Ladies and gentlemen, thank you for standing by and welcome to the Alvera Therapeutics Second Quarter 2021 Financial Results Conference Call. At this time, all participants are in a listen only mode. After the speakers' 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.
Good morning, everyone. With me is Doctor. 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 and 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 assumed 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-nineteen 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-nineteen 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 Doctor. Brady.
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-two thousand one hundred and ninety one, the lead product candidate in our retinal disease pipeline for the treatment of 2 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 1 in 4,000 people worldwide.
As noted in this morning's news release, we plan to initiate a Phase 2 clinical trial of ADX-two thousand one hundred and ninety one in patients with retinitis pigmentosa this year. ADX-two thousand one hundred and ninety one has now received orphan drug designation for 3 distinct clinical indications that affect the 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. Together, these designations highlight the broad platform potential of ADX-two thousand one hundred and ninety one 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-two thousand one hundred and ninety one 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 all secondary endpoints. Patient enrollment continues in our Phase III TRANQUILITY trial of reproxalap for dry eye disease with enrollment in the identical TRANQUILITY II trial on track to begin this quarter. Ocular redness is the primary endpoint of these 2 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 Q4 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 tier 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 II trials in asthma, psoriasis and COVID-nineteen of ADX-six twenty nine, our 1st in class orally available and irreversible covalent inhibitor of pro inflammatory RASP are anticipated in the Q4 of 2021 or the Q1 of 2022. In addition to the disease areas currently under study, we're evaluating the possibility of expanding clinical testing of ADX-six 29 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 Q2 financial results.
Thank you, Todd. Cash and cash equivalents as of June 30, 2021 were $249,700,000 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 if approved and continued development of our product candidates in ocular and systemic immune mediated diseases. Turning now to our Q2 2021 results, research and development expenses were $11,500,000 for the quarter ended June 30, 2021 compared with $4,900,000 for the same period in 2020. The increase of 6 point $6,000,000 is primarily related to the increase in clinical research and development expenditures. General and administrative expenses were $3,100,000 for the quarter ended June 30, 2021 compared with $2,200,000 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 Q2 of 2021 was $14,900,000 or $0.28 per share compared with a net loss of $7,500,000 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, ETIG, 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.
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, Joshua and I will be happy to take your questions. Operator?
Thank Your first question comes from the line of Mark Goodman with SVB Leerink.
Yes, good morning. Can you talk about this new indication for 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 nephyltrexate off label being used for this indication before?
Maybe you could just give us a little history of that. And then is there screening that takes place since this is a genetic disease? Just curious about that. And then also on the Phase 2 to optimize the wrap, the RAS level study that you talked about there, is that an FDA requirement? Is this going to be one of those supplements, FDA file?
Just curious who's requiring that? Thank you.
Mark, good morning and thanks for the excellent question and the focus 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 suggests that methotrexate is particularly important in rhodopsin misfolding. Rhodopsin is a protein that's critical in the light sensation cascade in the retina. And methotrexate seems to be able to prevent rhodopsin misfolding in 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 retinitis pigmentosa, but this particular subtype, this genetic subtype of retinitis pigmentosa that seems to respond well to methotrexate. Regarding your question about the Phase 2 trial in dry eye 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 tiers. 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 1st company ever to demonstrate that a topical drug can affect the target of that drug in the tiers of patients. We are 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 II trial, which as we mentioned is designed to optimize tier collection, obviously, a pivotal process in
the assessment of Nochomovitz with Citigroup.
Hi, great. Hi, 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 tier 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 2 Tranquility Phase 3s?
III? Of
course. Good morning, Yigal, and thanks for the question. I'm happy to clarify the Phase II RASP trial. The TRANQUILITY trials are identical and based on the highly successful run-in cohort from January. And 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 a dry disease, hence our selection of ocular redness. Nonetheless, as I mentioned in response to Mark's good question prior, we're still very interested in assessing RASP and presenting RASP data to The Street and potentially including RASP data in our product label. This is why we've initiated this study. Tear collection is tricky.
As you know, in dry eye patients, tiers are at a premium. There just aren't very many tiers in many subjects. The result of that is it's difficult to measure RASP. We require about 3 microliters of tiers to generate a RASP signal from a single subject. And believe it or not, about 25% of the subjects in the run-in cohort for Tranquility were not able to produce 3 microliters or more of tiers.
This is why we are altering optimizing the tier collection process and that ultimately is what this trial is about. As I mentioned though, Ygal, ocular redness remains the primary endpoint here in this Phase II trial.
Got it. Thank you. And I just had a few housekeeping questions on your plans and process for disclosing TRINQUILITY. Firstly, will both trials be reported at the same time? 2nd, 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 KRASP level data, the SHERMIS test data and the dry eye symptoms in the top line release? Thank you.
Yes. I do think that we will disclose the TRANQUILITY trials together just given timing issues. 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 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 Schirmer test and TRAS levels as we've discussed. Schirmer test and TRAS levels will be secondary endpoints and represent 2 other FDA designated signs of dry eye disease. We're also assessing dry eye disease symptoms. So in terms of secondary endpoints, you'll see a couple of different signs as well as dry disease symptoms within the chamber.
And your next question comes from the line of Edwin Zhang with H. C. Wainwright.
Hi, thanks for taking my question. For RECONITUS 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 II trial? My second question is a quick one. For allergic conjunctivitis, have you learned any feedback from the FDA?
What's the regulatory pathway going forward in AC? Thank you.
Thanks, Edwin, for the questions. The retinitis pigmentosa paper that cited in our corporate deck is a remarkable scientific work. The investigators screened tens of 1000 of compounds against certain genetic subtypes of retinitis pigmentosa And methotrexate surface to the top of those in terms of preventing rhodopsin 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 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 2 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 a clarity on that series of discussions.
Holly, I think we're ready for the next question.
Okay. And your next question comes from the line of Tom Schroeder with BTIG.
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 patient? Just a
sense of how noisy that data set is going to be. Thank you.
Great questions, Tom. Thank you. The intent of the 3 Phase II trials that we're running for ADX-six twenty nine is to clarify how the drug is working, particularly in terms of cytokine and RAS profile, which cytokines are elevated, which cytokines are depressed, which RASPs are controlled, how quickly do those biomarker signals 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 trials.
I think with ADX-six twenty nine, 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 2 different ends of the inflammatory cascade psoriasis, sort of a TH1 autoimmune disease, atopic asthma, obviously an allergic TH2 hypersensitivity disease. 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 AAAAI some years ago. And what you can see is the activity of reproxalap, which is closely related to ADX-six twenty nine structurally is remarkable. All the inflammatory cytokines, Th1, Th2 that we tested seem to be reduced following therapy, whereas IL-ten, which is the key anti inflammatory cytokine that was up regulated. 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, this, but one reason we tested reproxalap in dry eye disease and allergic conjunctivitis is that those two diseases also sit at sort of opposite ends of the inflammatory cascade, a TH1 type disease, an autoimmune type disease in dry eye and a TH2 TH2 or hypersensitivity type disease in 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-six twenty nine, we'll see activity across the board at least in terms of a biomarker standpoint. To the point to the question about clinical readouts, of course, we'll attempt to measure PASI scores and pulmonary function tests and normal things that any sponsor would attempt to assess in these indications, but we 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.
Thank you. That was perfect.
Your next question comes from the line of Krakhar Agrawal with Jones Trading.
For ADX-two thousand one hundred and ninety one, 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 energy connect devices, updates on the timelines there that would be super helpful? Thank you.
For sure, Pritar, 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 in 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 activity of ADX-two thousand one hundred and ninety one in terms of biomarker assessments and OCT, other types of radiographic and morphological assessments that are typically used to gauge the activity of 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 sometime this year and obviously we'll keep The Street updated on next steps.
And your next question comes from the line of Justin Kim with Oppenheimer.
Hi, this is Isabelle on for Justin. Thanks for taking the question. Just as you think about a potential filing timeline, do you anticipate the safety experience of Tranquility 12 to be sufficient based on current enrollment progress?
Hi. Good morning, Isabelle. Thanks for the question. The gaining 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 SAFE 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 6 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.
Great. Thanks.
Thanks for the call.
And your next question comes from the line of Kelly Hsieh
with Jefferies.
This is Hao calling for Kelly Hsieh. So my question is about the Phase II RETRO trial trial in dry eye disease. So about the trial design, is it going to be the same as the 2 transcritical trials with the focus on optimizing the TIERASP collection? And then my second question is about the commercialization of retrovirus and AC. Like what's your thoughts right now, potential maybe launch yourself or collaborations?
Good morning, Hong. 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 I and TRANQUILITY II.
In that, the Phase II is a 2 day trial. Day 1 is 4 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 1:45, 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 tiers, particularly on day 1, with a different schedule of that.
There's lots of ways to connect to collect tiers. The most the 2 most common ways are 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 5 to 10 minutes, tiers by capillary action are sequestered in the tube. The other way is to use a Schirmer test strip. As you know, Schirmer tests are small strips of paper that are placed in the cul de sac in the tear leg 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 II 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 in the chamber and the redness assessment in the chamber. But really, the Phase 2 is focused on day 1 and the tier collection there to optimize the RASP signal more so than we might see in the TRANQUILITY trial. And actually, GOL's earlier question about what will we see in terms of secondary endpoints, in the run-in trial, we did announce a 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 RUN and trial, we announced the RASP data after the top line data from the other endpoints was released. The reason for that is that the tiers need to be shipped to a 3rd party laboratory, where a qualified and validated process is used to analyze the RASP levels and tiers. 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 II and Phase III 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.
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 $250,000,000 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.
Thank you and congrats on getting the additional open designation for 2 on network.
Yes, thanks Hans. We're thrilled.
And your next question comes from the line of Esther Hong with Berenberg.
Hi, good morning. Thanks for taking my questions. So on ADX-two thousand one hundred and ninety one, 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.
Thanks, Esther. Good to hear your voice.
I'm glad you asked about ADX-two thousand one hundred
and ninety one. This is a program that I think has been largely ignored by investors. Yet, as I said in my prepared comments, 2,191 represents a near term high value commercial opportunity.
And not only in one clinical indication, but in
3 clinical indications. The PVR program is going well. We have, as of this morning, reiterated our guidance that we'll complete enrollment in the GARD 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 PBR is already Methotrexate.
And we're really thrilled to be able to present to the retinal community controlled 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 on 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 2,191. I really do believe that 2,191 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 anti fibrotic drug with 100 of thousands of patients' worth of clinical experience. Well, as you know, it turns out that methotrexate is injected into the eye per my prior comments regarding proliferative vitreoretinopathy and now ocular lymphoma. In terms of which indication will 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 at in the beginning of my response to your question, we're just so thrilled about 2,191 and the potential for our company and for patients and physicians, all of these indications that we're pursuing have no approved therapies.
Thanks. Super helpful. And then just safety data to date on 2,191. Thanks. One advantage
of 2,191 is that we do have lots of patients exposure data with ocular injection. Some of that data is in our corporate deck with regards to the mass eye and ear 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've 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 and practice for the treatment of these rare diseases. Holly, next question.
And your next question comes from the line of Matt Cross with Alliance Global.
Hey, guys. Good morning. Thanks, Ruth, for squeezing me in here. Just had 2 quick ones. 1 on the Phase 2 tier collection trial that we're asking quite a bit about.
I guess I might have missed this earlier in the call. Apologies, it's a busy morning. But I was curious if when this study completes, how that may impact, I know there was 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?
I know there as you mentioned, Tranquility 12 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 TRINQUILITY 2. And then the second question I had was just around enrollment for both of the TRINQUALITY studies, given that that TRINQUALITY II 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 II as you are enrolling patients in TRANQUILITY I, even if that hasn't that second trial hasn't officially opened up yet? Thanks.
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 II and the implications of the Phase II to not only but to our regulatory package. The intent of the Phase 2 RAS 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 eye drop that we're aware of that has been able to prove target engagement. And the fact that we know how to improve that mechanism of action in the tiers of the tribe 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 II, 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 staining scores or their Schirmer tests and so forth. So we're really thrilled to have demonstrated the ocular redness activity that we've shown so far in 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 II.
I'll point out though that the size of the Phase II is approximately half the size of the TRANQUILITY trials. In Phase II, we're expecting about 75 patients per arm or 150 patients total, which is half that of the TRANQUILITY trials. 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 12, 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 I. Once TRANQUILITY I completes, we'll then switch to TRANQUILITY II. The beauty of the TRANQUILITY trials is that they're 2 day trials, which is awfully convenient for subjects.
In theory, a subject could screen on 1 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 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. They don't expect at this point any issues with TRANQUILITY II.
We have seen to date little impact of COVID on our enrollment in the TRANQUILITY trials. And as we mentioned, the 2 day nature of these trials may have something to do with that in terms of being attractive to subjects.
Perfect. That's super helpful extra detail, Todd. I appreciate it. And yes, hoping to see that RAS data in the label and kind of prove out what you're already showing, I think, between that's the correlation between RASP and redness. So much appreciated.
Thanks.
Perfect. Thanks, Matt.
And at this time, there are no further audio questions. We'll now turn the conference back to Doctor. Brady for closing
remarks. Well, thank you for joining us this morning. And as always, we look forward to keeping you updated on our progress.
And thank you. This concludes today's conference call. Thank you for your participation. You may now disconnect.