Marinus Pharmaceuticals, Inc.
Q1 2021 Earnings Call Transcript

Published: 17 May 2021

[Operator:]

Greetings and welcome to the Marinus Pharmaceuticals First Quarter 2021 Business Update Call. And it is now my pleasure to introduce to your host, Sasha Damouni, Vice President of Investor Relations and Corporate Communications. You may begin, Ms. Damouni.

[Sasha Damouni:]

Thank you. With me from Marinus are Dr. Scott Braunstein, Chief Executive Officer; Dr. Joe Hulihan, Chief Medical Officer; Christy Shafer, Chief Commercial Officer; Steve Pfanstiel, Chief Financial Officer; and Kimberly McCormick, Vice President, Regulatory Affairs. Before we begin, I would like to remind everyone that some of the statements made today are forward-looking statements under the securities laws. These forward-looking statements involve substantial risks and uncertainties that could cause our clinical development programs, future results, performance or achievements to differ significantly from those express or implied by such forward-looking statements. These risks and uncertainties and risks associated with our business are described in the company’s reports filed with the Securities and Exchange Commission, including Form 10-K 10-Q and 8-K. I will now turn the call over to Scott.

[Scott Braunstein:]

Thank you, Sasha and welcome to our first quarter 2021 business and financial update. This year is off to a tremendous start. We have continued to make progress across our oral and IV clinical programs, have intensified preparations for commercial launch, deepened discussions with potential European partners, have made exciting headway in our next generation formulation research, and have strengthened our management team, scientific advisory board and Board of Directors. To support this continued progress, today, we announced that $125 million credit financing that is being funded by Oaktree Capital Management, a global asset management firm specializing in alternative investment strategies. This financing provides us with access to additional capital to support our research programs and commercialization efforts as well as extending our cash runway through the end of 2022. The completion of this agreement assists in our ability to monetize the rare pediatric disease priority review voucher we anticipate would be granted with this potential approval of ganaxolone next year. We believe the financing exemplifies Oaktree’s confidence in our NDA submission, our company’s ability to deliver on upcoming clinical milestones, while providing capital to support our ongoing and future research and development programs as well as preparing for our first potential commercial launch. The NDA for the use of ganaxolone in CDKL5 deficiency disorder, or CDD is on track for submission by the middle of this year. This is the first step in developing a sustainable oral franchise to address the meaningful opportunities that we envision over the long-term. As a reminder, the sufficiency of the Marigold dataset to support approval will be determined during the FDA review process. The Marigold study showed strong efficacy and a favorable safety profile and the open label data from that study continues to display durability that has been noted since ganaxolone’s early preclinical studies.

[Christy Shafer:]

Thanks, Scott and thank you everyone for joining our call today. As Scott mentioned, we are fully engaged in developing our commercial launch strategy and plans. The commercial team continues to broaden its capabilities by solidifying the internal and external strategic plan. During Q1, Marinus finalized the senior leadership construct by welcoming its market access, sales and marketing, operations and commercial supply chain leaders who are in turn developing the operational and tactical plans. Our most recent addition to the team is Lisa Lejuwaan as Vice President of Sales who joins us from Alexion. We will continue to grow the commercial team commensurate with planning for a mid-2021 NDA submission of ganaxolone in the treatment of epileptic seizures associated with CDKL-5 deficiency disorder and a midyear 2022 launch if approved. Our strategy is consistent with basic principles of orphan disease launches. First, we plan to keep the organization lean with 16 to 20 account managers and 4 payer representatives, 1 specializing on Medicaid. Our sales and marketing efforts will be focused on top traders and high influencers as most of the commercial opportunity is concentrated in a limited number of facilities. We have completed several core pieces of market research that is informed to the assumptions and conclusions underlying our go-to-market strategy. We have now finalized several key critical elements in our process, such as the patient journey, account segmentation, deployment strategy, and market size and structure. This work has given us the foundation upon which to build our branding, messaging, print and digital platforms. We are in the final stages of selecting our external marketing agency, an important decision to be made collaboratively amongst the Marinus cross-functional team, with an emphasis on a cohesive and targeted messaging platform design that will prioritize the unmet needs of our CBD patient population. From a pricing perspective, we want to ensure our value proposition is reflected. As part of those efforts, we are generating health economics and outcomes research to bolster our value proposition. This includes managing the reimbursement and payer landscape to ensure timely access and assuring we can mitigate any potential complicating restrictions. Additionally, we continue to monitor the competitive landscape and engage market access experts across the U.S. and Europe. We are confident that these efforts will characterize true value for our patients living with CBD, their families and for the physicians that treat them.

[Scott Braunstein:]

Thank you, Christy. Two additional comments from me before I turn the call over to Joe. Joe will walk you through the updates to the CDD data and Kim will discuss our regulatory activities, but I am confident that we have been diligent with our preparations of the NDA and in our interactions to-date with the U.S. and EU regulatory authorities. Timing is on track for both our FDA and EU submissions, which are a top priority. The final data analysis does not affect the statistical and clinical conclusions of the study as reflected in our May 2021 corporate deck. Finally, we continue to progress our oral reformulation and pro-drug endeavors and evaluate other opportunities for ganaxolone in additional refractory epilepsy indications. We still expect to move at least one of these formulations into the clinic in the first half of 2022. As we announced this afternoon, we are planning on initiating a Phase 2 trial in Lennox-Gastaut Syndrome, or LGS in the middle of 2022 and if all proceeds as planned with a potential new formulation. Given the overlap in seizure types and the etiologies with other disorders, where ganaxolone has shown meaningful potential specifically CDD as well as early encouraging data in the TSC patient population, we believe the future investment is warranted. We understand that the LGS market is highly competitive and would look to enter the market with the best chance of a differentiated clinical profile. With that, I would now like to turn the call over to our Chief Medical Officer, Joe Hulihan. Joe?

[Joe Hulihan:]

Thank you, Scott and welcome everyone to our business update call. Let me get right into it. I will start with our program in refractory status epilepticus, or RSC. In the RAISE RSC trial, even with COVID-19 delays, we are still expecting to have more than half the sites open by the middle of the year, with the vast majority of sites open by the end of the third quarter. We are encouraged to see that sites are screening appropriate patients and we are pleased with the rate of enrollment to-date. Our experience with screening reinforces our conviction that we have the right study design and we thought very carefully about response rates in the control arm. Let me explain that a bit. The protocol requires that patients have failed two second line AEDs. We have asked sites to pre-screen potential study candidates after they failed the first second line AED, so they can be enrolled quickly after failing another. We believe that requiring failure of two second line AEDs will lessen the response to standard of care. In fact, some patients have actually responded to the second of those AEDs. If we had enrolled those patients in the trial, it’s likely they would have been placebo responders. So, we believe that requiring failure of two second line AEDs is the correct strategy for defining the population in this study.

[Kimberly McCormick:]

Thanks Joe. Since we have been receiving an uptick of regulatory questions from the investment community, we wanted to discuss our interaction in communications with the FDA and EMA, a pre-NDA CMC meeting was held with the FDA in August of 2020 for the Marigold study. During the meeting, the FDA provided very constructive feedback and overall agreement on the format and content of a CMC section of the NDA was achieved. Subsequently, in January, we had a Type A meeting with the FDA to review our proposal, that one Phase 3 study would be adequate to support our NDA submission for CDD. Prior to the meeting at the FDA’s request, in addition to the details of the Marigold study, we provided information on legacy epilepsy studies conducted by the company that has failed to show efficacy, most notably, a Phase 3 study of focal seizures in adults. We reviewed key aspects of that study in the Marigold trial, in particular differences in dosing and PK that we believe explain the discrepancy in study outcomes and support the efficacy that ganaxolone demonstrated in the Phase 3 CDD trial. Following review of the data and information we provided, the FDA agreed that the Marigold study would be adequate to support our NDA filing, and that the adequacy of the data for NDA approval would be determined by the review of the NDA during the process. We completed a pre-NDA meeting with the FDA at the end of the first quarter. The FDA has been very engaged and responsive, and provided constructive feedback in the pre-NDA meeting on what information they wanted to see in the NDA and in what format. Rapid Response Teams are being set up to quickly respond to any potential requests from the FDA. We believe that the final data analysis for the Marigold study fully supports the submission and we remain on track with our U.S. and EU regulatory filings. It’s worth noting that we had successful pre-MAA meeting with EMA in March 2021. Overall agreement was achieved on the format and content of the MAA. A meeting with the rapporteur and co-rapporteur to discuss the MAA is planned for the end of May. Now I would like to turn the call over to Steve for a review of our financials.

[Steve Pfanstiel:]

Thank you, Kim. I am pleased to be able to share our financial results. For the first quarter of 2021, we have recognized $1.8 million in federal contract revenue related to the BARDA contract. This contract was signed in September 2020, so there are no revenues associated with this from the first quarter of the prior year. As a reminder, our base BARDA contract extends approximately through the third quarter of 2022 and is expected to provide a total of $21 million of non-dilutive funding over this time. The potential exists to extend the BARDA contracts further based on success based milestones, with potential total funding of up to $51 million. Research and development expenses increased to $18.6 million for the 3 months ended March 31 2021, as compared to $15 million for the same period in the prior year. The change versus the prior year was due primarily to costs associated with increased clinical activity, including startup of the RSE Phase 3 trial and increased resourcing primarily within our clinical and CMC teams. General and administrative expenses increased to $10.4 million for the 3 months ended March 31, 2021, compared to $3.9 million for the same period in the prior year. The primary drivers of the change over the prior year were increased support for scale up of the company’s operations, as well as preparation for commercialization. The company reported a net loss of $27.1 million for the 3 months ended March 31, 2021, compared to $18.7 million in the same period a year ago. These totals include non-cash stock-based compensation expense of $5 million and $1.9 million in Q1 2021 and 2020, respectively. The first quarter of 2021 included $2.1 million of stock based compensation related to a severance agreement with our prior CFO. Cash used in operating activities increased to $16.2 million for the 3 months ended March 31, 2021, compared to $14 million for the same period a year ago. As of March 31, 2021, we had cash and cash equivalents of $123.5 million. This balance, combined with the net upfront proceeds of Oaktree credit agreement will enable us to fund the company’s current scale of operating expenses and capital expenditures through the second quarter of 2022. As a result of the credit facility, our focus on executing a European partnership and our plans to monetize the priority review voucher associated with an anticipated CDD approval, we look to accelerate several key investments within the business including the TSE and RAISE 2 Phase 3 trials, activities to support European approval, and additional formulation work related to ganaxolone. As a result of this, we estimate operational expenses of between $113 million and $118 million for the fiscal year 2021. This total includes approximately $16 million of stock-based compensation. Offsetting these expenses, we estimate BARDA revenues of between $9 million and $12 million for the fiscal year 2021. In addition to the first quarter financial results, I would like to provide additional details of the credit facility with Oaktree Capital signed on May 11, 2021. Under this agreement, we have the ability to access up to $125 million of credit financing subject to certain conditions to be taken down in tranches upon successful completion of certain milestones. We have already received the initial $15 million upfront payment in connection with our signing. Two additional tranches of $30 million each occur based on progression of the CDD indication, with one funded at FDA acceptance of the NDA filing and a second funded upon FDA approval. The remaining $50 million will be available at our discretion upon successfully achieving certain clinical, financial and commercial milestones. Importantly, this facility provides the potential to extend our cash runway significantly based on just the CDD indication alone, and does not encumber our ability to monetize the potential priority review voucher. With that, let me say I am excited to be a part of Marinus and work alongside such a talented and top notch group of experts. My first few weeks at Marinus have been incredibly productive, and I am excited to see this company become a commercial leader in rare epilepsies. Now, turning the call back to Scott, who will provide concluding remarks.

[Scott Braunstein:]

Thanks Steve and once again welcome aboard. Before concluding our prepared remarks, I want to thank the entire Marinus team who has been responsible for the significant progress we have made and continue to strive to bring ingenuity and solutions to challenges. Our headcount has hit a milestone of close to 100 employees, and I could not be more enthusiastic about the next stages in the company’s history. Operator, can you now open the call to questions?

[Operator:]

And your first question comes from line of Joe Thome with Cowen & Company.

[Joe Thome:]

Hi there. Good morning and thank you for taking my questions. Maybe just one on the RAISE 2 study design. Is there any consideration for which specific AEDs can be used in conjunction with ganaxolone? And is there any worry that there could be drug interactions or any exacerbations of potential AEDs when you do the combination of ganaxolone in other AED? Thanks.

[Scott Braunstein:]

Joe, thanks for your question. No, there is no limitation on the other AEDs. It’s the investigators choice. The number of available AEDs isn’t that many. And so, but we do expect we will get randomization will balance out what drugs are used and that reflects standard of care. In terms of drug interactions, no, there is potential interaction with CYP3A4 enzyme inducing drugs. But in an oral epilepsy study, we didn’t see any effect, any difference in efficacy based on the use of the other drugs. And the dose of ganaxolone used in the trial is high enough. We wouldn’t expect to see any interaction, especially which you would use. I don’t think that will be a factor at all.

[Operator:]

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

[Alethia Young:]

Hi, thanks for taking my question and congrats on the progress. This has been...

[Scott Braunstein:]

Thank you.

[Alethia Young:]

For the full of TSC readout, what additional data will we see? And how do you think about what is comparable data versus competitors? Thanks.

[Scott Braunstein:]

Joe, why don’t you take it?

[Joe Hulihan:]

Yes. To do anything today, I am going to let everyone else do all the work. So, hi Alethia. Yes, I think this Phase 2 study focuses are kind of key efficacy and safety data. So, there will be some other ways to look at the seizure data, obviously, the usual safety data. And then one of the things we are interested in with this study is how – if we see any differences with different drug combinations, particularly EPIDIOLEX or Afinitor and also seizure types. The seizure types in this disorder are different in some ways than those we see in CDD. So, those are the main things we are looking at. In the Phase 3 study we will have a range of patient reported outcomes and other assessments, but we are focusing on the key data from the Phase 2.

[Operator:]

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

[Joon Lee:]

Hi. Thanks for taking our questions and for the updates. For the loan from Oaktree, what are the interest terms with each draw? And are there any call-back provisions if the outcome doesn’t reach certain expectations? And is there any flexibility for further funding for additional indications?

[Scott Braunstein:]

So before I turn over to Steve for the details, let me just hit on the big picture, Joon and thanks for the question. First of all, we are thrilled to do this deal with the Oaktree team. They have been great. They have been a fantastic partner. And I will have Steve walk you through the specifics of this deal. But I think we believe that this is a partnership that could expand in many different forms over time. And I think they have taken a lot of time to be quite thoughtful in this deal. So, happy to have them as a partner. But Steve, why don’t you walk through all the details of the deal for Joon?

[Steve Pfanstiel:]

Yes. Hi, Joon. Yes, certainly happy to walk you through. So, I think we have mentioned it’s up to $125 million of financing obviously tranche the first $75 million we can take relative to the CDD indication alone. The remaining $50 million is driven by clinical, financial, as well as commercial targets. The interest rate on it is 11.5%. It’s interest-only for the first 3 years and then it’s full maturity after 5 years. There is a ticking fee that starts 120 days after funding of the $30 million tranche from the CDD filing acceptance, that first $30 million tranche of funding, I think it’s worth noting, there is a couple things worth calling out, we can still monetize the PRD, we still have the ability to do a U.S. based synthetic royalty and we are able to do a European partnership. So, those are those are kind of a number of the key things. In terms of expanding further, I think that’s something we can discuss further as we go along and we look at this as a relationship, a long-term relationship with Oaktree.

[Operator:]

And your next question comes from the lime of Marc Goodman with SVB Leerink.

[Marc Goodman:]

Yes, hi. Joe, can you talk about LGS a little bit what proof-of-concept data you have that made you want to pursue this indication? Thanks.

[Joe Hulihan:]

Yes. So, we did have LGS is a diagnosis. It’s not a specific genetic diagnosis. It’s multiple etiologies. So, we had some patients in the CDD study that also carried a diagnosis of LGS. And so we are – we started to analyze that data. But without giving too many specifics, I think it gives us confidence that an LGS study, not a large number of patients, but it heads in the right direction. And so we have had a previous study in multiple seizure types, developmental in epileptic encephalopathies. And there was a small number of LGS patients in that, but that study really didn’t capture the data in a way that we could use it to see whether there is a proof-of-concept. The other thing that gives me confidence about LGS is the seizure types are largely similar to CDD. And so I’d expect to see the same efficacy in other etiologies as we did in CDD. And if we pursue it, it would likely be with a reformulation. It’s going to give us some better and more even exposure to the drug. So, I think that’s a plus too.

[Scott Braunstein:]

And Joe and Marc, I will add one additional comment Marc. We have updated our slide deck. And we have now included in that slide deck, the PK analysis that Joe and Alex have performed on at least the failed three focal onset study. And I think we are seeing clear differences in PK levels in studies that were previously performed by the company. We think that it’s just a function of dose titration over the course of a month, 3x a day dosing. And I think when we look back at the LGS study you are seeing a consistent signal or inconsistency signal in terms of PK, which we think is very different than what we have seen in the CDD study. Thanks for the question Marc.

[Operator:]

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

[Douglas Tsao:]

Hi, good morning. Thanks for taking the questions. I am just curious in terms of the RAISE 2 trial I know you mentioned the opportunity to potentially sort of expand the utilization of drugs. Have you engaged with the FDA or do you plan to engage with the U.S. FDA about whether that would meet standards to have inclusion in terms of the label and sort of potentially sort of move up the treatment paradigm?

[Scott Braunstein:]

So, Joe, do you want to start?

[Joe Hulihan:]

Yes, no, maybe I could turn this one over to Kim for the regulatory piece of it.

[Kimberly McCormick:]

Sure. Thanks, Joe. I can take that. So, we have not yet discussed the RAISE 2 study with the FDA. The current plan is once we have the data from that study, we will then discuss the FDA, how and what our potential options are for spending delay what that time.

[Scott Braunstein:]

Yes. And let me just give a little more color. I think we understood – I think we have to step back and say, hey, we knew we would require a different regulatory path with the European agency. I think we have gotten to a very good place with the European regulatory agency. And given that study design, we do believe it is so complimentary to what we are doing in the U.S. that it wouldn’t be logical for us to have that interaction with the agency. We would love to have sites in the study in the U.S. as well. I think from a timing perspective, we would only initiate those sites in the U.S. when the RAISE trial itself was significantly enrolled that we wouldn’t see that as a conflict. So, we think it’s a pretty logical discussion for us to have. And certainly we would love to have their buy-in from where we are today. But I think as we all know anytime we do additional studies, it’s always going to be a discussion or a filing with the agency in terms of a potential label expansion. Thanks for the question.

[Operator:]

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

[Jay Olson:]

Hey, guys. Congrats on the progress and thanks for taking our questions. We are curious about CDD. Can you talk about any feedback you have gotten from payer discussions or other pre-launch activities? And do you think the 50% seizure frequency reduction for CDD that you saw in the first 12 months of OLE could improve beyond 12 months or is that a plateau effect? And then I had a follow-up question, if I could.

[Scott Braunstein:]

Chris, do you want to jump right in to take that?

[Joe Hulihan:]

Go ahead.

[Christy Shafer:]

Sure.

[Scott Braunstein:]

I am sorry, Joe. I was going to have Christy start on the commercial question.

[Joe Hulihan:]

No, please. Please, yes.

[Christy Shafer:]

Hi, there, Jay. Good morning. So, from a payer perspective, we have done a significant amount of research just understanding the marketplace how they view CDD and the expectations that they have. We have finalized that research and we are moving into our phase of just to the internal discussions of that research and how we move into a more strategic plan. I will say though, because this will be the first and only, payer discussions have been very, very, very positive. So we are increasingly more secure in our value proposition in this patient population. I will also say that based on the market research that we have done with payers and physicians, there is an incredible appetite for a new medication for these patients that is over that 25% reduction standpoint. So, that lower threshold certainly supports our communication. So, from a clinical perspective, I will certainly turn it over to Joe.

[Joe Hulihan:]

Yes. So in terms of the long-term follow-up, yes, there is a potential right now. Patients are still moving through. And I think we need to see more patients with the longer term follow-up to see what happens. I think at a minimum, they will maintain the efficacy. But there is an opportunity, especially some patients could potentially become seizure free or we can see a change in the overall median, but no, I think there is possibility we could continue to see improvement.

[Scott Braunstein:]

Operator, why don’t we go to the next question? Yes, thanks. Sorry.

[Operator:]

No problem. And your next question comes from the line of Brian Skorney with Baird.

[Brian Skorney:]

Hey, good morning, everyone. Thank you for taking the questions and thanks for all the color and transparency on the call. I guess, when it comes to the CDD indication, I was wondering if you could just kind of walk us through what the kind of gating factors here are for the NDA submission and can you just review are both the CDD and PSC pathways under the division of neurology too? And last for TSC, you said that at the upcoming FDA meeting will be based on an interim analysis. I guess it’s an open label study. So, maybe you can talk a little bit about what you have learned from the study so far, if anything to kind of give the confidence into moving into Phase 3 and if you sort of already have an idea of the interim analysis you will be discussing in that meeting? Thanks.

[Scott Braunstein:]

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

[Kimberly McCormick:]

Sure. So in regards to the NDA submission, we are actively in the process of preparing the NDA submission for filing targeted by the end of June. So there is a lot of work ongoing at this time and a lot of preparations, but we are still on track to have everything delivered and submitted by the end of the month. In regards to the TSC study, we are planning to use the data cut from the open label study to submit a request to the FDA for an end of Phase 2 meeting in July and hopefully having that meeting in the August-September timeframe to support the initiation of our Phase 3 study. I will also be discussing the study with the European agency as well in parallel with slightly staggered timeframe for those discussions.

[Joe Hulihan:]

Yes. And yes, I can comment on the TSC in terms of what we are looking for. I mean, I think the most recent benchmark would be EPIDIOLEX. And so obviously, we would like to see magnitude of effect similar to that. It is an open label, single arm study. So in terms of predicting the placebo response, we have to use historical control, but really, it’s the magnitude and the direction of the effect? And we are seeing in the interim look, we are seeing things head in the right direction and we will present the full dataset, I think later this summer, we should have that.

[Operator:]

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

[Michael Higgins:]

Thank you. Good morning, guys. Congrats on the continued execution. Certainly a lot going on these days. I am looking forward to seeing that continued progress. Question for you coming out of Europe, we have discussed for some time now about the differences in the protocols between U.S. and European ED departments. And I think that’s driving the difference in design of the RAISE 2 study over there, but also poses some challenge, because of the placebo response that you mentioned. Can you help us a little bit in understanding what your expected efficacy rates would be for the two different regions, RAISE versus RAISE 2? Thank you.

[Scott Braunstein:]

Sure. Yes, it’s a bit complicated. I think the endpoints are different. As I mentioned, in the EU, they tend not to use IV anesthesia nearly as much. It’s the standard practice really neurologists in ICUs by the time it gets to that stage of status. And so, the second part of the endpoint is any escalation of care rather than escalation to IV anesthesia. That’s one accommodation we have made to that. And actually, the endpoint itself is different in the U.S. it’s two co-primary endpoints, they each have to hit on their own. In the EU, it’s a combined endpoint responder analysis that – so a given patient has to have an early response as well as a durable response. And I think that because they have to have the early response in particular that the power of the study has actually increased because of that. And also I think escalation of care, I think you can actually or obviously will show superiority there to standard of care alone. And so, the overall magnitude of the effect is the same in the U.S. We are expecting to see a 30% delta between ganaxolone and placebo. But for different reasons, the parameters for that are different and that’s reflected in the sample size. Initially, we were going to do a combined study with the U.S., pool the data. But with this complimentary rather than identical design, the study is being done on its own but we can achieve the same power with a much smaller number of patients, the plant sample in Europe 70 is patients. And so again, that’s a reflection of the increased power with the responder endpoint.

[Michael Higgins:]

Very helpful. Appreciate it. Thanks, guys.

[Scott Braunstein:]

Thank you for the question.

[Operator:]

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

[Andrew Tsai:]

Hi, good morning and thanks for all the progress. So, my question is on CDD. Should we expect an Adcom panel once you file what do President suggests in rare epilepsies? And just wanted to confirm investors should assume a 12-month standard review once you submit? Thanks.

[Scott Braunstein:]

Thanks for the question, Andrew. I am going to turn it over to Kim. We all heard typing in the background. We thought it was us. I guess it was Michael who is keeping us all a little bit on our toes. Thanks, Andrew. Kim, why don’t you take the question?

[Kimberly McCormick:]

Sure. Thanks, Scott. So the FDA will actually determine if there is a need for an Adcom as part of any typical NDA planning. We are actively preparing for a potential Adcom until we hear confirmation from the FDA whether or not we will or won’t. So at this point in time, we are preparing as if we are going to have one until we hear otherwise from the agency. In regards to the filing duration, as this is an orphan in a rare disease, we will be requesting priority review as part of the NDA submission and are very confident that we will be able to obtain that priority review for this very high unmet medical need, therefore, getting the reduced review time of the 6 months versus the typical standard 10-month filing. So, we do anticipate when you consider the 60-day filability timeframe plus the 6-month review that we are targeting to have approval on by the end of first quarter of next year. Does that answer your question?

[Operator:]

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

[Jason Butler:]

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

[Scott Braunstein:]

Thanks, Jason. Appreciate it. This is Scott. I will take it. So we recognized the formulation program will be a multi-stepped approach. And I think it starts with the basics that we understand the current bioavailability. And the variability of the current formulation is significant. And so what we want to do as a first step is replicate TID dosing and really give patients, physicians the ability to all obtain a therapeutic blood level and potentially allow physicians to titrate that blood level. And so right now, our three programs as we mentioned in prepared remarks, any three could go into the clinic next week are all about better bioavailability, but really replicating that TID dosing paradigm. After that, we will work very aggressively on a drug delivery technology platform to stretch dosing from either TID to BID or even TID to QD. But I think more importantly, from a drug delivery standpoint, the formulation standpoint, we want to minimize Cmax and make sure we have stable Cmins. And I think we don’t know very clearly from Marigold that we don’t want our Cmins to go below 75 nanograms per ml. And I think we can ultimately create a formulation which is better tolerated, gives physicians flexibility on dose titration, ultimately will be incrementally easier for patients and family members to administer to patients. But I think what I will see the BID or QD formulation is much more importantly about having good control of Cmax and Cmins. So that’s how we are thinking about it. And we are excited about the progress we have made to-date and we are going to try to move very quickly, but we also have a long-term vision for the franchise, which we are thinking about quite a bit.

[Scott Braunstein:]

So with that operator, we are going to make that the last question that’s coming upon 9

[Operator:]

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