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spk12: Hello, and welcome to the Iverick Bio, Inc. First Quarter 2022 Earnings Conference Call. All participants will be in listen-only mode. Should you need assistance, please signal a conference specialist by pressing the star key followed by zero. After today's presentation, there will be an opportunity to ask questions. To ask a question, you may press star, then one on your touchstone phone. To withdraw your question, please press star, then two. Please note, today's event is being recorded. I'd now like to turn the conference over to Kathy Galante. Ms. Galante, please go ahead.
spk07: Good morning and welcome to Ivericbio's conference call. Representing Ivericbio today are Mr. Glenn Splendorio, Chief Executive Officer, Dr. Praveen Dougal, President, Keith Westby, Chief Operating Officer, David Carroll, Chief Financial Officer, Dr. Double Desai, Chief Development Officer, Chris Sims, Chief Commercial Officer, and Tony Gibney, Chief Business and Strategy Officer. I would like to remind you that today we will be making statements relating to Iberic Bio's future expectations regarding operational, financial, and research and development matters. These statements constitute forward-looking statements for purposes of the Safe Harbor provision under the Private Securities Litigation Reform Act of 1995. These statements cover many events and matters that are subject to various risks that could cause actual results to differ materially from those expressed or implied by any forward-looking statement. I refer you to our SEC filings and in particular to the risk factors included in our annual report on Form 10-K filed on February 24, 2022 for a detailed description of the risk factors affecting our business that could cause actual results or events to differ materially from the forward-looking statements that we make. In addition, any forward-looking statements represent our views only as of today and should not be relied upon as representing our views as of any subsequent date. While we may elect to update these forward-looking statements at some point in the future, we disclaim any obligation to do so except as required by law. I would now like to turn the call over to Glenn.
spk03: Thanks, Cathy, and good morning, everyone, and thanks for joining our first quarter conference call. This is an exciting time for ivericbio as we prepare for top line data readout from Gather 2, our second phase three clinical trial for Zamora for the treatment of geographic atrophy, or GA, in the third quarter of this year. This is approximately one year after the enrollment of the last patient, plus some time needed for database lock analysis, which Keith will discuss in more detail in a moment. Our key objective and plan is to make Zimora commercially available to physicians and their patients with GA as quickly as possible, assuming a positive data outcome from Gather 2 and regulatory approval. As we prepare for Gather 2 results, we are working diligently to assemble a thorough and complete new drug application, or NDA. Following a potential positive outcome of Gather 2, we plan to submit applications with the FDA and the European Medicines Agency for marking approval of Zomora for GA. As a reminder, we received a written agreement from the FDA under a special protocol assessment, or SPA, for the overall design of Gather 2 in July of 2021. For those who may not be familiar, the SPA process is a procedure by which the FDA provides a clinical trial sponsor with an official evaluation and written guidance on the design of a proposed protocol intended to form the basis for an NDA. As we get closer to reporting the Gather 2 top line, we made a number of new hires to lay the groundwork for a successful launch. IFSAMURA is approved. We are well positioned and with an established medical affairs team already in place and continue to build out our commercial infrastructure with a team that has extensive experience in launching drugs for retinal diseases with large market potentials. As we announced in our press release this morning, we continue to provide additional exploratory analysis from GATHER-1, which we believe further supports the consistency of the positive data that we previously reported for GATHER-1 and inform future potential development opportunities for Zamora and other indications. Both Dr. Dougal and Dr. Desai will review the details of the analysis in a few moments. We also continue to execute our IP strategy for Zamora. In March of this year, the US Patent and Trademark Office granted us a patent with claims covering methods of use to treat GA. This issue patent is expected to expire in 2034, which we which will extend our market exclusivity in the U.S. by several years. We also plan to initiate a clinical trial studying Zamora in patients with intermediate AMD in the fourth quarter of 2022. Our development strategy in this indication is subject to global regulatory feedback from the FDA and other regulatory authorities, which we plan to obtain before initiating this trial. Looking ahead at the potential of Zamora, we continue to invest in additional lifecycle initiatives for Zamora in order to expand the patient population with additional indications, and we are also evaluating multiple sustained release delivery technologies. We look forward to the exciting opportunities that lie ahead of us in 2022, including receiving top-line data for GATHER2, and being closer to reaching our goal of providing patients and physicians with a treatment for GA for which there are currently no treatment options available. I'd like to now turn the call over to Keith.
spk11: Thank you, Glenn, and good morning, everyone. We are pleased to report that GAD2 continues to exceed our expectations for patient retention and injection fidelity. As we enter into the home stretch for obtaining and reporting year one data for GATHER2, a major priority for us is to continue to aggressively drive patient retention and thereby further de-risk the clinical trial. We continue to target patient retention for the GATHER2 clinical trial as measured by injection fidelity rate through month 12 of greater than 90%. Injection fidelity is calculated by dividing the total number of actual injections, drug, and sham for all patients by the total number of expected injections, drug and sham, based on the total number of patients in the trial. We consider injection fidelity to be the most important and stringent measure of patient retention because it reflects the timely administration of study drug into the patient's eye. As of today, we continue to maintain an injection fidelity rate of well above our 12-month target of greater than 90%. As a comparison, the 12-month injection fidelity rate for our GATHER-1 trial in which we observed a statistically significant reduction in GA progression at 12 months was 87%. We continue to focus on injection fidelity, not only to de-risk and protect the integrity of our data, but also to potentially observe the early and increasing reduction in GA growth that we previously observed in GATHER1. To date, we are excited we have reached a trial completion rate of 94% for year one of GATHER2 clinical trial. the time point for the primary efficacy analysis, after which, based on a positive outcome, we plan to apply for FDA and EMA approval. Therefore, with only approximately 6% of year one visits remaining in Gather 2, we are encouraged to see that our efforts to maximize patient retention in Gather 2 have resulted in even greater patient retention than was observed in Gather 1 through the same time period. As you may recall, we completed patient enrollment in Gather 2 in July 2021, four months ahead of our original schedule. Based on this timeline, we expect top line Gather 2 data to be available in the third quarter of this year, approximately one year after the enrollment of the last patient, plus the time needed for database lock and analysis. We are actively working internally and with our third party vendors to prepare for the Gather 2 database lock to be as efficient as possible. We believe patient retention is an integral part of the GATHER2 outcome. Patient enrollment in STAR, our Phase 2b screening clinical trial of Zomora for the treatment of autosomal recessive Stargardt disease is ongoing. The results of this trial are expected after the top line results of GATHER2. Turning to IC500, our HTRA1 inhibitor. We initiated a number of preclinical tolerabilities and pharmacokinetic studies last year, and we are planning for IND-enabling toxicology studies to begin this year. We expect to submit an investigational new drug application, or IND, to the FDA for IC500 during mid-2023. Thank you for your time. I will now turn the call over to Double.
spk01: Thank you, Keith, and good morning, everyone. As Glenn mentioned, we're excited to share with you today the results of a new post hoc analysis from Gather One. This analysis evaluated the reduction in GA lesion growth in patients receiving Zimora as compared to patients receiving sham based on the distance of a patient's GA lesion to the foveal center at baseline. This analysis is scheduled to be presented this Friday, May 13th at the Retinal World Congress in Fort Lauderdale, Florida by Dr. Glenn Jaffe, Robert Mockamer, Professor of Ophthalmology and Chief of the Retina Division at Duke Eye Center. In line with the overall results of GATHER-1, we observed a reduction of lesion growth in patients receiving Zomora compared to patients receiving sham. This reduction was consistent across all baseline distances from the foveal center. In addition, The greater the distance of the GA lesion from the foveal center of baseline, the greater the reduction in growth in the Zumura group as compared to the Shan group. Previous studies have shown that GA lesions further away from the foveal center grow faster, and that these faster growing GA lesions may show a greater growth reduction following complement inhibition. Our observations were consistent with these previous studies. We believe the results from this post hoc analysis suggest that early administration of Zimora, when GA lesions are further away from the foveal center and growing the fastest, may be the most beneficial. We believe these results are consistent with the previously reported results for GATHER1, and we look forward to testing this hypothesis further with the larger data set from GATHER2. Please see the press release we issued earlier this morning for details of this analysis. Thank you for your time. I will now turn the call over to Praveen.
spk08: Thank you all for joining the call this morning. I hope that all of you are well. And thank you, Davil. Great work by you and your team. As we continue to provide these exploratory analyses from GatherOne, We continue to see a pattern of the potential for us to observe in GATHER2 a reduction in the rate of GA growth for patients receiving Zimora as compared to patients receiving sham similar to that observed in GATHER1. Equally importantly, we continue to see consistent results, which gives us a great deal of confidence in the robustness of the GATHER1 data. At this year's angiogenesis exudation and degeneration conference, results from a post-hoc analysis that evaluated various GA growth parameters to explore the rate of disease progression within various regions of the fovea in a subset of patients from Gather 1 were presented. Consistent with the overall results of Gather 1, in the post-hoc analysis, a reduction in lesion growth in five standardized regions surrounding and including the central foveal area was observed for patients receiving Zumora 2 milligrams as compared to patients receiving sham over a period of 18 months. We believe the preservation of the central foveal region may be associated with clinical and functional outcomes important for GA patients. To summarize, we believe this data has the potential to bridge the anatomical results that we observed to functional outcomes. By preserving the central phobia, we hypothesize that patients may have the opportunity to continue to drive, read, live independently, et cetera, for longer periods of time as compared to the natural history of the disease. It must be stressed, however, that this is an exploratory post-hoc analysis that requires further confirmation, and we anticipate performing a similar analysis for GATHER-2 to further build upon these insights. Last month, working with an independent and mass reading center, we provided the results of a post-hoc analysis of the cases of choroidal neovascularization, or CNV, in the Zamora 2mg group, 67 patients total from Gather 1. As we previously reported, the incidence of investigator-reported CNV in the study eye in the Zamora 2mg group in Gather 1 was 6 patients, or 9%, at 12 months and 8 patients or 11.9% at 18 months. The post hoc analysis was performed by the internationally recognized Center for Ocular Research and Evaluation, also known as CORE, at the Cole Eye Institute of the Cleveland Clinic. The reading center read optical coherence tomography or OCT images for the eight patients in the Zamora 2mg group who developed CMV in the study I. OCT images were read to determine the number of CMV cases that were macular neovascularization, or MNV, which is neovascularization that affects the macula versus peripapillary neovascularization, where the neovascularization is located around the optic nerve and not encroaching on the macula. All eight cases were MNV. For those eight cases, the Reading Center further classified cases as either exudative or nonexudative based on the following OCT criteria. Exudative MNV is MNV that presents with new onset fluid in either the subretinal space or the intraretinal space. The subretinal space is the area on OCT between the retinal pigment epithelium and photoreceptor cells. The intraretinal space is the area on the OCT containing the photoreceptors and other neurosensory cells of the retina. Based on this definition, among the eight CMV cases in the Zmura 2mg group in GABA-1 at month 12, four cases of exudative MMV translating to 6% of patients and two cases of non-exudative MMV translating to 3% of patients were reported. And at month 18, six cases of exudative MMV translating to 9% of patients, and two cases of non-exudative MMV translating to 3% of patients were reported. The Reading Center also reviewed the baseline OCT images for the eight patients in the Zamora two milligram group who developed CMV in the study eye looking for the presence of a double layer sign at baseline. A study published in 2019 in the peer-reviewed journal Ophthalmology Resna found that the presence of a double-layer sign is correlated with the presence or development of non-exudative MNV in eyes with AMD. And the clinical experience has shown that this type of non-exudative MNV often progresses to exudative MNV. Based on scientific literature and clinical understanding among the retina community, we believe the presence of a double layer sign on OCT may be a useful biomarker to predict the future onset of cases of exudative MMV and may potentially be a biomarker that allows for a personalized management and follow-up strategy. In this retrospective review, the Reading Center found that among the six Gather 1 patients in the Zamora 2 milligram group who developed exudative MMV over 18 months, five of those patients had a double layer sign at baseline. The Reading Center also found that neither of the two Gather 1 patients in the Zamora 2 milligram group who had non-exudative MMV at 12-month and 14-month and 18-month time point had it. a double layer sign at baseline. For this retrospective review, OCT images were graded at the reading center by two masked independent readers with the gradings confirmed by two additional masked independent senior readers. All OCT gradings for those patients were unanimous among all readers. All of the readers remained masked to treat an arm throughout the review. We are excited to share these Gather 1 analyses with you. We plan to perform the same analyses on the Gather 2 data. Thank you for your time. I will now turn the call over to Dave.
spk02: Thank you, Praveen, and good morning, everyone. I'd like to highlight a few items from our press release of this morning. and provide some guidance on our expected year-end cash balance and our expected cash runway. For the quarter, our net loss totaled $34.5 million, or $0.29 per share, compared to a net loss of $26.8 million, again, or $0.29 per share, for Q1-21. This increase in net loss was driven by increases in both R&D and G&A expenses. R&D expenses increased primarily due to the continued progression of our Gather 2 clinical trial, increased manufacturing activities for Zamora, and increased personnel costs, including share-based compensation associated with R&D staffing. G&A expenses increased primarily due to increased personnel costs, including share-based compensation associated with preparations for the potential commercial launch of Zamora. Turning to our expected year-end cash balance and cash runway. As of March 31st, our cash totaled approximately $346 million. We continue to estimate that our year-end cash balance will range between $215 million and $225 million. We estimate that our cash will be sufficient to fund our planned capital expenditures and operating expenses through at least mid-2024. These estimates are based on our current business plan, which includes the continuation of of our ongoing clinical development programs for Zamora NGA and Stargardt's, the initiation of an intermediate AMD clinical trial, the preparation of potential filing of an NDA and MAA for Zamora NGA, continuing preparations for the potential commercial launch of Zamora NGA, investing in sustained delivery technologies for Zamora, and the advancement of our IC500 development programs. Excluded from these estimates are any potential approval or sales milestones payable to the Archimedes Corporation, or any potential expenses for the actual commercial launch of Zamora, including Salesforce expenses, and any additional expenses related to potentially studying Zamora in indications outside of GA, Stargardt's, or intermediate AMD, or resulting from the potential in-licensing or acquisition of additional product candidates or technologies or any associated development that we may pursue. Thank you for your time. I'll turn the call back over to Glenn.
spk03: Thank you, Dave, and thank you for your time this morning and your continued support of the company. We look forward to providing you data in the third quarter and updates as they come throughout the year. Now turn the call over to the operator so that we can open up the line for any questions. Operator?
spk12: Yes, thank you. As mentioned, at this time, we will begin the question and answer session. To ask a question, you may press star, then 1 on your touchtone phone. If you are using a speakerphone, please pick up your handset before pressing the keys. To withdraw your question, please press star, then 2. At this time, we will pause momentarily to assemble the roster. And the first question comes from Yorgi Yardov of the Cowan & Company.
spk10: Thank you so much for taking our questions, and congratulations on all the progress. So, just a few from us. First, on the analysis of new onset CNV cases in gutter one, are these new results more closely comparable to the results presented from your competitors? And related to that, maybe if we can talk about in discussions with KOLs, Where is usually their focus on when comparing the safety of different GA assets? And then maybe start with that one, and then I'll have just a couple shorter follow-ups.
spk03: Okay, Yorgi. I think we'll turn it over to Praveen.
spk08: Thank you, Glenn. Yorgi, thank you for the questions. In regards to the first question, you know, I can't really give you a great answer on that because, you know, I really would prefer to talk about our data. I don't want to pretend to know what our competitors' definitions are, but what I will tell you is that this notion of exudation is very important, and it's important to understand the way we went about grading this. What we did was we went to the Cleveland Clinic, and we had four graders, as mentioned, who were completely masked. The analysis was unanimous, and we asked them to simply grade new onset sub-RPE fluid, new onset sub-retinal fluid, and new onset intra-retinal fluid not related to atrophy. And once those were graded, which was really a very, very systematic procedure, we asked them to define what they would define as exudation. And what they said was, we would define exudation as new onset sub-retinal fluid and new onset non-atrophy-related cystic fluid. And based on that, that is our definition of exudation. And we gave that definition and the numbers about as transparently and openly as we possibly can. In regards to your question about safety, I think it's important to put the safety in two different buckets. One bucket would be non-exudation-related safety, and the other would be exudation-related safety issues. In terms of the non-exudation related safety issues, I think it's important to look at inflammation as well as endophthalmitis or infection of the eye. We believe that our safety profile is excellent. There are no cases, as you know, from Gather 1 in regards to inflammation or endophthalmitis. The other bucket, as we've discussed in detail, is the conversion bucket, which is the conversion to a CNV bucket, which you know in detail and we've described also with the traditional definition of CNVM as well as this exudation that we've discussed in detail today. So I hope that answers your question, but thank you for your question.
spk10: No, that's great. And just a couple of sort of follow-ups. I guess first, you mentioned impressive injection fidelity rate that continues to trend above your target. You also took a number of measures to improve the amount of missing data in GADR 2. Do you have any update on are we still tracking above the GADR 1 levels? And then secondly, regarding the NDA filing, how soon after the data is disclosed later this year would you be in position to file, and what are the remaining gating items?
spk03: Yeah, Yorgi, I'll take the second question. on the NDA, and then I'll turn it back to Keith to talk a little bit about what's going on in Gather 2. So obviously, we're doing a lot of work now to get the data out. I think one thing that you should take note of, we had said originally the second half of the year for data, I think because of the great work being done by the team, we're able to now refine that. And in today's call, we talked about having the data in the third quarter. So you can tell the team is working on everything they can. We're in a very fortunate situation to have one of two trials completed, so it gives our regulatory team, who have been working on the NDA for some time, the opportunity to work with one data set. Obviously, you need the second to prepare. Second, it goes back to some of the comments I made. We are highly motivated to hopefully get this drug to patients as soon as possible. So I think as a team, it's an experienced team, we're doing everything we can to narrow that time between positive data readout, if that comes, and getting the NDA in. So more to come on that. It would be very difficult, even if I laid out plans today, to do that with precision until obviously we see the data. But I think the important takeaway there is the motivation of the company to get this in for review as quick as possible, and most importantly, to get this new drug to patients. Keith?
spk11: Sure. Thanks for your question, Jorge, on patient retention and injection fidelity. So, you're absolutely correct. We put a target out there for ourselves of greater than 90% for injection fidelity. As of today, we're well above that target. Also, in terms of Also, I'll mention for Gather One, we were at 87%. For the patient retention efforts that we've put in place, started at the beginning of the trial and then continued to ensure that we had the right efforts in place throughout the duration of the recruitment as well as up until this point. But we're really happy to see that our efforts to maximize patient retention have resulted in greater retention that we had in GATHER-1 through this time point. So we're really tracking well to de-risk the study as much as possible.
spk03: I'll add one to Keith's comment that may be helpful. Keith also in his commentary talked about being at the 94% visit completion. So I think that's also an important metric there as you think about where we are and getting closer to data.
spk10: No, that's great. Thank you so much, and congratulations again on all the progress.
spk03: Thanks. Appreciate your questions.
spk12: Thank you. And the next question comes from Annabelle Samami with Stifel.
spk00: Hi, good morning. This is Stacy calling in for Annabelle. Congratulations on the post hoc analysis, and thank you for taking our questions. We have two, if we may. The first is, the best rate of reduction in growth of lesion that are further from the phobia is consistent with everything you guys have been telling us to date and seems to justify treating early. But to what extent do the patients have impairment when the lesions are 1 through 1.5 millimeters from the center, which is where the rate of reduction was the greatest? So in other words, this is validating for treating early, but will this motivate patients to get treated early? And secondly is how is intermediate GA defined? Is it by location of lesions? And how might you go enrolling the intermediate trial given what you know about the rate of reduction and weight that has on what patients will feel the most clinical benefit? Thank you.
spk03: Stacey, great questions. I'm going to ask Double to address both of those questions, and Praveen may have some comments as well.
spk01: Yeah, Stacey, thanks for the question. So as it relates to your first question regarding the degree of impairment for these lesions that are further out, I think it's highly variable depending upon which patients that we're talking about. Certain folks that are in professions that kind of use a lot of that peripheral vision could be highly impacted by this, where others may not. I think the important thing to remember here, though, is that like most chronic diseases, the sooner you get in and you treat them, the less likely they are to have impact on downstream health. And when we're talking about vision, that becomes even more critically important. And so let me ask Praveen to weigh in here as well as a physician that has seen these patients for many, many years.
spk08: Yeah, that will thank you. And Stacey, thanks for the questions. Really, really good questions. Let me answer one at a time. The first thing that I would like to point out is what you mentioned, Stacey, which is the consistency of the data. We started out by saying there's a good biologic reason to assume that complement inhibition will work best and have the biggest delta in the fastest growing lesions. And sure enough, that's been shown because extra foveal patients have a larger delta than patients where the phobia is affected. And that's been shown many times, including by our competitors. And I think one of the big take-home messages here is that we've targeted a patient population that is absolutely correct and appropriate, and I believe we've de-risked our trial greatly by targeting this patient population. After that, what we've also shown in the angiogenesis presentation is that within that area of extra-phobia lesions, If you look in a micro way at the lesions area that would be expected to grow fastest, which is in a circumferential pattern, indeed that is exactly where the delta is even greater. And that's the presentation that Glenn Jaffe presented in angiogenesis. And now what we've shown is that the fastest growing lesions that are the furthest away indeed have the largest delta. So in effect, there are three different patterns or three different analyses that we have shown that show exactly the same results and the same consistency. So I think the first thing that I would stress is the consistency of the data, which makes this data a lot more robust. Now, how this translates clinically, here's what I would say, and you've probably heard me say this before, If anybody wears glasses, the easiest way to translate this is by putting the smallest piece of scotch tape that you possibly can on the sides or the bottom of your glass away from the center of your vision. And I guarantee that you won't be able to work during the day. My point of saying that is that it's not about visual acuity. It's really about any amount of distortion, any amount of a blind spot that you may see that will prevent you from doing your job. If you're an architect, and there's a slightest bit of distortion that's off-center, it's very difficult to work. If you're a lawyer that can't finish reading a sentence because there's a blind spot that prevents you from completing your sentence, that's a problem. There are many, many, many of those patients out there, and those patients tend to be younger, they tend to be in the workforce, and those patients will be specially motivated. So we are very happy that we have potentially a treatment for these patients The other one that I would tell you in terms of the intermediate AMD is that the definition is really not our definition. It's the definition that's been adopted by the community, the retina community, which is the size of the drusen, as well as changes that occur on top of the drusen, which are changes in the photoreceptor cells that we call irora or incomplete RP and outer retinal atrophy, which will then progress to cirora or complete RP and outer retinal atrophy. We also look at other items such as hyperreflective foci, which reflects the RPE cells that move out from their natural area onto the retina. So there are a number of these criteria that are OCT-based that will define what we call intermediate geographic atrophy. So Stacey, thanks for the question. I hope I answered it. I'm sorry to take such a long time answering your questions.
spk00: That was super helpful. Thank you so much.
spk03: Thank you, Stacey.
spk12: Thank you. And the next question comes from Tiago Falls with Credit Suisse.
spk09: Thanks for taking the question. So we've discussed this a little bit in the past, but there's still a lot of debate and detailed cross-trial comparisons between GATHER-1 and Bellasus trials, despite all the warnings for not to do so, and a lot of focus on how baseline characteristics might be impacting the efficacy and safety results. Again, if you can just kind of highlight the most significant baseline characteristics and differences in inclusion-exclusion criteria between the GATHER studies and the program that was run by your competitors. We know the LOI TNP criteria is fairly different, for example. But perhaps emphasizing how that may actually help to contextualize either efficacy or safety results for the GATHER studies. I know it's an imperfect comparison, but at least prospectively, what might some of those differences translate to in terms of advocacy and safety? Thanks.
spk03: Well, thanks, Tiago, and thanks for the questions. So let me start out from the top, and I'll ask Keith to get into some of the details and for Vian to give his view. The way we are looking at this is the results of GatherOne. We look at that on its own. The safety profile and also the efficacy profile. The data from both, the safety and also the efficacy, are quite good, and when we look at what is out there in the market with other trials that are going on or have been completed, the results are the best that are out there, and that means those are potentially the best for patients. We have the potentially if GATHER2 replicates GATHER1, the best efficacy profile, And second, potentially the best safety profile. So that's the way we look at it. And you're right, cross-trial comparisons are very difficult. Sometimes they're misleading. So I'm focusing on our data and what we can do for patients. If Gather 2 does replicate that, we have a very strong data set that we believe the regulators will take a look at, especially in light of the fact that there's unmet medical need and we believe that it has a very good chance of gaining approval and getting to patients. So that's kind of my top level, trying to avoid the comparisons, because at the end of the day, we do not know all the details of those other trials, so it's very hard to make that comparison. Second, you know, we're making an assumption, which we believe is supported by data that we see from GATHER-1 and all the additional analysis, whether it be on exudative CNV or the data that Dovel spoke about today about location of lesions. So we're feeling really good about our data. I'm not sure that we've seen those types of analysis from other companies or the depth of definition behind those analyses. So I know that's not answering your question specifically, but that's the way we're approaching it. Praveen, thoughts from you?
spk08: Yeah, thank you, Glenn, and Tiago, thank you for the question. You know, I just want to sort of step back and ask you to take a look at GatherOne. What I would say is the emphasis here really should be in the consistency of the data. You've got two independent arms that are therapeutic, completely independent of each other. One is a 2-milligram arm, the other is a 4-milligram arm. the efficacy profile of those two arms are almost identical. To statistically, you know, forget biology, but just statistically have two different arms that are entirely independent of each other have an efficacy profile that's almost identical with a dose response, both on the efficacy side as well as the safety side, and to have all that happen by chance, you know, is really infinitesimal. The fact that there is the consistency of the data that we see in GATHER-1 and then in the post-hoc analyses as we've discussed, that same consistency with the biology that complement inhibition should have a bigger delta in the areas that grow faster is repeated over and over and over again. It gives us a great deal of confidence that if we're able to simply get the drug in the eye and have patient retention as defined by injection fidelity, that we will be able to de-risk gather two and replicate the data set that we have in gather one. So I think we feel very confident that in the inclusion criteria we will get the same patient type because our inclusion criteria really hasn't changed at all. And I think the consistency of the data in gather one and the consistency that we see over and over again in the sub-analyses that we do, the post-hoc analyses in gather one gives us a great deal of confidence that Gather 2 has the potential to replicate the results of Gather 1. But thank you for your question.
spk09: Thanks again for talking to me, Patrick.
spk12: Thank you, Theodore. And the next question comes from Chris Howard in with Jefferies.
spk05: Hey, good morning. Thanks, everybody, and appreciate you taking the questions. Good morning, Chris. Hey, thanks, Glenn. So I wanted to start off in maybe something that I wrote in a note previously around anti-VEGF use in that perhaps that could be used as a good proxy for important safety events that happen in one of these GA trials. And subsequently, obviously, I've had the benefit of the conversations with the team, so I guess... My question to you is that how should we view VEGF use in your trials, and how might that translate to some of the personalized approaches that you mentioned in your prepared remarks, Praveen?
spk03: Praveen, I think Chris asked that of you.
spk08: Yeah, thank you, Glenn, and Chris, good morning. Thank you for the question. The first thing that I would say is the difference between GATHER-1 and GATHER-2 is not an inclusion criteria, but there is one slight change in the exclusion, which is that in GATHER-1, when we started that trial, the Duke Reading Center did not know whether in those few patients who developed a coroneal vascular membrane, whether the lesion could be accurately measured or not. So because they did not know, and in order to protect the integrity of the data, what we did was to exclude those patients from further measurement of the geographic atrophy. Retrospectively, Duke has now reconsidered that data and is convinced that those lesions can be accurately measured. So what we're doing in GATHER2 is we're continuing to follow those patients. However, we are also asking that those patients be treated with an anti-VEGF. We're supplying a labeled anti-VEGF, ILEA or Lucentis, and we're requiring that those patients be treated on label. Now, we know from previous studies that Zumora has been used with an anti-VEGF, namely Lucentis. We have two separate studies. These are small open-label studies that have been done with quite impressive results, which is that 60% of patients are three-line or more gainers. So we have evidence that these two products can be used simultaneously without any ill effects whatsoever, and in fact, it may be a beneficial effect. So we're requiring that they be used on label. Now, the other part of the question, Chris, is, is the anti-VEGF use a proxy to the rate of neovascularization? And the answer is absolutely not. And I say this because, unlike our competitors, all of our patients at baseline had an intact phobia. So we have every reason to make sure that these patients have their phobia protected we will require on-label use for that reason because we want to be absolutely certain that these patients get optimal treatment and continue to have the phobia protected. So I hope that answers your question. Chris, thank you again for your question.
spk05: Yeah, no, that's great. And my apologies, Glenn, for earlier. I guess if I may, a follow-up question to some of the discussion around the intermediate AMD study that will be started later this year. You know, what is your view on the end point there and kind of, you know, the palatability of running that type of study, given that, you know, competitors have decided not to pursue that opportunity?
spk03: Yeah, thanks, Chris. I'm here with Devil, and he's going to take that.
spk01: Yeah, thanks, Chris. I think one of the things that we always think about when we think about our development programs here is how do we continue to push the disease curve left? And intermediate AMD obviously is the next step for us in doing that. Now, given some of the news that has come out lately about endpoints and what the FDA will and won't accept, our plan here is we think we have a clear line of sight on what the agency might accept as a proposed endpoint, and we're planning on meeting with them later this year to confirm that. I think it's probably a bit premature to say this or that as an endpoint, but we have a host of different endpoints that we think the agency will kind of buy in on, and we're committed to taking that to the agency and getting their feedback on that shortly. So stay tuned. More news to come on that a little bit later on this year.
spk05: Okay. All right, well, thank you very much, and I appreciate you taking the questions.
spk12: Thank you, Chris. Thank you. And the next question comes from Colleen Cussey with Bayard.
spk06: Great, thanks. Good morning, and thanks for taking our questions. So for the post hoc analysis that you shared today, how many patients are included in this subset analysis? And are you able to share the patient numbers for the different distances from the fovea? And as a thought to that, I guess, is there anything in place that would ensure they gather two would have a roughly similar breakdown of patients in terms of their distance from the fovea, in terms of a similar rate to the other one.
spk01: Hey, Kali, thanks for the question. So the number of patients that were used in the analysis were the same that were used in the analysis that was presented at angiogenesis. And these are 47 eyes from the 2-milligram group, 57 from the 4-milligram group, and 79 from sham. And you'll see that as Glenn Jaffe presents that data later next week at the RWC Congress. As it relates to whether Gather 2 will break down the same way, it's impossible to say. The good thing that we've seen is, you know, the consistency of the data that we've seen in Gather 1, there's no reason for us to believe we haven't changed any of the inclusion-exclusion criteria that it would be significantly different But we won't know that until we open up that database to see exactly where these lesions fall.
spk06: Great. Thank you. That's helpful. And realizing this is a very heterogeneous disease, so it might be hard to answer, but when the roughly 70% of incident patients present with GA in the extra foveal region, how far from the foveal center do those lesions typically present? as part of why I ask is, could the real-world benefit in newly prevalent patients actually be much higher than what we'd be seeing in a clinical trial?
spk01: Yeah, so I'll take the first part of that, and then I'll ask Praveen to jump in with his clinical experience. I think it really just depends on where these patients are coming from. I think most patients that you wind up seeing in retina clinics these days are referred there from either the GO or the OD based on having disease that is either encroached onto the foveal center or is getting very close. And so you'll typically tend to see now patients that have disease that's probably pretty close. As treatments become available and more eye care physicians and professionals understand that they can refer these patients earlier, I think we will see a movement of those lesions being further and further out and patients potentially getting more benefit from treatments like these as it gets into the retinal offices earlier. Praveen, do you have additional thoughts?
spk08: Yeah, I mean, double thank you for, and Colleen, thank you for your question. Look, we've seen this movie before, and we saw this with the anti-VEGF story, right, where in the beginning, and I'm old enough to remember this, you know, where patients, we would say, look, we would just have patients come in if, you know, the other eye is damaged and, you know, you're looking at a monocular patient that's coming in, late in the course of disease with bad vision. And then we realized that the anti-VEGFs will actually do better if we treat them earlier. And now we're treating patients, you know, really as early as possible as soon as we see any neovascularization whatsoever. And I think exactly the same thing is going to happen here. The difference here, Colleen, is that we've got data to actually prove that. And this is what you see consistently, which is that the earlier you treat with a complement inhibitor, the better the results. So I fully expect that these patients will come in earlier and earlier. And I think that all the numbers that we have are really, you know, quite a large underestimate of the number of patients that are out there. We'll have a better idea once we have the treatment and hopefully we'll have the treatment in the market. But, yes, I do believe that these patients will come in earlier and earlier. These patients may not have a decrease in visual acuity, but they certainly have a great compromise in terms of visual function.
spk06: Got it. That's helpful. Thank you. And one more quick follow-on, if I can. You mentioned plans to file in Europe, assuming GATHER2 is positive. Have you spoken to regulators there on whether this study would be supportive of filing? And what sort of market exclusivity would you expect in the European markets?
spk03: Yeah, Colleen, it's Glenn. And no, we have not yet spoke to the regulators. We've been preparing, working with our consultants and our regulatory team. But we do have a plan to engage them, which will give us the guidance on filing strategy. As you know, we've had those discussions already with FDA here. And the second was on market exclusivity in Europe. Was that the question, Colleen? Yeah, so we would expect that we would have market exclusivity through 10 years, which is allowed in Europe.
spk06: Great. Thanks for taking our questions.
spk12: Thank you.
spk03: Thanks.
spk12: Thank you. And this concludes the question and answer session. I would like to turn the floor to Glenn Sondorio for any closing comments.
spk03: Yeah. Thank you, Keith, and appreciate you hosting the call today. And thank you, everybody, for listening. I think you hear it in the voices today, and I hope you can, the excitement here. about Gather 2 and how we're getting to the point where we're going to get to see data. A few takeaways. Gather 2 execution by the team has been outstanding through a pandemic in which we put in a number of operational things that benefited patients and the investigators to hopefully finish with an injection fidelity rate that's well above the target that we set. I think you heard a lot about that today and It's really a testament to the patients to come to these visits, the investigators' commitment to continue to treat these patients and the team at Iverick. The second thing I want to mention that I am truly excited about is the build-out of our commercial team that will be engaging health care providers in the future, and that is the building out of the medical team by Dovel and the commercial team by Chris. As we do this and as we get out and engage, different aspects of commercializing this product. We're learning a lot about the market and the ways that we can shape this market with a great drug. And finally, we did refine our guidance on data output from the second half to the third quarter, and we look forward to having that discussion with you in the near future. So thanks, everybody, for listening, and have a great day.
spk12: Thank you. The conference has now concluded. Thank you for attending today's presentation. May now disconnect your lines.
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