Aldeyra Therapeutics, Inc. (ALDX) Earnings Call Transcript & Summary

Good afternoon, and welcome to the Aldeyra Therapeutics Conference Call. [Operator Instructions] I would now like to hand the conference over to Joshua Reed, Chief Financial Officer. Thank you. Sir, please go ahead.

Thank you, and good afternoon, everyone. On the call with me is Dr. Todd Brady, Aldeyra's President and Chief Executive Officer. Please turn to Slide 2. This presentation and various remarks, which may be made during this presentation contain forward-looking statements regarding Aldeyra and its investigational drug candidate, reproxalap. Forward-looking statements involve known and unknown risks, uncertainties and other factors that may cause Aldeyra's actual results, performance or achievement to be materially different from any future results, performance or achievements expressed or implied by the forward-looking statements. These statements reflect Aldeyra's current views with respect to future events and are based on assumptions and subject to risks and uncertainties, including the development, clinical and regulatory plans or expectations for Aldeyra's product candidates and systems-based approaches. The risks that results from earlier clinical trials, portions of clinical trials or pooled clinical data may not accurately predict the results of future trials or the remainder of a clinical trial and Aldeyra's continuing review and quality control analysis of clinical data. As a result of the COVID-19 pandemic, clinical site availability, staffing and patient recruitment have been negatively affected and the timelines to complete our clinical trials may be delayed. 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 current and potential future impact of the COVID-19 pandemic on our business, 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 afternoon and our annual and quarterly reports filed with the Securities and Exchange Commission. I would now like to turn the call over to Dr. Brady.

Thank you, Joshua. And thanks to all of you for tuning in today to hear about our important announcements concerning achievement of the secondary endpoint of Schirmer test in the TRANQUILITY trial and accordingly, the addition of Schirmer test to our primary end point of the TRANQUILITY-2 trial. Before we discuss the TRANQUILITY results on Slide 3, I'd like to take the opportunity to review the U.S. FDA requirements for dry eye disease efficacy. According to its draft guidance, the FDA requires 2 positive adequate and well-controlled trials demonstrating improvement over vehicle and a subjective symptom of dry eye disease and 2 positive adequate and well-controlled trials demonstrating improvement over vehicle in an objective clinical sign of the disease. Either Phase II or Phase III trials can be submitted as pivotal, provided that the trials are adequate and well controlled. The 12-week symptom trials we intend to submit are presented here for objective signs of dry eye disease in addition to other signs, either ocular redness or Schirmer test may qualify. Slide 4 summarizes the multi-center double-masked parallel group TRANQUILITY trial which enrolled 306 patients randomized equally to receive either 0.25% reproxalap or vehicle for 2 days. Day 1 was comprised of 4 doses of test article. The Schirmer test, which involves using a strip of paper to wick tears from the eye and therefore, quantify tear volume, was measured before and after the fourth dose of test article on day 1. Dry eye disease symptoms were also assessed before dosing on day 1 and after the third dose on day 1. On day 2, subjects received a dose of test article before entry and after 45 minutes in a dry eye chamber. The 90-minute chamber consisted of low humidity air, controlled airflow and forced visual tasking in order to exacerbate dry eye disease symptoms and signs. Ocular redness and symptoms were assessed approximately every 10 minutes in the chamber. The primary endpoint was ocular redness, which was measured via digital photography over duration of the dry eye chamber. The lead secondary endpoint was Schirmer test. Slide 5 presents the ocular redness and Schirmer test results for TRANQUILITY, the TRANQUILITY RUN-IN, which was announced in January and the recently completed Phase II trial. In contrast to the TRANQUILITY RUN-IN results and the Phase II trial, TRANQUILITY did not achieve the primary endpoint of ocular redness, highlighting the inherent variability of dry eye disease clinical trials performed over different seasons with different levels of humidity and ocular irritants such as pollen. Unlike ocular redness, the Schirmer test results have been largely consistent across all 3 recent signed trials. In TRANQUILITY, the Schirmer test achieved a highly statistically significant p-value of 0.0001. In addition, both the TRANQUILITY RUN-IN and the Phase II clinical trial approach statistical significance for Schirmer test. As is presented on Slide 6, the clinical relevance of the TRANQUILITY Schirmer test results was confirmed post-hoc with the industry standard and FDA sanctioned responder analysis of greater than or equal to 10 millimeters. Responder rates in reproxalap-treated patients were nearly double those of vehicle-treated subjects and with an odds ratio of 2.6, an effect that was highly statistically significant with a p-value of less than 0.0001. Turning to Slide 7. Although TRANQUILITY was not powered to detect differences in secondary endpoints, ocular dryness and itching symptom improvement over -- reproxalap over vehicle approached statistical significance after a single day of dosing. Slide 8 outlines the protocol of TRANQUILITY-2, the design and dosing regimen of which is identical to TRANQUILITY. Given the positive Schirmer test results from TRANQUILITY, the primary endpoint of TRANQUILITY-2 has been modified to include Schirmer test using an alpha-sharing approach such that at either Schirmer test or ocular redness is statistically significant in favor of reproxalap over vehicle, the primary endpoint would be considered to have been met. To increase statistical power, we have increased the target enrollment of tranquility to, to up to 400 subjects. Based on data from TRANQUILITY and the Phase II trial, either Schirmer test or ocular redness was achieved in more than 90% of simulation outcomes using an alpha of 0.025 for each assessment. As a result of the expanded enrollment, we now expect to report TRANQUILITY-2 top line results mid-2022. If TRANQUILITY-2 is positive for Schirmer test, then TRANQUILITY and TRANQUILITY-2 are expected to be submitted as pivotal. If TRANQUILITY-2 is positive for ocular redness, then we intend to submit the recently completed Phase II clinical trial and TRANQUILITY-2 as pivotal. If TRANQUILITY-2 is positive for Schirmer test and ocular redness, then pending discussion with the FDA, the Phase II clinical trial and both TRANQUILITY trials are anticipated to be submitted as pivotal, potentially representing the first time that a dry eye disease drug will have qualified for the demonstration of activity for 2 objective signs. As is noted on Slide 9, the timing of the TRANQUILITY-2 results, if positive, is not expected to affect the timing of our NDA submission. As we have said previously, the gating factor for the NDA is the standard 12-month safety trial. Ending enrollment of the safety trial and the outcome of TRANQUILITY-2, NDA submission is expected to occur mid-2022. The allergic conjunctivitis NDA is expected to be filed after the dry eye disease NDA, and as requested by the FDA following completion of an additional allergen chamber trial, if successful. Aldeyra has completed 2 positive Phase III clinical trials in allergic conjunctivitis, the ALLEVIATE conjunctival allergen challenge trial and the INVIGORATE allergen chamber trial. And as is illustrated on the right side of the slide, an additional positive Phase II allergen chamber trial has also been completed. Reproxalap has now been tested in over 1,500 patients with no observed safety concerns. Consistent with other trials, the most common adverse event reported in TRANQUILITY was mild and transient installation site discomfort. No moderate or severe adverse events were reported in TRANQUILITY, and no patients discontinued TRANQUILITY due to an adverse event. In summary, while TRANQUILITY missed the primary endpoint, the highly statistically significant result in Schirmer test for the first time with reproxalap offers a new option to satisfy NDA signed requirements. And pending FDA agreement and the results of TRANQUILITY-2, could allow reproxalap to be the first drug to qualify for activity in 2 objective signs of dry eye disease. At the intended commercial dosing regimen, 0.25, reproxalap has now demonstrated activity in 4 late-stage clinical trials in dry eye disease. Reproxalap, therefore, continues to advance toward NDA submission. With that, Joshua and I are happy to take your questions. Operator?

[Operator Instructions] Your first question comes from the line of Edwin Zhang with H.C. Wainwright.

Looking at the results, it seems that there's a lot of variability into dry eye patients, have you thought of any method or strategy to manage the patient heterogenicity in your clinical trials? For example, have you or do you plan to modify the patient enrollment criteria or the timing of the trial, as you mentioned?

Thanks for the question. As you point out, dry eye disease is an inherently variable condition, consistent with the prepared comments that I've made. I do think that it is unlikely we're going to modify the enrollment criteria. Firstly, TRANQUILITY-2 is well underway. Secondly, I do think there is something to performing dry eye clinical trials during the same season, whereas performing clinical trials, not just in dry eye disease, but generally over a variety of seasons is not always the greatest idea. Fortunately, TRANQUILITY-2 is being performed in the fall and winter. These are classically excellent months to perform dry eye disease trials, primarily because the air is drier. There are less particulates, such as pollens in the air and one would expect, therefore, a more uniform result from TRANQUILITY-2 given the seasonality of that trial.

Your next question comes from the line of Justin Kim with Oppenheimer & Company.

Maybe just a few on Schirmer care test. In the scenario that Schirmer is positive for TRANQUILITY-2, do you expect to gain agreement with the agency on the acceptability of TRANQUILITY-1 demonstrating sort of improvement on Schirmer care test? Just wondering how much being a secondary plays a role with their thinking and whether you would be able to get some level of understanding as you think about changing the primary?

For sure. And thanks for the question, Justin. I do expect that we'll be able to gain agreement with the agency regarding the use of TRANQUILITY in the event that we file on or submit on Schirmer test. The reason I say that is, first, I think there's a historical precedent for that. And the definitive result in Schirmer test that notwithstanding Schirmer test being a secondary endpoint, I think, helps those negotiations. Another approach is always to run other trials aside from TRANQUILITY-2 with Schirmer test. But frankly, I don't think we'll need to do that. The good news is that Schirmer test is tested after 1 day of dosing, which means that clinical trials are efficient, they are fast. And I think we're in a really good position in discussing the applicability of TRANQUILITY in a Schirmer test submission situation.

Got it. Got it. And under the proposed change to the primary endpoint, with the shared alpha, does that place the powering somewhere in between the Phase II study run with redness and TRANQUILITY-1 now?

It does, in fact. The shared alpha approach is a good one if there are 2 endpoints that are reasonable to achieve. In our simulations, as I mentioned in our prepared comments, we assessed each Schirmer test and each -- the Schirmer test and the redness assessment at an alpha of 0.025, which is half of the 0.05 alpha. I think the exact alpha share will be a subject of discussion internally at Aldeyra over the next month or so. But what it does is allow us optionality in terms of declaring either assessment as positive. And again, as I mentioned in my initial comments, there is always the possibility that both endpoints would be hit, potentially allowing us to file or submit with 2 signs.

Got it. And maybe just if I can squeeze 1 more in? On RASP, I know before sort of those data take a little bit longer to analyze or get back, but is that something that's still out and pending? Just wondering any thoughts on the Phase II study and just any thoughts in terms of TRANQUILITY-2 and expectations there?

So the RASP data will come in more slowly than the other data. And the reason for that is that RASP needs to be analyzed at a separate lab. They are analyzed after the patients are treated and so forth. Given that Schirmer test has been achieved in this trial, and now we have 2 options for signs for NDA efficacy requirements, RASP have become unimportant from a NDA submission process. The idea, I think, would be to announce RASP data from all 3 trials subsequently perhaps at an R&D day in the future.

Your next question comes from the line of Yigal Nochomovitz with Citigroup.

Just had a few here. First of all, I was just curious, why did you guys bother with the post-hoc assessment of the Schirmer's test for the responders when you already hit on Schirmer's in the overall population? Shouldn't it just be sufficient to hit in the overall population?

It is. It is sufficient. We don't need the post-hoc. However, given the strength of the Schirmer results of the raw data, we felt it an interesting analysis to go ahead and confirm the responder analysis. The 10-millimeter or greater response is the classic that responder analysis that according to draft guidance from the FDA, if that assessment is hit twice, then companies don't even need to file with symptom data. So it just was another interesting assessment that we ran that I think supports the validity of the -- and then the strength of Schirmer findings and TRANQUILITY.

Okay. Got it. And then on TRANQUILITY-2, I just want to check, have you discussed this modification of the primary endpoint with FDA yet? And then also, given now that you're going from a p of 0.05 to 0.025 for each of the endpoints, I was a little surprised that you're only adding 100 patients when you're splitting the p-value in half. I just was curious if adding 100 is enough and if your simulation showed that adding 100 was sufficient?

Well, the addition of 100 patients really, I think, support the either/or scenario rather than supporting either of the assessments alone. During the simulations, obviously based on the Phase II data as well as the TRANQUILITY data, the Schirmer test performed surprisingly well. And I think you can see that given the data that we've presented here today, the consistency of the Schirmer test across now 3 trials is quite remarkable. So you would anticipate that based on the Schirmer test data, as shown in Slide 5, that TRANQUILITY-2 at 300 or 400 patients is relatively well powered. I think the question is more around ocular redness, which seems to be more variable. As I mentioned in response to Edwin's question though, I think that has to do with performing trials over different seasons. Spanning seasonality may not benefit the assessment of ocular redness, and that's something we're clearly not doing with TRANQUILITY-2.

And then just any comments on the first part of my question with regard to when you plan or have you plan to discuss the end-point change for TRANQUILITY-2 with the agency?

Thanks for the reminder. We have not discussed yet the primary endpoint with the FDA. I don't anticipate that will be a problem for a couple of reasons. One is that both redness and Schirmer test are acceptable end points for demonstration of an objective sign in dry eye disease. And the second reason is alpha sharing is part of FDA guidance. When adjusting for multiplicity, there's a whole guidance document that features alpha sharing and other approaches related to alpha sharing for primary and other endpoints. I do not anticipate that those particular discussions will be an issue at all.

Your next question comes from the line of Matthew Cross with Alliance Global Partners.

I guess starting off with the primary focus here with TRANQUILITY. Just had a question about -- I know the effect sizes and variability in redness were brought up. I was curious, given the comparison you also had on Schirmer's across a couple of these studies, given that, I guess, the effect size here in TRANQUILITY for Schirmer's -- well, solid at a kind of a top level you just described looks about the same as what you saw in the Phase II or I guess it wasn't hit, obviously, different powering assumptions, but just wanted to get some commentary on whether a repeat effect size of that nature and equivalently sized TRANQUILITY-2 is what you would deem sufficient?

Matt, thanks for the question. I do think that we would expect to see a similar effect size in TRANQUILITY-2. And the reason I think that is because we've now seen it in 3 different trials. Now the run-in trial was only 23 patients. But it's remarkable to me to see the consistency and effect size after a single day of dosing with reproxalap. I don't really have any reason to believe that a Schirmer test would perform any differently. We have the 3 different trials, all performed at different times. With slightly different dosing regimens on day 1, all of them seem to behave in a very consistent manner with regard to Schirmer test and therefore, I would think TRANQUILITY-2 behave similarly. Now the dosing and Schirmer test assessment in TRANQUILITY-2 is identical to that of TRANQUILITY, which is all the more reason to believe that we would achieve, I think, similar results in Schirmer test.

Got it. Okay. And then just a follow-up. I know this is -- again, not the the primary focus, but [indiscernible] here. I was curious about your commentary that there'd be an additional allergen chamber study required for AC in that process. Just wanted to get a little bit more insight here. Obviously, you've had a couple of different studies in both direct and allergen chamber controlled setting studies. It seems like you kind of crossed the requirements for the FDA. I was curious if there's any additional feedback you can give us on where the kind of expectation lies in the data pack that you have? And what to kind of expect to complete that part of the pipeline?

Yes. Good question, Matt. We've received the recent feedback from the agency. And I think the discussion is around replicating an adequate and well-controlled allergen chamber study. There has never been, that I'm aware, an approval in allergy based on the allergen chamber. The FDA has no problems with the allergen chamber, but it could be that because we are, in a way, trendsetting that the agency wishes to see 2 identical models that is allergen chamber in 2, but large, well-controlled, adequate trial, hence the requirement for an additional chamber trial. We put the allergy data in this deck for the reason that you bring up, that is we have very consistent data in our results in the allergen chamber, showing highly statistically significant changes in itching and redness. I don't see any reason why an additional chamber would differ from those 2 previous results that we've presented here.

Perfect. Okay. And if I can squeeze in 1 more quick one. Just to back track a little bit. I know there's been discussion for some time and this is something that I agree with around the meaningfulness of redness is the sign endpoint as far as patients are concerned and kind of commercial differentiation. Obviously, we have a couple of different scenarios that could play out here. But in a setting where you do file based selectively on Schirmer's, could you just maybe kind of recap? I know this is early days because you're just getting top line results. But give us some insights into how that may affect your commercial strategy if you kind of do focus more on Schirmer's, where more of the market has demonstrated for [indiscernible] end point?

I don't think that the Choice of submission of Schirmer test or ocular redness affects our commercial strategy. I still agree that redness matters to patients. However, what patients really care about is symptoms. They are uncomfortable. Dry eye disease is persistently disturbing. It is a quality of life issue, primarily due to symptoms. And I think that's going to be most of how the marketing is and the commercialization is oriented. Regarding Schirmer test, that is of interest to clinicians. And I think it could be used in a commercially advantageous way. But as far as we're concerned that symptoms are what matter to patients, it would be nice to have ocular redness on the label. And as I mentioned in response to a prior question, these trials are 2 days long. And if TRANQUILITY-2 does not hit redness, maybe we'll run other trials that hit redness and eventually redness winds up in the label. But either way, I think we're well positioned.

Your next question comes from the line of Marc Goodman with SVB Leerink.

This is Rudy on line for Marc. I have 2 questions. So first, regarding the concurrency data, it seems like the ocular redness endpoint slightly favors placebo versus active drug in study. Do you have any possible explanation for the inconsistency, as you demonstrated positive data in ocular redness in 4 prior chamber studies? And secondly, it sounds like the filing is slightly delayed from early 2022 to mid-2022 as the 12-month safety trial remains the gating factor. Can you provide more color on the progress?

Right. Let me take your second question first. It is correct that we're nudging the NDA submission date out to mid-year. But that is primarily, as you point out, because of the safety trial. And the difficulty with safety trials in dry eye disease and other chronic conditions is they're 12 months long. So convincing patients to remain in the trial, convincing patients to sign up for trials, particularly in the COVID era that are 12 months in duration is challenging. I totally expect that we'll be able to reach our enrollment target. I expect we'll be able to file on -- or submit on 6 months of safety data. But that process is, again, challenging in today's environment. I think the answer to your question around the variability and the redness endpoint, which, by the way, as you can tell from the data we presented today is simply equivocal, is really probably due to, a, the inherent variability in dry eye disease patients; and b, the fact that trials are run across the different seasons. The TRANQUILITY trial was particularly long in duration and interspersed with the Phase II trial that we announced recently. So we had patients across all segments of the year more or less enrolled in that trial. And I think that may explain some of the variability, but maybe not all of the variability. Dry eye disease inherently is something that is just a variable from trial to trial.

That's very helpful. I have one follow-up question. Are we still expecting RASP data like by the end of the year or early next year? The reason I'm asking was that, that is supposed to be like we using that as one of the endpoint for clinical studies. So I was just wondering.

Right, right, Rudy. The RASP data, we think we're going to, as I mentioned previously, combine across trials. Now that the Schirmer test has been achieved for reproxalap, RASP is not needed for NDA submission. I think RASP is interesting from a mechanism standpoint. We already have data from our Phase IIa trial in dry eye disease that has been published, showing that reproxalap diminishes RASP levels over time in dry eye disease patients. So you might hear about RASP across the TRANQUILITY program at a later date.

[Operator Instructions] Your next question comes from the line of Tom Shrader with BTIG.

Certainly a surprise. Todd, you've mentioned season about 6x now. Did the average redness drift around during the trial? Or was it either very high or very low?

Tom, that's a good question. I don't know the answer to it though. You would expect redness to differ depending on the time of year. Generally, redness would get worse in allergy patients and pollen seasons but these aren't allergy patients. And so I don't know the answer to your question, I can tell you there was a considerable difference in baseline across TRANQUILITY and the Phase II trial, and that may explain some of the results as you suggest.

So the baseline was higher or lower this time?

Lower in TRANQUILITY.

Interesting. And then how robust is this result that TRANQUILITY, the redness gets worse? Is it true for kind of a mean and a responder? Can you dig in that way? Or is it a real assumption that there's no treatment effect? Can you give us a p-value?

I can tell you that we have looked at redness across a variety of subgroups and responder scenarios. There is no consistency in redness here one way or the other. And thus, as I've said previously, I think this result is equivocal. I do not think it's fair to say that the vehicle did better than drug. You can see from the confidence intervals that the dotted line is clearly overlapped. And I don't really say that I don't think we can make one claim either way regarding the activity of redness here.

And is there a p-value you can give us?

We don't typically announce p-values. I think we haven't announced p-values over 7 years that are more than 0.1 because, frankly, they're meaningless, something that's not significant, and more than 0.1, we would argue that is not meaningful.

Your next question comes from the line of Yale Jen with Laidlaw & Company.

In terms of TRANQUILITY-2 study, do you guys have a timeline when you're going to start the study and what's your thought in terms of the recent COVID, particularly the Omicron has any potential impact or not?

It's an interesting question regarding Omicron. I don't know the answer to that. We have not yet seen a slowdown in enrollment. TRANQUILITY-2 has been enrolling for some time since the fall started. And the addition of the extra 100 of patients-or-so, I don't think it's going to delay us substantially. But we'll have to see how the Omicron wave develops and how enrollment proceeds to give you a finer timeline for the completion of TRANQUILITY-2. But I think middle of the year is a good estimate at this point.

So the study will start maybe first quarter of next year?

The study is ongoing and enrolling.

Okay. Great. And maybe just one more question in terms of AC. In terms of the size of the study that the FDA requires, would that be similar to the last one or any other details of the study design of this one?

I think the trial size for the next allergen chamber study will be similar or smaller -- similar to or smaller than our previous chamber trials. And the reason I say that is because the p-values for these trials are all exceedingly low. All of them have p-values of less than 0.0001. Thus, I don't think we need to enroll as many subjects as we have enrolled in the past. As you recall, these are crossover trials. So each subject is exposed both to drug and vehicle in a randomized order. And that eliminates a lot of the variability that you see across allergen chamber trials, and there's one reason I think we can get such low p values and probably command a lower enrollment rate.

Okay. Great. And maybe just squeezing one more. In terms of Schirmer's test, you have in the -- both Phase II and the RUN-IN study -- TRANQUILITY RUN-IN study show a favorable towards the treatment. Do you -- can you remind us in terms of the p-value for each of those, which I understand that the design may not necessarily be relevant in terms of powering assumption at the time?

Correct. The p-values were very close. I think we disclosed a p-value of 0.07 or so for the Phase II and the p-value was significant or borderline significant with the RUN-IN depending on the statistical model that was used. So in each case, these these p-values were near significant. And I think really do suggest that Schirmer tests across trials, even smaller trials, is quite consistent.

Your next question comes from the line of Kelly Shi with Jefferies.

I have a quick one. So on the ocular redness readout, I'm just wondering, are the 2 arms well balanced on day 1 for the at a pre-dose trial? Also curious for the -- from Phase II to TRANQUILITY, are those 2 trials conducted at the same location?

Kelly, thanks for your questions. Yes, the arms are well balanced. We did analyze various baseline characteristics and so forth across arms. And I really don't see any differences there. Regarding Phase II and TRANQUILITY, the differences and TRANQUILITY-2 differences in sites, they are performed at different sites. There may be some minor overlap. But as you recall, the allergen chambers themselves are trucks. I think there's 5 or 6 trucks that drive from site to site. And so the way that the CRO controls the chambers is by having a limited number of mobile chambers, and those are the same chambers that we'll be using for TRANQUILITY-2.

So you don't think that locations could be a factor for variation, but more also like a patient baseline like the root cause of dry eye symptoms?

We have included site as a term -- clinical site as a term and a statistical model, and that often helps across many trials, not just dry eye disease, and we'll continue to include clinical site. However, I don't see a major difference in the performance of clinical sites. I think the reason for that has to do with the fact that the chambers -- these mobile chambers are all the same and that humidity and airflow and so forth is all rigorously controlled.

Your next question comes from the line of Prakhar Agrawal with Jones Trading.

My first question on redness. Just curious, were there any differences on the baseline redness goes just before chamber entry that is on day 2 between the treatment and vehicle arm?

Not that I'm aware. I don't think that there was a huge difference between baseline redness just before entering the chamber. Now in the TRANQUILITY RUN-IN and in the Phase II trial, we saw decreases in redness over day 1 as the 4 doses of test article were delivered. We didn't see that here. And again, that could be related to how the trials were run or when the trials were run or other sort of variable aspects of dry eye disease, I just don't know.

Got it. And secondly, were Schirmer's test collected on day 2, that is in the chamber or post dosing the chamber at any time? If not, what's your level of confidence on regulatory acceptance on measuring Schirmer's test on just day 1 of dosing?

Schirmer test was not conducted on day 2, only on day 1. We have discussed this protocol with the FDA for some time. I have not heard any feedback that only day 1 testing would be an issue. The FDA's stance on objective signs of dry eye disease appears to be that the duration of dosing is not relevant. What is relevant is that that the sponsor is able to demonstrate into adequate and well-controlled trials changes in an objective sign that don't just relate to anesthesia or some other neurobiological activity in the eye and that's exactly what redness and Schirmer and other objective signs that are used, do.

All right. I don't think we have any additional questions.

Thank you. There are no further questions at this time. I would like to turn the call back over to Dr. Brady for closing comments.

Well, thank you, Nora, and thank you for participating in today's call. As you can tell from our comments today and we believe that in aggregate, the safety and efficacy results to date continue to demonstrate the clinical benefit of reproxalap in dry eye disease and that reproxalap remains poised to potentially be the next novel entrant to the dry eye disease marketplace. As always, we look forward to keeping you updated on our progress.

Thank you very much, everyone. Enjoy the rest of your day.