Q3 2021 Aldeyra Therapeutics Inc Earnings Call
Yeah.
Ladies and gentlemen, thank you for standing by and welcome to Dr. <unk> Therapeutics third quarter 2021 financial results Conference call. At this time, all participants are in a listen only mode. Afterwards.
After the speaker's presentation, there will be a question and answer session I would now like to hand over the conference door 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 Aldara.
This morning, we issued a press release reporting our financial results for the quarter ended September 32021.
A copy of the press release is available on the investors and media section of our website www dot out there a dotcom.
Please note that this morning's conference call contains forward looking statements regarding future events and the future performance of Aldara.
Forward looking statements include statements regarding submission of potential new drug application 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 out there is current views concerning future events.
They are based on assumptions and subject to risks and uncertainties, including the development clinical and regulatory plans or expectations for out there its product candidates and systems based approach at the risks that results from clinical trials or portions of clinical trials may not accurately predict the results.
Future trials for the same or different indication and out there is 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.
Are there assumes no obligation to update these statements as circumstances change.
Future events and actual results could differ materially from those projected in the company's forward looking statements, including the current and potential future impact of the COVID-19 pandemic on our business results of operations and financial position.
Additional information concerning factors that could cause results to differ materially from our forward looking statements are described in greater detail in the company's press release issued this morning, and our filings with the SEC.
I will now turn the call over to Dr. Brady.
Thank you Joshua.
This morning, I'm excited to share with you an important progress we've made.
And the development of our novel therapeutic approaches for ocular and systemic immunological diseases.
As we continue to strive to improve the lives of patients.
With significant unmet medical needs.
Let me begin by updating you on our anterior segment ocular programs.
This quarter, we expect to report topline results from the tranquility and tranquility to clinical trials of our proxy lap in dry eye disease.
The primary endpoint of these trials is ocular redness, which is arguably the only objective sign of dry eye disease that matters to patients.
Secondary endpoints are tier rasp level, schirmer test and dry eye symptoms.
Additionally, enrollment has completed in a multicenter double masked randomized vehicle controlled parallel group phase two clinical trial for proxy lap in dry eye disease.
The purpose of the phase two trial is to optimize the tier collection process to measure RASK.
Pending ongoing discussions with the FDA and the timing of clinical results, including our 12 month safety trial of approximately <unk>.
And consistent with prior guidance.
We expect to be in a position to file a new drug application or NDA early next year for dry eye disease. In addition, we remain in discussions with the FDA regarding NDA requirements for allergic conjunctivitis and.
And expect to be able to provide an NDA update for proxy.
By the end of this year.
During the year several peer reviewed journals have published articles highlighting the safety and efficacy profile of our proxy lap in dry eye disease and allergic conjunctivitis most.
Most recently the journal clinical Ophthalmology reported results of the clinical trial evaluating the subjective eyedrop experience of two formulations of approximate app versus <unk> in patients with dry eye disease. The paper entitled a post acute ocular tolerability comparison of our proxy lap and the fit a graft.
He is open access and available on part of that.
Turning to our retina programs as many of you know AVX 21, 91 has been granted orphan drug designation for three distinct clinical indications that affect the retina retinitis pigmentosa proliferative vitriol, retinopathy or PBR and primary vitreoretinal.
Lymphoma.
Retinitis Pigmentosa is a group of rare genetic eye diseases that affects an estimated 80 to 100000 individuals in the United States and approximately one in 4000 people worldwide.
Last quarter, we announced our plan to initiate a phase II clinical trial of AVX 21, 91 in patients with retinitis Pigmentosa.
And we remain on track to do so by the end of this year.
The primary endpoint of the trial will be safety and Tolerability of AVX 21, 91 secondary secondary endpoints include visual acuity central retinal sensitivity dark adapted retinal sensitivity and retinal morphology.
PBR is a sight threatening condition and the leading cause of failure of retinal detachment surgery. We remain on track to conclude enrollment at the end of this year for part one of our ongoing phase III Guard trial in PBR.
And we expect results from guard next year.
We continue to be excited about the broad AVX 21, 91 platform and the potential of AVX 21, 91 to treat rare immune mediated retinal diseases that today have no currently approved therapies.
Turning to our systemic disease program, we remain on track to report phase two proof of concept clinical results from <unk> six to nine.
And asthma, psoriasis, and COVID-19, and the fourth quarter of 2021 or the first quarter of 2022.
AVX six to nine is our orally available rasp inhibitor. It represents a first in class systems based therapeutic approach for the potential treatment of many immune mediated diseases that are currently treated with single target drugs that can lead to toxicity.
We've also continued to evaluate the possibility of expanding clinical testing for AVX six to nine and other indications.
We're rasp may mediate pathology, and where current therapy is either an adequately effective or toxic.
We expect to update you on our progress later this year.
With that I'll turn the call back over to Joshua to review, our third quarter financial results.
Thank you Todd.
Cash and cash.
Cash and cash equivalents as of September 32021 were $241 $4 million base.
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 initial commercialization over Approximal App, if approved and continued development of our product candidates and ocular.
And systemic immune mediated diseases.
Turning now to our third quarter 2021 results.
Research and development expenses were $12 9 million for the quarter ended September 32021, compared with $6 1 million for the same period in 2020.
The increase of $6 $8 million is primarily related to increases in clinical research and development expenditures and consulting costs, partially offset by decreases in personnel related costs, including stock based compensation and manufacturing activities.
General and administrative expenses were $2 $5 million for the quarter ended September 32021, compared with $2 $3 million for the quarter ended September 32020, the increase of $200000 is primarily due to an increase in miscellaneous administrative expenses.
The net loss for the third quarter of 2021 was $15 $8 million or 27 cents per share compared with a net loss of $8 9 million or 23 per share for the quarter ended September 32020.
Looking at our upcoming Investor calendar, Todd and I will be participating virtually in conferences hosted by Jefferies Baron Berg and BTG.
On November 11th Todd will be presenting at I celebrate her at a O 2021 featured event I Hope next month American Academy of Ophthalmology 2021 annual meeting in New Orleans.
Please check the events and presentation section of our website for details.
If you are attending any of the conferences and would like to schedule a one on one please email our investor relations team at a L. D X at Investor Relations Dot Com.
Now I'll hand, the call back to Todd for closing comments.
Thank you Joshua we continue to make meaningful progress in developing safe and effective treatments for ocular and systemic diseases.
In addition to the present quarter, we have several busy and exciting quarters with significant clinical development milestones ahead.
We are excited about the first line potential for approximate app as a treatment for anterior surface inflammatory diseases that are not being adequately controlled by standard of care approaches versus a significant percentage of patients.
And beyond the anterior segment, we're developing innovative medicines for retinal inflammatory diseases.
We believe will create near term high value commercial opportunities for our company.
And we are committed to expanding our therapeutic applications to systemic inflammatory diseases, representing a broad array of conditions that are not sufficiently treated by current therapies today.
With that Joshua and I'll be happy to take your questions operator.
Thank you Sir and as a reminder, if you wish to ask a question simply press Star then the number one on your telephone keypad.
Question is from the line of Tom Shrader from <unk>. Your line is now open.
Hi, Good morning, Thank you for taking the questions.
Had a question on the commercialization front, we've seen some young company's first product companies use of short term commercial alliance with an existing company and Thats something thats easy to set up in this space have you have you thought about that or do you think whatever you do you're likely to do on your own.
So thanks for thanks for the question Tom let.
Let me start off by saying.
The data that shows were approximately apps early onset of activity.
<unk> readiness.
And broad symptom improvement profile is unmatched by existing products in <unk>.
D and dry eye this makes our commercial prospects extremely attractive.
Of course that is if the product is approved assuming success of our clinical trials and our NDA submission.
The anticipated topline could support us building, a commercial infrastructure on our own.
And it makes it attractive for potential strategic partners. So we have lots of options available to us, including the one that you mentioned.
Using a different organization to commercialize for us at least on a short term basis is something thats extremely easy to set up but again with reprocess labs.
Commercial potential we have lots of options available to us.
Okay, and if I can ask an unrelated follow up we've seen the enormous power of the Schirmer test in the eyes of the FDA, it's almost like a loophole.
The flip side is that if you hit redness, but not schirmer. So patients are clearly benefiting but a very different way than conventional eyedrops does the label does the generic label still makes sense or do you think you'd be back to negotiation just your thought on how important schirmer is because it's.
It's fundamentally different than readiness.
Hi, Tom Good morning, it's Todd Thanks for the question.
Hi.
I still resonate with that question because it seems that there are so many products beginning with restasis.
Years ago.
That focused on Schirmer test.
As the objective Heine.
For dry eye disease.
As I mentioned in my prepared comments this morning.
I don't think that patients care about objective signs of dry eye disease that is signs that can be assessed by physicians or staff.
With one major exception and that is ocular redness.
Which is a sign of dry eye disease, and it's obvious why patients care about redness no one wants to have a redeye.
Now I don't think having ocular redness and our label is in any way a detriment in fact I think it is a significant commercial advantage for.
For physicians health care providers, optometrists and patience to see that there is a drug available potentially.
Widens there is that diminishes ocular redness I think it's very very powerful.
Commercially and a tremendous advantage.
Relative to drugs on the market today for.
For chronic treatment of dry eye disease, we continue to be asked about Schirmer test Schirmer test is a secondary endpoint.
And our.
Current dry eye disease trials that I described in my prepared comments this morning, but in the end.
We're focused on ocular redness for all the reasons that I just described.
Okay. Thank you.
Your next question is from the line of just thinking from Oppenheimer <unk> Company. Your line is now open.
Hi, good morning, all and thanks for taking the question.
Maybe just a couple on on dry eye.
With the phase two dry eye data being first available.
Ken and the team comment a little bit as to what might be disclosed and available from this study and how we can think about those results informing the anticipated phase III program.
Okay.
Just an excellent question.
And thanks for that.
The phase II trial.
As I mentioned in my prepared comments is designed to optimize the RASK signal.
In particular.
To optimize the collection tiers, so that we're able to collect more tears from.
Dry eye patients as you can imagine.
Collecting tears from a patient population that suffer from lack of tiers.
Is a challenging process.
The phase III trial is roughly half the size of the two tranquility trials each of the tranquility trials is approximately 300 subjects.
Phase II trial is 150 subjects.
And I think your assumption that the phase III trial.
Will.
Complete or results will be available first is correct simply because as we've announced this morning enrollment is complete in that phase II trial and that trial is smaller than the tranquility trials.
I think it's also reasonable to assume that we'll be able to SaaS.
The data from the phase III trial.
Order to optimize the completion of the of the tranquility trials in itself that phase II RASK trial is not pivotal it is not critical path for NDA filing.
Inc that trial, depending on the results could be both of those things, but we'll just have to see the data.
I think weather.
We have a data release that concerns that phase II trial is a materiality question.
That will need to answer once we have the data in our possession, otherwise I think that data from that trial.
The RASK data and so forth.
B announced in conjunction with.
Other data releases.
Understood understood and maybe on the point that you had mentioned about sort of the size of the studies and considering sort of the timing of the initiation of those studies is it fair to sort of assume that tranquility is at least half enrolled in tranquility too.
At least a little less than half sort of given the timing of the initiations in the study sizes.
Well, we typically don't comment on the trial enrollment at least not until enrollment has been completed.
I do think it's fair to assume that tranquility, one is well on its way.
Towards completion as you mentioned given the start dates.
Of those trials.
One option based on the data from the Phase II trial is to expand enrollment in either of the tranquility trials if needed.
That is if the data from the phase II to suggest that either of the tranquility trial is not sufficiently powered.
We have the option prior to database lock up either tranquility trial of expanding those trials.
So in a sense, we don't quite know when enrollment is complete in either tranquility trial until we have the phase III data.
Okay, great very helpful. Thanks for the question.
Thanks, Jonathan.
Your next question is from the line of <unk> <unk> from Citigroup. Your line is now open.
Hi, Todd and Josh Thank you for taking the questions.
Could you just explain a little bit more detail. The purpose for this additional phase two for <unk> in dry eye. If the goal is to optimize the measurement of tier ASP levels could you just clarify why this phase two it wasn't completed before heading into the tranquility trials, where rasp levels as a trs levels as a secondary endpoint.
Okay.
Hi, Good morning, a call I think thats a good question as well.
Let me begin by explaining why we're interested in RASK.
RASK was designated as a sign of dry eye disease by the FDA.
Last year.
However, as I mentioned in my response to Tom's question earlier this morning.
We think that ocular redness is a more relevant sign.
To providers and patients and that's why we're focusing on readiness. In addition to the fact.
Yet we continue to demonstrate positive redness data.
<unk> allergic conjunctivitis and the redness data in the run in cohort of Tranquility announced in January of this year was also very positive. However.
The ability to include RASK modulating.
Modulating data in the pharmacology of mechanisms section of our potential drug label I think it's also commercially differentiating and.
And that's why we're so interested and showing that we can diminish RASK in tears of patients RASK is the target of approximately <unk>.
And I believe we would be the first eyedrop ever to demonstrate target modulation in a clinical trial.
The phase III trial.
Altered the mechanisms by which we collect tiers there are two primary ways to do that.
The first is a small glass capillary that's inserted in the tier Lake.
After the lower lead has retracted that capillary can remain.
In our near the surface of the eye for approximately 10 minutes, we need about five micro liters of fluid.
Be extracted.
For RASK analysis.
And remarkably there are many patients with dry eye disease that don't have five micro liters of fluid just for reference your typical eyedrop, it's 40 micro liters.
So if you take an eyedropper at home you drop a drop on you put in place a drop in the Paul Your hand, you look at that that's about 40 micro liters and amazingly many of the dry eye patients in our trials simply don't have enough volume.
To assess RASK, which is why we ran the phase II trial, we've switched around.
Some of the.
Capillary extraction processes.
And then that changed the order of the other method to extract tiers, which is the schirmer test the.
The Schirmer test as you know is a small strip of paper also inserted into the tier Lake following lower lid retraction. The strip can remain in the eye for about 10 minutes or so as the <unk>.
Here are fluid is wicked up into the strip. The strip can then be removed spun down in our centrifuge and that fluid can then be analyzed.
As you point out and as I was describing in response to Justin's question I think it's reasonable to assume that we will have the phase II results prior to the tranquility results and.
Timing of the RASK data.
Somewhat different from the timing of our other clinical data redness incentives and so forth.
Reason for that is it the tears has to be shipped to.
Third Party laboratory. The tiers are then analyzed using an Elisa, which is a process to measure that RASK levels.
Those data are then.
Transferred back to our statisticians and we'll analyze them separately in the run in cohort announced in January we announced our clinical data first redness symptoms and so forth.
Subsequently, we announced the RASK data.
Similar pattern that may evolve with our clinical trials here in that the RASK data could come after that clinical data.
Does that answer your question Yigal.
Yes. Thank you.
And I just had one for Josh.
I think you mentioned in the press release that you have cash to support initial commercialization of our products.
Wondering if you could just be a bit more specific about the definition of initial and what that encompasses.
Thank you Gal.
Essentially what that what im referring to there is building out of the home office.
And another factor to think about there is.
As our runway out to 2023, so I think it's important to not signal.
That will be we have enough cash that will support an entire commercialization effort.
Well after the product launch.
Got it thank you.
Your next question is from the line of Marc Goodman from SBB Leerink. Your line is now open.
Yes. Good morning, I was wondering if you could just walk us through tranquility, one shrink libbey two you get the data.
Talk to us about from there whats left so that we understand all the boxes being checked towards when you actually file.
Yes.
Hi, Mark good morning, happy to comment on the.
Remaining.
Boxes to check prior to NDA filing as you know the FDA required symptoms and signs.
For NDA submission.
In dry eye disease.
We believe we have completed our symptom requirements that those data are prominently highlighted in our corporate deck with 212 week.
Pivotal trials that using <unk> as our symptom.
The remaining trials, particularly the tranquility, one and two trials are focused on the sign requirement for NDA submission and as we've discussed this morning.
That sign is ocular redness, though we are also assessing RASK.
And.
Schirmer test.
In addition to the efficacy requirements for NDA submission our safety requirements.
Consistent with NDA filing NDA submissions generally there is a safety trial.
<unk> must be part of the submitted the package as I said in my prepared comments this morning.
We are currently running a 12 months.
Safety trial.
To support the chronic use for <unk>.
Dry eye disease I continue to believe that the 12 month safety trial will be the gating factor for us in terms of NDA submission timing. In addition, they're our chemistry manufacturing and control requirements for NDA submission.
I believe that we are.
An excellent position with regard to our CMC requirements, and I think that rounds out the basic components.
We need to file the NDA.
So youre thinking that the 12 month safety is going to run into early next year and that's the gating issue and as soon as that's done that's when the filing occurs so that will be whatever early next year means that's that's the gating issue.
The FDA require six months of data from.
From the safety trial.
And I believe 100 drug treated patients for submission.
And that will be the timing of that will be.
One of the gating factors for NDA submission.
The 120 day update after NDA submission.
<unk> six months that is months seven through 12.
Just be submitted.
To the FDA so at the time of NDA submission.
Roxanne minutely eight months or so of safety data would be required so that by the 120 day update.
The remaining safety data is complete.
And.
So also on six to nine.
I'm noticing that Youre, saying is the data could come in the fourth quarter could come in the first quarter has there been any enrollment impact by COVID-19 or anything like that or is this basically it's always been around the end of the year early next year in your mind.
Certainly the latter.
We've always thought that the.
Results of the trials could be available towards the end of this year early next year.
We have had a COVID-19 impact.
On some of these trials.
Particularly the asthma trial.
There.
Respiratory disease patients are understandably concerned.
About presenting to clinics or hospital environments are enrolling in clinical trials given COVID-19.
We've also seen recent impact on our Covid trial itself the.
The reason they are being vaccinations, and boosters and therapeutic antibodies and new drugs to treat.
Covid has diminished interest in the Covid trial Nonetheless.
We do expect to be able to announce data.
Per our guidance, we also expect to announce all three of those trials in aggregate.
To remind.
The listeners on the call. These are proof of concept phase III trials. They are not designed nor are they powered statistically to indicate clinical results.
Rather the trials are designed to India.
Indicate pharmacodynamic activity.
AVX six to nine which includes a cytokine levels that RASK levels and potential early clinical signals as we evaluate future trials, particularly phase <unk> clinical trials that can be run with AVX 69 that starting next year.
Thanks.
Thanks Mark.
Your next question is from the line of Kelly <unk> from Jefferies. Your line is now open.
Thank you for taking my question.
Two questions regarding the Sparks, Nevada.
Michael.
Thank you Robert.
Sure.
While the one next call.
Alright.
Cough patients.
If at all.
Thanks Kimberly.
Yes.
<unk>.
What are your observations.
Scott and tranquility.
Alright, and what's not.
<unk> our pro forma.
No go off into phase III of tranquility.
Trial and also a relevant question.
You are going to see that.
Q2 trial right.
Hello, Rod Hall.
One is to end the call.
Thank you there are formidable.
Semi annual.
Number.
To critics Shadow shed light on that.
Bob.
Tom.
Thank you.
Kelly. Thanks for the question and you are better at Maths and I am. So forgive me ahead of time for simplistic cancers.
Okay.
Allergy trials are somewhat different.
On the dry eye trial both trials.
Both the invigorate trial for example, an allergy and the tranquility trial.
Trials in dry eye disease are in chambers.
However.
Obviously, the allergy trials are.
With Allergan and the chamber and the dry eye trials are with low to no humidity error in the chamber the patient populations are related but different for.
For obvious reasons I think there is approximately a 50% overlap entity patient populations between allergic conjunctivitis and dry eye disease.
What I'm, saying is that there are some similarities across the allergy chamber trials and the dry eye chamber trials, but there are also some important differences.
Another important difference statistically.
The allergy trials, where crossover trials.
Which as you know we will diminish standard error.
And that the intra patient differences can be controlled.
That is not the case with the dry eye Chamber trials. These are parallel group trials. So intra patient differences are not control.
I would expect the standard errors to be slightly higher for that reason.
However, without having the data we don't know.
We did.
Yes, the powering.
The tranquility trials using the tranquility run in cohort.
As we have described previously we believe at this point that the tranquility trials based on the run and cohort are approximately 90% powered for ocular redness given that delta.
That was evidenced in the run in cohort.
And the standard errors.
It is possible to back into the standard error or standard deviations that we use to powertrain quilty.
Knowing what I, just said that the tranquility trials are approximately 90% powered at 300 patients or 150 patients per arm and using the delta that was observed in the run in cohort.
I, particularly resonate with the last part of your question Kelly regarding the use of the phase two RASK trial to inform us on future conduct of tranquility.
One of the things that I've mentioned previously today is that we will have the ability to change.
Yes.
The enrollment numbers of tranquility if we.
We received phase II data that suggests that shrink quality is not sufficiently powered.
And that is by design.
We have purposefully sequenced.
The phase III trial, and tranquility, one and tranquility too so that between each of those trials will have the ability to make.
Powering changes if needed.
I think that answers your questions Kelly, but forgive me if I.
Haven't covered all the mathematical details you were asking about previously.
Thank you very much Super helpful. If I may also has that is that real quick.
And then the Rins.
Model.
Florida, that's what analysis. Thank you John.
From quality.
Thank you Charles.
I wonder how much of that Alameda called Marin.
Hey, Thank Barbara Ryan.
Hi, David how should I expect similar.
Number.
Sure change.
On the call there.
Right.
Generally I am a big fan of Inova and Kohl's in MRM.
Because those statistical techniques.
Now for assessment of repeated measures.
Which is a fancy way of saying that each subject is assessed at multiple time points.
I believe in the tranquility chamber there are 13 different time points.
During which ocular redness.
Symptoms and so forth are assessed.
Those are referred to statistically as repeated measures because within each subject. There are 13 different values and the standard error is accounted for differently.
Based on the fact that those measures are repeat it.
The covariance matrix that you referred to is a method of.
Adjusting for the correlation between time points.
In fact, a correlation matrix is mathematically related to covariance matrix.
It makes sense that within a particular subject.
Adjacent time points are correlated.
Time 10 minutes, it's probably fairly similar to time five minutes or time 15 minutes and that is exactly what the covariance matrix attempts to adjust for we typically have used the same covariance matrix matrices.
Across clinical trials for the very reason that I. Just described that is there is a fairly clear relationship.
Amongst adjacent.
Time points, we haven't disclosed the exact statistical model.
Perhaps one day, you'll see it when the.
SaaS is posted on clinical trials dot Gov, but for now I think you have a fairly good understanding of how we are.
Think about.
Repeated measures and the correlation between time points.
Thank you for those very thorough answer.
Thanks Kurt.
Thanks Kelly.
Your next question is from the line of Edwin Jen from HC Wainwright. Your line is now open.
Hi, Thanks for taking my question a question on the new trial of <unk> 21 91.
Retinitis Pigmentosa.
Can you briefly talk about the trial design for the efficacy endpoint, what should we look at and what improvements do we.
We expect from this phase two trial.
And lastly are you going to see some data of this trial next year. Thank you.
Yes, Thanks Edwin for the for the question, we're still working on getting that design up.
And and running I.
I do expect that we'll be able to be in process. This year as I mentioned in my prepared comments.
This morning.
Essentially this is an open label trial and we are going to.
SaaS a couple of different dosing.
Vince.
And as I mentioned, the primary endpoint will be.
<unk>.
Safety.
Because.
This particular.
Particular compound <unk> hundred 91 has not been previously.
It has not been previously tested.
Before.
In particular as we posted in our corporate deck headwind you can see that.
We expect this to be a single center trial.
We're looking at approximately I don't know four or five patients per dosing cohort a couple of different dosing cohorts and more or less at three months evaluation period, but we're looking at all of the standard secondary endpoints that most retinitis pigmentosa trials focus on.
And including obviously visual acuity, but also retinal function and retinal morphology.
Great. Thanks.
Your next question is from Doug.
Your next question is from the lineup.
Our outgrow from Jones trading your line is now open.
Hi, good morning, and thanks for taking my questions. My first is on allergic conjunctivitis.
On your comment around the NDA update for this indication by end of the year is it more of a question of.
Getting clarity around how much safety exposures needed could you confirm whether you have the necessary efficacy data for submission in allergic conjunctivitis.
Then I had a couple of follow ups.
Sure.
Thanks for car no. It is not a function of safety data.
The question.
Currently under discussion with the FDA have to do with efficacy requirements.
I can go into a bit more detail along those lines in particular, we have two phase three trials that have been completed both of which were highly statistically significant and hit there.
Primary and key secondary endpoints.
Hey.
It should be pointed out though that those trials are different so the alleviate trial, which was announced.
I believe in 2020 or 2019 has to do with conjunctiva Allergen challenge, which is a method of directly exposing the ocular surface to pollen.
In this case, whereas the invigorate trial that was released earlier. This year is an allergen chamber trial, which is a more real world.
The pollen exposure in that case, Paul on his aerosolized into a chamber and subjects are exposed in that manner. So the two phase III trials are different.
And as you know.
That requires discussion with the agency, which is currently.
Ongoing and thats be the subject of those discussions.
Got it.
An early stage pipeline you have previously talked about testing the rasp inhibition for backup Dr indications.
Just wondering if there are any updates there or is that something we can expect to hear in the next six to nine months. Thanks for taking my questions.
We are committed for car to continuing to develop the new rasp inhibitors.
As you can.
Tell from my excitement. This morning, we remain very positive on the potential of RASK broadly.
And immunological disease.
We are in the process of discovering optimizing testing pre clinically a variety of new rasp inhibitor analogs.
With extended.
Patent lives and so forth and we look forward to updating you on the street.
Our new approaches along those lines at some point next year.
Your next question is from the line of Esther Hong from Bahrenburg. Your line is now open.
Good morning.
So just wanted to know if you could remind us of the findings.
Publication that you mentioned regarding the comparison with <unk> versus <unk>, and then second whats the feedback youre getting from practicing physicians regarding <unk>.
Currently available therapies for dry eye disease, and where perhaps how that might fit in.
<unk>.
Good morning Esther.
Speaking with key opinion leaders both on the ophthalmology side of the fence in the optometry side of the fence.
Is something that is.
Of key importance to us that these days. So your question is particularly appropriate.
Well, we are getting very positive feedback.
Particularly for the reasons that I think we all know, namely that <unk> in dry eye disease appears to be the only therapeutic option.
Either in late stage development or currently available that works quickly.
Within minutes. According to the data presented in January from the dry eye Chamber. It's.
It's also the only drug that can be in theory used chronically.
That is widening that eliminates or reduces ocular redness, which as we discussed earlier. This morning, I think is a key commercial.
Advantage.
Hey.
Paper that you reference is open access and available.
On Pubmed.
The idea was to compare tolerability.
Between a couple of different formulations of Approx flap, including the one that we're currently advancing.
That we call the standard formulation.
And a novel formulation and the difference between those two formulations is minor.
Increase the percentage of an excipient.
In an attempt to delayed release of drug.
On the ocular surface, but as you can see from the results of the paper. The two formulations perform similarly, you can also see that in our corporate deck.
Based on the 12 week symptom data that we present.
One trial is a standard formulation in one trial is from the novel formulation.
The tolerability evidenced in the paper.
Is considerably better for.
Both formulations of Approx slab compared to lithograph lift.
<unk> is often plagued by.
Acute.
Discomfort.
Disturbances and blurry vision those are the three elements that are tested directly in the paper and.
You can go see.
How <unk> performed relative to to look at a graph in the manuscript.
Itself the only other thing I'll say is that ocular discomfort score.
Which was I would say one of the key symptoms as assessed in the paper.
Has also been used.
As a pivotal symptom.
Score for the approval of at least one compound in dry eye disease. That's the same measure that is evidenced in the paper and I think could represent a direct head to head comparison of dry eye disease activity, not just tolerability, but activity.
Approx left versus lithograph.
Got it thanks.
Thanks Esther.
Once again, if you wish to ask a question simply press Star then the number one the new telephone keypad.
Question is from the line of <unk> Jain from Laidlaw <unk> Company. Your line is now open.
Good morning, Thanks for taking the questions.
My first question is just trying to confirm that.
For the phase two study.
Okay.
But the main purpose is for ultimately determine whether the <unk> quality study.
Study you might if you will.
Need to increase the size of the <unk> study is mostly for potential would reach the.
Statistical significance for RASK.
But not yes, not for the retina or the schirmer score so correct.
Good morning, Neil and thanks for the question well. The reason we performed the phase two study is to optimize the RASK RAF signal.
I think.
We will be able to use the data from the phase II to power train quality for all of the endpoints if.
If we wish.
<unk> included Redness included Schirmer test symptoms.
Over I think it prudent for any biotech company to use <unk>.
Current and available clinical trial data to adjust powering of ongoing trials and Thats exactly what were doing with the phase two trial.
When we have designed the trial will be initiated the trial when the trial was ongoing in terms of clinical conduct.
And patient treatment and so forth. The idea really was to optimize RASK then as I mentioned adjust the timing and the sequencing in the order of tiered collection processes I think an added advantage, though of the trial is exactly what you've mentioned and that is we're able to take the data from the phase.
Two and adjust the powering if needed for tranquility, but we could do that with any of the endpoints that we wish.
But should we assume that at least at this moment in terms of tranquility.
The size is.
Reasonably powered.
Assume that well powered for detecting.
The redness.
Yes.
So thats the current assumptions.
I think that's an excellent point that.
But I have not made this morning.
That is.
Both the phase II and the tranquility trials.
Our powered for ocular redness.
While the phase two was designed to optimize the RASK signal. The phase two was also powered based on ocular redness that primary endpoint of the phase II with ocular redness.
Question, Dan as well, how can you reach 90% power with 150 subjects and one trial in 300 subjects in another trial and the answer is we use slightly different powering techniques and for those of you that are interested in the mathematics in one case, we used individual group standards.
Deviations and in another case, we used pooled group standard deviations the latter being much more conservative obviously by a factor of approximately two in this case.
So I think that both the phase II and the phase III trials are adequately powered for ocular redness and if we believe the powering calculations then.
And the powering calculations reflect reality, then there should be no need to adjust.
Powering going forward, but again the run in cohort was 23 patients.
The phase II trial of 150 patients.
As I mentioned I think it's prudent for any biotech company to take the most recent.
And fulsome clinical data to power.
Or just the power for ongoing clinical trials.
Okay, Great that's very comprehensive.
So answer maybe one question on the 21 91.
Actually the two up here the first one is for the RP.
Yes.
After the phase two study.
Have you thought about what might be the potential approval endpoints.
For RP.
Have you spoke with your consultants or with the FDA about this.
Thanks for asking about RFP and I know Edwin brought up RP as well I should say at the outset that we're extremely excited about retinitis pigmentosa.
There is no approved drug for retinitis Pigmentosa.
Mendes unmet medical need there is a tremendously.
The endpoints need a trend da submission at that point.
And it made the last one also in 21 91 is that you mentioned recently that it's the drunk also a potentially can be useful lymphoma vitriol red no lymphoma any.
Any thoughts in terms of the discussion on this print.
Glen foam as it occurs in the primary sense in the eye as a serious condition.
I believe the median survival is about five years. The challenge is that those cancers, often metastasized to the C N S or the brain.
There is currently one drug that is used to treat.
Primary ocular the former R. P B R L and that is methotrexate.
Which is the active ingredient in 21 91.
There is a considerable amount of literature.
Literature.
Scientific literature on the use of methotrexate.
Both in terms of systemic administration and enter ocular administration for the treatment of lymphoma and.
Our discussions with the agency involved.
The scientific literature as well as.
Other mechanisms, we may be able to use.
For.
For NDA submission for lymphoma, and those discussions are ongoing.
Yeah.
Okay, great. Thanks, a lot and congrats for all of the progress is.
Yeah. Thanks, Thanks for the excellent questions.
There are no further questions I will have to call over back to Doctor Brady Foreclosing comments.
Yeah.
Thank you all for joining us this morning.
As always we look forward to keeping you updated on our progress.
And with that this includes today's conference call. Thank you for it ending you may know disconnect.
Yeah.
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