Q1 2023 Marinus Pharmaceuticals Inc Earnings Call
Greetings and welcome to the Marinus Pharmaceuticals, first quarter 2023 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.
And now it is my pleasure to introduce your host Sasha <unk> Ellis Senior Vice President of Corporate Affairs, and Investor Relations you may begin Mr. Minneapolis.
Thank you and good morning with me for Meredith Pharmaceuticals are Dr. Scott Braunstein, Chairman and Chief Executive Officer, Chris.
Christy Schaefer Chief commercial officer.
Doctor, Alex the Matti, Chief Scientific Officer, and Defense Hill, Chief Financial Officer, and Chief operating Officer.
Before we begin I would like to remind everyone that some of the statements. We're 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.
Thank you Sasha and welcome to our call during.
During the first quarter of 2023, we made important progress advancing our oral and IV <unk> program further establishing Meredith as the leader in the development of innovative treatment options for patients with rare genetic epilepsy and refractory seizure disorders.
We continued to make considerable strides with the launch of this told me are pleased with our first quarter sales of $3 $3 million.
Track to meet our previously stated full year 2023 guidance of $15 million to $17 million Christy Schafer, our chief commercial officer will be reviewing some of the key initiatives for 2023 that we believe will support the continued growth of this Halloween.
We've also made significant progress in our commitment to bring <unk> to more patients around the world let.
Let me start with an update on our European marketing authorization application.
As part of the day 195 assessment report the European Medicines agency communicated that the major objection related to the choice of regulatory starting material has been resolved we expect to receive the cgmp opinion, Tommy and CBD by the end of May.
Confident with the progress that we've made to date.
As a reminder in August of 2021, we entered an exclusive agreement with the Orion Corporation for the commercialization of <unk> in Europe and had been collaborating with them to prepare for the potential launch we look forward to sharing the foremost the HMP opinion with you later this month.
Furthermore, we are pleased to have entered into an exclusive distribution and supply agreement with biologics tawny.
Several markets in the Middle East and North Africa.
<unk> is a multinational pharmaceutical company based in Dubai.
We hope to have the telling me available for patients in the Mena region in early 2024.
In parallel we are working closely with Tunisia, our partner in China, and expect them to file a new drug application by the end of this year.
We are engaged in active discussions with several strategics or interested in bringing our products to market in Japan.
Our current and future ex U S partnerships are a central part of our commitment to reach the global patient community.
Moving to our clinical pipeline, we are excited to announce our plans to conduct an interim analysis of the phase III <unk> trial.
Factory status epilepticus.
Later this year.
Alex will discuss the process in more detail shortly but if the results meet the predefined stopping criteria. We expect to report interim top line data in the second half of this year.
Our leadership continues to prepare for a potential RSC finally, including a growing effort from our commercial regulatory CMC and medical science teams. Additionally.
Additionally, we are gratified that physicians across the U S are requesting the use of IV <unk> Epsilon for their most severe super refractory patients.
Some have seen important clinical improvements.
We're actively recruiting for the phase III Trust TST trial in the U S Europe , and Canada and expect the vast majority of clinical sites will be ready to enroll patients by mid year, including new sites in Israel, Italy, Belgium, Australia and China.
Due to administrative and regulatory delays in certain ex U S countries. Many of these which have now been resolved we expect top line data no later than the middle of 2024.
Importantly, we learned with CBD efficacy and Tolerability are key attributes to success in the refractory epilepsy population and we are confident that the current protocol design maximizes our opportunity for a clinically meaningful outcome.
Let me conclude with a few additional business updates we continue to advance our IP portfolio and recently received a notice of allowance from the U S patent and trademark office for a new method of use patent for <unk> and TLC.
When granted the term of this patent will run through 2040.
We have spent considerable time and energy broadening our patent portfolio and look forward to a final issuance of both this new method of use patent for the oral franchise in PSC.
And an additional dosing method of use patent for IV franchise in the treatment of RSV.
We believe that there are additional opportunities to expand our patent portfolio based on our scientific advancements in the next several years.
We look forward to our upcoming phase III data Readouts and our clinical progress and our second generation platforms. We expect the number of additional milestones before the end of the year, including enrolling our first patient in the race to trial and completing enrollment of the first cohort of patients in the reset trial and.
Status epilepticus.
We believe our second generation formulations have the potential to be the future of the Max loan franchise and are planning to initiate in multiple ascending dose study with our first new formulation in the third quarter with preliminary results expected by year end.
If these results are consistent with the single ascending dose modeling this formulation would be utilized in a future trial.
Yes, those syndrome with the clinical program design is expected to be finalized in the first quarter of 2024.
Finally, we are pleased to welcome Marvin Johnson to our board of Directors Marvin has over 34 years of diverse commercial operations experience at Merck and will be invaluable in supporting us at Tommy commercial efforts, while preparing for potential hospital launch of <unk>.
Now I would like to turn the call over to our Chief commercial Officer Christy Shafer.
Thank you Scott and good morning.
I'm pleased to provide you with an update on our continued progress as we execute on the U S commercial launch of the Tommy.
Today I'd like to focus on three topics.
Hi. This is Tommy launch is progressing what we're going to accelerate growth and adoption of this important new medicine and.
And how we are preparing for a potential IV launch of <unk> in the hospital and an expanded indication in TSA.
Net sales as the Tommy in the U S. In the first quarter were $3 3 million with approximately 100 commercial patients active on therapy.
End of the quarter.
We continue to see a steady build of treatment naive commercial patients with prescriptions coming from our growing and diverse prescriber base as is our 100 unique sessions.
Total payer coverage for the Tommy increased to approximately 225 million lives, including both commercial and government programs.
The Tommy has received favorable coverage determinations from over 40 payers, representing approximately 130 million commercial lives in Medicaid access has been confirmed in all U S States as well as Washington, D C and Puerto Rico, representing approximately 95 million lives.
What are you foreseeing do meaningful uptake in all CDK, all five centers of excellence with encouraging trends persisting and surrounding areas where patients are managed routinely for ongoing treatment.
Using sophisticated data sources, we've seen an uptick in the usage of the <unk>.
10 code J $40 42, and continue to see this trend rising with educational efforts and awareness campaigns with over 700 unique patients since 2020.
We're evolving our commercial efforts in response to what we've learned this included investments in higher quality data sources more sophisticated analytics, new educational materials around genetic testing and training and ultra rare market dynamics.
Understanding the crucial role of the caregiver, we continue our commitment to providing ongoing support to the CDK all five community.
Recently, we hosted an educational webinar featuring Dr. Raj Roger Amen, a prominent pediatric neurologists from UCLA, a CBD centre of excellence and Dr. Alex <unk> <unk>, Chief Scientific officer to address the questions received from the community.
Additionally, we are in the process of kicking off our caregiver engagement program to educate patients and families by sharing experiences that families who have initiated treatment with autonomy and what that experience has meant for them and their loved ones.
These stories will be incorporated into our branded promotions for CBD and will also include healthcare provider. If you can speak to the clinical profile of the Tommy.
We continue to plan for and are making significant progress as we look to expand our oral franchise and build out our acute care franchise and preparation for a potential hospital launch of IV <unk>.
For our expansion efforts the remainder of 2023 will be focused on building on our robust and comprehensive understanding of the U S TSA market.
These efforts will include initiating and emotional and functional patient journey market Research project Treater identification analyses and a new ex TSB landscape assessment to identify leverage points existing behaviors and beliefs to create a brand strategy that enables the optimization.
Of the introduction of the Tommy to the U S TSA market.
For IV, our commercial planning investments are ramping up significantly with priority on strategies that we believe will drive early launch success.
To maximize the total market potential we are in the final stages of an innovative data project that it's first of its kind as it relates to the identification and tracking of status epilepticus patients.
Leveraging data across four distinct claims providers to generate patient progression through each episode resulted in a sophisticated and comprehensive look at inpatient pathways and outcomes associated with usual care.
These key findings and insights deepen our understanding of the specific unmet needs as patients progress along the status continue on and we will shape our commercial strategy.
Finally, we are preparing to address the inherent challenges with inpatient reimbursements and complex args and do plan to pursue an end cap is one component of our access and reimbursement strategy.
As a reminder, the <unk> or the new technology add on payment designation enables additional payment to hospitals above the standard Medicare severity diagnosis related group payment amount.
Under this policy for eligible technologies Medicare pays the applicable and Thats DRG payment rate up to an additional 65% of the cost of the approved new technology.
The team is closely monitoring CMS proposed changes to filing requirements. While also determining an optimal filing approach that allows our hospital customers to maximize the <unk> period post approval.
We look forward to providing more details in our investor and analyst day in September with Sascha will discuss in more detail at the end of the call.
We feel there are many opportunities to continue to grow our brand and are committed to supporting CBD families in new and meaningful ways, while expanding our commercial infrastructure in line with our clinical development programs.
I'll now hand, the call over to our Chief Scientific officer, Alex to Matti <unk> to discuss our ongoing development programs.
Thank you Christy and Hello, everyone.
I am pleased to step in for Dr. Joe <unk>, our Chief Medical officer to provide an update on our clinical programs today.
<unk> is currently in China meeting with our strategic partner to further strengthen our R&D collaboration.
He will be participating in a local CVD advisory board attending a TSA investigator meeting and connecting with doctors around the country, who have expertise in CVD TFC in status epilepticus.
Now I'll provide an update on our clinical programs.
As a reminder, the trust GSE trial is 162 patient double blind placebo controlled trial in patients experiencing a minimum of eight countable seizures per month, despite adequate treatment with existing therapies, including recently approved anti seizure medications.
This is a highly refractory pediatric and adult population and we believe the estimated number of patients with refractory seizures to be between 25 and 40000 patients in the U S.
Based on our observations from the Phase II open label trial, where we saw a higher rate of reported Somnolence then our Marigold study, we developed a new titration schedule for this phase III study.
The new titration schedule is designed to slowly increase the dose early on and increase more rapidly towards the end of the four week schedule to successfully titrate GSE patients to target doses.
We believe that slower titration, initially will optimize tolerability and lead to improved efficacy.
The low discontinuation rate observed in the trust TLC studied to date gives us increased confidence that the changes we made to the phase III dose titration are having the desired effect.
We continue to actively enroll patients in the trust TFC trial at sites in the U S Europe and Canada.
Due to administrative and regulatory delays getting certain ex U S sites up and running we now anticipate top line data mid 2024.
The team has been working hard to overcome these country specific delays and we are confident that the vast majority of sites in the trial will be ready to enroll by the summer.
We expect to begin enrolling patients at new clinical sites in Israel in China. This quarter with additional site Activations planned in Italy, Belgium, and Australia by mid year.
With these new initiations, we expect to see increased enrollment across our global sites.
To further support study recruitment and enrollment Meredith has sponsored two educational webinars in the U S and Europe , featuring prominent key opinion leaders.
The first was held in April for U S families and hosted by the <unk> Alliance and the second one will be hosted by the <unk> Association with a European focus and will be recorded later this month as we continue to build and strengthen our relationships with global TLC advocacy groups.
Now I would like to provide an update on our clinical programs in status epilepticus.
Our phase III raise trial studying intravenous or IV <unk> alone in refractory status epilepticus continues to advance.
We have dedicated considerable cross functional resources to prioritize site engagement and scientific education and are confident that it has had a positive impact on enrollment and overall study awareness.
Today, we announced that we are planning to conduct an interim analysis in the second half of the year.
The rave study protocol provides for a pre specified interim analysis to evaluate the co primary endpoints of status epilepticus cessation within 30 minutes and no progression to IV anesthesia for 36 hours when two thirds of the patients or approximately 82 patients have completed the trial.
The interim analysis is more than 90% power to show a 40% treatment effect.
We continue to enroll patients in the res trial that are representative of the phase II patient population, which gives us strong confidence in our robust and clinically meaningful treatment effect that can be observed at the interim analysis.
We expect that successful achievement of the co primary endpoints would serve as the basis for submission of our regulatory filing in the U S.
I would like to review the process of the interim analysis.
Upon completing enrollment of ADT patients with plans to clean and lock the database and an unblinded statistician, who will supervise the running of tables and quality checks to maintain integrity of the data.
These data would then be provided to the data monitoring committee or DMC to evaluate for efficacy and safety.
The DMC will then inform baroness as to whether or not the study met the pre specified efficacy stopping boundaries on the co primary endpoints.
If the study does achieve the pre specified efficacy stopping rules. The Meredith leadership team would then have the opportunity to evaluate the data and share top line results soon after.
If the trial is complete at the interim analysis, we will continue to enroll new patients and a planned open label extension to collect additional safety data, which we believe would be supportive for regulatory filings.
We also continued to progress our other trials in status epilepticus.
Enrolment in our phase III raised two trial in RSC for European registration is anticipated to begin in the second half of 2023.
On a successful interim analysis, we would plan to transition a significant number of our U S. Res sites to the raised two trial in an effort to expedite enrollment.
We also expect to complete enrollment of the first cohort of our phase III reset trial in established status epilepticus before the end of the year.
Finally, we continued to provide IV can ask loan to physicians, who requested for their severe patients in super refractory status epilepticus under an emergency IND mechanism.
To date 16 patients with Super refractory status had been treated with IV <unk> excellent.
Some cases have already been presented at major medical meetings or S case reports in the literature and we anticipate additional cases to be published in the future.
I would now like to turn to our second generation product development efforts.
We have completed our single ascending dose study in healthy volunteers with our new oral formulation.
The new formulation exhibited linear pharmacokinetics at single doses of 100 to 200 milligrams overcoming some of the limitations of the current suspension.
Model data suggests effective trough levels can be obtained with <unk> dosing with this new formulation, enabling <unk> to be studied in additional rare epilepsy patient populations.
Our multiple ascending dose study is expected to initiate enrollment in the third quarter of 2023 with preliminary data by the end of the year.
In parallel we are aiming to finalize the clinical program designed for Lennox <unk> syndrome in the first quarter of 2024 pending results of the Mad study.
Our prodrug development continues to advance and a lead oral candidate has been selected.
We are targeting phase one data in 2024.
On the scientific affairs side of the organization, we continue to generate relevant and compelling data aimed at addressing the needs at the medical and caregiver communities.
We're excited about the data sets, we have plan to share with you all this year.
First we are planning to share the two year data from the CVD Marigold Open label extension study at this year's International Epilepsy Congress in Dublin, and then expanded data at the American Epilepsy Society meeting in Orlando.
In addition, we are planning to present multiple abstracts, including the complete single ascending dose study data from.
Some early real world data on <unk> in the U S as well as new preclinical data of IV can excellent and a severe status epilepticus model.
The Mariner scientific and medical teams will have a considerable presence at this year's neuro critical care Society child, Neurology Society, and the American Epilepsy Society annual meetings as we continue to educate about <unk> and the disease states in which it is being studied in as well as raise Meredith scientific awareness.
Yes.
All in all I am excited about the progress, we're making on our clinical programs and it's shaping up to be a very exciting year with multiple data catalysts along the way.
I would now like to turn the call over to our CFO and COO, Steve Fan Steele, who will provide you with a financial update.
Thanks, Alex and good morning to everyone I.
I am pleased to be able to share our financial results for the first quarter of 2023.
Before going through the details of our financial performance I want to touch on a few key updates for the business.
We are very pleased to have initiated significant startup work related to our API Onshoring initiative.
As you may recall BARDA exercised its option late last year to support this initiative, which included funding of up to $12 3 million.
Importantly, this work is expected to provide a second domestically sourced manufacturing capability for our can axon API and has the potential to drive a greater than 30% reduction in API supply cost, which represents a significant portion of the overall manufacturing costs for <unk> excellent.
We have also been active in our deal making over the past two years partnering with Orion for the European market in Asia, or China, and now biologics from Mena.
We remain active for further expansion with our current focus on Japan.
As we continue to advance <unk> development in ex U S markets, such as Europe , we have the potential to see royalty and milestones contributing to our cash inflows in the near term in addition to ongoing R&D reimbursement.
For the fiscal year 2023, we are maintaining our guidance with you as the Tommy revenues projected to be in the range of 15 million to $17 million.
And BARDA revenues to be in the range of $8 million to $11 million.
We continue to project, our GAAP operating expenses exclusive of SG&A and R&D expenses to be in the range of $165 million to $175 million of which we expect approximately $16 million to be noncash stock based compensation.
We expect that our current cash cash equivalents and short term investments of $199 $2 million will be sufficient to fund our operations into the second half of 2024 inclusive of maintaining the minimum required cash balance of $15 million under our credit agreement.
I'll now move into our financial results.
For the first quarter of 2023, we recognize product revenues of $3 3 million for the three months ended March 31, 2023. These revenues consist of the Tommy product sales, which was launched in the third quarter of 2022.
Separately, we recognize barter revenues of $7 million for the three months ended March 31, 2023, as compared to $1 5 million for the same period in the prior year.
The increase was driven primarily by activity associated with startup of our API Onshoring initiative and increased raise trial activity.
Research and development expenses increased to $27 9 million for the three months ended March 31, 2023, as compared to $18 million for the same period in the prior year.
Change was due to increased costs associated with our API onshoring effort increased TFC in RSV clinical trial activity and increased head count.
As a reminder, the API onshoring effort is approximately 70% funded by BARDA. The increase in R&D expenses was partially offset by the increased barter revenues reflected in the first quarter.
Selling general and administrative expenses increased to $15 2 million for the three months ended March 31, 2023, as compared to $11 7 million for the same period in the prior year.
Interest expense was $4 1 million for the three months ended March 31, 2023, as compared to $1 7 million for the same period in the prior year.
The increase was driven by drawdown of an additional $30 million of credit under the <unk> agreement in March 2022, upon FDA approval for Tommy and noncash interest expense related to a revenue interest financing with regard.
Interest income was $2 3 million for the three months ended March 31, 2023, as compared to less than <unk> 1 million for the same period in the prior year.
Increase in interest income was driven by the overall increase in cash cash equivalents and short term investments and increased yield on those balances.
The company reported a net loss of $34 7 million for the three months ended March 31, 2023, as compared to a net loss of $19 4 million for the same period in the prior year as a note. The 2022 net loss includes the onetime gain of $12 $7 million related to a recognition of a portion of the upfront payment associated with our Orion partnership.
These totals also include noncash stock based compensation expense of $3 7 million for the three months ended March 31, 2023, as compared to $3 4 million for the same period in the prior year.
Cash used in operating activities was $41 5 million for the three months ended March 31, 2023, as compared to cash used in operating expenses of $27 7 million for the same period in the prior year.
Now I'll turn the call back to Scott, who will provide concluding remarks.
Thanks, Steve 2023 is off to a strong start for Marinus and we are thrilled to have a strong balance sheet to support the continued positive momentum of the told me launch the advancement of our two late stage clinical programs and our second generation product development.
We are committed to delivering shareholder value and expanding opportunity to serve patients that may benefit from <unk> and IV <unk>.
I'd like to thank our employees for their hard work and dedication to advancing our mission and our investors for their support.
I'll turn it back to you.
Thanks Scott.
Planning is underway for an investor and analyst event in September , which we will share more details about in the coming months, we look forward to diving into our commercial planning and RSC and providing color around how we're advancing our strategic goal to prepare for a successful launch.
Operator can you now open the call to questions.
Thank you at this time I would like to remind everyone in order to ask a question Press Star then the number one on your telephone keypad.
We will take our first question from Andrew <unk> at Jefferies.
Hi, everyone. Thanks. Good morning, appreciate you taking my questions.
All the progress as well.
So maybe two questions on RSC today.
<unk>.
First question is.
I'm just curious how do you envision.
The interim topline release to look like presumably you'll be quantitative numbers drug versus placebo on the co primary endpoints, but.
Sounds like the DMC may look at safety as well so would you share safety and would you also share some details on the secondary endpoints as well. So the bottom line is just trying to gauge how robust other kind of top line release, we can expect at that another day.
Number two only to the extent you can share can you remind us what you are monitoring on a blinded basis in the phase III, whether its around the baseline characteristics, making sure you are enrolling the right patients or maybe even looking at the actual.
Blinded efficacy outcomes or even overall safety or are you looking at all three but just any color would be helpful. Thank you.
Thanks, Thanks, Andrew Let me, let me take the second question first and then I'll pass.
While we will provide that.
<unk>.
Remember that we have a central.
<unk> reviewer.
Who is looking at patients who are enrolled and I think most importantly that <unk> reviewer is sharing with us the consistency that the patients being enrolled from a baseline characteristics are hitting the appropriate seizure burden.
Be enrolled in the study that's really the only data point.
We have access to really not looking at the overall blinded data sets.
Wei.
Certainly we want to keep the integrity of the study so in our minds, it's really about what that baseline EEG looks like.
Severity of the patients entering the study.
Of course, the other piece of the puzzle that we see regularly are patients who fail screening and so we are still seeing about 50% of patients from first line to second line, who are responding to an anti epileptic interestingly it can be ours.
Sometimes it's eight to 10 hours before a patient is no longer considered.
A candidate for the study so thats a number we expected and I think as we look to the future, particularly with the raised two trial will really be focusing on that window of seizure resolution compared to standard of care today. So.
That's an important measure for us because we want to ensure a low placebo rate and we think those numbers have been very consistent. So thanks for the question. Alex you want to talk a little bit about what will provide to the DMC and most likely what will happen in <unk>.
Top line.
Yes sure. Thanks for the question Andrew as mentioned at our interim we will have pre specified efficacy stopping boundaries in place for our co primary endpoints also included in our foremost statistical testing hierarchy will also include the two key secondary endpoints that look at no progression to IV.
Steve at 72 hours as well as time to status epilepticus cessation.
We would plan to include our key secondary endpoints in our interim top line data release, if that interim does meet the pre specified stopping boundaries.
In regard to the other secondary endpoints, we have those secondary endpoints are all planned to be descriptive really analyzed and that includes a lot of various clinical outcomes functional outcomes are CGI modified Rankin scale as well as very important health care utilization metrics and our plan at this point.
Present, those at upcoming major medical meetings.
And then just quickly yes, absolutely absolutely safety will be included in that as well Thats a critical component to our data release at that time point.
Great. Thank you guys so much very clear.
Thanks, Andrew.
We'll move next to Charles Duncan of Cantor Fitzgerald.
Hey, good morning, Scott and team Thanks for all the update and congrats on the progress.
And a couple of questions ex U S and so wondered if you could provide any additional color.
On the resolution of the objection.
For the starting material the regulatory starting material how was that resolved and.
What's the process there and what gives you confidence in the upcoming positive opinion.
Okay.
Thanks for the question Charles.
Just to remind you and everyone on the call our process for creating can ask loan creating that API was agreed upon with the FDA about three years to four years ago, gosh, even maybe even a little bit longer.
And that is the same process that we suggested to the MAA and interestingly in the last three to five years. We have made this process incrementally better. So as an example, we started making the Maxwell five six years ago. The purity on the API was that 97%.
Now, it's well north of 99, 8%.
And quite honestly, our scientific team.
Now more about about starting materials than I ever care to really walk me through our process.
And.
We were just having a scientific debate with the EMEA I think no.
Rapid tours and we continued to provide the scientific rationale around our starting material the quality that was associated with this very high purity.
We tested for multiple impurities I think most importantly, we really walked back the agency step by step through the process and I think with that we got our rapid tours and the cgmp comfortable with this starting material.
The safety. It was one we always believed then it was one that I was very willing to <unk>.
Escalate if necessary, but at the end of the day, we are a scientific team.
Both the U S and European regulatory bodies are scientific teams and we were able to come to a conclusion that we believed was the right one and now we have support.
It's been multiple regulatory agencies. So in our minds that was the biggest issue. There was a lot of other work we had to do Charles to satisfy the European authorities that we're substantially.
Bigger in scope than the U S and we climb those mountains.
The team at Marin has put in hundreds of hours to get there.
And we're incredibly excited coming opinion, we're enthusiastic about our launch in the near term and.
This means a tremendous amount to families in Europe validation of our platform and the opportunity to really help additional patients.
In the European markets in June thereafter in Mena markets and soon thereafter and Chinese markets.
With can ex loan initially CVD and then and then our expansion. So it's a big milestone it was a very strong and healthy scientific process and I'm.
I'm incredibly proud of our team so thanks for the question.
Congratulations on that process.
Let me ask you about incidence and prevalence ex U S. You mentioned <unk> you mentioned, China, obviously, you I guess I'm wondering how do you see the ex U S versus U S are there any geographic.
Call it drivers to increased incidence or even prevalence.
And then can you provide any other color on the Japanese partnering process are you, having ongoing discussions and could that actually come to fruition yet this year.
So let me take the second part of the question Charles and then ill.
I'll, let Alex answer because it is our expert epidemiologist when it comes to the incidence of <unk> five.
On the Japanese front, our teams really started the engagement process.
Recently, we've seen a lot of interest from several companies.
I can't promise you a deal this year only because we have some big data sets coming up and I could imagine some companies waiting for those datasets that being said there is I think very distinct interest around the orphan part of our disease relative to the hospital side of the disease and certainly we would love to see.
The deal done before year end, that's our corporate goal, but understanding that some.
Sometimes some companies get a little get a little bit nervous in front of the datasets. So we're pushing hard I think we'd see more interested I would have initially expected.
Which is exciting I think the U S revenue trajectory now that European approval, we will be very supportive of.
From a strategic and Japan.
I'm going to push our business development team to get something done over the next few months I'm excited with those prospects.
Alex how about I turn it over to you to talk a little bit on the epidemiology.
Yes, certainly.
We believe that the birth rate or the incidents ex U S is very similar to how we think about it here in the U S, which is approximately 140000 live births I think what is a really important driver to think about is the rate and adoption of genetic testing to identify that patient population and I really think we are at.
Really exciting time in the field of epilepsy genetics and there continues to be increased momentum in the adoption and the realization of the clinical impact of providing a proper aetiological diagnosis. So a lot of the countries in western Europe for sure have been genetically testing their patients for.
Many years and we continue to see that rise and we're continuing to see it grow throughout the global regions.
That's helpful.
Charles.
Now seen the first centers of excellence in several countries throughout Europe . We know there are over 600 patients identified due to see detail the global CDK alliances in China, We know that there are several patients in.
Emirates waiting for the drug.
So we get a lot of inbound calls and nothing that we are seeing from our discussions globally make us believe that the incidence is any different across the globe I think the one kicker for me with Japan will be the birth rate.
And the lower birthrate in Japan, I think we'll have the incremental impact of the size of the Japanese.
Orphan disease market, not necessarily status epilepticus and AG.
<unk> population, but I think on the or.
Orphan side, just from a modeling perspective, I think it is a little bit smaller.
The U S given the birth rates.
So Keith nuance I appreciate the insights on genetic testing makes sense to me thanks for taking the questions.
We will take our next question from Brian Abrahams RBC capital markets.
Hi, there good morning, Thanks for taking my questions and congrats on all the continued progress I just had a few questions on IV can excellent I guess, maybe first off on the mechanics around the interim wondering if you could expand a little bit more on the gating factors and timelines, we should be thinking about for getting to the 82 patients cleaning the data.
And getting to the SMB evaluation.
If this doesn't hit the stopping criteria what would be the implications for the program both the raise trial and the other studies and then lastly, just as a follow up separately wondering if you could speak to any learnings or observations you can take away from those <unk> patients recognizing that they're in a different stage than using a different protocol.
Thanks, Brian Great question again, I'll start backwards, and then I'll turn it over to Alex.
The question started.
I think the Super refractory.
Patient population is increasingly interesting to me I think I've been pretty transparent with investors that it's a very long road for a phase III double blind placebo controlled trial.
That being said, we continue to get request and have incredible outcomes for a patient recently.
Ben we've been the last one the resort they had been transferred to a tertiary care center.
We believe that had they not gotten our drug they would have been discontinued from their ventilator.
And that patient was able to be discontinued from anesthesia.
And left the ICU as a result of IV <unk>. Our team is working on some new suggestions to physicians when they request <unk> on dosing.
Slightly a different dosing regimen than we're using an RSC those regiments.
<unk> filed as we speak so I can't talk much more about it but we would expect by the time of Aes to talk about that a little bit more.
And I think what we're really thinking about is there from all these learnings from <unk> is there an opportunity for us to do.
A single arm study and really help.
That's the field. So I think it's very exciting and we certainly know this is the population that needs help it's just the best way how to attack it from an organizational standpoint.
I actually forgot your middle question, Brian I'm, having a little phone service. So I'm not taking those so Alex why don't you talk a little bit about.
The process of data cleaning and the only thing I'll say is really the key point is when we get to that interim number.
That's when we make the decision of lock and load the dataset and Alex I'll turn it over to you to just talk about those mechanics, a little bit more specifically.
Yes, certainly thanks for the question, Brian I think one part of your question was how do we get to 82 patients that I can just say that there is again a lot of significant momentum in our enrollment in this study and really confident in us getting to that number here soon.
Again, we really dedicated a significant amount of cross functional resources to really make sure that we are engaging actively with our clinical sites and making sure that all the key stakeholders within the hospital system have the right amount of information to help identify.
Potentially eligible raise patient.
Eligible get them enrolled.
And a little bit more about mechanics.
Once we have the 82nd patient and there is a 30 day follow up so.
Four weeks to continue to collect all of the safety data from there we think that we can clean and lock the database and potentially three to five weeks. So call. It seven to 10 or so weeks from 80 <unk> patient in that data set will be shared with the DMC. The outstanding question is how long the DMC will take to fully.
<unk> evaluate and assess that dataset and provide that information to Meredith, whether yes, the pre specified efficacy stopping rules were met or two likely proceed as is.
On that and at that point as mentioned earlier.
The stopping criteria is met then we would look at that for a few days and announce those topline data.
I'll pass it to Scott to answer that last question that you had about if the interim does not have.
Yes. Thanks.
Alex and Brian .
And Sasha for reminding me about that question. So I think Brian there is.
No question that we can still hit statistical significance.
Hit the interim and maybe just to add onto Alex when we began that interim process will continue to enroll patients in a double blind fashion. If the SMB said to continue the study we can do so we think that would take a few additional months to complete the study we still have new sites.
Up and running and we're allowing new sites to come onboard through about the middle of the year. So I expect to be at 70 75 ish sites by the June timeframe, a lot of reasons for that which I can go through but to your question specifically.
We would enroll the study and then and then unblinded data at 124 patients that being said given the fact that this study has a very high probability of hitting interim should it not I think the likelihood that we have a clinically meaningful drug at the end of the study.
Without stopping at the interim is a low probability so I think we generally believe.
We set the bar for the interim and Alex talked about greater than 90% power to show, 40% clinical benefit versus placebo.
We think thats, where the drug needs to come in to have.
Clinical outcomes associated with it so.
We're making a very strong message that this drug is working and we will see a low placebo rate.
We'll have more than sufficient data to file at the interim and I think thats, where our heads at today Brian .
That's really helpful Scott and Alex Thank you guys. So much.
Thanks for the question.
We'll move next to Joseph Tom at TD Cowen.
Hi, there good morning, and thank you for taking my questions.
Thanks for walking through all the different steps here I guess, just in terms of what youre going to be telling the street I guess what is your disclosure strategy, what you say.
182nd patient is enrolled when you say when you are taking the interim or are we kind of just no ones.
The results of the <unk>.
DMC review are available and maybe on RSC as you see it from a CMC and safety database perspective.
How are you thinking about timelines of having everything together, assuming the positive area.
Yes.
Yeah. Thanks, Joe.
I haven't necessarily made a final decision we have the team haven't made a final decision on our communication strategy I think we've tried to be as transparent with you guys as possible and keep you up to date.
As everyone knows.
This is an incidence trial and there are great weeks and there are quite weeks.
And then again it is a complex data set so I just want to make sure that when we communicate.
We not only have hit our number of patients, but we have good confidence that we can clean and lock the database as Alex.
Described so we're going to what we're doing Joe.
Doing our best to clean and monitor the data as it comes through but it's a big process. These are sick patients.
And.
I think I'll feel very confident by the summertime that the timelines that Alex walked people through we can hit those in and look to exceed them, particularly in terms of data cleaning so bear with us give us a few more months, we will get there and we'll finalize our disclosure around exactly.
When we started this process.
Would you mind repeating the second question.
Yes, the second part was just on the.
CMC components and potential safety exposure.
Is that I guess gating to anything or on a positive in a room would you be ready to go.
Yes, no great question. Thank you. So P&C, we're super excited we have filed.
Amended R&D to start using our citrate buffer and yes, we are disclosing that the new buffers that trade today, so but.
So all those science geeks, who want to look up the solubility of citrate buffers.
Other than phosphate buffers.
Hub, we wanted to do something today.
We're expecting that the FDA will basically say.
You are free to use that product in the study we have batches with that ready to go. So we will incorporate that new citrate buffer product into the clinical study within the next few weeks.
We will start <unk>, two 100% with that new buffer, but as a good housekeeping measure as we did with the Tommy we will ask for pre NDA CMC meeting to review the package with the FDA and say look here's what we got do you have any and here's our questions is this sufficient as this.
Efficient with sufficient as an example, with the Tommy.
The SBA 10 questions and they said wed like to see more on two of the 10. So we had six to nine months before the finally to add some additional analytical testing. So we will do the same on the on the CMC side.
Credibly proud of the progress of the CMC team has made.
Made so much progress we've added.
New.
Formulation bottle size for launch and we'll talk about that more in September .
It may be a few months after launch, but it really we think it's going to be really important commercially so from a CMC perspective, I think we are locked in.
And loaded.
And I'm, sorry, Joe UFC, one other piece beyond CMC.
<unk> as well.
Not just the safety database.
Yes, yes, yes, no thats great question Joe.
And sleep over safety I think any drug has to have an efficacy safety balance we know the safety. We've had the SMB. We've had the DSM be reviewing the phase III, we've seen nothing new that we're aware of and nor have been informed by the SMB. We've got a ton of now open label data with 20% higher doses in <unk>.
<unk> refractory patients we've seen nothing.
Unexpected in that population as well, but to make sure that there is not an issue in terms of patient number. We have every intention of keeping our sites open rolling probably half of our sites into open label.
Treatment with <unk> alone again building.
Ability for physicians to use the drug in these very sick patients and of course, we will have additional double blinded data in the in the several weeks from the time, we choose to lock the data unblinded and of course once we unblinded data. We grew every site to either open label or to raise too.
When people ask me a lot more why.
Why would you cut the study at 82, well one we think we can get there without an issue from an efficacy and outcomes standpoint, and two we think we're used to as a really important add onto the franchise and we want to accelerate those timelines as well. So we have a lot of reasons to be enthusiastic about the center room and in the future.
Our expanded patient numbers, so I'm not at all losing sleep from an FDA perspective on safety. Thanks for the question excellent. Thank you.
We'll go next to Douglas Tsao at H C Wainwright.
Hi, good morning, Thanks for taking the questions.
Scott maybe.
First on the second generation product development I think in the release, you said that youre close to advancing.
Yes.
Oral candidate selected I'm, just curious from the you've talked about developing a pro drug IV formulation I'm, just curious what the update or how far along what progress you've made on that front.
Thanks, Doug does Hercules have a question and I'll just.
<unk>.
That's correct.
Yes.
Yes.
Hercules and sitting on it does lap you just enter the picture is awesome.
The beauty of it.
Looking up now.
Thanks.
<unk> does now.
Look we are moving aggressively on the IV side as well.
Do you believe that a formulation with no or significantly less captisol will have a lot of advantages in the pediatric population and <unk>.
Refractory status and of course, if we could substitute the entire franchise, we do have a 3% to 5% royalty stream with light and that was.
Negotiated before our team team to the organization and license with a great partner to date on Captisol is hard work.
We have an IV Kennedy a project selected it looks beautiful in.
In the human.
Selling models the problem right now is we don't have.
We don't see normal metabolism.
<unk> pro drug and any other animal model. So we're scratching our heads of how to use the tox work. When you don't have the appropriate animal model lots of companies run into this.
I've just run into this problem with another company that.
I've seen it several times in my career, we're going to talk to a few consultants to figure out how to advance that compound at the same time, our chemistry team. Our tenants are working on new formulations that effectively look and smell like the one we have now but would also have the same metabolism.
In animal models for us to do the Tox work, but.
We know that the prodrug is 80% 90% of <unk>, we know what that cleaved particle looks like and the safety of that particle.
In my mind, there is that.
Another way, we can overcome this move this a little bit more rapidly into the clinic that being said we've made tremendous progress in the two years that we've been working on this behind the scenes.
I'm hopeful we're going to have.
Our lead candidate chosen by year end and then it's about 18 months from lead candidate to IND, but once we get the R&D Doug.
Similarly to the oral formulation program, we know what blood levels, we need to hit and we would expect the pro drug behave very similarly to our cap ex.
Excellent excellent.
So thanks, Brian Great question.
Can I ask one follow up I think on RSC, you mentioned that Youll continue enrolling.
Even after you sort of move ahead with the interim analysis. If you ultimately do readout that studying you've enrolled patients can you switch those patients into raised two or do you just sort of continue to follow them as part of the raise one dataset.
Yeah, Great question, So, let's just say day X we.
We internally decide to.
Hit our 82 patients were going to clean that database.
That 82 patients that were going to be the basis of our filing and what we expect to be in RPI, but again to Alex's point it'll take eight to 10 weeks from the time, we choose to on blind.
Two two to data and so in that 10 weeks will still continue to enroll.
Double blinded fashion.
And to an earlier question in case, we don't hit at the interim then we would just continue to enroll to finish the study.
On the news in the DSM be that we should stop the study because there is a clear efficacy signal.
Would then stop all enrollment no longer enrolled double blind and either enroll those sites into a single arm open label can excellent news or into rates too and I guess today it'll be 30, 30, plus sites that go into each.
<unk>.
Each study.
But we wouldn't.
Those additional patients, let's say 10 or 15 that are enrolled in this.
In this window what were waiting for data would just be part of the safety data set for res, we wouldn't expect it as part of the pie, but we would submitted to the FDA as part of the safety we've been having a lot of discussions about this and I think that is the most likely outcome in the way the agency typically handles.
These additional datasets we've had some discussions like when you look at oncology studies, you can unblinded PFS outcome.
Outcomes and survival later on but I think for the purposes of being conservative we're going to assume that the 82 patients are going to be the basis of the label with additional safety data in those 10 or 15 patients who are in that unique double blind portion, while we're unlocking that that makes it clear.
Yes, that's very clear thank you so much.
Sure we've had a lot of internal discussions about this now so it's kept us pretty busy.
Thanks, Doug.
We will go next to Brian <unk> at Baird.
Hey, good afternoon, guys. Thanks for taking my question I guess two quick ones from me it sounds like there could be a few months between enrolling 80 documentation on a response from the GMP during which patients are still going to be enrolling in a double blind fashion I guess, given where enrollment is right now if you stop at the interim how many patients do you actually estimate well have random.
<unk> data for the submission of if it takes three months for DMC to get back to you do you think you could almost half of that study fully enrolled at that point.
And then Tim.
Hi, Brian .
Brian I just wanted to be clear we only.
We don't know it from the time, we give that data to the DMC how quickly they will turn it we don't think it will be three months for them to churn. It it could be a few days it could be one or two weeks, but what.
But let's.
Let's say entire 10 to 12 week process include us following a patient to 30 days cleaning. The database then giving the data to the DMC. So I'm estimating now we are estimating one to two weeks of the DS the DMV.
<unk>.
Come back to us to say you should stop the study I just wanted to be clear on that point, sorry, yes, sorry, I misspoke I meant if it was like.
Three months from the ADC from patient enrolled to why maybe.
<unk> jumps back to you.
Yeah.
Do you think that.
Could you give us like an estimate in terms of how many patients you think will actually you'll actually wind up having randomized data from.
Oh, I think look I think.
Is it a three months process, then I think it'll be.
Roughly 15 additional patients as part of as many as one potential patients.
From the from so.
Generally.
We think will be and we've said this we've talked about this probably leave that generally we've been enrolling $4 to five patients a month and we're still expecting acceleration as we open these new sites.
No.
It's three months at those type of enrollment numbers it'll be roughly <unk> 15.
Many of these 20 patients or more.
Great. Thanks, and then on the reformulated that then Exelon profile holds up on this I'm sorry, I know Youre next day, just focused on one access so but I'm wondering have you explored if there's value to kind of.
Looking into <unk> with this formulation and what sort of regulatory requirements you might need.
I wanted to kind of reference.
Labels on the current formulation for reformulation.
Yeah, No. It's a great question and we met as <unk>.
Strategic team about two weeks ago in Miami and this was that the.
Key topic.
I think right now, where we where we believe we will fallout from a regulatory standpoint is for the second generation product. We will reference the current forms the <unk>. We do believe as of today that that will allow us to do a single pivotal study for approval.
Our working hypothesis today of course that one.
<unk> study, we will go to the FDA and propose a phase III strategy.
I'm comfortable saying that we would see as a single study strategy with an expanded database given that the 912.
<unk> hundred <unk> IV formulations today have higher AUC use than our existing formulations. So we'd want to have additional safety data.
Thought long and hard about what's the right strategy with CBD Ntsc, we haven't come to <unk>.
Firm conclusions yet.
Those programs, but we do think if there is the potential to show stronger efficacy in those populations as well, it's logical to think about either studies switch studies or or efficacy studies in those populations.
No.
So nothing is off the table at this point in time, I would I think I've spoken to lots of investors and publicly that we'd love to have a strategic involved here I mean my view of this is that we can accelerate this second generation program into multiple indications we have an incredible.
Opportunity.
Second Gen product with a much broader deeper message for the rare refractory populations and we know that there are lots of them out there that are that are hungry for a drug where we're getting requests every day.
Several requests for Tommy for these refractory patients.
So we know they're out there and we think right now we're spending more energy and time than anyone else in the space. So.
To your question, we think there is a real opportunity to expand this program. We recognize we can only do so many things so to say.
They tuned and im looking forward to sharing that.
With you were little disappointed about the <unk>.
Slowdown, but I think we totally understand that.
We want this program to run smoothly from here. So thanks for the question.
Thank you.
For the sake of time, please limit yourself to one question to allow everyone an opportunity to ask a question.
We will go next to Jim Lee at Trust Securities.
Hey, and congrats on the quarter and thanks for taking my questions I apologize. If this was asked but if the study does not stop at interim and goes to full enrollment what's the timing of top line data.
For patients.
And is there any reason why I've included securities. Thank you.
Yes to I think kind of the two.
Earlier folks June .
Obviously it depends on the monthly enrollment curves I would expect by the time, we're ready to unbind. The study we're enrolling seven to eight patients per month, so roughly three to four month window from interim to full dataset.
Yeah.
From the time, we elect to do the interim to the full dataset. So the full data set should be done at least the last patient should be enrolled.
Would expect soon after that.
The DMC would come back to us.
Got it thank you.
We'll move next to Marc Goodman at STB Securities.
Good morning first question is.
The off label usage at all their 100 patients who said were on drug are they all CDK O five I'm just curious on that first.
Yes.
Okay.
Chris do you want to take it in humans would it be like.
Yes.
I mean, we've had Chris you're on the line there's been no commercial question, but the <unk> work.
Thanks, Scott, Yeah, I'm happy to take it.
As of Q1, we've seen greater than 100 patients on commercial therapy with the majority of them getting reimbursed we had about a 90% reimbursement rate right now and I will say that we have only had.
Handful of non CDB indicated patients today.
The majority of them would be for either Ges.
For example, <unk> again very minimal at this point.
The majority of our patients have a CDK diagnosis.
And since the drug is approved or are we seeing an increase in the actual number of patients out there with CDK five I'm just curious.
All of a sudden now there's more testing and we're finding more patients since you've mentioned it a year ago.
Yes, there is some great trends.
And diagnosis and identification today.
And at this point, we're still really cornered on that one in 40000 patients in the 2000 pediatric patients that we have in our funnel.
But to that point earlier here on the launch there are.
Really wonderful efforts.
Surrounding genetic testing it was probably the number one topic at Aes last year in December we had internal.
Progress made just to continue to identify potential patients that do have other syndromic diagnosis. So we still feel very confident in the numbers that we've communicated but we continue to uncover patients every single day.
And then maybe just quickly one when detail on raise can you just clarify around the IV anesthesia protocol are you, allowing IV anesthesia use if it was for intubation or are you, allowing it if it was attempted to be used as an anti seizure medications, even the phase two like half the patients enter the trial Intubated and most of them received IV and <unk>.
<unk> for intubation.
Alex you want to take that view I mean ticket.
Yes, sure I can take that.
The inclusion criterion and amendment III is any any exposure for IV anesthesia for less than 18 hours.
That at that time point. These are still patients that are not in super refractory status epilepticus. It's critical that these patients are not in super refractory status.
With that all said those two they also have to meet the eligibility criterion of the seizure burden prior to study drug administration. So as IV anesthesia is weaned again less than 18 hours of exposure. They still have to meet the electrographic status epilepticus definition of at least 20% seizure burden. So we.
We feel that these patients despite any exposure prior to that if theres still meeting that electrographic eligibility criteria and we think that they are eligible patients for good excellent and potentially could respond to.
Excellent that was administered.
Thanks.
And Mark I would add I think that's very real world by smaller community Hospital has a patron and status they give anesthesia. They incubate they transfer to a bigger center.
Those bigger centers and we had this two weeks ago patient didn't get enrolled but the center.
Basically you've got a patient and transfer lowered the anesthesia and patient had.
Status and that would be perfect for the trial and for the use of our drug in this case the patient had a contra indications so.
It was an eligible or another drug but.
But.
I think very real world that those are patients, we really want to capture and we used an 18 hour cut off because the literature really defined super refractory status is 24 or more but we certainly believe that there is a meaningful role for the drug in the acute setting.
I think it would work quite well after 24 hours, yes, it's probably as well, but we wanted to be safe, particularly for the purposes of this trial and not enroll patients that were effectively notes.
Super refractory nature, not responding to anesthetics.
So yes.
Yeah.
I think it's going to helps US study a lot I think it's very helpful for the real world.
Commercial opportunities.
We will take our next question from Jay Olson Oppenheimer.
Hey, Congrats on all the progress and thank you for taking the question can you talk about the expected product lifecycle for the town the in the U S based on the new patent and any other patents you have pending and then also the timeline for getting in and tap filed and approved and how long would the.
And tap fee in place if it's approved or has that require an annual renewal. Thank you.
Chris you want to start with the <unk> and then I'll talk about the patents for the Tommy.
I'd be happy to.
Much of what we're doing right now is really discussing on maximizing the benefit for our health care providers and for the system quite frankly, when we do file for an untapped.
Timing is very specific on how to maximize that current the Ips has proposed a change to the Fi.
Billings for the untapped that change will be and if yes.
If it goes forward that will go in August of this year that decision.
And it changes that just by a few months of when you would have to have to do so again, we've got quite a few scenarios in line right now again to maximize that benefit because when you do have a positive opinion through the untapped filing process you do have that for three years and if you don't have an approved product.
And to the time that the end cap is active so.
We will be looking at this are patient numbers iron enrolment trends to date, when we'll be filing so that we can file at the exact amount of time that we would need to maximize the benefit.
We'll move next to Michael Higgins at Ladenburg I'm, sorry, no.
Didn't answered the question operator on the patent sorry about that so quick reminder, on the IV side and we now have we have one method of use patent granted another one that has been that we expect to be.
Issued.
Well first is granted and issued the second is granted and pending issuance around the dosing paradigm and the resolution of status epilepticus with this high dosing for eight to 12 hours. So we feel great about those method of use on the oral side.
Of course, we have now a method of use patents that we then license from Amit for CVD that go to 38, we now have this new TLC patent method used that goes to 40, we also.
And we're really excited about the PSC, the new PSC patents and we have some additional patents pending around CBD around our new dosing titration schedule.
So we feel very confident about the growing method of use patents for the franchise in many of the unexpected findings that we've learned in the last three years that said, what I'm really excited about as well with our second generation programs is that that will bring seven years of orphan drug.
Particularly if we follow that path in the lgs and so in my mind that just another alternative strategy to really.
Guarantee that our oral franchise has strong IP and market exclusivity for many years to come so I really couldnt be happier with how much progress we've made and the comfort that we have in and extending the IV and the oral franchise and of course, if we're successful with pro drugs.
It would add even different levels of protection to the franchise. So we're feeling pretty good about the longevity of the franchise all around today and again.
Many of you know I said on the other side of this and set more tons than I ever carriage you on patent cases.
And we feel quite strongly that specific method of use patents are.
Strong as strong as we can build our franchise and all of them are scientifically driven so that's what gets me excited so thanks for the question and Michael will take your question. It's got to be our last question, we've run over quite long in books.
Get back to their day jobs.
Yes, I appreciate it thanks, Scott one as we look ahead the data back half of this year or into next year on Andres.
If you have.
In agreement with the agency to perspective, we look at the patients.
Patients in the outcome based on things like severity of neurological deficits seizure burden and other ways.
Or is this just everyone that's coming in.
For example, if you really hit on seizure burden in the 50%, but you completely missed somehow in 20% or vice versa can you still advanced the program or do you have to hit again on the overall thanks.
Yes.
Agreement with the agency is that we have to date each co primary endpoint at 1.15.
We feel extremely confident on.
On both but specifically when you think about the first primary be resolution within 30 minutes. Our phase two data we saw that in every patient by clinical bedside.
14 out of 15 by independent EEG reading and as a reminder, the independent EEG reader is not how the primary is defined as defined by the clinical bedside read the second endpoint again aboard its general anesthesia, we were at 100% in phase two we're giving incrementally a little bit more drug in phase III.
We bump from 713 to $8 30, so we have 12 hours of high dosing. So we feel very good about these very sick patients avoiding general anesthesia with the use of our drug not going to be perfect, but we would expect efficacy in the 70% to 80% range and we feel very confident about our placebo rate in this study.
For the first primary being close to zero in the second co primary be no higher than 20 or 25%. So we expect the delta in both of these co primaries to be north of 40% I think that's that's our expectation with 50 or 60% on the second co primary.
And I think our expectation on the personal primaries that were at least 50%. So that's our expectation going in we don't hit that we certainly will look at the data and understand what we have and whether or not there's a path forward of course, we don't hit that interim will go to the.
We'll finish the study and its entirety and have a larger data set to review, but that's the way we're thinking about it right now Michael so thanks for the question.
And operator I just wanted to say thanks to everyone for staying on the call I apologize that we went 20 minutes over but we did want to answer your question I'm, sorry, we didn't put Steve to work on this call he really.
Such a great job helping us.
And our balance sheet I'm glad those are not issues that we added tackle today and appreciate all your time and support and we look forward to catching applies.
In the future. So thanks, thanks for dialing in.
And that does conclude today's conference call. Thank you for your participation you may now disconnect.
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