Aldeyra Therapeutics, Inc.

Ladies and gentlemen, thank you for standing by and welcome to the Algea therapeutic full year 2022 financial results conference call. At this time, all participants are in a listen only mode. After the speaker's presentations, there will be a question and answer session. I would now like to hand the conference call over to Mr. Bruce Greenberg, the company's interim chief financial officer. Please go ahead, Bruce Greenberg.

Thank you, and good morning, everyone. With me today is Dr. Todd Brady, our President and Chief Executive Officer. This morning, we issued a press release reporting 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.aldera.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 new drug applications, potential commercialization, the anticipated timing of initiation of results from our clinical trials, a projected cash runway, are possible or assumed future results of operations, expenses and financial position, and potential growth opportunities. 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 and regulatory plans, or expectations for Aldera's product candidates and systems-based approaches. The risks 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 LDR's continuing review and quality control analysis of clinical data. LDR 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, and 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, Reproxilab 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 achieved this quarter 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. And they speak to the power of our drug discovery and development engine. Building on this strong foundation, we're 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 RASP 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 a 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 multicenter randomized crossover phase two clinical 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 two trial in moderate alcohol associated hepatitis The decision to pursue this indication stems from the positive results 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 RAS modulation in treating alcohol-associated liver diseases, an indication for which there are few treatment options. ADF629 has been administered to approximately 110 patients across multiple Phase I and Phase II 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 and ADX248. In the second half of 2023, early 2024, we plan to initiate a Phase I-II clinical trial of orally administered ADX246 for the treatment of systemic immune-mediated diseases and intravitrally injected ADX248 for the treatment of geographic atrophy, a severe form of macular degeneration. With regard to ADX2191, Last week, we were thrilled to announce that the FDA accepted for priority review our NDA for the treatment of primary vitreal retinal lymphoma, also known as ocular lymphoma. The FDA defined a PDUFA date of June 21st, 2023, four months from the acceptance of the NDA 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 III GARD trial of ADX2191 in patients with proliferative vitreoretinopathy. 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 and loss of vision. We plan to conduct a Type C meeting mid-2023 with the FDA to discuss the completion of clinical development of ADX2191 for the prevention of proliferative vitreoretinopathy. 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 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 proproxilab in patients with dry eye disease. Last week, we reported top line results of the vehicle controlled 12 month safety clinical trial for proproxilab in dry disease patients. Ocular safety was similar across Reproxilab 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. 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 safety trial potentially further differentiate Reproxilab in what we estimate is a $23 billion addressable market in the U.S. Now I'll 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 Reproxiloft 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 programs, 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 31st, 2022 were $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. That is precisely the course we're charting at Aldera. The development of Reproxilab has created a strong foundation for our RAS modulation platform which now features our orally administered candidate ADX629 and five Phase II clinical trials representing varied designs and two new drug candidates poised to enter the clinic. Through ADX2191, we're creating a potential first-line therapy for rare retinal diseases without FDA-approved therapies, beginning with ocular lymphoma, proliferative vitreoretinopathy, and 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 1 on your telephone keypad. If you would like to withdraw your question, please press star followed by 2. When preparing to ask your question, please ensure you are unmuted locally. So that's star 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 you know, that product and just the profile relative to, you know, what's on the market today. Obviously, the excitement is, you know, 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, you know, just the profile, the side effect profile stuff? Thanks.

Thanks, Mark. Very much appreciated fireside chat we had together the other day. And thanks also for highlighting our oral RAS modulation pipeline. I would say 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 breadth 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 ADF629. 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 Yigal Notremovic from Citigroup. Yigal, please go ahead. Your line is open.

Hi, thanks very much for taking the questions. Todd, with respect to the PDUFA for a proxyl after dry, obviously that's filed. Could you comment to an extent on the partnering discussions there and how 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 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.

Thanks, Igal. Happy to comment on partnering discussions and happy to comment on allergic conjunctivitis. As you know, the Reproxilab 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 Reproxlap 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 involved multiple parties across a wide array of terms. I do expect that partners would want to be involved with the Proxilab 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. 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 raproxilap and allergic conjunctivitis. We have two published papers, one a Phase II trial, one a Phase III trial, demonstrating activity of raproxilap in patients with allergic conjunctivitis across two different clinical trial models. The Invigorate II trial which is our second allergen chamber trial that 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 Aproxilab, that we can then make a decision about the need to submit a new drug application for Aproxilab in allergic conjunctivitis.

Great. Thank you.

Thank you all.

Thank you. Our next question comes from Justin Kim from Oppenheimer & Co. Justin, please go ahead. Your line is open.

Hi. Good morning, Todd and Kim. Thanks for taking the questions and congrats on all the progress. We're practically up in 2191 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 for 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. Reproxilab is obviously targeted towards optometrists and interior segment ophthalmologists. ADX2191 is targeted towards 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 ADX 2191 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 vitreoretinopathy 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 For Aproxilab, one of the efforts we're pursuing internally is initial commercialization. You can expect that 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.

Okay, great, great. And maybe just then on the systemic RASP program, can you just discuss 246 and its differentiation compared to 269? Just sort of any thoughts on indications that may be better suited for the sort of earlier stage asset, you know, with safety in tow.

Right. ADX246 is our most potent RAS 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. So not only is 246 more potent than 629, it also could have a more favorable dosage administration profile. 248 is similar, also a very potent RAF 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. Great. Thanks. Thanks, Justin.

Thank you. Our next question is from Kelly Shee from Jefferies. Kelly, please go ahead. Your line is open.

Our questions. 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 Rupro 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 trials, and then to the extent there is activity, that we could consider as 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 commercializations for both Reproxilab and ADX2191, and I hope the answers to the prior questions have given you a sense of how we're approaching those launches.

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.

Perfect. 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 Sungwon for Tom. Just thanks for taking our question. So just two for us. So for ADX2191, could you provide additional color on how the recent prior 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? Thanks.

Hi, Sung. Good morning. Both of those are superb questions. Our regulatory strategy for ADX2191 was quite intentional, and that is the idea is to submit an NDA for ocular lymphoma first. The reason is that methotrexate, 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 ADX2191 have already been evaluated in the original NDA submission. That's why I highlighted this morning the safety results from the Phase III GARD trial in proliferative pituitary retinopathy. 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 three guard results in terms of safety. In terms of proliferative vitreoretinopathy, it appeared to be actually safer to administer methotrexate at 2191 than it was not to administer 2191, which makes sense because methotrexate as a compound is anti-inflammatory and may mitigate some of the trauma associated with surgery. But 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.

Great. Thank you. Thanks, Tom.

Thank you. Our next question is from Catherine Novak from Jones 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. What was the change in visual acuity for the vehicle group in the safety study? And how clinically significant is this 37 improvement in logmar seen in the treatment group?

Good morning, Catherine. Both vehicle and drug improved vision from baseline. The improvement in the drug arm, the RAPROXLAP arm, was statistically significantly greater. in that 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 or 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 is 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 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 drug.

Got it. Thank you. That's very helpful. And then one last question. I'm wondering if you can talk about the rationale for RASP modulators in geographic atrophy. We know that inflammation, oxidative stress, et cetera, have been implicated in AMD. But at this point, most of the therapeutic approaches have focused on the complement cascade. So what led to the initiation of this 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 said another way, reduce inflammation from a variety of different fronts simultaneously, and that's exactly how rafts 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 raft modulation 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 RAS. So RASPs 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. And what happens is this accumulation of indigestible metabolites over time that lead to lipofusion and drusen. So we have two mechanisms with RASP 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 eyes as we age.

Thank you so much for taking my questions.

My pleasure, Catherine.

Thank you. We will now take our last question from Yeo Jen from Laid Law Company. Yeo, please go ahead. Your line is open.

Good morning, and thanks for taking the questions. In terms of Invigorate 2 study that you reported data, this half, but could you give a little bit update in terms of when the study started and what the current status of patient enrollment and others? And then I have a 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 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 III Alleviate trial, across our Phase II Allergen Chamber trial, across the Invigorate Allergen Chamber trial, the itching was significantly reduced relative to vehicle, and we've performed many analyses to confirm the clinical relevance of those findings. We hope to see the same thing in Invigorate II. As far as we know, assuming positive data, Invigorate 2 would conclude our efficacy trials for allergic conjunctivitis.

Okay, great. That's very helpful. Maybe one more here, which is for 2191 retinopatitis pigmentosa data readout. What should we anticipate from that data? data once you report it.

Well, thanks for highlighting retinitis pigmentosa. There are three major milestones for our company in this half. We just talked about invigory two. I've discussed chronic cough previously. And then retinitis pigmentosa is the third milestone. 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 representative of the milestones that we expect this half. Retinitis 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 incident patients with retinitis pigmentosa 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 of retinitis pigmentosa. The winner was methotrexate. And thus, investigators and many patients and certainly the staff here at Aldera are excited about the potential for ADX2191 in retinitis pigmentosa. This is an open-label trial. 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.

Exciting times, Yale. Thank you.

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.

Thank you, everyone, for joining today's call. You may now disconnect your lines and have a lovely day.