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spk02: Ladies and gentlemen, thank you for standing by and welcome to the Aldera Therapeutics second quarter 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 over the conference to the company's interim chief financial officer, Mr. Bruce Greenberg. Please go ahead, sir.
spk01: Good morning, everyone. With me today is Dr. Todd Brady, our President and Chief Executive Officer. This morning, we issued a press release reporting our financial results for the quarter ended June 30th, 2022 in recent corporate highlights. A copy of the press release is available on the investor and media section of our website at www.aldera.com. Please note that this morning's conference call contains forward-looking statements regarding future events in the future performance of Eldera. Forward-looking statements include, but are not limited to, statements regarding submission of potential new drug applications, potential commercialization, the anticipated timing of results from our clinical trials, our projected cash runway, our possible or assumed future results of operations, expenses and financial position and potential growth opportunities. These statements are based upon 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 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 Aldera's continuing review and quality control analysis of clinical data. As a result of the COVID-19 pandemic, clinical site availability, staffing, and patient recruitment have been negatively affected, and the timelines to complete our trials may be delayed. ELDIRA 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. including the current and potential future impact of the COVID-19 pandemic on our business, results of operations, and financial position. Additional information concerning factors that could cause results to differ materially from our forward-looking statements are described in greater detail in our press release issued this morning and in our filings with the SEC. I will now turn the call over to Dr. Brady.
spk06: Thank you, Bruce, and good morning, everyone. In reflecting on our accomplishments so far in 2022, a couple of things stand out to me. The first is the exceptional progress our team has made in advancing our lead investigational new drug, Reproxilab, to a planned new drug application submission in the second half of 2022. We've amassed what we believe is the comprehensive regulatory package ever for a dry eye disease drug candidate. Based primarily on what we believe to be an unparalleled rapid onset of action, we're excited about Reproxilab's 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 the recent completion of the crossover and phase three Tranquility II trials, we believe we put ourselves in a position to submit a thorough and extensive NDA based on robust symptomatic improvement and the achievement of three objective sign endpoints of dry eye disease, ocular redness, Shermer test, and the Shermer test greater than or equal to 10-millimeter responder analysis. As I previously stated, the key outcome of the crossover trial is affirmation of the potential rapid onset of activity of roproxilab which, based on the results of the trial, included observed improvement within minutes in ocular redness, tear production, and symptoms, including discomfort, dryness, burning, and stinging. For the primary endpoint of Shermer test on day one and ocular redness in the dry eye chamber on day two, the superiority of roproxilab was statistically significant with a p-value of 0.0004 for ocular redness and 0.0005 for Shermer test. I think the other important takeaway from our crossover trial results is the strength of Reproxilab's safety and tolerability profile. Our clinical experience with Reproxilab now encompasses more than 1,800 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 and mild installation site irritation, which in Reproxilab's case has generally lasted less than one minute in duration. I think it's also worth reiterating that to our knowledge, Aldera 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 as it relates 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 Proxilapse Phase 2 and Invigorate Phase 3 allergic conjunctivitis trials. In addition, the ongoing Invigorate II Phase III trial is a crossover trial. Looking ahead, we expect to submit our NDA in dry eye disease in the second half of the year following our Type B pre-NDA meeting with the U.S. Food and Drug Administration later this quarter. The other accomplishment that stands out is the progress of ADX2191, our investigational new drug platform for rare but serious retinal diseases with no approved therapy. The development program of ADX2191 encompasses three such conditions. Number one, primary vitreoretinal lymphoma, which is a near universally fatal condition. cancer. Two, proliferative vitreoretinopathy, or PVR, a site-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 FDA has granted orphan drug designation to ADX2191 for each of these indications, and ADX2191 is the first methotrexate formulation specifically designed to be compatible with the vitreous humor, the fluid in the back of the eye, and therefore represents what we believe to be a unique potential commercial opportunity for Alderaan. Results from our Phase III GARD trial in PVR are on schedule and are expected for the second half of this year. As a reminder, GARD is a multicenter, randomized, controlled, adaptive Phase III 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 vitreoretinal 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 II 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 intravitreal injections and the other half receiving twice monthly intravitreal 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 a Phase II clinical trial in acute alcoholic hepatitis and to initiate Phase II trials in Sjogren-Larsen syndrome and minimal change disease. Top line results of the phase two trial of ADX629 in 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 NDA submissions. And with two late stage candidates in what we believe to be a clear strategic path to market, Aldera represents a real opportunity to positively affect patient care in both mass market and rare diseases. Now let me turn the call back over to Bruce for the financial review.
spk00: Chris?
spk01: 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 Reproxilab, and 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 30, 2022, was $17.8 million, or $0.30 per share, compared with a net loss of $14.9 million, or $0.28 per share, for the comparable period of 2021. Losses have resulted from the cost of clinical trials and research and development programs, as well as from general and administrative expenses. Research and development expenses 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 30th, 2022 were 3.1 million compared with 3.1 million for the same period in 2021. Total operating expenses for the three months ended June 30th, 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.
spk06: 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 Citibank Annual Biopharma Conference. And additionally, we'll be exhibiting at a series of medical meetings in the fall, including Vision Expo West in Las Vegas. the American Academy of Ophthalmology Annual Meeting in Chicago, the 32nd Biennial Cornea Conference in Boston, and the American Academy of Optometry Annual Meeting in San Diego. Per my prepared comments, today now is a particularly interesting time to get to know Aldera, 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.
spk02: Thank you. If you would like to ask a question, please press star followed by one on your telephone keypad. If you would like to remove your question, please press star followed by two. And when preparing to ask your question, please ensure your phone is unmuted locally. The first question comes from Catherine Novak from Jones Research. Please go ahead, Catherine.
spk09: Hi. Thanks so much for taking my question. You know, I wanted to talk a little bit about the non-reproxylate programs for a second. I'm curious if you can talk about the 629 ethanol toxicity study. Has that been initiated, and can you give a sense of what the go-forward signal would be in this indication, and how clearly defined a registrational path is at this point?
spk06: Catherine, good morning. Thank you for joining us on a Friday morning. Thrilled to do that. I think when you think of Aldera, there are probably three main buckets, Reproxilab, ADX-2191, and our systemic RASP 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 Reproxilab, 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 I mentioned in my prepared remarks this morning, One of the largest markets in pharmaceuticals that exists is systemic inflammatory disease, and that is the subject of ADX629 and the sons and daughters of ADX629. We have, as you know, a robust drug discovery platform focused on RASP. 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 ADX629 or placebo ahead of time. The idea really is to see how 629 interacts with the primary metabolite of 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 test. 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 endpoint would be something like a time to discharge. The other option available to us is the classic chronic alcoholic hepatitis trial, which heretofore has involved a 90-day treatment period, and the outcome is mortality. Obviously, those are much sicker patients So I think one of the beauties of systemic inflammation and ADX629 in particular and even alcoholic hepatitis is we have a variety of different options and we're prepared to pursue those options assuming that the results are good from this first ethanol challenge trial.
spk09: Got it. That's helpful. And, you know, continuing with the non-riproxilab questions, You know, for 2191 in PBRL, can you clarify FDA's feedback on, you know, the NDA submission without performing clinical trials and what additional post-marketing requirements you might anticipate, you know, should you be able to submit the NDA?
spk06: For sure. The ADX 2191 program in PBRL that ocular lymphoma is particularly interesting in that the FDA has told us at least in writing that clinical trials are not required for NDA submission in ocular lymphoma. The reason for that is that the active ingredient of 2191, which is methotrexate, 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 ADX2191, 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 methotrexate, which principally involves taking the intravenous form of methotrexate and injecting into the eye. There are numerous challenges with that. First of all, the concentration is wrong. A 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 a GMP preparation of methotrexate, and that is exactly what ADX2191 is designed to be, while at the same time mimicking the pH of the tonicity, the density, and so forth of the vitreous.
spk09: Got it. And then just, you know, to touch on commercial preparations for Reproxilab, you know, can you talk about, you know, what your strategy is for commercialization and, you know, plans to do it on your own or seeking a partner would be helpful to get some color on that.
spk06: 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 Reproxilab. 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 physicians. 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 Aldera, but other companies, partnering is preferred. Regarding partnering, I think the good news is that, to our knowledge, there is no other novel late-stage or NDA-stage dry-eye asset available. 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 generalization of cyclosporine or have not yet marketed a dry eye drug previously and thus I would say for dry eye 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, we'll 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.
spk09: Got it. Thanks so much.
spk06: Thank you, Catherine.
spk02: The next question comes from from City Group. Please go ahead.
spk05: Thanks. Hi, time team. Hope you guys are doing well. I'm dry eye. I'm just curious regarding the pre-MDA meeting for dry eye. 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 filing strategy? And if so, what are those outstanding questions? Thank you very much.
spk06: Male Speaker 1 Yes, thank you, Egal. 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 II 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 test is on most of them, particularly the responder analysis. And I think the reason for that is the responder analysis is correlated with symptomatic improvement. So from the agency's perspective, the Shermer test responder analysis is an all-in-one. It's a sign and a symptom at the same time, or at least correlates with a symptom. at the same time, and that's something they're going to be very interested in seeing. But we've posed the question about the breadth of submission, obviously very eager to hear what they have to say along those lines.
spk05: Great. Thank you very much. Thank you, Gal.
spk02: Next, we have a question from Kelly Shi from Jefferies. Please go ahead, Kelly.
spk11: Thank you for taking my question. For 2191 in PBR, if I remember correctly, the Phase III GARD trial applied more frequent dosing than Phase I. Any impact has been observed on the success rate and the discontinuation rate, as well as the impact on the efficacy endpoint, the rare attachment success rate. And also, what should be the regulatory bar on the advocacy endpoints? Thank you.
spk06: Good morning, Kelly. Happy Friday. Your question is particularly interesting because what's happened since we started GARD 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 GARD trial. The reason for that is that we're enrolling a variety of severities in terms of the disease. And obviously, the more severe the disease, that is, the more severe the detachment, the greater number of prior PVR 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. 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, 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 PVR. In terms of the regulatory bar, another interesting question, back to what I said previously, the amount of data now that have 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 GARD. 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 the posters, the presentations, the data that have more or less come from real-world experimentation of methotrexate and PVR, in addition to the GARD results. As I mentioned earlier, the GARD results will provide key safety data that the FDA will want to see. The primary endpoint of GARD is detachment rate, or I should say redetachment 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 detachment rates in PBR and typically those are, redetachment rates are about 40%. So our aim is to be statistically lower than 40% in the treatment arm of GARD. We'll also look at the treatment arm of GARD versus the non-treatment arm of GARD. 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 a patient to no treatment given all the data now that's available for methotrexate to treat PBR.
spk11: Super helpful. Thanks, Todd, and happy Friday, too.
spk07: Thank you. Thanks for the question.
spk02: Next, we have a question from Tom Schrader from BTIG. Please go ahead, Tom.
spk04: Good morning. Congratulations. I guess we'll stay on the 2191 theme. Just quickly, are you certain that it will be the same formulation and dosing for everything? And are the price points equivalent? I mean, 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? Just commercially, what do you think we're looking at?
spk06: Good morning, Dr. Schroeder. 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 in response to Kelly's good question about the dosing regimen and PVR, how that evolves over time, I think, is to be determined. In the GARD trial, that's 13 injections. Now, in lymphoma, many patients are dosed monthly, more or less monthly. 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 vitreous 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.
spk04: Male Speaker 1 All right. Great. Thank you. We were happy with yes.
spk06: Male Speaker 1 Thanks, Tom.
spk07: Thanks, Tom.
spk02: Next is a question from Justin Kim from the Oppenheimer & Co. Please go ahead.
spk10: Hi. Good morning, Todd and team. Thanks for taking the question. Maybe just to talk a little bit more about 629. Can you discuss some of the blocking and tackling leading up to clinical trial initiation for SLF and MCD? Just sort of curious what work needs to be done. ahead of getting those studies up and running.
spk06: For sure, Justin. Good morning, and I want to give you credit personally in a public forum for your support of ADX629 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. 629 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, Sjogren-Larsen syndrome and minimal change disease. We're interested in particular in diseases that affect children. And one reason for that is the safety profile that's been exhibited with Reproxilab and been exhibited with ADX629. Ras modulation, because it does not directly inhibit or activate a single protein, in theory has significant safety advantages. We think of Ras modulation, instead of turning things on or off, as a sort of an analog approach where you're turning the volume down from a seven to a two, and that should afford safety advantages. 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 wean off corticosteroids. Steroids have significant toxicities, especially in growing children, 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 to do that. 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 SLS and has, I think, one of the largest SLS cohorts in the world. And then minimal change disease is an IND that will be sponsored by And we're just absolutely thrilled with the response we've received so far from the renal community on that.
spk10: Great, great. Maybe just as a follow-up there, do you think that steroid sparing is a sufficiently meaningful clinical benefit for MCD patients? I'm just sort of curious, maybe in light of recent M&A activity as well, with similar potential approaches and other indications.
spk07: Yes, I think it depends on the indication.
spk06: For many years, biotechnology companies have focused on steroid sparing. To your point, I think with variable results. Steroids are inexpensive. They're effective. They're a little bit like a hammer in treating many of these diseases. is the unintended side effects of steroids, which may not matter for diseases 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 ADX629 and minimal change disease.
spk10: Understood. Maybe just lastly, I'll stick one in for Reproxilab. Just any updates on the dry eye safety study and whether it remains on track for the sort of filing timelines and whether it's sort of on the critical path, let's say.
spk06: The safety trial does remain on track. One of the questions we'll be asking at the pre-NDA meeting is how does the agency want to see those data, in what format, and so forth. But at this point, prior to that meeting, 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, 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, and to some extent in the winter. 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.
spk10: Great. Thanks for taking the questions, and congrats on the progress.
spk06: Yeah, thank you, Justin.
spk02: Next, our question comes from Mark Goodman from SVB Securities. Please go ahead, Mark.
spk03: Hi, good morning. This is Basma on for Mark. I just was wondering if you can give us some color on the regulatory pathway for apoxilab and allergic conjunctivitis now after the finding in DD, and 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 ATX2191 Thank you so much.
spk06: Perfect. Perfect questions. Thank you for asking about allergic conjunctivitis. Dry eye disease has received a ton of interest at Alaldera and other companies. And I think there's a variety of reasons for that. Mostly dry eye disease is untreated. It affects tens of millions of people. It's been nicely promoted by the companies that have come before us in developing dry disease 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. One is pollution continues to increase, unfortunately. And the second reason is the level of pollens. is increasing, and the reason the level of pollen is increasing is because of global warming. Essentially, the growing season for grasses and weeds and other pollen-producing plants is growing, is increasing in duration, 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 in 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 eye 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 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 Invigorate 2, as we have said, is 2023. If the dry eye disease NDA is successfully submitted this year, then a 2023 result for Invigorate 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 GARD 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.
spk03: Thank you so much. That was helpful.
spk02: The next question is from Yael Jen from Laidlaw and Company. Please go ahead.
spk08: Good morning, and thanks for taking the questions. I recall the earlier time when you did the SLS study, mainly it's 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?
spk06: Thank you, Yale. That's a great question in that I think many investors have forgotten that we've previously worked with Dr. Rizzo on Sjogren-Larsen syndrome. Many years ago, we treated Sjogren-Larsen syndrome patients topically with a dermatologic formulation of roproxilab long before we had data in dry eye disease and allergic conjunctivitis, which was by and large effective. The challenge with that, though, is that these Sjogren-Larsen syndrome patients aren't just burdened with dermatologic disease. Many of their symptoms are neurologic. In fact, Sjogren-Larsen syndrome 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. ADX629 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 signs and 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 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.
spk08: Okay, great. That's very helpful. And the next question is probably a follow-up from the previous one. which is in the PVL discussion you will have with FDA are mostly centered around the PK and then maybe PD to see the equivalency, something of equivalency or something of that nature to decide what sort of filing pathway or process may be.
spk06: Yael, I don't think it's a PK PD 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 ADX2191, 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 at a lower concentration. The net result is the same amount of drug on a weight basis. So I 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, there are various characteristics of the vitreous that have been matched, pH being one, density being another, tonicity being another, that are important. with regard to intravitreal 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, Yale.
spk08: Okay, great. And maybe the last question here, a little bit forward-looking, that if both 2191 and the Reproxilab approved and you choose to market it yourself, just curious, are the typical call points for the cells, would that be the same or overlap or quite separate for these two drugs? And thanks.
spk06: There are some synergies on the sales side for Reproxilab 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 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 ocular lymphoma and PVR and retinitis pigmentosa. There aren't hundreds and hundreds of surgeons that treat patients by injecting methotrexate intravitreally. And thus, I think 2191 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.
spk08: Okay, great. That's very helpful, and congrats on all the progress.
spk06: Thank you, Yale. Always a pleasure.
spk02: 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.
spk06: 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 unmet medical need.
spk02: This now concludes today's call. Thank you all for joining. Please disconnect.
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