Harmony Biosciences Holdings, Inc.

Good morning. My name is Brittany and I will be your conference operator today. At this time, I would like to welcome everyone to the Harmony Biosciences fourth quarter and full year 2023 financial results conference call. All participant lines have been placed on mute to prevent any background noise. After the speaker's remarks, there will be a question and answer session. If you would like to ask a question at that time, please press star one on your telephone keypad. Please be advised that today's conference, it may be recorded. Lastly, if you should require operator assistance, please press star zero. I would now like to turn the call over to Lewis Denae, Head of Investor Relations. Please go ahead.

Thank you, Operator. Good morning, everyone, and thank you for joining us today as we review Harmony Biosciences' fourth quarter and full year 2023 financial results and provide a business update. Before we start, I encourage everyone to go to the investor section of our website to find the materials that accompany our discussion today, including the reconciliation of our GAAP to non-GAAP financial measures. At this stage of our lifecycle, we believe non-GAAP financial results better represent the underlying business performance.

Our speakers on today's call are Dr. Jeffrey Dano, President and CEO of Jeffrey Dirks, Chief Commercial Officer, Dr. Kumar Badur, Chief Medical Officer, and Sandeep Kapadia, Chief Financial Officer and Chief Administrative Officer. As a reminder, we will be making forward-looking statements today, which are based on our current expectations and beliefs. These statements are subject to certain risks and uncertainties.

Our actual results may differ materially, and we undertake no obligation to update these statements, even if circumstances change.

We encourage you to consult the risk factors referenced in our SEC filings for additional details. I would now like to turn the call over to Dr. Jeffrey Dana. Jeff?

Thank you, Louis. And thanks everyone for joining our conference call today. Harmony continues to be a growth story, as demonstrated by our team's accomplishments throughout 2023. We delivered another strong year of performance across the organization, growing revenue and average number of patients on WACICS. We advanced all our clinical development programs for Pitocin, moved the next generation or next gen formulations of Pitocin into the clinic. and expanded our pipeline and diversified our portfolio with the acquisition of Zynurba and the ongoing Phase III clinical trial in patients with Fragile X syndrome. Yesterday, we announced that FDA granted priority review for our supplemental NDA or SNDA for WACICs in pediatric narcolepsy with a BDUFA date of June 21st. Earlier this week, we also shared that FDA granted orphan drug designation for Pitocin for the treatment of Prader-Willi syndrome, or PWS, as we are preparing to initiate our pivotal phase three tempo study in patients with PWS down to age six. All of this reflects momentum across our organization, from our commercial business with Wachix and Narcolepsy to our clinical development programs, as well as positive interactions with FDA related to these programs. These outcomes also reflect excellence in execution and the dedication of our team to deliver on the strategy we have laid out and are executing on. In addition, we returned capital to shareholders via our share repurchase program and will continue to take an opportunistic approach to this program throughout this year. I am very excited for the year ahead and believe that Harmony is poised to accelerate our growth in 2024. For the fourth quarter, we reported weightage net revenue of $168.4 million last and full-year net revenue was $582 million, representing growth of 31% and 33%, respectively. This result demonstrates the significant underlying demand for WCAG and the durability of the brand going into year five in the market. Other factors that drive our confidence in our ability to grow WCAG include its meaningfully differentiated product profile, which results in its broad clinical utility. Couple that with our ability to reach the broad prescriber universe of approximately 9,000 HCPs who see and treat almost 100% of the diagnosed narcolepsy patient opportunity. We have seen growth in patients on WACICS and prescribers every quarter since launch, even with the entrance of new branded and generic OxyVe treatment options coming into the market over the past few years. Finally, while there are several investigational agents in the clinic for narcolepsy, we do not see any new or novel mechanisms of action coming to the market that will impact the growth of Wakex until late during its life cycle in this polypharmacy market. Based on these reasons, along with the vast market opportunity that remains in narcolepsy, we believe that we can continue to grow the franchise for years to come and remain confident that WAKIX represents a $1 billion-plus opportunity in adult narcolepsy alone, and we are well on our way. This is evidenced by our net revenue guidance for 2024, ranging from $700 to $720 million. In addition to our strong commercial performance, we also advanced and expanded our clinical development enterprise on several fronts. Kumar will provide more details on our clinical development programs later in the call, but first let me highlight some of our progress. Starting with pediatric narcolepsy, we are pleased that FDA granted priority review for our SNDA for WACICS. This expedites the review process, and FDA has set a PDUFA date of June 21st. We look forward to collaborating with the agency to potentially introduce a new non-scheduled treatment option for pediatric patients living with narcolepsy. Turning to idiopathic hypersomnia, or IH. After completing our review of the full data set, We continue to believe that, based on the totality of the data, along with Pitocin receiving orphan drug designation for IH, and against the backdrop of only one currently approved product, that there is a strong case to be made regarding the overall benefit-risk proposition of Pitocin for patients with IH. We will be engaging with the agency with this goal in mind, have a meeting scheduled with them next month and look forward to working with the agency on bringing a potential new non-scheduled treatment option to patients living with IH. Our current life cycle management programs for Pitocin, which include IH, Prader-Willi syndrome, and type 1 myotonic dystrophy, represent about 100,000 diagnosed patients in the U.S., So if successful, these new indications could contribute up to an additional $1 billion of revenue to the WCAG franchise. Given Ptolemy's novel mechanism of action and the success of WCAG in the market, we've been working on next-gen formulations of Ptolemy with the goal to generate new IP and extend the Ptolemy franchise out beyond 2040. These programs entered the clinic last quarter, and we are on track to report PK data in the first half of this year. Another key component of our growth strategy is business development to expand our pipeline beyond WakeX and diversify our portfolio beyond SleepWake. The Zynurba acquisition, which closed last October, represented an important step in that direction and was an excellent strategic fit for Harmony, bringing in two late-stage development programs focused on orphan rare neuropsychiatric disorders with significant unmet medical needs. And we are not stopping with the Zynurba acquisition and remain very active in business development, continually assessing the BD landscape with a focus on rare neurological disease assets and other rare disease assets with unmet medical needs. where we can leverage our existing infrastructure and synergies across our organization. We are looking for assets across a range of development stages with a preference for late-stage assets but open to early-stage assets where there is a strategic fit. With approximately $426 million in cash, cash equivalents, and investments at year-end, we are in a solid financial position to execute on BD opportunities which is a strategic priority for us. In conclusion, I am proud of our team's accomplishments in 2023 and what we were able to do to help patients living with narcolepsy while advancing our development programs in other rare disease patient populations. We experienced solid and durable growth in our core commercial business, strong momentum in our clinical development programs, and expansion and diversification of our pipeline assets. Based on the dedication and commitment across our organization, I am very excited for our opportunities in 2024 as we remain focused on developing and commercializing innovative treatments for patients living with rare neurological diseases who have unmet medical needs. I will now turn the call over to Jeffrey Dirks, our Chief Commercial Officer, to provide more details on our commercial performance. Jeff?

Thank you, Jeff. 2023 was a strong year of growth for WACICS in year four of our commercialization in adult narcolepsy. The fourth quarter represented the strongest revenue quarter in our history, with continued growth and momentum in our underlying business fundamentals and top-line performance metrics. Net revenue for the fourth quarter was $168.4 million, representing 31% growth from the same quarter prior year and our second consecutive quarter of over $150 million in net revenue. Full year 2023 net revenue was $582 million, a 33% increase from full year 2022. We continue to see strong double-digit growth in net revenue for WCAG heading into year five of our commercialization. reflecting continued high interest of WAKIX in the narcolepsy market. The solid performance and continued growth reinforces our long-term belief that WAKIX represents a potential billion-dollar-plus opportunity in adult narcolepsy alone. I'd like to share a few key highlights from our performance in the fourth quarter on slide five. The average number of patients on WAKIX in the fourth quarter increased to approximately 6,150. an increase of approximately 350 average patients sequentially from what we reported last quarter. The impressive growth in average patients in the fourth quarter was driven by strong top-line demand and new patient starts and speaks to continued product adoption. And more importantly, it highlights the remaining large diagnosed patient opportunity that we continue to tap into each quarter as the market allows. In addition to the strong growth in average number of patients on WAKIX, we also saw continued product adoption of WAKIX by the narcolepsy healthcare community, both in new and existing prescribers. The number of unique prescribers of WAKIX increased again in the fourth quarter. And importantly, we continue to see growth in product adoption of WAKIX in the prescriber base beyond OXYBATE REMS-enrolled healthcare professionals. Of the approximately 5,000 healthcare professionals not enrolled in the OxyBait REMS program, more than 30% of them have prescribed WAKIX to date, up from 25% reported on our last earnings call. In addition to the continued growth of our prescriber base, we also saw strong growth in the depth of prescribing within the approximately 4,000 OxyBait REMS enrolled healthcare professionals. Our ability to reach and educate the broad narcolepsy-treating healthcare professional universe allows us to access the full-diagnosed adult narcolepsy patient opportunity and gives us confidence in continued growth for WAKIX. The availability of new and generic oxibates hasn't impacted patient or prescriber growth or existing strong payer coverage for WAKIX, given its meaningfully differentiated product profile. WAKIX remains the first and only FDA approved treatment for EDS and cataplexy narcolepsy that is not scheduled as a controlled substance. An attribute that continues to appeal to a broader narcolepsy healthcare professional audience and patient population and is a driver of brand growth. In summary, 2023 was another year of strong commercial performance for WAKIX. Full year net revenue of $582 million, 33% growth versus the full year 2022. The fourth quarter represented the strongest revenue quarter for Harmony to date, with over $168 million in net revenue. The average number of patients on WCAG increased to approximately 6,150. The WCAG prescriber base within and beyond the OxyBait REMS-enrolled healthcare professional audience continued to grow. And lastly, payer coverage remained strong, even with the availability of new and generic OxyBait options. WAKIX continues to demonstrate durable growth in the narcolepsy market. We've seen growth in patients and prescribers every quarter since launch, even with branded and generic treatment availability and new launches during its first four years on the market. Looking ahead to 2024, we expect continued growth in the underlying business fundamentals for WAKIX, with net revenues expected to be between $700 and $720 million. We anticipate a similar quarterly rhythm to our business in 2024 with what we've experienced in previous years. Traditional seasonal payer dynamic headwinds that impact the entire industry as a whole in Q1. Tailwinds coming out of Q1 and Q2 with stronger prescription demand. Typical seasonal headwinds in Q3 with lower patient visits that are common for all products and diseases that are chronically managed. And tailwinds in the fourth quarter as we close out the year. With no new competition expected in 2024 and limited differentiation in generic and branded products in the near-term pipeline, coupled with the large remaining diagnosed patient opportunity, unmet need, and the polypharmacy nature of the narcolepsy market, WAKIX is well-positioned for continued growth. Our ability to educate the broad REMS and non-REMs narcolepsy training healthcare professional audience, and ability to tap into the full diagnosed patient opportunity, gives us confidence in the long-term potential for the brand to represent a billion-dollar-plus opportunity in adult narcolepsy alone. Our commercial business has been resilient, and I appreciate the dedication and impact of the entire commercial team and the passion that they have for the narcolepsy patient community. I would like to now turn the presentation over to Kumar Badur, our Chief Medical Officer, to provide an update on our clinical development pipeline. Kumar?

Thank you, Jeff. Last year was a defining year for Harmony R&D. We made great progress in advancing, expanding, and diversifying our portfolio, working on nine different development programs across five different assets, several of which are in late stage development. It is not just the numbers, but also the complexity of the program. as we target a broad set of indications in rare disease patient populations with significant unmet medical needs. As we grew our portfolio, we also built a strong, experienced, and dedicated R&D organization ready to take on new opportunities as we continue to build our existing portfolio with new assets via business development. I'm proud of the work that our team does every day as we look forward to delivering potential new treatment options for patients with rare diseases with high unmet needs. Our full clinical development pipeline is shown on slide number seven. Starting with pediatric narcolepsy, We submitted a supplemental NDA to the FDA for an indication in pediatric narcolepsy in the fourth quarter, and we are pleased with FDA's decision to grant a priority review. This decision highlights the need for new treatment options for the approximately 4,000 pediatric patients living with narcolepsy. The FDA has set a periodical date of June 21st. We look forward to working with the FDA to potentially bring a non-scheduled treatment option administered once a day in the morning for pediatric patients with narcolepsy. Moving on to our development program in idiopathic hypersomnia. We completed our review of the full data set and submitted an FDA meeting request in the fourth quarter to discuss a path forward, and the meeting is scheduled for March. We are optimistic that we will be able to find an efficient path forward to bring Pitolacent to patients with idiopathic hypersomnia. Our optimism is based on the totality of the data, which strongly supports Pitolacent's efficacy in patients with idiopathic hypersomnia, especially in the context of high-unmute need with only one drug approved, which is Kegel Class III control substance with a REMS program and the off-label use of class 2 control stimulants in significant safety issues. The data from the open-label part of the study, double-blind the randomized withdrawal part of the study, and the ongoing long-term extension study in conjunction with the denied safety profile offer a strong benefit-risk proposition in favor of Pitolafent for patients with idiopathic hypersomnia. We look forward to engaging with the FDA in the meeting scheduled next month and making a strong case for a positive benefit-risk profile for pitulocentin-D-dipathic hypostomnia. We will provide further updates on the IH program at our next earnings call. For Prader-Willi syndrome, we are on track to initiate the Phase III TEMPO study in the first quarter of this year. This will be a global, double-blind, randomized placebo-controlled study that will randomize approximately 134 patients to either Pitocin or placebo in a one-to-one ratio. The duration of the double-blind treatment period is 11 weeks. The age range is six years and older, and the primary endpoint is change in severity of excessive daytime sleepiness as measured by COM-SRI T-score from baseline to the end of double-blind treatment period compared to placebo. Based on the promising data from the phase two proof of concept study, we are also evaluating the irritable and disruptive behaviors which are common in PWI. This phase three registration study is designed not just to meet the requirements for an indication in PWI, but also fulfill one of the two requirements to gain pediatric exclusivity. We remain confident and committed to gaining pediatric exclusivity for vacuums, which will offer an additional six-month regulatory exclusivity on the back end of the montaged pathogen site. Based on the discussions with the FDA, we have a clear line of sight on the requirements for a PWR, which include data in pediatric narcolepsy patients and data from the phase 3 study in PWRs. we are making steady progress to meet these requirements. The pediatric narcolepsy SNDF submission in the fourth quarter and the initiation of phase III PWS studies this quarter are designed to support our efforts to gain pediatric exclusivity for babies. In myosinic dystrophy type 1, RDM1, we were pleased to report positive top-end results from the phase II proof-of-concept study, where we saw clinically meaningful improvements in not just excessive daytime sleepiness, as measured by the daytime sleepiness scale, but also in fatigue, which was assessed using fatigue severity scale. And these data are summarized on slide nine. It's important to note that these two symptoms, excessive daytime sleepiness and fatigue, are present in approximately 80 to 90% of patients with DM1, and these symptoms are as impactful as the core symptoms of myotonia and progressive other weakness. A clear and consistent dose response was also demonstrated, with the higher dose showing a greater response than the lower dose across the study endpoint. In addition, The safety profile in this patient population is consistent with the established safety profile of Pitocin. We are currently reviewing the complete data set to assess the opportunity and inform our next steps. As we have noted in the past, this is an indication which could be devoted to the next-gen Pitocin-based formulation, which will have a much longer pattern to unveil. We continue to make good progress on the next-gen Pitocin-based formulation, NG1 and NG2, with our partner BioProsaic, with the goal of generating new IPs, extending the Pitocin franchise beyond 2040, and bringing new treatment options for people living with rare diseases. Please note, we have updated the naming conventions for these two formulations according to their respective market entry timing. Next in one, our NG1 is a modified formulation of pitolafent with the potential for clinical differentiation and a fast market strategy based on the demonstration of bioequivalence. We expect to launch NG1 within the vehicle lifecycle. Next in two, our NG2 is an enhanced formulation of pitolafent designed to deliver an optimized PK profile and a higher dosage strength. This formulation will have a new IP, a full clinical development program, and is expected to be launched towards the end of May next life cycle. Both formulations, NG1 and NG2, entered in the clinic in the fourth quarter, and we expect peak data on both of them in the first half of this year. We were also pleased to expand and diversify our pipeline last quarter with the acquisition of Zynobar. This brought in ZYN-002, a pharmaceutically produced synthetic cannabidiol, devoid of THC, for transformer delivery, which, like VATICS, represents another portfolio in the product opportunity. We are currently enrolling patients in pivotal phase 3 V-connect trial in Sardar-like syndrome and are very excited about this opportunity. There are approximately 80,000 patients diagnosed with Farber-Leck syndrome in the U.S. with no approved treatment and significant unmet medical need. We had an opportunity to assess the timeline of the ReConnect trial and expect to complete patient enrollment in the first quarter of 2025 with top line data in mid 2025. RYM002 was also studied in an open-level phase II proof-of-concept study in patients with 22q deletion syndrome, known as the INSPIRE trial, which generated promising data. This represents another market opportunity of approximately 80,000 patients in the U.S., and we have been interacting with FDA about phase III programs in 22q. It is worth noting that ZYN-002 is a global opportunity for Harmony, and we look forward to exploring FUS opportunities to bring this novel treatment to people living with Fragile X syndrome and 22Q around the world. To conclude, we have made great progress at Harmony in advancing, expanding, and diversifying our portfolio, resulting in a pipeline with multiple late-stage programs. I look forward to sharing additional updates as we continue to make progress on our clinical development program. On behalf of Harmony, I would like to thank all the patients and their families who are participating in our clinical trials, as well as the clinical investigators and site personnel for their effort and commitment in helping us to advance our development program. I have now turned the call over to our CFO, Sandeep Kapadia, for an update on our financial performance.

Thank you, Kumar, and good morning, everyone. This morning, we issued our fourth quarter earnings release and filed our 10-K, where you'll find the details of our fourth quarter and full year 2023 financial and operating results. Our financial performance is also shown on slides 10 through 13. We finished the year with strong momentum across the business, helping us deliver solid growth across several key metrics, We reported $582 million in annual WCAG net revenue, achieved our third year of profitability, along with robust cash generation. In addition, we advanced our Cthulhu and Lifecycle Management program and executed on business development with the acquisition of Zenergo. We also deployed capital towards our share repurchase program. Overall, we remain well-positioned to execute on our growth strategy moving forward. So let me take a moment to review our financial results in more detail. For the fourth quarter of 2023, we reported our strongest revenue quarter in company history, with net revenues of $168.4 million compared to $128.3 million in the prior quarter, representing a growth of 31%. Performance in the quarter reflects the strong continued underlying demand for Wacom. In the fourth quarter of 2023, operating expenses were $85.1 million compared to $53.8 million in the prior year quarter. The higher operating expenses were primarily driven by our advancement of our clinical development programs, including ZYN-002, expenses related to the commercialization of Wakex, and one-time Zinurba transaction-related costs of $9.8 million. Operating income for the fourth quarter of 2023 was $40.2 million, compared to $47.6 million in the prior year quarter. Non-GAAP adjusted net income for the fourth quarter of 2023 was $42.8 million, or $0.73 for diluted share, compared to $61.9 million, or $1.01 for diluted share in the prior year quarter. We believe non-GAAP adjusted net income better reflects the underlying business performance. please refer to our press release for a reconciliation of GAAP and non-GAAP results. We ended the year with $425.6 million of cash, cash equivalents, and investment securities on the balance sheet. The balance reflects continued strong cash generation with approximately $77 million in cash from operations in the fourth quarter, offset by the Zinerva acquisition costs and share repurchase activities in the quarter. For the full year of 2023, we generated $219 million in cash flow operations. During the fourth quarter, we returned capital to shareholders and repurchased approximately 1.8 million shares of common stock for $50 million, bringing the full year total of repurchase activities to 3.2 million shares of common stock for $100 million. Moving forward, we expect to continue to opportunistically repurchase shares under the remaining share repurchase program authorization of $150 million. A strong balance sheet allows us not only to execute on return of capital, but also maintain financial flexibility to execute on business development. In the fourth quarter, we closed the acquisition of Sunerba, which was treated as an asset acquisition for accounting purposes. As previously disclosed, we paid approximately $60 million in cash for the closing of the transaction. We received approximately $26 million of cash and $45 million in deferred tax assets from the acquisition and assumed approximately $14 million in liabilities. Thus, we recorded $2.3 million in IT R&D charge related to the acquisition, along with $7.5 million in one-time restructuring costs. As a result, we were able to acquire two late-stage programs at very attractive deal terms. Going forward, we will recognize considerable operating synergies and expect ongoing incremental costs from the Zanarba Development Program of approximately $30 million for 2024. Turning to 2024 guidance, for the full year, we expect net revenues of $700 million to $720 million. This range reflects our thoughtful and balanced approach to providing guidance for the first time in company history. It also highlights that we are well on our way towards the $1 billion-plus opportunity in the Delta Narcolepsy loan that we have consistently communicated and remain confident in. And finally, a comment on seasonality as you think about the phasing of revenue for the first quarter of 2024. We expect to see the typical seasonal dynamics that the industry as a whole experiences each year in Q1. Higher gross net deductions due to insurance plans reset and higher copay obligations, along with a drawdown in trade inventories. In conclusion, we're very pleased with our strong financial performance in 2023 and remain well positioned to continue growth in 2024 and beyond. We look forward to leveraging our financial strength as we continue to expand and diversify the portfolio while also returning capital shareholders via our share repurchase program. And with that, I'd like to turn the call back to Jeff for his closing remarks. Jeff?

Thank you, Sandeep. In summary, Harmony continues to be a growth story as evidenced by the significant progress our team made in 2023. Looking ahead, We see durability in our core business, strong momentum in our development programs, and remain focused on continuing to grow our WakeX business and helping even more adult patients living with narcolepsy. Advancing our pipeline across both our Pitocin and ZYN002 clinical development programs. Working with our partner BioPergé on next-gen formulations to extend the Pitocin franchise to help even more patients living with rare neurological diseases. Continuing to build out our pipeline for business development to create a robust portfolio of rare disease assets covering all stages of development. And deploying capital to maximize shareholder value through our share repurchase program and business development opportunities. I am excited for what is to come this year and believe that we are poised to accelerate Harmony's growth in 2024. This concludes our planned remarks for today. Thank you for joining our call, and I will now turn the call back over to the operator to facilitate the Q&A session. Operator, can you please open the call to questions?

Thank you. At this time, if you would like to ask a question, please press the star 1 on your telephone keypad. If you wish to remove yourself from the queue, you may do so by pressing star 2. We remind you to please pick up your handset and to please limit yourself to one question and one follow-up. We'll take our first question from Amy Ferrara with Neom & Company. Your line is now open.

Good morning. Thanks for taking my question and thank you for giving all the updates on the pipeline. Firstly, I have two questions. First, can you talk about the two new Pitot-Dessin formulations on which you're going to be sharing data in the first half? What should we expect to see from the data? And just to set up expectations for investors, will we be able to get visibility into how these formulations may be differentiated from WCAG based on that data? And then the second question is regarding idiopathic hypersomnia. If you could shed any additional color on the analysis that you've put together for your meeting with the FDA. And if you could comment on whether there's any possibility of generating any additional data from the open-label portion of the study to support an approval. Thank you.

Yeah, Ami, good morning. Thank you for your questions. And I'll ask Kumar to, yeah, to comment on, you know, the next-gen formulations and, you know, some visibility there, and as well as our preparation for the FDA meeting on IH. Kumar?

Yeah. Good morning, Ami. Thanks for the question. In terms of next-gen formulation, as we mentioned, we made progress on next-gen formulation last year, and we were really pleased to bring both of those two formulations into the clinic in the fourth quarter. And as we previously said, we will provide data from the next-gen formulation in the first half of this year. In terms of next-gen one, or NT1, it's a modified adolescent formulation. with the potential for clinical differentiation, fast-market strategy by demonstrating bioequivalence, alongside a clinical study that will offer a meaningful clinical differentiation for patients. The nature of the clinical study and the potential differentiation that will be offered will be discussed at the next earnings call, along with the PK data. With the NextChange2, or NG2 formulation, It's an enhanced formulation of Pitocin designed to deliver optimized PK and also an ability to go to a higher dose strength. This is the formulation that will have a full development program, a new IP, and it will extend the Pitocin franchise well beyond 2040. And we plan to provide the PK data from this formulation at our next earnings call. Regarding your question about the idiopathic hypersomnia, I mean, the totality of the data from the open-label study, from the randomized period of the study, and the long-term extension study, the efficacy in patients with idiopathic hypersomnia. And in terms of the arguments of the discussions that we'll be having with the FDA, if the totality of the data the non-scheduled status of the total offense, the ease of administration, a relatively benign safety profile, especially in the context of only one drug that happens to be a scheduled three controlled substance, and the off-label use of class two controlled substance trusts that have their own safety profile. So all these factors offer a strong benefit-risk proposition to bring Pitolacent for patients with idiopathic hyposomnia, and we hope to have good discussions with the FDA and find an efficient path forward to bring Pitolacent to patients with idiopathic hyposomnia as soon as possible.

Thank you.

Thank you. Our next question from Charles Duncan with Cantor Fitzgerald. Your line is open.

Yeah. Hey, good morning, Jeff and team. Congratulations on a good year in 23. Thanks for taking our questions. I have one commercial question and then a pipeline question to follow. So regarding the commercial question, absolutely appreciate the 25 REVS guide. Looks good to me. I note that you've added about 350 patients on WakeX per quarter for the last three quarters, and that seems to be just a really consistent number. And I guess I'm wondering if you could speak to anything in the market dynamics or prescriber access that results in that 350, or is that just serendipity? Thank you.

Good morning, Charles. Thank you for your question. Yeah, I think Jeff Durst can provide some color on the patient ads and the continued market opportunity for wake-ups.

Good morning, Charles, and thanks for the question. We've been extremely pleased with the durable growth that we've seen in the average number of patients on WAKIX. And I think some of the things that we're seeing, Charles, is given the unique and meaningfully differentiated product profile, WAKIX has the ability and our sales team has the ability to engage with the broad 9,000 approximate healthcare professionals that see and treat the narcolepsy patients. And what that does is that affords us the opportunity to tap into the full diagnosed patient opportunity, both those individuals and healthcare professionals outside the Oxibate REMS program, which we continue to see meaningful growth in the number of unique writers every quarter. But even within the Oxibate REMS-enrolled healthcare professionals, even with the availability of generic and once-nightly Oxibate launches this year, we're seeing meaningful growth in terms of depth of prescribing in that audience. So I think really what we're seeing is the unique nature of the meaningfully differentiated product profile, the non-scheduled status, the broad clinical utility that Jeff Dano spoke about. That really affords us the ability to continue to tap into that broad diagnosed patient opportunity as the market allows around the traditional quarterly dynamics that we speak about each earnings call. But, Charles, we're extremely pleased with what we're seeing, as I'm hearing from you as well, and we're confident in continued growth in the average number of patients as we move into 24.

Okay, that's helpful added color, Jeff. Thanks. Quick question on the pipeline. Actually, a multi-part question. Sorry about that. And that is, appreciate the phase three tempo study data, or not data, excuse me, details. I'm wondering when you would anticipate data. How rapidly do you think that study can enroll given some competing programs? And then is the NDA, SNDA timing, I assume it would be gated by the open label extension or would you file perhaps before that's completed? And then the second part of the question is regarding the pediatric narcolepsy and priority review, It seems to say something about the agency's perspective on the safety of the product. So I'm wondering if you could provide any thoughts on that and recent priority review being granted.

Yeah, Charles, first let me say, you know, I think that we're excited to be initiating the phase three, you know, TEMPO study in patients with Prader-Willi. I'll have Kumar comment on that, and then I'll circle back on some thoughts about the priority review for, you know, the pediatric Norco SDS-NDA. Kumar?

Yeah. Hey, good morning, Charles. Thanks for the question. Regarding the PWS study, first of all, we are very pleased. to have the orphan drug designation from the FDA for PWS program. In terms of recruitment, we anticipate to complete enrollment in about two years. It is true, Charles, that there are multiple programs in this space, but then we are the only ones who are looking at excessive daytime sleepiness and the behavioral symptoms in PWS. The other programs are targeting more towards the hyperphasia in PWS. And as I mentioned previously, more than half of the patients with PWS have excessive data and sleepiness, and almost all of these patients have behavioral disturbances. And from our proof-of-concept study, we showed strong data supporting pituitary effecancy, both in excessive data and sleepiness.

Yeah. And Charles, can you repeat that second question about the PEG narcolepsy SNDA?

Yeah, I mean, the pediatric narcolepsy, you know, PDUFA and rapid time to respond, you know, just seems to say something about the safety of the product or the agency's perspective on that. Not speaking for the agency, of course, but that combined with the priority review. I guess, do you have any thoughts about the perspectives on that?

Yeah, Charles, I mean, what I would say, you know, I think that as we've shared this week, you know, we're very pleased with the interactions we've had with FDA, you know, with regards to the orphan drug designation for Pitocin for Prader-Willi and then followed by the decision priority review for the, you know, pediatric narcolepsy, SNDA. I think that it reflects with regards to the overall benefit-risk profile of Pitocin and what we have said all along and advancing the development programs. We don't have any concerns with regards to the safety profile has been consistent from the original pivotal development program in narcolepsy. and on through the life cycle management programs that we've been conducting with no real change in the overall safety profile and the favorable benefit-risk profile. I think that reflects the positive interaction we've had with the agency, the decisions that we've received, and we remain focused on the execution and advancement of those development programs to bring potential needs and options to those patient populations.

Very good. Thanks for the added info. Congrats on a good deal. Thanks, Charles.

Thank you. We'll take our next question from Fritz Wappersbrau with Oppenheimer. Your line is now open.

Hi. Can you hear me okay? Yes, Frank. Okay. Thanks for taking the question. So I was just wondering, in terms of the guidance, can you help us understand what the thought process was behind giving guidance for the first time here, and how should we be thinking about the revenues per patient in 2024? Thank you. Thanks, Frank. Sandeep?

Yeah, sure. Look, Frank, thanks for the question. I mean, our guidance represents what I'd say is the thoughtful and balanced approach. especially the first year that we're given guidance. You know, I think we certainly look for opportunities to provide an update as we go throughout the year with respect to the guidance.

And a comment on how we should think about, you know, pricing or maybe revenue expectations.

Yeah, I think, look, we did take a price increase earlier this year of about 7%. A good portion of that usually falls through the bottom line. So I think, you know, generally, you know, you'll see an impact from that as we go throughout the year. Obviously, in the first quarter, there's usually headwinds. regarding, you know, gross net pressure and normal, you know, things that happen typically in the seasonality that happens. So you generally don't see as much of that in the first quarter, but generally as we go throughout the year, you'll see the benefit. It's very similar to the pattern that we've had over the last, you know, three, four years.

Great. Thank you very much. Thanks, Craig.

Thank you. We'll take our next question from David Amselung with Piper Sandler. Your line is now open.

Yeah, thanks. So just a couple. First, regarding business development, I wanted to get more detailed thoughts on the extent to which you do a larger scale transaction versus something smaller scale along the lines of Zynerba. Just philosophically, how are you thinking about acquisitions in general. And tied to that question is also would you lever up and lever up significantly to do something? So that's number one. And then number two, wanted to pick your brain on the orexins. We've seen some data from Takeda, from Alchemies. There are others, of course. Wanted to get your view on the potential long-term impact of the orexin to receptor agonists to the extent one or more reach the market. Thank you.

Yes, thanks, David. Good morning. I think with regards to, you know, business development, you know, we are assessing the landscape very actively, and we're open to sort of all opportunities. You know, with regards to a deal similar to, you know, Zynerba, that's a good strategic fit, as well as something more, you know, transformational. We're in a strong sort of, you know, financial position to transact So we first look for good strategic fit, prefer sort of, you know, late-stage assets but open to earlier stage, and, you know, those that can launch both during the wake-up life cycle and after. In terms of capacity, I'll ask Sandeep to, you know, to comment on that.

Thanks, Jeff. Yeah, look, we have good financial strength and flexibility, you know, to execute on business development. We also have access to debt, if appropriate, as well as the capital markets. As also we mentioned, we had over $425 million of cash and cash equivalents available. We're generating significant positive cash flow. Last quarter, it was about $77 million in cash flow generation. as well as almost over $219 million last year in cash generation. So I think we have a good flexibility, as Jeff mentioned, to look at both small add-on transactions as well as potentially something that's more larger and transformative. But I think the important thing is the filter that Jeff mentioned up front in terms of making sure it's a good strategic fit for the company. And I think from a capital perspective, we have broad flexibility.

Thanks, Sandeep. And David, turning to a question about the orexin agonist, you know this space well, as do we, and we've followed it closely. Obviously, a lot of attention lately, given some of the data that has come out. I think at a high level, the programs are still early and they're obviously advancing. I think questions are being generated both on the safety side and the efficacy side based on the data that has been coming out. Obviously the target is interesting in terms of the next potential novel mechanism of action for narcolepsy and other central disorders of hypersomnolence. So I think we're following the space closely as the data come out, as more questions have been generated. And I think that they likely come to market as successful, you know, towards the end of the decade, towards the end of the wake-up life cycle. But importantly, it's our belief that narcolepsy will continue to be a polypharmacy market. New entrants, you know, can only help, you know, the space and, you know, more share of voice, more education. So interesting novel target. I think waits to be seen as these development programs advance. And... you know, will continue to be a polypharmacy market. And, you know, we'll follow them as things go forward. All right.

Thanks. Thanks, David.

Thank you. We'll take our next question from Jason Gerberry with Bank of America. Your line is open.

Hey, guys. Thanks for taking your questions. This is Pablo on for Jason. Our first question is with regards to Zygel asset. Where are you at with enrollment for the Phase III Fragile X Syndrome study and any added clarity as to what assumptions shape your view on mid-2025 readout timing? And then the second commercial question, what are your assumptions for average revenue per wake expansion? Is that a meaningful tailwind for revenue growth in 2024 in your guidance, or is growth mainly driven by volume?

Thank you. Great. Thanks for your questions. I'll ask another comment on the ZYN-002 phase three reconnect trial. Very exciting opportunity for us and can provide, you know, kind of some more color on where we are there? Yes.

Thank you, Jeff. So, yeah, we looked at the timeline as we mentioned previously that we will, and based on the historical recruitment plan and the anticipated recruitment in this particular patient population, we arrived that we will complete enrollment in the first quarter of 2025, and the top line will be in mid-2025. Now that the asset is within half, Obviously, we will bring all the additional resources and the expertise, not just from a clinical development perspective, but also from the advocacy group perspective as well to try and accelerate the recruitment.

Thanks, Kumar. In terms of revenue per patient, Jeff, do you want to comment on that?

Sure. So in looking ahead in 24, you know, question in terms of just price volume or average revenue per patient, as Sandeep shared, we took a 7% price increase in the beginning of the year. And as with previous years, we would expect to capture most of that price increase. And as you're looking at our guidance, right, from 700 to 720, you can see that we're expecting 20-plus percent growth. So you can see that the vast majority of the growth we're expecting in 24 is driven by volume. You know, we've talked a lot about the large remaining diagnosed patient opportunity, the meaningfully differentiated product profile for a week. So we see significant opportunity and room for growth, but hopefully that provides a little bit of context and helps you think about price versus volume assumptions in the average revenue per patient in 24. Thanks, Jeff.

And if I could have one follow-up question, what does the appetite for share buybacks in 2024 look like relative to the $100 million in share buybacks that you guys did in 2023?

You know, I think, as we said, we're looking to take an opportunistic approach. And, Sandeep, you want to comment further?

Yeah, look, we were very pleased last year that we were able to do approximately $100 million share repurchase activities, you know, for the last couple of quarters. And, you know, and I think it's really not a question of either or. We have the flexibility to do both. And, you know, and with respect to business development, you know, we obviously talked about our strategy there. And then in terms of the share buyback, again, we'd look at it more opportunistically and at the appropriate levels, you know, we would certainly, you know, in a great cash position to be able to execute. And we have approximately $150 million of capacity still remaining, so.

Thank you. Thank you.

Thank you. We'll take our next question from Danielle Brill with Raymond James. Your line is now open.

Hi, guys. Good morning. Thanks for the questions. I was also hoping you could provide some more color on the assumptions that went into your 24 guidance, specifically around expectations for patient ads. It looks like you're expecting a slowdown in that patient ad each quarter. Are you just being conservative here or is growth starting to moderate? And then as a follow-up, can you remind us what impact the label expansion into the pediatric knock-up feed population will have on the overall TAM for WCAG? Thank you.

Thanks, Danielle, and good morning. Yeah, with regards to, you know, I think that in terms of revenue and the revenue guidance and Sandy, do you want to?

Yeah, look, I think as we mentioned, we've taken a thoughtful and balanced approach in terms of providing guidance for the first year. We certainly look to provide an update as we go throughout the year. We're not in any way indicating. We see great momentum coming out of the fourth quarter, and we expect that momentum to sort of carry through for the year. I mean, Jeff, Dirk, do you want to comment at all in terms of just overall performance? with what you're saying.

Sure. And Daniel, in terms of looking at average patient growth and sort of the assumptions in the 24 guidance, I mean, we've seen demonstrated durable growth in the narcolepsy market, and we've grown average patients every quarter since launch, even with availability. But, you know, within that durable growth, that growth has evolved every year. And entering our year five of our rare orphan launch, we're going to expect that growth to continue to evolve. But follow the previous year's cadence of the quarterly growth as we tap into that large diagnosed patient opportunity. So you'll see the traditional payer headwinds in the first quarter that impact all brands and specialty products. You'll see the traditional, you know, fewer patient visits associated with chronically managed conditions and diseases in Q3. And then typically in previous years, we expect to have the traditional tailwinds in the second and the fourth quarter with stronger prescription demand. You know, again, but I think the takeaway is we're extremely pleased with what we're seeing, confident continued growth, and we really believe that WACICS is well positioned for future growth in 24. Thanks.

And then your next question on pediatric.

It was on pediatric TAM and how that expands the Quakix opportunity.

Yeah, I think Jeff can speak to that. I think, obviously, positive signals from the agency on the importance of that indication in pediatric narcolepsy patients.

So, Jeff, what does the opportunity look like? Sure. So, I mean, Daniel, we estimate there's about 4,000 pediatric narcolepsy patients in the U.S., and although it's not a large opportunity, it's an important one, and it's a very underserved patient population with only one FDA-approved treatment option being sodium oxibate, being a Schedule III REMS product right now. And I think we're very excited about the potential, if successful, to bring a non-scheduled treatment option, given what we've seen, the impact of narcolepsy on these individuals' lives.

Yeah. Thanks, Jeff. And Danielle, let me just also add with regards to the pediatric narcolepsy, that SNPA, it's also important that those data were also pursuing pediatric exclusivity, which is obviously an important commercial opportunity with regards to an additional six months. of regulatory exclusivity. So, you know, those data are one component of that, along with, you know, the data that we'll be generating in the phase three, you know, Prader-Willi, you know, tempo study. So, you know, both of these components are important, and we are advancing, you know, both of these and making progress in terms of pediatric narcolepsy data through that submission and then the initiation of the Phase III trial in Prader-Willi syndrome. And both of those components are what would be required as we pursue pediatric exclusivity and additional six months of protection.

Okay.

Thank you so much.

Thank you.

Thanks. Thank you. We'll take our next question from Greg Sabanovich with Mzuzo. Your line is open.

Hi, this is for Greg. I just have a question about the one about the Fragile X opportunity. I know you said that the timelines have been pushed a little bit due to enrollment, but were there any changes in the trial design as there originally were, which also caused delays? And then also on the pediatric opportunity, I know you said it's a pretty small opportunity, but do you anticipate growing the WCAG sales force

Thank you for your question. You know, with regards to the Fragile X, you know, study, Kumar? Yeah.

Thank you for the question, Avantika. With Fragile X syndrome, you know, the timeline was not pushed out. We had mentioned that we will evaluate the timeline once the asset is in house, and we had an opportunity to evaluate the timeline. And based on the historical recruitment plan, And the anticipated recruitment in this patient population, we are out at completing enrollment in the first quarter of 2025, with top line anticipated in mid-2025. And there is no change in the study design.

Yeah, and I would just add, I think that the opportunity is for, you know, for Harmony, for us to, you know, to put our resources, you know, towards driving the Phase 3 ReConnect trial forward. You know, with regards to the experience, you know, of the clinical development team, more capacity from an operational perspective, and really engaging with the patient community through our patient advocacy efforts as well to drive that forward toward a significant market opportunity of 80,000 diagnosed patients in the U.S. You know, turning to pediatric narcolepsy, you know, we keep hearing sort of small market opportunity, but an important one. And I think, you know, Jeff sort of alluded to this, you know, an important one in terms of potential new non-scheduled treatment options for pediatric patients with narcolepsy, you know, rather than Schedule II stimulants. So, you know, we are looking forward to working with the agency towards that. And then with regards to you know, the impact on the market opportunity, Jeff?

Sure. So in looking at, you know, the Salesforce coverage for pediatric narcolepsy, you know, we believe that we're optimized for the narcolepsy opportunity with our existing Salesforce footprint. There will be some new prescribers that we'll be adding to our target list if successful, but we believe that our current team that is, you know, very excited about the potential to bring this forward is optimized to be able to take on this new opportunity with these additional patients and with, you know, the addition of a handful of healthcare professionals, there's a high overlap between adult narcolepsy prescribing and pediatric narcolepsy prescribing. So we believe we've got, you know, relationships established with a good portion of those prescribers, but we are absolutely optimized with our team, and if successful, very excited to bring this new indication forward. Great.

Thanks, Jeff.

Thank you.

Thank you. And can I just squeeze in one more? Sorry. For growth to net, I know you said that there will be headwinds in the first quarter, but can you just quantify what you think it will be for the full year? Sandeep?

Yeah, hi, thanks for the question. As I mentioned, typically in the first quarter across the industry, you know, there are general headwinds from just higher co-pay obligations and insurance plans resets in the first quarter. So we'll see a couple of percentage points impact from that typically is what we've seen in the past in the first quarter. And that sort of, you know, improves as we go throughout the year generally.

Thank you. Thank you.

Thank you. I am showing no further questions. I would now like to turn the call back to management for closing remarks.

Thank you, Brittany. And thanks, everyone, for joining our call today and for your interest in Harmony. As you heard from us this morning, our strong execution in 2023 and solid momentum going into this year positions Harmony well for continued growth in 2024. We look forward to providing updates as we execute on our growth strategy. Thank you and have a great day.

This does conclude today's Harmony Biosciences fourth quarter and full year 2023 financial results conference call. You may now disconnect your line.