IVERIC bio, Inc.
Q4 2014 Earnings Call Transcript

Published: 24 Feb 2015

[Operator:]

Please standby, we are about to begin. Good day and welcome to the Ophthotech Corporation Fourth Quarter 2014 Earnings Results Conference Call. Today's conference is being recorded. At this time, I would like to turn the conference over to Kathy Galante, Head of Investor Relations. Please go ahead.

[Kathy Galante:]

Good afternoon and welcome to our fourth quarter year-end 2014 earnings call. Joining me today, I have Dr. David Guyer, Chief Executive Officer and Chairman of Ophthotech; Dr. Samir Patel, President and Vice Chairman; Mr. Michael Atieh, Executive Vice President and Chief Financial and Business Officer; and Mr. Todd Smith, Senior Vice President and Chief Commercial Officer. In addition, we have with us today, Dr. Pravin Dugel, Managing Director at the Retinal Consultants of Arizona and Clinical Professor, USC Eye Institute Keck School of Medicine. Dr. Dugel leads one of the largest retinal practices in the country and is an internationally recognized KOL. Dr. Dugel will discuss the preliminary results of an investigator sponsored study conducted by physicians at the Retinal Consultants of Arizona and presented recently at the Angiogenesis Meeting regarding Fovista combination therapy in anti-VEGF resistant patients. Before we begin, I would like to note that Dr. Dugel's comments today will reflect his own conclusions, opinions and analysis and do not necessarily reflect Ophthotech's conclusions, opinions, and analysis. And also to remind you that today we will be making forward-looking 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 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 in any forward-looking statements. I refer you to our SEC filings and in particular to the Risk Factor section in our quarterly report on Form 10-Q filed on November 12, 2014 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 obligations to do so, even if our views 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. 2014 was an important and very productive year for Ophthotech on multiple fronts. Let me briefly recap some of the highlights from the past year and early this year. We remain on track with respect to the execution of our pivotal Phase 3 program evaluating the safety and efficacy of Fovista, our PDGF antagonist administered in combination with anti-VEGF therapy for the treatment of wet AMD. We are pleased with the recruitment rate in our Phase 3 program and believe that in the near future we will be in a position to provide more specific guidance with respect to the timing for completing patient enrollment. We expect to have initial top line data from the Phase 3 program available in 2016. We believe that Fovista in combination with anti-VEGF therapy may alter relevant tissue responses in wet AMD, which could translate not only to enhance visual gain, but also prevent the inevitable vision loss typically seen in the anti-VEGF monotherapy treated eyes over the longer course of the disease. We have initiated our focus to expansion program to evaluate this potential functional benefit in our anti-fibrosis trials. As part of our Fovista expansion program we are pleased to announce the initiation of our treatment burden reduction program to investigate the potential of Fovista combination therapy in reducing the treatment frequency associated with anti-VEGF monotherapy. Furthermore, we expect to initiate this year a study in patients who have failed anti-VEGF monotherapy treatment and connection with the concept of anti-VEGF treatment failures as Kathy stated during introduction, Dr. Pravin Dugel will shortly discuss the rationale and role of PDGF inhibition in anti-VEGF treatment resistant patients as part of his groups' investigated sponsored trial pilot study. The results of this study were recently presented the Bascom-Palmer Eye Institute Angiogenesis, Exudation, and Degeneration Meeting in Miami. In addition, we are pleased to announce that ARGO [ph] has accepted this study the first presentation and congratulations for this acceptance are in order to Dr. Dugel and his colleagues. Let us now turn to Zimura, our complement factor C5 inhibitor. Complement factor C5 is a central component of the complement cascade believed to play a role in the development and/or progression of age-related macular degeneration. We have recently initiated a Phase 2 trial of Zimura in combination with anti-VEGF therapy for patients with polypoidal choroidal vasculopathy, a variant of wet AMD. On the dry AMD front, we previously completed a Phase 2a trial with monotherapy in geographic atrophy, a dry form of AMD. We are continuing internally and with our consultants to refine our clinical regulatory strategic and commercial plans for Zimura dry AMD deprogram and expect our Phase 2/3 dry AMD trial to begin in the second half of this year. As a reminder, in November 2014 we announced that we entered into an option agreement for tivozanib for non-oncological ocular indications. This is a highly potent, selective small molecule VEGF tyrosine kinase inhibitor. These properties are attractive for successful development of sustained release formulation which we believe will be important for the long-term or maintenance phase of wet AMD management. We have begun work on an ocular formulation and we hope to provide more guidance in the second half of 2015. Before handing the call over to Samir and Dr. Dugel, let me briefly turn to our Fovista Ex-U.S. licensing and commercialization agreement with Novartis. Last year we entered into one of the largest Ex-U.S. partnering deals in biotech. Thus far we have received a total of $250 million in upfront fees enrollment milestone payments. These fees received from Novartis consisted of $200 million upfront fee upon the execution of the agreement in May of last year and $50,000 enrolment based milestone fee received in October, an additional $80 million in potential enrollment based milestone payments remain available under the agreement. In addition, we are eligible for contingent future U.S. marketing approval in sales milestones totaling up to $700 million which include marketing approval milestones totaling up to $300 million and Ex-U.S. sales milestones totaling up to $400 million, as well as a mid-30% range royalty on Ex-U.S. net sales of Fovista as a standalone product throughout the world. Ophthotech retains all U.S. rights to Fovista. Finally, we ended the year with strong financial foundation of $463.6 million in cash, cash equivalents and marketable securities. This strong financial foundation will enable us to execute on our business plans for 2015 and prepare us for 2016. With that, I'd like to turn the call over to Samir.

[Dr. Samir Patel:]

Thank you, David. Our Phase 3 program for Fovista and treatment naïve is recruiting well and designed to investigate the superiority of Fovista in combination with antibiotic therapy compared to anti-VEGF monotherapy. The underlying rationale is based on overcoming anti-VEGF resistance by PDGF inhibition? Anti-VEGF were effective in wet AMD owing to the anti-permeability property, that is by addressing leakage associated with visual loss in wet AMD. Typically they are ineffective at disrupting or modifying the underlying pathology of neovascularization. Pericytes are cells which cover and protect the endothelial cells over these abnormally growing new blood vessels. They are dependent on PDGF for survival, and therefore blocking PDGF with Fovista has been shown to induce stripping of pericytes. The resulting neovascular tissue is therefore highly vulnerable to anti-VEGF effects. This enhanced anti-angiogenic effect often manifests as a reduction or resolution of the neovascular complex and potential inhibition of its sequelae such as fibrosis. We believe this potential disease modifying effect by dual antagonism of PDGF and VEGF may translate into visual improvement in wet AMD patients. One application of his mechanism of anti-VEGF resistance could be in patients with suboptimal response to anti-VEGF monotherapy. Dr. Dugel and his partners recently investigated this treatment resistance as part of a pilot IFT study. We're delighted to have Dr. Dugel join us today to discuss the design and findings of that ongoing pilot study. Dr. Dugel?

[Dr. Pravin Dugel:]

Thank you, Samir and I appreciate the opportunity to discuss the findings from my group regarding our IFT pilot study. We had a large retinal practice covering the State of Arizona; therefore most of our patients are diagnosed with age-related macular degeneration or AMD. This well established that anti-VEGF monotherapy results in a majority of wet AMD patients not achieving significant visual gain. On average or in the long-term patients either have low vision further actually continue to lose vision. As Samir pointed out, overcoming anti-VEGF resistance by PDGF inhibition may help our patients in a number of clinical scenarios which can be conveniently studied in patients with treatment naïve disease or anti-VEGF improvement resistant patient groups. First, for the patients with treatment naïve disease, rationale and proof of concept has been well established by Ophthotech's Phase 1 in particularly 449-patient Phase 2b study Fovista combination therapy. I look forward to the results of the ongoing large confirmatory Phase 3 study. In addition, other companies such as Regeneron have also announced anti-PDGF related programs. This provides greater confidence on the target and hopefully multiple options for physicians like me and for my patients in the near future. Second, is the issue related to patients previously treated with anti-VEGF do have a poor response. Given the limitation of anti-VEGF monotherapy over the long-term, we predictably have a large pool of patients with optimal response to anti-VEGF monotherapy. How do we manage these patients has been a challenge in our practice as well as elsewhere. So, we really don’t have many effective options. Typically most of us switch anti-VEGF agents in this setting because all the currently used anti-VEGF agents are similar in efficacy. Predictably most switch studies show no clear randomization [ph] despite an improvement in OCT in some reports. If the concept of addressing anti-VEGF resistance is applicable to treat the majority of patients, there is no reason to believe that a similar rationale does not exist in anti-VEGF resistant patients. We have an ongoing open-label, 24-month, anti-fibrosis pilot study at our practice which was a precursor to Ophthotech's current large multicenter anti-fibrosis study. 30 patients have been enrolled and all have crossed the three-month time point. The vast majority and to be exact, 27 out of these 30 are anti-VEGF treatment resistant. As defined in most prior studies, we have similar demographics, that is they have persistent or recurrence to it with no improvement in visual function. Importantly, they had previously received an average of 25 anti-VEGF injections prior to enrolment into our study. What we found at the three months time point, which is after three doses of Fovista administered in combination with Eylea or Avastin is that on average patients gained 7.07 letters on standardized visual acuity charts. They get really exciting, is that the rationale for this pilot anti-fibrosis study was the hypothesis that pretreatment with anti-PDGF prior to combination therapy may lead to an enhanced anti-angiogenic effect. In fact, the 10 patients who received treatment with Fovista gained an average of 11.10 letters versus 4.70 letters in those without pretreatment at the three-month time point. It is quite encouraging when one considers the strong scientific rationale and functional improvement compared with most anti-VEGF switched studies. However, one caution, that there are drawbacks to this study. Out of most other anti-VEGF switch studies our study was not controlled, had a small sample size and standardization and visual acuity measurements and/or prior drug regimen was not uniform. We eagerly await a well designed post effective trial to answer important questions regarding anti-VEGF treatment resistance given the significant unmet need for our patients. For completeness, the remaining three patients in our study of 30 patients who were treatment naïve after three monthly doses of Fovista combination therapy gained an average of 17.66 letters in vision. Thank you, Samir.

[Dr. Samir Patel:]

Thank you, Dr. Dugel. We appreciate the effort of the group in this trial in sharing the preliminary results. I would now like to share other updates prior to turning the call over to Mike. We are excited to announce the formation of a Translational Scientific Advisory Board. Joining this board are two distinguished members, Drs. Rakesh Jain and David Cheresh. Both are global leaders in the Basic Science and Therapeutic Application of Pathologic Angiogenesis. Dr. Rakesh Jain is currently the Andrew Werk Cook Professor of Tumor Biology at the Harvard Medical School, and Director of the Edwin L. Steele Laboratory for Tumor Biology at the Massachusetts General Hospital. Dr. Jain has been a recipient of numerous awards and elected to the Institute of Medicine, the National Academy of Sciences and the National Academy of Engineering. He has over 600 publications to his credit and his pioneering concepts of normalization of pathologic neovascularization following anti-angiogenic therapy has provided the key scientific underpinnings for the development of Fovista in combination with anti-VEGF for wet AMD. Dr. David Cheresh is currently the Distinguished Professor in the Department of Pathology, at the UC San Diego School of Medicine and previously Professor at The Scripps Research Institute in the Department of Immunology. Dr. Cheresh has been a leader in identifying key pathways in mediators of pathologic angiogenic facing tumors. With over 200 publications to his credit his seminal publication in Nature highlighting VEGF as a negative regulator of pericyte function and vessel maturation has provided the rationale for the ISD that Dr. Dugel just discussed in our ongoing anti-fibrosis study. Last at the American Academy of Ophthalmology meeting in November 2014 Dr. Usha Chakravarthy presented retrospective data from our Phase 2b trial regarding the potential anti-fibrosis effect of Fovista 1.5 mg combination therapy. These were in independent mass to review. At the Macular Society this week Dr. Chakravarthy will provide a further update regarding dose response relationship with respect to the potential anti-fibrotic effect of Fovista combination therapy in wet AMD. I will now turn the call over to Mike.

[Michael Atieh:]

Thank you, Samir. Here is a brief update on our results of operations. Collaboration revenue which we recognized under the Novartis agreement was $1.7 million and $41.3 million for the quarter and year ended December 31, 2014. As a reminder, the company did not have revenue during the comparable periods in 2013. Research and development expenses were $22.2 million for the quarter ended December 31, 2014, compared to $15.4 million for the same period in 2013. R&D expenses were $88.4 million for the year ended December 31, 2014, compared to $33.2 million for 2013. The increase in R&D expense in the quarter and year ended December 31, 2014 relates primarily to the Fovista Phase 3 clinical program, including clinical trial costs and cost to manufacture Fovista and increase compensation expenses associated with additional research and development staffing. Also contributing to the increase during the year, with the milestone payments of $19.8 million that we made to a third-party licensor in June 2014 in connection with entering into the Novartis agreement. General and administrative expenses were $10.7 million for the quarter ended December 31, 2014, compared to $5.1 million for the same period in 2013. G&A expenses were $33.4 million for the year ended December 31, 2014, compared to $14.2 million for the same period in 2013. The increased general and administrative expense in the quarter and year ended December 31, 2014 relates primarily to increases in cost to support the expansion of the Company’s operations including the Company’s public company infrastructure and the higher and additional management and corporate staffing, increased professional services and consulting fees and increased share-based compensation. The company reported a net loss for the quarter ended December 31, 2014 of $35.9 million, or $1.06 per diluted share, compared to a net loss of $20.4 million or $0.65 per diluted share for the same period in 2013. The company reported a net loss for the year ended December 31, 2014 of $98.2 million, or $2.95 per diluted share, compared to a net loss of $57 million or $6.34 per diluted share for the same period in 2013. Cash, cash equivalents and marketable securities totaled $43.6 million at December 31, 2014, compared to $210.6 million at December 31, 2013. And now, I will turn the call over to David.

[Dr. David Guyer:]

Thank you, Mike. In summary, we continue to move the company forward with our Phase 3 Fovista program, the initiation of our Fovista expansion programs and the continuing development of Zimura. Thank you for your time this afternoon and for your continued support. I will now turn the call over to the operator so we can open up the lines for any questions.

[Operator:]

Thank you. [Operator Instructions] And we will take our next from Yigal Nochomovitz with Oppenheimer.

[Yigal Nochomovitz:]

Hi, great, thanks very much for taking the question. May be if I could just start with Dr. Dugel, you saw solid effect as you mentioned of the pre-treatment regimen before dosing the anti-VEGF. So, I'm just wondering if you see any room there for further optimizing that pre-treatment window with Fovista? And then for David or Samir, I'm just wondering assuming you do validate that idea of pre-treatment in the ongoing anti-fibrosis trial, is that a concept, is that pre-treatment concept something that you might consider advancing into a treatment that you study down the road which obviously would be an interesting strategy relative to some competitors that are aiming to co-formulate these mechanisms? Thanks.

[Dr. Pravin Dugel:]

That’s a great question and thank you for asking that, of course what gives me confidence in pre-treatment as that it is really based on robust and good scientific data. Every time we inject anti-VEGF we up regulate PDGF and it would make intuitive sense to go ahead and blunt that up regulation and that’s why we have decided to see if could test that hypothesis of pretreatment. Now pretreatment in this trial has been done one day apart, whether that could be lengthened, whether it could be changed with really be data based and I think we have lot more work to do, but I think it’s very exciting that this concept of pre-treatment which is so based on science may actually be encouraging as far as the IFT is concerned. As I said, it is a small study we have to cautious, but it is encouraging.

[Dr. Samir Patel:]

Great, this is Samir, thanks Dugel. First, you know in the Phase 3 program it is designed to establish the relevance of the combination therapy enhancing visual outcome compared to monotherapy and really that is predicated on the results in our Phase 2 study. If we were to go ahead and draw the analogy from lessons we’ve learned from anti-VEGF therapy, most of the registration trial, initial registration trials really were based on either monthly therapy of the anti-VEGF agents or in the case of Eylea for an induction dose bimonthly regimen. Yet the way physicians typically use the anti-VEGF agents in the marketplace is more of a flexible regimen and differing flexible regimen. So, with that data and that as a the background when we look at the IFT data that Dr. Dugel has and you also look at our anti-fibrosis study which consists both of treatment experienced patients and treatment-naïve we will have some data to go by for confirmation and so based on that we certainly think in light of the IFT that the treatment resistant population will look at some pre-treatment regimen there. And to your specific question on the treatment-naïve, yes we think that we were going to look at it. We will look at what the data shows on the anti-fibrosis and if it's confirmatory certainly it’s just like an anti-VEGF monotherapy era that we see people looking at different to optimize the regimen for outcome is something we would certainly consider.

[Yigal Nochomovitz:]

Okay, great, thanks, Samir. And then I had a question on the reduction of treatment burden study. I guess we don’t really know too much in the way of details about the design of that study, could you provide us anything more there, in terms of whether it’s going to be randomized or single arm and if it is randomized just a little bit more detail on how the scheduling would work for the two arms? Would there be cases where you might dose Fovista without the anti-VEGF because you are seeing the need for less anti-VEGF or would you know just space everything out so that the patients that are getting less anti-VEGF would also just get Fovista at more distant time points?

[Dr. Samir Patel:]

Yigal, this is Samir. Just to be clear, is this for treatment burden you are talking about?

[Yigal Nochomovitz:]

Yeah, yeah, yes, yes.

[Dr. Samir Patel:]

Sure. So you know, I think first when we talk about treatment burden the way we approach that is currently in most trials with monotherapy anti-VEGF notwithstanding the bi-monthly regimens that Eylea has shown to be effective after the induction dose, any quarter the regimen to the best of our knowledge has not shown to be beneficial. And so, when we think about reduction in treatment burden basis is as follows, that you know neovascular regression and disease modification occurs via combination therapy. And if we were to take a lesion and make it a smaller lesion if you will, then perhaps there aren’t any side effects produced driving the disease and its activity and perhaps less frequent need for injections will be necessary. I think there is some suggestion with anti-VEGF monotherapy that smaller lesions don’t require as much treatment. So with that at the background that’s what we think combination therapy falls. As far as the specific design is concerned, although all anti-VEGFs are roughly similar with respect to their safety and efficacy, the ideal regimen has yet to be established and yet to be established particularly with combination therapy in a quarterly regimen. So what we are doing is we are looking at all the anti-VEGF agents Lucentis, Eylea, and Avastin and after the induction dose, after the induction regimen look at a quarterly regimen and see what the visual response is, because we know that none of the anti-VEGF agents have shown a sustained beneficial effect with quarterly regimen at least those that have been studied. So, we are able to establish that and we'll see which anti-VEGF agent that the regimen is most promising and we will look at the program in a more randomized fashion with one or any combination of other anti-VEGF agents.

[Yigal Nochomovitz:]

Okay, great. And then on the new trial you announced for Zimura, I guess, well number one, could you just say what anti-VEGF therapy you are planning to combine with or maybe it's all of them? And then just also why do you see Zimura as potentially better suited to treat this polypoidal choroidal vasculopathy versus all wet AMD and, I have also understood the PCV patients may respond a little better to further dynamic therapy versus ant-VEGF, so did you also consider the design with Zimura plus PDT in addition to the one you've just announced today with the plus anti-VEGF? Thanks.

[Dr. Samir Patel:]

Yigal, thank you, this is Samir again. I mean this is very exploratory because we don’t have the body of data with polypoidal lesions that we have with the non-polypoidal variety which are typically what are used in most of the trials. So, I think as we stand today, it’s very difficult to say what the true response is. So before committing ourselves to in a larger sample sized trial, we just want to look at if there is inflammatory component involved in these lesions. And although the studies typically have been conflicting, I think it’s reasonable to state that there is a belief that they don’t respond as well with anti-VEGF therapy. And to use for a dynamic therapy would provide, would introduce another confounder. So I think what we would like to see is, those patients at least in this pilot study that if failed how are they responding with the combination of anti-VEGF and Zimura and those that are treatment-naïve are we getting a uniform response before we go into a larger study, but we would not be using photodynamic therapy in that setting. I mean it's strictly pharmacotherapy. As far as anti-VEGF agents to the best of my knowledge, I think physicians can use any anti-VEGF agent of their choice.

[Yigal Nochomovitz:]

Great.

[Kathy Galante:]

If this could be the last question, so we make sure we get to the other people in the queue as well.

[Yigal Nochomovitz:]

Oh, I'm sorry, sure. David, just real quick, for Tivo, could you say anything more about the type of sustained release technology that you are exploring, and what have you learned about the viability of that approach since the deal back in November? Thanks.

[Dr. David Guyer:]

Nothing more that we can say at this point, but you know we will have updates as we make further progress.

[Yigal Nochomovitz:]

Great, thanks so much.

[Kathy Galante:]

Thank you.

[Operator:]

And we’ll take our next question from Terence Flynn with Goldman Sachs.

[Terence Flynn:]

Hi, thanks for taking the questions. I was just wondering if you can share anymore details on design of the Zimura Phase 2, 3 dry AMD trial? Is that going to be all comers, how many doses you are looking at if there is any interim data that is going to come out of the Phase 2 portion? And then my second question was just can you give you us any update on the potential explore combinations of Fovista with any of the Novartis anti-VEGF drugs? Thanks.

[Dr. David Guyer:]

Sure, so we are presently finalizing our review both internally and with our consultants on the clinical regulatory strategy, strategic and commercial for the Zimura dry AMD geographic atrophy program. So really we can’t provide anything more now, but we will be doing that shortly. As far as again, the Novartis proprietary anti-VEGF, since they are taking the lead there and it’s their compound we can’t make any comments about that program either.

[Operator:]

And we’ll take our next question from Eric Joseph with JP Morgan.

[Eric Joseph:]

Hi, guys, just following [indiscernible] here, may be a couple of questions for Dr. Dugel to start, just wondering how non-responded wet AMD or resistive patients are generally define, both in this study, both in your pilot study and also in practice, and wonder if you have insight into the durability of the persistency of the activity that you observed today, and whether there is anything preclinical here or clinically that would point to the maintenance of possible waiting of the flexible time?

[Dr. Pravin Dugel:]

Yeah, thank you for the question and what you need to know that in our study the patients that were included again those are 30 patients study, 27 of those patients were previously treated. And then average number of injections that they had that’s anti-VEGF injections prior to enrollment into the study was 25. And the treatment interval between the injections was less than six weeks or less in 89% of patients. So these patients were treated often and we treated a lot prior to enrollment into our study. So these patients were defined as patients who are persistent fluid or recurrent fluid with anti-VEGF monotherapy. And this is a large pool of patients that we have in real life and these are the patients that really have the unmet need.

[Eric Joseph:]

Okay, great, and on the point of durability of activity?

[Dr. Pravin Dugel:]

Well, this is the three-month study that I reported, I just reported the results of three-month look at that study. This is a 24-month anti-fibrosis IST that I am conducting, so there will be lot more data coming out. The next data set that will come out will be as David earlier said in a post driven ARBO [ph].

[Eric Joseph:]

Okay, great, thanks. And maybe a question for Samir or David if I could, may be, just wondering if you could talk a little bit about how you view the size of the resistant wet AMD population relative to the overall population, and also wonder if you could provide little more detail around the size and scope of the non-responded trial that is currently in planning? Thanks.

[Dr. Samir Patel:]

Sure, hi this is Samir. So, you know, I think it’s hard to put real numbers, but I don’t think anybody would deny that it’s a very large population because at one end of this spectrum if you just take the simple randomized studies, there were registration trials which demonstrated that monthly administration of anti-VEGF at one year time point, two-thirds of the patients are not able to achieve significant patient gain and about half of the patients aren’t able to get major acuity of 20

[Eric Joseph:]

Okay great, thanks very much.

[Operator:]

[Operator Instructions] And we'll take our next question from Joseph Schwartz with Leerink Partners.

[Joseph Schwartz:]

Thanks very much. You've already done a lot of work to provide a lot of strong scientific support around your clinical approaches. So, I was just curious if you could talk a little bit more about what your goals with the Translational Scientific Advisory Board are and what we can look forward to hearing more from you on that front?

[Dr. Samir Patel:]

It's a big question Joe, it's Samir and I think we are so fortunate to have two individuals that we really, their work is at the heart and soul of why we developed Fovista in the first place. The whole concept of normalization of the vasculature is consistent with what we see with anti-VEGF monotherapy. I mean, if we look at patients who present with neovascular AMD and you don't treat them at all, maybe Dr. Dugel can comment more on this in days prior to anti-VEGF monotherapy. Typically those patients ended up with, involved with a disease and in six months quiescence with profound loss of vision. In the anti-VEGF era these patients clearly have done a lot better and yet it's over a four, five, six year period where there is continued activity. And what that really means is compared to having no treatment, normalization has taught us that by anti-VEGF therapy you cause maturation of the vessels and as a result they continue to exist and sensation of anti-VEGF therapy leads to reactivation. So if we understand that, that's how we designed our Fovista trials to go ahead and create a neovascular immature event so that neovascular aggression could be effected and you can hopefully decrease the lifecycle of the disease and modify the underlying disease there. Dr. Cheresh's work is really the main impetus why we decided the pre-treatment in the first place. I mean, this is a very transformational study in nature that he published showing VEGF is a negative regulator of PDGF and really every time you inject anti-VEGF you get a rise in PDGF. And interestingly, Dr. Jain showed that many years ago in patients with rectal carcinoma where administration of anti-VEGF led to increased pericytes coverage. So both individuals worked intimately ties to what we're doing with pre-treatment. So we believe we'll continue to leverage their expertise. They continue to give us guidance on additional ways to look at regimen for treatment in neovascular. Dr. Dugel, I don't if you'd like to comment on the concept of maturation and what you're seeing clinically?

[Dr. Pravin Dugel:]

Well, as a clinician I can certainly comment on that and I'm certainly old enough to remember when we had no treatment and patients ended up going blind and they had fibrosis and a disciform scar. So there's no doubt in my mind that anti-VEGFs have revolutionized the way we treat patients. But our clinical trials run for a year or two years or maybe three years, but in real life the patients that I see and these patients aren't one or two or three year patients, these patient's are in my practice for many years, sometimes for decades and what I see in the real world is that these patients continue to require treatment and as other studies have shown gradual elucidation and clearly there's a large unmet need here. So from a clinical standpoint as a clinician, I have a pool of patients now that could really use a treatment and the possibility of the treatment coming forth I think is very exciting for me. From a scientific point of view it also makes sense that every time you inject with an anti-VEGF agent you up regulate PDGF, we lower PDGF dose, which is that it recoups and matures pericytes and matures the neovascular membrane forming a protective armor. We also know that PDGF is very pro-fibrotic and over time fibrosis is the biggest reason why patients lose vision and that has been shown in many studies including the CATT trial and IVAN. So, I'm excited about the fact that this treatment strategy, the studies that are being done, the clinical trials that are being designed are really based on a variable robust and firm biological foundation that exists and I'm also now very excited that we'll have answers at the end of the day we are going to have a data. There's a lot of things that we do right now that's really not based on data, things like treatment extent, things like switching agents and so forth. And I commend Ophthotech for designing studies proactively that will eventually allow me the data to make detailed scientific judgments to treat my patients.

[Joseph Schwartz:]

Thanks very much.

[Operator:]

And we'll take our next question from Stephen Willey with Stifel.

[Stephen Willey:]

Yeah, hi thanks for taking the question. Maybe just a quick one for Dr. Dugel. Obviously understanding this is a 30-patient uncontrolled study, we're just wondering if there was any attempt to quantify the level of sub-retinal hyper-reflective material in these patients at baseline and I guess in your clinical experience does the magnitude of the changes in the SHRM correlate well to the changes that you see in visual acuity?

[Dr. Pravin Dugel:]

Well, thank you for the question. First of all, again, I do want to caution you that this is a 30-patient study, in fact 27 patients who were reported as treatment resistant. So it is an exploratory study and all the shortcomings that this study has as I have explained that switch studies have as well. So you have to make sure that we realize that this is certainly not a definitive study, but again we will have data. There's a larger anti-fibrosis study ongoing. You've heard about the treatment resistant studies, you've heard about the treatment burden studies, so again the good news is that we are going to have data, we are not going to be left hanging. As far as SHRM is concerned, again a lot of confidence in the Phase 2b study, which showed a direct relationship with the improvement in visual acuity with a reduction in SHRM. So it gives me great confidence that all the biological molecules are consistent with what we're seeing and of course we'll have data from the larger Phase 3 study. We'll also have some data from our IFT [ph] as well as all the other Fovista extension studies that I have mentioned. But I think the concept that I'd like to bring forth here is that we're seeing consistent with the biology and we will have data to make our judgment calls on.

[Stephen Willey:]

Okay and then I know there was a mention of pre-treatment in a previous question and forgive me if I missed the details, but I understand that the company is also sponsoring a open-label Phase 2a study evaluating pre-treatment versus simultaneous and I am just kind of wondering if there is any opportunity for there to be an interim data emerging out of that study that could maybe in correlation with the findings that Dr. Dugel is talking about?

[Dr. Samir Patel:]

Hi it's Samir Stephen, I am not aware of a study that we've disclosed that as pre-treatment, certainly I mentioned that we would certainly be considering that and there is a pre-treatment component in the anti-fibrosis study, but you know, based on recruitment that's what really drives an interim data. I mean, at this point all I can state is that recruitment is quite strong and we know we're going to do everything we can to complete the recruitment and when and if the interim data are available we'll certainly give you additional guidance.

[Stephen Willey:]

Okay, thanks.

[Operator:]

And we'll take our next question from Yigal Nochomovitz with Oppenheimer.

[Yigal Nochomovitz:]

Hi, thanks very much for taking the follow up. David, just quickly, I know you mentioned that you were going to be giving more specific guidance on the timing of enrollment in the Phase 3 soon, so we'll look forward to that, but I was just wondering when you do report the Phase 3, is it, should it be our expectation that all phase 3 trials will report out at the same time or could we see sort of a staggered data release depending on timing of the three studies? Thanks.

[Dr. David Guyer:]

Yeah, sure. You know, as I mentioned in the near future that we will have a specific guidance that we will discuss, we're getting close.

[Yigal Nochomovitz:]

Okay, and Dr. Dugel, real fast. If I could just ask, you know, I was aware that in your interesting study there were some differences in the visual acuity gains with the Avastin patients versus the Eylea patients and I was just wondering if those differences could be explained based on the Avastin patients having the pre-treatment preferentially versus the Eylea patients? Thanks.

[Dr. Pravin Dugel:]

Well, I think the Fovista works with all anti-VEGFs. I think it's completely agnostic to any anti-VEGFs and the biology would seem to indicate that as well. Again, it's a small study, there are only 27 patients that were analyzed. So I just don't think we can make any conclusion about one anti-VEGF or another. As far as I'm concerned, it worked with both and it should be agnostic to all anti-VEGF agents.

[Yigal Nochomovitz:]

Great, thank you.

[Operator:]

It appears there are no further questions at this time. I would now like to turn the conference over to Dr. David Guyer for any additional or closing remarks.

[Dr. David Guyer:]

Great. I just want to thank everyone for your interest today and we look forward to further updates in the near future. Thank you.

[Operator:]

This now concludes the presentation. Thank you for your participation.