DBV Technologies SA at Jefferies Healthcare Conference

DBV.PA - DBV Technologies SA
DBV Technologies SA at Jefferies Healthcare Conference
Jun 07, 2016 / 07:30PM GMT 

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Corporate Participants
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   *  Charles Ruban
      DBV Technologies SA - Chief Commercial Officer

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Conference Call Participants
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   *  Eun Yang
      Jefferies LLC - Analyst

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Presentation
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 Eun Yang,  Jefferies LLC - Analyst   [1]
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 Good afternoon. This is Eun Yang, a biotech analyst with the Jefferies. Our next presenting company is DBV Technologies. Presenting from DBV is Charles Ruban, our Chief Commercial Officer. Charles?



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 Charles Ruban,  DBV Technologies SA - Chief Commercial Officer   [2]
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 Thank you very much. Welcome to this session. My name is Charles Ruban, I'm the Chief Commercial Officer of the Company, also President of the North American operations that we recently opened. I'm really happy to have such a crowded team, and to actually present this innovation, which is the epicutaneous immunotherapy. So if this works, well, this is a disclaimer.

 So, at a glance, what DBV is and what we are actually trying to achieve here is to be the specialist, the worldwide specialist of food allergy. We are the creator of a technique and a method that is called epicutaneous immunotherapy which is basically delivering an allergen through the skin and really leveraging the immune competencies of the skin. It's a novel pathway for performing allergy immunotherapy. It offers a non-invasive and a very well-tolerated treatment and it is especially very well suited for pediatric patients as you will see now in our clinical trial program.

 We are focusing on food allergy as I was saying at the beginning. We have established strong proof of concept trials that have been repeated over and over. We have a lead product in peanut allergy today, followed by milk development and egg, we have a food portfolio. Especially on the peanut allergy which is really our first product, the clinical data you will see show that we always repeat meeting the efficacy end point, as well as the tolerability and the safety profile, which is really very positive.

 We've been granted by the FDA breakthrough therapy status. We are in Phase III, the trial is actually very, very active initiating Q4 2015 and we are really on track, right on track to be the first product registered in this indication. Beyond food allergies, this is a broad platform, we are exploring other areas such as vaccines, such as IBD, autoimmune and inflammatory diseases. And the global commercial strategy of the Company is to market, to develop, register and market the product by ourselves.

 This is our pipeline. You will see at the very top the Viaskin Peanut and the Viaskin Milk program, very active, but egg will be coming soon. On allergic diseases, we also have a clinical trial in EoE Eosinophilic Esophagitis that is actually an investigator-sponsored trial conducted by Jonathan Spergel at The Children Hospital of Philadelphia. And we have also a vaccine development in pertussis.

 For those who don't know much about food allergy which is rare actually because it's a very prevalent disease, it's a high unmedical need, the prevalence is increasing extremely strongly. We are talking about one or two kids in a classroom, that's usually what the FARE, which is sort of major patient association is mentioning. The most prevalent allergy are peanut and milk, and today the avoidance is the rule. So this patient only have avoidance and [anaphylaxis] to actually protect themselves against any accident that could arise. The objective for those patient is not obviously to eat peanut. They usually hate peanut, they don't like it at all, but they like to be protected against active mental exposure to peanut. That is to say protecting the trances that may appear in food at any kind of eating occasions.

 So the need is actually first to protect this patient against this accidental exposure but to do that in a very safe and convenient manner. And so far, you'll see that if you look at the history of development of this field, safety and compliance have been barriers to development of this drug. I mean, starting with the first of continued trial that is to say injecting the allergen to the skin leading to death actually in clinical trial. Oral immunotherapy which was also (inaudible) has not been brought to the market because of its safety profile and here the method that we are actually offering really offers a new route of administration of the allergen that offers an excellent safety and excellent compliance as well as a very good efficacy.

 So this is couple of slides on really mechanism of vaccine from very simple source. I don't want to bother you too much with a lot of science, but here you basically have a cross-section of the skin and here the allergen has been labeled with a fluorescent marker and you'll see that actually the skin barrier is actually very active, the allergen doesn't go through the skin, except that you have very tiny cells that I call Langerhans cells that are actually able to go up in the epidermis and capture this allergen. They -- those cells we're actually we're draining to the lymph nodes and initiate the differentiation process that actually they would go and contact with the other T-cells, generating a specific subset of Treg cells and rebalancing globally the immune system. And what is nice about it is not only that we are actually able to activate those Langerhans cells and generating those Tregs but also the fact that the antigen doesn't go through the skin, not to going into the systemic -- to have a systemic exposure and then preventing any kind of systemic reaction that we actually call anaphylaxis and which are actually very problematic.

 This is the patch. Unfortunately, I don't have patch but it's this slide basically, it's very small, very I would say, sleek, very simple. It's not a transcutaneous batch, it's an epicutaneous batch. Epicutaneous means that actually we activate the various phase of the skin and the allergen is not meant to go through the skin but to remain at the surface of the skin. And the way we do it is to this very elegant patch that actually we load an allergen, tiny amounts of an allergen on the surface of this platinum-coated patch.

 The way we do it is that we do that through a technique that is called the electrostat, the technique that come from the semiconductor industry. So with the de-allergenic strike go through an electric field, 20,000 watts in order to create an electrostatic bond between the allergen and the surface of the membrane. And once you open the patch, you put it on the skin, your natural perspiration would actually hydrate the condensation chamber, and dissolve and solubilize the allergen within water and make it available for the epidermis. Okay, then the Langerhans cell would be actually able to capture this and initiate the desensitization processes. So this is done on intact skin. So, you don't need to strip the skin, you don't need to prepare the skin, just do that on intact clean skin.

 The third thing we thought about is to make something simple, because we all know that actually complex treatment might be interesting to study in clinical development but once in real life they become extremely tough actually to implement and we know that dropout, absence of compliance really comes from complexity of treatments. That's exactly what we call the difference within efficacy and efficiency and this is actually an efficient treatment. Why, because it's a one dose product, it's self-applied on the skin. There is no titration and it can be seen. So that's actually very interesting as compliance on the compliance standpoint. So the kids would basically will not be able to hide any kind of product under the bed because actually the mother could see that the (inaudible) patches on and you'll see we have outstanding data as far as dropouts and compliance are concerned. It's safe, it's well tolerated and it's totally owned. I mean, the design of the patch is wholly owned by DBV.

 This is a snapshot of our clinical development for peanut allergy. It is the most comprehensive single development ever conducted in peanut allergy. The blue clinical trial that you see are really totally monitored and controlled by DBV. We've done the phase I, we are, we've had through the day of out of the Phase II, we are now in Phase III and moving forward very quickly. And this clinical development has been agreed upon with FDA and EMA. We've been granted with the fast track and breakthrough therapy status by the FDA and I would say the design of this trial, the clinical end point, any kind of clinical question have been solved before moving into Phase III.

 We have the chance to have very fruitful academic collaboration to start with the French Hospital Group on the left hand side which is the Arachild data which showed very promising elements, and the CoFAR data, which says the CoFAR, it's a consortium of food allergy research, it's a group of five center of expertise here in the US. It's NIH funded trial and actually they've released their clinical data on all products without any kind of contribution from DBV, except that providing the basically the patch and they basically replicate exactly the same data, exactly the same efficacy and safety data than the one we've had in our Phase II.

 So this is the design of our Phase II, it is called VIPES. So VIPES, what you'll VIPES in the first year of the trial and the two additional years of the trial are called OLFUS-VIPES. OLFUS is an open label follow up study. So as you see, it's a three-year treatment, and what is specific around this kind of trial is that actually you evaluate the desensitization of this patient by performing food challenges.

 So a food challenge is a very cumbersome very heavy procedure through which you basically expose the patient to increasing those peanuts at one point in time, it actually can last between two hours to five hours, it's a two day procedure because it's a blended procedure. Day one, you have (inaudible) day two, you have the placebo and thanks to this method that you need to be very reproducible, you are able to actually follow the level of desensitization that is to say an increase of doze the patient is able to inject to reduce patient of food challenge at the baseline. You see the end zero at the very beginning. And they are food challenged, 12 months after and we basically see an increase of desensitization through this method.

 So in this trial, basically we do evaluate three dosage against placebo. What we call a responder is a patient who is able to either reach a 1 gram, so 1 gram of peanut protein, it's a huge amount. Its four peanuts. So, for you and I, it's nothing but for those patient, its tremendous amount, or those patient are basically able to multiply by ten their initial dose, the initial dose they are reacting to, that's the end point for that trial. Once they have been treated for one year, all the patient crossover to the 250 microgram dose and they are challenged again, one year after at month 24 and we also have the data for this trial and we will be expecting the data for the [three year month 36] in October this year.

 This is the distribution of our patient at baseline. So you'll see a high diversity of facilitating dose. On the left-hand side of this slide, you will see very sensitive patient reacting to a dose as minimal as 300 as 1 milligram peanut protein. That is to say, a 300th of a peanut. It's hardly visible amount of peanut. They would have reaction, they would have an epilepsis which such kind of dose. And on the right-hand side, you will see less reactive patient that have still very strong reaction. Those patient are actually representative of the peanut allergic patient population. The study was built, was stratified, that is to say according to the age, children on the one hand and adolescent and adults on the other end. And you see that the average, I would say, the median value for reactive dose for children for instance is 30 milligram, it's a tenth of a peanut. So, those patients react to very low dose of peanut.

 First and foremost, compliance, really compliance is really necessary to really achieve good trial result and especially in real life and here you see that really the dropout related to the product is actually extremely low, less than 1% globally in the trial. And you have more than 97% compliance rate, which is extremely rare. In any kind of particular area but especially here in this area within the semi chronic treatment reaching a 97% compliance is extremely rare and very positive. And this is due to actually the safety profile of the drug.

 So, globally, the safety is excellent. You don't have any assay, you don't have any systemic reaction leading to interruption of the treatment. If you don't have any assay related to the product, you don't have any epinephrine injection which is a rescue treatment for that kind of disease. And the most frequent related AE are mainly local reaction at the side of application of the patch. So what you would get is some redness, some itching, some swelling at the side of application of the patch that we actually want so that I think it's really very common. I would say more than 90% of our patient basically experience that kind of reaction and those reactions tend to fade when the treatment duration expands.

 Primary endpoint was met in this trial leading to having 50% of patients responding after one year of treatment only and more interestingly in the six to eleven years old segments we basically have a better response rate and really still reaching statistical significance. You'll see that we also have a dodge effect in this clinical trial, very nice effects showing that actually the 250-microgram leads to an increase of those, the mean increase of reactive dose of more than 1,000 milligram peanut protein which is actually enormous as compared to placebo for which the change in the cumulative reactive dose doesn't change that much.

 And it is very well and nicely tolerated to immune changes. So on the left hand side, and sorry for the small gaps here, you have the IgE so the IgE basically represents the antibody against peanuts. So what we expect, as in the immune text book is actually an increase after three months of exposure to the treatment and then a decrease back to baseline value, which is exactly what we see in this trial, whereas on the right hand side, you have a constant increase of IgG4 with are more the protecting Igene immunoglobulins and this increase is actually linked to the dose and the highest increase that you have here is the one related to the 250-microgram.

 Then all these patients basically roll over into office on the open label study in the 250-microgram. So the rollover rate is rather significant and especially for children, again the safety of the trial is really accident, no drug related use of epinephrine, no SAE related to that in peanuts and the compliance is really maintained at a very, very high level. And if you look at the clinical efficacy, it is enhanced. Actually, we're basically moving from 60% plus of efficacy up to 80% of response after a year or two. And you see also on the right hand side of this slide that the cumulative reactive dose the patient are able to inject during the [future] has increased actually significantly to, showing that an extended duration of treatment is actually beneficial to those patients.

 If you look at the immune markers, again so on the left, the IgE and then the IgE now come back below the baseline value. So you remember they well had baseline value up to one year and then after two years, they are 40% below the baseline value showing an increased efficacy of the drug whereas the IgG4 basically are kept stable at a very high level at these for two additional years.

 Interestingly enough, in parallel to our development CoFAR, this NIH sponsored trial was actually performed with the same kind of product, 250 microgram, 100 microgram against placebo and they basically during the last AAAAI, the last allergy congress in Los Angeles this year, unveiled those data. So basically the trial is extremely similar. We're talking about enrolling patients, up to 300 milligram dose. They are considered as responders if they reach 5 grams or if they meet the 10x criteria. So it's even more stringent criteria than the one we have in VIPES. And what they end up with is exactly similar to what we've seen.

 The study meets its primary endpoint and we have a better efficacy in 4 to 11 years old, the younger patient display better efficacy. A third of the patients were actually able to tolerate more than 1 gram of peanut protein, which is important. And on display here the elements of the immunoglobulins, that's exactly very similar, you have a strong increase of IgG4, whereas the IgE actually go back to baseline value.

 The compliance is the same. This 96% magic number is there again and we don't have any SAE or epinephrine related to the drug, really repeating all the key treatment characteristic of what we've seen in the Phase II trial. So really, all-in-all, the take home on clinical development, huge clinical development, 450 patient, five clinical trials, excellent safety, the efficacy has been demonstrated within our clinical development but also through the NIH. Extremely convenient, very well suited for our population but you'll see that actually this treatment is very well, it's even more designed to treat very young patients.

 This is the design of our Phase III. So the next trial that we are doing now that'll actually start enrolling in December this year. So it's a trial for 4 to 11 years old, back on our Phase II later. 340 patients that have been included, the recruitment is ongoing, it's going on actually very well. 250 microgram which is the highest tolerated dose in the previous trial and the most efficient one, primary endpoint calculated at one year and the design is globally the same as the one for the Phase II.

 What's next, what's up there, so this trial actually will be the basis of the submission of our BLA, the Biological License Application that we'll be doing at the FDA, but we also have -- we don't have the clinical development here, so we have additional clinical trials in preparation.

 The next season trial is going to be the one to three years old study because back on those excellent efficacy and safety data when discussing with regulatory agency, it came to us that actually designing a program (inaudible) was actually very beneficial to patients and actually the willingness to be treated from those very, very young patient was strong. Why, they're patching very well, design for that, safety is excellent, efficacy is great, the younger you go, the better the efficacy and there is a global consensus in the field today, especially back on the [lead trials], you might have heard about this (inaudible) reintroduction of peanuts basically leads to less allergy in the future that actually treating patients very young has a strong impact for the allergy disease. And today the Viaskin patch is the only treatment that really can do that.

 So everyone is extremely excited about this one to three years old trial and when we actually are visiting the centers but obviously we're not forgetting the adolescent and adults, especially adolescents for which actually we're designing today a product that is more potent, that is to say we're going to titrate up the product. We're thinking about higher dose but also larger patches to increase the bioavailability of the drug and to be able to treat those adolescents.

 Quickly, we have a milk development ongoing. So the idea is to same. We have done the safety path of the trial, presenting to the DSMB, the FDA gave the green light. We are now in the efficacy part of the trials. So it's a dose ranging trial from 150 microgram to 500 microgram against placebo. The study is unrolling right now. Also (inaudible) from centers. As always, we have so many patients willing to be treated by (inaudible) to pick up -- out of those hundred patient coming in, those 20 who will basically have the chance to be treated. So it's really very successful and very motivating for us. Nevertheless, its long -- including the session is long because we have to perform food challenges again as we do for peanut. And this we intend to complete the recruitment of this trial by H2, at the end of each H2 this year.

 Basically, this is all the other target for development in allergies and food allergies and allergic disease. I talked about that already. We are thinking about also the patch, about the patch to prevent the course of food allergy, exactly like the leap kind of trial and we have other applications in other diseases obviously.

 I think this is basically our news flow for this year. We have presented a series of elements during the last [quarter] in 2016, especially (inaudible). We have had especially the CoFAR data which have been available. The EAACI is the next European Congress the next weekend and we'll be happy to -- we have more than 10 scientific publication and communication here on biomarkers, on scientific data, but also on CMC actually, because actually we are actually preparing to get the product on the market and on the CMC and industrial patient actually do matter very significantly, we are thinking about the product which is biologics.

 And obviously, we intend to have those practices vaccine data available by year end or early next year as well as the next data point of our first of three year data should be available by October this year. I already mentioned the completion of the recruitment of those three trial by the end of the year. And I think I don't need to go through those slide.

 Thank you for your attention. Thank you very much.






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