Ladies and gentlemen, thank you for standing by, and welcome to the Lexicon Pharmaceuticals Second Quarter 2015 Conference Call. [Operator Instructions] As a reminder, this call is being recorded today, Friday, August 7, 2015. I would now like to turn the conference over to Mr. Chas Schultz, Senior Director of Finance and Communications. Sir, you may begin your conference.

Thank you very much, good morning and welcome to the Lexicon Pharmaceuticals Second Quarter 2015 Conference Call. I'm Chas Schultz, and with me today are Lonnel Coats, Lexicon's President and Chief Executive Officer; Dr. Pablo Lapuerta, Lexicon's Executive Vice President and Chief Medical Officer; Jeff Wade, Lexicon's Executive Vice President of Corporate and Administrative Affairs and Chief Financial Officer; and John Northcott, Lexicon's Vice President of Marketing, Commercial Strategy and Operations. We expect that you've seen a copy of our earnings press release that was distributed this morning. During this call, we will review the information provided in the release, provide an update on our clinical programs and then use the remainder of our time to answer your questions. If you would like to view the slides for today's call, please access the Lexicon website, at www.lexpharma.com. You will see a link on the homepage for today's webcast. Before we begin, I would like to state that we will be making forward-looking statements, including statements relating to Lexicon's clinical development of telotristat etiprate and sotagliflozin. These statements may include characterizations of the results of and projected timing of clinical trials of such compounds and the potential therapeutic and commercial potentials of such compounds. This call may also contain forward-looking statements relating to Lexicon's growth and future operating results, discovery and development of products, strategic alliances and intellectual property, as well as other matters that are not historical facts or information. Various risks may cause Lexicon's actual results to differ materially from those expressed or implied in such forward-looking statements. These risks include uncertainties related to the timing and results of clinical trials and preclinical studies of our drug candidates, our dependence upon strategic alliances and ability to enter into additional collaboration and license agreements, our ability to obtain patent protection for our discoveries, limitations imposed by patents owned or controlled by third parties and the requirements of substantial funding to conduct our drug development and commercialization activities. For a list and a description of the risks and uncertainties that we face, please see the reports we have filed with the Securities and Exchange Commission. I will now turn the call over to Mr. Coats.

Thank you, Chas, and thank you, everyone, for joining us on today's call. Let me quickly go through today's agenda. I'm sure there will be a lot of new investors to the Lexicon story on today's call, so we will take a little bit -- talk a little bit about Lexicon before recapping the results from our TELESTAR trial. We will then discuss the second quarter financial results and open the call to questions. Let me start off by thanking the extraordinary men and women at Lexicon Pharmaceuticals who believe very strongly in translating our science into human benefit. This belief has been unwavering for over 20 years. And with this week's telotristat etiprate results, has been strongly validated. If I can level set for those who may be -- who may not be familiar with the Lexicon story, Lexicon Pharmaceuticals is built on a strong, scientific foundation that is comprised of multiple, high-value drug targets that were internally discovered from a comprehensive study of nearly 5,000 druggable genes. Today, we will focus on our 2 lead clinical candidates: telotristat etiprate for carcinoid syndrome and sotagliflozin for type 1 diabetes, both of which were internally discovered and developed at Lexicon. What's unique about these innovations is that each candidate has the potential to change standard of care and create significant stakeholder value. That's because both telotristat etiprate and sotagliflozin serve markets characterized by significant unmet needs. There are very few pharmaceutical innovations in these disease categories and there are even fewer or limited choices today. Our strategy is straightforward. Both compounds were discovered and developed by Lexicon. And therefore, we intend to commercialize both independently in the United States because we believe this will provide the greatest return for our shareholders over time. We will introduce these innovations to the…

Thank you very much, Lonnel. It's a pleasure to present the TELESTAR top line results, they represent a lot of dedication for many physicians, caregivers and patients. On the next slide, about TELESTAR. Let me provide you a general overview of the clinical trial design. TELESTAR was designed as a single pivotal Phase III study for its orphan indication, testing telotristat etiprate's 250- and 500-milligram doses compared to placebo, all on top of the standard of care continued somatostatin analog therapy. This is in a population whose symptoms of carcinoid syndrome were not adequately controlled on the somatostatin analog therapy alone. Our objective was to assess the efficacy of telotristat etiprate in reducing bowel movement frequency. The top line results applied in the 12-week double-blind period. Please note that for 36 more weeks, patients continued into an open-label extension and many patients are in that extension right now. A little bit more about the TELESTAR trial design on the next slide. TELESTAR enrolled 135 patients, making it one of the largest studies ever done in patients with carcinoid syndrome. It was a global program. There were 16 sites in the U.S. at leading centers and many in Europe, Israel, Australia and Canada. The main inclusion criteria, all patients had metastatic neuroendocrine tumors. They were all currently in somatostatin analog therapy and they continued that during the trial. The symptoms were severe, as reflected by diarrhea with more than 4 bowel movements per day. Next slide. The primary active measure of telotristat etiprate was a change from baseline in the average number of daily bowel movements over the 12-week double-blind period. Another primary objective was to address safety, examining the incidence of adverse events. Secondary outcome measures included change from baseline urinary 5-HIAA, a marker of serotonin synthesis. Another secondary endpoint…

Thank you, Pablo. I will provide a brief financial update. As indicated in our press release today, we have revenues for the 2015 second quarter of $0.4 million, a decrease from $0.7 million in the prior year period. Our revenues of $2.2 million for the first half of 2015 increased from $1 million in the prior year period. Our research and development expenses for the 2015 second quarter decreased 2% to $20.8 million from $21.2 million in the prior year period. Our R&D expenses of $41.6 million for the first half of 2015 reflected an 8% decrease from $45.1 million in the prior year period. In connection with our acquisition of Symphony Icon, we made an initial estimate of the fair value of our liability for the base and contingent payments. Changes in this liability, based on the development of the programs and the time until those payments are expected to be made, are recorded in our consolidated statements of operations. The associated decrease in fair value of Symphony Icon purchase liability was $12,000 in the second quarter and the liability increased by $1.7 million in the 6 months ended June 30, 2015. Our general and administrative expenses for the 2015 second quarter were $6.3 million, an increase of 22% from $5.2 million in the prior year period. The increase was primarily due to increased consulting costs in preparation for the commercialization of telotristat etiprate. Our G&A expenses of $12 million for the first half of 2015 reflected an 11% increase from $10.8 million for the prior year period. Our net loss for the 2015 second quarter was $28.1 million or $0.27 per share compared to a net loss of $26 million or $0.35 per share in the prior year period. Our net loss for the first half of 2015…

Thank you, Jeff. I just want to make a note of a correction on Slide 15. On the cash and the investments, it should say as of June 30, 2015, not March 31, just to make a note. Well, let me just sum up by saying that this will be a transformative year for Lexicon. Telotristat etiprate and sotagliflozin represent the tip of the iceberg of a deep, rich pipeline that should continue to bear similar results for years to come. As we have stated, we have completed our pivotal Phase III study to TELESTAR and we look forward to sharing more data on this trial at an upcoming scientific conference. NDA filing preparations and commercial preparations for this drug is very much on the way. And in addition to our Phase III and Phase II clinical studies that are progressing nicely for sotagliflozin, we're doing all the activities necessary to make sure that we're being responsible with how we spend our cash. We have, over the course of the next 12 to 18 months, a number of significant catalysts that Jeff has mentioned. On the heels of this Phase III top line results, we're moving expeditiously for NDA filing, a target of filing in the first quarter of next year. We also expect to have data from the JDRF study during the first quarter of next year as well as the data from the Phase III study in type 1 diabetes toward the end of next year. If we obtain priority review, we have the opportunity to potentially launch telotristat etiprate and have our first product on the market by the end of next year. So it is indeed a transformative year for Lexicon. So with that being said, I'll close as I always do, I want to again thank you for taking the opportunity to hear the Lexicon story and we will open up the floor for questions.

[Operator Instructions]. Our first question comes from Jessica Fye.

I guess, we've talked a lot about telotristat this week. Can you remind us or maybe walk us through how you think about peak sales for sotagliflozin? And then I know you commented on the timelines for data, but just anything on when we could hear enrollment completion for the Phase II JDRF study or the Phase IIIs?

Thank you very much, I'll have Jeff take that question.

So we're -- we think that sotagliflozin is a potential $1 billion plus drug in type 1 diabetes, that's the opportunity for that. And we will keep people updated with the timing of the enrollment of that study and we'll announce enrollment when it is completed.

And just to add on. I -- there's no doubt in my mind, you have 1.1 million adults living with type 1 diabetes, 3/4 of them are not meeting their ADA guidelines. And in fact, as we look at those who are controlling their reporting, they're having a difficult time just holding themselves where they are, we're just using insulin alone. I think it's a remarkable market with a remarkable opportunity for us to add on to standard of care. Insulin always would be at the baseline care for a type 1 diabetic patient. But there's a better way to control the disease without the anxiety of trying to manage it with injections. So we think we will indeed offer a better advantage and a better way to treat type 1 diabetics than what's offered up today. And if we should be successful, to Jeff's point, there's no question this is over a $1 billion opportunity.

Got it, thanks. And maybe just one follow-up on that. Can you remind us of the kind of competitive landscape in type 1? Are you seeing the other SGLT2s go into this space?

Yes. They have talked about going into this space. But I will just say, they have talked about going into the space. What I would say is more about what Lexicon's activities are. We believe very strongly, regardless of who comes into the space, they will still be missing the dual mechanism, particularly the SGLT1 mechanism that we think is the differentiation for type 1 patients on a postprandial basis. So regardless of who comes, we will have the market advantage in terms of having clinical meaningfulness, that's one. Two, because we are a very, very focused organization, we believe we'll be first. So I think we will offer the value being first, and for sure, be best once we come to market.

Our next question comes from Alan Carr.

I wonder if you can comment a bit about the -- you gave guidance for the rest of the year. Can you comment a bit about how that's going to be distributed? You started the Phase III already, but it didn't look like R&D moved up much. And then also, with respect to sotagliflozin. What, if any, other work is going to be needed in parallel with the Phase III trial? Any supportive studies? Preclinical or clinical that you'll be doing over the next 1.5 years?

Thank you, Alan. I'll turn that one over to Jeff.

So I'll answer the second question first. We're doing all of the activities that would be required for us to file in parallel with Phase III, and those activities are underway as we progress to the Phase III program. Now we're going to end up ramping up some expenses over the course of the balance of this year. So the expenses over the last couple of quarters are going to be higher than the expenses we've had from the first couple of quarters. So in terms of distribution, as we get that enrollment going up full speed, so it should be reasonably evenly distributed among the last couple of quarters of this year.

Can you -- okay, thank you. I guess can you outline some of those things that -- the activities that you're running in in parallel to the sotagliflozin trial?

Well, we just have an additional two. Among them, we have the Phase II JDRF study, which is probably one of the most significant ones. And that's in patients with high A1c and between ages 18 and 30. And then we also are finishing up some additional Phase I studies that are associated -- that are needed for us to be able to file just looking at some of the last things that we need to complete. We've made good progress on this already. So we expect -- and as we've noted previously, we've already conducted 16 clinical trials of this compound so we expect those to go well and to be completed and scheduled to allow us to file NDA within the timeframe that we're talking about.

And then the last thing, can you remind me the patent life for both drugs?

I'd say both run into the late 2020s without accounting for patent term extension, so second half of the 2020s.

Our next question comes from Liana Moussatos.

So with telotristat etiprate, you're going to go for approval for both the 250- and the 500-milligram doses. Do you anticipate the label will recommend starting patients on 250 and titrating up to 500? Or are there different patient situations that patients would directly go to 500? And then my second question has to do with the SGLT2 inhibitors in the trials in type 1 diabetics, some of them are having diabetic ketoacidosis. Have you seen anything like that? And do you think the SGLT1 part of your mechanism might reduce that risk?

I'll have Pablo start with the second part of your question.

All right. So the second part is about sotagliflozin and diabetic ketoacidosis?

Yes.

Yes, so with sotagliflozin, we are encouraged by our progress with the Phase III program so far from a safety standpoint and in terms of execution and enrollment. And when you talk about diabetic ketoacidosis, it's a part of type 1 diabetes, about 5% of patients with type 1 diabetes have an episode of diabetic ketoacidosis every year. We've been reassured with our safety experience. You ask though as well, is there could be SGLT1 mechanism of action be differentiating? And yes, it could with respect to diabetic ketoacidosis for several reasons, including that the SGLT1 mechanism of sotagliflozin provokes an increase in GLP-1. And GLP-1 may have a role in protecting from diabetic ketoacidosis.

Also I think of, Pablo, we would add -- we will add that the level of urinary or UGE with sotagliflozin is much less than when there are SGLT2s. And so when you have that much glucose depletion, that can also lead to DKA. You have lot less of that with sotagliflozin. So we think that would be a material advantage and hope that the studies prove that to be true. If I can go to your first question, around the dose. These things will be discussed with the agency and we'll get more of an answer as we finish up the 36-week extension trial for the 500-milligram dose. However, the agency will always ask you to start at the lowest dose, I believe. And so how it gets titrated or is done by subpopulation, we don't know at this moment until we have that discussion with the agency. But for certain, what I would say is, that 250-milligram dose is quite extraordinary. You have a robust response and you have a very good safety profile. And more than likely I think that will be the dose we start with and could be the prevailing dose.

Our next question comes from Cristina Ghenoiu.

One on telotristat etiprate. I was wondering for the 36-week extension. We expect in the anticipated standard decrease in bowel movement from baseline from deficiencies to be underactive there?

So I'm not sure we completely understood your question, there's a little bit of interference on the line. But we are -- so just to be clear, the open label extension, all patients are rolling into active treatment. So they will have the 500-milligram dose in addition to the standard of care. We do expect to, probably for the placebo patients to improve, on that basis as they go on [indiscernible] based on the results we've seen so far. If that was your question.

No, I was wondering about those who used to be on the active arm. Will they -- do you still expect further improvement from baseline compared to week 12?

We don't have that data. So -- and we will wait until that study is completed. But we have seen -- I will say that we have had patients, a very high proportion of patients roll over to the extension. We've had a high proportion of patients stay in the extension and our historical experience with -- in Phase II was that patients continue to benefit from telotristat etiprate over a long period of time. We have patients who have been on this drug for 4 years plus at this point.

I think in the absence of the data I don't think we want to make any conclusions until we have that data. But to Jeff's point, the vast majority of that, I think the number, and the team will correct me, 86% of the patients rolled over to active drug. That is a very big vote of confidence for the active drug and we expect that patients will continue to receive benefit - at what level of benefit, we will see once the study is complete.

Okay, thank you. And I was just curious, are there any other indications that may be suitable for the telotristat to be used in?

Excellent question. We think so. And we're working on that at this moment. Once you have had these kinds of results and when you start to look at the TPH mechanism, you start to think about other areas as certainly where we can apply this, particularly in the area of cancer. But that's the work we're going to do next and when we're ready to talk about exactly where we'll go next with it, we will certainly communicate that back out. But you're absolutely correct, there's another opportunity or 2 that we can advance this compound.

Thank you. And lastly, I was just curious about the conferences that you made with targeting. Any in particular?

Conferences?

To release the data.

Yes, conferences. So there is a conference in Europe called ESMO, which I believe will be this September. Then there is the NETs conference, which is made up of physicians here in North America that treats neuroendocrine tumors, that will be in October. And that there's ASCO GI, which I believe is the first of next year. So all 3 conferences we're targeting with these data.

[Operator Instructions] Our next question comes from Stephen Willey.

I think I heard in your opening comments kind of mention of the ex-U.S. partnership for sotagliflozin. And I guess I just wanted to make sure that you guys are thinking about that as a post-data versus a pre-data event? I'm just wondering if you could maybe provide some color around that.

I think, Stephen, as we advance sotagliflozin into late Phase III, I fully expect us to have substantial discussions about the rest of the world. I think the opportunity for us best to have those conversations will be beyond having the JDRF data on study 204. So it could be either way of the pivotal study. But I don't think it will be before we have the 204 data.

Okay, and then I think you had also talked about kind of a lot of the work the company has done on some of these first-in-class targets. And I know a lot of those are still sitting on the shelf somewhere in the bowels of Lexicon. So, I'm just kind of wondering if there is any objective or strategy here in place to maybe to try to monetize some of those earlier drug discovery efforts?

Very good question. And let me first start off with the answer is yes. We've had a long-standing relationship as we announced early with BMS where we found a target that we're going to advance into the clinic shortly for pain, for neuropathic pain. I think that's exciting. We have other discussions that we're having with other organizations on how we can help them around the target work that they're looking to do, whether to avoid things or to accelerate things and those conversations are ongoing. But as you all may know, we also have a search op for an R&D head that will help again to crystallize an overarching strategy for pulling our library forward, both working with academia as well as work with other pharma companies to properly characterize that entire library.

And that does conclude today's question-and-answer session. I will turn it back over to our host for any closing remarks.

Well, again, thank you very much for joining us this morning. As I've stated before, this is a remarkably exciting time for Lexicon. It is a transformative year for all of the new shareholders who've come on to Lexicon, I think you've come on at a great time. For all those who have been with us, I think, this transformative year will be a very high value-based year for us. And so thank you for believing in Lexicon and we look forward to the next conference call.

Ladies and gentlemen, thank you for joining us today. This concludes today's conference call. You may now disconnect.