Aldeyra Therapeutics (ALDX) Q2 2021 Earnings Call Transcript

Aldeyra Therapeutics (ALDX -1.05%)
Q2 2021 Earnings Call
Aug 05, 2021, 8:00 a.m. ET

Contents:

• Prepared Remarks
• Questions and Answers
• Call Participants

Prepared Remarks:

Operator

Ladies and gentlemen, thank you for standing by, and welcome to the Aldeyra Therapeutics second-quarter 2021 financial results conference call. At this time, all participants are in a listen-only mode. After the speaker's presentation, there will be a question-and-answer session. I would now like to hand the conference over to the company's chief financial officer, Joshua Reed.

Please go ahead, sir.

Joshua Reed -- Chief Financial Officer

Good morning, everyone. With me is Dr. Todd Brady, president and chief executive officer of Aldeyra. This morning, we issued a press release reporting our financial results for the quarter ended June 30, 2021.

A copy of the press release is available on the Investors & Media section of our website, www.aldeyra.com. 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 submission of potential new drug applications, potential commercialization, the anticipated timing of results from our clinical trials, our projected cash runway, our possible or assumes future results of operations, expenses and financial position, and potential growth opportunities among other things. These statements are based upon the information available to the company today.

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 risk that results from clinical trials or portions of clinical trials may not accurately predict the results of future trials for the same or different indications; 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 and 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 and our filings with the SEC. I will now turn the call over to Dr. Brady.

Todd Brady -- President and Chief Executive Officer

Thank you, Joshua, and good morning. We began this morning with the exciting news relating to our retinal disease program. Over the past few weeks, the FDA has granted orphan drug designation to ADX-2191, the lead product candidate in our retinal disease pipeline for the treatment of two additional rare disorders, primary vitreoretinal lymphoma, and retinitis pigmentosa. Primary vitreoretinal lymphoma is a rare, aggressive high-grade cancer that affects approximately 2,800 people in the United States with approximately 600 new cases diagnosed annually.

Retinitis pigmentosa is a clinical group of rare genetic eye diseases that affects an estimated 82,000 to 110,000 individuals in the United States and approximately one in 4,000 people worldwide. As noted in this morning's news release, we plan to initiate a phase 2 clinical trial of ADX-2191 in patients with retinitis pigmentosa this year. ADX-2191 has now received orphan drug designation for three distinct clinical indications that affected retina: primary vitreoretinal lymphoma; retinitis pigmentosa; and proliferative vitreoretinopathy, a sight-threatening condition, and the leading cause of failure of retinal detachment surgery and for which we have received fast track designation from the FDA. The prevention of proliferative vitreoretinopathy, as many of you know, is the focus of our ongoing phase 3 GUARD trial, Part 1 of which is scheduled to conclude enrollment at the end of this year.

To get there, these designations highlight the broad platform potential of ADX-2191 to treat a spectrum of rare, yet serious retinal disorders, none of which have approved therapies. Particularly as a result of the recent orphan designations in primary vitreoretinal lymphoma and retinitis pigmentosa, we will be updating you on future calls as to regulatory timelines and the development process for ADX-2191 across the retinal disease platform. Turning to our anterior segment ophthalmology pipeline. We remain on track to discuss results of our phase 3 INVIGORATE trial and our regulatory strategy for reproxalap in ocular allergy with the FDA this year.

The discussion follows the successful completion of INVIGORATE in April, where reproxalap demonstrated highly statistically significant improvement over vehicle for the primary endpoint of ocular itching, and the key secondary endpoint of ocular redness, as well as secondary endpoints. Patient enrollment continues in our phase 3 TRANQUILITY trial of reproxalap for dry eye disease with enrollment in the identical TRANQUILITY-2 trial on track to begin this quarter. Ocular redness is the primary endpoint of these two-day trials with RASP levels, Schirmer's test, and dry eye symptoms as secondary endpoints. We expect to enroll approximately 150 patients per arm in each trial, and top-line results are planned for the fourth quarter of this year.

In parallel with TRANQUILITY, we've initiated a multicenter, double-masked randomized vehicle-controlled parallel-group phase 2 clinical trial in dry eye disease. The purpose of this trial is to optimize the tear collection process to measure RASP. Similar to TRANQUILITY, the primary endpoint of the trial is ocular redness. In addition to our ocular programs, we remain excited about the extension of the therapeutic potential of RASP inhibition to systemic inflammatory disease.

Initial results from phase 2 trials in asthma, psoriasis, and COVID-19 of ADX-629, our first-in-class orally available and irreversible covalent inhibitor of pro-inflammatory RASP are anticipated in the fourth quarter of 2021 or the first quarter of 2022. In addition to the disease areas currently under study, we're evaluating the possibility of expanding clinical testing of ADX-629 and other systemic indications where RASP may mediate pathology and where current therapy is either inadequately effective or toxic. We look forward to updating you on our progress along these lines later this year. With that, I'll turn the call back over to Joshua to review our second-quarter financial results.

Joshua Reed -- Chief Financial Officer

Thank you, Todd. Cash and cash equivalents as of June 30, 2021, were $249.7 million. Based on our current operating plan, we believe that existing cash and cash equivalents will be sufficient to fund currently projected operating expenses through the end of 2023, including potential NDA submissions for reproxalap, initial commercialization of reproxalap, once approved, and continued development of our product candidates in ocular and systemic immune-mediated diseases. Turning now to our second-quarter 2021 results.

Research and development expenses were $11.5 million for the quarter ended June 30, 2021, compared with $4.9 million for the same period in 2020. The increase of $6.6 million is primarily related to the increase in clinical research and development expenditures. General and administrative expenses were $3.1 million for the quarter ended June 30, 2021, compared with $2.2 million for the quarter ended June 30, 2020. The increase of $900,000 is primarily due to an increase in personnel-related costs and other miscellaneous administrative expenses.

The net loss for the second quarter of 2021 was $14.9 million or $0.28 per share, compared with a net loss of $7.5 million or $0.25 per share for the quarter ended June 30, 2020. Looking at our investor calendar, Todd and I will be participating in a number of investor conferences in the coming months, including events hosted by Jefferies, Citi, BTIG, H.C. Wainwright, and Berenberg. Please check the Events and Presentations section of our website for details.

Now I'll hand the call back over to Todd for closing comments.

Todd Brady -- President and Chief Executive Officer

Thank you, Joshua. Aldeyra continues to make significant progress toward our goal of developing effective and highly differentiated new therapies to treat immune-mediated diseases with significant unmet medical need. We are excited about the first-line potential for reproxalap as a treatment for anterior surface inflammatory diseases that for a significant percentage of patients are not being adequately controlled by standard of care approaches. Beyond the anterior segment, we are developing innovative medicines for retinal inflammatory diseases that we believe will create near-term high-value commercial opportunities for our pipeline.

Finally, we're committed to expanding our therapeutic applications to systemic inflammatory diseases, representing a myriad of conditions that are today not sufficiently treated. With that, Josh and I will be happy to take your questions. Operator?

Questions & Answers:

Operator

Thank you. [Operator instructions] Your first question comes from the line of Marc Goodman with SVB Leerink.

Marc Goodman -- SVB Leerink -- Analyst

Yes. Good morning. Can you talk about this new indication for the ERP? So I guess, first of all, your other ideas there came from the docs at Mass Eye and Ear, and you bought the technology out. Did this one come from them, too? Or I'm just kind of curious where the idea came from, why starting the study now? Has the methotrexate off-label being used for this indication before? Maybe you could just give us a little history of that.

And then is there a screening that takes place because this is a genetic disease. Just curious about that. And then also on the phase 2 to optimize the RASP level study that you're talking about there, is that an FDA requirement? Is this going to be one of those supplements after you file? Just curious who's calling that. Thank you.

Todd Brady -- President and Chief Executive Officer

Marc, good morning, and thanks, as always, for the excellent question. And so on retinitis pigmentosa, a program about which we're very excited, I think, as you can tell from our prepared comments this morning. The genesis of retinitis pigmentosa as it relates to methotrexate is a paper that was published out of Case Western and the University of Pittsburgh that's highlighted in our corporate deck that was updated and posted this morning. You can see the data in the deck, which suggest that methotrexate is particularly important in redoxin misfolding.

Redoxin is a protein that's critical in the light sensation cascade in the retina. And methotrexate seems to be able to prevent the redoxin that's holding and certain genotypes of retinitis pigmentosa. So the answer to the second part of your question is that patients in the upcoming clinical trial will be screened genetically not only to identify retinitis pigmentosa, but this particular subtype is genetic subtype of retinitis pigmentosa that seems to respond well to methotrexate. Regarding your question about the phase 2 trial in dry disease that we mentioned this morning in the prepared comments.

This is not an FDA requirement. But as you know, we're particularly interested in assessing RASP levels in tears. RASP is the target of our drug. If we can successfully demonstrate changes in RASP following drug administration, then I believe we will be the first company ever to demonstrate that a topical drug can affect the target of that drug in the tears of patients.

We're also interested potentially in highlighting the changes in RASP in the pharmacology section of our potential drug label if commercialized. So we're taking the assessment of RASP very seriously. Hence, this phase 2 trial which, as we mentioned, is designed to optimize tear collection, obviously, a pivotal process in the assessment of RASP. Thanks, Marc.

Operator

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

Yigal Nochomovitz -- Citi -- Analyst

Great. Todd and Josh, thank you very much for taking the question. I just wanted to follow up on the phase 2 trial that you're running, the new one that you've just announced. You're saying the purpose is to optimize the tear collection process to measure RASP.

Could you just help us understand a little bit better why this wasn't possible within the context of the two TRANQUILITY phase 3s?

Todd Brady -- President and Chief Executive Officer

Of course. Good morning, Yigal, and thanks for the question. I'm happy to clarify the phase 2 RASP trial. The tranquility trials are identical and based on the highly successful run-in cohort from January -- then as part of tranquility, we've identified ocular redness as the primary endpoint.

Ocular redness has numerous advantages. Not to mention the fact that we've consistently demonstrated activity in ocular redness with reproxalap, not only in dry eye disease but also ocular allergy but also because ocular redness is probably the sign, the exclusive dry disease sign that matters to patients. Patients do not care about Schirmer's test. Patients do not care about ocular staining or any other so-called signs of the dry disease, hence, our selection of ocular redness.

Nonetheless, as I mentioned in response to Marc's a good question prior, we're still very interested in assessing RASP and presenting RASP data to the street, and potentially including RASP beta in our product label. This is why that we've initiated this study. Tear collection is tricky. As you know, in dry eye patients, tears are at a premium.

There just aren't very many tears in many subjects. The result of that is difficult to measure RASP. We require about three microliters of tears to generate a RASP signal from a single subject. And believe it or not, about 25% of the subjects in the running cohort for TRANQUILITY were not able to produce three microliters or more tears.

This is why we are altering optimizing the tear collection process. And that ultimately is what this trial is about. As I mentioned, though, Yigal, ocular redness remains the primary endpoint here in this phase 2 trial.

Yigal Nochomovitz -- Citi -- Analyst

Got it. Thank you. And I just had a few housekeeping questions on your plan to process for disclosing TRANQUILITY. Firstly, will both trials be reported at the same time? Second, will you be conducting any type of a pooled analysis of these two trials? And then finally, what should we expect with respect to the top line release beyond ocular redness? Are we also going to see the tear RASP level data of the Schirmer's test data and the dry eye symptoms in the top-line release? Thank you.

Todd Brady -- President and Chief Executive Officer

Yes. I do think that we will disclose the TRANQUILITY trial serially. They are run in a staggered fashion. I do not expect that we will announce the results of both trials together, just given timing issues.

We're big fans of pooling, as you know, and pooling is part of the NDA submission process. I do expect you'll see a pooled data at some point, though it may not be at the data releases for obvious reasons. Ocular redness is the primary endpoint. We are also interested in a Schirmer test and tear RASP levels, as we've discussed.

Schirmer Test and tear RASP levels will be secondary endpoints and represent two other FDA designated as signs of dry disease. We're also assessing dry disease symptoms. So in terms of secondary endpoints, you'll see a couple of different signs, as well as a dry disease symptoms within the chamber.

Yigal Nochomovitz -- Citi -- Analyst

Thank you very much.

Todd Brady -- President and Chief Executive Officer

Thanks, Yigal.

Operator

And your next question comes from the line of Edwin Zhang with H.C. Wainwright.

Edwin Zhang -- H.C. Wainwright & Co. -- Analyst

Hey, thanks for taking my question. For retinitis pigmentosa, have you done any in-house work before you decide to go after this genetic disease? Do you need to do any preclinical or clinical test before you start the phase 2 trial? My second question is a quick one. For allergic conjunctivitis, have you learned any feedback from the FDA? What's the regulatory pathway possibly going forward in AC? Thank you.

Todd Brady -- President and Chief Executive Officer

Thanks, Edwin, for the questions. The retinitis pigmentosa paper that cited in our corporate deck is a remarkable scientific work. The investigator screened tens of thousands of compounds against certain genetic subtypes of retinitis pigmentosa and methotrexate surface to the top of those, in terms of preventing adopt in misfolding. The investigators have presented a variety of preclinical data, including animal injections, single injections, multiple injections.

And I think as a body of work, the paper, and the results are remarkably compelling, which is why we've -- and why we intend to initiate a clinical trial in retinitis pigmentosa. Nonetheless, to your question, we have now confirmed the activity of methotrexate in vitro in human cell lines that have been genetically modified in two different laboratories. So yes, we have confirmed the work. We typically will attempt to replicate the scientific literature before we initiate a clinical trial.

I can tell you that the investigators for the upcoming trials are ecstatic about the potential of a new therapy in retinitis pigmentosa. As I mentioned, there is no approved therapy. The disease is difficult to treat, and in many cases, leads to blindness. So I think from the patient perspective, the investigator perspective, and certainly from our perspective, we're all very excited about getting this trial going and translating this exciting preclinical work into a clinical trial.

In terms of allergic conjunctivitis, we are still in dialogue with the FDA. As we mentioned, we expect those discussions to occur this year. And of course, we'll be updating the street accordingly once we have that clarity on that series of discussions. I think we're ready for the next.

Operator

And your next question comes from the line of Tom Shrader with BTIG.

Tom Shrader -- BTIG -- Analyst

Good morning. Thanks for taking the questions. A couple of questions on 629 as we get close to data. For the psoriasis readout, do you expect there's enough data there to make a reasonable comparison with psoriasis standard of care? And for atopic asthma, who are the patients here? Are these patients well-controlled on current medications or a quite impaired patients? Just a sense of how noisy that data set is going to be.

Thank you.

Todd Brady -- President and Chief Executive Officer

Great questions, Tom. Thank you. The intent of the three phase 2 trials that we're running for 629, ADX-629, is to clarify how the drug is working, particularly in terms of cytokine and RASP profile. Which cytokines are elevated? Which cytokines are depressed? Which RASPs are controlled? How quickly do those biomarker signals that change? There probably will be some clinical data of relevance that can be derived from these studies.

But obviously, they're not powered to detect statistical changes in clinical endpoints. And really, the clinical changes aren't the point of the trial. I think with ADX-629, we've taken a very deliberate, systematic approach to identifying the kinds of diseases that might respond to the drug, which is why we chose psoriasis and asthma, which sit at two different ends of the inflammatory cascade, psoriasis sort of a TH1 autoimmune disease. Atopic asthma, obviously, an allergic TH2 hypersensitivity disease, and we're all very eager to see how the drug behaves particularly from a biomarker standpoint in these two different flavors of inflammation.

COVID is a mix of all of the above. As you know, some of these patients have cytokine response syndrome or cytokine storm. And there, we're interested in seeing how the drug works broadly. I'll note that in our corporate deck, we have cytokine data from reproxalap.

Some time ago, I believe we presented those data at Quad High some years ago. And what you can see is the activity of reproxalap, which is closely related to ADX-629 structurally, is remarkable. All the inflammatory cytokines, TH1, TH2 that we tested, seems to be reduced following therapy, whereas IL-10, which is the key anti-inflammatory cytokine that was upregulated. And that's why we say that RASP are pre-cytokine systems-based mediators of inflammation.

And if you can inhibit RASP with reproxalap or -629 or other molecules in our platform, the idea is to flip a switch from pro-inflammatory to an anti-inflammatory state. And again, this is why we've selected the spectrum of diseases. Many people don't know this, but one reason we tested reproxalap in dry eye disease and allergic conjunctivitis is that those two diseases also fit that sort of opposite ends of the inflammatory cascade. A TH1 type disease, an autoimmune-type disease in dry eye, and a TH2 or hypersensitivity-type disease and allergic conjunctivitis.

Well, lo and behold, we have activity in both of those conditions. So I think it's possible that with regard to ADX-629 we'll see activity across the board, at least, in terms of a biomarker standpoint. To the question about clinical readouts. Of course, will attempt to measure PASI scores and pulmonary function tests, and normal things that any sponsor would attempt to assess in these indications.

But I don't expect to have a large data set along those lines, at least, clinically. In terms of the patient population in asthma, atopic asthma is interesting. These are patients that are triggered by allergen, hence, the hypersensitivity TH2 nature of the patient population. And in that way, we require patients to have an allergic response in terms of pulmonary function testing and so forth to certain allergens, and we will challenge those patients.

This is a crossover trial. So each patient will be exposed to drug and placebo at different times and the response to that challenge will be key in terms of our biomarker and clinical assessments.

Tom Shrader -- BTIG -- Analyst

Thank you. That was perfect.

Operator

[Operator instructions] Your next question comes from the line of Prakhar Agrawal with JonesTrading.

Prakhar Agrawal -- JonesTrading -- Analyst

Hi. Good morning, and thanks for taking my questions. For ADX-2191 in the retinitis pigmentosa, what endpoints could you study in phase 2? And any clarity on what a regulatory pathway could look like? And secondly, any clarity on the planned NDA submission for allergic conjunctivitis? Updates from the timelines there, that would be super helpful. Thank you.

Todd Brady -- President and Chief Executive Officer

For sure, Prakhar, and thanks for the question. It is early to comment on the regulatory pathway for retinitis pigmentosa. I can tell you that other sponsors have explored clinical challenges as primary endpoints for later-stage trials, such as walking through a maze and the dark. And there are a variety of creative clinical outcomes that can be tested in later-stage trials.

The point of the current trial that we disclosed this morning is not that. The point is to assess the activity of ADX-2191 in terms of biomarker assessments and OCT, other types of radiographic and morphological assessments that are typically used to gauge the activity of a drug and retinitis pigmentosa. One positive aspect about testing rare retinal disease is that the retina can be observed directly. In fact, it's the only aspect of the central nervous system that can be observed directly with fundoscopic exams.

That will be the focus of the upcoming phase 2 trial. And we will disclose more about that trial subsequently in terms of design and endpoints and so forth. As I mentioned, we're very excited about testing the compound because retinitis pigmentosa remains a clinical challenge with no approved therapy and thus derives a great deal of optimism and excitement from patients and physicians. In terms of allergic conjunctivitis, as I mentioned in my prepared comments, we remain in discussions with the FDA.

And I would expect it will have clarity on the regulatory path at some time this year. And obviously, we'll keep the street updated on next steps.

Operator

And your next question comes from the line of Justin Kim with Oppenheimer.

Unknown speaker

Hi. This is Isabelle on for Justin. Thanks for taking my question. Just as you think about a potential filing timeline, do you anticipate the safety experience of TRANQUILITY-1 and -2 to be sufficient based on current enrollment progress?

Todd Brady -- President and Chief Executive Officer

Hi. Good morning, Isabelle. Thanks for the question. The gating factor for the NDA filing for reproxalap, as I have mentioned on prior calls, is not TRANQUILITY.

It is the safety trial, as you point out. The FDA for most NDA submissions requires a detailed and dedicated safety trial usually longer than the typical efficacy trial. In our case, our chronic efficacy trials were 12 weeks long for symptom assessment. In the case of the safety study, that trial is 12 months long.

And so the idea is to estimate NDA filing based on the last patient, last visit in that safety trial. We do believe that we'll be able to file or submit the NDA based on six months of patient safety data. We continue to reiterate prior guidance that the NDA for reproxalap will go in late this year or early next year. But the exact timing, as I mentioned, depends on the nature of enrollment and the timing of enrollment in the safety trial.

Regarding your point about the safety database, which is different from the safety trial, we think we're well within the normal safety database bounds for numbers of patients just based on the number of phase 2 and phase 3 trials that we have performed in dry disease. So we don't anticipate any issues in terms of the size of the patient safety database.

Unknown speaker

Thanks for that.

Operator

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

Unknown speaker

This is Hao calling in for Kelly Shi. So my question is about the phase 2 retro trial in dry eye disease. So about the trial design, is it going to be the same as to TRANQUILITY trials with a focus on optimizing the tear RASP collection? And then my second question is about the commercialization of retro in and AC, like what's your thoughts right now potential maybe launch yourself or collaborations?

Todd Brady -- President and Chief Executive Officer

Excellent question. About the phase 2 RASP trial in dry eye, I really did not highlight the trial design in my prepared comments. The answer to your question is yes. The trial design is substantially similar to TRANQUILITY-1 and TRANQUILITY-2.

In that, the phase 2 is a two-day trial. Day 1 is four doses of drug. Day 2 is a dose of drug prior to a 90-minute dry eye disease chamber. And in the middle of that chamber, at approximately one minute 45, there's a second dose of drug.

What has changed in terms of the protocol for the phase 2 RASP trial is that we're collecting tears, particularly on Day 1 with a different schedule of that. There's lots of ways to collect tears. The two most common ways are the use of a capillary, which is a small glass tube that's inserted into the eye, just above the lower lid, and over a period of five to 10 minutes tears, by capillary action, are sequestered in the tube. The other way is to use the Schirmer Test strip.

As you know, Schirmer Tests are small strips of paper that are placed in the cul de sac, in the tear lake, and tears are absorbed into that strip. The strip can then be frozen and subsequently spun down and analyzed that way. The timing of capillary extraction versus the timing of Schirmer strip extraction, the order of those procedures is what's being optimized in the phase 2 trial, particularly for the assessment of RASP. I don't expect that those protocol changes will have any effect on the chamber data on Day 2, particularly in terms of the symptom assessment, the chamber, and the redness assessment of the chamber.

But really, the phase 2 is focused on Day 1 and the tear collection there to optimize the RASP signal, more so than we might see in the TRANQUILITY trial. And actually, earlier question about what will we see in terms of secondary endpoints. In the run-in trial, we did announce the Schirmer test. We announced the symptoms.

We announced ocular redness, all relatively quickly after the completion of the trial. RASP assessment takes a longer period of time. And in the running trial, we announced the RASP data after the top-line data from the other endpoints was released. The reason for that is that the tears need to be shipped to a third-party laboratory, where a qualified and validated process is used to analyze the RASP levels in tears.

All that takes more time and is more complicated than standard dry eye disease sign assessments. In this case, we're not yet clear as to when the RASP data will be released relative to the other data from these phase 2 and phase 3 trials, we'll be updating investors as we get closer to those data readouts. Maybe for the commercialization approaches for reproxalap, I'll turn that answer over to Joshua, who can comment further.

Joshua Reed -- Chief Financial Officer

Sure. Thanks for the question. From a commercialization standpoint, we are committed to following the path that is in the best long-term interest of Aldeyra and our shareholders. On the business development front, our discussions are robust.

The early onset of activity and broad symptom improvement profile of reproxalap continue to generate significant interest from potential strategic partners. So that addresses sort of the BD side of the equation. With respect to going it alone, we have approximately $250 million in cash, which is sufficient to begin initial commercialization efforts for reproxalap. So we have a number of different options that we're exploring here, and we believe that we're well-positioned to capitalize on the opportunity.

Unknown speaker

Thank you, and congrats on getting the additional orphan designation for two on that one.

Joshua Reed -- Chief Financial Officer

Yes, thanks. We're thrilled.

Operator

And your next question comes from the line of Esther Hong with Berenberg.

Esther Hong -- Berenberg Capital Markets -- Analyst

Hi. Good morning. Thanks for taking my questions. So on ADX-2191, can you give us an update on the ongoing phase 3 study in PVR? And then also with multiple ongoing programs, which could possibly advance the quickest? And then I just got a quick follow-up.

Thanks. 

Todd Brady -- President and Chief Executive Officer

Thanks, Esther, and good to hear your voice. I'm glad you asked about ADX-2191. This is a program that I think has been largely ignored by investors. Yet as I said in my prepared comments, -2191 a near-term high-value commercial opportunity, and not only in one clinical indication but in three clinical indications.

The PBR program is going well. We have as of this morning, reiterated our guidance that will complete enrollment in the GUARD phase 3 program this year. I'll point out that one thing we've observed with the GUARD trial is that many retinal surgeons are already treating PVR with methotrexate off-label, if you will. That is it seems like the de facto standard of care, treatment of PVR, is already methotrexate.

And we're really thrilled to be able to present to the retinal community control data along these lines, eagerly anticipating the results of the GUARD trial because I do think that the results have the potential to validate what is sort of done in a standard-of-care basis today in terms of treatment of the disease. And we look forward to announcing those results sometime next year. There are multiple programs, as you point out, with -2191, I really do believe that -2191 represents a platform approach. As you know, methotrexate has been used in many, many different indications.

It is a known and potent anti-inflammatory and antifibrotic drug with hundreds of thousands of patients worth of clinical experience. Well, as you know, it turns out that methotrexate is injected into the eye, from my prior comments, regarding proliferative vitreoretinopathy and now, ocular lymphoma. In terms of which indication, who'll make it to the market first, we don't yet know. We're optimistic about all of them.

I would say that retinitis pigmentosa is the newest of the indications that we're testing. I would probably place that in terms of timing behind PVR and ocular lymphoma. But we're excited to update the street on timelines and regulatory process and so forth, if not later this year, earlier next year. And as I mentioned in the beginning of my response to your question, we're just so thrilled about -2191 and the potential for our company and for patients and physicians, all of these indications that we're pursuing have no approved therapies.

Esther Hong -- Berenberg Capital Markets -- Analyst

Thanks. Super helpful. And then just safety data to date on 2191. Thanks.

Todd Brady -- President and Chief Executive Officer

One advantage of -2191 is that we do have lots of patient exposure, the data, with ocular injection. Some of that data is in our corporate deck with regards to the study on PVR -- in the scientific literature, the safety of intraocular injection of methotrexate is well-described and well-known, which represents a real advantage to this compound, relative to newer compounds. I don't expect that with regard to any of the indications that we described that safety will be an issue simply because the doses that we're using, the injection schedule that we're using, all have been well-described and are in common use in practice for the treatment of these rare diseases.

Esther Hong -- Berenberg Capital Markets -- Analyst

Thanks, Todd.

Todd Brady -- President and Chief Executive Officer

Thanks. We're ready for the next.

Operator

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

Matt Cross -- Alliance Global Partners -- Analyst

Hey, guys. Good morning. Thanks for squeezing me in here. Just had two quick ones.

One on the phase 2 tear collection trial that we're asking quite a bit about. I guess I might have missed this earlier in the call. Apologies, a busy morning, but I was curious if -- when the study completes, how that may impact? I know there's some kind of discussion of how this may impact the labeling, but are there any takeaways that you might evaluate from this phase 2 that could impact anything you're doing in TRANQUILITY? Is this just going to be for post-marketing studies? Or could there be some modification? Another, as you mentioned, TRANQUILITY-1 and -2 will complete serially with a little gap in between. So I wasn't sure if this could probably not given timing, but impact things you may do in TRANQUILITY-2.

And then the second question I had was just around enrollment for both the TRANQUILITY studies, given that TRANQUILITY-2, that will be starting up shortly. But I was wondering, given that you're still committing to having both of those data sets in Q4, whether you've been pre-identifying patients for TRANQUILITY-2 as you were enrolling patients in TRANQUILITY-1, even if that hasn't -- that second trial hasn't officially opened up yet. Thanks. 

Todd Brady -- President and Chief Executive Officer

Thanks, Matt, for the question. I know you're busy. There are lots of earnings this time of year, and we appreciate taking the time to join our call. Excellent questions regarding the phase 2 and the implications of the phase 2 to not only TRANQUILITY but to our regulatory package.

The intent of the phase 2 RASP trial in dry disease really is to augment the pharmacology section of the label. I would not classify in any way the phase 2 as mission-critical for the NDA submission or the NDA approval process. But as I mentioned in my prior answers, the idea of getting RASP data in the pharmacology of the section -- pharmacology section of the product label is commercially differentiating. There is no other topical eyedrop that we're aware of that has been able to improve target engagement.

And the fact that we know how we prove that mechanism of action and the tears of trial patients, I think, is quite remarkable and should distinguish reproxalap mechanistically from the other approaches out there in the dry eye disease market. The primary endpoint of the phase 2, nonetheless, is ocular redness. We've been consistent in our ability to demonstrate improvement in redness and allergy and dry eye disease, as I've mentioned, previously. We remain optimistic about the commercial implications of ocular redness.

That patients generally care about how they look. They are less interested in their stating scores or their Schirmer test and so forth. So we're really thrilled to have demonstrated the ocular redness activity that we've shown so far and other trials, and that made perfect sense to include ocular redness as the primary endpoint in the phase 2. To the point of your question, obviously, it is a good sign if ocular redness is -- improvement in ocular redness is demonstrated in the phase 2.

I'll point out though that the size of the phase 2 is approximately half the size of the TRANQUILITY trial in phase 2. We're expecting about 75 patients per arm or 150 patients total, which is half that of the TRANQUILITY trial and thus, the powering is not as robust in the phase 2 as it would be in the phase 3. But then again, we're not really running the phase 2 for redness. We're running it for RASP.

In terms of TRANQUILITY-1 and -2, the trials, as I mentioned, are being performed serially. The same patient population is being enrolled in both trials. The enrollment criteria are identical. And what we've decided is to focus on enrollment of TRANQUILITY-1.

Once TRANQUILITY-1 completes full, then switch to TRANQUILITY-2. The beauty of the Tranquility trials is that there are two-day trials, which is awfully convenient for subjects. In theory, a subject could screen on one weekend, qualify and then the next weekend, finish the trial. The Day 1 and Day 2 can be performed rapidly.

I think that's an attractive advantage that relative to longer trials, particularly for subjects, I would say that enrollment so far in TRANQUILITY-1 and the phase 2 trial has been robust. I don't expect, at this point, any issues with TRANQUILITY-2. We have seen to date little impact of COVID on our enrollment in the TRANQUILITY trial. And as I mentioned, the two-day nature of these trials may have something to do with that in terms of being attractive to subjects.

Matt Cross -- Alliance Global Partners -- Analyst

Perfect. That's super helpful extra detail, Todd. I appreciate it. And yes, hope and see that RASP data in the label and kind of prove out, which you're already showing, I think, between the correlation between RASP and redness so much appreciate it.

Operator

And at this time, there are no further audio questions. We'll now turn the conference back to Dr. Brady for closing remarks.

Todd Brady -- President and Chief Executive Officer

Well, thank you for joining us this morning. And as always, we look forward to keeping you updated on our progress.

Operator

[Operator signoff]

Duration: 52 minutes

Call participants:

Joshua Reed -- Chief Financial Officer

Todd Brady -- President and Chief Executive Officer

Marc Goodman -- SVB Leerink -- Analyst

Yigal Nochomovitz -- Citi -- Analyst

Edwin Zhang -- H.C. Wainwright & Co. -- Analyst

Tom Shrader -- BTIG -- Analyst

Prakhar Agrawal -- JonesTrading -- Analyst

Unknown speaker

Esther Hong -- Berenberg Capital Markets -- Analyst

Matt Cross -- Alliance Global Partners -- Analyst

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