Q4 2020 Marinus Pharmaceuticals Inc Earnings Call

[music].

Ladies and gentlemen, thank you for standing by and welcome to Marinus Pharmaceuticals fourth quarter 2020 financial results. At this time all participant lines are in a listen only mode. If you require any further assistance at any time. Please press <unk>.

Operator: Ladies and gentlemen, thank you for standing by, and welcome to Marinus Pharmaceuticals' fourth quarter 2020 financial results. At this time, all participant lines are in a listen-only mode. If you require any further assistance at any time, please press... (inaudible).

Zero on your telephone after the Speakers' remarks, there will be a question and answer session. If you would like to ask a question. During this time simply press Star and then number one on your telephone keypad to withdraw your question press the pound key I would now like to turn the call over to Sasha Mooney Vice President of Investor Relations.

Unknown Executive: of Investor Relations and Corporate Communications, please go ahead.

Unknown Executive: Thank you and good morning everyone. With me from Marinus are Dr. Scott Braunstein, Chief Executive Officer, Dr. Joe Hulihan, Chief Medical Officer, Dr. Alex Aimetti, Vice President of Scientific Affairs, and Ed Smith, Chief Financial Officer. Also on the call to participate in the Q&A are Christy Shafer, our Chief Commercial 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 could be termed as forward-looking under the securities laws. These forward-looking statements are subject to certain risks and uncertainties that are associated with our business and covered in part in the company's Form 10-K and 10-Q as filed with the Securities and Exchange Commission.

And corporate Communications. Please go ahead.

Thank you and good morning, everyone with me from Meredith are Dr. Scott Braunstein, Chief Executive Officer, Dr. Joe will ahead, and Chief Medical Officer, Dr. Alex <unk>, Vice President of scientific Affairs and.

Smith, Chief Financial Officer also on the call to participate in the Q&A is Christi Schaffer, our chief commercial officer, and Kimberly Mccormack, Vice President of regulatory Affairs.

Before we begin I would like to remind everyone that some of the statements made today could be termed as forward looking under the securities laws.

Forward looking statements are subject to certain risks and uncertainties that are associated with our business and covered and part and the company's form 10-K, and 10-Q as filed with the Securities and Exchange Commission and I.

Unknown Executive: I will now turn the call over to Scott. Thank you, Sasha. Good morning, everyone.

I will now turn the call over to Scott.

Thank you Sasha.

Morning, everyone and welcome to our fourth quarter and fiscal year end 2020 business and financial update.

Scott Braunstein: And welcome to our fourth quarter and fiscal year-end 2020 Business and Financial Update. The fourth quarter was another period of tremendous progress, providing strong momentum for what is shaping up to be a very exciting 2021 for Marin. Before I touch on this year, let me share with you some of the highlights from the fourth quarter, which included compelling clinical trial and research presentations at the American Epilepsy Society annual meeting focused on the use of Ganaxolone in treating both CDD and suprarefractory status epilepsy, raising $70 million in a December equity offering and enhancing our investor base, as well as launching an expanded access program in the United States for patients suffering from CDD If we look at 2021, this year has already been incredibly exciting, as we have announced several important milestones.

The fourth quarter was another period of tremendous progress providing strong momentum for what is shaping up to be a very exciting 2021 for mariners.

Before I touch on this year, let me share with you some of the highlights from the fourth quarter, which included compelling clinical trial and research presentations at the American Epilepsy Society annual meeting focused on the use of <unk> alone and treating both C D D and Super refractory status.

Simple epic is raising $70 million and a december equity offering and enhancing our investor base as well as launching and expanded access program in the United States for patients suffering from C. D D, who did not participate in Rfps three clinical trial.

If we look at 'twenty 'twenty. One this year has already been incredibly exciting as we have announced several important milestones. Firstly, we are enthusiastic to share, prompting topline data from the phase two violet trial and PCB reached 19 related epilepsy.

Scott Braunstein: Firstly, we are enthusiastic to share promising top-line data from the Phase 2 VIOLET trial in PCVH19-related epilepsy, which Alex will review following my opening remarks. Next, we are happy to report that enrollment will complete this week in the ongoing phase two trial evaluating the efficacy and safety of adjunctive gonaxalone treatment in patients with tuberous sclerosis complex, or TSC. The top-line study results are on track and expected in Q3 of this year.

Which Alex will review following my opening remarks next we are happy to report that enrollment will complete this week and the ongoing phase two trial evaluating efficacy and safety of adjunctive <unk> treatment in patients with tuberous sclerosis complex or T. S C.

The top line study results are on track and expected in Q3 of this year importantly, after analyzing and interim evaluation of the calm study the open label Phase two trial and T. S T.

Scott Braunstein: Importantly, after analyzing an interim evaluation of the COM study, the open-label Phase 2 trial in TSC, we are confident that the data supports moving to a global, randomized, double-blind, placebo-controlled Phase 3 registration trial. Joe will review this in more detail, but our hope is to meet with the FDA to discuss the design of the Phase 3 trial by the middle of Q2. In conjunction with this news, we are happy to report that the NDA for the use of gonaxalone in CDD-related epilepsy is on track for submission by mid-2021.

We are confident that the data supports moving to a global randomized double blind placebo controlled phase three registration trial.

Joe will review this in more detail, but our hope is to meet with the FDA to discuss the phase III trial design by the middle of Q2.

In conjunction with this news we are happy to report that the NDA for the use of <unk> saloon and C. D. D related epilepsy is on track for submission by mid 'twenty 'twenty. One we also reported having enrolled our first patient in the phase III clinical trial of intravenous can ask alone there.

Scott Braunstein: We also reported having enrolled our first patient in the phase three clinical trial of intravenous Ganaxolone, the RAISE trial for the treatment of refractory statocephalopathy. We continue to screen and enroll additional patients in the trial and look to have the vast majority of sites fully activated by the middle of this year. Despite the challenges that have been created by the COVID pandemic, we continue to believe that we are on track for top-line data from the RAY study in the first half of 2022.

<unk> trial for the treatment of refractory status epilepticus, we continue to screen and enroll additional patients and the trial and look to have the vast majority of sites fully activated by the middle of this year. Despite the challenges that had been created by the Covid pandemic, we continue to believe that.

We are on track for topline data from the <unk> study and the first half of 'twenty 'twenty two.

Scott Braunstein: Before expanding on our 21 plans, I would like to turn the call over to Dr. Alex Aimetti, Head of Scientific Affairs, to discuss our results in the VIOLET trial, our proof-of-concept study in patients with PCDH19-related epilepsy. Thank you, Scott.

Before expanding on our 'twenty, one plans I would like to turn the call over to Dr. Alex Committee headed scientific affairs to discuss our results from the pilot trial, our proof of concept study and patients with PTT, each 19 related epilepsy Alex.

Thank you Scott I'm very excited to share with you the topline clinical data from our phase two placebo controlled study in P. C. D H 19 related epilepsy.

Alex Aimetti: I'm very excited to share with you the top-line clinical data from our Phase 2 placebo-controlled study in PCDH19-related epilepsy. As a reminder, in May of 2020, we announced the truncation of the study as a strategic business decision. As a result of this decision, the study was not adequately powered to demonstrate statistical significance between treatment arms.

As a reminder, in may of 'twenty, and 'twenty, we announced the truncation of the study as a strategic business decision.

And as a result of this decision. The study was not adequately powered to demonstrate statistical significance between treatment arms.

Alex Aimetti: Nonetheless, we believe the results are very encouraging as they were generated from a well-controlled study and are directionally consistent with the results observed in CDD, further validating the effects of three times a day Ganaxalone doses. First, I wanted to remind you of the study design. The study included an 8 to 12 week baseline period in which patients tracked their baseline seizure frequency. Patients were then randomized to receive Gynaxolone or placebo added to standard of care anti-seizure medication.

Nonetheless, we believe the results are very encouraging as they were generated from a well controlled study and are directionally consistent with the results observed and C. D. D. Further validating the effects of three times, a day and acts alone dosing.

First I wanted to remind you of the study design.

The study included an eight to 12 week baseline period in which patients track their baseline seizure frequency.

Patients were then randomized to receive it and exelon or placebo added to standard of care anti seizure medications.

Alex Aimetti: Seizure frequency was then tracked for the 17-week treatment period. The primary efficacy endpoint was the percent change in primary endpoint seizure frequency during the treatment period relative to the baseline period in all patients randomized. 21 patients were randomized, with 10 patients in the ganaxalone arm and 11 patients in the placebo arm. Patients in the gonaxalone arm experienced a median 61.5% reduction in primary endpoint seizure frequency compared to a 24.0% reduction in the placebo arm. This directional improvement resulted in a p-value of 0.17.

Seizure frequency was then track for the 17 week treatment period.

The primary efficacy endpoint was the percent change in primary endpoint and seizure frequency during the treatment period relative to the baseline period and all patients randomized.

21 patients were randomized with 10 patients and they're gonna ask alone arm and 11 patients and the placebo arm.

Patients and they can exelon arm experienced a median and 61 five per cent reduction and primary endpoint seizure frequency compared to a 24.0 per cent reduction in the placebo arm.

This directional improvement resulted in a P value of 0.17.

Alex Aimetti: This study was originally designed to further evaluate the hypothesis that baseline endogenous allopregnanolone sulfate levels may predict ganaxalone's response. Contrary to the hypothesis, the Ganaxalone response observed in this study was independent of allopregnanolone sulfate levels, providing preliminary evidence that Ganaxalone's effects may be observed across the broader PCVH19 patient This finding was consistent with our observation in CDD and provides further confidence that Gonaxalone may have anti-seizure effects across broad treatment-refractory epilepsy.

The study was originally designed to further evaluate the hypothesis that baseline endogenous allo pregnant alone sulfate levels may predict <unk> response.

Contrary to the hypothesis that get excellent response observed in this study was independent of allo pregnant alone sulfate levels, providing preliminary evidence that can ask loans effects may be observed across the broader P. C. D. H 19 patient population.

This finding was consistent with our observation and CVD and provides further confidence that can excellent may have anti seizure effects across broad treatment refractory epilepsies.

Alex Aimetti: Lastly, Ganaxalone was generally well-tolerated, with only one Ganaxalone patient discontinuing the study due to an adverse event. All in all, we are very encouraged by these data, despite the study's small sample size. With that, I'll turn the call back to Scott to round out his remarks. Thank you, Alex.

Lastly, and Exelon was generally well tolerated with only one can exelon and patient discontinuing the study due to an adverse event.

All in all we are very encouraged with these data despite the studies small sample size.

With that I'll turn the call back to Scott to round out his remarks.

Thank you Alex we are very pleased with the results of the Violet study.

Scott Braunstein: We are very pleased with the results of the Violet study. The data are highly consistent with our expectations and support our belief in Ganaxalone as an anti-epileptic compound with broad applicability. I would like to thank the Marinus team, our physician investigators, patients suffering from PCDH19, and their families for supporting us through this journey. With the help of Alex and his team, we expect to present data at a scientific meeting later this year, as well as seek a medical journal for publication.

The data are highly consistent with our expectations and support our belief and get and Exelon as an anti epileptic compound with broad applicability.

And would like to thank the mayor and his team are physician investigators patients suffering from P. C D and 19 and their families for supporting US through this journey with the help of Alex and his team we would expect to present data at a scientific meeting later this year as well as seek a medical journal for publication.

As a reminder, this is the first double blind placebo controlled trial and patients suffering from P. C D and 19 related epilepsy.

Scott Braunstein: As a reminder, this is the first double-blind, placebo-controlled trial in patients suffering from PCVH19-related epilepsy. Now, I would like to turn back to the other important events for Marinus as we look forward to the rest of 2021 and beyond.

I would like to turn back to the other important events per Mariners as we look forward to the rest of 'twenty 'twenty, one and beyond we remain guided by our basic principles that the organizations work should be both scientifically sound and fill a meaningful unmet medical need.

Scott Braunstein: We remain guided by our basic principles that the organization's work should be both scientifically sound and fill a meaningful unmet medical need. We believe that our NDA submission for the use of Ganaxalone in the treatment of CDD-related epilepsy, is the next step in developing a sustainable oral franchise to address the meaningful opportunities that we envision over the long While we intend to intensify our commercialization planning efforts in front of a potential mid-year 2022 TDD launch, We continue to progress our oral reformulation and pro-drug endeavors, maintain a focus on our intravenous RFC Phase III Registrational Trial, and evaluate other opportunities for Ganaxalone in additional orphan epilepsy indications.

We believe that our NDA submission for the use of <unk> alone and the treatment of C. D. D related epilepsy is the next step and developing a sustainable oral franchise to address the meaningful opportunities that we envision over the long term.

While we intend to intensify our commercialization planning efforts in front of a potential mid year 2020 two TDD launch we continue to progress our oral reformulation and pro drug endeavors and maintain a focus on our intravenous and our S. E phase three registrational trial.

Oh, and evaluate other opportunities work and acts alone and additional orphan epilepsy indications.

Scott Braunstein: Based on our progress to date, we believe that Ganaxalone's success in CDD, PCDH19, and our early interim analysis in TSC may pave the path for additional future indications. Our investment decisions will be driven by the scientific rationale for using Ganaxolone in other rare epileptics. The commercial opportunities are a growing clinical data set focused on TID dosing and a thorough evaluation of previous Marinus studies, examining trial design, PK data, as well as patient dosing paradigms.

Based on our progress to date, we believe that can excellent success and C. D. D. P. C D. Each 19, and our early interim analysis and T. S. C me pave the path for additional future indications.

And our investment decisions will be driven by the scientific rationale of using index alone and other rare epilepsies. The commercial opportunities are growing clinical data set focused on tid dosing and a thorough evaluation of previous Marinus studies.

Salmon and trial design PK data as well as patient dosing paradigms we.

Scott Braunstein: We believe that Gynaxolone has the potential to become an important drug in a range of rare seizure disorders. To support these efforts, we continue to build the team and strengthen the organization. We've bolstered our commercial, clinical, legal, regulatory, and other operations personnel. During the quarter, we added several members to the leadership team, including Ian Hunt as Vice President, Market Access and Channel Strategy.

We believe that can that saloon has the potential to become an important drug in a range of rare seizure disorders.

To support these efforts, we continue to build the team and strengthen the organization.

We bolstered our commercial clinical and legal regulatory and other operations personnel.

During the quarter, we added several members to the leadership team, including and Hunt as Vice President market access and channel strategy.

Scott Braunstein: And I'll be reporting to Christy Shafer, who has been building out her commercial team, conducting market research, and developing a reimbursement strategy for both franchises. Dr. Ian Miller has officially joined the organization as the Vice President of Clinical Development, reporting to Dr. Joe Hulihan. Ian brings several decades of treating patients with rare epilepsies, has been considered a top-ranked key opinion leader in the field, and has worked with several advocacy organizations in the rare epilepsy space. We are equally pleased to announce that Fred Halperin has joined the organization as Vice President of Marinus Technologies.

And we will be reporting to Christy Shafer, who has been building out her commercial team conducting market research and developing a reimbursement strategy for both franchises.

Dr. <unk> and Miller has officially joined the organization as the Vice President of clinical development and reporting to Dr. Joe Houlihan.

Ian and bring several decades of treating patients with rare epilepsies has been considered a top ranked key opinion leader in the field and has worked with several advocacy organizations and the rare epilepsy space.

We are equally pleased to announced that Fred helper and has joined the organization as Vice President Meredith technology.

Scott Braunstein: Behind the scenes, we've continued to build out our MSL presence and have been focusing on strengthening our patient advocacy relationships, our messaging, and identifying the key centers that are critical to our future success. Finally, a shout out to Sasha, our commercial and strategic leadership, and the creative team for coming up with a fantastic new Marinus logo and helping align our company mission, which encompasses commitment, innovation, and community. I want to stop for a moment and quickly give kudos to the entire Marinus team. They have battled tirelessly to overcome the many obstacles presented by COVID-19.

Behind the scenes, we've continued to build out our MSL presence and had been focusing on strengthening our patient advocacy relationships, our messaging and identifying the key centers that are critical to our future success.

Finally, a shout out to Sasha are commercial and strategic leadership and the creative team for coming up with a fantastic new Marinus logo and helping align our company mission, which is encompasses commitment and innovation and community.

I want to stop for a moment and quickly give kudos to the entire marinus team. They have battled carts tirelessly to overcome the many obstacles presented by COVID-19.

Scott Braunstein: Their efforts have resulted in extremely positive feedback on the quality and thoughtfulness of our clinical trials, and specifically the Phase III RAISE trial. As we see signs of hope that the pandemic has begun to subside, we are now fielding several inbound calls from sites interested and ready to be involved in our own ongoing clinical trials. We believe that both our IV and oral programs will yield important therapeutics in major markets around the world.

Their efforts have resulted in extremely positive feedback on quality and thoughtfulness of our critical trials, specifically the phase III <unk> trial.

As we see signs of hope that the pandemic has begun to subside. We are now fielding several inbound calls from site interested and ready to be involved and our own ongoing clinical trials.

We believe that both our IV and oral programs will yield important therapeutics and major markets around the world. So let me quickly provide the highlights of our IV and oral trials before turning over the call to Joe for a more detailed discussion.

Scott Braunstein: So, let me quickly provide the highlights of our IV and oral trials before turning over the call to Joe for a more detailed discussion. Looking first at our oral programs, I am pleased to announce that interim data from the phase two open-label trial to evaluate the safety and tolerability of adjunctive Gnaxolone treatment in patients with TSE met our safety and efficacy criteria to proceed to a phase three trial, with the first patient expected to be enrolled in the fourth. Once the trial is initiated, we will confirm our expectations for the timing of the top line data. Our goal is to significantly shorten the window between our potential CDD and TSC launches.

Looking first at our oral programs I am pleased to announce that interim data from the phase two open label trial to evaluate the safety and Tolerability of adjunctive <unk> treatment in patients with T. S. C met our safety and efficacy criteria to proceed to a phase three trial.

With the first patient expected to be enrolled in the fourth quarter.

Once the trial is initiated we will confirm our expectations for the timing of the topline data.

Our goal is to significantly shorten the window between our potential C. D. D. N T. S. He launches we also plan to submit and orphan drug designation request for the use of <unk> and T. S. C. Later this year.

Scott Braunstein: We also plan to submit an orphan drug designation request for the use of Ganaxalone in TSC later this year. In January, we received a positive response from the FDA, indicating that the efficacy and safety data from our Phase III marigold study in CDD appear sufficient to support the filing of a new drug application. And as a reminder, the sufficiency of the data to support approval will be determined during the FDA review of the application. We will shortly have our one-year stability data for the oral suspension, as well as a formal update through February of this year from the ongoing Open Label Marigold trial. We are expecting to complete our NDA package by the end of Q2 and make the NDA submission by the middle of this year. This will be followed by a planned Q3 EU submission.

In January we received a positive response from the F D a indicating that the efficacy and safety data from our phase III <unk> study and C. D. D appear sufficient to support the filing of a new drug application and as a reminder, the sufficiency of the data to support approval.

We will be determined during the FDA review of the application.

We will shortly have a one year stability data for the oral suspension as well as a formal update through February of this year from the ongoing open label Marigold trial.

We are expecting to complete our NDA package by the end of Q2 and make the NDA submission by the middle of this year.

This will be followed by a planned Q3 EU submission, we look forward to connect balloon as the first potential FDA and EMEA approved medication, specifically indicated for the treatment of seizures as a result of CDK L <unk> deficiency disorder.

Scott Braunstein: We look forward to Gynastolone as the first potential FDA and EMEA approved medication specifically indicated for the treatment of seizures as a result of CDKL5 deficiency disorder. Keep in mind that if approved, we expect to receive a rare pediatric disease voucher from the FDA. We believe this voucher could be used to significantly strengthen our balance sheet in 2022.

Keep in mind that if approved we expect to receive a rare pediatric disease voucher from the FDA. We believe this voucher could be used to significantly strengthen our balance sheet and 2022.

Scott Braunstein: We are also enthusiastic that we can drive a strategic partnership outside the U.S. for both the oral and IV franchises, and we are targeting to have a specific European partner in place over the summer. This will be critical for a European launch if Ganaxalone is approved in the second half of 2022. Our IB program for the treatment of refractory status epilepticus, the RAISE trial, as mentioned, continues to make good progress. With the gradual reduction in COVID-19 restrictions, we are opening high-quality sites, screening patients, and seeing encouraging trends in early enrollment. We now expect the vast majority of sites to either be enrolling or to be opened by the second quarter.

We are also enthusiastic that we can drive a strategic partnership outside the U S for both the oral and IV franchises and we are targeting to have a specific European partner and place over the summer.

This will be critical for European launch if can ask the loan is approved and the second half of 2020 two.

Our IV program for the treatment of refractory status epilepticus. The raise trial as mentioned continues to make good progress.

With the gradual reduction and COVID-19 restrictions, we are opening high quality sites screening patients and seeing encouraging trends in the early enrollment.

We now expect the vast majority of sites to either be enrolling or to be opened by the second quarter.

Scott Braunstein: As a result, we believe that we are on track to report top-line data in the first half of 2022. Planning continues for a separate RSE trial to be conducted in Europe to support an EU registration, and the trial is planned to commence in the first half of 2022.

As a result, we believe that we are on track to report topline data in the first half of 2020 two.

Planning continues for separate RSC trial to be conducted in Europe to support and EU registration and.

The trial is planned to commence and the first half of 2020 two.

Scott Braunstein: In addition, we continue to receive requests from physicians to use Ganaxalone in the treatment of supra-refractory status epileptic, the most advanced stage of status where patients have failed to respond to IV anesthetics. We firmly believe that cannabis alone can provide a rapid onset of action and a durable effect in patients with SC, and that it can potentially play an important role in preventing the devastating consequences of the most severe forms of uncontrolled seizures.

In addition, we continue to receive requests from physicians to use can ask alone and the treatment of Super refractory status epilepticus. The most advanced stage of status where patients have failed to respond to IV anesthetics.

We firmly believe that <unk> can provide a rapid onset of action and a durable effect in patients with SC and then it can potentially play an important role and preventing the devastating consequences of the most severe forms of uncontrolled seizures.

Scott Braunstein: Before turning the call over to Joe for more detailed clinical discussion, I want to thank our CFO, Ed Smith, who is leaving Marinus to pursue other career opportunities. We have made meaningful progress since Ed joined the company, and he has been a valuable part of our continued development. I speak on behalf of the management team in thanking Ed for his contribution to our success and wishing him well in his future business pursuits. We are happy to announce that Steve Pfanstiel will be joining the organization as our new Chief Financial Officer. Steve has had a diverse career in finance and strategy, with the majority of his professional experience at Johnson & Johnson and, more recently, in leadership roles at Opti-Nose and Life.

Before turning the call over to Joe for more detailed clinical discussion I want to thank our CFO, Ed Smith, who's leading mariners to pursue other career opportunities. We've made meaningful progress since Ed joined the company and he has been a valuable part of our continued development.

I speak for the management team and thanking Ed for his contribution to our success and wishing him well and his future business pursuits.

We are happy to announce that Steve fan steel will be joining the organization as our new Chief Financial Officer.

Deepest set of diverse career in finance and strategy with the majority of his professional experience at Johnson, and Johnson and more recently and leadership roles and often nodes and lifescan.

Joseph Hulihan: We look forward to having him join the organization in the mid-April time. With that, I would now like to turn the call over to our Chief Medical Officer, Joe Hulihan.

We look forward to having him join the organization and the mid April timeframe.

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 good morning, everyone. Marinus is focused on a well-defined and strategically targeted program in the treatment of rare epilepsy, where there is high unmet need and where we believe Ganaxalone has true potential to significantly improve patient outcomes. This year, we expect several key data readouts and regulatory meetings and filings, including submission of an NDA for CDKL5 deficiency disorder or CDD. These activities will further advance ConnexLine formulations in the treatment of rare and often devastating illnesses.

Thank you Scott and good morning, everyone.

Marinus is focused on a well defined and strategically targeted program and the treatment of rare epilepsies, where there is high unmet need and where we believe can exelon has true potential to significantly improve patient outcomes.

This year, we expect several key data readouts and regulatory meetings and filings.

Submission of an NDA for CDK, <unk> deficiency disorder, where CBD.

These activities will further advance and excellent formulations and the treatment of rare and often devastating epilepsy.

Joseph Hulihan: Turning first to our Oral Ganaxialone franchise and Tuberous Sclerosis Complex (TSC). We are conducting a phase two open-label study called the CALM study, where we have targeted enrollment of at least 25 patients at eight sites. I am pleased to report that we expect to reach our enrollment goal within the next few days.

Turning first to our Oregon excellent franchise.

And tuberous sclerosis complex or TFC.

We are conducting a phase two open label study called the <unk> study.

Where we had targeted enrollment of at least 25 patients at eight sites.

And I'm pleased to report that we expect to reach our enrollment goal within the next few days.

Based on current enrollment.

Joseph Hulihan: Based on current enrollment, we've conducted an interim analysis that showed that the study has achieved our efficacy and safety targets for proceeding to phase three. In addition to overall safety and efficacy, the interim analysis provided support for efficacy of Ganaxalone across seizure types, as well as when used as adjunctive treatment with currently available medication, including newer AEDs such as Afinitor and Epidiolex. Top-line data from the study is on track to be available in Q3 2021.

Conducted and interim analysis that showed that the study has achieved our efficacy and safety targets for proceeding to phase III.

In addition to overall safety and efficacy at the interim analysis provided support for efficacy of can actually own across seizure types as well as when used as adjunct treatment with currently available medications, including newer agencies, such as AR inventory and other dialects.

Topline data from this study is on track to be available in Q3 2021.

Based on the interim results, we are planning and and the phase II meeting with the FDA and the second quarter and our meeting with EMA and the third quarter of this year.

Joseph Hulihan: Based on the interim results, we are planning an end of phase 2 meeting with the FDA in the second quarter and a meeting with EMA in the third quarter of this year. We plan to have the first patient enrolled in a phase three trial in the fourth quarter. We are proposing to the FDA that the study will be a double-blind, placebo-controlled, multi-center trial with a planned enrollment of 160 patients from 1 to 65 years of age with genetically confirmed tuberous sclerosis after obtaining baseline data on seizure frequency.

And plan to have the first patient enrolled and a phase III trial and the fourth quarter.

We are proposing to the FDA.

Study will be a double blind placebo controlled multicenter trial with a planned enrollment of 160 patients from 1% to 65 years of age with genetically confirmed tuberous sclerosis complex.

After obtaining baseline data on seizure frequency.

Joseph Hulihan: Study participants will be randomized to ganaxalone or placebo and enter a 16-week double-blind phase. After a titration period lasting four to six weeks, they will receive Ganaxalone at a dose of up to 1,800 milligrams per day in three divided doses or matching placebo, then enter a maintenance phase lasting for the remainder of the double-blind phase.

Participants will be randomized to connect one or placebo and enter a 16 week double blind phase.

After titration period lasting four to six weeks they will receive can actually at a dose of up to 1800 milligrams per day, and three divided doses or matching placebo.

And then enter a maintenance period lasting for the remainder of the double blind phase.

Following this they will have the opportunity to enter and open label extension and which all participants will receive can excellent.

Joseph Hulihan: Following this, they will have the opportunity to enter an open-label extension in which all participants will receive GNAC, positive data, and CD. The encouraging Interim Phase II data in TSC and the PCVH19 data that Alex presented are all supportive of what we believe to be Ganaxalone's broad-spectrum efforts across different seizure types, both focal and general. Returning to CDD, I'm pleased to report that we've had fruitful and encouraging discussions with the FDA in advance of our NDA filing.

Our positive data and C D D.

And encouraging interim phase two data and TLC and the P. C. D. H 19 data that Alex presented are all supportive of what we believe to be can excellence broad spectrum efficacy across different seizure types, both focal and generalized.

Returning to CBD and I'm pleased to report that we've had fruitful and encouraging discussions with the FDA and advance of our NDA filing.

And we appreciated the concern of the FDA that the robustly positive results of the Marigold study and CVD follow older studies that failed to demonstrate efficacy and particular, a phase III study of focal seizures in adults that was discontinued in 2016.

Joseph Hulihan: We appreciated the concern of the FDA that the robustly positive results of the Marigold study in CDD follow older studies that failed to demonstrate efficacy, in particular a phase 3 study of focal seizures in adults that was discontinued in 2016. A key insight from our review of the data from that and other studies was the importance of three times a day dosing, as we used in the Marigold study, versus twice daily dosing in the focal onset seizure trial.

A key insight from our review of the data from that and other studies was the importance of three times a day dosing as we used and the Marigold study.

Versus the twice daily dosing and the focal onset seizure trial.

Joseph Hulihan: We believe that this information and the consistent results of the Marigold study satisfied the agency that the data from a single study in CDD could support the NDA file. We plan to follow the filing of the NDA very quickly with our EU submission.

We believe that this information and the consistent results from the Marigold study satisfy the agency the data from our single study and CBD could support the NDA filing.

We plan to follow filing of the NDA very quickly with our EU submission.

Yeah.

The open label extension of the Marigold study is ongoing.

Joseph Hulihan: The open-label extension of the Marigold study is ongoing, and we're planning analysis of long-term data to evaluate the durability of effective Ganaxalone and CDD, a disorder that's characterized by a loss of effect of AED treatment over time. The data from the Open Label Extension will be included in our NDA submission. The Marigold study demonstrated the efficacy of the Ganaxalone three times a day regimen in C. Analysis of the PK-PD profile from this and other studies gives us great confidence in the ability of Ganaxalone to demonstrate anticonvulsant efficacy in other refractory epilepsy in our IV franchise.

And we're planning analysis of long term data to evaluate the durability of effect you can ask alone and C. D D.

A disorder that is characterized by a loss of effect of H E D treatment over time.

The data from the open label extension will be included in our NDA submission.

The Marigold study demonstrated the efficacy of book and excellent three times, a day regimen and CTD.

Analysis of the PK and PD profile from this and other studies gives us great confidence and the ability of can exelon to demonstrate antique and ballston efficacy and other refractory epilepsies.

And our I V franchise, we announced that we have enrolled our first patient and the raise trial in refractory status epilepticus, and we continue to screen and enroll additional patients.

Joseph Hulihan: We announce that we have enrolled our first patient in the RAISE trial in refractory status epilepsy, and we continue to screen and enroll additional patients. However, in the early phase of study startup, the COVID-19 pandemic diverted hospital resources and slowed site activity. However, the pace of hospitals coming back online for study enrollment has accelerated, and we expect to have most sites activated by the end of the second quarter. We're getting positive feedback that investigators are excited about the study and eager to begin enrolling patients. We clearly see momentum building.

And the early phase of study start up the COVID-19, pandemic diverted hospital resources and slowed site activation. However, the pace of possible is coming back online for study enrollment has accelerated and we would expect to have most sites activated by the end of the second quarter.

We're getting positive feedback from investigators are excited about the study and eager to begin enrolling patients.

And we clearly see momentum building.

Joseph Hulihan: Based on this and the early signals about the pace of enrollment, we remain on track for a top-line data readout in the first half of 2022. As we mentioned last quarter, we're initiating a trial evaluating Ganaxolone earlier in the treatment continuum of status epileptic, in the stage known as established status epilepticus or ESE, where patients have failed the first line of treatment with benzodiazepine. It's estimated that there are approximately 50,000 to 75,000 cases of ESE per year in the U.S.

Based on this and the early signals about the pace of enrollment we remain on track from a topline data readout and the first half of 2020 two.

As we mentioned last quarter, we are initiating a trial evaluating can actual earlier and the treatment continuum status epilepticus.

And the stage known as established status epilepticus or ESC.

Where patients have failed the first line of treatment with benzodiazepines and.

Estimated there are approximately 50 to 75000 cases of ESC per year and the U S.

Joseph Hulihan: The trial is targeting patients presenting to the emergency room with convulsive status epilepsy, with a study design and patient population that parallel those of the ESET trial published last year in the New England Journal of Medicine. We believe one of the keys to a successful trial in ESC is the engagement of centers with experience in obtaining community consent and in conducting studies involving the urgent care of patients with status epilepsy. That's why we're enlisting many of the same centers that participated in ESET.

The trial is targeting patients presenting to the emergency room with convulsive status epilepticus with.

And with the study design and patient population the parallel those of the he set trial published last year and the New England Journal of Medicine.

We believe one of the keys to a successful trial and ESC is engagement of centers with experience and obtaining community consent.

And and conducting studies involving the urgent care of patients with status epilepticus.

That's why we're and listing many of the same centers that participated and <unk> studies.

We anticipate that patients seen and emergency departments and this earlier stage of status and who have convulsive, rather than nonconvulsive status, maybe more treatment responsive compared to patients enrolling and the raise study.

Joseph Hulihan: We anticipate that patients seen in emergency departments in this earlier stage of status, and who have convulsive rather than non-convulsive status, may be more treatment responsive compared to patients enrolling in the RAISE study, who will have refractory, primarily non-convulsive seizures. This means that the dose of Ganaxalone necessary for status control will likely be lower than that in the race. So we are thinking carefully about the doses and the duration of therapy that will be required.

Who will have refractory primarily nonconvulsive seizures.

This means that the dose who can actually necessary for status control will likely be lower than that and the raise study.

So we're thinking carefully about dosing and the duration of therapy that will be required.

The study design, we plan to propose to the FDA involves the initiation of IV can ask alone at the same time as the first AEP following benzodiazepine failure.

Joseph Hulihan: The study design we plan to propose to the FDA involves the initiation of Ivecanaxelone 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 Ganaxin, with the optimal dose progressing to a double-blind phase two study versus placebo. We plan to initiate the ESE study in early 2022 after we've completed the process of exception from informed consideration.

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

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

We plan to initiate the <unk> study in early 2022. After we've completed the process of exception from informed consent.

Joseph Hulihan: It's important to note that patients who qualify for this trial have a condition distinct from those with refractory status epilepsy who would enter the RAISE trial. Thus, we can consider the same sites for our established status trial without compromising enrollment in the race.

It is important to note that patients who qualify for this trial have a condition distinct from those with refractory status epilepticus.

And enter the raise trial.

So we can consider the same sites for our established status trial without compromising enrollment and the rate study.

Joseph Hulihan: Quickly following up on Scott's comments about the emergency use of Ganaxalone in super refractory status epileptics, we continue to supply medication in response to emergency IND requests. Though this condition is not on the immediate horizon for a formal trial, we are learning a lot about the dosing paradigm for gonaxalone in this very serious condition, which is informing our knowledge about its dosing and potential efficacy throughout the treatment continuum of status epilepsy. Once again, I'd like to thank the patients and their families who participate in these trials.

Quickly following up on Scott's comments about the emergency use or can ask alone and.

Super refractory status epilepticus.

We continue to supply medication and response to emergency IND requests.

So this condition is not on the immediate horizon for a formal trial.

We're learning a lot about the dosing paradigm for Kodak's alone and this very serious condition.

Which is informing our knowledge about what's dosing and potential efficacy throughout the treatment continuum of status epilepticus.

Once again I'd like to thank the patients and their families who participate in these trials.

Joseph Hulihan: Through your support, we're making significant progress in our efforts to improve the lives of all patients and families suffering from these often debilitating neurologic disorders. With that, I'll turn the call over to Dr. Alex Aimetti. Thank you, Joe. I share Scott and Joe's excitement about the progress that we have achieved across our entire clinical development pipeline, as well as the promise of what lies ahead. So, let me provide some additional insight into each of those areas.

Through your support and we're making significant progress and our efforts to improve the lives of all patients and families.

Suffering from these often debilitating neurologic disorders.

With that I'll turn the call over to Dr. Alex and Eddie.

Alex.

Thank you Joe.

I share Scott and Joe's excitement about the progress that we have achieved across our entire clinical development pipeline as well as the promise for what lies ahead.

So let me provide some additional insight into each of those respects.

Alex Aimetti: First, in December, we presented additional clinical data from the Marigold study in CDD at the annual American Epilepsy Society meeting. There, we communicated data indicating a consistent efficacy signal for Ganaxalone across multiple patient subgroups, demonstrating the potential for Ganaxalone across the broad CDD population. In addition, we provided evidence suggestingive of Ganaxalone's anti-seizure durability in a preliminary analysis of the open-label data, which demonstrated that patients experienced a median 52.7% reduction in major motor seizure frequency when on Ganaxalone for approximately one year.

First in December we presented additional clinical data from the Marigold study and CBD at the annual American Epilepsy Society meeting.

There, we communicated data, indicating a consistent efficacy signal a FERC and acts alone across multiple patient subgroups, demonstrating the potential for <unk> across the broad CDB population.

In addition, we provided evidence suggestive and excellence anti seizure durability and a preliminary analysis of the open label data, which demonstrated that patients experienced immediate and 52, 7% reduction and major motor seizure frequency when I'm going to ask loan for approximately one year.

We believe this supports a durable effective and exelon and as we have said before durability of anti seizure medication is of enormous need to the CTD community and see this as a potential key differentiator from existing therapies.

Alex Aimetti: We believe this supports a durable effect of Ganaxolone. And as we have said before, durability of anti-seizure medication is of enormous need in the CDD community, and we see this as a potential key differentiator from existing therapy. We look forward to sharing additional open-label data demonstrating the longer-term effects of Ganaxalone at upcoming medical meetings. And lastly, we presented data suggesting higher average gonaxal and plasma concentrations correlated with improved seizure frequency reductions in CDD patients.

We look forward to sharing additional open label data demonstrating the longer term effects have been excellent at upcoming medical meetings.

And lastly, we presented data, suggesting higher average can excellent plasma concentrations correlated with improved seizure frequency reductions in <unk> patients.

Alex Aimetti: These data provided additional evidence of Ganaxalone's drug effect and further supported three times a day dosage. And as a reminder, the Marigold study was the first phase 3 study of Ganaxalone that evaluated three times a day dosing, which aims to improve trough concentrations to levels that we believe are important to show a meaningful anti-seizure effect compared to 2 times a day dosing. Consequently, we feel confident that these findings demonstrate the broad anti-seizure effects of Ganaxalone when dosed appropriately and can be extended to other chronic epilepsy patient populations, including TSC, as well as other future rare epilepsy indications with high unmet need, where three times a day dosing would be appropriate.

And these data provided additional additional evidence of <unk> drug effect and further support three times a day dosing.

And as a reminder, the Marigold study was the first phase III study of <unk> that evaluated three times, a day dosing, which aims to improve trough concentrations to levels that we believe are important to show a meaningful anti seizure effect compared to two times a day dosing.

Consequently, we feel confident that these findings demonstrate the broad anti seizure effects of gyn exelon, when dosed appropriately and can be extended to other chronic epilepsy patient populations, including TLC as well as other future rare epilepsy indications with high unmet need where three times a day dosing.

And would be appropriate.

Ed Smith: In addition, these findings support our ongoing efforts to develop improved oral Ganaxalone formulations aimed to deliver higher, more consistent Ganaxalone levels, which could expand the opportunities to broader patient populations in need. Again, I'm very excited about our recent pipeline progress and the future scientific and clinical direction that Marinus is headed. With that, let me turn the call over to our CFO, Ed Smith, for a review of our financials. Thank you, Alex, and good morning, everyone.

In addition, these findings support our ongoing efforts to develop improved Oregon excellent formulations aimed to deliver higher more consistent and ex loan levels, which could expand the opportunities to broader patient populations and need.

And again I'm very excited about our recent pipeline progress and the future scientific and clinical direction that Meredith is headed.

With that let me turn the call over to our CFO Ed Smith for a review of our financials.

Thank you Alex and good morning, everyone.

Ed Smith: Our results for fiscal 2020 reflect results from operations and capital initiatives in support of Ganaxial on development and commercial preparedness activities. As a result of the BARDA contract, we recognized $1.5 million and $1.7 million in federal contract revenue for the three and 12 months ended December 31, 2020, respectively. There were no such revenues a year ago.

Our results for fiscal 'twenty, and 'twenty reflect results from operations and capital initiatives in support of Exelon development and commercial preparedness activities.

As a result of the BARDA contract, we recognized $1 5 million at $1.7 million and federal contract revenue for the three and 12 months ended December 31 2020, respectively.

And there were adult like revenue a year ago as a reminder, our base BARDA contract. Initially provides $21 million of non dilutive funding over the approximately next 24 months most of which will be directed towards our phase III program and refractory status epilepticus with auctions based on success milestones there.

Ed Smith: As a reminder, our base BARDA contract initially provides $21 million of non-dilutive funding over the approximately next 24 months, most of which will be directed towards our Phase 3 program in refractory status epilepsy. With options, based on success milestones, their funding may increase to $51 million. Research and development expenses increased to $13 million and $51.1 million for the three and 12 months ended December 31, 2020, respectively, as compared to $12.5 million and $43 million for the same periods in the prior year.

Funding may increase to $51 million.

Research and development expenses increased to $13 million and $51 1 million for the three and 12 months ended December 31, 2020, respectively as compared to 12, and a half million and 43 million for the same periods and the prior year.

Ed Smith: The increase over the year-to-year period was due primarily to costs associated with enrollment in our CDD trial. Expenses in the current year also reflect increased drug development activity, including preclinical studies and manufacturing activities in preparation for a potential NDA filing for CDD, as well as the recently initiated Phase III clinical trial in RSC. General and administrative expenses increased to $6 million and $18.6 million for the three and 12 months ended December 31, 2020, respectively, compared to $3 million and $11.5 million for the same periods in the prior year.

The increase over the year to year period was due primarily to costs associated with the enrollment and our CVD trial expenses and the current year also reflect increased drug development activity, including preclinical studies and manufacturing activities in preparation for a potential NDA filing for CBD as well as the recently in this.

<unk> phase III clinical trial and RSC.

General and administrative expenses increased to $6 million and $18 6 million for the three and 12 months ended December 31, 'twenty, and 'twenty, respectively, compared to $3 million and $11 5 million for the same periods and the prior year.

Ed Smith: The primary drivers of the increase over fiscal 2019 were increased legal and consulting fees of $2.7 million. Personnel costs also rose by $1.5 million from a year ago, as we increased headcount to support the scaling up of the company's operations and prepare for potential commercialization. Compared to a year ago, non-cash stock-based compensation was up $1.6 million.

The primary drivers of the increase over fiscal 2019 were increased legal and consulting fees of $2 7 million.

Personnel costs also rose by one and a half million from a year ago as we increased headcount to support the scaling up of the Companys operations and prepare for potential commercialization.

Compared to a year ago noncash stock based compensation was up $1 6 million.

Ed Smith: The company reported net losses of $17.5 million and $67.5 million for the 3 and 12 months ended December 31, 2020, respectively, compared to $15.4 million and $54.1 million in the same period a year ago. Cash used in operating activities increased to $60.9 million for the year ended December 31, 2020, compared to $48.6 million for the same period a year ago. At December 31, 2020, we had cash, cash equivalents, and investments of $140 million, which will enable us to fund the company's current scale of operating expenses and capital expenditures into the second quarter of 2022.

The company reported net losses of $17 5 million and $67 5 million for the three and 12 months ended December 31, 2020, respectively compared to $15 4 million and $54 1 million and the same period a year ago.

Cash used in operating activities increased to $69 million per the year ended December 31, 2020, compared to $48 6 million for the same period a year ago.

At December 31, 2020, we had cash cash equivalents and investments of $140 million, which will enable us to fund the company's current scale of operating expenses and capital expenditures into the second quarter of 2022.

Ed Smith: We project spend in the range of $18 to $20 million per quarter, offset by approximately $2 to $3 million per quarter in revenue from BARDA. This spend could kick up in the third quarter with the initiation of the TSE trial and ongoing expenses associated with the RSE trial. Keep in mind that these projections do not include potential resources that could be realized through the monetization of the Priority Review Voucher or through European partnership.

And we project spend and the range of $18 million to $20 million per quarter offset by approximately two to 3 million per quarter and <unk>.

Revenue from BARDA this spend could tick up in the third quarter with the initiation of the <unk> trial and ongoing expenses associated with the RSV trial.

Keep in mind. These projections do not include potential resources that could be realized through the monetization of the priority review voucher or through European partnership.

Ed Smith: Before heading to call back to Scott for some closing remarks, as Scott mentioned, I will be leaving Marinus. I would like to thank our investors for their continued support and confidence in our program. While I've enjoyed and will miss working with many friends and colleagues at Marinus, I am excited for Marinus' future, and I am proud of the finance organization that I now turn over to Steve, who will lead the next leg of what promises to be an exciting journey.

Before handing the call back to Scott for some closing remarks, as Scott mentioned I will be leaving Marinus I would like to thank our investors for their continued support and confidence and our programs, while I've enjoyed and we'll miss working with many friends and colleagues at Marinus I and exciting for Marinus as future and I am proud of the finance organization.

And that I now turn it over to Steve who will lead the next leg of what promises to be and exciting journey.

Ed Smith: I expect a smooth transition and will be on the sidelines as a Marinus shareholder, rooting for Scott and the rest of the Marinus team in what promises to be a bright future. I will now turn this call back to Sasha Damouni to highlight some of the efforts in advocacy and branding.

I expect a smooth transition and will be from the sidelines as emeritus shareholder rooting for Scott and the rest of the Marinus team and what promises to be a bright future.

I will now turn the call back to Sochi Mooney to highlight some of the efforts and advocacy and branding Sasha.

Sasha Damouni Ellis: Thanks, Ed. We recognize the value of meaningful partnerships and collaborations with patient organizations who serve communities that we are striving to bring beneficial change to. Recently, we've made considerable efforts to strengthen existing and build new relationships with key organizations within the CDD, tuberous sclerosis, PCDH19, status epilepticus, and broader epilepsy communities. We aim to work alongside these groups to help increase disease awareness and education in an effort to improve the overall quality of care. We thank the organizations for their partnership and believe we can more efficiently progress the field by working together.

Thanks, Ed.

And is the value of meaningful partnerships and collaborations with patient organizations, who serve communities that we're striving to bring beneficial change tail recently, we've made considerable efforts to strengthen existing and build new relationships and key organizations within the C. D. D. Tuberous sclerosis P. C D H 90.

<unk> status epilepticus and broader epilepsy communities.

We aim to work alongside these groups to help increase disease awareness and education and an effort to improve the overall quality of cash we think the organizations for their partnership and believe we can more efficiently progress the field by working together.

As mentioned earlier, we have rolled out our expanded access program, providing access to <unk> for patients who did not participate and the Marigold study and we are working closely with the advocacy groups for awareness throughout the patient community.

Sasha Damouni Ellis: As mentioned earlier, we have rolled.

Sasha Damouni Ellis: We have out our expanded access program, providing access to Ganaxalone for patients who did not participate in the Marigold study, and we are working closely with advocacy groups for awareness throughout the patient community. I'd also like to mention that Marinus has launched a new branding campaign and logo to highlight our guiding principles of commitment, innovation, and community. We believe we are at an inflection point in our company's history, with the potential launch of our first treatment, and believe that we should communicate these principles broadly to our important stakeholders, including patients, their families, the epilepsy community, the medical community, and our investors. With that said, I would like to turn the call back to Scott before we enter the Q&A portion of the webinar.

I'd also like you mentioned that Meredith has launched a new branding campaign and logo to highlight our guiding principles of commitment and innovation and community. We believe we are at an inflection point and our company's history with the potential launch of our first treatment and believe that we should communicate broadly these principles two hour and.

Important stakeholders, including patients their families the epilepsy community the medical community and our investors.

With that I would like to turn the call back to Scott before we enter the Q&A portion of the call Scott.

Operator: Q&A portion of the call.

Scott Braunstein: Thank you, Sasha. Once again, on behalf of everyone here at Marinus, I want to wish Ed the best of success in his future endeavors. Before opening the call to questions, just let me conclude with a few final thoughts. Importantly, we are dedicating resources to future oral formulation development in the hopes of achieving improved PK properties that could ultimately lead to incremental clinical efficacy. We have recently filed a series of patents that support two of these ongoing research efforts. Our current goal is to have at least one second-generation formulation in the clinic by 2022.

Thank you Sasha once again on behalf of everyone here at Marinus I want to wish and the best of success and its future endeavors.

Before opening the call to questions. Just let me conclude with a few final thoughts and importantly, we are dedicating resources for future oral formulation development and the hopes of achieving improved PK properties that ultimately could lead to incremental clinical efficacy.

We have recently filed a series of patents that support two of these ongoing research efforts. Our current goal is to have at least one second generation formulation in the clinic in 2022.

Scott Braunstein: Additionally, we continue to expand and strengthen our organization. We have added recent high-quality hires throughout the team, including Clinical Operations, Regulatory, Human Resources, and Legal, to name just a few. We are thrilled to have Steve Fansil, our incoming CFO, join the team next month. We expect to have heads of both sales and marketing hired by the middle of this year as Christy Shafer continues to round out her senior leadership team for the commercial organization.

Additionally, we continued to expanded strength in our organization, we have added reach and high quality hires throughout the team, including clinical operations regulatory human resources and legal to name just a few we are thrilled to have Steve and sell our incoming CFO join the team next month.

We expect to have head of both sales and marketing hired by the middle of this year as Christie Schieffer continues to round out our senior leadership team for the commercial organization.

Scott Braunstein: And finally, let me echo the sentiments of everyone here at Marinus when I say how grateful we are for the continued commitment and dedication of the study site personnel, our investigators, our patients, and their families, as well as everyone who has been supportive of the company's efforts through these trying times. I also want to thank the Marinus team that has worked tirelessly through what feels like thousands of Teams and Zoom calls and has not been deterred by the headwinds created by the ongoing pandemic. And with that, we will now open the call for questions. Operator, Thank you. If anybody would like to ask a question at this time, please press star 1 on your telephone keypad.

And finally, let me echo the sentiments of everyone here at Marinus when I say, how grateful we are for their continued commitment and dedication of the study site personnel, our investigators our patients and their families as well and everyone who has been supportive of the company's efforts through these trying times.

Also want to thank the mayor and his team that has worked tirelessly through what feels like thousands of teams and zoom calls and have not been deterred by the headwinds created by the ongoing pandemic and.

And with that we will now open the call for questions operator.

Thank you if anybody would like to ask a question at this time case press star one on your telephone keypad again and that would be star one on your telephone keypad.

Operator: Again, that would be star 1 on your telephone keypad. Your first question comes from Joseph Thome from Cowen & Company. Your line is open.

First question comes from Joseph Thome from Cowen and company. Your line is open.

Joseph John: Hi there. Thank you for taking my questions and congratulations to Ed and the rest of the team on some great progress. The first question for me is just on TSC. You indicated that the interim analysis met the efficacy and safety targets that you had laid out. If you could just give us a little bit more detail on maybe what that efficacy target was that gave you the confidence to move into Phase 3. And then second, as you are approaching CDD and have some positive TSC data here, maybe how are you thinking about initial pricing decisions and kind of what information has gone into that? Thank you.

Hi, there. Thank you for taking my questions and congratulations to Ed and the rest of the team on that and some great progress.

First question for me is just thought and T. S. C. You indicated the interim analysis.

The efficacy and safety targets that you had laid out.

You could just give us a little bit more detail on maybe what that efficacy target was that that gave you the confidence to move into phase III.

And then second as you are approaching C. D D and have some positive GSE data here, maybe how are you thinking about initial pricing decisions and kind of how and what information has gone into that thank you.

Scott Braunstein: Good morning, Joe. Thanks for the question. This is Scott.

Good morning, Jos Thanks for the question says Scott, Let me, let me handle the TFC question.

Scott Braunstein: Let me handle the TSC question. As Joe mentioned in his prepared remarks, we looked at several criteria for the Phase 3 go-no-go decision. We looked at overall efficacy, and we were looking for a consistent signal similar to what we've seen now in CDD and PCDH19. That is, a meaningful number of patients overall having what we view as an important clinical response. Secondly, Joe spent a lot of time looking at seizure types, and we wanted to see a differentiation in improvement between different seizure types, and I'll let Joe expand on that.

So so as Joe mentioned in his prepared remarks, we looked at several criteria for the phase III go no go decision, we looked at overall efficacy and we were looking for a consistent signal similar to what we've seen now and TDD and <unk> 19, and that is a meaningful number.

Patients overall, having what we view as an important clinical response and secondly, we Joe spent a lot of time looking at seizure types.

And we wanted to see a differentiation in improvement and different seizure types and I'll, let Joe expand on that third I think it was critically important from a commercial standpoint that we see efficacy in patients who were refractory to all standards of care, including Epidiorite.

Scott Braunstein: Third, I think it was critically important from a commercial standpoint that we see efficacy in patients who were refractory to all standards of care, including epidiolex, and we had several patients in the Phase 2 study who were either on epidiolex or who had failed epidiolex, and that was an important go decision for us. And I think, finally, we were looking for what we typically would think about as a responder analysis where patients are having 40 or 50 percent response rates and looking at the percent of patients who are having meaningful clinical responses.

And.

And then and we've had several patients from the phase two study, who who are either on <unk> sales at the dialogues and we are in a week that was an important go decision for us.

And I think finally, we were looking for what what we typically would think about as you know.

A responder analysis, where patients are having 40 or 50% response rates and looking at the percent of patients who are having meaningful clinical responses. So all of those factors played into our decision and we're not going to give any more specifics on that.

Scott Braunstein: So all of those factors played a role in our decision. But we're not gonna give any more specifics on that. Before I turn it over to Christy to talk a little bit more about pricing, Joe, anything else you wanna add to our TSC decision? Yeah, well, hi Joe. Scott mentioned seizure types, and you know, we know from CDD, the drug has efficacy across what we call major motor seizures, drop attacks, and convulsions. Those are generalized seizures. In TSC, the patients predominantly have focal seizures because they have lesions in the brain.

Before I turn it over to Kristy to talk a little bit more about pricing Joe anything else you want to add on our on that.

On our TLC decision.

Yeah, well hydro and Scott mentioned seizure types and.

We know from TDD.

The drug has efficacy across.

What we call major motor seizures drop attacks and convulsions those are generalized seizures and TLC.

And is predominantly a focal seizures because they have lesions often in the brain.

Joseph Hulihan: So the seizures start in one location, focally. And I just wanted to make sure that we showed the same trend in efficacy in the focal seizures as we did in the generalized seizures. And we saw a good signal there. So that was part of the decision to proceed. Christy, would you like to jump in and talk a little bit about pricing? Yeah, absolutely. Thanks, Scott. It's a pleasure to meet you, Joe.

So the seizure start in one location and hopefully and I just wanted to make sure that we showed the same trends and efficacy and the focal seizures as we do and the generalized seizures and we saw good signal there so that.

And that was part of the decision to proceed.

Christie you want to jump in and talk a little bit about pricing.

Yeah, absolutely, thank Scott and it's a pleasure to meet each other thanks for the question.

Christy Shafer: Thanks for the question. As you can imagine, we're dedicating a significant amount of time to our pricing and value construct for both the oral suspension and our IV franchises. So specific to CDD, to establish our value, we've done quite a bit of work that's been dedicated to understanding our patient journey, their treatment landscape, and any access hurdles there are for our patients. So understanding that for CDD, we'll be the first and only indication brings a lot of optionality.

You can imagine we're dedicating a significant amount of time and to our pricing and value contract from both the oral suspension and our other franchises. So specific to C. D day to establish our value we've done quite a bit of work that's been dedicated to understanding our patient journey and.

Their treatment landscape and any access hurdles there are for our patients so understanding that for Citi D and.

And we will be the first and only indicated and brings a lot of optionality. However, we're designing our thoughts around both indications.

Christy Shafer: However, we're designing our thoughts around both indications. So both CDD and TSE fall into a traditionally defined orphan disease model, and we have prior launches both in and out of the space to look to as reference points. So nonetheless, we have confidence in Ganaxone's ability to address the significant unmet need and the fact that it's highly differentiated. So where we ultimately land on price will reflect that.

Both C D and TSA fall into a traditionally defined orphan disease model and we have prior launches both in and out of the space to look to as reference points. So nonetheless, we have confidence and connect line's ability to address the significant unmet need and the fact that it's highly differentiated so where are we ultimate.

<unk> price will reflect that.

Christy Shafer: And your next question will come from Douglas Tsao from H.C. Wainwright. Your line is open. Hi, good morning. Thanks for taking the questions.

Great. Thank you so much.

And your next question will come from Douglas Tsao from H C. Wainwright Your line is open.

Hi, good morning, Thanks for taking my questions.

Douglas Dylan Tsao: Joe, as a follow-up to that last comment, obviously, with the TSC data, we've now gotten some evidence of effect in both general as well as focal onset seizures. I'm just curious, you know, for you Joe as well as Scott, what does that potentially mean in terms of future development? How does that affect your thinking about development across epilepsy? Yeah, that's a good question.

Joe as a follow up to that last comment obviously with the TSA data, we've now gotten some evidenced of.

And while general as well as focal onset seizures and I'm just curious.

For for you guys as well as Scott you know what does that potentially mean.

In terms of the future development, how does that affect your thinking about development across epilepsy.

Yeah, that's a good question.

Joseph Hulihan: I am. I think it gives us confidence about the drug being a broad spectrum agent. As I mentioned in the remarks, one of the older studies in focal seizures, the phase three study failed to show efficacy in phase three, although it didn't in phase two; the larger study it did not. So now this gives us confidence about the seizure types and then also further reinforces the PK aspect of it, with three times a day dosing. With this formulation, it's important to have adequate levels throughout the day, so I think it tells us something about that as well.

I am.

I think it gives us confidence about the drug being a broad spectrum agent.

As I mentioned and the remarks.

One of the older studies and focal seizures, a phase III study failed to show efficacy.

And in phase III, although it didn't face to the larger study did not so now this gives us confidence about the seizure types and then also further reinforces.

The PK aspect of it was three times a day dosing.

And with this formulation that's important too.

And have adequate levels throughout the day so.

You could tell us something about that as well.

And.

Scott Braunstein: And, you know, Scott, you've also spoken a lot about sort of new formulations. How quickly do you think those could be sort of advanced into the clinic? And obviously, how do you sort of weigh that balance between advancing with the current formulation, which seems to be having quite a good effect, versus, you know, perhaps slowing down, but advancing with the formulations that could have, you know, better commercial potential or just sort of clinical effect? Thank you.

Scott you've also spoken a lot about sort of new formulations and how quickly do you think those could be sort of advanced into the clinic and and.

And obviously, how do you sort of weigh that balance between advancing with the current formulation, which seems to be having quite a good effect versus perhaps slowing down but advancing with the formulations that that could have better commercial potential or just sort of clinical effect. Thank you.

Scott Braunstein: Yeah, thanks for the question, Doug. I think at least what we've shared with you in the CDD trial, certainly in the PCDH19 trial, and our early look at the TSC data, we're seeing a consistent signal of somewhere between 7 and 8 out of 10 patients having a meaningful clinical response. And we think that meaningful clinical response is clearly tied to drug PK, bioavailability, absorption, and serum concentrations. So we know from our market research that if we have a meaningful effect that's durable in these patients, that's a very important drug.

Yeah. Thanks for the question, Doug I think at least what we've shared with you and the CTD trial, certainly and the PCH 19 trial and are our early look at the T. S. C data, we're seeing a consistent signal of somewhere between seven and eight out of 10 patients having a meaningful clinical response.

And we think that meaningful clinical responses and clearly tied to drug PK bioavailability absorption and serum concentrations. So we know from our market research that if we have a meaningful effect that's durable and these patients that's a very important drug and.

Scott Braunstein: And to your comments, Doug, we feel very good and the best I've ever felt about our current oral suspension three times a day dosing. That being said, I think we can make this drug incrementally better. I would like to see all patients have good absorption. I'd love to give physicians the opportunity to dose titrate. If patients, let's say, are absorbing and having blood levels somewhere between 50 and 75 nanograms per ml and still having seizures, physicians could titrate them to 100 to 150 nanograms per ml.

And to your comments, Doug we feel very good and the best certainly I've ever felt about our current oral suspension and three times a day dosing that being said I think we can make this drug incrementally better I would like to see all patients have good absorption I'd love to have physicians give physicians the opportunity to dose.

Titrate if patients let's say are.

Absorbing and having blood level somewhere between 50, and 75 nanograms per ml and still having seizures debt positions could titrate to a 100 to 150 nanograms per ml. We are quite convinced that that would have a meaningful effect on the number of seizures patients are having so we're really targeting.

Scott Braunstein: We are quite convinced that that would have a meaningful effect on the number of seizures patients are having. So we're really targeting those two parameters in our second generation programs, and we certainly believe it will incrementally improve the efficacy of the drug. We've talked about it a lot, Doug, that we have a few different formulation plans in place. They're not expensive.

Two those two parameters and our second generation programs and we certainly believe it will incrementally improve the efficacy of the drug we we've talked about it a lot Doug that we have a few different formulation plans in place theyre not expensive we've made a tremendous amount of progress as I commented on the cash.

Scott Braunstein: We've made a tremendous amount of progress. As I commented on the call, we've now filed a series of patents on at least two different novel formulations. We're excited about that, and we think we can move pretty quickly.

We've now filed a series of patents and at least two different novel formulations and we're excited about that.

And and and we think we can move pretty quickly and and our hope is to have one of these compounds in the clinic and 22, possibly too.

Scott Braunstein: And our hope is to have one of these compounds in the clinic in 22, possibly two in 22. And again, we'd be looking to incrementally drive the efficacy of the drug. And I think it never would hurt to smooth the peaks and troughs of a drug that you're looking for a study, so let me stop there and operator, thanks Doug, let's move on to the next question because we're a little tight on time. Okay.

In 'twenty, two and again, we'd be looking to incrementally drive the efficacy of the drug and it and.

And I think it never would hurt to smooth the peaks and troughs of a drug that youre looking for steady state doses.

So let me stop there and operator, thanks, Doug let's move on to the next question because we're a little tight on time today.

Operator: Okay, your next question will come from Althea Young from Canter. Your line is open.

Okay. Our next question will come from Alethia Young from Cantor Your line is open.

Althea Young: Hey guys, thanks for taking my question, and Ed, wishing you all the best and great working with you. So, a couple of questions. Can you just talk a little bit about RSE, your decision to make a separate study in Europe, is that potentially due to kind of different treatment protocols there for refractory status? And then just another question, can you just talk a little bit more about the safety event, the series A that was seen in the CCDH study that was attributed to Naxalone?

Hey, guys. Thanks for taking my question and Ed wishing you all the best and and Great working with you. So a.

A couple one can you just talk a little bit about with R&D. You know your decision to make a separate study in Europe and that potentially do that kind of different treatment protocols there for refractory status.

And then just another question can you just talk a little bit more about the the thinking of that in theory and that was seen.

And I think he'd be a study that was attributed to the Max alone I mean do you think they can make.

Althea Young: I mean, do you think there's anything to be made there, you know, as it relates to the assay? I mean, I know it's well characterized and it's pretty low rate, but I just wanted to get some color there, I think.

There.

The asset and I know with well characterized and it's pretty low range that doesn't like bold color there. Thanks.

Scott Braunstein: Yeah, Scott, I could take those. So in terms of the serious adverse event, I'll take that one first. It was what the investigator characterized as psychogenic seizures and attributed to the drug. I won't say anything that, you know, minimizes the event.

Yes, Scott and I can take those.

So in terms of the serious adverse event.

And I'll take that one first it was but what the investigator characterized psychogenic seizures and attribute it to the drug.

And I won't say anything that minimises the event I think that.

Joseph Hulihan: I think that the patient needed to be admitted for EEG monitoring to characterize the event. And because it was a hospitalization, that means it's a serious adverse event. The severity was characterized as moderate. You know, psychogenic seizures are sometimes called, not by more contemporary terms, non-epileptic seizures. Meaning there's no electrical discharge in the brain.

The patient needed to be admitted for EEG monitoring.

And to characterize the event and because it was a hospitalization that means it's a serious adverse event.

The severity was characterized as moderate.

Psychogenic seizures are sometimes called not more contemporary terminus and non epileptic seizures.

Meaning theres no electrical discharge and the brain is felt to be a behavioral symptoms and not something we see much of a.

Joseph Hulihan: It's felt to be a behavioral symptom and not something we see much of. And in terms of the US versus Europe, you know, initially, that was the rationale for having a separate study. The treatment is different in Europe. They're less inclined to progress patients to IV anesthesia for treatment of refractory status than in the US and tend to use a number of different anti-epileptic drugs before taking that step, particularly for non-convulsive status. And so it has evolved over time.

And in terms of the U S versus Europe and.

Initially that was the rationale for having a separate study the treatment.

And is different in Europe.

And are less inclined to progressed patients to IV anesthesia.

For treatment of refractory status and then in the U S and 10 Qs.

Number of different anti epileptic drugs before taking that step for particularly for Nonconvulsive status.

And so evolved over time and evolved into a different study based on our design considerations and regulatory feedback I think we've got now a complimentary study to the U S study.

Joseph Hulihan: It evolved into a different study based on our design considerations and regulatory feedback. I think we've now got a complementary study to the US study. In the US, they have to have failed at least two IV AEDs. In the EU, it's going to be at least one. And there are other design differences that make it actually a study that complements rather than duplicates the US study.

And the U S. They have to and failed at least two.

DS and the EU, it's going to be at least one and there are other design differences that make it actually are starting to complements rather and duplicate the U S. Study. So we're very pleased with how things are going there.

Joseph Hulihan: So we're very pleased with how things are going there. Great, thank you. And your next question comes from Joon Lee from Tourist Securities. Your line is open.

Great. Thank you.

Sure.

And your next question comes from James Lee from <unk> Securities. Your line is open.

Joon So Lee: All right, thanks for taking our questions.

Hi, Thanks for taking our questions.

Scott Braunstein: So the TSC program, are you able to disclose how many of the planned 25 total patients were part of the interim look? And are there any strategic reasons for meeting with the FDA in the second quarter with interim data as opposed to meeting in the third quarter with the full data? Have you done any statistical work that would suggest that no further changes in the full data set are expected? And lastly, did the TSC study also stratify based on LOX, and if so, did you also not see any sort of difference based on that baseline and just see a broad effect across the board?

So the PSC program are you able to disclose how many of the planned 25 total patients were part of the interim look and is there any strategic reasons for meeting with DSP and second quarter with interim data as opposed to meeting and third quarter with the whole data have you set any statistical at work that would suggest that no further changes and the <unk>.

Ole data status, it's expected and and lastly that the PSC study also stratify based on allo at and if so did you also not seeing any sort of defense based on debt baseline and just see broad effect across the board. Thank you.

Scott Braunstein: Thank you. So, uh, it's a great question, Joon. Kim, maybe you want to just talk about the regulatory strategy for TSC, and then if Joe has anything to add, and then we can have Alex jump in and talk about the allocation. Sure, so we do plan to submit a me request to discuss the phase 3 study with the FDA.

So it's a great question Joon Kim maybe you wanted to just talk about the regulatory strategy for T. S. T. And then if Joe has anything to add and then we can have out Alex jump in and talk about the outlet signal.

Sure. So we do plan to submit and new request and Scott to Phase III study with the FDA.

And kind of cut we're not waiting until the completion of the entire study and.

Kimberly A. McCormick: [inaudible]

And there is time it takes to get the briefing document happening and so that meeting this target by the end of second quarter and then subsequently on and Europe. Shortly after that.

Kimberly A. McCormick: Shortly after that, so the plans are to take the.

Kimberly A. McCormick: [inaudible] Sure, I think the agency is very, and what's most important...

Our plans are and it takes me the income look to the FDA.

And to support a phase III, assuming that we and we feel that the data and robust enough to quite the Pacer program and therefore there.

Kimberly A. McCormick: What's important is the safety of the data portafilter as well as the signal.

Tim maybe a little bit more specifically June was really asking why the interim cut rather than the final cut. So maybe you should talk a little bit about our goal in terms of safety and meeting with the agency.

Kimberly A. McCormick: Interim Cut that will have a strong enough safety

Kimberly A. McCormick: Support from the study supported by our CDB and our other large database to take the agency, so I don't think it'd be required to have the full data set in order to begin to get collaboration and agreement on the phase 3 study. Does that answer the question, Scott? Yeah, I think that's good.

Sure I think the agency is very.

With most of them firsthand.

The safety of the day before and I think and there's lots of signal and I think we felt strongly that based on the interim cut that will have.

And it's strong enough safety.

And support from the study supported by our CDB and our other largest database, particularly agency.

And it would be required to have the full dataset.

And I think that collaboration and agreement on the Phase three study design does that answer the question Scott.

Scott Braunstein: In June, just to complete the thought, we looked at about half the study population who had received the drug for at least four weeks. And as a reminder, when we looked at the Marigold study, the efficacy of Gnaxolone is really the same at the four-week period as it is at the 12-week period. So we were able to look at about half the study and take at least a four-week look. Alex, do you want to talk a little bit about the biomarkers? Sure.

Yeah, I think thats, good and June just to complete the thought we looked at about half. The study population who had received drug for at least four weeks and as a reminder, when we looked at our the Marigold study.

The efficacy of Ganache Sloan is really the same at the four week period as it is at the 12 week period. So we were able to look at about half the study and.

And take at least a four week look at the dataset, Alex do you want to talk a little bit about the biomarker.

Alex Aimetti: Thanks, Scott. And thanks for the question, Joon. So before I talk about allopregnanolone sulfate in TSC, I just wanted to quickly comment on the use of it in PCDH 19. As everyone is aware, that study was designed to appropriately test the hypothesis of whether endogenous allopregnanolone sulfate levels could potentially have a predictive effect on gonaxalone response. And as a result of that proper clinical trial design, I can say today with a higher degree of confidence that that does not appear to be the case.

Sure. Thanks, Scott and thanks for the question Joon, So before I talk about the allo pregnant alone sulfate and TSA I just wanted to quickly comment on the use of it and PCB age 19 as everyone's aware that study was designed to appropriately test the hypothesis, whether endogenous allo pregnant alone sulfate levels could potentially have a.

They've effect on good excellent response, and as a result of that proper clinical trial design and I can say today with a higher degree of confidence that that does not appear to be the case and although we recognize that a predictive biomarker for Apple FC is of high value again, I think these data that we've shown here the positive effects seen now and the broad CVD population and the suggested.

Alex Aimetti: And although we recognize that a predictive biomarker for epilepsy is of high value, again, I think these data that we've shown here, the positive effects seen now in the broad CDD population and the suggestive beneficial effects in the broad PCDH 19 population with three times a day dosing are probably, not surprisingly, a better predictor of gonaxalone response. Now to your specific question, we are going to explore baseline allopregnanolone sulfate levels in TSC patients, but they are not stratified in that study, and the primary efficacy endpoint is in all patients enrolled.

Beneficial effects and the broad PTH and 19 population with three times a day dosing is probably not surprisingly a better predictor of an excellent response to your specific question. We are going to explore baseline allo pregnant alone sulfate levels and CIC patients, but they are not stratified and that study and the primary efficacy endpoint.

And all patients enrolled.

Alex Aimetti: Thank you. And your next question will come from Marc Goodman from SVB. Lyrinc, your line is open.

Thank you.

And your next question will come from Marc Goodman from SBB Leerink. Your line is open.

Marc Harold Goodman: Scott, can you just talk to us about European partnership and how you're thinking about it? What is the optimal kind of deal and economics?

Scott can you just talk to us about European partnership and how you're thinking about it what is the optimal kind of deal and economics and.

Scott Braunstein: You know, just to give us some baseline of how you're thinking about that. And then, secondly, can you just remind us of what is going on behind the scenes with increasing testing, just so when your product hits the market, will there be complete testing for CDD? Will there be testing for, you know, TSC, just to make sure we understand that. Thank you.

Just to give us some baseline of how youre thinking about that and then just secondly can you just remind us of what is going on behind the scenes with increasing testing just so when your product hits the market will there be complete testing.

For C D D well there'd be testing for.

T S C just to make sure we understand that thank you.

Scott Braunstein: Thanks, Marc. And maybe I'll pass a little bit of the testing over to Christy as well, because we're getting a lot of feedback from our market research in terms of where some of the trigger points are in terms of early diagnosis. But specifically on the partnership, Marc, we've had some great discussions with several organizations. The vast majority are focused in Europe, but several have some reach outside of Europe.

Thanks, Mark and maybe I'll I'll pass a little bit of a testing over to kristy as well because we're getting a lot of feedback from our market research in terms of where some of the trigger points are in terms of early diagnosis.

But specifically on the partnership Mark.

We've had some great discussions with several.

Organizations. The vast majority are focused and Europe. Several have some reach outside of Europe. We have some folks who are primarily focused on the orphan disease business.

Scott Braunstein: We have some folks who are primarily focused on the orphan disease business. They have more of a specialty focus, and certainly that's intriguing to us. We have other strategic partners, interestingly, who have an interest in both orphans and the hospital space, and that certainly has a different level of strategic interest to us.

They're they have more of a specialty of focus and and certainly that's intriguing to us we have other strategic partners Interestingly, who have an interest and both orphan and the hospital space and that certainly has a different level of strategic interest to us now.

Scott Braunstein: Now that we have good confirmation on what's needed in Europe for the IV program, we certainly want to make sure that we take full advantage of thinking about pricing and the commercial opportunities sooner rather than later. So we still have a really important strategic decision ahead of us, and I think there's a rationale for partnering both programs with a single partner. There's rationale for just partnering on the oral program, and we would continue the development of the IV program ourselves.

We have good confirmation on what's needed in Europe from the for the IV program.

We certainly want to make sure that we take full advantage of thinking about pricing and the commercial opportunity sooner rather than later, so we still have a really important strategic decision ahead of us, which I think theres rationale for partnering both programs to a single partner Theres rationale for just partner.

And the oral program and we would continue development of the IV program ourselves.

Scott Braunstein: And I think either way, Marc, we're going to lead the research effort for both the global TSC program and the European IV program. In terms of the economics, we're really thinking about the long-term MPV of the business. We have a lot of confidence in the business.

And I think either way Mark we're going to lead the research effort for both the global T. S. C program and the European IV program in terms of debt economics, where we're really thinking about the long term MPV of the business, we have a lot of confidence and the and the business our balance sheet is.

Scott Braunstein: Our balance sheet is certainly much stronger than it was, but some upfront payments and reimbursement around research and development will certainly extend our runway. So a combination of upfront commercial and research reimbursements is important to us. But certainly, as you would expect, we are really interested in what the royalties are going to look like, particularly as the product grows. And again, I think a key focus for us is reaching NPVs that are really equitable for both parties. So I think I covered your question, Marc. Was there another question that I missed?

Certainly much stronger than.

And it was but but from upfront payments and reimbursement around research and development will certainly extend our runway so a combination of upfront.

Commercial and and.

And research reimbursements are important to us.

But certainly as you would expect we are really interested in and what the royalties are going to look like and particularly as the product grows and and again I think a key focus for us is reaching mpv's debt that are really equitable for both parties.

So I think I covered your question Mark did you ever did was there another question and I missed I apologize.

Scott Braunstein: I apologize. So just on the genetic testing. Oh, genetic testing. Sorry. Chris, do you want to jump in and take that? Sure. So for CDD specifically, over the past six to seven years,

But just on the genetic testing.

Testing sorry, Chris do you want to jump in and take that.

Sure So for C. D D specifically over the past six to seven years. It has become widely widely acceptable and it uses genetic testing preceding day. When these patients present early in life typically within the first few months of life and it's widely acceptable to have.

Christy Shafer: It has become widely, widely acceptable, and it is used genetically.

Christy Shafer: Genetic testing for CDD. When these patients present early in life, typically within the first few months of life, it's widely acceptable to have a panel, and there are several that physicians look to do these genetic tests. So early diagnosis in CDD is something that we will rely on. As we all know, these patients tend to cycle through different antiepileptics in their first few years of life. So by the time they get to us at the age of two, they will have, you know, 85% of these patients will be considered refractory. So we believe again in early diagnosis.

The panel and there are several debt physicians look to to to do these genetic tests. So early diagnosis and C. D D.

And it's something that we will rely on and as we all know these patients tend to cycle through different anti epileptics and their first few years of life. So by the time they get to us at the age of two they will have you know 85 per cent of these patients' well being considered and refractory. So we believe again early.

Diagnosis and the high refractory rate will bring us a large part of the patient population.

Christy Shafer: and the high refractory rate will bring us a large part of the patient population.

Christy Shafer: a large part of the patient population. Thanks, Marc. And, Operator, we have time for one more question. And before we also wrap up and take the last question, we just wanted to remind the investor community that we have posted a new set of slides on our website. And those slides do include a little bit more detailed analysis of the PCDH-19 trial, as well as our Phase III TSC trial design. So, just as an FYI for individuals. Operator, why don't we move to our last question? Okay, so our final question today will come from

Thanks.

Thanks, Mark and operator, we have time for one more question and before we also wrap and take the last question.

And just wanted to remind that the.

Investor community that we have posted a new set of slides on our website and those slides do include a little bit more detailed analysis of the PCH 19 trial as well as our phase III PSC trial design and so just as an FYI per individuals operator, why don't we move to our last question Okay.

So our final question today will come from Jay Olson from Oppenheimer. Your line is open.

Operator: will come from Jay Olson from Oppenheimer. Your line is open. Oh, hey, congrats on all the progress.

Oh, Hey, congrats on all the progress and thanks for taking the question can you share any anecdotal feedback you've gotten from physicians or patients who received compassionate use of <unk> for Super refractory SC and I think you said that a clinical trial in Srs he's not on the table at this time, but would you consider one and the future.

Jay Olson: Oh, hey, congrats on all the progress and thanks for taking the question. Can you share any anecdotal feedback you've gotten from physicians or patients who received compassionate use of Ganaxone for super refractory SE? And I think you said that a clinical trial in SRSE is not on the table at this time, but would you consider one in the future? And what are some of the lessons learned from the SAGE study and SRSE that didn't work out that might influence your decision to do a study or not or how to design that study? Thank you.

And what are some of the lessons learned from the stage study and Src that didn't work out that might influence your decision to do study or not or how to design and that study. Thank you.

Well, let me thanks, Jay and let me take a little bit of that question and then I'll pass over to Joe for you from the clinical experience but.

Scott Braunstein: Thanks Jay, let me take a little bit of that question and I'll pass it over to Joe for the clinical experience, but certainly, we are going to support the research community. If drug is requested on an EIND basis for patients with super refractory status, we are certainly going to provide the drug when we can. We're learning that these patients can be extremely difficult.

Certainly we are going to support the research community.

And if it's.

This drug has requested an and <unk> basis for patients with Super refractory status. We are certainly going to provide drug when we can we're learning that these patients can be extremely difficult. We've already been dosing patients at higher doses that are phase III dose over a 1000 milligrams per.

Scott Braunstein: We've already been dosing patients at higher doses than our phase three dose, over a thousand milligrams per day, where we're going up to 63, or physicians are going up to 63 grams of captozole. And so we know there are real differences in this population compared to the RSE population or the ESE population, so I think we want to continue to support the research and understand the differences before we could even consider any type of trial design.

Day, where we're we're going up to 63 or physicians are going up to 63 grams of Captisol and so we know there are real differences in this population compared to the RSC population or the ESC population. So I think we want to continue to support the research and understand the difference.

This is before we could even consider any type of trial design, but as we've said consistently since the beginning of our IV program dosing really matters in the acute setting and we want to get that right and we don't want to make the same mistake, others have made and I feel very good about.

Scott Braunstein: But as we've said consistently since the beginning of our IV program, dosing really matters in the acute setting, and we want to get that right, and we don't want to make the same mistakes others have made. I feel very good about where we are with RSE.

Where we are with RSC were.

Scott Braunstein: We're taking a different approach in ESE and, certainly, ultimately, a different approach in super refractory status as well. And I will say, you know, we are now creating some new formulations which may unleash our ability to be linked to captizol down the road as well, but you know, we have a few years of development ahead of us on that path. But Joe, let me turn it over to you for the clinical gestalt on SRSE before we wrap up the call. Yeah, no, I agree with Scott.

Taking a different approach in E. S C and certainly ultimately a different approach in super refractory status as well.

And I will say.

We are now, creating some new formulations, which may unleash our ability to be.

Linked to Captisol down the road as well, but you know a few years.

Of development ahead of us on that path, but Joe Let me turn it over to you for the clinical Gestalt on Srs and <unk> before we wrap the call.

Yes no.

And I agree with Scott the main thing, we're learning about and dosing, there and and using a higher dose the importance of getting high levels and initially and I don't think we have enough experience yet.

Joseph Hulihan: The main thing we're learning about is dosing there and using a higher dose, the importance of getting high levels in initially. I don't think we have enough experience yet. I think seven or eight patients so far have been treated under emergency INDs. I don't think we have enough experience to look at patient types and age. Some patients have done very well, responded very quickly, and so there may be a role of etiology; some patients are tougher to treat.

I think it's been seven or eight patients. So far have been treated under emergency and I don't think we have enough experience to look at patient types age.

Some patients have done very well responded very quickly and and so there may be a role of etiology from patients tougher to treat.

Joseph Hulihan: And, as Scott mentioned, you know, the blood levels. I think that's probably the main lesson learned about PK from the SAGE study and the doses they were, you know, the dosing was constrained. And so it's important to get high levels. And, you know, connexalone may differ a bit from allopregnanolone. So anyway, we're continuing, we'll continue to respond and continue to explore different ways of dosing the drug and suprafrac restats.

And.

And as Scott mentioned.

The blood level I think that's probably the main lesson learned and PK from the stage study and the and the dosage day work.

The dosing was constrained.

And so it's important to get the high levels.

And and.

And excellent may differ a bit from our break non alone.

So and.

The way, we're continuing and will continue to respond and.

And continue to explore different ways of dosing and the drug and Super refractory status.

Joseph Hulihan: Great, thank you very much. Well, I'm going to wrap up the call, and I'd like to thank everyone for joining us today and for your continued support and confidence, and we look forward to providing updates in the coming months. Operator, back to you.

Great. Thank you very much.

Sure.

Uh huh.

Well I'm going to wrap up the call and I'd like to thank everyone for joining us today and your continued support and confidence and we look forward to providing updates in the coming months operator back to you.

Operator: Okay, thank you everyone for joining us today. This will conclude today's conference call. You may now disconnect.

Okay. Thank you everyone for joining us today.

Well conclude todays conference call you may now disconnect.

[music].