Q1 2021 Marinus Pharmaceuticals Inc Earnings Call

[music].

Greetings and welcome to the Meredith Pharmaceuticals, first quarter 2021 business update call.

At this time, all participants already listen only mode.

A brief question and answer session will follow the former price presentation.

Sasha Damouni Ellis: There will be a question, star one on your Now, my pleasure, host, Sasha. President Investor.

There will be a question and answer session.

To ask a question during the session you will need to press star one on your telephone.

As a reminder, this conference is being recorded.

And it is now my pleasure to introduce your host Sasha the Mooney.

This president Investor Relations and corporate Communications, you may begin Mr. Moody.

Thank you with me from Meredith are Dr. Scott Braunstein, Chief Executive Officer, Dr. Joe Houlihan, Chief Medical Officer, Christy Schaefer, Chief Commercial Officer, Steve Fan still Chief Financial Officer, and Kimberly Mccormack Vice.

Unknown Executive: Thank you. With me from Marinus are Dr. Scott Bronsstein, Chief Executive Officer, Dr. Joe Hulahan, Chief Medical Officer, Christy Schaefer, Chief Commercial Officer, Steve Fansfield, Chief Financial Officer, and Kimberly McCormick, Vice President of Regulatory Affairs. Before we begin, I would like to remind everyone that some of the statements made 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.

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Before we begin I would like to remind everyone that some of the statements made 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.

Unknown Executive: 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 Forms 10K, 10Q, and 8K. I will now turn the call over to Scott. Thank you, Sasha, and welcome to our first quarter 2021 Business and Financial Update. This year is off to a tremendous start.

These risks and uncertainties and risks associated with our business are.

Are described in the Companys reports filed with the Securities and Exchange Commission, including forms 10-K, 10-Q and 8-K.

I will now turn the call over to Scott.

Thank you Sasha and welcome to our first quarter 'twenty, 'twenty, one business and financial update.

This year is off to a tremendous start we've continued to make progress across our oral and IV clinical programs have intensified preparations for commercial launch deepened discussions with potential European partners have made exciting headway on our next generation formulation research and have strength.

Scott Braunstein: We've continued to make progress across our oral and IV clinical programs, have intensified preparations for commercial launch, deepened discussions with potential European partners, have made exciting headway in our next generation formulation research, and have strengthened our management team, scientific advisory board, and board of directors. To support this continued progress, today we announced a $125 million credit financing that is being funded by Oaktree Capital Management, a global asset management firm specializing in alternative investment strategies.

And our management team scientific Advisory Board and board of directors.

To support this continued progress today, we announced a $125 million credit financing that is being funded by Oaktree capital management, a global asset management firm specializing in alternative investment strategies. This financing provides us with access to additional capital to support our research.

Scott Braunstein: This financing provides us with access to additional capital to support our research programs and commercialization efforts, as well as extending our cash runway through the end of 2022. The completion of this agreement assists in our ability to monetize the rare pediatric disease priority review voucher we anticipate would be granted with this potential approval of Ganaxelon next year. We believe the financing exemplifies Oak Tree's confidence in our NDA submission and our company's ability to deliver on upcoming clinical milestones while providing capital to support our ongoing and future research and development programs, as well as preparing for our first potential commercial launch.

Grams, and commercialization efforts as well as extending our cash runway through the end of 'twenty to 'twenty two.

The completion of disagreement assist in our ability to monetize the rare pediatric disease priority review voucher, we anticipate would be granted with the potential approval of <unk> next year, we believe the financing exemplifies oak trees competence in our NDA submission, our company's ability to deliver on.

On upcoming clinical milestones, while providing capital to support our ongoing and future research and development programs as well as preparing for our first potential commercial launch.

Scott Braunstein: The NDA for the use of Ganaxalone and CDKL5 deficiency disorder, or CDD, is on track for submission by the middle of this year. This is the first step in developing a sustainable oral franchise to address the meaningful opportunities that we anticipate over the long term.

The NDA for the use of <unk> alone in TDK L. Five deficiency disorder or C. D. D is on track for submission by the Middle of this year. This is the first step in developing a sustainable world franchise to address the meaningful opportunities that we envision over the long term.

Scott Braunstein: As a reminder, the sufficiency of the Marigold data set to support approval will be determined during the FDA review process. The Marigal study showed strong efficacy and a favorable safety profile, and the open-label data from that study continues to display durability that has been noted since Ganaxelone's early preclinical study. Let me give you a quick update on Europe.

As a reminder, the sufficiency of the Marigold dataset to support approval will be determined during the FDA review process. The Marigold study showed strong efficacy and a favorable safety profile and the open label data from that study continues to display durability that it's been noted since can excellence early preclinical studies.

Let me give you a quick update on Europe. The company has had encouraging interactions with the European medicines agency surrounding our planned Oregon ex loan you submission and we remain on track to submit a pre marketing authorization application by the end of the third quarter.

Scott Braunstein: The company has had encouraging interactions with the European Medicines Agency surrounding our planned Orelganax-Salone EU submission, and we remain on track to submit a pre-marketing authorization application by the end of the third quarter. We continue to have constructive discussions with potential European commercial partners and hope to have a partner selected over the coming weeks to month. We would expect oral Gennaxalone, if approved, to be commercially available in Europe beginning in the middle of next year.

We continue to have constructive discussions with potential European commercial partners and hope to have a partner selected over the coming weeks to months, we would expect Oregon ex alone if approved could be commercially available in Europe, beginning in the middle of next year.

Scott Braunstein: We have been intensifying our commercial planning efforts in front of a potential mid-year 2022 CDD launch in the U.S. This is the first call where you will hear prepared remarks from our chief commercial officer, Christy Schaefer.

We have been intensifying our commercial planning efforts in front of potential mid year 'twenty 'twenty two C. D. D launch in the U S. This is the first call that you will hear prepared remarks from our Chief commercial officer, Christy Shafer, Christy had been building a fantastic team built with experts in both the orphan disease space as well.

Scott Braunstein: Christy has been building a fantastic team filled with experts in both the orphan disease space as well as the hospital arena. Our medical science liaisons are working diligently to prepare for their educational efforts with the clinical community. Our message will focus on the mechanism of action of Ganaxalone and its modulation of the extrassnaptic gaboreceptor and the unique characteristics and results of that binding.

The hospital Arena, our medical Science liaisons are working diligently to prepare for their educational efforts with the clinical community.

Our message will focus on the mechanism of action of <unk> alone and its modulation of the extra synaptic Gaba receptor and the unique characteristics and result of that binding.

Scott Braunstein: We believe that Ganax Saloon will have a differentiated profile based on efficacy, safety, and durability. More to come on our commercial plans from Christi. Now, let me move to our TSC program.

We believe that can exelon will have a differentiated profile based on efficacy safety and durability.

More to come on our commercial plans from Christie.

Let me move toward PSC program, we expect to share top line data from the 23 patient phase two study with the investment community around the middle of the third quarter.

Scott Braunstein: We expect to share top-line data from the 23-patient Phase 2 study with the investment community around the middle of the third quarter. We have completed the study design for our planned phase three trial of Ganaxelone in tuberoschlorosis complex, or TSC, and an end of phase two meeting with the FDA, based on an interim data analysis, is expected early in the third quarter. As a result, we are planning for site initiations to begin for the phase three trial in the latter portion of the summer, while the first patient enrolled is anticipated in the fourth quarter of 2021.

We have completed the study design for our planned phase III trial of <unk> alone in tuberous sclerosis complex or T. S. C ended end of phase two meeting with the FDA based on an interim data analysis is expected early in the third quarter.

As a result, we are planning for site initiations to begin for the phase three trial in the latter portion of the summer while the first patient enrolled is anticipated in the fourth quarter of 2021.

Scott Braunstein: We are targeting completion of site selection by the end of Q3, and we expect to share our timelines for the Phase 3 study by the end of September. We also plan to meet with EMA early in the fourth quarter to obtain scientific advice on the Phase 3 trial and clinical development program. We plan to submit an orphan drug designation request for the use of Ganaxelone in TSC in both the U.S. and EU later this year. We believe that Axlone has the potential to play a critical role in the chronic treatment of refractory epilepsy.

We are targeting completion of site selection by the end of Q3, and we expect to share our timelines for the phase III study by the end of September.

We also plan to meet with E N. A early in the fourth quarter to obtain scientific advice on the phase three trial and clinical development program. We plan to submit an orphan drug designation request for the use of <unk> alone in T. S E. In both the U S and EU later this year.

We believe an excellent has the potential to play a critical role in the chronic treatment of refractory epilepsies to further support our expanded clinical efforts, we announced today that we have strengthened our scientific advisory board with the appointment of several leading experts in clinical neurology and pediatric seizure disorders.

Scott Braunstein: To further support our expanded clinical efforts, we announced today that we have strengthened our scientific advisory board with the appointment of several leading experts in clinical neurology and pediatric seizure disorders. Joining our SAB are new members, Dr. Elizabeth Teal from Massachusetts General Hospital and a professor of neurology at Harvard Medical School, Dr. Ilana Pisana Knight, pediatric epileptologist in the pediatric epilepsy section at the Cleveland Clinic, and Dr. Nicholas Specio, head of the epilepsy unit in the Department of Neuroscience at Bambeno Jesu Children's Hospital in Rome, Italy. I'd like to ship gears and move to the IV program.

<unk> S a b or new members, Dr. Elizabeth Teal from Massachusetts General Hospital, and a professor of Neurology at Harvard Medical School Doctor a lineup to stay on a night pediatric epilepsy apologists in the pediatric epilepsy section at the Cleveland Clinic and Dr. Nicholas Becchio head of the epilepsy unit and the <unk>.

Apartment of Neuroscience F N B, New Jersey Children's Hospital room, Italy.

I'd like to shift gears and move to the IV program, our phase III clinical trial of IV, you can ask alone for the treatment of refractory status epilepticus or RSC. The raise trial continues to advance I know that many of you have been tracking both the rate of new COVID-19 infections and hospitalizations in the U S and we.

Scott Braunstein: Our Phase 3 clinical trial of Ivy Ganaxalone for the treatment of refractory status epilepticus, or RSEE, the Rays trial, continues to advance. I know that many of you have been tracking both the rate of new COVID infections and hospitalizations in the U.S., and we are thankful that the numbers continue to significantly move in the right direction. COVID hospitalizations are below 40,000 U.S. patients for the first time in almost a year and are showing continued progress, which is encouraging news.

Were thankful that the numbers continued to significantly move in the right direction.

COVID-19 hospitalizations are below 40000 U S patients for the first time in almost a year and showing continued progress which is encouraging news.

Scott Braunstein: Despite these challenging hospitalization numbers, interest in the study over the past several months has continued to be robust. Our clinical operations team has done a tremendous job opening sites in major academic centers in the middle of this pandemic. We continue to open sites and evaluate enrollment accordingly.

Despite these challenging hospitalization numbers interest in this study over the past several months has continued to be robust.

Our clinical operations team has done a tremendous job to open sites in major academic centers in the middle of this pandemic.

We continue to open sites and evaluate enrollment accordingly, we are happy to report that currently total patient per site numbers are tracking in line with our expectations. Thanks to the diligent interactions from our clinical development team, including Dr. Henry the cabbage and Doctor module gas your it is still earn.

Scott Braunstein: We are happy to report that, currently, total patient per site numbers are tracking in line with our expectations, thanks to the diligent interactions from our clinical development team, including Dr. Henry de Cabbage and Dr. Maggi Gassior. However, it is still early in the study. However, at this time, we are reiterating top-line data readout for the Rays trial in the first half of 2022, despite the persistent COVID headwinds that have affected site activations for the past six months. More than half the trial sites are expected to be opened by the end of the second quarter, with the vast majority open by the third quarter.

Early in the study however at this time, we are reiterating topline data readout for the res trial in the first half of 'twenty 'twenty two despite the persistent COVID-19 headwinds that have affected site activations for the past six months.

More than half the trial sites are expected to be open by the end of the second quarter with the vast majority open by the third quarter.

Scott Braunstein: Planning also continues for a separate European RSC trial recently named the Race 2 trial to begin in the first half of 2022. A meeting was recently held with the EMA where we engaged in a very constructive dialogue that Joe will describe in further detail. Our European strategic discussions encompass both the oral and IV franchises, and we believe a partner would bolster our ability to execute on a second appropriately powered IV registration trial.

Planning also continues for a separate European RSC trial recently named the raised two trial to begin in the first half of 'twenty 'twenty. Two a meeting was recently held with the E. M E where we engaged in a very constructive dialogue and that Joe will describe in further detail our European.

In strategic discussions encompass both the oral and IV franchises and we believe a partner would bolster our ability to execute on our second appropriately powered IV Registrational trial.

Scott Braunstein: Our hope is that we will have a partner in place to help fortify our execution efforts, specifically around site selection and medical education. We currently believe that the raised trial would not only serve as a pivotal registrational trial for European approval but has the potential to have important clinical implications for the global market. More to come from Joe.

Our hope is that we will have a partner in place to help fortify our execution efforts specifically around site selection and medical education. We currently believe that the <unk> two trial would not only serve as a pivotal registrational trial for European approval.

But has the potential to have an important clinical implications for the global market.

More to come from Joe.

Scott Braunstein: As we continue to build the team and strengthen the organization, this will be the first business update conference call for our newly appointed CFO, Steve Fansdial. Steve has been a major contributor in the completion of the credit financing, and his amazing effort and strong leadership skills could not have come at a better time for the organization. Steve has only been with us for a few weeks, but the entire leadership team is thrilled with his ability to jump right in and contribute in a meaningful way.

As we continue to build the team and strengthened the organization. This will be the first business update conference call for our newly appointed CFO Defense deal Steve has been a major contributor in the completion of the credit financing and ease the amazing effort and strong leadership skills could not have come at a better time for the organization.

Steve has only been with US a few weeks, but the entire leadership team is thrilled with his ability to jump right in and contribute in a meaningful way.

Scott Braunstein: Finally, we are pleased to welcome Dr. Sarah Noctcher to our board of directors. Sarah brings tremendous experience and success in managing global regulatory and drug development and has been involved in the approval of several novel drugs for rare diseases. Sarah is currently serving as Al-Nanilum Pharmaceutical's Chief Diversity, Equity, and Inclusion Officer. We plan on tapping into her expertise as we continue to build our corporate culture and drive to achieve our core values at Marinus, commitment, innovation, and community. I would now like to turn the call over to Christy Schaefer. Christy joined us as our first chief commercial officer six months ago.

Finally, we are pleased to welcome Dr. Sarah knocked her to our board of directors Tara brings tremendous experience and success in managing global regulatory in drug development and has been involved in the approval of several novel drugs for rare diseases.

Sarah is currently serving as Alan Island Pharmaceuticals, Chief diversity equity and inclusion officer, we plan on tapping into her expertise as we continue to build our corporate culture and drive to achieve our core values at Marinus commitment innovation and community I.

I would now like to turn the call over to Kristy Shafer, Christy joined US as our first chief commercial officer or six months ago I am pleased to have or provide more on her early thoughts as we plan for our first potential commercial launch.

Christy Shafer: I am pleased to have her provide more on her early thoughts as we plan for our first potential commercial law. Thanks Scott, and thank you everyone for joining our call today. As Scott mentioned, we are fully engaged in developing our commercial launch strategy and plan. The commercial team continues to broaden its capabilities by solidifying the internal and external strategic plan. During Q1, Marin finalized the senior leadership construct by welcoming its market access, sales, and marketing, operations, and commercial supply chain leaders, who are, in turn, developing the operational and tactical plan.

Thanks, Scott and thank you everyone for joining our call today.

As Scott mentioned, we are fully engaged in developing our commercial launch strategy and plan.

Our commercial team continues to broaden its capabilities by solidifying the internal and external strategic plan.

During Q1, Marinus finalized as senior leadership construct by welcoming its market access sales.

In marketing.

The ration and commercial supply chain leaders, who are in charge of developing the operational and tactical plans.

Christy Shafer: Our most recent addition to the team is Lisa Leggian as Vice President of Sales, who joins us from Alexion. We will continue to grow the commercial team commensurate with planning for a mid-2020 NDA submission for Ganaxelone in the treatment of epileptic seizures associated with CDKL-5 deficiency disorder and a mid-year 2022 launch, if approved. Our strategy is consistent with basic principles of orphan disease launches. First, we plan to keep the organization lean with 16 to 20 account managers and four payer representatives, one specializing in Medicaid.

Our most recent addition to the team as Lisa let Joanne as Vice President of sales, who joined us from Alexia on.

We will continue to grow the commercial team commensurate with planning for a mid 2021 NDA submission of excellent on in the treatment of epileptic seizures associated with P. D K outside deficiency disorder, and a mid year 'twenty 'twenty two launch if approved.

Our strategy is consistent with basic principles of orphan disease launches.

First we plan to keep the organization lean with 16 for 'twenty account managers and for payer representing day, one specializing on Medicaid.

Christy Shafer: Our sales and marketing efforts will be focused on top treaters and high influencers, as most of the commercial opportunity is concentrated in a limited number of facilities. We have completed several core pieces of market research that have informed the assumptions and conclusions underlying our go-to-market strategy. We have now finalized several key critical elements in our process, such as the patient journey, account segmentation, deployment strategy, and market size and structure. This work has given us the foundation upon which to build our branding, messaging, print, and digital platforms.

Our sales and marketing efforts will be focused on top treaters and high Influencers as most of the commercial opportunity is concentrated in a limited number of facilities.

We have completed several core pieces of market research that have informed to the assumptions and conclusions underlying our go to market strategy.

We have now finalized several key critical elements in our process such as the patient journey.

Segmentation deployment strategy and market size and structure.

This work has given us the foundation upon which to build our branding messaging print and digital platforms.

Christy Shafer: We are in the final stages of selecting our external marketing agency, an important decision to be made collaboratively amongst the Marinus cross-functional team with an emphasis on a cohesive and targeted messaging platform design that will prioritize the unmet needs of our CDD patient population. From a pricing perspective, we want to ensure that our value proposition is reflected.

We are on the final stages of selecting our external marketing agency and important decision can be made collaboratively.

Net cross functional team with an emphasis on a cohesive and targeted messaging platform design that will prioritize the unmet needs of our C. D D patient population.

From a pricing perspective, we want to ensure our value proposition is reflected.

Scott Braunstein: As part of those efforts, we are conducting health economics and outcomes research to bolster our value proposition. This includes managing the reimbursement and payer landscape to ensure timely access and ensuring we can mitigate any potential complicating restrictions. Additionally, we continue to monitor the competitive landscape and engage market access experts across the U.S. and Europe. We are confident that these efforts will deliver true value for our patients living with CDD, their families, and for the physicians that treat them. I'd like to turn the call back to Scott now. Thank you, Christy.

As part of those efforts, we are generating health economics and outcomes research to bolster our value proposition.

This includes managing the reimbursement and payer landscape to ensure timely access and ensuring we can mitigate any potential complicating restriction.

Additionally, we continue to monitor the competitive landscape and engage market access experts across the U S and Europe.

We are confident that these efforts will characterize true value for our patients living with C. D D. Their families and for the physicians that treat them.

I'd like to turn the call now back to Scott.

Thank you Christie two additional comments from me before I turn the call over to Joe.

Scott Braunstein: Two additional comments from me before I turn the call over to Judge. Joe will walk you through the updates to the CDD data, and Kim will discuss our regulatory activities, but I am confident that we have been diligent with our preparations for the NDA and in our interactions to date with the U.S. and EU regulatory authorities. Timing is on track for both our FDA and EU submissions, which are our top priority. The final data analysis does not affect the statistical and clinical conclusions of the study, as reflected in our May 2021 corporate death.

Joe will walk you through the updates to the C. D D data and Kim will discuss our regulatory activities, but I am confident that we have been diligent with our preparations of the N D E and in our interactions to date with the U S and EU regulatory authorities timing is on track for both our F D. A.

You submissions, which are top priority. The final data analysis does not affect the statistical and clinical conclusions of this study as reflected in our May 2021 corporate deck.

Scott Braunstein: Finally, we continue to progress our oral reformulation and pro-drug endeavors and evaluate other opportunities for Ganaxalone in additional refractory epilepsy indications. We still expect to move at least one of these formulations into the clinic in the first half of 2022. As we announced this afternoon, we are planning on initiating a phase two trial in Lenox Gasto Syndrome, or LGS, in the middle of 2022, and if all goes as planned, with a potential new formulation.

Finally, we continue to progress our oral reformulation and pro drug endeavors, and evaluate other opportunities for <unk> alone in additional refractory epilepsy indications, we still expect to move at least one of these formulations into the clinic in the first half of 'twenty 'twenty two.

As we announced this afternoon, we are planning on initiating a phase two trial and the Linux gusto syndrome or lgs in the middle of 'twenty 'twenty, two and if all proceeds as planned with the potential new formulation given.

Scott Braunstein: Given the overlap in seizure types and ideologies with other disorders where Ganaxalone has shown meaningful potential, specifically CDD, as well as early encouraging data in the TSC patient population, we believe the future investment is warranted. We understand that the LGS market is highly competitive and would look to enter the market with the best chance of a differentiated clinical profile. With that, I would now like to turn the call over to our chief medical officer, Joe Houlihan. Okay, Joe?

Given the overlap in seizure types and etiologies with other disorders. We're gonna Exelon has shown meaningful potential specifically C. D D as well as early encouraging data in the T. S. C patient population, we believe that future investment is warranted, we understand that the lgs market its highly competitive and.

We'd look to enter the market with the best chance of a differentiated clinical profile with that I would now like to turn the call over to our Chief Medical Officer, Joe Houlihan Joe.

Joseph Hulihan: Thank you, Scott, and welcome everyone to our business update call. I'll get right into it. Start with our program in Refractory Status Epilepticus, or RSE. In the RSE trial, even with COVID-19 delays, we're still expecting to have more than half the sites open by the middle of the year, with the vast majority of sites open by the end of the third quarter. We're encouraged to see that sites are screening appropriate patients, and we're pleased with the rate of enrollment to date. Our experience with screening reinforces our conviction that we have the right study design, and we've thought very carefully about response rates and controls. Let me explain that a bit.

Thank you Scott and welcome everyone to our business update call.

Let me get right into it.

I'll start with our program in refractory status epilepticus or RSC.

And the rays RSC trial, even with COVID-19 delays.

We're still expecting to have more than half the sites open by the middle of the year with the vast majority of sites opened by the end of the third quarter.

We're encouraged to see that sites are screening appropriate patients and we're pleased with the rate of enrollment to date.

Our experience with screening reinforces our conviction that we have the right study design and we've thought very carefully about response rates in the control arm.

Let me explain that a bit.

Joseph Hulihan: Protocol requires that patients have failed two second-line AEDs. We've asked sites to pre-screen potential study candidates after they failed the first second-line AED, so they can be enrolled quickly after failing another. We believe that requiring the failure of two second AEDs will lessen the response to standard of care. In fact, some patients have actually responded to the second of those AEDs. If we'd enrolled those patients in the trial, it's likely they would have been placebo responsive. So we believe that requiring failure of two second-line AEDs is the correct strategy for defining the population in this study.

The protocol requires that patients had failed to second line Aedes.

We have assets to pre screen potential study candidate after they failed. The first second line 80 day. So they can be enrolled quickly after failing another.

We believe that requiring failure of two second line 80, DS will lessen the response to standard of care.

In fact, some patients have actually responded to the second of those aedes if.

If we would enroll those patients in the trial, it's likely that they would have been placebo responders.

So we believe that requiring failure of two second line Aedes is the correct strategy for defining the population on this study.

We're continuing plans for an RSA pivotal registration trial in Europe.

Joseph Hulihan: We're continuing plans for an RSE pivotal registration trial in Europe, which we have named the Raise 2 trial, targeted for launch in the first half of 2022. We had a very productive dialogue with the European Medicines Agency and reached agreement on the major features of the study design and endpoint. Since one of our goals is establishing leadership and the treatment of status epileptic, we were pleased to hear that our approach to studying RSE could influence the next version of the EMA treatment guidelines for epilepsy. The U.S. and European studies have similar enrollment criterion study design. But there are some key differences.

Which we have named the raised two trial.

And for launch in the first half of 2022.

We had a very productive dialogue with the European Medicines Agency and reached agreement on major features of the study design and endpoints.

Since one of our goals is establishing leadership in the treatment of status epilepticus.

Were pleased to hear that our approach to studying RSC could influence. The next version of E. M. A treatment guidelines for epilepsy.

The U S and European studies have similar enrollment criteria and study designs, but there are some key differences.

Joseph Hulihan: Both studies are double-blind placebo-controlled trials. And in both, patients must have failed initial treatment with a benzobasopine, such as lorazepam or medazilin. However, in the U.S., as I mentioned, patients must then fail at least two second-line IVAED. But in the European study, they will need to have failed only one. The reason for this is that, unlike in the

Both studies are double blind placebo controlled trials.

And in both patients must have failed initial treatment with a benzodiazepine such as low raise a pam on the dazzling.

However in the U S trial as I mentioned patients must then fail at least two second line IV aedes, but in the European study they will need to have failed only one.

The reason for this is that unlike in the U S study.

Joseph Hulihan: In raise 2, iVeganaxone or placebo is started at the same time as the second standard of care AED. We are aware that treating earlier in the course of RSE could allow a better response to standard of care, thereby producing a higher placebo response. However, we've anticipated that possibility and have incorporated other features into the study design intended to maintain the placebo response at a low rate. The U.S. trial has two co-primary endpoints. One, assessing early response, and the other, prevention or progression to IV anesthesia within 36 hours, looking at durability of response.

And raised two IV can actually on or placebo started at the same time as the second standard of care AED.

We're aware that treating earlier in the course of RSC could allow a better response to standard of care, thereby producing a higher placebo response. However, we've anticipated that possibility and have incorporated other features into the study design intended to maintain the placebo response at a low rate.

The U S trial has two co primary endpoints.

One assessing early response and the other prevention of progression to IV anesthesia within 36 hours looking at durability of response.

Joseph Hulihan: Since physicians don't use IV anesthesia for the treatment of status nearly as much in Europe as in the U.S., we modified the durability endpoint for the European trial to be any escalation of care, whether an IV anesthetic or another AED is used to treat status. Importantly, instead of co-primary endpoints in the U.S., EU regulators preferred that we use a combined endpoint, i.e A responder analysis. A responder is defined as having cessation of status within 30 minutes and no escalation of care within 36 hours.

Since physicians don't use IV anesthesia for the treatment of status nearly as much in Europe as in the U S. We modified the durability endpoint from the European trial to be any escalation of care, whether an IV anesthetic or another AED to treat status.

Importantly, instead of co primary end point is in the U S. EU regulators preferred that we use a combined endpoint I E. A responder analysis.

A responder is defined as having cessation of status within 30 minutes and no escalation of care within 36 hours.

The differences in design and study endpoints, meaning that these trials are now complementary to each other.

Joseph Hulihan: The differences in design and study endpoints mean that these trials are now complementary to each other, further increasing the chance for success of the overall program, and having the potential to broaden the efficacy claim for iVeganaxalone and RSA. Next, I'd like to give you an update on our trial in established status epilepticus, or ESC. ESE is earlier in the treatment continuum of status epilepticus and RIS and is defined as status that continues following failure of benzodiazepines.

Further increasing the chance for success of the overall program and.

And having the potential to broaden the efficacy claim for IV <unk> RSC.

Next I'd like to give you an update on our trial and establish status epilepticus or E. S.

E. S. C is earlier in the treatment continuum of status epilepticus and RSC.

And it was defined as status that continues following failure of benzodiazepines.

Joseph Hulihan: The ESE study will enroll patients from emergency departments with convulsive rather than non-convulsive status. We plan to initiate the study in early 2022 after we've completed the process of exception from informed consent and gained alignment with the FDA. It's important to note that patients who qualify for the ESE trial have a type of status distinct from those who would enter the Rays trial, who will have predominantly non-convulsive status epilepsy. So we can consider the same sites for our established status trial without compromising enrollment in the raise. In the ESE study, Enaxelon is intended to act as an adjuvant to standard of care, which will be the initial second-line I The ESET study in established status epilepticus showed that response rates to the standard of care AEDs were less than 50% within the first hour.

The study will enroll patients from emergency departments with convulsive, rather than Nonconvulsive status.

We plan to initiate the study in early 'twenty 'twenty two after we've completed the process of exception from informed consent and gained alignment with the FDA.

It is important to note that patients who qualify for the ESC trial have a type of status distinct from those who would enter the raise trial.

Who will have predominantly nonconvulsive status epilepticus.

So we can consider the same sites for our established status trial without compromising enrollment in our res studies.

In the <unk> study and Exelon is independent to act as an adjuvant to standard of care, which will be the initial second line IV a day.

The he set study and establish status epilepticus showed that response rates to the standard of care Aedes is less than 50% within the first hour.

We believe that <unk> has the potential to reduce the time to response and increase the durability of effect of standard of care IV a these.

Joseph Hulihan: We believe Kinexloan has the potential to reduce the time to response and increase the durability of effect of standard of care, IVAED. Our goal in the study is to find a safe and well-tolerated dose of Ginnaxon. The study design proposed to the FDA involves the initiation of Canaxalone at the same time as the first AED following benzodiazepine failure. The trial utilizes a novel sequential design to assess the safety and efficacy of several doses and infusion durations of Ginnaxil, with the optimal dose regimen progressing to a double-blind phase two study versus placidium.

Our goal on this study is to find a safe and well tolerated dose of <unk> excellent.

The study design, we proposed to the F. D. A involves the initiation of can ask alone at the same time as the first AED following benzodiazepine failure.

The trial utilizes our novel sequential design to assess the safety and efficacy of several doses and infusion durations are getting excellent with.

With the optimal dose regimen progressing to a double blind phase II study versus placebo.

Now I'd like to give you a quick update on our Oregon excellent programs.

Joseph Hulihan: Now I'd like to give you a quick update on our oral Glax loan program. In PCDH-19 related epilepsy, we still plan to submit the results from our Phase 2 study for presentation at an upcoming scientific meeting and for publication in a medical journal. We recognize that this condition is a difficult one to study due to the intermittent and variable nature of seizure activity.

And P. C D. H 19 related epilepsy, we still plan to submit the results from our phase II study for presentation at an upcoming scientific meeting and for publication in a medical journal.

We recognize that this condition is a difficult one to study due to the intermittent and variable nature of seizure activity.

Joseph Hulihan: Importantly, we will continue to offer Ginexelone to any patient who participated in the study and wishes to continue treatment. And in CDD, as Scott mentioned, we're on track for a mid-year FDA submission and for filing with the EMA in the third quarter. We also plan to submit a series of abstracts for the upcoming AES meeting in December, including the one-year open-label extension data from the Marigolds. So far, with data on 48 patients who reached one year of open label treatment, we're seeing percent reductions from baseline during open label months 11 and 12 of 46.5 percent in patients who are on Ganaxelone and are double blinded. Those who had been on placebo and transitioned to open label Glaxalone achieved a percent reduction of 53.8%.

Importantly, we will continue to offer can exelon to any patient who participated in this study and wishes to continue treatment.

And then C D D. As Scott mentioned, we're on track for a mid year FDA submission and for filing with the EMA in the third quarter.

We also plan to submit a series of abstracts for the upcoming Aes meeting in December including the one year open label extension data from the Marigold study.

So far with data on 48 patients who reached one year of open label treatment, we're seeing percent reductions from baseline during open label months 11, and 12 of.

46, 5% in patients who are on getting Exelon and double blind.

Those who had been on placebo and transitioned to open label going on Exelon achieved a percent reduction of 53, 8%.

We continue to work with several centers across the U S who have shown interest in the C. D D expanded access program.

Joseph Hulihan: We continue to work with several centers across the U.S. who have shown interest in the CDD expanded access programs, and we are committed to making Ginexelon available to patients prior to a potential U.S. approval. However, we recently discovered that the top line data that we previously presented included duplicate seizure diary entries resulting from a data transfer error.

And we are committed to making an excellent available to patients prior to a potential U S approval.

We recently discovered that the topline data that we've previously presented included duplicate seizure diary increase resulting from a data transfer error.

Joseph Hulihan: This affected less than 2% of the over 73,000 total diary entries; though there were some small differences between the top-line seizure reduction data and the validated data set for regulatory submission, final statistical analysis of the primary endpoint showed that the percent change in major motor seizures in Gnexelon was 30.7%, and for placebo, it was 6, with a P value of 0. Previously reported top-line data analysis showed a reduction of 32.2% for Ganaxelone and 4% for placebo, with a P value of 0.002.

This affected less than 2% of the over 73000 total diary entries, though there were some small differences between the topline seizure reduction data and the validated data set for regulatory submission.

The final statistical analysis of the primary endpoint showed that the percent change in major motor seizures and make an excellent group was 37%.

And for placebo it was six 9%.

With a P value of 0.0036.

The previously reported top line data analysis showed a reduction of 32, 2% for good excellent and 4% for placebo with a P value of 0.00 too.

Joseph Hulihan: These changes do not affect the statistical or clinical conclusions of the study, and there were no changes in key secondary endpoints, safety data, or other study outcomes. With regard to TSC, we're planning an end of phase two meeting with the FDA early in the third quarter and with the EMA in the fourth quarter. We're also anticipating a second meeting with the FDA to receive scientific advice on our I&D submission. We expect to initiate our Phase 3 TSC study with the first patient enrolled in the fourth quarter of this year. The study will enroll 160 patients who have failed at least two prior AEDs.

These changes do not affect the statistical or clinical conclusions of the study and.

And there were no changes in key secondary endpoints safety data or other study outcomes.

With regard to T S C.

We're planning an end of phase II meeting with the FDA early in the third quarter and with the MAA in the fourth quarter.

We're also anticipating a second meeting with the FDA to received scientific advice on our IND submission.

We expect to initiate our phase III T. S. C study with the first patient enrolled in the fourth quarter of this year.

The study will enroll 160 patients who failed at least two prior aedes.

We anticipate that study participants, we'll be taking a range of concomitant medications and unlike the Epidiorite study our trial will allow enrollment of patients taking the M. Tor inhibitor Afinitor Everolimus, which is used for treatment of seizures and also for T. S T associated tumors.

Joseph Hulihan: We anticipate that study participants will be taking a range of concomitant medication. And unlike the Epidialic study, our trial will allow enrollment of patients taking the mTOR inhibitor, finitor or everoloma, which is used for treatment of seizures and also for TSC-related tumors. We expect that roughly 50% of patients will enter the study taking or having failed epidial. We're also exploring new indications this year, including Lenox Gastos syndrome. Our current thinking is that this would complement our work in other pediatric epilepsy, as we've had several patients in our CDD and TSC studies who carried the diagnosis of LGS. Unlike genetic epilepsy, LGS represents a clinical syndrome that can have a number of different underlying etiologies.

And we expect that roughly 50% of patients will enter the study taking or having failed up of dialogues.

We're also exploring new indications this year, including Lennox <unk> syndrome.

Our current thinking is that this would complement our work in other pediatric epilepsies as we've had several patients in our C. D. D. N T. S. C studies, who carried the diagnosis of lgs.

Unlike a genetic epilepsy diagnosis lgs represents a clinical syndrome. They can have a number of different underlying etiologies.

Joseph Hulihan: We'll share more of our thinking about a clinical trial sometime later this year. As always, in closing, I would like to thank the patients, families, medical professionals, and advocacy groups who've been so supportive of our research. Now I'd like to turn the call over to Kim for a regulatory review. Thanks, Joe.

We will share more of our thinking about our clinical trial sometime later this year.

As always in closing I would like to thank the patients.

Please medical professionals and advocacy groups, who have been so supportive of our efforts.

Now I'd like to turn the call over to Kim from a regulatory review.

Thanks, Joe since we've been receiving an uptick a regulatory question from the investing community with why don't you discuss on interaction and communications with the FDA and EMEA.

Kimberly A. McCormick: Since we've been receiving an uptick of regulatory questions from the investment community, we wanted to discuss our interactions and communications with the FDA and EMA. A pre-NDA CMC meeting was held with the FDA in August of 2020 for the Marigold Study. During the meeting, the FDA provided very constructive feedback, and overall agreement on the format and content of the CMC section of the NDA was achieved.

A pre NDA CMC meeting was held with the FDA in August of 2020 for the Marigold study during.

During the meeting the FDA provided very constructive feedback and overall agreement on the format and content of the CMC section of the NDA was achieved.

Kimberly A. McCormick: Subsequently, in January, we had a type A meeting with the FDA to review our proposal that one phase three study would be adequate to support our NDA submission for CDD. Prior to the meeting at FDA's request, in addition to the details of the Marical Study, we provided information on legacy epilepsy studies conducted by the company that failed to show efficacy, most notably a phase three study of focal seizures in adults. We reviewed key aspects of that study and a numerical trial.

Subsequently in January we had a type a meeting with the FDA to review our proposal at one phase III study would be adequate to support our NDA submission for C. D D.

The meeting at the Fda's request. In addition to the details of the Americold study, we provide information on legacy epilepsy studies conducted by the company that I failed to show efficacy, that's notably a phase three study of focal seizures in adults.

Wherever you key aspects of that study and American trial in particular differences in dosing in PK that we believe explain that discrepancy in study outcome and support the efficacy that can excellent demonstrated in the phase III C. D D trial.

Kimberly A. McCormick: In particular, differences in dosing and PK that we believe explain the discrepancy in study outcomes and support the efficacy that Ganaxelan demonstrated in the Phase 3 CDD trial. Following review of the data and information we provided, the FDA agreed that the Miracle study would be adequate to support our NDA filing and that the adequacy of the data for NDA approval would be determined by the review of the NDA during the process.

Saddam a view of the data and information we provided the FDA agreed that the American study would be adequate to support our NDA filing and the adequacy of the data for NDA approval would be determined by the review of the NDA during the process.

Kimberly A. McCormick: We completed a pre-NDA meeting with the FDA at the end of the first quarter. The FDA has been very engaged and responsive and provided constructive feedback in the pre-NDA meeting on what information they wanted to see in the NDA and in what format. Rapid Response teams are being set up to quickly respond to any potential requests from the FDA.

We completed a pre NDA meeting with the FDA at the end of the first quarter. The FDA has been very engaged and responsive and provide a constructive feedback in the pre NDA meeting on what information they wanted to see in the NDA and in what format.

Rapid response teams are being set up to quickly respond to any potential requests from the FDA.

Kimberly A. McCormick: We believe that the final data analysis for the Marical Study fully supports this submission, and we remain on track with our U.S. and EU regulatory filing. It's worth noting that we had a successful pre-MAA meeting with EMA in March 2021, where overall agreement was achieved on the format and content of the MAA. A meeting with the rapporteur and co-apporteur to discuss the MAA is planned for the end of May. Now, I would like to turn the call over to Steve for a review of our financials. Thank you, Kim. I am pleased to be able to share our financial results with you. For the first quarter of 2021, we recognized $1.8 million in federal contract revenue related to the Barta contract.

We believe that the final data analysis for the Miracle study fully supports the submission and we remain on track with our U S and EU regulatory filings.

It's worth noting that we had a successful pre MAA meeting with EMA in March 'twenty, 'twenty, one or overall agreement with cheap on the format and content on the M. A a.

And maybe with the rapid tour and come up with her.

C N. A E is planned for the end of May now I would like to turn the call over to Steve for a review of our financials.

Thank you Kim.

I am pleased to be able to share our financial results.

For the first quarter of 2021, we recognized $1 8 million in federal contract revenue related to the BARDA contract.

Steve Fansfield: This contract was signed in September 2020, so there are no revenues associated with this from the first quarter of the prior year. As a reminder, our base part of this contract extends approximately through the third quarter of 2022 and is expected to provide a total of $21 million of non-dilutive funding over this time. The potential exists to extend the bar to contract further based on success-based milestones, with potential total funding of up to 51 million.

This contract was signed in September 2020.

So there are no revenues associated with this from the first quarter of the prior year.

As a reminder, our base BARDA contract extends approximately through the third quarter of 2022 and is expected to provide a total of $21 million of non dilutive funding over this time.

The potential exists to extend the BARDA contracts further based on success based milestones with potential total funding of up to $51 million.

Research and development expenses increased to $18 6 million for the three months ended March 31 2021.

Steve Fansfield: Research and Development Expenses increased to $18.6 million for the three months ended March 31, 2021, as compared to $15 million for the same period in the prior year. The change versus the prior year was due primarily to costs associated with increased clinical activity, including startup of the RSC Phase 3 trial, and increased resourcing primarily within our clinical and CMC team. General and Administrative expenses increased to 10.4 million for the three months ended March 31st, 2021, compared to $3.9 million for the same period in the prior year.

As compared to 15 million for the same period in the prior year.

The change versus the prior year was due primarily to costs associated with increased clinical activity, including startup of the RSV phase III trial and increased resourcing, primarily within our clinical and CMC teams.

General and administrative expenses increased to $10 4 million for the three months ended March 31, 2021, compared to $3 9 million for the same period in the prior year.

Steve Fansfield: The primary drivers of the change over the prior year were increased support for the scale-up of the company's operations, as well as preparation for commercialization. The company reported a net loss of $27.1 million for the three months ended March 31st, 2021, compared to $18.7 million in the same period a year ago.

The primary drivers of the change over the prior year were increased support for scale up of the company's operations as well as preparation for commercialization.

The company reported a net loss of $27 1 million for the three months ended March 31, 2021, compared to $18 7 million in the same period a year ago.

Steve Fansfield: These totals include non-cash, stock-based compensation expense of $5 million and $1.9 million in Q1 2021 and 2020, respectively. The first quarter of 2021 included $2.1 million of stock-based compensation related to a severance agreement with our prior CFO. Cash used in operating activities increased to $16.2 million for the three months ended March 31, 2021, compared to $14 million for the same period a year ago. As of March 31st, 2021, we had cash and cash equivalents of 123.5 million.

These totals include noncash stock based compensation expense of $5 million and $1 9 million in Q1, 2021 and 2020, respectively.

The first quarter of 2021 included $2 1 million of stock based compensation related to a severance agreement with our prior CFO.

Cash used in operating activities increased to $16 2 million for the three months ended March 31, 2021 compared to 14 million for the same period a year ago.

As of March 31, 2021, we had cash on cash equivalents of $123 5 million.

Steve Fansfield: This balance, combined with the net upfront proceeds of the Oak Creek Credit Agreement, will enable us to fund the company's current scale of operating expenses and capital expenditures through the second quarter of 2020. As a result of the credit facility, our focus on executing a European partnership, and our plans to monetize the priority review voucher associated with an anticipated CDD approval, we look to accelerate several key investments within the business, including the TSC and Raise 2 Phase 3 trials, activities to support European approval, and additional formulation work related to Knax. As a result of this, we estimate operational expenses of between 113 and 118 million for the fiscal This total includes approximately 16 million in stock-based compensation.

This balance combined with the net upfront proceeds of the Oaktree credit agreement will enable us to fund the company's current scale of operating expenses and capital expenditures through the second quarter of 2022.

As a result of the credit facility are focused on executing a European partnership.

And our plans to monetize the priority review voucher associated with an anticipated C. D D approval.

We look to accelerate several key investments within the business, including the T. S C and raised two phase III trials.

Activities to support European approval, an additional formulation work related to can ask alone.

As a result of this we estimate operational expenses of between 113 and $118 million for the fiscal year 2021.

This total includes approximately $16 million on stock based compensation.

Steve Fansfield: Offsetting these expenses, we estimate barter revenues of between 9 and 12 million for the fiscal year 2021. In addition to the first quarter financial results, I would like to provide additional details of the credit facility with Oak Tree Capital signed on May 11, 2021. Under this agreement, we have the ability to access up to 125 million of credit financing subject to certain conditions to be taken down in tranches upon successful completion of certain milestones. We have already received the initial 15 million upfront payment in connection with our signing.

Offsetting these expenses, we estimate BARDA revenues of between nine and $12 million for the fiscal year 2021.

In addition to the first quarter financial results I would like to provide additional details of the credit facility with Oaktree capital signed on May 11, 2021.

Under this agreement we have the ability to access up to $125 million of credit financing subject to certain conditions to be taken down in tranches upon successful completion of certain milestones.

We have already received the initial $15 million upfront payment in connection with our signing.

Steve Fansfield: Two additional tranches of 30 million each occur based on progression of the CDD indication, with one funded at FDA acceptance of the NDA filing, and a second funded upon FDA approval. The remaining 50 million will be available at our discretion upon successfully achieving certain clinical, financial, and commercial milestones. Importantly, this facility provides the potential to extend our cash runway significantly based on just the CDD indication alone and does not encumber our ability to monetize the potential priority review vouchers. With that said, let me say, I'm excited to be a part of Marinus and work alongside such a talented and top-notch group of experts.

Two additional tranches of 30 million each occur based on progression of the C. D. D indication with one funded at FDA acceptance of the NDA filing and a second funded upon FDA approval.

The remaining 50 million will be available at our discretion upon successfully achieving certain clinical financial and commercial milestones.

Importantly, this facility provides the potential to extend our cash runway significantly based on justice CTD indication alone and does not encumber, our ability to monetize the potential priority review voucher.

With that let me say I'm excited to be a part of Marinus and work alongside such a talented and top notch group of experts.

Scott Braunstein: My first few weeks at Marinists have been incredibly productive, and I am excited to see this company become a commercial leader in rare epilepsy. Now, turning the call back to Scott, who will provide concluding remarks. Thanks, Steve, and once again, welcome aboard.

My first few weeks of Marinus had been incredibly productive and I'm excited to see this company become a commercial leader in rare epilepsies.

Now turning the call back to Scott, who will provide concluding remarks.

Thanks, Steve and once again welcome aboard before concluding our prepared remarks I want to thank the entire Marinus team, who has been responsible for the significant progress we have made and continue to strive to bring ingenuity and solutions to challenges our head count has hit a milestone of close to 100 employees.

Scott Braunstein: Before concluding our prepared remarks, I want to thank the entire Marinus team, who have been responsible for the significant progress we have made and continue to strive to bring ingenuity and solutions to every challenge. Our head count has hit a milestone of close to 100 employees, and I could not be more enthusiastic about the next stages in the company's history. Operator, can you now open the call to questions? reminder to ask on your telephone. To withdraw your question, press the pound or hash key.

And I could not be more enthusiastic about the next stages in the company's history.

Operator can you now open the call to questions.

As a reminder to ask a question you would need to press star one on your telephone to withdraw your question press the pound or husky.

Operator: We also ask that you limit yourself to one question only to allow everyone in queue to ask a question. Please stand by, your first question, with Cohen. Hi there, good morning, and thank you for taking my question. Maybe just one on the raised two study design. Is there any consideration for which specific AEDs can be used in conjunction with Ganaxelone?

So as debt you limit yourself to one question only to allow.

Everyone in queue to ask a question please.

Please standby, while we compile the Q&A roster.

And your first question comes from the line of Joe <unk> with.

With Cowen and company.

Hi, there good morning, and thank you for taking my question.

Maybe just one on the raise to study design is there any consideration.

Consideration for which specific <unk>.

These can be used in conjunction with can ask alone and.

Joseph Hulihan: And is there any worry that there could be drug-drug interactions or any exacerbations of potential AEs when you do take the combination of Gnaxlone and other AEDs? So thanks for your question. No, there's no limitation on the other AEDs.

Is there any worry that there could be drug drug interactions or any exacerbations of of potential aes. When you do do the combination of excellent another AED.

Yeah.

Joe Thanks for your question.

No there's no limitation on the other aedes.

It's the investigator's choice.

Joseph Hulihan: It's the investigator's choice. The number of available AEDs isn't that many, and so, but we do expect we'll get, you know, randomization will balance out what drugs are used and that they'll reflect standard of care. In terms of drug interactions, no. There is potential interaction with SIP-3-4 enzyme-inducing drugs.

The.

The number of available Aedes.

It isn't that many.

And so.

But we do expect we'll get you know randomization will balance out what drugs are used in debt that will reflect standard of care.

In terms of drug interactions no.

Oh there is.

No potential interaction with the Sip three four enzyme inducing drugs.

Joseph Hulihan: But in an oral epilepsy study, we didn't see any effect, any difference in efficacy based on the use of other drugs. And the dose of Ganaxalone used in the trial is high enough. We wouldn't expect to see any interaction, especially with acute use. Um, I don't think that'll be a factor at all. Hi, thanks for taking my question and congrats on the progress. This is Nina and for OET.

But.

In our oral epilepsy study, we didn't see any effect any difference in efficacy based on the use of the other drugs and the dose of <unk> used in the trial was high enough, we wouldn't expect to see any interaction, especially with acute use.

I don't I don't think I don't think that'll be a factor at all.

And your next question comes from the line of Alicia Young with Cantor Fitzgerald.

Hi, Thanks for taking my question and congrats on the progress on this is Neil on for Alethia.

Thank you.

Unknown Executive: Thank you. For the full TSC readout, what additional data will we see, and how do you think about what is comparable data versus competitive? Joe, why don't you take it? I don't have to do anything today.

For the fall on T O see read out what additional data on what we see and how do you think about what is comparable data versus competitors. Thanks.

Joe why don't you take it.

Yeah to do anything today, I'm going to let everyone else do all the work.

Joseph Hulihan: I'm going to let everyone else do all the work today. So, hi, Lisa. Yeah, I think this phase two study focuses on kind of key efficacy and safety data. So there'll be some other ways to look at the seizure data, obviously the usual safety data, and then one of the things we were interested in with this study is, you know, whether we see any differences with different drug combinations, particularly, you know, so epithelix or finitore, and also seizure types. The seizure types in this disorder are different in some ways than those we see in CDD.

So.

Yeah I think on.

This phase II study focuses on key efficacy and safety data.

I'm sure there'll be.

So on some other ways to look at the seizure data obviously the usual safety data.

And then one of the things we're interested in with this study is.

How are we seeing any differences from different drug combinations, particularly those at the dielectric on a tour and also seizure types. The seizure types in this disorder are different in some ways from those we see in C. D D.

Joseph Hulihan: So those are the main things we're looking at. In the phase three study, we'll have a range of patient-reported outcomes and other assessments, but we're focusing on the key data for the phase three study. Hi, thanks for taking our questions and for the update. For the loan from Oak Tree, what are the interest terms with each draw, and are there any callback provisions if the outcome doesn't meet certain expectations?

So those are the main things we're looking at in the Phase III study.

We'll have a range of.

Patient reported outcomes and other.

Other assessments, but we're focusing on the key data from the phase two.

And your next question comes from the line of Joon Lee with Truest Securities.

Hi, Thanks for taking our questions on for the updates for the loan from Oaktree, what are the interest terms, but each draw and are there any clawback provisions at the outcome investing certain expectations and is there any flexibility we sold train for further funding or just kind of indications.

Unknown Executive: And is there any flexibility with Oak Tree for further funding for this general indication? Before I turn over to Steve for the details, let me just hit on the big picture, June, and thanks for the question. First of all, we're thrilled to do this deal with the Oak Tree team. They've been great.

Before I turn it over to Steve for the details let me just hit on the Big Picture June and thanks for the question first of all we're thrilled to do this deal with the Oaktree team they've been great they've been a fantastic partner.

Unknown Executive: They've been a fantastic partner. And I'll have Steve walk you through the specifics of this deal, but I think we believe that this is a partnership that could expand in many different forms over time. And I think they've taken a lot of time to be quite thoughtful in this deal.

And I'll I'll have Steve walk you through the specifics of this deal, but I think we believe that this is a partnership that could expand in many different forms over time.

And I think they've taken a lot of time to be to be quite thoughtful in this deal. So happy to have them as a partner, but Steve why don't you walk through all the details of the deal for June.

Unknown Executive: But Steve, why don't you walk through all the details of the deal? Yeah, hi, June, yeah, certainly happy to walk you through. So, yeah, I think we've mentioned it's up to 125 million in financing, obviously, tranche, the first 75 we can take relative to the CDD indication alone. The remaining 50 is driven by clinical, financial, as well as commercial targets. The interest rate on it is 11.5%.

Yeah, Hi, Junior certainly happy to walk you through so yeah, I think we'd mentioned it it's up to $125 million financing, obviously tranche. The first 75, we can take a relative to the CTD indication alone. The remaining 50 is driven by our clinical and financial.

As as as well as commercial targets the interest rate on it is 11, 5%. It's interest only for the first three years and then it it.

Steve Fansfield: It's only interest for the first three years, and then it, you know, is at full maturity after five years. There is a ticking fee that starts 120 days after funding of the 30 million tranche from the CDD filing acceptance, that first 30 million tranche of funding. I think it's worth noting there are a couple of things worth calling out. We can still monetize the PRD. We still have the ability to do a U.S.-based synthetic royalty, and we are able to do a European partnership. So those are kind of a number of the key things.

Is it full maturity after five years.

There is a there is a ticking fee that starts of 120 days after funding of the $30 million tranche from the C. D filing acceptance on that that first 30 million tranche of funding.

I think it's worth noting there's a couple of things worth calling out we can still monetize the PRD, we still have the ability to do a U S based synthetic royalty and.

And we are able to do a European partnership.

So those are those are kind of a number of the key things in terms of expanding further I think that that's something we can discuss further as we go along and you know we look at this as a zone a relationship on a long term relationship with Oaktree.

Steve Fansfield: In terms of expanding further, I think that's something we can discuss further as we go along. And, you know, we look at this as a relationship, a long-term relationship with Oak Tree. And you're next. Yeah, Joe, can you talk about LGS a little bit, what proof of concept data you have that made you want to pursue this indication? Yeah, so we did have, you know, LGS is a diagnosis; it's not a specific genetic diagnosis; it's multiple etiologies.

Uh huh.

And your next question comes from the line of Marc Goodman with SBB Leerink.

Yeah, Hi, Joe can you talk about L. G S. A little bit what proof of concept data you have that makes you want to pursue this indication. Thanks.

Yeah.

So we are we did have you know L. T S has a diagnosis.

Not a specific genetic diagnosis multiple etiologies. So we had some patients in the CBD study that also carried a diagnosis.

Steve Fansfield: So we had some patients in the CBD study that also carried a diagnosis of LGS. And so we're, you know, we started to analyze that data, but, you know, without giving too many specifics, I think it gives us confidence in an LGS study. Not a large number of patients, but it heads in the right direction. And so, you know, we've had a previous study in multiple seizure types, developmental and epileptic encephalopaties. And there was a small number of LGS patients in that, but that study really didn't capture the data in a way that we, uh, could use it to see whether there is a proof of concept.

Of lgs and so.

Where were you.

To analyze that data but.

But you know what.

Without giving too many specifics I think it gives us confidence that on Lgs study are not not a large number of patients, but it heads on the right direction.

And so.

We've had on our previous study.

In multiple seizure types developmental and epileptic encephalopathy.

And the there was a small number of lgs patients from that but that study really didn't capture the data in a way that we are.

You could use it to see whether it's a proof of concept. The other thing that gives me confidence about lgs is on the seizure types on our largely similar to a C. D D.

Joseph Hulihan: The other thing that gives me confidence about LGS is that the seizure types are largely similar to CDD. And so I'd expect to see the same efficacy in other ideologies as we did in CDD. And if we pursue it, it would likely be with a reformulation. It's going to give us some better and more even exposure to the drug. So I think that's a plus two.

And so I'd expect to see the same efficacy.

And in other etiologies is as we didn't see D D and if we pursue it it would likely be with a reformulation, it's going to give us some.

Better and and more even exposure to the drug.

So I think that's a plus too.

And Joe and Mark.

Scott Braunstein: And Joe and Mark, I'll add one additional comment. Mark, we've updated our slide deck, and we've now included in that slide deck the PK analysis that Joe and Alex have performed on at least the failed three focal onset study. And I think we're seeing clear differences in PK levels between studies that were previously performed by the company. We think that is just a function of dose titration over the course of a month of three times a day dosing.

I'll add one additional comment Mark we've updated our slide deck and we've now included in that slide deck.

The PK analysis had Joe on Alex have performed on at least the failed three focal onset study and I think we're seeing clear differences in PK levels and studies that were previously performed by the company.

We think that it's just a function of dose titration.

Over the course of about three times a day dosing.

Scott Braunstein: And I think when we look back at the LGS study, you're seeing a consistent signal or inconsistent signal in terms of PK, which, you know, we think it's very different than what we've seen in. Thanks for the question. Douglas Salis. Hi, good morning. Thanks for taking the questions. I'm just curious in terms of the raised two trial. I know you mentioned the opportunity to potentially sort of expand the utilization of the drug.

And I think when we look back at the Lgs study, you're seeing a consistent signal or inconsistent signal in terms of PK.

Which we think is very different than what we've seen in the <unk> study.

Thanks for the question Mark.

And your next question comes from the line of Douglas Tsao with H C. Wainwright.

Hi, good morning, Thanks for taking the questions I'm just curious in terms of the raise to trial I know you mentioned the opportunity to potentially sort of expand.

And utilization have you engaged with the FDA or do you plan to engage with the at the U S. FDA about whether that would meet standards to have inclusion in terms of the label and sort of potentially sort of move up the treatment paradigm.

Scott Braunstein: Have you engaged with the FDA, or do you plan to engage with the U.S. FDA about whether that would meet standards to have inclusion in terms of the label and sort of potentially sort of move up the treatment paradigm? Go ahead, Joe. You want to start?

Okay.

Go ahead, Joe you woke up on you're going to start yet no maybe I could turn this one over to Kim for the regulatory piece of it.

Kimberly A. McCormick: Yeah. No, maybe I could turn this one over to Kim for the regulatory piece of it. Sure, thanks, Joe. I can take that.

Alright, Thanks, Jackie I can take that so we have not yet if that's the way to study with the FDA to.

Kimberly A. McCormick: So we have not yet discussed the Rays for study with the FDA. The current plan is that once we have the data from that study, we will then discuss with the FDA how and what our potential options are for explaining the way that Yeah, and let me just give a little more color. I think we understood. I think we have to step back and say, hey, we knew we would require a different regulatory path with the European agents.

So once we have the data from that study will then on.

Got you okay.

And what are potential options are from expanding the label at that time.

Yeah, and let me, let me just give a little more color.

I think we you know we we understood I think we have to step back and say Hey, we knew we would require a different regulatory path with the European agency I think we've gotten to a very good place with the European regulatory agency and given that study design. We do believe it is so complementary to what we're do.

Kimberly A. McCormick: I think we've gotten to a very good place with the European Regulatory Agency, and given that study design, we do believe it is so complementary to what we're doing in the U.S. that it would be logical for us to have that interaction with the agency. We'd love to have sites in the study in the U.S. as well.

In the U S debt it would be logical for us to have that interaction with the agency.

Would love to have sites in this study in the U S. As well I think from a timing perspective, we would only initiate those sites in the U S. When the raise trial itself was was significantly enrolled that we didn't wouldn't see that as a a conflict. So.

Scott Braunstein: I think from a timing perspective, we would only initiate those sites in the U.S. when the Rays trial itself was, you know, was, significantly underway. We wouldn't see it as a conflict. So we think it's a pretty logical discussion for us to have, and certainly we'd love to have their buy-in from where we are. But I think, as we all know, any time we do additional studies, it's always going to be a discussion or a filing with the agency in terms of potential. Thanks for the question.

We think it's a pretty logical discussion for us to have and certainly we would love to have their buy in.

From where we are today, but I think as we all know anytime we do additional studies, it's always going to be a discussion or a filing with the agency in terms of a potential label expansion.

Thanks for the question.

And your next question comes from the line of Jay Olson with Oppenheimer.

Scott Braunstein: Oh, hey guys, congrats on the progress, and thanks for taking our questions. We're curious about CDD. Can you talk about any feedback you've gotten from paired discussions or other pre-launch activities? And do you think the 50% seizure frequency reduction for CDD that you saw in the first 12 months of the OLE could improve beyond 12 months, or is that a plateau effect? and then I had a follow-up question, if I could. Chris, do you want to jump right in and take this? Oh, go ahead. Oh, I'm sorry, Joe.

Oh, Hey, guys. Congrats on the progress and thanks for taking our questions were curious about C. D. D. Can you talk about any feedback you've gotten from payer discussions or other prelaunch activities and do you think the 50% seizure frequency reduction for C. D D.

That you saw on the first 12 months of the OLED could improve.

On 12 months or is that a plateau effect.

And then I had a follow up question if I could.

Chris Young millennial shopper I didn't take that I'll go ahead.

Christy Shafer: I was going to have Chrissy start on the commercial side. No, please. Please, yeah.

I'm sorry, Joe is going to have Christine on the conversion now please please yeah.

Christy Shafer: Heather, Jay, good morning. So from a payer perspective, we've done a significant amount of research, just understanding the marketplace, how they view CDD and the expectations that they have. We have finalized that research, and we're moving into our phase of just the internal discussions of that research and how we move into a more strategic plan. I will say, though, because this will be the first and only payer discussions we have.

Hi, there Jay good morning, so from a payer perspective, we've done a significant amount of research just understanding the marketplace, how they view C D D and on the expectations that they have we have finalized that research and we're moving into our phase of just the internal discussions of.

Research and and how we move into on more strategic plan and I will say, though is because this will be the first and only on payer discussions have been very very very positive. So we're we're increasingly them more secure in our in our value proposition in this patient population I will also say that.

Christy Shafer: The results have been very, very, very positive. So we're increasingly more secure in our value proposition in this patient population. I will also say that based on the market research that we've done with payers and physicians, there is an incredible appetite for a new medication for these patients that is over that 25% reduction standpoint. So that lower threshold certainly supports our communication.

Based on the market research that we've done with payers and physician.

There is an incredible appetite for a new medication for these patients that is over that 25% reduction standpoint, so that lower threshold certainly supports our communications. So from a clinical perspective, I'll certainly turn it over to Joe.

Joseph Hulihan: So from a clinical perspective, I'll certainly turn it over to Joe. Yeah, so in terms of the long-term follow-up, yeah, there is potential right now. Patients are still moving through, and I think we need to see more patients with the longer-term follow-up to see what happens. I think at a minimum, they'll maintain the efficacy.

Yeah. So in terms of the long term follow up yeah. There is a potential right now.

Patients are still moving through and.

I think we need to see more patients with longer term follow up to two to see what happens I think at a minimum to maintain the efficacy.

Operator: But, you know, there is an opportunity, especially for some patients, to potentially become seizure-free, or we could see a change in the overall medium. But, you know, I think there's a possibility we could continue to see improvements. Operator, why don't we go to the next question?

But.

There is there is an opportunity, especially you'll some patients could potentially become.

She is a free oh.

Or we could see a change from the overall median.

But.

No I think theres a possibility we could continue to see improvement.

Yeah.

And operator, why don't we go to the next question, yes, sorry.

Operator: Yes, thanks. No problem. And the next question comes from the line of Brian. Hey, good morning, everyone.

No problem and your next question comes from the line of Brian <unk> with Baird.

Hey, good morning, everyone. Thank you for taking my questions and thanks for all the color on transparency on the call I guess when it comes to the CTD indication I was wondering if you could just kind of walk us through what the kind of gating factors here are for the NDA submission and can you just review our both the C. D D N P. S C.

Operator: Thank you for taking the questions, and thanks for all the color and transparency on the call. I guess when it comes to the CDD indication, I was wondering if you could just kind of walk us through what the kind of gating factors here are for the NDA submission. And if you just review, are both the CDD and TSC pathways under the division of neurology, too?

Pathways under the division of Neurology, two and glass for T. S. C. You said that the upcoming FDA meeting will be based on an interim analysis I guess, it's an open label study so.

Kimberly A. McCormick: And last, for TSC, you said the upcoming FDA meeting will be based on an interim analysis. I guess it's an open-label study. So, you know, maybe you can talk a little bit about what you've learned from the studies so far, if anything, to kind of give you confidence to move into phase three. And if you sort of already have an idea of the interim analysis you'll be discussing in that meeting. Thanks, Brian.

So maybe you can talk a little bit about what you've learned from the study so far if anything to kind of get the confidence into moving into into phase three and if you sort of already have an idea of the interim analysis you'll be discussing.

That meeting thanks.

Thanks, Brian Kim do you want to kick off on the where we are with the NDA filing and your thoughts about the DSC meeting them and if Joe wants to add anything he can hop in afternoon.

Kimberly A. McCormick: Kim, you want to kick off on where we are with the NDA filing and your thoughts about the TSC meeting, and then if Joe wants to add anything, he can hop in there. Sure, so in regards to the NDA submission, we're actively in the process of preparing the NDA submission for filing as targeted by the end of June. So there's a lot of work ongoing at this time and a lot of, preparations but we're still on track to have everything delivered and submitted by the end of the, In regards to the TSC study, we are planning to use the data cut from the open label study to submit requests to the FTA for an end of phase two meeting in July, and hopefully having that meeting in the August, September timeframe, to support the initiation of our phase study.

Sure Dan Mccarthy NDA submission, we're actively in the process of preparing the NDA submission for filing a targeted by the end of June because there's a lot of work ongoing at this time there are a lot of preparations, but we're still on track.

Clarence maybe by the end of the mine.

In regard to the PSC study, we are planning to use a data cut from the open label study.

May I request.

Okay Fernando Phase two meeting.

In July and hopefully having that meeting in the August September timeframe.

And essentially are facing study.

Kimberly A. McCormick: I will also be discussing the study with the European agency in parallel, but at a slightly staggered time for those discussions. Yeah, and, um, yeah, I could comment on the TSC in terms of what we're looking for. I mean, I think the most recent benchmark would be epidilex, and so obviously, we'd like to see a magnitude of effect similar to that. However, this is an open-label, single-arm study, so in terms of predicting a placebo response, we have to use historical control. But really, you know, it's the magnitude and the direction of the effect.

Also be discussing the study with the.

The European agency as well in parallel, but slightly staggered time sensitive discussion.

Yeah.

Yeah, I can comment on the PSC on term.

So what we're looking for I mean, I think the most recent benchmark would be up of dialects and so obviously, we'd like to see.

Magnitude of effect similar to that.

It is an open label single arm study.

So in terms of predicting a placebo response, we have to using on historical control.

But really you don't see the magnitude and the direction of the effect and and we're seeing you know when the interim look.

Joseph Hulihan: And we're seeing, you know, in the interim look, we're seeing, you know, we're seeing things head in the right direction, and we'll present the full data set. I think later this summer we should have, And your next question comes from the line of Michael Higgins with Leidenberg. Thank you. Morning guys, congrats on the continued execution. Certainly, there is a lot going on these days.

We're seeing things heading the right direction and.

And we will present the full data set later this summer we should have that.

And your next question comes from the line of Michael Higgins with Ladenburg Thalmann.

Thank you good morning, guys. Congrats on the continued execution certainly a lot going on in these states where to seize on continued progress.

Operator: We look forward to seeing the continued progress. Question for you coming out of Europe: we've discussed for some time now the differences in the protocols between the U.S. and European ED departments. And I think that's driving the difference in the design of the raised two study over there but also poses some challenges because of the placebo response, which you mentioned. Can you help us a little bit in understanding what your expected efficacy rates would be for the two different regions raised versus placebo? Thank you. Sure. Yeah, it's a bit complicated, but I think the endpoints are different. As I mentioned, you know, in the EU, they tend not to use IV anesthesia nearly as much.

For you coming out of Europe.

Discussed for some time now about the differences in the protocols between U S and European.

Departments.

And I think that's driving the difference in the design of the relay race two study over there, but also imposed on some challenge because of the placebo response that you've mentioned can you help us a little bit in understanding what your expected efficacy rates would be for the two different regions raise versus race too. Thank you.

Sure.

Yeah, it's a bit complicated I think that the endpoints are different as.

As I mentioned in the EU they tend not to use.

IV anesthesia nearly as much it's the standard practice really neuro.

Joseph Hulihan: It's the standard of practice, really, neurologists in ICU by the time it gets to that stage of status. And so the second part of the endpoint is any escalation of care rather than escalation to IV anesthesia. That's one accommodation we've made to that. And actually, the endpoint itself is different. In the U.S., it's two co-primary endpoints, and they each have to hit on their own.

Urology and IC used by the time it gets to that stage of status.

And so.

The second part of the endpoint.

Is.

On the escalation of care rather than escalation to IV anesthesia, that's one accommodation we've made to that.

And actually the end point itself is different in the U S. It's two co primary end points. They each have a ticket on their own.

Joseph Hulihan: In the EU, it's a combined endpoint, a responder analysis. So a given patient has to have an early response as well as a durable response. And I think that because they have to have the early response, in particular, the power of the study is actually increased because of that. And also, I think, you know, escalation of care, I think Giacillan, obviously will show superiority there to standard of care alone. And so the overall magnitude of the effect is the same in the U.S. we're expecting to see, a 30% delta between Ginoxelone and placebo, but for different reasons. The parameters for that are different, and that's reflected in the sample size.

He was a combined endpoint a responder analysis.

On that so given patient has to have an early response as well as a durable response and I think that because they have to have the early response in particular.

On that.

The power of the study is actually increase because of that and also I think you know escalation of care I think you can excellent obviously will will show superiority there too to standard of care alone.

So.

The overall magnitude of the effect is the same in the U S. We're expecting.

To see.

A 30% delta between can ask alone.

On placebo.

But for different reasons the parameters for that are different and that's reflected in the sample size. Initially we were going to do it.

Operator: Initially, we were going to do a combined study with the U.S., you know, pool the data, but with this complementary rather than identical design, the study is being done on its own, but we can achieve the same power with a much smaller number of patients. The plant sample in Europe is 70 patients.

Combined study with the U S. We have a pool the data.

But with this.

Complementary rather than identical designs.

The study is being done on its own but we can we can achieve the same power with a much smaller number of patients the planned sample and in Europe 70 patients.

Operator: And so, again, that's a reflection of the increased power with the responder input. Very helpful. Appreciate it. Thanks, guys. No, thank you for the question. And your next question comes from Andrew Usai with Jeff. Hi, good morning, and thanks for all the progress. So my question is on CDD. Should we expect an adcom panel once you file, and what do precedents suggest in rare epilepsies

And so.

Again, that's a reflection of the increased power with a responder endpoint.

Very helpful. Appreciate it thanks guys.

Thank you for the question.

And your next question comes from the line of Andrew Tsai with Jefferies.

Hey, good morning, and thanks for all the progress. So my question is on C. D D.

Should we expect an AD comm panel once you file what two precedent suggests and rare epilepsies and.

Operator: And just wanted to confirm, you know, investors should assume a 12-month standard review once you submit your application. Thanks. Thanks for the question, Andrew. I'm going to turn it over to Kim. We all heard typing in the background.

Just wanted to confirm.

Investors should assume a torn month 12 month standard review once you submit.

Thanks for the question, Andrew I'm going to turn it over to Kim.

We all heard typing in the background, we thought it was us I guess it was Michael who.

Kimberly A. McCormick: We thought it was us, but I guess it was Michael who kept us all a little bit on our toes. Thanks, Andrew. Kim, why don't you take the questions? Sure, thanks, Scott. So the FDA will actually determine if there is a need for an ACOM. As part of any typical NDA planning, we are actually preparing for a potential ADCOM until we hear confirmation from the FDA whether or not we will or won'

[laughter], keeping us all a little bit on our toes. Thanks, Andrew why don't you take the question.

Sure I think that so oh actually for a minute there is a need for an ad com.

Any typical NDA planning on we are actually preparing for potential AD com until we hear confirmation from the FDA, whether or not from us all that well. So at this point in time, we are preparing as if we are going to have one until we hear otherwise from the agency.

Kimberly A. McCormick: So at this point in time, we are preparing as if we are going to have one until we hear otherwise from the agency. In regards to the filing duration, as this is an orphan and a rare disease, we will be requesting priority review as part of the end-day submission and are very confident that we'll be able to obtain that priority review for this very high medical need. Therefore, getting the reduced review time of six months versus the typical standard 10-month filing.

In regards to the filing duration assets.

Is that in orphan and rare disease will be requesting price with you as part of the NDA submission and are very confident that we'll be able to obtain that paired with you for this very high unmet medical need therefore on.

On getting me against revenue time of the six months versus a typical standard 10 my follow on so we do anticipate.

Operator: So when you consider the 60-day filability timeframe plus the six-month review, we do anticipate that we're targeting to have approval by the end of the first quarter of next year. Does that answer your question? And your next question is about the line with Jason Butler with JMP.

When you consider the 60 day viability timeframe plus the six months our view that we're targeting to have a simple on by the end of first quarter of next year.

Does that answer your question.

And your next question comes from the line of Jason Butler with JMP Securities.

Operator: Hi, thanks for taking the question and congrats on the progress. Just one on the formulation work you're doing, can you just give us your kind of thoughts on the target profile for the first formulation in terms of bioavailability and PK dynamics and how you're thinking about prioritizing the indications that you could move into with the different formulations? Thanks, Jason. Appreciate it. This is Scott.

Hi, Thanks for taking my question and congrats on the progress just want on the formulation work Youre doing can you just give us your current thoughts on on target profile for the first formulation in terms of bioavailability and PK dynamics and how you're thinking about prioritizing the indications that you could move.

Then to work with the different formulations. Thanks.

Thanks, Jason appreciate it this is Scott I'll take it.

Scott Braunstein: I'll take it. So we recognize the formulation program will be a multi-step approach. And I think it starts with the basics, that we understand the current bioavailability and the variability of the current formulation are significant. And so what we want to do as a first step is replicate TID dosing and really give patients and physicians the ability to all obtain a therapeutic blood level and potentially allow physicians to titrate that.

So we recognize the formulation.

Program will be a multi step approach and I think it starts with the basics that we understand the current bioavailability and the variability of the current formulation is significant and so what we want to do it. The first step is replicate tid dosing.

And really give patients physicians the ability to all obtain a therapeutic blood level and.

And potentially allow physicians to titrate that blood level and so right now our three programs as we mentioned in prepared remarks any three could go into the clinic next week are all about better bioavailability, but.

Scott Braunstein: And so right now, our three programs, as we mentioned in prepared remarks, any three could go into the clinic next week, are all about better bioavailability but really replicating that TID dosing parity. After that, we will work very aggressively on a drug delivery technology platform to stretch dosing from either TID to BID or even TID to QD. But I think more importantly, from a drug delivery standpoint, and from a formulation standpoint, we want to minimize CMAX and make sure we have stable C-MINS. And I think we now know very clearly from Marigold that we don't want our C-MINS to go below 75 nanograms per ML.

Really replicating that T I D dosing paradigm.

After that we will work very aggressively on the drug delivery technology platform.

Two stretch dosing from either T. I D to B, I D or even tid QD, but I think more importantly from a drug delivery standpoint.

The formulation standpoint, we want to minimize C. Max and make sure we have stable see mens and I think we don't know very clearly from Marigold that we don't want our Siemens to go below 75 nanograms per ml and I think we can ultimately create a formulation which is better tolerated gives physicians.

Scott Braunstein: And I think we can ultimately create a formulation that is better tolerated, gives physicians flexibility on dose titration, and ultimately, it'll be incrementally easier for patients and family members to administer the medicine. But I think, quite honestly, the BID or QD formulation is much more important for having good control of CMAC. So that's how we're thinking about it, and we're excited about the progress we've made to date, and we're going to try to move very quickly, but we also have a long-term vision for the franchises we're thinking about. So with that operator, we're going to make that the last question.

On dose titration, ultimately will be incrementally easier for patients and family members to administered to patients but.

But I think quite all feed of the B I D or QD formulation is much more importantly about hum.

Having good control of C Max and seen it.

So so that's how we're thinking about it and we're excited about the progress we've made to date and we're going to try to move very quickly but.

But we also have a long term vision for the franchise, which which we're thinking about quite a bit.

So with that operator, we're going to make that the last question its coming upon 930, we want to thank everyone for dialing in certainly it was great to have you. All we know there was a lot in the press release to digest. So it will be available for follow up calls and.

Operator: It's coming upon 930. We want to thank everyone for dialing in. Certainly, it is great to have you all. We know there was a lot in the press release to digest, so we'll be available for follow-up calls. And, you know, I just want to thank the team again. They've just done a great job of helping us move the ball forward. I'm thrilled to have the Oak Tree team on board and to have Steve, Christy, on this call with Joe Kim, myself, Sasha, and we didn't hear from Alex today.

I just want to thank the team again, they've just done a great job of helping us.

Moving the ball forward thrilled to have the Oaktree team on board and having Steve Christie on this call with Joe Kim myself, Sasha and we didn't hear from Alex today, I, just I'm thrilled about where our team is today and in US moving forward as an organization. So thanks, everyone and we'll talk to you soon.

Operator: You know, I just am thrilled about where our team is today and us moving forward as an organization. So thanks, everyone, and we'll talk to you. I prayed for him. And this concludes today's conference call. You may now discuss

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And this concludes today's conference call. Thank you for your participation you may now disconnect.