Stephen Kilmer - IR Daniel White - CEO Richard Beckman - Chief Medical Officer Glen Noronha - Chief Scientific Officer Charles Deignan - CFO.

Annabel Samimy - Stifel Nicolaus Anupam Rama - JPMorgan Liana Moussatos - Wedbush Securities Donald Ellis - JMP Securities Serge Belanger - Needham & Company.

Good day, ladies and gentlemen and welcome to the Second Quarter 2017 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 be given at that time.

[Operator Instructions] I would now like to introduce your host for today's conference Mr. Stephen Kilmer, Investor Relations. Please go ahead, sir..

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 purposes 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 or quarterly report on Form 10-Q as applicable and filed 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; Glen Noronha, our Chief Scientific Officer; and Dr.

Richard Beckman, our Chief Medical Officer. With that said, I'll now turn the call over to Daniel..

Thank you, Steve. Good morning, everyone and thank you all for joining us on the call today. For the benefit of those who are new to Clearside Biomedical story, I'd like to take a moment to highlight our company's mission. Clearside is developing transformative elegant precise solutions to restore and preserve vision.

We focus on treatments for diseases affecting the retina and the choroid of the eye, especially diseases associated with Macular Edema.

Our treatments are injected into the suprachoroidal space or SCS of the eye, using our proprietary SCS microinjector by leveraging the exclusive access to and proprietary technology for suprachoroidal injection of drugs to access the retina and choroid, we believe the clinicians can more effectively treat sight threatening diseases like uveitis, Retinal Vein Occlusion or RVO, Diabetic Macular Edema or DME and wet age-related macular degeneration or Wet AMD.

We believe that drug administration by suprachoroidal injection provides higher levels of drug at the retina and choroid, which may offer improved onset of action to reach vision goals more quickly than other rich administration may require fewer injections and may provide additional efficacy data higher bioavailability.

And finally, in the case of corticosteroids may offer a better risk benefit ratio over intravitreal or periocular injections of the same drug. With that mission in mind, I'd like to begin with a brief update on where we currently stand with our clinical development programs.

Let's start with our first most advanced program which is in late-stage testing CLS-TA via suprachoroidal administration for the treatment of Macular Edema associated with non-infectious uveitis. CLS-TA in the name of our drug, a proprietary suspension formulation of the corticosteroid triamcinolone acetonide.

Non-infectious uveitis is a set of inflammatory conditions affecting the eye as well as the world's leading cause of blindness. Uveitis occurs in approximately 350,000 patients in the U.S.

alone, Macular Edema occurs in approximately one-third of all non-infectious uveitis cases, and is the dominant contributor to vision impairment and vision loss in these patients. Earlier this week, we announced the completion of enrollment in the pivotal Phase 3 PEACHTREE trial.

Patient follow-up of the PEACHTREE trial is six months after initial treatment. Accordingly, we currently expect to report top-line results from the trial in the first quarter of 2018. Our second most advanced program is suprachoroidal CLS-TA used together intravitreal administered Eylea for the treatment of Retinal Vein Occlusion or RVO.

As RVO is one of the most aggressive retinal diseases that can lead to vision impairment and potential permanent vision loss, there was a strong need to develop new treatment approaches that are both effective and more durable than currently approved therapies.

To that end, we are continuing to enroll patients in the Phase 3 clinical trial SAPPHIRE which we initiated in the first quarter of 2017. SAPPHIRE is the multi-centered multi-country, randomized mass-controlled trial - to assess the safety and efficacy of suprachoroidal CLS-TA used with intravitreal Eylea in patients with RVO.

The primary objective of this trial will be to determine proportionate patients in each arm with best visual acuity improvement of at least 15 letters from baseline at eight weeks after initial treatment. Several secondary efficacy and safety outcomes will also be evaluated.

A work in RVO also lay the groundwork for us to expand our development programs, CLS-TA to include another retinal vasculitis disease, DME. While the current standard of care in treating patients with DME is through the use of intravitreal anti-VEGF agents. There is still significant unmet need in this large patient population.

That is driven by the fact that approximately 40% of DME patients have insufficient response to VEGF inhibitors.

With this potential to access the retinal choroid high amount, we believe there is an opportunity for more effectively treat DME by administering suprachoroidal CLS-TA concomitantly with intravitreal Eylea when compared with intravitreal anti-VEGF or intravitreal corticosteroid therapy treatments used alone.

We are very pleased to announce about a month ago the enrollment of the first patient in the Phase 2 clinical trial in DME called TYBEE.

The primary outcome measure will be a comparison between two study arms of change from baseline and best corrective visual acuity of three months and we currently expect to report preliminary data in the first half of 2018.

Our CMO, Rick Beckman and CSO, Glen Noronha will provide some more detail on the TYBEE trial and our other programs in a few moments.

Before turning the call over to Rick and Glen, I'd like to thank this opportunity to thank Derek Yoon who has retired from Clearside's Board of Directors for his many contributions to the company and also welcome his successor, George Lasezkay to the Board.

George brings to Clearside a unique combination of clinical executive and legal experience but he's played a critical role in developing corporate strategy and providing counsel on strategy partnership in this development programs and licensing transactions for - company.

Not but least of these was Allergan, where his 30 years of progressive experience included a number of executive positions including Corporate Vice President for Corporate Development, number of the company's executive committee, general counsel of commercial affairs and general counsel for the agent region.

I'm excited that Clearside has attracted someone of George Lasezkay's caliber to the Board and very much look forward to working with him. I now turn the call over to Rick Beckman to lead off a more in-depth updates and discussion of our pipeline.

Rick?.

Thank you, Daniel. With the very recent completion of enrollment of 160 patients in the pivotal Phase 3 PEACHTREE trial of suprachoroidal CLS-TA for the treatment of Macular Edema associated with non-infectious uveitis, I would like to start by briefly refreshing everybody on that study.

In our previously reported Phase 2 Dogwood trial of suprachoroidal CLS-TA in patients with non-infectious uveitis, we observed statistically significant improvements from baseline month to in both Macular Edema and best corrected visual acuity.

Based on the feedback from the end of Phase 2 meeting with the FDA, we believe our pivotal PEACHTREE trial will be the only Phase 3 clinical study required to support the potential filling of the new drug application.

This Phase 3 trial is a controlled randomized masked multicenter trial to evaluate the safety and efficacy of suprachoroidal injected CLSTA in patients with Macular Edema secondary with non-infectious uveitis. This two-arm trial compares to treatment arm to a share arm where no treatment is given.

The primary outcome will be a comparison of best corrected visual acuity between the two arms of six months follow-up after initial treatment. We expect to report preliminary results from the study in the first quarter of 2018.

I would also like to take this opportunity to comment briefly on the safety profile that has emerged thus far in our testing of patients who have received 4 milligrams of suprachoroidal CLS-TA across all of our completed and ongoing clinical trials. So far more than 200 subjects have been treated and no safety signals have been detected.

Since safety data from ongoing clinical trials has masked and because as Glen will discuss shortly, the ongoing studies are quite large, it will be sometime before it can provide more detail.

However, we remain optimistic that the positive safety profile observed in the early phase studies will continue to the course of the pivotal trials moving forward. With that, I will turn the call over to Glen to discuss Clearside's RVO and DME programs..

Thank you, Rich. As Daniel mentioned, in our view we are exploring with the suprachoroidal CLS-TA along with intravitreal Eylea as a - therapy can provide improved visual acuity, reduced Macular Edema and reduced treatment frequency as compared to administration of intravitreal Eylea alone as monotherapy.

Corticosteroids and anti-VEGF agents each have known advantages in the treatment RVO. At the Annual Macular Society Meeting has earlier this year in June, Dr. Charles Wykoff presented preliminary results from a non-interventional follow-on trial of the RVO patients who have been in the Phase 2 TANZANITE trial.

As background, patients in the combination of TANZANITE trial achieved both additional acuity improvement and Macular Edema adoptions over a three-month period, following initial dosing with suprachoroidal CLS-TA and intravitreal Eylea as compared to patients in the control arm who had only received intravitreal Eylea baseline.

Based on the fact that so few patients in the TANZANITE combination received additional treatment, the current need for frequent office visits and injections required in this patient population and after feedback from our investigators, Clearside conducted this follow-up trial with a retrospective analysis of patient charts to better assess the duration of effect of the combination treatment and the potential to reduce the burden of therapy.

In the retrospective analysis presented by Dr.

Wykoff, 14 of the 23 patients in the combination on the TANZANITE trial of 74% did not receive any additional treatment over a decent nine-month timeframe that included three months from the TANZANITE trial and at least the six months follow-on period compared to only 4 of 23 patients or 17% in the Eylea during the same period of time.

We believe the data from the TANZANITE trial and the follow-on trial implied the suprachoroidal CLST-A in combination with intravitreal Eylea may result in improvements in vision seen as early as month one and maintain through month three as well as a substantial prolongation of the time required for additional treatment compared to the effect seen from intravitreal Eylea alone under the as needed additional treatment conditions used in this evaluation.

We are encouraged by these data, which suggest that suprachoroidal CLST-A in combination with intravitreal Eylea for the treatment of RVO and treatment naïve patients has the potential to not only provide better vision at an earlier time point, but also to lower the need for additional treatment when compared to intravitreal Eylea monotherapy.

February of this year, we initiated our first randomized controlled double mass multi-center, multi-country Phase 3 clinical trial for the potential treatment of patients with RVO. This trial is being conducted at approximately 150 investigational sites across approximately 18 countries and we've enrolled approximately 460 patients with RVO.

Patients would be randomized either to a combination on which patients will receive suprachoroidal CLST-A together with intravitreal Eylea enrolling approximately 230 patients auto control arm in which patients will receive intravitreal Eylea alone also enrolling approximately 230 patients.

That primary objective of this trial, the SAPPHIRE trial is to determine the proportion of patients in each arm with the best corrected visual acuity, improvement of greater than or equal to 15 early treatment diabetic retinopathy study or ETDRS letters from baseline at eight weeks after initial treatment.

In the TANZANITE Phase 2 trial and patients with RVO, where additional treatments were on an as needed basis after initial randomization, 61% of patients would receive the suprachoroidal CLST-A along with an intravitreal Eylea - injection of Eylea at baseline achieved a greater than or equal to 15 ETDRS letter improvement in BCVA at eight weeks.

While 39% of patients had received only intravitreal Eylea baseline showed a greater than or equal to 15 ETDRS letter improvement in BCVA, in the same timeframe that is at eight weeks. I now want to turn our attention to our other major retinal vascular conditions, we are seeking to treat DME in which we have our third clinical program.

In our DME program, we have an ongoing Phase 1, 2 clinical trial, the HULK trial that patient enrollment was completed in April this year. In this trial, we are evaluating suprachoroidal CLST-A with or without intravitreal Eylea and patients with DME.

While safety is the primary outcome from this study, we'll also be evaluating changes in best corrected visual acuity and in Macular Edema over the six-month evaluation period. We expect to report preliminary results from the HULK trial later in this year.

Further and as Daniel mentioned, in July this year, we announced the enrollment of the first patient in a multi-center randomized mass controlled Phase 2 trial in DME called TYBEE to evaluate suprachoroidal CLST-A along with intravitreal Eylea compared to intravitreal monotherapy in patients with DME over a six-month evaluation period.

In this mass randomized controlled trial, patients with DME will be assigned in one-to-one fashion to a combination on with suprachoroidal CLST-A and intravitreal Eylea or to a control arm with only intravitreal Eylea. The trial will have a fixed treatment portion for the first three months followed by an as needed portion.

While safety and efficacy will be evaluated in this trial, the primary outcome measure will be best corrected visual acuity where the combination treatment data will be compared to the monotherapy Eylea data. We expect to report three-month preliminary data from this study in the first half of 2018.

All-in-all, the development teams at Clearside have had a busy introductive second quarter in 2018 and we really appreciate all of their efforts. I'll now turn the call over to our Chief Financial Officer, Charlie, to review our second quarter 2017 financial results.

Charlie?.

Thanks, Glen.

As we reported this morning, our research and development expenses were $11.5 million for the second quarter 2017, compared to $4.2 million for the same period in 2016, with the increase driven by our ongoing clinical development programs for CLS-TA and also manufacturing costs partially offset by a decrease in cost from completed clinical trials and Clearside's discontinuation of preclinical trials in the Wet AMD program.

General and administrative expenses in the second quarter of 2017 were $2.3 million compared to $1 million in second quarter of 2016. The increase was primarily due to higher employee related expenses, marketing expenses and cost related for us to be public company.

In the second quarter of 2017, net loss was $13.8 million or $0.54 per share compared to $5.1 million or $0.62 per share for the same period in 2016. As of June 30, 2017, cash and cash equivalents in short-term investments totaled $66 million.

As Daniel, Rick and Glen highlighted earlier on this call, we have been advancing our development programs with the completion of the patient enrollment of the Phase 3 trial for non-infectious uveitis in this month to continuing enrollment of patients in the phase 3 program for RVO the completion of enrollment of Phase 1/2 trial for DME in April 2017, and the enrollment of first patient in Phase 2 trial for DME in July 2017.

As we mentioned on our Q1 call, we expect our research and development expenses to continue to increase as we conduct these clinical trials. That said, we currently expect our cash reserves and resources to take us forward into the fourth quarter of 2018. With that, I'll turn the call back over to Daniel for his closing remarks..

Thank you, Charlie. 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 during the second quarter of 2017.

We have a strong and highly capable team of professionals and a consistently delivered on our key goals and we appreciate their commitment to our mission. With that, we will now open up the call for questions.

Operator?.

Thank you. [Operator Instructions] Our first question is from of the line of Annabel Samimy of Stifel. Your line is open..

Hi, guys. Thanks for taking my questions. So, just a few questions first on SAPPHIRE, how has enrollment proceeded relative to the PEACHTREE trial? And have any of the TANZANITE patients have been able to roll into the SAPPHIRE trial? Has that been a good source of patients for you? And the second question I had was related to the DME trial.

I guess I'm curious what the rationale was of starting highly before the whole trial essentially where you are looking from the HULK trial that you would be okay with the TYBEE trial, going forward with TYBEE trial without the information. Thank you..

Thank you, Annabel. This is Daniel. First of all, I want to commend our team on the SAPPHIRE trial, specific to the array of enrollment. I've been very impressed by the interest by investigators and the community with the trial particularly supported by the outcomes of the Phase 3 study and the team's ability to get many of the sites up and going.

So that's compared to the PEACHTREE study, there is a pretty much a nine-day difference, I would say from enrollment. But let me turn it over to Glen to let him answer some of the more specific questions as far as the TANZANITE patients and the HULK study..

Thank you for your question, Annabel and thank you, Daniel. We don't have any patients from TANZANITE, who will be eligible for SAPPHIRE. Our study takes treatment naive patient, so that means in what's going to happen is that the TANZANITE patients have already been treated are not eligible for SAPPHIRE.

So that's relatively a clear requirement in terms of being on SAPPHIRE. So, PEACHTREE investigators have been a great resource for us as well as our TANZANITE investigators as well as the entire retina community, but TANZANITE patients don't qualify for SAPPHIRE. With regard to diabetic Macular Edema, so rationale for TYBEE and HULK.

So, HULK and TYBEE have different objectives. So, HULK, let's start up with HULK, HULK has two arms, they're independent of each other. It's an open-label study. There is a treatment naive arm and then a treatment experienced arm. So, in the treatment experienced arm, we're using CLS-TA alone.

And in the treatment naive arm, it's exploratory to get some safety information that we're getting on an ongoing basis. The TYBEE trial is controlled mass randomized and in some ways, is a clone in part of our TANZANITE trial in RVO. So, it's got objective that are specific to DME, but uses similar principles to TANZANITE.

So, the idea is that how can we get randomized controlled mass data in DME to educate us to go forward, whereas what HULK will do is it will explore one is a different patient population, a treatment expense population and it will also give us some basic safety data which had - it has been giving and which Rick commented on in general we haven't seen any signal.

So, both of them have independent objectives that continue to help us in our overall development of what we want to do in these three programs in which we are in the clinic..

Okay, can I just ask one more follow-up on the safety.

It is observed so far with this safety relative to the control on that you are seeing or is it just safety and looking adverse than profiles relative to what you know about other steroids that are better used?.

So, this is Daniel again. So, the safety is really - I'll let Rick answer this after I make one comment.

It's important that we understand it now safety that we are seeing is in a large number of patients we've had multiple injections and that's a clear initial step for the company as far as what we've seen and this being consistent with what we've seen previously and our other clinical programs.

We are looking at this, I think more from a - not only the safety of the procedure safety of the drug itself and as it relates to the two corticosteroid treatments and then we will be able to look at the comparison of the safety between these programs as we see some of these spaces roll-off, the mass studies.

So, Rick, do you have anything further to comment on that..

Daniel, I think what you said exactly true, we take into account all of the past information we have on our drug, on other drugs that are similar and we monitor the safety data as we along, it's all mass data and what we are really looking is for any type of signal that would cause us problems as we move along we have not seen any signals at all to get to the fine details of comparative safety and things like that, that requires us to complete the clinical trials to be able to unmatched the data and understand it, it not just in aggregate but also individuals and we don't have that type of information at this point..

Okay, fair enough.

And just really quickly, do you have any thoughts on how long it might take to enroll SAPPHIRE?.

So, Annabel, we haven't given any guidance on the time in which enrollment will take place, we are still getting Europe off the ground and we have had our investigatory meeting in Asia Pacific, but that's in the early phases.

Most of the activity we have seen today has been in the U.S., so until we see those regions begin to take shape I am reluctant to give you any target as far as enrollment is concerned at this point..

Okay. Thank you very much..

Thank you. Our next question is from Anupam Rama of JPMorgan. Your line is open..

Hey, guys. Thanks so much for taking the question. Maybe I could follow up a little bit on the prior question related to the HULK trial.

You talked about the two different populations there maybe you could help us think about the benchmark when we are thinking about the efficacy side and what would be a win scenario in the two different populations? Thanks so much..

So, Anupam, thank you. Let me make Glen kind of review what's currently being done in the DME as it relates to anti-VEGF..

Thank you, Daniel. So, let me take Daniels lead and giving you a synopsis of what we know from the literature and then I'll talk about HULK specifically. So, HULK is our initial open label exploratory.

So, with that in mind, anti-VEGF agents whether Eylea and there are differences between them based on protocol -T, give you on average between 8 and 12 letters in terms of gain, so that's seen after monthly injections.

They usually given as monthly injections with some kind of - it's usually for six months based on the Phase 3 trial that have been done.

And then Eylea goes to once every two months whereas Lucentis continues on monthly and they have once every two months after six months of loading in Eylea has shown that it has good results compared to what you see from Lucentis.

Now, in the comparative trials that we've shown that in people with worst vision, Eylea did better than Lucentis, which did better than Avastin. But in the overall, the three of them seem to do on average about 10 letters of gain with monthly injections.

The corticosteroids have been studied, there is triamcinolone which is studied by Protocol I and the [indiscernible] has its Phase 3 data, Alluvia has its Phase 3 data.

And the corticosteroids in general have shown that they have issues with cataract formation and increases an endrocular pressure, but when you take pseudo patients, they seem to match what the anti-VEGF agents do. So, it gets about 8 to 10 letters again. So that's the setting with monthly injections given as a loading.

So, we're not looking for any specific victories in HULK. It's simply exploratory, it's not powered, the treatment naive arm is going to get the combination and after that it's completely PRN.

So, we'll be looking in that study to look at the response in terms of, A, we'll be looking for safety clearly, and then we'll be looking for the visual acuity response in the Macular Edema response in that trial. Then of course it's going to be PRN after that from month two within HULK.

And our objective will be to see how few injections you can give or how many injections you need to give. We'll collect all the information but it's not powered to show any specific victory in HULK..

Got it. Thanks so much.

You're welcome..

Thank you. Our next question is from Liana Moussatos of Wedbush Securities. Your line is open..

Thank you for taking my questions congratulations on your progress. Now that in your in the home stretch for PEACHTREE and enrolling the final patients. And your other trials you're also focused on Macular Edema with different diseases. So regulatory strategy get approval for NIU Macular Edema and then as the other Phase 3s finish out.

Since you're only doing one Phase 3 for NIU, I presume only one Phase 3 for sNDA and for commercialization are you thinking partnerships looking to do it on your own?.

Thanks, Liana. So, we've always said that we fully intend to commercialize our products on our own. We - this is one of the most ideal specialty pharmaceutical markets with the right products that reaching this population of physicians is very doable.

When we look at the landscape of retina physicians, it's only 1700 that are out there many are collective within clinical centers. So, reaching them is, we're seeing success with sales force side as low as 35 or 40 reps and then that's something that we will intend to look at carefully as we can move forward.

So, we find no interest or need to partner lead program at this point. Now we have a fairly robust collaboration activity going on right now with our team. But that's the proprietary compounds and we're not really spending much time talking about that.

The first indication that we'll be addressing is Macular Edema associated with non-infectious uveitis. We've begun setting the groundwork of that already with a small group within Clearside and consultants that are laying the groundwork. We only require one clinical trial as far as the development is concerned.

The other study can be supported with literature study. And we already looked at that groundwork of that as well. And really, we believe we're optimistic about the success in that.

So, as we continue down this path, and maybe little bit seem with our new board member, we're looking at bringing in the more commercial resources particularly when we began to see the data from the PEACHTREE study..

And longer-term approval for RVO and DME single trials, single Phase 3 trials and sNDA?.

So, I can't tell you the answer to DME, I can't tell you the answer to Retinal Vein Occlusion. There are two studies required for Retinal Vein Occlusion with Macular Edema. I'll let Glen to kind a give you a little bit more color on how the agency is thought about that..

So, in general therapeutic areas are not considered to be overlapping. So, they all have their own requirements based on the disease and length of the studies and what the agency is specifically the FDA willing but not accept. So, in non-infectious uveitis we have one clinical trial as a pivotal trial that's been done. So, there is safety and efficacy.

In Retinal Vein Occlusion, we are doing a what would be called an unfixed combination with an anti-VEGF agent. So that requires two studies in terms of our discussions with the agency. So, they are going to be specific to each disease and what's required in the disease and till then R&D some of the no answers within that.

We will interact, we have had phenomenal interactions with the agency and we have - we'll do our best in terms of whatever we can, but it's one in a bit in non-infectious and doing our view or so far..

Thank you..

Thank you. Our next question is from Donald Ellis of JMP Securities. Your line is open..

Thank you and good morning.

Three questions, the first one is, after a CLS-TA is approved, can you give your thoughts on the reception you expect to get from managed care and the retinal docs? And the second question is what kind to training will be required for the microinjector? And third question for Char, regarding operating expenses for the remainder of this year.

Are they going to be in line with the second quarter? Thanks..

Great, thanks Don. So, let's talk a little bit about managed care, we have been working with some consultants and hired a full-time person for market access and then looking into different models that require for pricing discussions.

From what we've looked at so far, we haven't had two great approach to managed care, but we still believe we're in line with price points between $800,000 is very convincible to me, but I think the models that we've took for. The ability to for market acceptances based upon some of the data that we're seeing.

We'll have the first label for Macular Edema associated with non-infectious uveitis for successful in our Phase 3 clinical trial. It will be for all types of uveitis.

So, we - and if the safety profile continues to go to practice going, we believe, we'll have a very strong argument to go to the payers where the price point in that range and maybe even higher. So, we haven't sell or anything else, we just noted our models are pointing us towards that direction.

We also have to consider the retinal vascular studies that we are looking at as well. They impact that to make and some of this - if we want to look at some other feature clinical activity that could help to support.

Now, but we see the same thing we did in RVO and for the combination that can support an even higher price and more convincing arguments. We're definitely getting the feedback from the physicians and strong and I've been very impressed with support or getting from that from the community.

This large training is concerned, when we typically go out and spend time with the physicians is really the training process is just teaching them a little bit about just the procedure itself. And the major point in which we focus our training is having them used to the whole concept of this loss of resistance.

And to refresh your memory, when we insert the injector into the eye, the clarity is very difficult to inject into, but once you're just beneath the clarity, you can feel the release of the drug and we refer to that as loss of resistance.

And so, it has its smaller curve somewhere about $5 million and for the physician to feel that response and for them to apply that, now into the clinic to the cut, so we've been quite successful and the physicians picking in up refining as they do kind of firm their own style, I guess and where they hold the new or where they want to approach the patient.

But everything else is the same as an intravitreal injection. So, we're not changing any physician practice have its much whatsoever. So, Charlie, why don't you cover the operating expenses..

Yes, Dan. So, we don't give specific guidance in terms of our quarterly estimates but I can tell you we spend about $11 million in Q2. As I said, our R&D expenses are going to continue to increase. Just to remind you, our SAPPHIRE RVO trial is pretty much tripled the size of PEACHTREE.

So as that study continues to expand and enroll, costs are going to continue to increase. So, we'll have multiple Phase 3 programs and the Phase 2 programming, program going on at once. So, I would expect the cost to continue to rise and again. As we said earlier, we have enough cash to get into the fourth quarter of next year..

Okay great. Thank you. One additional question for Daniel. Regarding managed care, the reception I was referring to is you guys clearly going to have an impact on the amount of VEGF, Eylea and Lucentis that might be used by a practice and reimburse by managed care.

What kind of response do you get from them if you are reducing the therapy burden and the response from managed care versus response from the retina specialist?.

It's also - it's four-fold. So, the reduction in the amount of VEGF that we see and again Glen went over some of the follow-on extension study we looked at with TANZANITE, 75% of these patients only have one treatment during the whole course of their therapy.

That was a pretty strong signal that we could potentially greatly reduce the whole the amount of VEGF given for any of these patients. And now we don't know if that will be 1, 2, 3, we still got to figure that out on our clinical programs.

However, being able to go to the manage care and discuss the fact that we are giving them fewer VEGF injections at $2,000 pop when you typically see six monthly injections and treatment extend after that, so the average course of therapy for - somewhere between 7 and 9 treatments during the course of the year.

Than you are able to demonstrate that you can save these payers what could be somewhere between $10,000 to $14,000 per patient per year. That's a very powerful argument.

For the retina specialist, they are getting a ton of any anti-VEGF injections and then that reimbursement has been reduced one time somewhere around $900 to $950 fitting on the safety down to nearly a $100 today and that maybe lower on that we noted in the 2017.

So, they don't see anti-VEGF injections as a money-making venture as they may have once thought and I think that the amount of baby boomers come through the system get patients of the age of RVO and DME, we see that this is an opportunity for them to have fewer injections.

I think that is the number one market need when you see the surveys given to these physicians. And we also don't want to forget the patient and the caregiver, they weren't having fewer treatments as pretty obvious.

At least for hours were a patient to leave, once they leave their house to get the physician and go to whole process, and going through - sitting in the wedding room and getting intravitreal injection.

And for a caregiver that's a lot of time and that's very tough on the caregiver and they see that as an opportunity as well, they much rather go on and have their diagnostic check them out once a month or maybe even if we can extend that as well. So that reset that we see all along and we are mapping all that out for our care, for the managed care..

Okay, thank you..

Thank you, our next question is from Serge Belanger of Needham & Company. Your line is open..

Hey guys, thanks for taking my questions. Just a couple on the uveitis program.

We're going to see this Phase 3 results in the first quarter of 2018, can you talk a little bit about the timing of the NDA filing and what are the I guess critical requirements that kind of going to guide the timing of the filing?.

Yes, Serge why don't I turn this over to Rick Beckman and Rick can become our project leader on the uveitis program and he is thinking about that very thing as well.

Rick?.

So, assuming that we get good data, which we have no reason to believe that we will than we have an experience team that's in place and we have the appropriate consultants and companies they will be in place to support an electronic filing for an NDA as you know the process of the approval process is basically on the order of about 12 months and our team plans to work as feverishly as possible to be able to do the submission within this earlier timeframe so that we could start the clock turning and get a PDUFA date as quickly as possible..

So as 2018 out of the questions in terms of timing?.

I would leave that question for Daniel, he's the boss..

Yeah, 2018, sorry. The NDA I won't comment on the FDA's timing, but in the NDA, we anticipate it will happen in the second half of '18..

Okay, great. And then in terms of the potential label, I assume you're expecting a comprehensive uveitis label, no matter the location whether in interior or posterior uveitis. And then when you think as a market opportunity, is the CLS-TA will be displaced intravitreal - the IVT injections of triamcinolone..

So that one I can take from you. So, in terms of the label, the label that we anticipate is going to be for Macular Edema associated with non-infectious uveitis and that would be in any region of the eye because we're allowing patients from all four diagnostic categories for non-infectious uveitis, so we expect a broad label.

With regard to the competitors in the market, we believe that the main competitors in the market would be intravitreal agents that are used, but although, the potential to displace sub-teams use of more generics with the better safety profile is also out there.

And that's all going to come down to what the data shows, but that's what we're looking to do..

Great. Thank you..

Thank you. I'm not showing any further questions in queue. I like to turn the call back over to management for any further remarks..

Well, thank you once again for joining us on the call today. We appreciate your continued interest in Clearside, and we look forward to updating you on our progress in the months ahead. Operator, you may now disconnect..

Everyone have a great day..

Thank you..

Thank you..