Greetings, and welcome to Avadel Pharmaceuticals Second Quarter 2023 Earnings Call. At this time, all participants are in a listen-only mode. A question-and-answer session will follow the formal presentation. As a reminder, this conference is being recorded. It is now my pleasure to introduce Austin Murtagh with Stern Investor Relations. Thank you.

You may begin..

Good morning, and thank you for joining us on our conference call to discuss second quarter 2023 earnings. 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 regarding the success of commercialization effects for LUMRYZ, expectations regarding the potential market impact, anticipated market availability and sales opportunities of LUMRYZ and the impact of competitive products and pricing.

These and other risks are described more fully in Avadel’s public filings under the Exchange Act included in the Form 10-K for the year ended December 31, 2022, which was filed on March 29, 2023, and any 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 today are Greg Divis, Chief Executive Officer; Dr.

Jennifer Gudeman, Senior Vice President of Medical and Clinical Affairs; Richard Kim, Chief Commercial Officer; and Tom McHugh, Chief Financial Officer. At this time, I’ll turn the call over to Greg..

First, REMS certifications, which is the first step before prescription can be written, are now greater than a thousand targeted prescribers who are certified. That's up from 625 as previously reported.

Second, new patient enrollments into RYZUP, our patient services center, which is the first step to a potential future dispense of LUMRYZ are now greater than 400-patient enrollments up from 140 as previously reported.

And third, progress on the reimbursement front, which is also performing ahead of expectations, which now includes the addition of LUMRYZ to the Express Scripts National Formulary, and now hot off the press, CVS Health has removed the new to market block for LUMRYZ on its commercial formularies in a non-preferred position.

This decision now allows a pathway to coverage for more than 30 million additional commercial lines. In summary, from a leading KPI perspective, while recognizing we're only in the first full quarter of launch right now with significant work ahead of us, we are pleased with these early indicators of our launch progress.

Looking at future quarters as our launch progresses, we expect the KPIs that provide a current picture of launch to evolve and our goal, as it always has been, is to be transparent as we report metrics that capture our launch progress.

Further, we expect to give all launch KPI updates on our quarterly earnings calls where all data provided will be as of quarter end.

Looking toward the future in the continued growth of Avadel, our strategy is to target opportunities that allow us to expand our patient reach in the rare sleep space with the goal to provide innovative therapies like LUMRYZ to more eligible patients.

In this regard, our team is on track to submit a supplemental new drug application for potential FDA approval of LUMRYZ in the pediatric narcolepsy population before the end of the 2023 calendar year. Additionally, we are progressing the clinical planning to initiate a multi-center randomized control trial in idiopathic hypersomnia.

And lastly, we continue our preclinical stage formulation work of a potential no or low sodium once-at-bedtime oxybate formulation for the small subset of sodium sensitive oxybate eligible patients who could potentially benefit from this type of innovation.

We look forward to providing updates as appropriate as physicians and patients have expressed significant interest in Avadel developing these needed treatment options.

Although, it's very early with much more to accomplish during the first few full quarters of launch, we are very pleased based on our early launch KPIs with our initial execution and continued pursuit of greater than the $1 billion peak sales potential opportunity that is there for LUMRYZ.

I will now turn the call over to Richard to provide an update on our launch progress.

Richard?.

Hey, thanks Greg, and good morning, everyone. Our LUMRYZ launch is off to a strong start and I'm excited to share our continued progress. Now, over the last 20 years, there has not been any innovation in improving the delivery of oxybate to people with narcolepsy.

The fundamental problem of forcibly waking patients who often already suffer from disturbances in nocturnal sleep existed until once-at-bedtime LUMRYZ was approved and launched in June.

With LUMRYZ, we have a simple and compelling proposition, and what we are seeing and hearing in the early weeks of our launch is a validation of our brand proposition and the market insights we had pre-launch.

Safe to say, we believe LUMRYZ provides a meaningful benefit to the narcolepsy community and, of course, this was further validated through the receipt of our Orphan Drug Exclusivity from the FDA. Turning to the commercial launch itself, we are approximately two months in.

We are encouraged by the strong progress thus far and the positive feedback we received from the narcolepsy community. Many from our leadership team and I have had this privilege of being on the road with members of our field force and speaking with sleep specialists and their teams firsthand.

Considering that collectively we are a relatively new team in the sleep field, the energy of our team and the engagement of sleep specialists has been terrific.

As our launch continues, we are focused on continuing to drive demand among high volume oxybate prescribers, encouraging patients to advocate for the use of LUMRYZ, securing payor coverage and delivering best-in-class patient services and reimbursement support.

From a launch team perspective, as of the end of July, all roles are now filled and trained and August we'll mark the first month with a fully deployed team. We continue to see very high interest and levels of engagement from sleep specialists and their staff.

Our sales team impact continues to grow, and we have now engaged with a vast majority of the top 1,600 prescribing offices that represent roughly 80% of total oxybate prescriptions. With the completion of our full team, we expect to continue to grow our reach and frequency to high volume oxybate prescribers.

As a reminder, we see the oxybate market in three key segments. First, 1,600 patients who are currently treated with twice-nightly first-generation oxybate. Second, around 16,000 patients from the last few years who have tried to discontinue to twice-nightly first-generation oxybate.

And third, around 3,000 annual new patient starts who are naive to oxybate treatment from the greater than 25,000 who are eligible for, but have not yet been treated with an oxybate.

We have seen high interest from our target HCPs and people with narcolepsy from all three patient segments as evidenced by the greater than 1,000 REMS certifications for HCPs and greater than 400 RYZUP patient enrollments in the first two months of launch.

For REMS, we are pleased to see the majority of certifications are coming from high volume oxybate prescribers, although we have also had HCP certified who have never previously prescribed and oxybate as well.

RYZUP patient enrollments have also been impressive, as enrollment in this patient services program begins a process for having LUMRYZ prescription filled and delivered to a person with narcolepsy.

Our data informs us that the majority of the greater than 400 RYZUP enrollments are switches from first-generation oxybate and that we are also getting patients naive to oxybate as well as previously discontinued to oxybate patients.

For RYZUP, while our processes are similar to what most offices do already to prescribe specialty REMS or controlled substances, systems and services can be viewed as different, and that is true for us with RYZUP.

For example, we did extensive research to determine key services to offer through RYZUP, like our access and affordability programs, including a $0 commercial copay program for eligible patients.

Our patient and temporary assistance program, along with personalized RYZUP nurse care navigators individually assigned to each person with narcolepsy and their sleep specialists.

It's been really great to see both people with narcolepsy and HCPs take advantage of our services and for our nurse care navigators, seeing them build relationships with the people they support. Before I provide a payor update, I'd like to summarize a few themes that from the time I've been in the field and from speaking with sleep specialists.

First, we have yet to meet a sleep specialists who does not see a need for LUMRYZ. In general, it's actually quite the opposite, where HCPs are really excited to learn about our once-at-bedtime sodium oxybate.

Second, we encourage to see some offices bring in several patients quickly, but we believe that most patients will visit their sleep specialists in their standard follow-up period, which is typically every three to six months.

And third, sleep specialists are getting used to our RYZUP services and they are trying them out to gain initial familiarity for themselves and their staff. Building the familiarity has been driven through our field reimbursement team who have been instrumental in educating offices on our services..

At Commercial Day, we announced the first of three GPO contracts had been finalized and signed as we secured Express Scripts coverage on the National Preferred Formulary effective July 1st.

We have now been listed with the majority of sent PBM covered lives, and as Greg just mentioned, CVS Health has removed the new market block for LUMRYZ on its commercially -- commercial formularies in a non-preferred position.

Having secured the opportunity for commercial reimbursement in major PBMs from two of the three GPOs in the first two months of launch, in addition to the others previously announced from Kaiser and many of the Blue Cross Blue Shield plans is certainly a leading positive performance indicator and a reflection of the great work done by our market access team.

Up to now, the majority of early prescriptions are being processed through medical necessity for which there is usually more paperwork and more time required to navigate these prescriptions.

We announced on our Commercial Day that we are pleasantly surprised that in the first few weeks that we already had some reimbursed patients on LUMRYZ, and since then we are -- have been extremely pleased to see the increasing reimbursement success our teams are having with LUMRYZ in the first couple months of launch.

And now with more commercial reimbursement for LUMRYZ that has been secured, we look forward to even more people with narcolepsy who will be able to access LUMRYZ in the future.

I covered a lot of ground today, and we believe that the early launch indicators have us well-positioned to have a significant impact and are confident that we will be able to capture a significant portion of the large oxybate market opportunity.

Our research shows us that the market opportunity for LUMRYZ could be much greater than that of current first-generation, twice-nightly oxybate market of about 16,000 patients on therapy with more than 50,000 potential eligible patients for LUMRYZ and the peak sales potential of greater than $1 billion.

Although, these are still the first couple months of launch, we could not be prouder of the launch execution that our team is delivering, and the receptivity we have received from the narcolepsy community. We look forward to providing more updates on future calls.

And with that, I'll turn the call over to Jennifer for details on our current -- on our recent scientific data presentations.

Jennifer?.

Thanks Richard, and good morning. It's been a monumental quarter for us, supporting the LUMRYZ launch, along with our strong presence at SLEEP 2023, and the publication of additional data that underscores the need for LUMRYZ.

Starting with SLEEP 2023, we were incredibly pleased to have delivered a meeting clinical presence of 12 posters and six oral presentations, which collectively support the strong LUMRYZ clinical profile and insight into patient needs.

For example, data from a social network study showed that more than 60% of people with narcolepsy consider among their most troubling symptoms, various sleep disturbances, including poor quality, sleep disrupted, nighttime sleep, fragmented sleep, and insomnia.

Among all the narcolepsy treatments, only LUMRYZ does not cause insomnia or require chronic middle of the night dosing. Once again, we presented ongoing data from RESTORE, the open-label study, which has now been underway for more than three years and continues to bolster the known safety and tolerability profile of LUMRYZ.

Most importantly, 94% of those switching from twice-nightly oxybate preferred the once-nightly dosing regimen. Turning to two new peer reviewed publications. First, we published in SLEEP a post hoc analysis of LUMRYZ REST-ON data divided by narcolepsy type.

No published data previously existed prospectively evaluating oxybate treatment on NT2 or narcolepsy without cataplexy. We have demonstrated a consistent efficacy profile for LUMRYZ in both in NT1 and NT2. These data are important as there is a perception of some suite clinicians and patients that oxybate should be reserved for NT1.

With this publication, we have the clinical study data to show favorable efficacy in NT2 as well. Lastly, we published a new Discrete Choice Experiment in advances in therapy.

As you may recall, we previously published a DCE among patients showing that the number one driver of sodium oxybate preference is the dosing regimen, with a strong preference identified for a single bedtime dose. We followed up with the second DCE this time among 100 clinicians and included sodium content as an attribute to assess.

The once-nightly dosing, which only LUMRYZ provides was more than twice as important for overall oxybate choice than the next two attributes, which were adverse reaction and sodium content, respectively. Our scientific data aligns with what we are now seeing in the real-world. LUMRYZ is fulfilling a significant unmet need.

I'll now turn the call over to Tom for an update on the company's financial.

Tom?.

Thank you, Jennifer. We are pleased to announce that we generated our first sales of LUMRYZ and reported $1.5 million of net revenue for the quarter ended June 30th, 2023, which represents initial stocking orders from all three of the specialty pharmacies in our distribution network.

And while we are not providing revenue guidance at this time, I can share that subsequent to June 30th, we generated additional sales from all through the specialty pharmacies as the launch of LUMRYZ has progressed.

We also reported a total of $51 million of GAAP operating expenses during the quarter ended June 30th, 2023, which is comprised of approximately $47 million of SG&A costs and $4 million of R&D costs.

I want to highlight approximately $18 million of expenses that impacted the quarter that drove OpEx higher than what we expect our cash operating expenses will be on a go forward basis. First, there was approximately $9 million of non-cash expenses.

The majority of which is tied to stock-based compensation, which includes a cumulative catchup adjustment of $6 million for previously granted equity awards. The $6 million cumulative catchup adjustment was recorded upon reaching the milestone objective of our first commercial sale of LUMRYZ.

Second, there was also a cumulative catchup adjustment of approximately $2 million for cash incentive awards that were tied to reaching the same milestone. Third, we incurred approximately $5 million of legal and other professional fees of which $3 million were contingent on receiving FDA approval and launching LUMRYZ.

And finally, we expensed approximately $2 million of commercial LUMRYZ inventory through R&D that was purchased prior to receiving FDA approval. Post FDA approval, commercial inventory purchases will be capitalized and expensed through cost of products sold.

After adjusting to these items, cash operating expenses in the quarter ended June 30th, 2023 were approximately $33 million, and we expect that quarterly cash operating expenses for the remainder of 2023 will be in the range of $35 million to $40 million. Finally, just a few comments on the balance sheet.

During the quarter ended June 30th, 2023, we completed the exchange of $106.3 million convertible notes for 12.3 million common shares. Effective with this exchange, we have just $21.2 million of convertible notes remaining, which matures in October of 2023, and our intent is to sell the principal and interest in cash.

And I'll wrap up with our cash position. At June 30th, we had approximately $161 million in cash, cash equivalents and multiple securities. In addition to that, last week, we received $30 million from the first tranche of the $75 million royalty financing commitment we secured earlier this year.

A second tranche of $45 million remains committed from the royalty financing is available if we achieve $25 million of quarterly net revenue by June 30th, 2024. But as a reminder, we're now required to drive the $45 million in the royalty.

We believe based on current plans and expectations that cash on hand at June 30th plus $30 million from the royalty financing and expected cash receipts from sales of LUMRYZ are sufficient to support the launch of LUMRYZ and bridge the company to cash flow breakeven.

For additional detail on our financial results for the quarter ended June 30th, 2023, please refer to the 10-Q or the press release issued earlier this morning. And I'll now turn the call back to Greg for closing remarks..

Thank you, Tom. We believe our strong foundation has supported our successful initial and very early launch of LUMRYZ, and we've remain laser focused on continuing to execute the commercial launch. We believe we've made significant progress in this area and look forward to potentially expanding our pipeline to reach more patients in the future.

We're excited to be in the field and actively changing the treatment paradigm for patients and are fully committed to realizing the value of LUMRYZ, which we believe has the potential to achieve peak sales greater than $1 billion. We thank you for your support and look forward to providing future updates on our progress.

And with that, let's open up the call for questions.

Operator?.

Thank you. [Operator Instructions] Our first question comes from Francois Brisebois with Oppenheimer. Your line is open..

Hi. Thanks for taking the questions. Congrats on the progress here. So, the first one, I just want to better understand RYZUP and just that metric. You have 400 -- sorry -- you 400 from the 140 that you had shared previously.

I just want to understand how should we think about those numbers and how they correlate to ultimately sales?.

Yeah. Thanks Frank.

Richard, do you want to talk about that?.

Yeah. Sure. Hey, good morning, Frank. Thanks for the question. So, first, we're super pleased with the progress that we've been making so far. And although, we're not providing specific guidance, what are doing right now is, it's hard to predict exactly how many of those patients will convert into sales.

But what we can say, and as I mentioned on our prepared remarks, is we have been really having increased success in getting reimbursements. In fact, one of the things I can mention as well is, we're probably not using our temporary assistance programs as much as we thought early on.

So, although, it's difficult to predict how many of those patients will convert, what I can say is no one is more motivated than us to get those patients on to product to LUMRYZ fulfilled for them as well..

Great. And then in terms of, are you ever going to share the average number or exit number of patients that are on drug, or should we expect these metrics to be the metrics going forward? And then just maybe a quick comment on the CVS news, is that earlier than expected, or kind of in line here? Thank you..

Yeah. On the metrics, again, as we shared back in the Commercial Day, we believed during these first few months, the most important leading indicators for us were REMS certifications, RYZUP enrollments, and reimbursement, because they -- those all feed into ultimately converting someone into a paid drug.

We absolutely agree that as we go forward and in future quarters, reporting patients on therapy is an important metric, right? And as Richard noted, and as what we said back in June, we were pleased just in the first month to see some patients already convert in a much sooner way than we thought.

We've only seen that accelerate, and we've -- as Richard noted, we haven't been required, are necessary to use our temporary assistance programs as much as we thought we may need. So, again, I think everything from our perspective is, is on track, and that will be a metric as we get go forward. We certainly were reporting.

And I'll just remind you that we're two months into the launch and this is our second update, and we haven't had our first full quarter yet. So, again, I think you'll see those data points start coming out in the future. In terms of your comment on CVS, Richard, is that on course and timing wise, or earlier than what we may have thought with.

Richard, feel free to answer..

Yeah. No, we're thrilled to actually have two significant payor reimbursement wins this early on two months post-launch. It's really been impressive to see.

I think it's a real testament to the work that both our medical and our market access team have been explaining the proposition of LUMRYZ to the payors and clearly them sort of seeing our value proposition and great negotiations.

So, the fact that we have two big wins already this quickly amongst many other smaller ones, is a real testament to sort of the early performance from our team..

Thanks Frank..

Thank you..

One moment for our next question. Our next question comes from Andrew Tsai with Jefferies. Your line is open..

Hey, thanks. Congrats on the progress. Appreciate the updates and thanks for taking our questions. Appreciating you do not necessarily want to share too much, but I'll try to ask in another way.

Of the 140 patients who have signed up as of June, and how many of them have been converted to a treated patients, just so we can gauge the speed as well as the depth of conversions.

And secondly, can you just also remind us how many patients remain in your open-label study right now, and when could they start rolling over to being a commercial patient? And if they were to be rolled over, would they be counted as a new patient in RYZUP, or would they automatically be classified as a treated patient? Thank you..

Yeah. Thanks. Thanks Andrew. Again, I think, we're early into the launch and the specific metric around actual patients on therapy will be something we talk about in subsequent quarters. We're very focused on the leading indicators into that. And we've made great progress there.

I would say that we've seen through -- what we noted at the end of June was we were pleasantly surprised again to see patients begin to get reimbursed in a fairly efficient way and go on commercial drug. And again, in July that's only accelerated. And in many ways, and Richard, you can comment, it's just these patients take some time.

So, the earlier patients are likely the ones converting sooner unless you're are converting -- unless you're in a benefit design that adjudicates fairly quickly. And we have a few of those for sure.

But I think what you're seeing is, the time that requires the move from the top of the funnel, which is what we'll characterize RYZUP is to out as a dispense, takes time navigating the medical necessity process until these more formal coverage policy decisions begin to take hold.

But at this point, I would say we're very pleased with how we're seeing that conversion occur, even back to the 140 versus what we had assumed, and perhaps equally as important is the lack -- the less dependency on what we call our temporary assistance program, which you may refer to as some sort of bridging or free drug program, but -- and not being required to use that at a level that we had assumed because of the team's ability to navigate the reimbursement process.

In terms of your open-label question, as we previously talked about, we had a little under 100 who were still in the trial at the time. I would say of the RYZUP enrollments, they represent the very small minority today. They are being processed into the system. They would count technically as a new RYZUP enrollment because it's independent of that.

We've seen some of those already transition into commercial drug. But I would say that that's in the works now and with a whole lot more to actually process through and ultimately move on to commercial drug..

Very clear. Thank you again..

One moment for our next question. Our next question comes from Ami Fadia with Needham & Company. Your line is open..

Hi. Thanks for taking my question. I guess, I'm going to try to understand that same metric in a slightly different way.

Can you talk about what are the steps that are required from the time a patient gets enrolled in the RYZUP hub and goes through all the steps before they can start to receive drug? And at which point, do you need to make the decision of whether you want to support that patient with free drug? If you could sort of talk to that process? And of the patients that are receiving drug today, what percent are receiving free drug, that would be helpful..

Yeah.

So, Richard, do you want to take those?.

Yeah. Sure. Hey, thanks for the question, Ami. So, I always remind myself that getting a new specialty product to a patient early in launch is just -- it's complicated for any product launch, right? And that's why we really overinvested in our services through RYZUP and our delivery reimbursement team.

So, the general process is this, you have to send in a RYZUP enrollment form that will begin the process. Sometimes information is complete and sometimes it isn't. Benefits investigation will begin. We'll start to identify. RYZUP will identify which specialty pharmacy is used, that will be done.

And then, a prescription will be sent in that can now go through the process. But especially before any criteria is set for prioritization from a payor, it generally is going to go through medical necessity, which is a much more manual process where an office has to write specific reasons why they're looking to use this product.

It goes to the payor, goes back and forth a couple times. So, the point is it takes a while. Once that is approved, then, of course, the pharmacy has to line up when that prescription will actually be fulfilled. So, prior to any coverage decisions being made through medical necessity, this takes well over a month for those things to happen in general.

So, not measuring in a few days or a few weeks, but definitely several weeks. And that's why getting some of these reimbursement wins with the payors is so important, because that should decrease the time of sort of going through the process as well. So, we're super pleased with how it's working because it is complicated.

But at the same time, as Greg and I have mentioned, we're also super pleased to sort of see the level of reimbursement that we're getting. And to your point, I won't comment on the percentage of free product, but what is -- what we're seeing is a lot more reimbursement wins than we had expected or projected at least.

And in general, the decision about when someone goes onto our temporary assistance program is really the decision between the patient and the provider. Because oftentimes they're -- if they're existing switch patients, they will have other product already or there's other things going in their life.

So, it is there to be offered, but a lot of times the decision of the patient and the provider, that's what we listen to and figure out when should we kick-in a lot of these programs as well.

And the last comment I can give is we actually have had drug that we were about to administer through our temporary assistance program where we did get approval for reimbursement right before we were about to send it out as well. So, this is a very dynamic period of launch.

And like I said, we're just really excited that A, we're getting patients on LUMRYZ and B, we're getting more reimbursement success than maybe we had first anticipated..

Maybe a follow-up to that, Richard, is just to sort of understand how -- you guys are trying to make sure that you don't lose these patients, while some of these steps are being undertaken.

It's good to see that over 400 patients are enrolled in RYZUP, but what I'm trying to understand is, are those going to eventually convert into patients on drug, or is there likelihood that a percentage of those patients will, maybe get lost through the process, either because the process was taking time or at some point the patient changes their mind, or what drug they want to be on?.

Yeah. Ami, it is a great question. Unfortunately for any product that's prescribed in the United States, there is abandonment that goes on from either the provider or the patient. But once again, that's why we invested as much as we did into our RYZUP services.

Our nurse care navigators have individual relationships with both patient and with the office, because that communication -- I think where people struggle the most is when they don't know what's going on.

And that's why our nurse care navigators really take the time to invest in the relationship, follow up with those patients as well, so they understand where they are in their process.

So, it's really hard to sort of say what patient -- what percent we'll stay on right now, but what we can say is that's why we really invested as much as we did into our services, because handholding patients and offices, especially early on, is so important so that they have a good experience and likely -- are likely to stay in the process than get -- than want to give up as well..

Yeah. The only thing I would add is that, we've built our programs to support patients at any point along this process. We are prepared to initiate our temporary assistance program as early as that patient and provider wants. The good news for us -- and that's what we assumed was going to be happening.

The good news for us is that that's not what's happened.

We've been able to keep them on and no one's more incentivized to keep them in the kind of system than us to keep them on and through the process and getting to a reimbursed product without having to use our temporary assistance program at a much, much lower rate than what we had originally assumed..

Got it. Thank you. I'll jump back in the queue..

One moment for our next question. Our next question comes from Marc Goodman with Leerink. Your line is open..

Yes. Good morning. First, anecdotal stories that your reps are talking about? Just what's go going on in the marketplace? Just you've got generics out there for Xywav, how Xywav is doing, you're taking share, obviously, just any stories that you're hearing out there.

And secondly, Tom, can you talk about what are sales that are needed to breakeven for the company? Thank you..

Richard, do you want to start?.

Yeah. Hey, Mac, thanks. Anecdotes are awesome and that's why also getting in the field, it's been terrific. Overall, what I can sort of say is there's been just really great receptivity from the offices that we have been in. Maybe a couple.

One anecdote I'll sort of share that's happened several times across the country is, we're a relatively new company and our representatives go speak to the receptionist and they don't know the doctor yet. And we leave their call, they say, come back in a few weeks.

And then we've had doctors literally call or chase our reps in the parking lot to sort of say, can you please come in if you've got that once-at-bedtime therapy? So, I think it's just been really cool to see. Clearly, we're in a very competitive marketplace, but we have a very clear strategy, we have very clear messaging.

And we really think the conversations have been great. So, thus far I think it's been really a thrill and an honor to be out there. And there's a lot of energy from our team because the receptivity from the specialist offices has been great. And I guess we'll turn the next question over to Tom..

Yeah. Hi, Mac. Thanks for the question. I think rather than thinking about it in terms of sales, which I, of course, understand your question, I think about it in terms of paid patients on therapy.

If I use what I described as our expected cash run rate of $35 million to $40 million per quarter, you annualize that, you think about number of patients, paid patients on therapy of, something in the range of about 1,500 patients. At that level, we're probably -- the sales required to achieve breakeven profitability..

Thanks..

One moment for our next question. Our next question comes from David Amsellem with Piper Sandler. Your line is open..

Hi, thanks. This is [indiscernible] on for David. Just a couple questions.

First, realizing it's still early, but just based on some early feedback, can you comment on the patient types where you've seen the most actual uptake or demand so far? Whether this is patients that are currently on twice-nightly oxybate, but just prefer the once-nightly, or have been on twice-nightly in the past, or oxybate naive.

And then in terms of the payor landscape, I'm wondering what your current expectations are for whether any plans are making patients step through generic oxybate or if you're expecting that in the future. Thanks..

Thanks. Richard, do you want to -- those are for you..

Yeah. No problem, and thanks for the question. So, yeah, as far as the patient types we're sort of seeing coming into RYZUP, the majority thus far are patients who are currently on a first generation twice-slightly Oxybate. However, we are also seeing patients who are naïve to oxybate and also patients who have previously discontinued.

So, a nice mix overall. But the majority thus far are patients who are previously on -- or sorry -- currently were switching from a first-generation oxybate. And as far as your second question is concerned, our whole strategy has been to get parity access with the best of the first-generation oxybate.

Thus far, we are not seeing any impact for a step through a generic for LUMRYZ. Our strategy has been for that not to happen. So -- and thus far, the plans that we have been listed with do not require a step to go through any oxybate prior to us as well.

So that's really our strategy is to really make sure that the payor -- we're not disadvantaged through a payor perspective from an oxybate access. And we really focus on sort of the communications and what we do in the offices with the sleep specialist as well..

Great. Thank you. That's helpful.

And if I could just ask one more, just how are you thinking about the opportunity for LUMRYZ IH? Do you think that a once-nightly option is more suited to this population? Do you have any thoughts on that?.

Richard, do you have -- you have any commentary and then maybe Jen?.

Yeah. For IH, through our ad boards and speaking through our top specialists, the general feedback we receive is as strong as our value proposition is in narcolepsy for LUMRYZ.

It may even be slightly stronger in IH, especially when you consider the sleep inertia that patients with IH have and sometimes their inability to wake up and take their medication or another dose. So, I think there's a lot of interest in that.

And that's why we have been spending collective time really looking at the opportunity to get our clinical program going.

But Jen, anything you'd like to add?.

I'll just emphasize what you mentioned, Richard, and that is the sleep inertia. That is the reason with the twice-nightly formulation, they allowed for once-nightly dose up to six grams because patients simply could not wake up to take the second dose.

But it is really important to note that you could only go to six grams, and that is sub-therapeutic for a number of patients. And so, we certainly hear through our MSLs, through all of our interactions that there is a massive need to have LUMRYZ available for the IH population..

Helpful. Thank you all..

One moment for our next question. Our next question comes from Matt Kaplan with Ladenburg Thalmann. Your line is open..

Hi. Thanks for taking the questions. Just a quick follow up on the prior question on IH opportunity.

Can you talk a little bit about the timeline, that you envision for LUMRYZ in this to develop it in this indication?.

Yeah. I think, Matt, it's a little early right now to be that -- to be precise on that. We -- there's a number of steps we have to go through from clinical supply quota to, getting our protocol finalized and approved and filing our IND and all that, all -- we're in all the works of that now. And we'll certainly update as we cross you key milestones.

It's certainly going to be an event that -- I wouldn't envision to kind of level set that we would be initiating a clinical trial in 2023. There's just a lot more work that has to be done to get us to that point, and we certainly wanted to make sure we got through our approval with LUMRYZ in narcolepsy first, so that's in full force with our team.

And so, we'll update as we go forward..

Great. Great.

And then, question maybe for Richard, in terms of the mix of patients understanding that what you're seeing mostly now, or the majority are the switches, how do you see that evolving over time? Or are the switches kind of, let's call them the low hanging fruit, or the patients who were previous on oxybate therapy and coming back to therapy.

Are those -- do you see a shift to those being the majority of patients over time?.

Yeah. Matt, great question. And yeah, if we just think about our patient segments, there are more patients who have been on an oxybate than the other segments right now. So, yeah. Right now, just from the sheer number of patients who sort of go through, there's probably more of those patients currently on therapy.

I think over time we will start to see a little bit more of a balance across the three different segments there. So, I think early on we're sort of seeing a lot of the usage being consistent with the market research that we've done.

And what that showed us is over time, we should also be able to grow sort of the new patient segment as well beyond the 33,000 patients who currently go on annually for first-generation oxybate..

Okay. Thank you.

And then last question in terms of, on the theme of anecdotes in the field, what are you hearing in terms of counter detailing from Jazz in the field on you guys?.

Well, I think those are always better questions to ask them. But I think, in general, they've been very consistent. I think the message is mostly focused on sodium and clearly as a new company, just -- the challenges in getting a new product sort of reimbursed. But we are so well prepared for that. We've been clear and focus on that from day one.

So, Matt, what I can sort of say is nothing unexpected and our team is in a great position to handle any objections that come to them clinically or from the competition as well. So just happy to be out there and having our teams in front of these specialists now..

And maybe just one more follow up.

I guess, given the significant amount of awareness of LUMRYZ prior to the launch, do you think the rate of patients enrolling into the RYZUP system will -- I guess was there a warehousing of patients waiting for the approval and kind of eager to get in line there? Or do you think that pace of enrollment should continue, or accelerating?.

Yeah. I think, Matt, I think as we shared, I think some of our insights from being in the field is that there are certainly examples of an office who has a number of patients who they are processing and prosecuting, I don't know if I'd call them warehouse, so to speak.

But I think our view is that what we've heard in the field, at least from treaters is that they'll see patients in their ordinary course, which is why it's important for us to execute on our direct to patient campaigns and to really deploy our strategies and tactics to activate patients to advocate for their therapy and go seeking out LUMRYZ as well.

So, those are things that we're doing, of course, that will have impact over time. But I think our view is that, and we've seen this early in the launch, like you would expect, we've seen a cumulative increase kind of as time gone on in terms of enrollments and dispenses and things like that. So, our view is that that should continue.

And listen, if somebody has a large bolus that are ready to come into our system and to RYZUP, we will deploy our resources to support them. And we're prepared and have the capabilities to handle that. But I think our assumptions are that, that things will happen in the ordinary course..

Great. Thanks. Thanks for taking questions..

One moment for our next question. Our next question comes from Chase Knickerbocker with Craig Hallum. Your line is open..

Morning, everyone. Thanks for the question. Just another one on RYZUP for me. Maybe hit a different vein. Talk us through the patient mix you have converted onto the drug at this point. I understand it's a fair mix of switch naive, previous discontinuation in the funnel. But maybe talk us through the mix you've pulled out of the funnel at this point.

Is it a much easier process I would imagine from the medical necessity and PA process for switch patients? And then -- but is it slightly less success you have pulling naive patients or discontinued patients out of the channel? Or is it a fairly similar process that is being required? Thanks..

Yeah. I think the short answer in that is -- Richard, feel free to weigh in, but I think it's reasonably representative of how they've come into the funnel and some of that is time dependent, right? So, if there's more -- when they come in and how long it takes them is individual from that standpoint.

We've had patients come in early who maybe come from all three of those groups that have prosecuted quickly. But I think generally given how it's been distributed coming in at the top of the funnel, I think, directionally it represents that coming out of the funnel. So, Richard, feel free to weigh anymore..

Yeah. Spot on..

I mean, maybe talk just to the difference in medical record requirements in the process between the three and if they're kind of a -- if they're kind of a similar pull through the bottom? Is it fair to think that they're not -- one in particular isn't a lot more cumbersome than the rest?.

Richard, feel free to add..

Yeah. Chase, it's hard to get into that level of detail because here's what happens in medical necessity. You may actually deal with one insurer, but you may actually deal with many different case reviewers.

So, it's a little bit of who do you get on what day of the week do you get? So, I think, overall, we've just been very impressed that we have been able to get as many through as we have already. And I think that really talks to both payors and actually clinicians being very clear about the clinical value proposition that LUMRYZ has.

So, the fact that this isn't a me too, that fact that this isn't me, is the fact that this is fundamental to how narcolepsy should be managed. So, to us that's really been maybe the best upside is the fact that it appears to us that both the clinicians and the people reviewing these cases understand our clinical value proposition..

Yeah. I think the other way to think about it, Chase, is that if there's not a formal coverage policy decision, then we're going through medical necessity and it's going to go through those steps, whether it's a de novo naive or a previous or a switch.

So, in many ways, it kind of operates the same way until there's this decision that the prior authorization criteria is set, the coverage policy is in place, then it operates differently from that standpoint..

Okay. That makes sense. Yeah. That's helpful color. And maybe just one on another kind of vein on color from the field. Maybe talk about sort of additional boon you've received from the clinically superior opinion from the FDA that's implied in the orphan designation.

Maybe feedback from the reps and how they've been effective at kind of outlaying that message in the receptivity of physicians..

Richard?.

Yeah. No, it's a great question, Chase. It's a very candid. It's a little bit overwhelming for some of our customers to hear that, because they're not used to hearing that.

And what we've really had to do is break down why we received, not only our drug exclusivity to make through the major contribution patient care, but in essence almost get into the steps of why we are deemed to be clinically superior. The fact that it's important not to disrupt nocturnal sleep.

You're trying to avoid sleep fragmentation and with LUMRYZ you can avoid that. So, I think once you explain the steps, it becomes a lot more digestible, because the statement on its own is almost -- in some ways almost too powerful, right? So, we've really had to make sure we can explain the why behind it as opposed to just the statement itself.

And I think once the why is explained, there's a lot more head nodding that goes on than just giving the statement on its own. So, it's a great message for us clearly, and we're just learning how to make sure it is better digested from our customers as well..

Got it. That's it for me. Thanks guys..

One moment for our next question. Our next question comes from Myriam Belghiti with LifeSci Capital. Your line is open..

Hi. Good morning and congrats on the progress. Just one quick question for me.

What color can you provide on the one month discontinuation rate in these early adopters of LUMRYZ? And thoughts on how this compares to Xyrem or Xywav?.

Yeah.

Richard or Jen -- maybe, Richard, do you have any commentary on that first?.

Yeah. Hey, Myriam, good morning. Thanks for the question.

It's really early, right? So, we're just beginning to get patients on, so it's -- what's difficult when you look early on is sort of at what point in time do you consider someone discontinued? And generally most of our rules, we sort of have step up rules once a month has gone by without a refill or three months has gone by or six months.

But you also have to recall that not every patient does get things in a standard order. So, it's really too early for us to comment on this. And I think we're going to have to sort of get through probably a couple quarters before we'll really understand a lot more of what that looks like..

Got it. That makes sense. Thank you..

And I'm not showing any further questions at this time. I'd like turn the call back over to Greg Divis for any closing remarks..

End of Q&A:.

Well, thank you everyone, and thank you for your time and for joining us today on our second quarter call. Have a great rest of the day. We look forward to providing updates as we go forward. Thanks..

Ladies and gentlemen, this conclude today's presentation. You may now disconnect and have a wonderful day..