Earnings Call: Q3 2019

Nov 7, 2019

Good morning, ladies and gentlemen, and welcome to the Axsome Therapeutics Third Quarter 2019 Financial Results Conference Call. Currently, all participants are in a listen only mode. Later, there will be a question and answer session. Instructions will follow at that time. As a reminder, today's conference call is being recorded. I would now like to turn the conference over to your host, Mark Jacobson, Senior Vice President of Operations at Axsome Therapeutics. Please go ahead. Thank you, operator. Good morning and thank you all for joining us on today's conference call. Our earnings press release providing a corporate update and details of the company's financial results for the Q3 of 2019 crossed the wire a short time ago and is available on our website at axome.com. During today's call, we will be making certain forward looking statements. These statements may include statements regarding, among other things, the efficacy, safety and intended utilization of our investigational agents, our clinical and non clinical plans, our plans to present or report additional data, the anticipated conduct and funding of future clinical trials, regulatory plans, future research and development and possible intended use of cash and investment. These forward looking statements are based on current information, assumptions and expectations that are subject to change and involve risks and uncertainties that may cause actual results to differ materially from those contained in the forward looking statements. These and other risks are described in our periodic filings made with the Securities and Exchange Commission, including our quarterly and annual reports. You are cautioned not to place undue weight on these forward looking statements, and the company disclaims any obligation to update such statements. Joining me on the call today are Doctor. Herriot Tabuteau, Chief Executive Officer, who will begin the call by highlighting our recent achievements and upcoming clinical milestones Doctor. Cedric O'Gorman, Senior Vice President of Clinical Development and Medical Affairs Dave Merrick, our Chief Commercial Officer and Nick Pizzi, Chief Financial Officer, who will provide a financial update. I'd now like to hand the call over to Ariel. Thank you, Mark. Good morning, everyone, and thank you all for joining us on the call today. So far, 2019 has been very productive for Axsome. We have significantly advanced our 3 clinical stage CNS product candidates, which are being evaluated in 6 efficacy trials, including 5 Phase 3 trials and 1 Phase 2 trial across 5 different indications. It is a highly active time for Axsome and a potentially important time for patients and clinicians as these studies are fast approaching completion with top line results expected by year end for several of these clinical trials. If successfully developed, our 1st in class or best in class investigational medicines have the potential to transform the lives of many of the millions of patients who are currently failed by existing treatments for their CNS disorders. Before I provide an update on our programs and upcoming clinical milestones, I would like to introduce you to our Chief Commercial Officer, Dave Marek, who joined the Axsome team in August. Dave joins us from Amgen, where he was Vice President and General Manager of the Neuroscience Business Unit. Prior to Amgen, he held executive positions at WebMD and at Saatchi and Saatchi Healthcare Advertising. Earlier in his career, he maintained commercial roles in CNS therapeutic areas at both Eli Lilly and Company and AstraZeneca. I'd like to turn it over to Dave. Dave? Thank you, Herriot. Let me say how excited I am to join the Axsome team and lead the commercial efforts to ensure our novel investigational medicines bring the therapeutic advantage needed for many of the millions of people affected by CNS disorders. It's an exciting time to have such important data unveiled in the coming weeks and possibly lead to 2 NDA filings next year. The Axsome leadership team has been focused on thinking differently and efficiently in accelerating our clinical programs. And I'll ensure our commercial efforts follow the same philosophy of effectiveness, efficiency and maintaining our patient focus at the center of everything we do. As a commercial lead, it will be my responsibility to ensure the attractive clinical profile of our products is matched with proper physician education as well as fair and timely payer access to ensure patients who need better treatment options can actually benefit from our therapies. Herriot? Thank you, Dave. I will now provide an update on our programs and upcoming clinical milestones. Beginning with AXS-five, our novel, oral, investigational NMDA receptor antagonist with multimodal activity. AXS-five is being evaluated in 2 Phase 3 depression studies. The GEMINI placebo controlled trial of AXS-five in major depressive disorder or MDD and STRIDE-one active controlled trial of AXS-five in treatment resistant depression or TRD. We completed patient enrollment in the GEMINI study and are on track to report top line results from this trial before year end. Patient screening in the STRIDE-one Phase 3 active control trial of AXS-five in TRD will conclude by the end of November. This approach allows for meaningful proportion of patients with TRD to be included in the long term safety database, helping to assure a robust NDA filing. Based on this timing, top line results from this trial are now expected in the Q1 of 2020 versus previous guidance of the Q4 of 2019. Importantly, the anticipated timing of our NDA filing for AXS-five remains unchanged. We are looking forward to the readouts for the GEMINI and STRIDE-one trials. Based on the results of the FDA Break Therapy Meeting for AXS-five held earlier this year, positive results from either GEMINI or STRIDE-one would be sufficient along with the previously completed ASCEND trial of AXS-five in MDD to support an NDA filing for AXS-five for the treatment of MDD. Pending the readouts of these studies, an NDA filing for AXS-five is targeted for the second half of twenty twenty. AXS-five is also being evaluated for the treatment of agitation associated with Alzheimer's disease in our ongoing ADVANCE Phase twothree trial. The ADVANCE trial is approximately 70% enrolled and top line data from this trial is anticipated in the first half of twenty twenty. Turning now to AXS-seven, our novel oral investigational medicine with distinct dual mechanisms of action for the acute treatment of migraine. Axsome has completed enrollment in the MOMENTUM Phase 3 trial of AXS-seven in the acute treatment of migraine in patients with a history of inadequate response to prior acute treatments. Momentum is being conducted pursuant to an FDA special protocol assessment and incorporates the potent active comparator rizatriptan. We remain on track to report top line results for momentum before year end. Based on FDA feedback, this trial, if positive, will be the only efficacy trial required to support an NDA filing for AXS-seven for the acute treatment of migraine, which is targeted for the second half of twenty twenty. Last month, we initiated the INTERCEPT trial, a Phase 3 placebo controlled trial in which patients are to administer AXS-seven at the earliest sign of migraine pain. INTERCEPT is designed to enhance the market readiness of AXS-seven by generating additional information on its potential real world use. As the vast majority of specialists believe it is very important for patients to administer their acute treatment at the earliest sign of migraine pain. Top line results from INTERCEPT are anticipated in the Q1 of 2020. Turning now to AXS-twelve, our novel oral potent and highly selective norepinephrine reuptake inhibitor for narcolepsy. We have completed enrollment in the Phase 2 CONCERT trial, which is a randomized multicenter, double blind, placebo controlled trial evaluating the effect of AXS-twelve in patients with narcolepsy. We remain on track to report top line results from this trial before year end. In summary, between now and the end of the year, we expect top line results from the Phase 3 GEMINI trial of AXS-five in MDD, the Phase 3 MOMENTUM trial of AXS-seven in the acute treatment of migraine and the Phase 2 CONCERT trial of AXS-twelve in the treatment of narcolepsy. We anticipate a continuation of significant milestones into next year with top line results from the Phase 3 STRIDE-one trial of AXS-five in TRD and the Phase 3 INTERCEPT trial of AXS-seven in migraine both expected in the Q1 of 2020. We also anticipate top line results from the Phase twothree trial of AXS-five in Alzheimer's disease agitation in the first half of twenty twenty and potentially 2 NDA filings for AXS-five in MDD and for AXS-seven in migraine in the second half of twenty twenty. Now I'd like to turn the call over to Nick for a financial update. Thank you, Herriot, and good morning, everyone. I will focus on key highlights in the quarter and provide some financial guidance. R and D expenses were $15,800,000 for the quarter ended September 30, 2019 versus $6,000,000 for the comparable period in 2018. The increase was primarily due to trials that were initiated in 2019 and fully enrolled in the year, which include the GEMINI, MOMENTUM and CONCERT trials, along with the initiation of the INTERCEPT trial and AXS-five and AXS-seven open label safety studies. R and D expenses are expected to decrease substantially in subsequent quarters as multiple trials are or are close to being fully enrolled. G and A expenses were $3,100,000 for the quarter ended September 30, 2019 $2,200,000 for the comparable period in 2018. The increase was primarily due to higher stock compensation expense and personnel costs. We ended the Q3 with $43,600,000 in cash compared with $53,800,000 at the end of the second quarter. We believe that our current cash position fully funds all ongoing clinical trials and will be sufficient to fund our anticipated operations based on our current operating plan into the Q2 of 2021. As previously disclosed, we do not anticipate any new equity financings prior to the readout from our Phase III efficacy trials. That concludes our Q3 2019 financial review. I will now turn the call back to Mark to lead the Q and A discussion. Thank you, Nick. And operator, may we have our first question, please? Yes, sir. And your first question comes from the line of Charles Duncan with Cantor Fitzgerald. Good morning, guys. Thanks for taking our questions and congrats, Herriot and team to all the progress this quarter and this year. Been an interesting year, could continue to be so. Had a quick question though on Gemini and AXS-five. I'm wondering if you can provide a sense of as you're looking at the blinded conduct of that trial, how does the patient sample look relative to your expectation in terms of characteristics of the patients? And then in terms of the dropout rate that you had assumed? Well, thank you, Charles, for the question. As a reminder, the one of the things that we tried to do with the GEMINI trial was we tried to design that study to replicate the ASCEND trial as much as possible. I believe that we've achieved that goal. And in terms of what we've been seeing with regards to the types of patients that we've enrolled thus far in GEMINI versus ASCEND, It's early. The study enrolled quite rapidly. But I'll turn it over to Cedric to see if he has a sense of what the patient demographics might look like between the two studies. Yes. Thank you, Ariel and hi, Charles. So as you know, we worked very strong. We're very keen to make sure that the design of the GEMINI trial was similar to the ASCEND study with some important distinctions. But we wanted to confirm that they had a diagnosis of MDD, that their symptomatology was moderate to severe. And we're pleased to say that the conduct and the trials that what we've seen so far in terms of because you mentioned discontinuation, for example, that it's been very similar to the ASCEND trial. So we're happy with the design and conduct. And I think that's about it. Okay. And then if I could ask just a follow-up on AXS-five regarding the ADVANCE trial in Alzheimer's agitation. There was, I think, an unexpected result out of arguably a mind share competitor with a deuterated form with a drug that contained a deuterated form of dextromethorphan. And I'm just kind of wondering what you think that says about either conducting studies in Alzheimer's agitation patients or even a drug containing dextromethorphan because that one didn't meet its endpoint and you would have anticipated that it did. Is there anything different about deuterating a dextromethorphan that could make an impact? So as you pointed out, the study which you're referring to did use deuterated dexamethorphan as part of their product candidate that was one of the components. And AXS-five, as you know, uses non deuterated dexamethorphan. That may be an important difference because the whole point of deuterating a compound is to change its pharmacology somehow, either the way that it metabolized or unintentionally, maybe the way that it interacts with CNS receptors. There is preclinical data that has been published, which does indicate that deuterated dexamethorphan works by different biological pathways than non deuterated dexamethorphan. So those basic pharmacological differences may be important. The other aspect of the study that was reported most recently with deuterated exmethylofan that is different from what we're doing is the length of the trial. So that study was a 12 week trial and our study is a 5 week trial. Interestingly enough, previous studies with dexamethorphan and a metabolic inhibitor, did report very positive results with non deuterated dexamethorphan and mixed results with deuterated dexamethorphan when those studies were conducted over a 5 or 6 week period. So there are methodological differences also, which should be considered in interpreting the reported results versus for deuterated eximethorphan versus what might be seen with AXS-five. We've always been pretty confident in the rationale for AXS-five and Alzheimer's disease agitation, and we're looking forward to the results of our study, which we expect to have in first half of next year. That's helpful added color, Herriot and Cedric. I had questions on AXS-seven, but I've already taken enough time. So I'll hop back in the queue. And your next question comes from the line of Gautam Suneja with Guggenheim. Hey, good morning, everyone. Thanks for taking my question. Just following up on the question that Charles asked earlier about the GEMINI enrollment. I mean, given that you enrolled the trials so rapidly, could you maybe talk about the steps that you might have taken to make sure that you enroll the right patient population? There is a notion that there are some of these professional patients. So maybe talk about the steps. And then in terms of the baseline MedDRA and HamD, could you maybe tell us what the cutoff was for enrollment? Should we anticipate the average Madra or Hamdi for Gemini to be similar to Ascend? And then I do have a follow-up. Well, thank you, Yan, for the question. With regards to your the first part of your question, which speaks to quality, we do agree that controlling quality and having a high quality trial, having high quality patients in the study is paramount. And we were really proud of the conduct of the ASCEND trial, where one of the things that we implemented was high quality control, including confirmation of patient diagnosis for the patients who are enrolled in the trial. Now, there are professional patients, as you mentioned, which are out there. That's the problem with all clinical trials and especially in the U. S. There are various measures which can be taken to minimize the enrollment of professional patients. For example, there are patient databases which help. But I think the other way to help to control not just for that, but to control for inappropriate patients in general is to have some kind of third party confirmation of the diagnosis of these patients. And we did implement such a procedure in the ASCEND trial and we're replicating it in the GEMINI trial. And because we also had experience with ASCEND, we were able to even further enhance those measures. So Gemini did enroll very quickly. We were aware that it might enroll quickly. And so we put in place a lot of measures to assure that quality was maintained along with the speed of enrollment. Now with regards to just the demographics of the patients in the GEMINI trial in terms of baseline moderate scores. I'll turn it over to Cedric. Yes. Thanks Herriot. And a few points I would add is with our experience through the positive SEND study and STRIDE, we have established relationships with clinical sites. So there's a lot of what you would call good infrastructure there based on our prior experience. And we wanted to make sure that the adjudication and judgment and confirmation of diagnosis and symptomatology was approached in the same way for the Geminis study as we had done previously. So in terms of a cutoff, well established cutoff on the MADRIS total score of 25 points or higher allows one to identify patients who are of moderate to severe severity. Again, that was the same as what we had done previously in Ascend. And 3rd party confirmation allows us to make sure that the patient demographic we're seeing, similar age group, gets in and that you avoid the potential to recruit professional patients, which of course we know can contribute to flow of readings and elevated placebo response. So there have been a number of measures, as Herriot mentioned, that we implemented to ensure that the quality of the patients coming into the trial is optimal and that the integrity of this trial, just like the prior ones, is maintained. Got it. And then just 2 more. Can you maybe comment on the NDA filing like to get a broad MDD label, what is needed? Do you have an agreement on the FDA and what would be the gating factors if you have one of these ongoing trials positive? And then just finally, if you can also comment on the STRIDE-one, like what was the main reason to push the timeline into Q1? Was it to enroll more patient or to build a safety database? But it seems like you hit the required number earlier in May. Thank you. Sure. With regards to the requirements for NMD filing, as you pointed out, the requirements are 2 positive trials. So should either Gemini or STRIDE be positive, those positive results in conjunction with the completed ASCEND trial would be sufficient to file an NDA. So that was the result of the breakthrough therapy meeting, which we had and which we previously reported on. In terms of the timeline for an NDA filing, we are targeting an NDA, assuming that we have success with one of these studies by the end of 2020. With regards to the question around the timing of stopping screening in the STRIDE-one trial, As a reminder, the reason why we continued screening beyond the target enrollment in the STRIDE-one trial was to capture patients who have TRD into the safety database. That is a requirement for the NDA filing. So the driving factor was to assure as robust as possible an NDA package without affecting the timeline to an NDA filing. We launched the open label safety extension trial to capture those TRD patients in July. And now we have a very good sense of the number of patients who have come out of STRIDE and who have gone into the open label safety extension. And given the increased interest in the STRIDE-one trial recently, the number of patients who are in the queue, we felt it was prudent to capture those patients to get to a target number, a target proportion of patients with TRD in the open label safety extension. Now the team, meaning the clinical team and the regulatory team gave us quite a bit of thought. And I'll turn it over to Cedric just to give you a little bit of color in terms of how we thought about the proportion of TOD patients who should be in the safety database. Yes. So to ensure that the NDA filing was as robust as possible, we wanted to capture a proportion, an appropriate proportion of TRD patients that approach that which you see in the real world general MDD population. So as Herriot said, we over enrolled the study where approximately 300 subjects randomized in STRIDE. And by screening and rolling until the end of November, this allows us to achieve the proportionate representation of TRD patients, which again reflects real world or approaches and the real world MDD population. Now importantly, this does not change our timeline for the NDA filing in the second half of twenty twenty. And in fact, only strengthens it, making it more robust. And your next question comes from the line of Joon Lee with SunTrust. Hi, thanks for taking my question. Regarding STRIDE 1 study that's now reporting in Q1 of 2020, given the continued recruitment into the study through the end of this month compared to the original plan, does that improve the powering of the study in any way? And also given STRATA is an important study, not just because of it's a TRD study, but also because it has a significant amount of the safety database now. If STRIDE-one reads out negative, does that compromise the legitimacy of the safety database in any way and impact the NDA filing for MDD? And lastly on this part, can you tell us what the proportion of the safety databases coming from Fend, GEMINI and STRIDE-1? Thank you. Thank you, June, for the question. With regards to what would happen if STR1VE were negative. As a reminder, should either Gemini or STR1VE be positive that would allow us to file an NDA for MDD. So we're in a pretty advantageous position there with regards to optionality. The difference of course would be that should STR1 be positive that that would be included the data would be included in the product label. However, just to be clear, the indication in either under either scenario would be for MDD. Now with regards to the proportion of patients coming out of STRIDE versus Gemini that who are in the open label safety extension trial. We have not yet disclosed that exact percentage That is in flux. But I think one thing that we can guide you to is the fact that as Cedric mentioned, we currently are at 300 subjects who are randomized in the STRIDE-one trial. And we had reached the target enrollment of about 2 50 subjects back in the second quarter. And the yes, and so that should give you a sense of how many patients potentially could have come out of STRIDE and entered into the open label 50 extension. Now to your very first question around powering, One of the results of over enrolling the study to capture additional STRIDE-one patients or TURD patients into the open label safety database is the fact that there are more patients in the study who will be in the efficacy analysis. So yes, so that would have the effect of increasing the power of the trial. And I have a couple on the migraine as well. Correct me if I'm wrong, but for AXS-five, my understanding is that you have an open label safety study ongoing with expected enrollment of up to 300. Could you tell me what the percentage of patients completing MOMENTUM are? Had that have rolled over into the open label study? I don't know if you have an exact number yet, but we are capturing a fair number of the patients who are exiting the MOMENTUM trial into the open label safety extension. So we have not done the calculations. So we're not going to give you an exact number. But I think we're capturing a significant percentage of those patients. Okay. And the very last question, help us understand what exactly is the difference between MOMENTUM and INTERCEPT? Specifically, it seems like you're encouraging patients to take the AXS-seven as soon as they have symptom, they notice the symptom of migraine. So what's a typical lag between onset of migraine symptoms before taking the drug in both studies, if that's the goal? Yes. So I'll lead off and I'll let Cedric provide some color. One overarching comment is that in typical acute migraine trials, patients are required to wait until their pain reaches moderate or severe intensity prior to dosing. And so that's how the MOMENTUM trial is being conducted. And in the INTERCEPT trial, that is not the case. So in the INTERCEPT trial, patients are required to or instructed to treat their migraine at the earliest sign of migraine pain. And so now interestingly enough, that is how a specialist and other clinicians who treat migraine patients instruct their patients to take acute treatments in the real world setting. So I'll turn it over to Cedric who can give you a little bit more color in terms of what we would expect to gain from INTERCEPT. Yes. Thanks, Herriot, and thanks for the question. I think the real distinction here is momentum being a registrational trial for the purposes of filing an NDA and it's positive we would only need one study to file for the pre treatment of migraine. But what we see in the real world, and that's the real key term here is real world, is that patients don't want to wait until their pain becomes moderate to severe and neither do physicians with nanny surveys speaking to the fact that clinicians believe that patients treat their migraine at the earliest sign of pain. So in order to generate additional real world data and to fully understand the potential clinical utility of AXS-seven in the treatment of migraine, we wanted to see exactly what it would look like in patients who treated their migraine at the area of sinus pain. We're excited to have that additional data generated through the INTERCEPT trial. Thank you. And your next question comes from the line of Marc Goodman with SVB Leerink. Yes, good morning. I was wondering if Dave could make some comments about joining the company and obviously coming from a company that has a migraine drug. I was curious your thoughts about this migraine drug and how it's going to be positioned? Yes. Well, good morning, Mark, and thank you for the question. I think, first of all, I couldn't be more excited to join Axsome. I think that when you look at kind of meaningful work that we all do, I'm proud to be surrounded by a team of professionals who kind of work day in and day out in the service of accelerating treatment options for people in need. And certainly my most recent experience within the CNS category has been in migraine. I have prior experience in other CNS areas, including depression. I think when I look at the potential for AXS-seven, I'm tremendously excited. And when you place it in the context of the marketplace, over the past year to 2 years, we've seen a greater focus on migraine that is certainly well deserved, not only with patients, but with clinicians. And we're also seeing an elevation of treatment expectations. And when we look at those treatment expectations, the information continues to point to what both patients and physicians are looking for in the acute treatment of migraine. And that's consistently improved efficacy. So when you look at the AXS-seven program, it is fully designed to deliver just on that improved efficacy with not only speed of onset, but with degree of onset and the ability to hold that response longer, so sustained pain freedom. And so when we look at that opportunity, I couldn't be more excited about having a program or a trial in momentum where we're looking specifically at patients who have had a suboptimal response to prior therapies and we're putting AXS-seven head to head against what is commonly viewed as one of the more effective acute agents in rizatriptan. And that's really what clinicians are looking for is improved efficacy and we have a head to head comparative trial that's going to give them the evidence to really make a solid clinical decision and hopefully serve acute migraine needs much more sufficiently than what's been done in the past. So I'm very excited about the opportunity for AXS-seven. Thanks. One other thing, Herriot, can you just tell us now given that the TRD and the MDD studies are not really going to come out at the same time. Are you planning on putting out a press release on MDD before the end of the year and then on TRD early next year? Is that kind of the plan to be separate press releases? So we're very confident in top line results from the GEMINI trial and MDD by year end. The team is working very hard towards that. We've completed enrollment in the trial. So we're very confident in that timeline and not just the GEMINI trial, but also the CONCERT trial with AXS-twelve and narcolepsy as well as the MOMENTUM Phase 3 trial in the acute treatment migraine. So all those studies, we're confident will come out by year end. And with regards to TRD, we're also confident that that study will read out in the Q1 based upon the fact that enrollment has been completed and we know exactly when we're stopping screening. Allowing the patients who are currently in screening in STRIDE to go through the trial, which is our goal. That would put data from STRIDE in the Q1. It would put last patient, last visit out in the middle of the first quarter, which would imply data sometimes thereafter, so in the second half of the first quarter. Thanks. And your next question comes from the line of Robert Hazlett with BTIG. Yes. Hi, guys. This is Jake on the line for Bert. Thanks for the question. If I could just follow-up, I guess, one more on STRIDE-one. I just wanted to confirm if patient accrual and rollover into the open label was in line with your expectations? Yes. Patient accrual and rollover into the open label is in line with our expectations. Okay. Thank you. And then maybe this is a little bit early, but just thinking NDAs in the second half of next year. Can you just comment on where you are with establishing a commercial manufacturing supply chain? Thank you. So with regards to manufacturing, we're in excellent shape. We are conducting our Phase III trials with commercial supplies. So in other words, commercial scale up has already occurred and there will be no need to transfer manufacturing once we file the NDA. Thanks. Congratulations on the progress. Thank you. And your next question comes from the line of Robert Burns with H. C. Wainwright. Hi guys, thanks for taking my questions. So my first one, just based I just want to get a little sense as to the feedback you've gotten from physicians as well as payers about their willingness to prescribe which are like AXS-five as frontline therapy? And what kinds of prior authorization or set edit programs might be applied ahead of AXS-five deployment? So we've gotten excellent feedback on the profile thus far of AXS-five in MDD. As you know, we did report out results from the ASCEND trial. Those results have been presented at various scientific conferences. So that has allowed feedback from the KOL community and the broader physician community. And it has been all very positive based upon the fact that the study did show rapid onset of action for AXS-five and also the fact that it was conducted versus an active comparator. So we're encouraged by that. Clinicians also really like the fact that AXS-five uses a new and differentiated mechanism of action, which is NMDA receptor antagonism, the fact that it is orally administered. So there is quite a bit of excitement, we think from the clinicians who've seen the data and who've looked at it. And now of course, what we need to do is we need to replicate those findings and we're looking to do that in the GEMINI trial and also in the STRIDE-one trial. With regards to payers and step edits, I think it's premature to have those discussions before we actually have full data on the product candidate. But I'll turn it over to Dave who gives just some top line thoughts. Yes. And thank you for the question. When we think about AXS-five and working with payers, I think kind of the foundational element in working with payers and determining access is really understanding the clinical profile. And as Herriot alluded, we still will be seeing much of those clinical data in the coming weeks. But that is why I'm really excited about the way that we are conducting our clinical trials to provide the type of information that we think payers will utilize to make appropriate coverage decisions. And one could understand the specific patient types and patient populations where it might make sense to use AXS-seven as perhaps a first line therapy or I'm sorry, AXS-five as perhaps a first line therapy, but also given the fact that 70% of the time the first therapy fails the patient in depression, then certainly there is a robust population out there in which AXS-five would be used after first line. So we would work with payers directly to demonstrate the clinical utility, the specific patient population and then of course we always pull in the economic realities of effective treatment into those discussions as well. And if I could just add the fact that for decades, the existing antidepressants have had the same mechanism of action. So with the potential approval of AXS-five, we could potentially be the 1st novel mechanistic and the first oral NMDA antagonist, which would represent a new mechanism of action. So I think there's also a compelling case to be made for why a new mechanistic oral agent would have a place in first line treatment for MDD. Awesome. Thank you on that. And then just one more. So given that enthusiasm you guys have for AXS-five as well as the physician community, what sorts of pre commercial preparations are you currently undertaking in anticipation of a Prudential launch, if any at this point? Yes. I mean, I think when we look at pre commercial efforts, a lot of those efforts are around making sure that we have the appropriate understanding of the marketplace, the appropriate understanding of the patient types that would most benefit, the appropriate understanding of the specific physicians who would be in the best position to serve those patients. And I think then we want to make sure that there's the proper education out there in terms of not only the unmet need, but the potential for, ASS-five to help fulfill that need. So those would be some of the key things that we would think about. Awesome. Thank you. And your next question comes from the line of Myles Winter with William Blair. Hi, guys. Thanks for taking the questions. Just on momentum, I'm curious to know whether patients enrolled in that trial, have any of them actually had an inadequate response to the triptan class in general or razotriptan specifically? And also the documented inadequate response, does that mean that you're sort of enriching for a patient population that might have nausea as the most bothersome symptom? I've just heard from a few docs that that tends to be the most bothersome symptom that it's most difficult to treat. So an inadequate response might actually be enriching in that population. Anything you could tell me there would be helpful. So, Miles, thank you for the question. As a reminder, all the patients who are enrolled, who are randomized into the MOMENTUM trial, must have a history of inadequate response to prior acute treatments. And we confirm that using an instrument called the migraine treatment optimization questionnaire. The prior acute treatment will vary amongst the patients. And so many of those patients will have been on triptans and their inadequate response will have been to triptans, but it could have also been to other acute migraine treatments. And in terms of the question around nausea and whether or not we're enriching for patients with that most positive symptom. I'll turn it over to Cedric for any thoughts. Thanks. Well, so we're not enriching specifically around nausea, but I agree with your observation that sometimes patients who experience nausea as the most positive symptom are in fact the ones who have inadequate response. We haven't looked into the data in that way. Obviously, we're still running the trial. But I think it's an astute observation that knowledge you may contribute to inadequate response. And we're looking forward to tackling that element of the patient need also. Okay. Thanks for that. And then maybe a follow on question for Dave. Just in the clinician interviews that you're no doubt doing, do they have a sort of difference of opinion when they're looking at potentially prescribing 5 in depression as to whether Gemini or STRIDE-one read out positive or negative? Have you looked into that scenario analysis? And also a history of the company being very, very capital efficient and probably, from what I've heard not going to use a massive neurology sales force. If you could just give us some top level on some unique marketing strategies that you might be thinking about that's not going to see the SG and A of the company skyrocket if you do have to go to market yourself. Cheers. Yes. Well, Myles, thank you very much for the question. I think, first of all, when we look at our commercial efforts and certainly the sizing of commercial efforts, there are a number of factors that we'll consider. So first of all, of course, as we've mentioned, it starts with kind of what's the clinical benefit of the therapies, as we've mentioned. And then also looking at what are those specific patient audiences, whether that's MDD or TRD that we would be prepared for. And then starting to look at the physicians that have the greatest potential reach that target audience. And we would also look at what the prescriber kind of adoption patterns are. And then we've also addressed kind of the reimbursement environment and that can have geographical implications as well. And then the other key component that I mentioned in my opening comments was really focused around efficiency. When you look at kind of a CNS portfolio of products as well as indications, one of the things we'll be very keen to understand is where we can drive efficiencies across that portfolio to make sure that every dollar that we spend from a commercial perspective is really well directed towards ensuring that the appropriate patients actually receive the benefit of these therapies. And then I think we also will look at not only personal promotion through highly qualified sales professionals, but what's the right mix of reaching some of those target prescribers through non personal promotion. So when I size up the opportunity, there's a number of factors that we'll look for, but the general tenants will be to really understand our customers to the greatest level that we can, what their potential to reach our target audience and then the most efficient and most effective ways in which we can reach them. Great. Thanks for the questions. And your next question comes from the line of Matt Kaplan with Ladenburg. Hi, guys. Good morning and congrats on the progress. Just wanted to dig in a little bit into the CONCERT study, AXS-twelve for narcolepsy. Given the unique design in terms of crossover design, can you give us a sense in terms of what type of signal you're looking for in terms of impact on cataplexy events in that study? Thanks, Matt, for the question. So as a reminder, the AXS-twelve study in narcolepsy, it is a placebo controlled trial. So it's a randomized double line placebo controlled trial using a crossover design. It is a 20 patient trial, but because it uses a crossover design, it effectively provides the power of a 40 patient study. Now, so in other words, roughly 20 patients per treatment arm. We're looking forward to see what the data show, but depending on if there is an effect and the magnitude of the effect, that design should put us in a good position with regard to measuring an effect on cataplexy. One thing that we can point you to is if you look at the prior trials in cataplexy, which were conducted with sodium oxybate in the package inserts, those studies had around 30 patients, 30 to 33 patients per treatment arm. So although our trial is on the small size, we're effectively around 20 patients per treatment arm. So I don't know if that gives you some sense, but depending on the effect, the magnitude of the effect, if there is an effect, it would put us in a good position to be able to demonstrate that statistically. Okay. That's very helpful. Thank you, Aaron. And your next question comes from the line of Charles Duncan with Cantor Fitzgerald. Hi, guys. Thanks for taking the follow-up. I had a follow-up on AXS-seven in the migraine space generally, probably for Dave and maybe Cedric. With regard to the evolving migraine space, obviously, lots of activity in monoclonal antibody land, which you have experience with, but also orals coming to market. I'm just kind of wondering where you see the potential differentiation for 7? Would it be that you'd like to see efficacy in terms of magnitude of response relative to placebo or speed of onset or durability? What do you think is the key thing that you'd like to show? So I'll make some overarching comments just about the design of the trial just as a reminder and then we'll turn it over to Dave for some questions. I'm sorry, Forrest, for some further thoughts. Just as a reminder, the way that the MOMENTUM trial is designed, we are enrolling patients who are difficult to treat. I I think that's really important. And the second point is that we do have the active comparator rizatriptan. And the way that the study is designed in order to meet the FDA's combination products rules is we have a key secondary endpoint of sustained pain freedom or the rizatriptan component. So in other words, in order to show superiority to rizatriptan, we have to show superiority of AXS-seven to rizatriptan based on sustained pain freedom. So not only does a patient have to be pain free at 2 hours, but that pain freedom has to be maintained through 24 hours. Now that gives you a sense of the potential benefits of AXS-seven. One is just generally increased efficacy. And secondly, it's a reduction in symptom recurrence, which we think it has good rationale based upon the long plasma half life of the meloxicam component. So that's how we think about it. So coming out of the study, if we do have success, what it will show will be the efficacy of AXS-seven in a difficult to treat patient population and potentially against an active comparator. So I'll turn it over to Dave to talk about what that might mean in the marketplace. Thank you, Herriot, and thank you for the question, Charles. I think when we look at our understanding of the marketplace, One thing that is very consistent is whether it is survey information from patients or from clinicians, there is a high degree of consistency in what the greatest unmet need in the marketplace is today. And while there may be a lot of variables that have the potential to deliver on unmet need, overwhelmingly all the roads lead back to improved efficacy. Clinicians are looking for a greater percentage of success, meaning pain freedom when they're prescribing for their patients. And when you look at the trial design, as mentioned by Herriot, the fact that we would have head to head data against what is largely considered one of the more effective therapies for acute treatment in a difficult to treat patient population. We think it will give physicians tremendous confidence to satisfy that unmet need of how can we get better efficacy versus what I'm using today. And I think that will be the pivotal data that will be most compelling, not only for patients and clinicians, but even when we start to engage payers, because many new therapies that launch don't have that head to head comparison data with current standard of care. And I think one thing that we don't talk as much about that many times gets overlooked is this is also being delivered in the route of administration that patients and clinicians overwhelmingly prefer. So not only can you get the potential for improved efficacy, but you can do it in an oral administration. And I think that is something that again, the combination of improved efficacy against current standard of care as well as an oral administration, we think makes this very compelling. And when we engage physicians with that type of a profile, it's not surprising to see their willingness to prescribe AXS-seven tremendously high. I like that 24 hour durability efficacy measure could be a clear differentiator. But I'm wondering if you think about triptans generally and a view that they should not be used in patients with known or suspected cardiovascular risk. Wondering if that has been a consideration in the development program and if you anticipate that, that would show up in the I'm I'm a little surprised that you don't have to do one for say 6 months or 9 months with intensive dosing or 12 months excuse me. Sure. So Charles, thanks for the additional question. So AXS-seven, it does combine Mosaic meloxicam, so our Mosaic technology, which just speeds the absorption of meloxicam along with rizatriptan. So because it does contain atriptan, we would expect that any that the profile of rizatriptan in terms of any types of warnings that are on the current rizatriptan label would also make it into the label for AXS-seven should the product be approved. With regards to the percentage of patients who are contraindicated against kriptans because of cardiovascular factors, risk factors. It is interesting, we did recently we did recently commission a survey of neurologists as well as other migraine treating physicians. And the survey was conducted by Medicorp. And the percentage of patients who currently are contraindicated for triptans was 12% from that survey according to clinicians. And we were comforted by that number since I think it roughly approximates what you might have seen in a survey conducted by your firm, which I believe is around 16%. So those values are pretty consistent. And with regards to the multi dose question, our efficacy trial, so in other words, the MOMENTO trial is a single dose study. However, we are required to conduct a long term safety study, which is ongoing. That study was launched in the beginning of July until patients are treated for up to 1 year. So they are being treated for multiple attacks over that 1 year period. And your final question comes from the line of Yatin Suneja with Guggenheim. Hey, guys. Thank you for allowing the follow-up. Just a real quick question that I've been getting from investor. Could you maybe comment on how many patients did you end up enrolling in Gemini? And of the patients that you are able to enroll, can you confirm how many have been validated by the independent assessor as to have a confirmed MDT diagnosis? Thank you. So the GEMINI study targeted approximately 300 patients. And so we reached the we completed enrollment. Now you never end up with the exact number of patients that you target as you know. What we can say is that the study did reach that number and surpass it. So we did over enroll somewhat the exact number. Of course, we will provide in a few weeks when we announce the results of the trial. And in terms of the percentage of patients who were evaluated by the independent assessor, so every patient that is randomized is evaluated through that process. And that's a very important component of the quality control of the trial. And so I hope that answers your question. Yes, wonderful. Thank you so much. Thank you. Thank you. And I'll now turn it back over to Ariel. Well, thank you. Thank you all for joining us on the call today. We it's just a public service announcement. We will be having an upcoming migraine key opinion leader conference call and webcast on November 25. And so we hope that you will join us for that. That event will feature presentations from doctors Richard Lipton as well as Doctor. Stuart Tepper, and it will focus on AXS-seven and the unmet needs in the acute treatment of migraine. Now the Axsome team is committed to developing differentiated medicines for difficult to treat CNS disorders. We look forward to reporting top line results from our clinical trials over the balance of the year. And this concludes today's conference call. Thank you for your participation. You may now disconnect.