Good morning and welcome to the Aldeyra Therapeutics Third Quarter 2020 Financial Results Conference call. After the speaker's presentation, there will be a question and answer session. If you would like to ask a question during that time, please press star, then the number one on your telephone keypad.

At this time, I would like to turn the call over to Mr. Joshua Reed, the Company's Chief Financial Officer. Please go ahead, sir..

Thank you. And good morning, everyone. On the call with me are Dr. Todd Brady Aldeyra’s President and Chief Executive Officer, and David McMullin, our Chief Business Officer. Dr. Brady will begin with an overview of our recent highlights and expected upcoming clinical milestones.

I will discuss our third quarter financial results and then we'll take your questions. Please note that this morning's conference call contains forward looking statements regarding future events and the future performance of Aldeyra.

Forward looking statements include statements regarding the timing of planned clinical trial initiations, Aldeyra’s possible or assumed future results of operations, expenses and financial position, business strategies and plans, research development and commercial plans or expectations, trends, market sizing, competitive position, industry environment and potential growth opportunities among other things.

These statements are based upon the information available to the Company today. 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 Company's press release issued this morning containing financial results for the quarter ended September 30, 2020 and the Company's filings with the SEC.

And with that, I'll turn the call over to Dr. Todd Brady, our President and Chief Executive Officer..

Thank you, Joshua, and good morning, everyone. This has been an unprecedented year, one that has demonstrated the incredible resilience of doctors, nurses and other health care professionals on the front lines of the global fight against Covid-19.

The resolve and speed with which the potential lifesaving therapies and vaccines are being developed remind us daily of why we are exceedingly proud to be part of the life science industry.

Despite the many external challenges this year, we have made significant progress against our clinical objectives in our ocular disease programs, our lead candidate reproxalap continue to advance toward NDA submission in dry eye disease and allergic conjunctivitis, two of the world's most common ocular surface conditions affecting more than 100 million patients in the United States alone.

This quarter we're on track to initiate a randomized double-masked parallel-group Phase 3 clinical trial to assess the activity of reproxalap and an objective sign endpoint of dry eye disease.

Consistent with prior guidance and subject to finalization of trial design, the 28-day pivotal trial will measure the effect of reproxalap on tear RASP levels after single and multiple doses of drugs.

The trial will include exposure to a controlled environment chamber to assess the effect of acute changes in dryness on a range of objective signs, including tear RASP levels, ocular redness and Schirmer score. The purpose of the chamber is to exacerbate dry eye disease signs and symptoms with low humidity, high airflow and forced visual tasking.

Importantly, we have previously tested the activity of reproxalap in an allergen chamber in which reproxalap demonstrated acute improvement in ocular itching and redness almost immediately after drug dosing. The Phase 3 trial will include a 20 patient run in phase with 10 drug treated patients and 10 vehicle treated patients.

The run in phase is expected to be completed by year end. To confirm the accuracy and applicability of RASP assay methods, we recently initiated a natural history study in which we collected tear samples from approximately 20 dry eye disease patients.

In the coming weeks we plan in vitro analyses of the tear RASP levels at baseline and following exposure to drugs or vehicle. Per standard NDA submission requirements, a separate safety study of reproxalap in dry disease patients is on schedule to begin next month.

From a safety perspective reproxalap has been evaluated in more than 1,100 patients with no observed safety concerns. Overall, we remain on track to file an NDA submission in dry disease by the end of 2021.

Importantly, all of our expected timelines are subject to a number of factors, including finalization of trial design, completion of assay development, positive clinical results, regulatory review, potential disruptions due to Covid-19 and other factors that may not be in our control.

Enrolment has restarted in the Phase 3 INVIGORATE trial of reproxalap in patients with allergic conjunctivitis.

As a reminder, INVIGORATE is being conducted in an allergen chamber and trial initiation was paused in the second quarter to avoid the confounding effects of environmental pollen during what was an unusually early and extended allergy season in the beginning of the year.

INVIGORATE is a randomized double-masked crossover vehicle controlled Phase 3 clinical trial, with a planned enrolment of approximately 126 patients. Consistent with prior allergic conjunctivitis trials the primary endpoint will be subject reported ocular itching score.

Top-line results are expected in the first half of 2021 and NDA submission is expected by the end of next year pending positive results and regulatory review. Over Phase 2A, Phase 2B and Phase 3 trials, reproxalap has consistently demonstrated a uniquely durable response that likely outlast that of standard of care antihistamines.

In addition to durability, the rapid onset of response will be highlighted in a poster presentation next week at the American Academy of Ophthalmology 2020 virtual annual meeting.

The poster features new data from responder analyses of our Phase 2 allergen chamber trials, as well as new data on ocular tearing and post chamber activity of drug after exposure to allergen has ceased.

The data further support the clinical utility of reproxalap suggesting the possibility of rapid efficacy in reducing redness and itching in allergic conjunctivitis. For these reasons, we remain particularly excited about the potential of reproxalap as the first novel mechanistic approach for late stage allergic conjunctivitis in decades.

Turning to the posterior segment of our ocular disease pipeline, we expect to complete enrolment in part one of the Phase 3 GUARD trial of ADX 2191 for the prevention of recurrent retinal detachment due to proliferative vitreoretinopathy or PVR by the end of 2021.

PVR is the leading cause of retinal detachment surgery failure affecting roughly 4,000 patients per year in the United States and nearly twice as many in Europe and Japan combined.

Recruitment for the GUARD trial is underway at more than 20 clinical sites across the United States and as I noted in our Q2 call, the pace of enrolment has been slower than anticipated particularly due to delays caused by Covid-19.

ADX 2191 may also have the potential to treat Primary Vitreoretinal Lymphoma or PVRL, a rare, aggressive high grade cancer that affects approximately 2,900 people in the United States, with about 600 new cases diagnosed annually. There are no approved treatments for this severe type of ocular cancer.

As for our systemic disease programs, in September, we received a study may proceed letter from the FDA clearing the way to start Phase 2 testing of ADX 629 our orally available RASP inhibitor for the treatment of adult patients hospitalized for Covid-19. We continue to expect the trial to begin by year end.

This quarter we also plan to initiate Phase 2 clinical trials of ADX 629 for the treatment of severe inflammation associated with TH2 types cytokine production represented by atopic asthma and TH1 type cytokine production represented by psoriasis.

As I noted on our Q2 call, testing in an animal model of cytokine storm suggested that RASP inhibitors have the potential to act as immunological switches that may broadly modulate immune systems from pro inflammatory states to anti-inflammatory states.

Target engagement of ADX 629 was confirmed in our Phase 1 clinical trial, in which reduction in the commonly described pro inflammatory RASP malondialdehyde was observed in treated subjects. ADX 629 was well tolerated and no treatment related adverse events were observed in the trial.

We head into the final two months of the year in excellent financial condition.

Based on current operating plans we believe we are well capitalized and expect our cash runway to fund operations through 2022, including potential NDA submissions for reproxalap in dry disease and allergic conjunctivitis, assuming positive clinical trial results and regulatory review.

Now, I'll turn the call over to Joshua for the third quarter financial review..

Thanks Todd. For the quarter ended September 30, 2020, we reported a net loss of $8.9 million compared with a net loss of $18.7 million for the quarter ended September 30, 2019. Net loss per share was $0.23 for the quarter ended September 30 2020, compared with $0.69 for the same period in 2019.

Losses have resulted from the cost of clinical trials and research and development programs, as well as from general and administrative expenses. Research and development expenses were $6.1 million for the quarter ended September 30 2020, compared with $16.2 million for the same period in 2019.

The decrease of $10.1 million is primarily related to a reduction in clinical research and development expenditures and lower personnel related costs, partially offset by increases in manufacturing and preclinical development costs.

General and administrative expenses were $2.3 million for the quarter ended September 30, 2020, compared with $2.8 million for the same period in 2019. The decrease of $500,000 is due to lower personnel related costs and other miscellaneous administrative costs.

For the quarter ended September 30, 2020 total operating expenses were $8.4 million compared with total operating expenses of $19 million for the same period in 2019. Cash, cash equivalents and marketable securities were $86.2 million as of September 30, 2020.

Based on current operating plans our cash, cash equivalents and marketable securities as of September 30, 2020 are expected to be sufficient to fund operations through the end of 2022, including potential NDA submission for reproxalap in dry eye disease and allergic conjunctivitis, pending clinical trial results, regulatory review, potential disruptions due to Covid-19 and other factors that may not be in our control.

Use of cash, cash equivalents and marketable securities are also expected to include part one of the Phase 3 GUARD trial in PVR and Phase 2 clinical testing of ADX 629 in orally administered RASP inhibitor in inflammatory diseases. Now I’ll turn the call back to Todd for closing comments..

Thanks, Joshua. As you can tell, we have a busy several quarters ahead highlighted by significant clinical development milestones beginning this quarter and throughout 2021.

We look forward to keeping you updated on our progress as we execute on our strategic plan to bring forward potential best in class immune modulating therapies that improve the lives of patients with serious unmet medical needs.

This month we will be participating in the Jefferies Virtual London Health Care Conference and the Alliance Global Partners Virtual Health Care Symposium. Please check the events and presentation section of our website for details. In addition, I would encourage you to register for tomorrow's Eyecelerator 2020 Virtual Conference.

Eyecelerator is a new partnership between the American Academy of Ophthalmology and the American Society of Cataract and Refractive Surgery. Aldeyra is one of a number of companies participating in the event at Eyecelerator. com. With that, Josh, David, I'll be happy to take your questions.

Operator?.

Operator:.

Hi, this is Samantha on for Yigal. Thanks very much for taking our question. A couple for me. Todd, thanks for the details on the RASP trial. Just curious, what are the gating factors before you start that trial later this quarter? And it seems like you're sort of combining both the chronic setting of the 28 days and the more [heat] [ph] setting.

Curious what the FDA has a preference on which of those settings is more important to them or are they equally important?.

Good morning, Samantha, and thanks for the question. There is no preference from the FDA as to the chronicity of dosing. In fact, we clarified with the agency that single or multiple doses could be used to demonstrate physically significant changes in signs between drug and vehicle.

I don't think there are any gating factors in particular regarding the start of the pivotal trial. We do intend, as I mentioned in my prepared comments today, to complete analysis of the natural history study in dry patient, where we extracted tears from about 20 dry-eye subjects.

And those tears will be analysed for RASP levels to confirm the RASP assay and confirm parts of the pivotal trial protocol. However, at this point, we are comfortable with our guidance that not only will the pivotal trial begin this year, but it will be in a position to complete the 20 patient run in phase of that trial by year end..

Okay, great. And you're going to run two RASP trials.

Is it fair to assume that both of them are going to have the same design?.

I think the design of the second trial depends on the outcome of the first trial and particularly the outcome of the 20 patient run in of the first trial. If, for example, we're able to demonstrate changes in RASP over two days of dosing, it doesn't make sense in the second trial to treat patients for 28 days.

I think there are probably some other protocol design changes that we may choose to make depending on the outcome of the first trial. So I think we'll have to wait and see for the data to arrive before we can comment in particular on that second protocol design..

Okay, got it. That makes sense. And then I remember we had some conversations in the spring about the allergen chamber for allergic conjunctivitis, given the context of Covid-19 and now you're using a similar chamber designed for the RASP trial.

Are you implementing testing prior to entry into the into the chamber? And how are you thinking about that for both dry-eye disease and allergic conjunctivitis going forward?.

Testing is required for entry to either chamber, either the dry chamber or the allergen chamber. Patients must meet certain criteria at baseline, for example, a history of either dry eye disease or allergic conjunctivitis. And I think now with Covid-19, there's a variety of other measures that must be met prior to trial entry.

The other thing I would note is that for patients to qualify in either the dry eye disease trial or the allergic conjunctivitis trial at baseline, certain criteria must be met. Patients must exacerbate in the chamber. In the case of dry eye disease, patients must exacerbate after a dose of vehicle in the dry eye chamber.

So we're quite careful about precisely who we enrol in the trial. And obviously we're attempting to optimize screening criteria such that the differences between drug and vehicle are expanded..

Okay, great, that's helpful. And then just one last one for me, I'm curious if you have any updates on where you stand for ADX 2191 Primary Vitreoretinal Lymphoma, I believe last we spoke on that, you said you were looking to see what data you would need in order to file with the NDA with the FDA, any update you have there would be helpful..

You're absolutely correct, Samantha, that methotrexate is the standard of care for the treatment of ocular lymphoma. There really is no other therapy that's routinely used to treat the condition. However, there is no methotrexate formulation that's approved for intravitreal injection to treat the disease.

So thus there is a tremendous unmet medical need. Today physicians treat that condition by compounding methotrexate, which has a long series of issues associated with it, including potential infection, the standardized drug doses and so forth that are very difficult to control with compounding.

This is why our interest in ocular lymphoma is quite strong. And you are correct that at this stage we're in the process of discussing how best to advance ADX 2191 in ocular lymphoma with the FDA, and we look forward to guiding on next steps I hope early next year..

Okay, great. Thanks very much for taking the questions Todd..

Thanks..

Thank you. And your next question comes from the line of Louise Chen with Cantor Fitzgerald. Please go ahead..

Hi, this is Jennifer Kim on for Louise. Thanks so much for taking our question.

My first question, I just wanted to clarify the Phase 3 trial that's being initiated for reproxalap this quarter, is that the first of the two planned RASP trials you've talked about before? So are top line results for that trial still expected by the end of 2020? And I was wondering if you have any updates on the timing of the second trial..

Hi, Jennifer. Good morning. Yes, the first of the trials for the objective sign in dry eye disease, the first of the pivotal trials will begin this year.

By the end of the year, we will have results from the first 20 patient run in which is important for the reasons that I explained earlier in the call in that that 20 patient run in will, a) give us an indication as to how well the RASP assay is working. It will confirm a protocol for the remainder of the trial.

It will confirm the statistical power for the remainder of the trial, and it will probably indicate the protocol for the second pivotal trial..

Got it.

And maybe one other question, considering that the Phase 2 trials for ADX 629 are starting by the end of 2020 and reproxalap is also starting by the end of 2020, I'm just wondering how should we think about the impact of the timing of these trials on R&D costs or maybe the fourth quarter and going to 2021? And then on a similar note, SG&A cost you know, it's been managed pretty, pretty well.

I'm just wondering, how should we think about that as we get into 2021 as well?.

Thanks for the question. So with respect to SG&A, you should continue to expect that to be relatively consistent in the way that you see quarter over quarter. And you're right, given the trial initiations later this year and into 2021, you should expect to see an increase in R&D costs this quarter in Q4 and into next year..

Okay, helpful, thank you..

Thank you. And your next question comes from the line of Justin Kim with Oppenheimer. Please go ahead..

Good morning, this is Jackie Yan for Justin. Thanks for the question. So my first question is, do you have any additional updates on how you think about RASP as an endpoint and how you plan to measure it in upcoming clinical studies based on any additional assay work or feedback from the agency? Thank you..

Hi, good morning and thanks for the question. I think as we've discussed in prior calls, there are two main methods to measure RASP levels depending on the kind of RASP that are measured. RASP exist in free forms. They also exist in protein bound forms. So the typical method to measure free levels of analytes is mass spec.

And the typical method to measure proteins bound analytes is ELISA, which is an antibody based approach. So both of those methods are what we are assessing currently with the dry eye disease natural history trial where we've taken tear samples from dry disease patients.

That's an in vitro assessment that's occurring and will indicate, I think, the precise method that we use in the pivotal trial, the top line results of which, as I mentioned, we expect by year end..

Thank you. And then perhaps for Dave, you know, as your [indiscernible] described activity on RASP and ocular discomfort score ODS in combination with treatment of allergy.

How do you think about the commercial launch and what features will drive adoption of the reproxalap?.

Yeah, thanks for that question. It's a great one. We - when I think about reproxalap and our target product profile, you're right, there's a lot of different legs of differentiation. At the core of the profile is differentiation on the dry eye disease front and in the marketplace this is a symptom driven disease.

And so the aspects of reproxalap that are really exciting are the early and broad improvement in symptoms. We think it's remarkable what we've seen with reproxalap where with this product that can treat the chronic inflammation, you can also see improvement in symptoms at one week.

So if we're successful, you'll have for the first time a safe and effective anti-inflammatory addressing the core of the disease that you're able to use to treat the condition chronically. But that can also benefit the patient very rapidly.

In addition, we see in our profile the ability to reduce or improve the symptoms, symptoms that the patients are experiencing across the spectrum. And so that broad advocacy, we believe, is indicative of how it will translate into more patients and more doctors having a positive experience with the product itself.

Those are two things that we know that the market is looking for. The current solutions aren't a great fit and they don't meet those needs, and so there are unmet currently. In addition, dry eye disease is an ocular surface disease. It's not the only one. It's one of three big ones.

The biggest one is - one of the biggest ones is allergic conjunctivitis and allergic conjunctivitis and dry disease overlap tremendously.

And all you have to do is to market research, to learn and see how these two conditions of overlapping can make to treat - the effective treatment of these patients difficult for physicians and can make it very frustrating for patients. What's currently available is not a great fit for that overlap.

And here with reproxalap, we have again a unique solution. We've seen the ability of this drug not only to address the signs and symptoms of dry eye disease, but also allergic conjunctivitis. And so we're seeing a future where you would have one product that simplifies a lot of things for the doctors and for the patients.

And while the profile of the marketplace is different for dry eye disease and allergic conjunctivitis, we're developing reproxalap with our first focus on dry disease and then allergic conjunctivitis as an added differentiator to that profile.

Our development programs are such that we as announced today we anticipate that we will be able to submit a concurrent NDAs for both indications..

Great. This is super helpful. Maybe, if I may, my last question is just given a resurgence recently seen in Covid-19 cases, can you talk about specific criteria or conditions that would make site initiation or program initiation. And again, thanks for all the question..

We have not heard from our CROs that Covid is going to dramatically impact enrolment at this point. As you mentioned, the caseload around the world is increasing and it is certainly possible that Covid-19 infections could impair enrolment.

But at this point, we have not heard from CROs that Covid-19 will dramatically impact either the rate of enrolment or the ultimate number of patients. I will say that many sites, including sites we're working with, are testing for Covid.

This has been viewed as a benefit in some cases by potential subjects in clinical trials because the Covid test is essentially free and that it's required for entry to the trial. I expect that kind of testing to continue. And our hope is that as even as cases arise around the country and around the world, that enrolment continues per plan..

Got it. Thank you..

Thank you. And your next question comes from the line of Matthew Cross with Alliance. Please go ahead. And Mr. Cross, your line may be muted..

Apologies, thank you. Hey, guys, thanks for the progress updating and looking forward to seeing you at the conference later this month. Just had a couple of quick questions.

First off, in terms of the kind of sign trial design changes here, updates, rather, I just wanted to confirm whether the decision to include multiple signs here was in fact FDA directed or was, you know, more internally devised and whether you could comment on how those may be handled statistically, considering RASP, redness and Schirmer, you consumers need to kind of hit on all of these or if there will be some kind of composite end points, just any kind of thoughts at this stage?.

Matt, good morning and thanks for the question. The activity of reproxalap is broad, so it made sense to us to test a variety of signs, is the short answer. The FDA did not require that multiple sign assessment. I do not expect to take statistical penalties or adjust for multiplicity as a result of testing multiple signs.

I think the reason for testing signs is to continue to generate evidence for the broad activity of reproxalap in dry eye disease. There is good reason, I think, to believe that reproxalap will have an effect on redness.

Those data we have released from allergen chamber studies for quite a while now, you will see more redness data at the American Academy of Ophthalmology poster shortly. That is one reason we're testing at least redness and dry eye disease after acute dosing.

And then, as you recall, our Schirmer test results are very good in our Phase 2b trial released back in 2018 in dry eye disease. Those are the reasons we're looking at a variety of additional signs, particularly because I think the breadth of activity of reproxalap is a major differentiator for this drug within the dry eye disease landscape..

Yeah, no, I wholeheartedly agree, and that makes complete sense. Thanks for the clarity there. And then just another one around the - it looks as though the path forward for dry eye is adapted in a number of different ways.

I guess one starting with this this kind of run in portion and the natural history study analysis prior to the actual, you know, full second trial.

I guess just wanted to get a little bit of understanding of whether post run in by the end of this year, at that point, even in the first of these RASP trials, you may take a second to adjust some of these parameters. I know we've discussed the [pushing] [ph] down versus freely circulating rasp assessments, single versus multi dose.

But is it fair to assume that once the running is gone on and certainly completed, you would kind of, you know, at that point commit to one form of method of measuring RASP and one kind of treatment protocol, or if that may change mid this first study post running?.

Matt, as usual, you are absolutely correct. We have intentionally designed a couple of clinical data outputs to help us plan the pivotal aspect of the trial.

The first of those is the natural history study, which I've mentioned a few times this morning, which is really functioning as an in vitro Phase 3 to assess RASP levels in the tears of dry eye patients. And as I mentioned in my prepared comments, the tears from those patients will be tested at baseline.

They'll also be tested after exposure to drug and vehicle. After the dry eye disease natural history study we’ll have a very good idea of how well the assays I've described earlier are working.

The 20 patient run-in serves a very similar function, which is to confirm the RASP assays and the protocol design before the main cohort of the of the pivotal trial is initiated. To your point, the protocol may change somewhat depending on the results of both the natural history study and the run-in.

The good news is RASP are the first new novel sign in dry eye disease in decades. The bad news is this has not been done.

And so I think that part of the rationale for the natural history studies and part of the rationale for the run-in phase of the pivotal trial is to confirm the protocol and the assays and so forth in an area that I think is very novel and exciting..

Perfect. Yes, no, another very creative design from you guys, so I appreciate you confirming that and looking forward to the very forthcoming progress interview the end of the year. Thanks Todd..

Thank you very much, Matt..

[Operator Instructions]. And your next question comes from the line Julian Harrison with BTIG, please go ahead..

Hi, good morning, thank you for taking my questions and congrats on the quarter.

On the assays I was wondering if you could talk a little about your experience measuring RASP with ELISA and mass spec so far beyond the natural history study and how you're applying any learnings there to your ongoing efforts?.

Julian, thanks for the question and I'm glad you asked.

I think it's important to remind everyone that back in Phase 2a in dry eye disease, we demonstrated statistically significant changes from baseline after drug treatment of RASP in dry eye disease, which is another reason why ELISA is part of the assay mix, not only for the natural history study, but also for the pivotal trial.

ELISA is an interesting approach because protein bound RASP, again, which we showed change after drug treatment in Phase 2a are chronic indicators of inflammation and change over time. I think what is also possible, based on the literature and based on the Phase 2a trial, is that RASP - protein bound RASP levels may also change acutely.

And so as part of the natural history study and part of the run-in will be using ELISA for both acute and chronic assessments of RASP changes alongside mass spec, which is primarily designed to measure acute changes in RASP..

Okay, great. Thank you, that's very helpful.

And then sorry if I missed it, but on the safety requirement for the dry eye disease NDA, how much can you lean on prior data and what work still needs to be done there?.

The safety package, which is part of every NDA submission, as you know, generally needs to be quite extensive. As I mentioned in my prepared comments, reproxalap has been tested in more than a 1,000 patients. We have no serious adverse events.

We have no safety findings that relate to biomicroscopy or fundal assessment or visual acuity or intraocular pressure or any other toxicity that would be significant. So we're quite confident in our safety package.

Those 1,100 patients or so that have been exposed to reproxalap are added to the number of patients in the safety trials, and that will comprise the safety population assessment for the NDA submission.

I think with any indication there is a dialog between the sponsor and the FDA as to precisely how many patients are required for the safety portion of the NDA, that is a function of the number of patients that have been exposed in your prior clinical trials and the number of patients that you intend to test in your safety trial.

I think, though, we're in an excellent position with reproxalap given the safety results and what amounts to be the complete lack of safety issues that we've observed across numerous clinical trials in over a 1,000 patients to date..

Great. Thanks very much..

Thanks, Julian..

And our final question comes to the line of Kelly Shi with Jefferies. Please go ahead..

Hey, thank you for taking my question. The first question is also on the trial design of RASP trial. [Indiscernible] by same criteria as [indiscernible] part one. And also the Phase 2 study that has generated dataset on RASP reduction. And secondly,[do you select patients] [ph] based on the baseline level of RASP.

And what is the impact of the baseline level of RASP on the trial outcome? Thank you..

Kelly, thanks for that. Thanks for the question. Good to hear your voice. I think that the criteria are, if not identical, substantially similar for enrolling patients in RENEW and the upcoming pivotal trial. There is more or less a standard group of enrolment criteria across all dry-eye disease trials.

Patients must have certain symptoms and certain signs to qualify as dry eye patients and thus be enrolled in clinical trials. Our intent is not to deviate from those more or less standard criteria extensively. Your question about baseline RASP levels is particularly fascinating to us.

I do not expect at this point we will require certain RASP levels for enrolment in our trial. That may change depending on the results of the natural history study and the results of the run in phase for the pivotal trial. But at this point, I expect we will enrol all comers as it relates to tear RASP levels.

We'll know a lot more towards the end of this year. Regarding the answer to your question, what effect does baseline RASP level in tears have on the ultimate activity of drug? A priori, I do not expect the effect to be dramatic for two reasons.

One is that from our Phase 2a trial, we know that essentially all dry eye subjects have elevated RASP levels, rasp are a hallmark of inflammation. We know the dry eye disease is an inflammatory condition and thus RASP should theoretically be elevated in all patients.

The second reason I don't think baseline level will play a major role in the activity of drug is that the levels of RASP in tears, as has been published, is probably in the low micro molar range at most, maybe higher for [down] [ph] level of RASP. The drug is millimolar in concentration.

So as we've expressed previously, the administration of a single drop of reproxalap to the anterior surface of the eye essentially represents a thousand fold or more of excess drug relative to levels of RASP.

So whatever the baseline concentrations of RASP are in the micromolar range are unlikely to be affected by the large excess of reproxalap; recall that reproxalap binds to RASP in a one to one stoichiometry. So I think after acute administration of drug, there should theoretically be a near total elimination of RASP whatever the baseline level..

Thank you very much. It's very helpful. And also, I have a second question regarding the this case study.

And do you expect any specific requirement from FDA since reproxalap hold a novel mechanism of action from other dry eye drugs?.

I do not. The novel mechanism of action of reproxalap RASP inhibition has been discussed with the agency extensively from the very beginning across dry eye disease and allergic conjunctivitis.

I think the fact that the agency awarded RASP as an objective sign end point in dry eye disease speaks to the agency's confidence in RASP as a - RASP inhibition as a beneficial mechanism for the treatment of ocular inflammation. We have heard from the agency no specific concern about RASP inhibition as it relates to safety.

And again, based on my prior comments and the number of patients that have been tested with reproxalap, I do not expect that to change..

Great to hear. Thank you very much. That’s all for me..

Thank you very much, Kelly..

Ladies and gentlemen, thank you for your questions. Now, I would like to turn the call back over to Dr. Brady for any closing comments..

Well, thank you again for joining us and on behalf of everyone out there, please stay safe and healthy during the holidays. And as always, we look forward to keeping you updated on our progress..

Ladies and gentlemen, thank you for your participation. This does conclude today's conference call. You may now disconnect..