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spk07: Greetings and welcome to the Marinus Pharmaceuticals second quarter 2022 financial results and business update call. At this time, all participants are in a listen-only mode. After the speaker's presentation, there will be a question and answer session. If you would like to ask a question during that time, please press star then one on your telephone keypad. To remove your question, please press star one again. And now it is my pleasure to introduce your host, Sasha Damouni-Ellis, Vice President of Corporate Affairs and Investor Relations.
spk08: You may begin, Mr. Mooney-Ellis. Thank you, and good morning.
spk00: With me from Marinus are Dr. Scott Bronstein, Chief Executive Officer, Christy Schaefer, Chief Commercial Officer, Dr. Joe Houlihan, Chief Medical Officer, and Steve Fansil, Chief Financial 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, Scott Braunstein.
spk03: Thank you, Sasha, and welcome to our call. We ended the first quarter with the exciting news that Satomi received FDA approval for the treatment of seizures associated with CDKL5 deficiency disorder in patients two years of age and older, and are pleased to now be receiving our first prescription and completed patient enrollment forms. Our sales force has been in the field engaging and educating physicians at CDD Centers of Excellence and National Epilepsy Centers and we are encouraged by the strong early interest in zetalamin. In addition to the April publication of the phase three Marigold results in the Lancet Neurology, the first international consensus recommendation for the assessment and management of individuals with CDKL5 deficiency disorder was published in Frontiers in Neurology in June. Among the survey results in the publication, respondents, which include an international panel of expert clinicians and researchers, all supported offerings autonomy for the treatment of seizures associated with CBD. Both of the publications are timely for the launch, which Christy will discuss in more detail shortly. I would like to once again thank the patients, families, and investigators who participated in the clinical program for all they have done to help us achieve this momentous milestone. We have a number of other operational updates that we will be sharing during the call. And I would like to start with the first data set from our next generation product development program. We have seen promising initial results in our phase one healthy volunteer study utilizing the first of our next generation formulation, which Joe will discuss in detail later on the call. The PK profile is showing several differentiated features compared to our current oral suspension, which makes us believe that we can ultimately achieve our desired goal in chronic dosing. Key goals of the second generation formulation are to improve bioavailability and to drive higher steady state blood levels of Ganaxalone, which we believe will enhance efficacy. We also believe it will be important to improve upon Zetalme's dose frequency as we think about the potential for additional new indication that are well-suited to address areas of unmet need, including Lennox-Gasso syndrome. We have several important updates on our late-stage clinical pipeline that I am excited to share. Let me start with the IV program. We've had productive interactions with the FDA and have reached preliminary alignment on our proposed IV Ginexilin formulation change, specifically the modification of the buffer system. The FDA agreed that, in principle, A buffer change in Ganaxalone IV formulation is acceptable and acknowledges Marinus' plans to transfer the production of IV Ganaxalone to a new manufacturing facility for future clinical supplies, including the ongoing RAISE trial in Stata Sebelius. Importantly, this alignment provides us confidence that our new batches will meet the necessary FDA requirements upon the filing of a new drug application. Early stability assessments of IV Ganaxolone using a new buffer has shown promising initial results that are likely to support greater than 24 months of shelf life at room temperature. We expect to begin producing our NDA batches in the fourth quarter of this year, utilizing our new manufacturing site and buffer for our IV formulation. I'm extremely proud of the work done by both our CMC and regulatory teams to continue a productive dialogue and scientific exchange with the FDA. Let me comment on the phase three RAISE trial. As previously communicated, we are implementing important changes to the RAISE protocol, expanding eligibility criteria to accelerate enrollment. The protocol amendment is expected to be adopted across the majority of clinical sites by the end of the third quarter. Moving to our Phase III TRUST-TSD trial in tuberous fluorosis complex, we are pleased to share that the first patient has been randomized and dosed. We continue screening patients at US sites with European activations on track to begin in the third quarter of this year. We are targeting 80 global clinical sites, predominantly in the US, Western Europe, Canada, and Israel. We continue to believe that the new Phase III titration schedule will have a meaningful improvement on tolerability and efficacy and look forward to the anticipated data readout in the first quarter of 2024. We have been actively engaging with the TSC community, including our participation during the recent TSC World Conference. After our team's interactions with both clinicians and families, we continue to believe that there is a significant unmet need for patients suffering with refractory seizures associated with TSC, and Zytomi has the potential to be an important option for these patients. Finally, some comments on how we plan to bring Zytomi to patients and families globally. In parallel to the U.S. commercial activities, we continue to work with regulatory authorities to advance Zytomi in other key regions. In Europe, we are targeting submitting complete responses to the EMA Day 120 list of questions for the CDD marketing authorization application by November, which would result in a CHMP opinion by the end of the first quarter of 2023. There have been significant efforts from both the Marinus team and our strategic partner, Orion Corporation, in anticipation of a European commercial launch. In addition, we believe that there is a broader global opportunity to help patients and are exploring further ex-US commercial alliances to expand Gidaskalone's footprint. Now, I would like to turn the call over to our Chief Commercial Officer, Christy Schaefer, for updates on the commercial launch of Zatomi.
spk10: Thank you, Scott. Today, I'm excited to share our early progress on the commercial launch of Zatomi in the U.S. Since the approval in March, we've continued to see a high level of enthusiasm for Zatomi from both physicians and caregivers, reflecting the need in this community and the potential that ZTOMI could provide in seizure management. In the first two weeks of launch, we are strongly encouraged by the early volume of completed patient enrollment forms and are actively fielding questions regarding enrollment and prescriptions. Initial launch feedback from the field has confirmed strong interest from a unique base of physicians in prescribing ZTOMI. In addition to referrals from the U.S. CDC Centers of Excellence and National Epilepsy Centers, We're also very encouraged by early interest coming from outside our key accounts. Additionally, we continue to establish relationships with key payers representing a large proportion of covered lives in the US and have already begun to see positive coverage criteria being published to support patient access. As a reminder, We shared in June that Zatomi received a Schedule 5 designation by the Drug Enforcement Administration, which is the least restrictive schedule. We are pleased with this designation, which further builds our confidence in how parents, healthcare providers, and payers will view Zatomi as an important treatment option for seizures associated with CDKL5 deficiency disorder in patients two years of age and older. The major strategic objectives of our commercial launch are to continue educating healthcare providers and caregivers on the compelling efficacy and safety profile of Zotomi and to enable seamless patient access from prescription through fulfillment. Our marketing team has developed a suite of communication tools that provide important information to educate healthcare providers and caregivers about the benefits and important safety information of Zotomi. These are available at zetalme.com patient caregiver website and zetalmehcp.com healthcare professional website. Physicians can access information at the HCP website about prescribing Zetalme and the prescription fulfillment process. We selected Orsini Specialty Pharmacy based on their strong track record and experience, which is aligned with our indication and dedication to the rare disease community. we believe it is critical to have a single specialty pharmacy to provide individualized support to CBD patients and caregivers throughout the patient journey. As part of Marinus' commitment to helping patients who are prescribed Zotami receive the support they need, we, in collaboration with Orsini, have launched Zotami One, a comprehensive patient support program that facilitates access to treatment and provides ongoing prescription drug support and education throughout the treatment journey. This includes prescription benefit and prior authorization support, medication delivery, financial support programs for patients with no insurance, limited insurance or gap in coverage, and a co-pay savings program that helps commercially insured eligible patients who meet the program terms and conditions pay as low as $0 per fill for Zatomi prescriptions. In addition, the Zatomi One support team includes patient care coordinators available Monday through Friday with pharmacists available 24-7. Our team of 16 field representatives who have significant rare disease and epilepsy experience are now educating physicians on the efficacy and safety profile of Zatomi. targeting close to 300 hospitals, large practices, and epilepsy centers, including eight distinct CDD centers of excellence and 40 key national epilepsy centers. In parallel to our education outreach, we are also focused on supporting access to Zotami for those patients who participated in the Marigold Open Label Extension Study and the U.S. Expanded Access Program. being mindful of the individual circumstances of each patient. The availability of the approved label has also allowed us to advance our ZTALME coverage discussion with patients. As a reminder, we expect approximately 60% of CDD patient population will access coverage through both fee-for-service and managed Medicaid, with the remaining 40% being managed commercially and the top PBMs covering the most U.S. lives. Along with top national and regional commercial payers, we continue to establish relationships with government payers. Our conversations thus far indicate we should be able to achieve broad access to Zytomi, and based on the level and tone of engagement, we believe payers recognize the impact of the disease on patients and families, limitations within the CDD treatment landscape, and Zytomi's profile as the first product approved specifically for seizures associated with CDD. Consistent with our expectation, early coverage criteria support a confirmed CDD diagnosis in patients two years of age and older who have failed one or two prior anti-epileptic drugs. Our initial priority is on the 22 states that we believe include the largest concentration of CDD patients and where the centers of excellence are located. The CDD ICD-10 code G4042 which was established in November 2020, is being increasingly implemented into practice by physicians. Recent healthcare claims data suggests the database is on pace for 20 to 30% year-over-year growth of unique patient claims. We believe this consistent and increasing usage of the code will help ensure access alignment with payers. Early ICD-10 code usage shows that 75% of patient visits are in pediatric patients, with 25% in patients 18 years or older. We recognize that coverage determinations can take time during the Alicia launch period. Our expectations are that the majority of commercial and state Medicaid policies will be published within six to eight months. However, we have every expectation to field medical necessity requests prior to and separate from the publication of formal payer policies. As a reminder, as a part of our commitment to patients, Zatomi One will help support eligible patient access prior to established coverage criteria. We are confident in the road ahead and look forward to continuing to work with patients, caregivers, physicians, and payers over the coming months. I'll now hand the call over to our Chief Medical Officer, Joe Houlihan, to discuss our ongoing development program.
spk04: Thank you, Christy, and hello, everyone. I'd like to begin with our second generation formulations, where we've seen promising initial results. We believe the new formulation could be the future of the Ganaxalone franchise. The goal is to improve the relationship between the amount of Ganaxalone administered and the plasma concentration, allowing greater and more predictable individualization of dosing. The target pharmacokinetic profile includes an increase in overall exposure relative to peak concentration. which could provide the potential for twice-daily dosing with enhanced efficacy and a low rate of dose-related adverse effects. Initial data from a phase one single ascending dose study in healthy volunteers demonstrated encouraging results, which we believe support further clinical development. Study participants received single doses ranging from 100 to 900 milligrams, with the current oil suspension given as a reference control. Plasma levels were measured through 72 hours following the maximum administration. Total exposure was measured by area under the curve, or AUC, and this increased linearly in proportion to the administered dose, in contrast to doses above 600 milligrams with the current oral suspension. The increase in AUC was approximately 37% when escalating doses of the new formulation from 600 to 900 milligrams. without a significant rise in C-max. Tolerability was consistent with prior Ganaxalone studies with the vast majority of adverse effects being mild in severity. The PK profile of this formulation could allow for further upward titration for efficacy without a concomitant elevation in C-max related adverse effects such as somnolence. Next steps in the evolution of this program include additional phase one studies in healthy volunteers with higher single doses above 900 milligrams to determine whether further increases in exposures relative to peak concentration can be achieved. We will also be performing PK modeling to determine next steps, including the need for a study with multiple ascending doses. We currently anticipate selecting one of the second generation of Naxalim formulations for a phase two study in Lennox-Gastaut syndrome to begin in 2023. Lennox-Gastaut syndrome is a rare epileptic encephalopathy. It can result from many structural or genetic causes. It's highly treatment refractory, and we believe the new formulation will provide more consistent and predictable exposure to Ganaxolone, which should allow physicians to individualize dosing to achieve an optimal response for each patient. Additionally, there are several pro-drug candidates that could offer further improvements in efficacy and tolerability, ease of manufacturing, and dose individualization. Lead oral and IV pro-drug candidates have been selected for additional IMD enabling studies with phase one data targeted for 2024. Now, moving to our IV programs and status epilepticus. I'd like to dive a bit deeper into the RAISE protocol amendment that Scott mentioned and how we believe this will help drive enrollment. First, I'm pleased to share that the results from our Phase II trial on refractory status epilepticus were published in Epilepsia in June. As a reminder, this Phase II trial enrolled patients who had failed at least one second-line IV AED. None of the patients progressed to third-line IV anesthetics within 24 hours, leaving their primary endpoint in the study. Of note, 11 out of 17 participants were intubated prior to or during the study, and all patients with follow-up data, 16 out of the 17, were successfully extubated. We're optimistic that the Phase 3 study will validate this finding and support the potential for Ganaxolone to change the treatment paradigm in refractory status epilepticus. With this in mind, I'd like to discuss the three key changes in the RAISE protocol amendments. which is expected to be adopted across the majority of clinical sites in the third quarter. First, raised enrollment criteria were amended to allow inclusions of patients who had received IV anesthesia for up to 18 hours during the current episode of status. The original protocol inadvertently excluded many patients who had received IV anesthesia, particularly those transferred from outside hospitals or the emergency department. These patients were an important part of the Phase II population and can now be included under the amended protocol. The second key change involves the required number of prior failed treatments. The protocol initially required failure of an IV benzodiazepine and two or more second-line IV AEDs, at least three prior agents in total. The amended protocol requires failure of at least two treatments rather than three. Additionally, the investigator must indicate that IV anesthesia would likely be the next line of therapy if study treatment fails to control seizures. The underlying rationale for this change involved two issues. First, more centers are advancing to IV anesthesia after failure of the initial second-line IV AED. Second, patients in the ICU settings may receive a second-line agent without progressing through treatment with a benzodiazepine. usually because they already had received multiple benzobascine doses for sedation. As with the first change, this will allow enrollment of patients with a profile similar to those in Phase 2 to enroll in the Phase 3 study. We're confident that this will support a high rate of progression to IV anesthesia in study drug treatment failures. This will expand the pool of clinically appropriate patients who qualify for enrollment. We believe these two changes could potentially increase the sensitivity of the study by fostering progression to IV anesthesia and study drug failures, thereby reducing the placebo response. The third significant protocol change aligns EEG determination of study qualification more closely with clinical workflow. Rather than requiring an investigator to quantify the EEG seizure burden in the 30 minutes immediately prior to administration of study treatment, The protocol now allows an hour for this determination. This is more consistent with usual ICU patient care in which the physician will diagnose status epilepticus, then arrange for treatment to be administered, which can take 15 to 30 minutes. This change better aligns with the phase two paradigm and should also facilitate enrollment of clinically appropriate patients. We've received highly positive feedback from our study sites about the potential for increasing the number of eligible patients under this new amendment, and we will be holding an investigators meeting later this month to review and discuss the changes to the protocol. Furthermore, we've established an initiative of executive outreach by our scientific affairs and clinical development leaders to study sites to ensure a smooth transition adopting the amended protocol. Looking to the future of the RAISE trial, we will continue to actively monitor what's working well and how we can further refine enrollment criteria to support the recruitment of additional patients and potentially broaden the Ganaxalone label. For example, the trial currently enrolls patients aged 12 and older. We will shortly receive data that may allow us to broaden the entry criteria to include even younger patients. Given the higher incidence of status epilepticus in children, This change could further support timely study enrollment. As previously disclosed, we have the option for an independent data monitoring committee to conduct an interim analysis when two-thirds of participants have completed the study, which would be approximately 82 patients. At that time, the committee would recommend stopping the study for efficacy or continuing to full enrollment. US site activations in the RAISE trial continue to advance and we anticipate initiating 10 new sites in Canada beginning in the third quarter. We continue to expect top line data in the second half of 2023. In the phase two reset study in established status epilepticus, the community consent process, known as exception for informed consent, is well underway. We are pleased to share that we have activated the first site and are on track to begin U.S. enrollment in the second half of the year. We plan to limit site activation initially to four or five to focus on gaining a comprehensive understanding of enrollment trends before making a larger investment. Also, the RAISE-2 protocol is now finalized. Site selection is ongoing, and we expect enrollment to begin in the second half of 2023. This trial is designed to serve as a critical piece of the European approval strategy And we believe it also has the potential to further broaden the indication for IVG and Axalone in the U.S. Now, I'll turn the call over to our CFO, Steve Fanstiel, who will provide you with a financial update.
spk16: Thanks, Joe, and good morning to everyone. Before diving into our financial results for the second quarter of 2022, I would like to provide a few highlights on our progress since the prior earnings call. In July, we announced that we have entered into a definitive agreement to sell our rare pediatric disease priority review voucher for $110 million. The sale of the PRV, which is expected to close within the third quarter, significantly strengthens Marinus' financial position and we believe extends our cash runway into the fourth quarter of 2023. Inclusive of the proceeds from the PRV, we have raised well over $200 million of funding over the last 18 months from non-dilutive sources, including our credit agreement with Oaktree, our European commercialization agreement with Orion, and from our federal BARDA contract. These funds have been critical to enabling us to execute in our pipeline, including our phase three trials and reformulation efforts, as well as the commercial launch of Zotomi. Furthermore, under the Oak Tree Credit Facility, we have the opportunity to further strengthen our cash position through a synthetic royalty monetization agreement related to U.S. sales of Ganaxone, and have the option to draw an additional $25 million of funding under the facility subject to achievement of certain clinical and financial milestones. As we look to the balance of 2022 and into 2023, we will focus and prioritize our investments and resources on our key programs, specifically our Phase III trials in RSE and TSE, as well as the commercial launch of Satomi. These programs are critical to Marinus' future and delivering shareholder value. We want to ensure they remain on track and are funded for success. As an example, we have invested in additional global sites and trial resources for both the Phase III RAISE and TRUST TSC trials. While we will continue to advance our other investments, such as our earlier stage pipeline programs, these will be a lower overall priority from a timeline and funding perspective. As Christy discussed, we are excited about the launch of Zotami. As a reminder, we previously communicated our pricing and dosing expectations for Zotami. Zatami's wholesale acquisition cost is $2,425 for a 110-milliliter bottle. Our sales force is focused on the pediatric population, and initially we expect the average patient to be approximately 4 1⁄2 years old and weigh 16 kilograms. This translates to an average annual wholesale acquisition cost of approximately $133,000, and expected gross net deductions, including mandatory government discounts, are projected to be in the low 20%. As a note, our age and weight estimates are based on our expectations within the pediatric population, with any usage in an adult population representing upside to these projections. As the launch advances, we look forward to providing updates on our progress. Initially, we will be focused on patient enrollment metrics, including completed patient enrollment forms, new patients on therapy, and total active patients on therapy. We will also look to provide average dose related metrics for the treated patient population, along with relevant prescriber and payer metrics. For the launch, we do not expect a significant stocking impact to occur as we are utilizing a single specialty pharmacy and we will be coordinating closely with them. Additionally, once patient enrollment forms are complete, initial coverage determinations may take as long as one to three months to process. I'll now move to our financial results. For the second quarter of 2022, we recognize $1.8 million and $16 million in total revenue for the three and six months ended June 30, 2022, respectively, as compared to $1.9 million and $3.7 million in each of the same periods in the prior year. Revenues are recognized as a result of both our BARDA federal contract and our European collaboration with Orion Corporation. The increase in 2022 revenue was driven by a one-time revenue recognition of $12.7 million in the first quarter of 2022 related to the previously received upfront payment associated with the Orion collaboration. Excluding the Orion revenue, the company recognized $1.8 million and $3.3 million in BARDA federal contract revenue for the three and six months ended June 30, 2022, respectively, as compared to $1.9 million and $3.7 million for the same periods in the prior year. Research and development expenses increased to $21.5 million and $39.5 million for the three and six months ended June 30, 2022, respectively, as compared to $18.6 million and $37.2 million for the same periods in the prior year. The change was due primarily to costs associated with increased R&D headcount and startup of the Phase III Trust TSC trial. General and administrative expenses increased to $17.1 million and $28.8 million for the three and six months ended June 30, 2022, respectively, as compared to $6.8 million and $17.2 million for the same periods in the prior year. The primary drivers of the change were preparation for Zotami commercialization and additional support for scale-up of the company's operations. Additionally, during the six months ended June 30, 2022, A one-time cost of IP license fee of $1.2 million was recognized as expense in the first quarter of 2022 associated with in-licensing of patents and patent applications from Abbott Therapeutics. The company reported net losses of $39.4 million and $58.8 million for the three and six months ended June 30, 2022, respectively, as compared to net losses of $23.8 million and $51 million for the same period in the prior year. These totals include non-cash stock-based compensation expense of $3.8 million and $7.2 million for the three and six months ended June 30, 2022, respectively, as compared to $3 million and $8 million for the same periods in the prior year. Cash used in operating activities was $61.3 million for the six months ended June 30, 2022, as compared to cash used in operating activities of $39.1 million for the same period in the prior year. As of June 30, 2022, we had cash and cash equivalents of $92.3 million. We believe this balance, when coupled with the expected net proceeds of the PRV sale, will be sufficient to fund our operations into the fourth quarter of 2023 while maintaining the minimum cash balance required under our debt facility. For the fiscal year 2022, we are providing updated guidance with barter revenues expected to be in the range of $7 million to $10 million and our GAAP operating expense estimate, inclusive of G&A and R&D expenses, to be in the range of $150 million to $155 million, which includes approximately $15 million of non-cash stock-based compensation. These values represent a slight reduction to our GAAP operating expense estimate, which was previously projected to be between $152 million to $157 million, including approximately $17 million of non-cash stock-based compensation. Now, I'll turn the call back to Scott, who will provide concluding remarks.
spk03: Thanks, Steve. We are very excited about the first commercial launch of Natalme and the results from our second-generation development program, continued advancement of our two ongoing Phase III trials, and the strong foundation we've built. We are confident this launch is the first of many to come and will continue to prioritize these critical work streams to allow us to help more patients suffering from seizure disorders. Operator, can you now open the call to questions?
spk07: Thank you. As a reminder, if you would like to ask a question, please press star then 1 on your telephone keypad. Our first question is from Andrew Say with Jefferies. Your line is open.
spk11: Okay, thanks. Good morning, and thanks so much for taking my questions. Congrats on the progress, especially the launch recently. So maybe one on CDD first. Thank you. One on CDD first. You know, I thought I'd ask is, you know, how many patients, you know, have indeed been treated over the past few weeks or are a bulk of them still in the coverage form phase? I ask because just curious how we should be thinking about Q3 sales coming up.
spk08: Thanks. Well, it's a great question, Andrew.
spk03: As a reminder to everyone, we formally kicked off the launch about two weeks ago. That allowed physicians to fill out prior authorization forms and prescription forms. As we've talked about, we've expected those prior authorization forms to take up to three months to get approval from insurance coverage. I'll let Christy talk a little bit more about that. and let Steve talk a little bit about the numbers. But as a reminder to all, we're really going to share with you patient numbers on a quarterly basis starting next quarter in terms of new starts, approvals, and we recognize that that's the most important metric that you guys will want to follow. But maybe, Christy, I'll turn it over to you for a little more commentary and then Steve, to kind of round out what you're going to be talking about in terms of future guidance.
spk10: Sure. Thanks, Scott. And Andrew, thanks so much for the conversation here. We have, again, in the past two weeks, seen really, really great enthusiasm from a prescription and enrollment standpoint into ZTALM-E1. We have every expectation that our payers will start to evaluate us very significantly right now. We have several published policies already. And again, in this early period, we believe that it will take between one and three months to get through that process. We'll be fielding medical necessity requests simultaneously. But again, we think that we'll be having patients on therapy in the near future.
spk16: And Andrew, this is Steve. You know, just to kind of specifically address the question, we'll defer providing patient metrics and enrollment metrics until we get through the end of the quarter. I think it'll be appropriate to do that on a quarterly cadence. But, you know, we're absolutely committed to providing kind of the right patient enrollment metrics in terms of, you know, kind of completed patient enrollment forms, new patients on therapy, total active patients on therapy, and we'll provide other payer and associated metrics as well. So we look forward to doing that on the quarters on a routine basis.
spk11: Fantastic. And just a quick follow-up, shifting gears to RSC. Sounds like you had a great FDA discussion about the recent changes. So maybe remind us the latest and greatest, you know, whether you are confident or not a bridging study is needed with the modified IV canaxilone formulation. A little bit more clarity would be great. Thanks.
spk03: Sure, I'm happy to Andrew. So we you know, as we've done in the past, we've been very proactive with our interactions with the FDA. I mentioned on the call, you know, we have great CMC team, terrific addition to the leadership team on that side, and our regulatory team, you know, we we've been incredibly transparent with the agency, what we want to do change in our buffer system, new manufacturing facility, uh and you know do their communications with us they see that as a very reasonable approach they they commented specifically that by their guidelines the new buffer system is you know in the in the guidelines for for um sndas and uh reference products and we at this point in time um we don't see any reason why we need to do bioavailability do a bioequivalence study and in fact you know, their green light about using this new product in the phase three study, you know, presuming those first batches all hit our specs, you know, that gives us a tremendous amount of confidence, right? So, it's not as though we're going to only be using our current product and then filing with a new product. They've given us the ability to use this new product in the current phase three. So, we have a lot of confidence in the manufacturing team, what this new buffer data has looked like very early on. And just a reminder to everyone, the current buffer system is absolutely commercially viable. However, we don't want to launch with a one-year shelf life. So, the goal of the new buffer system is to really make this commercially much more interesting from a shelf life perspective, lack of refrigeration perspective. And again, ultimately, we see moving to IV bags over a two or three-year period. as the final steps in our development process. So, you know, I think the transparency that we have, the agency, we're sharing with you, and we feel very confident that the manufacturing piece of our DMC filing will not be a gating factor for approval of the IV Ginexilin program.
spk08: Thanks so much for the call, and congrats again.
spk07: The next question is from Charles Duncan with Cantor Fitzgerald. Your line is open.
spk12: Hey, good morning, Scott and team. Thanks for taking our questions and congratulations on a great quarter of progress. Exciting to see first launch. Thanks, Scott. My first question is for you or for Christy. I'm wondering if you could characterize that initial response by both the payer community as well as the prescriber community Is it in line with what you had expected, or is it beyond what you had expected in terms of the interest in Satomi?
spk03: Well, let me just give a few opening comments that I'll throw out to Christy. I think we feel fantastic that going into any payer discussion, we've got a published phase three study. We've got editorials from independent physicians supporting that. We have guidelines in the public domain that also are strongly supportive of the use of . And so I think going into all of these discussions, we've got a robust scientific package. And so we had high, we certainly had high expectations. But let me turn it over to Christy and let her more specifically.
spk10: Sure. Thanks, Charles, for the question. And it's a great question for a commercial person to give some perspective to. But look, I think we all plan for a little bit of the worst that supports some high expectations when the day actually comes. So we had a high level of enthusiasm. I'd be remiss if I didn't say that our excitement is pretty robust on the commercial side of the world right now. not only just with the enrollments that we've seen on day one through day 14, which is today, but also the payer community has been very supportive of our efforts. We have several known published policies, and it just really is a testament to the two years' worth of work that was done from all sides of the business, medical, CNC, and the commercial side. So we're enthused at this point.
spk12: Okay, very good.
spk03: We put a lot of thought into the pricing work, and that was an organizational effort. And I think that's a critical piece here, too. I think we priced the drug very fairly for the value proposition that I think is critically important for these patients. And I think the payers are respecting that as well. I'm sorry. Go ahead. Why don't you give us your next question?
spk12: Yeah, that seems to be the case. So just moving on to the raise program and that is or the ID program and them and specifically with regard to rate. I'm just, I'm just wondering if you could give us a sense of when that interim could occur obviously between now and second half of 23 But when would you have about 82 patients through the required period to possibly trigger that interim result?
spk03: That's a great way to ask the question, Charles. I think most importantly, the discussions with the FDA gives us the flexibility to pull the trigger on the interim. I think most importantly, We've had, you know, we reinitiated the trial in the May timeframe. We knew it would take several weeks for sites to get up and running full gear. We really feel like the vast majority of sites are now up and running full gear. We'll have this protocol amendment coming now at sites currently. And so we really feel like we're going to be, we're going to have as much of the winch to our back by the September timeframe as we can have in this study. We'll be adding some additional sites in the third and fourth quarter too with Canada as really, you know, an important backup strategy. And I think really by year end, we will make a decision as an organization about where we stand in terms of monthly enrollment, where the TSC study stands in terms of monthly enrollment, how those two studies overlap. And I think by early next year, we'll make a corporate decision on what we want to do. But we're not quite there yet. And we're looking forward to the next few months of enrollment trends for both studies. And I think, again, having the flexibility in this case creates a lot of opportunity for us to do what's right for the clinical studies, for our investors, and for patients as well. Joe, anything you want to add on a raise? Just overall commentary about the study?
spk04: Yeah. Actually, I've been out to some sites recently, and the response to the protocol amendment that we'll be implementing is extremely positive. And there's a lot of confidence on the part of sites that that's going to help them boost enrollment. And so, like Scott, I'm very confident that we'll by the end of this year, be able to see a boost in the enrollment and how the trends are going.
spk07: The next question is from Douglas Zal with HC Wainwright. Your line is open.
spk17: Hey, good morning. Thanks for taking the questions. As you move into the launch and the remainder of the year, just raising the profile for Conaxlo, I'm just curious about presentations at medical meetings through the rest of the year, and in particular AES, and what your plans are there.
spk03: Thank you for the question, Doug. Joe, why don't you talk about what's happening on the scientific affairs side with Alex's team and your team, and then we'll pass it over to Christy to give a commercial update.
spk04: Sure. Well, we'll have a presence at Child Neurology Society, Neurocritical Care Society. There's a conference in Salzburg on status epilepticus in September where we'll be presenting two posters. And then for AES, We've submitted four posters, four abstracts for presentation at AES. We're going to submit an additional two late-breaking abstracts to the meeting. And, you know, while we're on the topic of AES, the American Epilepsy Society chose to publish on its website recently on its clinical corner, on its clinical corner page, an article on Ganexolone and CBD. The lead author of the Lancet Neurology paper, Ilya Pastaninait, discussed in a video the use of Zetalmin and CBD with two other epilepsy experts. And I'd also mention that international consensus guidelines on CBD treatment were published in June in Frontiers in Neurology. We were glad to see that. All of the respondents, when asked whether Ganexolone should be offered for CDD responded, yes. So it was a unanimous opinion about using an axolotl. And getting back to AES, we expect to have a big presence there overall in addition to the publications.
spk00: I'll jump in here really quick. Sorry, Doug.
spk17: Oh, no, no. Go ahead, Christy. Sorry.
spk10: Yeah, I'll just jump in quickly from a commercial perspective. As you can imagine, AES is kind of our coming out party for Zatomi this year. So we're going to have a pretty robust commercial presence that will be including our first commercial conference booth. We will also have a clinical data review by way of a product theater that will be provided by a top KOL. And then as you could imagine, really significant KOL and physician engagement from the commercial team.
spk17: Okay, great. And then just, Christy, I'm just curious, what's the sort of, if there is the most commonly asked questions about Ziton in the early engagements? You know, is there generally sort of accepted awareness of the product? And I'm just curious about what people are focusing on from clinicians.
spk10: That's a great question. I think it's twofold at this point. In this community of physicians and with families that are living with cdd we kind of are focusing on a push and pull strategy we know that this is going to be 50 percent guided by the physician and 50 percent guided by the families that are um treating or that are um caring for children with cdd and so when you talk about the families their their major concern is access right now these these These families are dealing with multiple medications for these kids, and it can be quite an arduous process to get their kids the medicines that they need and deserve. So that's why we built a very robust Zotomi One program to make sure that it is seamless access and that anyone that is appropriate for Zotomi gets the medication. Now, if you're talking about the physician presence, I think they really want to understand our mechanism of action. They want to see how this could be different than how they've treated patients previously and potentially how this is an additive effect to what they're already on. So those are the two kind of push and pull major questions and things that we address in the field on a daily basis.
spk17: Okay, great. And just, Scott, maybe a quick one on the IV formulation in terms of the two-year shelf life. Do you think Can you just walk us through how that would be incorporated into the NDA? Would that data, the two-year stability data, be ready at time of filing, or would that be added later on?
spk03: It's a great question, Doug. Well, a few different things. One, typically, we want to have stability data at least a year ahead of the filing so that when you file the NDA, you have one-year stability data on hand. That's the big reason that we're going to make sure that we have a manufacturing batch to begin in the fourth quarter of this year, right? So that would give us one-year data by the end of 23 in this case. We've also run, we have some accelerated models that we've used that we've already tested with the new formulation, which are showing very strong results. And we will be discussing with the agency accelerated models But remember, from the time of filing, we'll have at least six more months of stability data by the time of the NDA decision. And, you know, this is a back and forth with the agency and one that we're not too worried about. And so over the next 18 months, we'll be having those discussions with the agency. As an example, will they take our accelerated filings? or accelerated stability data as a proxy for two-year shelf life, et cetera. So, a few different strategies we can explore having the actual data. Again, about the time of approval, I would expect to have a minimum of 18 months of shelf life. That would be, you know, quickly amended. Or we can use this accelerated approach, which would give us two years plus. Right now, the solubility curves are really logarithmically different for the new buffer. And so we've got a pretty convincing early data package and don't see it at all as a major concern for us by the time of approval.
spk07: Okay, great. Thank you so much. Sure. The next question is from Joseph Tomei with Callen. Your line is open.
spk15: Hi there. Good morning, and thank you for taking my questions. Maybe the first one on RAISE. Just in terms of between now and when you can make that decision to take the interim look for the study, I guess what's going to go into that decision point? Is it really just a bandwidth on readout between TSC and RAISE, or are you going to be able to see some unblinded data or look at kind of the enrollment criteria of the patients that are coming on the study to help make that decision for you?
spk03: I would say I think right now it's a going to be driven by a corporate decision. I mean, Joe can talk about it, but we certainly have a DSMB that's in place that will be reviewing our data sets, but of course, we'll be blinded to that. And so, I don't see any, you know, we can't really allow the blinded data per se to really affect our decision. And of course, and I think, so this is, in my mind, really a corporate decision based on the monthly enrollment trends, the time to the conclusion of the study, where we are with TSC. And, you know, we'll look at all those factors to make the decision. But again, I think by us asking the agency well in advance, can we do this, just gives us a lot of flexibility. And certainly, we feel very good that if we choose to do an interim, we have an 80% power to hit what we think is a key secondary endpoint around ICU days, mechanical ventilation, which, you know, my view going into the launch, Joe, and I haven't talked about this, was that this would be, you know, this study is so incredibly important for the data to drive reimbursement in the hospital, and we all know that's a difficult environment. What's really changed from the time we started this program is our commitment to now doing of RUN RAISE 2, and so we will now have, you know, two double-blind placebo-controlled trials over the early years of this launch, a bigger data set. And that's also, in my mind, an influence on our decision about how big RAISE needs to be and what type of data we need to generate. So, you know, I can't say we're not going to make any decisions, but I think we're thinking about all of those things. And certainly, you know, I don't know, Joe, if there's anything else you want to comment on from the clinical side. But, again, it's hard to imagine we're going to see a lot to push us one way from the data set itself.
spk04: Yeah. Yeah. No, I mean, it takes some time to do the interim. It's an independent statistician that does it. The data's all got to be cleaned. And enrollment in studies typically, you know, accelerates as they go along. And so it could be that by the time we got the interim done, there'd be substantially more enrollment. And in that case, we would just likely wait for the final data. But as Scott said, it's really a consideration about the rate of enrollment.
spk15: Perfect. Thank you very much. And then maybe a follow-up just on the novel formulation. How much higher do you think you can push the dose here? And maybe... what are you looking for specifically to go forward into that LG study? Are you going to look at multiple doses, or do you think you're going to be able to nail one down to take forward? Thank you.
spk04: Yeah, I can take that one. So there are a lot of decision points along the way. We've got a lot of choices, reformulation candidates and the pro-drug. We do hope that, and we've seen early promising results that we can increase the overall exposure and blunt the C-max and keep going. Right now, the highest we go on dosing is a single dose of 600 milligrams, and we hope to be able to go over that in individualized dosings, particularly in Lennox-Gastaut and other epileptic encephalopathies. Most patients tolerate the drug very well, and there could be the potential to go higher. Our current label caps daily dosing at 1,800 milligrams per day. So we'd hope that the kinetics and efficacy and tolerability would allow us to go higher if patients need it. And we're still waiting to see some of the human PK data. For example, we're completing the single ascending dose study with the first reformulation candidate. We'd want to see multiple ascending dose studies with repeat dosing. and then decide whether, you know, what step to take next, a single-arm, you know, or two-arm phase 2B against placebo, even potentially go straight to phase 3. But we don't have the data yet to inform that decision. And it's going to be a few weeks, months, until we really know what path we want to take for clinical development in phase 2 and 3.
spk03: Yeah, and Joe, the only thing I'd add to that from Joe Houlihan is that, you know, our goal when we started this program was to have a formulation and or a pro drug that could deliver steady state blood levels of at least 100 nanograms per mL, and certainly critical to be able to go above that. And, you know, I think our back of the envelope is it'd be great to test 150 nanograms per mL as a steady state blood level. and correlate that with seizure reductions and potentially 200 nanograms per mL and correlate that with seizure reductions and tolerability. And I think we believe in what we've seen and what our modeling has showed us that we can achieve that with this formulation quite reasonably. So, we want to replicate that and feel confident about it. And I think we have some important decisions to make around dosing and a modified release formulation. Certainly the data to me is encouraging that we may, you know, be able to create a daily formulation with this, a once a day formulation. Right now I think twice a day is well within our grasp. And certainly now we're really getting to think a little bit harder about where do we want CMAX to land? How much can we bring in CMAX in terms of tolerability? And I think now truly a focus on trough levels as well. and really maintaining job levels where we think they should be. So this is, in my mind, this is just incredibly exciting to that the data we've generated to date is aligning, it's very nice with what we'd like to perform out of the program. Now, remind everyone, you know, we believe in the Marigold data. that blood levels of 150 nanograms are going to, you know, drive efficacy. That was a strong signal in Marigold. Certainly in our IV program, blood levels drive efficacy quite clearly between 400 and 500 nanograms. But we haven't proven that, but we certainly believe there's a very strong possibility, and I think everyone can imagine, that this is a very well-tolerated drug at incrementally higher blood plasma concentrations at a steady state, has a very high probability of driving a higher efficacy. So that's the full disclosure, but we feel pretty good about the odds of success where we stand today.
spk08: Perfect. That's very helpful. Thank you.
spk07: In the interest of time, we ask that you please limit yourself going forward to just one question. Our next question is from June Lee with Truist Securities. Your line is open.
spk13: Hey, thanks for taking our questions. Does the use of CDDI-CV10 codes require genetic diagnosis, or is this based on a clinical suspicion, and has the payers required genetic diagnosis of CDD for approval of the drug? Thank you.
spk08: Chris, do you want to take the second, or you're welcome to take the first two, if you like?
spk10: Yeah, I'll address the second first. You know, I mentioned earlier that we have seen some early published policies And each of them is directly in line at a very, very minimum with our label. So we set some expectations that a good payer policy would be in line with our label that is inclusive of patients two years and older, confirmation of a CDD diagnosis that is inclusive of a genetic test, and failure of at least two AEDs. We have certainly seen published policy that is in line with that, and we've seen policy that is less restrictive of that, including that of a genetic test. So currently, right now, we have a few, a handful of published policies. And again, we have every determination that we think that all published policies, maybe going forward, will have a genetic test component to it. However, we've seen a little bit of both.
spk03: knowing that it is um highly used from a genetic testing component across the united states it is again very likely that that would be included and june just to be clear you know just to back up for everyone on the call um as a good reminder you know we're fortunate to have an ncb10 in place that was really the work of our advocacy groups uh where lulu foundation and isdr made a strong push for an ICD-10 code for CDKL5. That's been in place for a little bit more than 18 months. And so what's been so interesting to us is before Marinus was out in the field with their MSL team, our MSL team first, and now our commercial team, we were seeing physicians use that ICD-10 code in increasing numbers. And so, and we would expect that to continue to increase, and we certainly will provide additional education in that regard. But us being able to track that ICD-10 code just has been invaluable for our strategic planning about where we want to go. how we align with the ICD-10 codes, our centers of excellence, and key epilepsy centers that we would like to make sure that, you know, the commercial team is meeting with. And finally, if we see ICD-10 codes from places that are not on our A-list, we have somewhere else to really evaluate. So, it's really a nice tool in our toolbox that will complement the data sets that we will use for the commercial team. And I think, you know, it's a little bit more of a, it's a relatively simple tool to add to the reimbursement form. So, you know, in our, and of course, what we're, we've also seen is that ICD-10 code is identifying patients across all age spectrums. And it has been really interesting to us that right now about 25% of the patients identified via the ITD-10 codes are adults or young adults. And that obviously will have some important implications for the way we're thinking about the business and ultimately what drives the average wage around our revenue.
spk14: Hey, Scott, quick follow-up. What are some of the top differentials that are maybe being coded alongside that CDDI 10 code that might give you some hints as to where you might want to go next?
spk03: Oh, I think the most logical place is that we would, you know, start to look at data sets for other anti-epileptics that, you know, are used in refractory patients as a tool for the commercial team. But quite honestly, June, I mean, I think the way, and Christy's on the call, I'll let her jump in. I mean, the team's doing fantastic work today. We're going to start our KOL speaker programs shortly. We, you know, I think we're going to get a great boost. Joe told you that we already have AES helping us talk about the value proposition of Gnass Loan. So, I think in the next three to six months, we're going to be incredibly busy with what the specific targets that we think are vital to the marketplace. And we've said this all along, the only way we can do this with a small sales organization successfully is that we've got these great centers of excellence, that we have really a meaningful number of refractory epilepsy centers. But I think the way we're thinking about our continued success in 23 is by, you know, maximizing the data sets available to us to make sure that we're going to the right physicians. Christy, anything you want to add?
spk10: Just a small thing here, and June, it's a great conversation, one that we have quite regularly here on the commercial team, but in the past few weeks, again, we are educating on the use of the code. It guides us in our conversations of where to go today, but additionally, because we've had such unique interest across not only our targeted accounts, but also non-targeted accounts, we're learning other codes that are being used that are informing our data team to help some continued mapping to understand and inform our deployment strategy even farther. So again, we have a very distinct education plan on the use of the ICD-10, but then again, we're also learning other codes that are being used that are guiding our mapping even farther.
spk08: Thank you.
spk07: The next question is from Jay Olson with Oppenheimer. Your line is open. Oh, hey.
spk01: Congrats on all the progress, and thank you for taking the question. Our question is related to RSE. Can you talk about any physician feedback you received on the Phase II data that was published in Epilepsia, and have you seen any impact on Phase III RAISE enrollment rates as a result of the increased awareness from publishing the phase two data?
spk08: Thank you. Yeah, this is Joe.
spk04: Yeah. I mean, the feedback on the phase two study has always been positive. And again, as I said, I've been out visiting sites and we do get into discussing the data. And in the context of the amendment that's coming up for the RAISE study, Because with these changes in the protocol, it really reflects the population in the phase two study much better. And so in discussions about the amendment, I do bring that up. And the alignment with that population because of the features of the amendment, we do get positive feedback about enrollment. You know, a lot of the patients in the RAISE study, as we mentioned, you know, were intubated either when they came in eight were intubated when they came in to the phase two study, I mean, and three got intubated along the way. And we have follow-up for all but one patient and every patient was extubated. And so, you know, that's, to me, that's an incredibly positive, um, finding and, and we haven't quite framed it that way. And so in discussions moving forward, um, you know, in the few so far where I've brought up the data in that way, the response has been incredibly positive. And so, and this amendment, again, will mirror the population in the phase two study. And we see that as a great recipe for success.
spk08: Thank you.
spk07: The next question is from Mark Goodman with SVB. Your line is open. Yeah, good morning. Just curious, Europe, you mentioned it a little bit, but have you gotten the response from Europe? Are we all set here? Does it look like it's going to be pretty clean and you'll be able to get approval?
spk03: Yeah, so Mark, we're working on that. So we'll formally respond to the list of 128 questions by the end of the third quarter or early in the fourth quarter. We have It was a pretty big list of additional studies. Almost actually all were preclinical in terms of additional requirements. We've talked about it. The Europeans wanted some additional work with our syringes. That was the biggest impact. And I think we, you know, Joe actually has done a great job going back and looking at the data. As you well know, Mark, you know, that 50% response rate is incrementally more important in Europeans. And, you know, we have some really interesting data that we are going to give to the Europeans about the statistical impact on the maintenance phase in the Marigold study. So, I think we have done everything we can do to answer the questions that the Europeans are seeking. And, you know, we're enthusiastic about the outcome early next year.
spk07: And are you still having discussions with some other regions to license out other regions?
spk03: Yeah, we expect to have another geography strategic partner in place by year end. And I think we would certainly expect to have another significant region in place next year as well. This is This is a tough one for us, Mark, I mean, in a good way, because there's huge demand, but because these indications are more orphan-like, we really are forced to have deals with the regional players, and that just creates a lot of work for our organization. We love Orion as a strategic partner in Europe, but it's a lot of work to teach them what we know, And certainly they're bringing a lot of skills to the table. But, you know, we are now the authorities on CDKL5 deficiency disorder. And I think, you know, that will be the same whether it's Japan or China. And I think we're just trying to do this in a measured fashion that's bringing some meaningful economics to the company that will support our R&D efforts and our commercial efforts in the short term, but doesn't overwhelm the team. And, you know, I feel pretty confident that, China and Japan are going to be important markets for this drug. And certainly there's, you know, real interest and demand in MENA regions and in other regions. And so we're going to knock them off one at a time, but we're trying to start with the most meaningful from a patient number standpoint, ones that we can really handle organizationally. And that creates some value and, you know, some economic payments that allow us to continue to do all the things we're doing. So, yeah, we feel very confident about those discussions.
spk07: Also, Scott, in the past you've talked about potentially doing a royalty deal. I didn't know if that was even something still considered. Is it even necessary anymore? Thanks.
spk16: Yeah, hi, this is Steve. I'll answer that one. Yeah, I mean, look, the The PRV was critical. We were really excited to get that contract in place. And frankly, with it being at the high end of the range, that gives us the flexibility to look at a number of options. We're really reassessing the royalty options still very much in play. But I think, you know, with the PRV sale, we feel like we've bought some time and flexibility there.
spk07: Thank you. The next question is from Brian Scorny with Barrett. Your line is open.
spk02: Hey, good morning, everyone. Thanks for taking my question. I guess mine's sort of a combined one for Christy and Steve. I was hoping you could maybe walk us through conversion from a prescription to receipt as Tommy and actual booking of revenue here. Is there inventory held at a specialty pharmacy that's recognized as revenue, or is it effectively just-in-time delivery? And will the reported revenue we get be pure demand sales? And based on the payer mix, What do you see as sort of the hurdle as far as the average co-pays going? How much are you able to offset that through the Zipomi one? Thanks.
spk16: Yeah, Brian, so I'll start with a little bit of kind of the revenue recognition piece, and then I'll allow Christy to chime in as well here. You know, we will sell to the specialty pharma partner who will then, you know, distribute to the patient. So we'd expect to recognize that when we sell it to the specialty pharma partner. Obviously, we'll have metrics to be able to estimate gross to nets and account for those appropriately in our gross to net deductions. I would not expect, as we mentioned, any significant stocking impact. We're going to be coordinating very closely with them, so there's no need for them to order kind of excess inventory or have any of that on hand. It will be not quite just in time, but really not far from that. So, you know, I think we'll be able to really manage very tightly the expectations and understanding of the gross to net deductions and inventory very closely with Maybe I'll turn it over to Christy now to talk through that conversion process.
spk10: Sure. So thanks, Brian. For the conversion of a naive patient from the prescription and enrollment into Zotami One, it really sparks a very clean line to fulfillment, which is we start a benefit investigation that simultaneously, once enrolled in Zotami One, will necessitate the need for what the out-of-pocket would be for patients. So after the benefits investigation, we assume that all will need a prior authorization. Once that BI is done, the prior auth will then be initiated through Orsini. Again, simultaneously, that need for any patient services support for commercial patients, for copay, and again, for any patients who have limited insurance or no insurance, that process will also start. Once the PA is through, you know, we determine that those will take in this early period anywhere between one and three months, just considering we are a new drug to market. And then when we're talking about what we think that average copay will be, you know, you've seen one plan, you've seen one plan. For our Medicaid patients, we think that it will be a minimal out-of-pocket. And for our commercial patients, we think that, again, that will be a minimal out-of-pocket. Again, we will be buying down to zero for any patients who are available for that need. So, again, a pretty clear line moving with one specialty pharmacy partner right now where patient services are under our one roof.
spk08: Great. Thanks. That's very helpful.
spk07: The next question is from Michael Higgins with Landberg Thalman. Your line is open.
spk06: Thanks, Aubrey. Good morning, guys. I'll behave here and try to limit my question to just one topic. And congrats again on the progress with the Ptolemy Amendments and Aggie Manufacturing. You have a lot going on. With the Ptolemy having a launch underway here, if you could remind us what your percent reach is that you're looking at today, you've noted a focus in 22 states, the states where there are centers of excellence. How's that evolving with the new ICD information that you've noted? What are your plans and the timing for expanding that outside of what your reach is today? Thanks.
spk10: Hi, Michael. I'm happy to take that. Currently today, we estimate, again, two weeks into launch, that we'll probably have about an 80% reach with that. We certainly, with the early data in the ICD-10 that's being increasingly used, that has confirmed that. Again, to my earlier point that other codes in certain situations are being used, I think will inform that. I personally believe that where we have our reps today, I don't think that we'll need to have any increased reach at that point. We are reaching our top accounts. Again, we have about 300 centers that we're targeting today. um both from a cbd center of excellence national epilepsy centers but also down to you know smaller community accounts again that we are being able to target very easily with the sales force that we have you can also say i mean the world's different today right we don't need a salesperson to help a physician and a family find this drug we have had that happen already so
spk03: it's not clear that we need to actually be nice, but it's not critical for the success or the ability to capture that last 20% by having a Salesforce call on that position, right? And the team's done an amazing job to make those materials available. They're very straightforward. We've got our great data. I mean, I was in practice for a lot of years and didn't see a sales rep that wrote prescriptions, and I think we're already seeing that
spk08: today, which is very exciting and gives us confidence that we are right-sized for this launch.
spk07: The next question is from Jason Butler with J&P Securities. Your line is open.
spk05: Hi. Thanks for taking the question. Just one on the RAISE protocol amendment. Obviously, as you said, the IV inclusion of IV anesthesia, you have those patients in the phase two, so you should have some level of confidence there. But can you just speak to your level of confidence around the change associated with prior failed agents? Thanks.
spk04: Sure. Yeah, well, I think for a lot of reasons, we're confident about that, too. Again, that parallels... Patients in the phase two study as well. And we didn't see a difference in patients who had taken fewer versus more IV AEDs previously. The other piece of that is, well, it's going to help enrollment because of a couple of reasons. Patients in the ICU, they may not get a dose of benzodiazepine as is required in the current protocol. They may progress right to a second line IV AED. because they've gotten so much propofol, midazolam or whatever for ventilator management. That's one. And the other is more centers are progressing straight to IV anesthesia earlier in the treatment sequence after the first failed second line IV AED. So by just requiring two agents, either a benzodiazepine and one second line or two second line IV AEDs, we'll be able to capture more patients the other piece of it is the current protocol specifies that IV anesthesia mustn't be a contraindication now because we're going earlier in the treatment sequence and want to treat appropriate patients it's now an inclusion that were it not for intervention with the study drug IV anesthesia needs to be the next intervention that they would consider or likely the next intervention that they would consider That does a couple of things besides, you know, making sure we're treating patients of appropriate severity for an investigational agent. It also strengthens, it also increases the chance that IV anesthesia would be the very next treatment considerably. And since the second co-primary endpoint depends on that, we think this change actually increases the sensitivity of the study rather than decreases it. And so, You know, we're, you know, with all these things together, and it's bolstering enrollment and some of the changes strengthening the study further. I'm actually optimistic about that in terms of the effect on the study.
spk08: Yeah, and Joe, thank you.
spk03: I think that was great. And Jason, I'll just add, you know, we've powered the study, and we've talked publicly about a 40% placebo number as our powering assumption. We've also talked that we believe that... you know, this placebo rate is much more likely to be closer to 20% around, you know, the progression to general anesthesia. And to Joe's point, we really believe that these changes to the protocol have the ability to drive that number even lower because some of these patients are already going to be on mechanical ventilation. So if you turn down their anesthetic agents, they go into status, they either get drug or placebo, If they get placebo and they're still in status, it's going to be a very easy decision to crank up their anesthesia, right? So we feel very good about this only having a potential positive effect for the study and a lowering placebo effect overall. That was going to be our last question. I just want to thank everyone for being on the call. I know we've run late. We've got a lot going on, and we are happy to take questions around the launch. We're super excited about the new formulation and certainly the progress that we're making on our phase three trial. So thanks, everyone, for dialing in, and have a good day. Operator, back to you.
spk07: Thank you, ladies and gentlemen. This concludes today's conference call. Thank you for participating. You may now disconnect.
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