Okay. Good morning, everyone. My name is Yatin Suneja, one of the Biotech Analysts here at Guggenheim. Welcome to our third annual Healthcare Innovation Conference. Our first presenting company is DBV. From the company, we have two executives here. We have the Chief Executive Officer, Daniel Tassé, and we also have Chief Commercialization Officer, Kevin Trapp. Daniel and Kevin, thank you so much for your time.
Thanks for having us.
Maybe, Daniel, why don't you make some opening comments? Since we have Kevin here as well, I will go into the pre-commercial launch preparation later. But why don't you make some opening comments, and I've prepared a little Q and A for you.
Sure. Oh, about the-
Just a general
the business, okay.
Yeah.
Sorry about that. DBV Technologies, company focusing on immunology, specifically the immune properties of the skin, which are quite powerful. The way we're exploiting it is through a unique patch technology, epicutaneous immunotherapy. Our platform is called VIASKIN. That's what we do, focusing on food allergy, pediatric population mostly, as there's highest unmet need. Our lead product is in peanut allergies, and we filed our first BLA in children four to seven in September.
Got it. This epicutaneous immunotherapy platform, can you just talk very briefly about it, what it is, why it is unique, and is it only for food allergy, or could you go in other area, or it has broad applicability?
It's not only for food allergy, since we're exploiting the fact that the human skin has shown to have rather remarkable immune properties. We think about it's a barrier to things outside. The skin plays a role recognizing whether those external agents are good or bad, and with that, triggers an immune response. The founders of the company found a way to work or exploit the immune properties of the skin by making sure that minuscule amount of allergen exposed to the skin, as long as the skin is intact and the allergen penetrates the first layer of the skin, so the technology is all about that, recruits an immune response to Langerhans cells. Langerhans cells, we have trillions of them. They recognize the antigen, and through that, distally, through mostly Treg-mediated response, desensitize the patient.
The technology is about re-educating the immune system as to not recognize that allergen as being dangerous. Yes, it's a platform. We start with food allergy. There's applications also to aeroallergens and other forms also of immunotherapy. But right now, our focus is first and foremost in food allergy. It's a really high unmet need for which there are very few treatment options.
Got it. What type of patient population you are going after? It seems like you have two strategies, right? Kids and toddlers. Could you just frame for us what are these opportunities, what you have seen in these two buckets of patients?
It's an important question. You look, we have the indication in toddlers, children one to three, indication in children age four to seven. That division was a matter of regulatory choice we've made in development a few years ago. The one to seven population, if you put the two indications side by side, we're targeting because it's the intersection of three things that matter very much. The age of diagnosis is typically between the age of one and four, making one to seven the population that's most ready to be treated given the diagnosis. It's also the age where the parents are the most concerned, so they obviously are most mobilized to do something. Lastly, and importantly, younger patients respond better to all forms of immunotherapy. They respond particularly well to our form of immunotherapy.
One to seven is a sweet spot of diagnosis, willingness to treat, and helpful biology.
Got it. In four to seven, could you maybe tell us what you have demonstrated so far, what level of efficacy you are seeing, and what are safety consideration, if any?
We have a study, pivotal trial that was in coordination with the agency, which walloped the primary endpoint on efficacy. Important to talk about this. These are three to five-year treatment. That's the norm in immunotherapy. The FDA has a primary endpoint showing sufficient desensitization at one year to satisfy the regulators. But to be clear, the second through fourth year of treatment are really important, so we have an OLE in our program here. We've shown 47% efficacy on active, 14% on placebo at one year. To be clear, that efficacy is really a big jump up in the dose of allergen necessary to trigger an allergy in these kids. The idea here is to pole vault to success.
You have many patients who might not have hit the primary endpoint at one year, but have a benefit, and we expect that to continue to years two, three, and four.
Got it. The BLA for four to seven has been filed.
Yes.
You took a little bit of time to file it because there was a lot of back and forth with the FDA. Could you maybe help us understand where exactly we are on that acceptance timeline? What do you expect after it gets accepted? What is the review timeframe, and how should we think about the FDA back and forth?
Thank you. We filed on September 28th, so if you add 60 days, September 29th, I am sorry, if you add 60 days, so that takes us to late November for the action date on file acceptance. The FDA has been very helpful, a very fruitful discussion that started in May, played throughout the summer, where the FDA wanted to make sure that the two most complex part of any BLA, and to be clear, this is a large BLA, moreover, a technology that has no analog, so we are exploiting essentially a read of the regulation for the first time, so that the CMC file and the way the biostats data was captured was structured to the way that was most satisfactory to the agency.
That has been the back and forth to land on what we believe is a BLA that not only has all the right data in it, but more importantly, structured in a way that is going to be most helpful to the FDA. I want to say one thing to be very clear. There is not a single piece of data in this discussion with the agency that we had to generate. Everything was there.
Got it.
How do we organize it was the point.
Packaging it is-
Packaging, traceability, and architecture. A lot of documents in the BLA have the parent, grandparent, and great-grandparent structure to it to make sure it was structured the right way.
This is a breakthrough product, so should we anticipate a priority review?
We have asked for priority review. We have breakthrough designation, so that was the ask of the agency.
Okay. Is there going to be an AdCom, and when will we find out if there's an AdCom or not?
As you know, the AdCom decision is made during the review. In the pre-BLA minutes, the FDA shared with us they don't believe an AdCom would be necessary, with the usual caveat, subject to review. So we'll see during the review if that changes. At this point in time, we're preparing for one out of discipline, and good preparedness, but at this point in time, we're not expecting one.
Got it. On the last quarter call, you provided incredible details on this warning letter that one of your CMO, Fareva,
Yeah
had received. Could you maybe remind us what was the issue?
Yeah.
Where do we stand now? Where is the FDA involvement in that?
Thank you. Thanks for acknowledging it. We put a lot of detail out there because obviously it is something that is not as commonly diligenced by investors as clinical data would be. The situation is very straightforward, to be clear. Warning letters happen all the time in our industry, so this is not a once-in-a-generation event here. The situation is the following, rather typical. Observations in a different part of the facility in Amboise, which is where the product is made, Fareva Amboise, having to do with sterile manufacturing of a veterinary product, had some observations that the FDA thought that the company had not dealt with the right way. That has nothing to do with our patch, but the observations when you get a warning letter are never limited to the product that was problematic.
They touch on the whole quality systems and quality training of the entire site. Every product being made there is now touched by that warning letter. Fareva has been very helpful, very collaborative, very transparent. We have good visibility to what they do, with the limitation, obviously, of what is confidential about manufacturing processes for other companies we cannot see. We have visibility to the pace by which they are addressing the issues, and we are satisfied with that pace.
Got it. The issue that was identified, obviously it was a veterinarian product. Is it more to do with the process or the quality of the product, or just a little bit more? Because I think the concern that we hear from our investor is that, again, like you mentioned, that maybe Wall Street has not, or not known to, or not very good at, let us say, knowing all the nitty-gritty about these CMC stuff. So there is always a concern that maybe something like this might linger and might not get resolved by the time your FDA, your review is there.
To be clear, the risk is very much there that it might not be resolved, which is why, again, we went through great detail, at least as much as was reasonable to share on the call as we have with investors. This is very process-like. There are tons of consultants who make a living helping companies manage warning letters. There is a process. It is rigorous, it is thoughtful, and Fareva is using such a process. Our confidence that they are doing all the right thing is high. Thus, our confidence this will be resolved prior to our pre-approval inspection is also very high. Thus, the reason we shared that level of detail was to hopefully communicate to investors it is an unfortunate situation, one that happens and is manageable and managed, I think, very well.
Got it. When generally do you expect these inspections to happen? Like, how, during the life of the, let us say, review, when do they happen?
They typically happen. Again, I'm not going to answer for DBV here because we have not provided that guidance.
Yeah.
What is common in our industry is you invite the FDA to come visit the plant for the pre-approval inspection, sometime post the mid-cycle review, which is halfway through the cycle by definition, simply because that's when the FDA takes stock of what they should put their resource to work on in the latter half of the review, which includes inspection, or telling the company, for example, "You should prepare for an AdCom.
Yeah.
We touched on that earlier on. We don't expect one. Most sponsors invite the FDA to come for the PAI post mid-cycle review, which is what we've done.
Got it.
And we are confident this will take place after the remediation of the warning letter at Fareva will have been addressed satisfactorily.
Got it. Will there be an announcement to your investor or to public that this has been resolved?
We would be wise to do that. We would be wise to do that, yes.
Got it. Maybe then let's move to the toddler side, and I'll come back to the commercial prep for Kevin. Where are we on the toddler side? When are you expecting to submit? What do you need to generate before you submit a BLA?
Yeah, we don't need to generate much to submit a BLA in one to three. The CMC file is very similar to the one we have in four to seven, as you would imagine, same manufacturing process. The pivotal study had its topline readout already a few years ago. COMFORT obviously needs to be folded into that. The discussion with the agency around the best not only timing
but process for filing it is taking place. The agency were kind enough to point out to us they have one review team reviewing two BLAs in parallel. There's a risk of a bottleneck here. I'm using the word bottleneck, not the agency, but that's where we are. So, we've agreed that we would file the BLA in one to three in a way that's most convenient for the agency to ensure an expeditious review of one to three on the back of our learnings would come in four to seven. So details to come after we finalize those discussions with the agency.
Got it. Yeah, I think most companies would wait for the first BLA to approve because you're going to learn a lot from the first and you can incorporate in the second BLA.
Including learnings for this guy on
Yeah
labeling and the. Yeah.
Okay. And then with regard to the safety supplement, anything particular there that maybe the FDA has an interest or is defined as an expected safety finding that is of an interest there?
No, there isn't. The agency, there's no safety signal we're chasing. As you know, the safety profile of VIASKIN is rather impressive. The agency wants 600 patients on active for about six months or more for the safety database. So the purpose of COMFORT was to add those 480 patients, sorry, let me get the math right here, 360 patients to the 240 we had in EPITOPE to get to 600. We're not chasing a safety signal, so it's a study that's being done, and I guess if there's a filter of success, it's an adverse event profile that will replicate what we've already seen with our product in 1,300 patients.
Got it.
Sorry, 2,300 patients with 800 patients.
Okay. Maybe then move on the commercial side. I mean, this is going to be a faster review than what we expect because of the breakthrough designation. So Kevin, talk about how you are thinking about the commercial strategy. What about the patient population? What do you hear about XOLAIR? Because that sort of is a competition to you. So just put all that in perspective for us.
Yeah. Thanks, Yatin. Commercial strategy, I mean, let me just frame out the market. I mean, 80% of kids persist for a lifetime, right? So you're thinking about that over the horizon. The four-year-old today will be the 40-year-old tomorrow. We're seeing one in five kids go to the ER for peanut allergy in this age range every year. As Daniel said, the biology maps well. So we think we've got a target product profile that meets the needs of these families. When we look at the treatments out there's very few children receiving active treatment. So that's really how we think about the opportunity. That gives around 600,000 kids, according to prevalence data. We look at claims for a narrower population that has the diagnosis codes and the testing that's related to that. Split that, the four to seven comes first.
Predominantly allergists will treat this. They're the ones doing the diagnostic criteria. They're the ones who understand immunotherapy. So we'll focus on them with a team of about 50 to 70 specialty sales reps on talking about the product. An important lever here is the consumer, right? The parents live day-to-day with the fear of their child going to the ER that I just mentioned. So we'll activate them with direct-to-consumer efforts, focusing on more digital. These are families that are very active on social media, various blogs with advocacy groups. So, we can do that without broad television in a very focused way. Then we've been discussing with payers now for a couple of months, what's the value proposition here? What's the unmet need in peanut allergy? How do we address that with them as we move towards a label?
Got it. Maybe on the competition for a sec. In, let's say, one to seven patient population, how much of a XOLAIR use is there right now? What are your estimates?
Yeah, it's very limited. Claims data has shown around 1% of kids get XOLAIR. What we hear from allergists is kind of the long-term use of a selective immunosuppressant in young children. What we hear from parents is children are afraid of needles, and so that can become a traumatic experience. That said, I think options are good, right? We're never going to say options aren't a good thing, but we haven't seen significant penetration in this age category.
Got it. So the VIASKIN product is only going after the peanut allergy, right? But the numbers that you talk about, 600,000, these are food allergy patients. Number one, could you talk about what percent have just peanut-specific allergy? Then as you talk to caregiver or parents, what is top of their mind? Is it peanut or other allergies that they focus on?
Yeah, it's an important question. The 600,000 is peanut allergy. They may have concomitant foods. In fact, in our study, 54% of kids had a second food allergy, at least one food allergy. Peanut is ubiquitous in society. It's in food chain production for packaged goods. It's in the ice cream scoop that may have cross-contact at the ice cream store, or the bite of a cookie at a bake sale or at a party. That's what parents worry about. It's that threshold of where the reaction happens, which is very small amounts. About a third of a peanut is where the average accidental consumption happens. The goal with Viaskin is to raise that threshold where they get that protection and reduce their risk.
What is that percentage for peanuts? So it is about 54% in your study. Is that the general number?
Yeah. About a third had peanut only.
Only.
Right?
I see.
Another 40%, 50% had peanut plus milk or egg, which I mentioned eight out of 10 persist with peanut. Eight out of 10 resolve with milk and eggs, so those tend to go away. But what we hear from parents is peanut is the one that is most concerning.
Yeah.
It's a severe anaphylactic reaction that can happen, and because of the food supply having it kind of everywhere, it's the one they would like to take off the table for their child, even if they're polyallergic.
Got it. I think a lot of people still bring up the OIT or PALFORZIA experience. What was unique about that experience which is different than what VIASKIN offers?
Yeah, I mean, a lot. I mean, routes and burden. You're taking it orally, and you have to go to the allergist multiple times on updosing. There's no updosing with VIASKIN. So that's a burden on family life to get to the allergist that many times. Then frankly, there becomes a concern around the safety profile of the product. It needed a REMS. So all of those things are things we think we've got with the target product profile here that meets those needs that families want. PALFORZIA, there's also only 100 doctors that really do OIT allergists at scale, so there was kind of a structural problem with how many allergists could actually write this. We see this as something that the community allergists can do. The parents aren't traveling as far as many times.
This is one patch on the back, first dose observation, and then after that, it's an at-home immunotherapy for children.
Got it.
Parents administer.
All right. Is PALFORZIA a good proxy in terms of the pricing for us?
Yeah, pricing's not finalized. We're doing a lot of work on it, Yatin. This will be based on the research. We've had plenty of discussions with payers to date, and we'll continue to have more. Obviously, it's dependent on the label. Folks can look up the PALFORZIA price and XOLAIR price. What we will do is plan for a specialty pharmacy distribution, leveraging a hub. Think about this as a specialty pediatric biologic. Make sure all of those services are there to get through a prior authorization process, and for commercial patients, we'll think about a copay. We haven't landed on the price. We're continuing to do that work.
Got it. Maybe a question for Daniel, and then maybe Kevin, you can also opine on that. Can you talk about how quickly these patients feel better, what the onset is, how quickly you are able to raise this threshold, so that parents are comfortable sooner rather than later?
Yeah. I'll take the front end of this. I'm sure you have some thoughts on that, Kevin. We assess efficacy after 12 months of treatment, so we don't know what is the protection after three weeks or three months. We do not. So that question is one for which we don't have clinical data. I think Kevin will reinforce to you, that's not a question that parents are asking, though, this need for validation that it works. For some parents, it matters. For most of them, it does not. The fact that the allergist prescribes it, and obviously, the daily application is valuing to the parents, "I'm doing everything I can to protect my child," seems to be sufficient, but you may have picked up something else in market research.
Yeah. No, I mean, look, these are parents that are already carrying epinephrine in their purse, the car, the school nurse. So they're already very vigilant in worrying about the anaphylactic reaction. We hear with active treatment that that's something they want to do. I think we had important data at AAAAI last year where we showed treating patients, 83% on the VIASKIN arm increased their eliciting dose, which confers risk reduction, where one in four that didn't treat actually went backwards in their ability to tolerate. So, I think those are important things we'll communicate as we launch. But as Daniel said, we're not going to know exactly where they are three months, six months. But that point of putting this small patch on the back every day and knowing that you have a high potential of building that threshold is an important that we hear.
And obviously, we do do quality of life studies after the one-year point, and we've seen that relief. So, that's what we hear.
Got it. Where are we on the commercial side? Once the product gets approved, number one, how quickly you can be in the market, and who is doing the manufacturing? Do you need another site for manufacturing, and if there is a lot of demand for it?
Yeah.
Manufacturing, I touched on. It's Fareva Amboise. We expect to be resolved in time for the launch, so that's a non-gating factor that we're working through. And for unit launch readiness, you're getting there.
Yeah. No, we are. I think supply chain being the key thing here. We would expect weeks from PDUFA. We still need to get the product from France and through U.S. distribution. We've got a 3PL, third-party logistics distributor. We've selected our specialty pharmacy, so all that work is in place. We're building the patient services element there. That's where we're focusing that and the payer lens right now. These are the investments we have to make because there's long lead time. Anything that's related to bringing the representatives on, we'll want to bring them on before approval to make sure that they're trained. But those are obviously on the regulatory milestones we have ahead, and the consumer efforts are in full throttle as well. It'll be weeks after PDUFA to get it into supply, but we can start detailing, obviously, at PDUFA.
Understood. Okay. Maybe one final question. How is the financial health of the company? How is the current runway?
We currently have a runway into Q3 of next year. That includes all the investments that must be made in commercialization, in launch readiness, including building up inventory. That takes us through the launch if the breakthrough designation turns out to be priority review. Obviously, access to more capital is something that we're always thinking about. The good news for us is we're getting closer to commercialization. The number of tools we have for financing the company are numerous, and obviously, that's part of our thinking right now.
Perfect. Well, thank you. Thank you so much, gentlemen.
Yeah. Thank you.
Thank you.
Thank you.