Avadel Pharmaceuticals PLC (AVDL) 2021 Q1 法說會逐字稿

Greetings, and welcome to the Avadel Pharmaceuticals First Quarter 2021 Earnings Call. (Operator Instructions) As a reminder, this conference is being recorded.

It is now my pleasure to introduce Tom McHugh, Chief Financial Officer. Thank you. You may begin.

Good morning, and thank you for joining us on our conference call. This morning, we issued a press release providing a corporate update and financial results for the quarter ended March 31, 2021. The release can be accessed on our website, www.avadel.com. As a reminder, before we begin, the following presentation includes several matters that constitute forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Forward-looking statements are subject to risks and uncertainties that could cause actual results to differ materially from those contemplated in such forward-looking statements.

These risks include risks that products in the development stage may not achieve scientific objectives or milestones or stringent regulatory requirements. Uncertainties regarding market entry and acceptance of products and the impact of competitive products and pricing.

These and other risks are described more fully in Avadel's public filings with the Exchange Act, including the Form 10-K for the year ended December 31, 2020, which was filed on March 9, 2021, and subsequent SEC filings.

Except as required by law, Avadel undertakes no obligation to update or revise any forward-looking statements contained in this presentation to reflect new information, future events or otherwise.

On the call with me today are Greg Divis, our Chief Executive Officer; Richard Kim, our Chief Commercial Officer; and Dr. Jennifer Gudeman, our VP of Medical and Clinical Affairs.

At this time, I'll turn the call over to Greg.

Thank you, Tom. Good morning, everyone, and thank you for joining us on our first quarter 2021 conference call. I will begin by providing an update on our business, highlighting the significant progress we continue to make towards achieving FDA approval of and preparation for the potential commercialization of once-nightly FT218. If approved, FT218 will be the first and only once-nightly oxybate treatment available for people suffering from the debilitating orphan disease of narcolepsy.

I will then turn the call over to Jennifer, who will offer an overview of the progress we've made with our medical affairs and scientific communication plans for FT218. Richard will then provide an update on our commercialization and launch planning, as we move closer to the PDUFA date and the potential approval. Finally, Tom will provide a review of the financial results for the quarter, and we will conclude with a Q&A session. With that as an outline for the call, let's get started.

As we are now nearly halfway into 2021, I can say that it has already been a significant year for Avadel with several key regulatory, clinical and launch readiness milestones achieved as we continue to rapidly advance our investigational once-nightly FT218 program. Most notably being the acceptance of the NDA filing with an assigned PDUFA date of October 15.

Considering this progress and the momentum we are experiencing across the entire FT218 program from NDA execution, the data dissemination and launch readiness, the second half of 2021 is lining up to be both exciting and potentially historic for Avadel and for people suffering from narcolepsy. In this regard, the progress we are making on the regulatory front is arguably the most relevant and important near-term milestone for Avadel.

As we have said in the past, as it relates to our public disclosures on the NDA process, and specifically, our regulatory filing strategy, we've said no news is good news. And as such, I am pleased to report as it relates to our regulatory filing strategy perspective, we have no news to share.

As we are now approaching the midpoint of the review time line for the NDA and based on the actual review to date, we still have not been asked by the agency to certify Paragraph IV against any Orange Book list of patents, and we don't believe, based on the data and regulatory filing strategy of our FT218 NDA submission there is any basis to request such a certification.

Our team over the last 2 years has executed this program and specifically this NDA exceptionally well, and we remain highly confident in our regulatory filing strategy as we head toward our October 15 PDUFA date. Furthermore, as Jennifer will cover, the data from the REST-ON study for key secondary endpoints recently presented at the American Academy of Neurology Conference, confirms the clinical profile and promise of our investigational once-nightly FT218.

We look forward to even more data being presented and disseminated throughout the scientific community during the balance of 2021. Lastly, this promise of FT218 can only be realized through both the successful execution of our NDA and the subsequent commercialization of FT218, if approved. Over the past few months, we've accelerated our launch planning and execution with the appointment of Richard Kim as our Chief Commercial Officer; and Richard has quickly immersed himself into our plans, continues to actively engage with key stakeholders and is building a team of exceptional and proven industry professionals that is quickly advancing our level of readiness across multiple work streams.

The caliber of the people who are raising their hand wanting to join us in this journey is some of the best I've seen in my over 30 years of industry experience, which we believe is reflective of the opportunity and the value that once-nightly FT218 can deliver. As many of you know, it was just a little more than 24 months ago when we decided to focus our business on the prospects and the potential of our investigational once-nightly FT218.

That is exactly what we have done and our execution on that decision has brought us to where we are today with a strong balance sheet, having over $200 million of cash on hand to support our launch readiness and a regulatory pathway to a potential approval and future launch. Our team has remained incredibly focused, has executed at the highest level and is building great momentum across the company and in the narcolepsy community as we seek to establish our investigational once-nightly FT218 as the oxybate of choice and disrupt this multibillion-dollar narcolepsy market.

So to summarize, the overall key takeaway from today's call is that we remain on track across all aspects of the once-nightly FT218 plan. This includes NDA execution, which continues to advance according to plan, and we remain confident in our regulatory filing strategy as we head toward mid-cycle review. Furthermore, the opportunity for FT218 only improves as we continue to announce new, relevant data and actively engage the medical community, while accelerating our overall launch readiness. We look forward to what will be an exciting second half of 2021 and beyond. And with that as the backdrop, let's get into some of the details.

And for now, I'll turn the call over to Jennifer.

Thanks, Greg. It's great to be here today to discuss the progress we've made with our scientific communications for FT218. While the Avadel team has known for some time, how robust the broader REST-ON data set is, we are now fully engaged in externalizing these data so that the medical and payer community can also fully appreciate our positive findings with once-nightly FT218.

Additionally, we have expanded our medical affairs team to further our connectivity in scientific exchange with key opinion leaders. As Greg mentioned, we were excited to present new positive secondary endpoint data at the 2021 American Academy of Neurology Annual Meeting, which was held last month.

There are 2 key takeaways from these secondary data, including: first, FT218 demonstrated significant consolidation of sleep, significant increase in time in deep sleep and significant decrease in light sleep compared to placebo for all doses evaluated, 6 grams, 7.5 grams and 9 grams, beginning by week 3.

Disturbed nocturnal sleep is a frequent and bothersome complaint of patients living with narcolepsy. While most therapies for narcolepsy address only daytime symptoms, this newly presented sleep data from REST-ON, supports that once-nightly FT218, if approved, could address nighttime symptoms of narcolepsy without having to wake up in the middle of the night.

Second, FT218 demonstrated a significant improvement in the Epworth Sleepiness Scale, a patient-reported outcome as well as significantly improving patient perceptions of both the quality and the refreshing nature of sleep, also for all doses evaluated. The Epworth Sleepiness Scale is commonly used in clinical practice as it evaluates 8 domains to ask patients about their likelihood of dosing off during various activities, such as watching TV or when stopped at a traffic light.

At all doses in beginning at week 3, which was the first formal evaluation, FT218 significantly improved, that has reduced the Epworth Score. For context, a score of 16 out of 24 is characteristic of narcolepsy, a score of 10 or below is considered normal. At week 13, with the 9-gram dose, the endpoint mean was a score of 10.4, indicating not only market improvement from baseline, but also approaching a normal Epworth Score or many of the participants.

As a reminder, we have previously shared the top line data from the pivotal Phase III REST-ON trial. Which reported the FT218 met all 3 co-primary efficacy endpoints compared to placebo for all 3 doses evaluated. These results were highly statistically significant with all P-values less than 0.001 and clinically meaningful, as assessed by the maintenance of wakefulness test clinical global impression improvement and mean weekly cataplexy attacks.

With the new secondary endpoint data presented at AAN, clinicians can now begin to more fully appreciate the totality of the positive results demonstrated with FT218. The upcoming annual Sleep Congress, which commences in exactly 1 month, is dedicated to clinicians focused on sleep disorders.

As such, I am really looking forward to our expansive data dissemination strategy that we have scheduled. We will be presenting a total of 6 posters with 1 oral presentation. These educational assets, along with a newly created mechanism of action video will be housed in our virtual medical affairs booth as we look to engage with these narcolepsy specialists.

Additionally, we are supporting a symposium titled, how narcolepsy management is evolving, which will be priced of an expert panel discussion conveying 3 primary points. First, it is often necessary to manage both daytime and nighttime symptoms. Second, the importance of shared decision-making and criticality of considering the patient's perspective for treatment of this chronic condition. And third, reviewing the nearly 20 years' worth of immediate released sodium oxybate data showing no signal of increased cardiovascular risk.

Turning now to our publication plans. As you would expect, there are numerous publications planned and already in process. We very recently reached an important milestone with the submission of our primary manuscript from the REST-ON trial, with an excellent group of key opinion leaders and investigators as co-authors.

I look forward to providing updates on the content and timing of this primary manuscript as well as additional publications in the future. As a final remark, what really excites me is the perspective we hear from key opinion leaders for what FT218 could mean for their patients suffering from this chronic condition.

Whether it is working on publications, holding advisory boards or simply one-on-one meetings, the consistent takeaway from our interactions is that FT218, if approved, will provide a significant clinical advancement in the treatment of narcolepsy as the only once-nightly oxybate product.

Let me now hand the call over to Richard for an update on the commercial planning activities. Richard, the floor is yours.

Thanks, Jennifer. And let me say that I am excited to be on the call today and provide an update on our launch preparations for once-nightly FT218. During the March earnings call, I shared some of my initial insights and enthusiasm for joining the Avadel team and for the amazing opportunity we have to transform the narcolepsy market. Well, I can say that over the last few months, I've had a chance to validate my initial impressions that, if approved, once-nightly FT218 has the potential to gain market-leading share in the oxybate class.

Previously, I shared from our market research, some key insights about unmet needs in the oxybate market, including that, almost half of patient's report refusing twice nightly sodium oxybate when offered by a physician. Primarily due to the need to take a second dose in the middle of the night, 2.5 to 4 hours later. And almost 60% of patients reported negative treatment experiences.

What we see is that despite a time of diagnosis of about 8 to 15 years, patients on average are usually initiated with pharmacotherapy around 3 months post diagnosis. In addition, patients tend to have narcolepsy treatment switched or supplemented relatively quickly, with the average time to modify treatment from first to second-line being about 1.5 months, and the average time to modify from second to third-line treatment being about only 2 weeks.

From this research and other work we have done, the data sheds light on the challenges with twice-nightly oxybate treatment and the propensity for patients to seek new options when available. As they continue to search for new ways to get more control over the daily impact that narcolepsy has on their lives.

In the last couple of months, I have also had the opportunity to speak with treating physicians as well as patients living with narcolepsy. Here are a few key insights that continue to stick with me from those conversations. It's hard for someone who does not suffer from narcolepsy to really understand the challenges that those with it go through every day.

Like the choices some patients make to not participate in happy life events because of the fear that positive emotions will trigger a major cataplectic event. Like when I heard about a father, not attending his daughter's wedding. Narcolepsy can have a profound impact on what most of us would consider regular day-to-day activities, like cooking, driving or sleeping through the night.

One of the amazing patients I spoke with said that since her diagnosis and treatment of stimulants, antidepressants and twice-nightly oxybate. She has not slept through the night in 21 years. At the end of the day, like most of us, people with narcolepsy are seeking more normalcy in their lives and the opportunity to live more independently.

I have also learned that oxybate therapy can be a game changer for some patients, but also that the challenges of twice-nightly therapy go well beyond having a wake-up during the middle of the night. I'm so appreciative of the time people spent with me. As the conversations have been both emotional and inspirational. And overall, I continue to appreciate just how relentless narcolepsy can be. That's why we will continue to base our decisions on what we learn from patients, physicians and payers. And why we will also be relentless in how we bring once-nightly FT218 to the market, if approved.

Now let me transition to an update on some of our specific launch preparations. Overall, we continue to make significant progress in ensuring we are ready to launch once-nightly FT218 and that we develop and execute programs focused on bringing exceptional clinical value to all of our customers. On the REMS, patient hub and distribution fronts, we've made significant progress choosing our partners to ensure our network is ready and will deliver customer-focused support when ACPs and patients are seeking against once-nightly FT218, if approved.

We also continue to focus on gaining more patient insights under the guidance of pre-approval information exchange which provides the opportunity to engage with payers about once-nightly FT218. In addition, our team keeps advancing on other key launch initiatives like targeting, deal force sizing, data integration, pricing and messaging. And we will roll out our first corporate narcolepsy campaign to coincide with the Sleep Congress next month as we ramp up our customer engagement activities.

To support these and other commercial planning activities, we are also actively growing our launch team, and we have momentum in the marketplace, attracting top-tier talent to lead our launch. For example, we have recently made key leadership hires in marketing, patient services and distribution and insight and data analytics and are making great progress against our overall hiring plan. It's been really cool to see that our top candidates clearly understand our value proposition and embrace what we are doing to reshape the narcolepsy market for patients.

Well, it's been a quick first 3 months for me, but I am really pleased with our progress in our launch preparations. I am more convinced today that we have a unique opportunity to transform a market, to build a world-class team, to create exceptional clinical value, deliver strong shareholder returns, and most importantly, potentially bring an essential once-nightly treatment option to patients suffering from narcolepsy.

I look forward to providing further updates on our progress on future calls. I will now turn the call back over to Tom to provide an overview of our financial results for the quarter. Over to you, Tom.

Thank you, Richard, and I'm pleased to provide an overview of Avadel's financial results. From a financial -- from a balance sheet perspective, we ended the quarter with a strong cash position with $205 million of cash, cash equivalents and marketable securities.

And as a reminder, in addition to the cash on hand at March 31, we expect to collect the remaining $8.3 million from the sale of sterile injectable drug portfolio that we sold last year on June 30, 2020. Turning to our income statement. As a result of the sale of the sterile injectable products, we did not record any revenue in the quarter ended March 31, 2021, and we also did not record any expense for cost of products, intangible asset amortization and changes in fair value of contingent consideration.

The total of our R&D and SG&A expenses in the first quarter of 2021 were $14.8 million compared to $13.4 million in the prior year. As our preparations for the launch of FT218 continue to accelerate, we expect that our operating expenses will increase quarter-over-quarter during the remainder of the year and be more heavily weighted in the second half of 2021 as we approach the PDUFA date in Q4.

With regards to R&D, expenses decreased $1.6 million year-over-year to $3.9 million in the first quarter of 2021 versus $5.5 million in the prior year. The decrease is due primarily to the completion of the Phase III REST-ON clinical study for FT218, which concluded during the first quarter of 2020. SG&A expenses increased $3.1 million year-over-year to $11 million in the first quarter 2021 versus $7.9 million in the prior year.

The majority of the year-over-year increase is attributable to cost for planning and preparing for the launch of FT218, if approved. Income tax benefit was $2.6 million in the first quarter 2021, compared to $9.5 million in the prior year. The year-over-year decrease is primarily due to benefits recognized in 2020 from the coronavirus aid relief and Economic Security Act.

Net loss for the first quarter of 2021 was $13.4 million or $0.23 per diluted share compared to a net loss of $0.9 million or $0.02 per diluted share for the same period in 2020. The increase in net loss and diluted loss per share is primarily result of the year-over-year decrease in revenue due to the sale of the sterile injectable products. Diluted shares outstanding increased to 58.4 million shares this year versus 41.1 million shares last year.

The increase in the number of shares is due primarily to the $190 million of gross proceeds raised from equity issuances during the first half of 2020. Finally, as Greg noted earlier, we are incredibly pleased with our progress to date and the momentum we are carrying into the rest of the year. We believe we're in a strong financial position with $205 million of cash on hand to fund the financial investments needed to complete the NDA review process, compile additional supporting scientific data to position FT218 in the market and continue to ramp up our launch preparations for FT218.

Before turning the call back to Greg for closing remarks, we're going to open up the call for Q&A. And I'll now turn the call over to the operator.

(Operator Instructions) Our first question has come from the line of Paul Matteis with Stifel.

Great. I appreciate the call and the question. So you guys have said again that no news is good news. I guess how do you think about certain inflection points in the review? And if there's any kind of -- like, I guess, this mid-cycle or are you meeting or some other kind of scheduled interaction where key issues either related to certification and possible labeling are going to come up.

Just kind of curious if there's anything that you'd point to or how we should think about the timelines as it relates to freedom to operate? And then separately, I wanted to ask, are you expecting to get orphan drug exclusivity? How should we think about that? And if you do, what do you think that means for other once-nightly sodium oxybates that are in the pipeline, even those that might be low sodium?

Yes. Thanks, Paul. Appreciate the questions. I think as it relates to the review, I think our commentary, we've tried to provide a little bit of context here that we're very -- again, we haven't been asked as certified. We're very pleased with the progress we made on this front. And really, the types of questions or the comments we've received during the review process to date, right?

I think the 1 thing we'll say is that the FDA doesn't typically notify an applicant when some portion of NDA is kind of complete and they checked the box and moved on. They really just move on. So as we enter the second half of the review, we'll certainly move to label negotiations and things of that matter that we would expect, I would say that our position remains the same, we certainly are not aware and don't believe there's any basis for certification on our side whatsoever, given the data we've provided, how that is reflected in our label and our overall regulatory filing strategy.

That being said, even if we've been confirmed already or we learn at a later date in the review process that we've effectively navigated through any sort of certification risk we certainly aren't going to speak on it publicly in advance of the FDA, making the first comment publicly in the form of their decision on or around October 15.

That being said, I think we feel really good about where we are, how we've progressed this aspect of the NDA and where the -- and where we sit today currently. As it relates to orphan drug, you're correct. We have -- we were granted orphan drug designation on the plausible hypothesis that once-nightly FT218 could be clinically superior to the reference product, right?

We believe that we've provided a robust and complete rationale for our exclusivity request that has been and is part of our NDA review. So we certainly look forward to the FDA's decision on it. It's not something we're relying on for our exclusivity protection because I'll remind you that we've had a number of intellectual property patents granted already and many more in the queue, so to speak, that we believe will build the appropriate protection for the company.

It was the first 1 to innovate and demonstrate a modified or extended-release control GHB related product that can work for patients. And we certainly are going to protect that in every way, shape or form. So as its impact on other potential products that could come in the marketplace, if we're granted orphan drug, it would be something that they would have to demonstrate that they're clinically superior to our once-nightly product is how we think about it.

Our next question is come from the line of David Amsellem with Piper Sandler.

Just a couple. So on the review, I don't know if you can talk about this, but has the REMS portion of the discussion come up? And when or when in the review does the REMS piece actually come up? I'll just understand that, if you can?

And then secondly, on the commercial landscape, I'm sure you're going to get this question an awful lot, but I have to ask it, which is with Jazz converting a significant number of patients over the low sodium, what are your thoughts on getting some of those patients, capturing some of those patients? And I guess as part of that, with Jazz's success here, does that mean you have to contract more aggressively in order to try to capture some share. So how philosophically do you think about that?

Yes. Thanks, David. I'll take the first question. And then Richard, maybe I'll turn it over to you to have any perspective on the commercial question. As it relates to the REMS program, I would say, again, I think for context and background, it is a -- it is not a topic that we -- that the first time we would be engaging the FDA on it would be during the review.

It something we would have obviously given the criticality of it, engaged with the agency in advance of our -- even our initial submission, and I just remind everyone that as of 505(b)(2) application, it's not it's not subject to any sort of single shared system. And we can, in essence, have our own REMS program from that perspective, that will be obviously geared and specific to our own label, should we get approved.

In terms of the review process, I would say that there's a little -- I think we can say specifics around it other than overall, I would say we're quite confident that the FDA has been through all aspects of our NDA, and it wouldn't get accepted if it wasn't in there already.

And for sure, because it's part of our submission. So I would say, generally speaking, whether it's REMs or anything else, we're quite confident the FDA has been through at least initially all aspects of our NDA.

Yes. And thanks, Ray. I'll take over the rest of the question from you, David. So I guess, first, from our perspective, David, it's always great to see new treatment options come to the market, no matter how large or small the benefit is that's added. I think the key thing that we think of the early uptake of mix salts is that it really shows us -- confirms our market research that there -- in general, there's a high degree of patient willingness to try new treatments to gain more normalcy in their lives and a fair degree of dissatisfaction in the market.

We actually think this bodes well for the value proposition that for once-nightly FT218 is we believe that the majority of patients switching to mix salt now they'll continue to demonstrate a propensity to seek new ways to improve their treatment as they go forward, especially with a significant advancement like a once-nightly oxybate coming to the marketplace.

So -- and for us, we remind ourselves that sodium is really not much of an issue. It's clearly when there's no other options, it makes sense. But we also know that from the systematic literature view that's been done, that experts in the field have concluded that the sodium and sodium oxybate really doesn't create any additional cardiovascular risk for patients.

So at the end of the day for us, the sodium oxybate has demonstrated a lot of great utility over the last couple of years and nearly 2-decade safety profile. And then that's really why we believe that ultimately, when given options, narcolepsy patients will also focus on getting more consolidated sleep without the need to take a second dose during the middle of the night.

And as far as the payers are concerned, they've always been our position there, we're going to fight this battle on our clinical value proposition. We don't want this to turn into convenience or salt play. So having said that, we are clearly going to be very active with the payers. We don't want to get into pricing wars anything, but we also know that at some point in time in the United States, there usually is some sort of contracting that we will build in. But we are beginning that next level of discussions with payers, and we're looking forward to providing some more updates in the future.

Our next question comes from the line of François Brisebois with Oppenheimer.

In terms of the data at AAN, is there anything -- some of the data for Xyrem is extremely old, but any comparisons here to twice nightly for the extra secondary endpoints? Or is it mostly placebo? Any kind of -- I know it's difficult to do, but any cross comparisons that are out there?

Jennifer, do you want to answer that?

Yes. François, thank you for your question. My general philosophy is that I think FT218 data should stand on its own. We know that there are inherent challenges whenever we're having any sort of cross-study comparisons, obviously, potentially differences in trial design as well as in patient demographics or clinical characteristics.

That being said, I talked a little bit about the Epworth Score in my opening remarks and perhaps relevant to highlight, we're extremely pleased with the fact that our end of study score with the 9-gram dose was 10.4. As I mentioned, the score of 10 or below is considered normal.

And with all of the caveats that I described in terms of limitations with cross-study comparisons, I think it is still relevant to recognize with the twice nightly-sodium oxybate, they're in the study score with the 9-gram dose was 12. So as Richard had mentioned in his remarks, our belief is that patients who have this chronic condition that once they're diagnosed, they're living with for the rest of their life, their aspiration is returning to normal.

And with our Epworth Scores, coupled with the fact that 1 does not need to wake up in the middle of the night to take that second dose. We believe that, that's going to be a very attractive option for patients suffering from this condition.

Yes, Frank, and I would just add to Jen, thanks. Great comments. As she noted, it's hard to make those comparisons. And I think just to reiterate the point, I think everything we present and all the data we've looked at and the data that we're going to share on sleep only continues to just reinforce and support the overall pivotal study results that really -- like you can't quite -- our data is compelling and with an adverse reaction profile that looks exceptionally well, strong as well.

So we're just excited about the prospects of how FT218 looks and the data it presents. And I think the more we get an opportunity to share this data with the medical community. You can see the more interesting and excited they get about it as they're learning more about us from that perspective.

That's great. And just in terms of the education, maybe this is more for Richard, I would assume that this is a fairly straightforward kind of new product in terms of comparing it to twice-nightly. Is this something when you speak to physicians that is -- you feel like the physician education will be difficult or at conferences from your interviews, is this something that's pretty straightforward, and they get it?

Frank, I've learned to realize in my life, not to take anything for granted. So I think the messaging is straightforward and simple. But I think the great news is with the work that Jennifer has done is now we have this great scientific foundation to go forward with. And if approved, of course, it will really give us a great foundation to really have a very clear, simple message. So the good news is, as you know, physicians are very deeply familiar with using oxybate treatment. We just hope this message and deliver something that's simpler for them and their patients to be able to use.

So yes, I look forward to getting out there and having more of those conversations when we can. But I think they should be our goal is to make this a simple communication to build off of their experience that physicians already have.

Okay. Great. And then just all that data that you guys are working on, the extra secondary endpoints, that -- now that it's all filed and accepted. There's nothing here on the NDA or that can affect the label? Or is this still something that the FDA can look at?

Yes. I think when you think about the label, it's predominantly your primary endpoint data that will be most represented in our label. So I don't -- any post-hoc analysis that we'll do that you'll see at the Sleep Meeting will not be in our label at this stage.

But it's additional analysis, we think, is relevant for the clinical community to understand in different patient populations. As an example, that we think is important for as they think about the use of once-nightly FT218 in the future to have more data to look at and really just to round out the complete clinical profile of FT218.

Okay. Okay, great. And I guess my point was a little more from the sales rep's perspective, if it's not in the label, how much can they discuss it? And on that note, have you shared how many reps or when you would hire them?

Yes. Rich, do you want to take that?

Absolutely Greg. Sorry. And Frank, as far as the label, I mean, first, Jennifer's team is doing a fantastic job in beginning this real push for our clinical data that will be out there. So we really believe and trust in the work that they continue to do and as far as the sales force is concerned, we haven't made any final decisions yet.

I think we're getting into those stages now where we're really starting to get zone in some of the numbers. We sort of traditionally guided towards 50 or 60. But I think for us, we're still assessing sort of the face-to-face, the digital communications that will go on. And the other thing for me as well is that, ultimately, we know that this is a relatively concentrated marketplace as we've spoken about, around 1,600 physicians make up 80% of the prescription volume and less than 500 make up 50%.

So the good news for us is that we'll give us some flexibility on how we want to go to this marketplace. So those decisions will be coming up in the upcoming months as we get ready to support the launch of once-nightly FT218.

Our next question comes from the line of Marc Goodman with SVB Leerink.

This is (inaudible) on for Mark. We just had a question on sort of when you're thinking of disclosing other products that you are internally developing that leverage your controlled release technology?

Yes. Thank you. I think it's a great question because we certainly know how important it is as we move through a potential approval and launch, the what's next question will certainly come about. And I would describe it this way. We've done quite a bit of planning and have even initiated some early work on what we would characterize as what's next beyond FT218 but I don't think we're at a place where we'll discuss specifics at this stage. I mean, we're very focused on executing against the current regulatory and launch readiness strategy, which is very important for us.

But I think as you think about it, right, in potential future areas for expansion, you can think about it in the form of life cycle management. You can think about whether it's a pipeline and a product, you can think about our leveraging technology, our technology platform, both in sleep or in relevant adjacencies from that standpoint as kind of a couple of legs of the stool, if you will. In terms of how we think about growing what's next. But I would say, at this stage, we remain very focused on 218, while we plan and begin to do a little work on the other aspects of our portfolio and at the right time, we'll come forward and provide some more insights to our shareholders for sure.

Our next questions come from the line of David Sherman with LifeSci Capital.

I was wondering if you could talk a little bit more about how you're planning to engage with non-prescribers in an effort to expand the existing oxybate prescriber base? And then I was curious to hear a little bit more about just how you're planning to kind of engage and advertise to consumers down the road if it's approved?

Richard, do you want to go for?

Yes, sure. Thanks for the question, David. So as far as non-prescribers, we know that sort of within any sort of given a year, there is around 4,000 to 4,500 physicians who prescribe oxybate. So we believe that's relatively concentrated. So to your question around non-prescribers. To very candid, I think the initial thrust of our focus will be on current prescribers of oxybate who have the experience, but because of the proposition of a once-nightly FT218, where I think you're going is we do believe that there is opportunity to expand the treater base going forward as well.

So I think what we see is interest has grown in the narcolepsy class with other new novel therapies who have come to the marketplace. So we intend to sort of capture some of this momentum. And just -- I think also, we're not going to be too specific around who's going to be invited to some of our speaker programs going forward as well. And as far as sort of how to sort of connect with a lot of the patients that are out there, we believe that the patient voice is really critically important in the treatment of narcolepsy.

As there really aren't, as you know, markers, blood markers or scans that really help assess impact of this disease. So our commitment is really to sort of focus on getting the appropriate education through the venues that patients seek information today. And we think there's really good opportunities for us to get out there because the narcolepsy community is, in general, pretty active online. So that really digital communication provides a very focused opportunity for us to reach out and make sure that the proper education information is out there on what we're doing in narcolepsy and upon approval, for once-nightly FT218 as well.

Yes. David, just 1 additional comment to Richard's comments around market expansion, our prescriber expansion. I want to differentiate those a little bit only because we believe within the current prescriber audience of these 4,000-plus per year, and those who are -- and within that subset to prescribe a lot more, there is a fairly reasonable-sized cohort of patients and every practice is a little bit different.

But in aggregate, that our sodium oxybate eligible as defined by those current prescribers, who aren't going on sodium oxybate, as Richard described a little earlier, whether that's because the physician has decided not to treat them, or the patient has decided not to go on it, the predominant reason is dosing related.

So in that category, we believe there's expansion opportunities within the current prescriber base, which makes it even that much more efficient for us accordingly.

Our next questions come from the line of Robin Garner with Craig Holland.

You shared some new patient insights earlier in the call. For context, can you share with us a ballpark of how many patients you've been able to engage during your market research?

Yes. Thanks, Robin. Yes. We -- patient market research is 1 of the interesting things that we do here as well. And I would say, in general, what we've seen is we've been able to engage with hundreds of physicians, patients and payers. We don't want to sort of break out the exact numbers of what we've done there. But it's fair to sort of say that it's more than -- it's dozens upon dozens of patients.

And then what we've also done is also been individual conversations as well to get more qualitative perspective. So -- and going forward, we will continue to do this not only through market research, but our engagement through patient advocacy and other sources as well.

So I can say from my perspective, the feedback from the payer work that we've done, if it's in market research, speaking to advocacy groups or individuals is generally pretty consistent. And I think for -- even though that there are some individual needs of patients out there as well. So hopefully, that gives you some of the perspective from what we do in a patient research.

Yes. And Robin, I'll just add 1 more comment to that, and that to Richard, and that is in particular, as time continues to go and the market continues to evolve, we're doing robust research. And it is a combination of both qualitative insights, as Richard described, but statistically, and market research-based quant studies that are robust and appropriately designed and with demographics that are meant to represent our target audience and geographically dispersed accordingly.

So we try to get quant work that's large to give us the right views and not make decisions based on very, very small sample sizes, but on large robust work products.

Okay. And then just lastly, will you be presenting any new data pain points at the Sleep Congress?

So just to be clear, are we presenting any new data at the Sleep Congress is what you asked?

Yes, that's right. Yes. Okay. Jen, do you want to answer that?

Yes. Robin, thank you for your question. So the new data that is being presented our post-hoc analyses, and this is data that we think is really relevant for clinicians to understand the abstracts have been published for the Sleep Congress. And our 3 post-hoc's are looking at efficacy stratified by subgroup. So in T1 and in T2, looking at efficacy by the subgroups of stimulant use or no stimulant use and also examining the weight loss that occurred with FT218.

And as I mentioned in my opening remarks, the consistency of benefit that is seen with FT218 underscores just how robust these findings are and how consistent the efficacy is. And so we look forward to having that full presentation in just a month's time.

Our next questions come from the line of Oren Livnat with H.C. Wainwright.

I just want to return back to the review process. With the caveat, we understand you can't comment on anything you can't comment on. But I'm getting a lot of questions as we get closer towards the PDUFA regarding any unknowns. Obviously, your tolerability profile look really good in Phase III, at least as good as Xyrem, but people are asking me, what do we know?

Or what have you already submitted with regards to the safety or risks around your drug delivery technology in general? Specifically, I'm getting asked about dose dumping work you've done or food effect, what you've done and how that might factor into the benefit risk calculation?

And then also just in the review, on the manufacturing front, I think in the past, you've mentioned bridging studies that you need or plan to do. Can you just remind us, is that just for your backup domestic supplier for a post approval? And how confident you're that FDA can inspect your original European manufacturer in time?

Yes. Great questions. As it relates to the technology itself, although I would say that this formulation is unique on its own to a certain extent, the technology has been approved in a prior product Coreg CR, which is Carvedilol, it's a beta-blocker commercialized by another product, another company in the past.

So the technology has been through, if you will, an FDA process, so to speak, from that perspective, although, again, this is an application of that technology and that process with its tailored to sodium oxybate in that regard.

But I would say that as it relates to the -- all of the nonclinical work that we had to do in our submission, again, we believe it's robust, it's complete, whether that's our food effect data or otherwise and the work we provided to validate this formulation and how this formulation performs in different settings that are required relative to our NDA, we feel really good about our submission. And obviously, that includes the drug-drug interaction data that we provided as well as part of our NDA submission.

As it relates to our CMC, yes, we have a primary supplier who's been making this product for well over 5 years. We filed with over 3 years of stability data. During the review process, we'll tick over 4 years actually of stability data. So they've been making it at this scale for quite some time.

So we feel we have a robust manufacturer who's been doing it for a long time, but we also recognize we wanted to have another source and a backup source. We've done all that work. We've completed those bridging studies, if you will, and that will be an action that will occur post-approval, as you referenced.

And with regards to access to your European facility given COVID dynamics...

Yes, sorry. Again, that -- we've seen some of the recent guidance from the FDA that has recently come out about how they'll prioritize inspections, the limited number, less than 0.5% or so that they claim of facilities that didn't get inspected tied to a review over the last 18 months that they needed to inspect.

That being said, this facility was recently inspected just prior to the pandemic and with no observations, no 43s, if you will, we've done all of our work to prepare for any sort of PAI with our partner, our CMO.

So at this stage, I would say there's nothing more to say on it at this point. And if anything comes up, we'll certainly update accordingly. But we see no reason that a PAI would be a deterrent at this point. But again, we have to work and see how the NDA process unfolds.

Our next questions come from the line of Matt Kaplan with Ladenburg Thalmann.

This is Raymond in for Matt. Congrats on all the progress so far. Maybe just a question on the market research. You mentioned that there were high levels of treatment refusals and high discontinuations after treatment starts?

And you said the second dosing as a main issue, but can you provide any color on any other sources of refusal and discontinuation and how FT218 might be positioned to capitalize on that? And my other question is just any updates you can provide on the switch study enrollment?

Yes. Richard, do you want to start with the first 1 and maybe Jen take the second?

Sure. No problem. Thanks, Raymond. So yes, as far as the research is concerned, we often focus on the inconvenience of getting up during the middle of the night for a second dose for the twice-nightly oxybate. But beyond that, there's a lot of other concerns that go on around the fear of waking up a partner, the leaving out your medications out at the nights with kids running around the house.

So there's a lot of stress on these patients that we find from the research in regards to more than just getting up during the middle of the night. And I think what we generally sort of see there is it's not easy. Also a lot of -- some of the patients have now gone to adjusting your dose, it's called asymmetric dosing to maybe take more of their dose earlier on and less later on during the middle of the night. So I think there's a lot of factors that continue to go on there. With these patients that go beyond just the perceived inconvenience of the second dose.

And I'll pass it over now to Jen on the second part of your question.

Thank you, Richard, and thank you for the question, Raymond. So we are now at just about 60 patients or approximately a 20% increase from our last call. We've got a number who are in the screening process right now. So we're looking to add to that overall number. We're also continuing to activate sites and of course, all of this is happening still in the remainder of the backdrop of worldwide pandemic.

There's also the unique aspect with FT218 because it is not yet FDA approved, it's considered a schedule 1 medication, which necessitates having to come in once a month to pick up the medication. What we're really pleased with in regard to this open-label witch study are the insights that we're gathering. And the primary purpose, of course, is long-term safety and tolerability. And we're also seeing, in addition to good results there, a sustained efficacy with FT218 as well.

And then lastly, it's preliminary, but the feedback that we're getting in regard to the preferred dosing regimen once or twice-nightly, has been extremely positive for once-nightly FT218.

There are no further questions at this time. I would like to turn the call back over to Greg Divis for any closing comments.

Thank you, again, and thank you, everyone, for your questions. In closing, to say I'm proud of every team member's contributions to where we are today would be an understatement. It's been a very, very busy few months but it's also exciting to see us closing in on the PDUFA date and ramping up our preparations for the next chapter in our company's history.

And I just want to reiterate and rest assured that this entire team is working very hard every day to deliver the best possible results for all key stakeholders. That includes patients and providers, but also importantly, it also includes our shareholders. And we'll continue to keep you apprised of our progress. And with that, we thank you for joining the start of the week and the start of your day with us and wish you a great rest of the day. Thank you.

Thank you for your participation. This does conclude today's teleconference. You may disconnect your lines at this time. Have a great day.