DBV Technologies S.A. (DBV) Earnings Call Transcript & Summary

Welcome to DBV Technologies Conference Call Webcast. My name is Darryl, and I'll be your operator for today's call. [Operator Instructions] Please note that this conference is being recorded. I will now turn the call over to Anne Pollak. Anne, you may begin.

Thank you. This afternoon, DBV Technologies issued a press release outlining an regulatory strategy and clinical development plan for a modified Viaskin Peanut patch. This release is available in the Press Release 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 potential design of our proposed Phase III trial, the timing and results of interactions with regulatory agencies. Our forecast our cash runway and the ability of any of our product accounted 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 the company's actual results to differ materially 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 the call. Daniel Tassé, Chief Executive Officer of DBV; and Pharis Mohideen, Chief Medical Officer, are joining me today. Daniel, I will now turn the call over to you.

Thank you, Anne, and thank you all for joining us this evening. On today's call, Pharis and I will share a summary of our recent communications with the FDA and EMA about the regulatory pathway for Viaskin Peanut in the U.S. and in the EU. Although we'll discuss several changes on the call today, it's important that I stress what has not changed. First and foremost, is a dedication perseverance to the entire DBV team to work on behalf of children with food allergies every day, and our commitment to pursuing approval of Viaskin Peanut in both the U.S. and the European Union. And second, and it's just behind is our unwavering confidence in the significant therapeutic and commercial potential of Viaskin Peanut, which has only been bolstered by the enhanced lesion profile we have seen in the modified patch. Now with that in mind, we evaluate potential clinical regulatory path forward on the speed in which they bring Viaskin Peanut to the food allergy community, most importantly, children with peanut allergy. Before I turn the call over to Pharis to discuss the U.S. regulatory and clinical updates in detail, I will touch on the key update in today's press release. On the U.S. side, we have decided to conduct a pivotal Phase III study with an efficacy assessment with the modified Viaskin Peanut patched in children with peanut allergy. We will not pursue the MVP regulatory pathway defined by STAMP and EQUAL, which FDA requested we conduct in a stepwise approach. Running EQUAL and STAMP sequentially requires at least 5 rounds of FDA exchanges before we can initiate STAMP. That approach is no longer faster more predictable than a pivotal trial and continue down that pathway does not best serve patients. Conducting a pivotal trial with the modified patch has several advantages. Most importantly, it is the shortest available pathway to BLA submission. Secondly, we'll be able to define a critical path to BLA submission more precisely and map out a time line accordingly. And finally, data from the trial will further strengthen the Viaskin Peanut label and enhance its commercial potential. And now turning to the EU. As of late last week, we have withdrawn the marketing authorization application Viaskin Peanut and whom you notified the EMA of our decision. Initial filing was supported by positive data from a single -- the single controlled Phase III pivotal trial, the study we know STPay the formal 712 301. The decision to withdraw was based on the current view of CHAMP in the data available to date from a single pivotal study were not sufficient to preclude a major objection at day 180 in the review cycle. As previously disclosed, the major objections, questions, the limitation of the data, for example, the clinical relevance and effect size supported by a single pivotal study. We believe data from the second Viaskin pivotal study will support a more robust path for licensure of Viaskin Peanut in the EU. We intend to submit EMA when that data set is available. And now I'll turn the call over to Pharis to review the U.S. update in detail. Pharis?

Thank you, Daniel. Many of you on the call know the U.S. regulatory history of Viaskin Peanut quite well. And for those of you who are less familiar, I'll provide a brief background summary. On August 3, 2020, DBV received a complete response letter from the FDA regarding our biologics license application for Viaskin Peanut. The CRL identified the FDA's concerns regarding the impact of patches as it relates to efficacy and indicated the need for patch modifications as well as a new human factor study. The FDA also requested additional chemistry, manufacturing and controls data. The agency did not raise any safety concerns related to Viaskin Peanut. In late October of 2020, we submitted a Type A meeting request and briefing book that proposed potential resolutions to 2 main concerns identified by the FDA in the CRL, the impact of patch adhesion and the need for patch modifications. In our exchanges with the FDA related to the Type A briefing, we proposed a pathway for a modified Viaskin Peanut patch BLA submission that was faster than conducting a pivotal trial with a modified patch. In January, we received an FDA response that provided a well-defined regulatory path forward for a modified Viaskin Peanut patch that did not necessitate an efficacy study. The regulatory path included the following key points and requests. FDA agreed that DBV's proposed modification to the Viaskin Peanut patch would not be considered a new product entity since the core structure of the occlusion chamber and 250-microgram amount of peanut protein was to remain unchanged. The FDA asked for 3 clinical data sets. First, demonstrate that the occlusion chamber of the modified patch performs similarly to that of the current patch in order to leverage existing Phase III efficacy data. To do this, FDA requested an assessment comparing the uptake of allergen between the existing and modified patches in peanut allergic children ages 4 to 11. We named that assessment equal, which stands for equivalents in uptake of allergen. Second, the FDA recommended conducting a 6-month well-controlled safety and adhesion study to assess the modified Viaskin Peanut patch in the intended patient population. This study we called STAMP, which stands for safety, tolerability and adhesion of modified patches. Third, FDA asked for a new human factor instructions for use study. This is standard for any device product that has undergone changes. Based on the FDA feedback, we defined 3 parallel work screens to identify a modified patch, which we call mVP and it generates a supportive clinical data FDA requested. The first work stream was to develop a modified patch mVP. This was well underway in January. And by March, we assessed adhesion performance of 5 modified patches relative to the current patch in a healthy adult study. We called this study CHAMP. Based on this study, we selected the modified patch to advance to further clinical testing in the intended patient population. The modified patch is about 50% larger in size relative to the current patch and circular in shape. The modified patch outperformed the current patch in the CHAMP study. CHAMP was a 6-month safety and adhesion study in the intended population, which was expected to be the longest component of the mVP clinical plan. But we prioritize the STAMP protocol submission so that we could begin the study as soon as possible. The safety and adhesion assessment in STAMP were to be similar to those done in topics. There were no food challenges in this study since efficacy was not an outcome measure. The third work stream EQUAL as designed, would have been a shorter study relative to STAMP. The main data set was to be an assessment of protein uptake comparison between cVP and mVP over the course of 24 hours. The complexity of EQUAL hinged on the lack of established clinical and regulatory criteria to characterize allergen uptake in an epicutaneous patch. Unlike a transdermal patch, systemic in-vivo measurements of maximum concentration and area under the curve are not possible for the Viaskin technology. Our product is not like a transdermal patch where PK PD parameters correlate directly with adhesion to the skin. Consequently, we anticipated needing multiple exchanges with the FDA to align on a final EQUAL protocol. To support those exchanges, we outlined our proposed approach to demonstrate allergen uptick equivalent between the 2 patches and allotted time to generate informative data through 2 additional studies. The first was PREQUAL, a Phase I study in adult healthy volunteers to optimize the allergen sample collection methodology and validate the assays we intended to use in equal EQUAL. EQUAL in adults was a second Phase I study with adult healthy volunteers to compare the allergen uptake of cVP and mVP. We submitted our proposed STAMP protocol to the agency in early May. And in mid-October, we received an advice information request matter from the FDA. In this letter, the FDA requested a step-wise approach to the mVP development program and provided partial feedback on the STAMP protocol. eVP would need to conduct the allergen uptake comparison studies submit the data for FDA review and feedback prior to starting the STAMP study. The FDA's explanation was that the results of the allergen OPTIC study may affect the design of the STAMP study. This step-wise request was a new development. In the same communication, the FDA stated that further guidance was forthcoming on the allergen uptake comparison of the 2 patches. The forthcoming guidance was received just before Thanksgiving in another advice information request letter that referenced the EQUAL in adults protocol we had submitted in July. In this letter, the FDA requested additional information on the planned EQUAL in adult study, which would have necessitated further exchanges between DBV and the FDA to gain alignment prior to initiating the study. Now let me hand it back to Daniel.

Thank you. So where does that feedback leave us? Essentially with the same very clear pathway forward, the FDA describes the guidance you received in January. The FDA has not altered its request to see 6-month safety and adhesion data and data demonstrating decision chamber works similarly in both patches, cVP and mVP. We are thankful to the agency, but there will be output into helping us map out STAMP and EQUAL. What has changed, and to be clear, it has changed significantly is the sum total of the time line for the mVP clinical development plan. The FDA's request, for a step-wise approach means that we would have at least 5 rounds in exchange with the FDA to navigate before we could initiate STAMP. This entails alignment on 3 protocols, EQUAL results, EQUAL in the intended patient population and STAMP and the FDA need to review and provide a feedback on 2 data sets, namely EQUAL in adults and EQUAL in children with peanut allergy. By our estimation, we should have top line results in a pivotal study around the same time we'd be in a position to initiate STAMP under the stepwise approach. In our official post-CRL exchanges, the FDA response time has averaged 120 days. Therefore, a target BLA resubmission date would not only be pushed out significantly in a stepwise approach. But our ability to precisely outline the time line in critical path to resubmission but also significantly decrease. The STAMP's EQUAL alternative to a second pivotal trial is no longer a faster or more predictable path to BLA submission. As such, we have decided to conduct a Phase III placebo-controlled trial with an efficacy assessment to support an MVP modified Viaskin Peanut BLA. We have communicated our decision to the FDA, and the agency has confirmed their support of this new approach. Pharis will now walk you through our high-level thinking on the design of pivotal study. Pharis?

Thanks, Daniel. A new pivotal study refocuses our exchanges with the FDA on the product profile of Viaskin Peanut as innovative allergen immunotherapy. Furthermore, the safety and efficacy data generated in the pivotal study will strengthen the Viaskin Peanut label if approved. We will align on the final protocol with the FDA before initiating this trial. This may include a formal meeting request depending on the nature of the future interactions. We anticipate protocol submission to the FDA by the end of February 2022. The new pivotal study will be similar to PEPITES, but we have learned a lot since then about our product, our clinical studies as well as the peanut allergy treatment landscape. We will, of course, incorporate these learnings in the new study. For example, we have developed a new set of application instructions for the modified patch, which we feel further improved upon on already simple-to-use product. We have done multiple post hoc analysis of the PEPITES data set some of which included analysis of adhesion and efficacy, which were published in 2020. We are confident that the new pivotal study should provide robust data to advise the Viaskin development program. We considered 2 additional factors when we evaluated the speed of a pivotal trial versus STAMP/EQUAL. The first is the upcoming PDUFA reauthorization cycle. PDUFA 6 will expire in September 2022, and we are pleased that allergenic extract products such as Viaskin Peanut are currently included in the PDUFA 7 FDA commitment letter. If PDUFA 7 is enacted with language consistent with the commitment letter allergenic extract products licensed after October 1, 2022, will be entitled to the PDUFA standardized review procedures, meeting opportunities and time lines for the first time. We believe navigating Viaskin Peanut through the FDA review process as a PDUFA product will increase the predictability of the regulatory time line. The second factor is the ongoing COVID-19 pandemic. Viaskin Peanut is classified as an allergenic extract product and therefore, is under the jurisdiction of the office of Vaccine Research and review, the same division responsible for the COVID-19 vaccines. This division has done a tremendous job of reviewing 3 different COVID-19 vaccines for 3 different age groups and 2 separate indications, primary vaccination and booster doses. The United States led the world in speed to approved vaccines and it was significantly due to the stellar work of OVRR. This work, as you can imagine, has taxed the division's resources and time. Our hope is that the impact of COVID has substantially lessened when we submit the modified Viaskin Peanut BLA. I'll now turn the call back to Daniel to talk about the next steps from here.

Thanks, Pharis. So the most important next step is gaining alignment with the FDA on the pivotal trial protocol. We will share key study elements and provide more clarity on time lines as soon as we have the alignment with FDA. In parallel, we continue to be vigilant of our expenditures and maintained a very significant reduction in our average quarterly cash burn compared to the first half of 2020. And we'll consider all options for financing the future growth of DBV. Our current stock price, in our opinion, does not reflect the significant potential of the Viaskin platform. As such, we will explore all forms of financing strategy, including non-diluted financing -- sorry, nondilutive financing strategy that could leverage Viaskin Peanuts commercial potential among with every other options available to us. The good news is that we believe we have enough cash to further advance Viaskin Peanut before needing to raise money. A mix of financing tools done incrementally are very much amongst the potential options we are exploring. I want to thank everyone on the phone and webcast for joining us today and operator at this time, let's open the line for questions, please.

[Operator Instructions] And we do have a question from Jon Wolleben from JMP Securities.

And thanks for all the updates today. A few for me. You mentioned in the release that FDA has confirmed the change in strategy is goal via oral and written exchanges. I was hoping you could give a little bit more color on what they agreed to here since it is different from their initial request.

Yes. Let's -- since had the verbal contract remote he e-mail I haven't complement this. I want to remind everybody that among the options we had when we received the CRL in August of 2020 was do another pivotal trial or signing another approach with science-based to show the close of the 2 patches. So we had chosen that other path with EQUAL and STAMP being those bridging studies term. But to do another pivotal was always something that the agency was accepted to. So as we go back to them, we're not asking them to do a U-turn. We're just going to be borrowing 1 of the 2 paths you had defined for us. And Pharis, if you want to add maybe a bit of details to your conversations with the agency.

Yes. No, that's exactly it. We just asked for clarification that we were going to move down the new pivotal trial path, as Daniel had said, Jon, that was an option originally. And it was just getting clarification and alignment with them that in view of the step-wise approach, we would go to this new pivotal study. Does that answer your question?

Yes. And then I guess maybe just a follow-up on that with the design. You said similar PEPITES, but can you tell us a little bit more of a PEPITES was a year long in FDA requested for a 6-month safety and adhesion. So are you thinking a year, and also about the size of the study is PEPITES was around 32 patients, but enrolled very quickly. So any sense on the size, and I'm guessing this is going to be a food challenge study as well. So any more color on what this new pivotal could look like?

Pharis, do you want to take that one?

Sure. Yes. So you're exactly right, Jon. So right now, pending finalization of a protocol with the FDA. It will be similar to PEPITES in that. So we envision it as a 12-month placebo-controlled efficacy fruit calling study. You're right that the PEPITES recruited quite quickly. We anticipate a similar landscape. But those are the parameters around what we're thinking about right now. Obviously, we have to do a final alignment with the FDA.

Jon, sorry -- I was going to add something to Pharis' comments here to help everybody understand it. Yes, STAMP was a 6-month study PEPITES, or PEPITES-like pivotal trial would be a 12-month study. Studies without food challenges enrolled this more quickly than studies with food challenges. Now we've got to realize now that we're not doing STAMP versus the pivotal. We have to do STAMP after we do EQUAL, which would require 5 interactions with the agency. So those 5 interactions with the agency that add up to become the rate limiting and also difficult for us to forecast because the agencies very busy with the pandemic has not gone away here. So company plus EQUAL back-to-back versus a pivotal and STAMP EQUAL with 5 interactions with the agency. That's why we believe that we can get to a BLA resubmission faster with that path than we would by sticking with STAMP and EQUAL moreover we also get a chance to run the second pivotal trial, everything we've learned, enrich the label. So that was our core thinking.

I think you mentioned -- it is. And you mentioned your timing expectations in those 2 scenarios. What is your expectation for when you could have data from this new pivotal and get a resubmission to FDA?

Pharis, I believe we're going to be submitting the protocol by the end of February.

That's correct. So this is a step-wise approach, Jon. So we submit the protocol by the end of February. The FDA does the review cycle. We get alignment on the key parameters, which obviously is critically important. And then we envision, as you said, time line is similar to the PEPITES study, just as a reference point, the PEPITES study from start to top line was 24 months. So once we've locked that in -- one of the things that, as Daniel mentioned, is our ability then to project on the back end a BLA submission time line. Obviously, we control many more parameters in that with this new pivotal. The one we don't control the FDA review time line. So once we have the final protocol back in a much better position to lay out specifics of the trial design, size, other things and then as well as a BLA time line.

[Operator Instructions] And we don't have any more questions at this time.

Okay. But use the opportunity to everybody on the call today, and to reiterate the key element of this. We need to have 1 interaction with the agency, and I take more than 1 round of discussion to get the agreement of the protocol. As you know, we've been thinking about this as not turn past a couple of weeks now. We have some thoughts on that protocol, we'll be submitting it as we said by the end of February. And after that one set of interactions, which will land us a completely agree in alliance protocol for that new pivotal with the agency, then we will get sooner after share with patient advocates as well as investors, the key elements of that protocol as that matters, obviously. And then we'll be able -- because we then control the time line, the study is run entirely by us at that point in time, be able to give much more precise guidance investors to when we expect to complete the study and refile our BLA. So that's going to be the next set of communication coming back to investors on the back of agreement on the protocol. I thank you all for your availability today. And if we don't talk soon, the faces and happy about it is. Thank you.