Bobby Faulkner, Manager of Investor and Public Relations Dr. Arthur Sands -President and CEO Dr. Philip Brown - SVP of Clinical Development Jim Tessmer - VP of Finance and Accounting

Sharon Seiler - Ladenburg Thalmann. Jason Kantor - RBC Capital Markets. Edward Tenthoff - Piper Jaffray

Welcome to the Lexicon Pharmaceuticals second quarter 2008 conference call. At this time, all participants are in a listen-only mode. There will be a question-and-answer session to follow. Please be advised that this call is being taped at Lexicon's request. At this time, I would like to introduce your host for today’s call, Bobbie Faulkner, Manager of Investor and Public Relations. Please go ahead Ms. Faulkner.

Good afternoon and welcome to the Lexicon Pharmaceuticals second quarter 2008 conference call. I am Bobbie Faulkner and with me today are Dr. Arthur Sands, Lexicon's President and Chief Executive Officer; Dr. Philip Brown, Lexicon's Senior Vice President of Clinical Development; and Jim Tessmer, Lexicon Vice President of Finance and Accounting. We expect you have 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, then use the remainder of our time to answer your questions. The call will begin with Dr Sands who will discuss our key accomplishment for the second quarter. Dr Brown will then discuss the status of our drug development program and Mr. Tessmer will review our financial result for the second quarter and discuss our financial guidance for 2008. We will then open the call to your questions. For those who wish to view the slide to which we will refer, please access the Lexicon website at www.lexpharma.com. You will see a link on Home page under today's webcast. Before we begin, I would like state that we will be making forward-looking statements, including statements relating to, without limitation, Lexicon's research and development of LX6171, LX1031, LX1032, LX2931, and LX4211. This call will also contain forward-looking statements relating to Lexicon's growth and future operating results, financing arrangements, cash and investments, discovery and development of products, strategic alliances, and intellectual property. Various risks may cause Lexicon's actual results to differ materially from those expressed or implied in such forward-looking statements, including: Uncertainties related to our ability to enter into additional collaborations; alliances and license agreements; the success and productivity of our drug discovery efforts; the timing and results of preclinical studies and clinical trials of our drug candidates; our ability to obtain patent protection for our discoveries; limitations imposed by patents owned or controlled by third parties; our dependence upon strategic alliances; and the requirements of substantial funding to conduct our research and development 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 turn the call over to Dr. Sands. Dr. Arthur Sands: Thank very much Bobbie and good morning everyone. Welcome to our quarterly call. I would like to begin by a brief discussion of Lexicon’s emerging pipeline under the 10TO10 program, which for those of you who can see the slide is the first slide, picturing our 10 program. In green on the slide, you will see our small molecule programs and their progression through clinical development. The blue are two emerging anti-body programs as well. I think that most of the time there where we will spend a lot of time discussing further LX1031, is the recent announcement, which I hope you have seen, our press release pertaining to its report of the Phase I clinical trial results. So we will spend most of the time discussing those, as well as our plans to progress into Phase II in this program. In addition, this quarter we received fast tracks of LX1032, another very important event, after that joint program. I would like to mention, though, there is an emerging pipeline as well of three clinical programs that feed into our 10TO10 program: LX4211, I think are leading the pack as a future IND client for the end of the year; and then LX710, a very exciting glaucoma program, both small molecule programs, also moving forward. So with that in mind, I think this call, everything you hear today needs to be interpreted in the context of promoting and moving this pipeline forward, and so we will come back to this pipeline slide at the end of the call as well. On the next slide, a few highlights from the most advanced clinical programs in Lexicon's portfolio. I will just mention LX6171 briefly; it continues to regress in Phase II clinical trials in age-associated memory impairment, and that program remains on track. LX2931 for rheumatoid arthritis is in its multi-dose Phase 1b trial, which we initiated in May of this year. We anticipate data by the end of the year in this program as well. Of course LX1031, more of that in a few moments, and LX1032, also in a multi-dose phase of Phase 1B, our fast track program for carcinoid syndrome, and then again, LX4211. I think what is important here, if you look at this collection of four programs in clinical development as well as the fifth, we anticipate being in by the end of the year, you see that many of our programs will have very important clinical results coming forward, as we enter the second half of 2008. So now, to focus more closely on our clinical programs, Phil Brown. Dr. Philip Brown: Great, thanks very much Arthur. It has been a strong quarter for Lexicon, as we continue to progress our lead development programs and of course we are preparing to bring 4211 forward into the clinic towards the end of this year. As Arthur mentioned, we have these four programs that are advancing through our early stage development, and we have recently reported our clinical results for one of our lead programs. So with that, let me turn to LX1031 to start with. IBS is a very common disorder that is characterized by abdominal pain and changes in bowel function. This is a very prevalent condition of course. It is estimated that up to 20% of the US population experiences IBS, and it is one of the most common disorders that is managed by gastroenterologists and even primary care physicians. LX1031 our compound directed towards IBS, and it modulates an enzyme called tryptophan hydroxylase or TPH. TPH, the target of LX1031 was identified through the Genome 5000 program here at Lexicon and the small molecule inhibitor LX1031 was developed by our medicinal chemistry team. Serotonin pathways in the GI tract have been associated with both the symptoms, as well as the management and treatment of these symptoms in the setting of IBS. LX1031 acts locally in the GI tract to influence or inhibit tryptophan hydroxylase and this is designed to decrease peripheral serotonin levels and thereby influence and modulate the symptoms associated with IBS. Now in this slide, just to refresh your memory with what we originally observed in the knockout. On the left-hand portion of the slide are intestinal levels of serotonin. You can see that there is a virtual absence of serotonin in the periphery, in the knockout mouse. Now importantly, what was also observed with a preservation of normal levels of serotonin in the brain of this knockout. Now, if we compare the pharmacology of LX1031 on a normal mice, which is depicted on the right-hand portion of the slide, what we observed with the dose-dependent would decrease in peripheral serotonin, which effectively recapitulated this knockout phenotype. These important scientific observations provide background for considering now the clinical results that we are describing today. We recently completed a further dose escalation evaluation of LX1031. The study design with the double-blind multiple-dose escalation study in normal volunteers, and it was conducted primarily to confirm what had been observed in prior results and continued to evaluate further dose escalations. In this study we successfully evaluated doses of 250, 500, 750 and 1000 milligrams, all of which were given four times daily over a period of 14 days. Importantly all these dose levels were well tolerated and we also observe production in the urinary metabolite of serotonin 5-hydroxyindoleacetic acid or 5-HIAA, at of each of this dose level. In this next slide, we depict the biomarker data from the study and the graph depicts the change from base-line in this urinary metabolite of serotonin over this 14 day exposure period. The green line near pool will see both data. Individuals which were randomized to LX1031 showed this significant decrease in urinary 5-HIAA, which was consistent with what had been observed in our initial multiple dose study at the 500 milligram dose levels, which was given four times daily. These data confirmed of overall pharmacology activity of 1031 and strengthens our enthusiasm for the use of the compound in the studying of functional GI disorders, such as irritable bowel syndrome. So in summary, we have confirmed the pharmacology activity of LX1031 in men, through a reproducible effect on this urinary metabolite of serotonin. LX1031 has been extremely well-tolerated over a 14 day period in all doses evaluated to-date. This emerging safety profile is a very important consideration for any compound, which may have utility and functional GI disorders. Also we had a very well behaved pharmacokinetic profile with LX1031 that has consistently reproduced what was observed in our preclinical study. We have extremely low levels of clinical exposure to the compound, illustrating its local effect in the gastrointestinal tract and we have seen no evidence of accumulation of a repeat dosing with the compound. We are now moving to initiate the proof-of-concept study with LX1031 in patients with irritable bowel syndrome, and as Arthur mentioned, I hope you saw our press release on this today and these results will also be available on our corporate website as a video presentation. Now shifting gears to a related program, LX1032, this compound was designed by medicinal chemist to gain greater systemic exposure. Now this is important, because we will direct this compound towards indications, where systemic serotonin levels are elevated and associated with a condition, which occurs in the setting of carcinoid syndrome. Carcinoid syndrome results from metastasis of serotonin secreting tumors, primarily to the liver, which results in a variety of symptoms including severe diarrhea, abdominal cramping, as well as other symptoms associated with the condition. One, LX1032 is an oral small molecule agent that reduces serotonin production in the periphery peripheral to the central nervous system by inhibiting TPH. This is a condition with a significant unmet medical need, and at present there is only one agent that is approved for use in the setting of carcinoid syndrome, and this is an injectable agent. So we believe 1032 offers a significant opportunity for patients with this condition. We have completed our initial First-In-Man study, and are currently in the midst of conducting our multiple-dose study in normal, healthy volunteers. I think many of you may have seen that we have obtained Fast Track status for this program this quarter, which really underscores the importance of exploring new approaches in managing this condition, and we are anticipating data from our multiple-dose tolerance study towards the end of this year. LX2931 is being developed in the setting of autoimmune and inflammatory conditions such as rheumatoid arthritis. The target of 2931 is S1P lyase, which is an enzyme responsible for the breakdown of an important immune system signaling molecule, sphingosine-1-phosphate or S1P. We believe this will be an important mechanism in managing the symptoms associated with many inflammatory conditions that exist with autoimmune disorders, such as rheumatoid arthritis. Last quarter, we announced completion of our single-ascending dose tolerance study, where doses up to 180 milligrams were well-tolerated. We have moved the compound forward and initiated a multiple-dose tolerance study, again in normal volunteers in May of this year. We are anticipating clinical results being available from this study by year-end, and this is an important study for us because we will use these results to support a drug-drug interaction study with methotrexate, which will assist in positioning the compound for evaluation in patients with rheumatoid arthritis. For LX6171, we reported the initial target of this compound at the American Academy of Neurology meeting in April. The target of LX6171 is a brain-specific, high-affinity proline transporter. We have, as many of you know, and as we reported previously, initiated our Phase II study in age-associated memory impairment and importantly, our accrual is on track as we had originally projected, and we are anticipating completion of this study by year-end. We certainly look forward to updating you, as these data become available. I will now turn the call over to Jim Tessmer our Vice President of Finance.

Thank you Phil. We issued a press release this morning detailing our second quarter finance results, which you may find in our website, if you have not already reviewed it. Lexicon's revenues for the three months ended June 30, 2008 were $9.6 million, a decrease of 24% from $12.6 million for the corresponding period in 2007. The decrease resulted primarily from the completion in 2007 of the project funded by our awards in the Texas Enterprise Fund and the target discovery portion of our alliance with Takeda Pharmaceutical Company Limited and our progress towards completing the target discovery portion of the N.V. Organon alliance, offset in part by higher technology license fees. Our second quarter revenues were primarily attributable to work in our collaborations with Bristol-Myers Squibb, Organon, and Genentech and technology license fees. For the six months ended June 30, 2008, revenue decreased 29% to $18.5 million from $26.1 million for the corresponding period in 2007. Research and development expenses for the 2008 second quarter were $30.3 million, an increase of 19% from $25.6 million for the corresponding period in 2007. This increase is due primarily to higher preclinical and clinical cost, related to the advancement of Lexicon's drug development program. Research and development expenses for the quarter also reflected severance cost associated with reduction in personnel in May 2008. For the six months ended June 30, 2008, research and development expenses have increased 10% to $58.2 million from $52.9 million for the corresponding period in 2007. General and administrative expenses for the 2008 second quarter were $5.6 million, an increase of 12% from $5 million for the corresponding period in 2007. This increase is due primarily due to severance costs associated with reduction in personnel in May. For the six months ended June 30, 2008 general and administrative expense increased 8% to $11.1 million, from $10.3 million for the corresponding period in 2007. Lexicon's net loss for the three months ended June 30, 2008, $20 million or $0.15 per share, compared to a net loss of $13.6 million or $0.17 per share in the corresponding period in 2007, net loss for the six months ended June 30, 2008 was $38 million or $0.28 per share compared to a net loss of $32.5 million or $0.41 per share for the corresponding period in 2007. For the three and six months ended June 30, 2008, net loss included non cash, stock-based compensation expense of $1.6 million and $3.4 million respectively. For the three and six months ended June 30, 2007, net loss included non cash, stock-based compensation expense of $1.7 million and $3.2 million respectively. Let me turn to our cash and investments. As of June 30, 2008, Lexicon had $200.5 million in cash and investments including $26.9 million in cash and investments held by Symphony Icon, that compared to $228.8 million as of March 31st, 2008 and $258.8 million as of December 31st, 2007. We continue to progress with our investment position in auction rate securities. Since the auctions relating to our securities began to fill in mid February, we have been able to sell $18.3 million in auction rate securities at par value and ended the quarter with approximately $59.8 million in par value auction rate securities. Based on assessment of fair value of these securities as of the end of the quarter, we have recorded an unrealized loss of $3.2 million, reducing the value of these securities reflected in our balance sheet to $56.6 million. Our holdings of auction rate securities are reflected as long-term investment on our balance sheet. As a reminder, our auction rate securities are AAA rated municipal securities, consisting of bonds issued by various state and open municipal agencies for the purpose of financing student loans, public projects, and other activities. We do not hold any collateralized mortgage backed securities, collateralized debt obligations, or other such securities. We believe that the working capital available for Lexicon excluding the funds held in auction rate securities will be sufficient to meet our cash requirements for at least the next 12 months. I would now like to turn to our forward-looking financial guidance for 2008. Revenues from existing contracts for payments for 2008, attributed primarily to our collaborations with Bristol-Myers Squibb, Organon, and Genentech, are now projected to be in the range of $31 million to $33 million, an increase from our previous guidance of $29 million to $31 million. Operating expenses for 2008 are now projected to be in the range of $140 million to $145 million, a decrease from our previous guidance of $145 million to $155 million, primarily as a result of our reorganization in May 2008. Non-cash expenses will be approximately $14 million of this total, including $6 million and stock-based compensation and $8 million in depreciation and amortization. Taking into account cash received for existing contracts, contractual relationships only, we expect our 2008 net cash used in operations to be in the range of $105 million to $115 million, down from our previous guidance of $109 million to $119 million, and our 2008 capital expenditures to be approximately $3 million to $4 million. Thank you, and now I will turn the call back to Arthur. Dr. Arthur Sands: Thank you, Jim. So, and we can take questions.

Thank you. First to Sharon Seiler with Ladenburg Thalmann. Sharon Seiler - Ladenburg Thalmann: Good morning. A couple of questions on your clinical programs. First of all, with the Alzheimer's program, I think you said that you expected to complete that trial by year-end. My question here is, will we have results by year-end by way of press release or wait till you release them in a consent. The second question would be, can you give us some detail on the trials you plan in patients for LX1031 and LX1032, and can you maybe provide some color on which programs you are looking to for additional INDs, either this year or next, as you go through your 10 programs by 2010? Dr. Arthur Sands: This is Arthur Sands. All right. Okay, let's turn that over to Phil. Dr. Philip Brown: So, thanks for the question Sharon . I think with regards to our Phase 2a study with 6171 in age-associated memory impairment, we are anticipating results by the end of this year. I anticipate being able to update you, the public in general with the top-line results when they become available. We'd certainly like to position them in at a major medical meeting as well, and obviously we'll have to evaluate them as they become available. With regard to how we're going to pursue our patient studies with the 103 compounds. So 1031, we've announced today that we will initiate a study in irritable bowel syndrome in patients for a proof of concept to probe the importance of this mechanism in the setting of these patients. We're still refining the details associated with that study, but as we've done with 6171, I feel that it's going to be an adequately powered or structured study in order to assess for the activity of the compound. So we'll certainly update you as we refine the protocol for that particular proof of concept study. 1032 of course is going to be positioned in patients with carcinoid syndrome. We are moving the compound through this multiple dose study in normals in order to select more rational dosing for use in patients. In other words, we believe that higher doses of the compound will be required in patients. So we want to make sure we understand that pharmacokinetic safety profile before we initiate that proof-of-concept study. Lastly, the additional INDs anticipated for this year as Arthur mentioned are 4211, we are on track, we believe at present to support a filing in that, with that compound, which will be targeted for diabetes. Sharon Seiler - Ladenburg Thalmann: Okay, thanks. Can you just give us some sense of what you see in the pipeline after LX4211? Dr, Arthur Sands: Sharon this is Arthur. I think the glaucoma program is looking very interesting. It's at an important stage now, undergoing evaluation as a potential clinical candidate and that's an internal evaluation. So, that is one program of high interest. I think the antibody programs, both 842 and 843 are also advancing, but it's still a little bit early in the year for us to forecast which one will be next. I think one point, that is not on our typical 10TOT10 slide is also very important and very exciting that may well might become important in 2009, that's the potential clinical candidate. We have a number of new discovery programs that I think are, very important and towards the end of the year we plan to have a research day, during which we will have more time to highlight the earlier stages pipeline. I think this covers what's your question is getting at. So I think we will have to defer some of this until then when we can really go through the science of those in detail. Sharon Seiler - Ladenburg Thalmann: Okay. Thank you. I'll get back in queue.

Next to Jason Kantor with RBC Capital Markets. Jason Kantor - RBC Capital Markets: Hi! Just some questions on the 1021 data. First of all, do you think that you need to be looking at lower doses. It seems like there is dose response but perhaps you might want to determine a more minimally backed up dose. Also on dosing, you are treating four times a day, which pharma companies typically see as a non starter. Do you think that you can go to three times a day or two times a day, given the PK of what you know now about the pharmacodynamics? Dr. Philip Brown: Thanks Jason for the questions. Your first question, I would look at these data, first of all, we have an excellent safety profile emerging from even repetitive and relatively high doses of the compound. I think that's a critical factor to consider when you are looking at IBS in particular where the compounds that were originally approved were pulled out because of safety issues. I think that's the current landscape of IBS, which is going to require an incredibly safe agent. I am very encouraged by the safety profile that's beginning to emerge around 1031. I am also encouraged by the fact that we see a virtual overlay of fact even at the lowest dose study which was 250 milligram QID in this particular study. I don't think we have adequately defined a minimally effective dose. Remember, really what we are trying to do at Phase I is probe for the safety and PK profile of the compound. I think we have the added benefit of evaluating the pharmacology by utilizing these biomarkers. Clearly, we're going to have to do some dose ranging work as we move into irritable bowel syndrome. With regard to QID regarding our four-time daily dose administration being problematic. I am less concerned by that, at this stage of development. We are working with an initial type of formulation that allows us to probe the utility of the compound. I believe there will be further opportunity if we show that the mechanism has utility in the setting of IBS to improve on this dosing regimen to make it a much more attractive pharmacological agent clinically or from the marketing standpoint. It's just early and we need to really probe the mechanism of action at this point. Jason Kantor - RBC Capital Markets: You mentioned the formulation, are you going to have to do formulation in work, before starting your next clinical trials for that, and what kind of formulations might you be exploring also on the 2931? Do you want to do drug-drug interaction phase of methotrexate or are you going to wait till you've completed the ongoing studies, or is that something you can run in parallel? Dr. Philip Brown: We anticipate moving into IBS with 1031 with the current formulation, in order to probe the proof-of-concept with the mechanism. Assuming we were to see an effect, I think we have the opportunity to improve on the formulation of the compound, as we advance it into further stage development thereafter. With regard to 2931 and the methotrexate interaction study, we're anticipating getting that up and running, after completion of this initial multi-dose tolerance study in normals. We need to assure the safety profile and the pharmacokinetic effect of the compound, before we can design a protocol and that it can accommodate use with methotrexate. Jason Kantor - RBC Capital Markets: Thank you. Dr. Arthur Sands: Thank you, Jason.

Next to Edward Tenthoff with Piper Jaffray. Edward Tenthoff - Piper Jaffray: Great. Thanks and thanks for asking those questions. Touching back to 6171 for a minute, just remind me in the slide went by pretty quick, it's 120 patients, is it a two-months endpoint and what is the cognitive end-point that you're using? Do you think two months or that period is enough to show some sort of [links] between placebo? Dr. Philip Brown: Thanks Ted, I appreciate the question and I do run through slides pretty quickly; as we had a lot to cover, so my apologies for that. So the study is a double-blind, randomized study in subjects with age-associated memory impairment. The end as you suggested is correct, a 120, and we're exploring two-dose levels, a high dose, a low-dose to the placebo arm. Edward Tenthoff - Piper Jaffray: So, 40 each. Dr. Philip Brown: That's correct. Edward Tenthoff - Piper Jaffray: Yeah. Dr. Philip Brown: And it's a four-week exposure period. Edward Tenthoff - Piper Jaffray: Okay. Dr. Philip Brown: The cognitive instruments that are being utilized are the CDR battery, which have been utilized in our Phase I studies as well as, which is a computerized instrument, and we're also utilizing paper metrics, a delayed word recall assessment, as well as subjective and objective instruments to assess for cognitive improvement in these subjects. We believe this is an adequate period of time to probe for an effect of the compound. Edward Tenthoff - Piper Jaffray: Okay, I look forward to that. Another quick question, if I may, kind of switching over to the finances, really two quick questions here. Firstly, on licensing revenues, it's jumped around a little bit. We have actually been looking for license revenues to start to tail off in the back half. Can you just remind us what goes into the subscription fees, and license revenues, what's comprising that, give or take $1.3 million -$1.6 million, and how should we be forecasting that going forward? Then my second financial question which really has to do with the non-controlling interest in Symphony and I should know this by now, considering we have worked on Symphony deals for a couple of them, but there is the 26 million in cash -- $27 million in cash, but I think it's $19.2 million in non-controlling interest. In this my question is, is that all that you're able to write off, going forward, the $19.2 million.

Okay, let me address that one first. Under current accounting list here right now, this is year, the non-controlling interest, that $19.2 million is all that we would be able to write-off. There is new guidance out there, that's effective January 1, 2009, which should enable us to actually write-off, all the way up to the cash amount of $26.9 million. Edward Tenthoff - Piper Jaffray: Okay.

The other question had to do with sub-license revenue fee? Edward Tenthoff - Piper Jaffray: Oh, yes. Subscription fees and licensing fees.

We did sign an additional agreement where we did bring in about a $1.03 million this quarter on a sub-licensing deal. As far as projecting for the future, I mean these are trailing off, most of these agreements when we signed them, there is an upfront and then there aren’t additional payments. We do have a few of them that do have annual payments. Those are starting to wind down so, so when we give our financial guidance on revenues, all we are doing is providing the contracts with committed revenue. Edward Tenthoff - Piper Jaffray: Great. Thanks. That's very helpful. Dr. Arthur Sands: Thanks Tenthoff.

We will now take a follow-up from Sharon Seiler with Ladenburg Thalmann Sharon Seiler - Ladenburg Thalmann: Yes, I do have a financial question and can you quantify what you spent on severance cost this quarter and do you expect to have more severance costs going forward or those are all done already.

So we spent about $1.9 million in severance costs in the second quarter. And that is the full amount of the expense related to this reorganization. Sharon Seiler - Ladenburg Thalmann.: Okay. Thank you.

Sure.

At this time it appears that we have no further questions. So I would like to turn the call back over to Mr. Sands for any additional or closing remarks. Dr. Arthur Sands: Thank you very much everyone for participating. If you look at this last slide, pictured again our 10TO10 program slide. As we look back on a quarter, I think the two most exciting events that we see in our clinical development front are LX1031 having progressed through it's Phase 1 studies and now completed them. We have plans to move forward, a very important event and LX1032 receiving Fast Track status from the FDA. Of course, there is many other things progressing at the company, as well, but in this sort of setting we can only highlight them. And we look forward to keeping you posted on the broader progress of Lexicon. Thank you very much.

This concludes today's teleconference.