ZGNX (2021 - Q3)

Welcome to the Zogenix, Inc. Third Quarter 2021 Financial Results Conference Call. As a reminder, all participants are in listen-only mode, and the conference is being recorded. After the presentation, there will be an opportunity to ask questions. [Operator Instructions] I would now like to turn the conference over to Brian Ritchie of LifeSci Advisors. Please go ahead, Mr. Ritchie. Brian Ri

Thank you, operator, and thank you all for joining the Zogenix management team this afternoon. On today�s call are Chief Executive Officer, Dr. Stephen Farr; Chief Commercial Officer, Ashish Sagrolikar; Chief Development Officer, Dr. Gail Farfel; Chief Medical Officer, Dr. Brad Galer; and Chief Financial Officer, Michael Smith. This afternoon, Zogenix issued a news release providing a business update and announcing financial results for the three and nine months ended September 30, 2021. Please note that certain information discussed on the call today is covered under the Safe Harbor Provision of the Private Securities Litigation Reform Act. We caution listeners that during this call, Zogenix management will be making forward-looking statements. Actual results could differ materially from those stated or implied by these forward-looking statements due to risks and uncertainties associated with the company�s business. These forward-looking statements are qualified by the cautionary statements contained in Zogenix� press release issued today and the company�s SEC filings, including in the annual report on Form 10-K and subsequent filings. This conference call also contains time-sensitive information that is accurate only as of the date of this live broadcast, November 4, 2021. Zogenix undertakes no obligation to revise or update any forward-looking statements to reflect events or circumstances after the date of this conference call. Now, I�ll turn the call over to Dr. Stephen Farr. Dr. Farr?

Thank you, Brian, and good afternoon to everyone, and thank you for joining us. I'm delighted to be here with you today to provide updates on another strong consecutive quarter for Zogenix, as we continue to execute on the commercial launch of FINTEPLA in Dravet syndrome, prepared for potential launch in Lennox-Gastaut Syndrome, or advanced or late stage development programs both for FINTEPLA and MT 1621. Positive momentum for the launches of FINTEPLA in the U.S. and Europe continue, and once again, we achieved solid quarter over quarter growth in the number of prescribed results, patients form a net sales of FINTEPLA in both regions. In a moment, Ashish will provide additional color and perspectives on FINTEPLA market dynamics that are leading to success and continued growth. We also remain excited with upcoming opportunities to potentially expand FINTEPLA as a treatment option in other severe refractory childhood-onset epilepsy syndromes. Towards this goal in September, we submitted a supplemental NDA to the FDA seeking to expand the label indication of FINTEPLA to treatment of seizures associated with Lennox-Gastaut Syndrome or LGs. There are an estimated 30,000 to 50,000 patients suffering from LGS in the United States, and notably the majority of patients have uncontrolled seizures, despite taking existing approved anti-seizure medications. Also, we're now getting close to starting our global Phase 3 trial of FINTEPLA in patients with CDKL5 deficiency disorder or CDD. Several sites in the United States have recently begin screening patients. And we anticipate the first patient enrolling in the study within the next few weeks. Gail Farfel, our Chief Development Officer will provide more detail on both of these programs later on the call. Last, during the quarter, we were pleased with the progress we made through regulatory interactions and ongoing development studies for the MT 1621 program, or investigational substrate enhancement therapy for thymidine kinase 2 deficiency or TK2d. Brad Galer, our Chief Medical Officer will walk you through this progress in more detail on this call. I also would like to remind you that our upcoming virtual investor events on November the 8, that will feature presentations by key opinion leaders on disease overview and natural history of TK2d and their experience with MT 1621 as a treatment option for the TK2d in patients. With that, I�ll now hand the call over to Ashish, Ashish?

Thank you, Steve. The continued solid growth for FINTEPLA in the third quarter, completing our first year of commercialization, all within a restrictive COVID environment, and in single rare indication is reflective of the strong support we are seeing from patients, caregivers, healthcare providers, and payers. That support paid with potential in multiple new indications and geographies provides us with confidence in FINTEPLA�s commercial growth outlook in the short, medium and long-term. Starting with the U.S., during the third quarter, over 130 new patients were referred to the REMS program and 133 new patients started reimburse therapy with FINTEPLA. This progress reflects a steady cadence of new patient as similar to the prior quarters from this year. By the end of the third quarter, over 990 patients in the U.S. have been prescribed FINTEPLA and refer to the REMS program. Adherence to the FINTEPLA therapy also remained strong and remarkably consistent with our experience in the long-term clinical trial and expanded access program. Since launch, the discontinuation rate is around 14% overall, and 11% within Dravet syndrome patients. We believe these rates are substantially lower than typically observed with other anti-seizure medications, commonly used to treat refractory epilepsy. We estimate that in the U.S. our market penetration among eligible Dravet syndrome patients is currently about 15% to 20%. Our internal research indicates that we should be able to increase the market penetration by at least three fold with time. For example, brand awareness for FINTEPLA among U.S. neurologist and epileptologist has almost doubled since late 2020, and is now higher than 80%. To take advantage of this momentum, we recently completed the expansion of our field based sales and medical teams by adding experienced professionals with deep understanding of the epilepsy market. The field based team is now configured to educate and support an expanded list of healthcare providers about FINTEPLA in Dravet syndrome. While it's still early, we have already seen some positive trends with respect to increased physician engagement, leading to new prescribers in the fourth quarter. We continue to be very pleased with the payer coverage for FINTEPLA law in both private and government sector. Typically, it takes two to four weeks for a new patient to receive FINTEPLA once they are referred to the REMS program. And payer coverage continues to be strong, with effectively all patients receiving positive insurance determinations. During the third quarter, we supported the Dravet community through various local and virtual events, including a unique FINTEPLA photo diary contest through social media. More than 700 caregivers participated in that event. As you all probably know, November is epilepsy awareness month. In this month, our team is participating in more than 30 community events, both virtually and in-person to support and educate Dravet patients and caregivers. In Europe, the launch of FINTEPLA in Dravet syndrome in Germany is continuing to progress very well. And our patient and prescriber base continues to grow steadily. We continue to add new patients to reimburse therapy in France through the temporary authorization of use program and currently in eight additional countries through our Zogenix access program. We have made significant progress in our pricing and reimbursement negotiations in the major European markets, with objective of reaching final determinations and executing commercial launches next year. Following the submission of our sNDA for LGS, we are now ramping our launch preparations for this new and potentially significant indication for FINTEPLA. We are conducting market research advisory boards and one on one discussions with healthcare providers, caregivers and payers to best understand the need of the LGS community. These preparations are already helping us to refine our go to market strategies and along with our expanded commercial team will position us to launch FINTEPLA law immediately upon potential approval in 2022. In summary, we are pleased with our strong sales growth in the United States, continued positive momentum in Europe, and preparations for the potential commercial expansion of FINTEPLA into LGS. We anticipate continued growth in all key geographies, and look forward to updating you in the coming months. Now, I will turn the card over to Gail, to share exciting new data on FINTEPLA. Gail?

Thank you, Ashish. I'll echo the enthusiasm expressed by Steve and Ashish around our submission of the sNDA for LGS, which was submitted on September 27 with a request for priority reviews, which if granted, would set a FDA goal to take action on a submission in six months. A standard review would establish a 10-month review timeline. The submission consisted of safety and efficacy data from 263 LGS patients, who participated in our positive Phase 3 trial, which met the primary and key secondary endpoints. The sNDA submissions also contain non-clinical chronic toxicology and carcinogenicity studies, and no new safety concerns were observed. Furthermore, prospective assessment of cardiac valves in these studies did not reveal any microscopic changes at any dose level. Next, we recently presented results from the interim analysis of our ongoing 12-months Phase 3 open label extension study of FINTEPLA in LGS patients at the 2021 Annual Meeting of the Child Neurology Society. The results demonstrated that FINTEPLA produced highly statistically significant improvement in the frequency of drop seizures in the 247 patients enrolled in the extension. The median reduction in drop seizure frequency was 39.4% at three months, and at 51.8% for patients who were assessed over months 10 to 12. And the reductions of both time points at p value less than 0.001 compared to the baseline. Of the 170 patients evaluated in the interim analysis at months 10 to 12, 51.2% reached the 50% improvement threshold, and 25.3% reached the 75% improvement threshold, which is considered a profound level of improvement. Each results highlight the durable and positive effect on long-term FINTEPLA treatment and LGS patients. Today, the safety profile of the LGS study is comparable with results seen in the Dravet syndrome trials and our experience in the post marketing setting. This profile in conjunction with FINTEPLA unique mechanism of action, highlight the potential of FINTEPLA to become a meeting treatment options for LGS patients and their families, particularly considering the highly refractory nature of this condition. I�d also add that we remain on track to submit a J-NDA in Japan to Japan's pharmaceutical and medical devices agency by the end of 2021. Now, let's move on to our newest FINTEPLA program in CDKL5 deficiency disorder or CDD. CDD is a rare, severe and highly refractory childhood on-set epilepsy, in which patients experience multiple symptoms such as gastrointestinal, visual and sleep disturbances in addition to treatment resistant seizures. Zogenix has joined Loulou Foundation, University of Pennsylvania and other industry collaborators to support a three year non-interventional study of patients with CDD to characterize developmental trajectories and clinical features of this disorder. In a small open label study conducted by Dr. Oren Dubinsky, the NYU Langone Medical Center, has presented at the American epilepsy society annual meeting in 2020. Treatment with fenfluramine produced clinically meaningful reductions in seizure frequency, and a 90% reduction in generalized tonic-clonic seizures, and a 55% reduction in tonic seizures in a case series of six patients with CDD with a median treatment duration of 5.3 months. These initial compelling results formed the basis of our decision to launch a study of FINTEPLA in CDD patients, and we anticipate the first patient will enroll shortly. The placebo controlled fixed dose two-arm trial will enroll 80 patients randomized to either 0.7 milligrams per kilogram per day FINTEPLA or placebo. FDA confirmed earlier this year in a pre-IND meeting at a single positive randomized controlled trial could form the basis of a supplemental NDA in this indication. With that, I'll turn it over to Brad, for an overview of our MT 1621 program.

Thank you, Gail. We made meaningful progress on our MT 1621 program throughout the quarter, expanding and enhancing our plan dataset that will be included in our NDA submission in 2022. Among these additional data was an updated analysis of our primary efficacy trial Study 101 formally termed retro study for the final CSR that will be included in the NDA. The study data continued to be highly compelling and consistent with previously reported results. The primary efficacy endpoint for Study 101 and updated survival analysis, using a time dependent Cox regression model shows that the difference in probability of survival between treated patients and untreated natural history control patients was consistent with previously reported results, highly statistically significant at p equals 0.0007. In addition to this compelling survival benefit, the majority of MT 1621 treated patients also demonstrated clinically meaningful improvements in motor, respiratory and our feeding abilities, with some patients reacquiring previously lost motor milestones. As the literature described and our clinical data is confirming, TK2d is a progressive disease in all patients, regardless of age of onset, and that spontaneous improvements in motor milestones are rarely seen in this patient population. We're continuing to make good progress on the clinical and non-clinical studies for the NDA submission. The timing for completing Study 107, which is a retrospective chart review study to collect the vital status of any untreated and treated patients in the U.S. and Europe, not involved in our sponsored studies, has been impacted by the pandemic, and has moved into the first quarter of 2022 from the end of this year. We're not planning for a pre-NDA meeting in second quarter of next year, and an NDA submission in the second-half of 2022. In addition to our regulatory progress in the U.S., we are preparing for a scientific advice meeting with EMA first quarter of 2022. With that, let me hand it over to Mike. Mike?

Hey, thanks, Brad, and good afternoon, everyone. Today we issued a press release announcing our business and financial results for the third quarter ended September 30 2021. In the third quarter of �21, we achieved $21.4 million in FINTEPLA net product sales globally, representing 20% growth over the second quarter of 2021. This includes FINTEPLA net sales of $18.4 million in the U.S. and $3 million in Europe. The sustained sales growth reflects the significant interest to initiate FINTEPLA therapy we continue to observe across the Dravet communities. We recognize $22.6 million in total revenue during the third quarter of �21, which was an increase of 20% as compared to $18.8 million recorded in the second quarter of 2020. Of the $20.6 million total revenue again $21.4 million was in the form of product sales of FINTEPLA, and $1.2 million of which related to our collaboration with Nippon Shinyaku for FINTEPLA and Dravet syndrome and LGS in Japan. Our total revenue for the corresponding prior year period was $2.9 million. R&D expenses for the third quarter were $33.3 million, a decrease as compared to the $34.4 million recorded in the corresponding period of 2020. The decrease was a result of overall R&D operating costs decreasing 24% to $26.3 million, as some operating costs and activities related to FINTEPLA, Dravet and LGS late stage development programs have concluded. This decrease was offset by a one-time $7 million charge associated with an agreement to amend our original FINTEPLA license and collaboration agreement with regards to revenue sharing on our past and future collaboration in Japan with Nippon Shinyaku, as well as the increased investments in MT 1621 development. SG&A expenses for the third quarter ended September 30 2021 totaled $39.5 million and this compares to $24.6 million for the third quarter of the prior year. The increase of approximately $15 million is primarily driven by the continued investment related to the launches of FINTEPLA in the U.S. and Europe. Net loss for the third quarter ended September 30 2021 was $58 million or $1.04 per share. This compares to a net loss of $60 million or $1.08 per share in the third quarter ended September 30 2020. We ended the third quarter with a strong balance sheet, with cash and cash equivalents and marketable securities totaling $343 million. And with that, I'll turn the call over to the operator to start our Q&A session. Operator, can you please open up the line for questions?

Thank you. We will now begin the question-and-answer session. [Operator Instructions] Our first question is from Paul Matteis with Stifel. Please go ahead.

Hey, thanks so much for taking the question. Appreciate it. Good to see that new patient adds were relatively stable. I guess the one question I had is just, it looks like patient as to the REMS program were sequentially a little bit lower. Is there anything behind that? And maybe could you comment on just what you saw for demand throughout the quarter on a monthly basis? And kind of how you feel so far in October if you're comfortable? And then just second, I would be curious if you wouldn't mind breaking out U.S. and rest of world. Thanks again.

Thank you for your question, Paul. I'm going to hand that over to Ashish to address it for you. Ashish, are you on mute?

I�m sorry. So Paul, for the Q3, despite the resurgence of COVID, the new patients add were consistent with the prior quarter. And when you look at month by month, we have seen the consistent growth. We haven't broken that out. But what we have seen is especially when you say towards the July and August when we had lot of closures because of the resurgence of Delta variant, we did see a little dip there. And I think that contributed to where we are. But when you look at the overall numbers of 133 starts, which is a growth over last quarter has been steady. In terms of U.S. and rest of the world, we haven't broken down the patient numbers because as you know, in Europe finding number of patients actually it's very difficult because of the regulations. So every patient number that we are reporting is purely from the U.S. perspective. Hope that answers your question?

Yeah, thank you so much, Ashish. Can you break out U.S. and Europe in terms of FINTEPLA revenues?

Yeah, in the quarter $18.4 was in the U.S. and $3 million was in Europe.

Great. Thanks so much. Appreciate it.

Paul, I think you had a question about what we�re seeing during this quarter, as much as we can say. I just want to remind you that we did move forward with an expanded sales team, which became effective in the field at the beginning of the quarter, obviously, it'll take them a few weeks to get acclimated and to start to have conversation with physicians. But we've been very pleased so far this quarter with our expanded team to increase physician engagement. So that's a very positive sign for us. And we know that has led to new prescriptions. So, obviously it's early days still, I�m sure Ashish would say that, but we feel encouraged with what our expanded team is doing right now.

Okay. Thanks, Steve. Appreciate it.

The next question is from Jason Butler with JMP Securities. Please go ahead.

Hi, thanks for taking the questions. Just first one, as you're preparing for the LGS launch, can you speak to any work that you've done with payers or planning to do with payers to get them ready for the label expansion? And then on MT 1621, can you just give us some context of any prior dialogue that you've had with regulatory consultants or KLOs in Europe to give insights on how the -- what the approval path could look like there? And what you're looking to get out of the scientific advice meeting?

Thanks, Jason. I'm going to ask Ashish to take your first question and Brad will get ready to respond to the second one. Ashish?

Yeah, Jason from the LGS launch, as I�ve said in the prepared remarks, we are doing one on one as well as advisory boards with payers as well as every other stakeholder. What we are hearing consistently is that LGS is a challenging and unpredictable disorder, and payers too think that the data is meaningful. And they are excited. And they also are aware and appreciate that LGS is a pretty refractory condition. We are going to be doing these conversations, we started them doing last week at AMCB and we will be continuing that in this quarter as well as next quarter. As soon as the indication is approved, our plan is to reengage them with the label and ensure that the product gets covered.

Brad, over to you?

Hi, Jason, with regards to MT 1621 In Europe, we definitely are engaging with multiple regulatory consultant experts and KOLs to help us with our path there. The KOLs are very excited, especially the ones that have utilized MT 1621. As a matter of fact, one of which will be on the call on Monday. And she'll be discussing her experience as well. We're very excited about treating with this medication, as they are seeing tremendous benefit, as I mentioned in survival, but also other non-survival benefit. The regulatory path as well outlined on Monday, maybe a bit different with a different indication. Whereas in U.S., we're looking for an indication for all patients, in Europe, the EMA has been a little more difficult and requesting a little bit more data, especially with the adult onset patients. So it may be a different indication with a younger age of onset patients. But I'll be providing more information on Monday.

Just around to the majority of the patients the [indiscernible] are in fact early onset. So children, as opposed to later on [indiscernible], just reflects the fact Jason that we have more data on young onset of early onset we use for later onset. And that's really, I think, the issue that the EMA is addressing right now.

Okay. That's helpful. Thanks. And I look forward to the call on Monday.

Next question is from Yatin Suneja with Guggenheim Securities. Please go ahead.

Yes. Hi, this is Eddie on for Yatin. Just a couple from me, can you talk about what the potential risks are to the LGS filing? Like, why is there even a debate around potential acceptance? Is there anything in the non-clinical work that could create a risk? And then, assuming approval in LGS can you talk about the cadence of patient adds next year? And do you think that will be affected by the level of off label use you're seeing? Can you remind us what the off label use you're seeing on a per FINTEPLA in 3Q? Thanks.

Thank you. Gail, would you like to take first question?

Sure. Happy to. Thanks for the questions. Well, we are unaware of anything in the filings that would pose such a risk. Certainly the non-clinical data are straightforward and those studies are complete. In terms of the clinical data, the same has happened we had comprehensive and fruitful discussions with the agency in the pre- sNDA meeting, as well as in the Phase 3 meetings. And we�re able to come to good agreement about what should be included in the filing. And of course, we've done diligence and check our datasets for submission. So we believe that a submission will be accepted all the time.

And Ashish, could you address the second question?

Sure. Hey, Eddie, in terms of cadence of patient adds after the LGS, I'll give you a perspective in terms of number of patients. As you know, in LGS, it's at least five times or six times larger than Dravet, so you will consequently see the number of patients coming in is going to be higher than what we have for Dravet syndrome. As for your second question, will that have any impact in terms of how it is being used right now? One thing I would just like to remind you and everyone is that we have only indication for Dravet syndrome and we promote only in Dravet. However, the data tells us that and this as we said previously, it's around 20% of our patients who are being prescribed for FINTEPLA are for indications other than Dravet. And LGS is the majority of that particular cohort and that stay true and Q3. Given the significant number of LGS patients and the feedback that we are hearing from the excipients in the sense that the data is meaningful for them, they are excited to have a novel treatment options. And they are looking forward to have FINTEPLA in their toolbox, because of these reasons and also the current treatments are somewhat inadequate to have seizure control. We expect that that will not be a huge factor.

Thank you so much.

The next question is from Rohit Bhasin with Needham and Company. Please go ahead.

Hi, this is Rohit on for Serge. Thanks for taking my question. Are you noticing any particular prescriber trends for FINTEPLA thus far? And then in terms of payer coverage, should we expect any changes for 2022?

Ashish, I�ll hand out to you again.

Sounds good. So, in terms of prescriber trend Rohit, we see consistent increase month after month. And as we said previously, what we are seeing is that physicians as we are connecting with them, as we educate them on the FINTEPLA, and the transformational efficacy in Dravet syndrome. As they get comfortable with the process of the REMS, as well as the entire Zogenix central, they start using the product. And once they start using the product, it kind of snowballed from that. So we are getting good response from them. And we are not only getting prescriptions from the epileptologist, but also from the community neurologist and the neurologist at large. So that's something has been very promising and very reassuring. In terms of payer coverage, as I said in my prepared remarks, almost every patient who is prescribed FINTEPLA is able to get it and they have been able to get positive determination. And based on the feedback that we have from the payers, not only for Dravet, but also what we are doing on LGS the conversations we are having, we do not see any roadblocks there and any concerns there.

Great. Thank you.

The next question is from Esther Rajavelu with UBS. Please go ahead.

Hi, thanks for taking my questions. I guess a couple for me, two on Zogenix and one TK2d. The first one, you referred to increasing prescriptions for new doc, so can you give us a sense for whether these are community epileptologist or part of larger comprehensive treatment centers? And then on the drop off rate, at what point in the therapy are patients dropping off, and if you can share the average duration of therapy, that would be helpful. And then lastly, on TK2d, if you can talk about what steps you may have to take next year as you're going through the regulatory process to identify patients? Or do you expect the majority of these patients to be readily available for treatment if the therapy is approved?

Thanks for your questions. I'm going to ask Ashish again to take the first two for you.

Yep. So, Esther I think in terms of the prescriptions from new docs, as we add more physicians, majority of them are community neurologist, as you can imagine. The all epileptologist, who were part of our clinical trials and at the large centers are already prescribing the product and are signed up for the REMS program. So every new prescriptions that or every new physician that we are bringing in, they're coming from this community neurologist group, and also from centers, because quite frankly, there are many centers where we did not have access to physicians for a long period of time because of COVID. I think slowly they are opening up and as we make inroads with them, we have seen prescriptions from that. As far as your second question on the drop off, usually it takes around five months at an average. The range is between four and six. So the patients who have dropped off, they try the product for at least five months between four and six. And then they try and reach the maximum dose that they can tolerate and see the impact. One great thing about FINTEPLA is that as you escalate the dose it will start working for you. But if it doesn't, you will know that pretty quickly. And I think that has been the range that we have seen. And usually they stay on the therapy for that long and then they decide to drop off. And majority of this drop offs because the product did not work for them. And when you take that out, the patients who have started the therapy, they're still on the therapy. So we have patients who started last August, when we launched the product, they are still on therapy. And we also have majority of the patients who are part of our open label extension and the expanded access program, still on the therapy. So the average duration is much, much longer at this point in time. For TK2d, I'll hand it over to Brad.

I'll take that for Brad. In terms of the question about trying to increase the number of identified patients. Obviously, when you are in the [indiscernible] space, this becomes very critical activity in conjunction the work you're doing in developments get this product approved. So we're working in a number of areas right now. I want to give another advertisement for our Investor Day that�s coming up next Monday, where we'll talk a lot more about this. But, we clearly have ongoing activities right now relating to increasing disease awareness, also to increase a diagnosis, helping physicians to be able to identify TK2d earlier. And a key component of that is no surprises is genetic testing. We have a number of activities associated with improving the availability of genetic testing for TK2d. So we'll be thrilled to tell you all about that on Monday.

Okay.

Our next question is from Tim Lugo with William Blair. Please go ahead.

Hey, this is Lachlan on for Tim. Thanks for taking the questions. So I was wondering, with what sounds like potentially several launches across European markets next year, do you already have the commercial infrastructure you'll need in those markets in place? Are you going to be building as you sort of get closer to the reimbursement decisions there? And then, secondly, I was wondering for the CDKL5 study, are you comfortable sharing any details around the powering of that, and maybe some of the assumptions you use there?

I can take those for you. With respect to power, and we haven't really probably talked about that. But the type of powering that we use for duration Dravet is sort of where I would lead you as opposed to the power and that we needed for LGS. The reason for that is that CDKL5 is monogenetic epilepsy, very similar to Dravet syndrome. And we feel comfortable within equals 40 per group that we've ever had significance. Just remind me of your first question again.

I was wondering, I think you said you have eight markets with reinvestment into that. Do you already have the commercial infrastructure built out in those countries? Are you going to be building that out between now and when you expect?

Yeah, we are playing for very much a stage approach. So we have certain functions which are centralized and important for Europe, based in in Maidenhead, and UK. And then we are building our presence in various countries as and when the product becomes commercialized there. So for example, today, we have a presence in Germany, where we've launched at the beginning of this year, as you know, we have about 10 employees in Germany, and that's probably the largest country office that we will have in Germany. So we will sort of build up these country presences once we have reimbursement approved.

Good. Thanks.

Thank you for your questions.

The next question is from Danielle Brill with Raymond James. Please go ahead.

Hey, this is Alex on for Danielle. Thanks for taking our question. So correct me if I'm wrong, my notes for MT 1621 said that we'd be getting data by year-end and that the NDA was looking to be submitted like first-half �22. And today you're now guiding to second-half �22. Could you share the reason for this delay? And then was that informed by anything that came up in the FDA Type B meeting? And then additionally quickly, forgive me if I missed this, how many doctors are now enrolled in the REMS program?

Brad, can you take the question on Study 107 being the right into step to the NDA submission.

So in our meeting, there were no � in our type B meetings there are no new studies. As I mentioned earlier, the delay is due to Study 107, which is identifying patients outside genic sponsored studies, both untreated and treated patients. And the delay is because of the pandemic, the sites having delays in the IRB meetings, and they're signing clinical trial agreements. And, that�s as you know, a problem across the industry and that's why we pushed that out one quarter.

Okay. Great. And then, just on the REMS registration, do you have an updated number on those?

Yeah, at the end of last quarter, there were over 720 prescribers that were enrolled in the REMS program, and approximately half of those were writing prescriptions for FINTEPLA.

Okay, great.

Thank you for your questions.

[Operator Instructions] Our next question was from Arvind Patel [ph] with Bank of America. Please go ahead.

Hi, good evening. This is Buvan Patel [ph] on for Jason Gregory. Thanks for taking my questions. So first, on the LGS filing for FINTEPLA with a few weeks left ahead of the 60-day deadline to get priority review, I just want to hear your thoughts on what degree of confidence do you have that you'll be granted the priority review? And then, I also want to ask with regards to getting new physicians REMS certified, if you could quantify the number of Doc certified at the end of 3Q. And so it looks like you had 720 like in �20 you just mentioned at the end of 2Q, so how likely are you to meet or even exceed the goal of 1400 by year-end, given you've mentioned, identifying and adding more prescribers to your call list as well? And then finally on MT 1621, just wanted to get your thoughts on the pass-through market for that asset? And what can you tell us about any data that we can expect at the event next Monday? Thank you.

Hey, thanks for your questions. Gail, if you'd like to take the LGS question?

Sure. As you know, granting of priority review is an FDA decision. And there are a number of other products that are approved for LGS. However, let's say to the patient community, there is still great unmet medical need among the community to have better treatment options. And FINTEPLA with the unique mechanism of action was provide a brand new alternative. Importantly, this study the LGS pivotal study meets the requirements of a pediatric written request from FDA. And the standard review time for submissions in response to a pediatric written request is six months. So we believe that we would be granted or have a good chance of having granted the priority review timing because of his response to characterization.

Okay. And I�ll just -- in case I misspoke, the number of certified doctors in the REMS program was over 720 at the end of September, so at the end of Q3. Maybe Ashish, you can talk about what we're doing to increase the number of subscribers enter the REMS program.

Yeah, so one other thing I'll say is that our focus is on getting more patients prescribed FINTEPLA at the top of the funnel. And in terms of getting number of physicians certified, and as we said a few quarters back, these physicians get certified once they have a patient and once they realized the value of FINTEPLA. So what we focus on a day to day basis is getting to all these physicians who have Dravet patience, and we have just expanded that list from 1400 to almost 3600. And the goal is to get to them, educate them on the transformational efficacy in Dravet syndrome. And once they are educated and then they decide to prescribe and that's the time they get certified. Certification is pretty easy process, and it's people can do it on cellphone. But our focus is now more on getting physicians to write the product and getting more patients on the top of the funnel. And that's something we have been focused on in last few months. But one thing I can tell you is that between Q2 and Q3, we increased the number more than 75 physicians came on certified for the REMS. And in terms of number of physicians, we have more than 44 new physicians started prescribing in Q3, along with the physicians who are already prescribing. Hope that answers your question.

Thank you. And then, I just wanted finally on the MT 1621. Just what can you tell us about any data that we can expect at the event next Monday? Thank you.

Yeah, thanks allowing me to advertise. I won't give it all away. But the KOLs one from U.S. and one from Europe, both our investigators will be showing their own patient videos pre and post-treatment, which you will see viewing be quite impressive. In addition, I'll be running presenting some non-survival data. But in addition, as I mentioned, Study 107 is delayed till next year. And also we'll be analyzing the prospective Study 102. Next year, it will be a lot more non-survival data as well. So a lot more to come that I'll be presenting in the KOLs next Monday, be an ongoing pool great data coming out.

Thank you.

The next question is from Neena Bitritto-Garg with Citi. Please go ahead.

Hey guys, thank you for taking my question. So I was just wondering if you could clarify how many patients were actually on drug actively at the end of September. And then also, if you could provide the number of total cumulative starts since launch as of the end of September that would be great? Thank you.

Ashish, I�ll handover to you.

Yes, I'll take that. So, we didn't mention on the call the number of patients, but we continue to add on a monthly basis patients. And we will continue to do that in foreseeable future. The focus is for us to get them on the top of the funnel. And we know that once they are prescribed FINTEPLA almost all of them, if not every one of them gets positive determination. And we are able to ship the product in two to four weeks. In terms of the new patient starts, I think that was your second question. We are 130 started in the Q3. And in terms of cumulative start, that number is well over 860.

Perfect. Thank you.

We have a follow-up question from Yatin Suneja with Guggenheim Securities. Please go ahead.

Yeah, thanks for taking my follow-up here. Just quickly, you guided last quarter for about 50 patient add per month. And given you sort of missed that slightly this quarter, I was wondering for 4Q if you're still sort of consistently thinking about 50 patients per month or more of a consistent to 3Q numbers? Thanks.

I'll take that, Steve. So, I think one thing I'll say is that in Q3 and we are really happy with what we in number of adds because of the resurgence of COVID that we have experienced significantly in July, as well as in August. And those new patients when you normalize for that have been consistent with the prior quarters. And in Q4, as you know, we have expanded our team. And the reason for that expansion was we wanted to reduce the geographies which will allow for more face to face interaction. This will also -- we have expanded our call list and the list of prescribers because we are finding more prescribers, caring for Dravet patients, and we want to call on them. And because of COVID, we couldn't call on them because the large geographies that expansion help them. It's very early, but what we are seeing the impact that our ability to make this face to face call with FCB [ph] is increasing. We are educating them on FINTEPLA, especially through the speaker programs, but also our one on one visits. And we are very encouraged by the progress we have made, progress made by the team since start of this quarter. And we do see and we do expect to see a very meaningful impact of this expansion in the coming months in Q4, and beyond.

This concludes the question-and-answer session. I'd like to turn the conference back over to Dr. Stephen Farr for closing remarks.

Thank you for joining us on today's call and particularly appreciate the questions that you asked us as well. Very happy to report on a strong quarter with growing FINTEPLA sales, submission of the sNDA for our second indication, and close to initiating a Phase 3 trial and a third indication for FINTEPLA. I'm also very pleased to cover MT 1621 today, and especially excited to have our first mitochondrial disease focused investor event next Monday. I hope you're all able to attend this meeting virtually. And thank you all again, and enjoy the rest of your day. Goodbye.

This concludes today's conference call. You may disconnect your lines. Thank you for participating, and have a pleasant day.