Hello, and welcome to the Aldeyra Therapeutics Conference Call to discuss regulatory update on reproxalap in dry eye disease. My name is Alex, and I'll be coordinating the call today. If you'd like to ask a question at the end of the presentation, you can press star followed by one on your telephone keypad. If you'd like to remove your question, you may press star followed by two. I'll now hand it over to your host, David Burke, Head of Investor Relations. Please go ahead. Thank you, and good morning, everyone. With me today is Dr. Todd C. Brady, President and Chief Executive Officer of Aldeyra. Yesterday, on November twenty-seventh, we issued a press release announcing receipt of a complete response letter for reproxalap for the treatment of dry eye disease, as well as Aldeyra's expectations regarding the timing and cost of an additional clinical trial and potential NDA resubmission. The copy of the press release is available on the Investor and Media section of our website, www.aldeyra.com. The press release contains important information and should be read and considered in conjunction with the slides presented and the prepared remarks made on today's call. Turning to slide two, this presentation and various remarks which may be made during this presentation contain forward-looking statements regarding Aldeyra, its investigational drug candidate, reproxalap, and its plans, expectations, and opportunities, including potential clinical trials and regulatory activities. Forward-looking statements involve known and unknown risks, uncertainties, and other factors that may cause Aldeyra's actual results, performance, or achievements to be materially different from any future results, performance, or achievements expressed or implied by the forward-looking statements. These statements are based upon the information available to Aldeyra today and reflect Aldeyra's current views with respect to future events that are based on assumptions and subject to risks and uncertainties, including the development, clinical and regulatory plans or expectations for Aldeyra's investigational drugs, including reproxalap. There are risks that result from earlier clinical trials or portions of clinical trials may not accurately predict the results of future trials or the remainder of a clinical trial. Aldeyra assumes no obligation to update these statements as circumstances change. Future events and actual results could differ materially from those projected in the company's forward-looking statements, including the results of operations and financial position. Additional information concerning factors that could cause results to differ materially from our forward-looking statements are described in greater detail in the press release issued this morning and in our filings with the Securities and Exchange Commission. I would now like to turn your attention to slide three and introduce Dr. Todd Brady. Thank you, David. Yesterday on November 27th, and consistent with the 8-K we filed on October 16th of this year, we received a Complete Response Letter notification from the FDA that the reproxalap New Drug Application for the treatment of dry eye disease was not approved due to the need for an additional clinical trial to demonstrate the activity of reproxalap in improving the symptoms of dry eye disease. In particular, the letter stated that the NDA did not demonstrate efficacy in treating ocular symptoms associated with dry eyes, and that at least one additional adequate, well-controlled study to demonstrate a positive effect on the treatment of ocular symptoms of dry eyes should be conducted. Per FDA Draft Dry Eye Disease Guidance, efficacy may be demonstrated with two clinical trials, demonstrating activity in improving symptoms, and two clinical trials demonstrating activity in improving signs. Among other clinical trials, Aldeyra previously conducted two trials for ocular redness, a dry eye disease sign, as well as a dry eye disease symptom trial. No Chemistry, Manufacturing, and Controls or safety issues were identified in the Complete Response Letter. As is summarized on slide four, based on FDA feedback subsequent to the late cycle review meeting, we believe that a single dry eye chamber crossover clinical trial, or the proposed trial, substantially similar to the crossover chamber trial announced in July of last year, would be sufficient and successful to allow for potential resubmission of the NDA as soon as the first half of 2024. On November 16, we submitted a Special Protocol Assessment, or SPA, feedback from which we expect next month based on the 45-day SPA review guidelines. The proposed trial, the primary endpoints of which are symptoms, is expected to cost less than $2 million, with top-line results expected in the first half of next year. If successful, the proposed trial could potentially enable NDA resubmission in the first half of next year. NDA review is expected to be six months. If the SPA and proposed clinical trial results are successful and the resubmitted NDA is approved, we expect that reproxalap and the reproxalap label could represent the first label with acute and chronic symptomatic benefit, as well as acute improvement in ocular redness, which is potentially the only dry eye disease sign of importance to patients. Illustrated on slide five is the proposed trial design, which in all material respects, is identical to the previously completed dry eye chamber crossover clinical trial announced last year. The crossover design consists of two days of one treatment, followed by a 7-14-day washout period of no treatment, followed by two days of the other treatment for a total per patient duration of approximately three weeks. In the proposed trial, patients are equally randomized to receive either reproxalap first or vehicle first. Approximately 70 patients are expected to be randomized in total, half to receive reproxalap followed by vehicle, and half to receive vehicle followed by reproxalap. As was the case in all previously disclosed dry eye chamber clinical trials for reproxalap, each visit is expected to consist of two days, four doses of test article on day one, followed by a 90-minute dry eye chamber on day two. For day two, ocular symptoms are expected to be measured approximately every 10 minutes in the dry eye chamber, and test article is to be administered just before the chamber and 45 minutes after chamber entry to assess prophylactic and treatment activity, respectively. The dry eye chamber, which is described in draft FDA guidance on dry eye disease, is an acute exposure to temperature and flow-controlled, low or no humidity air during forced visual tasking. In contrast to the previously completed dry eye chamber trial, the primary endpoints of the proposed trial are patient-reported dry eye symptoms, in particular, Eye Dryness Score and Ocular Discomfort Score, the two most important symptoms reported by dry eye disease patients. The Hochberg Procedure is expected to be used to control for multiplicity across the two symptom endpoints, and across both endpoints, the trial is expected to be more than 90% powered. Other symptoms, burning, grittiness, and stinging, will be assessed as secondary endpoints. The Dry Eye symptom results, which were secondary endpoints in the previously announced crossover dry eye chamber trial, are presented on slide 6. The secondary symptom endpoints were achieved for all dry eye disease symptoms assessed within and before and after the dry eye chamber. Both prophylactic and treatment effects were demonstrated for all symptoms tested in the dry eye chamber, and the overall effect within the chamber was highly statistically significant in favor of reproxalap over vehicle, with P values ranging from 0.0068 to less than 0.0001. For every symptom measured in the dry eye chamber, reproxalap was numerically lower than vehicle at each time point, including the first time point assessed, 10 minutes after chamber entry. The results of the previously completed crossover trial suggest the symptomatic activity of reproxalap in the trial was rapid, statistically reducing a wide range of symptoms within 90 minutes in the dry eye chamber. Slide seven summarizes the potential path to NDA resubmission. Earlier this month, we reported $143 million as of September 30, 2023, in cash, cash equivalents, and marketable securities, which we believe positions us favorably against an expected clinical trial cost of less than $2 million. Previous run rate guidance, which had assumed an approval and launch of reproxalap this year, was extended into late 2025, including clinical trial costs associated with the potential NDA resubmission. The initial commercialization and launch plans for reproxalap, if approved during the second half of 2024, and continued early and late-stage development of our product candidates in ocular and systemic immune-mediated diseases. The runway guidance excludes any potential product or licensing revenue associated with reproxalap. We look forward to SPA feedback, which we expect next month, and pending SPA feedback, top-line results from the proposed trial in the first half of next year. Assuming successful outcomes with the SPA and the proposed trial, we expect a potential NDA resubmission in the first half of next year, followed by a six-month NDA review. Operator, at this time, I'd like now to open the call for questions. Thank you. As a reminder, if you'd like to ask a question, you can press star followed by one on your telephone keypad. If you'd like to remove your question, you may press star followed by two. Please ensure you're unmuted locally when asking your question. Our first question for today comes from Tom Schrader of BTIG. Your line is now open. Please go ahead. Good morning, this is Sung for Tom, and thanks for the update. So for reproxalap, I actually had a question regarding allergic conjunctivitis. So I understand that a Type C meeting is planned for first half 2024, but given that the potential NDA resubmission for dry eye disease may happen at a similar timeframe, could you maybe elaborate on what strategies are being considered for optimizing the use of data from the INVIGORATE trial? Thanks. Yes, good morning, Sung, and thanks for the question. As you point out, reproxalap is also in development for allergic conjunctivitis. The INVIGORATE- 2, phase 3 results were reported earlier this year. And, as we said in the press release issued yesterday, we intend to go speak with the agency about remaining requirements for submission of an NDA in allergic conjunctivitis. I think it's important, though, to consider that dry eye disease at this point is in pole position in terms of our regulatory strategy. Our goals are to first allow a resubmission of the NDA in dry eye disease. And our conversations with the agency about allergic conjunctivitis are obviously secondary to whatever happens in dry eye. As you point out, I think there is a lot of synergy between the two diseases. Many patients have both of these diseases. Approximately half of dry eye disease patients also exhibit some form of ocular allergy and vice versa. I think that clinical fact is an important consideration with the FDA, and how we approach getting reproxalap in the hands of both sets of patients will be important going forward as we continue our conversations with the FDA. Great. Thank you for the color. Thank you. Our next question comes from Marc Goodman of Leerink. Mark, your line is now open. Please go ahead. Yes, good morning, Todd. Can you talk about the comment in the press release about chronic and acute being on the label, and what makes you think you can get that? And have you had any discussions with FDA before about that? Is that in the SPA, such that you'll know soon whether that can possibly be on the label, and how important do you think that is? Thanks. Thanks, Mark. That's a great question. I want to clarify that by chronic and acute, we're referring to data. That is, the label we would intend to submit, pending a positive SPA and trial results, would include data that exhibit both chronic and acute activity of reproxalap. Now, as we've disclosed previously, reproxalap has completed a couple of 12-week field trials. Obviously, those data are chronic, but the data that I referred to this morning and referenced on slide six is obviously acute. That's dry eye chamber data, the first time point being measured 10 minutes after a dose, and the entire symptom data being measured over 90 minutes. A massive problem in dry eye disease is the drugs we have today, that are available today, do not work quickly. By quickly, I mean within minutes, which is a major complaint among dry eye patients. No one wants to take a drug for weeks before deciding whether or not that drug is effective. Reproxalap theoretically offers a new kind of therapy that allows for rapid assessment of activity and from the patient's perspective rapid relief. That's what I'm hoping would wind up on the label in terms of data in the clinical section of the label. Thanks. Thanks, Mark. Thank you. Our next question comes from Kelly Shi of Jefferies. Your line is now open. Please go ahead. Thank you for taking my questions. Firstly, I'm curious what the criteria actually are for being granted for a Special Protocol Assessment? If the current trial design is not accepted by FDA, what is the plan B? Thank you. Hi, Kelly. Good morning. Always nice to have plan B. I think your point about the SPA is a good one. These days, my understanding is that to even submit an SPA, there has to be some agreement with the agency about the kind of trial that's gonna be submitted. And I think technically, the sponsor and the agency are supposed to have a meeting that then grants the sponsor the opportunity to submit an SPA. I think the good news is that based on the late-cycle review meeting regarding the dry eye disease NDA for reproxalap and subsequent communications with the agency following that meeting, we were permitted to submit an SPA, which as was disclosed in the press release yesterday, was submitted on the sixteenth of November. Obviously, we're being proactive. I think it's quite unique to submit an SPA even prior to receiving a complete response letter. But the communications from the agency were very clear, as we had disclosed in October via an 8-K, that another trial was needed. We immediately initiated communications with the agency to define the parameters of said trial, and hence, an SPA was submitted previously. I think the review for the SPA is 45 days, and we should know next month where the FDA is. I do not expect there will be major issues with the trial itself. We have used a chamber crossover design previously. Those are the data that I presented this morning. And our expectation is that we will have sufficient feedback next month to go ahead and initiate that trial, which in theory could provide data and the potential NDA resubmission if the data are positive in the first half of next year. So what is plan B? Plan B is if a chamber trial is not acceptable or the crossover design is not acceptable, I think we have other tools in our toolkit, as I mentioned previously in response to Mark's question. We've run a 12-week field trial. The good news in those trials is the separation between drug and vehicle, or reproxalap vehicle, occurred relatively early in the process. I think we could be in a position to run a shorter field trial, perhaps six weeks. But all this is speculation at this point. I think first we need to hear back from the agency on the SPA. Obviously, we're optimistic about the SPA process, given the dialogue we've had with the agency, and then we can go from there. Thank you. Thanks, Kelly. Thank you. Our next question comes from Yigal Nochomovitz of Citi. Your line is now open. Please go ahead. Yeah. Hi, Todd. Thank you for taking the question. So it seems like the FDA is making a very technical distinction here between what you submitted with the original NDA and what they've now requested. I mean, after all, you followed the recipe basically to the T in terms of two signs, two symptoms, albeit the second set of symptoms was secondary endpoints, and now they're basically saying, "Do another one, do another crossover, trial with making some of those primary," which I think is this distinction, if I'm correct. So it would be helpful if you could elaborate a little bit on why that happened, especially given how transparent Ophthalmology Division obviously always is, and, you know, if Wiley Chambers says, do X, Y, and Z, and the company does X, Y, and Z, then those studies work, then you're good. So it'd be helpful if you could just elaborate a little bit on how the stance changed and why this is necessary, because obviously, you followed the recipe as directed by the guidance. Thanks. Yeah, thanks, Yigal. A couple of points I would make at the outset. As you know, we submitted 2 12-week field trials. One of those trials was the RENEW trial, announced in 2019, I believe. The co-primary endpoint for that trial was symptoms and staining. Staining is a sign of dry eye disease. We hit symptoms, and we missed staining. And while the symptom data were remarkably positive, in fact, in the RENEW trial, we hit every symptom, presenting, I think, some of the largest effect sizes ever presented in dry eye disease in terms of symptomatic control. We technically didn't hit the primary itself because the primary was comprised of two endpoints, that is, symptoms and staining. Staining was not hit over 12 weeks. It was hit over four weeks, but not over 12 weeks. So there is a technical distinction between achieving the primary endpoint of RENEW and not. And when a co-primary is in place for the trial to be successful, end quote, both primaries need to be achieved, which was not the case in RENEW. I think the division drew a distinction there for the RENEW data. The data from the trial I reviewed this morning, the crossover chamber trial announced in July of last year, as you pointed out, those endpoints are secondary endpoints. So technically, what the division is asking for is a prospectively designed trial where symptoms are specified as the primary endpoints, and that trial would need to be successful to confirm activities and symptoms. Okay, thanks. And then with regard to AbbVie, any comment at all there in terms of their disposition as far as pursuing the partnership? Are they waiting for this SPA agreement application to be accepted by the agency before they're willing to commit further capital, or what is their stance currently? The AbbVie option agreement, which was recently disclosed in a press release and also in more detail in an 8-K, specifies that on December or by December 15, AbbVie makes a decision to extend the option or not. The extension fee due by December 15, if AbbVie elects to extend, is $5 million. My impression is that December 15 date allows AbbVie sufficient time to review the results of PDUFA. But as you're aware, we've disclosed the need for an additional clinical trial as part of this NDA, well before we disclosed the relationship with AbbVie in terms of the option with AbbVie. So AbbVie, prior to executing the option, or, or I should say initiating the option agreement, and also, as part of the current ongoing option agreement, is well up to speed regarding our conversations with the agency. So I think the next step for the AbbVie relationship is on December the 15th, Yigal. Okay, got it. Thank you. Thank you. Our next question comes from Justin Kim of Oppenheimer. Justin, your line is now open. Please go ahead. Hi, good morning, Todd and team. Maybe just a clarification question, but given the cycle of 45 days for the FDA, does that potentially allow for an update to slip into the early part of next year? Well, it's an interesting question, Justin, because I think the SPA process, in theory, is an iterative process, where there is information shared back and forth between the sponsor and the agency during the 45-day SPA review. So in theory, we'll have some feedback before the end of December, but nominally, the FDA would get back to us 45 days from the sixteenth of November, which is prior to the end of the year. If agreement is, is reached, or if there's a sufficient amount of positive feedback that we can go ahead and initiate the proposed trial described this morning, then I would expect we would announce that. If there is, on the other hand, continued dialogue between the agency and Aldeyra regarding the trial, or there's certain, critical disagreements on the various aspects of the trial and that, that negotiation's ongoing, I think, you wouldn't hear from us, by the end of the year. Either way, though, Justin, I think per my previous comments today, we would expect that the basic trial design, the basic way of assessing our endpoints, and so forth, are more or less pre-agreed, just given what we've already submitted, in the NDA itself. As you know, the proposed trial is more or less a replicate of a trial that has been thoroughly reviewed by the agency as part of the NDA review process. Okay, understood. And just in terms of the for execution of this additional study, is there sort of a timeframe in which you would anticipate enrollment being concluded to maybe not necessarily run into sort of seasonality effects that maybe have been previously highlighted before in dry eye? Well, the good news is, our best data in dry eye occur during the winter months. The reason for that, as you point out, is this concept of seasonality, whereby pollen, in particular, exacerbates the dry eye disease. To some of the comments I've made earlier in the Q&A session, there is this significant comorbidity between ocular allergy and dry eye disease, that they exacerbate each other. And so when you're testing patients that are suffering from both conditions at once, I think elucidating drug effect becomes more complicated. The good news is, just given the SPA, the timelines you were asking about, our expectation is that we'll be able to enroll more or less the entire trial during winter months. Again, which would allow us to present data to the street in the first half of next year, and assuming that the SPA and trial feedback or the trial is positive, then, you know, resubmit in the first half of next year as well. Got it. Got it. Maybe if I could just squeeze in one final one. In terms of the option agreement and the discussion with AbbVie, what has been sort of the, I guess, feedback or interest in AC as part of maybe that sort of broader overall interest? Well, I can't speak for AbbVie directly, but I can tell you that AbbVie is acutely aware of all of our clinical data with reproxalap. And ultimately, whoever commercializes reproxalap, whether it be AbbVie or Aldeyra, I think a decision needs to be made, per Sung's question at the beginning of the Q&A session, about how do we integrate dry eye disease with allergic conjunctivitis? That I'm aware, there is no dry eye disease drug, possibly except for steroids that has any activity in allergy. And that allows for a tremendous market opportunity, not only in terms of differentiation in dry eye disease, but also in terms of the number of patients that could be treated. About a third of allergic conjunctivitis patients do not adequately respond to antihistamines, which are sort of the market leader in ocular allergy. And so, how Reproxalap is commercialized with regard to those two diseases, I think is to be worked out. As I mentioned previously, our first and foremost concern is navigating the regulatory environment for dry eye disease, and then allergic conjunctivitis, I think, represents you know upside relative to whatever happens with dry eye. Okay, great. Thanks so much, Todd. Thank you, Justin. Thank you. Our next question comes from Yale Jen of Laidlaw & Co. Your line is now open. Please go ahead. Good morning, and thanks for taking the questions. Just two questions here. The first one is that in comparison to your prior chamber study for the symptom sign, as well as the RENEW study, this proposed study seems to have a much smaller patient size. So, is there any rationale behind that? And then I have a follow-up. Yale, I think you've surfaced a very interesting phenomenon with dry eye disease. At least acutely, when we're speaking of symptoms, at least acutely, I think the patient-to-patient difference is substantial. Meaning that what is important to you may be less important to me. A score of 30 for you may be a score of 90 for me. The way to get around that, and again, I'm talking from an acute symptomatic standpoint, is to compare each patient to his or herself. That is the crossover design, where each patient is exposed to reproxalap and vehicle in a randomized order. The inter-patient variability, that is comparing you to me, is minimized, and the intra-patient, that is within each patient, effect size is what matters, statistically comparing the drug to vehicle. The crossover design is a very effective way of minimizing inter-patient variability. I think in dry eye disease, Aldeyra was the first to demonstrate that a crossover trial, at least as it relates to acute assessment in a dry eye chamber, is a very effective way of testing patients for all the reasons that I just mentioned. A field trial is more difficult to do in a crossover setting, and that's because you have to test patients chronically. To Mark's point about chronic and acute data on the label, a field trial is chronic data. To cross over a patient after 12 weeks of therapy with some washout period would require a very long period of time, across many seasons, several seasons, probably, throughout the year. I just think it would be less feasible to crossover patients in a field setting. Thus, because of the inter-patient variability in a field setting, more patients are required. That, Yale, is why you see more patients in a field trial than you would for a crossover trial. Okay, great. That is very helpful and clear. Maybe one more question here, which is that you have a co-primary endpoint. I understand the dryness, eye dryness scores. Just curious why you choose ocular discomfort scores, and what others will be used for secondary endpoint? And thanks. Thanks, Yale. I want to distinguish between a co-primary endpoint and two primary endpoints to Yigal's question about the RENEW trial. The RENEW trial had a co-primary, and for that setup to be successful, both primaries have to be met. That's not what we're proposing for the new crossover trial. For the new crossover trial, we have two primaries, either one of which could satisfy or could allow achievement of the primary endpoint of the trial. And the way that's possible is adjustment of multiplicity. That is, your alpha or your statistical significance is adjusted because you have two endpoints. There's something called the Hochberg Procedure, which I mentioned in my comments this morning, that is sort of a ranking of P- values, and if both endpoints are less than 0.05, then both endpoints are met, you can claim success for either endpoint. If one endpoint fails, if that is higher than 0.05 in the P- value, then the next endpoint needs to be assessed at a 0.025, an alpha 0.025. Either way, it allows the potential for one or more endpoints to be deemed successful in a clinical trial. Your question about why discomfort is interesting, as you can see on slide 7—I'm sorry, on slide six, our discomfort data in the prior crossover trial were more statistically significant than our dryness data. My understanding from the FDA is that symptoms are important, and the actual symptom is less important. By that, I mean, what you might call dryness, I might call discomfort, or what I might call stinging, you might call burning. I think the primary concern of the agency is, do symptoms improve, rather than does a particular symptom improve? We'll know more once the SPA feedback is received. The good news is, whether it's dryness or whether it's discomfort, that the data from the prior trial were remarkably positive, and we would anticipate to see something similar in the next trial. Okay, great. That's very clear, and thanks and congrats. Thank you, Yale. Thank you. Our next question comes from Catherine Novack of Jones Research. Catherine, your line is now open. Please go ahead. Hi, good morning, thanks for taking my question. So I just kind of wanted to ask, there was a lot, so much focus in the prior studies on, you know, getting significance on signs of dry eye. Was there, at any point, when you questioned the strength of the data for symptoms? And then, you know, is there any indication whether the issue with the data is not just about phase 3 RENEW, but also regarding data from the formulation phase 2, which you have mentioned was another study using you were using for ocular dryness? Right. Good morning, Catherine. I think you've correctly summarized our position going into the NDA review, which is, our symptom data appeared to be quite strong. We had the RENEW data, we had the formulation phase II data that you just mentioned. We had the secondary symptom endpoints that I presented this morning. From a totality or preponderance standpoint, our assumption, again, prior to the NDA review, was that our symptom data were quite strong, and we were quite eager to see where the FDA came out on the signs. I don't think that there were any review issues associated with the formulation phase II. Those, that symptom data were very strong, number one, and number two, the only primary endpoint of that trial was symptoms, and that primary endpoint was achieved. The FDA has told us in writing previously that the formulation used in the phase II, which is slightly different than the proposed commercial formulation, in their eyes, would be deemed substantially similar. That is, they don't distinguish between the formulations we used across our clinical trials, which is good news. So I didn't see any I am not aware of any issues with the formulation phase II. I think it was simply a matter of pre-specifying a single primary endpoint or primary endpoints associated with symptoms, running that prospectively in a trial and achieving that endpoint. Okay, that makes sense. I just wanted to clarify, you know, from a previous comment, you have two primary endpoints for the crossover chamber trial, but both of the, you know, studies from the previous package submitted were for ocular dryness. You know, why include the Ocular Discomfort Score? Do you have, you know, data from a previous study for that? Right. The discomfort data from the crossover chamber trial that I presented this morning were remarkably robust. They were more robust than the dryness data. You know, as I mentioned in response to Yale's question about dryness versus discomfort, I don't have the understanding at this point that the FDA is likely to distinguish between dryness and discomfort. All that could change, we do not have SPA feedback yet, obviously. We're eager to hear what the division says about dryness versus discomfort. But my understanding, based on previous conversations with the agency, is that symptoms matter to patients, and the agency appears to be less concerned about particular symptoms. As I said in response to Yale's question, I think the reason for that is fairly clear, and that is, what one patient may describe in terms of words, discomfort, dryness, stinging, burning may be different from what another patient describes in terms of words. But the bottom line is that both patients are symptomatic. dry eye disease is not a comfortable disease. Patients never present to healthcare providers arguing about symptoms or complaining, I'm sorry, complaining about signs, but they do complain about symptoms. "My eye hurts. It doesn't feel well. It feels like sandpaper every time I blink. I'm constantly stinging. I'm constantly aware of my eye in terms of discomfort." The word discomfort comes up frequently when discussing symptoms with Dry Eye patients. It may be a little less clear to individual patients what dryness means. Does my eye feel dry? In reality, I think for most patients, their eye is uncomfortable, and maybe that's why the effect size of discomfort, again, that I described, from the crossover trial released last year, is greater than that for dryness. But either way, as I mentioned to Yale's question, in response to Yale's question, we're in a good place regarding dryness or discomfort, and we'll adjust if need be, pending SPA feedback. Got it. Thanks very much, and looking forward to FDA feedback. Yep. Thank you, Catherine. Thank you. As a reminder, if you would like to ask a question, you can press star followed by one on your telephone keypad. Our next question comes from Matthew Caufield of H.C. Wainwright. Your line is now open. Please go ahead. Hey, good morning, Todd. Can you hear me okay? Yep. Good morning, Matt. Great, thanks. Okay. We appreciate the update today, so thank you for, for all the clarity. So one question we had: so if the trial design is ultimately needed, that differs from the dry eye chamber crossover design from slide six, would you still be prioritizing the clinical demonstration of both the chronic and acute symptom benefit for, you know, as you mentioned, the differentiated perspective labeling? And, you know, based on different potential trial designs, is there any scenario where the chronic and acute labeling becomes less of a priority? Thanks again. Matt, I think the answer to that question depends on the SPA feedback. And I thought Kelly made an excellent point about plan B. If the FDA comes back to us and has some sort of fundamental issue with the crossover chamber design, which I do not expect, again, based on what has been previously reviewed as part of the original NDA submission, then we can always go back to the field trials. As I mentioned, the RENEW trial and the formulation phase 2 trial were 12-week trials. But the separation, that is, the improvement noted with reproxalap relative to vehicle appeared relatively soon, and I would say within two to four weeks of treatment. So that may allow us to run a shorter field trial. It may allow us to highlight an improvement in drug relative to vehicle that occurs relatively soon. And in that sense, I wouldn't exactly call the data acute, but the data would occur within a week or so, ideally, after drug administration, and that's a potential route we could go, if we're in the position of repeating another field trial. Again, just based on the fact that we were allowed to submit an SPA, I think there is likely going to be general agreement between Aldeyra and the FDA on the chamber design. I think the crossover aspect is important. Back to Yale's question about sample size and the advantages of crossover, my previous comments I would reiterate regarding interpatient differences, that is, patient-to-patient differences in describing symptoms, are likely very significant in terms of acute symptomatology, and that's why a crossover trial would be optimal in this situation. And I think the data from the crossover trial announced last year that I reviewed this morning are certainly important in that regard. Very helpful. Thanks for that, Todd. Yep. Thank you, Matt. Thank you. At this time, we currently have no further questions for today. So that concludes today's conference call. Thank you all for joining. You may now disconnect your lines.