Clearside Biomedical Inc (CLSD) 2018 Q2 法說會逐字稿

Good day, ladies and gentlemen, and welcome to the Q2 2018 Clearside Biomedical Earnings Conference Call. At this time, all participants are in a listen-only mode. Later, we will conduct a question and answer session and instructions will follow at that time. (Operator Instructions)

I would now like to introduce your host for today’s conference, Mr. Steve Kilmer from Investor Relations. Sir, you may begin.

Thank you. Good morning, everyone, and thank you for joining us. Before we begin, I would like to remind you that during today's call, we will be making certain forward-looking statements. Various remarks that we make during this call about the company's future expectations, plans and prospects, constitute forward-looking statements for the purpose of the Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by these forward-looking statements as a result of various important factors, including those discussed in the Risk Factors section of our most recent annual report on Form 10-K for the year ended September 31, 2017, on file with the SEC, which can be accessed on the EDGAR database at www.sec.gov and the other filings we make with the SEC from time to time.

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 future point, we specifically disclaim any obligation to do so even if our views change. These forward-looking statements should not be relied upon as representing our views as of any date subsequent to today.

On the call today representing Clearside are Daniel White, our President and Chief Executive Officer; Charlie Deignan, our Chief Financial Officer; Glenn Noronha, our Chief Scientific Officer; and Brion Raymond, our Chief Commercial Officer.

With that said, I will now turn the call over to Daniel.

Thank you, Steve. Good morning, everyone, and thank you all for joining us on the call today. Before we begin, let me briefly lay out the agenda for today’s call. I will be catching you up on the Clearside story. Brion will provide an update on our commercial organization as we approach our near-term market opportunity in noninfectious uveitis. Glenn will then take you through the details of our clinical development programs and Charlie will discuss our financial results. And finally, I will summarize our discussions. We well then have time at the end of the call for some Q&A.

The positive top line data from PEACHTREE marked a potential inflection point for Clearside and it could help pave the way for a transition from a clinical phase to a commercial stage company. To lead the transition, we recruited Brion Raymond as our Chief Commercial Officer early in 2018. Brion brings a tremendous amount of relevant ophthalmic experience in retina specialist relationships to Clearside. So too does Carol Hoang, who joined us just a few weeks ago as Vice President of Medical Affairs. Among their other past accomplishments, both Brion and Carol were key members of the team at Genentech, responsible for launching the widely use of (inaudible) with drug Lucentis. In a few moments, Brion will provide more details on the attractive uveitis market opportunity.

We’ve made significant progress in this past quarter in advancing our pipeline. In that regard, I’d like to begin with a brief update on where we currently stand with the three most advanced clinical development programs. In each of them, suprachoroidal injected CLS-TA, a proprietary suspension formulation of the corticosteroid triamcinolone acetonide, is being evaluated either alone or in combination with an anti-VEGF agent as potential treatment for sight-threatening diseases of the retina or the choroid.

Let’s start with our first most-advanced program, suprachoroidal CLS-TA is being developed for the treatment of macular edema associated with noninfectious uveitis. As I had mentioned, we announced positive top line results from our Phase 3 clinical PEACHTREE trial of suprachoroidal CLS-TA in patients with macular edema associated with noninfectious uveitis in March. The PEACHTREE trial met its primary endpoint with statistically significant improvement in the proportion of patients getting 15 letters or more in visual acuity as measured on the Early Treatment Diabetic Retinopathy Study scale. All, we may refer to that as ETDRS. All key secondary endpoints in the trial were also achieved. We expect to submit a new drug application for suprachoroidal CLS-TA in patients with macular edema associated with noninfectious uveitis to the FDA in the fourth quarter of 2018. In addition, following discussions with regulatory agencies in Europe and other jurisdictions, we intend to pursue marketing authorizations outside of the US.

While suprachoroidal CLS-TA is being studied as a monotherapy in patients with macular edema associated with noninfectious uveitis, Clearside has also studied suprachoroidal CLS-TA together with an intravitreal anti-VEGF agent and two other retinal vascular diseases, retinal vein occlusion or RVO and diabetic macular edema or DME, both of which have a high vascular endothelial growth factor response to their diseases. RVO is particularly aggressive eye disease resulting from an occlusion to the vein carrying blood out of the retina. This blockage can lead to rapid onset of complications such as sudden declines in vision. Accordingly, there is a significant need to develop new treatment approaches that are both effective early on and that are more durable than current approved therapies. To that end, our objective of our Phase 3 RVO program is to demonstrate that suprachoroidal CLS-TA used together with an intravitreal anti-VEGF agent like the currently marketed drug Eylea can result in better visual outcomes in the early phase of the disease than treatment with an intravitreal anti-VEGF agent alone. This is what we saw in our Phase 2 Tanzanite trial where 52% of the patients receiving combination treatment recovered 3 lines of vision by month 1 compared to 39% receiving Eylea alone.

In June, we announced completion of patient enrollment of our first of two Phase 3 clinical trials at RVO called SAPPHIRE. SAPPHIRE is evaluating suprachoroidal CLS-TA used in combination with Eylea in treatment naïve patients with RVO. If we achieve similar results in SAPPHIRE to that we saw in the Tanzanite trial, we believe that this trial has a potential to demonstrate the ability of suprachoroidal CLS-TA to lead to recovered vision earlier and potentially preserve those vision gains over the long term. We look forward to reporting top line 8 week primary endpoint data from the Phase 3 SAPPHIRE trial in the fourth quarter of 2018.

In March, we also announced enrollment of the first patient in TOPAZ, a second Phase 3 clinical trial of suprachoroidal CLS-TA used with intravitreal anti-VEGF agent in patients with RVO. The design of TOPAZ is similar to SAPPHIRE with one key difference. In the second trial, we were evaluating suprachoroidal CLS-TA used together with one of two different intravitreal anti-VEGF agents either LUCENTIS or AVASTIN. If the primary endpoints are met in both SAPPHIRE and TOPAZ trials, we intend to seek a class label in the United States, which would if included as part of the marketing authorization approved by the FDA, allow suprachoroidal CLS-TA to be used together with any intravitreal anti-VEGF agent for the treatment of retinal vein occlusion. In addition, based on recent feedback from the European Medicines Agency, we believe that data from our RVO Phase 3 development program should be sufficient to support potential market and authorization application in the EU.

Our work in RVO in part also led the groundwork for us to expand our development program for CLS-TA to include another retinal vascular condition with a large population, DME. DME is the most common cause of visual loss in people with diabetes mellitus. A consequence of diabetic retinopathy, DME is swelling of the retina caused by leaking blood vessels. DME affects up 30% of people who have had diabetes for 20 years or more and if untreated, approximately 20% to 30% of people who have it will experience moderate vision loss.

In May, we announced positive top line data from TYBEE, our multicentered, randomized, masked, controlled Phase 2 clinical trial evaluating the safety and efficacy of suprachoroidal CLS-TA used with intravitreal Eylea in 71 patients with DME over a 6-month evaluation period. The question we were most interested in understanding from this exploratory trial was whether vision gains to be maintained with fewer treatments since monthly injections imposed a significant treatment burden on patients with DME. In the timed trial, we observed not only statistically similar vision results at every time point in patients treated less frequently with a combination treatment as compared to those treated monthly with Eylea alone, but we also observed significant improvement in resolution of retinal statements by month 1 after the treatment with suprachoroidal CLS-TA. We believe CLS-TA used with anti-VEGF agent has the potential to provide a most lasting response to treatment, thereby substantially lowering the treatment frequency and burden for DME patients.

In a few moments, Glenn Noronha will provide more details on the TYBEE results. But before he does, I'll now turn the call over to Brion to provide a brief commercial update on uveitis. Brion?

Thanks, Daniel. Uveitis is a set of inflammatory conditions affecting the eye and is one of the world's leading causes of blindness. The global uveitis market is expected to reach over $1 billion by 2024 and in the United States affects approximately 350,000 patients. Macular edema occurs in approximately one third of these patients and is the largest contributor to vision loss. Suprachoroidal CLS-TA, if approved by the FDA for the treatment of macular edema associated with noninfectious uveitis, would be the first therapy indicated for this disease and represents an attractive market entrance opportunity.

Over the past two quarters, we've made great progress building our commercial team to capitalize on this opportunity. Our team has decades of experience in ophthalmology in broad relationships within the retina and uveitis communities. Our commercial team leaders built their expertise at companies such as Genentech, [Santin], Eyetech and OptiTech and has executed new product launches across all commercial areas, including marketing, access and reimbursement, market analytics and sales. We're confident if the FDA approves suprachoroidal CLS-TA that we will be ready to rapidly and efficiently reach the uveitis and retinal specialists who manage these patients in the United States.

I will now turn the call over to our Chief Scientific Officer, Glenn Noronha, to provide some additional details on the PEACHTREE data as well as the TYBEE results in DME and our programs in RVO as well. Glenn?

Thank you, Brion. As we have discussed the PEACHTREE top line results on previous calls, I'll provide a brief summary of the data to focus this discussion. PEACHTREE enrolled 160 uveitis patients across 64 clinical research sites in the US, India, and Israel. Patients were randomized 3 to 2 to receive two suprachoroidal CLS-TA injections or two sham procedures 12 weeks apart with 96 and 64 patients randomized in each arm respectively. As Daniel mentioned, this trial met its primary endpoint. In PEACHTREE, 47% of patients who received suprachoroidal injected CLS-TA gained at least 15 ETDRS letters in best corrected visual acuity from baseline as measured at week 24, the primary endpoint, compared to 16% of patients who underwent sham procedures. This improvement was statistically significant with a p value less than 0.001.

For a key secondary endpoint, administration of suprachoroidal CLS-TA resulted in a mean reduction from baseline of 153 microns in central subfield thickness at week 24 in the CLS-TA arm compared to 18 micro metered option in the sham arm, a result that was also statistically significant with a p value less than 0.001. Suprachoroidal CLS-TA was generally well tolerated with no treatment related serious adverse events in the trial. 97% of patients completed this trial.

As we continue to analyze the data some key positive observations include the following: approximately two-thirds of the patients in the CLS-TA arm were at any level of inflammation at baseline showed resolution with scores of 0 in each of the 3 commonly used findings of inflammation in the eye, namely anterior chamber cells, anterior chamber flares, or vitreous haze. In all three of these finds of information, there was significant improvement in resolution of uveitis when comparing the CLS-TA arm to the control at week 24.

More recently, during an oral presentation at the 2018 American Society of Retina Specialists annual meeting in Vancouver held recently, Dr. Steven Yeh who is the Louise M. Simpson Professor of Ophthalmology and the Uveitis and Vitreoretinal Surgery Director in the Uveitis and Vasculitis Service at the Emory Eye Center at Emory University, shared data from PEACHTREE which provided further support to suprachoroidal CLS-TA as a potential treatment option for macular edema associated with noninfectious uveitis. One such analysis pointed to the functional significance of the vision improvements observed in the PEACHTREE trial. Specifically, 52% of patients in the CLS-TA arm could read 70 or more ETDRS letters at week 24, which is the legal requirement for driving in most states, compared to 22% of patients in the control arm. Also, based on further safety analysis, which now includes patients who received rescue therapy, elevated intraocular pressure adverse events pertaining to corticosteroid use were reported for 11.5%, that's 11 out of 96 patients in the CLS-TA arm compared to 26.3%, 10 out of 38 patients, in the control arm who were rescued with local corticosteroids such as intravitreal OZURDEX and subtenon on a intravitreal triamcinolone acetonide resulting in an overall elevated intraocular pressure of 15.6% of patients in the sham control arm through 24 weeks, regardless of whether or not these patients received rescue therapy.

We're in the process of receiving our final datasets and completing the various sections of the NDA. All aspects of these efforts remain on track. We're expecting to submit our NDA for suprachoroidal injected CLS-TA for uveitis macular edema in the fourth quarter of this year. We also plan to pursue marketing authorizations outside the United States.

Let's turn our attention to our RVO program. As Daniel highlighted, in addition to our use of suprachoroidal CLS-TA as monotherapy in uveitis, in RVO we are exploring that the suprachoroidal CLS-TA along with an intravitreal anti-VEGF agent as a combination therapy can provide earlier outcomes of improved visual acuity, reduced macular edema, and reduced treatment frequency as compared to administration of intravitreal anti-VEGF agent when used alone. The literature provides evidence that corticosteroids and anti-VEGF agent each have known advantages in the management of RVO when used intravitreally.

In mid-June, we completed patient enrollment in our first randomized controlled double max multicenter, multi-country Phase 3 clinical trial for the potential treatment of patients with RVO. The trial is called SAPPHIRE. This trial enrolled 460 patients in approximately 115 investigational sites across 18 countries. Patients in SAPPHIRE are being randomized to either combination arm in which they receive suprachoroidal CLS-TA along with intravitreal Eylea or the control arm in which patients received intravitreal Eylea alone. Patients will be evaluated every 4 weeks with safety and efficacy analyses performed at week 8, week 24, and at the end of the study. After week 24, patients in both arms will be followed for approximately an additional 6 months. The primary endpoint of the SAPPHIRE trial is to determine the clinically meaningful proportion of patients in each arm with an ETDRS improvement of 15 or more letters from baseline 8 weeks after initial treatment. We expect to report top line data from SAPPHIRE in the fourth quarter of 2018.

As Daniel also mentioned, we are now enrolling patients in our second Phase 3 RVO trial, TOPAZ, the design and scale of which are similar to SAPPHIRE, but which is evaluating suprachoroidal CLS-TA in combination with one of two other intravitreal anti-VEGF agents, LUCENTIS or AVASTIN, in treatment naive patients with RVO.

I now want to turn our attention to the other major retinal vascular condition we are seeking to treat, diabetic macular edema. In May 2018, we completed a Phase 2 clinical trial, which we refer to as TYBEE, evaluating the safety and efficacy of administering a combination of intravitreal Eylea and suprachoroidal CLS-TA to patients with DME as compared to intravitreal Eylea alone. 71 patients were randomly assigned 1 to 1 to receive either quarterly treatments of suprachoroidal CLS-TA together with intravitreal Eylea at month 0 and 3 in the combination arm or 4 monthly treatments of intravitreal Eylea at months 0, 1, 2, and 3 in the control arm, with patients in both arms receiving intravitreal Eylea treatments at months 4 and 5 as needed. Patient follow up in TYBEE was 6 months after initial randomization.

The TYBEE trial met its primary endpoint. In each arm of the trial, there was a statistically significant mean improvement in best corrected visual acuity from baseline over 6 months with a p value of 0.001. These improvements in best corrected visual acuity in each arm were clinically and statistically similar with a combination arm and the Eylea arm gaining 12.3 and 13.5 ETDRS letters, respectively, with a p value that showed that these two numbers are not different from each other. Additionally, administration of suprachoroidal CLS-TA together with intravitreal Eylea met a key secondary endpoint with a mean reduction from baseline of 208 microns in central subfield thickness of the retina at 6 months compared to 177 micron mean reduction in the Eylea alone arm with a p value of 0.156. There was significantly better resolution of edema in the combination arm as compared with the control arm at week 4 with a p value less than 0.01.

As we summarized in a table included in our press release this morning, the additional CLS-TA reduction of the combination arm was observed at week 4 and was sustained through the end of the trial. Suprachoroidal CLS-TA in combination with intravitreal Eylea was generally well tolerated with no treatment-related serious adverse events reported in this trial through the 24 week evaluation period. Elevated IOP adverse events were reported for 8.3% or 3 out of 36 patients in the combination arm compared to 2.9%, 1 out of 35, in the control arm. Both combination and control arms reported cataract adverse events with approximately 5.6%, 2 of 36 patients, in the combination arm and 2.9% or 1 of 35 patients in the control arm. As we receive the individual patient data, we will continue to work closely with our scientific and medical advisors to evaluate the outcomes of the TYBEE trial and to develop a path forward for this important program.

As you can see, the development teams have had a busy and productive second quarter and we really appreciate all of their efforts. I'll now turn the call over to our Chief Financial Officer, Charlie Deignan, to review our second quarter 2018 financial results. Charlie?

Thanks, Glenn. As we reported this morning, our research and development expenses were $17.3 million for Q2 2018 compared to $11.5 million for the same period in 2017. As expected, we had an increase in R&D costs associated with our clinical development programs in RVO and DME, partially offset by a decrease in costs associated with our uveitis program as PEACHTREE was completed. As Daniel and Glenn highlighted in their opening remarks today, we have been advancing our development programs with the reporting of top line data from our Phase 3 trial for macular edema associated with noninfectious uveitis in March and from our Phase 2 trial for DME in June and two continuing Phase 3 trials for RVO.

General and administrative expenses in the second quarter were $3.6 million, up from $2.3 million in the 2017 second quarter. This increase was primarily due to higher employee-related costs and marketing expenditures to support the potential commercialization of CLS-TA. The Q2 2018 net loss was $20.7 million or $0.65 per share compared to $13.8 million or $0.54 per share for the same period in 2017. Cash used in operating activities for business in the 2018 second quarter was approximately $19.5 million.

As of June 30, 2018, cash, cash equivalents, and short-term investments totaled $84.4 million. We believe we have sufficient cash on hand and borrowing capacity under our debt facility to fund operations and begin commercialization activities in advance of potential launch of our first product.

As Daniel and Glenn mentioned, our goal is to report data from the first Phase 3 SAPPHIRE trial on RVO before the end of the year and we expect to have enough cash to take us into the fourth quarter of 2109.

With that, I'll turn the call back over to Daniel for his closing remarks. Daniel?

Thank you, Charlie. I want to personally thank our shareholders for their continued support for the Clearside strategy, which continues to demonstrate a greater utility of treating complex, sight-threatening eye diseases using a unique drug distribution provided by suprachoroidal delivery.

To summarize, we've made great progress so far this year in advancing our pipeline, including reporting positive results from our Phase 2 PEACHTREE trial in uveitis and meeting the primary endpoint in our Phase 2 TYBEE trial in DME. Moving forward, we're on track for our key milestones in the second half of the year, including our first NDA filing, the release of top line Phase 3 SAPPHIRE data in RVO.

This concludes our prepared remarks for today. Before I open the call to questions, I'd like to express my thanks to the entire Clearside team for the significant progress we've made in the second quarter. We have a strong and highly capable team of professionals and have consistently delivered on our key goals and we appreciate their commitment to our mission.

With that, we will now open the call up for questions. Operator?

(Operator Instructions) Our first question comes from the line of Anupam Rama from JP Morgan.

This is Tessa, on for Anupam this morning. Thank you for your updates here and for taking our questions. One from us maybe on any further physician feedback you all have gotten following TYBEE around BCVA, CST, additional Eylea injections required and maybe also safety in the context of the unmet need in the disease here? And then secondarily, what are the outstanding endpoints to monitor in the total data set that will inform the design for the pivotal trial? And then related, if I could, can you comment on the extent of the read through from DME that you anticipate so RVO expected now in 4Q? Thanks so much, guys.

Thanks, Tessa. Let me maybe answer your last question first. So, there's and then I'll turn over to Glenn to kind of talk about some of the physician feedback over on -- that there is a big difference between patients who have diabetes who may have had diabetic retinopathy for a long period of time and then they're finally seeing their central vision begin to be affected and that creates diabetic macular edema with central vision. And this is the field in which we really pay attention to because that's where vision loss is occurring. A big difference in that compared to RVO is that RVO is a catastrophic vision loss where you see occlusion causing more like a stroke on your retina and that is causing just a huge amount of VEGF to be produced. And you see really good outcomes because you see these very, very large changes in people's vision with RVO. And so that's some of the hallmarks that you tend to think about. Corticosteroids have been known to work in DME. We see a couple of approvals out there. But we want to find the right place and right cases in our evaluation of the TYBEE data.

The one thing that we've been hearing from physicians consistently is they're very impressed by how quickly we're able to improve central retinal thickness in the patients. They do understand that it's a bit tougher patient population, but we do hear that comment consistently. And as far as the side effects, they see those side effects as consistent with natural history of the patient population and also that they could see that is consistent with our other trials where we see this very low event of intraocular pressure compared to what we would expect in the literature and what we're also seeing now comparing our sham control in PEACHTREE along with control with topical drops so we're happy about that.

Glenn, why don't I turn it to you about kind of where we stand on the data evaluation and what are some of the next steps we think about?

Thank you, Daniel. So I want to highlight the fact that DME is a unique disease all by itself and we are continuing to analyze data. We are focusing in on all the information that we have as well as the information to come. We have clearly found that the anatomical information is providing some unique outcomes, including the fact that we have a statistically significant resolution that occurs at month 1 with a p value less than 0.01. And these anatomical outcomes that are achieved with a lower frequency of treatment are key to some of the items that we'll be continuing to look at in greater detail.

Clearly, we matched the visual acuity outcomes statistically and clinically that are seen from monthly intravitreal aflibercept Eylea. And so as we continue to tune on in these data, we'll be focusing in on frequency, the reduction of treatment burden and as well as the anatomical outcomes. But we'll keep everybody informed through medical conferences and other information as we continue to find the key pieces of information that will help us to inform the program as it goes forward.

Tessa, this is Daniel again. The last physician feedback I've been receiving has been if you think about the everyday practice of DME that we're, one consistent complaint we have is that around compliance. Where we see in many practices, nearly 20% of patients don't return in a timely fashion for their second or third injection. And by under treating these type of patients, we're seeing real-world outcomes more like 5 letters of improvement. And as you can see in our clinical trial, we saw 12.3. Thank you.

Appreciate all the color, guys, and thanks for the updates.

Our next question comes from the line of Annabel Samimy from Stifel.

Good morning. This is Nick Rubino on for Annabel Samimy. Thanks for taking our question. Starting to think about the competitive landscape in uveitis. There are other products in development with 3 month implants or 1 year implants. How might this impact your opportunity in uveitis?

Thanks, Nick. This is Daniel. You know I think it's best I let Brion Raymond answer that as he's preparing for the launch and really comparing our data with what others are doing in the marketplace.

Sure, thanks, Daniel. I think there are a couple of ways to answer that question. First is indication. Our indication is expected to be or if the FDA approves us, macular edema following noninfectious uveitis and it's agnostic to the location of the uveitis. So, two things there, one we'll be the only ones with that indication and we'll also be the only ones that should we be approved, would be reimbursed for all types of uveitis as long as they have macular edema. So we're going after the more severe patients and we're showing visual gains that I don't believe have been shown before with other drugs.

Second is we're targeting first line therapy. If there's macular edema when the patient walks in the door, we would like to be the first line therapy for those patients to eliminate that edema and bring vision back to patients. So, I think we're just positioned differently in the marketplace and we hope to be first line, where some of the longer therapies are more of a maintenance approach.

So, Nick, this is Daniel. I just want to share something with you guys. This gets to me as a CEO of a vision company and hopefully all of my team thinks about it as well. I think there's like 2.7% of patients who came into that trial could see 20/40 or better. And that means they were driving. They had to have some assistance making it to the clinic. They have to bring it back to, how they're going to make it to their next visit. And then, by the end of the trial, even by the, there were about 52% of patients were seeing 20/40 or better. And that means they're walking through their house and they're doing the day-to-day functions and more and maybe even driving. And these are the things that help us kind of wake up every morning and come to work.

So I think PEACHTREE data going after being the first company to go after the best corrected visual endpoint as a target in this particular disease, ended up becoming a very meaningful outcome and I think the physician feedback we're getting off that is that we are managing the patients well. We're meeting the best corrective visual acuity. And in most cases, sending us over two-thirds of the patients are seeing resolution of their signs of uveitis in all compartments of the disease and that's exciting because it's really, really playing a role in the disease.

The next question comes from the line of Serge Belanger from Needham.

A couple questions for me on uveitis. It sounds like your ex-US strategy is being developed here. Just wanted to hear your thoughts on what you're thinking in terms of filing and partnering for commercialization? And then I guess can you just talk about the market opportunities in uveitis for -- in Europe as well as other ex-US territories?

So, yes, thanks, Serge. When we can -- when I think about any product that we'd want to develop, we consider this on a global -- as a global approach. When you look at all of our studies in both in uveitis, we have multi-country in India and Israel. And as you can see in RVO, we're multi country, multi continent in our approach. And we believe that we will have the dataset that will be supported. As of right now as it relates to uveitis, we're probably going to take the data first that we have for the NDA and the discussions that we've had with the FDA have been positive. And so we're going to submit the NDA, initially with the FDA and then turn our attention to the EMEA for submission in Europe. But we will have started discussions with them as far as the next steps. As far as the data inclusion, we have had positive discussions with EMEA and feel that we have the right clinical trial that will be supportive of the future submissions in those territories as well.

As far as the European or landscape or worldwide landscape, I can let Brion Raymond maybe comment on that.

Yes, so the -- you know the European market is an attractive one, both from a prevalence of disease as well as the use of steroids. They're more actively used outside the US and I think if you look at some of our competitors' sales results, you'll see the ex-US sales are greater than the US sales, which is counter to the anti-VEGF. So, we believe Europe is an attractive market for us, potentially equal to or larger than the US market. And we've received some recent research saying that we should have some pricing power in the EU as well, encouraging I would say pricing power in the EU compared to some of the other therapies that are already approved on the market there.

And just a couple on the DME program. Do you think we can get an update on the program by the end of this year? And maybe too early for this, but what are you thinking at this point in terms of potential Phase 3 trial designs in terms of patient numbers and endpoints?

Thanks, Serge. I'll let Glenn comment on that at this time.

Thank you, Daniel. Serge, we'll keep you informed as we are ready to speak about this. You know it's likely that we should have greater amount of input as the year goes by, but we'll definitely keep you and everybody else informed. I do not want to comment on trial designs. The FDA has fairly traditional requirements for what's done for the other approvals within the framework of each of these diseases and we're really doing things that would be similar to that, but of course the specifics of what we're looking at will be unique to us and we'll of course share that once we have that ready.

Thanks for the update.

Our next question comes from the line of Liana Moussatos from Wedbush.

Thank you for taking my question and congratulations on your progress. I just have a little follow up on DME. Have you made a date for an end of Phase 2 with the FDA? And what are your next steps before you can say anything to us? What do you have to do?

Okay, thanks, yes, thanks Liana. As we ran TYBEE, what we did is -- in order to -- for us to make -- to run a study without any bias, we typically use CROs to do that. And the CROs which we current -- what we use have just now gathering most of the individual patient data. So we're just now getting that in really as we speak today. So it's not like it's very -- we've had an opportunity to really gather into that. Before we're able to submit anything to the FDA for in a phase team meeting, we'd have to create a briefing document. So we haven't done that as well yet. So these are all things that we're putting together and currently we wanted to -- it's within our time line of the proper so we continue to make with this program. We'll know a lot more by the next time we talk on the phone.

Okay and when in Q4 do you think the RVO data will come out? Will it be early or late or can you say?

That's a great question. RVO has been recruiting -- well we closed our SAPPHIRE data back in the June time frame I believe that was when it was done. And obviously we're going to want to let these [picks] go the full 2 months before we can begin to gather the data. It's a large multi-location, multi continent clinical trial. It'll take us a little time to do that. So, I'm not really pointing to a direction in fourth quarter at this point. I'm really just waiting to see. Want to make sure that the data comes in correctly and clean and something that's the highest priority.

(Operator Instructions) Our next question comes from the line of Francois Brisebois from Laidlaw.

I just had a couple questions in terms of the commercial effort here. Can you comment on your efforts for prepping in terms of reimbursement and also in terms of reps hiring, there's a number and timing that you would have to do here?

Yes, Brian, that's a good -- feel free to grab that one.

Sure. I think reimbursement is probably the most advanced part of our program right now. We've been working with payers' cost effectiveness models and trying to understand the market and also figure out how we can -- we'll be positioned within the payers' minds. And all I can say is that the results that we've received back have been encouraging across the board from the model and from the payers as well. And on the sales front, you know we are targeting a sales force that's a little bit smaller than current retina sales force, but it'll be a small group, an efficient group to reach, you know between 1,900 and 2,100 physicians would be our target market. Timing wise, I think we'll start planning the hiring in Q4 and based on our filing time lines and FDA feedback, we'll start accelerating hiring in the beginning of next year.

All right. Thank you, that's helpful. Yes, no it does. And just lastly here, before ASRS, you guys didn't show the sham data, the 15.6 rise in IOP. I’m just wondering why you took the ones out that were rescued. And then was the chatter mostly at ASRS around the data, mostly about the IOP advantages or was it on you guys being the first ones to look at visual acuity as an endpoint?

Yes, that's a good question. It was a little confusing but so what we did is in our sham arm of the PEACHTREE data, we have multiple ways which patients might be considered quote, unquote rescued. The first ways that they've got uveitis and they see this uveitis and they want to treat it, that occurred in a number of products. So they give them an eye index or intravitreal or (inaudible) to learn and that we've called it local treatment. And that's what we saw where 10 out of 26 patients, 28, 28 patients, sorry, 10 out of 28 patients or had intraocular pressure event from that. So that would have occurred probably 4 to 8 weeks at least post from the original initiation of the trial. And then these patients are already getting treated -- percentage of that was how? 28%? 26%, sorry. So that's (inaudible).

That was for local treatment. But there are other reasons why these patients may also be rescued. So they could have increases in some eye systemic problem in which they require a systemic therapy for their disease and they would be considered rescued from that. Or they received topical drops for some reason that they would be given for 8 more -- that model would be excluded anterior segment disease. That could be occurring as well. So, we just wanted to compare what a local treatment would be to a local treatment and we saw that 26% verse the 11% was the better number that we tend to show physicians.

And so the feedback we received from our physicians in our ad board was they feel like they were showing profound improvement on the efficacy, both on just the best corrected visual acuity assigned to the patient as well as the fact that there are so few patients that were rescued in our arm versus the sham, 86% of the patients made it through the complete study at our arm without being rescued. And that means less patient management of a very complex patient group.

Lastly, seeing the -- saw symptoms of improvement were of interest to the KOLs as well. But also on the safety side, they see this as a much greater benefit from an intraocular pressure point of view and from a cataract point of view. They're really not worried about cataracts as much. But the main interest they have is that not only are they are impressed by the lower rate of expected intraocular pressure events, but the lower rate of surgical events associated with those as well. And if you have these patients who aren't required for further treatment than topical drops, they feel like that's very manageable from the physician point of view.

Actually, no that's very helpful. And then just to make sure, in terms of the sales reps hiring that when you mentioned fourth quarter, was that fourth quarter '18 or '19?

Ideally, we would have a final plan by the end of fourth quarter and begin hiring the leadership team in Q1 of '19.

Thank you and that's the final. There are no further questions. I'd like to turn the call back over to Daniel White for any closing remarks.

All right, thanks once again for joining us for the call today. I didn't hear you quite well, operator, sorry about that. We appreciate your continued interest in Clearside. Look forward to updating you on our progress in the months ahead. Operator, you may now disconnect.

Ladies and gentlemen, thank you for your participation in today's conference. This does complete the program and you may all disconnect. Everyone have a great day.