Q2 2022 Marinus Pharmaceuticals Inc Earnings Call

Greetings, and welcome to the Marinus Pharmaceuticals second quarter 2022 financial results and business update call.

Greetings and welcome to the Meredith Pharmaceuticals, second quarter, 2022 financial results and business update call.

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And now it is my pleasure to introduce your host, Sasha, Damouni-Ellis, Vice President of Corporate Affairs and Investor, Relations.

And now it is my pleasure to introduce your host Sasha do many Ellis Vice President of corporate Affairs and Investor Relations.

You may begin, Mr. Damouni-Ellis.

You may begin to somebody else.

Yeah.

Thank you, and good morning.

Thank you and good morning.

With me for Marinus are Dr. Scott Bromstein, Chief Executive, Officer, Christy Shafer, Chief Commercial Officer, Dr. Joe Hulihan, Chief Medical Officer, and Steve Pfanstiel, Chief Financial Officer.

With me for Meredith are Dr. Scott Braunstein, Chief Executive Officer, Christy Schaefer, Chief Commercial Officer, Dr. Joe Houlihan, Chief Medical Officer, and see Stanfill, Chief Financial Officer.

Before we begin, I would like to remind everyone, that some of the statements we are making today are forward-looking statements under the securities laws. These forward-looking statements involve substantial risks, and uncertainties that could cause our clinical development programs, future results, performance, or achievements to differ significantly from those expressed or implied by such forward-looking statements.

Before we begin I would like to remind everyone that some of the statements. We're making today are forward looking statements under the securities laws. These.

These forward looking statements involve substantial risks and uncertainties that could cause our clinical development programs future results performance or achievements to differ significantly from those expressed or implied by such forward looking statements.

These risks and uncertainties and risks, associated with our business are described in the company's reports filed with the Securities and Exchange, Commission, including Form 10-K, 10-Q, and 8-K.

These risks and uncertainties and risks associated with our business are described in the company's reports filed with the Securities and Exchange Commission, including forms 10-K, 10-Q and 8-K.

I will now turn the call over to our CEO, Scott Bromstein.

I will now turn the call over to our CEO Scott Braunstein.

Thank you, Sasha, and welcome to our call.

Thank you Sasha and welcome to our call. We ended the first quarter with the exciting news that totally with you.

We ended the first quarter with the exciting news, that Zitomy received FDA approval for the treatment of seizures associated with CDKL5 deficiency disorder in patients two years of age and older and are pleased to now be receiving our first prescription and completed patient enrollment forms.

SBA approval for the treatment of seizures associated with <unk> deficiency disorder in patients two years of age and older.

Pleased to now be receiving our first prescription and completed patient enrollment forms.

Our shell force has been in the field, engaging and educating physicians at CDD Centers of Excellence and National Epilepsy Centers, and we are encouraged by the strong early interest in Zitomy.

Our sales force has been in the field engaging and educating physicians at <unk> Center of excellence and National epilepsy centers and we are encouraged by the strong early interest and just tell me.

In addition to the April publication, of the Phase III marigold result in the Lancet Neurology, the first international consensus recommendation for the assessment and management of individuals with CDKL5 deficiency disorder was published in Frontiers in Neurology in June.

In addition to the April publication of the Phase III Marigold result in the lancet neurology. The first international consensus recommendation for the assessment and management of individuals with <unk> deficiency disorder with publishing frontiers in neurology in June .

Among the survey results in the publication, respondents, which include an international panel of expert clinicians and researchers, all supported offering Zitomy for the treatment of seizures associated with CDD.

Among the survey results in the publication respondents would you include an international panel of expert clinicians and researchers all supported offerings. Good policy for the treatment of seizures associated with G. D D.

Both of the publications are timely for the launch, which Christy will discuss in more detail shortly.

Both of the publications are timely approval launch, which Christie will discuss in more detail shortly.

I would like to once again thank the patients, families, and investigators who participated in the clinical program for all they have done to help us achieve this momentous milestone.

I would like to once again, thank the patients families and the investigators who participated in the clinical program for all they have done.

GE this momentous milestone.

We have a number of other operational updates, that we will be sharing during the call, and I would like to start with the first data set from our Next Generation Product Development Program.

We have a number of other operational update so we will be sharing during the call and I would like to start with the first dataset from our next generation product development program. We have seen promising initial results in our phase one healthy volunteer study utilizing the first of our next generation formulations.

We have seen promising initial results, in our Phase I Healthy Volunteer Study, utilizing the first of our Next Generation formulations, which Joe will discuss in detail later on the call. The PK profile is showing several differentiated features compared to our current oral suspension, which makes us believe that we can ultimately achieve our desired goal in chronic dosing. Key goals of the second-generation formulation are to improve bioavailability and to drive, higher steady-state blood levels of gonaxalone, which we believe will enhance efficacy.

Which Joe will discuss in detail later on the call.

The PK profile showing several differentiated features compared to our current oral suspension, which makes us believe that we can ultimately achieve our desired goal in chronic dosing.

He called the second generation formulation are to improve bioavailability and to drive higher steady state blood levels of <unk>, which we believe will enhance efficacy.

We also believe it will be important to improve Zitomy's dose frequency as we think about, the potential for additional new indications that are well-suited to address areas of unmet needs, including Lennox-Gasso syndrome.

We also believe it will be important to approve upon the told me those frequency as we think about the potential for additional new indications that are well suited to address areas of unmet need including Lennox <unk> syndrome.

We have several important updates on our late-stage clinical pipeline that I am excited to share.

We have several important updates on our late stage clinical pipeline that I am excited to share let me start with the IV program.

Let me start with the IV program. We've had productive interactions with the FDA and have reached preliminary alignment, on our proposed IV gonaxalone formulation change, specifically the modification of the buffer system. The FDA agreed that, in principle, a buffer change in gonaxalone IV formulation is acceptable, and acknowledged Marinus' plans to transfer the production of IV gonaxalone to a new manufacturing facility for future clinical supplies, including the ongoing RAISE trial in status epileptics. Importantly, this alignment provides us confidence that our new batches will meet the necessary, FDA requirements upon the filing of a new drug application.

We've had productive interactions with the FDA and have reached preliminary alignment on our proposed IV formulations.

Formulation change specifically the modification of the buffer system. The FDA agreed that it in principle, a buffer change in <unk> IV formulation is acceptable.

Knowledge marriage plans to transfer the production of IV <unk> to a new manufacturing facility for future clinical supply, including the ongoing raised trial in status epilepticus.

Importantly, this alignment provides us confidence that our new batches will meet the necessary FDA requirements upon the filing of a new drug application.

Early stability assessments of IV gonaxalone using a new buffer has shown promising initial, results that are likely to support greater than 24 months of shelf life at room temperature. We expect to begin producing our NDA batches in the fourth quarter of this year, utilizing, our new manufacturing site and buffer for our IV formulation.

Or at least stability assessments of IV can ask alone using a new bucker has shown promising initial results that are likely to support greater than 24 months of shelf life at room temperature.

We expect to begin producing our NDA batches in the fourth quarter of this year utilizing our new manufacturing site in buffer for IV formulation.

I'm extremely proud of the work done by both our CMC and regulatory teams to continue a, productive dialogue and scientific exchange with the FDA.

Im extremely proud of the work done by both our CMT and regulatory teams to continue a productive dialogue and scientific exchange with the FDA.

Let me comment on the Phase III RAISE trial.

Let me comment on the phase III <unk> trial as previously communicated we are implementing important changes to the raised protocol expanding eligibility criteria to accelerate enrollment.

As previously communicated, we are implementing important changes to the RAISE protocol, expanding eligibility criteria to accelerate enrollment. The protocol amendment is expected to be adopted across the majority of clinical sites, by the end of the third quarter.

Protocol Amendment is expected to be adopted across the majority of clinical sites by the end of the third quarter.

Moving to our Phase III TRUST-TSD trial in tuberous sclerosis complex, we are pleased, to share that the first patient has been randomized and dosed.

Moving to our Phase III Trust TST trial in tuberous sclerosis complex. We are pleased to share that the first patient had been randomized in dose.

We continue screening patients at U.S. sites with European activations on track to begin, in the third quarter of this year. We are targeting 80 global clinical sites, predominantly in the U.S., Western Europe, Canada, and Israel.

We continue screening patients that U S site with European Activations on track to begin in the third quarter of this year.

We are targeting 80 global clinical sites predominantly in the U S. Western Europe , Canada, and Israel, We continue to believe that the new phase III titration schedule will have a meaningful improvement of tolerability and efficacy and look forward to the anticipated data readout in the first quarter of 2024.

We continue to believe that the new Phase III titration schedule will have a meaningful, improvement on tolerability and efficacy and look forward to the anticipated data readout in the first quarter of 2024.

We have been actively engaging with the TSD community, including our participation during, the recent TSD World Conference. After our team's interactions with both clinicians and families, we continue to believe, that there is a significant unmet need for patients suffering with refractory seizures associated with TSD and that TAMI has the potential to be an important option for these patients.

We have been actively engaging with the TLC community, including our participation during the recent GSE World culture.

After our teams' interaction with both clinicians and family. We continue to believe that there is a significant unmet need for patients suffering with refractory seizures associated with GST and the telling me. It has the potential to be an important option for these patients.

Finally, some comments on how we plan to bring Zotomi to patients and families globally. In parallel to the U.S. commercial activities, we continue to work with regulatory authorities, to advance Zotomi in other key regions.

Finally, some comments on how we plan to bring to the totally to patients and families globally.

In parallel to the U S. Commercial activities, we continue to work with regulatory authorities to advanced autonomy in other key regions in Europe , we are targeting submitting complete responses.

In Europe, we are targeting submitting complete responses to the EMA's Day 120 list of questions, to the CDD Marketing Authorization Application by November, which would result in a CHMP by the end of the first quarter of 2023. There have been significant efforts from both the Marinus team and our strategic partner, Orion Corporation, in anticipation of a European commercial launch.

They they 120 list of questions for the <unk> marketing authorization application by November which would result in a <unk> opinion by the end of the first quarter of 2023.

There have been significant effort from both the Meredith team and our strategic partner Orion Corporation in anticipation of a European commercial launch.

In addition, we believe that there is a broader global opportunity to help patients and are, exploring further ex-U.S. commercial alliances to expand Gadasolone's footprint.

In addition, we believe that there is a broader global opportunity to help patients and are exploring further ex U S commercial lines to expand good excellent footprint.

Now, I would like to turn the call over to our Chief Commercial Officer, Christy Shafer, for updates on the commercial launch of Zotomi.

Now I would like to turn the call over to our Chief commercial officer, Christy Schaefer for updates on the commercial launch of the Tony.

Thank you, Scott.

Thank you Scott today I'm excited to share our early progress on the commercial launch of the economy and the U S.

Today, I'm excited to share our early progress on the commercial launch of Zotomi in the U.S.

Yes.

Since the approval in March, we've continued to see a high level of enthusiasm for Zotomi, from both physicians and caregivers, reflecting the need in this community and the potential that Zotomi could provide in seizure management.

Since the approval in March we continued to see a high level of enthusiasm for the Tommy from both physicians and caregivers, reflecting the need in the community and the potential that the Tommy could provide in senior management.

In the first two weeks of launch, we are strongly encouraged by the early volume, of completed patient enrollment forms and are actively fielding questions regarding enrollment and prescriptions. Initial launch feedback from the field has confirmed strong, interest from a unique base of physicians in prescribing Zotomi.

In the first two weeks of launch we are strongly encouraged by the early volume of completed patient enrollment.

And are actively fielding questions regarding enrollment and prescriptions.

Initial launch feedback from the field has confirmed strong interests from a unique base of physicians prescribing the Tommy.

In addition to referrals from the U S. CBD centers of excellence and National Epilepsy centers. We're also very encouraged by early interest coming from outside our key accounts.

In addition to referrals from the U.S. CDD Centers of Excellence and National Epilepsy Centers, we're also very encouraged by early interest coming from outside our key accounts.

Additionally, we continue to establish relationships with key payers representing, a large proportion of covered lives in the U.S, and have already begun to see positive coverage criteria being published to support patient access.

Additionally, we continue to establish relationships with key payers, representing a large proportion of covered lives in the U S and have already begun to see positive coverage criteria being published to support patient access.

As a reminder, we shared in June that Zotomi received a Schedule 5 designation, by the Drug Enforcement Administration, which is the least restrictive schedule. We are pleased with this designation, which further builds our confidence in how parents, healthcare providers, and payers will view Zotomi as an important treatment option for seizures associated with CDKL5 deficiency disorder in patients two years of age and older.

As a reminder, we shared in June that said Tony received a scheduled five designation by the drug enforcement administration, which is the least restrictive schedule. We are pleased with this designation with further builds our confidence in how parents health care providers and payers will view the Tommy as an important trade.

One option for seizures associated with CDK, all five deficiency disorder in patients two years of age and older.

The major strategic objectives of our commercial launch are to continue educating healthcare, providers and caregivers on the compelling efficacy and safety profile of Zotomi and to enable seamless patient access from prescription through fulfillment. Our marketing team has developed a suite of communication tools that provide important, information to educate healthcare providers and caregivers about the benefits and important safety information of Zotomi.

The major strategic objectives of our commercial launch are to continue educating health care providers and caregivers on the compelling efficacy and safety profile of the Tommy.

To enable seamless patient access from prescription fulfillment.

Our marketing team has developed a suite of communication tool that provide important information to educate health care providers and caregivers about the benefits and important safety information of the Tommy.

These are available at Zotomi.com patient caregiver website and ZotomiHCP.com healthcare, professional website.

These are available at the Tommy Dotcom patient caregiver website.

Tom H C P Dot com health care professional website.

Physicians can access information at the HCP website about prescribing Zotomi and the, prescription fulfillment process. We've selected Orsini Specialty Pharmacy based on their strong track record and experience, which is aligned with our indication and dedication to the rare disease community.

Physicians can access information at the HCP website about prescribing to Tommy and the prescription fulfillment process.

We selected Orsini specialty pharmacy based on their strong track record and experience, which is aligned with our indication and dedication to the rare disease community.

We believe it is critical to have a single specialty pharmacy to provide individualized, support to CDD patients and caregivers throughout the patient journey.

We believe it is critical to have a single specialty pharmacy to provide individualized support to CBD patients and caregivers throughout the patient journey.

As part of Marinus' commitment to helping patients who are prescribed Zytomy receive, the support they need, we, in collaboration with Orsini, have launched Zytomy I, a comprehensive patient support program that facilitates access to treatment and provides ongoing prescription drug support and education throughout the treatment journey. This includes prescription benefit and prior authorization support, medication delivery, financial support programs for patients with no insurance, limited insurance or gap in coverage, and a co-pay savings program that helps commercially insured eligible patients who meet the program terms and conditions pay as low as $0 per fill for Zytomy prescriptions.

As part of Mariner East his commitment to helping patients who are prescribed the Tommy received the support they need we in collaboration with Orsini have launched the Tommy won a comprehensive patient support program that facilitates access to treatment and provides ongoing prescription drug support and education through.

The treatment journey.

This includes a prescription benefit and prior authorization support medication delivery financial support programs for patients with no insurance limited insurance or gap in coverage and a co pay savings program that helps commercially insured eligible patients who meet the program terms and conditions.

Pay as low as zero dollars per cell for the Tommy prescription.

In addition, the Zytomy I support team includes patient care coordinators available Monday, through Friday, with pharmacists available 24-7.

In addition does the Tommy wanted support team includes patient care coordinators available Monday through Friday with pharmacist available 24 seven.

Our team of 16 field representatives who have significant rare disease and epilepsy experience, are now educating physicians on the efficacy and safety profile of Zytomy, targeting close to 300 hospitals, large practices, and epilepsy centers, including eight distinct CDD Centers of Excellence and 40 key national epilepsy centers.

Our team of 16 field Representatives, who have significant rare disease and epilepsy experience are now educating physicians on the efficacy and safety profile of the Tommy targeting close to 300 hospital large practices and epilepsy centers, including eight distinct ABB Center.

Excellent.

40 key national epilepsy centers.

In parallel to our education outreach, we are also focused on supporting access to Zytomy, for those patients who participated in the Marigold Open Label Extension Study and the, U.S. Expanded Access Program, being mindful of the individual circumstances of each patient.

In parallel to our education outreach. We're also focused on supporting access to the Tommy for those patients who participated in the Marigold Open label extension study and the U S expanded access program being mindful of the individual circumstances of each patient.

The availability of the approved label has also allowed us to advance our Zytomy coverage, discussion with patients.

The availability of the approved label has also allowed us to advance ours, the Tommy coverage discussion with payers.

As a reminder, we expect approximately 60% of CDD patient population will access coverage, through both fee-for-service and managed Medicaid, with the remaining 40% being managed commercially and the top PBMs covering the most U.S. lives.

As a reminder, we expect approximately 60% of CBD patient population well access pop range through both fee for service and managed Medicaid.

The remaining 40% being managed commercially and the path P. B M covering the most U S lives.

Along with top national and regional commercial payers, we continue to establish relationships, with government payers.

Along with top national and regional commercial payers, we continue to establish relationship with government payers.

Our conversations thus far indicate we should be able to achieve broad access to Zytomy, and based on the level and tone of engagement, we believe payers recognize the impact of the disease on patients and families, limitations within the CDD treatment landscape, and Zytomy's profile as the first product approved specifically for seizures associated with CDD. Consistent with our expectations, early coverage criteria support a confirmed CDD diagnosis, in patients two years of age and older who have failed one or two prior anti-epileptic drugs.

Our conversations thus far indicate we should be able to achieve broad access at the Tommy and based on the level and timing of engagement. We believe payers recognize the impact of the disease on patients and families limitations within this day to day treatment landscape and its the Tommy's profile as the first product approved specifically for seizure.

Associated with D D D.

Consistent with our expectation early coverage criteria support a conspired with CBD diagnosis in patients two years of agent older who have failed one or two prior anti epileptic drugs.

Our initial priority is on the 22 states that we believe include the largest concentration, of CDD patients and where the centers of excellence are located. The CDD ICD-10 code G4042, which was established in November 2020, is being increasingly implemented, into practice by physicians. Recent health care claims data suggest the database is on pace for 20-30% year-over-year, growth of unique patient claims.

Our initial priority is on the 22 states that we believe include the largest concentration of C. D D patient and where the centers of excellence are located.

The city the ICD 10 code G 40, 42, which was established in November 2020 is being increasingly implemented into practice by physicians.

Health care claims data suggest the database is on pace for 20% to 30% year over year growth of unique patient claims.

We believe this consistent and increasing usage of the code will help ensure access, alignment with payers.

We believe that's consistent and increasing usage of the code will help ensure access alignment with payors.

Early ICD-10 code usage shows that 75% of patient visits are in pediatric patients, with 25% in patients 18 years or older.

Early ICD 10 code you said shows that 75% of patient visits are in pediatric patients with 25% in patients 18 years or older.

We recognize that coverage determinations can take time during the initial launch period.

We recognize that coverage determinations can take time during the Alicia launch period.

Our expectations are that the majority of commercial and state Medicaid policies will, be published within six to eight months.

Our expectations are that the majority of commercial and state Medicaid policy will be published within six to eight months.

However, we have every expectation to field medical necessity requests prior to and separate, from the publication of formal payer policies. As a reminder, as a part of our commitment to patients, Zotomi 1 will help support eligible, patient access prior to established coverage criteria.

However, we have every expectation to fail medical necessity request prior to and separate from the publication of formal payer policy.

As a reminder, as a part of our commitment to patient. So tell me one will help support eligible patient access prior to established coverage criteria.

We are confident in the road ahead and look forward to continuing to work with patients, caregivers, physicians, and payers over the coming months.

We are confident in the road ahead and look forward to continuing to work with patients caregivers physicians and payers over the coming months.

I'll now hand the call over to our Chief Medical Officer, Joe Houlihan, to discuss, our ongoing development program.

I'll now hand, the call over to our Chief Medical Officer, Joe Houlihan to discuss our ongoing development program.

Thank you, Christy, and hello, everyone.

Thank you Christy and Hello, everyone I'd.

I'd like to begin with our second-generation formulations, where we've seen promising initial, results. We believe the new formulation could be the future of the Ganaxalone franchise. The goal is to improve the relationship between the amount of Ganaxalone administered and, the plasma concentration, allowing greater and more predictable individualization of dosing. The target pharmacokinetic profile includes an increase in overall exposure relative, to peak concentration, which could provide the potential for twice-daily dosing with enhanced efficacy and a low rate of dose-related adverse effects.

I'd like to begin with our second generation formulations, where we've seen promising initial results.

We believe the new formulation could be the future of the <unk> franchise.

The goal is to improve the relationship between the amount of <unk> administered in the plasma concentration, allowing greater and more predictable individualization of doses.

The target pharmacokinetic profile includes an increase in overall exposure relative to peak concentration, which could provide the potential for twice daily dosing with enhanced efficacy and a low rate of dose related adverse effects.

Initial data from a phase one single ascending dose study in healthy volunteers demonstrated, encouraging results, which we believe support further clinical development. Study participants received single doses ranging from 100 to 900 milligrams, with the current, oil suspension given as a reference control. Plasma levels were measured to 72 hours following Ganaxalone administration. Total exposure was measured by area under the curve, or AUC, and this increased linearly, in proportion to the administered dose.

Initial data from our phase one single ascending dose study in healthy volunteers demonstrated encouraging results, which we believe support further clinical development study participants receive single doses ranging from 100 to 900 milligrams with the current oral suspension given as a reference controls plasma level measured through 72.

Two hours following an excellent administration.

Total exposure was measured by area under the curve or AUC and this increased linearity in proportion to the administered dose and contrast at doses above 600 milligrams with the current oral suspension.

In contrast, the doses above 600 milligrams with the current oil suspension. The increase in AUC was approximately 37% when escalating doses of the new formulation, from 600 to 900 milligrams, without a significant rise in CMAX.

The increase in AUC was approximately 37% with escalating doses of new formulation from 600 to 900 milligrams without a significant rise in Cmos.

Tolerability was consistent with prior <unk> studies with the vast majority of of adverse effects being mild in severity.

Tolerability was consistent with prior Ganaxalone studies, with the vast majority of adverse, effects being mild in severity.

The PK profile of this formulation could allow for further upward titration for efficacy, without a concomitant elevation in CMAX-related adverse effects, such as somnolence.

PK profile of this formulation could allow for further upward titration for efficacy without a concomitant elevation C. Max related adverse effects such as somnolence.

Next steps in the evolution of this program include additional phase one studies in healthy volunteers with higher single doses above 900 milligrams to determine whether further increases in exposures relative to peak concentration can be achieved.

Next steps in the evolution of this program include additional phase one studies in healthy, volunteers with higher single doses above 900 milligrams to determine whether further increases in exposures relative to peak concentration can be achieved.

We will also be performing PK modeling to determine next steps, including the need for, a study with multiple ascending doses.

We will also be performed PK modeling to determine next steps, including the need for a study with multiple ascending doses.

We currently anticipate selecting one of the second-generation Gnaxilin formulations for, a Phase II study in Lennox-Gastaut syndrome to begin in 2023.

Currently anticipate selecting one of the second generation Maxwell and formulations for a phase II study in Lennox <unk> syndrome to begin in 2023.

Lennox-Gastaut syndrome is a rare epileptic encephalopathy that can result from many structural, or genetic causes.

<unk> syndrome is a rare epileptic encephalopathy result for many structural or genetic causes it's highly treatment refractory and we believe the new or formulation will provide more consistent and predictable exposure to can excellence, which should allow physicians to individualized dosing to achieve an optimal response for each patient.

It's highly treatment refractory, and we believe the new oral formulation will provide, more consistent and predictable exposure to Gnaxilin, which should allow physicians to individualize dosing to achieve an optimal response for each patient.

Additionally, there are several prodrug candidates that could offer further improvements in efficacy, and tolerability, ease of manufacturing, and dose individualization.

Additionally, there are several pro drug candidates that could offer further improvements in efficacy and tolerability ease of manufacturing and dose individualization.

Lead oral and IV prodrug candidates have been selected for additional IND-enabling, studies, with Phase I data targeted for 2024.

Lead oral and IV pro drug candidates have been selected for an additional IND, enabling studies with phase one data targeted for 2024.

Now, moving to our IV programs and status epilepticus, I'd like to dive a bit deeper, into the RAISE protocol amendment that Scott mentioned and how we believe this will help drive enrollment.

Now moving to our IV programs in status epilepticus I'd like to dive a bit deeper into the Res Protocol Amendment that Scott mentioned and how we believe this will help drive enrollment.

First, I'm pleased to share that the results from our Phase II trial on refractory status, epilepticus were published in Epilepsia in June. As a reminder, this Phase II trial enrolled patients who had failed at least one second-line, IV AED.

First I'm pleased to share the results from our phase III trial in refractory status Epilepticus were published epilepsy in June .

As a reminder, this phase III trial enrolled patients who had failed at least one second line.

None of the patients progressed to third-line IV anesthetics within 24 hours, leaving the, primary endpoint in the study. Of note, 11 out of 17 participants were intubated prior to or during the study, and all patients, with follow-up data, 16 out of the 17, were successfully extubated.

<unk>.

None of the patients progress to third line IV anesthetics within 24 hours meeting the primary endpoint in the study.

Of note 11 out of 17 participants were intubated prior to or during the study and all patients with follow up data 16 out of the 17 were successfully extra basis.

We're optimistic that the Phase III study will validate this finding and support the, potential for gonaxalone to change the treatment paradigm in refractory status epilepticus. With this in mind, I'd like to discuss the three key changes in the RAISE protocol amendments, which is expected to be adopted across the majority of clinical sites in the third quarter. First, RAISE enrollment criteria were amended to allow inclusions of patients who had received, IV anesthesia for up to 18 hours during the current episode of status.

We're optimistic that the phase III study will validate this finding and support the potential for <unk> to change the treatment paradigm of refractory status epilepticus.

Okay.

With this in mind I'd like to discuss the three key changes in the race protocol amendments, which is expected to be adopted across the majority of clinical sites in the third quarter.

First raise enrollment criteria were amended to allow inclusions with patients who had received IV anesthesia for up to 18 hours during the current episode of status.

The original protocol inadvertently excluded many patients who had received IV anesthesia, particularly those transferred from outside hospitals or the emergency department. These patients were an important part of the Phase II population and can now be included, under the amended protocol.

The original protocol and then Burton we excluded many patients who had received IV anesthesia, particularly those transferred from outside of the hospitals or the emergency Department. These patients were an important part of the phase II population and can now be included under the amended protocol.

The second key change involves the required number of prior failed treatments. The protocol initially required failure of an IV benzodiazepine and two or more second, line IV AEDs, at least three prior agents in total. The amended protocol requires failure of at least two treatments rather than three. Additionally, the investigator must indicate that IV anesthesia would likely be the next, line of therapy if study treatment fails to control seizures.

The second thing change involves the required number of prior failed treatments. The protocol initially required failure of an IV benzodiazepine and to a more second line <unk> at least three prior agents in total.

The amended protocol requires failure of at least two treatments rather than three.

Additionally, the investigator must indicate that IV anesthesia would likely be the next line of therapy with study treatment sales to control seizures.

The underlying rationale for this change involved two issues. First, more centers are advancing to IV anesthesia after failure of the initial second line IV AED.

Underlying rationale for this change about two issues.

More centers are advancing to IV anesthesia after failure of the initial second line Ibs D.

Second, patients in the ICU settings may receive a second-line agent without progressing through, treatment with a benzodiazepine, usually because they already had received multiple benzodiazepine doses for sedation.

Second.

Patients in the ICU setting as we receive second line agent without progressing through treatment with a benzodiazepine.

Usually because they already had received multiple benzodiazepine doses per station.

As with the first change, this will allow enrollment of patients with a profile similar, to those in Phase 2 to enroll in the Phase 3 study.

As with the first change this will allow enrollment of patients with a profile similar to those in phase II to enroll in the phase III study.

We're confident that this will support a high rate of progression to IV anesthesia in study, drug treatment failures.

We're confident that this will support a high rate of progression to IV anesthesia and studied drug treatment failures. This will expand the pool of clinically appropriate patients who qualify for enrollment.

This will expand the pool of clinically appropriate patients who qualify for enrollment.

We believe these two changes will potentially increase the sensitivity of the study by fostering, progression to IV anesthesia in study drug failures, thereby reducing the placebo response.

We believe these two changes will potentially increase the sensitivity of the study by fostering progression to IV anesthesia studied drug failures, thereby reducing the placebo response.

The third significant protocol change aligns EEG determination of study qualification more, closely with clinical workflow. Rather than requiring an investigator to quantify the EEG seizure burden in the 30 minutes immediately, prior to administration of study treatment, the protocol now allows an hour for this determination. This is more consistent with usual ICU patient care, in which the physician will diagnose, status epilepticus, then arrange for treatment to be administered, which can take 15 to 30 minutes.

The third significant protocol change aligns EEG determination of study qualification more closely with clinical workflow.

Rather than requiring an investigator to quantify the seizure burden in the 30 minutes immediately prior to administration of study treatment Proto.

Protocol now allows an hour for this determination.

This is more consistent with usual ICU patient care in which the physician will diagnose status Epilepticus, then arrange for treatment to be administered which can take 15 to 30 minutes.

This change better aligns with the Phase 2 paradigm and should also facilitate enrollment, of clinically appropriate patients.

This change better aligns with the phase II paradigm and should also facilitate enrollment of clinically appropriate patients.

We've received highly positive feedback from our study sites about the potential for increasing, the number of eligible patients under this new amendment, and we will be holding an investigators meeting later this month to review and discuss the changes to the protocol. Furthermore, we've established an initiative of executive outreach by our scientific affairs, and clinical development leaders to study sites to ensure a smooth transition adopting the amended protocol.

We have received highly positive feedback from our study sites about the potential for increasing the number of eligible patients under this new amendment and we will be holding an investigators meeting later this month to review and discuss the changes to the protocol.

Furthermore, we have established an initiative of executive outreach by our scientific affairs and clinical development leaders to study sites to ensure a smooth transition adopting the amended protocol.

Looking to the future of the RAISE trial, we will continue to actively monitor what's, working well and how we can further refine enrollment criteria to support the recruitment of additional patients and potentially broaden the Ganaxialone label. For example, the trial currently enrolls patients age 12 and older. We will shortly receive data that may allow us to broaden the entry criteria to include, even younger patients. Given the higher incidence of status epilepticus in children, this change could further support, timely study enrollment.

Looking to the future of the raise trials, we will continue to actively monitor what's working well and how we can further refine enrolment criteria to support the recruitment of additional patients and potentially broaden the <unk> label.

For example, the trial currently enrolled patients aged 12 and older we.

We will shortly receive data that may allow us to broaden the entry criteria to include even younger patients.

Given the higher incidence of status epilepticus and children. This change could further support timely study enrollment.

As previously disclosed, we have the option for an independent data monitoring committee, to conduct an interim analysis when two-thirds of participants have completed the study, which would be approximately 82 patients. At that time, the committee would recommend stopping the study for efficacy or continuing, to full enrollment.

As previously disclosed we have the option for an independent data monitoring committee to conduct an interim analysis. When two thirds of participants have completed the studies, which would be approximately 82 patients at that time. The committee would recommend stopping the study for efficacy or continuing to full enrollment.

U.S. site activations in the RAISE trial continue to advance, and we anticipate initiating 10, new sites in Canada beginning in the third quarter.

U S site Activations in the Res trial continue to advance and we anticipate initiating 10, new sites in Canada, beginning in the third quarter. We continue to expect top line data in the second half of 2023.

We continue to expect top-line data in the second half of 2023.

In the Phase 2 RESET study in established status epilepticus, the community consent, process, known as Exception for Informed Consent, is well underway.

And the phase III reset study and establish status epilepticus community consent process known as exception proved informed consent.

Is well underway we.

We are pleased to share that we have activated the first site and are on track to begin U.S, enrollment in the second half of the year. We plan to limit site activation initially to four or five to focus on gaining a comprehensive, understanding of enrollment trends before making a larger investment.

We are pleased to share that we have activated the first site and are on track to begin U S enrollment in the second half of the year.

We plan to limit site activation initially to four or five focus on gaining a comprehensive understanding of enrollment trends before making a larger investment.

Also, the RAISE II protocol is now finalized.

Also the raised two protocol is now finalized site selection is ongoing and we expect enrollment to begin in the second half of 2023.

Site selection is ongoing, and we expect enrollment, to begin in the second half of 2023.

This trial is designed to serve as a critical piece of the European approval strategy and.

We believe it also has the potential to further broaden the indications for <unk> in the U S.

This trial is designed to serve as a critical piece of the European approval strategy, and we believe it also has the potential to further broaden the indication for Ibogaine Axalone in the U.S. Now I'll turn the call over to our CFO, Steve Pfanstiel, who will provide you with a financial, update.

Now I will turn the call over to our CFO , Steve <unk>, who will provide you with a financial update.

Thanks, Joe, and good morning to everyone.

Thanks, Joe and good morning to everyone before diving into our financial results for the second quarter 2022, I would like to provide a few highlights on our progress since the prior earnings call.

Before diving into our financial results for, the second quarter of 2022, I would like to provide a few highlights on our progress since the prior earnings call. In July, we announced that we have entered into a definitive agreement to sell our rare pediatric disease priority review voucher for $110 million. The sale of the PRV, which is expected to close within the third quarter, significantly strengthens Marinus' financial position, and we believe extends our cash runway into the fourth quarter, of 2023.

In July we announced that we've entered into a definitive agreement to sell our rare pediatric disease priority review voucher for $110 million.

The sale of the <unk>, which is expected to close within the third quarter significantly strengthens <unk> financial position and we believe extends our cash runway into the fourth quarter of 2023.

Inclusive of the proceeds from the PRV, we have raised well over $200 million of funding over the last 18 months from non-dilutive sources, including our credit agreement with, Oaktree, our European commercialization agreement with Orion, and from our federal BARDA contract. These funds have been critical to enabling us to execute in our pipeline, including our, phase three trials and reformulation efforts, as well as the commercial launch of Zotomi. Furthermore, under the Oaktree credit facility, we have the opportunity to further strengthen, our cash position through a synthetic royalty monetization agreement related to U.S. sales of Ganaxone and have the option to draw an additional $25 million of funding under the facility subject to achievement of certain clinical and financial milestones.

Inclusive of the proceeds from the <unk>, we have raised well over $200 million of funding over the last 18 months from non dilutive sources, including our credit agreement with Oaktree, Our European commercialization agreement with Orion and from our federal BARDA contract.

Bonds have been critical to enabling us to execute on our pipeline, including our phase III trials and reformulation efforts as well as the commercial launch of the Tommy.

Furthermore, under the credit facility, we have the opportunity to further strengthen our cash position through a synthetic royalty monetization agreement related to U S sales of can axon and have the option to draw an additional $25 million of funding under the facility subject to achievement of certain clinical and financial milestones.

As we look to the balance of 2022 and into 2023, we will focus and prioritize our investments and resources on our key programs, specifically our phase three trials in RSE and TSC, as well as the commercial launch of Zotomi. These programs are critical to Marinus' future and delivering shareholder value. We want to ensure they remain on track and are funded for success. As an example, we have invested in additional global sites and trial resources for both, the phase three RAISE and TRUST-TSC trials.

As we look to the balance of 2022 and into 2023, we will focus and prioritize our investments and resources on our key programs, specifically, our phase III trials in RSV and TSV as well as the commercial launch of the Tommy These programs are critical to Meredith future and delivering shareholder value. We want to ensure they remain on track and are funded for success.

Yes.

As an example, we have invested in additional global sites and trial resources for both the phase III raise and trust DSC trials.

While we will continue to advance our other investments, such as our earlier stage pipeline programs, these will be a lower overall priority from a timeline and funding perspective.

While we will continue to advance our other investments such as our earlier stage pipeline programs. These will be a lower overall priority for my timeline and funding perspective.

As Christy discussed, we are excited about the launch of Zotomi.

As Chris discussed we are excited about the launch of the Tommy as a reminder, we previously communicated our pricing and dosing expectations versus the Tommy.

As a reminder, we previously, communicated our pricing and dosing expectations for Zotomi. Zotomi's wholesale acquisition cost is $2,425 for a 110-milliliter bottle. Our sales force is focused on the pediatric population, and initially we expect the average patient to be approximately four and a half years old and weigh 16 kilograms. This translates to an average annual wholesale acquisition cost of approximately $133,000, and expected gross net deductions, including mandatory government discounts, are projected to be in the low 20 percents.

Tommy wholesale acquisition cost is 2425 or 110 milliliter bottle. Our sales force is focused on the pediatric population and initially we expect the average patient to be approximately four five years old and wait 16 kilograms. This translates to an average annual wholesale acquisition cost of approximately 133000 and expected growth.

Deductions, including mandatory government discounts are projected to be in the low 20 percents.

As a note, our age and weight estimates are based on our expectations within the pediatric population, with any usage in an adult population representing upside to these projections.

Note our agent weight estimates are based on our expectations within the pediatric population with any usage in an adult population representing upside to these projections.

As the launch advances, we look forward to providing updates on our progress.

As the launch advances, we look forward to providing updates on our progress initially we will be focused on patient enrollment metrics, including completed patient enrollment forms new patients on therapy and total active patients on therapy. We will also look to provide average dose related metrics for the treated patient population along with relevant prescriber and payer.

Initially, we will be focused on patient enrollment metrics, including completed patient enrollment forms, new patients on therapy, and total active patients on therapy.

We will also look to provide average dose-related metrics for the treated patient population, along with relevant prescriber and payer metrics.

For the launch, we do not expect a significant stocking impact to occur as we are utilizing, a single specialty pharmacy and we will be coordinating closely with them.

<unk>.

For the launch we do not expect a significant stocking impact to occur as we are utilizing a single specialty pharmacy, and we will be coordinating closely with them.

Additionally, once patient enrollment forms are complete, initial coverage determinations, may take as long as one to three months to process.

Additionally, once patient enrollment forms are complete initial coverage determinations may take as long as one to three months to process.

I'll now move to our financial results.

I'll now move to our financial results.

For the second quarter of 2022, we recognized $1.8 million and $16 million in total revenue, for the three and six months ended June 30, 2022, respectively, as compared to $1.9 million and $3.7 million in each of the same periods in the prior year. Revenues are recognized as a result of both our BARDA federal contract and our European, collaboration with Orion Corporation. The increase in 2022 revenue was driven by a one-time revenue recognition of $12.7 million, in the first quarter of 2022 related to the previously received upfront payment associated with the Orion collaboration.

For the second quarter 2022, we recognized $1 $8 million and $16 million in total revenue for the three and six months ended June 32022, respectively, as compared to $1 9 million and $3 7 million in each of the same period in the prior year.

Revenues are recognized as a result of both our BARDA federal contract and our European collaboration with Orion Corporation the.

The increase in 2022 revenue was driven by a onetime revenue recognition of $12 7 million in the first quarter of 2022 related to the previously received upfront payment associated with the Orion collaborations.

Excluding the Orion revenue, the company recognized $1.8 million and $3.3 million in BARDA federal, contract revenue for the three and six months ended June 30, 2022, respectively, as compared to $1.9 million and $3.7 million for the same periods in the prior year.

Excluding the Orion revenue the company recognized $1 8 million and $3 $3 million in BARDA federal contract revenue for the three and six months ended June 32022, respectively, as compared to $1 9 million and $3 7 million for the same periods in the prior year.

Research and development expenses increased to $21 5 million and $39 5 million for the three and six months ended June 32022, respectively, as compared to $18 6 million and $37 2 million for the same periods in the prior year.

Research and development expenses increased to $21.5 million and $39.5 million for the, three and six months ended June 30, 2022, respectively, as compared to $18.6 million and $37.2 million for the same periods in the prior year. The change was due primarily to costs associated with increased R&D headcount and startup of, the Phase III Trust TSC trial.

The change was due primarily to costs associated with increased R&D head count and startup of the phase III <unk> trial.

General and administrative expenses increased to $17.1 million and $28.8 million for the, three and six months ended June 30, 2022, respectively, as compared to $6.8 million and $17.2 million for the same periods in the prior year. The primary drivers of the change were preparation for Zotomi commercialization and additional, support for scale-up of the company's operations.

General and administrative expenses increased to $17 1 million and $28 8 million for the three and six months ended June 32022, respectively, as compared to $6 8 million and $17 2 million for the same periods in the prior year.

Primary drivers of the change were preparation for autonomy commercialization and additional support for scale up of the company's operations.

Additionally, during the six months ended June 30, 2022, a one-time cost of IP license, fee of $1.2 million was recognized as expense in the first quarter of 2022 associated with in-licensing of patents and patent applications from Avid Therapeutics.

Additionally, during the six months ended June 32020 to a one time cost of IP license fee of $1 2 million was recognized as expense in the first quarter of 2022 associated with in licensing our patents and patent applications from avid therapeutics.

The company reported net losses of $39.4 million and $58.8 million for the three and, six months ended June 30, 2022, respectively, as compared to net losses of $23.8 million and $51 million for the same periods in the prior year. These totals include non-cash stock-based compensation expense of $3.8 million and, $7.2 million for the three and six months ended June 30, 2022, respectively, as compared to $3 million and $8 million for the same periods in the prior year.

The company reported net losses of $39 4 million and $58 8 million for the three and six months ended June 32022, respectively, as compared to net losses of $23 8 million and $51 million for the same periods in the prior year.

These totals include noncash stock based compensation expense of $3 8 million and $7 2 million for the three and six months ended June 30 of 2022, respectively, as compared to $3 million and $8 million for the same periods in the prior year.

Cash used in operating activities was $61.3 million for the six months ended June 30, 2022, as compared to cash used in operating activities of $39.1 million for the same period in the prior year.

Cash used in operating activities was $61 3 million for the six months ended June 32022, as compared to cash used in operating activities of $39 1 million for the same period in the prior year.

As of June 30, 2022, we had cash and cash equivalents of $92.3 million. We believe this balance, when coupled with the expected net proceeds of the PRV sale, will be sufficient to fund our operations into the fourth quarter of 2023 while maintaining the minimum cash balance required under our debt facility. For the fiscal year 2022, we are providing updated guidance with BARDA revenues expected, to be in the range of $7 million to $10 million and our GAAP operating expense estimate, inclusive of G&A and R&D expenses, to be in the range of $150 million to $155 million, which includes approximately $15 million of non-cash stock-based compensation.

As of June 32022, we had cash and cash equivalents of $92 $3 million.

We believe this balance when coupled with the expected net proceeds of the <unk> sale will be sufficient to fund our operations into the fourth quarter of 2023, while maintaining the minimum cash balance required under our debt facility.

For the fiscal year 2022, we are providing updated guidance with BARDA revenues expected to be in the range of 7 million to $10 million and our GAAP operating expense estimate inclusive of G&A and R&D expenses to be in the range of $150 million to $155 million, which includes approximately $15 million of noncash stock based comp.

These values represent a slight reduction to our GAAP operating expense estimate, which, was previously projected to be between $152 million to $157 million, including approximately, $17 million of non-cash, stock-based compensation.

Sensation.

These values represent a slight reduction to our GAAP operating expense estimate, which was previously projected to be between $152 million to $157 million, including approximately $17 million of noncash stock based compensation.

Now I'll turn the call back to Scott, who will provide concluding remarks.

Now I'll turn the call back to Scott, who will provide concluding remarks.

Thanks, Steve.

We are very excited about the first commercial launch of the Ptolemy, and the results from, our second-generation development program, continued advancement of our two ongoing, Phase III trials, and the strong foundation we've built.

Thanks, Steve we are very excited about the first commercial launch of this total knee and the results from our second generation development program continued advancement of our two ongoing phase III trials and the strong foundation. We built we are confident this launch is the first of many to come and we will continue.

We are confident this launch is the first of many to come, and will continue to prioritize, these critical workstreams to allow us to help more patients suffering from seizure disorders.

To prioritize these critical work streams to allow us to help more patients suffering from seizure disorders. Operator can you now open the call to questions.

Operator, can you now open the call to questions?

Thank you.

Thank you as a reminder, if you would like to ask a question. Please press Star then one on your telephone keypad.

If you would like to ask a question, please press star, then 1 on your telephone keypad.

Our first question is from Andrew Fay with Jefferies.

Our first question is from Andrew <unk> with Jefferies. Your line is open.

Your line is open.

Okay.

Thanks.

Okay. Thanks, good morning, and thanks, so much for taking my questions. Congrats on the progress, especially the launch recently.

Good morning, and thanks so much for taking my questions.

Congrats on the progress, especially the launch recently.

So maybe one on CDD first.

So maybe one on <unk> one on <unk>.

Thank you.

One on CDD first, you know, I thought I'd ask, is, you know, how many patients, you, know, have, indeed, been treated over the past few weeks, or are a bulk of them still in the coverage form phase?

<unk>.

Hi, I thought I'd ask is you know how many patients.

Have indeed been treated over the past few weeks or are a bulk of them still in the coverage form phase.

I ask because just curious how we should be thinking about Q3 sales coming up.

I asked because just curious how we should be thinking about Q3 sales coming up.

Thanks.

Oh, well, it's a great question, Andrew.

Hello.

It's great question Andrew.

As a reminder to everyone, you know, we formally kicked off the launch about two weeks ago. That allowed physicians to fill out prior authorization forms and prescription forms. As we've talked about, we've expected those prior authorization forms to take up to three, months to get approval from insurances and insurance coverage.

As a reminder to everyone.

We formally kicked off the launch about two weeks ago that allow physicians to fill out prior authorization forms and prescription forms.

As we've talked about Ebix that did those prior authorization forms to take up to three months to get approval from insurances.

Insurance coverage I'll, let Christian talk a little bit more about that.

I'll let Christy talk a little bit more about that in terms of Steve and let Steve talk, a little bit about the numbers.

Sure Steve.

And I'll, let Steve talk a little bit about the numbers, but.

But, you know, as a reminder to all, we're really going to share with you patient numbers, on a quarterly basis starting next quarter in terms of new starts, approvals, and we recognize that that's the most important metric that you guys will want to follow.

As a reminder to all.

We're really going to share with you a patient numbers on a quarterly basis, starting next quarter in terms of new starts approvals and we recognize that.

The most important metric that you guys will want to follow but maybe Christy I'll turn it over to you for a little more commentary and then.

But maybe, Christy, I'll turn it over to you for a little more commentary and then Steve, to kind of round out what you're going to be talking about in terms of future guidance.

Seem to kind of round out what youre going to be talking about in terms of future guidance.

Sure.

Thanks, Scott.

Sure Thanks, Scott and Andrew Thanks, so much for the conversation here.

And, Andrew, thanks so much for the conversation here.

We have, again, in the past two weeks seen really, really great enthusiasm from a prescription, and enrollment standpoint into Zotomi 1.

We have again in the past two weeks seen really really great enthusiasm from a prescription and enrollment standpoint in kids. The Tommy while we have every expectation that our payers will start to evaluate us very significantly right now we have several published policies already.

We have every expectation that our payers will start to evaluate us very significantly, right now.

We have several published policies already.

And, again, in this early period, we believe that it will take between one and three months, to get through that process.

And again in this early period, we believe that it will take between one and three months to get through that process, we'll be fielding medical necessity requests simultaneously, but again, we think that we'll be having patients on therapy in the near future.

We'll be fielding medical necessity requests simultaneously, but, again, we think that, we'll be having patients on therapy in the near future.

Andrew, this is Steve.

And Andrew This is Steve just to kind of specifically address the question.

Will defer providing patient metrics enrollment metrics until we get through the end of the quarter I think it would be appropriate to do that on a quarterly cadence, but we're absolutely committed to providing kind of the right patient enrollment metrics in terms of kind of completed and patient enrollment forms new patients on therapy total active patients on therapy, and we will provide other.

Just to kind of specifically address the question, we'll defer providing, patient metrics, enrollment metrics, until we get through the end of the quarter.

I think it will be appropriate to do that on a quarterly cadence.

But we're absolutely committed to providing kind of the right patient enrollment metrics in terms of kind of completed patient enrollment forms, new patients on therapy, total active patients on therapy, and we'll provide other payer and associated metrics as well.

So we look forward to doing that on the quarters on a routine basis.

Payer and associated metrics as well so we look forward to doing that on the quarters on a routine basis.

Fantastic.

Fantastic and just a quick follow up shifting gears to the RSC. It sounds like you had a great FDA discussion about the recent changing changes so maybe remind us the latest and greatest.

And just a quick follow-up, shifting gears to RSC.

Whether you are confident or not a bridging study as needed with the modified IV you can accident formulation.

A little bit more clarity would be great. Thanks.

It sounds like you had a great FDA discussion about the recent changes.

Sure happy to Andrew So we as we have done in the past we've been very proactive with our interactions with the FDA I mentioned on the call we have great CMC team.

So maybe remind us the latest and greatest, you know, whether you are confident or not a bridging study is needed with the modified IV Gonaxin formulation.

And to the leadership team on that side and our regulatory team we've been incredibly transparent with the agency what we wanted to do change and our buffer system new manufacturing facility.

And do their communications with us they see that as a very reasonable approach.

They commented specifically that buy their guidelines and new buffer system.

In the in the guidelines for four <unk>.

<unk>.

Referenced product.

At this point in time.

We don't see any reason why we are going to do bioavailability do a bioequivalence study and in fact.

Their green light about using this new product in this space in the phase III study.

Those first batches all hit our specs.

That gives us a tremendous amount of confidence right. So it's not as though we're going to only be using our current product and then filing with the new product they've given us the ability to use this new product in the current phase III. So we have a lot of confidence in the manufacturing team on what this new buffered data has looked like very early on and just to.

Everyone. The current buffer system is absolutely commercially viable.

However, we don't want to launch with a one year shelf life. So the goal of the new buffer system is to really make this commercially much more interesting from a shelf perspective lack of refrigeration perspective, and again ultimately we see moving to IV bags over a two or three year period as the <unk>.

Final steps in our development process.

I think the transparency that we have the agency, we're sharing with you and we we feel very confident that the manufacturing piece of our CMC filing will not be a gating factor for approval of the IV you can excellent program.

Thanks, so much for the color congrats again.

The next question is from Charles Duncan with Cantor Fitzgerald. Your line is open.

Hey, good morning, Scott and team thanks for taking our questions and congratulations on a great quarter of progress and exciting to see.

First launch my first.

Scott. My first question is is for you or for Christy I'm wondering if you could characterize that initial response by both the payer community as well as the prescriber community is it in line with what you had expected or is it is it beyond what you had it.

Specced in terms of the interest in <unk>.

A little bit more clarity would be great.

Well, let me just give a few opening comments and then I'll turn over to.

Christy.

I think we feel fantastic then going into any payer discussion. We've got published Phase III study, we've got editorial from independent physicians. According that we have guidelines in the public domain that also are strongly supportive of Av.

Thanks.

The use of <unk>.

So I think going into all of these discussions we've got a robust scientific package.

And so we have we certainly have high expectations, but let me turn it over to Christine and lesser or more specifically.

Sure.

Yeah sure. Thanks, Charles for the question.

It's a great question.

Commercial person to give some perspective, two but look I think we all plan for a little bit of the worst that supports them some high expectations when the when the day actually so we had a high level of enthusiasm I I'd be remiss, if I didn't say that our excitement.

Is pretty robust on the commercial side of the world right now.

Not only just with the enrollment that we've seen on on day, one through day 14, which is today, but also to the payer community has been very supportive of our efforts. We have several known published policies and it just really is a testament to the two years' worth of work that was done from outside.

The business medical fancy on the commercial side, so werent there at that point.

I'm happy to, Andrew.

Okay very good.

Go ahead please.

We put a lot into the pricing work and that was an organizational effort.

And I think that's a critical piece here too that I think we priced it drove very fairly for the value proposition.

Critically important for this patient these patients.

The payers irrespective of that as well.

I'm sorry go ahead.

Give us your next question.

So we, you know, as we have done in the past, we've been very proactive with our interactions with the FDA.

Yes that seems to be the case, so just moving on to the race program and that is or the IV program and them and specifically with regard to rates I'm. Just I'm. Just wondering if you could give us a sense of when that interim could occur obviously between now and <unk>.

I mentioned on the call, you know, we have great CMC team, terrific addition to the leadership team on that side, and our regulatory team, you know, we've been incredibly transparent with the agency, what we want to do, change in our buffer system, new manufacturing facility, and, you know, do their communications with us.

It can have a 'twenty three but when would you have about 82 patients through the required period to possibly trigger that interim.

Resolved.

Okay.

Yeah.

That's a great way to ask the question Charles.

Most importantly, the.

The discussions with the FDA gives us the flexibility that.

Pulled the trigger on the interim I think most importantly, we've had we initiated the trial in the May timeframe.

We knew it would take several weeks to a site to get up and running full gear, we really feel like the vast majority of sites are now.

Up and running full gear will have this protocol amendment coming.

Now at sites.

Currently and so we really feel like we're going to be we're going to have.

As much of the winds to our back bye.

By the September timeframe as we can have in this study we'll be adding some additional sites in the third and fourth quarter two with Canada.

As you really.

The important backup strategy and I didn't really by year end, we will make a decision as an organization about where we stand in terms of monthly enrollment where the PSC study stands in terms of monthly enrollment how those two studies overlap and I think by early next year, we'll make a.

Our corporate decision.

What we want to do but we're not quite there yet and we're looking forward to the next few months of enrollment trends for both studies.

And when I think again, having the flexibility in this case creates a lot of opportunity for us to do what's right for the clinical studies for our investors and for patients as well Joe anything you want to add on <unk>.

Just overall commentary about the study.

Yeah.

Actually I've been out to some sites recently and the response to.

The protocol amendment will be implementing is extremely positive.

And Theres a lot of confidence on the part of sites that that's going to help them boost enrollment.

And.

So like Scott I'm very confident that we will buy.

By the end of this year be able to see a boost in enrollment and how the trends are going.

The next question is from Douglas Tsao with H C. Wainwright Your line is open.

They see that as a very reasonable approach.

Hey, good morning, Thanks for taking my questions and just as you move into the launch and the remainder of the year just raising the profile for <unk>. One I'm just curious about presentations at medical meetings through the rest of the year and in particular Aes and what your plans are there.

Thank you for the question Doug.

They commented specifically that by their guidelines, a new buffer system is, you know, in the guidelines for SNDAs and reference products, and at this point in time, we don't see any reason why we'd need to do a bioavailability, do a bioequivalence study, and in fact, you know, their green light about using this new product in the phase 3 study, you know, presuming those first batches all hit our specs, you know, that gives us a tremendous amount of confidence, right?

So it's not as though we're going to only be using our current product and then filing with a new product.

Joe talked about Joe why don't you talk about what had been done on the signed difficult their side with Alex's team and your team and then we'll pass it over to Christie to give the commercial update sure.

They've given us the ability to use this new product in the current phase 3, so we have a lot of confidence in the manufacturing team, what this new buffer data has looked like very early on, and just a reminder to everyone, the current buffer system is absolutely commercially viable.

Well, we will have a presence at.

Child Neurology Society.

Neuro critical care Society Theres a conference.

Conference in Salzburg on status uplift because in September we'll be presenting two posters none for aes.

Submitted for posters four abstracts for presentation at Aes were going to submit an additional two late breaking abstracts to the meeting.

And while we're on the topic of Aes, The American Epilepsy Society.

Choose to publish on its website recently on its clinical corner.

On its clinical corner page.

An article on can Exelon CBD the lead author of the lancet neurology paper able to postpone a night.

Discussing the video usage of Tommy in CBD with two other epilepsy experts.

<unk>.

I'd also mentioned that the international consensus guidelines on CBD treatment were published in June in Frontier is in neurology and we were glad to see that all of the respondents.

Asked whether <unk> should be offered for CVD responded yes.

The unanimous opinion about Easter can ask alone.

Getting back to yes, we expect to have a big presence there.

Overall in addition to the publications.

And just as an inherent with follow up I am sorry, Doug.

Oh No no go ahead Christie sorry.

However, we don't want to launch with a one-year shelf life, so the goal of the new buffer system is to really make this commercially much more interesting from a shelf life perspective, lack of refrigeration perspective, and again, ultimately, we see moving to IV bags over a 2- or 3-year period as the final steps in our development process.

Yeah, I'll just jump in quickly from a commercial perspective as you can imagine a S is kind of our coming out party for the Tommy This year. So they were gonna have a pretty robust commercial presence and that will be including our first commercial conference Davis.

So, you know, I think the transparency that we have at the agency, we're sharing with you, and we feel very confident that the manufacturing piece of our DMC filing will not be a gating factor for approval of the IV Ganaxone program.

Thanks so much for the caller.

We will also have a clinical data review by way of a product theater that will be provided by a top kols and then as you can imagine really significant K O L and physician engagement from the commercial team.

Congrats again.

The next question is from Charles Duncan with Cantor Fitzgerald.

Okay, Great and then just Christy I'm just curious what's the sort of if there is the most commonly asked questions about autonomy and in the early engagements.

It's generally sort of accepted awareness of the product and I'm just curious about what people are focusing on from commissions.

Your line is open.

That's a great question I think it is it's twofold at this point.

Hey, good morning, Scott and team.

Thanks for taking our questions, and congratulations, on a great quarter of progress.

This community.

<unk>.

Sessions and west families that are living with C. D D.

Our focusing on our push and pull strategy. We know that this is going to be 50% guided by the physician and 50% guided by a family it's better.

Exciting to see first launch.

Thanks, Scott.

My first question is for you or for Christy.

Trading or that are caring for children with a D day and so when you talk about the families. There their major concern of access.

I'm wondering if you could, characterize that initial response by both the payer community as well as the prescriber community.

Now these days.

Families are dealing with multiple medications for these kids and it can be quite an arduous.

<unk> to get their kids, the medicines that they need and deserve. So that's why we built a very robust that's only one program to make sure that it is seamless access and that anyone that is appropriate for that Holly gets the medication now if youre talking about the physician presence I think they really I want to understand our mechanism it back.

Is it in line with what you had expected or is it beyond what you had expected in terms of the interest in Zotomi?

Let me just give a few opening comments and then I'll turn it over to Christy.

I think, we feel fantastic that going into any payer discussion, we've got a published phase three study.

We've got editorials from independent physicians supporting that.

We have guidelines in the public domain that also are strongly supportive of the use of Ganaxone, Zotomi.

I think going into all of these discussions, we've got a robust scientific package.

<unk> they wanted to see how this could be different than how they've treated patients.

He has played and potentially how this is an additive effect to what they're already on so those are the two kind of push and pull of major questions and things that we address in the field on a daily basis.

We, certainly had high expectations, but let me turn it over to Christy and let her comment more specifically.

Sure.

Okay, Great and just got maybe a quick one on the IV formulation in terms of the two year shelf life do you think.

Thanks, Charles, for the question.

Can you just walk us through how that would be incorporated into the NDA with that data the stability to two year stability data be ready at time of filing or would that be added.

Later on.

It's a great question for a commercial person to, give some perspective to, but look, I think we all plan for a little bit of the worst that supports some high expectations when the day actually comes.

We had a high level of enthusiasm. I'd be remiss if I didn't say that our excitement is pretty robust on the commercial side of the world right now, not only just with the enrollments that we've seen on day one through day 14, which is today, but also the payer community has been very supportive of our efforts.

It's a great question, Doug well a few different things would typically we would we would have we want to have stability data at least a year ahead of the filing so that when you file the NDA.

We have several known published policies, and it just really is a testament to the two years' worth of work that was done from all sides of the business, medical, C&C, and the commercial side.

So, we're enthused at this point.

Okay, very good.

Charles, I would just add, we put a lot of thought into the pricing work, and that was, an organizational effort.

I think that's a critical piece here, too.

Have one year stability data on hand that and Thats. The big reason that we're going to make sure that we have a manufacturing batch.

I think we price the drug very fairly for the value proposition that I think is critically important for these patients, and I think the payers are respecting that as well.

I'm sorry, go ahead.

To begin in the fourth quarter of this year right. So that would give us one year data by the end of 'twenty. What does case. We've also won we have some accelerated models that we've used that we've already tested with the new formulation, which are showing very strong results and we will be discussing with the agency accelerated model.

Why don't you give us your next question?

Yeah, that seems to be the case.

But remember from the time of filing we will have at least six more months of stability data.

By the time of the NDA vision.

And this is a back and forth with the agency and one that we're not too worried about.

And so over the next.

Over the next 18 months, we'll be having those discussions with the agency as an example will they take our accelerated filing.

Our accelerated stability data.

Oxy or two year shelf life et cetera, So few different strategy than we can afford having the actual data again about the time of approval I would expect that to have a minimum of 18 months of shelf life that would be quickly ended or we can use this accelerated approach, which would give us two years plus.

Right now the solubility curves are really logarithm equally different for the new buffer.

And so we've got a pretty convincing early data package and don't see that all as a major concern for us by the time of approval.

Okay, great. Thank you so much.

Sure.

The next question is from Joseph <unk> with Cowen Your line is open.

So, just moving on to the RAISE program, and that is, or the IV program, and specifically with regard to RAISE, I'm just wondering if you could give us a sense of when that interim could occur.

Hi, there good morning, and thank you for taking my questions maybe the first one on raise just.

Obviously, between now and second half of 23, but when would you have about 82 patients through the required period to possibly trigger that interim result, that interim book?

Just in terms of between now and when you can make that decision to take the interim look.

That's a great way to ask the question, Charles.

For the study I guess, what what's going to go into that decision.

A decision point is it really just a bandwidth on readout between GSE and raise or are you going to be able to see some unblinded data or look at kind of the enrollment criteria that patients that are coming on the study to help make that decision for you.

Yes, I would say I think it's the right now it's going to be driven by a corporate decision Joe can talk about it but we certainly have a D. SMB. That's in place that will be reviewing our datasets that of course will be blinded to that and so I don't see any.

We can't really allowed the blinded data per se truly et cetera, our decision.

And of course.

Yes, I think so so this is in my mind really a corporate decision based on the monthly enrollment trends.

Until the conclusion of the study where we are with TFC.

And we'll look at all of those factors did make the decision, but again I think by US asking the agency well in advance can we do this.

I think most importantly, the discussions, with the FDA gives us the flexibility to pull the trigger on the interim.

It gives us a lot of flexibility and certainly we feel very good that if we choose.

Used to do in the interim we have an 80% powered to hit what we think is the key secondary endpoint around ICU days mechanical ventilation, which.

I think most importantly, we've had, you know, we re-initiated the trial in the May timeframe. We knew it would take several weeks for sites to get up and running full gear. We really feel like the vast majority of sites are now up and running full gear.

My view going into the launch of Joe I haven't talked about this was that this would be this studies so incredibly important for the data to drive reimbursement in the hospital and we all know that's a difficult environment.

We'll have this protocol amendment coming now at sites.

Currently, and so we really feel like we're going to be, we're going to have as much of, the wins to our back by the September timeframe as we can have in this study.

We'll be adding some additional sites in the third and fourth quarter, too, with Canada, as really, you know, an important backup strategy.

What's really changed from the time, we started this program is our commitment to note.

<unk> raised two and so we will now have.

And I think really by year end, we will make a decision as an organization about where, we stand in terms of monthly enrollment, where the TSC study stands in terms of monthly enrollment, how those two studies overlap.

And I think by early next year, we'll make a corporate decision on what we want to do.

Two double blind placebo controlled trials over the over the early years of this launch.

But we're not quite there yet, and we're looking forward to the next few months of enrollment, trends for both studies.

<unk> dataset and that's also in my mind it influenced our decision about how big raise needs to be and what type of data we need to generate so.

I can't say we.

We're not going to make any decision, but I think we're thinking about all of those things and certainly.

And you know, when I think, again, having the flexibility in this case creates a lot, of opportunity for us to do what's right for the clinical studies, for our investors, and for patients as well.

Well.

I don't know Joe if there is anything else you want to comment on the clinical side.

But but again.

Hard to imagine where it would be a lot to push us one way from the data center itself.

Joe, anything you want to add on or raise, just an overall commentary about the study?

Yeah.

Yeah, No I mean, it takes some time to do the interim it's an independent statistician.

Actually, I've been out to some sites recently, and the response to the protocol amendment, that we'll be implementing is extremely positive, and there's a lot of confidence on the part of sites that that's going to help them boost enrollment.

And so, like Scott, I'm very confident that we'll, by the end of this year, be able to, see a boost in the enrollment and how the trends are going.

That does it the data is all going to be cleaned and.

And enrollment in studies typically accelerates.

They go along.

And so it could be that by the time, we got the interim done there'll be substantially more enrollment and in that case, we would just likely wait for the final data.

As Scott said, it's really.

It's a consideration about the rate of enrollment.

The next question is from Douglas Zhao with HC Wainwright.

Perfect. Thank you very much and then maybe a follow up just on the novel formulation.

How much higher do you think you can push the dose here and maybe.

What are you looking for specifically to go forward into that LG study or are you going to look at multiple doses.

Or do you think you're going to be able to nail one down to take forward. Thank.

Thank you.

Yeah I can.

I can take that one.

So there are a lot of decision points along the way we've got a lot of choices re formulation candidates and the prodrug, we do hope that.

And we've seen early promising results that we can increase the overall exposure.

And blunt the C Max.

And and keep going right now are the highest we go on dosing as a single dose of 600 milligrams and we hope to be able to go over that and individualized dosing, particularly low Nox gusto and other epileptic encephalopathy.

Patients tolerate the drug very well there could be the potential to go higher.

Current label caps daily dosing of <unk> thousand 800 milligrams per day.

So we'd hope that the kinetics and stuff.

Efficacy and Tolerability.

Allow us to go higher if patients needed in and we're still waiting to see some of the human PK data for.

For example.

We're completing the single ascending dose study with the first.

<unk> formulation candidate.

We'd want to see multiple ascending dose studies with repeat dosing.

Then decide whether.

What steps to take next is single arm.

Sure.

Im pleased to be against placebo.

Even potentially go straight to phase III, but we don't have the data yet to inform that decision.

And it's going to be a few weeks months until we really.

No what path, we want to take for clinical development in phase II and III.

And Joe the only thing I'd add to that Tom.

Joe Houlihan is that our goal when we started this program was to have a <unk>.

Formulation <unk> pro drug that could deliver.

Eddie State blood levels of at least <unk> per ml, and certainly critical to be able to go above that.

I think our back of the envelope has been great to test. The 150 nanograms per ml is the steady state blood level and correlate that with these reductions.

And potentially 200 nanograms per ml.

Correlate that with seizure reductions and Tolerability and I think we believe from what we've seen and what our model and this showed us that we can achieve that with this formulation.

Sure.

Quite reasonably.

So we want to replicate that and feel confident about it and I think we have some important decisions to make around dosing and a modified release formulation.

Certainly the data to me is encouraging that we made.

Be able to create a daily.

Formulation with this a once a day formulation right now is in twice a day is well within our grasp.

And certainly now we're really getting to think a little bit harder about where do we want to back to land.

How much can we bring into Max in terms of Tolerability.

And I think now truly focus on trough levels as well.

Really maintaining trough levels, where we think they should be so this is in my mind. This is just incredibly.

Exciting too that the data we've generated to date.

Declining incorrect, it's very nicely with what we'd like to perform out of the programme now.

Everyone. We believe the Marigold data the blood levels of 150 nanograms are going to be drive efficacy that was a strong signal in marigold certainly in our IV program blood levels Jive efficacy quite clearly between four and pathogen nanograms.

But we haven't proven that but we certainly believe there is a very strong possibility and I think everyone can imagine that this is a very well tolerated drug an incrementally higher blood plasma concentrations at a steady state.

Has a very high probability of driving a higher efficacy so.

That's the full disclosure, but we feel pretty good about the odds of success.

Where we stand today.

Perfect. That's very helpful. Thank you.

In the interest of time, we ask that you. Please limit yourself going forward to just one question. Our next question is from Joon Lee with <unk> Securities. Your line is open.

Your line is open.

Hey, good morning.

Thanks for taking the questions.

Hey, thanks for taking our questions.

And just, as you move into the launch in the remainder of the year, just raising the, profile for Conaxone, I'm just curious about presentations at medical meetings through the rest of the year, and in particular, AES, and what your plans are there.

They used to be.

<unk> ICD 10 code required genetic diagnosis or is this based on a clinical suspicion and has the payers require genetic diagnosis CVD for approval our Petra. Thank you.

Thanks for the question, Doug.

Let me, Joe, talk about, Joe, why don't you talk about what's happening on the scientific, affairs side with Alex's team and your team, and then we'll pass it over to Christy to give a commercial update.

Chris do you want to take the second in Europe can take the first two if you look.

Sure.

Yeah, I'll I'll address the second first and you know I mentioned earlier that we have seen some early published policies.

Well, we'll have a presence at Child Neurology Society, Neurocritical Care Society.

There's a conference in Salzburg on status epilepticus in September, where we'll be presenting, two posters.

And then for AES, we've submitted four posters, four abstracts for presentation at AES.

And each of them is directly in line at a very very minimal with our.

Our label So we set some expectations that a good payer policy would be in line with our label that is inclusive of patients 10 years and older.

Confirmation of our C. D D diagnosis that is inclusive of a genetic test and failure of at least two aedes.

We have certainly seen published policy that is in line with that and we've seen policy that is less restricted because of that including that of the genetic tact. So currently right now we have a few a handful of published policies and again, we have that very determination that we think that all published policies.

Maybe going forward will have a genetic test component to it however, we've seen a little bit of both knowing that it is highly is from a genetic testing component across the United States. It is again very likely that that would be included.

In June just to be clear just to back up for everyone on the call.

As a good reminder, we're fortunate to have an NCD in place that was really the work of our advocacy groups, where Lulu Foundation and <unk> made a strong push for an ICD 10 code for CDK L. Five that's been in place for a little bit more than 18 months.

So what's been so interesting to US is before emeritus was out in the field with the MSL team our MSL team first and now our commercial team we were seeing physicians use that ICD 10 code increase.

Increasing numbers.

So and we would expect that to continue to increase and we certainly will provide additional education in that regard.

But.

US being able to track that ICD 10 code.

Has been invaluable for our strategic planning about where we want to do how we align with the ICD 10 code our centers of excellence and key epilepsy centers that we would like to.

To make sure of that.

The commercial team is meeting with and finally, if we see ICD ICD 10 codes from places that are not on our list.

We have somewhere else to really evaluate so it's really a nice tool in our toolbox that will complement the datasets that we will use for the commercial team.

And I think it's a little bit more but.

It's a relatively simple tool to add to the reimbursement for them. So.

In arm and of course, what we are.

We've also seen is that ICD 10 code as it is.

Identifying patients across all each spectrums and it has been really interesting to us that right now about 25% of the patients identified via the ICD 10 codes are adults or young adults.

That obviously will have some important implications for the way we're thinking about the business.

And ultimately what drives the average weight.

Around our revenue.

Hey, Scott quick follow up.

What are some of the top differential that are maybe being coded alongside that CD ICD 10 code that might give you some hints as to where you might want to go next.

Oh I think the most logical place that we would start to look at data sets for other anti epileptics that are used in refractory patients.

<unk> as a tool for the commercial team, but quite honestly Julien I mean, I think the way Christy is on the call I'll, let her jump enemy.

The team is doing fantastic work today, we're going to wait to start or.

We're going to submit an additional two late-breaking abstracts to the meeting.

And while we're on the topic of AES, the American Epilepsy Society chose to publish, on its website recently, on its clinical corner, on its clinical corner page, an article on Conaxone and CBD, the lead author of the Lancet Neurology paper, Ilia Postano-Knight, discussed, in a video the use of zetalamine and CBD with two other epilepsy experts.

And I'd also mention that international consensus guidelines on CBD treatment were published, in June in Frontiers in Neurology, and we were glad to see that all of the respondents, when asked whether Conaxone should be offered for CBD, responded yes, chose a unanimous opinion about use of Conaxone.

R. R R.

Teo speaker programs shortly.

We I think we're going to get a great boost Joe told you that we already have aes, helping us.

And getting back to AES, we expect to have a big presence there overall, in addition, to the publication.

Talk about the value proposition of <unk>. So I think the next three to six months, we're going to be incredibly busy with what.

I'll just jump in here really quick.

Sorry, Doug.

Specific targets that we think are vital to the marketplace and we've said this all along the only way we could do this with a small sales organization successfully is that we've got these great centers of excellence that we have.

Really.

Meaningful number of refractory epilepsy centers, but I think the way we're thinking about our continued success in 2003.

Is by maximizing the data sets available to us to make sure that will go into the right positions Kristi any anything you want to add.

Just a small thing here and Jamie it's a great conversation one that we have quite regularly here on the commercial team, but in the past few weeks.

And again, we are educating on the use of the code we it guides us in our conversations of where to go today, but additionally, because we've had such a unique interests across not only our targeted accounts, but also non targeted accounts. We're learning other codes that are being used that are informing our data.

Team to help some continued mapping to understand and inform our deployment strategy. Even further so again, we have a very distinct education plan on the use of the ICD 10, but then again. We're also learning other codes that are being used that are guiding our mapping even farther.

Thank you.

The next question is from Jay Olson with Oppenheimer. Your line is open.

Oh, no, no.

Oh, Hey, congrats on all the progress and thank you for taking the question.

Go ahead, Kristin.

Our questions related to the RSC can you talk about any physician feedback you've received on the phase two data that was published in epilepsy and have you seen any impact on stage three raise enrollment rates as a result of the increased awareness from publishing the phase two data. Thank you.

Sorry.

Yeah, I'll just jump in quickly from a commercial perspective.

As you can imagine, AES is kind of our coming out party for Zotomi this year, so we're going, to have a pretty robust commercial presence. That will be including our first commercial conference booth.

We will also have a clinical data review by way of a product theater that will be provided, by a top KOL.

And then, as you could imagine, really significant KOL and physician engagement from the commercial, team.

Yes, so yes.

Okay, great.

The feedback on the on the Phase II study has always been positive.

And again as I said I've been out visiting sites and we do get into discussing the data in.

And in the context of the amendment Thats coming up for re study.

Because with these changes in the protocol.

Really reflects the population in the phase II study much better now.

So in discussions about the amendment.

I do bring that up and.

And the alignment with that population because of the features of the amendment, we do get positive feedback about enrollment.

Lot of the patients in the Res study as we mentioned.

Were intubated either when they came in eight were intubated when they came in to the phase III study I mean.

And three got Intubated, along the way and we have follow up for all but one patient and every patient was ex debated.

And so that's.

To me, that's an incredibly positive.

Finding and we havent quite framed it that way.

And so in discussions moving forward.

In the few so far where I brought up the data in that way. The response has been incredibly positive.

So.

And this amendment again will mirror the population in the phase III study.

And we see that as a.

Great recipe for success.

Okay.

Thank you.

And then just, Kristi, I'm just curious, what's the sort of, if there is, the most commonly, asked questions about Zotomi in the early engagements?

The next question is from Marc Goodman with SBB. Your line is open.

You know, is there generally sort of accepted awareness of the product?

Okay.

Yes. Good morning, just curious Europe , you mentioned it a little bit but have you gotten the response from Europe or we all sat here or does it look like it's going to be pretty clean.

And I'm just curious about what people are focusing on from clinicians.

That's a great question.

I think it's twofold at this point.

You'll be able to get approval.

In this community of physicians and with families that are living with CDD, we kind of are focusing, on a push and pull strategy.

Oh.

Yeah, So mark we're working on.

We will formally respond to the list of 120 day question by the end of the third quarter or.

Early in the fourth quarter, we have.

There's a pretty good list of additional studies almost.

Actually all of our preclinical in terms of additional requirements, we've talked about at the Europeans wanted some additional work with our syringes that was the that was the biggest impact.

And I think Joe actually has done a great job going back and looking at the data as you well know mark.

We know that this is going to be 50% guided by the physician and 50% guided by the families, that are treating or that are caring for children with CDD.

And so, when you talk about the families, their major concern is access.

Right now, these families are dealing with multiple medications for these kids. And it can be quite an arduous process to get their kids the medicines that they need, and deserve.

That's 50% response rate is incrementally more important in Europeans and.

So, that's why we built a very robust Zotomi One program to make sure that it is seamless, access and that anyone that is appropriate for Zotomi gets the medication.

Now, if you're talking about the physician presence, I think they really want to understand, our mechanism of action.

They want to see how this could be different than how they've treated patients previously, and potentially how this is an additive effect to what they're already on.

So, those are the two kind of push and pull major questions and things that we address, in the field on a daily basis.

We have some really interesting data that.

That we are going to get to the Europeans about.

The statistical impact on the maintenance phase.

The Marigold study. So I think we have done everything we can do to answer the question that the Europeans are seeking.

We're enthusiastic about about the outcome over the next year.

And you're still having discussions with some other regions to license out.

Other reasons.

Yes.

We expect to have another another geography.

<unk> is a partner in place by year end.

And I think we would certainly expect it to.

I have another significant region in place.

Next year as well.

This is this is a it's a tough one for us mark.

Good way, because we have huge demand.

But because these indications are more orphan like.

Really all of our force.

Have deals with the regional players and that just great.

A lot of work for our organization.

We love Orion as the strategic partner in Europe , but it's a lot of work to <unk>.

And what we know.

And certainly they are bringing a lot of skills to the table, but we are now the authorities on CDK <unk> deficiency disorder.

And I think that.

That will be the same whether it's Japan or China.

We're just trying to do this in a measured fashion to bring in some meaningful economics to the company that will support our R&D efforts and our commercial efforts in the short term, but doesn't overwhelm the team I.

I feel pretty confident that China, Japan are going to be important markets for this drug.

And certainly there is real interest and demand.

Mena region and in other regions and so we're going to knock them off one at a time, but we're trying to start with the most meaningful.

Patient number standpoint, once that we can really handle organizationally.

And that create some value and.

Some economic payments that allow us to continue to do all the things we are doing so yes, we feel very good about those discussions.

Also Scott in the past you've talked about potentially doing a royalty deal I didn't know if that was even something still considered is even necessary anymore. Thanks.

Okay.

Yeah, Hi, this is Steve I'll answer that one yes, I mean look the PRP was critical.

Great.

And then, just, Scott, maybe a quick one on the IV formulation in terms of the two-year, shelf life.

Do you think...

Can you just walk us through how that would be incorporated into the NDA?

Really excited to get that get that contract in place and frankly with it being at the high end of the range that gives us the flexibility to look at a number of options.

We're really reassessing the royalty option still very much in play.

But I think with with the <unk> sale, we feel like we bought some time and flexibility there.

Thank you.

The next question is from Brian <unk> with Baird. Your line is open.

Would that data, the two-year stability data, be ready at time of filing or would that be, added later on?

Hey, good morning, everyone. Thanks for taking my question I guess mine is sort of a combined one for Christine Steve.

Hoping you can maybe walk us through conversion from a prescription.

Receipt of Tommy and actual booking of revenue here is there is there inventory held at the specialty pharmacy that is recognized as revenue or is it effectively just in time delivery and.

While the reported revenue, we got be pure demand styles and based on the payer mix, what do you see as sort of the hurdle as far as the average co pay is going to how much we're able to also about through <unk> one.

Thanks.

It's a great question, Doug.

Yes, Brian So I'll start with a little bit of kind of the revenue recognition piece and then I'll know Christy to chime in as well here.

We will sell to.

To the specialty pharma partner, who will then distribute to the patient. So we would expect to recognize that when we sell it to to the specialty pharma partner.

We will have metrics to be able to estimate gross to nets and account for those appropriately and our gross to net deductions I would not expect as we mentioned any significant stocking impact we're gonna be coordinating very closely with them. So there's no need for them to order kind of excess inventory or have any of that on hand, it will be not quite just in time, but really not far from.

That so.

We will be able to really manage very tightly the expectations and understanding of the gross to net deductions and inventory very closely maybe I'll turn it over to Christina to talk through that conversion process.

Well, a few different things.

One, typically, we would have... We want to have stability data at least a year ahead of the filing so that when you, file the NDA, you have one-year stability data on hand.

And that's the big reason that we're going to make sure that we have a manufacturing, batch to begin in the fourth quarter of this year, right?

So, that would give us one-year data by the end of 2023, in this case.

We've also run... We have some accelerated models that we've used that we've already tested with the new, formulation, which are showing very strong results.

Sure. So thanks, Brian for the conversion of a naive patient from the prescription and enrollment into the Tommy one it really sparks a very clean line to fulfillment, which is we started a benefit investigation that simultaneously once enrollment at the time, they won well well less.

That's a tape and need for what the out of pocket would be for patients.

The benefit investigation, we assume that all will need a prior authorization once that is done the prior off will then be initiated through Orsini again simultaneously that need for any patient services support for commercial patients.

Co pay and again for any patients who have limited insurance or no insurance that that process will also start so once the P. A us through them.

We determined that there is I'll take them in this early period anywhere between one and three months just considering we are new drugs to market.

And then when we're talking about what we think that average co pay will be you know.

You know you've seen one plan you've seen one plan.

As for our Medicaid patients, we think that that'll be a minimal out of pocket and for our commercial patients. We think that again that will be a minimal out of pocket again, we wont be buying down to zero for any patient who are available for that need. So again, a pretty clear line moving with one specialty pharmacy partner right now where patient starts.

And we will be discussing with the agency accelerated models.

With us are under our run rate.

Great. Thanks, that's very helpful.

The next question is from Michael Higgins with Lindbergh.

Your line is open.

Thanks, Good morning, guys behavior and try to limit my question to just one topic.

And congrats again on the progress with autonomy and lenses.

And manufacturing.

There are a lot going on.

With Vitol, having a launch underway here.

If you could remind us what your percent reaches that youre looking at today, you're you've noted.

Our focus in 22 states the states, where there are centers of excellence.

How does the evolving how is that evolving with the new ICD information that you've noted what are your plans and the timing for expanding that outside of what you read yesterday.

Yeah.

But remember, from the time of filing, we'll have at least six more months of stability, data by the time of the NDA vision.

Hi, Michael I'm happy to take that.

And this is a back and forth with the agency and one that we're not too worried about.

Currently today, we estimate again two weeks into launch that we'll probably have about an 80% range with that.

We certainly with the early data and the kind of thing increasingly is that has confirmed that again to my earlier point that other codes.

Certain situations are being used I think will inform that I personally believe that where we have our reps today I don't think that will need to have any increased rates at that point.

And so, over the next...

And over the next 18 months, we'll be having those discussions with the agency as an example.

Reaching our top accounts again, we have about 300 centers that we're targeting today.

Both from a city center of excellence National epilepsy centers, but also down to smaller community accounts again that we are being able to target very easily with the sales force that we have.

I appreciate it.

You can also save in the world with different today right, we don't need a salesperson to help a physician and a family find this drug.

Has that happened already.

So.

It's not clear that we need to actually make the dice, but it's not critical for the success or the ability to capture that last 20%, but having the salesforce Paul on that position.

And the team has done an amazing job to make those materials available very straightforward you've got great data.

I was in practices for a lot of years and didn't see a sales rep that wrote prescriptions and I think we're already seeing that today, which is very exciting.

And gives us confidence that we are right sized for this launch.

Okay.

Will they take our accelerated filings, our accelerated stability data as a proxy for, two-year shelf life, et cetera?

The next question is from Jason Butler with JMP Securities. Your line is open.

So a few different strategies that we can employ, having the actual data, again, about, the time of approval, I would expect to have a minimum of 18 months of shelf life that would be quickly amended, or we can use this accelerated approach, which would give us two years plus.

Hi, Thanks for taking the question just one on the Res Protocol Amendment.

I mean, right now, the solubility curves are really logarithmically different for the new, buffer.

And so we've got a pretty convincing early data package and don't see it at all as a, major concern for us by the time of approval.

Obviously as you said the IV inclusion of IV anesthesia, you have those patients in the phase II. So so should have some level of confidence there, but can you just speak to your level of confidence around the change associated with prior failed.

Okay.

Great.

Thank you so much.

Sales agents.

Sure.

Sure.

The next question is from Joseph Tomei with Cowan.

Yeah, well I think for a lot of reasons, we're confident about that too.

Again that parallels pay.

Patients in the phase III study as well.

And we didn't see a difference in patients who had taken fewer versus more.

<unk> previously.

The other piece of that as well, it's gonna help enrollment.

A couple of reasons patients in the ICU.

They may not get a dose of benzodiazepine as is required in the current protocol. They may progress right to a second line <unk>.

Because they've gotten so much protocol midazolam or whatever for ventilator management.

That's one and the other is more centers are progressing straight to IV anesthesia earlier.

Earlier in the treatment sequence.

After the first failed.

Second line IV, so by just requiring two agents.

Either a benzodiazepine and one second line or to second line IV Aep's, we'll be able to.

Capture more patients.

The other piece of it is.

The current protocol specifies that IV anesthesia mustn't be a contra indication.

Now because we are growing earlier in the treatment sequence and want to treat appropriate patients. It's now an inclusion that were it not for intervention with the study drug IV anesthesia needs to be the next intervention that they would consider for likely the next intervention that they would consider that does a couple of things besides mix.

Sure, we're treating patients who are appropriate.

They already for an investigational agent.

Also strengthens.

It also increases the chance that IV anesthesia would be the very next treatment considerably and since the second.

Co primary endpoint depends on that.

We think this change actually increases the sensitivity of the study rather than rather than decreases.

So you know we're with all of these things together that both bolster.

Bolstering enrollment and some of the changes strengthened in the study further.

I'm actually optimistic about that in terms of the effect on the study.

Yes, Joe Thanks, Greg I think that would be great.

Great.

And Jason I'll, just add we've powered the study and we've talked publicly about a 40% placebo number as our powering assumptions. We've also talked that we believe that.

This placebo rates much more likely to be closer to 20%.

Around.

The progression to general anesthesia to Joe's point.

We really believe that these changes to the protocol have the ability to drive that number lower.

Because some of these patients are already can be held mechanical ventilation. So if you turned down there.

At a static agents they go into status, they either get drug or placebo.

Placebo when theres still in status.

Is going to be a very easy decision to crank up there and Asia. So we feel very good about this only having a potential positive effect.

For the study and a lower than placebo effect overall.

That was going to be our last question I just wanted to thank everyone for being on the call I know we've run late.

Your line is open.

Hi there.

Good morning, and thank you for taking my questions, maybe the first one on RAYS.

Just in terms of between now and when you can make that decision to take the interim, look for the study, I guess what's going to go into that decision point?

Is it really just a bandwidth on readout between TSC and RAYS, or are you going to be able, to see some unblinded data or look at kind of the enrollment criteria of the patients that are coming on the study to help make that decision for you?

It's an independent statistician that does it.

Got a lot going on and we were happy to take questions are around the launch we're super excited about the new formulation and certainly the progress that we're making on Rfps III trials.

I would say I think right now it's going to be driven by a corporate decision.

The data's all got to be cleaned, and enrollment in studies typically, you know, accelerates, as they go along.

I mean, Joe can talk about it, but we certainly have a DSMB that's in place that will be reviewing, our data sets, but of course, we'll be blinded to that.

And so it could be that by the time we got the interim done, there'd be substantially more enrollment.

And so, I don't see any, you know, we can't really allow the blinded data per se.

And in that case, we would just likely wait, for the final data.

It really affects our decision.

But as Scott said, it's really a consideration, about the rate of enrollment.

And of course, and I think, so this is, in my mind, really a corporate decision based, on the monthly enrollment trends, the time to the conclusion of the study, where we are with TSC, and, you know, we'll look at all those factors to make the decision.

And I think we believe from what we've seen, and what our modeling has showed us that we can achieve that with this formulation quite reasonably.

Perfect, thank you very much.

But again, I think by asking the agency well in advance, can we do this, this gives us, a lot of flexibility.

So we wanna replicate that and feel confident about it.

And then maybe a follow-up just from the novel formulation.

And certainly, we feel very good that if we choose to do an interim, we have an 80% power, to hit what we think is a key secondary endpoint around ICU days, mechanical ventilation, which, you know, my view going into the launch, Joe, and I haven't talked about this, was that this would be, you know, this study is so incredibly important for the data to drive reimbursement in the hospital, and we all know that's a difficult environment.

And I think we have some important decisions, to make around dosing and a modified release formulation.

How much higher do you think you can push the dose here?

What's really changed from the time we started this program is our commitment to now run, RISE-2.

Certainly the data to me is encouraging, that we may be able to create a daily formulation with this a once a day formulation.

And maybe what are you looking for specifically, to go forward into that LG study?

And so, we will now have, you know, two double-blind placebo-controlled trials over the early years, of this launch, a bigger data set.

Right now I think twice a day is well within our grasp.

Are you gonna look at multiple doses?

And that's also, in my mind, an influence on our decision about how big RISE needs to, be and what type of data we need to generate.

And certainly now we're really getting, to think a little bit harder about where do we want TMAX to land?

Or do you think you're gonna be able, to nail one down to take forward?

In the interest of time, we ask that you please limit yourself going forward to just one question.

So, you know, I can't say we're not going to make any decisions, but I think we're thinking, about all of those things.

How much can we bring into TMAX in terms of tolerability?

Thank you.

Our next question is from June Lee with Truist Securities.

Thanks, everyone for dialing in and have a good day.

And certainly, you know, I don't know, Joe, if there's anything else you want to comment, on from the clinical side, you know, but, again, it's hard to imagine we're going to see a lot to push us one way from the data set itself.

And I think now truly a focus on trough levels as well, and really maintaining trough levels where we think they should be.

Yeah, I can take that one.

Your line is open.

Joe?

So this is in my mind, this is just incredibly exciting to that the data we've generated to date.

So there are a lot of decision points along the way.

Hey.

Yeah.

It's very nice with what we'd like to perform out of the program.

We've got a lot of choices, reformulation candidates, and the pro-drug.

Thanks for taking our questions.

No, I mean, it takes some time to do the interim.

Now I'll remind everyone, you know, we believe from the Marigold data that blood levels of, 150 nanograms are going to, you know, be, drive efficacy.

Operator back to you.

We do hope that, and we've seen early promising results, that we can increase the overall exposure and blunt the C-max and keep going.

Does the use of CDV, ICD-10 codes require genetic diagnosis, or is this based on a clinical, suspicion, and has the payers required genetic diagnosis of CDV for approval of the drug?

That was a strong signal in Marigold.

Right now, the highest we go on dosing, is that a single dose is 600 milligrams. And we hope to be able to go over that, in individualized dosings, particularly in Lennox-Gastaut and other epileptic encephalopathies. Most patients tolerate the drug very well, and there could be the potential to go higher.

Thank you.

Thank you ladies and gentlemen. This concludes today's conference call. Thank you for participating you may now disconnect.

Certainly in our IV program, blood levels drive efficacy quite clearly between four, and 500 nanograms, but we haven't proven that, but we certainly believe there's a very strong possibility, and I think everyone can imagine, that this is a very well-tolerated drug at incrementally higher blood plasma concentrations at a steady state has a very high probability of driving a higher efficacy.

Our current label caps daily dosing, at 1800 milligrams per day. So we'd hope that the kinetics and efficacy, and tolerability would allow us to go higher if patients need it.

Chris, do you want to take the second, or do you want to take the first, too, if you, like?

So, you know, that's the full disclosure, but we feel pretty good about the odds of, success where we stand today.

And we're still waiting to see some of the human PK data. For example, we're completing the single ascending dose study, with the first reformulation candidate.

Yeah.

Perfect.

We'd wanna see multiple ascending dose studies, with repeat dosing and then decide whether, what step to take next, a single arm or two arm phase 2B against placebo, even potentially go straight to phase three.

Thank you for participating.

I'll address the second first.

That's very helpful.

But we don't have the data yet to inform that decision.

You may now disconnect.

You know, I mentioned earlier that we have seen some early published policies, and each, of them is directly in line at a very, very minimum with our label. So, we set some expectations that a good payer policy would be in line with our label that, is inclusive of patients two years or older, confirmation of a CDD diagnosis that is inclusive of a genetic test, and failure of at least two AEDs.

Thank you.

And it's gonna be a few weeks, months, till we really know what path we wanna take for clinical development in phase two and three.

We have certainly seen published policy that is in line with that, and we've seen policy, that is less restrictive of that, including that of a genetic test.

And Joe, the only thing I'd add to that from Joe Houlihan, is that our goal when we started this program was to have a formulation and or pro drug that could deliver steady state blood levels of at least 100 nanograms per ML and certainly critical to be able to go above that one.

So, currently, right now, we have a few, a handful of published policies, and again, we have every determination that we think that all published policies, maybe going forward, will have a genetic test component to it.

And I think our back of the envelope, would be great to test 150 nanograms per ML as a steady state blood level and correlate that with seizure reductions and potentially 200 nanograms per ML and correlate that with seizure reductions and tolerability.

However, we've seen a little bit of both.

[music].

Knowing that it is highly used from a genetic testing component across the United States, it is, again, very likely that that would be included.

And, June, just to be clear, you know, just to back up for everyone on the call, as a, good reminder, you know, we're fortunate to have an ICD-10 in place.

That was really the work of our advocacy groups, where Lulu Foundation and ISDR made a strong, push for an ICD-10 code for CDKL5.

That's been in place for a little bit more than 18 months, and so, what's been so interesting, to us is, before Marinists was out in the field with their MSL team, our MSL team first, and now our commercial team, we were seeing physicians use that ICD-10 code in increasing numbers.

And so, and we would expect that to continue to increase, and we certainly will provide, additional education in that regard.

Us being able to track that ICD-10 code has been invaluable for our strategic planning, about where we want to go, how we align with the ICD-10 code, our centers of excellence and key epilepsy centers that we would like to make sure that the commercial team is meeting with.

Unfortunately, if we see ICD-10 codes from places that are not on our A-list, we have, somewhere else to really evaluate.

So it's really a nice tool in our toolbox that will complement the data sets that we, will use for the commercial team.

And I think it's a little bit more, but it's a relatively simple tool to add to the reimbursement, form.

And of course, what we've also seen is that ICD-10 code is identifying patients across, all age spectrums.

And it has been really interesting to us that right now about 25% of the patients identified, via the ICD-10 codes are adults or young adults.

And that obviously will have some important implications for the way we're thinking about, the business and ultimately what drives the average wage around our revenue.

Hey, Scott, quick follow-up.

What are some of the top differentials that are maybe being coded alongside that ICD-10, code that might give you some hints as to where you might want to go next?

Oh, I think the most logical place is that we would start to look at data sets for other, anti-epileptics that are used in refractory patients as a tool for the commercial team.

But quite honestly, June, I mean, I think the way, and Christy's on the call, I'll let, her jump in.

I mean, the team's doing fantastic work today.

We're going to start our KOL speaker program shortly.

I think we're going to get a great boost.

Joe told you that we already have AES helping us talk about the value proposition of GNAS, Loan.

So I think that in three to six months, we're going to be incredibly busy with what the, specific targets that we think are vital to the marketplace.

And we've said this all along, the only way we can do this with a small sales organization, successfully is that we've got these great centers of excellence, that we have really a meaningful number of refractory epilepsy centers.

But I think the way we're thinking about our continued success in 23 is by, you know, maximizing, the data sets available to us to make sure that we're going to the right physicians.

Christy, anything you want to add?

Just a small thing here, and June, it's a great conversation, one that we have quite, regularly here on the commercial team.

But in the past few weeks, again, we are educating on the use of the code.

It guides us in our conversations of where to go today.

But additionally, because we've had such unique interest across not only our targeted accounts, but also non-targeted accounts, we're learning other codes that are being used that are informing our data team to help some continued mapping, to understand and inform our deployment strategy even farther.

So, again, we have a very distinct education plan on the use of the ICD-10, but then, again, we're also learning other codes that are being used that are guiding our mapping even farther.

Thank you.

The next question is from Jay Olson with Oppenheimer.

Your line is open.

Oh, hey.

Congrats on all the progress, and thank you for taking the question.

Our question is related to RSC.

Can you talk about any physician feedback you received on the Phase II data that was, published in Epilepsia, and have you seen any impact on Phase III-raised enrollment rates as a result of the increased awareness from publishing the Phase II data?

Thank you.

Yeah.

This is Joe.

Yeah. I mean, the feedback on the Phase II study has always been positive.

And again, as I said, I've been out visiting sites, and we do get into discussing the data.

In the context of the amendment that's coming up for the RAISE study, because with these, changes in the protocol, it really reflects the population in the Phase II study much better.

And so in discussions about the amendment, I do bring that up, and the alignment with, that population because of the features of the amendment, we do get positive feedback about enrollment.

A lot of the patients in the RAISE study, as we mentioned, were intubated either when, they came in, eight were intubated when they came in, not to the Phase II study, I mean, and three got intubated along the way.

And we have follow-up for all but one patient, and every patient was extubated.

And so to me, that's an incredibly positive finding, and we haven't quite framed it that, way.

And so in discussions moving forward, you know, in the few so far where I've brought, up the data in that way, the response has been incredibly positive.

And so, and this amendment, again, will mirror the population in the Phase II study, and, we see that as a great recipe for success.

Thank you.

The next question is from Mark Goodman with SVB.

Your line is open.

Yeah, good morning.

Just curious, Europe, you mentioned it a little bit, but have you gotten the response from, Europe?

Are we all set here, or does it look like it's going to be pretty clean and you'll be, able to get approval?

Yeah.

Oh, so, yeah, so, Mark, we're working on that.

So we'll formally respond to the list of 128 questions by the end of the third quarter, or early in the fourth quarter.

We had, it was a pretty big list of additional studies, almost, actually all were preclinical, in terms of additional requirements.

We've talked about it.

The Europeans wanted some additional work with our syringes.

That was the biggest impact.

And I think we, you know, Joe actually has done a great job going back and looking at, the data.

As you well know, Mark, you know, that 50% response rate is incrementally more important, in Europeans, and, you know, we have some really interesting data that we are going to give to the Europeans about the statistical impact on the maintenance phase in the Marigold study.

So I think we have done everything we can do to answer the questions that the Europeans, are seeking, and, you know, we're enthusiastic about the outcome early next year.

And are you still having discussions with some other regions to license out other regions?

Yeah, we expect to have another geography, a strategic partner in place by year end.

And I think we would certainly expect to have another significant region in place next year as well.

This is a tough one for us, Marc, I mean, in a good way, because there's huge demand.

But because these indications are more orphan-like, we really are forced to have deals with the regional players.

And that just creates a lot of work for our organization.

We love Orion as a strategic partner in Europe, but it's a lot of work to teach them what we know.

And certainly they're bringing a lot of skills to the table.

But we are now the authorities on CDKL5 deficiency disorder.

And I think that will be the same whether it's Japan or China.

And I think we're just trying to do this in a measured fashion that bring in some meaningful economics to the company, that will support our R&D efforts and our commercial efforts in the short term, but doesn't overwhelm the team.

And, you know, I feel pretty confident that China and Japan are going to be important markets for this drug.

And certainly there's, you know, real interest and demand in WENO regions and in other regions.

And so we're going to knock them off one at a time.

But we're trying to start with the most meaningful from a patient number standpoint, ones that we can really handle organizationally.

And that creates some value and, you know, some economic payments that allow us to continue to do all the things we're doing.

So, yeah, we feel very confident about those discussions being on the table.

Also, Scott, in the past you've talked about potentially doing a royalty deal.

I didn't know if that was even something still considered.

Is it even necessary anymore?

Thanks.

Yeah, hi, this is Steve.

I'll answer that one.

Yeah, I mean, look, the PRV was critical.

We were really excited to get that contract in place.

And, frankly, with it being at the high end of the range, that gives us the flexibility to look at a number of options.

We're really reassessing the royalty option, still very much in play.

But I think, you know, with the PRV sale, we feel like we've bought some time and flexibility there.

Thank you.

The next question is from Brian Scorney with Barrett.

Your line is open.

Hey, good morning, everyone.

Thanks for taking my question.

I guess mine is sort of a combined one for Christy and Steve.

I was hoping you could maybe walk us through conversion from a prescription to receivables economy and actual booking of revenue here.

Is there inventory held at a specialty pharmacy that's recognized as revenue, or is it effectively just-in-time delivery?

And will the reported revenue we get be pure demand sales?

And based on the payer mix, what do you see as sort of the hurdle as far as the average co-pays go, and how much are you able to offset that through the economy one?

Thanks.

Yeah, Brian, so I'll start with a little bit of kind of the revenue recognition piece, and then I'll allow Christy to chime in as well here.

You know, we will sell to the specialty pharma partner who will then, you know, distribute to the patient. So we'd expect to recognize that when we sell it to the specialty pharma partner.

Obviously, we'll have metrics to be able to estimate gross to nets, and account for those appropriately in our gross to net deductions.

I would not expect, as we mentioned, any significant stocking impact.

We're going to be coordinating very closely with them, so there's no need for them to order kind of excess inventory or have any of that on hand. It will be not quite just-in-time, but really not far from that.

So, you know, I think we'll be able to really manage very tightly the expectations, and understanding of the gross to net deductions and inventory very closely.

Maybe I'll turn it over to Christy now to talk through that conversion process.

Thanks, Brian.

For the conversion of a naive patient from the prescription and enrollment, into Zutomay One, it really sparks a very clean line to fulfillment, which is we start a benefit investigation that simultaneously, once enrolled in Zutomay One, will necessitate the need for what the out-of-pocket would be for patients.

So after the benefit investigation, we assume that all will need a prior authorization.

Once that BI is done, the prior auth will then be initiated through Orsini.

Again, simultaneously, that need for any patient services support for commercial patients, for co-pay, and again, for any patients who have limited insurance or no insurance, that process will also start.

So once the PA is through, we determine that those will take, in this early period, anywhere between one and three months, just considering we are a new drug to market.

And then when we're talking about what we think that average co-pay will be, you know, you've seen one plan, you've seen one plan.

For our Medicaid patients, we think that it'll be a minimal out-of-pocket.

And for our commercial patients, we think that, again, that will be a minimal out-of-pocket.

Again, we will be buying down to zero for any patients who are available for that need.

So again, a pretty clear line moving with one specialty pharmacy partner right now where patient services are under our one roof.

Great.

Thanks.

That's very helpful.

The next question is from Michael Higgins with, Landberg-Thalman.

Your line is open.

Thanks, Heather.

Good morning, guys.

I'll behave here and try to limit my question to just one topic.

And congrats again on the progress with Ptolemy, the amendments, and IV manufacturing.

You have a lot going on.

With Ptolemy having a launch underway here, if you could remind us what your percent reach is that you're looking at today.

You've noted a focus in 22 states, the states where there are centers of excellence.

How is that evolving with the new ICD information that you've noted?

What are your plans and the timing for expanding that outside of what your reach is today?

Thanks.

Hi, Michael.

I'm happy to take that.

Currently today, we estimate, again, two weeks into launch, that we'll probably have about an 80 percent reach with that.

We certainly, with the early data in the ICD-10 that's being increasingly used, that has confirmed that.

Again, to my earlier point that other codes in certain situations are being used, I think will inform that.

I personally believe that where we have our reps today, I don't think that we'll need to have, any increased reach at that point.

We are reaching our top accounts.

Again, we have about 300 centers that we're targeting today, both from a CDD center of excellence, national epilepsy centers, but also down to smaller community accounts, again, that we are being able to target very easily with the sales force that we have.

I appreciate that.

You can also say, I mean the world's different today, right?

We don't need a salesperson to help a physician and a family find this drug.

We have had that happen already.

So, it's not clear that we need to actually, it may be nice, but it's not critical for the success or the ability to capture that last 20% by having the sales force call on that physician.

Right?

And the team's done an amazing job to make those materials available.

They're very straightforward.

We've got our great data.

I mean, I was in practice for a lot of years and didn't see a sales rep that wrote prescriptions and I think we're already seeing that today, which is very exciting.

And gives us confidence that we are right sized for this launch.

The next question is from Jason Butler with J&P Securities.

Your line is open.

Hi, thanks for taking the question.

Just one on the RAISE protocol amendment.

Obviously, as you said, the IV inclusion of IV anesthesia, you had those patients in the phase two, so you should have some level of confidence there.

But can you just speak to your level of confidence around the change associated with prior failed agents?

Thanks.

Sure.

Yeah, well, I think for a lot of reasons, we're confident about that, too.

Again, that parallels patients in the phase two study as well.

And we didn't see a difference in patients who had taken fewer versus more IV AEDs previously.

The other piece of that is, well, it's going to help enrollment because of a couple of reasons.

Patients in the ICU, they may not get a dose of benzodiazepine as is required in the current protocol.

They may progress right to a second line IV AED because they've gotten so much propofol, midazolam or whatever for ventilator management.

That's one.

And the other is more centers are progressing straight to IV anesthesia earlier in the treatment sequence after the first failed second line IV AED.

So by just requiring two agents, either a benzodiazepine and one second line or two second line IV AEDs, we'll be able to capture more patients.

The other piece of it is the current protocol specifies that IV anesthesia mustn't be a contraindication. Now, because we're going earlier in the treatment sequence and want to treat appropriate patients, it's now an inclusion that were it not for intervention with the study drug, IV anesthesia needs to be the next intervention that they would consider or likely the next intervention that they would consider.

That does a couple of things besides, you know, making sure we're treating patients of appropriate severity for an investigational agent.

It also strengthens.

It also increases the chance that IV anesthesia would be the very next treatment considerably.

And since the second co-primary endpoint depends on that, we think this change actually increases the sensitivity of the study rather than rather than decreases it.

And so, you know, we're, you know, with all these things together, it's both bolstering enrollment and some of the changes strengthening the study further.

I'm actually optimistic about that in terms of the effect on the study.

Yeah, and Joe, thank you.

I think that was great.

And Jason, I'll just add, you know, we've powered this study and we've talked publicly about a 40% placebo number as our powering assumptions. We've also talked that we believe that, you know, this placebo rate is much more likely to be closer to 20% around the, you know, the progression to general anesthesia.

And to Joe's point, we really believe that these changes to the protocol have the ability to drive that number even lower because some of these patients are already going to be on mechanical ventilation.

So if you turn down their anesthetic agents, they go into status, they either get drug or placebo.

If they get placebo when they're still in status, it's going to be a very easy decision to crank up their anesthesia, right?

So we feel very good about this only having a potential positive effect for the study, and a lowering placebo effect overall.

That was going to be our last question.

I just want to thank everyone for being on the call.

I know we've run late.

We've got a lot going on and we were happy to take questions around the launch.

We're super excited about the new formulation and certainly the progress that we're making on our phase three trials.

So thanks everyone for dialing in and have a good day.

Operator, back to you.

Thank you.

Ladies and gentlemen, this concludes today's conference call.