Q3 2020 Marinus Pharmaceuticals Inc Earnings Call

Greetings and welcome to the Meritas Pharmaceuticals third quarter 2020 earnings call.

Operator: Greetings and welcome to the Marinus Pharmaceuticals third quarter 2020 earnings call. At this time, all participants are in a listen-only mode.

At this time all participants are in a listen only mode.

Operator: A brief question and answer session will follow the formal presentation. If you would like to ask a question, dial star 1 on your telephone keypad. As a reminder, this conference is being recorded. And it's now my pleasure to introduce your host, Sasha Damouni-Ellis, Vice President, Investor Relations and Corporate Communications. You may begin, Ms. Damouni-Ellis. Thank you, and good afternoon, everyone.

A brief question and answer session will follow the formal presentation if.

If you would like to ask a question dial star one on your telephone keypad hazard.

As a reminder, this conference is being recorded.

It's now my pleasure to introduce your host Sasha Many Ellis Vice President Investor Relations and corporate Communications you may begin Mr. movie Ellis.

Thank you and good afternoon, everyone with.

Sasha Damouni Ellis: With me from Marinus are Dr. Scott Braunstein, Chief Executive Officer, Dr. Joe Hulihan, Chief Medical Officer, and Edward Smith, Chief Financial Officer. 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, of course, are subject to certain risks and uncertainties that are associated with our business and that could cause our future results to differ significantly from those expressed or implied by the forward-looking statements. For a description of these risks and uncertainties, see the Company's Form 10-K and 10-Q as filed with the Securities and Exchange Commission.

With me from Meredith are Dr., Scott Braunstein, Chief Executive Officer, Dr., Joe Houlihan, <unk>, Chief Medical Officer, and Edward Smith, Chief Financial Officer.

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.

Well worth looking statements of course are subject to certain risks and uncertainties that are associated with our business and that could cause our future results to differ significantly from those expressed or implied by the forward looking statement for a description of these risks and uncertainties in the company's form 10-K and 10-Q.

As filed with the Securities and Exchange Commission I will now turn the call over to Scott.

Sasha Damouni Ellis: I will now turn the call over to Scott. Thank you, Sasha. Good afternoon, everyone.

Thank you saw show good afternoon, everyone and welcome to our third quarter Twentytwenty business and financial update.

Scott Braunstein: And welcome to our third quarter 2020 Business and Financial Update. I want to begin by saying this is one of the most exciting periods in Marinus' history. Our team is growing quickly and working incredibly hard to help drive our operations forward. Consider what the organization has accomplished in just the last few months. Firstly, we achieved the primary endpoint in the Marigold study, the pivotal phase 3 clinical trial evaluating oral gonaxalone in children and young adults with CDKL5 deficiency disorder or CDDs. Secondly, we've been awarded a five-year, potentially $84 million cost-sharing contract with BARDA for refractory status epilepsy. Finally, we remain highly focused on our Phase III IV-Ganaxialin clinical trial in refractory status epilepticus, or the RAISE trial. Our team has continued to work diligently to finalize sites, and it is our expectation that we will have the vast majority of these sites activated by the end of Q1 2021, which is incrementally earlier than we had anticipated a year ago, prior to the world being affected by COVID-19 In addition to these three major accomplishments, we continue to enjoy similar success advancing our multiple programs and initiatives. I would like to highlight them for you.

I want to begin by saying this is one of the most exciting period in Marin says history or team is growing quickly and working incredibly hard to help drive our operations for work.

Consider what the organization has accomplished in just the last few months Firstly, we achieved the primary endpoint in the Marigold study the pivotal phase three clinical trial evaluating wogan actual loan in children and young adults with TDK IL five deficiency disorder or TDD.

Secondly, we've been awarded a five year potentially 84 million dollar cost sharing contract with BARDA for refractory status epilepticus.

Finally, we remain highly focused on all of these three I've eaten excellent clinical trial in refractory status epilepticus or the raise trial. Our team has continued to work diligently to finalize site and it is our expectation that we will have the vast majority of these sites activated by the end.

Q1, 2021, which is incrementally earlier than we had anticipated a year ago prior to the world being affected by COVID-19 buffers.

In addition to these three major accomplishments, we continue to enjoy similar success advancing or multiple programs and initiatives.

I would like to highlight them for you or two worth sclerosis complex or T.S.P. phase two study enrollment curve is showing market improvement likely due to the positive topline marable study data. The additional number of new sites that have opened or partnering with the T.S.C. lines and the easing of COVID-19.

Scott Braunstein: Our tuberous sclerosis complex, or TSC phase two study enrollment curve, is showing marked improvement, likely due to the positive top-line marival study data, the additional number of new sites that have opened, our partnering with the TSC Alliance, and the easing of COVID-19 restrictions. This open-label design gives us the opportunity to perform an interim data analysis and consider an end-to-phase 2 meeting with the FDA sometime in the first half of next year, should we see a consistent clinical signal. We strongly believe that dosing these patients three times a day and up to 1,800 milligrams is a critical piece of the study design, replicating the marigold dosing schedule. A meaningful number of patients with TSC continue to suffer from significant seizure burdens despite currently available therapy. We are on track for top line data in the summer of 2021.

Strict sheets.

This open label design gives us the opportunity to perform an interim data analysis and considering into these two meeting with the FDA sometime in the first half of next year should we see a consistent clinical signal.

We strongly believe that the dosing of these patients three times, a day and up to 1800 milligrams is a critical piece of the study design replicating the marigold dosing schedule he.

A meaningful number of patients with TSC continued to suffer from significant seizure burden. Despite currently available therapies.

We are on track for topline data in the summer of 2021.

Scott Braunstein: Let me next turn to the Violet Study, our Phase 2 double-blind placebo-controlled clinical trial examining the use of oral Ganaxolone in PCVH19 patients. As a reminder, a proportion of children with PCVH19 suffer from intractable cluster seizures despite treatment with multiple anti-epileptic therapies. Recruitment will be completed in July, and all patients will finish the double-blind portion of the trial in Q1 of 2021. Once again, the dosing paradigm is identical to the Marigold study.

Let me next turn to the pilot study our phase two double blind placebo controlled clinical trial examining the use of World index loan in P.T.D.H. 19 patients.

As a reminder, the proportion of children with P.C.D., each 19 suffer from intractable cluster seizures, despite treatment with multiple anti epileptic therapies.

Recruitment completed in July and all patients will finish the double blind portion of the trial in Q1 of 2021.

Once again, the dosing paradigm is identical to the Marigold study.

Scott Braunstein: The Violet Study will not only evaluate the efficacy of Gnaxolone when compared to placebo, but it will also examine the role of alloprenanolone sulfate as a biomarker-directed therapy. We currently believe that both our IV and oral programs will yield important therapeutics in major markets around the world. Accordingly, we successfully submitted the EU status epilepticus request for scientific advice to the European Medicines Agency and expect to engage in a pre-submission meeting to review that trial design in the first quarter of next year. As a reminder, European regulators prefer clinical trial programs that compare a novel therapy to a currently existing agent.

Violets study will not only evaluate the efficacy of cognex alone when compared to placebo, but it will also examine the role of Allopregnanolone salty has the biomarker directed therapy.

We currently believe that both our I'd be an oral programs will yield important therapeutic in major markets around the world across.

Accordingly, we successfully submitted he used status epilepticus requests for scientific advice with the European Medicines agency and expect to engage in a pre submission meeting to review that trial design in the first quarter of next year.

As a reminder, the European regulators prefer clinical trial program that compare a novel therapy to a currently existing agent.

Scott Braunstein: We will share the study protocol in detail with you once we have met with the EU regulators and are confident in our path forward. Let me provide a brief overview of both our IV and oral clinical programs before turning the call over to Joe for additional detailed discussion. Starting with our IB franchise, we've been making tremendous progress with our status epilepticus program. Having quickly satisfied the FDA's protocol-specific questions, we now have activated our first sites, and those sites are ready to screen and enroll refractory status epilepticus patients. We expect the number of eligible sites to grow steadily over the next several months. Currently, over 75% of the sites have been approved and pre-selected to participate in the study. And we expect the vast majority of these sites to be finalized by the year end and open by the end of the first quarter of 2021.

We will share the study protocol in detail with you once we have met with the E U regulators and are confident in our path forward.

Let me provide a brief overview of both our Ivy and all clinical programs before turning the call over to Joe for additional detailed discussion.

Starting with our Ivy franchise, we've been making tremendous progress with our status Epilepticus program.

Having quickly satisfied the STB protocol specific question.

We now have activated our first site and news sites are ready to screen and enroll refractory status epilepticus patients.

We expect the number of eligible sites to grow steadily over the next several months old.

Over 75% of the site had been approved in pre selected to participate in the study and we expect the vast majority of these sites to be finalized by year end and opened by the end of first quarter Twentytwenty one.

Scott Braunstein: The Marinus team has done a tremendous job meeting with sites and choosing the best centers to participate in the study. The team of recently hired medical science liaisons, or MSLs, have partnered with our clinical operations team and together have been instrumental in focusing on neurocritical care and neurointensivists since those positions are on the front lines of treating patients experiencing RSH. Our clinical operations team and our MSLs are also increasing awareness and engagement of the RAISE trial through the review of the Phase II clinical trial data and critical scientific exchange, respectively. As a reminder, our patient population in the RAISE trial is primarily non-convulsive status epilepticus, and that is expected to be a determining factor in driving enrollment. We believe that the clinical trial paradigm used in the Phase 2 study drove rapid enrollment, and we will use a very similar informed consent procedure and treatment algorithm in the Phase 3 study.

The mayor and his team has done a tremendous job meeting with site in choosing the best centers to participate in the study.

The team we have recently hired medical science liaison or MSL have partnered with our clinical operations team and together have been instrumental in focusing on neuro critical care and neuro intensive is to those positions are on the front line of treating patients experiencing RSP.

Our clinical operations team and our and the cells are also increasing awareness and engagement of the race trial do the review of the phase two clinical trial data and critical scientific exchange respectively.

As a reminder, our patient population in the Reais trial is primarily Noncurrent boasted status epilepticus and that is expected to be a determining factor in driving enrollment.

We believe that the clinical trial paradigm used in the phase two study drove rapid enrollment and we will use a very similar informed consent procedure and treatment algorithm in the phase three study.

Scott Braunstein: We firmly believe that Gonaxalone can provide a rapid onset of action, have a durable effect in patients with status epilepticus, and potentially play an important role in preventing the devastating consequences of uncontrolled seizures. We believe that our trial sites share our enthusiasm for this novel therapy. There is no question that we are competing with COVID-19 for both resources and time across U.S. hospitals. However, despite the intense pressure that U.S. hospitals are feeling today, our investigator community and interested sites have been highly engaged with Marinus. Our team has continued to be creative and work hard to keep our site activations on track. As a result, we still expect to report top-line data in the first half of 2022.

We firmly believe that connects loan can provide a rapid onset of action have a durable effect in patients with status epilepticus and potentially play an important role in preventing the devastating consequences of uncontrolled seizures.

We believe that our trial site share our enthusiasm in this novel therapy.

There is no question that we are competing with COVID-19 for both resources and time across U.S. Hospital.

However, despite the intense pressure that you as hospitals are feeling today, our investigator community and interested sites have been highly engaged with meritas.

Our team has continued to be creative and work hard to keep our site Activations on track and as a result, we still expect to report topline data in the first half of Twentytwenty two.

Scott Braunstein: As an interesting aside, several physicians have requested, on an emergency IND basis, access to Gonaxalone to treat patients with supra-refractory status epilepsy. Our entire team takes such requests very seriously, and we feel it is our obligation to offer an option for patients who have been unable to come off general anesthesia following their bout with status epilepsy. We have thought very hard about how to best dose and treat these patients. I want to thank Dr. Joe Hulihan and the entire clinical team for their efforts. These patients are truly left with no other alternative.

As an interesting the side several physicians have requested on an emergency R&D basis access took an absolute to treat patients with super refractory status epilepticus.

Our entire team take such request very seriously and we feel it is our obligation to offer an option for patients who had been unable to come off general anesthesia. Following there about what status epilepticus.

We thought very hard about how to best dose and treat these patients.

One of the things Dr., Joe Houlihan and the entire clinical team for their efforts. These patients are truly left with no. Other alternatives will share more details on the city, yes, where we expect to have a notable presence this year.

Scott Braunstein: We'll share more details on this at AES, where we expect to have a notable presence. To help lead our SE programs, Dr. Henry McCabbage, who served on our Scientific Advisory Board and as the Principal Investigator in our Phase II RSC study, has been appointed Vice President of Clinical Development. Henry's knowledge surrounding neurosteroids, his vast clinical experience, and his insight and contributions to our scientific approach will help us further advance Ganaxalone in additional indications in clinical trials, including the upcoming study in Europe that I just mentioned. Furthermore, we are planning a trial in an earlier treatment line to RFC known as established status epilepticus. The vast majority of these patients are suffering from convulsive status and have been treated with and failed benzodiazepines.

To help lead our FC programs Dr. Henry bid cabbage, who served on our scientific Advisory Board and as the principal investigator in our phase two RSV study has been appointed Vice President of clinical development and Louise knowledge trending or steroid is vast clinical experience and his insight.

And contributions to our scientific approach will help us further danskin actual loan in additional indications in clinical trials, including the upcoming study in Europe that I just mentioned.

Furthermore, we are planning a trial in an earlier treatment line to RSC known as established status epilepticus.

The vast majority of these patients are suffering from convulsive status and had been treated with and failed benzodiazepines.

Scott Braunstein: Treatment success rates in established status are slightly below 50%, and as a result, it is an equally important unmet medical need. We estimate this market to be approximately 50,000 to 75,000 additional patients in the U.S., and these patients are primarily treated in the emergency room. Further details of this trial design will also be discussed at AES.

Treatment success rate in established status or slightly below 50% and as a result, it is equally important unmet medical need.

We estimate this market to be approximately 50 to 75000 additional patients in the U.S. and.

And these patients are primarily treated in the emergency room.

Further details of this trial design will also be discussed at eight yes.

Scott Braunstein: Finally, we have ongoing preclinical work for the intramuscular formulation of Ganaxalone and continue to drive additional formulation partnerships and research projects to enhance our intermediate and long-term strategies for the oral franchise. Before I leave the IB program, I would like to spend a little time highlighting our BARDA contract that we announced in September. As briefly mentioned, BARDA agreed to fund up to $51 million of an $84 million contract for programs related to RSC development.

Finally, we have an ongoing preclinical work and the intramuscular formulation of the next loan and continue to drive additional formulation partnerships and research projects to enhance our intermediate and long term strategies for the oral franchise.

Before I leave the IB program I would like to spend a little time, highlighting our BARDA contract that we announced in September.

As briefly mentioned BARDA agreed to fund up to $51 million of an 84 million dollar contract for programs related to our assay development degree.

Scott Braunstein: The agreement covers a base period during which BARDA will provide subject matter expertise and $21 million to fund, on a cost-share basis, additional preclinical work, and the company's planned Phase III clinical trial of Ganax loans for the treatment of RSC. We believe that this preclinical work and our planned phase 3 trial will be the foundation of a long-lasting business relationship with the BARDA team. We've already held our BARDA kickoff, and it was a large collaborative team effort comprised of several scientists and multiple other experts from both sides. We see the BARDA team as an important resource, and we are pleased to be working with them. Their interactions to date have been thoughtful and extremely valuable to our scientific process.

The agreement covers the base period during which border will provide subject matter expertise and $21 million to fund on a cost share basis additional preclinical work and the company's plans. These three clinical trial of the next loan for the treatment of RCC.

We believe that this preclinical work and our planned phase three trial will be the foundation of a long lasting business relationship with the BARDA teeth.

We've already held our BARDA kick off and it was a large collaborative team effort comprised of several scientists and multiple other experts from both sides.

We see the BARDA team as an important resource and we are pleased to be working with them.

Their interactions to date have been thoughtful and extremely valuable to our scientific process.

Scott Braunstein: We are grateful to BARDA for their collaborative approach throughout this process and the opportunity to continue to innovate in the field of seizure disorder. Now, let me turn to the oral franchise and the tremendous progress we have made in the last several months. As I previously noted, we recently reported positive top-line data from the Pivotal Phase 3 Marigold Study. This was the first double-blind placebo-controlled trial to provide evidence of efficacy specific to the CDD patient population and the first phase 3 trial to examine three times a day dosing of Gonadazolone in pediatric patients. We had a chance to share the top line data with the CDD community in October. The next few months will be equally exciting.

We are grateful to BARDA with a collaborative approach throughout this process and the opportunity to continue to innovate in the field that seizure disorders.

Let me turn to the oral franchise and the tremendous progress we have made in the last several months as I. Previously noted we recently reported positive top line data from the pivotal phase three mericle study.

This was the first double blind placebo controlled trial to provide evidence of efficacy specific to the CDD patient population and the first phase three trial to examine three times a day dosing I'm going to ask alone in pediatric patients we.

We had a chance to share the topline data with the CDD community in October.

The next few months will be equally exciting meritas is planning to meet with the FDA in the first quarter of 2021 to support an indie submission by mid 2021.

Scott Braunstein: Marinus is planning to meet with the FDA in the first quarter of 2021 to support an NDA submission by mid-2021. We also expect to launch our Expanded Access Program in early December this year, enabling patients who are unable to participate in the Phase 3 trial access to the drug. Our early feedback on the EAP program has been extremely positive to date.

We also expect to launch our expanded access program in early December this year, enabling patients who were unable to participate in the phase three trial access to the drug.

Our early feedback on the EAP program has been extremely positive to date.

Scott Braunstein: We feel that it is important for us as an organization and as part of the biotech community to offer ganacolone to patients who are suffering from CDD and were not able to participate in our phase three trial. We expect further external commercialization discussions in CDD, especially as it pertains to strategic alliances and our global commercialization strategy, as well as continued interaction with the community of medical professionals focused on treating epilepsy at the American Epilepsy Society annual meeting in December. We believe that AES provides a fantastic platform to discuss novel anti-FLFC therapies, and we are focused on making that meeting an important success for GennX. We plan to present further details of the Marigold study, including pharmacokinetic data, at AES in December, which will be a critically important roadmap for the future development of oral ganassaline.

We feel that this is important for us as an organization and as part of the biotech community to offer an excellent to patients who are suffering from CDD and were not able to participate in our phase three trial.

We expect further external commercialization discussions in TDD, especially as it pertains to strategic alliances and our global commercialization strategy.

As well as continued interaction with the community of medical professionals focused on treating epilepsy at the American Epilepsy Society annual meeting in December.

We believe that EPS provides a fantastic platform to discuss novel anti epilepsy therapies, and we are focused on making that meeting an important success for an excellent.

We plan to present further details of the Merrell study, including pharmacokinetic data S. In December which will be critically important roadmap to the future development of oral gaslog we.

Scott Braunstein: We believe the data will strongly support our confidence in the results of the Marigold study as a pivotal trial. We will be holding a separate investor event at AES, which Sasha will go into further details later on. Our CDD commercial strategy continues to evolve, and I am pleased to announce that concurrent with our Q3 business update this afternoon, we also announce and welcome Christy Shafer to Marinus as our Chief Commercial Officer.

We believe the data will strongly support our confidence in the results of the Marigold study is a pivotal trial.

We will be holding a separate investor event at a guess, which Sasha will go into further details later on.

Our CDD commercial strategy continues to evolve and I'm pleased to announce that concurrent with our Q3 business update. This afternoon. We also announce and welcome Kristi cheaper to Meredith as our Chief commercial Officer, Chris.

Scott Braunstein: Christy's rare disease expertise and tremendous sales and marketing background provide the experience and leadership needed to prepare the U.S. commercial launch of Gnastilone and CBD and a potential debut of Gaddafi's Sloan in Status Epilepticus soon after. Christy has spent almost 20 years in the biotech, pharma, and medical device spaces, most recently at Alexion Pharmaceuticals. Christy is energetic and a fantastic leader, and we are thrilled to have her on board.

Christie's rare disease expertise and tremendous sales and marketing background provides the experience and leadership needed to prepare the us commercial launch of connects loan and TDD and.

And a potential debut of good actual loan in status epilepticus soon after Chris.

Christy has spent almost 20 years in the biotech pharma and medical device space. Most recently the lexicon Pharmaceuticals, Chris.

Christie's energetic and a fantastic leader and we are thrilled to have her on board.

Scott Braunstein: We've also begun to build our team of MSLs to help drive a publication strategy, continue to build our relationship with advocacy groups, and expand our scientific plan for 2021. This team has been instrumental in helping identify clinical research sites for all our trials and leading our AES presence. On the IP front, as noted in our 10Q, Avid Therapeutics contacted us and disclosed that it owns two recently issued method of use patents that include claims for the use of Gynapsolone to treat CDD and PCVH19. As you are aware, we have been developing Ganaxalone for the treatment of vocal onset seizures and rare genetic epilepsies since 2005. On the other hand, both Ovid patents originated from a provisional patent application that was filed on August 11, 2016.

We've also begun to build our team of themselves to help drive a publication strategy continued to build our relationship with advocacy groups and expand our scientific plan for 2021. This.

This team has been instrumental in helping identify clinical research sites for all our trials and leading our espresso.

On the IP front as noted in our 10-Q, obviously therapeutics contacted us and disclosed that it owns two recently issued method of use patent that include claims to the use of good NAPSLO and treat CDD and PCB HNT.

As you are aware, we have been developing good next loan for the treatment of vocal onset seizure and rare genetic epilepsies since 2005.

Meanwhile, both avid tens originated from a provisional patent application that was filed on August 11 2016, we.

Scott Braunstein: We do not believe the Ovid patents will impact our timeline for development, NDA submission, and regulatory approval, nor do we believe that the Ovid patents will delay our planned law. I have asked our lawyers to investigate these patents and all the possible options with respect to them, including challenging the patents at the USPTO and in the courts. Another solution could certainly involve a royalty payment based on an in-licensing of the patent state.

We do not believe the Abbott patents will impact our timeline for development and the commission regulatory approval, nor do we believe that the other patents will delay our planned launch.

As to our lawyers to investigate these patent and all the possible options with respect to that including challenging the patents at the U.S.P.T. O and or in the courts. Another.

Another solution could certainly involve a royalty payment based on an in licensing of the patent state.

Scott Braunstein: At this time, we are not going to say anything further, but we are confident that our plans for ConnexLon will not be delayed or disrupted. Regarding our partnership conversations, including those for the ex-US rights to CDDs, those are ongoing. We remain committed to this process and other means of non-diluted financing for the company.

At this time, we are not going to say anything further but we are confident that our plan for the next loan will not be delayed or disrupted.

Regarding our partnership conversations, including those for the ex Us rights to Cds. Those are ongoing we remain committed in this process and other means of non dilutive financing for the company.

Scott Braunstein: These endeavors are the product of our broader clinical strategy to unlock the potential of Ganaxolone across a range of rare fissure disorders. Our plans to expand the Ganaxalone franchise into TSC will continue to move forward. We remain on track to report top-line data in the first half of 2021. Finally, our Violet study is also making steady progress.

These endeavors are the product of our broader clinical strategy to unlock the potential of connects alone across a range of where seizure disorders. Our plans to expand connects loan franchise into TSC will continue to move forward. We remain on track to report topline data in the first half of 2021.

Finally, our violent studies also making steady progress earlier this year, we transitioned this trial to a proof of concept study evaluating aloe as as a biomarker in patients with a confirmed PCB each 90 mutation.

Joseph Hulihan: Earlier this year, we transitioned this trial to a proof-of-concept study evaluating AlloS as a biomarker in patients with a confirmed PCVH19 mutation. We believe the trial has the potential to detect a meaningful signal as a proof of concept for the allopredaniline sulfate biomarker hypothesis, as well as for the three times a day dosing regimen, which is intended to This trial is on track, and data should be released in the first half of 2021, with the company's intention to subsequently submit the results of the study for publication. With that, I would now like to turn the call over to our chief medical officer, Joe Hulihan. Joe?

We believe the trial has the potential to detect a meaningful signal as a proof of concept for the allopregnanolone sulfate biomarker hypothesis as well as for the three times a day dosing regimen.

Which is intended to inform future development and education selection.

This trial is on track and viewed issued a report out in the first half of 2021 with the company's intention to subsequently submit the results of the study for publication.

With that I would now like to turn the call over to our Chief Medical Officer, Joe Houlihan Joe.

Thank you Scott good afternoon, everyone.

Joseph Hulihan: Thank you, Scott. Good afternoon, everyone. Let me just quickly echo Scott's sentiment that these are indeed exciting times, so I'd like to update you on our clinical programs to illustrate the reasons why. First, I feel incredibly enthusiastic about the IV program. We've selected more than 75% of the sites for the phase 3 trial of iveconexalone in refractory status epilepsy, which we're calling the RAISE study. Site identification and activation are focused on neurocritical care units and neurointensive care units who are on the front lines of treating patients experiencing RS. The study is a randomized, double-blind, placebo-controlled trial in patients with status epilepticus who have failed benzodiazepines and two or more second-line IV AEDs. It will enroll approximately 125 patients who will be randomized to receive Conaxolone or placebo in addition to their usual standard of care.

Let me just quickly echo Scotts sentiment could these are indeed exciting times, so I'd like to update you on our clinical programs to illustrate the reasons why.

First I feel incredibly enthusiastic about the IB program.

We have selected more than 75% of the sites for the phase three trial by Beacon next loan in refractory status epilepticus, which we're calling the rave study.

Site identification and activation is focused on neuro critical care units in neuro intensive as we're on the front lines of treating patients experiencing RSC.

The study is a randomized double blind placebo controlled trial in patients with status epilepticus, who have failed benzodiazepine and two or more second line IB AG.

It will enroll approximately 125 patients who will be randomized to receive can actually to placebo. In addition to their usual standard of care.

Joseph Hulihan: The study will have greater than 90% power to detect a 30% efficacy difference between Ganaxalone and Plisipotamib. Patients randomized to Ganaxalone will receive an IV bolus, followed by a 36-hour infusion, then a 12-hour taper, for a total treatment period of 48 hours. This regimen targets a plasma concentration of greater than or equal to 500 nanograms per ml for the first 12 hours; maintenance of this plasma concentration of dinaxilone for eight hours was a key aspect in controlling status in our phase two study in a similar patient population.

The study will have greater than 90% power to detect a 30% efficacy difference between can actual owned and placebo.

Patients randomized to can actually don't receive an Ivy bolus.

Followed by a 36 hour infusion than a 12 hour caper.

For a total treatment period of 48 hours.

This regimen targets, a plasma concentration of greater than or equal to 500 nanograms per ml for the first 12 hours.

Maintenance of this plasma concentration of can actually for eight hours was a key aspect and controlling status or phase two study in a similar patient population.

Joseph Hulihan: In Phase 3, formulation improvements will enable us to maintain Ganaxalone at that target blood level for 12 hours, 50% longer than in phase two. There are two co-primary endpoints for this study. These are first, the proportion of patients with cessation of consciousness within 30 minutes of treatment initiation, without the use of other medications for control of status, and second, the proportion of patients who do not progress to IV anesthesia within 36 hours. These two co-primary endpoints address the major components of efficacy and status epilepsy, stopping it rapidly and maintaining control. We expect top-line data in the first half of 2022. As part of our IV strategy, we plan to evaluate Ganaxalone earlier in the treatment continuum of status epileptic, and we are beginning to design a study in patients who experience the convulsive form of status, in which patients have major convulsions or tonic-clonic seizures that continue for more than five minutes.

In phase three formulation improvements will enable us to maintain can axle on that that target blood level for 12 hours.

50% longer than in phase two.

There are two co primary endpoints for the study.

These are first the proportion of patients with cessation of status within 30 minutes of treatment initiation.

Without the use of other medications for control of status and second.

Proportion of patients, who do not progress to IB anaesthesia within 36 hours.

These two co primary endpoints addressed the major components of efficacy in status epilepticus, stopping it rapidly and maintaining control.

We expect topline data in the first half of 2022.

As part of our IP strategy, we plan to evaluate an actual on earlier in the treatment continuum of status epilepticus and are beginning to design. The study in patients who experienced the convulsive forms status in which patients have major convulsions or tonic clonic seizures.

Continue for more than five minutes.

Normally a seizure terminates on its own within a minute or two.

Joseph Hulihan: Normally, a seizure terminates on its own within a minute, and Kimball Substatic, seizures are continuous over a prolonged period and occur so rapidly in succession that the patient does not regain awareness. It is a condition requiring urgent treatment to avoid potential medical complications or permanent neurologic impairment. If patients fail initial treatment with a benzodiazepine and an initial second-line IV antiepileptic drug, the treating physician will typically intubate the patient and administer IV anesthesia, often progressing to this stage of treatment within minutes.

Convulsive status seizures or continuous over a prolonged period.

Our curve so rapidly in succession that the patient is not regain awareness.

It is a condition requiring urgent treatment to avoid potential medical complications or permanent neurologic impairment.

If patients fail initial treatment with the benzodiazepine.

And an initial second line Ivy anti epileptic drug.

The treating physician will typically intubate, the patient and administer IB anesthesia.

Often progressing to the stage of treatment within minutes.

The patient population for this study were planning will mirror that multicenter stablex status epilepticus treatment trial, he set whose.

Joseph Hulihan: The patient population for the study we're planning will mirror that of the multicenter established status epilepticus treatment trial, or ESET, whose results were published last year in the New England Journal of Medicine. This study compared the three most commonly used second-line IV AEDs, levofenetoin, valproate, and it found that none of the three drugs was superior to the others in stopping convulsive status within one hour; efficacy rates were 45 to 47% with no statistical separation between the treatment arms. As Scott mentioned, the RAISE study will recruit patients from the ICU setting who have the non-convulsive form of status epilepsy, which is more often treatment refractory and requires the use of two or more second-line AEDs in succession. Unlike the RAISE study, the second study will focus its enrollment in the emergency department setting.

Whose results were published last year in the New England Journal of Medicine.

This study compared to three most commonly used second line Ibds, we've addressed the Tam Phos phenytoin and Valproate and.

And found that none of the three drugs with superior to the others in stopping convulsive status within one hour after.

Efficacy rates were 45% to 47%.

No statistical separation between the treatment arms.

As Scott mentioned, the rave study will recruit patients from the ice you setting who have the non convulsive form of status epilepticus.

Which is more often treatment refractory you requires the use of two or more second line hdds and succession.

Unlike the race study the second study will focus its enrollment in the emergency department setting.

We anticipate the patients earlier in the course of status, who have convulsive seizures will be more treatment responses.

Joseph Hulihan: We anticipate that patients earlier in the course of status who have convulsive seizures will be more treatment responsive. Therefore, we need to think carefully about dosing of inaxolotl and the duration of therapy, and we'll begin our clinical program in the earlier phase of status with dose finding work. We've been talking to investigators about clinical study design, and this is an area where Henry's deep knowledge and expertise will prove particularly valuable. On the other end of the treatment spectrum, we've been receiving requests for emergency use of Ganaxalone in super refractory status, or SRSE. This is an extremely complex clinical situation in which, as you know, another controlled trial of neurosteroid treatment has failed. We have continued to supply medication in response to these emergency IND requests for SRSE. And through this, we're working to understand the best dosing paradigm for its treatment through the treatment of these patients, some of whom have been in status for weeks and have no other options.

Therefore, we need to think carefully about dosing in actual and the duration of therapy.

And we'll begin our clinical program in the earlier phase of status with dose finding work.

We've been talking to investigators by clinical study design and this is an area, where henry's deep knowledge and expertise will prove particularly valuable.

On the other end of the treatment spectrum.

We've been receiving requests for emergency use of Tenax loan in Super refractory status or Srs see this.

This is an extremely complex clinical situation in which as you know another controlled trial neuro steroid treatment as fail.

We have continued to supply medication in response to these emergency I in D. request for Srs see since.

And through this we are working to understand the best dosing paradigm for its treatment.

Through the treatment of these patients some of whom have been status for weeks and have no other options.

Or thinking hard about how we can engage the FDA and investigators to understand how to best address this unmet clinical need.

Some preliminary data in Srs C will be presented at the upcoming American Epilepsy Society annual meeting.

Finally, as Scott noted earlier, we've just submitted a request for scientific advice to the European Medicines Agency's committee for medicinal products for human use to obtain feedback on the design of a second RSU study to be conducted in Europe.

Joseph Hulihan: We are thinking hard about how we can engage the FDA and investigators to understand how to best address this unmet clinical need. Some preliminary data on SRSE will be presented at the upcoming American Epilepsy Society annual meeting. Finally, as Scott noted earlier, we've just submitted a request for scientific advice to the European Medicine Agency's Committee for Medicinal Products for Human Use to obtain feedback on the design of a second RSC study to be conducted in Europe. The study would be part of a filing strategy in Europe only.

The study would be part of a filing strategy in Europe only.

We expect feedback over the coming months and we'll share that update you accordingly.

Now turning to our Oregon excellent franchise as Scott just noted one of the highlights of the quarter was the success of the Marigold study.

Our global Phase three trial in CDK L five deficiency disorder.

The trial enrolled 101 patients between the ages of two in 19 to kind.

Joseph Hulihan: We expect feedback over the coming months, and we'll share that update with you accordingly. Now, turning to our Oregon Axiom Franchise. As Scott just noted, one of the highlights of the quarter was the success of the Marigold study, our global phase three trial in CDKL5 deficiency. The trial enrolled 101 patients between the ages of 2 and 19 who had a confirmed genetic mutation involving the CDKL5 gene, which is important for normal brain development and function. The study showed a statistically significant result with patients given oral Ganaxolone showing a reduction in the frequency of major motor seizures with Ganaxolone compared to placebo.

Got it confirmed genetic mutation involving the CDK L five gene.

Which is important for normal brain development and functionally.

The study showed a statistically significant result with patients given Oregon acts alone showing a reduction in the frequency of major motor seizures with an excellent compared to placebo.

This was the study's primary endpoint.

The median reduction in seizures was 32.2% and they can actually own group and 4% in the placebo group, yielding a P value of 0.00 to <unk>.

The next one was generally well tolerated with a safety profile consistent with previous clinical studies with the most frequent adverse event being someone's.

Despite the rarity of CBD, we were able to fully enroll the targeted sample of 100 patients on time.

Based on the robust results of the study we're confident that it provides evidence for efficacy and safety and we'll address an important treatment need for patients and their families.

Joseph Hulihan: This was the study's primary endpoint. The median reduction in seizures was 32.2% in the Ganaxialone group and 4% in the placebo group, yielding a p-value of 0.002. The next one was generally well tolerated, with a safety profile consistent with previous clinical studies, with the most frequent adverse event being somnolence. Despite the rarity of CDD, we were able to fully enroll the targeted sample of 100 patients on time. Based on the robust results of the study, we're confident that it provides evidence for efficacy and safety and will address an important treatment need for patients and their families. We look forward to meeting with the FDA to discuss an NDA submission in mid-2021. This study also provides a rich data set for further analysis, and next month at the American Epilepsy Society meeting, we'll be presenting results of analyses that further support the efficacy of Ganax Marigold also shows for the first time that canaxalone is efficacious when given as a three times a day regimen.

I look forward to meeting with the FDA to discuss and da submission in mid 2021.

This study also provides a rich dataset for further analysis.

Next month at the American epilepsy side. The meeting we will be presenting results of analyses that further support the efficacy of an actual own in CBD.

Marigold study also shows for the first time that connects loan is efficacious when given as a three times a day regimen.

This demonstration of the PK PD profile gives us great confidence in its ability to demonstrate any convulsing efficacy in our upcoming studies.

We've also taken a preliminary look at data from the open label extension of the Marigold study.

That suggests that patients remaining on an x. loan can have a durable effect.

We're also planning to provide for access to an x. loan for CDD patients, who are not able to participate in the Marigold study.

More on that at the upcoming Ats meeting.

Let's move next to tubular sclerosis complex or TSC.

Our newest clinical program.

As we noted this represents the next step in the assessment of our biomarker hypothesis.

Recall that the decision to conduct a TSC trial resulted from our discovery of a novel biomarker Hello, Perignon loan sulphate ore LLS during our phase two study in P. CDH 19 related epilepsy.

Joseph Hulihan: This demonstration of the PK PD profile gives us great confidence in its ability to demonstrate anticonvulsant efficacy in our upcoming. We've also taken a preliminary look at data from the Opal label extension of the Marigold study that suggests that patients remaining on Ganaxolone can have a durable effect. We're also planning to provide access to Ganaxolone for CDD patients who are not able to participate in the Marigold study. More on that at the upcoming AES meeting.

Patients with CBD, PCH 19, and TBSI all appeared to make abnormally low levels of this inhibitory neuro steroids and we now know that patients with TSC not only have low levels of euro steroids, but also functional abnormalities involving GABAA.

This study will help determine whether allopregnanolone plays a role in the pathophysiology of TSC.

And if abnormal neuro steroid production provides an opportunity for demonstration of a response biomarker in TSC and potentially other rare genetic epilepsies.

Joseph Hulihan: Let's move next to Tuberous Sclerosis Complex, or TSC, our newest clinical program. As we noted, this represents the next step in the assessment of our biomarker hypothesis. I recall that the decision to conduct a TSC trial resulted from our discovery of a novel biomarker, allopregnanolone sulfate, or AlloS, during our Phase II study in PCDH19-related epilepsy. Patients with CDD, PCDH19, and PTSD all appear to have abnormally low levels of this inhibitory neurosteroid. And we now know that patients with PTSD not only have low levels of neurosteroids but also functional abnormalities involving GABA. This study will help determine whether allopregnanolone plays a role in the pathophysiology of TSC and if abnormal neurosteroid production provides an opportunity for the demonstration of a response biomarker in TSC and potentially other rare genetic epilepsy.

As Scott mentioned, we've instituted efforts to boost enrollment in the phase two TSC study, including listing additional sites and having discussions with the investigators about participant recruitment.

And the initial results have been encouraging.

We realize that there are other factors that could also be playing a role.

Including response to the participating physicians to the topline data in CBD.

As well as decreases in the relocation of medical services to deal with Coke.

Regardless of the reason, we're seeing increase in patient screening.

I can also provide a bit more detail about the ongoing phase two TSC study, which will evaluate the safety and tolerability of adjunct took an actual loan for treatment of the refractory seizures in PSC.

We plan to enroll approximately 30 patients per image two to 65.

Enter four week baseline period, followed by a 12 week treatment period during which they will receive up to 600 milligrams have been excellent three times daily.

The study will also have a 24 week extension, which qualifying patients can continue can actually on treatment.

Joseph Hulihan: As Scott mentioned, we've instituted efforts to boost enrollment in the Phase 2 TSC study, including enlisting additional sites and having discussions with the investigators about participant recruitment, and the initial results have been encouraging. We realize that there are other factors that could also be playing a role, including response of the participating physicians to the top line data and CDD, as well as decreases in the reallocation of medical services to deal with COVID. Regardless of the reason, we're seeing an increase in patient screening. I can also provide a bit more detail about the ongoing Phase 2 TSC study, which will evaluate the safety and tolerability of adjunctive ginaxolone for treatment of the refractory seizures in TSC. We plan to enroll approximately 30 patients from age 2 to 65 who will enter a 4-week baseline period followed by a 12-week treatment period during which they'll receive up to 600 mg of Ganaxalone 3 times daily.

We expect that patients in this study as in the CBD trial will have highly refractory seizures that have been unresponsive to multiple anti seizure medications.

The primary endpoint is the percent change in the 28 day frequency of the most significant types of seizures seen in TSC during the treatment period relative to the baseline.

And we will also analyze aloe s. levels and their relationship to treatment response.

We plan to report topline data during the third quarter of 2021.

Our goal is to meet with the FDA in 2021 based on an interim analysis of the trial data and to share initial safety data in advance of initiating a phase three study.

We plan to conduct a double blind placebo controlled trial with the ultimate goal of filing unison da for TSMC as closely to our CBD filing as possible.

Finally, a quick update on the pilot study our proof of concept study in P. CDH 19 related epilepsy.

We've completed patient enrollment.

Each has the potential to provide additional support for the LLS biomarker hypothesis as well as for the improved PK PD and the three times a day dosing regimen.

Joseph Hulihan: The study will also have a 24-week extension in which qualifying patients can continue gonaxalone treatment. We expect that patients in this study, as in the CDD trial, will have highly refractory seizures that have been unresponsive to multiple anti-seizure medications. The primary endpoint is the percent change in the 28-day frequency of the most significant types of seizures seen in TSC during the treatment period relative to the baseline, and we will also analyze ALOES levels and their relationship to treatment response. We plan to report top-line data during the third quarter of 2021. Our goal is to meet with the FDA in 2021 based on an interim analysis of the trial data and to share initial safety data in advance of initiating a We plan to conduct a double-blind placebo-controlled trial with the ultimate goal of filing an SNDA for TSC as closely to our CDD filing as possible. Finally, a quick update on the Violet Study, our proof-of-concept study in PCDH19-related evidence.

[music].

The study will stratify patients into one or two biomarker groups based on our west levels.

And who were then randomized to connex lunar placebo within each of these strategies.

The study has a prospective baseline period, followed by a 17 week double blind treatment phase.

Patients randomized to get Axlon tight trade over four weeks to a dose of up to 600 milligrams of oral liquid suspension three times, a day and maintain that dose for an additional 13 weeks.

We expect to complete the double blind phase of the trial with approximately 20 patients and anticipate topline data in the first half of 2021.

And while the pilot study is not intended to support registration for an indication in PC DH 19 related epilepsy.

It will provide important information for the biomarker hypothesis for an excellent.

These studies represent a well defined and strategically targeted program focused on rare epilepsies with high unmet need.

Joseph Hulihan: We've completed patient enrollment, which has the potential to provide additional support for the ALOES biomarker hypothesis, as well as for the improved PK PD of the three times a day dosing regimen. The study will stratify patients into one or two biomarker groups based on LOS level, and who will then be randomized to ganaxalone or placebo within each of these strata. This study has a prospective baseline period followed by a 17-week double-blind treatment. Patients randomized to Ganaxalone titrate over four weeks to a dose of up to 600 milligrams of oral liquid suspension three times a day and maintain that dose for an additional 13 weeks. We expect to complete the double-blind phase of the trial with approximately 20 patients and anticipate top-line data in the first half of 2021. And while the Violet Study is not intended to support registration for an indication in PCDH19-related epilepsy, it will provide important information for the biomarker hypothesis for connection.

Where we believe can axlon has true potential to improve patient outcomes.

2020 has certainly been exciting, but we see 2021 is equally full of promising opportunity.

Well have several significant data readouts regulatory meetings filings, including in the submission of the NDA for CBD in the treatment of rare and often devastating seizure disorders.

Before I turn the call over to Ed to review our financials I.

I would like to thank the patients and their families who participate in these trials to record a treatment for rare genetic epilepsies.

We can't thank you enough for your support to improve the lives of all patients and families suffering from these often debilitating neurologic disorders.

With that I will turn the call over to Ed.

Thank you Joe and good afternoon, everyone. Our financial results for the third quarter of 2020, but at least this afternoon reflect results from operations in support of excellent development and commercial preparedness activities.

I'm pleased to report that this quarter is a first quarter for which we have recognized federal contract revenue in connection with our BARDA contract, which we entered into in September.

Federal contract revenue for Q3 was just under $200000 for the three months ended September Thirtyth 2020, compared to no such revenue for the same period a year ago.

Joseph Hulihan: These studies represent a well-defined and strategically targeted program focused on rare epilepsies with high unmet needs, where we believe Nexon has true potential to improve patient outcomes. 2020 has certainly been exciting, but we see 2021 as equally full of promise and opportunity, and will have several significant data readouts, regulatory meetings, and filings, including the submission of the NDA for CDD in the treatment of rare and often devastating seizures. Before I turn the call over to Ed, I want to review our financials. I would like to thank the patients and their families who participated in these trials directed at treatment for rare genetic epilepsy. We can't thank you enough for your support to improve the lives of all patients and families suffering from these often debilitating neurological disorders. With that, I'll turn the call over to Ed. Thank you, Joe. Good afternoon, everyone.

Revenue recognized in connection with our BARDA contract represent reimbursement for activities within the contract's scope it will vary quarter to quarter based on the timing of these activities.

As Scott mentioned earlier, our base BARDA contract initially provides $21 million of non dilutive funding over approximately the next 24 months most of which will be directed towards our phase three program in refractory status epilepticus with options based on success milestones that may expand.

To up to $51 million in total BARDA funding.

Research and development expenses were $11.3 million and $38.1 million for the three and nine months ended September Thirtyth 2020, compared to $11.6 million and $30.5 million for the same period in 2018.

Changes reflect the winding down of our PPD program and focused development efforts and resource investments on seizure disorders, including the phase three study in CVD phase two studies in PTD, eight thinking and TSC and gearing up for our phase three study in RSC.

Ed Smith: Our financial results for the third quarter of 2020, released this afternoon, reflect results from operations in support of GennX loan development and commercial preparedness activities. I'm pleased to report that this quarter is the first quarter for which we have recognized federal contract revenue in connection with our BARDA contract, which we entered into in September. Federal contract revenue for Q3 was just under $200,000 for the three months ended September 30, 2020, compared to no such revenue for the same period a year ago.

As well as preclinical and manufacturing activities in preparation for a potential anda filing in CD.

General and administrative expenses were $4.6 million and 12.5 million for the three and nine months ended September Thirtyth, 2020, which compares to $2.3 million and $8.5 million for the same periods last year.

Ed Smith: Revenue recognized in connection with our BARDA contracts represents reimbursement for activities within the contract scope and will vary quarter to quarter based on the timing of these activities. As Scott mentioned earlier, our base BARDA contract initially provides $21 million of non-diluted funding over approximately the next 24 months, most of which will be directed towards our Phase III program in Refractory Status Epilepticus, with options based on success milestones that may expand to up to $51 million in total BARDA funding. Research and development expenses were $11.3 million and $38.1 million for the three and nine months ended September 30, 2020, compared to $11.6 million and $30.5 million for the same period in 2019. Changes reflect the winding down of our PPD program and focused development efforts and resource investment on seizure disorders, including a phase three study in CDD, phase two studies in PTDH-19 and TSC, and gearing up for our phase three study in RSE, as well as preclinical and manufacturing activities in preparation for a potential NDA filing in CDD. General administrative expenses were $4.6 million and $12.5 million for the three and nine months ended September 30, 2020, which compares to $2.3 million and $8.5 million for the same periods last year.

The primary drivers of the increase were increased legal and consulting fees as we scale up our operations and prepare for potential commercialization.

Non cash stock based compensation expense.

Our net loss for the third quarter of 2020 was $15.7 million or 51 cents per basic and diluted share compared with a net loss of $13.8 million or one dollar five per basic and diluted share loss for the same period in 2019.

Our net loss for the nine months ended September Thirtyth, 2020 was 58.9 million or $2.29 per basic and diluted share compared to 38.7 million or $2.95 per basic and diluted share for the same period in 2018.

At September 32020, we had cash cash equivalents and investment balances of 91.3 million compared with approximately $91.7 million at the end of 2019.

Without taking into consideration any potential inflows to the company other than expected federal contract revenue from our BARDA contract, we believe that our cash cash equivalents and investments as of September Thirtyth 2020 will enable us to fund operating expenses and capital expenditure requirements into.

Through 2022, assuming our current scale of operations.

I'd like to thank our investors for their continued support and confidence in our programs I also want to of course, thank the entire management team and all marish employees for their hard work and dedication to our mission.

We look forward to continued momentum and progress as we round the corner into it another exciting year for Meritas I'll now turn the call back over to Scott before reenter the queue in a portion of the call Scott.

Thanks, Ed it's important for me to say that we are grateful for the continued commitment and dedication of the Marin team study site personnel and our investigators they.

Ed Smith: The primary drivers of the increase were increased legal and consulting fees as we scale up our operations and prepare for potential commercialization, as well as non-cash stock-based compensation expenses. Our net loss for the third quarter of 2020 was $15.7 million, or $0.51 per basic and diluted share, compared with a net loss of $13.8 million, or $1.05 per basic and diluted share loss for the same period in 2019. Our net loss for the nine months ended September 30, 2020 was $58.9 million, or $2.29 per basic and diluted share, compared to $38.7 million, or $2.95 per basic and diluted share for the same period in 2019.

They have enabled us to successfully navigate these unprecedented in challenging times to which our entire organization has risen to the occasion.

Twentytwenty has been an exciting year and we believe the best is yet to come.

Thank you and with that we will now open the call for questions.

As a reminder to ask a question you will need to press star one on your telephone.

Withdraw your question press, the pound or hash key please stand by what we compiled acuity roster.

Your first question comes from the line of Joseph <unk> from Cowen and company. Please go ahead.

Hi, there. Thank you for taking my questions and congratulations on all the great progress.

Maybe the first one on T.S.C. when.

When we see those data next year is there a 28 the seizure frequency reduction that you're targeting to give you confidence to go forward in the phase three or.

Or is there something else in the data package.

Looking for outside of just the seizure reduction.

Ed Smith: At September 30, 2020, we had cash equivalents and investment balances of $91.3 million compared with approximately $91.7 million at the end of 2019. Without taking into consideration any potential inflows to the company, other than expected federal contract revenue from our BARDA contract, we believe that our cash, cash equivalents, and investments as of September 30, 2020 will enable us to fund operating expenses and capital expenditure requirements into 2022, assuming our current scale of operation. I'd like to thank our investors for their continued support and confidence in our programs. I also want, of course, to thank the entire management team and all Marinus employees for their hard work and dedication to our mission.

And then maybe one more if I if I can I know youve previously indicated pursuing potential partnerships for either the Oregon ex loan in CBD alone or sort of the entire oral franchise does that open communication regarding the method of use patents in CDD Mpcs 19 effect tire thinking about partnership discussions at all.

Thank you.

Thanks for the question, Joe Let me tackle TSC, and then I'll flip it over to Joe and then I'll happily come back to the question. So on TSC. When we did our work and we talked to several consultants about the phase two trial many of them recommended the majority of them recommended a similar path than others.

Uptake and feel that a single arm study looking for a specific.

Efficacy signal, particularly.

I think that that message has been you've been reinforced and the positive TDD data, Joe why don't I flip it over to you to talk a little bit more about the efficacy signal you'd like to see and what you'll be looking at to truly help us design the phase three.

Scott Braunstein: We look forward to continued momentum and progress as we round the corner into another exciting year for Marinus. I'll now turn the call back over to Scott before we enter the Q&A portion of the call.

Sure Yes, Thanks, Scott I think the study is going to help us design.

A phase three study.

More than anything else.

In addition to whatever absolute reduction we see it.

Something in the range of two.

Scott Braunstein: Thanks, Ed. It's important for me to say that we are grateful for the continued commitment and dedication of the Marinus team, study site personnel, and our investigators. They have enabled us to successfully navigate these unprecedented and challenging times to which our entire organization has risen to the occasion. 2020 has been an exciting year, and we believe the best is yet to come.

The the placebo rates in other studies have been the range 15, 20%, so we'd like to see.

Probably at least 15% above that so 45%, but I don't think.

We'd lived liver guy on the absolute reduction.

We can look at seizure types and how the drug perform.

Performs not just overall ntsc whether there.

Differences based on fusion type.

It may have different seizure types and tea season in CBD. So.

Operator: Thank you. And with that, we will now open the call for questions. As a reminder, to ask a question, you will need to press star 1 on your telephone. To withdraw your question, press the pound or hash key.

So we've got to be the first look in that population.

And also potentially give us another look at the biomarker hypothesis.

So there is a lot we can get out of that study.

Beyond the absolute reduction in seizure frequency.

Operator: Please stand by while we compile the Q&A roster. Your first question comes from the line of Joseph Tomei from Cowan & Company. Please go ahead.

And safety also we can save a read on safety, which we expect to be fine.

So Joe let me take your question on I've, It and as a reminder for everyone on the call. We are in multiple strategic discussions both with the.

Joseph John: Hi there, thank you for taking my questions and congratulations on all the great progress. Maybe the first one on TSC, when we see the data next year, is there a 28-day seizure frequency reduction that you're targeting to give you confidence to go forward into phase three? Or is there something else in the data package, you know, that you'll be looking for outside of just the seizure reduction?

With strategics, who are interested in some global commercialization as well as other strategics, who who see this franchise is as very meaningful and one that we could potentially monetize and we've raised this topic with our strategic for with strategic partners for the CDD and.

In the entire world franchise, and we know that biopharmaceutical companies and other strategics, who who are seriously engaged with us understand and are highly knowledgeable and Pat matters and to this degree we do not see this issue at all as a significant.

Scott Braunstein: And then maybe one more, if I can, I know you've previously indicated pursuing potential partnerships for either oral Gonaxalone and CBD alone or for the entire oral franchise. Does that OVID communication regarding the method of use patents in CDD and PCH-19 affect how you're thinking about partnership discussions at all? Thank you. Thanks for the question, Joe. Let me tackle TSC first, and then I'll flip it over to Joe, and then I'll happily come back to the question.

Impediment to us.

Completing the deal.

And just finally is as we previously mentioned I really can't comment further on the other pads.

At this time other than to say that we are extremely confident with our plans on going ex loan and we do not expect to be delayed or disrupted with our launch plans.

Operator next question.

Your next question comes from the line of Marc Goodman from SVB Leerink. Please go ahead.

Scott Braunstein: So, on TSC, when we did our work and talked to several consultants about the Phase II trial, many of them, the majority of them, recommended a similar path that others have taken in the field, that is, a single-arm study looking for a specific efficacy signal. In particular, I think that message has been reinforced since the positive TDD data. Joe, why don't I flip it over to you to talk a little bit more about the efficacy signal you'd like to see and what you'll be looking at to really help us design a piece? Sure.

Hi, This is Judy online from Mark. Thanks for taking my question I just have a quick question regarding the ROI R&D spending because threeq you spending for R&D seems to be lives. So can you provide some color on the R&D spending going into Fourq, you 20 on a 2021 and.

How should we model these tendencies for status epilepticus given data you're studying two pivotal trials anyhow in U.S houseware earlier lying out these programs.

Thanks.

Hi, This is Ed I'll take that question. Thanks, Thanks for the question.

As as Weve discussed on the call. We've been we've essentially have completed and are just essentially moving into the open label phase of our CBD study.

Joseph Hulihan: Yeah, thanks, Scott. Well, I think the study is going to help us design and conduct a phase three study more than anything else. In addition to whatever absolute reduction we see and something in the range, the placebo rates in other studies have been in the range of 15, 20%.

And so there has been some drop off in expenses in that regard, but that at the same time we're in.

On that point in time, where we're going to be gearing up expenses associated with the phase three program and refractory status epilepticus. So.

Joseph Hulihan: So we'd like to see at least 15% above that, so 45%, but I don't think, You know, we'd live or die on the absolute reduction. We can look at seizure types and how the drug performs, not just overall in TSC, whether there are differences based on seizure type. They may have different seizure types in TSC than in CBD.

<unk> expenses on the R&D side tend to ebb and flow but.

But as I say I think if you look historically.

Say over the last 12 months look at our R&D line.

I think things are really going to be rather consistent from an expense standpoint through the end of this year. When you normalize over the course of the last 12 months and it's our expectation that expenses will start to gear up in the front half of next year.

Scott Braunstein: So we'll get to be the first look in that population and also potentially give us another look at the biomarker hypothesis. So there's a lot we can get out of that study, beyond the absolute reduction in seizures and safety. Also, we did a read on safety, which we expect to be fine. So Joe, let me take your question on AVID.

So as we prepare for it and then da filing in CGD and then.

And then secondly.

Scott Braunstein: And as a reminder for everyone on the call, we are in multiple strategic discussions, both with strategists who are interested in some global commercialization, as well as other strategists who see this franchise as very meaningful and one that we could potentially monetize. And we've raised this topic with strategic partners for the CDD and the entire oral franchise. And we know that biopharmaceutical companies and other strategists who are seriously engaged with us understand and are highly knowledgeable in patent matters. And to this degree, we do not see this issue at all as a significant impediment to us completing a deal. And just finally, as we previously mentioned, I really can't comment further on the AVID patents at this time other than to say that we are extremely confident with our plans for Ganaxone, and we do not expect to be delayed or disrupted by our launch plan. Operator, next question.

As we start to think about commercialization there will be expenses that ramp up in the back half of next year.

And Ed This is Scott I'll just add two as a reminder, we made an important strategic decision to truncate. The PC the age 19 study.

Ed limit that to a 20 patient study and that will have important savings as we move forward as well so that was a hard decision for us, but unequivocally we believe the right one and certainly that incrementally and it is helping on the R&D spend and we think it's much more important that that spend go into TSC.

We go into the RSC program and and I think we have some interesting Charles we're planning for the second half of 21, you'll hear about more about those.

Yes.

Got it thanks for the color and congrats on the quarter.

Thank you.

Your next question comes from the line of Joon Lee from Trust Securities. Please go ahead.

Operator: Your next question comes from the line of Marc Goodman from SVB Learink. Please go ahead. Hi, this is Rudy on the line for Marc.

Hi, Thanks for taking our questions and providing the update.

Marc Harold Goodman: Thanks for taking my question. I just have a quick question regarding R&D spending because 3Q spending for R&D seems to be light. So can you provide some color on R&D spending going into 4Q20 and 2021? And how should we model these pensions for status epileptics, given that you are studying two pivotal trials and you have new trials for earlier lines of this program? Thanks. Hi, this is Ed.

We fully appreciate the sensitivities around the IP issues, but.

The patent and trade spend only be enforceable on the PCB indication or other indications as well.

And what types of royalty rates would be appropriate and also can you guide us to the timing of the resolution of the pen issue.

And I have a follow up.

Thanks for the question June.

Ed Smith: I'll take that question. Thanks for the question. You know, as we discussed on the call, we've essentially completed and are just essentially moving into the open-label phase of our CDD study. And, you know, there have been some drop-off in expenses in that regard, but then at the same time, we're at that point in time where we're going to be gearing up expenses associated with the phase three program and refractory status epilepticus. So, you know, expenses on the R&D side tend to ebb and flow.

Let me start with the first piece of that question. Those the other patents are very specific method of use patents for CVD and P. CDH thinking only.

So they have no impact on either our status program or our TSC program I can't guide you to specific rate, but I can certainly reference encourage you to look into patent settlement cases.

That.

That are specific for method of use patent rather than composition of matter patents and they typically can be associated with specific royalty rates, but again, we're not commenting or being more specific at this time of what we what our ultimate a business decision will be certainly patent settlement is one of the things we consider and.

Ed Smith: But, you know, I think if you look historically, say over the last 12 months, look at our R&D line, you know, I think things are really going to be rather consistent from an expense standpoint through the end of this year when you normalize them, you know, over the course of the last 12 months. And it's our expectation that expenses will start to gear up in the front half of next year as we prepare for an NDA filing in CDD. And then secondly, as we start to think about commercialization, there'll be expenses that ramp up in the back half of next year. And Ed, this is Scott.

In licensing those patents, but certainly we are considering other business options as well at this time.

I Miss it did I Miss a piece of the question Jude or did I get them. All no that was very helpful. And the follow up question is how much of the 21 million in the initial funding from the barter are you expecting to receive over the next two to four quarters and what's the likelihood of.

Scott Braunstein: I'll just add, too, as a reminder, we made an important strategic decision to truncate the PCDH-19 study and limit that to a 20-patient study, and that will have important savings as we move forward as well. So, that was a hard decision for us, but unequivocally, we believe the right one, and certainly, that incrementally is helping on the R&D spend, and we think it's much more important that that spend go into TSC, go into the RSC program, and I think we have some interesting trials we're planning for the second half of 21. You'll hear more about those at AES. I got it. Yeah, thanks for the color and congrats on the quarter.

That additional 30 million.

Triggered and when do you expect that to be triggered.

Ed you want to take the first half and I'll take the second half.

Sure I'd be happy to the $21 million fund the initial funding of the grant its our expectation that that will come in.

Ratably over approximately the next 24 months now it's not going to come in on a straight line basis. This is a cost share contract. So based on completion of activities essentially we bill BARDA for the work that's been completed so it'll ebb and flow, but it's our expectation that.

Like I said, the bulk of that $21 million will come in over the next call. It.

Seven day quarters Scott.

Scott you want to take it from here.

Yeah, I'll take the second half so June the real key triggers for the next step of the BARDA program would be preclinical work, which is very much in line with the preclinical work that's done before basically the the rodent models that look at nerve gas toxicity in the treatment of good acts loan of four that acute.

Joon So Lee: Thank you. Your next question comes from the line of Joon Lee from Truist Securities. Please go ahead. Hi, thanks for taking our questions and providing the update. We fully appreciate the sensitivities around the IP issues, but would the open patent infringement only be enforceable on the CCD indication or other indications as well? And what types of royalty rates would be appropriate?

The treatment paradigm. So we run very similar studies before so.

So we're very confident about that and the other major trigger is the actual phase three itself and on a successful phase three then that would that would trigger the next step in the BARDA contract a big piece of that is a manufacturing scale up piece BARDA as you can imagine is very interested in the us.

Scott Braunstein: And also, can you guide us to the timing of the resolution of the patent issue? And I have a follow-up question. Thanks for the question, Joon. Let me start with the first part of that question. The OVID patents are very specific method of use patents for CDD and PCDH-19 only, so they have no impact on either our status program or our TSC program. I can't guide you to specific rates, but I can certainly encourage you to look into patent settlement cases that are specific to method of use patents rather than composition of matter patents, and they typically can be associated with specific royalty rates.

Supply chain, we think that could have some very important impact long term on our gross margins and certainly as we become a commercial stage company, having a more robust.

Supply chain and and certainly that would also allow BARDA the opportunity to ultimately purchase going ask saloon.

Ed Smith: Again, we're not commenting or being more specific at this time about what our ultimate business decision will be. Certainly, patent settlement is one of the things we could consider in licensing those patents, but we are considering other business options as well. Did I miss a piece of the question, Joon, or did I get it all?

At at a discounted rate via via the federal government pricing strategy, but we'd still be important business for us not it's not linked to any specific.

Amount of drug post approval.

We have some guidelines about typically what BARDA would be interested in purchasing but something that we're not talking about at this point in time and that purchase is separate than the contract itself just just to be clear.

Scott Braunstein: No, that was very helpful. And the follow-up question is, how much of the $21 million in initial funding from the borrower are you expecting to receive over the next two to four quarters? And what's the likelihood of that additional $30 million being triggered? And when do you expect that to be triggered?

Great well, thank you very much.

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Your next question comes from the line of only a few young from Cantor. Please go ahead.

Hi, This is Lee our colleagues thanks for taking our questions and want to add our congratulations.

Ed Smith: Ed, you want to take the first half, and I'll take the second half? Sure, I'd be happy to. The $21 million from the initial funding of the grant, it's our expectation that that will come in ratably over approximately the next 24 months. Now, it's not going to come in on a straight-line basis. This is a cost-share contract.

The first question is on your CBD program.

We each are positive top line I'm, just kind of curious what are the feedback you're hearing from physicians and how they're going to use the drug.

Thank you like a medicine that will be given to our patients or they are there particular hum.

Scott Braunstein: So, based on completion of activities, essentially, we bill BARDA for the work that's been completed. So, it'll ebb and flow, but it's our expectation that, like I said, the bulk of that $21 million will come in over the next, call it, seven to eight quarters. Scott, you want to take it from here? Yeah, I'll take the second half. So, Joon, the real key triggers for the next step of the BARDA program would be preclinical work, which is very much in line with the preclinical work that's been done before. Basically, the rodent models that look at nerve gas toxicity and the treatment of gonaxalone for that acute treatment paradigm.

Uh huh.

And I have a follow up.

Well. Thanks. Thanks for the question, we've got a lot of positive feedback on the data thus far we had the chance to present the data at the ash.

Annual CDD meeting that was held virtually just a few weeks ago.

Our scientific team was there Alex Committee, our head of scientific Affairs presented the data and got some great feedback from the KNL community. We really think the bigger showcase for us is going to be around yes, but certainly when we tested this profile with market research. We did a large third party market research.

Scott Braunstein: So, we've run very similar studies before, so we're very confident about that. And the other major trigger is the actual Phase 3 itself. And if it's successful, then that would trigger the next step of the BARDA contract. A big piece of that is the manufacturing scale-up piece.

Each project over the summer.

We used an absolute delta, 25% versus placebo and that profile was extremely well received our safety profile was incrementally better in the phase three so we have every reason to believe that the profile that we tested over the summer can be incrementally improved or is incremental.

Scott Braunstein: So, that would be a government pricing strategy, but it would still be important business for us. It's not linked to any specific amounts of drug post-approval. We have some guidelines about what BARDA would be interested in purchasing, but something that we're not talking about at this point in time. And that purchase is separate than the contract itself, just to be clear.

The improved.

We expect patient to be similar to what we've seen in the phase three trial.

The average age in the phase three with six years old the average patient had failed seven prior therapies and so we wouldn't expect many of these patients cycle through early drugs and have the opportunity to add onto next loan choose their current regiment and given the safety profile the tolerability of the drug.

Joon So Lee: Well, thank you very much. Of course. Your next question comes from the line of Alethea Young from Cantor. Please go ahead. Hi, this is Leon Filippia.

We we are expecting that that ultimately should we get approve that we would have very high demand in this patient population I think when we think about the TSC marketplace. We're thinking very similarly in terms of the patient population more refractory patients that have gone through several other medicines.

Alethea Young: Thanks for taking our questions, and we want to add our congratulations as well. Just the first question is on your CDD program. I mean, since you released your positive top line, just kind of curious, what are the feedbacks you're hearing from physicians and how they're going to use the drug? Do you think it's like a medicine that will be given to all patients? And I have a follow-up question. Well, thanks for the question.

That have limited options until we see those market opportunities for us much more similar than that than different.

Okay, and I know you had a you had a follow up.

Yes, just for the status rates trial, and now you have like 75% site selected.

Scott Braunstein: We've gotten a lot of positive feedback on the data thus far. We had the chance to present the data at the annual CDB meeting that was held virtually just a few weeks ago. Our scientific team was there.

So just wondering if you have any additional color on the placebo me at decides how to track back yard our original assumption.

Scott Braunstein: Alex Aimetti, our head of scientific affairs, presented the data and got some great feedback from the KOL community. We really think the bigger showcase for us is going to be around AES, but certainly when we tested this profile with market research; we did a large third-party market research project over the summer. We used an absolute delta of 25% versus placebo, and that profile was extremely well received. Our safety profile was incrementally better in Phase III, so we have every reason to believe that the profile that we tested over the summer can be incrementally improved or is already incrementally improved. We expect patients to be similar to what we've seen in the Phase III trial. The average age in the Phase III trial was six years old.

Oh, that's a great question, we haven't actually updated internally.

So it's a great question for me to go back and push the team on but but I'll remind you of the first 50 sites that we asked the question what do you expect to be the rate of general anesthesia. After two failed anti epileptics and the answer was about 75% are very consistent with what we expected.

Incrementally higher usage general anesthesia than were modeling per phase three result, so we'll we'll get that for you or for next quarter.

Scott Braunstein: The average patient had failed seven prior therapies, and so we would expect many of these patients to cycle through early drugs and have the opportunity to add Gonaxalone to their current regimen. Given the safety profile and the tolerability of the drug, we are expecting that, should we get approved, there will be very high demand in this patient population. I think when we think about the TSC marketplace, we're thinking very similarly in terms of the patient population. More refractory patients that have gone through several other medicines that have limited options, and so we see those market opportunities for us much more similarly than different trials, and I know you had a follow-up. Yes, just for the status of the trial, and now we have about 75% of sites selected. So just wondering if you have any additional color on the placebo rate at this site, and how does it track with your original assumption? Oh, that's a great question.

Once we have effectively all our sites ready to go and I think the other really important piece that we talked about in our prepared remarks that our sites are almost all driven by neuro Intensivists and I think those are the folks who really understand the pathway for non convulsive status and they are really going to be the users of the drug.

Doug and nervous and we really believe that's going to be the key to driving strong enrollment rates and that certainly was the case in phase two.

So thank you. It's a 524, we can take two or three more questions, but we want to break it by 30. So operator, maybe the next question. Please.

Your next question comes from the line of Douglas Tsao from H.C. Wainwright. Please go ahead.

Hi, good afternoon, thanks for taking the questions and congrats on all the progress so Scott maybe just as a starting point maybe provide your current thoughts on sort of the the or sort of what you plan to do with the oral business in terms of commercializing yourself I know it sounds like you continue to believe in talks.

Scott Braunstein: We haven't actually updated internally, so it's a great question for me to go back and push the team on. But a reminder, at the first 50 sites where we asked the question, what do you expect to be the rate of general anesthesia after two failed antiepileptics? And the answer was about 75%.

And then there is a kid of is your sounds like there was theres been some interest just curious what are you waiting to see is that data from the TSC on study or is it sort of independent of additional data and then just another question in terms of the RSV study I know just given.

Scott Braunstein: Very consistent with what we expected and an incrementally higher use of general anesthesia than we're modeling for phase three results. So we'll get that for you for next quarter once we have effectively all our sites ready to go.

The condition getting informed consent can be a challenge in sort of a limit or in terms of your ability to enroll patients have you made changes versus the phase two study that might ease that somewhat thank you very much.

Scott Braunstein: And I think the other really important piece that we talked about in our prepared remarks is that our sites are almost all driven by neurointensiveness. And I think those are the folks who really understand the pathway for non-convulsive status, and they're really going to be the users of the drug. And we really believe that's going to be the key to driving strong enrollment rates, and that's certainly what happened in phase three. So, thank you. It's 524.

Thanks, Joe you want to take the second question on.

Informed consent and then I'll talk about the Oregon.

Sure Yes.

No I think the main thing we learned from the phase two study was.

How to get consent from the sites.

Operator: We can take two or three more questions, but we want to break at 530. So, operator, maybe the next question, please? Your next question comes from the line of Douglas Tsao from H.C. Wainwright. Please go ahead. Hi, good afternoon.

No.

Particular Henry site.

Brigham and womens how to get consent and what the approach should be.

So getting consent early you know kind of pre consent patients who may be candidates for the study so that when the time comes they can be.

Douglas Dylan Tsao: Thanks for taking the questions and congratulations on all the progress. So, Scott, maybe just as a starting point, maybe provide your current thoughts on sort of what you plan to do with the oral business in terms of commercializing yourself. I know it sounds like you continue to be in talks and appear to be here. It sounds like there's been some interest. Just curious, you know, what are you waiting to see?

Credo than on entered.

Quickly so I think that's the key and.

And Weve educated the sites about that we've talked to them.

To make sure that they know they could they should.

You can send patients in so doing it that way.

We anticipate the content will be an impediment to enrollment it.

Scott Braunstein: Is it data from the PSC study, or, you know, is it sort of independent of additional data? And then, just another question in terms of the RSC study: given the condition, getting informed consent can be a challenge and sort of a limiter in terms of your ability to enroll patients. Have you made changes versus the phase two study that might ease that some way? Thank you very much.

And do you think that given that that you might be able to sort of have somewhat faster enrollment than what you saw or in terms of getting patients into the study from one though too we sort of meet the eligibility requirements.

Yeah, well I, certainly hope so, but I think for now until we get a better read on it.

I think we need to stick with the projection that.

The operations team has given in terms of how we would roll, but I would certainly like to see that enroll quickly.

Joseph Hulihan: Thanks, Doug. Joe, you want to take the second question on informed consent, and then I'll talk about oral consent. Sure. Yeah, no. I think the main thing we learned from the phase two study was how to get consent from the sites. In particular, Henri's site at... Brigham and Women's, how to get consent and what the approach should be.

And it depends on a lot of things so.

But I I think had minimum wage will have enrolled in the timeline for that.

Yeah, and Doug Let me just add to that I'd said this to many of you in our phase two we had four key active sites from the time I joined in February through the summer and we enrolled 0.5 patients per month per site 0.5 patients per month per site and with our 80.

Joseph Hulihan: So getting consent early, you know, kind of pre-consent patients who may be candidates for the study so that when the time comes, they can be, you know, treated and entered quickly. So I think that's the key. And, and we've educated the sites about that. We've talked to them to make sure that they know they could, they should pre-consent patients. And so doing it that way.

Sites in this phase three with those all activated by the end of Q1, our predictions or our calculation to get topline data in the first half 22 is roughly point too.

Patients per site per month, so we've taken a pretty cool.

Conservative approach to the numbers, but to Joe's point until we're up and running so we'll have to wait and see so we heard from one site. This week that they expected to enroll 10 to 20 patients in this study and we said sign them up but even that were kind of waiting and seeing on that one.

Joseph Hulihan: We anticipate that consent won't be an impediment to enrollment. And do you think that, given that, you might be able to sort of have somewhat faster enrollment than you saw, in terms of getting patients into the study from those who sort of meet the eligibility requirements? Yeah, well, I certainly hope so. But until we get a better read on it, I think, you know, we need to stick with the projection that the operations team has given in terms of how we'll enroll. But I would certainly like to see it enroll. It depends on a lot of things, but I think at minimum we'll have it enrolled in the timeline. Yeah, and Doug, let me just add to it.

On the on the oral side Doug a.

Lots changed in the last 12 months I think one we've really done a lot of work on the CDD franchise and I think to your point, we are our conviction that we can have a real opportunity in and make a difference in patients with TSC deak really robust and ends and as a reminder.

To every one the phase two TSC data is open label, which means we can take some looks at that data and really understand.

Scott Braunstein: You know, I've said this to many of you, in phase two, we had four key active sites from the time I joined in February through the summer, and we enrolled 0.5 patients per month per site. 0.5 patients per month per site. And with our 80 sites in this phase three, with those all activated by the end of Q1, our predictions, or our calculations, to get top-line data in the first half of 22 are roughly 0.2 patients per site per month. So we've taken a pretty conservative approach to the numbers, but to Joe's point, until we're up and running, we'll have to wait and see. So we heard from one site this week that they expected to enroll 10 to 20 patients in the study, and we said, sign them up. But, you know, even that. We're kind of waiting and seeing on that one. On the oral side, Doug, a lot has changed in the last 12 months.

Whether or not there is a strong signal and that's certainly going to have a big impact on how we view the franchise in terms of its size and its value to pacira.

Sorry to Meredith excuse me I was going to mention as well that our new Chief commercial officer, Krissy Shaffer fee and I worked together Pacira, that's why I have that little slip.

We were talking about the oral launch today and I think we both agree as has our early market research that getting out into the world market and talking about a novel mechanism of action and talking about the role of extra synaptic GABAA.

Receptors can really help us as we're thinking about seeding.

The Ivy market for status epilepticus, So we really see the strategic value of the franchise in the U.S. the oral to Ivy market being really potentially important for us and again, we know how difficult hospital launches can be so everything we can do to help build that franchise.

Scott Braunstein: I think, first of all, we've really done a lot of work on the CDB franchise, and I think, to your point, our conviction that we can have a real opportunity and make a difference in patients with TSC is equally robust, whether or not there is a strong signal. And that's certainly going to have a big impact on how we view the franchise in terms of its size and its value to Pacira. I'm sorry to Marinus. Excuse me.

From early days, we think is very important certainly we don't expect to go outside the U.S.

Scott Braunstein: I was going to mention as well that our new chief commercial officer, Christy Shafer, and I work together at Pacira. That's why I had that little slip. So we really see the strategic value of the franchise in the U.S., the oral to IV market being really potentially important for us. And again, we know how difficult hospital launches can be. So everything we can do to help build that franchise in the early days is very important. So, you know, we're really going to investigate all types of strategic options, but in a perfect world, we'd love the opportunity to launch the oral program in the U.S., particularly if we see a strong signal in TSC. And we think it's going to set us up very nicely for SC. So that's a big reason for my change of strategic thinking over the past few months. Thanks for the question. Thank you so much for that; that's really helpful.

And we're very actively engaging with with with strategic can help us outside the U.S., but I would say no.

I think my job as CEO is to really do better for our shareholders and if there's the right strategic deal for the entire oral franchise or some Permian permutation of that we have to think pretty hard about that as well so.

We're we're really going to investigate all types of strategic options, but in a perfect world, We'd love the opportunity to launch the oral program in the U.S., particularly if we see a strong signal in TSC and we think that's going to set us up very nicely for us. So that's that's a big reason for my might change of strategic thinking over the.

Past few months.

Thanks for the question Doug Yeah. Thank you so much right that's really helpful.

Operator: Yeah, sure. I think we can take one more operator and then we're going to have to call it. Your last question comes from Jay Olson from Oppenheimer. Please go ahead. Oh, hey, guys. Thanks for squeezing my chin.

Sure I think we'll take one more operator, and then we're going to have to call.

Your last question comes from Jay Olson from Oppenheimer. Please go ahead.

Hey, guys. Thanks for squeezing your stupid.

A couple questions on that it's.

Jay Olson: A couple questions on status. Do you share any thoughts on the recent approval of Spas-Senatone IV from CDOR by Pharma for status athleticus? Do you consider that to be a competitor, and what are some of the key points of differentiation for Gonaxalone? And then separately, for your Phase III study of Gonaxalone in Europe for RSC, what comparator would you consider putting into that study? And EMA except second-line benzos or other anti-epileptic drugs. Thank you. Thanks. Thanks for the question. And let me take the first half, and I'll pass it over to Joe for the second one, Jay.

Fair and thoughts on the recent approval of spar and Tom I.

Youre pharma for status epilepticus.

You consider that to be a competitor and.

What are some of the key points of differentiation for can act on and then separately.

For your phase three study of connects known in Europe for RSC.

What comparative is would you consider.

Putting into that study would would it.

In a except second line benzos or other antioxidant anti epileptic drugs. Thank you.

Thanks, then kind of question.

And let me take the first half and then I'll pass it over to Joe could that.

The second one Jade.

Scott Braunstein: In terms of the approval today, I think the big difference, at least from my perspective looking at the label today, is incrementally higher doses to help patients achieve higher blood levels faster. We know from the ESET study that all three different drugs that were tested in that frontline setting had less than a 50% response rate. We would expect drugs like Fosfenatone to be used in first and second line patients. We've talked to some big experts out there who said, you know, no patient is really treated for status unless they've gotten a sodium channel blocker, although the data really would suggest that these agents are used interchangeably. And our view is, as of today, we've got a drug that's going to have a very high success rate. I'm comfortable saying 80% or greater. I would expect it to be 90% or greater.

In terms of the approval today I think the big different at least my opportunity looking at the label today, it's incrementally higher dosing.

To help patients achieve higher blood levels faster, we know from me He said study that.

All all three different drugs that were tested in that front line setting.

Have less than a 50% response rate, we would expect drugs like Fox and it's going to be used in first and second line patients we've talked to some big experts out there who says.

No patient is really treated for status unless they've gotten it.

Tony I am channel blocker, although the data really would suggest that that these agents.

Our used interchangeably.

And our view is as of today, we've got a drug that's going to have a very high success rate comfort.

Comfortable thing, 80% or greater I would expect it to be 90% or greater so in the hospital setting. There is no up there's really no chance that we're going to be the runaway for stroke right. We're going to be a drug that typically is going to be second and third line at least in our early days of RSC. We certainly think there's an opportunity to move.

Scott Braunstein: So in the hospital setting, there's really no chance that we're going to be the runaway first drug, right? We're going to be a drug that is typically going to be used second and third line, at least in our early days of RSE. We certainly think there's an opportunity to move into the frontline setting in combination, and maybe that's the perfect lead for Joe to talk about, you know, what we may be comparing. Yeah, sure. Well, for the European study, one thing about Ganaxalone, I think we saw a very rapid onset of effect, and I think potency at that stage of status would be, I would think, superior to phosphonatoin We're not going to restrict that in any way. Phosphenetoin has limited availability in Europe. It's available in some countries, but not many.

Of into the into the frontline setting in combination and maybe that's a perfect lead for Joe to talk about.

What we may be comparing ourselves to in the future.

Yeah sure well for the European study we.

Thinking about Tenax alone I think.

We saw a very rapid onset of effect and I think potency at that stage of status I think.

It would clearly.

It will be I would think superior to foster the towing.

And in terms of the comparative years.

It'll be the investigators choice.

Not going to restrict that anyway.

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Cost phenytoin has.

Limited availability in Europe, it's available in some countries but.

Not many and so.

Joseph Hulihan: And so, andlevotirastam, as I understand it, is by far the first drug of choice. So that would leave valproate, leucosamide, where it's available, and phosphenetoin. And so it would have to be either a drug that they've already failed on, or we're allowing a redose, a higher dose, of a drug that's already been given if it's a substantial increase because otherwise the pool of drugs would be fairly limited. So it's really the investigator's choice. And we don't expect, actually don't expect the efficacy to be significantly different in the U.S. where it's given versus placebo versus in Europe where it will be against.

And we've addressed times understand is by far.

The first drug of choice, so that would leave appropriate lakos semis.

Wherever it's available for us to kind of toy.

And so.

We would have to be either a drug that they had already failed or we're allowing your re dos a higher dose of a drug that's already been given that gets a substantial dose.

Because otherwise the pool of drugs would be fairly limited. So it's really the investigators choice and we don't expect.

Actually don't expect the efficacy.

To be significantly different in the U.S., where it's given versus placebo virtusa in Europe, where it'll be against the comparisons.

Jay Olson: Great, thank you for taking the questions. I will now hand it over to the... Oh, thank you. Thank you so much. And first, I want to say thanks to everyone for dialing in. And really, I appreciate you mixing up the questions. Ed got great airtime tonight. It was nice to have the CFO answer a few questions on a biotech earnings call. So that was great without having real revenue.

Great. Thank you for taking the questions.

Oh sure.

I will now read out criteria over too.

Yes, okay. Thank you. Thanks, so much in the first I want to say, thanks to everyone for dialing in and really.

I appreciate you mix up the questions Ed got great airtime Tonight, with nice EVP and CFO answer a few questions on the biotech earnings call for that that was great with without having real revenue.

Scott Braunstein: And otherwise, I'd like to thank you all for joining us today. And we appreciate your continued support. Before we close, Sasha will run down some upcoming events that you may want to take note of. Okay, Sasha?

And otherwise I would like to thank you all for joining today and we appreciate your continued support before we close Sasha will run down on some upcoming event that you may want to take note of Sasha.

Sasha Damouni Ellis: Thanks, Scott. As mentioned throughout the call, we will have several presentations during the AES First World Meeting in December, including further analyses on the Marigold trial and SRFB. We will announce further details closer to the event. We also intend to hold a separate investor event on December 7 from 12pm to 2pm Eastern Time. Our leadership will also be presenting at a number of investor conferences over the coming weeks, so we encourage you to check out our website for more information. And finally, I want to acknowledge that Scott has accepted, on behalf of the entire Marinus organization, the Lulu Foundation's Company Making a Difference Award for Clinical in recognition of our work on the Marigold study. The Lulu Foundation is dedicated to helping those with CDKL5 deficiency disorder.

Thank God I'm as mentioned throughout the call. We have had several per hour. We will have several presentations during the first war meeting in December including providing further analyses on the marigolds trial.

R&D, we will announce further details closer to the event. We also intend to hold a separate investor event on December 7th from 12 PM to two PM Eastern time, our leadership will also be presenting at a number of investor conferences over the coming weeks. So we encourage you to check out our website for more information and finally.

I want to acknowledge that Scott has accepted on behalf of the entire Meritas organization. The Lulu foundations company, making a difference award for clinical.

In recognition of our work on the Marigold study that Lou Foundation is dedicated to helping knows with CDK, all five deficiency disorder and with that thank you everyone for joining the call today.

Sasha Damouni Ellis: And with that, thank you everyone for joining the call today. Ladies and gentlemen, this concludes today's conference call. Thank you for participating. You may now disconnect.

Ladies and gentlemen, Thanks concludes today's conference call. Thank you for participating you may now disconnect.

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