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spk05: Good morning, and welcome to the Axiom Therapeutics conference call. Currently, all participants are in a listen-only mode. Later, there will be a question-and-answer session, and 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, Chief Operating Officer at Axiom Therapeutics. Please go ahead.
spk06: Thank you, Operator. Good morning, and thank you all for joining us on today's conference call. This morning, we issued two press releases. Our earnings press release, providing a corporate update and details of the company's financial results for the first quarter of 2022, and the release relating to the FBA's action on the AXS07 NDA. These cross the wire a short time ago and are available on our website at axon.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 the source of future clinical trials, regulatory plans, future research and development plans, commercial plans, and possible intended use of cash and investments. These forward-looking statements are based on current information, assumptions, and expectations that are subject to change and involve risks and uncertainty 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. We are cautioned not to place undue reliance on these forward-looking statements, which are only made as of today's date, and the company disclaims any obligation to update such statements. Joining me on the call today are Dr. Ariel Cabuto, Chief Executive Officer, Nick Peavy, Chief Financial Officer, Lori Engelbert, Executive Vice President of Commercial and Business Development, and Dr. Amanda Jones, Senior Vice President of Clinical Development. Ariel will first provide an overview of the company and then review recent developments and upcoming milestones. Following Ariel, Lori will provide a commercial update, and then Nick will review our financial results. We will then open the line for questions. Questions will be taken in the order they are received. And with that, I will turn the call over to Ariel.
spk04: Thank you, Mark. Good morning, everyone, and thank you all for joining Axone Therapeutics' first quarter 2022 financial results and business update conference call. The past few months have been incredibly busy and productive for Axone. We have made progress in the FDA reviews of both of our NDAs, announced the agreement to acquire Synosee, and continue to advance the rest of our rich late-stage pipeline, which includes AXS05 in Alzheimer's disease agitation, AXS12 in narcolepsy, and AXS14 in fibromyalgia. Axon is poised to transform into a commercial entity, potentially as early as this month, a direct result of our team's focused execution. I will provide an update on the status of our NDAs. the pending Synose acquisition, and the rest of our pipeline before turning it over to Laurie and Nick who will provide a commercial and financial update. With regards to AXS07, this morning we announced that we have received a complete response letter or CRL from the FDA for the AXS07 NDA for the acute treatment of migraine. The CRL did not identify or raise any concerns about the clinical efficacy or safety in the NDA, and the FDA did not request any new clinical trials to support the approval of AXS07. The principal reason given in the CRL relate to chemistry, manufacturing and controls, or CNC considerations. The CRL identified the need for additional CNC data pertaining to the drug product and manufacturing process. We believe that all the issues raised in the CRL are addressable. We are excited by the prospects for AXS07. This excitement is driven by the strong clinical data and product profile of AXS07. The approval of AXS07 would offer a much needed new multi-mechanistic treatment option for the millions of people living with migraine. It is our goal to work closely with the FDA to provide them with the information they need so that we can make this important new medicine available to patients as quickly as possible. We intend to provide potential timing for a resubmission following consultation with the FDA. With regards to XSO5, review of the FDA is progressing. Based on feedback from the FDA, we believe that the previously disclosed CMC deficiencies have been resolved. In addition, we recently received and agreed the post-marketing requirements and commitments proposed by the FDA for AXSOSIs. Based on this interaction, we anticipate potential FDA action on the NDA in the second quarter of 2022. With regards to our Alzheimer's disease agitation program, Enrollment in the Phase III Accord trial of AXS05 in the syndication continues to progress. As previously disclosed, we are evaluating the design of this study and will provide an update following consultation with the FDA. Moving on to the Synose acquisition. In March 2022, we entered into a definitive agreement to acquire Synose or Solvianfetol from Jazz Pharmaceuticals. Synose is a dual-acting dopamine and norepinephrine reuptake inhibitor indicated to improve wakefulness in adults with excessive daytime sleepiness due to narcolepsy or obstructive sleep apnea. The Hart-Scott-Rodino waiting period for the acquisition has now expired, and so we expect the transaction to close this month. Between the pending FDA action on our NDA for AXS05 in depression and the expected closing of our acquisition of Synose, Axone is poised to potentially make two important new medicines available to patients living with serious CNS disorders in the coming months. The rest of our late stage pipeline continues to advance. For AXS12, our product candidate being developed for the treatment of narcolepsy, enrollment in the symphony phase three trial is progressing, and top-line results are anticipated in the first half of 2023. For AXS-14, our product candidate for the treatment of fibromyalgia, manufacturing, and other activities related to the planned submission of an NDA are ongoing. And we expect to submit the NDA for this product candidate in 2023. I will now turn the call over to Lori, who will provide a commercial update.
spk15: Thank you, Ariel, and good morning. The commercial team remains focused on preparations for potential commercial launches and simultaneously have been working hard to ensure a smooth transition of Synosi into the Axum infrastructure. I am extremely proud of the efforts from the entire Axum team, and immediately upon deal close, we look forward to welcoming the Jazz employees to Axum. Axiom is on the verge of becoming a commercial entity, and we are excited about the opportunity to bring potentially life-changing therapies to patients. The addressable diseases of focus for our near-term products are highly prevalent and have substantial unmet need. Our products, if approved, will bring a differentiated clinical profile to their respective markets. As a reminder, Synose is the first and only FDA-approved dual-acting DNRI to treat excessive daytime sleepiness in adults with narcolepsy or OSA. EDS associated with narcolepsy or OSA is a serious condition that is associated with impaired neurocognitive function and can have effects on attention, memory, and executive functioning. Narcolepsy is an orphan condition that affects close to 200,000 people in the U.S., all of whom experience EDS. OSA, on the other hand, is a highly prevalent condition that affects an estimated 22 million U.S. adults. An estimated 75% of OSA patients experience EDS. Many of them continue to experience EDS despite the use of continuous positive airway pressure or CPAP. Regarding AXS05 and major depressive disorder, the mental health crisis impacting the U.S. continues with an estimated 21 million US adults experiencing MDD each year. And recent studies estimate that number has likely increased threefold due to the COVID-19 pandemic. MDD is a common and serious medical illness that negatively affects how people feel, the way they think, and how they act. MDD is also the number one cause of disability worldwide. Given the personal and economic burden associated with mental health conditions, There's an urgent need to bring support to those affected. If approved, AXS-05 would be an important new treatment option for the many Americans living with depression. We are prepared and ready to commercialize if approved. Shifting to AXS-07. Despite recent innovation in the acute migraine market, there continues to be close to 70% dissatisfaction rate with currently available therapies, demonstrating high unmet need for the 37 million Americans who experience migraines. Regardless of any delay on AXS 07 due to the CRL, we have been actively preparing for launch and will be ready to do so if approved. Promotional efforts on stenosis combined with our near term planned potential launch for AXS 05 in major depressive disorder allows for a highly complimentary Salesforce effort. 40% of the current prescriber base for weight promoting agents is made up of psychiatrists and neurologists, our primary targets for AXS 05 and AXS 07. As a reminder, all Salesforce offers are contingent upon approval. Lastly, our first in class digital centric commercialization or DCC platform remains fundamental to our commercialization strategy. Our DCC platform was designed to augment our promotional efforts to allow for highly effective, efficient, and more meaningful engagement with physicians and patients. The goal of DCC is to meet customers where, and how they want to be engaged with the right content at the right time. Our commercial launch strategy is innovative and purposeful with the intent to bring important new products to the market in a meaningful way. The differentiated clinical profiles of Sanosi, AXS05, and AXS07 have the potential to bring significant benefit to patients and the physicians who treat them. I look forward to discussing in greater detail the commercial plans for AXS05 upon potential approval and for Synosy after the close of the transaction. We remain excited about the opportunity to potentially bring these important new products to market in the near term. I will now turn it over to Nick, who will review our financials.
spk09: Thank you, Lori, and good morning, everyone. Today, I will discuss our first quarter results and provide some financial guidance. We ended the quarter with approximately $85 million in cash compared to roughly $86 million at the end of the year, a net decrease of approximately $1 million. During the first quarter, we accessed our ATM facility, receiving net proceeds of approximately $31 million. R&D expenses were $12.6 million for the three months ended March 31, 2022, and $15.6 million for the comparable period in 2021. The decrease was driven by expenses related to the NDA filing, which occurred in the prior comparable period. G&A expenses were $25.7 million for the three months ended March 31, 2022, and $11.2 million for the comparable period in 2021. The increase was primarily related to pre-commercial activities and personnel expense, along with an increase in non-cash stock compensation expense. Net loss was $39.6 million, or $1.03 per share, for the three months ended March 31, 2022, compared to a net loss of $29.3 million, or $0.78 per share, for the comparable period in 2021. The net loss for the current period included $7.6 million of non-cash stock compensation expense, compared to $3.7 million in the comparable period. Regarding the Sanosi acquisition, the acquisition is being funded through our existing $300 million facility with Hercules Capital, plus an additional equity investment from Hercules Capital. We believe that our current cash balance, along with the remaining committed capital from the $300 million term loan facility, is sufficient to fund anticipated operations into 2024 based on our current operating plan, which includes the potential launch of AXS05 and MVD and the acquisition and commercialization of Synosy. That concludes our first quarter 2022 financial review. I will now turn the call back to Mark to lead the Q&A discussion.
spk06: Thank you, Nick.
spk11: Operator, may we please have our first question?
spk05: Thank you. If you'd like to ask a question, please press star followed by 1 on your telephone keypad. If for any reason you would like to remove that question, please press star followed by 2. Again, to ask a question, it is star 1. As a reminder, if you are using a speakerphone, please remember to pick up your handset before asking your questions. We will pause here briefly, ask questions, and register. Our first question is from Charles Duncan of Kantor Fitzgerald. Charles, your line is open.
spk16: Hey, good morning, Ariel and Thanks for taking our question. I have a couple of questions primarily on 07 and then on 05. Regarding 07 and the CRL, I guess, you know, I know you haven't met with the agency, but can you provide us any additional color on not only this subject, but of this CRL in terms of CMC, but what gives you confidence in your ability to address it? And how... How related is it, if at all, to the CRL, or not the CRL, the CMC issues that you received with O5?
spk04: Hi, Charles. Thanks for the question. I'll make some overarching comments, and then I'll turn it over to Mark, who maybe can provide some more details. With regards to the relationship question between O5 and O7, There is no relationship. The issues are distinct. And then also with regards to 205, we did also announce that the CMC-related deficiencies have been addressed and resolved. Now, with regards to the 07 CRL, it's important to reiterate that The CRL did not identify or raise any concerns around the clinical efficacy or safety of the data in the NDA. So we feel very good about that and think that it's great to get affirmation from the FDA at the end of a review with regards to our clinical data. We love the product. We think it's an incredibly exciting profile, and it's good to get to the end of a review. Now, with regards to the CMC questions and considerations, I'll turn it over to Mark.
spk06: Hey, Charles. Good morning. So as we mentioned, the questions and the requests for additional information, they principally relate to drug product and the manufacturing process. So just a reminder that ASIS07 incorporates our MOSAIC technology. We have a novel technology that Axiom developed, and so that does increase the complexity of the manufacturing process, the MOSAIC technology. And so we understand the basis for many of the questions, and we do believe they're addressable. And to give you just a little bit more detail, The technology is a molecular inclusion complex buffering system, and many of the questions relate to that. And one other bit of information that may be helpful just to try and address the different elements of your question is our impression of the facility inspection that we had previously shared that we were informed was required, that that was completed, and that there were no findings. as a result of that inspection.
spk16: So it sounds like really a distinct set of issues relative to O5, but you feel like they're addressable and you'll provide us timing after you meet with the agency. Do you have a sense of when that could be?
spk06: So that's correct that that will be the approach we plan to take and how we share with folks. So we want to do that expediently. We do want to make sure we take our time to prepare for the consultations. And we will do that expediently. And as soon as we have a sense of granularity for timing, we'll let you all know. And then related to timing, we would expect this to be a Class 2 resubmission. I think as everyone is aware, that's a six-month review.
spk16: Got it. And then one quick two-part question on 05, and that is great to hear that you've received some communication from the agency on post-marketing requirements. I'm sure that you can provide a lot of detail on that, but I'm wondering if the post-marketing requirements for O5, should it be approved, does that include a REMS? And if so, can you provide any color? And then the second part is, given the kind of changing therapeutic landscape to incorporate perhaps more intermittent treatment uh for example with saran alone um you know out of out of biogen sage they're they're filing do you anticipate there to be the same kind of demand or or opportunity set that you had seen when you initiated the program with a xs05 thanks sure uh thanks for all for for those follow-up questions uh with regards to uh
spk04: the question around the REMS. A REMS was not part of the PMRs or PMCs that were agreed to or discussed with the FDA. And there's some overarching comments on your question around intermittent treatment before I turn over to Lori who might be able to provide some additional details there. But some overarching comments are that the way that major depressive disorder is treated has always been intermittent treatment. So major depressive episodes are treated, of course, and then many patients, once they get better and they've been better for a while, clinicians would take them off their medications. The important aspect of treatment is that not only should patients receive relief from their depressive symptoms, but that that should be maintained. So durability is really important. And, you know, we've shown significant durability with AXS05 over a long treatment period. So we've treated patients out to one year. So we feel as good as ever, if not better, about the prospects for AXS05 and MDT.
spk15: Yeah. Hi, Charles. Good morning. You know, there's estimated up to 80 million prevalent MDD patients in the U.S. right now. And as we all know, you know, we're in the middle of a mental health crisis. So any new therapies coming to market, you know, we are excited about for patients and their ability to get treatment. What we know now with the current available therapies, you know, two-thirds do not achieve remission. And given the clinical profile of 05, you know, with the fast onset of action, the really fast achievement of remission and the durability, as Ariel was mentioning, we do believe it is differentiated and compelling for physicians, and we don't see this as hindering our demand at all.
spk16: Very good. Thanks for taking my questions. Congrats on the progress.
spk05: Our next question is from June Lee of TruSecurity. June, your line is open.
spk03: Thanks for taking our questions and thanks for the updates. So on 05, have you started labeling discussions yet?
spk04: June, thanks for the question. What we've said is that as soon as we enter into labeling discussions, we will let the street know.
spk03: Great. And then, can you remind us the conditions under which you can draw additional funds from the Hercules Loaf facility? Does it require approval of AXS05?
spk09: Yeah, sure. So, upon approval of AXS05, there is $100 million that is tied to that approval. However, we do have an amendment that we had signed and becomes executed upon the Senosi transaction. And that will accelerate the later tranches to fund up to $45 million of the Senosi transaction. I think it's also important to note that Hercules has also committed $5 to $8 million in a direct equity investment upon the closest transaction.
spk03: Thank you. And the last question is, Quickly, the trial amendment that you're contemplating for the Alzheimer's agitation study for AXS05, is that in any way related to sort of the discussion you're having with the FDA with regards to the depression indication?
spk04: No, it's not related to that.
spk11: Great. Thanks for the questions.
spk05: Our next question is from Vikram Piyotohit of Morgan Stanley. Vikram, your line is open.
spk20: Great. Thank you for taking my questions. So two on the pipeline from our side. So first, staying on the topic of the Accord study, so you did mention previously that relapse events have been below your initial projection. So I just wanted to see if you could give us an update on how those have been trending since you last provided us an update. And then also, do you have any sense of timing at this point on when you might be able to speak with the USDA about amendments to the study design that you might have in mind?
spk04: Sure. I'll let Amanda take that question.
spk14: Sure. Thank you. Regarding the, you know, rate of relapse currently, so we have not disclosed any numbers and we will disclose it when we provide top line data for this study. And in regards to the timing of discussion with the NDA, you know, we haven't provided any granularity, but we do intend to do so as soon as possible.
spk20: Okay. And as a follow-up, for AS514 and fibromyalgia, I know you've guided to an NDA submission in 2023. What needs to happen between now and then for that NDA submission? And do you know specifically when in 2023 that might be expected? Is it more like a first half event or a second half event?
spk06: Hey, Victor. It's Mark. So we haven't given granularity on the timing yet for 2023. As we get closer, we'll narrow that guidance for you all. And right now, the rate-limiting step continues to be the manufacturing and stability. We do have to recapitulate and are the manufacturing from the prior process, and that work is ongoing.
spk20: Okay. Understood. Thanks.
spk05: Our next question is from Mark Goodman of SVB Leary. Mark, your line is open.
spk02: Yes, good morning. Ariel, I think I heard you say that you have affirmation with respect to 07 that there is nothing else related to efficacy or safety. Can you make that same comment when it comes to 05?
spk04: It's impossible for us to make any comment like that with regards to 05 prior to an NDA action. So we're able to make comments with regards to 07 because now the review is officially completed and the FDA has formally provided us with the determination that the NDA is completed and what the outstanding issues are. So with regards to 05, while we are very positive on the efficacy profile and on our package. And while we are encouraged by the latest developments in the review process with the PMRs and the PMCs, as you can understand, it's not over until we get the FDA action, and we're very much looking forward to the FDA action hopefully soon.
spk02: Yeah. And just on 05, there seems to be just a concern out there that there could be a problem with how this thing gets labeled. I assume it's because of the dextromethorphan component. You mentioned specifically that there will be no REMs, so that's great news. Are there any other issues that seem to be out there with the FDA regarding dextromethorphan or You don't think that's going to end up being a labeling issue at all?
spk04: Well, all we can speak to is our product. And just as a reminder, the technology with AXS05 is we're using metabolic inhibition to inhibit the metabolism of dexamethophan. So therefore, the pharmacology is going to be different. which is why the FDA did require us to conduct a very large open label safety extension study and also to have exposure in thousands of patients. So we've done that, which is fantastic. We're confident in the data. We've released those data, and we're looking forward to the conclusion of the review and the action.
spk02: And then lastly, just on a big picture manufacturing, obviously it seems to be a discussion here on just about every product. Can you just remind us, are you using the same manufacturing companies with respect to all of these products, 07, 05, 14? Are we going to have the same kind of issues or what? Thanks.
spk04: There is some natural overlap, as you can imagine, amongst vendors. However, we do not think that the issues related to one MDA versus the other are related at all in any way. And then the other thing that I would mention, I'm sorry, the other thing that I would mention too is while it is disappointing obviously to get to the end of a review and have a CRL, There does seem to be, just more globally, if you look at the industry, an increase in the percentage of NDAs that receive CRLs, especially for manufacturing. That may be an indication of the climate at the FDA. But, for example, the rate of CRLs has been roughly 50% at least. in the first half of so far this year compared to around 15.5% historically, and most of those are related to CMC. So we fully understand the reasons why the agency would want to make sure that any new technology, any new manufacturing process is fully vetted.
spk02: Well, you're working on manufacturing right now for 14, so it just kind of lends the question of, you know, are you learning some things from, you know, the issues before? Is this the same manufacturing people who, you know, will learn from what the FDA needs with these other products? That's really the question.
spk06: Hey, Mark. So each program, we have selected CMOs that we think are best suited to commercialize the product candidates. And so if it's 14th, That's an entirely different, that has its own facility, its own company, the API, and drug product. With AX07, there are multiple facilities involved there. As we mentioned, one of them had a required inspection, and our understanding is there were no findings, so this question about, oh, is there an underlying issue with the CMO, we're not aware that that's the case. There is some overlap with the programs, but generally each is distinct.
spk04: Yeah, and another way of answering your question, Mark, is yes, there are learnings from every interaction with the FDA, from every NDA. And by the time that we file the NDA for fibromyalgia, you know, we would have gone through, you know, at least two, you know, maybe three NDA filings. And we will take every lesson that is possible. We'll mine those experiences to make sure that we increase our probabilities of success in the future. Thank you.
spk05: Our next question is from Vamil Devan of Mizuho Securities. Femil, your line is open.
spk18: Great, thanks for taking my questions and for all the info today. So maybe just a couple separate questions. So one on O5, I think we've still got a lot of questions from investors on sort of the payer dynamics here since this is sort of two older products. Obviously, we're still waiting for full approval here, but I'm wondering if you can give any sort of updated thoughts on kind of how you think payers will respond to this product and sort of what sort of hurdles my patients have to go through before they can get on to the product. And then for Sanosi, just had a question there on, I know you're probably so unlimited in what you can say before the deal officially closes, but your expectations for a billion-dollar product here are quite a bit above what the industry has generally thought of for this product. I assume it's because of the sort of newer indications that you're looking to move this product into. I'm just wondering if there's any more you could share at this point in terms of how you're hoping to expand this product out into other indications beyond what it's already approved for. Thank you.
spk04: Thanks for the question. I'll take the Sunosi question before turning it over to Lori to take the payer dynamics question on 105. Yeah, we're really excited about the Sunosi acquisition. We did put out an AK this morning announcing the HSR waiting period has now expired. So we do expect the transaction to close very shortly and we do anticipate having some kind of investor forum to discuss what the new indications are and the timing of that. The timing of making sure that we take the steps that we need to take to get to that $1 billion plus market potential, which we outlined when we first announced the signing of the acquisition. So we're really excited about Synelzy, and I'll turn it over to Lori to talk about the payer dynamics and to add anything more that you may want to add about Synelzy.
spk15: Sure. And hi, thanks for the question. So, you know, we started permitted payer discussions back on 2005 about a year ago. and nothing's changed. Payers continue to recognize the unmet need in MDD, and they continually express their understanding of the fact that AXS05 will bring a novel mechanism of action to market. They recognize that there's a need for fast and rapid onset of action, but also durability for those patients, and we look forward to telling you more once the potential approval comes and we engage more with theirs. In terms of the NOSI, we are excited about the current indication as well. We do believe that there's incredible untapped potential in the current indication for EDS, especially with narcolepsy or OSA. We're also really excited about how the JAS team that will come over to Axum has been been working during this transition period. Last week, in fact, you know, NBX, NBRX, and so new to brand prescriptions were the second highest of the year. And that came during, you know, a time of transition. So we are really excited about the caliber of JADS employees that will come over to Axiom and look forward to welcoming them upon the deal.
spk18: Okay, thank you.
spk05: Before we turn to our next question, I would like to remind everyone to limit their questions to two to three questions due to the high number of people in the question queue. Our next question is from Joseph Thorne of Cohen and Company. Joseph, your line is open.
spk19: Hi there. Good morning, and thank you for taking our questions. Maybe just on the AXS05 review, it's been a couple weeks now almost, I think, since since you announced that you agreed to the post-marketing commitments. Again, in the interim, do you continue to interact with the FDA? What's sort of the cadence of interactions around this? And I guess during that discussion, were you able to kind of find out maybe what the initial deficiencies noted in the July letter last year happened to be? Thank you.
spk04: Thanks for the question. As you can imagine, during... During this phase of the review, there are multiple interactions, so those continue. And with regards to the initial deficiencies, all we are aware of are what the deficiencies are that had been communicated to us, and those deficiencies were CMC, and as we've stated, We have addressed those deficiencies and they are now resolved. We have not been made aware of any other deficiencies.
spk19: Great. Thank you. Maybe just one follow-up. How are you thinking about Europe? And obviously, you'll get to see here, hopefully, in the third quarter. Is that something that you want to launch yourself? And when you think about AXS05 and AXS07, how far do you want to take those in discussions with Europe before making a decision on marketing? How are you thinking about that overall?
spk04: The way that Synosy factors into our European strategy is now it gives us an additional product in Europe, a product which is approved and marketed currently in Europe and which has also a rollout in multiple new European markets on the roster. So as it relates to our overall corporate strategy prior to the Synosy acquisition announcement, which was to out-license all product candidates outside of the U.S. This only puts us in a much stronger position, and as you can imagine, that might lead to greater interest from potential partners.
spk19: Thank you very much.
spk05: Our next question is from Ram Selvaraju from HC Wainwright. Ram, your line is open.
spk10: Thanks very much for taking my questions. Firstly, I just wanted clarification regarding the timeline for potential approval of AXS07. Since you mentioned that this is likely to be considered a Class II resubmission, is it appropriate for us to assume at this juncture that the earliest AXS07 could be approved in the U.S. would be in 2023? So, Ron, thanks for the question.
spk04: What we're looking to do is to meet with the FDA as expeditiously as possible. That's a type A meeting. We want to make sure that we get our ducks in a row prior to requesting that meeting and getting a date. Once we have that meeting and we get feedback from the agency, in other words, we confirm exactly what it is that should go into the resubmission so that we can have success, then we'll be in a position to provide you with updated guidance on timing Apart from what we've already said, which is that we do expect that once we resubmit, that the resubmission would likely be treated as a class to resubmission, leading to a six-month review.
spk10: Great. And then just two very quick additional ones from me. Can you comment on how you anticipate deploying the Synosy Salesforce that is coming over in the Jazz Acquisition Transactions? And if you anticipate a meaningful role for those sales representatives in the ultimate promotion of drugs like AXS05 and AXS07. And then also if you could comment on any plans that you may have with respect to deployment of either Synozy or AXS12 in the area specifically of idiopathic hypersomnia. Thank you.
spk04: So taking those backwards with regards to the additional indications that you mentioned, we're always thinking about additional indications. With regards to the specificity, we don't have any specifics to share with you right now. And I'll turn it to Lori to comment on the Salesforce question.
spk15: Hey, Rob. Thanks for the question. So I think it's very important for Salesforce, especially during launch periods, and in this case, you know, for Sanosi, potentially viewing this as somewhat of a relaunch coming over to us, you know, they need to stay focused on their priority targets. And so they will be deployed to high prescribing, high potential, high value prescribers in the markets, you know, respective markets. The exit for five Salesforce will primarily focus on those targets. related to AXS05 where we believe we will, you know, have the highest potential and the same for the Synose. However, we do know that there is a very high overlap between prescribers and, you know, as appropriate, we will leverage those synergies.
spk11: Thank you.
spk05: Our next question is from Jason Gerbery from Bank of America. Jason, your line is open.
spk07: Hey, guys. Thanks for taking my question. One clarification, just in terms of REMS, is that something that you learn about via label discussion or is it more something that you learn about with the post-market study requirements? And then there's been some recent narrow cycle launches that have exceeded investor expectations. So I'm just curious if you think there's read across. Is there any, you know, structural challenges at all contracting cycles. Thanks.
spk04: Sure. Yeah, just with regards to the question on the REMS, this is one of the first NDAs. Actually, these are our first two NDAs that we are going through. A REMS is not anything that we're thinking would be needed with regards to these product candidates. You never know, though, and until the review is over, we can't really assure you of the FDA's findings or decisions or requirements. What we can communicate to you are the PMRs and the PMCs, which we have agreed to and which have been communicated to us, and they have not included other REMs. Lori?
spk15: Jason, sorry, your second question kind of faded in and out. Would you mind repeating that question?
spk07: Yes. So curious if you think there's read across the AXS05 from what you're seeing. It seems like maybe payer coverage is coming online a little faster than expected. I mean, you guys will have effectively a mid-year launch. I don't know if that will be a 2023 challenge in terms of where you're at in the contracting cycle or not an issue?
spk15: Great question. Thank you. All we have are the permitted player discussions that we've had thus far and that we are highly encouraged by how the players are reacting to So, you know, once we get approval and we know the timing of that approval, we'll be happy to discuss more around what we expect from a player coverage standpoint then.
spk04: Yeah, and if I may add to that, Lori, I think just part of Jason's question related to a broader environment in neuropsych as it relates to recent launches recent neurocyte launches which have exceeded expectations, and is there something broader going on? It's hard to know if the performance of individual product launches, even though they coincide in time, reflect anything that's underlying. There is one underlying trend which is worth repeating, which is that we are in the middle of a mental health crisis. So there has been an increase, a significant increase in neuropsych disorders. We think, or scientists think that it's related to the COVID pandemic. So that is one backdrop that has been occurring. We know that that's the case, for example, in depression, certainly, but not just in depression, but even across, for example, migraine, the incidence of migraine has gone up. in patients who have experienced COVID-19. So there is that aspect to it, and I think what it speaks to more broadly is the high on that medical need in neuropsychiatry indications in general. You know, that's why, you know, Axome is a CNS-focused company, and that's why we're really excited about what we're doing. Got it.
spk07: Thank you, Esther.
spk05: Our next question is from Yatan Suneja from Guggenheim. Yatan, your line is open.
spk22: Thank you. A few clarification questions for me. So first is on AXS05. What are your expectations for labeling? Do you expect a box warning similar to what we see with valbuterine or other antidepressant?
spk04: So we, since bupropion is a component of AXS05, we would expect that aspects of the bupropion label would be reflected in the 05 label.
spk22: Okay. And then when you say that this, this is again related to 05, so when you say that the CMC issues have been resolved, Did you get an acknowledgement from the FDA that they are satisfied with your response or it has been resolved just that you have submitted the response? Just trying to get a little bit clarity here. What does the resolution mean here?
spk04: It's pretty clear to us that it's been resolved based on the communications and also the PMRs and the PMCs.
spk22: Okay. And then finally, how... quickly you might be able to launch once approved for 05. Thank you.
spk15: Yeah, we expect to launch within a quarter of approval.
spk22: Any comment on the pricing? How should we think about pricing? What work you've done? Any sort of recent comp for us to look at in terms of the price?
spk15: Yeah, we haven't communicated price yet, and we will do that upon approval when we announce price. We expect to price this product to recognize the clinical differentiation of the product, but we also have an eye towards providing patients with the appropriate access.
spk03: Thanks.
spk05: Our next question is from Chris Howerton of Jeffrey. Chris, your line is open.
spk13: Great. Really appreciate you taking all the questions this morning and all the extra info. So I think for me, I was just curious if you could provide any comments or color on how the 05 approval and launch plays into your current stated cash runway. And as a sequelae to that, if there was a delay or non-approval for O5, how might that affect your cash runway guidance? Thank you.
spk09: Yeah, sure. Thanks, Chris, for the question. So, again, upon O5 approval, there is $100 million tied to that approval with our Hercules facility. So, we feel that we are in a very good position to launch the product, and we are planning that for this quarter. We do have sufficient cash for over a 12-month period, and as I stated on the opening remarks, we did tap our ATM facility in Q1. for upwards of $31 million to bridge the delay in the approval of O5.
spk13: Okay. And maybe just as a quick clarification, if there was a further delay to O5, how might that affect your current kind of cash runway guidance?
spk09: If there's a further delay, you know, we'll reassess it at that time. But as I said earlier, we do have north of 12 months of cash on hand to fund our current operating plan.
spk13: Okay. All right. Thanks so much. Appreciate it.
spk05: Our next question is from Matt Kaplan of Landenburg-Solomon. Matt, your line is open.
spk17: Thank you. Good morning. Just wanted to have a little more detail perhaps on the AXS07 CRL. Beyond CMC questions, was there anything else detailed in the CRL that needs to be addressed?
spk06: Matt, so principally with all CMC, there was one item related to non-clinical, which was just a request for additional information, which we believe we can provide. So for us, the real focus is, the substantive focus is CMC.
spk17: Okay, very good. Thank you. And then I guess a question for Laurie. Can you give us some more metrics in terms of how you're thinking about the sales organization as you go into launch several products here in terms of some of the metrics around the size of the Genosi and dedicated force and 05 and 07 dedicated sales forces and how they'll kind of interact. Yeah.
spk15: Yeah, sure. So a couple of things to keep in mind as you think through how we plan to structure. We haven't revealed the size of the sales forces yet, but what I can tell you is that we plan to target, for AXS05, we plan to target at least 85% of high-value prescribers, which is more than 25,000 HCPs. We will not only have a sales force in place, but we will also intend to leverage our DCC platform. to help ensure that we have optimal reach to those high-value prescribers. For AXS 07, it will be a very similar approach in terms of how we structure the Salesforce, highly targeted, highly strategic, highly focused. We plan to have coverage of 50 to 60% of the high-value prescribers with 07. And then on Synosy, you know, virtually all the offers that we extended to the JAWS employees were accepted, and that Salesforce size, you know, we look forward to talking to you more about on the deal close. But it will be in exactly the same kind of structure and decision-making, highly focused on those high-value prescribers. To make sure that we hit our reach, we will augment with DCC.
spk11: Okay, great. Thanks for that in detail.
spk05: Our next question is from Bert Hasla of BTIG. Bert, your line is open.
spk21: Yes, thank you for taking the question. A quick follow-up to Matt. And is the additional ask for information regarding the CRL-407, is that related to Mosaic technology, or can you be any more specific with regard to the additional ask? Thank you. Then I've got one or two others.
spk06: Hey, Bert. I think we characterize it. I mean, much of it does relate to Mosaic and the process around that and drug product.
spk21: Okay. I'm just shifting to Accord for just a second. What are the goals of the interaction with the agent? What can you do with the study? Is it an issue where you might change the design of the study, might change powering? What are the goals of the discussions with FDA with regard to evaluating the study design?
spk04: So, Bert, The reason why it's prudent to have as much feedback as possible is this is a registration trial, and so we want to make sure that we take the right steps and avail ourselves of the fact that this is a breakthrough therapy-designated product to get that feedback.
spk21: Okay, thank you. Just one other for me. Smoking cessation, you talk about a pivotal in Phase 2-3 later this year. Do you think you can get away with one, or is that something you're going to do sequentially with regard to two pivotals for smoking cessation for OFOD? Thanks.
spk04: We expect that we would need two pivotal studies, and currently the plan would be to do those sequentially.
spk21: Okay, thank you.
spk11: Thank you for taking the question.
spk05: The next question is from Miles Mentor of William Blair. Miles, your line is open.
spk08: Hey, thanks for taking the questions. Just on the 05 timing guidance that you put out when the PMRs and the PMCs were agreed upon, you said this quarter. I'm gathering that was based on precedence of some sort, but was that directly communicated to you by the agency, that timing, or was that from your regulatory consultants? Was that from work that you've done? Obviously, the streets used to seeing labeling discussions triggering that one-month clock, but just wondering how you got that clarity from the PMR, PMC stage. Thanks.
spk04: So, Miles, thank you for that question. Just to be clear, There is no need for due for date. So the FDA is not beholden to any particular date. What we try to do is to provide the street with actionable information, so any change in terms of our internal estimates as quickly as possible. So what drove our statement are the PMRs and the PMCs. So with regards to those discussions, sometimes there are timing elements tied to those. And so that has allowed us to focus our estimate. But again, this is our estimate, and it's not tied to any formal PDUFA date.
spk08: Okay, thanks. And then just on the PMRs and PMCs, obviously not disclosing the nature of them, but if we were to look at the guidelines the fda guidance documents for antidepressant drug development are they 100 encapsulated in the language in there so like maintenance uh dosing studies that might be required post marketing or safety in certain populations or are there certain pmrs and pmcs within those that are you know would be unique to the product that might not be talked about in those guidance documents thank you
spk04: So, as you can imagine, the PMRs and the PMCs would necessarily incorporate both items that are normally required for an indication, which might be included in guidance, as well as items that are specific to the individual product. What we can say is that the PMRs and the PMCs that were discussed and that have been agreed to are consistent with our expectations, and there was nothing surprising. We're happy with them. We do not expect them to, in any way, impede commercialization of XSO5 for NDD.
spk11: Beautiful. Thanks for the questions. Two final questions.
spk05: Our next questioner is David Huang from SMBC. David, your line is open.
spk12: Yeah, thanks for taking the questions. Just had one on commercialization and the Salesforce. In terms of your digital component there, what's your level of confidence that that's going to be able to supplement the Salesforce at the current size that you plan to bring on board? And is this something that, you know, you would have a high-level confidence in, or would you consider potentially expanding the, you know, the number of reps down the line?
spk15: Hey, David, thanks for the question. So, you know, our DCP platform, the way that we designed it was really to ensure that engagement with HCPs and patients are optimized, meaning we have the ability, you know, to have efficiency promotional efforts, but also effective promotional efforts. So what I can tell you is that we're not gonna sacrifice to not have those effective promotional efforts. So we believe, based on not only research, physician preference data, historical data of how physicians are engaging, how physicians continue to engage, how patients are showing up at physician's offices or not, meaning the level of virtual engagement in our target therapeutic areas still remains extremely high. So we feel very confident in the augmentation that DCC will provide our field force.
spk11: Okay. Thanks a lot. Our final question is from Esther Hong of Barenburg.
spk05: Esther, your line is open.
spk01: Hi, good morning. So on AXS07 and the CMC issues, I was wondering, number one, did the FDA find this issue? And then number two, did this occur after the facility inspection? Thanks.
spk06: Hey, Esther. Good morning. I don't know that it's a finding from the inspection. As we mentioned, there were no findings that we're aware of. Our sense is this is the result of their review during the course of the review cycle. And so that's our impression. But they didn't give us feedback when they identified these needs for additional information.
spk01: Okay, got it. Understood. Thanks so much.
spk18: Thank you.
spk05: That ends our question and answer session. So I would now like to pass the conference back to the management team for any closing remarks.
spk04: Well, thank you again for joining us on the call today. We are committed to bringing potentially life-changing medicines to people living with serious CNS conditions. We look forward to updating you over the coming months on our continued pipeline and commercial progress. Have a great day.
spk05: That concludes the conference call. Thank you for your participation. You may now disconnect your lines.
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