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

Good morning, and welcome to the Aldeyra Therapeutics conference call. My name is Bailey, and I'll be the moderator for today's call. [Operator Instructions] I would now like to hand the conference over to Bruce Greenberg, Vice President of Finance, Interim Chief Financial Officer and Treasurer. Thank you. Sir, please go ahead.

Thank you, and good morning, everyone. With me is Dr. Todd Brady, President and Chief Executive Officer of Aldeyra. This morning, we issued a press release reporting top line results for the Phase III TRANQUILITY-2 clinical trial of our investigational new drug candidate, reproxalap, in patients with dry eye disease. A copy of the press release is available on the Investors & Media section of our website, www.aldeyra.com. The press release should be read and considered in conjunction with the slides presented and prepared comments made on today's call. Please turn to Slide 2. This presentation and various remarks, which may be made during this presentation, contain forward-looking statements regarding Aldeyra; its investigational new drug candidate, reproxalap; and its plans and expectations. 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 investigational new drugs, including reproxalap and system-based approaches. The risks that result 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 or post-hoc review and quality analysis of clinical data. As a result of the COVID-19 pandemic, clinical site availability and staffing and patient recruitment have been negatively affected, and the time lines 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 future potential 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 morning and in 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, Bruce. Today marks a monumental and broadly significant milestone for Aldeyra as we announced this morning achievement of both primary endpoints of the Phase III TRANQUILITY-2 trial, which we expect to conclude the pivotal clinical development efficacy program of reproxalap for the treatment of dry eye disease. To our knowledge, the TRANQUILITY-2 results could facilitate the first new drug application in dry eye disease that includes pivotal trials for improvement in symptoms as well as 3 distinct objective signs, potentially representing the most comprehensive package submitted for this condition to date. The 5 late-stage adequate and well-controlled trials that we intend to submit to the NDA as pivotal offer an unparalleled assessment of both acute and chronic designs, suggesting rapid and sustained activity repeated across a number of clinical endpoints. We remain impressed with the activity of reproxalap in ocular inflammation demonstrated to date. And we're hopeful that health care providers and patients may soon have a new and differentiated option for the treatment of a disease that today features a standard of care that is widely regarded as limited and inadequate. Before I discuss the results of TRANQUILITY-2, I'd like to remind the participants of today's call the past several weeks have been exciting for Aldeyra. We announced on May 18 that automated reassessment of ocular redness data from the TRANQUILITY trial, the primary endpoint of that trial and an approval sign of dry eye disease indicated statistical significance of reproxalap over vehicle, complementing the previously announced Phase II clinical trial that also achieved statistical significance in ocular redness last year. Our pivotal symptom trials, in addition to the Phase II and TRANQUILITY clinical trials that we intend to submit as pivotal, are presented on Slide 3. While we believe that the data presented here may be sufficient to satisfy the efficacy requirements for dry eye disease NDA submission, which, with certain exceptions based on FDA draft guidance, requires 2 positive symptom trials and 2 positive sign trials, the secondary endpoint of Schirmer test after a single day of dosing in addition to a post-hoc Schirmer test responder analysis were also positive in the TRANQUILITY trial as is shown on Slide 4. The Schirmer test, a measure of ocular tear production, is the most commonly utilized objective signed for FDA dry eye disease marketing approvals. And according to draft dry eye disease FDA guidance, the Schirmer test responder analysis of 10 millimeters or greater, if demonstrated in 2 adequate and well-controlled clinical trials, may be solely sufficient for demonstration of efficacy given that the responder analysis is a surrogate for clinically relevant symptomatic improvement. Thus, on May 24, and as summarized on Slide 5, we announced that we had changed the primary endpoint of TRANQUILITY-2 to focus exclusively on the Schirmer test. As a result, positive data in TRANQUILITY-2 would then allow for a potential NDA submission of symptoms, redness, Schirmer test scores and possibly the Schirmer test responder analysis representing an unprecedented demonstration of drug activity that to our knowledge has not been previously submitted to a dry eye disease NDA. The protocol of TRANQUILITY-2 was substantially similar to that of the TRANQUILITY trial, albeit slightly larger in size, enrolling 361 patients randomized equally to receive either reproxalap or vehicle over 2 days of dosing to assess acute activity of drug. To control for multiplicity associated with the 2 primary endpoints of Schirmer test and the Schirmer test responder analysis, a so-called fixed sequence assessment was prespecified, such that Schirmer test was assessed. First and if positive, the responder analysis would then be assessed. The fixed sequence allowed for the claim of success for both endpoints if statistical significance was met. TRANQUILITY-2 achieved both primary endpoints. As is shown on Slide 6, in a manner consistent with the TRANQUILITY trial, TRANQUILITY-2 demonstrated highly statistically significant improvement of Schirmer test scores in reproxalap-treated patients relative to vehicle-treated patients with a p-value of 0.0001. As was the case with the TRANQUILITY trial, the clinical relevance of those changes was confirmed with the 10-millimeter or greater responder analysis, demonstrating a nearly threefold increase in odds of responding following treatment with reproxalap versus vehicle, an effect that was also highly statistically significant, yielding a p-value of less than 0.0001. The increase in response over vehicle of approximately 17% is greater than that published for currently available topical therapies, which typically ranged from 7% to 10% and have generally been assessed over much longer periods of time from 3 to 6 months. To our knowledge, the TRANQUILITY and TRANQUILITY-2 results are the first assessments of Schirmer test over a single day of dosing and, therefore, suggest putatively unmatched, rapid and clinically relevant activity. Now tested in over 1,700 patients for up to 12 months, no clinically significant safety signals have been observed following administration of reproxalap, including slit-lamp examination, fundoscopy intraocular pressure and visual acuity. Consistent with all clinical trials of reproxalap, the most commonly reported adverse event in TRANQUILITY-2 was mild and transient instillation site ocular discomfort, the duration of which has been specifically quantified and characterized in hundreds of patients and most commonly last one minute or less in duration. With the positive results of TRANQUILITY-2, we believe that the clinical efficacy requirements for a potential dry eye disease NDA submission have been met. As is summarized on Slide 7, we intend to submit an NDA covering symptoms, ocular dryness and 3 signed endpoints, ocular redness, Schirmer test and Schirmer test responder analysis, across 5 adequate and well-controlled clinical trials. The submitted clinical data is expected to encompass acute as soon as a single day of dosing and chronic up to 12-week assessments, potentially offering unparalleled analysis of rapid and sustained activity across a combination of challenge and field-based assessments. If approved, reproxalap has the potential to be the first dry eye disease drug with at least two labeled objective signs. With a comprehensive in what we believe to be a compelling package in hand, a type B pre-NDA meeting is expected to be held with the FDA in the third quarter of 2022 followed by a potential NDA submission soon thereafter. Aside from the 12-month safety trial, which remains on track relative to prior guidance, the only other active clinical trial for reproxalap in dry eye disease is a randomized, double-masked crossover dry eye chamber trial, where subjects receive both reproxalap and vehicle with a 2-week washout period in between treatments. Enrollment is substantially complete in the crossover trial, which is intended to be adequate and well controlled and, if positive, is expected to be submitted to the potential NDA as a supportive trial. With symptom results shaded in purple and sign results shaded in green, Slide 8 presents a compendium of data that to our knowledge has not been surpassed by any investigational new dry eye disease drug to date. I would like to take this opportunity to thank the hard-working team here at Aldeyra that has spent countless hours over the past 5 years, designing clinical trials, overseeing the assessment of nearly 2,000 patients in completed and active studies, analyzing results, dialoguing with regulatory authorities and communicating with all of our stakeholders, including key opinion leaders and partners. Importantly, I'd like to thank the many patients, health care providers, stockholders, bankers and analysts and other stakeholders who have each in their own way made these truly remarkable results possible. Operator, it's my pleasure to open the line for questions.

[Operator Instructions] Our first question for today comes from Yigal Nochomovitz from Citigroup.

Congrats, Todd and team. Excellent achievement and very consistent with my 97% probability of success from my simulation. I just had 3 quick questions. The first one is, is there any difference in clinical interpretation between the basic Schirmer's test and then the Schirmer's responder proportion test or are those distinctions mainly in the purview of FDA for regulatory determination? Second is regarding the pre-NDA meeting in the third quarter. Could you just help us understand what are the outstanding questions that you'd like clarity from at that meeting? And then last, just quickly remind us why you still need to do that dry eye chamber crossover trials? Correct me if I'm wrong, but I thought that, that was just a backup trial in the very unlikely event that TRANQUILITY-2 didn't work.

Well, Yigal, I got to hand it to you. You are absolutely right with your simulation. We were thrilled to see those notes. And as you pointed out in your notes, there was, I think, some investor skepticism about whether Schirmer test would work. We had never, before TRANQUILITY-2, demonstrated the achievement of Schirmer test as a primary endpoint. And the notion that we would achieve Schirmer test as a primary endpoint in TRANQUILITY-2 had been questioned. I think your simulation analysis put some of those questions to bed. We're appreciative, and you are absolutely right. The question you had about difference between Schirmer test and Schirmer responder test is an excellent one. Some years ago, there was a paper published on the Schirmer test responder analysis, arguing that patients that responded with a 10-millimeter or more increase also demonstrated symptomatic improvement. And thus, that kind of change in Schirmer test is considered to be clinically relevant, which is why, according to draft dry eye disease guidance, the Schirmer test responder analysis on its own may be sufficient for demonstration of efficacy in a dry eye disease NDA. The challenge with the responder analysis, like any responder analysis, where patients are characterized as either yes or no, is that statistical power is lower, the bar for hitting responder analysis in any context, including the Schirmer test, is higher, which is why we are absolutely thrilled to see the results we've generated now in TRANQUILITY and TRANQUILITY-2 with the Schirmer analysis. I don't think, technically, there is a tremendous distinction at the FDA between the Schirmer test and the Schirmer test responder analysis other than what I just said, and that is, if a sponsor is able to show responder analysis changes alone that may qualify for demonstration of efficacy. The fact that we've now shown Schirmer and the responder analysis and redness and symptoms, I think, comprises a compelling NDA package that, as I said in my prepared comments, is absolutely unparalleled. The pre-NDA meeting is, in many cases, often perfunctory. Those meetings are designed to make sure that the content of the package to be submitted for the NDA is sufficient. And there are certain questions that are asked around the content of that package. I don't know that we have too many pressing issues along those lines. However, it's important to hold the meeting. It's important to make the FDA and the division aware of the content of the package that we're submitting. And honestly, I can't wait to have the meeting just given the package that we presented today. The crossover trial was indeed a trial performed, at least in part, as you said, Yigal, as an insurance policy. The reason for the crossover trial is that at least in allergen chambers we've shown remarkably consistent results with symptoms in ocular redness and other measures in allergy when patients are crossed over. The statistical advantage of crossing patients over, that is patients receive both drug and vehicle separated by a washout period, is that inter-subject variability is reduced. And as you know, in dry eye disease, the inter-subject variability is significant, which is why we only have 2 novel eye drops on the market today, and a crossover trial is one way of eliminating that variability. Because the trial has substantially completed enrollment, we're in a position now where those data will be submitted to the NDA. NDA submissions require a disclosure of any clinical data that are -- have been generated or will soon be generated, and this crossover trial is no exception. As we mentioned in our press release, we expect to see the crossover data in Q3, I would even add, early Q3, consistent with the time frames that we've outlined and consistent with our prior guidance.

Great. And again, congratulations on a tremendous milestone.

Thank you, Yigal. We appreciate your support.

The next question today comes from the line of Justin Kim from Oppenheimer.

Todd and team, let me also add my congratulations on these data today. Just 2 questions from me. As you think about the vehicle performance on [ FGT ], how do you think the hypothesis on seasonality have played out for TRANQUILITY-2? And has this been sort of a reason why we're seeing a perhaps dampened response -- vehicle response and perhaps a clear signal relative to TRANQUILITY?

Justin, that's a provocative question. The challenge with dry eye disease aside from the variability is that there are 2 confounding elements in controlled trials. One is a placebo effect, which is a central effect. That is patients are aware that they're doing something to address a persistently disturbing condition that most of them have had for many, many years. The eye is an extension of the brain. The eye is innervated entirely by cranial nerves. When we watch a sad movie, we cry and our eyes get red. A cause of that has nothing to do with the eye. So clearly, there is a central component to dry eye disease that cannot easily be addressed just with eye drops and cannot easily be controlled. The second issue is the one that you highlight, and that is a vehicle effect, which is distinct from the placebo effect. As the draft dry eye disease guidance says from the FDA, even water is effective in dry eye. Every vehicle for topical ocular solutions is, in some way, liquid, and thus will have an effect, and I think that is what we're seeing here. Whether that effect relates to seasonality, I do not know. We are focused entirely on putting together this NDA. And as the compelling package we presented today, I do not expect seasonality will come up in our regulatory discussions. But I'm sure you'll see future analysis and as has been discussing seasonality and other aspects along those lines.

Got it. Understood. And just maybe a second question. Regarding the sort of sufficiency of the data around the 3 sign endpoints, I think when we had spoken the sort of additional study ongoing afforded a little bit of optionality there. Just I know you've said that -- and stated that this is going to be supportive in nature. But how much of that optionality sort of rests on specific areas in terms of, is this study sort of a backup potentially in terms of like a misalignment and how the regulators view, what's been demonstrated thus far with Schirmer as sort of being another study that's prespecified with the primary endpoint on Schirmer? Or is this another way to demonstrate efficacy on redness or even maybe just get supportive RASP sort of action into a label? And just kind of wondering how you think about the crossover trial today as you think about the TRANQUILITY-2 results in hand.

Right. The first thing I'll say is that the FDA makes decisions by law based on the preponderance of evidence. As we have tried to make the point today in the press release and in the slides and in my prepared comments, we believe what we have to be the most comprehensive in terms of breadth NDA package ever for dry eye disease. And thus, preponderance of evidence arguments are much easier to make both from our standpoint and from the regulatory standpoint in theory. I mentioned that we have acute trials up to one day, as soon as one day. We have chronic trials as long as 12 weeks. We have a safety trial of 12 months. So we're literally spanning the gamut duration of dosing from one day to a year. We have field-based studies that is diary-based studies where subjects or patients go home, take the drug, report their symptoms, come into the clinic, are assessed by investigators. And we also have challenge-based studies. These are the dry eye chamber studies where patients are exposed to a noxious high air flow, low or no humidity environment. The crossover trial is yet another kind of trial design that, I think, if positive in any way, would be highly supportive. In fact, it's difficult for me, having been in clinical development now for almost 30 years, to think of another way of testing this drug in terms of clinical trial design. So for us, the crossover trial was the final piece of the puzzle. As Yigal pointed out in his question, technically, the crossover trial is not needed. As of some weeks ago, we believe that we have met the efficacy requirements for NDA submission. As of today, we believe we have met NDA efficacy requirements for submission for symptoms and 3 different sign endpoints, and thus the outcome of the crossover trial we have deemed to be supportive. I hope that answers your question, Justin.

The next question today comes from Marc Goodman from SVB Leerink.

Todd, can you talk about the long-term safety study a little bit, maybe update us on the number of patients that have gotten out to 12 months so far? I mean, what kind of discontinuation rates are we seeing? And then just remind us, just about the CMC portion. Are we all set there? Everything is done? All the work has been ready for FDA?

Yes. Great questions, Marc. As I said before, I think many investors forget about safety trials and CMC preparations, which are obviously critical to regulatory authorities and to NDA submissions and to marketing approval. The classic chronic 12-week -- sorry, 12-month safety trial is what is specified in draft FDA guidance for dry eye disease. And as I mentioned in my prepared comments, the safety trial remains on track for an NDA sufficient along the timing of what I have suggested today, which is third quarter. We don't know exactly which patient is in which group, drug or vehicle. That trial is masked. But we do have an idea based on randomization and enrollment numbers about the number of patients we expect to be on drug. Obviously, drug exposure is what matters. And at some point, that trial will be unmasked. But the unmasking will likely not occur until post-NDA submission pending agreement with the agency, and there is precedent along those lines for other drugs. So by and large, I think we're on track with the safety trial. We do not have any outsized dropout rates. If anything, and this is based on our best guess of masked data, more subjects are dropping out in vehicle group than the drug group, and that's probably because many patients do not derive benefit from vehicle treatment. But those data are to be determined and they will be subject to unmasking, of course. The CMC portion is important. And I think we have put together a gold-plated CMC package for the agency. The drug product is stable, and it is -- has been sufficiently packaged. All of that has been characterized. We've had a preliminary pre-NDA type meeting regarding CMC questions, which was, in our view, remarkably successful. And I don't see anything changing along those lines regarding the CMC. But thanks for asking the question, Marc.

And then just one additional one. How did the red eyes endpoint do in the study?

The secondary endpoints were not achieved in TRANQUILITY-2. The good news is we have now 2 positive symptom trials. We have 2 positive redness trials. We have 2 positive Schirmer test trials. We have 2 positive Schirmer test responder trials. And as I mentioned in my response to Justin's question, this is the most comprehensive package, to our knowledge, ever submitted to a dry eye disease NDA. The preponderance of evidence, in our view, is absolutely overwhelming. And we're focused on the NDA submission, obviously, at this point.

The next question today comes from Kelly Shi from Jefferies.

Todd and Aldeyra team, congrats on the tremendous success. So my question on the commercial side. After this TRANQUILITY-2 result, have you started engaging with the physician community? And what kind of feedback have you heard so far in terms of product differentiation from other dry eye drugs? And also my second question is, if the drug got approval, how should we think about the pricing relative to other marketed products?

Kelly, thanks for the question. I look forward to seeing you shortly at your conference this week. Happy to address the commercial questions. The feedback from the optometry and the ophthalmology community has been remarkable. As you know, about half of the scripts in dry eye disease, if not more than half, are written by optometrists. So we have undertaken a rigorous effort to reach out not only to ophthalmologists but also to optometrists. And the response to the profile that reproxalap has generated to date, particularly given the data released this morning, has been absolutely tremendous. I think what matters most to health care providers and patients is symptoms. Patients want to feel better. Providers want their patients to feel better. The challenge with today's standard of care is that feeling better takes a long time, weeks, if not months. The beauty of reproxalap, as you can see from the slides we released this morning, is that the drug symptomatically works quickly. Symptoms are improved rapidly. And that is the most differentiating and important factor from a commercial standpoint. I think the fact that there is potential to get redness on the label is important. As I have stated before and will continue to state, redness is the only sign that patients care about. And then finally, a Schirmer test, as was mentioned by one of the key opinion leaders in our press release this morning, is the most commonly utilized sign for approval of dry eye disease drugs. That is what health care providers are used to seeing on a drug label. And so we're thrilled potentially to have 2 different kinds of Schirmer test in our -- Schirmer test analysis in our label. So all in all, I think, the KOL feedback has been absolutely superb. Pricing is still being worked out. We had a pricing group here at Aldeyra, an access group. And those conversations with payers, distributors and other stakeholders are ongoing. I will just point out our comparables are $600 to $700 a month, that is RESTASIS and Xiidra. RESTASIS, and cyclosporine broadly, has since gone generic. Obviously, those generics are sold at a discount, but I would say not at a tremendous discount to RESTASIS. We do not see a price erosion in the near term for either Xiidra or a potential reproxalap product, if approved. I think the reason for that is that many, many patients have failed cyclosporine. And cyclosporine takes typically a long time to work, especially symptomatically in many patients. And that by and large, the medical need remains and is substantial for a noncyclosporine product in the future, Kelly.

Congrats again.

Thank you, Kelly.

The next question today comes from Tom Shrader from BTIG.

Congrats on the data. I actually had a broad question on the filing strategy. You have 2 positive redness tests, one of which uses a novel approach to measure; and then 2 positive Schirmer tests, one of which Schirmer wasn't the primary endpoint. Why are you choosing the redness? Is it lower risk? Could you file on Schirmer's? And is part of the strategy to force the FDA to opine on this novel redness test to optimize the chance you get it in the label? It's kind of a broad question on why this way.

Tom, interesting question. I think the strategy in a nutshell is to present an aggregate of evidence that is overwhelming. The Code of Federal Regulations, under which the FDA operates, specifies preponderance of evidence in favor of safety and efficacy, and that is the package we will submit. Exactly what gets on the label, exactly how the label looks is a discussion to be had during the NDA review process. I will say with regard to redness, I am not concerned about using automated assessments. As you know, automated assessments have been used for many years now for other NDA submissions. They have been used in other areas of the eye. I do not expect a significant pushback on the use of an automated assessment, per se, particularly given the data that we have. How that appears in the label, I think, is a subject of negotiation. But we're proud of the data we've generated. We're proud of the fact that we went back and looked for a more sensitive method to assess an objective sign of dry eye disease. The results were strong, they worked, and we're broadly thrilled with our redness assessment.

If I can ask one quick follow-up. You said secondary endpoints were not achieved. Have you tried the automated assessment yet on TRANQUILITY-2 for redness? Or will that take time?

We have. We have not -- these are top line results. We don't have all the data, but the answer to that question is yes. To be honest, we're focusing on the submission. We're focusing on achieving 2 positive trials for symptoms and signs. We've done that now, we believe, in 2 symptom trials and in 6 sign trials. Maybe at some point, we'll get around to thinking about other things. But our mission -- our steadfast mission is to get this drug in the hands of patients and providers. And as I said before, we're focusing on the NDA.

The next question today comes from Catherine Novack from Jones Research.

Congrats on the data. I just have a couple. One is on when we're going to see the full safety data and were there any other notable signals besides this transient ocular discomfort. And then I wondered if you could talk a little bit more broadly about the recent decision. Does it make Schirmer as the primary endpoint back in May? If you can discuss a little about what factored into that decision ahead of this readout.

Thanks for the excellent questions. Typically, what happens is post-NDA submission, a series of papers, posters, presentations are released that detail clinical data across all trials, particularly the 5 adequate and well-controlled trials that we expect to submit as pivotal. And I don't think we will deviate from that practice. So we will keep you busy and entertained with a full data set in the future. I will say, particularly based, for example, on the final slide of our deck today, I think Aldeyra discloses clinical data more -- in a more fulsome manner than most companies. And we're just thrilled with the results that we're able to post today. There have been no safety signals, as I said in my prepared remarks. Typically, for topical ocular drugs, there are 4 main assessments. One is the slit-lamp exam, which most of us have had, where a narrow beam of light is moved across the surface of the cornea and the integrity of the cornea is assessed. The other is fundoscopy, which is another way of saying retina exam. That's the back of the eye. A third one is intraocular pressure, as would be important in a disease such as glaucoma, for example. And then the fourth one is visual acuity. We've had about -- we've had over 1,700 patients now in completed trials. We have another 200 to 300 or so in active trials, including the safety trial. We have never seen a single example of a clinically significant safety concern. And I think the reason for that is the mechanism of the drug in part, which is modulation of RASP, unlike almost all other drugs on the market today, the reproxalap, ADX-629, other RASP modulators, do not activate or shut down a single protein. Most drugs in the market today are receptor agonists or receptor antagonists or antibodies against the protein or inhibitors of a particular enzyme. The good news there is specificity. The bad news is toxicology. When you're turning off or turning on specific proteins that are not meant to be turned on or turned off in normal physiology, I think, there is the potential for adverse events relating to safety. That is not what RASP modulators do, and I think that is consistent with the safety profile that we've generated to date. Let me talk about your second question, which is the designation of Schirmer test as a primary endpoint. Our decision matrix was pretty clear. We have hit 2 trials. We've achieved success in 2 trials with symptoms. We have achieved success in 2 trials for ocular redness. And the advantage of adding Schirmer test to that list was substantial for the reasons we've talked about today. And thus, statistically -- from a statistical standpoint, it made perfect sense to allocate all of our statistical alpha to Schirmer test, which is a fancy way of saying the odds of getting Schirmer test to work are increased when you're only testing Schirmer test, which is why Schirmer test and the Schirmer test responder analysis were the exclusive members of the primary endpoint family. Fortunately, that paid off and both of those tests were positive which, as an upside, now allows us potentially to submit 2 more signs in our NDA and potentially, as I said in my prepared remarks, have at least 2 objective signs dry eye disease that are labeled.

Excellent. Congrats again on the data.

Thank you, Catherine.

The next question today comes from Yale Jen from Laidlaw & Company.

Congrats on the outstanding data. My first question here is slightly different from -- typical -- similar to the one posted earlier, but in a slightly different approach, which is that if the all 4 signs and symptom being accepted and actually be in the label, for approval -- after approval, how would that differentiated from other drugs currently in the market as well as actually a potential competitor from Bausch + Lomb, the NOV03? Just curious how -- what's your thoughts.

Yale, I must admit I thought of you the other day. It seems like just yesterday we were on the phone talking about our first positive Phase II trial in 2016 in ocular allergy. We've been so appreciative of your support over the years, and it must be interesting for you to see our progress as we have moved from a Phase IIa result to the punitive completion of Phase III in dry eye disease. I think the commercial implications of today's announcement are substantial. Pending FDA review, pending label negotiation and so forth, the potential is remarkable for a label that is, in many ways, completely different from most of the other therapies used to treat dry eye disease today. As I mentioned in my prepared comments, the most commonly utilized approval mechanism, at least with the U.S. FDA, is the Schirmer test responder analysis. So if you look at the label for RESTASIS, you look at the label for other drugs and other drugs in development, I think what you'll find is a lot of Schirmer test. But to my response to prior questions, symptoms are really what matter commercially. And really, what matters about symptoms is how fast your drug is working, which is the key commercial differentiator in theory for reproxalap. I think the potential of having symptoms plus at least 2 signs on the label is remarkable in the sense that it allows discussion of many different aspects of how the drug is working. Not every dry eye patient is the same. My personal belief, and I think the belief of many key opinion leaders, is the etiology of dry eye disease is broad. So it makes sense then to have not only a rapidly active drug, but also a drug that spans the gamut of activity in terms of breadth. We've highlighted the comprehensive nature of this submission today. We've highlighted the breadth of our potential submission package. To the extent that even a little bit of that winds up on our drug label, I think, portends very favorably for reproxalap as a commercial prospect.

Okay. Great. That's very helpful. Certainly, it's a long way. And finally, it paid off wonderfully so far. And maybe the last question here is that, again, potentially, would there be any post-approval potential commitment in terms of any other study that you may think of? Or that's not necessarily the case in these situations?

Yale, based on the pre-NDA meeting request, based on the package we put together for the pre-NDA meeting, I do not expect any post-approval commitments. Obviously, that expectation is contingent on actually having such a meeting. But I think there's a huge amount of precedent in this space. We have been in regular and fruitful dialogue with the FDA over many years now. Anything is possible, but my expectation is that we will have no post-approval commitments, per se.

Okay. Great. And again, congrats.

Thank you, Yale.

Thank you. There are no additional questions awaiting at this time. So I'll pass the conference over to Dr. Brady for closing remarks.

Thank you, operator. Believe it or not, our potential NDA submission in dry eye disease is only one of a number of expected clinical milestones upcoming in the months ahead. And as always, we look forward to sharing the details of those with you in the very near future. Thanks again for joining us this morning for this truly exciting announcement.

That concludes the Aldeyra Therapeutics conference call. Thank you for your participation. You may now disconnect your lines.