Marinus Pharmaceuticals (NASDAQ:MRNS) provided a comprehensive update during their earnings call, focusing on the financial and clinical progress of their flagship product, ZTALMY. The company reported net product revenues of $8 million for the second quarter, showing significant growth. With successful patent litigation and expansion plans, Marinus is gearing up for the potential launch of ZTALMY for tuberous sclerosis complex (TSC) in the second half of 2025, aiming for profitability within 12 to 18 months post-launch. Furthermore, Marinus is preparing for a Type C meeting with the FDA to discuss study endpoints and design for ganaxolone.
Key Takeaways
- ZTALMY, used in treating CDKL5 deficiency disorder (CDD), is expected to launch in China in early 2025.
- Marinus anticipates a Phase 3 readout for TSC in the near future and plans to leverage existing infrastructure for a potential TSC launch.
- The company has successfully challenged a patent for IV ganaxolone, held by Ovid Therapeutics (NASDAQ:OVID).
- Financially, Marinus has extended their cash runway into the second quarter of 2025 and implemented cost reduction plans.
- The company is on track to meet its revenue guidance for 2024, aiming for net product revenues between $33 million and $35 million.
Company Outlook
- Marinus is focused on achieving corporate profitability within 12 to 18 months following the TSC launch.
- They are preparing for upcoming medical meetings which may influence ZTALMY prescription trends.
- The company plans to replicate ZTALMY's CDD success in TSC, anticipating a quicker uptake due to the significant unmet need.
Bearish Highlights
- Marinus reported a net loss before income taxes of $35.8 million for the quarter.
- The company has had to implement cost reduction plans and restructure credit agreements to manage finances.
Bullish Highlights
- ZTALMY's steady growth and adoption in treating CDD are positive indicators for the company.
- Positive Phase 3 RAISE trial results for IV ganaxolone and plans for an FDA meeting suggest potential for future approvals.
- Marinus has established commercial and distribution agreements in Europe, China, MENA, and Russia, indicating global market expansion.
Misses
- Despite growth, Marinus still faces challenges in achieving profitability, indicated by the reported net loss and the need for financial restructuring.
Q&A Highlights
- CEO Scott Braunstein discussed the company's plans for FDA meetings and emphasized the importance of demonstrating ganaxolone's value in hospital settings.
- The company is confident in its manufacturing capabilities and is investing in a second site to ensure product availability by 2027.
In summary, Marinus Pharmaceuticals is making strides with ZTALMY's growth and is strategically planning for future product launches. The company is navigating financial challenges with a clear focus on reaching profitability post-TSC launch. With upcoming medical meetings and FDA discussions, Marinus is positioning itself for potential success in the epilepsy treatment market.
InvestingPro Insights
Marinus Pharmaceuticals (MRNS) is actively preparing for the anticipated launch of ZTALMY and is focused on achieving profitability. As they navigate through financial challenges and clinical advancements, it is important to consider the company's financial health and market performance. According to InvestingPro data, Marinus Pharmaceuticals has a market capitalization of $65.37 million and has experienced a revenue growth of 30.53% over the last twelve months as of Q1 2024.
InvestingPro Tips indicate that analysts have revised their earnings downwards for the upcoming period, which could be a reflection of the challenges the company faces in achieving profitability. In addition, Marinus Pharmaceuticals is trading near its 52-week low, which suggests that the stock has been under pressure. However, it's worth noting that the company's liquid assets exceed short-term obligations, providing some financial cushioning.
For readers seeking to delve deeper into the company's financial metrics and analyst forecasts, there are additional InvestingPro Tips available at https://www.investing.com/pro/MRNS. These tips can offer further insights into Marinus Pharmaceuticals' cash burn rate, gross profit margins, and valuation implications, among other key financial indicators.
Full transcript - Marinus Pharmaceuticals Inc (MRNS) Q2 2024:
Operator: Greetings and welcome to Marinus Pharmaceuticals' Second Quarter Financial Results and Business Update Call. [Operator Instructions] It is my pleasure to introduce your host, Sonya Weigle, Chief People and Investor Relations Officer. You may now begin, Ms. Weigle.
Sonya Weigle: Thank you and good morning. With me from Marinus are Dr. Scott Braunstein, Chairman and Chief Executive Officer; Lisa Lejuwaan, Senior Vice President and Business Unit Lead, Rare Genetic Epilepsy; Dr. Joe Hulihan, Chief Medical Officer; and Steve Pfanstiel, Chief Financial Officer and Chief Operating Officer. Before we begin, I would like to remind everyone that some of the statements we are making today are forward-looking statements under the securities laws. These forward-looking statements involve substantial risks and uncertainties that could cause our clinical development programs, future results, performance or achievements to differ significantly from those expressed or implied by such forward-looking statements. These risks and uncertainties and risks associated with our business are described in the company's reports filed with the Securities and Exchange Commission, including Form 10-K, 10-Q and 8-K. I will now turn the call over to our CEO, Dr. Scott Braunstein.
Scott Braunstein: Thank you, Sonya, and thanks everyone for joining us this morning. On today's call, our team will highlight the significant commercial, clinical and operational progress that we have made throughout 2024. We'll also discuss our plans for the second half of the year and beyond, including how we're preparing for the upcoming Phase 3 readout in tuberous sclerosis complex and expanding access to ZTALMY for patients on a global scale. Starting with ZTALMY. It has now been two years since our commercial launch in CDKL5 deficiency disorder, and I could not be prouder of the success that we have achieved in growing the brand in the US and the regulatory accomplishments globally. Launching a new product, particularly in the orphan epilepsy space, is no easy task. But our commercial team has proven its ability to be highly effective, attaining profitability on a commercial investment in the first quarter of 2024, well ahead of our initial expectations. We believe these efforts will only be bolstered by a considerable number of scientific presentations across several medical meetings by year-end. I'm also proud of the progress that we have made to expand access to ZTALMY for patients around the world. In July, we announced that ZTALMY was approved in China as the first treatment for seizures associated with CDD in patients two years of age and older. Tenacia Biotechnology is responsible for commercialization of ganaxolone in China and expects to launch the ZTALMY as early as the first quarter of 2025. As a reminder, Marinus has established commercial collaboration agreements in Europe and China, distribution agreements in MENA and Russia, and a managed access program to make ganaxolone available on a name patient basis where permissible under local regulations without regulatory approval. We plan to work with our distribution partners in MENA and Russia to begin to supply ganaxolone immediately on a name patient basis before regulatory approvals are achieved in those markets. Additionally, we have engaged the Uniphar Group, a specialty healthcare company, to supply ganaxolone on a named patient basis in several additional countries, including Canada and Australia, and expect to have our first patient approved for use within the coming weeks. With ZTALMY now approved in the US, European Union, UK and China for patients with CDD, we have made important investments to expand our manufacturing capacity to be able to meet the expected increased demand. Based on our global forecast as well as our updated TST projections. It is critical to have a second manufacturing facility in place to help us achieve our mid and long-range forecast. The investment of the second facility has been ongoing for several months and is proceeding as planned. With the support of our international partners, we expect to have several ex-US launches kicking off in the near term, with the first currently anticipated by the end of this year or early next year. In Europe, Orion Corporation continues to prepare for commercial launches of ZTALMY in select EU countries, and as noted previously, Tenacia expects to launch into the Chinese market in early 2025. We also anticipate broader access for patients in MENA and Russia once local regulatory approvals are secured. Finally, we are targeting a Japanese partner to come on board in the first half of 2025 following our TSC Phase 3 dataset. Since the incidence of CDD outside the United States is similar to the US, we believe that the global opportunity will be meaningful to our ZTALMY forecast. For example, in China, where genetic testing was instituted only a few years ago, over 1,000 CDD patients have already been identified. Broader access to the ZTALMY will bring a new therapeutic option to patients and their families, as well as provide support for the company's larger financial objectives, specifically achieving corporate profitability over the coming years. Lisa Lejuwaan, who heads up the US ZTALMY business, will provide a more in-depth overview of our commercial strategy in her remarks, including our plans to continue to grow the CDD franchise and how the team is preparing for the potential TSC launch in the second half of next year. Let me move to our clinical pipeline. As Joe will detail in his remarks, our next major milestone is the readout of the global TrustTSC trial evaluating ZTALMY for the treatment of seizures associated with TSC. As a reminder, we completed enrollment in May and are on track for the last patient visit by mid-September. We expect to report top line data in the first half of the fourth quarter and our targeting submission of a supplemental NDA no later than April 2025 with a request for priority review. We are pleased to see both a low overall discontinuation rate and a high percentage of patients rolling over from the double-blind portion of the trial to the open label extension. Pending a positive outcome and FDA approval, the commercial team plans to leverage the existing ZTALMY infrastructure to hit the ground running. We have learned a tremendous amount in the last two years and are well-positioned to adapt our formula in CDD to achieve success in the larger TSC market. As I commented earlier, we are now setting our sights on achieving company profitability, which we believe can occur 12 to 18 months following the TSC launch. We also wanted to share that on September 20th, we will host an Investor and Analyst event focused on our oral franchise. Our leadership team will be joined by key opinion leaders to share a deep dive into the TSC patient journey, current treatment landscape, and the TSC market opportunity. We will review some of the new findings that continue to make us feel confident that ZTALMY will be successful in its current Phase 3 study and share our thoughts on why this data readout can create a unique growth potential for the organization. Finally, one added note. In March of 2023, Marinus initiated a PGR challenging Ovid's 817 SE patent for IV ganaxolone on the basis that the claims of the patent were invalid and should not have been issued by the USPTO. I am pleased to share that Marinus was successful in this PGR challenge, with the PTAB concluding that all challenge claims were unpatentable. With that, I'll now turn the call over to our Senior Vice President, Lisa Lejuwaan, who will be covering the commercial update for our Chief Commercial Officer, Christy Shafer.
Lisa Lejuwaan: Thank you, Scott. Good morning, everyone. I'm Lisa Lejuwaan, Senior Vice President and Business Unit Lead of Rare Genetic Epilepsy at Marinus. Today, I'll be highlighting the significant progress we have made to grow the ZTALMY brand since its launch in CDD two years ago and will provide an update on our commercial planning activities for potential expansion into TSC. With approximately 200 patients active on therapy, we continue to see steady growth and adoption of ZTALMY in CDKL5 deficiency disorder after two years of launch. For the second quarter, we generated net product revenue of $8 million, representing growth of over 85% compared to the same period in 2023. We believe we're on track to achieve our projected full year 2024 revenue guidance of between $33 million and $35 million. This growth highlights the vital role of ZTALMY in the comprehensive management of seizures associated with CDD. We continue to hear from HCPs that the ZTALMY is making a difference in patients' lives and changing the way they think about treating these patients. We see physicians increasingly prescribing ZTALMY for younger patients, signifying, we believe, a broader adoption in a patient population where parents are often more cautious about starting new treatments and a growing comfort with ZTALMY. We are very pleased with the patient experience as highlighted by low discontinuation rates with greater than 70% of patients remaining on active therapy since our launch. This matches our experience from the Phase 3 Marigold trial and CDD and is aligned with our expectations. In terms of coverage, we continue to see widespread acceptance across both commercial and government programs, reflecting the value that the ZTALMY brings to CDD patients and families affected by refractory epilepsy. Notably, no CDD patients have been denied coverage to date, underscoring the favorable reimbursement dynamics. Over the past two years, we've proven that our rare disease approach is working. We've built an infrastructure that is lean and efficient, and our sales team continues to reach KOLs and HCPs, both in special treatment centers and community settings, resulting in continued strong new patient enrollments and growth of new prescribers, driving demand. We continue to grow and evolve the ZTALMY brand and maximize its impact in the CDD market. We're implementing several key initiatives. First, we now have robust data analysis with more than 1,000 CDD patients identified. By using new data sources and analytics, we have identified patients not billed with the CDD ICD-10 code in third-party claims and patients who may have CDD, but do not yet have a diagnosis. We're educating physicians on the importance of having confirmatory genetic testing, which is supported by the American Epilepsy Society's goal of making sure every patient with unidentified seizures has access to genetic testing to understand the underlying cause of their disease. And second, by showcasing a range of voices and stories to the community, including family members of newly treated patients, we intend to engage more families to elevate the ZTALMY and CDD awareness. We are launching our on-demand SHINING MOMENTS series, where families can hear from experienced caregivers and families on how ZTALMY has affected their lives at a time that fits into their schedule. We continue engaging with the International Foundation for CDKL5 Research, most recently at their annual conference where over 100 families were in attendance. We're proud of the growing adoption of the ZTALMY and are planning to replicate the success of CDD in TSC, with a potential launch in the fourth quarter of 2025. Looking ahead, we plan to build upon the foundation of our proven CDD infrastructure to meet the needs of TSC patients who are also suffering from refractory seizures. With approximately five to six times the addressable patient population compared to CBD, we have the potential to unlock a significant growth opportunity. Our colleagues from the TSC alliance and our market research make it clear that there remains a significant unmet need in these patients and that a new therapy would be welcomed. Furthermore, when polled, physicians are excited about the potential for an effective and safe product that can be used concomitantly with other anti-seizure medications, is easily accessible, and has the potential to meaningfully improve quality of life. When we launched at CDD, we had relatively quick uptake due to the significant unmet medical need in this patient population. However, we anticipate even quicker uptake with TSC for several reasons. First, patient finding an ultra-rare disease is often the largest hurdle. However, this patient population is much easier to identify through a well-known ICD-10 code and through physical and neurological identifiers such as tubers, cardiac rhabdomyomas and refractory seizures. TrustTSC will be the first Phase 3 global trial executed in TSC that includes prior and concomitant usage of mTOR inhibitors and Epidiolex, giving HCPs and families confidence in combining medications and further underscoring the current needs in the TSC community. From a payer perspective, we expect rapid and broad access across the majority of payers, supported by the protected class of epilepsy and the label extension from CDD to TSC. Patient activation is expected to be straightforward. In refractory TSC patients, seizure control is the main priority, making adding or changing medication an easier choice. The unique GABAergic mechanism of action of ZTALMY is differentiated from other ASMs and supports ZTALMY's place in the treatment algorithm. Additionally, this will be the second completed global randomized trial of ZTALMY, which will have been on the market for over three years by the time of a TSC launch, giving physicians even greater confidence in the brand. The growth and continued uptake of the ZTALMY and CDD reinforces our confidence that we can replicate and accelerate the success in TSC, which is a significantly larger market opportunity. Our team looks forward to sharing further updates on our progress and plans at our TSC focused Investor and Analyst Day in September, where we will highlight the work that our commercial team has been doing behind the scenes to prepare for potential expansion into TSC. This will include key insights from our demand study, value proposition, key product positioning and patient services portfolio enhancements. I would now like to turn the call over to our Chief Medical Officer, Dr. Joe Hulihan, for an update on our clinical programs.
Joseph Hulihan: Thank you, Lisa. Good morning. I'm pleased to share an overview of our pipeline progress, which includes the upcoming Phase 3 data readout in TSC, preparation for our other rare genetic epilepsy programs, and a recap of our Phase 3 RAISE trial readout and next steps for that program. I'll start with the TrustTSC trial of oral ganaxolone in tuberous sclerosis complex. TSC is one of the most common genetic epilepsies and is caused by a defect or mutation of the TSC1 or TSC2 genes. Common symptoms include seizures, cognitive impairment, behavioral difficulties, and skin, kidney or lung abnormalities, among other manifestations. Epilepsy and TSC occurs in approximately 80% to 90% of patients with seizures, typically beginning in the first year of life. Seizures in TSC are often difficult to manage and remain resistant to treatment. Despite the introduction of disease specific anti-seizure medications, there is still a significant unmet need for treatments that provide effective seizure control. To address this unmet need, we're evaluating oral ganaxolone in TSC patients with refractory seizures in the TrustTSC trial. As Scott mentioned, we completed enrollment for the study in May and continue to expect to report top line results in the first half of the fourth quarter. TrustTSC is a global Phase 3, randomized, double-blind, placebo-controlled trial of adjunctive ganaxolone, which enrolled 129 patients with TSC associated seizures. As a reminder, the trial provides 90% power to detect a 25% difference in seizure reductions between ganaxolone and placebo. The trial consists of a four-week baseline period followed by a 16-week double-blind phase, with the primary endpoint being the percent change in 28-day seizure frequency. Then, for patients continuing to the open label extension, there's a four-week cross titration from double-blind study medications to opal label ganaxolone. Key secondary endpoints in the double-blind portion of the study are the percent change in seizure frequency during the maintenance period, the 50% responder rate, and clinical global impression scales reported by the treating clinician and the patient or their caregiver. This trial is the first double-blind study in TSC to allow enrollment of patients taking Epidiolex or mTOR inhibitors, including Afinitor, relatively newer additions to the range of medication used in TSC management. As a reminder, in Marinus' Phase 2 TSC trial, patients taking these medications had a 25% and 36% responder rate, respectively. As reported in May, patients entering the TrustTSC study had failed a mean of 4.8 anti-seizure medications, with approximately 27% having current or prior experience with Epidiolex and approximately 58% having experience with mTOR inhibitors. Patients had a median baseline rate of 50 TSC associated seizures per 28 days. As discussed previously, based on information from our Phase 2 TSC study, we modified the Phase 3 titration schedule. When we reviewed the Phase 2 study results, we believed that ganaxolone had been titrated too quickly, leading to increased somnolence and, unexpectedly, that this led to an associated decrease in efficacy with a discontinuation rate of approximately 26%. With the revised titration schedule, the discontinuation rate in the Phase 3 study is below 7%, which is consistent with what we saw in the CDD Marigold study. Importantly, only two patients have discontinued from the TrustTSC study to date due to somnolence-related adverse events. In addition, we are seeing over 90% of patients who complete the Phase 3 study transitioning into the open label extension, suggesting that patients are not only tolerating the drug well, but are likely also benefiting from treatment overall. I look forward to sharing updated information on baseline patient demographics and characteristics at our September Investor and Analyst event, including details on seizure types, use of concomitant medications, discontinuation rates, and average patient doses. We're targeting submission of a supplemental NDA in April 2025 with a request for priority review. Assuming all goes according to plan, we anticipate a PDUFA date in the fourth quarter of 2025. We plan to present the results at AES (NYSE:AES) in December following the announcement of our top line data in early Q4, with the goal of publication in a major journal prior to the commercial launch. In addition to TSC, we plan to expand our investment in ZTALMY to explore its potential in the treatment of other rare epilepsies. Planning is underway for a clinical trial that would assess oral ganaxolone for the treatment of a broad range of developmental and epileptic encephalopathies, including Lennox-Gastaut syndrome. LGS is characterized by the presence of developmental delay and refractory seizures. It affects approximately 48,000 patients in the US, which is four times larger than the refractory TSC population. Despite the availability of several anti-seizure medications approved for the treatment of seizures in LGS, there remains a considerable unmet need for effective treatment. We plan to initiate a proof-of-concept trial with ZTALMY in the first half of 2025, pending the TSC top line data. We believe the ganaxolone could be a valuable addition to the treatment options for LGS and DEEs overall, given its unique mechanism of action. The planned proof-of-concept trial can help guide us in the design and conduct of a future Phase 3 study. Additionally, we're continuing our efforts to develop a second generation ganaxolone product. Our goals are to optimize PK parameters for efficacy, tolerability, and dosing frequency. We've initiated IND enabling studies for a ganaxolone prodrug, which are expected to be completed by the end of 2025. Lastly, I'll briefly recap the results of our Phase 3 RAISE trial of IV ganaxolone and refractory status epilepticus, and we'll also share the next steps in our clinical and regulatory approach. We believe that the totality of the RAISE trial data showed that ganaxolone produced rapid cessation of status and evidence of durable cessation in a highly refractory patient population. Specifically, onset of effect was rapid, with 80% of patients receiving IV ganaxolone having status epilepticus cessation within 30 minutes, compared to 13% for placebo, a result that was statistically significant with a P value of less than 0.001. Unfortunately, the second co-primary endpoint, lack of progression to IV anesthesia within 36 hours, failed to achieve statistical significance. Our analysis of the RAISE data showed that the use of IV anesthesia was likely driven by clinical and treatment factors unrelated to status severity. In contrast, continuous EEG monitoring demonstrated objective and durable control of status. Specifically, analysis of 36 hours of continuous EEG data demonstrated a median 93% reduction in EEG seizure burden in the absence of IV anesthesia for ganaxolone treated patients, compared to 36% for placebo. Based on our assessment of the RAISE dataset, we plan to submit a request to the FDA this month for a meeting to discuss the trial results and determine next steps for the program. This was the first placebo-controlled trial conducted in refractory status. We're proud of our team's success in enrolling and completing a complex hospital-based study in this area of tremendous unmet need. We're hopeful that the RAISE dataset can support moving forward with our program for IV ganaxolone and the treatment of status epilepticus. I'd also mention that we've provided IV ganaxolone for treatment of super refractory status epilepticus for over 30 patients under emergency IND applications. Looking ahead results from the RAISE trial have been accepted for a platform presentation at the Neurocritical Care Society meeting in October, and we plan to submit additional data for presentation at this year's American Epilepsy Society annual meeting. In closing, our clinical research team is passionately committed to bringing safe, effective and innovative treatments to patients suffering the consequences of refractory seizures and status epilepticus. I'd now like to turn the call over to our CFO and COO, Steve Pfanstiel, for a financial update.
Steven Pfanstiel: Thanks Joe and good morning, everyone. I am pleased to be able to provide a financial update as well as share our financial results for the second quarter of 2024. In the second quarter of 2024, we took several significant actions as a result of the Phase 3 RAISE trial to further extend our cash runway, which is now projected into the second quarter of 2025. Cost reduction plans were initiated in April of this year and remain ongoing with the full impact of cost savings expected to be achieved in the third quarter. We now project our combined selling, general and administrative and R&D expenses to decrease by approximately 30% from $80.3 million in the first half of 2024 to between $55 million and $60 million in the second half of 2024. This new reduced cost structure also aligns with our near-term focus on the oral epilepsy franchise, which can be efficiently leveraged upon an indication expansion into TSC. In June of this year, we restructured our credit agreements with both Oaktree Capital and Sagard Healthcare. As a result, the $15 million minimum liquidity requirement has been removed from both agreements and amortization payments due to Oaktree in 2024 have been reduced by 50%. In return, Marinus has made a one-time principal payment of $15 million to Oaktree, reducing our outstanding principal with Oaktree to $60 million. As a result of these actions, we ended June 2024 with cash and cash equivalents of $64.7 million, extending our projected cash runway into the second quarter of 2025. As mentioned by Scott and Lisa, we remain committed to growing this ZTALMY franchise and have made important investments to expand our manufacturing capacity to support expansion outside of the US and in preparation of a potential launch in TSC. We are proud of the progress we have made to expand patient access on a global scale, while also creating meaningful revenue opportunities from markets outside the US. We expect to see positive returns from our managed access program before the end of the year and remain eligible to receive several milestone payments from our commercial partners upon the achievement of certain CDD and TSC related regulatory and commercialization activities. Full year 2024 guidance remains unchanged with projected ZTALMY net product revenues between $33 million and $35 million and combined SG&A and R&D expense in the range of approximately $135 million to $140 million, including noncash stock-based compensation expense of approximately $20 million. I'll now take a few minutes to summarize our financial results for the second quarter. We recognize ZTALMY product revenues of $8 million and $15.5 for the three and six months ended June 30, 2024 as compared to $4.2 million and $7.6 million for the same periods in the prior year. This represents robust quarterly growth of 87% over the second quarter of 2023. Separately, we recognize BARDA revenues of $0.1 million and $0.2 million for the three and six months ended June 30, 2024 as compared to $1.8 million and $8.9 million for the same periods in the prior year. As a reminder, the first quarter of 2023 included activity associated with startup of the API onshoring initiative and the base period funding was completed in the fourth quarter of 2023. Research and development expenses were $20.9 million and $45 million for the three and six months ended June 30, 2024, as compared to $21.4 million and $49.3 million for the same periods in the prior year. The year-to-date change was due to decreased costs associated with our API onshoring effort. Selling, general and administrative expenses were $16.7 million and $35.3 million for the three and six months ended June 30, 2024, as compared to $15.7 million and $30.9 million for the same periods in the prior year. The primary drivers of the change on a year-to-date basis were increased commercial and personnel expense. Restructuring costs were $2 million for the three months ended June 30, 2024. These one-time expenses reflect severance costs and the termination of trial related lease assets. Interest income was $1.1 million and $2.6 million for the three and six months ended June 30, 2024, as compared to $2.1 million and $4.5 million for the same periods in the prior year. The decrease in interest income was driven by the overall decrease in cash, cash equivalents and short-term investments. Interest expense was $4.6 million and $9 million for the three and six months ended June 30, 2024, as compared to $4.2 million and $8.4 million for the same periods in the prior year. The increase is primarily driven by interest expense associated with the $15 million prepayment to Oaktree. The company reported a net loss before income taxes of $35.8 million and $74.5 million for the three and six months ended June 30, 2024, as compared to a net loss before income taxes of $33.5 million and $68.2 million in the same periods in the prior year. These totals include noncash stock-based compensation expense of $4.9 million and $10.1 million for the three and six months ended June 30, 2024, as compared to $3.9 million and $7.6 million for the same periods in the prior year. Cash used in operating activities increased to $68.3 million for the six months ended June 30, 2024, as compared to cash used in operating activities of $65.8 million in the prior year. Before we move to the Q&A, I will make a few concluding remarks. We are proud of what we have been able to achieve these past two years in both delivering the first product to market specifically for patients with CDD and driving continued development of ganaxolone through our TrustTSC and RAISE Phase 3 trials. We remain committed to the further development of ganaxolone with a strong belief in the positive impact we can make on patients suffering from refractory epilepsy. Finally, as Scott mentioned, we will be hosting an Investor and Analyst Day event that will focus on TSC and our broader oral epilepsy franchise. The event will be in-person and webcasted on the morning of Friday, September 20. More details will follow in the coming weeks. We look forward to seeing many of you in attendance. Thanks again for your continued interest in Marinus. Operator, you may now open the call to questions.
Operator: Thank you. We'll now be conducting a question-and-answer session. [Operator Instructions] Thank you. And our first question today comes from the line of Charles Duncan with Cantor Fitzgerald. Please proceed with your question.
Charles Duncan: Yeah. Hi. Good morning, Scott and team. Thanks for the update and congrats on the commercial progress in the quarter. I wanted to ask you about ZTALMY specifically, and I did have a pipeline question, but I'll stick with one. In terms of the new patients additions in the quarter, could you provide a little bit more color on that? And then if Lisa could perhaps clarify a little bit of about her statement around 70% of patients remaining active on drugs since launch. Could you give us a sense of -- a little bit better sense of persistence on patients or that patients have on drugs? Thanks.
Scott Braunstein: Thanks, Charles. I'll kick it off and then I'll turn it over to Lisa. I think one of the things we've seen with this launch, almost from the get go, is a relatively steady growth in new patient ads every quarter. There's always some variation quarter to quarter. But I think we really understand that this is a patient population that has a lot on their plate. Very often it's months to get started on new therapy, one that we think is going to be very different than the TSC population, where seizure control is really a paramount issue in those patients lives. And so, I think we've generally been very consistent with the growth of the franchise since the time of launch. And certainly, there was a small bolus of patients in clinical trials from the beginning of our launch. In terms of the discontinuation rates, if you go back to Marigold, we saw about 70% of patients on long-term therapy, a good number that we lost two to three years in follow up. But the persistence of effect has really been one of the nicer experiences we've seen with the drug. And to date, our commercial experience really mirrors or incrementally better than what we saw in Marigold. So, we're still north -- Lisa's comments, north of 70% on persistence, seeing very durable effect. We're going to also show some durability data in the TSC population at the Analyst Day and then at AES. But Lisa, I'm happy to flip it over to you for some, additional comments on what you're seeing in the marketplace, both in terms of new patient starts and persistence.
Lisa Lejuwaan: Thanks so much, Scott. I think you covered most of it there. But I'll just add that we're extremely proud of the work the team has done to reach a significant portion of the market's CDD patients, with many more patients yet to find. Our team is also very proud of the durability of this drug. When you talk about a 30%, less than 30% discontinuation rate, this speaks to the unique mechanism of action of this drug and these patients, it's a very complicated mix of multiple therapies, and we're proud of the fact that these patients have remained on ZTALMY, signifying that they are getting the seizure reduction that they need with relatively few, if any, side effects. And it has such a wonderful drug interaction profile that the community is quite happy with this response.
Scott Braunstein: Thanks, Lisa. Charles. I'll make one other comment. The second half of the year tends to be stronger for us. A lot of the medical meetings are really back end weighted, certainly AES and some other additional pediatric meetings which are really critical to the messaging. There's really a paucity of medical meetings in the first half of the year. So, we are really looking forward to the second half of the year and the medical meetings and the interest that we see almost immediately following medical meetings for ZTALMY.
Charles Duncan: So that drives prescribing, or does it take prescribers out of the office? What are those countervailing? Yeah.
Scott Braunstein: Generally, we've seen very strong prescription trends following our medical meetings.
Charles Duncan: Okay. Got it. Thank you.
Operator: Our next question is from the line of Brian Abrahams with RBC (TSX:RY) Capital Markets. Please proceed with your question.
Unidentified Analyst: Hi, this is Jon [ph] for Brian. Thank you for taking our question. On CNC, can you talk about some of the subgroup analyses you've done for the Phase 2 open label study that gives you most confidence that Phase 3 study will read out positively. How consistent was the seizure reduction for those who stayed on the therapy until the end of the maintenance phase? And I guess, for the ongoing Phase 3 study, can you tell us how many patients had their last visit and entered into the open legal extension so far? Thank you.
Scott Braunstein: Yeah. Well, let me start with the last question, and I'll turn it over to Joe to talk a little bit about what we saw in the Phase 2. But we are well north of 100 patients now, close to 110 patients that are into the open label. The last patient visit is in September, the first or second week in September, we should have the last patient visit in the study. So, the vast majority of patients have now rolled into open label. And to the question, I think we continue to see consistency of those high percentages of patients rolling into open label. We're north of 90% of patients completing the study who are rolling into open label and staying on open label. So, we'll give the final numbers at the Analyst Day, but certainly from -- we haven't seen a bump in those discontinuations early on in the trial. We feel very confident that now north of 100 patients are really tolerating the drug extremely well. Very different than what we saw in Phase 2. As a reminder, we had a 26% discontinuation rate in the Phase 2. And I think we're in a different place today, much because of the work that Joe has done and the team has done to reconfigure the dosing paradigm. Joe, you want to talk about some of the highlights that we saw in Phase 2 and our confidence going into the Phase 3?
Joseph Hulihan: Yeah. Yeah, Scott. Yeah. As you mentioned -- Scott mentioned there were 26% discontinuations for side effects. So that was six patients. For side effects, it was four. So really, despite the rapid titration in Phase 2, we had four patients discontinued due to adverse events. Now, the one thing about the current open label study that's ongoing, patients from the Phase 2 study could roll into the open label. And so, we have a combined open label extension for the Phase 3 and the Phase 2. And we still have patients. The latest number is not at the tip of my tongue, but we have patients from Phase 2 who have continued to this point in the open label extension. And so, I think the titration really makes a big difference. I think you asked about subpopulations. We looked at patients with focal seizure types. They had a better response, 25% reduction compared to the overall population. And then we looked at patients on Cannabidiol and Everolimus, and they also had a good response, particularly 20% greater response than the population as a whole. So, again, encouraging signals. Did I answer your question?
Unidentified Analyst: Yes. Thank you. Thank you, Scott. Thank you, Joe.
Scott Braunstein: Yeah. Let me add one or two comments to Joe's comment. Joe hit the mark in terms of what we saw in the Phase 2. And as a reminder, what we've said publicly is about 70% of the seizure types, close to 75% that we're seeing in the blinded Phase 3, are focal in nature. So that's exactly what we had hoped to see. So, to Joe's point, strong signal in Phase 2, even with the tolerability issues, which is why we expect that number to be more robust in the Phase 3. And in the Phase 3, more than half the patients are coming into the study on mTOR inhibitors. And again, that was our strongest 50% responder number from the Phase 2. And certainly, we saw a robust responder number with the Cannabidiol group, which will make up about 25% of the population. So, we have all the right subtypes in the Phase 3, we have the right seizure types. And certainly, that's where the efficacy signals were strongest, even in the setting of some real tolerability issues in the Phase 2. So, we have a lot of confidence going into the Phase 3. Thanks for the question.
Operator: Our next question is from the line of Joseph Thome with TD (TSX:TD) Cowen. Please proceed with your question.
Joseph Thome: Hi, there. Good morning, and thank you for taking my question. Maybe a little bit of a follow on to your explanation from the last question, but the Phase 3 looks like the baseline seizure frequency is a little bit higher than what you saw in the Phase 2, and the number of prior therapies failed is also a little bit higher in the Phase 3 blinded data versus the Phase 2. I guess -- does that indicate that you think it's potentially going to be a little bit easier to show a benefit of ganaxolone in the Phase 3, or are these more challenging patients to treat? Based on your experience in CDD and the Phase 2, what's sort of your expectation there? Thank you.
Scott Braunstein: Yeah. Thanks, Joe. Let me kick it off, and then I'll turn it over to Joe. I will tell you my experience, at least from talking to some of our key investigators. What's really critical in a study like this is that we have patients who, for lack of a better, are seizing through their medications at a steady state, that there isn't an acute acceleration or worsening of their symptoms, which would tend to set yourself up for failure just as the disease is progressing, whether or not any therapy can kind of acutely address that. So, I think, I give Joe all the credit in the world that he really stuck to our guns and kept our enrollment criteria at more than eight seizures per month. And I think that's a critical factor for minimizing placebo rate. You can imagine that if a patient was allowed to enroll with only four seizures per month, and there was natural variability, the placebo response could be 25% if they went from four to three. So, Joe was really instrumental in driving the team and keeping us at eight seizures per month, which is higher than what you see in multiple seizure studies. But again, our view is, how do we minimize placebo rate to maximize success? So, I think controlling for placebo is going to be critical for us. Look, my experience from talking to our investigators is that we're getting a group of patients a little bit older, many who have gone through surgery, many have gone through multiple medications. I think it's a very classic phenotype in this population. Certainly, that's what Lisa's market research is showing. And again, to this discussion, I think just the high seizure burden really will minimize placebo effects. So, yeah, when you ask this, I think we feel good about the efficacy. We feel very good about placebo rates, not only because of baseline seizure type, but where we went, what countries we really enrolled in. I'll remind folks that if you go back to the GW study, the placebo rate was about 25%. Poland was a second largest enroller in that study. We had a very unfortunate experience in Poland with CDKL5. That was a very high placebo rate. Certainly, the GW study suggested a high placebo rate, so we chose to stay out of Eastern European countries to minimize the risk of high placebo. So, between that and the eight seizures per month, we feel very good about the placebo rate coming in somewhere in the high single digits, no more than low double digits, which gives us the best chance to win. Joe, you want to comment additionally on seizure types or anything else that we've seen in the blinded data and the Phase 3 in terms of seizures that give you comfort?
Joseph Hulihan: Yeah. Well, a lot of things. One, I mean, you mentioned seizure types. The vast majority of the patients coming into the Phase 3 have focal onset seizures, where we expect to see good efficacy and less variability in the response in the patients with focal onset seizures than we saw, say, with atonic or tonic seizures. Still a good effect size. And I'm talking about CDD, still a good effect size. But there was -- the variability is less in the patients with focal seizures. And to just tag onto what Scott said about patients coming in, it's really eliminating those patients with very few seizures. It's not really linear in terms of seizure frequency. The bigger the number baseline, the more response you get. But it's really just those patients with very low seizure numbers that there's that kind of mathematical problem with not being able to get much better. But once you get beyond eight or 10 seizures a month, the response doesn't differ that much depending on baseline seizure rate. Higher is better, but just really eliminating the very, very low patients. The other thing I'll mention, too, that gives -- well, a couple of things. One is we want to make sure the patients had disease stability coming in so that they didn't have regression to the mean when they came into the study. So, we want them to have seizures in each of the two months at a certain frequency, and no more than one week seizure free during those months to make sure the disease is stable when they come into the baseline. And the other thing, too, is the somnolence. The lower the titration rate and the lower discontinuation due to somnolence, we saw this odd relationship between somnolence, higher somnolence, and lower efficacy. And so, by reducing the somnolence, that also gives me optimism about the efficacy we're going to see in Phase 3.
Scott Braunstein: Okay. Let's go to the next question. Thank you.
Operator: Our next question is from the line of Joon Lee with Truist. Please proceed with your question.
Unidentified Analyst: Good morning. This is [indiscernible] for Joon. Thanks for taking the questions. Just curious, with the timing on the Type C meeting with the FDA is and what scenarios you think could come out of the meeting. And then, I know this was mentioned on the call, but you want to be sure what the discontinuation rate due to somnolence was in the Phase 3 TrustTSC trial and what that number was in the Phase 2 trial. Thank you.
Scott Braunstein: Thanks, Joon. Just to start backwards, we've only reported the total discontinuation rate of 26% from the Phase 2. Vast majority of those were related to tolerability issues. We believe all of them related to tolerability issues. And certainly, the other piece of that puzzle is more than 70% of the patients in the Phase 2 required dosing adjustments. So, they were -- patients were really struggling with the dosing, and it was really something we didn't become aware of until very effectively, until the trial was completed. One of the physicians who will be at our Analyst Day, I'm quite excited about, because he was in our Phase 2 and really struggled with the patients on the Phase 2 dosing regimen. It took a lot of personal convincing from our medical team and myself to get this physician to participate in the Phase 3. And I think he'll share with you at the Analyst Day, what a good response that he's had, at least in a blinded fashion, from Phase 3 thus far. Joon, I really apologize. I forgot your first question.
Unidentified Analyst: I was just curious about the timing on the Type C meeting with the FDA and what scenarios you think could come out of that. Thanks.
Scott Braunstein: Absolutely. Yeah. So, Joe, Alex, the regulatory team has been working incredibly hard putting together, going through the IV dataset and really understanding that data. And there's no question to Joe's comments. We are quite convinced that the drug was highly efficacious and had a durable effect. I think, unfortunately, the endpoint that we chose had a great deal of variability and did not really reflect the durability of the drug. It really reflected what we believe is more physician practice. And that's unfortunate. That's really counterintuitive to what we were told going into the study time and time again by the medical community and the experts that we talk to. So, our real goal for this meeting with the FDA is really to realign on endpoints that we think are much more objective, that we can define the durability of the product that will be the critical piece and really thinking about a study design. And certainly, we're going to share our dataset with the FDA and have what we hope is a very robust discussion. Our hope and goal is to get the filing in by the end of the month. And a typical Type C meeting is in 90 day review. So, our hope is to have that meeting in the early part of the fourth quarter. And I think, we really understand the dataset. Joe's done an amazing job looking at the EEG dataset, looking at practice patterns. And unfortunately, this -- I think we're learning an ICU study where physicians leave after 12 hours, new physicians come in. We've just seen a lot of practice patterns which are disheartening to me as a physician, but certainly it's helping us rethink how to best show the efficacy of this drug. I mean, there's nothing in this study that gave us pause for the efficacy of this drug. I think the other thing that will really align with the FDA is, is how we should think about enrolling this population. We saw some variability in terms of differences in patient outcomes, and we want to align on a stratification strategy with the FDA to make sure that there are no significant imbalances and we can really show the value prop of the drug. Last note is we'll be presenting the vast majority of this data at a medical meeting in October, the NCS meeting, and it will be a platform presentation. So folks will really get to see all of what we've seen in terms of the efficacy and the tolerability of the drug, and certainly, we're going to share all of that with the FDA as well. Thanks for the question.
Operator: Our next question is from the line of Andrew Tsai with Jefferies. Please proceed with your question.
Andrew Tsai: Hey, thanks. Good morning. Thanks for taking my question. And so, on top of the RSC. Thanks for sharing all those tidbits. If you had to run another study after the FDA meeting, how would you design it to not only succeed, but also have it done, say, within one to two years? Or is there anything you can think of to ensure? Thanks.
Scott Braunstein: Yeah. Well, I think, Andrew, first and foremost, thanks for the question. I think we -- we're going to be very, very thoughtful about the trial design. I think, once we got through our protocol amendment and our product issues, recall, we had some manufacturing issues that we were able to resolve, and we now have great stability and shelf life of the product. So, once we got through those issues, we were screening about 15 patients per month. And quite honestly, all of those patients and the vast majority would be eligible for what we think is the right patient population to study in a future study. So, I don't worry a tremendous amount about the enrollment. I think we know which sites are very powerful. I think they're eager to be involved in another study. But I think, to be honest, we really have to think about the financial impact of that to the company and where we want to place our resources. But fortunately, we have multiple strategics that we started engaging before the data. The vast majority of those strategics are still in our data room talking to us regularly, really curious, I think, about the FDA outcome. We're still in conversations with BARDA. BARDA unequivocally wants this product available commercially so that in the unfortunate case, and let's hope there never is a nerve gas attack within the United States, they would have access to Ganache's [ph] loan for that. And so, we are really thinking hard about ways to finance another trial with the help of another party. And certainly, I think getting alignment with the agency, thinking about the size of the trial, which I think we're thinking right now, roughly in the 150 plus or minus patient range, is really quite doable within a two-year window. But again, I think from a resource allocation standpoint, we're going to -- we put almost all our resources behind the oral program. We really want to see a future for the IV program, but we also have to recognize that it has to be a smart financial investment. So, we'll see how the meeting goes with the FDA. I think we're very optimistic we can get to an alignment on some of these key elements. We then feel we can really run the study in a reasonable amount of time, and we'll figure out the best way to finance that study with shareholder interest certainly in mind. So that's kind of where we stand, and I think we'll be able to walk away with this from our interaction with the FDA with a relatively clear path forward. I think we think the solution is relatively simple. I think the agency has been a great thought partner. So, we're looking forward to meeting with them and getting this drug to market. I think it's a critically important resource for physicians to have, but we recognize the hospital environment is one that we have to be able to show the value, and that's our plan. So that's how we're going to move forward, and we will be really excited to share those plans with you in the coming months. Thanks for the question. Appreciate it.
Operator: Our next question is from the line of Douglas Tsao with H.C. Wainwright. Please proceed with your question.
Douglas Tsao: Hi. Good morning. Thanks for taking the questions. Just in terms of the analysis of the IV program, Scott. Obviously, we've seen there were challenges in terms of physician behavior. I'm just curious if you had a chance to look at results by sites, by individual site, were there particular sites that really sort of deviated from your expectations and what your sort of expectation and understanding of treatment patterns would be, especially in terms of advancing patients to IV anesthesia? Or was it really just a broader phenomena that you saw in the study?
Scott Braunstein: Yeah. Thanks, Doug. Look, we did look at an analysis of how our larger sites did, and certainly, there was a stronger signal for the drug in our bigger sites, in our high enrolling sites. And I think, quite honestly, that was driven as much by the factor that those physicians advance care more commonly. We're not afraid or concerned about moving to IV anesthesia. So as a result, there were lower placebo rates, and certainly the delta was larger than the overall study. I think, to be quite fair, that matters a bit, but not necessarily. I think we would not feel comfortable enrolling another study where advancement to IV anesthesia is the end point. I think what we learned is that regardless of what physicians told us, which was they would move to IV anesthesia 80% of the time after failing two drugs. Patients who received ganaxolone in the study typically received three drugs, typically were in and out of status for about a day and a half. And even in that scenario, or in this case, the control group, physicians were only advancing care 50% of the time. So -- and that may have been changing EEG patterns. It may have been change in physicians. It may have been not necessarily following behaviors of the EEG. But I think we just learned that this is too subjective an endpoint, regardless of what physicians have told us time and time again. And remember, we did a very big survey. We specifically went to all our sites. We asked for their practice patterns. And I think, yes, we saw a much more consistent treatment pattern in our bigger enrolling sites, and I would say a variation in those patterns in sites that enrolled one or two patients. I think by nature, when you have a study and you have sites that are enrolling one or two patients, you do run the risk of site bias, that is, their site behavior influencing the outcome of the study. That certainly played a factor here, but I don't think the biggest factor. Joe, is anything you want to add? I mean, you spent so much time on data.
Joseph Hulihan: Yeah, yeah. No, I don't think there were particular sites, as you mentioned, Scott. It was kind of some patients at each site or not at every site, but no. And I think we're doing a lot to minimize the variability. If we do another study, I think we understand a lot. We learned a lot from the RAISE study, obviously, in terms of what end points to look at and patient selection. And Scott mentioned stratification. We want to make sure that we get a representative population, a population that's likely to respond in another study. So, I think that we've learned an incredible amount from RAISE, and that'll pay off when we come time to do another study.
Scott Braunstein: And I think, Doug, the big thing that we want to really discuss with the FDA is what is the right endpoint? We certainly saw very strong signals, as Joe has talked about with EEGs and the differences between EEGs of patients with ganaxolone and who receive placebo. Certainly, every SAB member, every expert we've shared that data with, feel unequivocally powerful that we should be discussing this and pushing for approval with the FDA. It's very nice to have their support. I recognize the reality of what we agreed upon with the FDA, but I think we have other very clear measures of durability in the study. We'll share those at the NCS meeting. But you can imagine thinking about how many drugs in escalation of care being a logical one, right? So, I think we really feel there is durability in this dataset that is clearly differentiated from placebo. Unfortunately, the alignment with the agency -- the agency never specifically demanded durability defined by avoidance of IV anesthesia. And I think we need to have a discussion with them of what other durability measures they would agree to. And I think we have several that we think are objective and is really the key piece of this puzzle. I think more than site variability, and I think we won't really even talk about that, per se, at our FDA meeting.
Douglas Tsao: Okay. If I can, one quick question on TSC. In terms of the long-term extension, are you really seeing any discontinuations once patients are able to sort of tolerate the drug for some amount of time and the continuation rate in the long-term extension so far?
Scott Braunstein: Well, so we are very fortunate that one of our investigators is going to be presenting the long-term extension data that submitted it for AES. It hasn't been accepted as of yet, right, so little early, but we expect a presentation. We'll share that top line data with you all at our Analyst Day in September. We are really encouraged that the durability that we see across disease states is really quite robust. And we really believe the 10 [ph] pan extrasynaptic activity of ganaxolone is something very unique. And time and time again, when we do our market research, it's not only about initial response rates, it's about durability, and it's about safety, as Lisa talked about, and ability to play nicely in the sandbox with other drugs. So, I think when we go into this TSC launch, we will have a lot of talking points, a lot of measures of durability, and certainly, you see that with other drugs. But I think, in particular, we've seen it in some disease states that you just wouldn't expect to see it, right? In comparing a little bit of apples and oranges that we've really tackled what I think are two of the most refractory seizure disorders out there. So, we think it's going to be an important message, and we're looking forward to sharing all that data with you guys at the Analyst Day. Thanks, Doug.
Operator: Thank you. Our next question is from the line of Marc Goodman with Leerink. Please proceed with your question.
Marc Goodman: Can you talk about any off label use you've seen with ganaxolone? And secondly, you mentioned eligibility for milestones. Can you elaborate a little bit for this year? Thanks.
Scott Braunstein: Marc, I'm sorry. I missed the first question on ganaxolone.
Marc Goodman: [Technical Difficulty]
Scott Braunstein: Yeah. I'm having a little interference. Steve, do you want to take those questions off label use?
Steven Pfanstiel: Yeah, sure. I can jump in here. I think, Marc, you're -- maybe I'll answer the second one first. You mentioned milestones. So, the nearest term milestone that we've talked about is a EUR10 million payment from Orion that would be due upon commercialization of CDD. So that happens when they launch in two of the major markets or no later than 18 months after their first market. There's a similar type of payment associated with TSC commercialization. And then, we also have commercialization payments with China, with our Tenacia partnership, those are a little further out and not quite to the same magnitude, but a nice amount as well. In terms of off label. I know we've got Lisa. Lisa, do you want to touch on kind of off label use with ganaxolone?
Lisa Lejuwaan: Absolutely. Thank you, Steve. We've got about 15% of our patients on therapy that do not have a CDD diagnosis and they're affected by other DEEs. I'll just add that most payers are covering the drug for these patients. Acknowledging a significant unmet need here.
Steven Pfanstiel: And maybe just to add a little -- I couldn't hear you. But the thing I'll add is I think we've heard a lot of back and forth about the GW launch in TSC. And I think we have several GW team members as part of the Marinus team. And between their expanded access program and the overlap with LGS that they went into their TSC launch with a substantial number of patients already on drug, I think we can confidently say there are close to no patients currently on ganaxolone today that are being reimbursed with the diagnosis of TSC or certainly that we don't -- we do not know of any in terms of those developmental encephalopathies. So, we really feel like the entire TSC market is open for us from day one. And they're certainly not a big part of our business today.
Marc Goodman: Thanks.
Operator: Thank you. The next question is from the line of Jason Butler with JMP. Please proceed with your question.
Unidentified Analyst: Hey, it's Roy [ph] on for Jason. Just a quick one, and maybe you just answered this, but for ZTALMY, Lisa mentioned the key initiatives, over 1,000 patients IV and patients who might have CDD, but not a diagnosis. I guess, what proportion of the patients today do have a diagnosis, I guess.
Scott Braunstein: Let me kick it off, then I'll flip it over to Lisa. Jason, remember the two major advocacy groups IFCR and Loulou foundation in the US fought very hard for CDKL5 code that went into effect a little bit more than a year before we launched. So, roughly three and a half years ago. To kind of put that in perspective, and we expect about 100 newborns a year. And in the last three, three and a half years they've gone from zero to 200 to 400 to now roughly 1,000 unique patient codes for CDKL5. So, what we expected, as we've always talked about, is roughly 2,000 patients below the age of 21 and certainly another 3,000 adult patients. But many of those adult patients won't be genetically tested. Certainly, some are being tested and some are being treated with totality [ph]. So, I think we have good line of sight of roughly 2,000 patients, a lot less line of sight of the other 3,000. So, I think we estimate probably more than 2,500 patients are out there, with a diagnosis or with the symptoms that haven't yet been diagnosed. And we're clearly seeing this exponential growth in the use of the ICD-10 code. And we know there's not more than 100 newborns a year, right? So, it's just physician recognition of the code. The advocacy groups pushing for the code, reimbursement around the code, all of those pieces of the puzzle are leading physicians to use the code. But we also know even as of a year ago, we had some centers of excellence that were not using the code appropriately. So, it's a little bit of the education around code, but I think we feel pretty good. The fact that there is already more than 1,000 patients that have a code of that we can find these patients. We don't really feel like the 200 or so patients that are currently on therapy. Close to 300 patients who have tried therapy or have been prescribed are the only patients out there. I think, we feel very good about finding additional patients to keep growing the business, and certainly, I think we're really focused on that. And Lisa, you can talk about that more. I think we're going to have to make this the last question. Operator, we've got over about 10 minutes. Lisa, anything else you want to add?
Lisa Lejuwaan: I think you covered it nicely. I'll just add that one thing that we've done is shift our strategy towards a more data-driven approach, because we have so many more HCPs utilizing the code over the past four years. The code has only been available for four years, and we've seen an increase in that data from 200 to 1,000 patients over time identified. There's also been an increase in general in genetic testing with the support from the American Epilepsy Society who really are putting it out there that every physician should genetically test patients who are seizing and have an unidentified underlying etiology for their disease. So, that combination has really driven up the CDKL5 diagnosis in general, and we are very confident in the patients that are out there left for us to still introduce [indiscernible].
Scott Braunstein: Thanks, Liza. Operator, I think we're going to take one more call. We have Charles Duncan on the line.
Operator: Yes, that's correct. Please go ahead, Mr. Duncan.
Charles Duncan: Yes. Thanks for taking the follow up, Scott. I'm going to make the simplifying assumption that TrustTSC works out well and that S&DA is filed and approved. I guess, the question that I have is relative to manufacturing capacity at the end of '25, I assume that you'll be able to get there and -- yeah, so that's the key question that I had to follow up with you on.
Scott Braunstein: Sure, Charles. I think we feel very good about our current manufacturing capabilities and our partner who effectively will dedicate much of their resources to helping us with ganaxolone. We're very fortunate the API has a five-year shelf life. We've been only growing the shelf life of branded ZTALMY. We're hoping to expand that shelf life as well. So, we really have the ability to continue to manufacture ZTALMY. And once we kick off these global launches to really start preparing for the TSC launch. But certainly, by our internal expectations, we're going to need additional supply, certainly by '27, and by our internal expectations, additional supply in '29. I think we feel very good about the opportunity in TSC in the US. And we really believe that a market that's at least five times and potentially as large as 10 times the CDD market is very realistic. And we still share some of those numbers with everyone during the Analyst Day. And I think equally important, we're expecting strong volumes across Europe, very strong volumes in China, expanding volumes throughout the world. And so, we're getting prepared and doing in a very stepwise and staged fashion. And certainly, we think it's critical to have a second unique manufacturing site to minimize risk. And that process we've made -- the investment for the equipment, the room build out will start shortly. And we want to make sure that in 2027 we have more than enough product. So, those plans are in place and we feel really good about the way we're preparing for that. And fortunate -- look, it was a very hard decision for us to let some people go in June and restructure the organization. But as we've said all along, we've always had high confidence in the TSC launch. We think it can drive profitability and we have not shortcut or short changed the oral franchise at all. And obviously, Christy has been a great -- she is a great Chief Commercial Officer. You can hear from this call that Lisa is incredibly qualified as well. We've got great leadership in place. We're thinking about the manufacturing. We're thinking about the global regulatory strategy. We are going to be quite ready to execute post this data. So, thanks so much for the call, Charles. Really appreciate it.
Charles Duncan: Thank you.
End of Q&A:
Scott Braunstein: Thanks everyone. I really appreciate you joining the call. We're about 15 minutes over, but great sharing some of our thoughts and we look forward to seeing you at the analyst event in September. And thanks again for dialing in.
Operator: This will conclude today's conference. You may disconnect your lines at this time. Thank you for your participation and have a wonderful day.
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