IVERIC bio, Inc. (NASDAQ:ISEE) Q1 2022 Earnings Conference Call May 4, 2022 8:00 AM ET
Kathy Galante - SVP of IR
Glenn Sblendorio - CEO
Pravin Dugel - President
Keith Westby - COO
David Carroll - CFO
Dhaval Desai - Chief Development Officer
Chris Simms - Chief Commercial Officer
Tony Gibney - Chief Business and Strategy Officer
Conference Call Participants
Georgi Yordanov - Cowen & Company
Annabel Samimy - Stifel
Tiago Fauth - Credit Suisse
Chris Howerton - Jefferies
Colleen Kusy - Baird
Hello, and welcome to the IVERIC bio, Inc. First Quarter 2022 Earnings Conference Call. [Operator Instructions] 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.
Good morning, and Welcome to IVERIC bio's conference call. Representing IVERIC bio today are Mr. Glenn Sblendorio, Chief Executive Officer; Dr. Pravin Dugel, President; Keith Westby, Chief Operating Officer; David Carroll, Chief Financial Officer; Dr. Dhaval Desai, Chief Development Officer; Chris Simms, 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 IVERIC 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 statements. 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.
Thanks, Kathy, and good morning, everyone, and thanks for joining our first quarter conference call.
This is an exciting time for IVERIC bio as we prepare for topline data readout from GATHER2, our second Phase 3 clinical trial for Zimura for the treatment of geographic atrophy, or GA, in the third quarter of this year. This approximately one year after the enrollment of the last patient plus sometime needed for database lock analysis, which Keith will discuss in more detail in a moment.
Our key objective and plan is to make Zimura commercially available to physicians and their patients with GA as quickly as possible. Assuming a positive data outcome from GATHER2 and regulatory approval. As we prepare for GATHER2 results, we are working diligently to assemble a thorough and complete new drug application, or NDA.
Following a potential positive outcome of GATHER2, we plan to submit applications with the FDA in the European Medicines Agency for marketing approval of Zimura 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 GATHER2 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 GATHER2 topline, we made a number of new hires to lay the groundwork for a successful launch.
If Zimura 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 GATHER1, which we believe further supports the consistency of the positive data that we previously reported for GATHER1 and inform future potential development opportunities for Zimura in other indications.
Both Dr. Dugel and Dhaval Desai will review the details of the analysis in a few moments. We also continue to execute our IP strategy for Zimura. In March of this year. the U.S. Patent and Trademark Office granted us a patent with claims covering methods of use to treat GA. This issued 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 Zimura 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 Zimura, we continue to invest in additional lifecycle initiatives for Zimura 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 topline 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.
Thank you, Glenn, and good morning, everyone.
We are pleased to report that GATHER2 continues to exceed our expectations for patient retention and injection fidelity. As we enter into the homestretch 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 GATHER1 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 derisk 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. Today, we are excited we have reached a trial completion rate of 94% for year one of GATHER2 clinical trial. The timepoint 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 GATHER2, we are encouraged to see that our efforts to maximize patient retention in GATHER2 have resulted in even greater patient retention than was observed in GATHER1 through the same time period.
As you may recall, we completed patient enrollment in GATHER2 in July 2021, four months ahead of our original schedule. Based on this timeline, we expect topline GATHER2 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 GATHER2 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 Zimura for the treatment of autosomal recessive Stargardt disease, is ongoing. The results of this trial are expected after the topline results of GATHER2.
Turning to IC-500, our HtrA1 inhibitor, we initiated a number of pre-clinical 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 IC-500 during mid-2023.
Thank you for your time. I will now turn the call over to Dhaval.
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 GATHER1. This analysis evaluated the reduction in GA lesion growth in patients receiving Zimura, 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 13, at the Retina World Congress in Fort Lauderdale, Florida by Dr. Glenn Jaffe, Robert Machemer, Professor of Ophthalmology and Chief of the Retina Division at Duke Eye Center.
In line with the overall results of GATHER1, we observed a reduction of lesion growth in patients receiving Zimura 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 at baseline, the greater the reduction in growth in the Zimura group as compared to the sham 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 Zimura, 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 Pravin.
Thank you all for joining the call this morning. I hope that all of you are well. And thank you, Dhaval, great work by you and your team. As we continue to provide these exploratory analyses from GATHER1, 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 Zimura 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 GATHER1 were presented.
Consistent with the overall results of GATHER1 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 Zimura two milligrams as compared to patients receiving sham over a period of 18 months. We believe the preservation of the central fovea 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 fovea, we hypothesize that patients may have the opportunity to continue to drive, read, live independently, et cetera, for a 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 GATHER2 to further build upon these insights.
Last month, working with an independent and masked reading center, we provided the results of a post-hoc analysis of the cases of choroidal neovascularization, or CNV, in the Zimura two-milligram group, 67 patients total from GATHER1. As we previously reported, the incidence of investigator reported CNV in the study eye in the Zimura two-milligram group in GATHER1 was six patients or 9% at 12 months, and eight 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 Zimura two-milligram group who developed CNV in the study eye. OCT images were read to determine the number of CNV cases that were macular neovascularization, or MNV, which is neovascularization that affects the macular 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 leading center further classified cases as either exudative or non-exudative 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 CNV cases in the Zimura two-milligram group in GATHER1 at month 12, four cases of exudative MNV translating to 6% of patients, and two cases of non-exudative MNV translating to 3% of patients were reported.
And at month 18, six cases of exudative MNV translating to 9% of patients, and two cases of non-exudative MNV translating to 3% of patients were reported. The reading center also reviewed the baseline OCT images for the eight patients in the Zimura two-milligram group who developed CNV 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 Retina 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 MNV, 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 GATHER1 patients in the Zimura two-milligram group who developed exudative MNV over 18 months, five of those patients had a double-layer sign at baseline.
The reading center also found that neither of the GATHER1 patients in the Zimura two-milligram group who had non-exudative MNV at 12-month, 14-month and 18-month timepoint had 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 treatment arm throughout the review. We are excited to share these GATHER1 analyses with you. We plan to perform the same analyses on the GATHER2 data.
Thank you for your time. I will now turn the call over to Dave.
Thank you, Pravin, 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 were $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 GATHER2 clinical trial, increased manufacturing activities for Zimura, and increased personnel cost, 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 Zimura.
Turning to our expected year-end cash balance and cash runway. As of March 31, our cash totaled approximately $346 million. We continue to estimate that our year-end cash balance to 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 continuation of our ongoing clinical development programs for Zimura in GA and Stargardt's, the initiation of an intermediate AMD clinical trial, the preparation of potential filing of an NDA and MAA for Zimura in GA, continuing preparations for the potential commercial launch of Zimura in GA, investing in sustained delivery technologies for Zimura and the advancement of our IC-500 development program.
Excluded from these estimates are any potential approval or sales milestones payable to the Archemix Corporation, or any potential expenses for the actual commercial launch of Zimura, including sales force expenses, and any additional expenses related to potentially studying Zimura in indications outside of GA, Stargardt's or intermediate AMD were 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.
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, I'll turn the call over to the operator, so that we can open up the line for any questions. Operator?
[Operator Instructions] And the first question comes from Georgi Yordanov with Cowen & Company.
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 GATHER1. Are these new results more closely comparable to the results presented from your competitors? And related to that, maybe if you could 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 of shorter follow-ups.
Okay. I think we'll turn it over to Pravin.
Thank you, Glenn, Georgi, thank you for the questions. In regards to the first question, I can't really give you a great answer on that because I'd 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 do is we went to the Cleveland Clinic and we had four graders, as mentioned, who were completely masked, the [technical difficulty] was unanimous and we asked them to simply grade new onset sub-RPE fluid, new onset sub-retinal fluid, and new onset intraretinal 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 intraretinal 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 GATHER1 in regards to information or endophthalmitis.
The other bucket, as we've discussed in detail, is the conversion bucket, which is the conversion to CNV bucket, which you know in detail and we've described, also with the provisional definition of CNV and 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.
No, that's great. And just a couple of sort of follow-ups. I guess, one, 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 GATHER2. Is there -- do you have any update on, are we still tracking above the GATHER1 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?
Yes, Georgi, 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 GATHER2. 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, need the second to prepare.
Second, it goes back to the 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?
Sure. Thanks for your question, Georgi, 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 mentioned for GATHER1, we were at 87%. For the patient retention efforts that we've put in place started at the beginning of the trial and then continue 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 GATHER1 through this timepoint. So we're really tracking well to de-risk the study as much as possible.
Yes, 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.
No, that's great. Thank you so much, and congratulations again on all the progress.
Thanks. Appreciate your questions.
Thank you. And the next question comes from Annabel Samimy with Stifel.
Hi, good morning. This is Stacy calling in for Annabel. 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 fovea is consistent with everything you guys have been telling us to-date, and since you justify treating early, but to what extent do the patients have impairment when the lesions are 1 millimeter to 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 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.
Stacy, great questions. I'm going to ask Dhaval to address both of those questions and Pravin may have some comments as well.
Yes, Stacy, 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 have -- 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 Pravin to weigh in here as well as a physician that has seen these patients for many, many years.
Yes, Dhaval, thank you, and Stacy, 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, Stacy, which is the consistency of the data, we started out by saying there is a good biological 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 extrafoveal patients have a larger delta than patients where the fovea 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 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 extrafoveal 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's three different studies or three different analyses that have been -- that we have shown that show exactly the same results in 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 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 of 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 are an architect and there is 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 RPE and outer retinal atrophy which will then progress to cRORA or complete RPE and outer retinal atrophy.
We also look at other items such as a hyperreflective foci, which looks -- 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, Stacy, thanks for the question. I hope I answered it, and sorry to take such a long time answering your questions.
Thank you. And the next question comes from Tiago Fauth with Credit Suisse.
Hi, congrats on all the progress, and thanks for taking the question. So we've discussed this a little bit in the past, but there is still a lot of debate and detailed cross trial comparisons between GATHER1 and so is trials but despite all the warnings connected to, so -- and a lot of focus on how baseline characteristics might be impacting the efficacy and safety results.
So 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 competitor, we know the color why at CNV criteria is fairly different for example. But perhaps synthesizing how they actually help to contextualize either efficacy or safety results for the GATHER studies. I know it's an impressive comparison, but at least prospectively what might some of those differences translate to in terms of efficacy and safety. Thanks.
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 Pravin to give his view. The way we are looking at this is the results of GATHER1. 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 GATHER2 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 is 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, we're making an assumption, which we believe is supported by data that we see from GATHER1, and will be additional analysis what would be on exudative CNV or the data that Dhaval 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 analysis. So I know that's not answering your question specifically, but that's the way we're approaching it. Pravin, thoughts from you?
Yes, thank you, Glenn, and Tiago, thank you for the question. I just want to sort of step back and ask you to take a look at GATHER1. 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 two-milligram arm, the other is a four-milligram arm.
The efficacy profile of those two arms are almost identical. To statistically -- 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 is really infinitesimal.
So the fact that there is the consistency of the data that we see in GATHER1 and then in the post-hoc analyses as we've discussed, that same consistency with the biology that complement inhibit and 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 GATHER2 and replicate the data set that we have GATHER1.
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 GATHER1 and the consistency that we see over and over again in the sub-analyses that we do and the post-hoc analyses in GATHER1 gives us a great deal of confidence that GATHER2 has the potential to replicate the results of GATHER1. But thank you for your question.
Thank you. And the next question comes from Chris Howerton with Jefferies.
Good morning. Thanks, everybody, and I appreciate you taking the questions.
Good morning, Chris.
I think to -- hey, thanks, Glenn. The -- so I wanted to start off in may be 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, Pravin?
Pravin, I think, best for you.
Yes, thank you, Glenn. And Chris, good morning. Thank you for the question. The first thing that I would say is the difference between GATHER1 and GATHER2 is not an inclusion criteria, but there is one slight change in the exclusion, which is that, in GATHER1, when we started that trial, the Duke Reading Center did not know whether in those few patients who developed the choroidal neovascular 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 the -- a labeled anti-VEGF Eylea or Lucentis and were requiring that those patients be treated on label. Now, we know from previous studies that Zimura 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. In fact, it may be a beneficial effect. So we are requiring that they'd 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 fovea, so we have every reason to make sure that these patients have their fovea 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 fovea protected. So I hope that answers your question. Chris, thank you again for your question.
Yes. No, that's great. And my apologies, Glenn, for earlier. The -- 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. What is your view on the endpoint there and kind of the palatability of running that type of study, given that competitors have decided not to pursue that opportunity.
Thanks, Chris. Here with Dhaval, and he's going to take that.
Yes, thanks, Chris. I think one of the things that we always think about when we think about the 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.
Okay, all right. Well, thank you very much, and I appreciate you taking the questions.
Thank you, Chris.
Thank you. And the next question comes from Colleen Kusy with Baird.
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 the subset analysis? And are you able to share the patient numbers for the different distances from the fovea? And as a follow-up to that, I guess, is there anything in place that would ensure that GATHER2 would have a roughly similar breakdown of patients in terms of their distance from the fovea in terms of similar rate to GATHER1?
Go ahead, Dhaval.
Colleen, 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 two-milligram group, 57 from the four-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 GATHER2 will break down the same way, it's impossible to say. The good thing that we've seen is the consistency of the data that we've seen in GATHER1, there is 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.
Great. Thank you. That's helpful. And realizing this is a very heterogeneous disease, so it might be hard to answer. But when roughly 70% of end-to-end patients present with GA in extrafoveal region? How far from the foveal center do those lesions typically present? It's part of I ask is, could the real-world benefit in newly, prevalent patients actually be much higher than what we be seeing in the clinical trial?
Yes, so I'll take that, the first part of that, and then I'll ask Pravin to jump in with this 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 GEO or the OD based on having disease that is either encroach on to the foveal center or is getting very close.
And so you'll typically tend to see now patients that had 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 getting more benefit from treat -- potentially getting more benefit from treatments like these as they get into the retinal offices earlier. Pravin, do you have additional thoughts?
Yes, I mean, Dhaval, thank you for -- and Colleen, thank for your question. Look, we've seen this movie before and we saw that it would be anti-VEGF story, right, where in the beginning, and I'm old enough to remember this, where patients we would say, look, we would just have patients come in, the other eye is damaged and you're looking at a monocular patient that's coming in late in the course of the 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 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 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.
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 and whether this study would be supportive of filing? And what sort of market exclusivity would you expect in the European markets?
Yes, 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 the FDA here. And the second was on market exclusivity in Europe.
Is that the question, Colleen? Yes, so we would expect that we would have market exclusivity through 10 years, which is allowed in Europe.
Great. Thanks for taking our questions.
Thank you. And this concludes the question-and-answer session. I would like to turn the floor to Glenn Sblendorio for any closing comments.
Yes, 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 GATHER2, and how we're getting to the point where we're going to get to see data. A few takeaways. GATHER2 execution by the team has been outstanding through a pandemic, in which we put it 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 IVERIC. 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 Dhaval 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 in 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.
Thank you. The conference has now concluded. Thank you for attending today's presentation. You may now disconnect your lines.