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spk03: Good day and thank you for standing by. Welcome to the Ocular Therapeutics first quarter 2023 earnings 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. To ask a question during the session, you will need to press star 1 1 on your telephone. You will then hear an automated message advising your hand is raised. To withdraw your question, please press star 1 1 again. Please be advised that today's conference is being recorded. I would now like to hand the conference over to your first speaker today, Donald Dottman, Chief Financial Officer. Please go ahead.
spk07: Thank you, Julia. Good afternoon, everyone, and thank you for joining us on our first quarter of 2023 Financial Results and Business Update conference call. This afternoon after the close, we issued a press release providing an update on the company's product development programs and details of the company's financial results for the first quarter ended March 31, 2023. The press release can be accessed on the investor's portion of our website at investors.ocutx.com. Leading the call today will be Anthony Malasich, our President and Chief Executive Officer, who will provide an update on our pipeline developments and the commercial progress of Dextenza. Also speaking on the call today will be Dr. Rabia Austin, our chief medical officer, and Steve Myers, our senior vice president commercial. Following their remarks, I will provide an overview of the financial highlights for the quarter before turning the call back over to Anthony for a summary and questions. For Q&A, we'll be joined by Chris White, our chief business officer, and Dr. Peter Kaiser, our chief medical advisor retina. As a reminder on today's call, certain statements we will be making may be considered forward-looking for the purposes of the Private Securities Litigation Reform Act of 1995. In particular, any statements regarding our regulatory and product development plans, as well as our research activities, are forward-looking statements. These statements are subject to a variety of risks and uncertainties that may cause actual results to differ from those forecasted. including those risks described in our Form 10-Q filed this afternoon with the SEC and our most recent annual report on Form 10-K filed March 6, 2023. I will now turn the call over to Anthony.
spk09: Thanks, Donald, and welcome everyone to the Ocular Therapeutics first quarter 2023 update. We're very pleased with our progress in the quarter, both on the development of our pipeline and the commercial side of the business. Importantly, on the heels of an ARVO meeting last month that highlighted the emergence of TKIs as an exciting new potential option for the treatment of retinal diseases, we thought it would be a good idea to reintroduce OTX TKI to the many new investors who have recently become interested in the space. We started on our OTX TKI program because we believe there is a desperate need for novel MOAs that enable new treatment paradigms for VEGF-mediated retinal diseases, like wet AMD, diabetic macular edema, diabetic retinopathy, and retinal vein occlusion. Despite the emergence of antibody treatments that have the ability to quickly reduce fluid in the retina, the problem is far from solved, and the constraints of current treatment paradigms result in many patients with a wet AMD remaining untreated. For those who are lucky enough to get treatment, real-world studies have demonstrated that the initial vision gains from treatment are not maintained. As a result, VEGF-mediated retinal diseases remain a leading cause of blindness. So why is there such a need despite seemingly effective therapies? We believe it has to do with deficiencies inherent in those therapies, deficiencies that OTX TKI is designed to overcome. Fundamentally, VEGF-mediated retinal disease is caused by cellular dysfunction that results in chronic disease. Existing antibody treatments, like ILEA, Lucentis, and Vivizimo, are only effective in binding to proangiogenic ligands in the extracellular space. Additionally, existing treatment affects only specific ligands, mainly VEGFR2, while data demonstrates that the presence of all the isoforms of VEGF, as well as PDGF, play a role in the disease process through other types of receptors. Most important of all, current therapies are delivered as bolus injections into the eye. This results in a period where drug levels are briefly thousands of folds above the IC50 and then quickly fall below therapeutic levels, which may leave the retina unprotected and exposed to disease reactivation. Because of the rapid elimination of these antibody therapies from the eye, there is a need for frequent injections, Frequent injections lead to poor compliance. Poor compliance leads to loss of vision. To reduce the real-world vision loss caused by the burden of frequent injections, retina specialists have created a new paradigm of treatment called Treat and Extend. Treat and Extend is an involved process with the goal of establishing individualized dosing intervals for each patient. It is analogous to a game of chicken with a disease process where the retina is left unprotected without therapeutic levels of medication, and the provider tries to time reinjection as closely as possible to disease reactivation. Treatment extend is also an imperfect process given the natural variability of the disease in a patient and the need for perfectly timed visits to be maintained, which is difficult to achieve in the real world. However, it is the best that can be done with the current treatment, and it is a testament to the inventiveness and patient centricity of the retina community. We believe the world needs a treatment that works inside the cell, binding at the receptor level, one that covers all the isoforms of VEGF and PDGF, and most importantly, one that can be delivered at a steady state over a long period of time with minimal injections so patients and providers can move beyond the current treat and extend approach. With OTX TKI, we are developing a therapy designed to treat VEGF-mediated retinal disease like a chronic disease, like the chronic disease that it is, with a baseline maintenance therapy that stays above therapeutic levels to avoid disease reactivation. Most importantly, it is possible that vision gains may be maintained in the real world with the easier compliance regimens of a long-acting maintenance therapy. In this new treatment paradigm, which we like to call Treat to Maintain, the antibody therapies would be reserved to do what they do best, removed extracellular fluid quickly, and would be reserved in the occasional circumstances when fluid might break through the maintenance therapy, much like a rescue hailer in the treatment of asthma. OTX TKI is designed to have all of the properties above, Exitinib, the active ingredient in Otek TKI, is highly selective for the VEGFR2 receptor, which we believe to be the most important contributor to retinal disease, and covers all the different types of VEGF and PDGF receptors, with negligible affinity to any other receptor. As a TKI, its mechanism of action is working inside the cell. Most importantly, its potency and solubility profile lends itself to formulation with Aralutix technology, allowing for the development of formulations that can deliver continuous therapy for 9 to 12 months from a single injection. In designing OTX TKI, the challenge to our formulers was to develop a product that could deliver 9 to 12 months of a continuous dose of exitinib with a single implant. We additionally challenged the team to deliver the implant through a 25-gauge or narrower needle and required that a retreatment window be created where an effective dose of exitinib is still getting to the target tissues after full bioresorption of the initial implant. This would ensure that the vitreous would never have more than one implant at any one time and that the patient would have leeway in scheduling an appointment to be redosed. From the data we observe in our clinical, preclinical trials, and in vitro trials, the formulations for OTX TKI appear to be supportive of this target product profile. It is worth saying something about our Alutix technology. The hydrogel technology that underpins Alutix has been used in the human body since 1992 and has demonstrated safety and effectiveness in over 5 million patients across 5 FDA-approved devices since that time. Our own approved product, Dextenza, has been used in nearly 300,000 eyes since launch with reported adverse events in less than 1 in 10,000 patients. The only factors that regulate the bioresorption of our elutrix polymers are temperature and pH of the aqueous environment. Since the human vitreous does not vary significantly in temperature and pH, and there's enough water in every retina to saturate our polymer matrix. We believe we can program the time to bioresorption so that the implant will be intact long enough to deliver the desired dose and duration of exitinib, and then be fully bioresorbed when it's time to redose. The added benefits of not creating an acidic microenvironment, easy elimination from the vitreous, leaving behind no harmful byproducts, and soft gel properties give us added comforts regarding the safety profile. This technology would potentially provide solutions not only for the durable therapies for wet AMD to decrease the injection burden, but also for other retinal indications which need frequent injections, like the new therapies treating geographic atrophy. However, no matter how ideal the formulation and active ingredient, OTXTKI needs to perform in the clinic, which it has. We put OTXTKI in a very challenging situation in its initial clinical trial in Australia by testing it as monotherapy in patients with uncontrolled disease in wet AMD. We saw in that trial that OTX TKI was able to eliminate fluid as monotherapy in some patients in a dose-dependent fashion, something that no other TKI development program has done. In a second trial, our current U.S.-based trial, we are evaluating OTX TKI to assess the durability benefits of continuous dosing in patients with controlled retinas, that is, retinas in a dry state. Interim data has shown that 73% of patients were maintained rescue-free for up to 10 months and the injection burden was reduced by 92%. These data were recently presented as an encore presentation by Dr. Andrew Moshfeghi at the 2023 ARVO meeting held in New Orleans. We augmented the results from this ongoing clinical trial with pharmacokinetics data from two animal models showing the uptake of axitinib from our hydrogel implant in the choroid and RPE cells where axitinib acts intracellularly to exert its VEGF receptor inhibiting effect. The data showed that clinically representative formulations of OTX TKI delivered sustained excitinib concentrations through 12 months that were well above the IC50 for VEGFR2 in phyno-monkey retina tissue and in choroid retinal pigment epithelium tissues. This excellent preclinical pharmacokinetics data aligns with the pharmacodynamics data we have observed in our ongoing U.S. clinical trial, namely that the high proportion of rescue-free subjects up to at least 10 months and suggests continuous VEGF receptor inhibition, which in turn would support this new treatment paradigm, treat to maintain in wet AMD care. As a note, we expect to release our 12-month data for the US-based trial of OTX TKI for the treatment of wet AMD at the clinical trial at the summit conference on June 10th. We anticipate seeing a reactivation of disease in some patients, which we believe would indicate OTX TKI continues to function as designed with accitinib concentrations beginning to fall below therapeutic levels as we approach and exceed one year of treatment. We believe the next steps with OTX TKI will be to prepare to commence our first pivotal trial in wet AMD as early as third quarter of this year, and our first pivotal trial in diabetic retinopathy as early as the first quarter of 2024. Our confidence in entering pivotal programs is based on the clinical program to date that ticks nearly all the boxes one would require from a robust Phase II program. First and foremost, we have proof of concept as monotherapy in uncontrolled retinas in the Australia study and in controlled retinas with anti-VEGF antibody induction in the U.S. trial. We were able to demonstrate a dose response in Australia and have settled on an optimal dose per day. We have comparative data from a mass trial comparing OTX TKI to ilea given every eight weekly. We also have at least 60, we will have at least 60 patients dosed with OTX-DKI prior to the commencement of our first pivotal, some of whom have had follow-up for nearly four years. As we continue to evaluate funding alternatives, including collaborative partnerships and finalized trial protocols, we hope to be able to give concrete guidance on precise plans in the near future. I would like to now hand the call over to Rabia, who will explain our ongoing clinical trials. where we are with our planned pivotal clinical trials in wet AMD and diabetic retinopathy, and our next steps for our OTX TIC and dry eye programs. She will then hand over the call to Steve Myers, our Senior Vice President Commercial, who will recap our commercial business, which is currently experiencing exciting in-market growth. But I hope you don't mind me giving a bigger picture overview of our elite technology and our OTX TKI story. It is increasingly clear, especially since ARVO, that the longer-acting antibodies are not going to solve the problems of the current therapy, and the gene therapy approaches to VEGF-mediated diseases are unlikely to replace current standard of care in any near-term horizon. We believe TKIs are really the most promising new therapies that will allow patients and providers to evolve beyond the imperfect and onerous treat-and-extend into a new area of treat-and-maintain, enabled by pan-VEGF receptor inhibition intracellular therapies like OTX TKI. Rabia?
spk01: Thank you, Anthony. Let me begin with an update on our back-of-the-eye program, OTX TKI. We are currently completing a multi-center prospective mass randomized controlled US-based clinical trial into one subject evaluating a 600-microgram OTX TKI dose in a single implant containing oxytocin compared to Afliberset administered every eight weeks in controlled VET-AMD subjects previously treated with anti-VEGF therapy. The trial is designed to assess the safety, durability, and tolerability of OTX TKI and to assess biological activity in subjects by measuring anatomical and functional changes of the retina. To date, we have reported interim data at two time points, seven months and 10 months, and have not observed any drug-related ocular or systemic series adverse events in OTX TKI-treated subjects. Importantly, the 73% of the OTX TKI-treated subjects who were rescue-free at month 7 interim analysis remained rescue-free at month 10, highlighting what we believe is best in class durability. Furthermore, we saw in the trial a 92% reduction in treatment burden for up to 10 months, while patients showed stable and sustained best-corrected visual acuity and central subfield polio thickness, comparable with the Aflibercept arm, dose every eight weeks. We believe the data highlights the potential of OTX TKI to become a differentiated product capable of providing a durable anti-VEGF response that improves upon today's standards of care in the management of WET-AMD. We continue to have productive dialogue with the FDA and recently completed a formal meeting with the agency that included a discussion of our data and clinical development strategy. Based on the feedback, we believe we have two potential designs for the pivotal trials. We will share more about the trial design that we plan to use in future and still intend to be prepared to initiate the first two required pivotal trials in wet AMD as early as the third quarter of this year, subject to obtaining the necessary financing. Moving to OTX TKI for the treatment of diabetic retinopathy. We continue to enroll subjects in a multi-center prospective, masked, randomized, controlled US-based trial in 21 subjects, evaluating a 600-microgram OTX TKI dose in a single implant containing oxytocinib compared to a sham injection procedure. We believe the same attributes that make OTX TKI a compelling product candidate for the treatment of wet AMD. the ease of use of an office-based injection and long-term durability could establish OTX TKI as the first standard of care in the treatment of diabetic retinopathy. Based on the feedback from the recent agency discussions, we believe we have a potential pivotal design for diabetic retinopathy that is consistent with the FDA's guidance and subject to top line data from our ongoing trial and obtaining the necessary funding, we believe that we will be well positioned to initiate a phase three clinical trial for this program as early as Q1 2024. We are also making excellent progress with another one of our late stage pipeline programs, OTXT-IC, Arthroprost intracameral implant using our ELITEX technology being developed for the treatment of patients with primary open angle glaucoma or ocular hypertension. The ongoing phase two trial of OTX TIC is currently enrolling, and we believe we are on track to complete the trial on schedule. OTX TIC is a program that we believe represents a significant opportunity for ocular therapeutics. While there are many medications available to lower intraocular pressure, or IOP, glaucoma remains a leading cause of blindness, in part because of unwanted side effects, improper technique, or simply forgetting to take their daily drops We believe most patients will fail to comply and may ultimately lose their vision. OTX TIC is being developed to close the gap between clinical trials and real-world outcomes by taking patient compliance out of the equation. We are enrolling approximately 86 subjects in this prospective multi-center mass randomized controlled US-based Phase II clinical trial evaluating the safety, tolerability, and efficacy of OTX-DIC for the reduction of IOP in subjects with primary open-angle glaucoma or ocular hypertension. The trial is designed to observe the changes in diurnal IOP from baseline at 2, 6, and 12 days and follow duration of IOP response over time against the risk step. We look forward to sharing Phase II top-line clinical data in Q4 2023, assessing the efficacy and durability of OTX-TIC, and as importantly, the preservation of endothelial cell health that could indicate that the product candidate is suitable for repeat dosing. Regarding our ocular surface disease programs, we remain committed to the development of our two dry eye programs. OTX-TED, a low-dose intracanalicular insert containing dexamethasone for the short-term treatment of the signs and symptoms of dry eye disease, and OTX-CSI, a cyclosporine intracanalicular insert for the chronic treatment of patients with dry eye disease. We initiated a small study in this quarter to evaluate the performance of OTX-TED versus placebo inserts. namely fast-dissolving collagen plaques, and no inserts at all. We plan to use the results of this trial to inform the selection of a more appropriate placebo comparator for use in future clinical trials for both the OTX-TED and the OTX-CSI that could potentially help the pivotal programs moving forward. I would now like to turn the call over to Steve for a commercial update. Steve?
spk08: Thank you, Rabia. On the commercial front, we finished the quarter with Dextenza net product revenue sales to specialty distributors at 13.2 million, representing growth of approximately 6% over the same period last year. Importantly, in-market billable units were up 25% versus the prior year period, which represent an increase of over 7,200 units. Measured against fourth quarter 2022, in-market billable units in the first quarter of 2023 grew by over 2,500 units, or 8%. Throughout the quarter, weekly and monthly Dextenza in-market sales continued to accelerate. In fact, in March, Dextenza recorded the highest in-market sales ever, surpassing 13,000 units in one month. We anticipate that with the full sales team in place, a revised pricing discounting strategy that was implemented in the third quarter of last year, and our strong market access, Dextenza will continue its growth in 2023. Looking at Dextenza Q1 net revenue, our recorded net revenues were slightly down versus Q4. The difference between Dextenza's recorded net sales and the growth of Dextenza's in-market billable units is due to distributor stocking patterns, not changes in gross to net. The specialty distributors closed March with eight fewer days of product on hand compared to Q4. However, with the continued strong in-market unit volumes recorded in April, we believe specialty distributors' inventories have been rebuilt to meet end-market demand of Dextenza. Looking ahead, I remain bullish for the remainder of the year. We have secured several national strategic account contracts over the past few quarters that are now in place and helping fuel our growth. We've also achieved exceptional market access coverage for Dextenza. including 100% coverage in Medicare Part B, over 90% coverage in Medicare Advantage, and over 70% coverage on the commercial payer side. Additionally, in Q1 2023, we launched a commercial assurance program to provide assistance with patients' out-of-pocket costs, and the early feedback has provided us more confidence to expand into the commercial patient population. Based on these dynamics, we remain confident reiterating our Dextenza net product revenue guidance for the full year 2023 to be between 55 and 60 million, representing potential growth of approximately 10 to 20% over 2022. With that, let me turn the call back to Donald to discuss our financial results.
spk07: Thank you, Steve. Total net revenue, which includes both gross to extensive product revenue, net of discounts, rebates, and returns, which the company refers to as net product revenue, and collaboration revenue, was $13.4 million for the first quarter of 2023, slightly ahead of first quarter of 2022 net revenues of $13.2 million, and slightly behind fourth quarter net revenue of $14.1 million. That extends in that product revenue grew from $12.5 million to $13.2 million over the comparable period in 2022, while collaboration revenue declined from $.7 million to $.2 million. Research and development expenses for the quarter of 2023, for the first quarter of 2023, were $14.7 million versus $13.1 million for the same period in 2022. driven primarily by an increase in expenses associated with clinical and preclinical programs. Selling and marketing expenses in the first quarter of 2023 were $10.8 million as compared to $9.1 million for the same quarter of 2022, reflecting primarily an increase in field force personnel. General and administrative expenses were $9.1 million for the first quarter of 2023, versus $7.6 million in the comparable quarter of 2022, primarily due to an increase in personnel-related costs, including stock-based compensation and professional fees. The company reported a net loss for the first quarter of 2023 of $30.3 million, or a loss of 39 cents per share on both a basic and diluted basis, compared to a net loss of $12.5 million, or a net loss of 16 cents per share on a basic basis and a loss of 22 cents per share on a do-lose basis for the comparable period in 2022. Net loss in the first quarter of 2023 included a $6.6 million non-cash item attributable to a change in the fair value of the derivative liability associated with the company's convertible notes, increasing total other expenses as the price of the company's common stock increased during the quarter. Non-cash charges for stock-based compensation and depreciation and amortization were $5.1 million in the first quarter of 2023 versus $4.8 million for the comparable quarter in 2022. As of March 31, 2023, the company had $79 million in cash and cash equivalents versus $102.3 million as of December 31, 2022. based on current plans and related estimates of anticipated cash inflows from the extenza and anticipated cash outflows from operating expenses, but excluding any expenses related to our planned pivotal clinical trials for OTX TKI. The company believes that its existing cash and cash equivalents are sufficient to enable the company to fund planned operating expenses, debt service obligations, and capital expenditure requirements to the middle of 2024. As of May 4th, 2023, the company had approximately 77.5 million shares outstanding. This concludes my comments on our first quarter, and I would like to turn the call back to Anthony for some final thoughts.
spk09: Thanks, Donald. So before opening the call up for questions, let me do a quick summary. OTX TKI continues to progress well, and we are pleased with ongoing FDA communication regarding our potential pivotal programs for both wet AMD and diabetic retinopathy. Enrollment continues to go well in the phase two trial of OTX TIC and glaucoma, and we plan to provide top line data in Q4 2023. Xtensa has had a strong start in 2023 with volumes in the first quarter running over 20% above the first quarter of last year. That leaves us confident in our ability to meet our 2023 guidance of 55 to 60 million in net sales. And we have a solid balance sheet with 79 million in cash that currently supports our ambitious plans and other plan pivotal programs into the middle of 2024. With that, I'll turn the call over to the operator for questions.
spk03: Thank you. At this time, we will conduct the question and answer session. As a reminder, to ask a question, you will need to press star 1 1 on your telephone and wait for your name to be announced. To withdraw your question, please press star 1 1 again. Please stand by while we compile the Q&A roster. Our first question comes from the line of John Wollobin of JMP. Your line is now open.
spk06: Hey, good afternoon, and thanks for taking the questions. A couple on the 12-month data and then a follow-up on the PIVIL trial, if I can. Just wondering if you could give us a little bit more granularity on what you expect to see in the 12-month update as exit nib is, you know, getting bioresorbed in the eye. You know, how is that going to manifest? Is it just going to be seeing fluid pick back up, or is there some other manifestation? And then at Arvo, you mentioned the average resorption was about nine months of the hydrogel, but wondering what kind of variability you saw in the patients within that nine-month average.
spk09: Well, I mean, what we expect to see at 12 months is that the disease should start to come back in some patients. What we saw in the trials to date is exactly what we anticipated, that the hydrogel goes away in a very tight window in about eight months and that there is a release of drug after that that stays in the retina for a couple of months. In some patients, it clears a little faster than others. So what we expect to see is the disease coming back. We enrolled patients in this trial that had a demonstrated need for anti-VEGF therapy. that as that therapy starts to wane that you would expect the disease process to come back and while we expect that to vary quite a bit in terms of you know individuals individual um we we would expect to see some of that back and that would be reassuring that would show that the pharmacodynamics actually are are representative of the pharmacokinetics okay and can you tell us a little bit more about you know why two different pivotal trial designs um and
spk06: When you say one could start in third quarter, how do you decide which to move forward? And then is it going to be two differently designed pivotal trials or a subsequent trial identical to the first one you start? Just, you know, trying to understand that dynamic a little bit better. Thanks.
spk09: Yeah, well, we have a lot of options. And even with the new guidance and the feedback from the FDA, there are a lot of paths that we could take. Clearly, we have a very active data room now, and discussions with strategics will potentially determine which path we take. So unfortunately, we don't really have the ability to kind of definitively say at this moment which protocol we would choose to go down, which protocol or protocols. But we hope to have that in the very near future. It's actually a very exciting time. There's a lot of possibilities. And as I said, the data room is extremely active. I'll talk to Ravi to see if she can sort of add to that a bit.
spk01: Yes, I mean, that's a really good description where we are now. John, I just wanted to answer your question whether our pivotals would be the same or not. Yes, it would be the similar design, two similar designs going forward. But as Anthony explained, we're just going to make that decision. move forward, but ultimately they need to be – they're going to be similar designs.
spk06: Okay. Thank you. I'll jump back in the queue.
spk01: Thank you, John.
spk06: Thanks, John.
spk03: One moment for our next question. Thank you. Our next question comes from the line of Joe Catanzaro of Piper Sandler. Your line is now open.
spk04: Hey, guys. Thanks for taking my questions. Maybe just one quick one from me on the potential pivotal design for the wet AMD studies. You know, I think I recall previously there was maybe some speculation that, you know, future pivotal design could maybe include two active arms, two different doses, exploring maybe two different formulations. I'm wondering if that is still a possibility between these two potential designs, or have you sort of formally committed to moving forward solely with the current formulation. Thanks.
spk09: And the quick answer to that is yes. One of the pivotal trial designs actually would use both formulations, and there's another that would only use one formulation. So we have the ability to go either direction.
spk04: Okay. Got it. I think that's all I had. So thanks for taking my question.
spk09: Thanks, Jeff.
spk03: One moment for our next question. Thank you. Our next question comes from the line of Tara Bancroft of Cohen. Your line is now open.
spk02: Hi. Thanks for taking the question. So I understand you're not disclosing specific details, but I was wondering if you can discuss hypothetically what you would consider the most favorable pivotal design, like perhaps elaborating on the pros and cons of choosing IVEA versus Lucentis as a comparator arm, and maybe the possibility of using a superiority endpoint. Thanks.
spk09: That's a great question, one that I'm not sure I can be suckered into answering at the moment. But there certainly are lots of options available. And Vibizimo is also a potential comparator if you're thinking about a superiority trial. But yes, it's all to play for. There's a non-inferiority design that looks very interesting, and there are superiority designs that also are good potentials. But I don't think we can say anything more other than that until we actually settle on the path that we take.
spk03: Okay, thanks. One moment for our next question. Thank you. Our next question comes from Colleen Cousy of Baird. Your line is now open.
spk02: Great. Thanks. Good afternoon, and thanks for taking our questions. So just to clarify, on the two WET-AMD trials that you're considering, it sounds like one might include two formulations, one might include one. Is there anything else that you're willing to share in terms of how you're thinking about the two different trial designs?
spk09: I don't think at this point it would be wise to do that, but I do appreciate the question and would love to be more fulsome in the response. But until we get them sort of actually nailed down, I think it's not wise to say anything more.
spk02: Fair enough. And then on diabetic retinopathy, have you discussed with the FDA what the bar for success would be, or do you have any internal hurdle on what you'd like to show to move into pivotal in diabetic retinopathy?
spk09: Diabetic retinopathy is far clear. I can defer to Rabia to fill you in on where we are with diabetic retinopathy.
spk01: In our Type C meeting, Colleen, we had a discussion on the diabetic retinopathy design as well. Therefore, we have the design agreed by the agency, the design we proposed to them. It would be TKI versus one injection of anything. For our understanding, sham injection is not a good comparator, but any injection would be accepted. That's why that design is clear. It's the injection of TKI at baseline versus any injection. on the other comparator, and the follow-up for 12 months. It's a very clear design, and we are ready to move forward as soon as we have, if Anthony was pointing out, our partnering process is done.
spk02: Okay, great. That's helpful. Thank you. And just one quick follow-up. On the ongoing study in diabetic retinopathy, how much follow-up would we expect to see in the initial readout from that study?
spk01: I don't think we disclosed how long the initial readout is going to be top line. That's why I'm just going to keep it for now. But we do follow up the patients 12 months and even more for the safety reasons.
spk02: Okay, great. Thanks for taking our questions.
spk09: Thanks, Helen.
spk03: One moment for our next question. Thank you. Our next question comes from Yi Chen of HC Wainwright & Co. Your line is now open.
spk05: Hi, thank you for taking my questions. Could you give us a rough estimate of the cost to complete the Phase III trial in what AMD and the Phase III trial in DR?
spk09: Insurance varies widely. It depends on the design of the pivotal, and that's really dependent upon whether we're going to go after a non-inferiority design or a superiority design. But we're looking at ranges of potentially $70 million for two pivotals in a DR or a superiority in wet AMD to $300 million for two pivotals in a non-inferiority. That's kind of wet finger in the air at the moment, but those are the numbers that we've quoted in the past.
spk05: Thanks. And regarding the Phase II trial in glaucoma, could you talk about your expectations for the top-line readout in the fourth quarter?
spk09: Ravi, you want to handle that one?
spk01: Sure. As we just mentioned, that trial is currently enrolling and enrolling well, and our expectation is to share the top line data in the fourth quarter of this year. That data, of course, would provide the IOP readings as required by the FDA, and also durability information. In addition, we're going to have the data on the corneal health, endothelial cell counts in that top line.
spk05: Okay, thanks. Last question is, when can we expect to see the results from the small study of OTX-TED?
spk01: Yes, we have recently initiated that trial and we have not guided any timeline to share the top line data yet. In future, we're going to share when the data should be expected.
spk05: Thank you.
spk01: Thank you.
spk03: As a reminder, to ask a question, you will need to press star 1 1 on your telephone Our next question comes from the line of Caroline Pommelec of Barenberg Capital Markets. Your line is now open.
spk00: Hi, thanks for taking the question. So on the expensa, you mentioned that there's revised pricing and the discounting strategy that you've implemented in the third quarter. Just wondering if you could elaborate more on that and particularly how that is affecting your growth to net. And then just to follow up on the business side, just wondering if also Do you have any guidance on operational spend for 2023? And I'll stop there. Thanks.
spk09: I'll defer this to Steve. I just want to point out that there has been no change in the gross to net from the fourth quarter of last year until the first quarter of this year. So the growth in in-market sales and the decrement in net sales is due entirely to stockholder to the distributor stock holding. So I'll transfer on to Steve for the changes in our discounting.
spk08: Yeah, thanks, Anthony. Last year from January until June, customers were purchasing Dextenza. The acquisition cost was higher than the reimbursement. And following the close of a quarter, the customers were getting a rebate. They didn't like the cost economics of that. In July, we changed our pricing strategy so that the customer would get a discount at the time of purchase. So we provided a discounted acquisition cost that they got that equaled reimbursement in July, starting in July of last year. It took about three months for our customers to get acquainted with this. But since then, we've seen tremendous growth in both Q4 and Q1. and customers now get a discount at the time of purchase, and then they also get rebates at the end of the quarter. That's determined by their aggregate purchases throughout the quarter.
spk00: That's helpful. Thanks.
spk03: Thank you. Thank you for your participation. This concludes our Q&A and today's conference call. You may now
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