IVERIC bio Inc (ISEE) 2013 Q4 法說會逐字稿

Good day, welcome to the Ophthotech Corporation fourth-quarter 2013 earnings results conference call. As a reminder today's call is being recorded.

And now at this time I would like to would like to turn the conference over to Ms. Kathy Galante. Please go ahead, ma'am.

Thank you, Alan and good morning everyone and welcome to Ophthotech's fourth-quarter earnings call. This morning we issued a press release that provides the details of the Company's financial results for the fourth quarter ended December 31, 2013, as well as update on Fovista and Zimura and other recent business highlights. The press release is available on our website at www.ophthotech.com.

Leading the call today will be Dr. David Guyer, Chief Executive Officer, Chairman and Co-Founder of Ophthotech who will provide a general overview. Dr. Samir Patel, President and our Vice Chair and Co-Founder will provide a brief discussion on our R&D efforts, and Bruce Peacock, Chief Financial Officer, will provide a financial highlight from the fourth quarter ended December 13, 2013.

As a result, during today's call we will be making some forward-looking statements. These forward-looking statements are based on current information and are functions and expectations that are subject to change and involve a number of risks and uncertainties that may cause actual results to differ materially from those contained in the forward-looking statements.

These risks are described in our filings made with the Securities and Exchange Commission including our quarterly report on Form 10-Q and the quarter ended September 30, 2013, and the final prospectus dated February 11, 2014, for our recent public offering for the common stock. You are cautioned not to place undue reliance on these forward-looking statements and Ophthotech disclaims any obligations to update such statements. I will now turn the call over to David.

Thanks, Kathy and thanks to everyone for joining us on the call this morning. 2013 was a transformational year for Ophthotech.

We completed one of the largest IPOs for the sector by raising $192 million in gross proceeds, advanced our Fovista clinical program to Phase 3 pivotal trials for the treatment of wet age-related macular degeneration in combination therapy, expanded our management team and ended the year with $210 million in cash and cash equivalents. I am pleased to say that we have begun 2014 with substantial momentum.

In January we achieved an enrollment milestone in the Phase 3 Fovista program triggering $41.7 million from a second tranche payment under our royalty financing agreement with Novo A/S. In February we completed a follow-on public offering of our common stock resulting in net proceeds to the Company of approximately $55.5 million. And just this week the Company received written confirmation from the European Medicine Agency's Committee for Medicinal Products for Human Use, also known as the CHMP, indicating that the CHMP and the Company are now in agreement with the Company's trial design and dosing regimens for the Fovista Phase 3 program which I will discuss shortly.

The strong financial foundation that we have built along with recent science driven findings on the role of anti-PDGF therapy and potentially inhibiting subretinal fibrosis in wet AMD patients, which Samir will speak about later in the call, provide the solid framework for advancing and expanding our Fovista and Zimura clinical programs. We are excited by the potential value creating opportunities these programs present for our shareholders.

In our Phase 3 clinical program for Fovista, patient enrollment for the two trials of Lucentis as the combination anti-VEGF agent remains on track. Today we are pleased to inform you that we have recently activated and initiated trial sites for the third clinical trial in our Phase 3 program with Fovista in combination with Avastin or a Eylea.

We expect to enroll a total of 1,866 patients in the three trials at more than 225 centers worldwide and to have initial topline data from the Fovista Phase 3 clinical program available in 2016 on schedule. As a reminder, the Phase 3 trials are designed to build upon results from our large Phase 2b trial in which the Fovista Lucentis combination therapy demonstrated statistically significant superiority over Lucentis monotherapy in terms of improving visual outcome.

As I mentioned on the regulatory front, we are pleased to report that we have received written confirmation from the CHMP indicating that they are now in agreement with the Company's trial design and dosing regimens for the Fovista Phase 3 program. The CHMP agrees with our position that with Fovista in combination with Eylea trial and one of the Fovista in combination with Lucentis trials should remain unchanged.

In the other Fovista in combination with Lucentis trial, the CHMP agreed with our recommendation that monthly dosing in the first year of the trial should also remain unchanged from our original design and agreed that we would slightly modify the dosing regimen in year two. Year two initially was a dose reduction regimen. This year two regimen remains a very similar dose reduction regimen but is now consistent with the EU label for Lucentis.

The CHMP agreed to our trial design after considering our pharmacological and scientific arguments which included recent scientific findings of a potential anti-fibrotic property of Fovista in decreasing subretinal fibrosis, which we believe may explain the expanding divergent curve seen in our Phase 2b Fovista Lucentis trial. The CHMP has confirmed that no bridging study will now be needed and thus our anticipated timing and overall expense of our Fovista Phase 3 program remain unchanged and continue as planned. With the Phase 3 program on track and moving forward as planned and the recent completion of our follow-on public offering we are expanding the global clinical program for Fovista and wet AMD and advancing our second product candidate, Zimura in both dry-AMD and wet AMD, which Samir I will shortly discuss.

All in all we have developed and expanded our clinical program with a plan now resulting in 10 clinical trials ongoing or to be initiated in 2014 and 2015 and data expected to begin in 2015. With that I would like to turn the call over to Samir who will provide more detail on some of the new clinical programs we will be starting this year and next.

Great. Thank you, David. Good morning everybody and thank you for joining us today.

As David stated before we are in the process of starting many exciting clinical programs at Ophthotech as part of our mission to develop the next generation of science driven AMD therapies to address significant unmet need. We believe there exists a strong rationale for anti-fibrotic effect of Fovista administration in wet AMD management.

Recent publications have demonstrated that on average monotherapy anti-VEGF as administered in the marketplace failed to improve visual outcomes for wet AMD patients over the longer term. In addition recent published studies have also shown that evolution of subretinal fibrosis in wet AMD patients treated with monotherapy anti-VEGF regimens is potentially associated with poor visual outcome.

Fibrosis under the retina can cause distortion and damage to the neural elements that are critical for processing of visual signals. In a preclinical model of retinal scarring and fibrosis Fovista has been shown to inhibit fibrosis.

In addition, PDGF promotes the migration of multiple cells believed to be participants in the formation of retinal scar, or fibrosis. The significant role of PDGF in pericytes driving fibrosis in other organs is also supported by studies from multiple independent labs.

Lastly, we believe new and evolving findings on the initial evaluation of retinal images in our Phase 2b trials suggest that combination therapy with Fovista 1.5 milogram plus Lucentis may inhibit fibrosis relative to monotherapy Lucentis in patients with poor visual outcome. Taken together it is our opinion that the preclinical and clinical studies provide strong support to investigate PDGF inhibition by Fovista in wet AMD patients receiving anti-VEGF therapy.

We are excited to initiate an anti-fibrosis trial in wet AMD patients. We hope to eventually demonstrate that antagonism by -- PDGF by Fovista in wet AMD patients receiving anti-VEGF therapy will result not only in enhanced visual outcome due to neovascular regression but also prevent sub-optimal visual outcome over the longer term. The anti-fibrosis trial will commence in 2014.

At our R&D Day on Friday, March 7, in New York City we will discuss the rationale for our planned studies for adding Fovista therapy to an anti-VEGF regimen in wet AMD patients to reduce treatment burden and address anti-VEGF resistance. We are excited to commence all three trials in 2014 and believe that the addition of Fovista to anti-VEGF regimens has the potential to significantly transform the lives of wet AMD patients by improving and stabilizing visual outcomes for wet AMD patients.

On the Zimura side we are excited about our planned trials studying geographic atrophy, a severe form of dry age-related macular degeneration which affects approximately 8 million people worldwide. There is no approved treatment for dry AMD and it is the most common type of AMD accounting for approximately 85% to 90% of cases worldwide.

Zimura inhibits the complement protein C5, a central component of the complement cascade. Studies indicate that complement-mediated inflammation plays a major role in pathogenesis of dry AMD. By inhibiting C5 we believe Zimura may decrease complement-mediated inflammation and cell damage in dry AMD.

Our Phase 2a clinical trial evaluating the safety and tolerability of Zimura administered as monotherapy to patients with geographic atrophy did not show any evidence of drug-related adverse events. Although our Phase 2a trial was not controlled a trend favoring the increased frequency of Zimura administration in the higher dose group was observed when compared to decreased frequency of administration for the relative reduction in the mean growth of geographic atrophy lesion area as measured by the independent reading center at week 24. The safety profile of Zimura in this trial and the trend indicating a potential drug effect coupled with strong science for a disease with a major unmet need leads us to continue the development of Zimura towards a Phase 2/3 design for geographic atrophy scheduled to initiate in late 2014 or early 2015.

We are also planning a Phase 2 trial with Zimura and Fovista in combination with anti-VEGF therapy for the treatment of anti-VEGF resistance wet AMD patients. This trial is scheduled to initiate in 2015. I will now turn the call over to Bruce Peacock.

Thanks, Samir. Operating expenses for the quarter ended December 31, 2013, were $20.4 million with $15.4 million attributable to research and development. This compares to operating expenses of $3.5 million and research and development expenses of $2 million for the same period in 2012.

The Company reported a net loss for the quarter ended December 31, 2013, of $20.4 million, or $0.65 per share. Operating expenses for the year ended December 31, 2013, were $47.4 million with $33.2 million attributable to research and development. This compares to operating expenses of $13.7 million in research and development expenses of $6.8 million for 2012.

The Company reported a net loss for the year ended December 31, 2013, of $57 million, or $6.34 per share. The increase in research and development expense for both the fourth quarter and full year ended December 31, 2013, related to the cost of our Phase 3 clinical program for Fovista. In addition, the increase in general and administrative expenses in 2013 relate primarily to an increase in personnel costs as we expand our management team and staffing to support a public company infrastructure.

As of December 31, 2013, the Company had $210.6 million in cash and cash equivalents. In January 2014 the Company received an additional $41.7 million for the second tranche payment under the Company's $125 million royalty financing agreement with Novo A/S. A potential third tranche of $41.7 million under this royalty agreement remains available based on achievement of a further patient enrollment milestone.

Additionally in February 2014 we completed a follow-on public offering of common stock which resulted in net proceeds of approximately $55.5 million for the Company. With that I'd like to turn the call back over to David.

Thank you, Bruce. As we look ahead we will continue to focus on the execution of our Fovista Phase 3 program, expanding our pipeline with additional Fovista trials in wet AMD and other areas of unmet medical need and initiating Zimura clinical trials in both dry and wet AMD. We look forward to providing you with updates as our programs progress.

As Samir mentioned earlier, we will host our first R&D Day on Friday, March 7 in New York City where we will review all of our programs in greater detail and host a panel discussion with leading retinal specialists. We hope you will be able to join us on that day.

Thank you for your time this morning and for your continued support. I will now turn the call over to the operator so he can open up the lines for any questions.

Thank you, sir. (Operator Instructions). Geoff Meacham, JPMorgan.

Hi, this is Carter on for Geoff. My first question is given the modification in the one Fovista plus Lucentis trial, I assume this will require an amendment and some bureaucracy in getting this rolled out across the different sites. Can you affirm that there won't be another delay in timelines and the time to data for that study?

And also with the dry AMD trial with Zimura, obviously the lampalizumab data last year validated somewhat the role of complement in the disease but this is a -- how do you reconcile this with the lack of efficacy signal in the Soliris trial? Thank you.

In connection to the trial, just to review, essentially the Lucentis trial is unchanged for one of the two Lucentis trials, as David stated, and the second one we're really talking about the year two. And the dosing regimen is not really that different from what we currently have and amendments are usual multiple amendments typically go on for a variety of reasons in a trial and this is for the second year. So it is not going to be an issue whatsoever in terms of moving forward.

This is David, just to add to that, we are very pleased with this outcome from EU regulatory and that the Eylea Avastin trial is unchanged to our original plan. The Fovista first Lucentis trial, as Samir said, completely unchanged in year one and two. And again in the one trial where we have a slight modification in year two, remember importantly, the approval milestone is a year one and that year one program end point remains completely unchanged.

The only small thing that we are talking about is a change, a very mild change in dose reduction of year two. We've already had a dose reduction in year two planned and we are just modifying it slightly so that it is consistent with the EU (inaudible), with their regimen.

And as long as amendments are done prior to the first patient in the trial entering year two of which we have until August, it is a very simple process that is done routinely for amendment. So it should not affect any delays and it's a very simple day-to-day thing that is done commonly in these trials.

Carter, it is Samir again. With respect to your second question, I believe your question was a failed trial for Soliris in geographic atrophy. Am I correct?

Correct. Yes.

So that administration was entered systemically and intravenously as well as intravitreally. And there are several examples where intravenous administration is not efficacious for posterior segment disease, just the nature of the circulation is such that penetration into the intraocular space is very challenging, in that mode of administration. So we are very excited about the strong science and the initial signal that we are getting.

Great. Thank you.

David Friedman, Morgan Stanley.

The question is about the fibrosis trial. If you could just discuss how fibrosis is currently assessed in a regular clinical practice and then what do you think the timeframe is to see meaningful changes in vision related to fibrosis and how do you tease that out from changes that you would see with better control of neovascularization? Thanks.

So I don't think there is much debate in the retinal community that evolution of fibrosis in the sub-macular space under the central retina is a very poor prognostic sign. I think that has been well established.

Secondly, the diagnosis of fibrosis is one that on ophthalmoscopy and photography you can actually see the fibrous tissue. So both of those are fairly straightforward.

With respect to the visual effect of neovascular tissue and fibrosis, it's a great question because I think we have to think about neovascularization as having two components, a pure neovascular component and the non-neovascular component. And the non-neovascular component plays a major role in fibrosis.

So we have shown in our Phase 2b trial that if you look at neovascular regression for example in patients with very good visual outcome, neovascular regression is associated with it both by fluorescein and by OCT. So we think that improvement of visual outcome will correlates quite well with regression of neovascularization.

And at the other end of the spectrum that patients with anti-VEGF monotherapy that typically have poor visual outcome we've certainly seen based on analysis of our images, that there is a reduction in subfluvial fibrosis in those patients as well, which gives us a good deal of confidence to move forward with a study of either reducing the onset of fibrosis or progression. And last, the study from CAT, which is a very large trial and also a study from Denmark, a very large trial as well, both indicate that roughly 40% of the patients develop fibrosis over a two-year period in wet macular degeneration and that is associated with quite significantly poor visual outcome.

That's great. Thanks very much.

Joseph Schwartz, Leerink Partners.

I was wondering if you talk a little bit more about your design that you are contemplating for the dry AMD study that's scheduled to be initiated later this year?

We haven't provided any details on that but I think suffice to say that it is intravitreal administration and because we have established safety with the dosage regimen that we had in our initial Phase 2a trial that didn't show any safety signal to me has been able to assume that we would increase the dosage and frequency of administration. But we continue to have dialogue internally with our -- and with our consultants, and have initiated some dialogue with the regulatory agency. So we will give you more clarity as we roll out the program in the future.

Okay, great. As far as the fibrosis hypothesis, which is very interesting, has it been possible to tease out how much the various components of vision loss are each responsible in terms of what might contribute in terms of what might contribute in terms of fluid leakage versus fibrosis on like an independent basis? Is that possible to tease out from all of the data across all the different studies and all of the imaging that has been captured?

That's a great question and we will certainly address it in more detail on March 7 at our R&D day and you'll have an opportunity to certainly hear from what we consider our great top leaders in this space. Let me just state that if you were to look at the whole body of literature that is out there in large sample size trials, I think it is safe to say that there are three factors that have been typically demonstrated to be associated with poor visual outcome.

One is emergence fibrosis in the subretinal space. Secondly, growth of neovascularization following treatment with anti-VEGF therapy. And third is atrophy of the central retina whether that's because of natural history or underlying therapy with anti-VEGF, remains to be sorted out, but I think it is fair to state that all three of those contribute to visual loss.

And I think is important to realize that if you look at the large body of data that are coming out now that anti-VEGF therapy is administered in the marketplace today in general at four to seven year period after therapy the patient's vision is really pretty much at baseline from when their disease onset occurred. So these three factors play a significant role in the unmet need that currently exists with the wet AMD therapy. So I think any interruption of or altering the course and evolution of those three elements could improve visual outcome.

Very interesting. I look forward to March 7. Thanks.

(Operator Instructions). Stephen Willey, Stifel.

Just wondering if maybe you could provide a little bit more characterization around CHMP feedback, specifically on the biological rationale for monthly dosing? They obviously granted the amendments, so we know that their viewing this positively, but just kind of wondering if they've provided any kind of granular feedback around the subretinal fibrosis hypothesis?

I don't think I'll get into all the details of it but I think it's suffice to state that the arguments on clinical and pharmacologic basis have been pretty much driven by the increasing benefit by monthly administration of the combination compared to monotherapy and the reduction of fibrosis and just the general mechanism of action all contributed to the importance of continued monthly administration. So we can determine that the true underlying efficacy is of the combination rationale.

Conversely, a less treatment administration was already in planning for us and was part of our protocol in the second year. And we are just taking one of the trials and using less frequent dosing which we were studying anyway to reflect the EU pathology in the second Year. So really in summary, if you look at the underlying scientific and clinical rationale of our combination therapy resulted in the current design that we have for our Phase 3.

Okay. And this might be kind of more of an R&D Day question, but just with respect to the triple combo that you guys are proposing in wet AMD in 2015 for Zimura, VEGF and PDGF, how should we think about the logistics of administration there?

And I guess would there be and co-formulation options that you could try to leverage with respect to both Fovista and Zimura? Thanks.

Again, I think it's a great question and we will certainly address it on March 7. Suffice to STATE that it is been fairly well-established that constant and mediated inflammation is involved in both forms of macular degeneration and that (inaudible). Also the (inaudible) regulation of VEGF and PDGF.

So it only makes sense that if you can put the upstream pathways and downstream pathways as with PDGF, that that should really address anti-VEGF resistance. We'll certainly touch more upon it at the science day.

Perfect. Thank you.

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

Great, well thank you all very much for your interest again. We would like to invite everyone on the line and the webcast to our first research day, R&D Day, next Friday, a week from tomorrow, March 7 in New York City.

If you haven't gotten an invitation please contact us. We think it's going to be a really exciting program with some great science, more description of our trials and some of the top KOL retinal doctors globally. Thank you again for your interest.

That does conclude today's call. We thank everyone again for their participation.