Q4 2022 Aldeyra Therapeutics Inc Earnings Call
Ladies and gentlemen, thank you for standing by and welcome to the Aldewa Therapeutics full year 2022 Financial Results Conference call. At this time, all participants are in a listen-only mode. After the speaker's presentation, there will be a question and answer session. I would now like to hand the conference call over.
recent corporate highlights and our financial results for the year ended December 31st 2022. A copy of the press release is available on the investors in media section of our website at www.aldira.com.
Please note that this morning's conference call contains forward-looking statements regarding future events and the future performance of LDR.
Forward-looking statements include but are not limited to statements regarding FDA review of our drug applications, of our new drug applications, potential commercialization, the anticipated timing of initiation of results from our
possible or assumed future results of operations, expenses and financial position, and potential growth
These statements are based on the information available to us today and reflect our current views concerning future events.
They are based on assumptions and subject to risks and uncertainties, including the development, clinical regulatory plans or expectations for Aldera's product candidates, and systems-based approaches.
The risk that result from clinical trials or portions of clinical trials may not accurately predict the results of future trials for the same or different indications in Eldira's continuing review and quality control analysis of clinical data.
LDRA assumes no obligation to update these statements as circumstances change.
Future events and actual results could differ materially from those projected in our forward-looking statements.
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 in our filings with the SEC.
I will now turn the call over to Dr. Brady.
Thank you, Bruce. Good morning, everyone, and thank you for joining us.
Let me begin by recognizing the entire ALDERA team.
as well as the clinical investigators and researchers and patients.
who have worked with us over the past year.
the time and dedication you've invested.
to advance our strategic priorities in 2022 have resulted in two FDA accepted new drug applications.
for Proxilap for Dry Eye Disease and ADX2191.
which was recently designated priority review for primary vitreoretinal lymphoma, a rare, aggressive, high-grade retinal cancer with no approved therapy.
We deeply appreciate your support in achieving a milestone that few companies of any size achieve this quarter.
and are proud to be actively working with the FDA to potentially bring two new therapies.
and are proud to be actively working with the FDA to potentially bring two new therapies to patients as quickly as possible.
These NDAs are catalysts for ALDERA's future.
They validate the novel platforms we've developed.
to treat both common and rare immune-mediated diseases characterized by inflammation.
they speak to the power of our drug discovery and development engine.
Building on this strong foundation, we are focused on advancing the next generation of our RAS modulation platform.
ADX629, ADX246, and ADX248.
in 2023.
For those of you that are new to Aldera, RASP are pro-inflammatory mediators that are elevated in ocular and systemic inflammatory disease and thus represent therapeutic targets for immune modulation.
Because RASP affects many proteins simultaneously,
The RAS Modulator platform represents a unique and novel pharmacologic approach.
Unlike almost all drugs in use today,
The platform is not designed to directly inhibit or activate a particular protein, but instead selectively target a family of small molecules that in turn modulate the activity and structure of many proteins simultaneously.
ADX629, our first-in-class orally administered RAS modulator product candidate, is being evaluated in Phase II clinical trials in multiple systemic indications.
including idiopathic nephrotic syndrome, which encompasses a broad group of renal inflammatory diseases.
including minimal change disease and is characterized by edema, proteinuria, and hypoalbuminemia.
Sjogren-Larsen syndrome, an autosomal recessive neurocutaneous inborn error metabolism.
that prevents degradation of specific rasp.
and atopic dermatitis, a chronic hypersensitivity condition that is characterized by dry, itchy, and inflamed skin.
The ADX629 clinical trials encompass a variety of clinical designs and are intended to develop to demonstrate activity across...
range of diseases where RASP are implicated.
Top line results from Sjogren-Larsen syndrome as well as part one of the atopic dermatitis.
and idiopathic nephrotic syndrome trials.
are expected in the second half of 2023. Our strategic approach is to identify multiple opportunities to establish the clinical relevance of ADX629 in both common and rare diseases.
where the unmet medical need is significant.
Toward this end, we also are conducting a multi-center randomized crossover phase 2 trial in approximately 50 patients with refractory or unexplained chronic cough.
We expect to announce top line results from the trial in the first half of this year.
Additionally, in 2023, we plan to initiate a Phase II trial in moderate alcohol-associated hepatitis.
The decision to pursue this indication stems from the positive results we reported in December of a placebo-controlled Phase II alcohol challenge clinical trial in which ADX629 improved signs of alcohol intoxication.
ADX629 was superior to placebo in reducing dermal flushing, increasing Romberg test balance time, and lowering levels of the ethanol RAS metabolite acetaldehyde.
following acute exposure to alcohol.
We believe these results support the potential role of brass modulation in treating alcohol-associated liver diseases.
indication for which there are few treatment options.
ADF 629 has been administered to approximately 110 patients across multiple phase 1 and phase 2 clinical trials for up to 90 days.
The drug has been observed to be generally well tolerated.
and has not resulted in any serious adverse events.
We have invested thoughtfully and strategically
to expand our RAS modulator pipeline.
The newest product candidates powered by our systems-based drug discovery and development engine are ADX246.
newest product candidates powered by our systems-based drug discovery and development engine are ADX246 and ADX248.
In the second half of 2023, early 2024, we plan to initiate a phase 1-2 clinical trial of orally administered ADX246.
for the treatment of systemic immune mediated diseases and intravitreal injected ADX248.
for the treatment of geographic atrophy, a severe form of macular degeneration.
With regard to ADX 2191, last week we were thrilled to announce that the FDA accepted for priority review our NDA for the treatment of primary vitreo retinal lymphoma.
also known as ocular lymphoma.
The FDA designed a PDUFA date of June 21, 2023, four months from the acceptance of the FDA for review.
The NDA is supported by a combination of more than 30 years of published literature on the safety and efficacy of methotrexate.
the active ingredient of ADX2191 for the treatment of ocular lymphoma.
The submission is further supported by safety data from the recently completed phase 3 guard trial of ADX2191 in patients with proliferative vitreo retinopathy.
An estimated 300 to 600 patients in the United States are diagnosed with ocular lymphoma each year.
And the median survival for newly diagnosed patients is less than five years.
If approved, we expect to launch ADX2191 in the United States in the second half of this year, which would make ADX2191 the first FDA-approved drug available.
for patients suffering from ocular lymphoma.
ADX2191 is also in development for two other retinal diseases without FDA-approved therapies.
Proliferative vitreoretinopathy, a rare condition that is the leading cause of failure of retinal reattachment surgery, and retinitis pigmentosa, a group of rare genetic eye diseases characterized by retinal cell death.
loss of vision.
We plan to conduct a Type C meeting mid-2023 with the FDA to discuss the completion of clinical development of ADX 2191.
for the prevention of proliferative vitreo retinopathy.
In addition, we plan to report top-line results from the Phase II clinical trial of ADX2191 in patients with retinitis pigmentosa in the first half of this year. With respect to Reproxilab, the PDUFA date is November 23rd.
to report top-line results from the phase 2 clinical trial of ADX2191 in patients with retinitis pigmentosa in the first half of this year. With respect to Reproxilab, the PDUFA date is November 23, 2023.
We continue to engage in potential partnering discussions with multiple parties for Reproxilab.
and are also preparing for commercialization internally.
Our commercial preparations are designed to exploit the unparalleled rapid onset and breadth of activity observed in clinical trials of perproxilab in patients with dry eye disease.
Last week, we reported top line results of the vehicle controlled 12 month safety clinical trial for Proxilab and Tri-Disease patients.
Ocular safety was similar across her proxy lap and vehicle treatment groups.
and no treatment emergent serious adverse events deemed at least possibly related to treatment were identified.
What we believe to be particularly significant about the results is the potentially landmark evidence that visual acuity in patients treated with Reproxilab was statistically superior to that in patients treated with vehicle.
The visual acuity in the Reproxilab group improved by approximately 37%, resulting in a p-value of less than 0.0001.
coupled with demonstrated broad activity and rapid onset of action.
If positive visual acuity data observed in the SAFE-E trial potentially further differentiate for Proxilab and what we estimate is a $23 billion addressable market in the US.
Now, I will turn the call back over to Bruce for the financial review.
Thanks, Todd.
Let me begin with our liquidity profile.
Cash, cash equivalents, and marketable securities as of December 31, 2022 were $174.3 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 into the second half of 2024.
This includes the initial commercialization and launch plans for Reproxilab and ADX 2191, if approved, and continued early and late stage development of our product candidates in ocular and systemic immune mediated diseases.
Net loss for the year ended December 31, 2022, was $62.0 million, or $1.06 per share, compared with the net loss of $57.8 million, or $1.07 per share, for the same period in 2021. Losses have primarily resulted from the cost of our clinical trials and research and development issues.
as well as from general and administrative expenses.
Research and development expenses for the year ended December 31, 2022 were $47.3 million compared with $44.9 million for the same period in 2021.
This increase was primarily related to an increase in drug product manufacturing expenditures, personnel costs, consulting expenditures, and external preclinical development costs, which were partially offset by a decrease in external clinical development costs.
General and administrative expenses for the year ended December 31, 2022, or $15.4 million, compared with $11.3 million for the same period in 2021. This increase was primarily related to higher consulting expenditures and higher personnel costs.
Total operating expenses for the year ended December 31st, 2022 were $62.7 million, compared with total operating expenses of $56.2 million for the same period in 2021.
Now, let me turn the call back to Dr. Brady for closing remarks.
Thank you, Bruce. 2022 was a transformational year for Aldera, highlighted by the achievement of key clinical and regulatory milestones across our drug development pipeline.
including the submission of two new drug applications.
That momentum continues in 2023.
As we move closer to our goal of validation of our platforms for immune mediated systemic and retinal diseases.
In our industry, success comes from forging one's own path.
based on evidence and science. And that is precisely the course we're charting at Aldera.
The development of a Proxel app has created a strong foundation for our RAS modulation platform, which now features our Orally administered candidate ADX 629 and 5 Phase 2 clinical trials representing very designs and two new drug candidates poised to enter the clinic.
Through ADX 2191, we're creating a potential first line therapy for rare retinal diseases without FDA approved therapies.
beginning with ocular lymphoma, proliferative vitreoretinopathy.
retinitis pigmentosa, all indications for which our drug has received FDA's orphan drug designation.
And with that, we'll be happy to take your questions. Operator?
Thank you very much.
If you would like to register a question, please press star followed by one on your telephone keypad.
If you would like to withdraw your question, please press star followed by two. When preparing to ask your question, please ensure you are unmuted lately.
So that's start off followed by one on your telephone keypad to register a question. Our first question today comes from Mark Goodman of SVB Securities. Mark, please go ahead, your line is open.
Good morning Todd, can you talk about the side effect profile that you've seen of the oral and how you think about that product and just the profile relative to what's on the market today. Obviously the excitement is a broad spectrum oral.
Just give us a sense of how you're thinking about it. What should we be looking for as far as just the profile, the side effect profile stuff. Thanks. Thanks, Mark. We very much appreciated the fireside chat we had together the other day. Thanks also for highlighting our oral RAS modulation pipeline.
I would say broadly that inhibiting or activating single proteins
day broadly that inhibiting or activating single proteins tends to lead to toxicity.
There's a reason why we have such proteins. There's a reason why they are neither constitutively turned off or constitutively turned on.
And therein lies the value of RAS modulation. ADX629, ADX246, ADX248 are all molecules that influence a family of mediators that in turn influence a family of proteins. So we're not turning any protein on or off. We liken RAS modulation.
to a master volume knob.
where we're dialing down inflammation say from a 7 to a 2. The value of that is safety and tolerability.
Not only do we have breaths of activity, but we have drugs that aren't individually affecting proteins and therefore should lead to less toxicity. We have seen that in trials observed to date with ADF 629. We have very few side effects, as I mentioned in my prepared comments. We have no
serious adverse events that have been deemed related to drugs. So as we continue to test patients and other indications, I expect that safety profile will continue based on the mechanism of action of the drug.
Thank you. Our next question is from Yigel No Term of It. From City Group. Yigel, please go ahead. Your line is open.
Hi. Thanks very much for taking the question. Todd, with respect to the PDUFA for Proxilab for dry, obviously, that's filed. Could you comment to any extent on the partnering discussions there now that that has a clear target date for FDA approval? And then related to that,
Obviously, you have the second phase three for AC coming up. I think in the past you've indicated that it may not necessarily be necessary to file there given the extensive overlap between the AC and dry eye patient populations. I'm just wondering how are you thinking about that? Is it potentially a situation where the partners...
may want to see that data and then make a determination as to whether it's even necessary to file in that second indication. Thank you.
and then make a determination as to whether it's even necessary to file in that second indication. Thank you. Thanks, Igal.
Happy to comment on partnering discussions and happy to comment on allergic conjunctivitis.
As you know, the Proxyl App NDA for dry eye disease has been accepted.
and thus, to some extent, regulatory risk has been removed, at least as it relates to the FDA's review of that FDA. As we've said before, we believe the NDA submission is the most comprehensive ever for a dry eye disease drug with three different signs.
and a variety of clinical trials that feature acute and chronic administration up to 12 weeks for efficacy and now 12 months for safety. All in all the data continue to suggest that Reproxlab is the only drug in development that can work quickly.
And I think that's a major commercial differentiator. Also, as I announced in my prepared comments.
Reproxilab appears to be the only topically administered drug ever to demonstrate an improvement in chronic visual acuity, something that normally doesn't happen as we age over 12 months.
Therefore, I would think that there are many potential partners that are interested in Reproxilab. I can tell you that our partnering conversations are robust. And as I mentioned in my prepared comments, involve multiple parties across a wide array of.
terms. I do expect that partners would want to be involved with the ProxswaLAP prior to label negotiations.
which in our case I would expect to occur in the September to October timeframe.
Regarding allergic conjunctivitis, we continue to see that indication as a major differentiator for any dry eye disease drug. As you mentioned, there's a considerable overlap between dry eye disease and allergic conjunctivitis. We continue to see that there's a significant overlap between dry eye disease and allergic conjunctivitis.
And it's difficult for many healthcare providers to distinguish between those two diseases. Thus, a compound or drug that can treat both of them simultaneously should be of considerable value. Our main goal at this point, Egal, is to demonstrate...
The activity of Reproxilab in allergic conjunctivitis, we have two published papers, one a phase two trial, one a phase three trial, demonstrating activity of Reproxilab in patients with allergic conjunctivitis across two different clinical trial models.
The Invigorate 2 trial, which is our second allergen chamber trial, will be announced, as I mentioned in my prepared comments this morning, in the first half of this year. And I think pending the results of those trials, pending the partnership discussions with the products web.
So we can then make a decision about the need to submit a new drug application for Proxilab and allergic conjunctivitis.
Great, thank you. Thank you, Gough. Thank you. Our next question comes from Justin Kim from Oppenheimer & Co. Justin, please go ahead, your line is open.
Hi, good morning Pat and Dean. Thanks for taking questions and congrats on all the progress. We're approximately up in 21.91, sort of locked in for regulatory review over the course of the year.
I just wanted to ask how you think about commercialization for these assets.
how they sort of may differ and how to think about the timeline for investment or commercialization as sort of the review process progresses.
Good morning, Justin. Thanks for the question. As Bruce mentioned in his prepared comments, we are...
well capitalized for initial launches for both compounds.
There are certain synergies, particularly in the back office.
for launching both compounds. The sales efforts though are different.
where Proxlap is obviously targeted towards optometrists and interior segment ophthalmologists.
ADX 2191 is targeted towards the retinal surgeons, particularly those that treat the rare retinal diseases.
that relate to 2191.
I think that the breadth of sales activity
and marketing activity regarding ADX2191 is quite limited. And the reason I say that is because A, retinal physicians are already using methotrexate to treat at least two of the diseases we've highlighted this morning.
And B, there's a limited number of physicians that treat these diseases. I think there are something like 50 to 60 ocular oncologists in the United States.
And therefore, I don't really consider ADX21 to be a sales and marketing effort per se, but rather more of a market access effort, making physicians aware that compounding methotrexate is no longer necessary, and making physicians aware that ADX2191 is...
in theory clinically superior to compounded methotrexate because the volume is lower, the volume for injection is lower, the density is higher, all of that designed to reduce the side effects that you typically see with methotrexate injection into the eye, which is something called punctate keratitis.
As we announced last year, as a result of the phase III GARD trial and proliferative vitreo retinopathy, the adverse event of keratitis was significantly lower than what one would expect with compounded methotrexate, at least as has been published in the scientific literature. So I'm really quite thrilled about the commercial prospects of ADX2191.
For all those reasons, the advantages of the drug combined with the fact that there's a targetable physician population combined with the fact that there's no therapy.
approved for these indications. For a Proxilap, one of the efforts we're pursuing internally is initial commercialization. You can expect that is a very thorough process that we will be prepared if necessary to launch.
internally. As I've said before with mass-market drugs it's not always optimal for small companies to launch but in the ocular space it is certainly feasible. We've seen it many times before. I think we're right on target to the extent that we need to do that if we're unable to secure a partnering deal that's acceptable.
And maybe just then on the systemic RAS program, can you just discuss 246 and its differentiation compared to 69? Just sort of any thoughts on indications that may be better suited for the sort of earlier stage asset? Yup.
it was safety and tough.
Right, ADX246 is our most potent Rasp modulator yet.
It is a direct product of our RAS Modulator platform.
which is really designed to select for new candidates.
that are effective RAS modulators, but also exhibit the kinds of pharmacokinetic properties we would desire for an orally administered drug.
ADX629, as you know, has been administered twice daily. There's the potential for 246 to be administered once daily. Not only is 246 more potent than 629, it also could have a more favorable.
dose of administration profile. 248 is similar, also a very potent RAFT trap, but in this case will be formulated specifically for intravitreal injection for geographic atrophy and dark adaptation in patients with the dry form of AMD.
Thanks. Thanks, Justin. Thank you. Thank you. Thank you.
Our next question is from Kelly Shieh from Jefferies. Kelly, please go ahead, your line is open.
So I want to follow up on the 246. Todd, can you give us more color on the systemic...
immune mediated diseases, any details on specific indications you are pursuing. My second question is on the runway, I just want to confirm that the runway to second half 2024 includes both the launch plan for RUPROL and 2191 and the projected revenue of both assets.
Thank you. Good morning, Sean. Thanks for your question. And I think your 246 question relates to Justin's question about indications for 246. ADF-246 will initiate a Phase I clinical trial first. The idea there is to confirm safety and some of the pharmacokinetic advantages that I was...
highlighting in response to Justin's question. My expectation is that ADX246 will inherit.
some of the indications where ADX629 is being trialed today. Examples might include chronic cough or atopic dermatitis or alcohol-associated hepatitis. I think we need to see the results from the ADX629 trial.
And then to the extent there is activity, we could consider shifting molecules to 246, particularly for some of the mass market indications. I'd also expect that ADX629 will remain on the orphan side of the equation. So as you know, we have two...
orphan indications that are being tested. Currently one is idiopathic nephrotic syndrome and the other one is Sjogren-Larsen syndrome.
Happy to briefly comment on cash and Bruce feel free to fill in as well. But the guidance is very clear. We have cash into the second half of next year. That cash supports initial commercialization.
for both Reproxilab and ADX2191. I hope the answers to the prior questions have given you a sense of how we're approaching those launches.
Yeah, I would just add that the forecast is conservative and does not include any revenue nor does it include any revenue from a license arrangement.
Terrific, thank you.
Terrific, thank you. Thanks John . Thank you.
Our next question is from Tom Schrader from BTIG. Tom, please go ahead, your line is open. Hey, good morning. This is Seong-Eun for Tom. Thanks for taking our question. So, there's two for us. So, for ADX 2191.
Could you provide additional color on how the recent priori review for ocular lymphoma may help other indications such as PVR and retinitis pigmentosa? And for the second question, so for the visual acuity data, what would be the best strategy moving forward? Is this something you will try to include when you submit the safety data?
on how the recent priority review for ocular lymphoma may help other indications such as PVR and retinitis pigmentosa. And for the second question, so for the visual acuity data, what will be the best strategy moving forward? Is this something you will try to include when you submit the safety data? Thanks.
Hi, Sun. Good morning. Both of those are superb questions. Our regulatory strategy for ADX2191 was quite intentional, and that is the idea is to submit as an NDA for ocular lymphoma first.
The reason is that not the Trexate, which is the active ingredient of 2191, is standard of care for treatment of ocular lymphoma. It's been injected in eyes for 30 years.
with acceptable safety and activity.
After that, subsequent NDA submissions are so-called supplemental.
NDAs where the
bar is somewhat lower because safety and the chemistry manufacturing controls aspects
of ADX 2191 have already been evaluated in the original NDA submission.
That's why I highlighted this morning the safety results from the Phase III guard trial in proliferative pitreoretinopathy.
Those are particularly important for the lymphoma submission because the FDA always assesses not only activity but also safety. And in this case, we have a new formulation designed to be vitreous compatible with a lower volume and a higher density and so forth.
and all that will be assessed from a safety standpoint as part of the lymphoma review. We were absolutely thrilled with the Phase III guard results in terms of safety. In terms of proliferative retroretinopathy, it appeared to be actually safer to administer.
methotrexate of 2191 than it was not to administer 2191, which makes sense because methotrexate is a compound, is anti-inflammatory, and may mitigate some of the trauma associated with surgery. So by and large, I think we have a compelling...
submission for lymphoma based not only on the safety but also on the activity from the scientific literature. The visual acuity data was quite remarkable and unexpected from the 12-month safety trial of Reproxilab.
There is a 120-day update as part of a standard NDA review, which focuses on safety in particular. Obviously, the 12-month safety trial, the final data from the 12-month safety trial will be highlighted in that safety update, including...
the visual acuity data. What actually winds up in the label, I think depends on negotiation with the FDA. But also we intend to publish the results of the safety trial, I think, relative to other 12-month safety trials in dry disease.
the visual acuity results are quite remarkable. And as I mentioned in my prepared comments, should stand to differentiate Reproxilab from our potential competition in the dry eye space.
remarkable. And as I mentioned in my prepared comments, should stand to differentiate Reproxilab from our potential competition in the dry ice space.
Great, thank you.
Great. Thank you. Thanks, Don.
Thank you. Our next question is from Catherine Novak from James Research. Catherine, please go ahead, your line is open.
Hi, good morning. Thanks for taking my question. Just wanted to kind of extend on the last question. You know, what was the change in visual acuity for the vehicle group in the safety study and how clinically significant is this 37 improvement in log mar seen in the treatment group?
Good morning, Catherine. Both vehicle and drug improved vision from baseline. The improvement in the drug arm, the Roprox flap arm, was statistically significantly greater than that of vehicle.
I think that speaks to a couple of phenomena. One is dry eye patients are inflamed. There is edema or swelling in the cornea which affects visual acuity.
As we're treating these patients either with vehicle or drug, we would expect that inflammation to improve.
What's remarkable is, again, if you go back to other 12-month safety trials in dry disease,
It's never been shown that either drug or vehicle can improve visual acuity.
And I think in this case, the improvement of visual acuity speaks to the activity of our drug product, that is the drug itself for Proxilab plus the vehicle in calming down the eye and potentially reducing that edema and improving inflammation broadly.
that facilitates an improvement in visual acuity.
Most of these patients by design and enrollment, Catherine, have normal acuity.
In other words, if patients have best corrected visual acuity, I think it's more than 2100 or worse than 2100.
They are not enrolled for obvious reasons. So to see any change, any improvement in visual acuity.
in a group of patients that are essentially normal, I think it's quite remarkable. As I mentioned in response to another question, as we age,
over 12 months you would expect to see visual acuity worsen.
slightly, particularly in the age group that is characteristic of dry disease, which is on average in your 60s.
So all in all I think these findings are quite remarkable. They're not something you would see with massively visually impaired populations. But here any improvement I think speaks to the activity of the drug and frankly there's little that's more clinically relevant.
in ocular disease than acuity. We have eyeballs to see, and if we see a little bit better, I think that speaks volumes for the activity of drugs.
Got it. Thank you. That's very helpful. And then one last question. I'm wondering if you can talk about the rationale for RAS modulators in geographic atrophy. We know that inflammation, oxidative stress, et cetera, have been implicated AMD, but at this point most of the therapeutics...
approaches have focused on the complement cascade. So what led to the initiation of the study and what do you think is differentiating about your approach? Well I could talk about this one for an hour.
We're particularly excited about geographic atrophy and dry AMD broadly as it relates to RAS modulation.
It could be that we look backwards in time decades from now and are somewhat embarrassed that we tried to treat a complicated inflammatory disease by targeting a single aspect of the complement cascade.
RAS modulation is entirely different, as I mentioned in my prepared comments. The idea of RAS modulation is...
to influence a broad group of proteins and set another way, reduce inflammation from a variety of different fronts simultaneously. And that's exactly how RAS behave. They are broadly pro-inflammatory. They affect many different proteins.
not just a single aspect of the complement cascade. That's part one of why we're excited about RAP modulation and geographic atrophy. Part two is characteristic of dry AMD and GA and related diseases such as Stargardt disease is the accumulation of undigestible
metabolites or macromolecules that build up in the back of the eye. These are the so-called drusen, which are comprised of a compound or group of compounds called lipofusion, which are directly derived from RASP.
So RASP are not only pro-inflammatory in GAA, but they also lead to the accumulation of these macromolecules, which the retina is not capable of getting rid of. What happens is this accumulation of indigestible metabolites over time that lead to lipofusion and drusen. They have two mechanisms.
with RAS modulation, a broad anti-inflammatory approach, and I think it's very clear that GA and dry AMD and Stargardt are related inflammation, but also the prevention of the formation of these metabolites that build up in the back of the eye as we age.
Thank you so much for taking my questions.
Thank you so much for taking my questions. My pleasure, Catherine.
Thank you. We will now take our last question from Yael Jen from Laidlaw Company. Yael, please go ahead, your line is open.
Good morning, and thanks for taking the questions. In terms of Invigorate 2 studies that you will report the data, this half, could you give us a little bit of an update in terms of when the study started and what the current status of patient enrollment and others?
And then I have the follow up. Thanks. Thanks, Yale. It wouldn't be an Aldera earnings call if I didn't thank you for all your support over the years. It's just been an absolute pleasure. Invigorate 2, I think, was started almost two years ago. And the reason I say that is because
For allergen chamber trials, you cannot treat patients when there's pollen in the air. When there's ambient pollen, that ambient pollen...
For allergen chamber trials, you cannot treat patients when there's pollen in the air. When there's ambient pollen, that ambient pollen confounds...
the activity you may or may not observe in the allergen chamber. And thus, most of these allergen chamber trials are run during the winter.
So we had last year's winter season, we have this year's winter season. The reason why we're guiding this half for Invigorate 2 is that pollen will arrive again early spring in the next month or two.
we will no longer be able to enroll patients, and thus enrollment, we would expect, will be complete relatively soon. As a reminder, the primary endpoint, really the only FDA-approved endpoint in ocular allergy is itching. That is a patient reported.
itching scale, typically zero to four. As you know, across the phase three alleviate trial, across our phase two allergen chamber trial, across the invigorate allergen chamber trial, the itching was significantly reduced relative to vehicle and we've...
perform many analyses to confirm the clinical relevance of those findings. We hope to see the same thing in Invigorate 2. As far as we know, assuming positive data in Invigorate 2 would conclude our efficacy trials for allergic conjunctivitis. That's very helpful. We do one more here.
which is for 2191 with retinal titis pigmentosa data readout. What should we anticipate from that data once you report it?
Well thanks for highlighting retinitis pigmentosa. There are three major milestones for our company in this half. We've just talked about invigorate 2. I've discussed chronic coughs that previously and then retinitis pigmentosa is the third.
What I think is remarkable about those three milestones is each milestone highlights a different aspect of our business I like to think of aldara in three parts for Proxilab being one ADX 2191 being two and the third being the oral pipeline and each of those aspects of our business are represented milestones that We expect this half
What I think is remarkable about those three milestones is each milestone highlights a different aspect of our business. I like to think of ALDERA in three parts, Reproxilab being one, ADX2191 being two, and the third being the oral pipeline, and each of those aspects of our business are represented as milestones that we expect this half. That night is pigmentosa is particularly interesting.
It is the largest of the three indications we're currently testing with ADX2191. To pick round numbers, one might think of roughly 400 incident patients with lymphoma, 4,000 incident patients with proliferative vitreoretinopathy, and something like 40,000 patients with retinitis pigmentosa that...
that relate to the particular mutations that appear to be sensitive to methotrexate administration. The basis for using ADX2191 and methotrexate in retinitis pigmentosa is cited in our clinical deck. There's been a remarkable series of experiments spanning many thousands of molecules in animal models.
This is the first time a methotrexate has been administered to retinitis pigmentosa patients. And we, as I mentioned, would expect to be able to announce results this half. Okay, great. That's very helpful and...
again, congrats for all these catalysts of this year.
for all these catalysts of this year. Exciting times, Yale. Thank you.
Thank you. I'll now turn the call back to Dr Brady for closing comments.
Thank you. I'll now turn the call back to Dr Brady for closing comments.
Thank you for joining us this morning. We're positioned for an exciting year in 2023. And as always, we look forward to bringing our novel therapies to patients with significant unmet medical need.