Q2 2022 Aldeyra Therapeutics Inc Earnings Call
rapid onset of action.
We're excited about reproxylapse potential to change the treatment paradigm in what is one of the world's most prevalent ocular surface diseases, which today is suboptimally addressed with drugs that require at least weeks of administration for even modest improvement.
With a recent completion of the crossover and phase three tranquility two trials
We believe we put ourselves in a position to submit a thorough and extensive VNDA based on...
robust symptomatic improvement and the achievement of three objective sign endpoints of dry eye disease, and ocular redness.
SHERMER test and the SHERMER test greater than or equal to 10 millimeter responder analysis.
As I previously stated, the T outcome of the crossover trial is affirmation of the potential rapid onset of activity of a proxel app.
which based on the results of the trial included observed improvement within minutes.
Then, ocular redness tear production.
and symptoms, including discomfort, dryness.
Burning and stinging.
For the primary endpoint of Schirmer test on day one.
and ocular redness in the dry eye chamber on day two, the superior arty of a proxylap which statistically significant with a p-value of 0.004, paracular redness and 0.005 for Schirmer test.
I think the other important takeaway
From our crossover trial results is the strength of reproxel apps.
safety and tolerability profile.
clinical experience with ProX Lab now encompasses more than 1800 patients.
The drug has been well tolerated with no observed safety signals in any patient.
Consistent with all of our prior trials and consistent with most topically administered ophthalmic drugs, the most common adverse event, is transient in mild installation site irritation, which in reproxelapse case has generally lasted less than one minute in duration.
I think it's also worth...
reiterating that to our knowledge, Valdera is the first sponsor.
to evaluate an investigational dry disease drug in an adequate and well-controlled crossover trial.
As I noted on our crossover data release call, a key learning from the trial is that the high degree of patient to patient variability that we've observed.
can be reduced with a crossover design.
And we believe that the crossover design is feasible, not only is it related to dry eye disease.
but also for other ocular surface disease trials involving therapies with potentially rapid activity.
The effectiveness of the crossover trial design has also been demonstrated in the successful completion for ProxylAps Phase II and invigorate Phase III allergic conjunctivitis trials. And invigorate Phase III allergic conjunctivitis trials.
In addition, the ongoing Invigorate 2 Phase 3 trial is a crossover trial.
Looking ahead, we expect to submit our NDA and dry eye disease in the second half of the year following our type B pre-NDA meeting.
with the US Food and Drug Administration later this quarter.
The other accomplishment that stands out is the progress of ADX 2191.
Our Investigational New Drug Platform for Rare, but serious retinal diseases with no approved therapy.
The development program of ADX-2191 encompasses three such conditions.
Number one, primary vitreoretinal lymphoma.
which is a near universally fatal.
Cancer.
Two, proliferative vitreoretinopathy or PVR, a sight-threatening condition that is the leading cause of failure of retinal reattachment surgery.
And number three, retinitis pigmentosa, which is a rare group of genetic eye diseases. The retinitis pigmentosa is a rare group of genetic eye diseases.
The FDA has granted orphan drug designation to ADX-2191 for each of these indications, and the ADX-2191 is the first.
Methatrexate formulation specifically designed to be compatible.
with a vitreous humor.
the fluid in the back of the eye.
And therefore, represents what we believe to be a unique potential commercial opportunity for Aldera.
from our Phase III guard trial and PVR are on schedule and are expected for the second half of this year.
As a reminder, GARARD is a multi-center.
randomized controlled adaptive phase 3 clinical trial of repeated intravitreal injections of ADX2191 for the prevention of PVR.
The primary endpoint is retinal detachment.
over a period of 24 weeks.
relative to primary vitro retinal lymphoma.
We plan to have a pre-NDA meeting with the FDA in the second half of this year to discuss the regulatory path forward.
for ADX 2191. And finally, the third key milestone for 2191 is the top line results from the Phase 2 trial.
in retinitis pigmentosa, which we anticipate to be reported in the first half of 2023.
Eight patients are expected to be enrolled in the trial.
with half receiving monthly intervittual injections and the other half receiving twice monthly intervittual injections over a period.
of three months.
Lastly, our oral RASP modulator platform, led by ADX629, continues to advance.
and represents a broad expansion of our pipeline from ocular inflammatory disease to systemic inflammatory disease.
which as many of you know represents in aggregate one of the largest markets in pharmaceuticals.
This year we expect to report top line results from phase 2 clinical trial and acute alcoholic hepatitis.
and to initiate phase two trials in show where the Larson syndrome and minimal change disease. Larson syndrome and minimal change disease.
Top line results of the Phase 2 trial of ADX 629 and Chronic Cough are anticipated in the first half of 2023.
I'd say in summary that we are full steam ahead on our programs in both anterior ocular and rare retinal diseases.
with a busy and quite remarkable regulatory calendar plan for the balance of 2022, featuring two pre-NDA meetings.
and two planned India submissions.
And with two late stage candidates in what we believe to be a clear strategic path to market.
Alderra represents a real opportunity.
to positively affect patient care in both mass market and rare diseases. Thank you.
Now let me turn the call back over to Bruce for the financial review.
All right. All right.
Thanks Todd.
Cash, cash equivalents and marketable securities as of June 30, 2022 were $196.7 million.
Based on our current operating plan, we believe that existing cash, cash equivalents, and marketable securities will be sufficient to fund currently projected operating expenses through the end of 2023, including potential NDA submissions and initial commercialization of our Proxel app.
in ADX 2191 if approved, and continued development of Aldera's product candidates in ocular and systemic immune mediated diseases.
Net loss for the three months ended June 30th, 2022 was 17.8 million or 30 cents per share compared with the net loss of 14.9 million or 28 cents per share for the comparable period of 2021.
Losses have resulted from the cuts of clinical trials in research and development programs as well as from general and administrative expenses. The results of clinical trials have resulted in the cuts of clinical trials and the results of clinical trials in research and development programs and the results of clinical trials in research and development programs and the results of clinical trials in research and development programs
Research and development expenses for the three months ended June 30, 2022, were $14.6 million, compared with $11.5 million for the same period in 2021. The increase of $3.1 million is primarily related to increases in external clinical and preclinical development costs and drug product manufacturing expenditures.
General and administrative expenses for the three months ended June 30, 2022 were 3.1 million compared with 3.1 million for the same period in 2021. Transcription by Philmost Est.
Total operating expenses for the three months ended June 30, 2022 were $17.7 million compared with total operating expenses of $14.5 million for the same period in 2021.
Now, let me turn the call back to Dr. Brady for closing remarks.
Thank you, Bruce.
I want to let the audience know that we have a full investor relations calendar planned.
over the next several weeks, which includes the BTIG Biotechnology Conference, the Wainwright Virtual Ophthalmology Conference,
The City Bank annual Biopharma Conference.
And additionally, we'll be exhibiting in a series of medical meetings in the fall, including Vision Expo West in Las Vegas.
The American Academy of Automology Annual Meeting in Chicago.
The 32nd Biennial Cornia Conference in Boston.
and the American Academy of Automatory Annual Meeting and San Diego.
For my prepared comments today, now is a particularly interesting time to get to know Aldeira, and we welcome the opportunity to meet with current and prospective stakeholders.
and invite you to contact our investor relations team to schedule a meeting.
Operator, we'd now like to open the call for questions.
Thank you. If you would like to ask a question, please press star, followed by one on your telephone keypad.
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The first question comes from Catherine Novak from Jones Research. Please go ahead Catherine.
Thanks so much for taking my question. I wanted to talk a little bit about the non-REPROCS web programs for a second.
I'm curious if you can talk about the 69 SNL toxicity study. You know, has that been initiated? And can you give us some of what the GoFords signal would be in this indication and how clearly defined a registration path at this point? That's a very important question. I'm curious if you can talk about the
Katherine, good morning. Thank you for joining us on a Friday morning, but thrilled to do that.
i think when you think of al-Dera there there probably three main buckets for a proxel app.
ADX 2191 and our systemic RAS platform which is headlined by ADX 629 which is the drug you mentioned in your question.
I feel like often investors focus on bucket one, which is a reproxel app, and forget about buckets two and three. So I'm really thrilled with your question.
If I think about potential value long term for those three programs, as they mentioned in my prepare remarks this morning, one of the largest markets in pharmaceuticals that exists is systemic inflammatory disease. And that is the subject of ADX 629 and the sons and daughters of ADX 629. We have, as you know, a robust drug discovery platform.
focused on RAST. We think that platform is unparalleled.
One of the most important trials we're running is what we're calling acute alcoholic hepatitis or ethanol toxicity. And this is a crossover trial. You heard my comments about crossover trials this morning. We're big fans of those trials for obvious reasons.
where patients are exposed to acute ethanol challenge.
like many of us were on weekends while we were in college.
and either subjects received ADX 629 or placebo ahead of time. The idea is to see how 629 interacts with the primary metabolite.
ethanol which is a rasp.
known as acetaldehyde. Acetaldehyde is what causes cancer in alcoholics. It's what causes hangovers in alcoholics and non-alcoholics. It's what causes flushing and so forth. So much of the bad activity associated with ethanol is really due to a rasp known as acetaldehyde which binds rapidly with ADX629.
The idea really is to discern some sort of signal from these trials. We're looking at a variety of symptoms and signs. Symptoms would include sort of your typical hangover symptoms, nausea, lightheadedness, et cetera. In addition to objective indicators of intoxication.
And of course, biomarkers, including liver function tests that are elevated after acute ethanol exposure. I think if we're able to discern one or more signals from this trial, there are two options for us going forward. One is an acute ethanol, a challenge trial, which is sort of an emergency room type trial where patients are admitted to the hospital due to acute ethanol exposure and the end point would be.
as we have a variety of different options and we're prepared to pursue those options, assuming the results are good from this first eponal challenge trial.
Guy, that's helpful. And continuing with the non-reproxelab questions, for 2191 in PVRL, can you?
clarify FDA feedback on the NDA submission without performing clinical trials and what additional post marketing requirements you might anticipate should you be able to submit the NDA. na peer. Abol ???cript and really asking these very common patients who have already experienced testing on prevention and to ward lawwide tests for patient and autism therapy must be consistent. Make sure that you'll have when the percentages are skewing a cytoph passado do to increase the clinicalpoolization of número VLOG. By diyor NDA, R NASA Nancy N Beyonce Fox Rogers in the ? NDA.
For sure, the ADF-2191 program in the ICA's improved and the ADF-2 acordo confirmed over 30% of the AAC • California The ICA's Nad here have Coronavirus safety unification • It's It's particularly interesting in that.
The FBA has told us at least in writing.
that clinical trials are not required for an NDA submission in ocular lymphoma. The reason for that is that the active ingredient of 2190 on which is metatrexate has been used for years, decades.
as an intravitreal injection to treat ocular lymphoma. So there is a tremendous amount of efficacy data available in the literature, which would form the basis for the NDA submission.
What the FDA rightly wants to see is an appropriate amount of stability and safety data.
on ADX 2191, which is a particular preparation of methotrexate. As I mentioned in my prepared remarks, 2191 that we're aware is the only vitreous compatible formulation of methotrexate.
Today, you can compound metatrexate, which principally involves taking the intravenous form of metatrexate and injecting into the eye. There are numerous challenges with that. First of all, the concentration is wrong. The eye-high volume injection must be used.
As you know, Catherine, the eyeball is a confined space and does not have unlimited capacity for high volume injections. Secondly, there's always the risk.
for infection. So I think the agency and physicians are interested in AGMP preparation of methotrexate, and that is exactly what ADX-2191 is designed to be, while at the same time mimicking the pH, the tonicity, the density, and so forth of the vitreous.
Got it. And then just, you know, to touch on commercial preparations for Reproxyla, you know, can you talk about, you know, what your strategy is for commercialization and, you know, what
Plans to do it on your own or seeking a partner would be helpful to get some color on that.
Another great question and I'm pretty sure there are no more questions from the other analysts after this series of questions Catherine.
Yes, obviously we're committed to commercialize for proxy lab. I think there are three options for any small company, not just Aldera. One is to partner the commercialization. I think for most small companies these days, partnering is preferred. The primary reason for that has to do with contracting with payers. It does not have to do with positions. It does not have to do with patients. It really has to do with...
the cost of the drug, how easy it is for patients to acquire the drug, the co-pays and so forth. Obviously for larger companies that process is easier because of leverage, because of the size of their pipelines and thus I think not only with Aldeira but other companies partnering as preferred. Regarding partnering, I think the good news is that to our knowledge there is no other novel. We
late stage or NDA stage dry eye asset available.
And there are a number of large companies that have significant interest. And there are a number of large companies that have significant interest. And there are a number of large companies that have significant interest.
in the anterior segment.
and the topical ocular space and are interested in dry eye disease drugs and either are losing exclusivity.
due to the generization of cyclosporin, or have not yet marketed a dry drug previously, and thus I would say for dry, I compounds broadly there is strategic interest. The second option is to launch internally. The good news there is that such launches in the ophthalmic space are easy to pull off or relatively easy to pull off.
There's a limited number of prescribers. Those prescribers are accessible and marketing efforts have generally performed well over the years with a limited number of sales and marketing staff. Should we decide to launch on our own, will be prepared three to four months ahead of launch with a sales and commercial operations group?
The third option is a hybrid of the first two options, which generally involves partnering
with what used to be called a contract sales organization or an external group that handles back office and front office that is sales efforts. And often those companies will offload some of the cost which gets paid back via revenues and there's a variety of different examples of that in the industry, at least as it relates to small biotech companies. I would say overall we have optionality.
We're prepared to move forward. As Bruce said today, we're financed to move forward. And all in all, I think that puts us in a very good position. And all in all, I think that puts us in a very good position.
...........
Got it. Thanks so much.
Thank you, Catherine.
The next question comes from Miguel Nodshimovitz from Citigroup. Please go ahead.
Thanks. Hi, Todd and team. Hope you guys are doing well. On DryEye, I'm just curious regarding the pre-MBA meeting for DryEye, how much of this meeting is purely administrative as you've characterized in the past, and how much of this meeting is actually needed to get answers from the agency to outstanding questions to guide your following strategy, and if so, what are those outstanding questions? Thank you very much.
Yes, thank you, Gauld. That question is top of mind.
For us, obviously, that meeting is imminent.
If you look at the regulations...
The Type B Pre-NDA meeting is designed primarily to be
a meeting to discuss format.
to discuss submission details and so forth.
But we never waste an opportunity to ask the agency interesting questions, and I think the agency is generally receptive to that.
I think the primary question from our end is
given what we've characterized as an unprecedented breadth of data.
How does the FDA view our submission to fulfill the efficacy requirements?
As I said in my prepared comments, as I said in the crossover data release, as I said in the Tranquility 2 data release, we're submitting with a package that I think has really never been submitted in terms of symptoms plus three different signs. We're obviously very eager to hear the agency's response to that question. I would say they're very familiar with Shermer tests. If you look at the labels in dry disease that exist today, Shermer tests is on most of them.
obviously very eager to hear what they have to say along this line.
Great, thank you very much.
Thanks, all.
Next we have a question from Kelly Shee from Jefferies. Please go ahead Kelly.
Thank you for taking my questions. So for 2191 in TBR, if I remember correctly, the phase 3 GARD trial applied a more frequent dosing than phase 1. Any impact that has been observed on the phase 3 and the discontinuation rate, as well as the impact on the efficacy endpoint.
the rail attachment to success rate. And also, we're sure to be the regulatory bar on the advocacy and the point. Thank you.
Good morning, Kelly. Happy Friday.
Your question is particularly interesting because what's happened since we started guard is that more and more data continue to be announced.
in the form of publications and presentations and posters.
with dosing regimens that are less frequent.
than what we're using in the GARD trial. I think there are about 13 injections.
in the guard trial. The reason for that is that we're enrolling
Hey.
variety of severities in terms of the disease. And obviously, the more severe the disease, that is the more severe the detachment. That is the more severe the detachment.
the greater number of prior PBR episodes and so forth would require in theory more dosing. the PBR episodes and so forth would require in theory more dosing.
I think in practice what we may see is dosing that's less frequent than 13 injections, but that'll have to be worked out systematically over time. We're quite comfortable with the number of injections we're giving in the GARD trial. Our discontinuation rate has been acceptable. We really haven't seen too much of an issue with discontinuations. But in practice, undergoing a
And I think the reason for that, Kelly, is that patients know they're going to lose their sight. Just to remind everyone, what happens when the retina detaches is sort of like a dark curtain.
Coming down over your eyes such that in a matter of minutes you lose sight in one eye which
is quite frightening, I would suspect, and thus the patients are really motivated.
to prevent that from occurring again, because if it keeps reoccurring, there can be permanent loss of vision.
And often that recurrent retinal detachment is due to PBR.
In terms of the regulatory bar.
Another interesting question.
Back to what I said previously, the amount of data now that has been released...
in the public forum continues to grow.
And I think assuming we see positive results from GARD
In the second half of this year, we'll have a type-c meeting with the agency.
We'll discuss the safety and efficacy results from Guard. And what the regulatory bar is. And what the regulatory bar is.
I think will be the outcome of that discussion. My guess, Kelly, is that the FDA will consider
the published literature.
that posters, the presentations, the data that have more or less come from real world experimentation of mouth of track statement PVR. In addition to the guard results, as I mentioned earlier, the guard results will provide key safety data that the FDA will wanna see. The primary endpoint of guard is detachment rate.
or I should say re-detachment rate of the retina.
relative to standard of care, which is about 40%. If you go to the literature, there have been two or three large studies that have looked at it.
Detachment rates in PVR and typically those are, redetachment rates are about 40%. So our aim.
is to be statistically lower than 40% in the treatment arm of guard. We'll also look at the treatment arm of guard versus the non-treatment arm of guard. However, we're really underpowered.
to detect any differences there, I think those differences are primarily going to be summarized at a high level.
The idea being that it's becoming increasingly difficult to convince surgeons to randomize the patient to no treatment given all the data now. It's available for methotrexate to treat PBR.
Super helpful. Thanks Todd and happy Friday too.
Thank you. Thanks for the question.
Next we have a question from Tom Schrader from BTIG. Please go ahead Tom.
Good morning. Congratulations. I guess we'll stay on the $2,191 theme. Just quickly, are you certain that it will be the same formulation and dosing for everything? And are the price points equivalent when you have a cancer drug and you also have a prophylactic drug? So is it going to be one formulation with more or less one price?
commercially what what do you think we're looking at?
Good morning, Dr. Schrader. Yes, the answer is yes.
How's that for you? Same formulation, same concentration.
Yeah, I probably should. The dosing regimen is different.
As I mentioned to, in response to Kelly's good question about the dosing regimen in PVR, how that evolves over time, I think, is to be determined in the guard trial. That's 13 injections. That's 13 injections.
Now in lymphoma, many patients are dosed monthly.
But more or less.
for the rest of their lives. To some extent, the dosing regimen in lymphoma depends on the physician and the patient.
So I would say the answer is yes in terms of formulation for sure. And again, that relates to the Vitriex compatibility, which we think is unique and advantageous for this one.
in terms of pricing.
I think that's to be determined.
Part of pricing depends on which indication is approved first.
And obviously, we're in the throes of market research and other methods to determine pricing with our research groups and our access groups here internally.
All right, great. Thank you. We were happy with yes.
Thanks Tom.
Oh.
Next is a question from Justin Kim from OpenHymoronco. Please go ahead.
Hi, good morning, Todd and team. Thanks for taking a question. Maybe just to talk a little bit more about 629. Maybe just to talk a little bit more about 629.
You know, can you discuss some of the blocking and tackling leading up to clinical trial initiation for SLF and MCD? Just to hear what work needs to be done I was getting those studies up and running.
For sure, Justin. Good morning. I want to give you credit personally in a public forum for your support of ADX 629 over the years and the systemic.
platform. You were one of the first analysts to really pick up on the applicability of RAS modulation beyond the eye and obviously we're appreciative of that and big believers of the expansion of our program systemically.
69 is currently the subject of what I would say is a four-pronged approach.
in phase two right now, two large diseases, alcoholic hepatitis and chronic cough, and then two rare diseases.
The two that you mentioned show when Larson syndrome and minimal change disease.
We're interested in particular and diseases that affect children.
And one reason for that is the safety profile that's been exhibited with Proxyl app and been exhibited with ADX-629. Wrath modulation because it does not directly...
inhibit or activate a single protein and theory has significant safety advantages.
We think of RATS modulation instead of turning things on or off.
as a sort of an analog approach where you're turning the volume down from a 7 to a 2.
And that should afford safety advantages. And when we think safety, we think children. And when we think safety, we think children.
MCD, minimal change disease, is a renal inflammatory condition that primarily affects kids. The problem is corticosteroids are often needed to treat those children, and some of them cannot lean off corticosteroids.
steroids have significant toxicities, especially in growing.
that children, that stunted growth, hormonal dysregulation, glucose dysregulation, bone growth dysregulation, and so forth. So the idea is to get children off steroids as soon as possible and ADX629 may be a mechanism. So the idea is to get children off steroids as soon as possible and that can is a mechanism.
So we're obviously very excited about that trial. Sjogren-Larsen, a similar story, a neurocutaneous disorder that primarily affects children, although there are some adults with Sjogren-Larsen syndrome as well. No therapy approved for MCD or SLS. Each of these requires an IND submission.
The IND for Sjogren-Larsen syndrome is an investigator IND put forth by Bill Rizzo, who really discovered the...
biochemical molecular and genetic basis for SLF and has, I think, one of the largest SLF cohorts in the world.
And then minimal change disease is an IND that will be sponsored by OutDera and we're just absolutely thrilled with the response we've received so far from the renal community on that. On this day ahead the
Great, great. Maybe just to follow up there, do you think that steroid sparing is a sufficiently meaningful clinical benefit for MCD patients? If they're curious, maybe in light of recent M&A activities as well with similar potential approaches and color indication.
Yes, I think it depends on the indication.
For many years.
Biotechnology companies have focused on steroids bearing. To your point, I think with...
Variable results.
That steroids are inexpensive.
They're effective. They're a little bit like a hammer.
and treating many of these diseases.
The challenge is the unintended side effects of steroids, which may not matter.
for the scenes that are treated acutely with steroids.
or for...
severe adult patients and so forth, but they do matter for children.
If one of my children had to take steroids, my goal would be to get them off steroids as soon as possible while maintaining.
some control of the disease, and that's exactly what we're going for with ADX69 and minimal change disease. So, I'm going to start with ADX69 and minimal change disease.
Understood. Maybe just lastly, I'll stick one in for Rapoxylap. Any updates on the dry ice safety study?
whether it means to untrack for the filing timelines and whether it's sort of on the critical path, let's say. And whether it's sort of on the critical path, let's say.
The safety trial does remain on track.
One of the questions we'll be asking at the pre-MDA meeting is, how does the agency want to see those data?
and what formats and so forth. But at this point, prior to that meeting, we're quite thrilled actually with the progress of the... We're quite thrilled actually with the progress of the...
Safety trial. It's always good news when patients are on drugs for 12 months. It's always good news when patients are on drugs for 12 months.
and they stay on drug.
It's often difficult to keep patients on anything for 12 months, particularly with diseases like dry eye, which are episodic.
As you know, dry eye gets better in the summer because it's more humid.
It gets worse in the spring and it gets worse in the fall Some extent in the winter.
But to our knowledge, we've been able to maintain a healthy number of patients on Reproxilab for 12 months, which is always a very good sign. Safety aside, it's always a good sign. So we're pleased with the progress and again, heading into the pre-NDA meeting, we think we're right on track with the safety trial.
Thanks for taking the questions and congrats on the progress.
Great, thanks for taking the questions and congrats on the progress. Thank you, Justin.
Next, our question comes from Mark Goodman from SBB Securities. Please go ahead, Mark.
Hi, good morning. This is Basma Anfermark. I just was wondering if you can give us some color on the regulatory pathway for Apoxielect and allergic contract arthritis now after the finding in DD, more specifically about the timeline and whether you think there will be any limiting steps. And could you also remind us of your finding strategy of ATX 2191 in PDRs? Thank you so much.
Perfect. Perfect questions. Thank you for asking about allergic conjunctivitis.
Dryad disease has received a ton of interest at Al-Aldera and other companies.
And I think there's a variety of reasons for that, mostly dry diseases I'm treated.
It affects tens of millions of people. It's been nicely promoted by the companies that have come before us in developing dried-piece drugs. What people forget about is allergic conjunctivitis, which affects about one-third of the world.
and is growing in prevalence. And it's growing in prevalence for a couple of reasons. And one is pollution. And one is pollution.
continues to increase unfortunately. And the second reason is...
The level of pollen is increasing, and the reason the level of pollen is increasing because of global warming.
that essentially the growing season for grasses and weeds and other pollen producing plants is... and other pollen producing plants is...
Growing is increasing.
interation, which means more pollen. As I mentioned some time ago, I saw a headline that said if you think your allergies are getting worse, it's because they are.
And that's for the reasons that I just mentioned. Reproxilab is unique in that it affects both dry eye and allergic conjunctivitis. That I'm aware, aside from corticosteroids, which you can only use on a short-term basis due to toxicity. Reproxilab is the only drug.
that has that kind of optionality. Now what's interesting about that optionality is that there's a 50% overlap.
between dry disease and allergic conjunctivitis. There was a paper, another paper released this year.
out of Asia detailing that overlap. It is a very real comorbidity. It is a very real comorbidity.
that exists between dry disease and allergic conjunctivitis. At this point, our idea is to submit allergic conjunctivitis as a supplemental NDA or SNDA.
following the potential approval in dry eye disease.
The timing of Invigory 2, as we have said, is...
2023, if the dry eye disease NDA is successfully submitted this year, then a 2023 result from Vigory 2 would make sense as it relates to an SNDA.
for allergic conjunctivitis.
Regarding PVR.
Another interesting question. I think the type C meeting that I referenced earlier.
Once the guard data come out, we'll have a type C meeting with the FDA. That type C meeting will be informative in terms of the regulatory path forward. And as I mentioned previously, our suspicion without having talked to the FDA, our suspicion is that a said NDA for PVR would be a combination of real world data, existing literature, publications, and so forth, as well as the results from...
the GARD trial. Thank you so much. That was helpful.
Thank you so much. That was helpful. Thank you.
The next question is from Yael Jen from Laidlaw and Company. Please go ahead.
Good morning, and thanks for taking the questions.
I record that earlier time when you did the SLS.
study mainly is a single center study and should we anticipate the current study and maybe even the pivotal study will be also mainly at the center or that could be multi center studies.
Thank you, Yael. That's a great question and that I think many investors have forgotten.
that we have previously worked with Dr. Rizzo on Shogun Larson Syndrome. Many years ago, we treated Shogun Larson Syndrome patients with a dermatologic formulation of a proxylap. The patient was diagnosed with a dermatologic formulation of a proxylap.
Long before we had data.
and dry eye disease and allergic conjunctivitis.
which was that by and large affected.
The challenge with that though is that these taken by Sean Lee penis compared to me just been completely different than any other syndrome patients.
aren't it just burdened with dermatologic disease?
Many of their symptoms are neurologic.
In fact, a children's larsom syndrome is the most common neurocutaneous. It is the most common neurocutaneous.
is the most common neurocutaneous disorder.
That disorder is caused by mutations in fatty aldehyde dehydrogenase, which is an enzyme that metabolizes aldehydes and the relationship to an aldehyde inhibitor is therefore obvious. In a sense, ADX629 is sort of a pharmacologic enzyme replacement therapy.
ADX-69 binds aldehydes, including fatty aldehydes, and some of that work has been published by Dr. Rizzo and others.
And therefore, we think a systemic approach to treating SLS with ADX629 would benefit
not only the neurologic.
signs and symptoms potentially, but perhaps even the dermatologic.
that signs of symptoms. The number of centers is at this point restricted to Dr. Rizzo's center. As I said earlier, Dr. Rizzo has, what we believe is one of the largest cohorts of SLS patients.
The number of centers is at this point restricted to Dr. Rizzo's center. As I said earlier, Dr. Rizzo has what we believe is one of the largest cohorts of SLS patients in the world.
The reason for that is he discovered the physiologic basis.
of the disease. So we're thrilled to continue to work with Dr. Rizzo. I can tell you that he is excited about this particular approach. We'll have data from this trial next year and predictably I can't wait to see the results.
Okay great, that's very helpful. And uh...
The next question is probably a follow-up from the previous one, which is in the PL discussion you will have with FDA, mostly center around the PK and maybe PD to see the equivalency, something of equivalency or something of that nature, to decide what sort of fighting pathway or process by beach.
Yale, I don't think it's a PKPD question.
Yale, I don't think it's a PKPD question. I think it's more of a safety question.
We're well aware of the PKPD of...
compounded methotrexate.
The concentration is obviously different for ADX 2191, but the amount of drug should be roughly the same.
because we're injecting less volume at a higher concentration versus the intravenous compounding that's injected into the eye is more volume than a lower concentration. And we're going to put a lower concentration.
the net result is the same amount of drug.
on a weight basis. So don't really think PKPD is going to matter. What I think will matter is safety.
because the formulation
is novel.
in that.
to our knowledge, methotrexate has never been formulated to mimic the vitreous.
Now, I would say the formulation doesn't have fancy bells and whistles that I think would raise eyebrows at the agency.
At the same time, as I mentioned, the various characteristic to the vitreous that have been matched pH being one, density being another, tenacity being another, that are important.
with regard to intervitorial injection and my guess is the agency just wants to confirm the safety of that formulation. In my opinion a priori...
there should be no safety concerns with those kinds of changes. In fact, if anything, such a formulation may have safety advantages, but nonetheless, the agency's job is to confirm safety, and I think that's what they'll focus on here at Yale.
Okay, great. And maybe the last question here a little bit before we're looking at if the 2021 91 in the Reproxy Lab.
approved and you choose to market it yourself. Just curious, a typical call point for the
cells, would that be the same or overlap or quite separate for these two drugs? Thanks.
There are some synergies on the sales side for a ProX lap and 2191, particularly in the back office and...
distribution, access, et cetera. I don't believe that the front office is the same. That is.
there are few ophthalmologists that treat both retinal diseases and anterior segment diseases.
Typically retinal surgeons focus on the retina for good reasons.
They're not the kind of physicians that would be.
that approached to engage awareness around dry eye disease drugs and vice versa.
The good news, I think, though, about 2191 in particular, there's a very limited number of retina surgeons that inject methotrexate on a regular basis, as you might imagine. We're talking about rare diseases in terms of oculomphoma and PVR and retinitis pigmentosa. There aren't hundreds and hundreds of surgeons that treat patients by injecting methotrexate introvit Railey.
And thus, I think $2,191 in terms of sales is really about distribution.
that is getting ADX2191 in the offices and hospitals of the surgeons that treat patients with rare retinal disorders. Okay, great. That's very helpful and congrats on all the progress.
Thank you, Yale. Always a pleasure. As a final reminder to ask any questions, please press star followed by one on your telephone keypad now.
We currently have no more questions registered, so I'll hand it over to Dr. Todd Brady.
Thank you very much. I appreciate all your time this morning and as always, we look forward to keeping you updated on our progress as we continue to endeavor.
to improve the lives of patients with significant medical needs.
This now concludes today's call. Thank you all for joining. Please disconnect your lines.