Good day, ladies and gentlemen, and welcome to the Ocular Therapeutix's Third Quarter 2014 Earnings Conference Call. At this time, all participants are in a listen-only mode. Later, we'll conduct a question-and-answer session, and instructions will be given at that time. [Operator Instructions] As a reminder, this conference call is being recorded. I'm going to introduce your host for today's conference, Brad Smith, Chief Financial Officer. Please go ahead, sir.

Thank you, and good morning everyone. Welcome to Ocular Therapeutix's third quarter 2014 earnings conference call. This morning, we issued a press release providing details of the company's financial results for the third quarter ended September 30, 2014. We also announced the first patients enrolled this morning in our Phase 2b clinical trial for OTX-TP, a sustained-release travoprost filed with an IND with the FDA for this product back in September. We also announced this morning top line results from our Phase 2 clinical trial for OTX-DP for the treatment of allergic conjunctivitis. These press releases are available on the investor portion of our Web site at investors.ocutx.com. Leading the call today will be Dr. Amar Sawhney, our President and Chief Executive Officer, who will review recent clinical developments for our lead programs along with the discussion on some of our upcoming milestones. I will then provide an overview of the financial highlights for the third quarter before opening the call up for questions. Also joining us on the call this morning is Scott Corning, Vice President of Sales and Marketing; and Eric Ankerud, our Executive Vice President of Clinical, Regulatory, and Quality. As a reminder, during today's call we'll 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 Safe Harbor provisions under 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 Factor section of our most recent quarterly report on Form 10-Q filed with the SEC. In addition, any forward-looking statements represent our views only as of today. It should not be relied upon as representing our views of any subsequent date. While we may elect to update these forward-looking statements at some time point in the future, 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 subsequent date of today. I will now turn the call over to Amar.

Thank you, Brad. Good morning everyone, and thank you for joining us today for our third quarter 2014 earnings call. Before we begin, I would like to welcome all of our new shareholders. If we have not yet had a chance to meet you personally, we look forward to having that opportunity in the near-term. For those of you who may be new to our story, Ocular Therapeutix is focused on the development and commercialization of innovative therapies for diseases and conditions of the eye, including both front of the eye and back of the eye, using our proprietary bioresorbable hydrogel technology platform. Our product candidates are designed to provide sustained delivery of therapeutic agents to the eye. The products we currently have in development address a $9 billion market opportunity in the U.S., and a market that is growing rapidly. Front of the eye diseases and conditions were developing therapy to replace the standard-of-care eye drop regimens without innovative drug eluting punctum plugs. These plugs are non-invasively inserted into a natural opening called the punctum, located in the inner portion of the eyelid near the nose and reside comfortably in the canaliculus below the punctual opening. Eye drop therapy presents numerous limitations, including significant peaks and values of drug concentration, lack of patient compliance, difficulty in administration, and side effects due to high concentrations of drug and presence of preservatives. We believe that our candidates will improve the compliance due to long-term sustained delivery, provide a more uniform amount of drug presence on the surface of the eye and ultimately increase treatment efficacy and reduce to these progression associated with patient noncompliance. We also believe that our product candidates can provide an improved safety profile, compared to eye drop regimens due to the lack of preservatives as well as…

Thanks, Amar. As Amar mentioned previously, during the third quarter of 2014, we closed our initial public offering and raised 75 million in gross proceeds including the exercise of the over-allotment option. After all fees and expenses, we received over 67 million in net proceeds. We are pleased to have secured Morgan Stanley, Cowen, RBC Capital and Oppenheimer as the underwriters of our IPO. Including the proceeds in the IPO, we had 81 million in cash and cash equivalents as of September 30, 2014. Our operating cash burn for the third quarter was 6.4 million. We expect our cash burn to increase over the next several quarters as we continue to advance our clinical development programs and expand our personnel to support the business. We continue to believe that we have sufficient cash and cash equivalents to fund the company to at least the first half of 2016 and through several important clinical and commercial milestones with our product development programs, including the initial commercialization of our lead OTX-DP program for post-surgical inflammation and pain, assuming favorable clinical results in the Phase 3 trials. And the continued clinical development of our OTX-TP product for the treatment of glaucoma and ocular hypertension, which is currently in Phase 2b trials. And we expect to advance in the Phase 3 trials with that program in the first half of 2016, assuming favorable results in the Phase 2 trials. So, we expected to have the money last and see some very important milestones for the company. For the third quarter ended September 30th, 2014, we reported a net loss of 7.3 million or a loss of $0.48 per share. This compares to a net loss of 3.5 million or a loss of $1.34 per share for the third quarter of 2013. The net loss…

Thank you, Brad. We're now ready to take your questions. In addition to Brad and myself, Scott Corning; Vice President of Sales and Marketing, and Eric Ankerud; Executive Vice President of Clinical, Regulatory and Quality, are also available to take your questions. Operator, can you please take our first question?

Thank you. [Operator Instructions] Our first question comes from Yigal Nochomovitz of Oppenheimer. Your line is open.

Hi, guys. Thanks, very much for taking the questions, and congrats on the progress. I just want to clarify one aspect on allergic conjunctivitis study. The press release stated that you didn't achieve a 1.0 unit difference on the majority of time points, but I just wanted to understand if we should take that to mean that you did hit the 1.0 unit threshold on one of them, since obviously there were three, and if you could say which one.

No. Yigal, this is Amar. No, the effect was close to 1.0, but not over 1.0. So, remember that these endpoints are basically with the guidance that the FDA, has done in the past for eye drop-related therapies and not for sustained-released therapies. And remember we are dosing only once through the whole 42-day duration, compared to drops that need to be dosed frequently. So we did hit the 0.5, I think what we need to do is to take these results and discuss with the FDA as to how and what the hurdles are for sustained-release therapy and how should we go about that process. So we have to be careful in interpreting anything beyond that because this is just guidance that the FDA has given in the past for the CAC challenge, which is not the modified CAC challenge that we are using, where we are repeatedly challenging over the long duration.

Okay. So that sort of lead into my next question, which I guess you sort of answered in terms of whether you need to hit on the 1.0 versus the 0.5, but it seems like you need to have the discussion with the FDA. I was just wondering, also, you mentioned in your remarks, would you consider another allergen challenge model, for example the environmental exposure chamber model to potentially increase the chances of having a better data. How would you do that option?

No. I don't think we will go to the environmental model. We're actually quite excited by these results and these are well within the expectation that we have. Remember that there are therapies that have been approved with less than a 1.0 treatment level and there have been therapies that have been approved only for itching and not for redness. For example, the leading therapy patter [ph] day right now. So I think, well, we feel that these are right in track with our expectations and we just need to have a discussion with the agents we as to -- how to regulate a product of this sort and how to label it. So we will -- once we have those discussions, we will keep you all fine.

Okay, great. And then on the Phase 2b glaucoma, which you just initiated, can you discuss a bit what you're looking for in terms of retention rates there, to feel comfortable with the product profile, moving into Phase 3, and would you expect to do another round of plug technology refinements after the Phase 2b, even if you hit your retention rate goals in this current study? Thanks.

So, we are as you know we've described this previously that the retention rates that we are expecting over here, will be in the 80% range for 60 days which is going to be the primary endpoint. We will be evaluating out to 90 days also and we expect that retention to be probably obviously below that number but maybe in the 60 plus percent kind of range. So, we would be comfortable with getting results in that domain. We are also looking at repeated administrations, should the plug be lost by virtue of it being visualized by the patients and using the blue-light technique that we have which allows the fluorescent plug to be visualized by the patients themselves. So in this study, the plugs will be replaced on and if in the event that they are noticed by the patient to have been lost. So we are continuing to do studies to further improve the retention. And those studies are ongoing, but those don't have to be drug studies, those are device-only studies that are done as non-significant risk studies. So, we continue to iterate but as we've discussed in the past that the drug studies are used earlier version compared to the latest studies that we might be doing in optimizing the plug performance. So we -- is an ongoing effort to improve the retention, but we feel that this study should at a minimum tell us whether we have reasonable levels of efficacy compared to Timolol which is the bar that the FDA has set for approval of a product of this nature, and also evaluate repeat administrations in the event if the plug is lost. So those are the key factors that we are seeking to evaluate as well as seeing if we can go to 60 days as the primary endpoint on efficacy as well as go longer than that. So, those are three set of objectives we're looking to realize from this study.

Okay. Thanks, very much.

Thank you. Our next question comes from Ken Cacciatore of Cowen. Your line is open.

Great, thanks. Hey, sorry guys, I'm a little bit late getting on to. I don't know if this was discussed, but I just wanted to understand the clinical relevance in that delta between 1.0 and 0.5 on the results, if understanding that the agency historically have it looked at. But just trying to put it frame it in the perspective of how a clinician would view it in your opinion. And then I have a couple of follow-up questions.

These studies were conducted with a modified CAC challenge model with the support of Ophthalmic Research Associates, which is an organization that has approved or helped get probably a dozen of the last 15 allergy products to the market. So, they have a fairly good sense for the performance and based on their feedback, they were highly encouraged to see a clinically meaningful level of effect, which was sustained and not only at the 14 day duration of the first evaluation period, but at 28 and 42 days. And it was quiet encouraging to see one single dose administration last thing, that long and having such a long lasting effect on both itching and redness to being statistically lower in the treatment group at all-time points and at all days. So from that standpoint, it was very encouraging. Remember that usually these studies are done with eye drops where you're looking at the onset of action of the duration of effect after the challenge is made and looking to see how long the drop might last and typically these drops would last for eight hours or maybe 16 hours or something of that duration, compared to the 42 day type of duration that we are seeing over here. So from that standpoint, very encouraging; the effect, however, did not reach the 1.0 level, which for eye drops has been in the past, in setup as something that people needed to meet for a majority of the time point. So, not all time points, but a majority of the time points, so this study was meant to kind of get sort of a sizing up of the effect, and exploration of the endpoints while we did state some of these endpoints, these were meant to explore what our study design, what a product like this needs to look like and that discussion needs to be had with the FDA. And it was not possible to have that discussion prior to having some results. So, we expect to take these Phase 2 results and have the conversation with the agency as to how to regulate a product of this sort and what is the right ways to look at this modified CAC challenge model and where the bar -- will and should be sent.

Okay. And again, I apologize if I'm going to go over anything that you've talked about, but just also on the hydrogel depot of the anti-VEGF program [indiscernible] is multiple potential partners here. Can you just give us a sense of what we should be thinking about when you say feasibility studies, what possible information could you disclose to us when you release those results. What does that look like in terms of how it should we be doing analysis, clearly duration is important. But can you frame it ahead of us seeing those results?

We will -- we have limited ability to release results over there, owing to the confidential nature of these discussions with the potential partners. Clearly, they don't want to be identified at this stage, given that this could be a process where they have sizeable amount of competition. So, we have a limited ability to disclose those results. I'll just preface my remarks with that.

Okay. So, when you say -- let's just pretend the answer is these six studies were successful, but to say they use the word "successful". Clearly, what should we, what would one imagine "successful" looks like, its -- you're seeing a level of duration, you're happy what you're clearly seeing the level of efficacy, without being able to give us the exact nuance. Can you just frame what the word "successful" would mean in the context, if you did say the feasibility studies were successful?

Sure. The "success" word be in sort of three different dimensions. One is that we are seeing a drug release out to a meaningful duration and meaningful as in the four to six month kind of range, probably closer to six months. Second thing would be that these are well tolerated by the animals in whichever animal model that the potential partner seeks to evaluate them. Some are doing it in rabbit models, some are doing it in primate models. And the third would be that these materials are giving a meaningful amount of drug in the various tissues of the eye that are being evaluated. So, for example, retinal concentrations are at a meaningful level, compared to what people expect to see for efficacy. So folks have pretty good ideas to what levels of anti-VEGF drugs give efficacy and if they see that or above that, I think that would qualify a success. So those would be the [indiscernible].

Okay. That's helpful context. And then in terms of, again, this is always difficult to predict, but in terms of the rapidity into the clinic, from there, do you think that we could see the initiation of clinical studies in 2015, if again successful?

You remember that if you have a six month duration product, a pre-clinical study with at least one dosing will take six months and it will take some time to start and will take some time to analyze and then there is a submission to the agency, etcetera. So, when you add up all of those timelines, this is why developing control only systems is more challenging, because it takes longer to do the product validations and longer to do the pre-clinical studies, but the rewards of creating category dominating types of products is that you have a much bigger upside. So, given the length of these therapies that will be hard to pull off initiating a clinical trial in 2015. So, we would expect if these has to be successful to only initiate studies in the 2016 time.

Okay. Yes. That makes a lot of sense. And lastly the last question was on the question or answer about the next maybe generation devices or I'm sorry "plugs" that you may be working on. And so, just wondering, I didn't hear within there, I know what we're going with, but is there just -- should we just assume there is constant innovation and that you're constantly refining or do we feel that this is the last generation that you're dealing with?

No, "We are constantly refining," would be the short answer.

Okay. Perfect.

That is an ongoing iteration process and an ongoing quest. So, we will continue to iterate but we do want to see if we get adequate levels of effect out for reasonable durations of time and that's what we are seeking to evaluate in this Phase 2b study.

Okay, great. Thank you, so much.

Thank you. [Operator Instructions] Our next question comes from Adnan Butt of RBC Capital Markets. Your line is open.

Hi, good morning, everyone. Couple of questions for you here, first, on the OTX-TP information in pain study; is there a way to measure safety differences along with the efficacy outcome from the ongoing Phase 3 program?

So, is your question related to the allergy study or is it related to the pain and inflammation study?

I'm on -- it's the Phase 3 pain information, post-ocular surgery, yes, for that study. So, for the Phase 3, that's ongoing, that will read out in the first quarter. Is there a way in that study to show safety differences along with measuring efficacy?

Yes. As we analyze the data, we'll be analyzing both efficacy and safety results for the Phase 3 program.

And what are the safety parameters that are typically looked at, so I think the [indiscernible] it obviously cause -- have had side effects associated with them, this is a much low-dose project. So, what kind of safety differences could manifest in this Phase 3?

That will be looking with some focus onto adverse event profile for both the treatment group and the control group through predefined analysis in our study protocol.

So, Adnan, this is Amar. What we would look at would be all the standard safety measures that are done post-cataract surgery, which would include slit lamp exams, ocular surface exams, periocular tissue exams, et cetera. These are standard tests that people look at and anything nonstandard will obviously also be reported, if they were an unexpected or any serious adverse events. Ocular or even non-ocular in nature, so we would collect all of that adverse event information and look at the two groups and try to see if there are any major differences and FDA will be provided all of that information.

Okay. More historically, do steroids, what kind of side effects do you expect from them in a study like this?

A chronic use of steroids can give intraocular pressure spikes, for example. So, if you -- so you'll get, so there are two types of pressure increases just so that we know, post-cataract surgery. One that would happen in the first day or two, which is usually associated with the presence of the viscoelastic that has not been taken out adequately from the eye, and that happens at a rate of about 8% to 9%, 10%, or so. But that will only happen in the first day or two, because that is associated with surgery. And then there is the more chronic intraocular pressure spike that comes from high dose and chronic use of steroids that may happen in the outer periods of time, typically after two week kind of duration. So, we would be looking at those post two week duration spikes with a degree of interest because [indiscernible] has indicated that up to 20% spike rates might happen with post-surgical use of steroids. And remember that in our Phase 2 study, we did not see many of those at all and that was one of the more exciting developments. So, we're going to watching that with interest.

Okay, great. The next question I have is on OTX-TP for glaucoma, the Phase 2 that's starting. The -- is the study power to show a difference between TP and Timolol?

It is, it does have statistical power built in. It is a Phase 2 study however, and so we are going to be analyzing it for statistical differences between the treatment group with OTX-TP and placebo drops compared to the placebo punctum plug and Timolol drops.

Okay, but to clarify, to show treatment difference?

Yes.

Okay.

On inferiority, I mean, it's basically not a study to look at superiority. It's a study to look at non-inferiority.

Okay. That's helpful. And then the sort of last question I have is that in terms of the hydrogel depot for anti-VEGFs, what is the technical hurdle here, you mentioned three things; it's durability, it's activity, so which one is the one that coins the toughest overcome, if you can say something about that?

I think we are fairly comfortable that we can entrap these anti-VEGF compounds within our materials and not change them, not denature them, not cause the protein activity to be compromised or the protein to be aggregated or structurally compromised. We're also reasonably comfortable that these will be released in the meaningful duration. We've seen that in vitro studies. We hope to replicate that in-vivo studies, the biggest challenge is about having tolerability over a long period of time of an implant which is being placed intravitreally. So, that is a higher hurdle and that is something that we are trying to understand. Also it is a little complex, since putting in a human protein into an animal can create an immune response in any case, through no fault of the depot itself. So, how to analyze that vis-à-vis tolerability that maybe by a compatibility question versus tolerability that is an immune reaction kind of question, those are things that we are trying to parse through over here and understand and our partners have some insights into that but I think we are kind of treading new ground over here because this is not something anybody has ever done before.

Thank you. I'm not showing any further questions in queue. I'd like to turn the call back over to Amar Sawhney for any further remark.

Thank you, everyone, for your time this morning to join the Ocular Therapeutix third quarter 2014 earnings review and business update. On behalf of the entire Ocular Therapeutix team, we appreciate your support, and look forward to communicating our progress in the coming months. Have a great day.

Ladies and gentlemen, thank you for participating in today's conference. This concludes today's program. You may all disconnect. Everyone have a great day.