Glaukos Corporation (GKOS) Earnings Call Transcript & Summary

Good morning, and welcome to the Glaukos Corporation's conference call to discuss FDA approval of iDose TR. Copies of the company's press release are available at www.glaukos.com. This call is being recorded and an archived replay will be available online in the Investor Relations section at www.glaukos.com. [Operator Instructions] I would now like to turn the call over to Chris Lewis, Vice President of Investor Relations and Corporate Affairs. You may begin your conference.

Thank you, and good morning. Joining me today are Glauko's Chairman and CEO, Tom Burns; President and COO, Joe Gilliam; CFO, Alex Thurman; and Chief Development Officer, Tomas Navratil. Please note that our remarks today are accompanied by a presentation that is available on our Investors section of our website at www.glaukos.com. Following our prepared remarks, we will have a Q&A session to ensure ample time and opportunity to address everyone's questions, We request that you limit yourself to 1 question and 1 follow-up. If you still have additional questions, you may get back into the queue. Please note that all statements other than statements of historical facts made on this call that address activities, events or developments we expect, believe or anticipate will or may occur in the future are forward-looking statements. These include statements about our plans, objectives, strategies and prospects regarding, among other things, our sales, products, pipeline technologies and clinical trials, U.S. and international commercialization, market development efforts, efficacy of our current and future products, competitive market position, regulatory strategies and reimbursement for our products, financial conditions and results of operations as well as the expected impact of general macroeconomic conditions, including foreign currency fluctuations on our business and operations. These statements are based on current expectations about future events affecting us and are subject to risks uncertainties and factors relating to our operations and business environment, all of which are difficult to predict and many of which are beyond our control. Therefore, they may cause our actual results to differ materially from those expressed or implied by forward-looking statements. Purview today's press release and our recent SEC filings for more information about these risk factors. You'll find these documents in the Investors section of our website at www.glaukos.com. With that, I will turn the call over to Glaukos Chairman and CEO, Tom Burns.

Thanks, Chris, and good morning to all. Thank you for joining us today on such short notice. Today marks a pivotal day for U.S. glaucoma patients and practitioners as well as for Glaukos. Beginning on Slide 4, we are delighted to announce the FDA approval of iDose TR, our revolutionary microinvasive injectable therapy designed to lower intraocular pressure in patients with open-angle glaucoma or ocular head retention. iDose is a first of its kind intracameral procedural pharmaceutical designed to deliver glaucoma drug therapy for up to 3 years. Today's approval of iDose TR represents the successful culmination of a 15-year development journey. Moving to Slide 5, iDose TR is truly a groundbreaking technology advancement in ophthalmology, designed to provide 24/7 continuous long-duration drug therapy to address ubiquitous patient noncompliance and chronic side effects associated with topical medications. Measuring just 1.8 millimeters. This tiny device holds 75 micrograms of proprietary preservative-free travel cost drug formulation and incorporates a novel EVA membrane designed for continuous drug elution over an extended period of time. Precision engineered iDose TR insertion system facilitates straightforward implantation procedure that aims to provide surgeons with confidence, reliability and reproducibility and securely anchoring iDose TR into the scleral tissue within the anterior chamber. Turning to Slide 6. consistent with iDose TR 505(b)(2) NTA regulatory pathway and in line with our expectations. iDose TR's approved indication is a prostaglandin analog indicated for the reduction of IOP in patients with open-angle glaucoma or ocular hypertension. This broad open field indication means that iDose TR can treat patients across the full range of glaucoma disease severity. As you already know, both Phase III pivotal studies successfully achieved the prespecified primary efficacy endpoint of non-inferiority to topical stimulus through 3 months with IOP reductions from baseline of 6.6 to 8.4 millimeters of mercury in the iDose TR arm and 6.5 to 7.7 millimeters of mercury in the timolol control arm. Subsequently, the FDA noted that iDose TR did not demonstrate non-inferiority to topical timolol over the next 9 months, which is not surprising to us given we only prospectively powered the studies to the 3-month primary efficacy endpoint. Today, we have also announced that our positive long-term results based on the completed 3-year Phase IIb study have been highlighted in a prestigious peer-reviewed journal called Drugs, and we expect to publish additional peer review data in the coming months that alongside the experience of our clinical investigators provides further evidence of the potential long-term duration of iDose TR. iDose TR demonstrated excellent tolerability and patient retention with 98% of iDose TR subjects continuing in the trial of 12 months versus 95% of timolol control subjects across both Phase III trials. The most common ocular adverse reactions and 2% to 6% of patients were increases in intraocular pressure, iritis, dry eye and visual defects most of which were mild and transient in nature. Notably, iDose TR had no adverse events of corneal endothelial cell loss, no serious corneal adverse events and no adverse events of periorbital fat atrophy through 12 months. As it relates to the ability to readminister iDose TR, the FDA elected to take a conservative approach, indicating that repeat administration has not -- have been approved. It is worth pointing out that this restriction is general in nature and is not included in the precautions and warning section label summary. Nor is it tied to any specific safety consideration such as endothelial cell loss based on our knowledge. After discussion with the agency, we ultimately decided to move forward with a near-term approval on this basis versus extending our PDUFA date to further evaluate potential alternatives and data. We look forward to engaging with the FDA in the coming months on a path forward for repeat administration of iDose TR, while in parallel, seeking to advance our next-generation iDose TREX, extended-release platform into late-stage Phase III clinical trials. As we move to Slide 7, as many of us know, glaucoma's progressive disease that has far too long been ineffectively treated with the serial and progressive use of topical eye drops. While patients may follow medication regimens in a clinical trial setting, we know a significant percentage of patients simply don't adhere to taking their eye drops in the real world, and drugs do not work very well on patients who don't take them. Ophthalmologists dabble with ubiquitous patient non-adherence rates associated with glaucoma topical medications is well known and has been shown in some studies to be upwards of 90%, creating severe unmet clinical need and a strong desire within the Ophthalmic community for safe, effective and sustained procedural pharmaceutical alternatives to traditional topical medications. Supported by strong data, we believe iDose TR provides ophthalmic surgeons with a compelling new interventional glaucoma alternative designed to provide foundational 24/7 IOP control over their patients in need. Moving to Slide 8. This provides a recap of our robust Phase III clinical program, which included 2 prospective randomized, multicenter, double-masked Phase III pivotal trials designed to compare the safety and efficacy of a single administration of iDose TR to topical timolol ophthalmic solution twice a day and reducing IOP in subjects with open-angle glaucoma or ocular hypertension. In total, the Phase III trials randomized 150 subjects across 89 clinical sites. Beyond the primary efficacy endpoint, we also highlight on the slide a subgroup analysis of the combined iDose Phase III trials which demonstrated statistically significant superiority of iDose's IOP-lowering effect versus topical prostaglandin therapy. We believe this first of its kind real-world effectiveness data further validates the game-changing potential of iDose TR and will resonate with real-world clinical decision-makers. Slide 9 demonstrates the totality of the iDose TR data set generated to date and puts us in an excellent position to successfully execute our commercial plans and drive positive real-world outcomes. Beyond the favorable primary efficacy endpoint achievements, the Phase III results also demonstrated 81% of iDose TR subjects were completely free of IOP-lowering topical medications at 12 months across both trials. This is a particularly powerful outcome considering that 23% of patients were on 2 or more topical medications at screening. Additionally, 93% of iDose TR subjects remain well controlled in 12 months on the same or fewer topical IOP lowering medications compared to screening after a single administration of iDose TR. These encouraging outcomes are further supported by the recently published Phase IIb 3 year results, in which 69% of patients remain well controlled on a single administration of iDose TR using the same or fewer baseline medications compared to 45% in the timolol control arm. On Slide 10, we are excited to share the results of a new iDose TR pharmacokinetic study, showing that iDose TR delivers therapeutically relevant and durable drug concentrations through 24 months. As you can see here, mean TFA fit levels remained above the CMS concentration at every time point and expanded -- and expanded iDose TR implants continued to show remaining drug payload at every time point through the 2-year duration of the study. This evidence which further supports the therapy's long-duration design has been submitted as an abstract at the upcoming ARVO Annual Meeting this May. The data summarized on Slide 11 confirms iDose TR's favorable tolerability and excellent safety profile across various trials and over extended evaluation periods. Of note, iDose TR saw 1, no adverse events of periorbital fat atrophy; 2, very low conjunctival hyperemia rates; 3, no adverse events of corneal endothelial cell loss and 4, very low or no incidence of iris color change. Slide 12 provides a glimpse into our plans for a robust set of peer-reviewed literature to be published in the coming months. Just this last weekend, as I previously mentioned, the first iDose TR publication was released and is currently available online. The article published in the journal Drugs summarizes the Phase IIb 3-year outcomes. Approximately 12 articles are currently in the works, including 3 manuscripts that have already been submitted to leading journals. Jumping to Slide 13. The long-term strategic focus for us is to improve our common care with interventional stand-alone therapies that can be used early in the treatment paradigm, helping to reduce disease progression and to preserve vision. Today's approval of iDose TR establishes a foundational cornerstone for this emerging interventional glaucoma mindset by providing practitioners and patients with a proactive and reliable treatment alternative that is safe, effective and durable. We will continue to work closely with surgeons and thought leaders globally to drive this broader evolution in the standard of care through the upcoming iDose commercial launch. As highlighted on Slide 14, today's approval is the culmination of more than 15 years of unrelenting research development and clinical efforts. I want to thank our dedicated employees who have put in countless hours to make this approval a reality. We are also deeply grateful to the clinical investigators and participants who participated in the clinical trials and played instrumental roles in bringing iDose TR to the U.S. It is important to note that there was no playbook to follow developing a product this novel and our incredible team delivered time and time again. As you can see on Slide 15, this journey has included the buildup of our completely new state-of-the-art nanotechnology manufacturing facility in San Clemente, California, to support the operational and manufacturing needs of our iDose TR commercial plans and growth objectives. As part of our NDA review, we successfully completed the required pre-approval inspection or PAI of this new facility, notably with known 43 observations. For a company going through this type of rigorous pharmaceutical review for the first time, I couldn't be more pleased with this unblemished outcome, and we would like to recognize the excellent work of our operations, development, quality teams that drove this result. And on Slide 16, you can see just a glimpse into our unique capabilities in micro scale manufacturing that we have developed over the past 20-plus years that are now being deployed in support of iDose TR. So with that, I'm going to turn the call over to Joe Gilliam, our President and Chief Operating Officer, to talk more about iDose commercial plans and patient access initiatives. Joe?

Thanks, Tom. I'd like to reiterate Tom's earlier comments on what a truly incredible milestone this is for Glaukos and really the broader glaucoma community. We've been preparing for this moment for several years now and are excited to commence execution of our detailed coordinated launch plan. Starting on Slide 17. As we've discussed before, our plan is for a methodical controlled launch over the first half of 2024, beginning with surgeon training primarily focused on glaucoma specialists. As we refine and optimize our training and skill transfer to our sales force and surgical community, we will continue to expand our training and broader launch efforts over the course of 2024. Alongside that, we will be advancing several market access reimbursement initiatives designed to drive full-some coverage and payment for the iDose TR procedural Pharmaceutical over time. On that front, we plan to submit for the permanent J-code imminently and expect it to become effective in the second half of 2024 based on the CMS cycles for J-codes. Until then, we will launch iDose TR with a temporary miscellaneous C-code and anticipate measured adoption over this initial period, building until the permanent J-code is in place, and we've expanded our surgeon training initiatives. Alongside the J-Code process, we will also be working to establish the new Category III CPT code 0660-T that will cover the procedural component of iDose TR. This includes the establishment of a facility fee, which will be driven by the APC-- by an APC classification from CMS which we expect to have in the first half of 2024. We will also be working with Max to secure professional fee coverage and payment over the course of the year. As we are successful in advancing our training and market access initiatives, we plan to accelerate our marketing campaigns in the back half of 2024 and into 2025 to support broader commercialization. As we move to Slide 18, we are in a powerful position with an established best-in-class glaucoma sales force and commercial organization. Our plan is to leverage this proven sales force and commercial organization to drive iDose launched next year. The training of our sales force has already begun and will further accelerate over the next month to support the commencement of initial commercial launch activities towards the latter part of the first quarter. We believe many patients afflicted with glaucoma will ultimately benefit from iDose TR. However, our initial focus will be on those patient groups with the greatest need, including those that are known to be noncompliant and tolerant to topical medications, suffering from underlying comorbidities such as dry eye, have physical limitations that impede their ability to utilize eyedrops or those patients seeking an improved quality of life related to topical drug use. Moving to Slide 19. With the launch of iDose TR we are pioneering a brand-new category of procedural pharmaceuticals that we believe has the potential to reshape glaucoma management as we know it today. We are excited to now be on the cusp of bringing this transformative technology to market and in so doing, expanding the treatment alternatives for patients suffering with glaucoma and ocular hypertension. We believe iDose TR offers a compelling value to patients. We and our advisers have had meaningful nonbranded and preliminary information exchange conversations with payers as well as key members of the patient advocacy and physician community regarding the value in relation to pricing. These factors have all informed our pricing decision, which also reflects the significant investments we've made to develop and make a new game-changing therapy for glaucoma patients. Based on this, along with a robust set of internal pharmaeconomic analysis, we have established a wholesale acquisition cost for iDose TR of $13,950 per dose for implant. We believe this provides a strong value proposition for physicians and payers, and we believe iDose TR is among the most cost-effective procedural pharmaceutical and ophthalmology when annualized based on its design to deliver up to 3 years of drug therapy. Moving to Slide 20. With the launch of iDose TR, we recognize the responsibility to support broad patient access. To support this critical focus of ours, we have built a robust patient services team known as Glaukos Patient Services or GPS that will help support patients and their providers through the treatment journey by providing a system inclusive of patient education, insurance counseling, financial co-pay assistance for eligible patients and comprehensive market access support, including billing and coding resources. We will also have specialty pharmacy options available for our customers at launch. Glaukos is committed to ensuring that every eligible patient who may benefit from iDose TR will have access regardless of insurance coverage restrictions or the pace of the ability to pay. As such, we have built an all-encompassing comprehensive patient advocacy and access program to support this goal. Moving to Slide 21. As part of this, Glaukos is very proud to introduce the iDose, yourDose philantrophic initiative. For every iDose TR sold, Glaukos pledges to make available an equal number of iDose TR units for qualifying charitable donation requests in the U.S. and around the globe for recipients to satisfy independent eligibility requirements. Finally, moving to Slide 22. Today, we are reaffirming our 2023 revenue guidance of $307 million to $310 million and introducing highly preliminary 2024 revenue guidance range of $350 million to $360 million. This preliminary range factors in our iDose launch plans over the course of 2024. MIGS combo cataract and iStent infinite landscape, as well as international glaucoma and corneal health expectations. We expect to refine this guidance range and provide additional commentary during the fourth quarter 2023 earnings call in February of 2024. And with that, I'll turn it back to Tom.

Okay. Thanks, Joe. So in conclusion, I think it is fitting to remind you of our company mantra. We'll go first. To me, this statement is less a statement of aspiration, it is a statement of fact. Today's approval is a great example of how we live out this mentality as an organization every day. We are fired up and excited to play offense in 2024 and beyond. Our foundation is strong, and we are ideally positioned to continue transforming vision for the benefit of patients worldwide. So with that, I'll open the call for questions.

[Operator Instructions] And your first question comes from the line of Ryan Zimmerman from BTIG.

Congrats on the approval. I know a lot of work went into getting to this point. I guess I'm going to start with some of the questions that have been asked this morning by investors around the label and some of the dynamics in the label, if I could. So the non-inferiority to timolol after 3 months, I'm wondering if you could kind of speak to that in the context of how you think payers look at your WACC pricing and say, "Well, yes, we can pay for this. But given the non-inferiority, I guess do you anticipate there will be questions about that and push back on that given those 2 dynamics?

Ryan, it's Joe. Maybe I'll start and then Tom can add any color if he'd like. I think if you think about the payer community, what ultimately matters most is the ones set of evidence that we'll be presenting to them for peer-reviewed journals. Tom obviously highlighted a lot of those in the prepared remarks. But as a reminder, you've seen that data both from the Phase II study as well as the various forms of the Phase III, exchange date, et cetera. all of which in variable, whether objective subjectively, point to the long duration that the product was designed for. I think that ultimately is what will carry the day primarily with the commercial payer community.

Okay. And then, Tom, you made some very pointed comments about the restriction on repeated usage. And it's clear that the FDA is taking a conservative tone on that. But again, the language is not as restrictive as what derisk this label is, and I'm wondering if you can just speak to kind of all the specifics of what you expect to do to turn the corner on repeated usage because you clearly are pressing forward with efforts to kind of go at that point post approval here?

Yes, I'd be happy to answer that. So let me address, first of all, the label. We really are unaware of any clinical data that would restrict the iDose TR for reimplantation. If you look at the data, we have invariably low rates of endothelial cell loss. And in fact, in the label itself. You won't see any indication on the warnings or precaution for ECL. We conducted a, what I would call a very facile exchange study and I think when it came down to it, it was the conservatism of the FDA, which ruled the day and gave us this initial label. So I can tell you that we're already actively hard at work in constructing a logical and compelling argument for moving forward to broaden our ability to reimplant this device. The good news is, given the duration of the iDose itself at 2 to 3 years, we have time. We have time to engage the FDA in a fulsome discussion, present data and meet the needs to be able to broaden the label.

And your next question comes from the line of Tom Stephan from Stifel.

Okay. Great. Congratulations. I might stick with readministration, but can you help us think about the importance of the label not achieving that readministration I guess in the context of the ramp and the peak sales opportunity for iDose, maybe to what extent does it impact, I guess, the DCF, if you will, on iDose. And then I have a follow-up. .

Tom, it's Joe. I'll probably leave the DCF modeling to you and the investment community in that context. But I guess that really made 2 points, and that really reiterates something Tom just said. The first is I think that, that restriction around a single implant really has a very limited impact in the context of the commercial dynamics as we think about them in 2024, 2025 and quite frankly, probably even well into 2026. And then as you think about when past that, clearly, as Tom mentioned, we have a variety of paths forward in engaging with the FDA around potential label expansion there. given the pristine safe -- safety profile exists with iDose TR. And then as Tom mentioned in the prepared remarks, we're also moving forward aggressively on the next generation of iDose with the iDose TREX platform. So I think there's a variety of things there that, quite frankly, I was doing that DCF modeling. I'm not sure there's much of an impact at all, and quite frankly, probably net-net with the totalis announcement, it only improved. .

Got it. That makes sense. And then I just want to ask about 2024. I appreciate the preliminary guidance. Maybe to start, can you provide any high-level thoughts on -- to what extent iDose is factored into that, even if it's sort of a ballpark or just directionally? And then any color on the construct of the guide sort of outside of that -- there's a lot of moving parts in the market next year. And so what gave you the confidence outside of iDose to guide at this point in the year?

Yes. Thanks, Tom. I mean, obviously, it is early for us to provide our forward look. But ultimately, I thought -- we felt that establishing an anchor of a baseline, if you will, for the year made sense given just the material news that we were announcing today in totality associated with iDose. And we felt like if we didn't give you all at least some directional preliminary guidance that -- we'd be leaving a little bit too much to you all to try to figure out and model from this announcement. So that was the rationale behind it. Obviously, as we move forward on the fourth quarter call and then from there, we'll give more granular feedback and expectations in terms of the variety of questions you typically would ask around guidance. And as it relates iDose TR, it obviously factored in here. And as we move forward, we recognize the importance from a reporting standpoint of providing incremental color associated with the iDose performance. and we'll address that in 2024 versus doing so here today on this call.

Your next question comes from the line of Matthew O'Brien from Piper Sandler.

This is Phil on for Matt. Congrats on the approval. For starters, can you outline your expectations around the rollout here for us? How many surgeons will be interested in using this without a permanent J-code and I guess to that end, can you speak to the code cycle here? And what more do you need to do before you're ready to submit for that permanent J-code? And could the company be in that first cycle in 2024?

Phil, it's Joe. I'll start on that and maybe start in reverse order based on the way you ask that. Let's talk about that cycle from a reimbursement standpoint that we outlined in the prepared remarks, but -- if you think about the J-code component and all of the preparatory work, our teams are already ready, and quite frankly, they started executing towards that plan yesterday immediately upon receipt of the approval. The expectation here would be that there's a series of submissions that happened between now and very early 2024 that will drive the following: Miscellaneous C-code out of the gate that we would expect over the course of the second half of 2024 would result in the establishment of the permanent J-code. We certainly expect that at a minimum, heading into the fourth quarter, we'll have that permanent J-code established. It may come as early as heading into the third quarter depending upon the exact timing of some of the submissions. As we think about the facility and the professional fee, the facility fee, as we noted, we would expect to be turned on by CMS in the first half of the year to support payment for those folks doing the procedure from a facility perspective. And like all of these procedures, including procedural Pharmaceuticals, we'll work with the Max to establish professional fees and recurring specialty schedules over the course that whole line of, I'll call it, milestones or items over the course of '24 combined against the training dynamics, obviously, we will move methodically out of the gate, training just a handful of surgeons first who provide feedback to our sales force and provide us with the pearls that ultimately help drive optimize training programs. And then we'll expand from there, both with our sales force as well as with the surgeon community. And the goal really is to get to a place where you're at full speed running in that second half and certainly by the time you're end of the fourth quarter, when the various market access, if you will, milestones are achieved. There's always a degree of practices and surgeons were more comfortable earlier in that paradigm. And then others that will wait until you have all of these sort of impediments knock down in terms of facility fee economics, professional fee economics or the establishment of the permanent J-code. So I really think it's something where , a term we often use that you'll crawl at the beginning of the year and you hope to be a place where you're drawing your running by the time you're in the fourth quarter.

Your next question comes from the line of George Sellers from Stephens.

Congratulations. In the early stages of this, how are you expecting it to be used either in the combo cataract market or more stand-alone? And how does that ultimately impact reimbursement how the Max think about it and the facility fee? And then also, can it be used in conjunction with an iStent?

I'll take the first part of the question, George, and then I'm going to turn over, this is Tom, over to Joe. As you can see and as we've talked about, we're going to approach this in a way where we're going to be focusing on the stand-alone use of the product in their early innings as we launch. We think that this is the exceptional product to drive this intervention of glaucoma mindset. And so you think about it the areas we're focusing on are going to be patients that are noncompliant, clearly patients that have comorbidity ocular surface disease. Patients who are looking for a substantial increase in quality of life, patients who are on multiple drugs seeking to reduce drug burden. These are the areas that we're going to be focusing on. And those clearly will be used both on a stand-alone basis or the surgeons will have ultimate discretion to use them in combination with any other procedure, including cataract surgery. So that's where we're focused. We think there's an entire unmet need that we'll be filling the gap of. We'll go out in a compensed way where we'll segment the marketplace. And I think by doing so, we'll drive -- ultimately drive more rapid and fulsome adoption, Joe.

Yes, I would just -- and adding that a little bit reiterating, I mean, ultimately, iDose TR is approved for providing therapy to a wide swap of patients for mycor hypotension glaucoma and as Tom said. And -- and that's really independent of whether or not the patient has any other underlying comorbidities and less specifically called out as a risk for the patient in the label. As it relates to the broader reimbursement environment, I'm not aware of any restrictions that would prevent surgeons from doing what they deem to be clinically necessary to support the patients in the combination of any of these procedures of iDose with an iStent or otherwise. And I think that will be a part of the evolving treatment paradigm as we move forward. But as Tom said, our focus commercially is absolutely on driving that stand-alone and interventional glaucoma message because that is paramount to the future of the company, the future of iDose and where we're heading.

Okay. That's really helpful. And then maybe 1 for Alex. I'm just curious how you all are thinking about how the balance sheet is positioned if there's any additional financing to ramp up commercialization of iDose that we should maybe contemplate?

Thanks, George, for the question. So the answer in short is no. We've built a balance sheet that's strong -- as I think we've mentioned historically, there's not a need to hire any sales force. This product will go into our existing sales force to launch and any marketing dollars that we have set aside, we can certainly cover. So no needed financing to that.

Your next question comes from the line of Larry Biegelsen from Wells Fargo.

Congratulations. Tom, a couple of questions here. So can you talk about how the efficacy compares to DURYSTA and why the label says, it's not non-inferior to timolol from month 3 to 12, whereas the Phase IIb paper says a greater percentage of iDose patients were well controlled on the same or fewer topical IOP meds through month 36. How do we reconcile those 2 statements? And those 2 statements? And then DURYSTA, what simply data can you point to that suggests this is more effective or greater duration? And I had 1 follow-up.

Okay. That's great, Larry. I'm actually -- we've got Tomas Navratil here, is our Chief Development Officer. And I think I'm going to ask Tomas to take that question.

Thank you so much, gentlemen. Thank you for the question. I think we have a very favorable comparison to DURYSTA. As noted on the prescribing information for the DURYSTA product by week 15 DURYSTA is inferior to timolol. Please note that in the other studies, the simple statement is that others was not non-inferior to timolol over 9 months. And so we have an advantage there. Please note that the Phase III program and Phase III studies were designed and powered to meet the primary efficacy over the first 3 months as required by the U.S. FDA. And these studies were not powered to demonstrate non-inferiority in the other months in the following 9 months. So we believe we have a very favorable comparison with regard to the longevity and duration of action versus DURYSTA.

Larry, I might just add over time, I think ultimately, what will matter here is the real world, right? And from that perspective, we know from this broad body of evidence that's been presented, what you'll continue to see from the peer review journals, some of the pharmakinetic data that Tom discussed earlier that the DURYSTA is here. We have, obviously, a very large group of clinical investigators who have their own experience associated with this. And I think the totality of that gives us the confidence of what really is happening here over a long period of time.

Yes. And I'll add to. I mean we look at this, 81% of patients have 1 year that are medication-free even though 23% around 2 or more medications to begin with. That's the data that I'd ask you to focus in on as you do your channel checks. And also, when we look at the 93% that are well controlled at the year in the pivotal trials on the same or fewer topical medications that as well is real-world compelling evidence, which is, I think, far our ways, what is arguably just a regulatory path to approval by comparing it with the topical timolol. I think it's important to acknowledge, again, as Tomas just did, our study was prospectively powered to determine non-inferiority to timolol at 3 months only. And midway through their recruiting of the clinical trial, the FDA asked us to add a secondary endpoint at a year. study was not powered to determine that. And so it's unsurprising that we found that we met the non-inferiority of endpoint at 3 months and didn't at 12 months. So all in all, we are more than satisfied with the compelling data we have. We're going to bring to market and the clinical investigators who have a evaluating value of some of these last several years, are entirely satisfied with the compelling nature of the efficacy data.

That's helpful. Just 1 follow-up. Joe, just to confirm that the 14,000 or so WACC is what Glaukos will receive? And Tom, can you talk about the pros and cons of administrating iDose in the ASC versus the office for DURYSTA and what's your plan to bring iDose to the office setting.

Yes, Larry, from the WACC is indeed the expectation there. Now I will say it's a buy-and-bill pharmaceutical product. And we do not anticipate any real discounting, if you will, when you think about that in the traditional pharmaceutical set. So the WACC should be pretty close to the realized ASP. Where we might see it be a touch lower over time. It will be based upon the providing the product in the various government arenas, so Medicaid or similar where you have the required government-related discounts. So I think over time, we'll probably see a little bit of a gap there in terms of our realized ASP per WACC, but certainly out of the gate, it will be pretty darn close to the 13,950 we're talking about.

And Larry, as I said all along, I'm agnostic to where the site of service is with the product. Some surgeons are going to prefer to do it. In the ASC. We think most of this -- of the iDose will be used in the near term in the ASC, but it's important to offer the in-office setting over the long term for the convenience of -- for the patient and for the consumer. And so in doing that, what we'll do over the course of the next several months is to work up a relative value -- work up of what surgeons will get since they'll have both facility fee by moving into the office. They need to have a nonfacility payment code and that will be worked out by us in conjunction with societies, and we'll approach the MAX on a serial basis in order to institute this and provide reimbursement for surgeons who seek to do this in the in-office setting. Clearly, both settings need to be a sterile environment and have full protection to support the patients. So there's very little difference there. It's really a difference of convenience for the consumer or in this case of the patient. And there is a desire for many surgeons to be able to have the ability, to have the flexibility to do this in office in the future. And so as I've said now, probably for the last 10 years, I'm agnostic, there are going to be some surgeons who prefer to continue to do this in the ASC because they see it as a profitable way to be able to call an additional facility code because, again, the J-code will be carved out and the facility payment will be fully unrestricted and unfettered and use and absorbed by the clinician. So this is how I see this going forward. It will be predominantly in the first several months and I think over time, I will be leaving an effort to drive this into the office to give clinicians the flexibility inside of service.

Our next question comes from the line of Margaret Kaczor from William Blair.

Thanks for getting up this early morning on the West Coast. Maybe just to start out with, I wanted to talk about comp plans to the existing sales force because you've now got iStent infinite, iDose -- we've got that change in economy last on the [indiscernible] reimbursement '24 as well. How do you think about that from a commercial perspective? What are the KPIs these guys are going to be focused on the growth in iStent trends accounts -- any details would be helpful.

Sure, Margaret. Thanks for the sentiment. I think I must say not going to get into great detail on this, but I think you know we really take 2 main principles whenever we're determining our comp plans. The first is our expectations on a quarterly or semiannual or annual basis around the overall revenue performance associated with a rep's territory. that's unchanged here. Obviously, we have to continue to factor in all the various drivers that are -- some of which you outlined in your question, as we set that. Behind that, we'll often have subsets of either economic drivers or to your point, KPIs. Those are not always based upon specific revenue, but oftentimes on the behaviors that -- or the type of things that we ask our sales force to do in the short term that we know will be driving the right long-term objectives of the company. And 2024 will be no different from that perspective. we'll have to be on top of it on a consistent basis, month in and month out and quarter-to-quarter out given what we think will transpire over the course of the year. But our historical strategy is unchanged going into 2024.

Okay. And then I got to try get it question at least relative to -- the street. So I'll take another crack at it for my colleagues. But the Street was maybe assuming 5,000, 6,000 items in 2024 for iDose. I know you're not commenting on how large iDose in that '24 guidance. But just kind of curious if you can comment at all on whether industry may be too bullish on volume and obviously, much lower at ASP and do those dynamics change, obviously, with the higher ASP relative to what we expected?

Sure. I won't get too granular as it relates to iDose component at this stage of the game. But I think clearly, and we respect the work that was done by the analysts and the investor community coming into this, obviously, a lot of which is opaque to you all and the process goes on behind pricing of pharmaceutical, procedural pharmaceutical like this. There are 2 sides to that equation. The ASP is 1 side of that or the WACC price. Other side, is that volume based upon the dynamics that I discussed earlier in terms of the training rollout as well as the various market access considerations. So I think one of the reasons why we wanted to provide the macro guidance that we had today is given that relative material upside in the pricing side of this equation versus what industry was expecting, that we kept that in check in terms of how that translates into the overall revenue performance for 2024, at least sitting here at this stage of bargain.

Your next question comes from the line of David Saxon from Needham.

Congrats on the approval here. Maybe 1 for Alex. I was wondering if you could talk about the iDose COGS profile and over time where overall gross margin could go as iDose launch ramps. I think original or prior expectations have been kind of the low to mid-80s for overall margins. So could that go to the high 80s as iDose ramps? Any color there would be helpful.

Yes. Thanks, Dave, for the question. So what we've always said historically is that we target this range of 83% to 84%. And in the short term, I think we're on record saying that we don't believe that, that range should change in the short term. We do believe iDose can be accretive to that margin over time, and we're just going to have to wait and see how it all plays out. And we'll probably give more guidance as the game is played on the field, so to speak.

Okay. Great. And then maybe a higher level question. In the slides, you've called out the iDose opportunity is 1 million eyes I think prior expectations or estimates were for 3 million eyes. So I guess what's the thinking behind the 1 million eyes? What assumptions changed there? And then what -- any impact was the -- not getting the exchange label in that.

Yes, David. The 1 million eye estimate really was independent don't having to do with the latter part of your question. it's actually somewhat straightforward math. The underlying views of the potential market opportunity are unchanged from what we discussed now several years ago in the 3 million eyes. What I'll point to is -- and you may have the recollection, the 3 million eyes was always assumed a 1-year duration of therapy. And so we wanted to update this based upon, obviously, the fact that the iDose TR was designed to last up to 3 years and based upon, obviously, all the clinical evidence that Tom walked us through earlier, we felt it more prudent to do that math for you and adjust the market estimate to the 1 million in new eyes.

Your next question comes from the line of Steve Lichtman from Oppenheimer & Company.

Congratulations. Most of my questions have been answered. So I just want to follow up with 1. On exchange, you obviously presented the positive exchange data earlier this year and submitted it to FDA. So can you talk a little bit more about FDA's response to that data? And any dialogue you've had in terms of what's going to be needed? Will there need to be another larger exchange trial? Any more color you can provide there would be great.

I'll be happy to take that, Steve. And again, as you're all aware, we did conduct at the FDA's assistance an exchange study, the 33 patients where we did show that with good facility, the product could be exchanged. And you saw the median time of that exchange and the fact that the rates of ECL loss, even in those patients over many years, in this case, over 5 were invariably low. So these were presented to the FDA. I can't get inside the mind of the FDA. I can't tell you there was actual comments study to us. Some of that was opaque and done in their own back room. I can't tell you that looking at that study, it will become an important component of several things that we're looking at as we petition the FDA for readministration of this -- of the implant over the next several months.

Your next question comes from the line of Anthony Petrone from Mizuho Group.

Congratulations to everyone on the team on the great achievement here. Maybe a couple of questions just to go back to non-inferiority in the spread where it was non-powered. Just wondering, as you go real world and potentially the implant stays certainly through 1 year and potentially longer. Is there anything just mechanically in the elution device where the potencies of the drop could become compromised in some way? Just anything on that expectation real world. And when you think about just the $13,000 wholesale acquisition cost, how much did the language in the labeling influenced that pricing? Or was the pricing strategy here just separate from the label. And again, congratulations on the great milestone.

Yes, I'll be happy to take that question. This is Tom. And so I think you need to really look back at the pharmacoeconomic data that we presented. And this is truly compelling data. And so in the case of this study, which was done overseas, 210 iDose patients were followed for 3 to 24 months. And in the course of that following, they took different cohorts in this case, I think there were 14 different cohorts, and they extracted the implant at every 3 months, and we're able to assess what remained inside the implants. And at the same time, they did aqueous taps to assess the concentration of the iDose TR in the [indiscernible] . And it's really important to understand that even after 24 months, there was still gas in the tank, 16% volumetric, a sustainability of the travel cost at 24 months. And importantly, to your question, the values or the concentration values were well above the EC50s's so this is why we think we see this robust long-term durability data that we see in the Phase IIb study now extending again with 70% of patients well controlled and the same with fewer medications than 3 years. So -- this is a compelling pharmacoeconomic validation of what we're seeing in the clinical studies.

I appreciate that. And just a follow-up on labeling versus the WACC price, it was the pricing strategy separate from label? Or was it influenced by the label Yes.

I can answer that one as well. And I can tell you that it was invariably separate, right? And so we did the -- as I've talked to you about for some time now, we've done a full cohort of pharmacoeconomic analysis, which gave us the position to move forward. But importantly, when you look at the cadre of procedural pharmaceuticals upon which we are compared, it really is the final analysis drove me to a position where we needed to be able to have a more compelling price for this breakthrough technology. When you see a litany of procedural pharmaceuticals and you implant iDose yearly rate -- economic rate against those, you're going to find that we're either in the mid or even lower ranges compared to some of what I consider breakthrough pharmaceuticals, both in the anterior segment and in the posterior segment. So it was a concerted process, highly shopable. We did as well as use the DURYSTA product, as I've talked to you about before as a predicate and you can see with the fact that we're lasting orders of magnitude longer, that helped drive the validation for this price, not only to ourselves, but I think it will to payers as well.

Your next question comes from the line of Sam Brodovsky from Truist Securities.

I'll reiterate the congratulations on the approval this morning. First question on the TAM. As we just think about that $1 million -- or excuse me, 1 million patient annual TAM there, can you give us any quantification as to the specific subset that you think about being a part of the initial target population with higher comorbids and compliance issues?

Sure, Sam. And I think over the course of next year, we'll provide more color and feedback on that specifically. For now, what I'd probably point you back to is the presentation we delivered in 2017 actually quite some time ago, where we really broke that down at that time to the point of the earlier question, we were doing it on a 1-year duration of therapy estimate. And so you have to make those adjustments to the numbers you see in that 2017 Analyst Day presentation, but clearly, we've taken the time to really think through the individual subsets of the patients that are in the greatest need. You also have to factor in the market access-related considerations when you think about what is the sort of realizable near-term addressable market versus where we expect this to drive over the next 5 to 10 years.

Great. And then just to try and sorry to keep going back to readministration, but just to try to nail it down here. Is that something you think you could get the label changed with existing data? Or is that something that's going to require a new study in your view?

I'm going to turn it to Tomas for this, Tomas?

Thank you for the question. I think what we are planning to do is following this approval, we plan to engage with follow-up dialogue with the U.S. FDA and try to amend the label without additional studies. Furthermore, as noted by Tom, we are already advancing the next-generation product into the Phase III stage by the end of the year.

And your last question comes from the line of Michael Sarcone from Jefferies.

Thanks for squeezing me in here. Also, congrats on the approval. So just again, 1 last follow-up on exchange and I'll just keep it to 1 question. You've got this great data. You've already mentioned how the FDA has taken this conservative tax and it's really impossible to read their mind. I guess when you really think about it and you sit in your strategy sessions, I mean, like how do you handicap your actual ability or the potential to get the FDA to change their conservative tax here?

Thank you for the question. This is Tomas again. I think we are going to present a very carefully crafted algorithm for readministration. We are going to rely also on the strength of the exchange data, where we followed patients across 2 implantation cycles and nearly 5-plus years of follow-up are showing no adverse events of corneal endothelial cell loss, and we believe the combination of the thoughtful algorithm for administration and the strength of the exchange data may lead to a productive dialogue on the amendment of delayed link for administration.

I think it's important to note, too, I think it's important to note that it was mentioned earlier that we plan to enter the clinical trial, Phase III clinical trial or our second-generation iDose TREX by the end of the year. So as we prognosticate and look at how we might finish, we may be in a position to target approvals over that product in late '27, early '28. in which case, we'll have the ability to have a traditional implant even if we're unsuccessful in moving the FDA over the next couple of years. And if you think about the duration of the implants that are going to go in, in the late '24 and '25 period, that takes us to that target time point. And so we have kind of a belt-and-suspenders approach to readministration that we think is very compelling.

And this ends our question-and-answer period. I will now turn the call back over to the company for some final closing remarks.

Okay. So this is Tom, and I'd like to thank all of you for all your time and attention and joining us on such short notice today. Thank you for your continued interest and support of Glaukos. With that, I'll say goodbye.

This concludes today's conference call. Thank you for your participation. You may now disconnect.