initiating COMFORT Toddlers in Q2. We will also keep you abreast of our developments. We thank you for your time, and we will wish you a very good evening.
The conference has now concluded. Thank you for attending today's presentation. You may now disconnect.