Glaukos Corporation

Your 2021 financial results conference call. A copy of the company's press release issued after the market closed today is available at www.quarkco.com. All lines have been placed on mute to prevent any background noise. After the speaker's remarks, there will be a question and answer session. If you'd like to ask a question during this time, press star followed by the number one on your telephone keypad. If you'd like to withdraw a question, press star one again. This call is being recorded and an archived replay will be available online in the investor relations section at www.glacos.com. I will now turn the call over to Chris Lewis, Vice President of Investor Relations and Corporate Affairs. Please go ahead.

Thank you and good afternoon.

Joining me today are Glacos Chairman, President and CEO Tom Burns, CFO Joe Gilliam, COO Chris Calcaterra, and Vice President of Finance Alex Thurmond. Following our prepared remarks, we'll open the call to questions. To ensure ample time and opportunity to address everyone's questions, we request that you limit yourself to one question and one 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 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, our products, our pipeline technologies, our US and international commercialization, integration, and market development efforts, the efficacy of our current and future products, our competitive market position, reimbursement for our products, financial condition and results of operations, as well as the expected impact of the COVID-19 pandemic 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. Review today's press release and our recent SEC filings for more information about these risk factors. You'll find these documents in the investor section of our website at www.globcos.com. Finally, please note that during today's call, We will also discuss certain non-GAAP financial measures, including results on an adjusted basis. We believe these financial measures can facilitate a more complete analysis and greater transparency into Glaucos' ongoing results of operations, particularly when comparing underlying results from period to period. Please refer to the tables in our earnings press release available in the Investors Relations section of our website for reconciliation of these measures to their most directly comparable GAAP financial measure. With that, I'll turn the call over to Glaucos Chairman, President, and CEO, Tom Burns.

Okay, thank you, Chris. Good afternoon, and thank you all for joining us today. We hope everyone is staying safe and doing well. Our mission at Glaucos is to truly transform vision by pioneering novel, dropless platforms that can meaningfully advance the standard of care and improve outcomes for patients suffering from sight-threatening chronic eye diseases. Our mantra will go first. embodies our commitment and determination to take chances, to push the limits of science, and to disrupt the legacy treatment paradigms in glaucoma, corneal disorders, and retinal diseases. Today, Glaucus reported fourth quarter net sales of 73.2 million, flat versus the year-ago quarter. For 2021, net sales rose 31% to 294 million from 225 million in 2020. Both the fourth quarter and full year 2021 results were up versus comparable 2019 periods on a pro forma basis. We're also providing a 2022 net sales guidance range of $265 million to $275 million. Joe and Alex will discuss our financial results and outlook in more detail later in the call. These results exceeded the top end of our guidance range and reflect solid execution across our glaucoma and cornea health franchises amidst both continued COVID-related volatility and headwinds globally and U.S. combination cataract glaucoma dynamics associated in particular with the 2022 CMS proposed rules regarding reimbursement rates that were not adjusted and finalized until November 2021. Within our U.S. glaucoma franchise, our commercial team continues to successfully train and educate our current and prospective surgeon customers on the favorable long-term risk-to-benefit profile of our iSEN family of technologies and advance MIGs towards the standard of care for glaucoma. We remain focused on maximizing the access to our site-saving technologies and overall care for glaucoma patients here in the United States. While we acknowledge that we may face headwinds and combination cataract glaucoma domestically based on the cuts and professional fee reimbursement that, despite improving in the CMS final rule, remains substantially below the more invasive alternatives, we have been preparing for this potential scenario and we are focused on executing our strategy. At the same time, we will remain prudent as it relates to forward guidance as we navigate the year ahead. Our international glaucoma franchise year-over-year growth during the fourth quarter was broad-based, but similar to the United States. We continue to experience intermittent COVID disruptions in many of our global markets that accelerated toward the end of the fourth quarter of 2021 and in early 2022. We remain in the early stages of our international penetration, and we are continuing to invest in our expanding teams and new markets as we drive broader adoption of MIGs around the globe. One such new market is in India, where we have commenced initial commercial launch activities for iSpent and Jacked. Corneal health growth during the fourth quarter was driven by record U.S. Petrexa sales of 13.5 million and continued healthy momentum in new U.S. account starts. Moving forward, our focus remains on executing our commercial and market development strategies and building upon the strong momentum we are experiencing within this emerging growth franchise for Glaucos. It is clear that the pandemic and subsequent global recovery continues to pressure labor markets, the global supply chain, and at times, commerce in general. We and our customers are not immune to these realities and risks as we move forward. We have been pleased with our ability to navigate the supply chain challenges associated with our commercial products thus far, but we continue to experience longer lead times, higher cost, and intermittent disruptions with third-party partners and suppliers associated with our manufacturing operations and R&D pipeline broadly. Further, the impact of the Omicron variant as we entered into 2022 is worth noting. Its impact has varied by geography, with more strict government-driven lockdowns in markets like Australia versus the US, where hospitals have at times had to restrict elective procedures, and all sites have dealt with the impact of increased numbers of staff members testing positive given how pervasive this wave of COVID has been globally. Overall, I am proud of our performance this past year and would like to recognize the continued dedication and resiliency of our teams around the globe who remain steadfastly committed to their work in the face of continued COVID disruptions and other unforeseen external circumstances. We are optimistic as things move forward here in 2022. Our ability to execute our plans illustrates not only our effective ongoing response to the current market environment, but also reflects the progress we continue to make towards our broader strategic vision. Consider our key 2021 accomplishments. One, we successfully executed in our current core franchises by driving new adoption and deeper penetration globally for our transformative MIGs and iLINK solutions, realizing considerable improvement in the CMS 2022 final rule for the new Category 1 combo cataract mix codes versus the proposed rule, and delivering a favorable IP settlement outcome. Two, we advanced our near-term pipeline, bringing a number of promising investigational therapies closer to becoming commercial realities, with favorable data announcements for IDOS-TR, ISTIN Infinite, and Epion. In addition, we completed patient enrollment and randomization in our ongoing Phase III clinical program for IDOS-TR, and advanced several other important products, including iPrime and the Pressure Flow Microshunt. Three, we progressed our earlier stage pipeline programs with the newly established licensing agreements with Adelaps, encouraging R&D progress on preclinical programs such as iDose T-Rex and iDose Rock, and most recently, the commencement of two Phase II clinical trials in dry eye disease and presbyopia. And four, we grew our global teams and infrastructure. included the implementation of a global systems upgrade, and we completed our Avigdor integration ahead of schedule despite the pandemic. We believe the strong financial profile and capital position we built has allowed us to remain on offense when it comes to successfully investing for our future, leaving us well-positioned for the next phase of our pioneering journey as we target several clinical, regulatory, and commercial milestones this year and the years ahead. As I look forward to 2022, we hope to, one, evolve our combo cataract mix franchise through new product offerings while entering into the standalone glaucoma market and expand our international glaucoma and corneal health franchises. Two, deliver our near-term pipeline with the recent FDA clearance of iPrime, targeted FDA clearance of Isin Infinite in the first half of this year, and targeted NDA submissions for Eidos PR and Epion by the end of this year. Three, to advance our early stage pharma platforms, including for the two phase two Iolution trials in dry and presbyopia that commenced last month and several planned IND and IDE applications for our next generation therapies. And finally, to continue to grow our global organization and infrastructure to support future growth. While we execute commercially, we continue to self-fund and successfully advance our robust pipeline of novel, promising platform technologies that we believe have the ability to significantly expand our addressable markets and fundamentally transform our company over time. Our novel platforms are designed to disrupt conventional treatment paradigms, advance the existing standard of care, and enrich the lives and treatment alternatives for patients worldwide suffering from sight-threatening chronic eye diseases. These platforms embody ambitious big ideas aimed at addressing large and chronically underserved eye diseases, including glaucoma, corneal disorders, and retinal diseases. One such big idea that has underlined each of our platforms to date is the disruption of conventional topical eye drop therapies through dropless alternatives. It is worth reminding investors that topical therapies are frequently the mainstay of ophthalmic treatment. They are often effective for many patients when taken properly, and thus will always have an important role. However, a primary issue the industry has been grappling with for decades is patient non-inherence. This problem is ubiquitous, rampant, well understood, and well documented. And even when patients may be compliant, they can be subject to a host of local side effects, such as hyperemia, hypochromia, periorbital fat atrophy, and corneal and conjunctival changes, as well as preservative toxicities, which can exacerbate underlying ocular surface diseases. With our novel droplets platforms, we are taking differentiated approaches to address these well-known issues in order to improve patient outcomes. Our key five technology platforms designed to disrupt traditional treatment paradigms and generate cascades of future innovation are as follows. Number one, iStent micro-scale surgical devices. Two, the iDose sustained release pharmaceuticals. Three, the iLink bioactivated pharmaceuticals, four eilutiant transdermal pharmaceuticals, and five retinal bioavailable sustained release pharmaceuticals. Let's take some time to dive into each of these platforms, beginning with our foundational iStent microsurgical device platform, which primarily involves the insertion of a microscale device designed to reduce intraocular pressure by restoring the natural aqueous humor outflow pathways for patients suffering from glaucoma. We believe our iStent portfolio is the industry's most comprehensive offering of minimally invasive tissue-sparing glaucoma solutions, supporting our goal to provide a full range of options to fit surgeons' individual glaucoma treatment algorithms that offer the best short- and long-term benefit-to-risk calculus at every stage of disease progression, from ocular hypertension through refractory disease, and of both combo cataract and standalone procedures. We are proud to be the corporate pioneer and global market leader in MIGS with our family of iStent technologies supported by more than 200 peer-reviewed publications, 20-plus years of clinical and commercial experience, and nearly 1 million iStent devices implanted worldwide since our inception. Today, within the U.S. market, our offering of iStent and iStent Inject W are FDA-approved for the treatment of mild to moderate primary open-angle glaucoma in combination with cataract surgery. After years of investment in strategic planning, we are excited to be on the cusp of expanding iSEN's market availability into the standalone glaucoma population with targeted FDA clearance of iSEN Infinite in the first half of this year. As a reminder, iSEN Infinite's strong, pivotal data results show profound efficacy and safety outcomes for patients with open-angle glaucoma who have failed prior surgical therapy. These outcomes also reinforce our confidence that this technology may also effectively serve as an earlier intervention for the treatment of glaucoma. We are delighted to receive, to recently announce, FDA clearance for iPrime, a highly complimentary new Visco delivery device designed to be a truly minimally invasive system to further support the needs of physicians and patients. We are planning for controlled commercial launch of iPrime in the second quarter. Regarding the Pressaflow Microshunt, the FDA has gathered and is evaluating the additional input provided by select glaucoma surgeons to ensure a complete evaluation of the clinical data submitted in the PMA. In the meantime, we've successfully commenced the initial commercial launch activities for Pressaflow in Canada and are preparing for controlled commercial launch in Australia. Moving on to our iDose sustained release pharmaceutical platform, which consists of a targeted minimally invasive injectable implant designed to deliver therapeutic levels of medication from within the eye for extended periods of time. iDose TR, which is comprised of Travoprost, a well-known prostaglandin analog, is our first investigational candidate. We're advancing, leveraging our iDose platform technology. We recently announced 36-month analysis of our Phase IIb trial that showed compelling results, with roughly 70 percent of I-dose subjects still well-controlled, with the same or fewer ILP-lowering topical medications at 36 months versus screening, compared to only 46 percent of subjects in the Timolol control arm. Further, in this responder group, average ILP reductions from baseline observed at 36 months were substantial. approximately 8.3 millimeters of mercury and 8.5 millimeters of mercury in the fast and slow-release Eidos DR arms, respectively. Importantly, a single Eidos implant is being compared to the Temerol control arm that received twice daily drops, or 2,190 eyedrops per eye per protocol over the 36-month evaluation period. As a reminder, IDOS-TR is implanted into the trabecular meshwork to avoid migration through a very facile procedure and is designed so the surgeon can safely exchange the IDOS-TR with a new implant when the original therapy has fully depleted its pharmaceutical payload. The most recent Phase II data readout demonstrated a favorable safety profile with no clinically significant corneal endothelial cell loss, no serious corneal adverse events, and no adverse events of conjunctival hyperemia reported to date in either IDOS elution arm. These latest Phase II results further underscore the potential of IDOS-TR to safely provide multiple years of sustained dropless therapy and 24-7 compliance to tackle the significant problem of patient non-adherence and chronic side effects associated with topical glaucoma medication regimens. These powerful data reaffirm our excitement about the potential commercial prospects of IDOS-TR and mark another critical step forward in the advancement of this potentially game-changing innovation. We completed patient enrollment on our Phase III clinical trials for IDOS-TR in June 2021, randomizing 1,150 subjects with open-angle glaucoma or ocular hypertension. The 12-month IDOS-TR Phase III trial results are expected to support Glockos' targeted NDA submission by the end of this year and targeted FDA approval by the end of 2023. Given our development success to date with IDOS-TR, we continue to invest resources to expand our pharmaceutical development capabilities and to develop future IDOS solutions. These investments include a next-generation IDOS extended-release implant, also known as IDOS-T-REX, which is in a similar size and form factor to the original IDOS-TR, but is designed to provide nearly twice the drug capacity to extend efficacy durations even longer, and additional drug classes such as ROC inhibitors, where we have seen encouraging rabbit model data and are establishing prototype implants for lead candidates. Next is our iLink bioactivated pharmaceutical platform, which consists of novel single-use drug formulations that are bioactivated by our proprietary systems through the delivery of ultraviolet light to the cornea to induce a biochemical reaction called corneal crosslinking that is designed to strengthen, stabilize, and reshape the cornea. Our first-generation iLink therapy, known as iLink EpiOff, uses a novel drug formulation called Photrexa for the treatment of keratoconus, a sight-threatening degenerative disease in which the cornea progressively thins and weakens, leading to vision loss. Even though keratoconus is a serious sight-threatening disease and the leading cause of full-thickness corneal transplants in the U.S., we believe it remains vastly undertreated, primarily due to underdiagnosis and the historical lack of an effective solution. Today, approximately 20% of keratoconus patients ultimately require a corneal transplant, a costly and invasive procedure with high failure rates. In fact, literature suggests 72% of corneal grafts fail within 20 years, and 98% fail within 30 years. Sadly, as the disease onset is often diagnosed in teenage years, keratoconus patients may require multiple transplants over their lifetime. In order to maximize the availability of this important protrexotherapy for patients, we have made substantial investments and executed upon a number of strategies designed to expand our commercial organization lower the barriers for adoption by practices, increase awareness of keratoconus across the optometric and ophthalmic community, streamline the referral patterns, and train corneal health professionals on our ILINC procedure. Looking ahead, we are advancing our next generation ILINC therapy known as Epion that utilizes a proprietary novel drug formulation called Epioxa, stronger UVA irradiation protocol and the ability to deliver increased levels of supplemental oxygen. The previously announced positive phase three results for Epion underscore our view that this therapy may provide the autonomic therapy and keratoconus patients with the first truly non-invasive bioactivated drug treatment alternative designed to reduce procedure times, improve patient comfort, and shorten ultimate recovery times. Epion's positive phase-through results are expected to support a U.S. NDA submission in 2022, and we are targeting FDA approval for Epion in 2023. As we do with all of our platforms, we continue to drive subsequent generations of future innovation, and we are targeting the commencement of clinical trials for a third-generation iLink therapy later this year. Moving on to our iLution transdermal pharmaceutical platform, which consists of patented, cream-based drug formulations that are applied to the outer surface of the eyelid for dropless transdermal delivery of pharmaceutically active compounds for the treatment of eye disorders. We believe Iolution's differentiated delivery approach on the eyelid may offer significant advantages over traditional topical therapy, including the potential for easier administration, faster onset of action, and fewer side effects such as reduced preservative-induced chorial and conjunctival sequelae all of which can help contribute to better compliance and improve patient outcomes. Last month, we announced commencement of patient enrollment in two Phase II clinical trials, including GLK301 for the treatment of signs and symptoms of dry eye disease and GLK302 for the treatment of presbyopia. These are the first two investigational drug candidates utilizing our ILLUSION platform, both of which utilize pilocarpine as its active pharmaceutical ingredient. The commencement of these phase two trials represents a significant milestone in the development of our Aleutian platform and for our company. And we are excited to have the opportunity to explore what these drug candidates can do for these respective large and underserved patient populations. We're also progressing preclinical programs to research and development investigational pharmaceutical compounds that target the eradication of demodex mites, leveraging our Aleutian platform. Demodex mites are the root cause of demodex blepharitis and are often associated with meibomian gland dysfunction, a leading cause of dry eye disease along with several other related ophthalmic diseases. Finally, I will also briefly touch on our bioavailable sustained release pharmaceutical platform known as RetinaXR designed to treat retinal diseases. The largest market in ophthalmology today estimated to generate $13 billion in worldwide revenue and expected to grow to nearly 10% annually through the year 2023. Our retinal R&D teams are actively engaged to develop multiple micro-invasive bio-erodible drug delivery programs designed to treat age-related macular degeneration, diabetic macular edema, and other retinal diseases. Our two primary sustained release development projects in our retina platform include a triamcinolone acetonide steroid targeting DME and a small molecule multi-kinase inhibitor targeting AMD, DME, and retinal vein occlusion. The goal of these preclinical programs is to provide retinal specialists and their patients with novel sustained pharmaceutical treatment options that offer a meaningfully longer duration of effect than the current standard of care dominated by short-lasting biological injections that often impose tremendous treatment burdens on patients because of the high frequency of the required treatments. We're aiming to advance at least one of these programs into the clinic over the next 12 months. As you can see, we have a lot to be excited about when it comes to the significant potential value that we believe our pipeline programs may create. As a testament to this, we are continuing to successfully invest in and advance our Folsom pipeline of core novel platforms supported by over 300 million of self-funded investment into our R&D program since 2018 alone. We anticipate and are planning for a robust cadence of new platform and product introductions over the coming years that have the potential to fundamentally transform Glaucos over time. Our plan is to utilize our established best-in-class commercial organization and global direct sales infrastructure to drive future scale and sales rep productivity in what we view as a very leverageable global ophthalmic sales channel. So in conclusion, we believe Glockos is different. We are change agents. We are pursuing game-changing innovation in glaucoma, corneal health, and retinal diseases. Our platforms are disruptive, our ideas are big, and our mission is ambitious. I'm confident we have the right people, the right strategy, infrastructure, pipeline, and balance sheet to execute our plans and to deliver on our future aspirations. So with that, I'll turn the call over to Alex Thurman to discuss our fourth quarter and full year 2021 financial results. Alex.

Thanks, Tom. As a reminder, I will be discussing our financial performance on a non-GAAP or pro forma basis and will summarize our GAAP performance later in my prepared remarks. I encourage each of you to review our gap to non-gap reconciliation, which can be found in today's press release, as well as in the investor relations section of our website. Glaucus' global consolidated net sales for the fourth quarter of 2021 were $73.2 million, which was flat versus the comparable prior year quarter and up slightly compared to the fourth quarter of 2019 pro forma for the acquisition of Avidro. Our fourth quarter performance reflects continued pandemic-related volatility as we experienced global headwinds due to COVID-19 that strengthened at the tail end of the quarter and accelerated in the early part of 2022. Now, turning to our U.S. glaucoma franchise specifically, our fourth quarter U.S. glaucoma sales were 41.2 million, down year over year, which we believe reflects a combination of pandemic-related dynamics, and the impact of the 2022 CMS combination cataract reimbursement on customer ordering patterns and competitive trialing activities, which occurred in advance of the final rates being implemented on January 1, 2022. Internationally, our glaucoma franchise delivered fourth quarter sales of 15.9 million, representing year-over-year growth of 8% and 31% growth compared to the fourth quarter of 2019. This performance reflects growing demand globally, partially offset by pandemic headwinds that reemerged in a few key European and Asia-Pacific markets in particular. In corneal health, fourth quarter net sales were 16.2 million, representing year-over-year growth of 9% and 30% growth compared to 2019 pro forma for the Avidra acquisition. The fourth quarter performance was driven by U.S. Betrexa record sales of 13.5 million on year-over-year sales growth of 8%, or 44% versus pro forma 2019, along with a continued trend of healthy new U.S. Vitrexa account starts, partially offset again by COVID-related headwinds. Shifting gears toward the remainder of our P&L, our non-GAAP gross margin in the fourth quarter was approximately 85% versus approximately 83% in the same quarter of 2020. It is worth noting that our non-GAAP adjustments to COGS include substantial amounts related to acquisition accounting for Avidro. Our overall non-GAAP operating expenses were $72.3 million in the fourth quarter of 2021, a 3% sequential increase versus the third quarter, as we continue to restore expansionary spending as the recovery warrants, a trend that we would expect to continue moving forward. Our non-GAAP SG&A expenses in the fourth quarter were $46.7 million, up 13% sequentially compared to the third quarter, reflecting increased commercial spending and administrative costs. Our non-GAAP R&D expenses in the fourth quarter were $25.5 million, down sequentially compared to the third quarter, which is primarily due to lower pilot operations spending associated with our Epion and iDOS programs. We finished the fourth quarter with a non-GAAP operating loss of 10.3 million and non-GAAP net loss of 14.3 million or 31 cents per diluted share. Our GAAP net loss was 21.9 million or 47 cents per diluted share for the fourth quarter of 2021. We invested in approximately 9.3 million of capital expenditures in the fourth quarter, which as expected remains elevated versus historical levels as we have advanced through the construction phase of the enhancement and expansion of our facilities in Southern California and Boston to create a best-in-class infrastructure to meet our growing innovation and operating needs, a trend that we expect to continue in 2022 before moderating to levels more consistent with historical norms. As of December 31, 2021, we had cash, cash equivalents, short-term investments, and restricted cash of approximately $423 million, compared to $414 million at the end of 2020 and $438 million at the end of the third quarter 2021. For the full year 2021, global consolidated net sales were $294 million, an increase of 31% versus 2020. Non-GAAP gross margin was approximately 85%, and non-GAAP operating expenses for the year were $271.7 million. With that, I'll turn the call over to Joe to discuss our forward outlook.

Joe? All right. Thanks, Alex. Looking forward, first as it relates to COVID-19, we were not immune from the incremental global headwinds that emerged during the fourth quarter and strengthened into January. Situation remains fluid, and we would caution conservatism as you consider any potential impact this may have on elective procedure markets in the first quarter and potentially more broadly in 2022. Regarding CMS reimbursement for our combination cataract products here in the U.S., while we were pleased with much of what improved in the final rule, the physician fee in the final rule remains at a significant disadvantage to several more invasive alternatives. And we expect this to have an ongoing impact on isent family combo cataract volumes in 2022. We also expect to face heightened competition in combo cataract mix globally in 2022. But as Tom mentioned earlier, we have been preparing for these dynamics for some time now, and look forward to potential early revenue contribution from iPrime, iSendInfinite, and other new products in 2022. As we put this all together in the context of our expectations going forward, our full year net sales guidance of $265 to $275 million takes these headwinds and potential new products into account, and we would remind investors to also factor in our typical underlying seasonality patterns and COVID-related trends and risks that are outside of our control. I also wanted to let investors know of a change in how we plan to handle our quarterly earnings disclosures and calls starting with the first quarter of 2022. You will notice a new section on our investor relations website under the title financials and filings quarterly results titled quarterly summary. We have posted our first report there this afternoon for the fourth quarter and fiscal year 2021. Our objective is to provide investors with a quick and easily accessible reference document that details the key facts associated with the quarter, the state of our business, and any forward statements or guidance we may make. Going forward, we will provide this document after the market close alongside our earnings release, make very brief prepared remarks, if any, during our earnings call, and then transition quickly to answering analyst questions. It is our hope that this change will make our quarterly process more efficient and impactful for investors and the analyst community going forward. With that, I'll now turn things back to Tom for a few closing remarks.

All right. Thanks, Joe. So before we close, I'd like to highlight several executive leadership changes we announced earlier this month. As a reminder, the following changes will become effective on April 1st. Joe Gilliam will assume the new role of President and Chief Operating Officer. Chris Calcaterra will assume the new role of Executive Vice President Global Commercial Operations. Alex Thurman, our current Vice President of Finance, will succeed Joe to become our new CFO. And Tomas Novotril, our current Senior Vice President of R&D, will assume the new role of Chief Development Officer. On behalf of the entire Glaucos organization, I'm delighted to congratulate Joe, Alex, and Tomas on these well-deserved promotions and pledge our full support to them in their new roles. These are outstanding and proven leaders, and I am confident they will successfully drive our organization forward in the next phase of our pioneering journey. At the same time, I want to extend my sincere congratulations to my friend and colleague, Chris Calcaterra, on his requested transition into his new role. Chris has been instrumental in the growth and development of Glaucos since joining our management team nearly 14 years ago. I'm confident he will continue to play an integral role in our success in his new position that will provide Chris the opportunity to step back from day-to-day administrative responsibilities and spend more time with his family while continuing to focus on our global commercial operations, his deep customer relationships built over the past 35 years, and ongoing strategic counsel to our executive and commercial leadership teams. So in closing, I'd like to reiterate our conviction in our long-term vision. We are continuing to invest in Glaucos to scale our team and to advance our mission to transform vision with disruptive, dropless, game-changing platform innovations. We are truly excited about our prospects, we're confident in our ability to execute our plans, and we believe we are entering into a transformative period for our company in the years to come. So with that, I'll open the call to questions. Operator?

Thank you. At this time, I would like to remind everyone, in order to ask a question, press star, then the number one on your telephone keypad. Your first question comes from Andrew Brackman from William Blair. Please go ahead.

Hi, guys. Good afternoon, and thanks for taking the questions. Chris, just wanted to say congrats to you and your family on this next step. Really impressive what you've been able to build here, and hopefully this means more football games in your future. But maybe just to start here, Guy, I certainly appreciate the commentary on the outlook and guidance for the year, but maybe just to get a bit more granular there, can you just sort of walk through in more detail some of the assumptions around key variables in that guidance, and maybe just elaborate a bit on some of those assumptions you're putting into play here?

Sure. Hey, Andrew, it's Joe. I'll start off, and if the team wants to add something, they can jump in. So in the forward guidance, We were talking about $265 to $275 million, and it really kind of takes into account four or five key variables, and we can talk at more length than any of these that you deem necessary. The first one is obvious, right? With the change in the reimbursement landscape in particular, the professional fee and the disadvantage that has relative to some of the more invasive competitive procedures, we had to factor in what we thought that would mean for volumes underlying our U.S. glaucoma combo cataract mix business. Second, I would say is the competitive dynamics associated, obviously, with the acquisition of the Hydrous device, what that means both domestically, where it's been available for some time now, but also internationally, I think, where folks have said that a lot of the focus is going to be around expanding the access to that particular product. In corneal health, we have to continue to think about the blocking and tackling associated with that business, right? We're really pleased with how things have gone since acquiring But we've got a lot of work ahead of us. And we're also starting to come up against the period where we'll be thinking about the transition from epi-op to epi-on, or certainly some of our customers will. I'd also mention, you know, COVID. You know, from an Omicron standpoint, it was pretty clear that emerged at the very end of last year. I'll call it the last couple weeks of December. Really peaked in January and started to, while still relevant, started to subside as we made our way through February. And it remains an unknown risk, I think for everybody, us no different in that. And then the last thing I point to is just the typical seasonality, which we mentioned. So as you recall, in a normal year, most of our businesses operate where the first quarter is about 22% of the full year sales, and then 25, 25 and 28 in the fourth quarter. So I think those are the key variables worth keeping in mind as you think about the model.

Okay, thanks for that. I'm sure others might have questions on that. Maybe I guess is my second question here. Maybe this one's more for Tom. But I think obviously, as you sort of laid out well, again, here today, you know, 2022 is sort of a massive year for the pipeline with several milestones expected. So can you just sort of talk about at a sort of high level, you know, your strategy for preparing the organization for this broader evolution that you talk about? And I guess moving forward here, you know, what sorts of other pieces of infrastructure do you think that you're going to need in order to really compete across these different end markets here? Thanks.

Yeah, happy to answer that, Andrew. So we've obviously have contemplated these changes for some time. We've expanded our R&D capabilities vastly by drawing a number of top executives from really key industry leaders like Allergan into the mix. I think that's given us a strong basis and depth to be able to pursue and to make this change, as we talked about earlier, from a more parochial medical device company into a hybrid medical device and pharmaceutical company. So that's been a massive focus as we built the business over time. And we continue to look at infrastructure changes. As you know, we've gone from 2017, where we were literally in two markets, the US and Canada, And we now have expanded into 17 international markets. And so we've had to put the back office support behind all of those different entities. And we have obviously already gone through an ERP transition, moving onto an Oracle platform to give us the ability to be able to provide back office support to these different entities. We have expanded commercially. We brought Avidra on to the business. That approach has been seamless. And I think they have been well integrated into the overall business. So our approach now is to say, how do we take the wealth of experience and talent we bring in, and how do we effectively place them over the innumerable numbers of programs that we have? And that's going to be both a challenge and an opportunity for us moving forward. But if you look at our track record, you look at what we've done, I can assure you I'm confident we're going to be able to move forward these programs. You'll notice that I call 2022 the year of the catalyst. We have a number of catalysts, both in terms of regulatory and commercial milestones, which will be seminal for the business. We're actively pursuing those. I think we have the pieces in place, and I'm confident of what we have and what we're building going forward.

Great. Thanks, guys.

Your next question comes from Chris Cooley from Stevens.

Please go ahead.

Good afternoon, everyone, and congratulations on a strong finish to the year. And Chris, all the best to the senior statesman of ophthalmology on your next step. And Joe and Alex, congratulations as well. I look forward to continuing to work with you guys actively. Maybe just two quick ones for me, if I may. When we think about just the coming year, I want to maybe follow up on Andrew's question there a little bit. Help us think, Joe, about the OPEX line, because this is probably the most prolific the pipeline has ever been. You've clearly invested in advance of this, and that's growth investment. But help us think a little bit about kind of that historical OPEX bogey that you had With this kind of a pipeline spend, I'm assuming 22 should be somewhat elevated relative to that in addition to, or is it still in line as you have some offsets from restrictions associated with COVID? And then I've got a follow-up question thereafter. Thanks. Sure. Thanks, Chris. It's Joe.

So, you know, we ended the year, the fourth quarter, with a little north of 72 million in what's called non-GAAP OPEX. You know, if you annualize that, that put you at a 290 number. If you just think about the inflation dynamics a second that all of us are experiencing, you know, that gets you certainly north of 300 million of OPEX spending. And then you factor in some reasonable expansion from there. Obviously, the SG&A line will be more leveraged depending upon what is going on in the top line of the business. But on the R&D side, as you said, we would expect to continue our march forward in accelerating that investment there. as we continue to mature the pipeline and deliver on the goals that Tom's talked about.

Understood. And then maybe just as a quick follow-up, and we really would love to focus on the pipeline, but obviously trying to just level set the model as we start in here, you know, the guidance looks favorable, but also when we think about the I think you've characterized it as the number of crosswinds in the past that we could see coming forward with FDA approvals potentially with acceleration into these newer markets. Can you help us kind of think maybe core versus new products in terms of contribution or maybe more broadly corneal health versus glaucoma just as we're thinking about first half versus second half? Thank you.

Yeah, I'm happy to take a stab at that, Chris. I guess I characterized the guidance we gave, I think, hopefully as prudent in the face of everything that we're looking at here, both some of the considerations as well as some of the potential positives. I think there's a couple different ways we can take this. The first is when you consider from a macro perspective, Omicron, COVID, and normal seasonality, And then you overlay what we hope is a successful new product cadence here. Clearly, that lines up to a second half that probably is more balanced or weighted towards the second half than the first half. That's generally true in our business anyway, but I think the additional dynamics around COVID and the new products probably amplify that a bit. When it comes to the individual businesses, I gave some of that, obviously, what we've tried to factor in. from a U.S. reimbursement perspective in the combo cataract franchise, international glaucoma. I think corneal health, for us, we hope is more blocking and tackling. I want to be cautious and conservative around how far you take that in light of COVID and just our continued building this business in a post-COVID world. But we feel good about where that franchise is at and where it's headed. I think beyond that, I'll probably stop a little bit short because I think we're evolving as a company, and I don't think it makes much sense for us strategically to get too far into the weeds on the individual components when really our goal is to drive the overall top line of the business.

Thank you.

Your next question comes from Larry Bigelson from Wells Fargo.

Please go ahead.

Hi, this is Charles on for Larry. A quick question about the reimbursement headwinds. So it looks like those headwinds from the destocking and competitive trialing in Q4, the US NAGS might have looked a little bit better than expected. Is that fair to say from you guys' perspective? And how has that looked so far? You've had almost two months of the lower reimbursement level. Or if you can give any qualitative detail on how that's shaken out versus your expectations so far?

Yeah, sure. So I think, Charles, first, you know, as it relates to Q4, you know, as we were looking into the end of the year, there was considerations around, you know, exactly how the extent of that destocking and what would occur. All the dynamics around the shift in reimbursement provided a fair amount of uncertainty. And so, yeah, I think it's fair to say that overall in the quarter things perform better than we expected. I think when you do your models, you'll see that a significant part of the outperformance in the fourth quarter came from our U.S. Blackoma franchise. If you think about the beginning of this year, I think it's a little early, right? I mean, I guess what I would say is There's a bit of cloudiness given the dynamics around Omicron in January in particular, and it's difficult to sort of separate that from whatever elements we're seeing as it relates to the U.S. reimbursement and the volume impact there. But I have no doubt that we are seeing some of that, and that's expected, and now it's up to us to continue to try to mitigate that as we move forward here.

Great. Thank you.

Your next question comes from John Block from Stifel.

Please go ahead.

Hey, guys. This is Tom Stephan on for John. Thanks for the questions. Just want to start off on guidance. First on U.S. glaucoma, and just going to take a stab here, but with what you're willing to share, is there any color around price and market share in that business that we should be thinking about? You know, understand if you don't want to get into too many details, so qualitative commentary would be very helpful as well. And then I have a follow-up.

Sure. Tom, I think, again, I'll start here.

As it relates to the U.S. glaucoma business, I think with the one element of the final rule that we were obviously more pleased with than the other was the final facility fee. And so I think we said on the last call that that got us back roughly in line with where reimbursement was in 2020. And so, you know, heading into 2022, we expect relative stability in the pricing environment in U.S. combo cataract mix. I think as it relates to, you know, the other dynamics there, you know, volumes, et cetera, you know, and market share, you know, inherent obviously when you peel back the model is an expectation that a combination, probably to a lesser extent competition, but more to a larger extent, the impact from the professional fee on U.S. volumes, we're obviously expecting some pullback in procedures. And we'll see how sustainable that is and how things play out over the course of the year. But underlying the model and the guidance we gave is certainly that assumption.

Got it. That's helpful. And then just to pivot to I-Prime, you talked about a controlled launch in 2Q22. I think the label or the indication of use seems to check all the boxes. Are there any hurdles in areas like reimbursement, billing, et cetera, or is it pretty much all systems go? And then can you help us at a high level with how we should think about this product in the context of guidance and when we can maybe expect a full launch? Thanks, guys.

Hey, Tom, this is Chris. And we were excited about getting approval for iPrime as early as we did, and we are planning for a Q2 launch. In terms of how that'll be used, that'll be up to the physician in terms of how he or she wants to utilize it, when he or she wants to utilize it, and that'll determine how it'll be reimbursed.

And then I think as it relates to the numbers, I mean, obviously, as I mentioned, it was included in the overall forecasting we did to come to the 265 or 275 guidance. It's not a significant contribution, obviously, given what we described in terms of the initial launch activities, and as we progress through the year, we'll keep you updated on that.

Great. Thanks, guys.

Your next question comes from Ryan Zimmerman from BTIG.

Please go ahead.

Hey, thanks for taking the questions. A couple things for me, and sorry to kind of hamper on some of the U.S. glaucoma dynamics. but obviously important right now. So, you know, reimbursement dynamics for combo cataract, Joe, you kind of talked a little bit about this. How pervasive do you think it's, you know, known in the community? And maybe, Chris, you have thoughts on this too. How pervasive is, you know, the current reimbursement rates for U.S. combination cataract for stents, but also for stents plus visco dilation? And the reason I ask is because, you know, some of the diligence would suggest that physicians are thinking about kind of using both Stents and I-Prime in combination where they can maybe offset some of those reimbursement dynamics. Thank you.

Hey, Brian. I would say that it's very pervasive. I think physicians as well as administrators have a very good understanding of what the new dynamics are from a reimbursement standpoint. both on the facility and on the prophy side of things. And in terms of combination therapy, I think that most are looking at that more from the focus of what's best for the patient, but most are also aware of the financial implications of combining therapies.

Got it. Okay. And I just want to ask also, so

You talked about your contribution from iPrime. There's contribution potentially from Infinite in guidance this year. What's assumed, and I know you're not going to give me a certain number, Joe, but what's assumed for presser flow, and when should we think that that can start to contribute at the worst-case scenario, I guess, in your mind?

Yeah, that's, I think, a fair question, Ryan. I mean, inherent in the guidance, we haven't included presser flow revenues. I think we want to see, given the situation with the FDA, an approval before we start, you know, really thinking about including that in the U.S. guidance. You know, as Tom mentioned in his remarks, we are commercial now in Canada and launching in Australia, so there's some presser flow revenues that are obviously built into the international side of the franchise. But, you know, look, we'll continue to keep you all apprised as we, you know, hopefully make progress here with the FDA and have more certainty around timelines and what it could mean for the business.

Okay. Let me squeeze one more in and then I'll hop back in queue. Anything assumed for royalties from Hydrus in terms of revenue in that guidance?

That is factored into the guidance. Okay. Thank you.

Your next question comes from Matt O'Brien from Piper Centler.

Please go ahead.

Hi, guys. This is Duran for Matt. Thanks for taking the questions and congrats to everyone on the new roles. I wanted to start off on Infinite here. You sound pretty confident in a clearance in the near term. Any updates on conversations with the agency? You know, focus of labels still on the advanced refractory population. And I know you're still doing some work to improve the facility reimbursement side of things, but can you just remind us what needs to be done to get that physician rate set once you have the clearance in hand?

Yeah, Drew, I'll be happy to take this. So, as you know, we've already filed for approval for ISTEN-IFIT. We've negotiated with the FDA. And it's likely our label will be certainly for late-stage patients and those patients on a standalone basis with glaucoma that have failed on ophthalmic surgeries. And so a sizable population, as we talked about before, about 125,000 patients annually have either trabeculectomies or aqueous shunts. And so that appears to be what we'll have going forward. And then just to remind investors, because of the superlative nature of the results of ISEN Infinite, we have moved that into discussions with the FDA to be able to advance in a new IDE for earlier stage patients. And this iStent Infinite will take the place of the iStent SA that we've talked about previously. And so we've committed and we are executing on our plan from the beginning, which was to begin to approach the FDA following the conclusion of the iDose recruitment of the trials. So we're excited. You know, our position is if iStent Infinite is working so well, even in these late stage patients, we're confident that it's going to be able to deliver an earlier stage glaucoma, and that will be the position going forward. In terms of iStent Infinite on the reimbursement side, as you recall, this happens to be a power alley for us. We'll approach MAX when we receive FDA approval. And if we look at historical context and predicate as any guide, it took us probably about nine months before we were able to fully get kind of a universal approach to the MAX across the country, and so in your expectations, you should be looking for that. And again, this won't all come at one time. We'll be approaching max, and typically they fall really singularly over time until we actually then invest the time to have all the max turn and have a fair price set for the professional fee for Einstein Infinite. Now, on the facility side, as you recall, The CMS has given us an underwhelming facility fee payment. So much like we approached the draconian cuts like we did with the professional fee proposed changes this past year, we were able to gain considerable ground. We'll be meeting with the FDA again over the course of 2022 to be able to persuade them to be able to place this APC in its rightful place, which really it has been over the last 10 years. I believe the APC was 5492. That's our intent. That's our target. If we're successful, that will be effective January 1st in 2023. And so we'll keep you posted and apprised as we go forward. There'll be the normal commentary period. And as you know, the CMS will weigh in in the fourth quarter of this year, whether or not we're successful in moving that. If we're unsuccessful, then we always have the opportunity this next campaign in 2023 to go at it again. So we intend to be tenacious and resilient and to make the appropriate changes there.

Okay, very helpful. Thank you.

And then you just mentioned it a little bit earlier in the call here, but I just wanted to get your thoughts about how you're thinking about the IVANTIS-ALCON combination, it sounds like you're incorporating a little bit of impact into your guidance, but, you know, anything you can speak to as far as, you know, what you're seeing so far, I guess, about a month in here, and what impact did Glauco set your bacon into that guidance? Thank you.

Hey, Drew. This is Chris. And it's really too early to say that we've seen much of an impact, if any. But, you know, ALCON, we've competed with them before. We have the highest regard and respect for them. We're expecting this acquisition, and we're prepared for them, and we will be prepared, and we'll see how it goes. But we have dialed that into our guidance in terms of what Joe has presented in terms of our year-long guidance.

Okay, thank you.

Your next question comes from Joanne from Citigroup. Please go ahead. Good evening, and thank you for taking the questions.

I have just a couple. First question has to do with gross margins in 2022. I would assume they're being pressured versus the 85% you just did in the fourth quarter, but is there any way to quantify that for the full year?

Yeah, Joanne, you know, I think we've, for a little while now been kind of pointing you all to an 83 to 84% gross margin. And, you know, I think it's been encouraging obviously the trend line that we've seen the last couple of quarters, but I'd still probably point in that direction as you think about 2022. I think there's a number of variables in play as you're describing, you know, competitive dynamics, but I think it's probably more about mix. is international becomes a more significant percentage of our business. Obviously, there's a little bit of margin impact there, and we'll see how much that's offset by the receipt of royalty revenues from Alcon.

And is there a way to quantify two different things? The first one is what may have happened in terms of destocking in the quarter, and then the second one is how much revenue you have in your forecast for things like I-prime or I-sent incident.

Yeah, I think, first, it is pretty difficult. I think a lot of those stocking dynamics were happening as you kind of exited third quarter and going into the fourth. Obviously, some accounts chose to reorder in normal patterns towards the end of the year, but not all, as they were probably waiting to see how folks reacted to the new rules once they came into play. So it's hard to get any sort of quantification of that. And then, you know, as you think about, you know, going forward here, you know, I think we've covered that pretty much at length already.

Okay. Thank you very much. Your next question comes from Alan Gong from JP Morgan.

Please go ahead.

Hey, guys. A lot of my questions have already been asked, so I'll just leave you with a quick one. When we look at your guidance range, you kind of already highlighted a normal, you know, sort of normal level of seasonality with all the puts and takes taken into account. But when we look at your peers, it seems like there's some variance in terms of what they're assuming for COVID-19 dynamics, especially in the back half of the year. You know, some are saying that there will be a, you know, maybe like a flu-like impact in the fall, winter, and some are even factoring in a potential new variant. So is that contemplated between the low end and the high end of your guidance, or is there kind of some flat level of COVID-19 impact baked in there for the back half of the year? Thank you very much.

Well, you know, hey, Alan, it's Joe. I think one thing that COVID-19 has taught us over these last two years is to not make any assumptions in terms of what the path forward will look like with any high degree of certainty. So what we've done is try to take into consideration specifically what we saw in January and coming into February from Omicron and what that would mean to the first quarter. We, you know, like others, I think have an assumption that things should improve here as we head out of the winter months and into the summer. But what lies beyond that in the fall and winter is very difficult to predict. So hopefully we built in a little bit of conservatism to, you know, account for that.

But I think relative to everything else, it's probably a bit of a rounding error.

Here, next question comes from Steven Litchman from Oppenheimer. Please go ahead.

Hey, guys. This is David Allen for Steve. I just wanted to follow up on the gross margin question from earlier. You know, when you talked about guiding towards that 83%, 84%, does that contemplate any inflationary pressures in 0.92 for, like, labor and or materials? And I just had a quick follow-up on the pipeline for the IDOS. I know it's a TR phase three trial. Should we expect the data to be out this year?

Okay, I'll take the first one. Yeah, I mean, the answer is yes. I mean, when we think about the 83 to 84%, we're trying to factor in all the variables that we know today, which includes what we expect our cost of goods sold to be in this, you know, certainly higher inflation environment.

And the question on IDOS-TR, as you said before, we are tracking to file our NDA by the end of the year, and it's our position that we'll seek to be able to present the data when it's available, which we're hoping will be the tail end of this year or early next year.

Great. Thank you.

And your next question comes from Zach Wiener from Jefferies.

Please go ahead.

Hey, thanks for taking the question. Just one for me on COVID. I guess, you know, you made comments on COVID impacting 4Q and impacting, I guess, the beginning of the first quarter. Is that patient's reluctance or is that more staffing-related issues? And then with those COVID headwinds, are you seeing any backlog? And then I guess the last one would be, you know, if there is any backlog, when do you expect to recapture that? Thanks.

Yeah, well, I'll start if Chris or Tom want to add anything in. They certainly can. I think, well, first, you know, the COVID impact we saw was at the very end of December. I mean, it obviously ties straight to when we started to see a lot more of the case, you know, increase post-Christmas and as we went into the new year. It clearly peaked in January. I think it's a combination of all of the above. I mean, the reality is in a stretch where we had as many patients testing positive as they were, you're going to have increased patient cancellations and disruption to the schedule. You're also going to have doctors, nurses, administrative staff testing positive themselves. And usually when that happens, a center can be shut down for a day, a week, or two weeks, depending upon, you know, the extent of the outbreak. So I think all of those things create disruption that, you know, puts those patients back into the funnel to be treated here in the coming, you know, months and quarters as things hopefully return a little closer to normal.

And there are no further questions at this time. I will turn the call back over to the company for closing remarks.

Okay. Thank you all for your time and for your attention today. And we certainly hope that everyone is staying safe. And I also want to thank you all for your continued interest in Glockos Corporation. Goodbye.

This concludes today's conference call. You may now disconnect.