IVERIC bio, Inc.
Q3 2016 Earnings Call Transcript

Published: 8 Nov 2016

[Operator:]

Good day everyone and welcome to the Ophthotech Corporation Third Quarter 2016 Earnings Results Conference Call. Today’s conference is being recorded. At this time, I would like to turn the call over to Kathy Galante. Please go ahead.

[Kathy Galante:]

Good morning and welcome to our third quarter 2016 earnings call. Joining me today, I have Dr. David Guyer, Chief Executive Officer and Chairman of Ophthotech; Dr. Samir Patel, President and Vice Chairman; and Mr. Glenn Sblendorio, Executive Vice President, Chief Operating Officer and Chief Financial Officer. Before we begin, I would like to remind you that today we will be making statements relating to Ophthotech’s future expectations regarding its financial results, potential receipt of milestone payments, clinical and regulatory developments, and commercialization plans. These statements constitute forward-looking statements for purposes of the Safe Harbor provisions under the Private Securities Litigation Reform Act of 1995. These statements may cover many events and matters that are subject to various risks that could cause actual results to differ materially from those expressed in any forward-looking statement. I refer you to our SEC filings and in particular to the Risk Factors section in our quarterly report on Form 10-Q filed on August 05, 2016 for a detailed description of the risk factors affecting our business. 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, even if our views do change. I would now like to turn the call over to David.

[Dr. David Guyer:]

Thanks, Kathy, and thank you to everyone for joining us on the call this morning. This is an exciting time for Ophthotech, as we prepare for initial topline data read out from two trials of Fovista focus during combination with Lucentis for the treatment of wet age-related macular degeneration. As we have previously stated, we are presently on track with final data cleaning and expect data lock and unmasking of data for both trials to be completed in time to allow us to report initial topline data from both of these pivotal trials in this fourth quarter. Now, our key objective and plan is to make Fovista commercially available to physicians for their patients with wet AMD, as quickly as possible, subject to positive data outcome for the Phase 3 program and successful regulatory approval. Between now and data, we continue to focus on compiling a new drug application shell in an effort to ensure efficiency for an optimized NDA submission to the FDA, again it’s subject to obtaining a positive outcome of the Phase 3 trials. As you will recall, the FDA granted fast track status for Fovista for wet AMD in September 2013. We believe Fovista is the most advanced anti-PDGF agent in development for the treatment of wet AMD. And if approved, it’s expected to be first to market in this class of novel therapies for wet AMD. The third Phase 3 trial which is investigating Fovista in combination with either Eylea or Avastin, completed patient recruitment in June 2016. The Company expects initial topline data from this trial to be available in the second half of 2017. I will now turn the call over to Samir.

[Dr. Samir Patel:]

Thank you, David. Thank you, everyone for joining us this morning. As David stated, we are actively engaged and busy working towards generation of a new drug application shell, assuming the positive outcome of the Phase 3 trial. We were pleased to announce last week that the results of our Phase 2b Fovista combination therapy study in wet age-related macular degeneration have been published in Ophthalmology, a journal of the American Academy of Ophthalmology. As you may recall, this prospective randomized, controlled of Phase 2b clinical trial of 449 patients with wet AMD indicates that Ophthotech’s Fovista 1.5 milligram administered in combination with Lucentis, met the pre-specified primary endpoint of mean change in visual acuity. Patients receiving the combination of Fovista 1.5 milligram and Lucentis gained a mean of 10.6 letters of vision on the ETDRS standardized chart at 24 weeks, compared to 6.5 letters for patients receiving Lucentis monotherapy a p value of 0.019. This represents a 62% additional benefit from baseline. No significant safety issues were observed for either treatment group in the trial. The safety, visual and anatomic outcomes of this study served as a basis for our Phase 3 Fovista in combination with anti-VEGF registration program. The published article “Dual Antagonism of PDGF and VEGF in Neovascular AMD”, and of course can be accessed on the Ophthalmology website. We would like to thank all of the coauthors for their time and commitment to the Fovista Phase 2b study. The Fovista expansion studies are designed to further to evaluate the potential of Fovista in addressing a variety of unmet need in wet AMD including investigating the potential role of Fovista in combination with multiple anti-VEGF agents to reduce sub-retinal and investigating the potential role of Fovista combination therapy to reduce treatment burden for wet AMD patients. These studies are progressing as planned. We continue to enroll patients into Phase 2/3 trial of Zimura in patients with geographic atrophy, an advanced form of dry AMD. In addition to Phase 2 trial evaluating the potential role of Zimura when administered in combination with anti-VEGF drugs for the treatment of wet AMD has also been activated. I will now turn the call over to Glenn.

[Glenn Sblendorio:]

Thank you, Samir and good morning everybody. This morning, I'll present a brief update on our financial results. Collaboration revenues for the quarter ended September 30, 2016, which were recognized under the Novartis agreement was $1.7 million, a decrease of $1.7 million compared to the same period 2015. The decrease in the quarter primarily related to a decrease in drug shipments to Novartis. Collaboration revenue for the nine-month period ended September 30, 2016 was $45.6 million, a decrease of $1.1 million versus the same period in 2015. As we look forward to Q4, we expect to recognize revenue primarily from our R&D activities and then planned shipments, additional shipments to Novartis during the period. Research and development expenses were $50.9 million for the quarter ended September 30, 2016 compared to $40.5 million for the same period in 2015. Research and development expenses were $136.9 million for the nine-month period ended September 30, 2016 compared to $97.1 million for the same period in 2015. The increase in R&D expense in both the quarter and the nine-month period ended September 30, 2016 relates to increased cost associated with our Fovista program, which includes manufacturing activities, our Phase 3 clinical program, and the FES studies as well as increased compensation expense associated with additional research and development staffing. We anticipate R&D expenses to increase as we continue our Fovista Phase 3 trials, also continue our enrollment in the Fovista Expansion Studies and continued enrollment into some more studies and ongoing manufacturing expense, including validation. As we’ve mentioned in previous calls, our R&D expense may fluctuate from quarter-to-quarter, as we continue to validate our Fovista manufacturing processes. In addition to that, we will continue to produce commercial grade Fovista API and continue to produce some more API for our ongoing clinical program. General and administrative expenses were $12 million for the quarter ended September 30, 2016 compared to $10.4 million for the same period in 2015. General and administrative expenses were $37.2 million for the nine-month period ended September 30, 2016, compared to $32 million for the same period in 2015. The increase in general and administrative expenses in both the quarter and the nine-month period ended September 30, 2016 relates primarily to increased cost to support the expansion of the Company’s operations, additional staffing, and increased share-based compensation. The Company reported net loss for the quarter September 30, 2016 of $60.9 million or $1.71 per diluted share compared to a net loss of $39.6 or $1.14 per diluted share for the same period in 2015. The Company reported net loss for the nine-month period ended September 30, 2016 of $127.1 million or $3.59 per diluted share compared to a net loss of $70.1 million or $2.03 per diluted share for the same period last year. Fully diluted weighted average common shares outstanding for the quarter ended September 30, 2016 were $35.6 million. Finally, turning to our balance sheet, cash, cash equivalents, and available for sale securities totaled $321.2 million as of September 30, 2016. Now, I would like to turn the call back over to David.

[Dr. David Guyer:]

Thank you, Glenn. Thank you everyone for your time this morning and for your continued support. I will now turn the call back over to the operator, so we can open up the lines for any questions. Thank you. [Operator Instructions] And will go first to Anupam Rama with JP Morgan.

[Unidentified Analyst:]

Hi, guys. It’s Eric in for Anupam. Thanks for taking the question. Just a question regarding the potential label assuming positive data at the end of the year. I know you've had a lot of questions about whether we should expect specific label or whether you would be seeking a broader anti-VEGF indication. But do you have a sense from regulators what would satisfy your broader VEGF label? And to the extent the concern is more potentially around safety than efficacy, do you have the ability to supplement the initial NDA with the data from the Avastin-Eylea combo study? Thanks.

[Dr. Samir Patel:]

So, I think we haven’t had level of specificity as you indicated about the label but in general, I think I can make the following comments which may be helpful to you. I think that in connection to the aspect of the sub-types of lesions and things of that sort, I think it's been shown we believe fairly convincingly that when you adjust for all the variables, there is really not much difference between those sub-types. And we think we will have a fairly good argument in connection to that, assuming the data are supportive. I think in connection to the breadth of label and different anti-VEGF that are utilized in combination, I mean, I think we have to just demonstrate that the addition of Fovista and its response is not really different amongst all the three anti-VEGF agents and specifically on the 1004 study is to show rough equivalent across the spectrum of efficacy and basic parameters. Does that answer your question?

[Unidentified Analyst:]

Yes, mostly. I guess I was just sort specifically wondering whether safety data from the ongoing third Phase 3 study is something that could be used to supplement the initial filing without looking efficacy at the end of specific matters that we think? [Ph]

[Dr. Samir Patel:]

Yes. So, I think in general in all these trials and safety, you look at all safety of exposure of the drug, not just the study that's forth coming 1004 but also previous studies, the Phase 1 studies being Fovista Expansion Studies, any exposure, because as you know the trials are powered by primary endpoint on the efficacy and the real understanding of safety is ongoing process, not only previous trials but the trial in question and future exposure as well.

[Operator:]

And we’ll take our next question from Yatin Suneja with SunTrust.

[Yatin Suneja:]

Thank you for taking my question; couple of questions, first one on the manufacturing. I mean, we recently saw you lined up the fill and finish provider. What else do you need to make sure you have in place before so that you can have a timely launch? And then, I have another question.

[Dr. Samir Patel:]

I thinkthat’s right. Fill and finish really was the last piece of the manufacturing chain. So, we were very happy to get that in place. I think on the API, we have -- we had been talking about validation and that continues to go well. Obviously, as time goes on, we’ll continue to look at second sources, which we’re actually doing now, both on the API and on the drug assessment side. So, I think we are well-prepared for getting ready for next year and data.

[Yatin Suneja:]

Got it. And then, just one more question. After the failure of Regeneron co-formulated product, I mean what’s your updated thought on what sort of expectations do you have from this trial? Do you think the failure of Regeneron PDGF co-formulation might affect [ph] the bar? And do you have any updated thoughts on the co-formulation work that you’re doing with Novartis? Thank you.

[Dr. David Guyer:]

Yes. Greetings, Yatin. Thanks for your question. So, I think with respect to our confidence on the Phase 3 trial and its outcome is really unchanged. I think that the strength of data, both from our Phase 1 and how we supported the Phase 2 trial design and its sample size, and the data outcome and the robustness of the Phase 2 study sort of speaks for itself, and the publication highlights some of the recent publication that we just discussed, highlight it’s particular strength and its support for confirmatory Phase 3. I think that there are other -- as we previously stated, we continue to believe, we are first in class and best in class; that’s something we’ve always self advocate. We also believe that targeting the ligand is definitely more beneficial than targeting the receptor. I think we’ve talked about that previously as well. And I think that it wouldn’t be appropriate for me to comment on all the data from the study you’re referring, simply because I don’t think we’ve seen the totality of the data. So, I don’t think it affects anything. I think if you look at the Phase 1 data that we are in that trial, we are not really surprised by the outcome in the Phase 2 trial. But absolutely no bearing on what we think is going to happen with the Phase 3 trial on our side. And regarding the co-formulation question, we’ve nothing more to add than what we have before that is we think that as you’ve seen and heard in various time space that we’ve had, the physicians’ prefer choice with respect to the availability of the anti-PDGF and anti-VEGF separate presentations, but we also are developing with -- and thinking about variety of other presentations, which includes co-formulation as one of them and not only that through Novartis that you referred but other revenues as well.

[Operator:]

And we’ll take our next question from Yigal Nochomovitz with Citibank.

[Yigal Nochomovitz:]

Hi, thanks for taking the question. Just firstly, on the timing of the data for the Phase 3 within Fovista, can you be any more specific about when in the fourth quarter, we expect the data to rise? Thanks.

[Dr. David Guyer:]

No, as we said earlier, we are in final data cleaning and very soon we’ll have the database lock within that. [Ph] The data in previous earnings call I think that one of the questions we went over just industry wise how long that takes. So, we believe we are on track as of now for data for this fourth quarter; so, sometimes between now and end of the year.

[Yigal Nochomovitz:]

Okay, thanks David. And then I had a few questions on the Phase 2b take or I just was curious -- I was expecting to see some data on retinal thickness reported in the Phase 2b given that you had OCT measurements taken at weeks 4, 8, 12 and 24. So, Samir, any thoughts on the why that wasn’t included in the study in the paper? Thanks.

[Dr. Samir Patel:]

Specifically I think as far as talking about the paper, it's written by co-authors. So, I think rather than talking but paper, I mean in general to your question, which are the same time of parameters that have been shared in previous meetings and as one, the thickness parameters are there but what really matters is what is it's relevant. So, if you look at the relevance, I don’t understand why, what happens at three months or four months or five months really is of relevance. If you take a look for example in some of the randomized, controlled trials, the group with the thickest retina is the best in one trial and another trial the thinnest one is the best. So, there is no correlation at all. So that's really that relevant. If you look at the CAT study, the patients who had the thinnest and the thickest retina had the worst outcome. So, what you really want to look at are the morphologic parameters. And thickness can involve a variety of different elements. It could reflect to help with the neurosensory retina, the amount of hyper reflective materials that's made up of fibrosis for example, if it's ways of retinal, pigment epithelial detachment, none of these have really that much relevance or vision. So I think that it doesn’t serve any purpose. What we've shown is I think much more relevance and showing the fluid in various compartments. And that I think is much more informative. And we believe it's a much more sophisticated treatment of the process. I will say this so, as far as the paper is concerned, the amount of information that was given, I think the editors probably saw it as more than what typically is shown, not a single question was came out about the thickness and parameters that you just discussed.

[Yigal Nochomovitz:]

Okay, thanks. And it was great to see the aero bars reported for the -- on the primary endpoint to see that there was a good separation for 1.5 milligrams and Lucentis control. I guess I was curious why you chose not show aero bars for some of the other anatomic endpoints specifically on the improvements in visual acuity as a function of base line CMD lesion size?

[Dr. Samir Patel:]

Yigal, if you are scientific about it in terms of clinical trials and you can discuss this to this day, those are all exploratory endpoints; and all not exploratory endpoints have just that hypothesis generating. And secondly, as far as the valuation is concerned, given the multiplicity, you can’t look at a point estimate and give aero bars. For example, just to give you an example, you could have a key value that's significant but it doesn’t necessarily mean that the inference is what one would want to gather in scripted statistic. So, they are not valid and for that reason it could be misleading. And the way to really look at the scripted statistics is look at the actual numbers and the totality of the data and trends that they give and any in front based on our aero bars or p value is not appropriate.

[Yigal Nochomovitz:]

Okay. Thanks and then just a few specific questions on the way that the Phase 3s are being run. I’m assuming that you’re using a sham injection for the control for the Phase 3 as we’ve done in the Phase 2b, is that correct?

[Dr. Samir Patel:]

Yes, all randomized files today, most of randomized files today that I’m aware of, it is sham injection but it doesn’t really penetrate if that’s what you’re asking to get the syringe itself -- in the standard for as much as -- as long as I can remember soon perhaps 2,000, all randomized controlled trials.

[Yigal Nochomovitz:]

And when Fovista is administered, 30 minutes later, do are the investigators really administering the anesthetic or is it just with the initial anti-VEGF?

[Dr. Samir Patel:]

I mean I think all the details on the protocols are there and whatever is publicly available, and I don’t know anything else to add at this point.

[Operator:]

We’ll take our next question from Tyler Van Buren with Cowen & Company.

[Tyler Van Buren:]

So, next month when the data reads out, there is clearly multiple ways to win here. And perhaps one of the scenarios that is more in the middle state scenario where both trials reach statistics, yet only show more like a 2.5 letter benefit, which is obviously about on ages statistics. How do you think about the clinical utility of that? And more importantly, what other data will be important to consider as you examine the overall clinical utility. For instance, will we see three line gainers or losers, and what delta would be meaningful, say like 5%, 10%, 20%, any insight would be helpful there.

[Dr. Samir Patel:]

So, it’s very important question and a very complex one and perhaps, I’ll try to summarize some of the fundamentals. First and foremost what is really important is the totality of the data looking at the safety and the totality in particular related to your question. You now there is no magic number, whether it’s 3, 4, 5 letters, whatever it is that constitutes either clinical meaningfulness or approval for that matter. You have to look at the totality of the data, the broad range of parameters for clinical meaningfulness, they are really complicated when you have mean change your vision because of different gate plans, variables the different endpoints. And these are lot of the ones you’ve talked about were binary endpoints of clinical meaningfulness. So, there is a fundamental disadvantage of creating of the binary variable and in that considerable amount of information is lost. You get reduction in power, you get all scores on one side of the touch point; they’re all weighted equally, there is lots of information, there is influence of ceiling and floor effect and you have to examine this for each trial and each of those combined. So, what I’m trying to say here is a great depth of analysis is necessary to put the proper context, so that you understand what the mean change of vision means. I would realize that some individuals often say, three is significant and four is and five and I understand the need to do that. But, it really is the totality of the data. And we share and agree with the FDA that that totality has to be valued. So, I'll give you a specific example to your question. If you look at protocol 3 for instance. I think you had a 3.6 lever or somewhere in that range difference in that particular study. Yet if you look at the page sub-group of patients that were in 2030, 2040, there wasn’t much of a difference but they when you enter 2050 or worse, it is approximately a 4.2 letter difference and that was considered very meaningful. I don’t even think that was -- what wasn’t -- not all of those aspects were evident if you look at the first primary end -- secondary endpoint, for example. So that's served as a good backdrop to see that the totality of the data requires thorough analysis so you understand what the meaning change in vision is.

[Tyler Van Buren:]

Okay, that's helpful. Is that possible that we would have the data stratified by base line visual acuity when it reads out potentially next month?

[Dr. Samir Patel:]

I mean that's clearly an analysis amongst what we have to do that I just talked about. I think that those kind of leveled details I would not expect in general and when I consider topline where you have to do a thorough analysis.

[Tyler Van Buren:]

And just to be clear, besides mean visual acuity gain would you look at three line gainers or three line losers as potentially the other most important visual acuity endpoint? And if so, kind of what delta has been observed there that it is meaningful in most clinicians asked?

[Dr. Samir Patel:]

So, again, it's not something you can just have a binary answer to as much as I’d like to share with you, I'll just do it by example. If you take a look for in Phase 2 for example, I think we had in one of the analyses using missing values that I think was a [indiscernible] roughly there was a difference in three line gain of 36 versus 30, which on surface looks like it could be a meaningful. But yes, you look at the four and five line gainers, you see a marked difference between the combination therapy meaning that the 36% in the combination were most of the patients kept on going on. And I you have a significant number that we are gaining four and five lines, yet because of the cut point issue I just mentioned earlier, it doesn’t expose the true benefit when you use a cut point. So, only if the context is presented that the example of the four and five line gainers can you analyze with any validity, what the three lines gain means, otherwise it's open to misinterpretation. Does that example helps kind of explains why it is that you have to look at the totality of the data with a greater depth of analysis?

[Tyler Van Buren:]

Yes, that's helpful. I appreciate your thoughts. Thank you.

[Operator:]

And we’ll take our next question from Geoff Meacham with Barclays.

[Geoff Meacham:]

David, you mentioned completing a lot of work ahead of the filing, just curious if you can go to little bit more detail what's the gating factor beyond the Phase 3; it CMC, is it talks of the preclinical, just kind curious what's left to be done?

[Dr. David Guyer:]

I was referring to writing out the show for all of the various sections as far as -- we’re in very good shape on a lot of them. It's really about getting the data, being able to put it in your shell and all of the components. And all of the components have been written or partially written or written we just need to fill things and I that’s the goal for us to get through by data.

[Geoff Meacham:]

Got you. Okay. And then for David or Samir, I just wanted to get your thoughts on the ANG2 mechanism and kind of what that -- based on the data so far or any of the work that you guys have done on that as a combination approach in the wet AMD or DME?

[Dr. Samir Patel:]

Yes. So we have looked at it, we don’t think it’s anywhere close to anti-PDGF and its potential in improving outcomes in wet AMD. I think most would agree that has any role, it would be for stabilization of endpoint anti-permeability [ph] and if you look in one of the studies, in Phase 1 studies from one of the pharmaceutical companies, you see that monotherapy administered anti-angiopoietin-2 did not affect the permeability at all and I believe there was one patient that lost letters and continued to get therapy and lost even greater amount of letters all the way through. When we see that kind of data, it’s gives us a little bit of pause. And so, we’ve looked at it, but we just don’t think it meets our standards for development into a clinical study.

[Operator:]

And we will take our next question from Joseph Schwartz with Leerink Partners.

[Joseph Schwartz:]

Thanks very much. I was wondering if you can talk about whether you’ve been doing any pricing work to position yourselves to have the most market impact heading on how the data in three Phase 3s looks. In other words, are you making your decision on pricing based on the data from the 2 Phase 3s in combo with Lucentis or do you think that you’re going to need to take into account the data you see in the next, the third Phase 3 in combo with Eylea or Avastin? There are different price elasticities in these different market segments and how are you thinking about having the most impact, based on the data that you see for Fovista on top of the various VEGFs?

[Dr. David Guyer:]

Yes. So, we’ve done a lot of work on pricing, but obviously, we really need to see the data before we can make our final recommendation that is something that we are not going to discuss publicly at this time, sure to say we’ve got a commercial team and Chief Commercial officer who launched the first anti-VEGF in the space, launched the first blockbuster XALTAN Pharmacia and comes from Alexion and his brought another from Alexion with him. We have a reimbursement expert that’s been full time with us for a number of years now. So we’ve got a very good team that’s done a lot of pre-launch work in this area. But really can’t share anything publicly at this point.

[Joseph Schwartz:]

Okay. And then maybe a question for Samir, is there any reason to believe that Fovista or PDGF inhibitors in general will produce more or less of a benefit in combination with different VEGF inhibitors? Obviously, the ranibizumab [ph] data was a surprise. Do you think that any of that could be due to the VEGF that’s being used in combo with a PDGF antibody or even after?

[Dr. Samir Patel:]

Yes, I think we can comment on the formulation, the geometry, the basis clinical data that served the basis for the data you’re talking about. I think suffice it to say, as far as your question about Fovista’s compatibility with other anti-VEGF agents, we've see no reason why there should be any issues. I think that's one of the benefits of [indiscernible] to begin with. I think you've seen the data at the Science Day, where those were real world patients, with very advance disease and the number of patients were limited and with the follow-up up to one year. Those were not with Lucentis, they were with other anti-VEGF agents and also there was ISD done by retina consultants in Arizona and even there the other anti-VEGF agents were used with compelling data as well. So, there is no reason to believe that Fovista would act any differently as of today with any of the anti-VEGF agents.

[Operator:]

And we’ll take our next question from Matthew Harrison with Morgan Stanley.

[Vikram Ashoka:]

Hi. This is Vikram on for Matthew. So, a lot of investors have been focused on baseline imbalance in lesion size as impacting the strength of the Phase 2 data. Could you give your views on how important lesion size is as a prognostic sector in these trials and if you think that impacted the Phase 2 data?

[Dr. Samir Patel:]

Yes, first, I think the publication speaks for itself and there is lot of discussion of that. I mean this is a very top journal and we’d expect that’s something -- and I think that tells you that there is no validity to the statement of impact with the data because of lesion size measurement in itself. So, just to give you some background, I don’t know why someone would think that would affect it to that level in terms of one to one correlation with lesion size, nor are we aware of any uniform or constant consistent trend. So, if you look for example at the Anchor trial, if you look at three line gain in the 0.5 milligram, the largest lesion did not have the worst outcome, as you would expect. The 0.3 milligram, the smallest lesion in Anchor did not have the best vision as you would expect. If you look at mean vision with 0.3 milligram in Anchor, the second quartile in fact had the best outcome, not the smallest lesion. In Marina there was no real difference in mean change in vision in the two smallest quartiles. Harbor had the publication for example stating different predicators of visual outcome and area [ph] lesion was not a predictor of outcome. In the view trials, I think it was view one, the smallest CMB side had the worst outcome and largest one had the best outcome. In the CAT, the second quartile had the best outcome, not the smallest lesion. So, you got your CAT view, Harbor, Marina, Anchor, and those are all randomized, controlled trials and we don’t see that type of directionality and consistency as some may want to implicate, it’s simply not true.

[Operator:]

And will take our next question from Stephen Willey with Stifel.

[Stephen Willey:]

I guess just another Phase 2b manuscript question. I know that there was analysis showing that there was a reduction in RPE atrophy with the combination. And I guess just wondering, one, if patients were actually precluded from having RTE atrophy at baseline? And then, two, what do you think is the underlying biology that's driving this trend towards reduced RTE in the combo arm?

[Dr. Samir Patel:]

Can you test -- I can give you the biologic but first part of the question I missed. What was the first part of the question, please?

[Stephen Willey:]

Were patients actually excluded from having RPE atrophy at baseline?

[Dr. Samir Patel:]

Sure. To the best of my recollection I think if they had atrophy in the center area, they are excluded for the simple reason that it would be very difficult to assess any drug effect. As far as the biology is concerned, so ultimately heard on choroidal neovascularization is a wound healing response. So, in that particular setting, you could expect epithelial-mesenchymal transformation for example to be occurring. And you can have migration of the retinal pigment epithelium to the side of choroidal neovascularization. And PDGF has been shown to be chemotactic for the retinal pigment epithelial cells. It’s been shown to be operative in segment in augmenting epithelial- mesenchymal transformation. So, there is a lot of possibility by inhibiting PDGF, you may be retarding the loss of pigment epithelium to those mechanisms. But of course it needs to be validated in a more randomized, controlled and prospective fashion. We look forward to the results to teach us something in connection to your question.

[Stephen Willey:]

Okay. And maybe just another question, I guess more preclinical. Some of the literature seems to suggest that there is some controversy around parasite biology just with respect to cell type of origin and the characterization of cell signatures. So I guess when you think about the parasites that you’re trying to ship off the vascular, do you feel that those have been adequately characterized with respect to the cell surface markers that those are supposed to be expressing? Thanks.

[Dr. Samir Patel:]

Yes. I think it’s a good question, the evolving field. I think that it’s always been a bit difficult to quantify all the parasites that are there because of either deferring receptor expression and all the stains at different phases of the parasites into chemical setting. For example, there is some heterogeneity depending on their stage and that flows on receptor expression, some of the host parasites, may not be expressing the receptors for PDGF for example where as the active [indiscernible] really highlights themselves are reactive cells and their origin and depending on microenvironment, they may take on a very different phenotypes which may typically be challenged to go ahead and characterize, I mean put some unique categories all the way through. But it is an involving science and we continue to f learn more about it. Good question.

[Operator:]

And we have time for one final question, which we’ll take from Ling Wang with BTIG.

[Ling Wang:]

Thank you for taking my question. First, congratulations on getting the Phase 2b data published. So for question I have, the first is I think you disclosed some of the secondary endpoints in your filings. I just wanted to understand whether there are additional anatomic endpoints or how should we be thinking about those endpoints, if they’re included relative to the clinical endpoint? And secondly, can you clarify whether -- you mentioned you were doing the final data cleaning now. Are you using a third party CRO or internal effort to clean the data? Thank you.

[Dr. Samir Patel:]

A word that I can say about the endpoints that you just referred to as I said previously in one of the questions to evaluate clinically meaningfulness requires a broad range of end points especially in descriptive statistics. The issue of secondary and supportive gets blurred in that particular setting and can be quite misleading. So, as far as -- good way to think about is what you were really alluding to which is the functional endpoints and the anatomic endpoints. Now as far as the functional endpoints are concerned for reasons that I mentioned earlier that there is lots of efficiency, the cleaning meaningful endpoints have touch points, they have a lots of data, the power issues, so, you have to look at all the real endpoints to understand the distribution and the sub groups that are affected. So, we will do that as part of our total analysis. As the imaging endpoints yes, there will be imaging endpoints as well. And what we would like to do always to go ahead and try to understand that they’re predictive biomarkers. Now you know in medicine in general predictive biomarkers have been quite illusive and anti-VEGF space is really no different as it's today as our Phase 2 paper indicates that to the best of our knowledge we’re not aware of a single biomarker that's predictive from a visual acuity perspective after the induction phase. So, our purpose will be if we are able to get clinically meaningful benefit to look for some of the predictive biomarkers and that would include imaging for sure and try to make some sense out of it. Hope that answers your question.

[Ling Wang:]

Yes, thank you. That's very helpful. Maybe you can answer my second question about the CRO or internal efforts for data cleaning?

[Dr. David Guyer:]

Yes, we work with the large outside CRO.

[Ling Wang:]

Got it> Thank you. Looking forward to the Phase 3 data.

[Dr. David Guyer:]

Thank you. And I would like to thank everybody for their attention and continued support, and we’ll now end the call. Thank you.

[Operator:]

Thank you. And that does conclude today’s conference. Thank you for your participation. You may now disconnect.