ANI Pharmaceuticals, Inc. (ANIP) Earnings Call Transcript & Summary

Good day, everyone, and welcome to today's ANI Pharmaceuticals NEW DAY Study Results Call. Please note, this call is being recorded. [Operator Instructions] It is now my pleasure to turn the conference over to Ms. Lisa Wilson. Ms. Wilson, please go ahead, ma'am.

Welcome to ANI Pharmaceuticals call today for the results from the NEW DAY clinical trial for ILUVIEN. This is Lisa Wilson, Investor Relations for ANI. With me on today's call are Nikhil Lalwani, President and Chief Executive Officer; Chris Mutz, Senior Vice President, Head of ANI's Rare Disease business; and Mary Pao, Chief Medical Officer of ANI. Also joining the call today is Dr. Michael Singer, Clinical Professor of Ophthalmology at University of Texas Health Science Center and Director of Clinical Research at Medical Center Ophthalmology Associates in Texas. You can also access the webcast of this call through the Investors section of the ANI website at anipharmaceuticals.com. Before we get started, I would like to remind everyone that any statements made on today's conference call that express a belief, expectation, projection, forecast, anticipation or intent regarding future events and the company's future performance may be considered forward-looking statements as defined by the Private Securities Litigation Reform Act. These forward-looking statements are based on information available to ANI Pharmaceuticals' management as of today and involve risks and uncertainties, including those noted in our press release issued this morning and our filings with the SEC. Such forward-looking statements are not guarantees of future performance. Actual results may differ materially from those projected in the forward-looking statements. ANI specifically disclaims any intent or obligation to update these forward-looking statements, except as required by law. The archived webcast will be available for 30 days on our website at anipharmaceuticals.com. For the benefit of those who may be listening to the replay or archived webcast, this call was held and recorded on July 23, 2025. Since then, ANI may have made announcements related to the topics discussed, so please reference the company's most recent press releases and SEC filings. And with that, I'll turn the call over to Nikhil Lalwani.

Thank you, Lisa. Good morning, everyone, and thank you for joining us. Before we get started, I would like to remind everyone of our disclaimers. Next slide, please. I will kick off today's call with an overview of the agenda and opening remarks, followed by Dr. Mary Pao, our Chief Medical Officer, who will provide brief background on ILUVIEN and its relevance for the treatment for DME. Next, Dr. Singer will walk through the NEW DAY study design and results. I really want to thank Dr. Singer for his participation in today's conference call and for presenting the data at Annual Meeting of the American Society of Retina Specialists, or ASRS. After Dr. Singer, I will return to provide closing remarks. And then Chris Mutz, our Head of Rare Disease; Dr. Mary Pao, our Chief Medical Officer; Dr. Singer and myself will take your questions. So to start, and we can stay on the same slide. So to start, we are pleased to be here today to discuss the results from the NEW DAY clinical trial, which explored the use of ILUVIEN as baseline therapy in patients with early diabetic macular edema, or DME. We acquired ILUVIEN in our 2024 acquisition of Alimera Sciences, and the NEW DAY trial was already well underway at that time. For context, NEW DAY is one of the largest studies comparing a corticosteroid therapy versus an anti-VEGF therapy arm in the treatment of DME. As we will discuss today, we believe the NEW DAY results further highlight its potential as an important option for DME patients and have the potential to support earlier usage of ILUVIEN as part of and its role in reducing treatment burden in DME. More broadly, the NEW DAY trial and our other ongoing clinical and scientific studies for our Rare Disease business and our Retina business are in line with our commitment to generating data to help physicians inform their clinical decision-making. To that end, we will continue to analyze the NEW DAY results and present the full trial data and potentially other analysis in the future to continue to support our customers and the patients they serve. Before I hand it over to Dr. Pao, we wanted to share a quick performance update on our retina products. These have been 8-K this morning. Our preliminary unaudited financial results for the second quarter ended June 30, 2025 for our retina products, which are ILUVIEN and YUTIQ. The company expects combined ILUVIEN and YUTIQ net revenues of $22.3 million for the 3 months ended June 30, 2025. Our retina product performance was in line with our expectations. The second quarter was an exceptionally busy one for our team. As we executed on the ILUVIEN launch under the combined label for chronic NIU-PS, non-infectious uveitis for the posterior segment of the eye and diabetic macular edema, DME, the transition from YUTIQ to ILUVIEN, which is now done and helping retina practices navigate the recent market access challenges for Medicare patients, all while expanding and strengthening our ophthalmology sales team with experienced reps. And with that, I will turn it over to Mary to share the NEW DAY results. Mary?

Good morning, everyone. Thank you, Nikhil. I'm Mary Pao, I'm the Chief Medical Officer, and thank you, especially to the West Coast people who are joining us so early. We can take a look at the -- this current slide. This is a slide with an overview of ILUVIEN, which is the product we're discussing. On the left, if you take a look, there are the approved indications. And on the right, you can orient yourself to a high-level description of its mechanism of action, which I'll discuss in a second. As many of you already know, ILUVIEN is a novel, long-acting intravitreal implant and it releases the corticosteroid fluocinolone acetonide in a constant and controlled manner for up to 36 months. It's indicated for the treatment of appropriate patients with diabetic macular edema or DME, which is a chronic disease that causes swelling in the macula of the eye. DME is actually the leading cause of vision loss in diabetic patients and symptoms can include blurry or double vision, difficulty seeing colors and ILUVIEN is indicated also for the treatment of chronic non-infectious uveitis, which affects the posterior segment of the eye, and we'll call that NIU-PS. NIU-PS is a long-lasting inflammatory condition in the eye that leads to pain, visual impairment and also results in vision loss. Delivering a corticosteroid to the eye helps inhibit the inflammatory response, that's a key driver in DME as well as chronic NIU-PS. Specifically, corticosteroids increase the production of a compound called lipocortin, which you look at on the right, and that blocks the production of phospholipase A2. Phospholipase A2 is a compound that drives inflammation with the downstream production of prostaglandins and leukotrienes. So you see how you're regulating the inflammatory response through all of these compounds. In addition, lipocortins also suppress cytokines, which we know are important in development of inflammation. Next slide, please. So on this slide, we're looking at a high-level view of the treatment journey for DME patients. The guidelines from the American Academy of Ophthalmology or the AAO recommend treatment with anti-VEGF compounds as the first-line therapy. In addition to regular monitoring that can lead to switching to a different anti-VEGF, improve or optimize results. For patients with more severe visual impairment or that have a suboptimal response on anti-VEGF therapy, guidelines recommend a switch with different anti-VEGF therapy, an intravitreal corticosteroid such ILUVIEN or laser therapy. In real-world practice, steroids such as ILUVIEN are used by physicians as a treatment of choice for patients who are not well served by anti-VEGF therapy. Why? Because they provide a different complementary mechanism of action focused on the inflammation associated with DME. On the next slide, we can dig a little bit deeper into the opportunity for steroids to treat patients not well served by anti-VEGF therapy. On the left, you can see we have a column that outlines the various reasons why a patient may have an incomplete or suboptimal response to anti-VEGF therapy. First, the burden of frequent injections can contribute to inferior real-world vision outcomes compared to clinical trials as demonstrated by a retrospective analysis that's shown that there are fewer anti-VEGF injections and poor 1-year visual acuity gains in the real world versus what's shown in the trial. Second, DME is a multifactorial disease. And so the underlying pathophysiology likely goes beyond just VEGF-driven angiogenesis and likely includes inflammatory, hypoxic and hemodynamic processes, which can contribute to the disruption of the blood-retinal barrier and the increase in vascular permeability that we see in DME, and those cannot be addressed by anti-VEGF therapies alone. Third, the disease may be heterogeneous. There are variations in genetics and phenotypes such as polymorphisms or differences in gene expression of VEGF that can infect individual responses to anti-VEGF therapy. An enhanced VEGF expression or pathway redundancy may impact the therapeutic efficacy. Fourth, glucose regulation in diabetic patients plays a crucial role in the effectiveness of anti-VEGF therapy in DME. Patients with higher hemoglobin A1c levels often show a less favorable response to treatment, and it often is seen that you need tight glycemic control to achieve the optimal anatomic and visual outcomes. Finally, last on this column, access to anti-VEGF therapy can really vary significantly based on a variety of factors that are associated with economics, which affects treatment frequency and visual outcomes or disparities based on rates, ethnicity, insurance coverage, access to care and adherence to clinic visits. On the right, we highlight data that shows the correlation between DME severity and inflammatory cytokines. This study implies that corticosteroid treatment, which suppresses inflammation is positioned as an important treatment for DME, especially for patients that are not well served by anti-VEGF therapy. I will now happily turn the call over to Dr. Michael Singer to discuss the NEW DAY clinical trial, and thank you, everyone.

Thank you, Mary. So we're going to talk about NEW DAY clinical trial. The NEW DAY clinical trial was really to assess the efficacy of ILUVIEN as baseline therapy in patients with early DME as well as assessing the safety and tolerability of ILUVIEN and aflibercept in combination in patients with DME. You can see on the slide that this is the basic schematic. Patients initially were given a steroid challenge because we wanted to treat them on label and the steroid challenge was with difluprednate. They were randomized 1:1 to ILUVIEN and aflibercept. The ILUVIEN arm got one shot followed by 4 placebo injections over a 5-month period of time. While aflibercept was given on label with essentially 5 injections every 4 weeks. And then what would happen during the maintenance phase was to see if supplemental aflibercepts were needed. And the key details, the intent-to-treat analysis essentially with everybody in the INSPIRE study population. And we wanted to know for the primary endpoint, the number of supplemental aflibercept injections that were needed from baseline to week 72. The secondary endpoints that we'll discuss was the time to supplemental therapy from the last injection, the percentage of people who gained 5, 10 or 15 letter ETDRS letters from baseline to week 72. The baseline change in central subfield thickness in the ITT population on OCT and the percentage of patients who did not require any supplemental therapy throughout the trial. Obviously, safety is important. So we track the rates of cataract surgery, the incidence of intraocular pressure and intraocular pressure surgery throughout the trial. Next slide, please. So in terms of inclusion criteria, you had to be over age 18 with Type 1 or Type 2 diabetes, you had to have OCT central subfield [indiscernible]. And from a vision standpoint, you had to have between 35 and 80 letters initially. What was excluded was patients with history of glaucoma or ocular hypertension, other conditions associated with macular edema, patients who had prior laser photocoagulation or grid, patients who had a history of intravitreal or periocular steroids or intravitreal injections of anti-VEGFs within 12 months, you could have had 1 within the last 12 months, but you can have 1 greater than 6 weeks. So essentially, you had to have it greater than 6 weeks but only 1 in the last year. We talked about the steroid challenge. Let's go in bigger detail that essentially, we gave people the medication. They could not have a pressure rise that's greater than IOP or greater than 8 millimeters from screening or they would not be included in the trial. And this was a 2-week course of difluprednate topical drops. Next slide, please. So looking at the intent-to-treat population, we initially had well divided, 154 ILUVIEN, 152 aflibercept, you can see the people who discontinued early, about 30 in the ILUVIEN arm and 34 in the aflibercept arm. You can see the reasons. Overall, you had about 124 people in ILUVIEN and 118 in the aflibercept arm in the total population. Next slide. Looking at the demographics, pretty well balanced. I mean, the most important thing we wanted to balance had to do with vision and had to do with lens status but essentially pretty well balanced in terms of the age, the genders, the race, the ethnicity. Next slide. Important for the baseline characteristics, like I said, mean visual acuity is something we wanted to stratify for and that was well put together. Everything else is pretty well stratified as well. I want to bring your attention to the fact that essentially, we did have relatively large numbers of people with high-risk NPDR. The other thing that's important in terms of [ this ] study, which is different from other ILUVIEN studies in the past had a very high percentage of phakic patients, which essentially you could see down here. And there were patients who were previously treated for about 10%, which was equal in both arms. Next slide. So we're going to talk about a second population, that we'll reference, which is called post hoc population. The story was not everybody followed the rules for lack of a better word. So again, we look at the post hoc population for people who essentially followed the rules. So the reason we differed from this initial population was patients who did not have a major study deviation. They were randomized, enrolled and they met criteria. They got the right -- they've made sure they got the right treatment and make sure they did not receive prohibitive treatment. There were 44 patients with 73 major deviations that exclude them from the post hoc analysis. Half of these deviations where in patients who were supposed to receive a supplemental injection and didn't. And 1/3 of these patients, patients got a supplemental injection and weren't supposed to get it based on protocol guidelines. If you look at the treatment population, what you can see is we dropped it from 154 patients in the ILUVIEN to 128 and 152 aflibercept to 134. Then you look at this population in terms of who discontinued early, your overall completed study population as post hoc was pretty balanced at 103 and 104. Next slide. So looking at the demographics, essentially well balanced just like the ITT population in terms of patient demographics. Next slide. In terms of baseline characteristics, same thing as well, very well balanced in terms of vision, IOP, ETDRS letters and DRSS scale. Next slide. So the primary endpoint, so the primary endpoint, it turns out you needed less supplemental injections in the ILUVIEN arm versus the aflibercept arm. However, it did not reach statistical significance. What did reach statistical significance, which is probably more important, is the mean time to supplemental therapy since the last injection was 185 days in the ILUVIEN arm and 132 days in the aflibercept arm and that p-value is highly statistically significant. And about 30% equal groups had no need for rescue therapy throughout the trial. Important to understand that although there was the numbers of the mean number of supplemental injections with 2.4 and 2.5, remember that the aflibercept group got 5 injections as a head start being treated on label. So if you add them together, essentially, you're looking at around 3 injections in ILUVIEN and 7.5 in aflibercept. Next slide. Looking at the per protocol population, we -- in the groups that actually followed the rules, the mean number of supplemental injections was statistically significant with 1.8 supplemental injections needing in ILUVIEN arm and 2.5 in aflibercept arm. In terms of time to last injection, just like in the ITT population, it was highly statistically significant with 189 days in ILUVIEN versus 131 days in aflibercept. And again, looking at the total number of injections throughout the study, the ILUVIEN arm needed 2.8 while the aflibercept needed 7.5. Because remember that the aflibercept had a head start with 5 extra injections. Next slide. So secondary endpoints, in terms of visual acuity, it was a 4-letter non-inferiority margin, which we met the 4-letter non-inferiority margin. If you look at the people who essentially who weren't rescued, this 4-letter group actually got even smaller for patients who actually didn't need rescue. One of the things we wanted to figure out was, was there a difference between having lens status or not. Because in other steroid studies, there was a difference. And it turns out whether you were phakic at the start, pseudophakic at the start or pseudophakic and after -- during the course of the trial, meaning had cataract surgery, none of these trends seem to have any difference on visual acuity. Next slide. Looking at 5-, 10- and 15-letter gainers, you can see there's an equivalent number of each group that were able to hit this marks with essentially 11.5% in ILUVIEN versus 10.3% in aflibercept. 23% versus 29% in 10-letter gainers or 2 lines and 41% versus 49% in 5-letter gainers. So important to understand that both of these medicines were very good at improving vision, regardless of how you measure it in terms of 5- or 10- or 15-letter gainers on the ETDRS chart. And this is the entire ITT population. Next slide. Looking at central subfield thickness, the overall graph on the left shows that the mean central subfield thickness over time, so it's an interesting trend. The trend is if you give aflibercept on label where you get 5 shots, aflibercept initially dries the retina better than ILUVIEN. But over time, the ILUVIEN group patches up. I look at this kind of like the hare and the tortoise. If you look at the change in BCVA over time, you see the same thing. So when you look from month 9 on in any of the 3 graphs you see, what happens is ILUVIEN actually catches up and drives the retina numerically better than aflibercept, whether you look at the overall mean change, whether you look at mean CST or you look at essentially the people who were nonrescued. All the trends are the same. And this makes sense with the mechanism of action that Mary explained before because of the fact that steroids take care of inflammation and inflammation are usually later than the VEGF effect. This is where steroids really hit their stride is over time, which really works well with the fact that this is an extended release medication. Next slide. In terms of safety summary, safety essentially a little more safety issues with the ILUVIEN group, but nothing that really draws you out. Next slide. This is the overall systemic safety effect, no major things that you see that favor one or the other. Next slide. Looking at ocular systemic -- ocular treatment-emergent adverse events, the reality was that there were more patients with cataracts, which should be expected given the fact that this is a steroid. This cataract surgery essentially happened later in the process. But overall, cataract potentially is a curable thing and is something we would expect typically when we give patients steroids. Next slide. The other thing people worry about with steroids is increase in intraocular pressure and you can see any patient that had any IOP event with 15% in ILUVIEN versus 3.3% in aflibercept breaking into buckets, which I like to do, you have about 2.6% of an IOP greater than 10, 11% greater than 25 and 1.9% greater than 35. Next slide, important to understand what happens to these people. In terms of any surgical procedures, there was 4.5 incidence of any surgical procedures. When we talk about surgical procedures, we have laser and incisional surgery. Lasers were both SLT and PIs. And that was 2.6% in the ILUVIEN Group and incisional surgery was 1.9% in the ILUVIEN Group, which essentially is consistent with other trials or maybe even a little bit better. Next slide. So in summary, the mean number of supplemental injections favored the ILUVIEN arm, but did not hit statistical significance. But in terms of secondary endpoints, there was a statistically significant increase in mean time from last injection in the patients with ILUVIEN of 185 versus 132 days, highly statistically significant. The visual acuity and anatomic changes were right within the non-inferiority arms and essentially 1/3 of the patients who were able to remain supplement pre -- actually in both arms, and showed similar safety in terms of cataract and IOP in previous fluocinolone trials with no retinal detachments or endophthalmitis in the ILUVIEN arm. And then looking at the per protocol population, it showed a statistically significant in mean number of supplement injections favoring ILUVIEN versus aflibercept and a lower total -- number of total injections needed, which is 2.8 versus 7.5, a lower number of injections actually regardless of whether you look at ITT or per protocol population. Next slide. I want to turn this over. I want to thank the -- all the investigator sites and patients who really made this possible, and I want to turn it back over to Nikhil.

Thank you, Dr. Singer. The NEW DAY results position ILUVIEN as an important option for DME patients. We look forward to sharing the results with retina specialists at the ASRS meeting and beyond as part of our broader strategy to position ILUVIEN for long-term growth. In the near term, the NEW DAY results provide an important opportunity to engage and educate customers on the key learnings from the trial, including the potential to support earlier usage of ILUVIEN and its role in reducing treatment burden in DME. Longer term, we also plan to share additional analysis from NEW DAY over time. We announced our preliminary unaudited financial results for the second quarter ended June 30, 2025. The company expects combined ILUVIEN and YUTIQ net revenues of $22.3 million for the 3 months ended June 30, 2025, which is a 38.5% growth over the first quarter 2025 of $16.1 million. Our retina product performance was in line with our expectation. And in closing, I again want to thank the NEW DAY study sites, patients and investigators for making this trial possible. With that, operator, I turn it over to you for questions.

[Operator Instructions] We'll go first this morning to Gary Nachman of Raymond James.

That was really helpful. First, I guess, for Dr. Singer, just how do you think of the relative benefit of having fewer injections with ILUVIEN versus the increased incidence of cataracts and IOP that you see? So maybe explain more what the issue is with a large number of injections and why you would want to reduce that as much? And what portion of your early DME patients you think you would want to transition them to this new type of approach?

Okay. I'll start with the beginning of the question, happy to answer. So essentially, why do we want something that's an extended duration medicine? If we look at diabetic patients, they are notoriously noncompliant and essentially understanding your diabetic patients as a general rule, a lot of them are working age. So if we look at the data, this data that came out, looking at the number of doctor visits that these patients go to who have diabetic macular edema over the course of the year, they have 25 inject -- visits to lots of specialists. And the time they get to you as a retina specialist is actually not very many visits and eye doctors in general have 4 visits. So the fact is you're not going to get as many intravitreal anti-VEGF injections in as you particularly want. So having a drug that essentially works over time, it's very valuable in this patient population. And I've written a number of articles about how noncompliant diabetic patients are. That being said, we can use this. Now, IOP and cataracts are well known, especially my feeling about cataract is interesting. If you're an older patient, cataract is inevitability, and it's sooner in diabetic patients. So we talk about cataracts. And one of the things that I understand is that the vast majority of patients who get intraocular pressure elevations are well controlled with topical medicines. It isn't a first-line therapy. Anti-VEGF will continue, but the thought is there is -- if you look at a number of studies, including an analysis of Protocol T, which is the DRCR network, they showed about 25% of people were essentially nonresponsive to aflibercept, which is, at the time, the strongest DME medicine that was tested in this one-to-one comparison with aflibercept, ranibizumab and bevacizumab. So you've got 25% of your population that are essentially inflammatory-driven more than VEGF-driven, having something that fixes that really has some great value. And as something that's long duration as you look at all the other plays, everybody is trying to play in the long duration race, look at the TKIs and everything else. This is a medicine that has a proven track record that you could see even in this trial, 30% of people was a -- were one and done.

And just to build on Dr. Singer's response, Gary, and good morning, and thank you for joining us. Look, we reported the safety data from the NEW DAY in our presentation this morning. And in general, ILUVIEN was well -- very well tolerated -- was well tolerated in this trial. With a safety profile that is consistent with data from prior ILUVIEN clinical trials and real-world views. And we also believe NEW DAY generated clinically meaningful safety data, including additional data around the IOP increase events in patients who passed steroid challenge. And notably, this is the first prospective steroid trial to use a standardized topical steroid challenge in the protocol, the difluprednate that was given 4 times daily for 2 weeks prior to visit 2.

Okay. That's helpful. And then just Dr. Singer, what portion of your early DME patients would you want to transition over potentially? Is it a significant portion of that patient group?

I mean I think the people that are nonresponsive will be the people that I would do. And what I typically do is I try people with anti-VEGF medicines first. If I look like I'm not making any headway, I'm going to start looking at steroids. And I mean I have an algorithm that I look at people that essentially, if I give you 3 anti-VEGFs and we're not making any -- that many progress, I'll give you -- after the fourth injection, I'll see you back in 2 weeks. If I don't see a 50% drying, okay, then I know it's basically inflammatory driven, and that's where I'll start using steroids. The good news is that by starting in earlier, I'm going to have a higher potential to maintain or increase the vision they have at a much higher chance of making sure they stay compliant. And as you can see from the OCT data that over time, they're going to get even drier than they would have with their anti-VEGF because this population is really inflammatory driven as opposed to VEGF driven as Mary talked about today.

And Gary, if I were to just to build on what Dr. Singer said. As previously communicated, we had identified a target addressable market of over 50,000 DME patients, specifically those with a suboptimal response, as Dr. Singer was talking about following treatment with 2 or more anti-VEGF agents and who've been previously treated with corticosteroids. This estimate is obviously based on -- the estimate was based on a combination of epidemiological data and quantitative market research. So we believe the findings from the NEW DAY study further confirm and validate this TAM, reinforcing the clinical relevance and unmet need within this specific patient population. And what it does is that we believe that this data reinforces our confidence and our ability to capture more of the TAM of 50,000 DME patients. Remember, where -- ILUVIEN is being given to less than 5,000 patients today on a yearly basis. And at this point, we're not speaking about the broadening of the TAM because we're at less than 5,000, we're out of 50,000, right so.

Yes. Okay. And then just another follow-up. Just there were a bunch of these protocol deviations. Just curious what was the biggest issue overall with those patients leading to the deviations. And do you think you need to show the per protocol results for it to be compelling enough? Or is the ITT enough? And then, Nikhil, maybe just talk about how you're going to promote the data, the physicians? And how long do you think it will take for some of the retina specialists to adopt this?

Right. So why don't I take these and then I can -- I'll get help from my colleagues as needed. So look, on the per protocol population, so upon -- we identified a total of 44 out of 306 patients who had major protocol deviations, which potentially confounded the analysis of the data, which is why we shared it. And those 44 patients experienced 73 major deviations that were excluded from the post hoc patient population analysis. And half of those deviations were cases in which a patient did not receive a supplemental injections when they should have and 1/3 of those deviations were cases in which a patient received a supplemental injection but they should not have. Look, the post hoc analysis was conducted on the remaining subset of patients, so 128 and 134, the per protocol population. So that's the answer to that question. Look, the NEW DAY study results are being shared -- going to your -- I think your first question, the NEW DAY study results are being shared with ASRS attendees through a presentation today, a paper on-demand presentation today. And we've added discussions, as you would expect, with some of the investigators, including Dr. Singer, their feedback has been that the NEW DAY study may support -- provides additional data that may support treating early with steroid implant, sorry, and has the potential to benefit patients with DME. And then I think your other question was around what are we doing with this data? So following the release of this data, several next steps are underway. We're preparing additional data presentations at upcoming national and international conferences to further share and contextualize these findings. In parallel, we're actively exploring the potential of including NEW DAY data in promotion aimed at increasing awareness and understanding of the study results, yes.

Okay. So are you still comfortable with the full year guidance for this year? You gave the 2Q sales, are you reaffirming that today for ILUVIEN and YUTIQ?

Yes. We look forward to providing an update on the guidance for the total company and the specific cuts that we provide, including rare disease, generics, et cetera, at the earnings, which is in a couple of weeks.

We go next to David Amsellem of Piper Sandler.

Just a quick one for me. For Dr. Singer, as you think about the anti-VEGF competitive landscape, it's certainly a more varied landscape. You have a number of anti-VEGF option that implantable. So to your point about duration. And so I guess my question here is there is the data that you presented, but I guess, how do you square the dominance of anti-VEGFs and the fact that it is a more varied anti-VEGF treatment landscape, so there's more product offerings and more options compared to, say, 5 years ago with how do you square that with trying to win over hearts and minds regarding earlier usage of the long-duration corticosteroids? So that's my first question. And then secondly, I guess, I'm struggling with how you can leverage post hoc analysis here to drive more usage or earlier usage of ILUVIEN. And I'm just kind of wondering about how that kind of data is going to be received by your peers in the community.

So let me start with the first question. Thank you for asking. So basically, yes, there are a number of anti-VEGF medicines out there. But -- and just understand that I've been involved in all these trials. So the reality is that they all essentially with the exception of one of them really target VEGF. So it's the same pathway. We may have stronger medicines. We may have longer medicines. But again, we're still looking at that proportion of patients that are VEGF receptive. And that's about 75% of people based on that Protocol T analysis I told you, and everyone's jockeying for that process. And even the faricimab product, which essentially is Ang-2 does not affect a lot of these inflammatory factors that Mary showed you in the Slide 4. So the story is that people know inflammation is an issue. What we wanted to know is how well does it stack up. What's interesting to understand is that NEW DAY is -- everybody wants to see NEW DAY because NEW DAY gave everyone a fair shot from scratch. A lot of the steroid trials, and I've written most of those articles, were people who were previously treated. So looking at patients square, understanding in the background that most of DME 3/4 is VEGF-driven. NEW DAY held its own, and it held its own relatively well because of the fact that it had 1 shot versus 5 shots of aflibercept. So in a race that was really stacked against ILUVIEN, it's still pretty much held its own. And then we're going to talk to doctors about that. And doctors do believe that there's more than VEGF in the process. And to your point, as more medicines come out and they talk about new things that are on the horizon, people are realizing that DME has inflammatory factors and that steroids still do a really good job of controlling them, and they have a relatively safe, good safety profile. I mean, as the steroid challenge really decreased the number of people who needed incisional surgery. And the laser surgery which I didn't spend a lot of time was, half of those weren't really due to increased steroid-induced intraocular pressure. PIs are not used for that. So the data is probably really better than before. I think there's a value in that. In terms of your per protocol population, obviously, doctors always kind of go, well, the post hoc analysis, they'll have a little bit of skepticism. What I think was really interesting is regardless if it was at the ITT population or the per protocol population, the time from last injection was highly statistically significant. So the duration play really plays strong. And if you look at all the TKIs that are being and the gene therapies that are being introduced to our landscape, they all played in the fact that they last longer. Nobody really says they're stronger, they last longer. Well, this medicine is approved. It's been out for a while, and I know this is [indiscernible] medicine. I've been involved in those trials. That's a surgical procedure. This is a simple intraocular injection that people have been doing for the last 10 years. Now we're getting it validated that it really can hold its own again the anti-VEGF and in a good set of population where VEGF isn't working, just we should start this earlier because we'll be able to keep the vision better and maintain the anatomy sooner.

Yes. And thank you for your question. I think just 2 things to build on what Dr. Singer said. One, that steroids are the treatment of choice for DME patients that are not well served by anti-VEGF therapy and Dr. Singer put out some numbers about total DME population and what percentage are served by the menu of anti-VEGF therapy that's available. So that's one. And then the second is what this study was evaluating was looking at -- assessing the efficacy of ILUVIEN as a baseline therapy in patients with early DME, right? So -- and assessing the safety and tolerability of ILUVIEN and aflibercept in combination in patients with DME. So there's no -- there's a clear understanding that anti-VEGF is the first-line therapy. What we were exploring with the NEW DAY study is the efficacy of ILUVIEN as a baseline therapy in patients with early DME and using a multimodal approach to treatment as is done in several therapeutic areas.