Ladies and gentlemen, thank you for standing by, welcome to Aquestive Therapeutics conference call. At this time, all participants are in a listen-only mode. After the speakers' remarks, there will be a question-and-answer session. To ask a question during the session, you will need to press star one on your telephone keypad. If you require any further assistance, please press star zero. I would now like to turn the conference over to your first presenter, Faith Pomeroy-Ward, Aquestive Investor Relations. Please go ahead, ma'am.
Thank you, operator. Good evening, welcome to today's conference call. On today's call, I am joined by Keith Kendall, Chief Executive Officer, Dan Barber, Chief Operating Officer, John Maxwell, Chief Financial Officer, who are going to provide an overview of the recent business developments. Additional members of the Aquestive team will be available for Q&A. We expect today's call to last approximately 60 minutes.
As a reminder, the company's remarks today correspond with the press release that we issued after market close today in a Form 8-K that was filed with the Securities and Exchange Commission containing prepared responses to anticipated questions during this call, relevant charts to the business developments we will be discussing tonight. A recording of today's call will be made available on Aquestive Therapeutics website within the investor relations section shortly following the conclusion of this call.
Before we begin, let me remind you that today's call will include forward-looking statements based on the company's current expectations. Such statements represent our judgment as of today only and are subject to risks and uncertainties that could cause actual results to differ materially from those described in these statements.
We undertake no obligation to revise or update these forward-looking statements in light of new information or future events, except as required by law. For information concerning risk factors that could affect the company, please refer to the Risk Factors section in the company's annual report on Form 10-K filed with the SEC on March 11th, 2020, and in its quarterly reports on Form 10-Q. With that, I'll now turn the line over to Keith. Thank you, Keith.
Thank you, Faith, and thank you, everyone, for reacting quickly and your flexibility in joining us this evening. Disappointingly, today, we received a complete response letter from the FDA on our new drug application for our product candidate, Libervant, a diazepam buccal film for the management of seizure clusters. As we outlined in our press release, the FDA issues a CRL to indicate that the review cycle for an application is complete, but the application cannot be approved in its current form. In the CRL, the FDA limited its comments to only one of the nine studies performed by Aquestive and included in our Libervant NDA. Importantly, other than procedural observations concerning a small number of blood draws, the FDA did not identify deficiencies on any other issues beyond their comments on this one particular study.
The study commented on by the FDA was Study 180323, which was a crossover study comparing the pharmacokinetic or PK profiles of Libervant and Diastat, the reference-listed drug to Libervant, in subjects diagnosed with epilepsy and actively taking anti-epileptic drugs or AEDs. As far as we are aware, this is the first pharmacokinetic study ever performed using Diastat in subjects with epilepsy. Study 180323 contained 28 subjects and from Aquestive's perspective, had solid results.
As many of you know, PK studies generally focus on three measures. Total exposure, referred to as area under the curve or AUC. The highest concentration of a drug at a known time point or Cmax. The time to reach the highest concentration of drug or Tmax. In Study 180323, Libervant exceeded the AUC measure when compared to Diastat, was within normal comparability ranges for Cmax, and had a Tmax within the published Diastat label.
We were quite pleased with these results. However, the FDA noted in its CRL that in Study 180323, there were two weight groups where the Cmax ratio comparing Libervant to Diastat were not as close to comparability as the FDA would like to see. The FDA noted that there were five subjects out of 28 who, when grouped together, had a Cmax ratio closer to 50% of Diastat. Importantly, four of these five individuals were within the same weight groups I mentioned before.
The FDA had no further comments on the study or on any of the other weight groups. We had extensive and collaborative discussions with the agency about this question right up until and through Monday of this week. From Aquestive's standpoint, this CRL is heartbreaking. We've put a robust package together that thoroughly characterizes Libervant as well as Diastat.
We have over 1,300 dosings in our safety study with promising results. This is an important product for patients, and we're very disappointed that our application was not approved for immediate distribution. In the short term, we believe this is a detriment to the epilepsy community, especially patients and caregivers. However, in our discussions with the FDA to date, we believe there is a logical path forward that will not require additional clinical studies.
Using the robustness of the data from our nine studies, we believe we can utilize modeling to adjust the dosing regimen for the weight groups noted in the FDA's CRL. In all of our studies, Libervant has proven to have excellent linearity, which is a basis for predictability when modeling dose and exposure levels. Over the coming weeks, we will update our dosing model and request a Type A meeting with the FDA.
A Type A meeting is a meeting that occurs typically within 30 days to discuss the development program to proceed to a path for approval. At this meeting, we intend to share the results of our modeling, as well as our new dosing regimen and propose the immediate resubmission of our NDA. If the FDA agrees with our proposal, we plan on resubmitting the NDA before the end of the year.
The review cycle for a resubmission of this kind is typically six months. Given the narrowness of the resubmission, we will request a shorter review cycle, as is our right. This decision will be completely at the discretion of the FDA. In summary, while we did receive a CRL from the FDA for our Libervant application, today's an important step forward for Aquestive and the patients who benefit from having access to Libervant.
The FDA's comments are limited to one study. The comments on the study are limited to two weight groups. We can use our modeling to update the dosing regimen for these two weight groups, and we believe that this solution presents a promising path forward to approval, and we're hopeful the FDA will agree in the soon-to-be-scheduled Type A meeting. This concludes my prepared remarks, and I'll now open the line for questions.
At this time, if you have questions, please press star then the number one on your touch-tone telephone. If your question has been answered or you wish to remove yourself from the queue, press the pound key. We will pause for a moment while we assemble the queue Your first question comes from the line of Randall Stanicky from RBC. Your line is open.
Hi, Randall. Are you there?
Oh, yeah. Sorry. This is Dan Busby on for Randall.
Hey, Dan.
Hey, Keith. First question, I know that you've talked about the linear relationship and weight-based dosing before. Just to be clear, do you intend to change the way you model that relationship itself, and would that have an impact on any of the other eight studies?
Thanks, Dan. This is Daniel Barber. Good to hear your voice. If you think about the modeling we use, the linearity is driven by all of those eight studies. It's actually the other way around. The studies created the linearity, which is what we can use to adjust our dosing regimen. To make it a practical example, in one of our weight groups, we are using 12.5 milligrams against the Diastat level of 15 milligrams. We will up our 12.5 milligrams to 15 milligrams, and we will then put that in the model to recast what those dosing regimen at that level would produce. The robustness of the model we have is actually what will benefit us now, rather than it being something that goes backwards and creates a problem for us in our past studies.
Okay. Got it. That's helpful. If FDA's concerns could be addressed with what sounds like a fairly straightforward adjustment, does it surprise you that FDA didn't simply ask for that information during the review, even if it meant potentially extending the PDUFA date by a few months?
As I said, we've been working with the FDA intensively for the last couple of weeks. The question came up very late, we addressed it with them. We've actually had two meetings with them in the last two and a half weeks to talk through it. I just don't think based on when the question came up and the work that had to be done with the model, that there was time left.
Got it. Understood. Just one more question from me. It sounds like your base case assumption is a six-month review. Can you talk about the factors that FDA might consider when deciding whether to grant a two-month versus six-month review?
As you I'm sure know, a two-month review is usually for minor adjustments, right? If you had an excipient that you were switching out the vendor, that would be a two-month review. When you get into clinical changes, that is typically the six-month review cycle. What we will argue in this case, though, is because we are using modeling and we are submitting no new clinical data, and our modeling changes in our dosing regimen are isolated to two weight groups, that the review cycle can be supported in a faster time. As Keith said, that is completely at the discretion of the FDA.
Got it. Thanks, guys.
Your next question comes from the line of Jason Butler from JMP Securities. Your line is open.
I just wanted to clarify. Did you, in discussions with FDA over the last couple of weeks, propose the modeling solution, and did they give you any feedback into that potential route to a solution?
Hi, Jason. Nice to hear your voice. This is Dan. Yes, we did talk to the FDA about modeling as a solution. We found their comments to be helpful. The FDA, of course, would never say on any program for any reason in absolutes. From our discussions, we do feel it's an appropriate and reasonable path forward that will have a very robust and positive conversation with the FDA.
Okay. I guess I'm looking at slide four here, where you're showing the PK levels. It looks like your PK profile is more consistent across the different weight groups versus Diastat, which has a higher Cmax in lighter patients, a lower Cmax in heavier patients. Have you had feedback from FDA that acknowledges that the PK profile may be more predictive and the product appears more consistent across a range of weight groups?
Yes, thank you, Jason. That's a very good observation. The FDA has acknowledged to us that at the study level, in particular, we have results that are within comparability and that our variability is better when compared to Diastat. You're absolutely also right that when you look at the weight bins, across those weight bins on slide four, you can see the tightness of our error bars and the tightness of our range when compared to Diastat, where at the low level, patients are getting a very high level, an unnecessarily high level in some cases. At the high weight group, they're getting a very low level and a level that perhaps is problematic for them. One of the things we did struggle with with the FDA is what level exactly are they looking for across all weight groups.
That's why on this slide, we included the overall Diastat Cmax level of 211. We do think that when we update our dosing regimen, we will be well within the range the FDA is looking for. One helpful way we have approached that in understanding that is there is public information out there on other programs. Obviously, we can't compare ourselves to other programs such as diazepam nasal spray. There's a product called VALTOCO.
We have noted that in their public information, their patient data has a Cmax level in patients with epilepsy of 145 nanograms per milliliter. For us, we get a lot of confidence when we see the VALTOCO level at 145, the Diastat level at 211, and we know we're already at the 211, and when we put our new dosing regimen in, we'll be well above that. I know that was long-winded, Jason, but hopefully, that helped with your question.
No, that's really helpful, Dan. Just one more question, Keith, and I get that you're going to have a limited amount to say here, but can you just comment as to, in terms of the KYNMOBI, the apomorphine royalty monetization, whether anything has changed in your plans or your broad timelines in securing that transaction?
Jason, you know how much I hate disappointing all of you. We're not going to make any comment about that. We'll provide an update on that in our earnings call in November.
Okay, great. Thanks for taking questions.
Okay.
If you have any question you may press star then number one on your telephoneYour next question comes from the line of Liana Moussatos from Wedbush.
Hi, this is Shweta for Liana. Thank you for taking my question.
Hi, Shweta.
Hi, Keith. Can you remind us of the different weight groups in the Libervant study? Then on the call, you mentioned four of the five patients were in the same group. Can you talk about which group they belong to?
Sure. I'll let Dan walk you through that.
Hi, Shweta. I think where Jason had pointed to slide four in the documents we sent around, that's a good slide to get an understanding of what was in the study. If you look at that slide, there are yellow and blue bars. The yellow bars are Diastat, the blue bars are Libervant, and they're divided into four buckets. Those four buckets represent the four weight groups that were in this study. If you see 51-62 and then on up all the way to 88 kilos and higher. Inside of those four weight groups, you also have the N at the top of the chart here. You can see the degree of subjects we had in each of the weight groups.
The four of the five patients, are they in the higher weight group?
The two weight groups that the FDA has issue with are the 51-62 kilo, and you can see that our Cmax is lower in that group compared to Diastat, and the 76-87 kilo group, where you can see that relationship as well. four of the five subjects are in those two buckets.
Got it. Okay. Can you talk about the protocol deviations in blood draw, and then what aspects of the study gives you confidence that you can adequately address the concerns without any additional studies?
Yeah. The protocol deviations were for blood draws that were well out, three days and out, in terms of time points. There was a very limited number of blood draws. While it was noted in the CRL, we don't anticipate that being a major issue.
Okay. Do you now anticipate the orphan decision to happen after potential approval in first half of 2021 for Libervant?
Well, all exclusivity matters for any drug only happen after the approvability package comes from CDER, the review division. Exclusivity of any sort would wait until that time period. We would anticipate when our next PDUFA date comes around, that's when the FDA would review the exclusivity provisions.
Got it. Okay. My last question is about the Type A meeting. When would you provide us with minutes or updates on discussions on the Type A meeting?
Once we have the meeting and we know the path forward, it would be our intent to update everybody on what happens next.
Got it. All right. Those were all my questions. Thank you.
Your next question comes from the line of Ram Selvaraju from H.C. Wainwright & Co. Your line is open.
Thanks so much for taking my question. Just to clarify, the FDA has not provided any commentary on the orphan drug status or the approvability of the NDA as it pertains specifically to the orphan drug status held by VALTOCO, is that correct?
The FDA provided no commentary whatsoever on the orphan drug issue. That's correct.
Then secondly, can you comment on what the implications are for commercial planning as that pertains to Libervant, obviously on potential delays in the approval to potentially end of the first half of 2021? Does that potentially impact any of the initiatives that you had originally planned to institute in order to prepare the market for the introduction of Libervant? Or will all of that pretty much stay on track since you already have an existing sales force in the field and there wasn't any significant additional sales and market infrastructure that you were envisaging putting in place?
Sure. There'll be certain actions that will push out, like building out the Libervant portion of the sales force. Obviously, there's no point in doing that today. The rest of the activities to continue to support Sympazan as the precursor footprint or prepare the market with literature and other types of things in support of a Libervant launch will continue on. Nothing has changed about our confidence in the strength and value of this market for epilepsy patients.
With respect to the Type A meeting, it is your view, just to confirm, that once that Type A meeting has been held, you'll have definitive clarity on what the requirements are, and the FDA will make it very clear at that juncture that no additional clinical studies are needed, right?
Ram, this is Dan. I wish there was an FDA meeting that was that clear. I think you know how that meeting will go. We will put our positions forward. We will get comments from the FDA. Typically, the comments from the FDA are very helpful in understanding the position that the FDA views your packaging, and we will resubmit from there. We do not anticipate any need for additional clinical studies, and we are confident that the population PK modeling approach will help with the deficiencies the FDA has outlined.
Okay. Thank you.
Operator, are there any more questions?
If there are no further questions at this time, I will now turn it back to Mr. Keith Kendall for closing remarks.
Well, again, thank you everyone for taking the time to adjust your schedules on a Friday night before you start your weekend. We appreciate you doing that and your flexibility. As this continues to unfold, we will keep everyone up to date on what's going on with this program. Again, thank you, and have a good night.
This concludes today's conference call. Thanks for participating. You may now disconnect.