Q4 2021 Aldeyra Therapeutics Inc Earnings Call
Ladies and gentlemen, thank you for standing by and welcome to the out there of therapeutics at full year 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 over the conference to the company's Chief Financial Officer, Mr. Joshua Reed. Please go ahead Sir.
Good morning, everyone.
With me is Dr. Todd Brady, President and Chief Executive Officer of out there.
This morning, we issued a press release reporting our financial results for the year ended December 31 2021.
A copy of the press release is available on the investors and media section of our website www dot out there of Dot com.
Please note that this morning's conference call contains forward looking statements regarding future events and the future performance of out there are forward looking statements include but not but are not limited to 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.
These statements are based upon the information available to us today and reflect our current views concerning future events there.
They are based on assumptions and subject to risks and uncertainties, including the development clinical and regulatory plans or expectations for all of <unk> product candidates and systems based approaches the risks that results from our clinical trials or portions of clinical trials may not accurately predict the result for future trials for the same or different.
<unk> and out there its 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 timeline to complete our clinical trials may be delayed.
Oh, there it seems no obligation to update these statements as circumstances change.
<unk> events and actual results could differ materially from those projected in our 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 our press release issued this morning, and our filings with the SEC I will now turn the call over to Dr. Brady.
Thank you Joshua.
And good morning, everyone.
2022 promises to be an exciting year for aldara.
As we enter a catalyst rich period, it will highlight not only what we hope will be the successful completion of clinical development for proxy lap in dry eye disease.
But also the emergence of our RASK modulator platform for the treatment of systemic autoimmune and inflammatory diseases.
And late stage regulatory milestones for E. D X 21 91.
For the treatment of certain rare retinal diseases.
We believe that our systemic and retinal platforms are broadly underappreciated and under exposed and we therefore are tend to aggressively build awareness of these platforms throughout 2022 and beyond.
Our plan to increase recognition of our systemic immune modulating platform is indeed near term.
Aldara Therapeutics R&D day will occur on March 29th.
During which we plan to announce top line data from our phase two proof of concept trials of <unk> six to nine.
Our first in class oral RASK modulator, and psoriasis asthma and COVID-19.
The goals of the AVX six to nine proof of concept trials are threefold.
First to demonstrate an acceptable safety and Tolerability profile for what represents the first time, a Ras modulator has been orally administered to humans.
Second to indicate pharmacodynamic activity of AVX six to nine across a variety of Biomarkers related 10 coordination.
And third to.
To elucidate signals of clinical activity consistent with what might be expected from small trials with varying levels of doses durations of therapy trial designs and disease States.
AVX six to nine and related molecules from our RASK modulator platform has the potential to be transformative for aldara.
Creating a broad range of new commercial opportunities and systemic disease.
And complementing our late stage retinal and topical ocular programs.
In addition to describing the initial phase two outcomes for AVX six to nine and potential future clinical indications.
We're particularly excited to welcome Dr. Jeffrey T. Lee has the featured speaker for R&D day, Dr. Tea leaves the room block Professor of internal medicine, and the division of Rheumatology at the University of Nebraska Medical Center.
He is a leader in the research of Melinda aldehyde acetaldehyde and other RASK.
As potentiate or of the inflammatory response.
Dr. <unk> brings a unique understanding of the science behind our RASK programs. We look forward to his perspectives on AVX six to nine and the potential for RASK modulation broadly as a novel approach for the treatment of inflammatory diseases.
Our next set of catalysts relate to approximate <unk> a first in class RASK modulator for the treatment of dry eye disease, and what we believe has the potential to be the next novel entrant in the dry eye disease marketplace.
Results from the phase III tranquility to try Oliver proxy lap and dry disease are expected during the middle of this year.
Pending the outcome of tranquility too and enrollment in the 12 month safety trial of a proxy lap in dry eye disease patients.
We plan to submit an NDA for Approx of lab and dry disease. After the completion of tranquility too.
The endpoint of the tranquility to trial will be met if either schirmer test or ocular redness demonstrate statistical significance in favor of a proxy over vehicle.
We've also initiated two additional trials a cross over dry eye disease Chamber trial, and a one day Schirmer test trial.
Either of which could serve as pivotal trials in support of an NDA submission.
In recent months, we've met with a number of ophthalmologist and optometrists across the United States to learn more about the substantial unmet medical need associated with treating dry eye disease, which we estimate affects $39 million or more adults in the United States.
Nearly 20 years since the approval of the first prescription drug for dry eye disease, the market remains significantly underserved.
Point supported by the millions of patients who report that first line therapies are ineffective.
Many of dry eye disease professionals express a keen interest in a rapid and durable treatment that can be used chronically.
And enables improved patient outcomes compared with the current standard of care.
We believe for proxy lab has the potential to be that treatment.
The clinical benefits of Approx lab are supported by a growing body of scientific research in January we reported the results of the phase II dry eye chamber trial, comparing patient reported ocular discomfort in ocular itching symptoms scores of our proxy app versus <unk> and approved.
Drug for the treatment of dry eye disease for both endpoints <unk> demonstrated statistically significant symptom improvement compared desired drug.
In a separate study published last year in clinical ophthalmology, <unk> eye drop experience, including a broad assessment of ocular sensations over one hour following administration with superior to that of <unk>.
An allergic conjunctivitis the phase III invigorate two allergen chamber trial was initiated in the first quarter of this year and.
Invigorate two is a randomized double masked crossover trial. The trial design is substantially similar to that of the phase III Invigorate trial, the results of which were announced in April 2021.
The invigorate trial demonstrated statistically significant superiority over proxy lap over vehicle in reducing ocular itching and redness, the key symptoms and signs of allergic conjunctivitis, respectively.
To avoid the confounding effects of pollen and the environment Allergen Chamber trials are conducted exclusively in winter.
And often require two winter seasons to enroll sufficient numbers of patients as was the case with the invigorate trial. Therefore, we expect results from invigorate two in 2023.
In addition to al there is advancement to systemic disease, we are committed to a significant development effort in retinal diseases.
Many of these diseases lead to loss of sight and are poorly treated today.
Especially retinal diseases that are rare.
Along those lines I am pleased to report the initiation of the phase two trial of <unk> 21, 91 in retinitis Pigmentosa and.
And then curable potentially blinding disease with no approved therapy.
A single Center open label trial will evaluate the safety and Tolerability of AVX, 21, 91, and patients diagnosed with retinitis pigmentosa due to specific genetic mutations animal models of which responded to methotrexate treatment.
The trial, which will be conducted at Duke University Medical Center is expected to enroll eight patients.
For patients receiving monthly and for patients receiving twice monthly <unk> injections of <unk> 21, 91 over a period of three months results are.
Our expected during the second half of this year.
In January we announced the completion of enrollment in part one of the Phase III Guard trial of AVX 21, 91 in patients with proliferative victory of retinopathy, or PV or another rare retinal disease that can lead to loss of vision, yet has no approved therapy.
<unk> is the leading cause of primary retinal detachment.
After surgical failure occurring in an estimate estimated 5% to 10% of retinal detachments.
Results from part one of guard are expected in the second half.
Of this year.
To our knowledge <unk> 21, 91 is the first methotrexate formulation, specifically designed to be compatible with the vitreous the fluid in the back of the eye.
Das ATX 21, 91 represents a unique commercial opportunity for example off label. Methotrexate example, injections are standard of care for the treatment of ocular lymphoma.
Together with retinitis, Pigmentosa and PV or the current indications for our <unk> 'twenty 191 platform spans three rare retinal diseases.
In each indication AVX 21, 91 has received the U S Fda's orphan drug designation.
Now I'll turn the call back over to Joshua for the financial review after which I will summarize our recent clinical progress and our future potential in developing novel platforms for the treatment of immune mediated disease.
Thank you Todd.
Cash and cash equivalents as of December 31, 2021, whereas $229 $8 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 new.
Drug application submissions initial commercialization of <unk>, if approved and continued development of our product candidates and ocular and systemic immune mediated disease.
Now let me review the P&L for the 12 months ended December 31 2021.
Net loss was $57 8 million.
Or $1 <unk> per share compared with a net loss of $37 6 million or $1 11 per share for the comparable period of 2020.
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 $44 9 million compared with $24 $7 million for the same period in 2020.
The increase of $22 million is primarily related to increases in our clinical research and development expenditures.
General and administrative expenses were $11 3 million compared with $10 million for the same period in 2020, the increase of $1 $3 million is primarily due to increases in legal insurance and consulting costs.
Total operating expenses were $56 2 million compared with total operating expenses of $36 4 million for the same period in 2020.
Now I'll hand, the call back to Todd for closing comments.
Thanks Joshua.
We enter 2022 from a position of financial strength.
And clinical success across a variety of therapeutic platforms.
Interestingly, while we believe that the Investor community is aware of the potential of approximate app to be the next dry eye disease market and trend and a novel therapeutic approach that addresses many of the shortcomings of currently available therapy.
We also believe that our systemic in retinal disease platforms are under recognized.
And present, a unique opportunity for value accretion and aldara as we expect to announce new clinical data and regulatory progress in systemic and retinal indications beginning at R&D day, this month and continuing throughout the remainder of 2022 and beyond.
I am pleased to state without reservation that we continue to execute on our mission to develop novel therapies for the treatment of immune mediated diseases.
We believe our future is catalyst rich.
Our potential remains strong and our commitment is unwavering.
With that Joshua and I will be happy to take your questions operator.
Thank you if you would like to ask a question you compress star one on your telephone keypad.
I would like to withdraw your question you May press Star two.
Our first question for today comes from Yigal <unk> of Citigroup.
Your line is now open.
Hi, Todd and Jonathan Thank you very much for taking the question on 629 I'm just curious.
Youre looking at three diseases psoriasis asthma COVID-19, just wondering if you have a sense as to where the best evidence is for potential therapeutic effect across these three inflammatory diseases. In other words do you think one of them is more likely to work than the others or is it really unclear and thus this is why youre.
We're running these studies thank you.
Good morning, all and thank you for the question it's.
It's something we've thought a lot about I remember years ago, a similar question about <unk>.
Did we expect for Approx lab to work better in allergic conjunctivitis.
Which is obviously a th two allergic type condition.
Or should we expect <unk> will have to work better in dry eye disease, which is more of an autoimmune th one type condition.
And at the time, they didn't really know.
As has been demonstrated consistently of Approx lap worked across the board.
<unk> nine is a close relative of approximate app. It is also a RASK of modulator and I think my answer to your question would be the same as it was for a approx lap, which is although we are not entirely clear until the data are presented I think we have reason to believe that RASK modulation is proximal.
It is upstream it therefore has the potential to influence all kinds of inflammation and I have a reasonable amount of optimism that will see activity in both psoriasis.
And asthma.
Now COVID-19 is a different animal COVID-19 is a and infectious disease and.
And be involved both arms of the immune system T. H, one N th two.
That is a new experiment for us.
Eager to present the data.
If we believe that both for <unk> and <unk> nine as RASK modulators affect inflammation approximately upstream then it is likely that we would see some kind of effect and COVID-19, as well notwithstanding the fact that COVID-19 is different from psoriasis and add.
And that.
That is an infectious disease.
Got it that's very very helpful. And then I just wanted to get your latest thoughts on allergic conjunctivitis, meaning obviously, there was a very heavy overlap in symptomology between dry eye and AC.
And so I know you've thought about this in the past, but I'm just wondering if you could give your latest latest perspective.
From a commercial perspective do you think you even need to file an AC to get physicians to prescriber practice a lot for this condition.
Thank you all your point is a good one the of the overlap between dry eye and allergic conjunctivitis is indeed substantial.
I, often wonder if dry eye disease and allergic conjunctivitis.
Variance of the same disease, the variance of ocular surface inflammation that are.
It's very closely related.
I think many health care providers, both ophthalmologists and optometrists.
Recognize that these two diseases are related the differential diagnosis process.
When a patient presents with ocular surface inflammation between dry eye disease, and allergic conjunctivitis is complicated.
And often not clear.
And therefore, I think many health care providers.
Believe that patients will have elements of both conditions and.
That prescribing for one condition is similar to prescribing for another condition.
Now.
Weather.
We file for allergic conjunctivitis.
Whether we submit an NDA for allergic conjunctivitis, which would occur subsequent to the NDA for dry disease. I think is a different question I think it depends on.
The dry disease data it depends on potential partnership that we may or may not have with a different company and launching <unk>.
We will have to answer that question later on in the future.
Great. Thanks, Todd.
Thanks Nicole.
Thank you next.
Next question comes from Kelly <unk> of Jefferies.
Your line is now open.
Hey, Todd this is hot economy meaningful Kenny and thanks for taking my questions. So.
First one is really.
For the most tangible result in the tranquility trial, it was very fast on that basis.
One day you see the efficacy. So do you think there's any thing so ml April and views that you can explain the paas.
At the onset of action and then do you.
Seems the effect is durable.
If FDA may require.
Awesome.
Evidence for the durability of the effect.
Great. Thanks for the question, how and those are important.
Questions to consider as we approach NDA submission for dry eye disease.
I wanted to build on <unk> question about the upstream nature of of Rasp inhibition, not only is RASK modulation something that.
Is broad and can affect a variety of different signs and symptoms of inflammatory diseases, but it is also rapid.
And to your question one reason why we believe that for cross sell App works. So quickly is because the mechanism of the drug involves a chemical reaction.
That is the binding of for proxy lab to RASK.
As we presented in our corporate deck and discussed previously that reaction is exceedingly fast.
Occurring within minutes and in vitro situations.
Our guess is that that's exactly what's happening in the ocular tissue that there is a rapid chemical reaction, which then can effect changes in signs and symptoms of <unk>.
<unk> rapidly.
The fda's position on signs.
At least per our discussions with the agency is that the signs of dry eye disease needs to be demonstrated in part to prove.
But that your drug is not an anesthetic.
That the drug is not simply numbing the surface of the eye.
And has a physiologic component that is beneficial for the treatment of disease.
Based on our conversations with the FDA the chronicity the duration.
Of modulation of signs.
Is not important what is important is that we can prove that the drug has physiologic activity beyond anesthesia.
And accordingly, we are being able to run a series of chamber trials in dry eye chambers.
Which allow us to demonstrate beneficial effects on signs, both redness and I'll Schirmer test.
Very rapidly.
The advantages of chamber trials are multifactorial. They are fast they are relatively inexpensive and most importantly from a commercial standpoint, they allow us as the developer of approximately <unk> to demonstrate very rapid activity at least from a science standpoint.
<unk> of the drug.
Thank you Todd.
Very helpful. Just a quick follow up so for the phase III trial, that's optimizing as Greg mentioned men's just wanted to check the status of that one and also you mentioned about the cost of <unk>.
Sumit pets, one day trial annual.
Opening just two.
To get a little bit understand by the timing and trial design if possible.
Okay.
Right the <unk>.
RASK assessment is occurring in all of these trials. The current plan is to.
Organize the RASK data in aggregate.
And present that data later.
The RASK assessment as I have described previously is more complex.
Dan clinical assessment and more complex.
The standard assessment of dry disease assigns so RASK data upon completion of tranquility too and the two other trials that you just brought up.
Will be announced separately in the future I'm.
I am glad you asked about the crossover trial and the Schirmer test trial.
Those are slightly alternative methods of measuring signs in dry eye disease.
Crossover dry eye Chamber trial is unique here.
Here to fore and tranquility and in tranquility too we have assessed patients in dry eye chambers, and a parallel group manner that is each patient either receives vehicle or drug.
The crossover trial is different and that each patient will receive vehicle and drug at different times in a random order we've been highly successful with crossover chamber trials.
And allergic conjunctivitis as you know the invigorate trial and the ongoing invigorate two trial and our phase two allergen Chamber trial, which has recently been published in clinical ophthalmology.
Our.
Subjecting subjects and have objected subjects to each test article.
Prior to entering a a chamber.
This is a powerful approach statistically because it eliminates subject to subject variability that is each subject is his or her own control.
We have to our knowledge that never seen a crossover dry eye disease Chamber trial, we're thrilled to be the first company that's running such a trial obviously based on the allergic conjunctivitis results. We're optimistic about the dry eye disease results and we look forward to describing those results.
Later this year for the Investor community.
The Schirmer test trial is a one day trial.
Again, highlighting the rapidity of onset for <unk> essentially the trial is similar to the tranquility and tranquility two trials, where subjects are dosed four times on a single day, Unlike tranquility and tranquility too there is not a dry eye.
Chamberlain on the following day, the Schirmer test is taken in and around the fourth and final dose.
On day, one for the upcoming trial, we believe as I mentioned in my prepared comments, how that at both trials if successful will support the NDA submission.
<unk> may not necessarily be needed for the NDA submission pending the outcome of tranquility too.
Great. Thank you Todd.
Thank you next.
Next question comes from Marc Goodman of SVP Leerink.
Your line is now open.
Yes, hi.
Todd first of all can you just give us an update on you had mentioned.
The safety data and the timing of filing for dry eye, which would be the study works in the middle of the year, we get the data and then if the safety data is there then you can file just give us an update on how the safety is going.
Or is that you need also CMC, just making sure that.
That study.
Sure we can get an idea of how soon after you would be able to file and are you planning on having a meeting with the FDA before you file just just give us a sense of all of that timing.
Kind of.
That's question number one and then question two here just so we're clear can you tell us what is the purpose of doing the crossover chamber trial. The Schirmer test trial that you just mentioned that would be does this just backups just in case. This other one tranquility doesn't work.
What other purpose doesn't serve thanks.
Thanks Mark.
And thanks for the excellent.
Questions I think as I've said, many times before investors often forget about the requirement for a safety trial.
And the CMC requirements, both of which are obviously critical for NDA submission.
I'm thrilled to report that our CMC progress to our knowledge is superb.
<unk> CMC, specifically with the FDA and at this point I don't foresee any issues regarding CMC as it relates to.
Commercial our registration batches stability and et cetera.
The safety trial is a significant undertaking for chronic drugs generally a 12 month safety trial is required per FDA dry disease guidance. As you know 100 subjects are our 100 patients are required to be exposed to the <unk>.
<unk>.
For the 12 months at least.
The NDA can be submitted prior to the completion of the safety trial, but by the generally by the 120 day update all the final safety data that is the 12 month data for this one.
Hundred patients that needs to be submitted in addition.
I think at this point, we remain on track to be able to submit the NDA mid year for dry eye disease based on the current enrollment and the safety trial.
Across the industry.
Not only in triad disease or in ocular diseases, but broadly.
We are experiencing.
Some challenges in retaining patients in trials.
Enrollment has not been as difficult as we move through various phases of Covid.
But as is the case with Covid broadly I think many people are evaluating life choices differently than they have in the past and retention again across the biotech industry in the clinical trial industry broadly.
Is a challenge.
Notwithstanding those comments I still believe we're on track for a mid year NDA submission.
Your questions about the crossover and the one day Schirmer test trial are good ones for sure I think either trial could serve as a backup but really we're running those trials because they answer a slightly different questions and what we've asked previously in particular.
<unk> that dry disease chamber crossover trial, which as I mentioned in response to Howard's question.
To our knowledge has never been done before as you know the FDA considers the preponderance of evidence.
Our position in submitting this NDA is that with <unk> App will come one of the most comprehensive NDA packages ever submitted for dry eye disease. The crossover trial. The Schirmer test trial are two examples of our efforts to expand the package to them.
<unk> the breadth of activity of the drug across not only a large number of patients, but different models and different trial designs.
Thanks.
Thank you Mark.
Thank you.
If you'd like to ask a question.
One on your telephone keypad.
Our next question comes from Thomas Shrader of BT LNG Thomas Your line is now open.
Hey, good morning, Bob and Josh just a song on for Tom.
As we wait data read upwards phone quality to from <unk>. One one of the concern was patients going into the trial had low.
Baseline ocular redness and I'll just wondering if you guys had an earlier read on sort of tranquility to patient.
Hi, good morning.
Yes.
<unk>.
Expressed are described I would say two major differences.
Yes.
The tranquility trial relative to prior trials that we've run.
One of them is that the tranquility trial was primarily run during pollen season.
This spring.
Paul and as you know is not only.
Allergic or pro Allergan in many cases, but even if subjects aren't allergic to pollen paulinism mechanical irritant and therefore can confound ocular surface disease assessment of ocular surface disease.
The other major difference that you highlighted in your question is that the baseline redness scores.
Going into tranquility were paradoxically lower.
And then they were with the previous phase III trial that demonstrated <unk>.
Testicle significance across <unk> and vehicle for ocular redness.
One reason for that May have been.
Use of anti histamines or use of Faisal constrictors or use of artificial tears, which of course are restricted and clinical trial settings.
But nonetheless occasionally occurs amongst patients that are suffering from.
Allergies and other effects that are evidenced during allergy season or pollen season.
I would say so far as we monitor the baseline scores on a blinded basis.
For tranquility to the baseline scores look better or higher than they did in.
And the prior phase II trial, but obviously the result that matters is the blinding of the trial and the differences between groups and.
As I mentioned in my prepared comments, we remain on track for a mid year data announcement for tranquility too.
Great. Thank you.
Thanks, Sean.
Thank you.
Next question comes from Matthew Cross of Alliance Global Partners. Matthew Your line is now open.
Hi, guys. Good morning, and thanks for taking a couple of questions from me here. So.
So pressing ahead in AC which invigorate too.
I was wondering if you could expand upon the measurement of redness in that Chamber study.
I guess could you confirm that the same baseline redness score of at least two I think that was used.
Invigorate will also be required and invigorate two given the design similarity you noted.
Is there any possibility of referencing data from invigorate and the kind of overall big data package for filing and given.
Given the kind of overlap and disease characteristics that we've covered here.
That's an interesting question, Matt Thank you.
Generally the FDA considers dry disease distinct from allergic conjunctivitis.
Notwithstanding the overlap that.
<unk> and others have highlighted on this call between allergic conjunctivitis and dry eye disease.
Suspect that in reviewing the dry eye disease NDA, the FDA will consider.
The reduction of readiness in allergic conjunctivitis.
So I doubt that readiness reduction of allergic conjunctivitis will be a primary consideration when assessing.
The sign activity of approximately <unk> <unk> in dry eye disease.
The <unk>.
Allergen Chamber trial protocols.
Are somewhat different than the dry eye disease.
Chamber protocols.
As I mentioned in my prepared comments the allergy trials can only be run in the winter.
And the reason for that is if you have pollen in the environment.
<unk> Khan sounds.
Allergen response in the chamber, which has aerosolized pollen in it.
Patients.
To your point.
Before entering an allergen chamber trial must demonstrate an increase in itching and redness to.
To qualify for the trial.
But prior to entering the chamber.
After dosing drug or a vehicle prior to entering the chamber patients must have essentially no readiness.
And the redness has to build and the chamber.
That is different in dry eye disease.
There subjects.
Two songs question must have a readiness.
Not only in the dry disease chamber to enter the trial, but generally as a.
As as drug is dosed and they enter the chamber for readiness assessment, so two different protocols.
Highlighted by the difference.
And Paul and the nature of the diseases.
Got it. Thanks, So I appreciate the thorough answer there and then just kind of a related point around invigorate. Two obviously, you've already conducted a positive second study in the form of alleviate.
Just wanted to now that you've kind of discussed plans officially to go ahead with invigorate too.
Which is largely a repeat of invigorate wanted to confirm whether you would received any additional feedback from the FDA kind of confirming or that maybe would explain to some degree better.
Why they adopted to.
Quest and I don't know if this was an FDA request or.
Maybe your answer.
Clarify that but to repeat that.
A more design and what was kind of the shortcoming of alleviate.
Based on our discussions with the agency.
Alleviate which was a contract titled Challenge trial that is pollen is directly administered under the surface of the eye and patients are assessed over an hour or so after that.
It was primarily designed to assess anti histamines obviously.
For <unk> is not an antihistamine.
And thus the FDA wanted two adequate and well controlled trials.
On a different model, which is the allergen chamber model.
I think I've expressed a considerable amount of optimism regarding invigorate too.
Mostly because we have a phase II trial, now recently published and the allergen chamber that was highly statistically significant for patient reported ocular itching in ocular tearing and investigator assessed redness.
And also because the invigorate trial.
Does highly statistically significant across itching, redness and tearing I don't expect anything different from invigorate two <unk>.
One reason for that is that the protocol for invigorate two is substantially identical.
To that of Invigorate and obviously, we've discussed the protocol and the assessment with the agency.
Previously.
The timing of invigorate too as we've described today will likely be 2023, that's because we can only run these trials in the winter. It often takes two winter seasons to enroll.
A sufficient number of patients.
But in response to other questions I've said today, the NDA submission for allergic conjunctivitis would occur subsequent to that of dry eye disease.
Understood. Okay. That's all very helpful. Thanks, Todd reported the data and the rest of the year.
Thank you Matt.
Thank you our final question of let's say comes from Yale Jen of Laidlaw and company your.
Your line is now open.
Thanks for taking the question Todd.
Just you mentioned that you don't want to start it continue.
Okay.
The Chamber study readiness.
Poland season should we assume that you will about to compete.
Enrollment.
For the study.
Yeah.
I think that is an excellent assumption.
As I said previously today and as we've discussed during the tranquility data call Apollon is a confounding factor not only in terms of dry disease development, but also in terms of the assessment of dry eye disease.
<unk>.
Issues with Paul and our.
Sure.
Parent with patients that are allergic to pollen and their apparent with patients that are not allergic to pollen.
One goal as you pointed out of.
Tranquility too is to perform that trial.
Outside of pollen season.
Which as you know is about to start.
And so.
I think your assumption is reasonable that.
We will not continue enrolling very much longer and that at some point in the relatively near future. We will have completed enrollment and then we would look forward to reading out the results again in the mid year timeframe.
One follow up question here is that for.
For $21 91.
In the PDR.
Should you have a positive data to be reported in second half of this year what might be to follow up on the indication.
That's another interesting question Yale.
The PBR trial the guard trial.
Completed enrollment late last year.
And.
The follow up is six months.
So one might reasonably assume.
That the last patient last visit in the trial is somewhere around mid year. This year.
Data would come out sub.
Subsequent.
To that.
I think then we need to discuss with the agency the next steps.
Which are interesting.
In that since we have started guard.
Methotrexate has been recognized at conferences and in papers that you can access online as a potential treatment for PBR.
If that's the case then it becomes difficult to enroll a trial like guard where patients are randomized.
To either receive AVX 21, 91 or <unk>.
Standard of care, because surgeons don't want to risk a patient being randomized to standard of care, which essentially is nothing it's a watch and wait approach. There is no approved therapy for PBR and thus.
The risk is a patient is enrolled in the trial and randomized to watch and wait and does not receive therapy.
Now in terms of methotrexate is more and more regarded as an effective therapy. Thus I don't think guard is practical trial like guard as practical to repeat Mike.
My guess is we'll end up discussing the guard results with the agency will end up discussing the literature that has emerged on methotrexate for the treatment of PBR, a subsequent to starting guard and that.
Potentially we can negotiate an NDA submission that involves the combination of real world data published data and guard data.
But that remains the subject of a of a future FDA meeting that would occur after the guard results assuming the guard results are positive.
Okay, Great that's very helpful and.
Best of luck.
First over there thanks.
Thank you Yale.
Thank you we have no further questions. So I will hand back to Dr. Brady for any closing remarks.
Well. Thank you all for joining us today and as always we look forward to keeping you updated on our progress.
Thank you for joining today's call you may now disconnect.
Okay.
Yes.
Okay.
Okay.
Okay.
Yes.
Okay.
Okay.
Okay.
Yes.