Q2 2025 Harmony Biosciences Holdings Inc Earnings Call
Madison: Good morning. My name is Madison, and I will be your conference operator today. At this time, I would like to welcome everyone to Harmony Biosciences Holdings Inc.'s second quarter 2025 financial results conference call. All participants 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 may be recorded. Lastly, if you should require operator assistance, please press star zero. I will now turn the call over to Brennan Doyle, Head of Investor Relations. Please go ahead.
Good morning. My name is Madison and I will be your conference operator today.
At this time, I would like to welcome everyone to Harmony biosciences. Second quarter, 2025 Financial results conference call.
Brennan Doyle: Thank you, operator. Good morning, everyone, and thank you for joining us today as we review Harmony Biosciences Holdings Inc's Q2 2025 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 a 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 Dayno, President and CEO; Adam Zaeske, Chief Commercial Officer; Dr. Kumar Budur, Chief Medical and Scientific Officer; and Sandip 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.
All participants have been placed on mute to prevent any background noise. After the speakers remarks, there will be a question and answer session. If you would like to ask a question at that time, please press star 1 on your telephone keypad, please be advised that today's conference may be recorded. Lastly, if you should require operator assistance, please press star zero. I will now turn the call over to Brennan Doyle head of investor relations. Please go ahead.
Thank you, operator. Good morning, everyone. And thank you for joining us today. As we review, how many biosciences second quarter, 2025 Financial results?
Is this 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 a Reconciliation of our gaap to non-gaap financial measures.
At this stage of our life cycle, we believe non-GAAP financial results better represent the underlying business performance.
Our speakers on today's call are Dr. Jeffrey do president and CEO.
Adam zaeske, Chief commercial officer. Dr. Kumar padur. Chief medical and scientific officer.
as a reminder, we will be making 4 looking statements today which are based on our current expectations and beliefs
Brennan Doyle: 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 our CEO, Dr. Jeffrey Dayno. Jeff?
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 reference in our SCC filings for additional details.
Jeffrey Dayno: Thank you, Brennan. Good morning, everyone, and thank you for joining our call today. I want to begin today's call by reaffirming something we believe is becoming increasingly clear. Harmony Biosciences Holdings Inc is a growth story. We have built something rare in our industry: a profitable, self-funding biotech company with an innovative, late-stage pipeline poised to deliver meaningful value for both patients and shareholders. Because of this unique profile, we continue to execute from a position of strength. Our foundational business, anchored by Wakix in narcolepsy, has now delivered another quarter of double-digit revenue growth. We reported $200.5 million in second-quarter net revenue, representing a 16% increase year over year. This performance extends our four-year streak of profitability and reinforces Wakix's strong momentum in its sixth year on the market, as reflected by the addition of 400 average patients during the second quarter.
I would now like to turn the call over to our CEO, Dr. Jeffrey do Jeff.
Thank you, Brandon.
Good morning everyone. And thank you for joining our call today.
I want to begin today's call by reaffirming something. We believe is becoming increasingly clear.
Harmony biosciences is a growth story.
We have built something rare in our industry. A profitable self-funding. Biotech company with an Innovative late stage pipeline poised to deliver. Meaningful value for both patients and shareholders.
Because of this unique profile, we continue to execute from a position of strength.
Our foundational business, anchored by Wix and narcolepsy has now delivered, another quarter of double digit Revenue growth.
We reported 200.5 million dollars in second quarter, net revenue.
Representing a 16% increase year-over-year.
Performance extends our four-year streak of profitability and reinforces weight, GX's strong momentum in its six years on the market.
As reflected by the addition of 400 average patients during the second quarter.
Jeffrey Dayno: Wakix remains the first and only non-scheduled treatment for narcolepsy, leading to broad clinical utility that is meaningful to both patients and prescribers. As demonstrated by the sustained momentum, we believe Wakix will achieve $1 billion plus blockbuster status in narcolepsy alone, well ahead of loss of exclusivity in 2030. Our story does not end with the success of Wakix because we are just getting started. What excites us most is what lies ahead. Today, Harmony is a multi-franchise company with three core areas of focus: sleep wake, neurobehavioral, and rare epilepsies. Each of these franchises includes late-stage development programs with $1 to $2 billion in peak sales potential across multiple indications. Let me walk you through what lies ahead in our pipeline, starting with our next major clinical catalyst coming from our neurobehavioral franchise and its innovative investigational product, Zygel.
Wake Remains the first and only non-scheduled treatment for narcolepsy, leading to Broad clinical utility, that is Meaningful to both patients and prescribers.
As demonstrated by the sustained momentum, we believe we will achieve over $1 billion in blockbuster status in narcolepsy alone.
Well, ahead of loss of exclusivity in 2030.
But our story doesn't end with the success of Wix because we are just getting started.
What excites us most is, what lies ahead.
Today, Harmony is a multi-franchise company with 3 core areas of focus.
Sleep wake.
Neurobehavioral and rare epilepsies.
Each of these franchises includes late stage development programs with 1 to 2 billion dollars in Peak sales potential across multiple indications.
Jeffrey Dayno: This is a 100% synthetic, pharmaceutically manufactured cannabidiol devoid of THC, delivered through a unique, proprietary, patent-protected, permeation-enhanced transdermal gel formulation. Our phase three registrational trial in patients with Fragile X syndrome completed enrollment in Q2, and we are on track to report top-line data later this quarter. This study, the RE-CONNECT study, was designed to confirm the positive findings of the primary outcome from the Phase 2/3 CONNECT study in the pre-specified group of patients with complete methylation of the FMR1 gene, the underlying genetic defect in patients with Fragile X syndrome. In fact, Fragile X is the most common known inherited cause of intellectual impairment and autism spectrum disorders. Stepping back a moment, in order to understand the potential significance of our Phase 3 RE-CONNECT study, there are roughly 80,000 people living with Fragile X in the U.S., similar in size to the diagnosed narcolepsy market.
Let me walk you through what lies ahead in our pipeline starting with our next major clinical Catalyst coming from our neurobehavioral franchise and its innovative investigational product zyn, 00002
This is a 100 percent synthetic.
Pharmaceutically manufactured canabidiol.
Devoid of THC, delivered through a unique. Proprietary patent protected, permeation enhanced, transdermal gel formulation.
Our phase 3, registrational trial in patients with fragile X syndrome completed enrollment in Q2 and we are on track to report Topline data later. This quarter
This study, the reconnect study was designed to confirm the positive findings of the primary outcome from The Phase 23, connect study in the pre-specified group of patients, with complete methylation of the fmr1 gene.
The underlying genetic defect in patients with fragile X syndrome in fact.
Fragile X is the most common known in herded cause of intellectual impairment and autism spectrum, disorders.
Stepping back a moment in order to understand the potential significance of our phase 3, reconnect study.
Jeffrey Dayno: However, unlike that market, there are currently no FDA-approved treatments for Fragile X syndrome. A positive readout from the RE-CONNECT study could represent a major breakthrough, the potential for the first and only approved therapy for Fragile X syndrome, and a transformational moment for people living with Fragile X syndrome and their families who have waited far too long for a therapy designed to address their needs. Kumar Budur will be sharing more detail with you on the reasons for our strong conviction in the upcoming top-line data readout. In our sleep wake franchise, as I mentioned, Wakix continues to grow, and our pitolisant lifecycle management programs are designed to both expand and extend this franchise well into the mid-2040s. We have major catalysts ahead for the two next-generation formulations of pitolisant, high-dose pitolisant or pitolisant HD, and a gastro-resistant formulation of pitolisant or pitolisant GR.
Similar in size to the diagnosed narcolepsy Market.
However, unlike that market, there are currently no FDA approved treatments for fragile X syndrome.
A positive readout from the reconnect study, could represent a major breakthrough.
The potential for the first and only approved therapy for fragile X syndrome.
And a transformational moment for people living with fragile X syndrome, and their families who have waited far too long for a therapy designed to address their needs.
Kumar will be sharing more detail with you on the reasons for our strong conviction.
In the upcoming Topline data readout.
In our sleep-wake franchise, as I mentioned, wake continues to grow, and our PTO life cycle management programs are designed to both expand and extend this franchise well into the mid-2040s.
We have major catalysts ahead for the 2 next generation formulations of Palace.
High dose paullus or pulsin HD.
Jeffrey Dayno: We are on track to initiate Phase 3 registrational trials in both narcolepsy and idiopathic hypersomnia with pitolisant HD in the fourth quarter of this year. We are also advancing a novel orexin-2 agonist with a potentially best-in-class profile and remain on track to enter the clinic and initiate first-in-human studies later this year, with clinical data anticipated in 2026. Our third franchise in rare epilepsy is also making steady progress. EPX-100 or clemizol hydrochloride is one of the most advanced 5-HC2 agonist compounds with a well-characterized mechanism of action and a strong safety record. It is now in Phase 3 registrational trials for both Dravet syndrome and Lennox-Gastaut syndrome, with pivotal data expected in 2026. Our commitment to patients with serious rare neurological disorders does not end here.
And a gastro-resistant formulation of pollen, or pollen GR.
And we are on track to initiate phase 3, registrational trials in both narcolepsy and idiopathic hypersomnia with pulsin HD in the fourth quarter of this year.
We are also dancing. A novel erects into Agonist with a potentially best-in-class profile.
And remain on track to enter the clinic and initiate first. In human studies later, this year with clinical data anticipated in 2026,
Our third franchise in rare epilepsy is also making steady progress.
Epx 100 or Clements all hydrochloride is 1 of the most advanced 5 HD2 Agonist compounds with a well-characterized mechanism of action.
And a strong safety record.
It is now in Phase 3, registrational trials for both Divi syndrome and linas costeaux syndrome with pivotal data expected in 2026.
Jeffrey Dayno: To that end, we recently entered into a research collaboration with Cirque Biosciences, a regenerative medicine company discovering novel therapies based on cellular reprogramming and focused on developing novel regenerative cellular therapies to replace and restore function in patients with advanced neurological disorders. Our collaboration with Cirque is strategically aligned with our current pipeline and focused on treatments for refractory epilepsy and treatment-resistant narcolepsy. This research could potentially result in the next generation of innovative disease-modifying therapies for these advanced chronic neurological disorders. Sandip will be commenting further on the terms of this deal. When you look at Harmony today, it should be evident that what we are building is one of the most robust pipelines in the industry for patients with rare neurological disorders. We now have eight innovative assets across 13 development programs, including up to six Phase 3 trials by the end of this year.
Our commitment to patients with serious rare neurological disorders does not end here.
To that end. We recently entered into a research collaboration with Circ biosciences.
A regenerative medicine company, discovering novel therapies based on cellular reprogramming, and focused on developing novel regenerative cellular therapies to replace and restore function in patients with Advanced neurological disorders.
Our collaboration with Cirque is strategically aligned with our current Pipeline and focused on treatments for refractory epilepsy and treatment resistant narcolepsy.
This research could potentially result in the next generation of innovative disease, modifying therapies for these Advanced chronic neurological disorders.
Sandeep will be commenting further on the terms of this deal.
When you look at Harmony today, it should be evident that what we are building is 1 of the most robust pipelines in the industry for patients with rare neurological disorders.
We now have 8 Innovative assets across 13 development programs, including up to 6, phase 3, trials by the end of this year.
Jeffrey Dayno: This pipeline is poised to deliver one or more new product or indication launches every year for the next several years. With more than $670 million in cash and cash equivalents on the balance sheet and a disciplined approach to capital deployment, we have the flexibility to continue to strategically expand our pipeline through targeted business development efforts in this favorable environment. What does all this mean? It means that in an industry where sustainable success remains elusive, Harmony has built something different and something unique: a commercially durable business with a robust late-stage pipeline and a clear path to delivering long-term value for patients, providers, and shareholders alike. That's what makes Harmony one of the most compelling growth stories in biotech today. With that, I'll turn the call over to Adam Zaeske, our Chief Commercial Officer, for an update on our commercial performance. Adam.
This pipeline is poised to deliver 1 or more new product or indication launches every year for the next several years.
And with more than 670 million dollars in cash and cash, cash equivalents on the balance sheet.
And a disciplined approach to Capital deployment.
We have the flexibility to continue to strategically expand our pipeline through targeted Business Development efforts in this favorable environment.
So what does all this mean?
it means that in an industry, where sustainable success remains elusive,
Harmony has built something different and something unique.
A commercial durable business with a robust late stage Pipeline and a clear path to delivering long-term value for patients, providers, and shareholders alike.
And that's what makes Harmony 1 of the most compelling growth stories in biotech today.
Adam.
Adam Zaeske: Thanks, Jeff. Harmony's Q2 2025 results demonstrate the enduring strength of our commercial business. Wakix delivered $200.5 million in net sales for the quarter, representing 16% year-over-year growth in its sixth year on the market. Wakix achieved 7,600 average patients in Q2, representing an increase of approximately 400 average patients for the quarter. This represents among the strongest quarterly results we've seen since launch and continues the steady, reliable growth we've seen for the past several years. This sustained performance is driven by Wakix's unique position as the only non-scheduled treatment option, with its broad clinical utility for the more than 80,000 patients with narcolepsy, as well as the strong focus and execution of our commercial teams with the support of the entire Harmony organization. We have a great deal of confidence in the continued growth, potential, and performance of Wakix.
Thanks Jeff harmonies Q2 2025 results, demonstrate the enduring strength of our Commercial Business.
Wix delivered 200.5 million in net sales for the quarter representing 16% year-over-year growth, in its sixth year on the market.
Wix achieved 7,600. Average patients in Q2 representing an increase of approximately 400 average patients for the quarter.
This represents a among the strongest quarterly results we've seen since launch and continues the steady reliable growth. We've seen for the past several years.
This sustained performance is driven by wix's unique position as the only non-scheduled treatment option with its broad clinical utility for the more than 80,000 patients with narcolepsy.
As well as the strong focus, and execution of our commercial teams with the support of the entire Harmony organization.
Adam Zaeske: In addition to its unique position as the only non-scheduled treatment option, Wakix has among the highest brand awareness in the market, is perceived as efficacious and well-tolerated, and is supported by broad payer coverage that has remained consistent for years. We see continued increases in prescribing among the approximately 4,000 Oxybate REMS-enrolled prescribing clinicians, as well as an increase in prescribing and addition of new prescribers with the approximately 5,000 non-Oxybate REMS-enrolled clinicians, where Wakix is the only branded option. This dual expansion, deepening usage within our core base while broadening our prescriber footprint, demonstrates Wakix's resilient position and reinforces our confidence in its continued growth trajectory. As we look to the second half of 2025, these strong Wakix fundamentals support our confidence in maintaining its growth momentum.
We have a great deal of confidence in the continued growth potential and performance of wix.
In addition, to its unique position as the only non-scheduled treatment option Wix has among the highest, brand awareness in the market is perceived as efficacious. And well, tolerated and is supported by broad payer coverage that has remained consistent for years. We see continued increases in prescribing among the approximately, 4,000, oxybate Rems enrolled prescribing clinicians as well as an increase in prescribing.
And addition of new prescribers with the approximately 5,000 non oate rims enrolled clinicians. We're wakes is the only branded option.
This dual expansion, deepening usage within our core base. While broadening, our prescriber footprint demonstrate wix's resilient position and reinforces our confidence.
in its continued, growth trajectory
Adam Zaeske: We are confirming our full-year revenue guidance of $820 million to $860 million, and we remain on track to achieve $1 billion plus in annual revenue in narcolepsy alone. Looking to the future, the pitolisant GR and HD formulations each target significant unmet patient needs while extending our growth potential with utility patents filed through 2044. Early feedback from physicians and payers on the HD formulation has been particularly encouraging, and we'll be able to fully leverage our commercial infrastructure to drive the next phase of growth through our pitolisant franchise formulation. We're also excited for the opportunity to expand beyond the sleep wake franchise and are eagerly anticipating the top-line data readout for ZYN-002 in our neurobehavioral franchise next quarter. Kumar will provide a progress update on these programs in a moment. In summary, the fundamentals of our business remain robust.
As we look to the second half of 2025, these strong wake exponentials support our confidence in maintaining its growth momentum. We are confirming our full year. Revenue guidance of 8.20 to 860 million and we remain on track to achieve 1 billion plus in annual revenue in narcolepsy alone.
Looking to the Future the pollus and gr and HD formulations each targets, significant unmet patient needs while extending our growth potential with utility patents filed through 2044.
Early feedback from physicians and payers on the HD formulation has been particularly encouraging, and we'll be able to fully leverage our commercial infrastructure to drive the next phase of growth through our polus and franchise formulation.
We're all so excited for the opportunity to expand beyond the sleep-wake franchise and are eagerly anticipating the topline data readout for Zyn002 in our neurobehavioral franchise. Next quarter, Kumar Budur will provide a progress update on these programs in a moment.
Adam Zaeske: Our strong second-quarter performance reflects the continued execution of our strategic priorities, and we are well-positioned to capitalize on the substantial opportunities before us. I'd like to now turn the call over to our Chief Medical and Scientific Officer, Kumar Budur, to discuss the advancements in our clinical development programs. Kumar?
In summary. The fundamentals of our business remain robust, our strong second quarter performance, reflects the continued execution of our strategic priorities.
And we are well, positioned to capitalize on the substantial opportunities before us.
I'd like to now turn the call over to our chief medical and scientific officer Kumar badur to discuss the advancements in our clinical development programs.
Tomorrow.
Kumar Budur: Thank you, Adam. Good morning, everyone, and thank you for joining us today. Please refer to slide number five for our pipeline chart. The clinical development highlights are on slide six through slide 11. In R&D, we are on track for our next major catalyst, the top-line data for Zygel in Fragile X syndrome in Q3. We have a high degree of confidence and conviction in the success of the Phase 3 registrational trial, the RE-CONNECT study, as it builds upon the data and insights from the large Phase 2/3 CONNECT study. The efficacy data from the CONNECT study, especially in patients with complete methylation, who accounted for approximately 80% of the patients, is one of the strongest efficacy data sets generated in patients with Fragile X syndrome.
Thank you, Adam. Good morning, everyone and thank you for joining us today.
Please refer to slide number 5 for a pipeline chart.
And the clinical development highlights are on slides 6 through 11.
in R&D, we are on track for our next, major Catalyst, the top line data for Z1 0002, in, fasal X syndrome in Q3
We have a high degree of confidence and conviction in the success of the phase 3. Registrational trial, the reconnect study, as it builds upon the data and insights. From the large Phase, 2 3, connect study,
The efficacy data from the Kinect study especially in patients with complete methylation, who accounted for Approximately 80% of the patients is 1 of the strongest efficacy. Data sets generated in patients with flex syndrome.
Kumar Budur: We saw over 50% of patients demonstrating clinically meaningful improvements in social avoidance, the primary endpoint, and irritability, disruptive behaviors, other core symptoms in patients with Fragile X. The RE-CONNECT study essentially seeks to replicate the statistically significant efficacy signals observed in patients with complete methylation in the CONNECT study, with several enhancements to further bolster the probability of success. We have completed enrollment, and we are on track to the top-line data later this quarter. If positive, the RE-CONNECT study is expected to support regulatory approvals in both the U.S. and EU, and Zynerba holds global rights. Zygel has the potential to be the first and only approved treatment for any symptom domains in patients living with Fragile X.
We saw over 50% of patients demonstrating clinically meaningful improvements. In Social avoidance, the primary endpoint and irritability. Disruptive. Behaviors other core symptoms in patients with fasal attacks.
To further bolster the probability of success.
We have completed enrollment and we are on track to the Topline data later. This quarter
If positive the reconnect study is expected to support regulatory approvals in both the US and EU and Harmony holds Global rights.
Z1, 0002 has the potential to be the first and only approved treatment for any symptom. Domains in patients living with facts.
Kumar Budur: Moving on to the scientific rationale for Zygel in this condition, Fragile X syndrome is a rare genetic disorder caused by the mutation of FMR1 gene on the X chromosome, and it is the most common known inherited cause of intellectual impairment and autism spectrum disorders. Fragile X syndrome is characterized by FMR protein deficiency resulting in endocannabinoid dysfunction. Zygel interacts with the CD1 receptors, modulates the system, and restores the endocannabinoid homeostasis, thereby improving the neurobehavioral symptoms. With Zygel, we also remain on schedule to initiate a Phase 3 registrational trial in 22q deletion syndrome later this year, pending the results from the Fragile X program. This rare disorder, with significant neurobehavioral symptoms similar to Fragile X, has no approved therapies and also affects approximately 80,000 individuals each in the U.S. and Europe. Moving on to our sleep-wake franchise, we have made significant progress across our next-generation pitolisant programs.
Scientific rationale for Z10 0002 in this condition.
Further X syndrome is a rare genetic disorder caused by the mutation of fmr1 gene on the X chromosome. And it is the most common known inherited cause of intellectual impairment and autism spectrum, disorders,
Flex syndrome is characterized by fmr. Protein deficiency, resulting in endoc cannabino dysfunction.
Z9 0002 interacts with the ct1 receptors. Modulates the system and restores the endocrine Aid, homeostasis, thereby improving the neurobehavioral symptoms.
With Z1 002. We also remain on schedule to initiate a phase 3 registration of trial in 22, Q, deletion syndrome. Later this year, pending the results from the fragile X Program
This rare disorder which significant neurobehavioral symptoms, similar to frazzle. X has no approved therapies and also affects approximately, 80,000 individuals age in the US and Europe.
Kumar Budur: The pitolisant HD program, a higher dose pitolisant formulation with an optimized PK profile targeting enhanced efficacy for excessive daytime sleepiness and pursuing a differentiated label with an indication for fatigue in narcolepsy, is on track for the Phase 3 initiation in Q4 2025. Similarly, the Phase 3 study with pitolisant HD in patients with idiopathic hypersomnia is also pursuing a differentiated label with an indication for sleep inertia and is also on track for initiation in Q4 2025. The target PDUFA dates for both programs are in 2028. Over to the pitolisant GR formulation, it is designed to address the potential for treatment-related GI side effects, especially since almost 90% of patients with narcolepsy experience GI symptoms. In addition, it also provides an ability to start at the therapeutic dose range, eliminating titration. This is a fast-market strategy we are demonstrating bioequivalent to Wakix formulation.
Moving on to our sleep week functions, we have made significant progress across our next Generation polos and programs.
The PTO and HD program is a higher dose formulation with an optimized PK profile targeting enhanced efficacy for excessive daytime sleepiness and pursuing a differentiated labor with an indication for fatigue. The no collapsing is on track for the Phase 3 initiation in Q4 2025.
Similarly, the phase 3 study with PTO recent HD in patients. With idiopathic hypersomnia, is also pursuing a differentiated labor with an indication for Sleep inertia and is also on track for initiation in Q4 2025.
The target would do for dates for both programs or in 2028.
Over to the pitos and gr formulation. It is designed to address the potential for treatment related GI side effects, especially since almost, 90% of patients with narcolepsy experience in GI symptoms.
In addition, it also provides an ability to start at the therapeutic dose range eliminating titration.
Kumar Budur: The top-line data from the pivotal BE study is expected in Q4 with a potential PDUFA in 2026. Utility patents have been filed for both pitolisant GR and pitolisant HD, with potential exclusivity to 2044, securing long-term franchise value. Beyond pitolisant, our sleep-wake portfolio continues to advance with TPM-1116, a highly potent RxN2 receptor agonist demonstrating best-in-class potential in preclinical studies. At the recent sleep meeting, we presented a comprehensive preclinical safety and efficacy data that demonstrated efficacy at very low doses across all parameters of interest in a standard transgenic mouse model. The program remains on schedule for IMPD submissions and first-in-human studies later this year, and we anticipate sharing clinical data in 2026. In our epilepsy franchise, we continue to actively enroll patients in two global Phase 3 registrational trials with EPX-100: the Argus study in Dravet syndrome and the Lighthouse study in Lennox-Gastaut syndrome.
This is a fast Market strategy. We are demonstrating bioequivalence to Vics formulation.
The top line data from the pivotal be study, is expected in Q4 with the potential to do for in 2026.
Utility patents have been filed for both pitos and gr, and pitos, and HD with potential. Exclusivity to 2044 securing, long-term franchise value.
Beyond the dollar sign. Our sleep break portfolio continues to advance with bp1 15205. A highly potent RX in 2 re demonstrating best-in-class potential in pre-clinical studies.
At the recent sleep meeting, we presented a comprehensive preclinical, safety, and efficacy data that demonstrated efficacy, very low, doses, across all parameters of interest in a standard transgenic Mouse model.
The program remains on schedule for impd submission and first in human studies later this year, and we anticipate sharing clinical data in 2026.
In our epilepsy franchise, we continue to actively enroll patients in 2, Global phase 3 registration, trials with epx 100
The August study interval syndrome and the lighthouse study in Lenox guest star syndrome.
Kumar Budur: In conclusion, our late-stage rare neurology portfolio is advancing with exceptional momentum, positioning us to potentially introduce multiple new products or indications every year over the next several years. Beyond the clinical and regulatory milestones, what truly drives us is the opportunity to transform care for hundreds of thousands of patients living with rare neurological disorders, many of whom currently have either no treatment options or therapies with suboptimal efficacy and/or significant safety tolerability limitations. As always, 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 all their efforts and commitment in helping us to advance our development programs. I will now turn the call over to our Chief Financial Officer, Sandip Kapadia, for an update on our financial performance. Sandip?
In conclusion.
Our latest is raise neurology portfolio is advancing with exceptional momentum. Positioning us to potentially introduce multiple new products for indications every year over the next several years.
Kids for hundreds of thousands of patients living with rare neurological disorders, many of whom currently have either no treatment options or therapies with suboptimal efficacy and or significant safety, tolerable delimitations.
As always on behalf of Harmony, I would like to thank all the patients and their families who have participating in our clinical trials, as well as the clinical investigators, and cite personal for all their efforts, and commitment in helping us to advance our development programs.
Sandip Kapadia: Thank you, Kumar, and good morning, everyone. This morning, we issued our second quarter 2025 earnings release and filed our 10-Q. You will find the details of our financial and operating results. We had a great first half of the year. We delivered another quarter of solid financial performance with continued double-digit top-line growth, sustained profitability, and robust cash generation. Our financial performance and profile positions us well to continue advancing our growth strategy for the remainder of the year and beyond. For the second quarter of 2025, we reported net revenues of $200.5 million compared to $172.8 million in the prior year quarter, representing a growth of 16%. Performance in the quarter reflects the strong underlying demand for Wakix, offset by a reduction in trade inventories of a few days as we head into the summer months.
I'll now turn the call over to our CFO sepia for an update on our financial performance Sunday.
Thank you, Kumar, and good morning, everyone. This morning, we issued our second quarter of 2025 earnings release and filed our 10-Q, where you'll find the details of our financial and operating results.
We had a great first half of the year. We delivered another quarter of solid financial performance,
With continued double-digit, Topline growth.
Sustained profitability and robust cash generation.
our financial performance and profile positions as well to continue advancing our growth strategy for the remainder of the year and Beyond
For the second quarter of 2025. We reported net revenues of 200.5 million compared to 1 7 2. 8 4.
Growth of 16%.
Performance in the quarter, reflects the strong, underlying demand for WX offset by reduction in trade inventories of a few days as we head into the summer months.
Sandip Kapadia: We recorded total operating expenses for the second quarter of $114.2 million compared to $119.3 million for the same quarter in 2024. The expenses during the second quarter of 2025 include investments in advancing our late-stage pipeline and the commercialization of Wakix in narcolepsy. We also recognized a $15 million IP R&D charge related to the Cirque research collaboration which Jeff mentioned. We have an option to acquire an exclusive license for each program. The agreement includes customary milestones and royalties based on continued development and potential commercialization. We continue to show solid net income and margins. Non-GAAP adjusted net income for the second quarter of 2025 was $53.8 million or $0.92 per diluted share, compared to $24.5 million or $0.43 per diluted share in the prior year quarter. We believe non-GAAP adjusted net income better reflects the underlying business performance.
We recorded total operating expenses for the second quarter of 114.2 million.
Compared to 119.3% in 2024.
The expenses during the second quarter of 2025 include investments in advancing our late-stage Pipeline and the commercialization of Wix and narcolepsy.
We also recognize that 15 million dollar iprd charge related to the surf research collaboration which Jeff mentioned.
We have an option to acquire an exclusive license for each program.
the agreement includes customary, milestones and royalties based on continued development and potential commercialization
We continue to show solid net income and margin.
Non-gaap adjusted net income for the second quarter of 20125. Was 53.8 Million for 92 cents per diluted share compared to 24.5 million for 43 cents per diluted share in the prior year quarter.
Sandip Kapadia: Please see our press release for a reconciliation of GAAP and non-GAAP results. Harmony ended the second quarter with $672 million in cash, cash equivalents, and investments on the balance sheet. The balance reflects strong cash generation from operations of approximately $79 million during the second quarter. Our cash position provides us the financial flexibility to execute on business development as well as continue investments in our growing pipeline. Looking ahead to the balance of 2025, our strong first half results give us increasing confidence in our full-year outlook. We are reiterating our revenue guidance of $820 million to $860 million, highlighting our progress towards a $1 billion plus opportunity with Wakix in narcolepsy alone. We expect continued quarter-over-quarter net revenue growth for the balance of the year.
We Believe non-gaap adjusted. Net income. Better reflects the underlying business performance.
Please see our press release for a reconciliation of GAAP and non-GAAP results.
Harmony ended the second quarter with 672 million in cash, cash, equivalents and Investments on the balance sheet.
The balance reflects strong cash generation from operations of approximately $79 million during the second quarter.
For cash positions. Provides us the financial flexibility to execute on Business Development, as well as continued investments in our growing pipeline.
Looking ahead to the balance of 2025.
Our strong first half results, gives us increasing confidence in our full year outlook.
We are reiterating our Revenue guidance of 820 to 860 million, highlighting our progress, towards a 1 billion, plus opportunity with Wix and narcolepsy alone.
We expect continued quarter over quarter, net of Revenue growth, the balance of the year.
Sandip Kapadia: With respect to expenses, we expect continued investment in R&D as we advance our late-stage pipeline with multiple programs in Phase 3 registrational trials. As previously noted, we expect to potentially incur $29 million in R&D milestones payments in 2025, including milestones for the completion of the Phase 3 trial for ZYN-002 and Fragile X syndrome of $15 million, on track for Q3, along with a potential milestone of $10 million for positive top-line data from this trial. In addition, we expect a milestone of approximately $4 million in Q4 related to the initiation of Phase 1 trial in our RxN2 program. In summary, we are having a very successful first half of the year and have confidence in the continued growth of Wakix along with the advancement of our late-stage pipeline in the second half.
with respect to expenses, we expect continued investment in R&D as we advance our late stage Pipeline with multiple programs, in Phase 3, registrational trials,
as previously noted, we expect the potentially incurred 29 million in R&D milestones for payments in 2025 including milestones for the completion of the phase 3 trial for zyn 002 in fragile X syndrome 15 million dollars on track for Q3.
Along with a potential Milestone of 10 million dollars per positive, Topline data from this trial.
To the initiation of Phase 1 trial in our erection 2 program.
Sandip Kapadia: With that, I would like to turn the call back over to Jeff for his closing remarks. Jeff?
In summary we have a very successful first half of the Year and have confidence in the continued. Growth of WX along with the advancement of our late stage pipeline in the second half.
And with that, I'd like to turn the call back over to Jeff for his closing remarks. Jeff.
Jeffrey Dayno: Thank you, Sandip. My thanks to everyone for joining our call today and for your interest in Harmony Biosciences. At this juncture of our company's journey, I have never been more proud of the Harmony team or more excited about what lies ahead. The reasons for my excitement are many, but to highlight a few: Wakix is on its way to a $1 billion plus opportunity in narcolepsy alone. A robust, catalyst-rich late-stage pipeline is poised to deliver one or more new product or indication launches every year over the next several years, with peak sales potential of $3 to $6 billion in total. We have a high degree of conviction and are very excited about our next major clinical catalyst coming later this quarter: the top-line data readout from our Phase 3 trial of Zygel in Fragile X syndrome.
Thank you Sandeep.
My thanks to everyone for joining our call today and for your interest in harmony biosciences.
At this juncture of our company's journey, I have never been more proud of the harmony team or more excited about what lies ahead.
The reasons for my excitement are many but to highlight a few.
Wake kicks is on its way to a 1 billion plus opportunity in narcolepsy alone.
Our robust Catalyst ricch late stage pipeline is poised to deliver 1 or more new products or indication launches every year over the next several years with Peak sales, potential of 3 to 6 billion dollars in total
And we have a high degree of conviction and are very excited about our next major clinical Catalyst. Coming later this quarter
Jeffrey Dayno: If positive, this could represent a transformational moment for both the Fragile X community and for Harmony Biosciences. We have built something rare in our industry: a profitable, self-funding biotech company with an innovative late-stage pipeline poised to deliver meaningful value for both patients and shareholders alike. Because of this unique profile, we continue to execute from a position of strength, and that is what makes Harmony one of the most compelling growth stories in biotech today. Thanks, everyone, and I will now turn the call back over to the operator for Q&A. Operator?
The Topline data readout from our phase 3 trial of zyn 002 in fragile X syndrome.
If positive, this could represent a transformational moment for both the fragile X community.
And for harmony biosciences.
We have built something rare in our industry. A profitable self-funding. Biotech company with an Innovative late stage pipeline poised to deliver meaningful value for both patients and shareholders alike.
Because of this unique profile, we continue to execute from a position of strength.
And that is what makes Harmony 1 of the most compelling growth stories in biotech today.
Thanks everyone. And I will now turn the call back over to the operator for Q&A operator.
Madison: Thank you. At this time, if you would like to ask a question, please press star one on your telephone keypad. If you wish to remove yourself from the queue, you may do so by pressing star two. We remind you to please pick up your handset and please limit yourself to one question and one follow-up question. We will take our first question from Jay Olson with Oppenheimer. Please go ahead.
Thank you. And at this time, if you would like to ask a question, please press 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 please limit yourself to 1 question and 1. Follow-up question, we will take our first question from Jay, Olsson with Oppenheimer. Please go ahead.
Speaker 10: Oh, hey. Congrats on all the progress. I wanted to focus on the RE-CONNECT top-line data readout, which I think you mentioned is still on track for this quarter. Can you please provide any additional color on the timing of when to expect that readout? It sounds like maybe it could be after Labor Day. Then, just in terms of framing the expectations, can you just describe what would be clinically meaningful and what is your target for a successful outcome in this registrational Fragile X study? Finally, if you could just remind us the evidence that supports your confidence in ZYN-002 achieving your target profile. Thank you.
Oh hey. Congrats on all the progress. I wanted to focus on the reconnect Topline data readout which I think you mentioned is still on track for this quarter. Could you please provide any additional color on the timing of when to expect that readout? It sounds like maybe it could be after Labor Day. And then just in terms of framing the expectations can you just describe what would be clinically meaningful? And what is your target for a successful outcome in this registration for agilex study? And finally, if you could just remind us, the evidence that supports your confidence. In zyn, 002 achieving your, your target profile. Thank you.
Jeffrey Dayno: Good morning, Jay. Thank you for your questions and thanks for your coverage. Harmony welcomes your initiation of coverage. I will allow Kumar Budur to address your questions about the RE-CONNECT study and the opportunity in Fragile X syndrome.
Kumar Budur: Thank you, Jeff. Good morning, Jay. Thanks for the question. Yes, we are on track for top-line data in Q3, and we are very excited about this opportunity, not just because it is a major milestone for Harmony, but for patients with Fragile X syndrome and their caregivers in general. Regarding the level of confidence, we have a high level of confidence and conviction in the Phase 3 RE-CONNECT study because we are essentially trying to replicate the statistically significant findings that we saw in the large Phase 2/3 CONNECT study on the primary endpoint of social avoidance in patients with complete methylation. In terms of how we will define success, a successful outcome will be defined by demonstrating a statistically significant outcome in the primary endpoint, which is social avoidance in patients with complete methylation, and the study is more than adequately powered to detect that difference.
Yeah. Good morning J. Um, thank you for your questions and um thanks for your coverage. The harmony. Welcome, you know, um appreciate your initiation of coverage. Uh, I will love to work and address, you know your questions about um, the the reconnect study and the opportunity and fragile X syndrome. Yeah.
Thank you, Jeff. Good morning, Jay. Thanks for the question. Yes, we are on track for Topline data in Q3, and we are very excited about this opportunity, not just because it's a major milestone for harmony. But for patients with Felix syndrome and their care give us in general.
Uh, regarding the level of confidence. Uh, we have a high level of confidence and conviction in the phase 3, reconnect study, because we are essentially trying to replicate the statistically. Significant findings that we saw in the large Phase. 2 3, connect study on the primary endpoint of social avoidance in patients with complete methylation.
Kumar Budur: If positive, we have an opportunity here to bring the first and only approved treatment for any symptom domains in patients with Fragile X syndrome, and that is what we are really excited about.
Uh, in terms of how we will define success, success of successful outcome, will be defined by demonstrating a statistically significant outcome in the primary endpoint, which is social avoidance in patients with complete methylation and the study is more than adequately, powered to detect that difference.
It's positive. We have an opportunity here to bring the first and only approved treatment for any symptom domains in patients with flex syndrome and that's what we really excited about.
Brennan Doyle: Super helpful. Thanks for taking the question.
Jeffrey Dayno: Thank you, Jay.
Super helpful. Thanks for taking the question.
Yeah, thank you. Jay
Madison: Thank you. Our next question comes from David Amsellem with Deutsche Bank. Please go ahead.
Thank you. And our next question comes from David Wong with Deutsche Bank. Please go ahead.
Speaker 11: Hi there. Good morning. Congrats on the progress and thanks for taking my questions. First, I also wanted to ask on Fragile X in terms of, I guess, the top-line readout. Could you just outline for us the data that the types of data you expect to disclose in the top line? At that time, would we have visibility on the result in the fully methylated versus partially methylated patients? When might we know, I guess, how you plan to approach your filing strategy with the FDA if you would be pursuing fully methylated or all comers? Then just quickly on Wakix, as we are now in the back half of the year, I was wondering if you could just talk a little bit about the pushes and pulls that get you to the upper versus the lower end of the guidance range. Thanks a lot.
Jeffrey Dayno: Good morning, David. Obviously, I will ask Kumar Budur to comment further on the strategy for Fragile X and the Zygel readout, and Adam Zaeske can address the question about Wakix. Kumar?
Hi there. Good morning. Congrats on the progress and thanks for taking my questions. Um, so first, I also wanted to ask on Fragile X in terms of, uh, I guess the topline readout. Could you just outline for us the, um, you know, the data that the types of data you expect to disclose in the topline at? And at that time, would we have visibility on the result in the fully methylated versus partially methylated patients? Um, and when might we know, uh, I guess how you plan to approach or filing strategy with the FDA, if you would be pursuing fully methylated or all comers? And then just quickly on weight kicks. Uh, as we are now in the back half of the year, I was wondering if you could just talk a little bit about the pushes and pulls that get you to the upper versus the lower end of the guidance range. Thanks a lot.
Kumar Budur: Yeah. Hey, good morning, David. Thanks for the question. So in terms of what we disclose at the top-line data for Fragile X syndrome, it will be a standard top-line data readout, which is the demographics data, safety and tolerability data, the efficacy on the primary endpoint, and the key secondary endpoints. In terms of how we will proceed next, look, if the study shows statistically significant outcome on the primary endpoint, we will move rapidly to have a pre-NDA meeting and submit an NDA. In an indication like Fragile X syndrome, where there are no approved treatments, I think it's fair to expect a priority review. If everything goes according to plan, hopefully, we will have an approved product by the end of next year.
Yeah, good morning, David. Yeah. Um, obviously, I'll ask Kumar to to comment comment further on, um, you know, the, the strategy for fragile X and the zyn readout, um, and Adam can address the, the question about, like, it's going to work. Yeah. Hey, good morning, David, thanks for the question. So, in terms of what we disclosed at the Topline data, for for the syndrome, it will be a standard Topline data readout, which is the demographic data, safety and tolerability.
Data, the efficacy on the primary endpoint and the key secondary endpoints.
Uh, in terms of what, how we will proceed next look, if the study show, statistical significant outcome on the primary endpoint, uh, we will move rapidly to have a pre-nda meeting and submit an NDA.
Uh in an indication like frazzle syndrome where there are no approved treatment. I think it's fair to expect a priority review and if everything goes according to plan uh hopefully we will have an approved product by the end of next year.
Jeffrey Dayno: Thanks, Kumar. Adam.
Speaker 10: Yes. Thanks for the question on Wakix. We are really pleased with the performance that we are seeing on Wakix at this stage. We are now in our sixth year on the market. We achieved $200.5 million in net revenue for the second quarter. That is a 16% year-over-year increase in year six, which is fantastic. We also achieved 7,600 average patients in the quarter. That is an increase of 400 average patients in Q2, and that is among the highest increases we have seen in any quarter since launch. The performance steady drumbeat continues. In terms of puts and takes, I would say that Wakix is a highly differentiated product, first and only non-scheduled treatment option for patients. We are supported by broad payer coverage with 80% of lives covered, and that has been the case for years. We do not expect any changes in payer coverage.
Just 2 more.
Speaker 10: We have a very experienced team. Many of our team members actually started at the launch of Wakix, and we have a unique commercial model that provides really high levels of service to HCPs, office staff, as well as patients. I would highlight that in terms of HCP prescribers, we continue to see increased preference share in the 4,000 Oxybate REMS-enrolled clinicians, and we see increased preference share and the addition of new prescribers in the 5,000 non-Oxybate REMS-enrolled HCP group as well. Those are probably the key drivers of that continued performance. Sandip, I do not know if you want to add anything.
Yes. Thanks, uh, for the question on Wix. We're really pleased with the performance that we're seeing on Wix, at this stage. We're now in our sixth year on the market, we achieved 200.5 million in net revenue for the second quarter. That's a 16% year-over-year increase in in year 6, which is fantastic. We also achieved 7,600, average patients in the quarter, that's an increase of 400 average patients in Q2 and that is among the highest increases we have seen in any quarter since launch. So the performance, uh, steady drum beats continues in terms of puts and takes, you know, I I would say that Wix is a highly differentiated products. First, and only non-scheduled treatment option for patients who are supported by broad payer coverage with 80% of lives covered. And that's been the case for years. We don't expect any changes in payer coverage. We have a very experienced team. Many
Jeffrey Dayno: No. I think, as you said, really a strong start to the year and really gives us increased confidence, certainly in our guidance range. Look, we are very comfortable with where things are at right now. It is really, at the end of the day, the underlying demand that really drives overall net sales. As you know, in terms of the pushes and pulls, it is the typical factors that will typically impact where we end up in the range, everything from, obviously, this continued net patient adds, certainly have an impact, any potential gross net impact, as well as trade inventory impacts as well. As you know, we have a fairly concentrated customer base overall, so just order patterns overall. However, look, we are very confident in the guidance range. Consensus currently falls right within the range, and that seems a very reasonable place. Thanks, David.
Of our team members uh actually started at the launch of Wix um and we have a unique commercial model that provides really high levels of service to hcps, office staff, as well as patients. And I would highlight that in terms of hcp prescribers, we continue to see increased preference share in the 4000 ocab, Rems enrolled clinicians, uh, and we see increased pre preference share, and the addition of new prescribers in the 5000, nonoxide Rems, enrolled hcp group as well. So those are probably the key drivers of that continued performance Sandeep. I don't know if you want to add anything. No, I think uh as you as you said, really a strong start to the year and and really gives us increased confidence certainly in our guidance range. Like we're very comfortable with where things are at right now, you know, it was it's really at the end of the day, it's the underlying demand that really drives overall net sales and and as uh, you know, in terms of the pushes and pulls, it's the typical
Factors that will typically impact where we end up in the range. Everything from obviously, this continued net patient ads, you know, certainly have an impact, any potential aggressors in that impact, as well as trade inventory impacts as well, you know, um, as you know, we have a fairly C. We have a, we have a concentrated customer base overall, so, just order. Order patterns overall, however, we're very confident in The Guiding range, you know, consensus is currently Falls right within the range and we're very that seems very reasonable place.
Thanks David.
Madison: Thank you. Our next question comes from Ash Verma with UBS. Please go ahead.
Thank you. And our next question comes from Ash Verma with UBS. Please go ahead.
Speaker 12: Hi. Thanks for the question. I just wanted to ask on Fragile X. I want to understand the implications of full methylation. Does choosing full methylation versus partial mean a haircut to the patient population? If you can give us a sense of what is the full methylation Fragile X patients in the U.S. versus the 80,000 that you mentioned? Secondly, can you talk about any kind of regulatory or clinical trial conduct analogs here? Has FDA accepted applications for these types of rare pediatric conditions with the data showing efficacy only in a fully turned-off gene? Thanks.
Means uh a haircut to the patient population. Uh just if we can give us a sense of like what is the full methylation? Uh fragile X patients, uh, in the US uh, versus the 80,000 that you mentioned, and then, secondly can you talk about uh, some any kind of like regulatory or clinical trial conduct analogues here. So as FDA accepted applications for these type of rare pediatric conditions with the data showing efficacy, only in a fully turned off uh Gene.
Thanks.
Kumar Budur: Hey. Good morning, Ash. Thank you for the question. In terms of this split between complete methylation versus partial methylation, approximately 60% to 70% of patients with Fragile X syndrome have complete methylation, and the rest have partial methylation. In terms of us choosing the complete methylation as the target population, this was a data-driven approach based on the findings that we saw in the CONNECT study, and this fits into the etiology, the pathophysiology of Fragile X syndrome that we know about. Basically, what happens in patients with the complete methylation is they have more than 200 trinucleotide repeats of CGG, which results in almost complete silencing of the gene, which means that they are hardly able to produce any FMR protein, which causes significant dysfunction of the endocannabinoid system. ZYgel interacts with CB1 receptors, resets the endocannabinoid system. These patients have a higher burden of symptoms.
hey, uh,
Good morning, guys, thank you for the question. So, in terms of this plate between complete methylation was the partial methylation approximately 60 to 70% of patients with, uh, Plaza like Syndrome have complete methylation and the rest have partial methylation. So in terms of using the complete methylation, as the target population, this was a data-driven approach based on the findings that we saw in the Kinect study and this fits into the ideology, the pathophysiology of frazzle syndrome that we know about basically what happens in patients with the complete methylation is they have more than 200 time, nucleotide repeats of vgg which results in almost complete silencing of the gene, which means that they are hardly able to produce any fmr protein. Which
Was a significant dysfunction of the endocrine system.
Kumar Budur: The mechanism of action fits nicely well in treating the symptoms in these patients. In terms of the FDA, yes, we actually have had extensive discussions with the FDA, and we have full alignment with the FDA on the study design, the target patient population, the primary endpoint. In fact, the study is designed not just to meet the requirements of FDA, but EMA as well. Should the study be positive, we will be pursuing an indication both in the U.S. and in Europe.
Jeffrey Dayno: Ash, I would just add that I think this strategy sort of follows the science as well as the data. The Phase 3 RE-CONNECT trial is designed to replicate the positive findings in the Phase 2/3 CONNECT study in patients with complete methylation. In addition, obviously, with no approved therapies with regard to where the bar would be set with a high unmet need in this patient population.
And Z10 02, interacts with CB1 receptors, resets the endocrine system. So these patients have a higher burden of symptoms, the mechanism of action fits nicely well in treating, the symptoms in these patients. Uh, in terms of the FDA, yes, we actually have had extensive discussion with the FDA and we have full alignment with the FDA on the study design, the target patient population, the primary endpoint. Uh, in fact, uh, the study is designed not just to meet the requirements of FDA but Imma as well. So should the study be positive. We will be pursuing an indication both in the US and in Europe.
Yeah, Ash. I would just add that, I think, you know, this strategy, you know, sort of follows, you know, you know, the science as well as the data and the phase 3 reconnect, you know, trial is designed to, you know, replicate the positive findings in the phase. 2 3, connect study in patients with with complete ventilation. Um, and then in addition in, um, obviously with no approved therapies, you know, with regards to, you know, where the bar would be set, um, with a high, you know, High unmet need in this patient population.
Speaker 12: Thank you.
Jeffrey Dayno: Thanks, Ash.
Thank you.
Thanks Ash.
Madison: Thank you. Our next question comes from Graig Suvannavejh with Mizuho. Please go ahead.
Thank you. And our next question comes from Greg Suvan with Missou. Greg, please go ahead.
Speaker 13: Thank you. Good morning. Thanks for taking my question. I was curious about your new Cirque collaboration. I was just wondering, can you walk us through these thoughts, especially from a BD and corporate strategy perspective? The cell therapy approach is interesting for sure, but I don't think it's been a proven area. I just wanted to get your thoughts on the collaboration, but also maybe future BD directions. Thank you.
Thank you. Good morning. Thanks for taking my questions. Um, I was curious about your new uh Cirque um collaboration. I was just wondering. Um can you walk us through the thoughts? Especially from a BD and corporate strategy perspective. Um, the cell therapy approach is interesting uh for sure but I don't think it's been up a proven area. And so just wanted to get your thoughts just on the collaboration but also maybe uh future be uh directions thank you.
Jeffrey Dayno: sure, Graig Suvannavejh. Good morning. Thanks for your question. I think in terms of the Teijin Pharma collaboration, we see it as an exciting opportunity, obviously a very early sort of discovery phase opportunity, but one that reflects our overall commitment to patients with serious rare neurologic disorders in an advanced stage. It's strategically aligned with our pipeline and potential cellular therapies for refractory epilepsy in one of the discovery programs and the other treatment-resistant narcolepsy based on sort of reprogramming the cellular platform. While it's still early, we see this as potentially resulting in kind of the next generation of innovative disease-modifying therapies for patients with advanced neurologic disorders. With that, Kumar Budur can comment a little further on the platform and what we saw in the opportunity.
Yeah, sure. Great. Um, good morning. Thanks for your question. Yeah, I think in, in terms of the circle collaboration, you know, we see it as, um, an exciting opportunity. Obviously a very early, uh, sort of Discovery phase opportunity, but 1 that, you know, reflects our overall commitment to patients, you know, with serious, you know, rare neurologic disorders, you know, in an advanced stage. Um, it's strategically aligned, you know, with our Pipeline and, you know, potential cellular therapies for refractory, um, epilepsy in 1 of the discovery programs and the other, uh, treatment resistant, narcolepsy, based on sort of reprogramming, you know, um, the cellular platform
Kumar Budur: Sure. Hey, good morning, Graig Suvannavejh. Thanks for the question. Look, with the Cirque, what really attracted and really fascinated us was the novel cellular reprogramming platform that Cirque utilizes that offers significant.
So, um, again, while it's still early, uh, you know, we see, uh, this is potentially, you know, the resulting in kind of the next generation of innovative disease, modifying therapies for patients, you know, with with Advanced neurologic disorders, um, with that, um, Kumar can comment a little further on, you know, on the platform and and you know what? We saw in the opportunity. Sure. Hey good, good morning Greg. Thanks for the question. Uh look with the sir uh what really attracted and really fascinated us.
Speaker 1: competitive and manufacturing advantages compared to embryonic or induced pluripotent stem cells. It overcomes many challenges, like, for example, the consistency and the reliability of readily sourced GMP-grade cell lines because these are fibroblast-derived cells that are induced to transfer into progenitor cells of interest based on a small molecule epigenetic modifiers and growth factors. This particular platform could potentially enable allogeneic cryopreserved ready-to-use therapies that require no manipulation at the point of care. Because we are not using the stem cells, there is less risk of tumorogenicity and manufacturing inefficiencies that are seen with the stem cells. We are very excited about the collaboration both in epilepsy and in narcolepsy, and look forward to data generation from CERK. We will provide more information as we make progress.
That Cirque utilizes set off for significant competitive and Manufacturing advantages compared to embryonic or induced fluid and stem cells it. Overcomes many challenges like say, for example, the consistency and reliability of readily sourced GMP grade cell lines because these are fibroblasts derived cells.
Speaker 2: Yep. Greg, I would add, I think, we see this as an opportunistic play, if you will. Again, very early discovery phase, strategically aligned. With regards to our other BD efforts, as you asked, obviously, our strategy is to continue to grow and build out our pipeline. With a very strong balance sheet, we see, in terms of we are always looking for opportunities to deploy our cash and drive value for shareholders. We continue to actively evaluate different opportunities across the spectrum, development phase from early to late, potentially on-market opportunities. Obviously, we are in a good position to execute on our growth strategy. As always, we take a disciplined approach, thoughtful, strategic to how we have built out the pipeline thus far and some of the opportunities we see ahead. We feel that we are just getting started with regards to some of the opportunities ahead of us.
That are induced to transfer into progenate cells of Interest based on a small molecule epigenetic, modifiers and growth factors. And also this particular platform could potentially uh enable allergenic chriop Reserve ready to use therapies that requires no manipulation at the point of care. And obviously because we are not using the stem cells. There is less risk of tumors in the city and Manufacturing in in every inefficiencies that are seen uh with the stem cells. So we are very excited about the collaboration both in epilepsy and in North Epsy and look forward to data, generation from fur and we will provide more information as we make progress. Yeah.
And Grace, I would add, I think, you know that we we see this as a, an, um, kind of an opportunistic play. If you will again, you know, very early Discovery phase strategically aligned with regards to our, you know um other bdfs. As you asked, you know,
Speaker 2: Sandip, any further comments on the capacity?
Speaker 3: Yeah, look, I mean, this quarter was a really strong quarter in terms of cash generation. We generated from operations $79 million, closing the quarter with over $670 million in cash. So I think we are in a highly strong position to be able to transact. I mean, look, we continue to look for opportunities, as you mentioned, Jeff, across the spectrum overall. We will continue to be disciplined in terms of how we deploy our capital. Our filters continue to be the same. So I think we are, it is hard to predict timing at the end of the day on these types of things, but I think we are really continuing to be in a strong position.
You know, obviously our strategy is, is to continue to grow and build out, um, our Pipeline and with, you know, a very strong balance sheet. Um, you know, we see, you know, in terms of we're always looking for opportunities to deploy, you know, our cash and drive value for shareholders. Um, we continue to actively evaluate different opportunities across the Spectrum. Um, you know, development phase from early to late, uh, potentially on Market opportunities. Um, obviously we we're in a good, uh, position to, um, execute on our growth strategy. Um, as always, you know, we take a disciplined approach thoughtful, strategic to, um, how we build out the pipeline thus far, um, and some of the opportunities, you know, we, we see ahead, we feel, um, you know, that we're just getting started, uh, you know, with regards to, you know, some of the opportunities ahead of us. Um, some deep, any further comments on on the capacity.
Speaker 3: We have a very unique profile as a company, highly profitable, generating positive cash flow, and the ability to deploy it in a market that is an attractive market at this point.
Speaker 2: Yeah. Thanks, Sandip.
Yeah, look I mean you know this quarter was really strong quarter in terms of cash generation. We generated from operations, 79 million closing, the the quarter with over 670 million in in cash. So I think you know, we're in a highly uh uh strong position to be able to to transact. I mean, look, we continue to look for opportunities. As you mentioned Jeff across across the Spectrum. Overall, you know, uh, we'll continue to be disciplined uh, in terms of how we deploy our Capital, um, you know, but our filter filters continue to be the same. So I think we're, you know, it's hard to predict timing at the end of the day on these types of things. But I think, you know, we're really continue to be in a strong position, we have a very unique profile as a company, highly profitable, generating, positive, cash flow, and the ability to deploy it in the market. That that is an attractive Market at this point. So
thanks indeed.
Madison: Thank you. Our next question comes from David Amsellem with Piper Sandler. Please go ahead.
Thank you. And our next question comes from David, am Psalm with Piper Sandler. Please go ahead.
Brennan Doyle: Thanks. Had some questions on the orexin. Sorry if I missed this, but with the data that you are anticipating next year, is that in healthy, sleep-deprived volunteers, or is that going to be in actual narcolepsy patients? Just help us understand what to expect for next year. To the extent you are not yet testing narcolepsy in IH patients, when do you expect to do so? That is number one. Number two, in terms of differentiation, I know you have talked about it as potentially being best in class, but we have got a number of more advanced orexins that have shown MWT improvements well north of 20 minutes. We have seen real validation here. What do you need to see in order to legitimately make that claim that your orexin is indeed best in class? Thanks.
Um thanks have some questions on the oryx and um and sorry if I missed this. But with the data that you're anticipating next year is that in healthy sleep deprived volunteers or is that going to be an actual, um, narcolepsy patients, or just help us understand? You know what to expect uh for next year and to the extent. You're not yet testing narcolepsy.
In IH patients, when do you expect to do so? That's number 1. And then number 2, in terms of differentiation, I know you've talked about it as potentially being best in class but we've got a number of more advanced or accents that have shown, uh, mwt. Um, you know improvements, well north of 20 minutes and and we've seen, you know, real validation here. So what do you need to see in order to uh legitimately make that claim that your orexin is indeed best-in-class. Thanks,
Jeffrey Dayno: Morning, David. Thanks for your question. Kumar, our position on the orexin programs?
Good morning, David, thanks for your question, um, to Mark our position on the the erections.
Speaker 1: Thank you, Jeff. Good morning, David. Thank you for the question. Regarding our orexin program, yes, David, you did not miss anything because we have not talked about how we are going to approach the first-in-human studies. We are on track for IMPD submission and commence first-in-human studies later this year. The way we are approaching this is to start with the single ascending dose study in healthy volunteers and in parallel also conduct a healthy volunteer sleep deprivation study because, as you know, BP1.15205 is the most potent orexin receptor agonist that is out there based on the data that is disclosed in the public domain. We do want to get a better idea in terms of the dose range before we progress this into patients.
Programs.
Talked about how we are going to approach and uh the first in human studies. Uh we are on track for impd submission and comments first in human studies later. This year, the way we are approaching, this is start with the single ascending dose study in healthy volunteers and in parallel also conduct
Speaker 1: What you can expect next year is data from healthy volunteers from single ascending dose study and healthy volunteers sleep deprivation study as well. How we are going to proceed after that is something that we are still thinking through, depending on what we are learning from others as well in this field. In terms of how do we differentiate, David, I think it's too early to comment. Based on the preclinical data, which we presented at the SLEEP meeting, we showed that potency is important, and potency translated to efficacy at very low doses. In fact, at 0.03 mg/kg in the narcolepsy mice model, we showed a statistically significant difference in wakefulness time, the lowest dose that is ever studied in this particular model.
A healthy, volunteer sleep, deprivation study because as you know, uh, bb1 15205 is the most important or extent receptor Agonist. That is out there based on the data that is disclosed in the public domain. And we do want to get a better idea in terms of the dose range. Before we progress this into patients, what you can expect. Next year, is data from healthy. Volunteers from single ascending dose study and uh, healthy volunteers sleep, deprivation study as well.
How we are going to proceed after that is something that uh we are still uh, thinking through uh, depending on what our uh, what we are learning, uh, from others as well in this field.
In terms of, how do we differentiate? Uh, David? I think it's too early to comment uh based on the preclinical data which we presented at the Sleep meeting. We showed that
Speaker 1: We anticipate the high potency and therefore low dose gives us the flexibility, the dosing flexibility to target all three central disorders of hypersomnolence, not just NT1 but also NT2 and idiopathic hypersomnia without having the safety or tolerability concerns. So this is our strategy right now.
potency is important and potentially translated to efficacy at very low doses. In fact, at 03 Nick per cake in North c. M model, we showed statistically significant difference in wakefulness time the lowest dose that is ever studied in this particular model.
Uh, we anticipate.
The high potency and therefore low dose gives us the flexibility. The dosing flexibility to Target. All 3 Central disorders of hyper formula and it's not just N1, but also N2 and EOP hypersomnia without having the safety or tolerability concerns, so that this is our strategy right now.
Speaker 2: Thank you. Thanks, David.
Thank you.
Thanks David.
Madison: Thank you. Our next question comes from Danielle Brill with Truist. Please go ahead.
Thank you. And our next question comes from Danielle bril with truist. Please go ahead.
Adam Zaeske: Hey, guys. Good morning. Thanks so much for the questions. As a follow-up to the prior question, I wanted to ask in general how we should think about the potential impact of Takeda's orexin 2 entering the market and how confident you are that the Wakix expansion can continue to grow with orexin 2s in the market. On the quarter, I wanted to clarify, it looks like the quarter-over-quarter growth was lower than what you typically observed in the past despite the high number of new patient adds in the quarter. Was this just an inventory drawdown, or can you speak to the dynamics that were at play here, such as growth to net compliance and any other factors? Thank you.
Hey guys, good morning. Thanks so much for the questions. Um, as a follow-up to the prior question, I wanted to ask in general, um, what how we should think about the potential impact if you could us or X into entering the market,
Um, and how confident you are that the Wake expansion can continue to grow with erecting tooth in the market and then just from the quarter, I wanted to clarify, it looks like the quarter over quarter growth was lower than what you typically observed in the past, despite the high number of new patient ads in the quarter, uh, was this, just an inventory, draw down, or can you speak to the Dynamics that were at play here such as gross to net compliance and, and any other factors? Thank you.
Speaker 2: Good morning, Danielle. Thanks for your questions. In terms of the impact of orexins, how we see as we follow these programs closely, I will ask Adam Zaeske in regards to we still continue to see this market as a polypharmacy market with multiple mechanisms and how you are seeing that from a commercial perspective going forward?
Kumar Budur: Thanks, Jeff. Thank you for the question. We are excited about orexins as a potential new treatment option for patients. As Kumar Budur mentioned, we are very confident in the molecule that we have in our pipeline. There are still some questions to be addressed as a class, I think: dosing, label, long-term safety and tolerability, not to mention pricing and access. With Wakix, this is the only non-scheduled treatment option. It has been on the market for now more than six years. Really steady performance quarter-over-quarter over that period. That is despite new brand and generic entrants coming in. I think that is because physicians see Wakix as highly differentiated. They perceive it to be well-tolerated and it has broad clinical utility. We expect that to continue.
Good morning, Danielle, thanks. Thanks for your question. Um in in terms of um you know the impact of a Rex and how we see, you know as we follow these programs closely I'll ask you know Adam in regards to we still continue to see this Market as a poly pharmacy market. You know with multiple mechanisms and um, how you're seeing that from a commercial perspective going forward? Yeah, thanks Jeff. And thank you for the question. You know, we're excited about our Rex is a potential new treatment option for for patients. And as Kumar mentioned, we're very confident in in the molecule that we have in our pipeline. You know there's still some questions to be addressed as a class. I think uh, dosing label, long-term safety and tolerability, not to mention pricing and access.
Know with Wix. This is the only non-scheduled treatment option that has been on the market for more than 6 years.
Kumar Budur: At the time of orexins launch, HCPs will have more than eight years of clinical experience. It is a very familiar therapeutic option. With the polypharmacy approach to treatment, we expect Wakix will continue to be added to therapy for patients broadly. Not to mention that there is evidence to suggest that orexin and histamine actually have a synergistic effect. So we are very confident in the continued growth and performance of Wakix.
Speaker 2: Thanks, Adam. With regards to the quarter's performance, Sandip, if you have comments on that.
Speaker 3: Sure. Happy to comment on that. I think, as I mentioned, generally, our results so far give us increased confidence in the revenue guide of $820 million to $860 million. The fundamentals are strong. We had strong growth even in the quarter of 16% versus prior year. In fact, in Q2, getting to your point, the underlying performance is probably even stronger than I would say the net revenues would indicate. As I mentioned in my Q1 call, we did anticipate and we did see a trade inventory drawdown of approximately a few days, as we head into the summer month. Typically, what happens with trade inventory, as you know, Q4, Q1 tends to be a little bit higher. Q2, Q3 tends to be a bit lower generally.
Really steady performance quarter over quarter over that period and that's despite new brand and generic entrance coming in. I think that's because Physicians C. Wix is highly differentiated. They perceive it to be well, tolerated and has broad clinical utility and we expect that to continue, you know, at the time of our exams launch hcps will have more than 8 years of clinical experience. It's a very familiar, uh, therapeutic option and with the Jeff mentioned that with the poly Pharmacy approach to to treatment, uh, we expect, um, wake up continue to be added to, uh, to therapy for patients. Uh, broadly. Um, not to mention that there's evidence to, to suggest that our X, and, and histamine actually have a synergistic effect. So we're very confident in the continued growth and performance of wikis. Yeah, thanks Adam with regards to the, uh, Porter's performance some deep, if you, uh, comments on that. Sure, I uh, happy to comment on that, you know, I think, uh, as I mentioned, uh, generally look our results so far, you know, gives us increased confidence in the revenue guide.
Speaker 3: The more important point is really looking at the fundamentals of our business and the forward demand of one of the strongest quarters we have had in terms of net patient adds. Generally, again, it gives us really strong confidence in the balance of the year. We expect very strong quarter-over-quarter growth for the next two quarters to finish out the year.
Speaker 2: Yeah. So, I think just to reiterate, I think underlying business fundamentals remain strong. I think some variability in inventory from quarter to quarter, as Sandip alluded to, obviously is the base. The base of patients increases. Then also with only three specialty pharmacies in terms of the ordering pattern. So, I think a couple of days of inventory with regards to that fluctuation. But overall, we are confident in reaffirming guidance for the year. We are comfortable with the street kind of estimates of where we are. This business continues to grow and I am excited as our pipeline advances and the opportunities ahead.
In the quarter, we are at 16% versus the prior year. And, you know, in fact, I mean, in Q2, uh, getting to your point, it's really the underlying performance is probably even stronger than I would say. The net revenues would indicate, as I mentioned in my Q1 call. Um, you know, we did anticipate and we did see, uh, trade inventory drawdown of approximately a few days. You know, as we head into the summer months, um, typically what happens with trade inventory, as you know, you know, Q4 and Q1 tends to be a little bit higher, while Q2 and Q3 uh, tend to be a bit lower, um, generally. But it's, you know, I think the more important point is really looking at the fundamentals of our business and the forward demand of, you know, one of the strongest quarters we've had in terms of net patient ads. And generally, again, it gives us really strong confidence in the balance of the year. And, you know, we expect very strong quarter-over-quarter growth for the next, uh, two quarters, uh, to finish out the year. So I think just to reiterate, I, you know, I think underlying business fundamentals remain strong. You know, I, I think, you know, some variability in inventory.
From from quarter to quarter as some people. Alluded to obviously is the base. Um, you know, as the base of patients, you know, increases and then also, you know, with only 3, you know, specialy and in terms of the ordering pattern. So I think a couple days of inventory, you know, with regards to that, that fluctuation. Um, but overall, um, we are confident in reaffirming guidance. For the year, we're comfortable with the streets, kind of estimates of where we are this business continues.
And um excited you know, as our pipeline advances and the opportunities ahead.
Madison: Very helpful. Thank you so much.
Speaker 2: Thanks, Danielle.
Very helpful. Thank you so much.
Thanks Danielle.
Madison: Thank you. Our next question comes from Corinne Johnson with Goldman Sachs. Please go ahead.
Thank you. And our next question comes from Karen Johnson. With Goldman Sachs. Please go ahead.
Sandip Kapadia: Good morning. This is Eric Ahn for Corinne Johnson. I just wanted to ask a question elaborating on the last little bit. Specifically, how should we think about net price for Wakix this quarter and specifically moving towards the back half of 2025 and beyond? To what extent are you using price as a lever to improve volume or drive broader adoption? Thanks.
Good morning. This is Eric on for recurring Johnson. So I just wanted to ask a question elaborating uh on the last little bit. Um specifically, how should we think about net price for Wix this quarter inclusively, moving towards the back half of 2025?
Speaker 2: Thanks for your question, Sandip.
Sandip Kapadia: I think in terms of net price evolution, it would be very similar to what we have seen in past years. Typically, the first quarter is the lowest, just as we have higher growth to net deductions. Typically, that happens with insurance plans resets and typically improves in the balance of the year. We did see some improvement as we went into Q2. As we go into the further quarters, we will continue to see improvement that will help realize a good portion of the price increase that we took earlier this year.
Um, and Beyond, and and to what extent are you using price? As a lever to improve volume or drive broader adoption? Thanks. Thanks your question. Um, from yeah, I think in terms of net price, Evolution, it would be very similar to what we've seen in past years. Typically, the first quarter is is the lowest just as we have higher growth than that deductions. Um, typically uh, that happens with the insurance plans to reset and typically improves in the balance of the year. So we did see some improvement as we went into Q2. But you know obviously uh as we as we go into the further quarters, we'll continue to see Improvement, um, that will help realize um, you know, a good portion of the price increase that we took earlier this year.
Speaker 2: Thanks, Sandip.
Thanks.
Madison: Thank you. Our next question comes from Patrick Trucchio with Cantor Fitzgerald. Please go ahead.
Thank you. And our next question comes from Pete. Several pillows with Cancer Fitzgerald, please go ahead.
Speaker 10: Hi, yeah. Thank you for taking my question and congrats on the quarter. I have two questions. The primary endpoint for Reconnect, the social avoidance, a domain for the ABC checklist for pitolisant. It is an observer surface scale, either parents or caregivers score. Can you just talk about this outcome, potential variability, the expected placebo response, and what measures you have taken to mitigate the placebo response? Are there any other major differences between Connect and Reconnect? The second question is for Adam Zaeske. You joined Harmony Biosciences Holdings Inc over 1.5 quarters ago. I am curious to hear your views on what levers you may be able to pull to accelerate growth and build off what is already a successful franchise and also plans for lifecycle management. Thank you.
Yeah, thank you for taking my questions, and congrats on the quarter. Um, I have 2 questions. Um, the primary endpoint for Reconnect, the social avoidance domain for the ABC checklist for Brazil X, you know, it's an observer, um,
Service scale, either, you know, parents or caregivers score? Can you just talk about this? Uh, outcome potential variability, uh, the expected placebo response.
Speaker 2: Yeah, Pete, thanks for your questions. Thanks for taking coverage on Harmony Biosciences Holdings Inc. Appreciate that. Kumar?
And what message you've taken to mitigate the Apple response and are there any other major differences between connect and reconnect? And the second question is for Adam, you know, you joined Harmony over 1.5 quarters ago. Um, curious to hear your views on, you know what levers, you know, you may be able to pull to to accelerate growth and um, build all you know, what is already a, a successful franchise. Um, and also plans for lifestyle cycle management, thank you.
Speaker 1: Yeah. Good morning, Pete. Thanks for the question. Regarding the social avoidance subscale within the broader aberrant behavior checklist, you are absolutely right. This is an observer-assisted scale. As you know, ABC has been used extensively, a very well-validated scale. We have a lot of experience with this particular scale. In terms of variability and placebo, great question. Look, in any neuropsych trial, these are some things that we carefully watch for. In this particular study, we have multiple checks and balances to manage, including rigorous inclusion-exclusion criteria. These are the patients biologically identified based on full mutation, complete methylation with a significant level of symptoms. We know the standard deviation for this particular instrument, not just in general, but in patients with father-like syndrome. We are obviously monitoring in the blinded data that we have. Thus far, where we are, we feel good about it.
Yeah, Pete. Thanks for your questions. Thanks for taking coverage on Harmony, appreciate that. Um, 2 more yeah. Uh, good morning Pete. Thanks for the question. Uh, regarding the social avoidance subscale within the broader, aberrant Behavior checklist. You're absolutely right. This is an observed scale as you know, ABC has been used.
Extensively uh very well validated scale. We have a lot of experience with this particular scale, in terms of variability and possible. Great question. Look in any neurosight trial. These are something that we carefully watch for. Uh in this particular study, we have multiple checks and balances to manage including rigorous inclusion exclusion criteria. These are the patients that have biologically identified based on full mutation complete methylation with significant level of symptoms.
Speaker 1: In terms of differences between Connect and Reconnect study, the primary endpoint, Pete, is still the same, which is social avoidance subscale within the broader ABC scale. The target population is patients with complete methylation only. We made some other enhancements, like, for example, we increased the duration of treatment by four weeks. We increased the dose in patients who weigh more than 50 kilograms. These were done based on the learnings from the Connect study to enhance the probability of success. As I mentioned earlier, a high level of confidence and conviction in this program and really the opportunity that is in front of us. If the study is positive, we have an opportunity to bring the first and only approved treatment for patients with father-like syndrome.
For this particular instrument, not just in general, but in patients with flex zone and we are obviously monitoring uh, in in the client data that we have and thus far where we are, we feel good about it. Um,
Speaker 2: Thanks, Kumar. Adam, your thoughts on levers for growth in the Wakix business?
Kumar Budur: Yeah, thanks for the question, Pete. Levers of opportunity is a term that we talk about so infrequently at Harmony. It is a big focus. I have to give credit to the team. The team here really does have a history of growth mindset and looking for continued improvement opportunities. What we have been discussing is how can we continue to improve our top-line demand growth, so average referrals per day, and then conversion of those referrals into dispensing events. So how can we make sure that our process is efficient and effective for patients to secure a dispense? Then retention over time. How can we provide the service that supports HCPs, the office staff, and the patient to ensure that they maintain or remain on therapy over time? We have identified levers that we are going after.
In terms of uh difference between connect and reconnect study, the primary end point it is still the same which is social avoidance of scale within the broader ABC scale. The target population is patients with complete methylation only and we made some other enhancements. Like, for example, we increase the duration of treatment by 4 weeks, uh, we increase the dose in patients, who weigh more than 50 kilograms. This, uh, this was done based on the learning from the Kinect study to enhance the probability of success. Uh, as I mentioned earlier, uh, high level of confidence and conviction, this program and really the opportunity that's in front of us. If the study is positive, we have an opportunity to bring the first and only option for patients with cross back syndrome. Yeah, thanks Kumar. Um, Adam, your thoughts on on levers for growth and in the wake of this business. Yeah, thanks for the
Kumar Budur: The work has started, and I am confident that the work of the team is going to continue to help drive that performance.
Speaker 2: Great. Thanks, Adam.
A question Pete and actually levers of opportunity is a term that we talked about un frequently, uh, at Harmony, uh, and it's a big focus and I have to give credit to the team that the team here really does have a history of growth mindset, looking for continued, uh, Improvement opportunities. Uh, what we've been discussing is, how can we continue to improve our Topline demand growth? So average referrals per day um and then conversion of those referrals into dispensing events so how can we make sure that our process is efficient and effective for patients to secure a dispense and then retention over time. How can we provide the service uh that supports hcps the office staff and the patient uh and to ensure that they maintain uh or remain on therapy over time. So we've identified levers that were going after the work has started and I'm confident that that the work of the team is going to continue to help drive that performance great. Thanks. Thanks, Adam.
Speaker 10: Thank you very much for taking my questions. Congratulations again.
Speaker 2: Thanks.
Great. Thank you very much for taking my questions and I'm not in Grass again.
Madison: Thank you. Our next question comes from Patrick Trucchio with H.C. Wainwright. Please go ahead.
Thanks.
Thank you. And our next question comes from Patrick tuio with HC, Wayne White. Please go ahead.
Sandip Kapadia: Hi, good morning. Just a couple of follow-up questions from us on the pipeline. The first is on pitolisant HD. I am just wondering, with the expectation to initiate Phase 3 trials in the fourth quarter, can you talk to potential trial design or differentiation goals with this program? Separately, regarding Fragile X, assuming a positive Reconnect readout, how are you thinking about the commercial build for Zygel? Specifically, I am wondering if you can discuss more about the engagement with KOLs, advocacy groups, and payers and what does this suggest about market receptivity and launch planning? Based on that engagement, would you anticipate a more gradual build or could you see very rapid uptake if it is approved?
Hi, good morning. Um, just a couple of follow-up questions from us in the pipeline. The first is on paullus and HD. I'm just wondering with the expectation to initiate phase 3 trials, in the fourth quarter. Can you talk to, you know, potential trial design or differentiation goals with this program and then separately, regarding, fragile X, assuming a positive reconnect, read out. How are you thinking about the commercial build for Z?
In 002 specifically, I'm, I'm wondering if you can discuss more about the engagement with kol's, advocacy groups and payers. And what does this suggest about market receptivity and launch planning? And, you know, based on that engagement? Would you anticipate a more gradual Builder? Could you see, you know, very rapid uptake if it's approved?
Speaker 2: Thank you, Patrick. Kumar, on pitolisant.
Speaker 1: Hey, good morning, Patrick. On pitolisant HD, we are on track to initiate two Phase 3 studies, one in narcolepsy and one in idiopathic hypersomnia in the fourth quarter of this year. At this stage, what I can say, Patrick, is that it is going to be a standard randomized double-blind placebo-controlled parallel arm study. We are going to provide more information on the endpoint, the recruitment rate, and all of the other things as we approach the study initiation.
Speaker 2: Yeah. So, I would say, standard trial design. In addition, looking at novel endpoints, fatigue and narcolepsy, sleep inertia, and IH to pursue a differentiated label in that regard. With regards to opportunities for ZYN-002 go-to-market, a lot of work has started. Adam, a few thoughts on that?
Thank you, Patrick. Um, Kumar on the Tolson HD. Hey, good morning. Patrick can you tell us Cent HD? We are on track to initiate 2. Phase 3, studies, 1 in North Carolina and 1 in edea Pathak hypothermia in the fourth quarter of this year. At this stage, what I can say, Patrick is, it's going to be a standard randomized, double blind, Placebo controlled parallel armed study. Uh, we are going to provide more information on the endpoints um the recruitment rate and all of the other things as we approach. Uh, the study initiation
Kumar Budur: Yeah. Thanks for the question. I will just go straight to the community. I think you mentioned receptiveness to new therapies. This is a very close-knit and tight community. You typically see that in rare disease, but especially so here because these are kids that are suffering from a range of symptoms across several domains, physical manifestations, cognitive impairment, as well as behavioral symptoms. They are very well aware of any treatment that is being developed that could potentially benefit their kids. We would expect very high awareness and high receptivity when we come to market. In terms of go-to-market model, yes, as Jeff said, our plans are underway. We are continuing to have discussions across the community with different stakeholders and really ensure that we are prepared for success.
Yeah, so I I, I would say, you know, standard trial designs and um, and then also, in addition, you know, looking at sort of novel end, points fatigue and narcolepsy sleep, inertia and IH to, to, uh, pursue a differentiated label in that regard with regards to opportunities for zoa and 002 go to market. A lot of work has started Adam, a few thoughts on that. Yeah and actually uh thanks for the question and I'll I'll just go straight to uh the community and I think you you mentioned receptiveness uh to new therapies. I mean this is this is a very
Speaker 2: I would just add, you know, I think, you know, this is what we do at Harmony, engaging with rare disease communities. We really have, I think, a best-in-class, a world-class patient advocacy team and a cross-functional team, you know, kind of working on, you know, our go-to-market strategy and that opportunity. So thanks.
Said, you know, I I think you know, this is what we do at Harmony engaging with rare disease communities, we really have a, I think a best-in-class, a world-class patient, advocacy team and across, functional team, you know, kind of working on, you know, our our go to market strategy and that opportunity. Um so thanks
Sandip Kapadia: Great. Thanks so much.
Great. Thanks so much.
Madison: Thank you. We will take our next question from Jason Gerberry with Bank of America. Please go ahead.
Thank you, and we will take our next question from Jason Gerber with Bank of America. Please go ahead.
Sandip Kapadia: Hey, guys. This is Bhavan Patel on for Jason Gerberry. A couple of questions from us focused on Zygel for Fragile X syndrome. First, based on prior Connect data, how are you modeling patient adherence to therapy if the drug replicates the subgroup data with FMR1 gene methylation? Specifically, what % of patients do you expect to stay on drug given response rates versus what % of patients might be expected to discontinue due to lack of response? My second question is, beyond achieving statistical significance on the social avoidance primary endpoint, what specific results from the key secondary endpoints like the irritability subscale or the caregiver global impression would give you the highest conviction in the data package for filing? Thank you.
Hey guys, this is bosinger bury. A couple questions from us focused on zelle for fragile X syndrome. Um, first based on prior connect data, how are you modeling? Patient adherence to therapy. If the drug replicates, the subgroup data, with fmr1 Gene methylation, and specifically, what percent of patients do you expect to stay on drug given response rates versus what percent of patients might be expected to discontinued due to lack of response? Um, and then my second question is beyond achieving statistical significance. On the social avoidance primary endpoint, what specific results from the key, secondary endpoints, like the irritability subscale, or the caregiver Global impression would give you the highest conviction in the data package for filing. Thank you.
Speaker 1: Yes. Hey, good morning. Thank you for those questions. There were several questions in there. I will start with the last one in terms of beyond social avoidance, what else we anticipate or what else we are monitoring. As we have disclosed, we are looking at several other behavioral symptoms. Obviously, social avoidance is the primary endpoint, but we are also looking at irritability behaviors, another core symptom in patients with Angelman syndrome. We saw a pretty good response on this domain of symptoms from the Connect study. In fact, we recently presented data on irritability at the American Association of Neurology meeting in April 2023, which was a podium presentation where patients exposed to Zygel showed sustained and clinically meaningful response in the irritability domain.
Speaker 1: In terms of the safety, tolerability, discontinuation, and persistence on treatment, the Zygel product has very unique attributes, and we have discussed this in many forums in the past. The adherence rate is very high. In fact, over 90% of the patients who completed the randomized double-blind study in the Reconnect study and also in the Connect study elected to participate in the long-term extension study. In those patients, we have data lasting for more than eight years still continuing to use Zygel, gaining efficacy, good benefits, with acceptable safety and tolerability profile. I do not think I understood your very first question on the modeling between Connect and Reconnect.
Yes. Hey, good morning. Thank you for those questions. All right, there was, uh, several questions in there. Uh, probably I'll start with the last 1 in terms of Beyond social our avoidance. What else, uh, we anticipate or what else we are monitoring, uh, as we have disclosed. Uh, we are looking at several other behavioral symptoms. Obviously, social avoidance is the primary end point, but we are also looking at uh irritability, behaviors. Another course, symptom, in patient process like syndrome and, uh, we saw pretty good response on this domain of symptoms from the Kinect study. And in fact, we recently presented, uh, data on irritability at the American Association of Neurology meeting in April this year, which was the podium presentation, where patients exposed to 3 years. Uh, for Z10 0002 showed sustained and clinically meaningful response in irritability domain uh
In terms of, uh, uh, the safety tolerability discontinuation and persistence on treatment. But Z1, 0002 product has very unique attributes. And we have discussed this in many forums, in the past,
The adherence rate is very high and in fact, over 90% of the patients, who completed the randomized, double blind, study in the reconnect study and also in the Kinect study elected to participate in the long-term extension study. And in those patients, we have data, uh, lasting for more than 8 years. Uh, still continuing to use Z1 0002 gaining efficacy. Good benefits with, uh, acceptable safety and tolerability profile.
Uh,
Speaker 2: Just asking about adherence rates and discontinuation rates, what is expected based on the prior Connect data?
Yeah. Uh, I don't think I understood your very first question on the modeling between connect and connect.
Just asking about adherence rates and discontinuation rates. What is expected based on the prior Connect data?
Speaker 1: Sorry, I do not think I still understood that question. Apologies.
Speaker 2: So, what percent of patients might be expected to discontinue the drug versus remain on the drug based on response rates that you saw in the prior published Connect data?
Speaker 1: Okay, got it. Sorry, I do not have that data off the top of my head, but I can certainly provide you that data. Sorry about that. Thank you.
I sorry I I don't think I still understood. That question. Apologies. What percent of patients might be expected to discontinue the drug versus remain on the drug? Um, based on response rates that you saw in the prior published connect data,
Speaker 2: No worries. I just think overall, very well tolerated. Again, this is an innovative product, a little different than the oral cannabidiol that is in the market for other indications as a transdermal gel. In terms of the GI side effects and others, I think overall well tolerated. Kumar Budur will get back with that information. Next question.
Oh, okay. Okay, got it. Sorry, I don't have the data off the top of my head, but I can certainly provide you that data. Sorry about that.
Thank you. Yeah, no worries.
Yeah, and I I just think oh overall very, you know, very well tolerated. Um, again, this is an Innovative product, um, a little different than, you know, the oral can have a dial that's, um, you know, that's sort of in the market for other indications as a transdermal gel. Um, in terms of the GI side effects and others. I think, you know, overall well tolerated, um and um, Kumar will get back, you know, with that information.
Um, next question.
Madison: Thank you. Our next question comes from Ami Fadia with Needham. Please go ahead.
Thank you, and our next question comes.
With AIA was named, please go ahead.
Adam Zaeske: Hi, good morning. Thanks for taking my question. Maybe two follow-ups on prior comments. Firstly, with regards to the Reconnect study, if Kumar Budur, you could sort of remind us what was the placebo response in the Connect study and what assumptions you've made for the Reconnect study. You mentioned that there's a standard deviation that you're sort of watching for, within which, as long as the response stays, you feel good about it. If you could sort of elaborate what that range is. Then with regards to the orexin space and the potential implication on Wakix, we've heard from physicians that with the orexins bringing patients to normalized levels, it might actually allow patients to move from polypharmacy to monotherapy in that context and maybe increasing their scrutiny on just cost of medicines.
Hi, good morning. Thanks for taking my question. Uh, maybe 2 follow ups on prior comments. Uh, firstly, with regards to the
You've made for the reconnect study and you you mentioned that there's a standard deviation. Uh
That, you know, you sort of watching for within which, you know, as long as the response stays, uh, you feel good about it. If you could sort of elaborate what that range is.
Adam Zaeske: Have you thought about potentially looking at some sort of a prospective study evaluating the complementary mechanisms between orexins and Wakix? Thank you.
And then with regards to the recent space and and the potential implication on Vex. Um, we've heard from Physicians that with your accents, bringing patients to normalized levels. It it might actually allow patients to move to from poly, Pharmacy to monotherapy, um, in that context. And uh maybe increasing pair uh scrutiny on uh just cost of medicines. Have you thought about potentially looking at um, some sort of a prospective study. Evaluating the complimentary mechanisms between a reference and break its, thank you.
Speaker 2: Ami, good morning. Thanks for your questions. Kumar, in terms of the Connect study and the findings.
Speaker 1: Ami, great questions. Good morning. Thank you. So in terms of the placebo response for the Connect study, the data is published by Barry Travis et al. in the Journal of Neurodevelopmental Disorders. Happy to share that paper. What we saw, the placebo response in the overall patient population was around 2.29 points on the placebo arm. In patients with greater than 90% methylation, we saw a lower placebo response, around 1.99. Similarly, we also saw an increase in the magnitude of efficacy in patients with complete methylation. This again goes to the earlier point that I was making. In patients with complete methylation, they have a higher burden of symptoms. The mechanism of action of ZYN-002 fits very well in interaction with the endocannabinoid system and the greater magnitude of response.
Yeah. Amy good morning. Thanks for your questions. Um, Kumar um, in terms of the um, you know, the Kinect study and the findings. Uh, yeah, yeah, uh, Army, uh, great question. Good morning. Uh, thank you. So in terms of the p**** for response for the Kinect study, uh the data is published uh bye bye. Bye. At all in the Journal of neural development and disorders. Happy to share that paper. What we saw the poor response in the overall patient population was around 2. 2 9.
On the platform, and in patients, with greater than 90% metallion. We saw lower Placebo response around 1.99. And similarly, we saw also an increase in the magnitude of efficacy in patients with complete methylation. This again, goes to the earlier point that I was making in patients with complete methylation. They have a higher burden of symptoms, the mechanism mechanism of action of Z1 and 0002 fits very well interaction with the endocrine orbit system and the greater uh magnitude of response.
Speaker 1: In terms of your question about the orexin and Wakix prospective study, there is some early preclinical data to show synergistic effect between orexin and orexin receptor agonists and H3 inverse agonists. We haven't shared that information. Just one final point I wanted to make is the study is over 90% powered to detect a one-point placebo-adjusted difference between the active and the placebo arms.
Uh, in terms of your question about the orexin and Vex, prospective study, there is some early preclinical data to show synergistic effect between oryx and, uh, um, orexin receptor, agonists and H3 inverse agonists. We haven't shared that information and just 1. Final point. I wanted to make is the study is over, 90% powered to detect a 1 Point, Placebo. Adjusted difference between the active and the possible arms
Speaker 2: Yeah. So, Ami, I think, in terms of your question about the orexin landscape, obviously, we are following the programs closely and looking at, ultimately, its overall kind of risk-benefit. I think durability of response and understanding, obviously, orexins working through kind of wakefulness and how the mechanism of action of Wakix working through histamine. We have contemplated the opportunity of a synergistic mechanism and the opportunity of concomitant, even a combination type of approach further down in our pipeline. That is something that we have contemplated to possibly address the opportunity of lower doses of orexin agonists, supported by pitolisant, working through a synergistic mechanism. In the meantime, we focus on advancing the next-gen pitolisant products and continuing to grow the Wakix-based business.
Yep. So I mean, I I think, you know, in terms. Yeah. In terms of your question about, you know, the erection landscape. Um, yeah. Obviously, you know, we're following the programs closely, um, and, you know, looking at, you know, ultimately it it it's overall kind of risk benefit. And, um, you know, I think, you know, durability of of response and understanding obviously erects working through, you know, kind of wakefulness and, um, you know, and how the mechanism of action of of Wicks, you know, working through. Histamine, we we have contemplated, you know, the opportunity of a synergistic mechanism and the opportunity of, um, you know, incompetent, you know, even a combination type of approach, um, further down in our Pipeline and and that is something that that we have contemplated to, you know, possibly, you know, address. Um, you know, the the opportunity of um, lower doses of erection Agonist um,
You know, supported by the tallest, you know, working through a synergistic mechanism.
In the meantime, you know, we focus on advancing the NextGen it's, you know, it's in products and, um, you know, continuing to grow the, the wake of space business.
Adam Zaeske: Thank you.
Speaker 2: Thanks, Ami.
Thank you.
Madison: Thank you. I am showing no further questions. I would now like to turn the call back for any closing remarks.
Thanks Army.
Thank you. I have no further questions. I would now like to turn the call back for any closing remarks.
Speaker 2: Thank you, Madison. Thanks, everyone, for joining our call this morning and for your interest in Harmony Biosciences Holdings Inc. Have a great rest of your day.
Thank you Madison. Um and thanks everyone for joining our call. Um, this morning and for your interest in harmony biosciences, uh, have a great rest of your day.
Madison: This does conclude today's Harmony Biosciences Holdings Inc. second quarter 2025 financial results conference call. You may now disconnect your line and have a wonderful day.
This does conclude today's Harmony Biosciences Holdings, Inc. second quarter 2025 financial results conference call. You may now disconnect your line and have a wonderful day.