EyePoint Pharmaceuticals, Inc.

Good morning. My name is Jonathan, and I will be your conference operator today. At this time, I would like to welcome everyone to the iPoint Pharmaceuticals' fourth quarter and full year 2021 financial results and recent corporate developments conference call. There will be a question and answer session to follow at the completion of the prepared remarks. Please be advised that this call is being recorded at the company's request. I would now like to turn the call over to George Elston, Chief Financial Officer of iPoint Pharmaceuticals. Please go ahead.

Thank you, and thank you all for joining us on today's conference call to discuss iPoint Pharmaceuticals' fourth quarter and full year 2021 financial results and recent corporate developments. With me today is Nancy Lurker, President and Chief Executive Officer, Dr. Jay Duker, Chief Operating Officer, and Scott Jones, Chief Commercial Officer. Nancy will begin with a review of recent corporate updates. Dr. Duker will then discuss pipeline developments for EYP 1901, and Scott will comment on recent progress made on our commercial activities. I will close with commentary on the fourth quarter and full year 2021 financial results. We will then open up the call for your questions. Earlier this morning, we issued a press release detailing our financial results as well as commercial and operational development. A copy of the release can be found on the Investor Relations tab on the corporate website, www.ipointpharma.com. Before we begin our formal comments, I'll remind you that various remarks we will make today constitute forward-looking statements for the purposes of the safe harbor provisions under the Private Securities Litigation Reform Act of 1995. These include statements about our future expectations, clinical developments, and regulatory matters and timelines, the potential success of our products and product candidates, financial projections, and plans and prospects. Actual results may differ materially from those indicated by these forward-looking statements as a result of various important factors, including those discussed in the risk factors section of our most recent annual report on Form 10-K, which is on file with the SEC, and in other filings that we may make with the SEC in the future. Any forward-looking statements represent our views as of today only. While we may elect to update these forward-looking statements at some point in the future, we specifically disclaim any obligation to do so, even if our views change. Therefore, you should not rely on these forward-looking statements as representing our views as of any date subsequent to today. I'll now turn the call over to Nancy Lurker, President and Chief Executive Officer of iPoint Pharmaceuticals.

Thank you, George. Good morning, everyone, and thank you for joining us. as 2021 was truly an exceptional year for iPoint Pharmaceuticals on all fronts. Let me begin by emphasizing the continued positive momentum we have had in the fourth quarter of 2021 and into 2022. We are well-positioned to create long-term value for our shareholders, and we continue to execute on our goal of being the leader in ocular drug delivery. In 2021, iPoint made transformational strides across our business, presenting validating clinical results for our lead pipeline program, EYP1901, significantly strengthening our balance sheet, extending our cash runway, and growing our commercial revenues. Throughout this exciting time, we remain committed to our overarching mission, which is improving the lives of patients with serious eye disorders and bringing our innovative products to patients in the United States and around the world. Prior to turning the call over to my colleagues, I'd like to highlight a few of our achievements from 2021 and this year so far. The Phase I Davio trial for our lead pipeline asset, EYP1901, is a great example of our team's execution. EYP1901 has the potential to be a new treatment paradigm, potentially providing patients the substantial benefits of longer-term disease maintenance. With EYP1901 administered every six months for a majority of patients, while supplementing as needed with large molecule anti-VEGF treatments for those patients who require more intensive therapy. This is a substantial improvement from today's current treatment paradigm, where most patients are treated every month or every other month. We believe, based on Davio results, that a majority of patients can be maintained up to six months with no supplemental therapy after an initial induction period with traditional anti-VEGF drugs. EYP-1901 is a true six-month sustained release treatment that provides a new mechanism of action with virolinib, a TKI that binds the VEGF receptor, coupled with our proven bio-erodible Duracert technology that delivers virolinib with zero-order kinetics. The combination of a new MOA and zero-order kinetics delivered with Duracert could sustain a majority of patients up to six months and greatly reduced the treatment burden for patients with wet age-related macular degeneration, or wet AMD. In 2021, we dosed the first patient with EYP1901, completed phase one trial enrollment, reported positive 30-day and three-month safety data, and presented positive interim six-month safety and efficacy data, all in under one year's time. Additionally, last month, in February, we followed up with continued positive interim eight-month safety and efficacy data at the angiogenesis, exudation, and degeneration 2022 virtual meeting. We believe EYP1901's potential to transform the treatment paradigm for wet AMD is more important than ever, as we continue to see significant unmet need across the wet AMD treatment landscape, especially in the longer-duration treatment category. Wet AMD is a serious and potentially devastating eye disorder, accounting for approximately 90% of all AMD-related blindness. But despite safe and effective FDA-approved medications on the market, treatment adherence and thus long-term compliance and effects remains an ongoing challenge for patients and physicians. As Jay will discuss in more detail later in the call, We are incredibly pleased with the intra-phase 1WO trial results, which showed positive safety data with no significant inflammation, as well as promising efficacy data at the six- and eight-month follow-up so far. EYP1901's results thus far demonstrate the sustained delivery potential of what our DuraCert technology can accomplish for patients, and we're confident that iPoint is on the right path to becoming the leader in ocular drug delivery. In December 2021, we also concluded a positive and informative Type C meeting with the US FDA, and we expect to initiate our 12-month Phase II study for EYP1901 in wet AMD in the third quarter of 2022, with the first look at interim six-month results in the second half of 2023. The impressive execution and dedication demonstrated by our team to reach this milestone emphasizes the entire organization's commitment to patients, and through the EyePoint team's combined efforts, we aim to bring this innovative technology to many eyes as quickly as possible. In addition to advancing a Phase II trial of EYP1901 for wet AMD, we look forward to expanding this potential paradigm-changing treatment to additional indications. With a Phase II study of EYP1901 for non-proliferative diabetic retinopathy, or NPDR, beginning in the second half of this year. We look forward to providing you all with an update on future indications and clinical activities for EYP1901 in the months to come. Turning to our commercial product pipeline, we are very pleased to report record customer demand for both our commercial products in the fourth quarter of 2021 and a 70% increase in net product revenue compared to 2020. Additionally, we expanded our U.S. commercial alliance with ImpromiseRx which has been a strong partnership since August 2020, as we've been able to focus our efforts internally on our pipeline program while continuing to grow our commercial business despite the ongoing pandemic. We look forward to bringing our approved commercial products to more patients in need of transformative ophthalmic therapies. As you'll hear from George later on, 2021 was also an exceptional year financially, as we successfully completed two upsized follow-on offerings equity offerings during the first and fourth quarters, raising our $230 million, allowing us to end the year with over $210 million of cash and investments on hand. Finally, we continue to grow our organization and leadership team. Earlier this year, we were very pleased to announce the appointment of Michael Pine as Chief Corporate Development and Strategy Officer. In this role, Mr. Pine will be responsible for overseeing all of I-Point's business development and strategy, He brings almost 20 years of business development and strategy experience to iPoint Pharmaceuticals, and we are thrilled to have him on board during this exciting time in the company's evolution. I also want to sincerely thank our fantastic team at iPoint Pharmaceuticals for our company's clinical, operational, and financial success to date. We've made tremendous progress in the last year, and we're so excited and motivated to advance the future of sustained ocular drug delivery. 2022 promises to be another productive and rewarding year for I-Point Pharmaceuticals, and we are committed to continue to execute on multiple clinical catalysts and continue to strengthen our commercial business. I'll now turn the call over to Dr. Jay Duker, our Chief Operating Officer, to provide an update on our lead program, EYP1901, as well as other pipeline initiatives. Jay?

Thank you, Nancy, and good morning, everyone. Before I begin, I want to reiterate what an exciting point this is in I-POINT's journey. Our team is positioned to execute on multiple clinical catalysts this year as we advance our pipeline. And as Nancy stated earlier, we're quite pleased with the results of our Phase 1 Davio trial for our lead pipeline program, EYP1901, an investigational sustained release delivery treatment for wet age-related macular degeneration being studied as a maintenance therapy following induction therapy with a standard of care anti-VEGF. Our goal is to sustain the majority of wet AMD patients' treatment interval up to six months or longer. I-Point's clinical and regulatory teams have been highly focused on successfully executing this Phase I trial, and the recent positive eight-month safety data and efficacy results give us increased confidence about EYP1901's differentiated profile for safety, efficacy, and tolerability in wet AMD. Before we review the data, I'd like to touch on EYP1901 use of Duracert technology and its differentiation from alternatives in the retinal drug delivery landscape. Duracert allows for true, sustained release of a drug with steady, zero-order kinetics. In its non-erodible form, DuraCert has a best-in-class proven track record of safety, tolerability, and consistent medication delivery. DuraCert has been safely administered to thousands of patients' eyes across four U.S. FDA-approved products, and the safety and efficacy results we have seen so far with the bioerodible form used in the Davio trial bolster our confidence in this differentiated drug delivery system. EYP1901 combines a bioerodible formulation of the Duracert sustained release technology I just described with Virolinib, a small molecule tyrosine kinase inhibitor. Virolinib binds to the VEGF receptors, blocking all isoforms of VEGF as well as PDGF. This is different from the antibody and antibody fragment molecules that are current anti-VEGFs on the market today. These bind to the VEGF ligands. Thus, this differentiated anti-VEGF mechanism of action, coupled with our bioerodible Duracert zero-order kinetic technology, can potentially change the current treatment paradigm to a much less burdensome approach with EYP1901. Turning now to our DAVIO study, DAVIO is a Phase I open-label dose escalation trial that enrolled 17 wet AMD patients across four dose groups. All enrolled patients were previously treated with standard of care anti-VEGF therapy. No reinjection with the study drug was performed during the study, and standard criteria for supplementation with a standard of care anti-VEGF was employed. We reported positive interim six-month safety and efficacy data of the DAVIO trial at the American Academy of Ophthalmology meeting in November of last year. and updated this with eight-month data more recently in February of this year at the Angiogenesis 2022 virtual meeting. We are quite pleased with the interim results we've observed so far. Importantly, we've seen impressive efficacy and durability with over 50% of patients supplemental anti-VEGF-free up to six months and 41% free up to nine months. as well as a significant reduction in treatment burden for patients, 79% reduction at six months and 75% reduction at eight months. Additionally, we saw stable visual acuity in central subfield thickness as measured by OCT with the updated eight-month data showing best corrected visual acuity of minus three ETDRS letters in central subfield thickness on OCT of approximately plus 13 microns. Furthermore, as demonstrated in the six-month data release, the eight-month data highlighted positive safety with no ocular serious adverse events and no drug-related systemic SAEs. Furthermore, no dose-limiting toxicity, no retinal detachments, no cases of endophthalmitis, no occurrence of implant migration at the anterior chamber, or any significant ocular inflammation was reported. Taken together, these promising early data represent EYP1901's differentiated clinical profile as a potential six-month treatment in the wet AMD treatment landscape. As Nancy mentioned, we plan to initiate a randomized controlled phase two study of EYP1901 for previously treated wet AMD in the third quarter of this year. The wet AMD phase two trial is expected to enroll 144 patients randomly assigned to one of two doses of EYP1901 either approximately two milligrams or approximately three milligrams, or a FliberSET control with efficacy endpoint of change in best corrected visual acuity, change in central subfield thickness as measured by OCT, time to first supplemental anti-VEGF, and overall safety. Looking ahead, we anticipate sharing interim six-month data from this phase two trial in the second half of 2023. We are also working towards clinical trial initiation, exploring the potential application of EYP1901 for the treatment of other severe eye disorders, including non-proliferative diabetic retinopathy and retinal vein occlusion. In the second half of this year, we plan to initiate a phase two trial of EYP1901 in non-proliferative diabetic retinopathy. We will continue to provide clinical updates on these additional indications throughout the year, as our rapidly growing pipeline advances. I will now turn the call over to Scott Jones, Chief Commercial Officer for the Commercial Update. Scott?

Thank you, Jay. We're excited to report a strong year for our commercial businesses with $35.3 million of net product revenue, a 70% increase compared to 2020, including record customer demand for both of our commercial products in the fourth quarter of 2021. We're pleased to see patients return to their doctor's offices and schedule their previously delayed surgeries and procedures. Our Q4 net product revenue for UTiQ and DexaQ was $5.8 million and $5.4 million, respectively. Customer demand was approximately 13,800 units of DexaQ and 650 units of UTiQ, compared to approximately 13,200 units and 555 units respectively for Q3 2021 customer demand. Customer demand for Dexi-Q stemmed from our strong commercial presence and our collaboration with our commercial alliance partner, InfirmisRx. We were pleased to expand the original partnership that was established in August 2020, when in the fourth quarter of 2021, we announced and expanded U.S. commercial alliance for Dexi-Q. Under the terms of the amended agreement, Impermis Rx gains full responsibility for U.S. sales and marketing activities of Dex-EQ, and they absorb the majority of iPoint's Dex-EQ commercial organization. iPoint Pharmaceuticals will retain the Dex-EQ MDA, revenue recognition, manufacturing, and distribution responsibility for all markets. Customer demand for UTIC remains strong, in part a result of the improved siliconized needle our customer team used our commercial team rolled out during last year, providing a consistently improving procedural experience for physicians and patients. We're incredibly pleased by the progress we've made this past year with our commercial businesses. iPoint's mission to provide a unique, sustained delivery system across all of our products that requires fewer visits to the doctor's offices, a key attribute of each product's value proposition that both patients and doctors rely on. We'd also like to thank all of our patients and physicians for their continued support and use of our products. We look forward to updating you on revenues and demand in the quarters to come. I would now like to turn the call over to George to review the financials. George?

Thank you, Scott. As the financial results for the three months and full year end of December 31st, 2021 were included in the press release issued this morning, my comments today will be focused on a high-level review for the quarter. To begin, In November 2021, we executed an upsized underwritten public offering with gross proceeds of $115.4 million, bringing total equity financings to over $230 million last year. The funds raised provide us with additional capital to roll out our pipeline strategy and strategically pursue potential opportunities for the company's future growth. For the quarter ended December 31, 2021, Total net revenue was $11.5 million compared to $7.1 million for the quarter ended December 31st, 2020. Net product revenue for the quarter was $11.1 million compared to net product revenues for the fiscal year ended December 31st, 2020 of $6.7 million. Net revenue from royalties and collaborations for the quarter ended December 31st, 2021 totaled $0.4 million compared to $0.5 million in the corresponding period in 2020. Operating expenses for the quarter ended December 31, 2021, totaled $29.6 million versus $19.9 million in the prior year period. This increase was primarily due to a $3.7 million increase in R&D expense, a $3.4 million increase in G&A expense, a $2 million increase in sales and marketing expense, and a $0.6 million increase in cost of sales. Non-operating expense net totaled $1.4 million, and net loss was $19.4 million, or $0.59 per share, compared to a net loss of $11.5 million, or $1.07 per share, for the prior year period. Turning to the full year ended December 31, 2021, total net revenue was $36.9 million, compared to $34.4 million for the full year ended December 31, 2020. Net product revenue for the full year ended December 31st, 2021 was $35.3 million compared to net product revenues for the full year ended December 31st, 2020 of $20.8 million. Net revenue from royalties and collaborations for the full year ended December 31st, 2021 totaled $1.6 million compared to $13.6 million in the corresponding period in 2020. Operating expenses for the full year ended December 31, 2021, totaled $92.2 million versus $71.7 million in the prior year period. This increase was largely due to an $11.1 million in increase in R&D expense, a $4.8 million increase in G&A expense, a $2.4 million increase in cost of sales, and a $2.2 million increase in sales and marketing expense. Non-operating expense net totaled $3.1 million. and net loss was $58.4 million, or $2.03 per share, compared to a net loss of $45.4 million, or $3.54 per share, in the prior year period. Cash and investments on December 31, 2021 totaled $211.6 million, compared to $44.9 million on December 31, 2020. We expect the cash and investments on hand On December 31, 2021, an expected cash inflows from our product sales will enable us to fund our current and planned operations into the second half of 2024. In conclusion, we are pleased with iPoint's progress in 2021 and are well capitalized to advance our product pipeline to key value inflection points. Thank you all very much for listening this morning, and I now turn the call over to the operator for questions.

Certainly. Ladies and gentlemen, if you have a question at this time, please press star then 1. On your touch zone telephone, if your question has been answered and you'd like to remove yourself from the queue, please press the pound key. Our first question comes from the line of Jennifer Kim from Cantor Fitzgerald. Your question, please.

Hey, everyone. Good morning. Thanks for taking my questions, and congrats on some really amazing progress since your last earnings. I have a few questions here. First, I'm wondering, what are your thoughts on I guess some of the recent shortfalls we've seen from competitors like Kodiak, and what does that mean for you guys? And on a similar vein, what are your thoughts ahead of potential TKI competitors that could come up with some phase one data in the second half of this year? And then my second question is, on your cash runway, does that include the RVO trial still set for the first quarter of next year? Thanks.

Hi, Jennifer. It's Nancy. Okay, so I heard three questions. One is, I believe you said the recent Kodiak data and how that might, our thoughts on that, if I'm correct? Yeah, or the competitor shortfalls. And then other TKIs coming up, their data readouts. And then last is on cash, which George will handle. Let me give a quick overview and then Jay can opine more in depth. I want to be very careful because obviously I don't really want to get into data on our competitors. It's just, A, it's not appropriate. B, we certainly don't have insights like they do. Just generally speaking, if you look at what's been happening, unfortunately, and I think it is difficult for patients, and I would say physicians and investigators, that this is a tough landscape. It's a tough field to be in. And so unfortunately, you're seeing dropouts occur with companies struggling with either drug delivery technology or just their their APIs, their active drugs, which are just not able to either have safe profiles or they're just, they can't hit efficacy endpoints. So, you know, you're starting to see this field really start to whittle down. Obviously, we had very good phase one results. Our eight and nine month data continue to look really good. So, you know, we have fewer competitors. Ultimately, that's probably good for us, but I don't think it's good for the community overall. As to the other TKIs, look, we look forward to their readouts. I think that what you'll see is as more TKIs read out, you're going to start to see how validated is the tyrosine kinase inhibitor target. Now, certainly we've seen with not only with our virolinib TKI, with the oral wet AMD study, that our partner did. It showed efficacy in wet AMD. It delivered it for ocularly. That was an oral study, though. And then we just announced, obviously, our Davio studies, which confirmed efficacy in wet AMD. If you look at the others, you know, I'll name them, ClearSight, Ocular, they both have shown good results with their TKI so far. And I would even say Graybug did. Their problem was more a drug delivery issue. So I think that the target has been validated, which is terrific because, again, you want to be able to give different targets, mechanisms of action for physicians to use on patients and not just continue to have only one target. Now, again, if you look at the large molecules, they attach at the ligand level. The TKIs, as you know, attach at the receptor level. and they cover a much broader number of kinase receptors. We don't know the effects of all those, but certainly there's some hints that you might have some positive differentials there. So I think it's good that we have different targets for patients that physicians can use, and so far the TKI targets look quite good. I'm going to ask if Jay wants to add anything to that.

Well, hi, Jennifer. Nancy, you've summarized it really well. You know, at the high end, What we're all trying to do here is really thread a needle of safety and improved efficacy or longevity for our patients. But with respect to what our EYP1901 is looking for, it really isn't to be the next ILEA or the next Verisimab. We are really looking at our drug being a maintenance therapy drug. taking patients who are stable but unable to be treated less frequently than say a month or two, and hopefully taking the majority of them and able to treat them much less frequently, maybe up to every six months or even longer. So that while, again, the failure in COTIX phase three is disappointing for practitioners and patients in the community, there are some learnings for us as well in how we may choose to design our pivotal trial. And again, as you all know, this is a very big space. And so having active competitors is fine, and it probably pushes us all forward to really improve things for our patients. The other question, I think, was financial. Hi, Jennifer, George.

Thanks for dialing in. So, yeah, we, on our cash guidance today, into the second half of 24, that premise does include the initiation of three studies, three phase two studies with 1901 in wet AMD, non-proliferative diabetic retinopathy, and then RVO at some point next year. And the way we've managed the business and the process is we've always wanted to have at least one year of cash on hand when that wet AMD study reads out, and that's sometime in the second half of next year, which we updated on our earnings release this morning.

Okay, thanks. If I could sneak one more in for Scott. Was there anything that particularly drove Utica and Dexacute sales this quarter? Was this more of a one-time pent-up demand, or is this demand sustainable? Thanks.

Thank you, Jennifer, for the question. We certainly hope that the demand is sustainable. Obviously, we know there is some seasonality in the ophthalmology market. especially as a Medicare market where patients are trying to get all their procedures in for the end of the year and their benefits reset at the beginning of the year. So we do see some seasonality, but we've seen a pretty consistent growth curve despite the pandemic, and we certainly think that that will continue moving forward, and certainly that is our hope.

Okay, great. Thanks, everyone.

Thank you. Our next question comes from the line of George Yordanov from Cowan. Your question, please.

Hey, guys. Thank you so much for taking our questions, and congratulations on all the progress. So maybe to start, could you talk about some of the initial observations from the Phase I trial that you've had some longer follow-up period for 1901? Specifically, there were patients who saw vision improvement despite the presence of fluctuating subretinal fluid How do you explain this result? And also, how do you think some of these observations could change medical practice, especially once we start having multiple longer-acting options on the market? And then just to follow up on the competitive disclosure question, one of the things that we found interesting from that data was that it did seem like it was a confirmation that there is a a sizable subset of wet AMD patients who are inadequate VEGF responders and could really benefit from a broader mechanism such as a TKI. Maybe if we can just hear your thoughts on this and if you thought that this was kind of like possible to see from their data and really the potential size of that patient population of inadequate VEGF responders in wet AMD patients.

Well, those are excellent questions, and I'll try to start at the top and just ask about learnings from our phase one trial. First of all, you know, we're very pleased that there were really no safety signals at all because it's very clear in this space, if you don't have safety, it doesn't matter what your efficacy looks like. And I would say so far so good with an N of 17 and a follow-up, you know, getting close to 10 months in everybody, things look quite good. Our other learnings are there's a significant percentage of wet AMD patients that appear to be able to be maintained with our drug for six months or longer without any supplemental anti-VEGF, and maintained means, again, primarily visual acuity. Fluid is important, and we use fluid via OCT as a marker for VEGF activity, but there is not a one-to-one relationship. We've known that for years. You can go way back in the earliest anti-VEGF and OCT studies show that the correlation coefficient between retinal thickness and vision is only about 0.6, which means it's good, not great. And we all have patients with a little bit of subretinal fluid who see pretty well. Stability in visual acuity and stability in anatomy is what we're trying to accomplish with EYP1901. We also heard from the recent Regeneron high dose study that 50% of ILEA patients still have fluid, the current dose of ILEA, even when treated monthly. So we strive to get our patients dry, but there's a lot of patients out there that you just can't get all the fluid to go away. And if it's a little sliver of subretinal fluid, that actually may be okay. So again, what we're trying to do is not necessarily dry better, We're trying to keep patients stable longer. Your second question was about learnings from... Oh, yeah. So, yeah, you know, again, I think specifically you were asking about Kodiak's results, and given that We're really just looking at a slide deck and press releases. It's hard to really know for sure, but you're looking at the early OCT data when the Kodiak drug was given monthly. It does look like they are not as good at improving visual acuity in OCT as Hylia is. Now, that's not to say that a certain percentage of patients can't do well long-term with their drug. But that's not how they tested it. They tested it as naive patients, all comers. And for a good percentage, it looked like over 50%. They could be maintained long-term. But the problem is there was another 40% that really overall did not do as well with the drug as ilea. That's how I interpret the data. So yeah, we've known for a long time the number one determinant in the fluid-free interval in a patient is not the drug, it's the patient. And there's some patients who have probably a high VEGF load and they need a lot of anti-VEGFs and some of those you can treat them monthly with the best drying agent out there and they're still gonna have fluid. Others, you know, you can dry them up and then they can go three months and sometimes even longer. But the trouble is that's only a minority of the patients with the current products available. And that's what we're trying to help is get it from 20%, 30% perhaps who can go three months or longer to 60% or more who can go longer than that. And all along, again, one of our goals is to try to identify the patients who are going to do well with our drug and direct the physicians Hopefully, once we have a label to say these are the patients who you're going to do really well with, that's the ones you want to treat with 1901.

Jorgie, let me just add to that as well, and I'm going to see if Jay can comment further on this, which is one of the other things that we've talked about, I want to emphasize, and it's a little bit back to your question about could patients benefit from a different mechanism of action. That's where we believe we're trying to change the the thinking and potentially the treatment paradigm, not only will these patients get on these longer-acting extended delivery therapies like EYP1901, but then you just continue to have that on board every six months. Some of these patients might need supplemental support from a large molecule antibody occasionally, some more than others. But you continue to have the tyrosine kinase inhibitor, hopefully EYP1901, on board providing that protective maintenance therapy longer term. So again, it's not back to you either put a patient on this drug or that drug. In some cases it might be, in fact we think a majority of patients, you continue to have EYP1901 on board after the patient's been treated and as dry or relatively dry as it can get. And then you provide the supplemental therapy as needed if they can't be maintained. But we do think a majority of patients will be able to be maintained. I'm going to see if Jay wants to comment on that.

Yeah, no, I think that summarized it really well. And obviously, in other areas of medicine, this is quite common. Look at high blood pressure. for example. And so that there are a lot of analogies out there for saying you've got a way to maintain a lot of patients on hopefully a safe and effective drug, but even if some of the patients break through with a little fluid, they're still at an advantage with the different methods of action where you can add another drug on top of that, but hopefully with a much less onerous schedule as what they were on before. That's the goal.

Thank you so much. That was really great. And again, congratulations on all the progress. Thank you.

Thank you. Our next question comes from the line, from Guggenheim. Your question, please.

Hi, this is Eddie on Friot, and thank you guys for taking my question this morning, and congrats on the quarter. Just a few from me. Can you remind us if you're using the same injection device and procedural techniques in the Phase 2 as you did in Davio, and if there are any other changes you're making due to learnings from Davio, including how you're thinking about, like, patient selection and avoiding potential non-responders?

And then...

Just as a follow-up, are you thinking about adding an arm in any future studies where you put in the device earlier, before six months, or a six-month interval to go across all the proposed indications? Thanks.

So, great questions. Thank you. First of all, yes, we've learned quite a bit even from the 17 patients that we enrolled in Davio. And just to remind everybody, our drug is delivered in the office intravitrally, a single injection, with local anesthesia. It is a 22-gauge needle, and we are able to inject up to three inserts with a single injection. So the medium dose for our Phase II wet AMD trial is approximately two milligrams. That would be two inserts. The high dose for the Phase II is approximately three milligrams, so obviously three inserts. Do need to educate the investigators on the fact that injecting three inserts takes a few seconds to do successfully, as opposed to a liquid which can be injected very, very rapidly with a quick bolus into the eye. That's really the only, I would say, any kind of change from the standard injection that retina specialists are used to. From the perspective of the intervals, I don't think it's likely that we would study an interval less than every four months. And we may not, again, in full disclosure, even look at every four months. We certainly believe that the sweet spot for our drug and for what retina specialists want is every six months. In saying that, we clearly can go longer than six months with some patients. In Davio, we got 41% out to nine months. Again, in retina, we call this individualized therapy. I think that if we get a label and we're being used, I think the doctors will figure out which patients can go how long in kind of a modified treat and extend version of what they're used to. But if our drug... is differentiated by both the delivery system and the methods of action from what we have out there. And injecting it monthly or every other month would not really be that differentiated. So, again, I think we have a lot of potential schedules for the injections that we're going to look at in the future, and we're going to let the data and the market drive where we go with that.

Thanks, and then can you just talk about the inclusion criteria or how you might be enriching the population in phase two?

Yep, so there were clearly, if you look at our phase one data, the 17 patients, we had three patients who required a supplemental anti-VEGF at month one. Now, just to remind everybody, everyone in that study had previously treated wet AMD. They could have had fluid coming in or no fluid, it didn't matter, but everybody got a standard of care injection on day zero. And about a week later, they got 1901. So if they had 75 microns of new fluid or more at month one, that was five weeks after a standard of care injection. So what that tells us is those eyes, they weren't doing well not just with 1901. They weren't doing well with standard of care. And again, I think it's logical to assume that the investigators are not going to put their best patients who are doing well into a phase one trial of a new drug. They're going to put the patients who aren't doing well. And I think that our Davio trial skewed towards that end, and those patients, you know, obviously are evidence of that. So in doing the analysis of who did well and who didn't, it certainly looks like patients who have been previously treated but still have more than 400 microns of CSD, those are patients who are failing, in my mind, standard of care also. and they're probably not gonna do as well in our drug. Now, you could argue, well, maybe if they're being treated monthly and still have 400 microns of CSD and you put 1901 on board, maybe you could treat them every two or three months with a standard care on board along with that. Well, that may be true, but that's not the paradigm that we're going for for FDA approval at this point. So we also made the observation that patients who still had significant intra-retinal fluid despite that anti-VEGF in previous treatment, as I explained, those patients required early retreatment also, so we're excluding them. In that fashion, along with the timing of the diagnosis of wet AMD for this next trial, I think we're gonna get a much broader patient population that reflects more the wet-empty population out there as opposed to what we got in Davio, which I think was more skewed towards patients who weren't doing well.

Thank you.

Thank you. Our next question comes from the line of Yi Chen from HC Wainwright. Your question, please.

Thank you for taking my questions. Could you comment on whether about 50% of patients that do not require a supplemental anti-VEGF up to six months will be good enough from a commercial perspective? And in real-world practice, Even though if a product says the on-label 50% patients could have a maintained efficacy up to six months, do you think doctors will still see these patients before six months? Thank you.

Yes, so excellent questions. And I think that we can kind of look into the mentality of the retina specialists and see how effective we adopted new treatments for these diseases in the past. So if we have a safe, effective, and tolerated drug, and 50% of the eyes can go every six months or longer, we have a terrific commercial opportunity, fantastic, especially if we can identify ahead of time who those 50% are. Because all of a sudden your success rate is going to be greater than 50%. You're going to ask the doctors not to do injections necessarily on the patients who aren't going to do well. Just pick out the ones who will. Of course, retina specialists figure it out. So how do we initiate new drugs? We don't necessarily go on label. We often will take the patients who we think will do best on it and we'll try them out and often we try them out monthly. And we watch them and we see if the new drug is safe and seems to work better than the older drug So while we don't have a monthly drug, I don't think that's going to be any different for 1901 I think patients who we help identify with the retina community who are likely to do well They'll try those patients on 1901 and they might get 50 60 70 percent of those patients to go six months without recurrent fluid or drop in vision in which case terrific and They'll continue every six months. Now at the beginning, do I think they'll let them go six months without a visit? No, I don't think so at all. Although if home OCT is widely available by then, I think that might be a nice adjunct to help monitor these patients at home. But certainly at the beginning, we're going to want to watch the patients a little more carefully. And even in the end, would I want to not see a wet AMD patient every six or eight months? Probably not. I want to monitor the fellow eye to see if they convert to wet AMD. The fellow eye may be acting differently. I think these patients will still be observed at least several times a year, even if they only require an injection every six to eight months. Now, there'll be another group of patients, and those are probably, you know, the ones who might be treated even with ileo or lucentis or perhaps frisomab every four weeks, every six weeks, every seven weeks. And every time we try to extend them more than that, we see fluid. Those are patients who may benefit from 1901 as well, because based on the Davio trial, we had several of those patients who required a supplemental anti-VEGF at four months or five months into the study and never required another one up to nine months. So we cut their injection rate from every six weeks or so to every three or four months. And so that's gonna be a benefit to those patients as well. So even if they do require an early rescue or supplement before the six month period, it still may be beneficial, especially because it's a different mechanism of action. It's not adding a ligand blocker to another ligand blocker. It's a different MOA. And I think there's gonna be another benefit as well. that I think there's going to be a certain peace of mind that retina specialists and patients will have, knowing that they have a long-term anti-VEGF on board. So what if they miss a visit? What if they get sick and get to the hospital? What if we have another pandemic and they can't get in? So they're not going to be as worried that one or two missed visits may result in a significant drop in their vision.

Thank you for the answer. Second question, could you give us an update on UTIC-50?

Yeah, so right now we are continuing to enroll patients, and we're waiting for the enrollment to complete, which is taking some time, and we're continuing to monitor the study.

How many patients will be enrolled for the phase three?

I think we aimed for 60. 60, that's correct, 60.

Okay. So the face-to-face study will report results in the second half of this year?

No, that was never the plan.

No.

We haven't guided on that yet. Yeah.

Okay. Remember, it's an orphan disease.

Right. It's hard to find. Exactly. These patients are a little harder to find and locate because, again, Georgia says it's an orphan disease.

And there are currently good treatments out there, including RUT20. Yes. Yeah.

Okay. And lastly, could you provide any general comments regarding the trend of prescriptions for, you expect, for UT can execute for 2022?

I'm going to actually turn this over to Scott. I just want to caution we don't give forward guidance. So I'll let Scott just comment on sort of the general environment that we're operating in right now.

Thanks for the question. And, you know, as Nancy said, we're not going to provide specific guidance relative to the number of prescriptions that we expect to receive in 2022. But what I can say, and I'll start with you, Teague, specifically, is that we are seeing an expansion of our customer base. We had a 57% expansion of our customer base in 2021, and we expect to continue to see that occur. And I would say specifically we're seeing the expansion within the retina segment, so not just the traditional uveitis segment of the business. So I think that would lead us to believe that we're certainly expanding the market, and we expect to continue doing so in 2022. On the Dexacute side, again, we've seen an increase in our customer base. More importantly, within that customer base, we're seeing growth an expansion of the utilization at each one of those ambulatory surgery centers. So the number of units per ambulatory surgery center did increase in 2021, and we certainly would like to see our commercial partner, InfamousRx, continue with that trend into 2022. Okay. Thank you.

Thank you.

Thank you. Our next question comes in line of Yale Jen from Laidlaw. Your question, please.

Good morning, and thanks for taking the questions. I'm going to start with a quick housekeeping one, which is for the fourth quarter, the SG&A seems to grow significantly quarter over quarter. Should we anticipate that number to be a base for 2022 in each quarter, or simply just some one-time events to occur at that time?

Yeah, I think that's probably a good base run rate. We have invested across our, not just the organization, but IP as well. So I would probably look to blend the two quarters, Yale, just if you're looking to blend. I'm happy to follow up with you on your models.

Sure. And the second question is that I know you guys are going to start at what AMD Phase II study in third quarter is. What are currently the gating factors for you guys to complete before a formally started trial?

Well, so there's a lot of kind of behind the scenes things that need to be done to initiate a trial. And things like manufacturing, packaging, and distribution of the drug, which we have already accomplished. You have to choose a CRO, which we've already accomplished. The CRO has to contact the sites, the sites have to agree to be in the study, then the protocols need to be approved by their IRBs, drugs need to be shipped directly to the site, and then we can get things going. So all of that is moving in a very nice pace. Again, it's a complicated dance that all companies do to get these studies up and running, and I'll just remind the audience that Our last patient was enrolled in Davio last May, and so we only got six months results in November. And that was just about four months ago, and we are well along with the plans to initiate the Phase 2 trial. So, we're really pleased with the choice of CRO. We're really pleased with the interest in the sites out there. Obviously, for a trial of this size, we had 11 sites in our Phase 1 trial. We're aiming to have, you know, multiples more sites for this trial. And that all takes a little bit of time. So there's no one gating thing. These are all occurring in parallel. But as of today, I remain confident that that third quarter start is on track.

Okay, great. And maybe my last question here is that at the recent medical meetings, there's reporting of the Aaliyah vaccine. I believe, eight milligrams of data. What do you think about that, and is there any impact on your thoughts in terms of the 1901 development?

Yeah, so the data's interesting in that, again, safety is number one. It did appear to be safe. There were a couple of ocular AEs in the high dose that weren't seen in the regular dose, but I don't think it didn't appear to be significant. Does appear to dry better, maybe even give better visual acuity, but again, that's not a competitor to us. We're agnostic to who dries the retina out for us, whether it's furosemab, it's high-dose ilea, it's regular ilea, or it's KSI's drug. Once doctors get the patients induced to as good as they feel the retina can look, that's when we'd like them to step in with 1901 to see if we can provide that longevity and assurance that there's a long-term anti-VEGF with zero-order kinetics that's safe on board. So, yeah, we welcome anything that's going to help patients in this space. That'd be terrific. And if the drying effect is better, that I think would work very nicely in conjunction with our drug.

Okay, great. And maybe squeeze one more in, just follow up what you just have said. In terms of potentially initiating your maintenance therapy after the initial induction treatment, was there any factors or, you know, how long you think the, obviously it depends on the patient, but how long you think the patient could start the maintenance therapy when you can guide that up?

Yeah, so that's a really good question. And again, I can put on my clinical investigator hat and say, boy, there's a whole lot of questions I'd like to answer about how 1901 works and which patient population and when to give it. But we're really focused on getting the drug FDA approved as quickly as possible. And some of those clinical questions are going to have to, I think, wait until FDA approval occurs. And the obvious one is, are you going to test your drug in treatment IU patients? Eventually, if the answer's probably yes, either we will or the retina community will test it that way. But we have no immediate plans to do it because it's again, in some ways, whether we work in naive as well as we work as maintenance is kind of irrelevant. As long as we offer something that none of the current drugs offer, which is the ability to go out six months or longer without another shot in the majority of patients.

Okay, great. That's very, very helpful. And, again, congrats on all the progress. I look forward to you guys to start a trial soon. Thank you, Yale.

Thank you for the questions.

Thank you. This does conclude the question and answer session of today's program as well as today's conference. Thank you, ladies and gentlemen, for your participation. You may now disconnect. Good day.