Lexicon Pharmaceuticals, Inc. (LXRX) Earnings Call Transcript & Summary

Good afternoon, ladies and gentlemen, and welcome to the Lexicon Pharmaceuticals Inc. full stated results from RELIEF-DPN-1. [Operator Instructions] This call is being recorded on November 14, 2022. I would now like to turn the conference over to Mike Kelly. Please go ahead, sir.

Thank you, Andrew. Good afternoon, and welcome to the Lexicon Pharmaceuticals conference call. Joining me today are Lonnel Coats, Lexicon's Chief Executive Officer; Jeff Wade, Lexicon's President and Chief Financial Officer; Dr. Craig Granowitz, Lexicon's Senior Vice President and Chief Medical Officer; and Dr. Anand Patel, Chief Medical Officer at Conquest Research. Earlier today, Lexicon issued a press release reporting full results from the RELIEF-DPN-1 Phase II proof-of-concept study of LX9211 in painful diabetic neuropathy, which was also presented at the 16th Annual Pain Therapeutics Summit by Dr. Patel. Copy of that press release as well as a webcast of this call and the slide presentation is available on our website at www.lexpharma.com. During this call, we will discuss the study results reported in the release and then use the remainder of our time to answer your questions. Before we begin, let me remind you that we will be making forward-looking statements, including statements relating to the safety, efficacy and therapeutic and commercial potential of LX9211 and other drug candidates. These statements may include characterizations of the RELIEF-DPN-1 study results and other research and development results relating to LX9211 and other drug candidates. These statements may also include expected timing of clinical trials for our drug candidates and the regulatory status and market opportunity for those programs. This call may also contain forward-looking statements relating to our growth and future operating results, discovery and development of our drug candidates, launch and commercialization plans for any approved products, strategic alliances and intellectual property as well as other matters that are not historical facts or information. Various risks may cause our actual results to differ materially from those expressed or implied in such forward-looking statements. These risks include uncertainties related to our NDA for sotagliflozin in heart failure, the timing and results of clinical trials and preclinical studies of our drug candidates, the success of our commercialization efforts with respect to any approved products, our dependence upon strategic alliances and other third-party relationships, 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 planned research developments 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 would now like to turn the call over to Craig Granowitz.

Thank you, Mike. Next slide, please. I'd like to introduce Dr. Anand Patel. Dr. Patel, was the Chief Medical Officer at Conquest Research and was the lead enrolling site from the RELIEF-DPN-1 study. Dr. Patel has served as a PI or Sub PI on more than 30 clinical trials and is a board-certified anesthesiologist with a subspecialty in pain medicine. Dr. Patel?

Thank you. I'll go ahead to the next slide, please. Next slide, thank you. So first of all, thank you for that lovely introduction. I as Craig just stated, we had the restriction of being the highest enrolling site for the RELIEF-DPN-1. My goal today was to walk you through a little bit of the background preclinical work that led to the discovery of this novel target and the discovery of LX9211. I'll then walk you through the RELIEF-DPN-1 study, focusing on the study design, talking a bit about the baseline patient characteristics. And then I'll present to you the efficacy and safety data. I'll conclude, and then we can open it up to questions. Next slide, please. Next slide, please. You can go to the next slide as well. Thank you. All right. So let's talk about AAK1 first through a very robust gene science pipeline that Lexicon oversaw. The AAK1 enzyme was identified as a novel target for the treatment of neuropathic pain. AAK1 is formerly known as AP2-associated protein kinase 1, and this enzyme is intimately involved in the regulation of clathrin-mediated endocytosis. It was also noted on this program that AAK1 was knockout mice were actually quite resistant to the development of neuropathic pain. So the next logical progression was to identify a molecule that would inhibit the activity of the AAK1 enzyme and the birth of LX9211. So LX9211 is a potent, highly selective small molecule inhibitor of the novel target AAK1. It also has been confirmed through this preclinical work that the clinical effects of inhibition of this enzyme are not exerted through the opioid pathway, but instead appear to be exported to the alpha-2 adrenergic receptor pathway. Next slide, please. Okay. So there's a lot to unpack in this slide, and I want to make sure I convey the study design in accurate detail. I think it's a very elegant set of design. So patients that were interested in the study were brought on site and after inform consent was obtained, we ran them through a fairly standard inclusion/exclusion criteria. That screening period was up to 2 weeks. Once patients were deemed eligible on the screening period, they then transition to the single-blind placebo run-in. So I think this part of the study is a port for a few reasons. The purpose of having a single-blind placebo run-in was twofold. Number one, we wanted to try to identify and eliminate patients who had high variability in pain scoring. Number two, the goal is to try to minimize to the best and to be possible, enrolling placebo responders. In addition, patients were asked to keep a daily diary. And on that diary, they were tasked with giving an average summary of their 24-hour average pain score. They were asked to basically rate how much sleep interference there was from their painful condition and they were asked to document rescue medications. They were asked to not use rescue medications for that 2-week single-blind placebo run-in to accurately convey their pain. The other piece that was being tested during the run-in was compliance. So patients need to have enough diary compliance at 70% of diary entries at drug compliance. They need to show IP compliance of 82% in order to move forward with randomization. Once patients returned, final [ I ] criteria was vetted if they were eligible on [ I ] criteria and on pain diary they then were randomized into 1 of 3 treatment arms. We have the placebo treatment arm, and then we have a low dose and a high dose arm. These doses were identified based on previous Phase I studies. The thought process was to have a loading dose on day 1. You can see in the low dose, the loading dose is 100 milligrams and high dose, it's 200 milligrams and then patients subsequently transitioned to a maintenance dose at 10% of the loading dose for daily consumption. They were asked to continue scoring their average daily pain scores. They were asked to continue documenting interference with sleep and they're asked to continue citing rescue medications. Patients returned on site every 2 weeks for follow-up visits where various scales were administered. At the 6-week point, patients will then transition to a placebo washout period with single-blind placebo washout as they continue to document pain score, sleep interference and rescue pain medication consumption and they were then brought back on site for a week 11 safety visit. Next slide, please. So a couple of key inclusion/exclusion criteria, I want to review. Patients needed to have a diagnosis of confirmed DPN for at least 6 months. And so they also need to have a stable regimen of treatment of their diabetes medications for 30 days prior to screening. Hemoglobin A1c to be less than 11% in order to qualify. And we did notice at the site level, but actually on pain scoring patients needed to have a pain score of at least 5 out of 10 and no more than 9 out 10 to be eligible for study. On the exclusion side, common exclusion criteria were utilized here typical of pain studies. Any patients that have any confounding pain conditions were deemed not eligible, any patients with active psychiatric disorders, any patients with adhesive drug or alcohol use were not eligible for the study. And any patients who had a previous history of neurolytic deemed ineligible. Next slide, please. One other interesting thing about the study was that patients were allowed to continue on one prescribed medication for DPN and still remain eligible for the study. These had to be typical medications for DPN, think of like gabapentin, pregabalin, antidepressants like duloxetine as long as it was 1 medication only and as long as it was stable in the 30 days prior to screening. Certain prohibited medications were also present in the protocol. Patients could not use opioids for chronic pain use in the 2 months prior to screening or for the duration of the study. And similarly, with NSAIDS patients were not allowed to use NSAIDS for chronic pain in the 2 weeks prior to screening or any time for the duration of the study. However, patients were provided at the PI discretion, acetaminophen of the rescue medication. They were allowed to use up to 3 grams per day as needed. Next slide please? All right. Let's talk a little bit about the patients that did qualify for the study. A total of 319 patients were enrolled in the study. The average age of the patient was 62 years old, and that's split into roughly 59% males and 41% female. On the race element patients -- 76.5% of patients identified as white, 18.5% identified as black or African American and 5% identified as others. I think it's important to point out that it's in line and consistent with current U.S. demographics and a positive feature of the study. Finally, for baseline DPN drug usage, almost half of the patients that enrolled the study were actually on concomitant medications for DPN. Across the board, it was 45% for all 3 cohorts and 55% for not on medications. And curiously, in the placebo group, just by chance, 55% actually ended up remaining on baseline DPN drug use while they were in the study. The most frequent medication seen were gabapentin, pregabalin and duloxetine. Next slide, please. Right. Now to get into the efficacy results. First, the RELIEF-DPN-1 study did achieve its primary endpoint. There was a statistically significant reduction in average daily pain score in the low-dose arm in comparison to the placebo arm. Internally, Lexicon deemed a P score of 0.028 to be statistically significant. The low dose group did meet that with a P score of 0.007. In the high-dose group, that result appear to plateau and that group fell just short of statistical significance at 0.030. It's also important to point out that this effect on average daily pain score was not to be consistent across the board for age, sex, whether or not the patient used baseline DPN medications and where they started regarding their pain scoring. Next slide, please. On this next visual, which I think prints a fairly vivid picture here, you can see because of the loading dose, there's appear to be a drug signal fairly early, as early as week 1, you can see separation of the low-dose and high-dose treatment groups in comparison to placebo, and as expected, that signal maintains throughout the 6-week treatment period. On the next slide, if you recall, patients were transitioned back to placebo during the single-blind placebo washout. And typically, because of the long half-life of the drug, you would expect a steady fading of that efficacy of pain reduction, and that's exactly what happened in the lower dose and high dose arms. You see both arms at erosion of their pain efficacy as they trend back towards their baseline pain score. What you do not see is evidence of any rebound pain or any indicators of withdrawal occurring in these patients. Next slide, please. In addition to meeting its primary endpoint, there were several additional key efficacy measures that were met throughout the study. When you commonly discuss the quality and characteristics of systems of patients who suffer from DPN, they'll commonly cite burning pain is a commonly cited feature. We were asking the patients at week 6 through a pain instrument to rate their burning pain specifically. And in both groups, the low dose and the high dose group, there was a statistically significant reduction in burning pain specifically with the P score study below on the right, both groups were significantly less than 0.028. Next slide, please. If you recall, also patients were asked to rate the interference of their sleep from their pain condition on a daily diary that continue not only during the treatment period, but also in the single-blind placebo washout. In both groups, low dose and high dose, there was a significant improvement in the sleep interference with both scoring statistically significant with P scores of 0.005 in the low dose and a P score of 0.002 in the high dose. Also, although I don't have the graphic, once patients stopped utilizing study drug and transition back to placebo, that fading of the signal and that return back to baseline did also occur in both the low and high dose group. Another way to infer pain relief is to evaluate the incidence rate of initiation of rescue medication. If you recall, patients were asked to not use rescue medication until the treatment period started. You can see here this graphic that in the placebo group, the incidence rate of initiating rescue medication was higher and that trended higher throughout the 6 weeks in comparison to the low dose and high dose group. Finally, at week 6, patients were asked to take a 7-point scale called the patient's global impression of change. This is a measure of a patient's subjective sense of how they feel that they are responding or doing on treatment in both the low dose group and the high dose group, there were a higher number of patients who reported improvement in their condition, while on study drug. So that concludes the efficacy data. The next item I'd like to cover is the safety data. Next slide, please. You can see on this graphic here that the most common AEs treatment-emergent AEs specifically were dizziness, headache and nausea. And just based on the frequency of the AEs, you can see what appears to be some sort of dose relationship. The low dose and the higher dose groups did report a higher instance rate of those treatment-emergent AEs. However, also important to point out is that these treatment emergent adverse events were independent of age, sex or use of baseline DPN medications. As clinician, the first question I'd ask is, is there a drug-drug interaction occurring if patients remained on their concomitant DPN pain medications, and it appears that, that is not the case here that those AEs were not compounded by being on both the concomitant DPN medication and the study drug appeared to be independent of that fact. Next slide, please. Once patients reach the week 6 period, they were washing out of drug. We saw a lower incidence of treatment-emergent adverse events during this period, and that was comparable across all treatment arms. Again, the most commonly cited were headache, dizziness and nausea. What we did not witness or patients did not report any evidence of drug withdrawal or rebound pain. There was a noted CPK increase in a few of the patients in all 3 groups, but there were no PI reported clinical scenarios for those rhabdomyolysis so that they have just been incidental. Regarding SAEs, there were a total of 6 that occurred in the duration of the study. None of them were tied or related to the investigational product and are [ seen ] by the investigator. In fact, 3 of them seem to occur in the placebo washout period. There were unfortunately also 2 deaths that occurred, 2 participants passed away while participating in the study. Again, neither was deemed related to the investigational product. So in conclusion on the safety side, the most common AEs documented were dizziness, headache and nausea. Almost all of them reported as mild to moderate. There appear to be no drug-related SAEs support in the study nor were there any drug-related deaths, and there was no reporting by patients of drug withdrawal or any type of pain rebound symptoms. Next slide, please. So in conclusion, I think there's 2 key takeaway points from the RELIEF-DPN-1 study. The first is that AAK1 inhibition has significant potential as a new mechanism of action for the treatment of neuropathic pain. And specifically, LX9211 carries a lot of potential as a treatment -- as the non-opioid novel treatment for diabetic peripheral neuropathic pain and warrants further advancement in studies.

Thank you, Dr. Patel for that, really nice summary overview of the data, including really providing additional context to the mechanism of pain relief and how those results might really be impacting patient quality of life. I think that really gets to the first question that I've heard from a number of people that have asked me about the study is the robustness of the results. And the fact that many of the trials really rely on this ADPS or daily -- average daily pain score. Could you comment how these results sort of fit into that narrative, particularly as it relates to other characteristics of the pain state?

Sure. So I think that the need for better neuropathic pain medication treatments is clearly there. So we have patients that are on concomitant pain therapies who are still citing very high pain scores. So it doesn't appear that the current drug options available are really moving the needle in a meaningful way. So I think that even a drop in pain scoring of 1 or 2 points poses significance. We saw this at the site level, so I can speak clinically. Again, we don't know which group patients were part of, but clearly, there were patients who subjectively reported a significant improvement while on drug. I think that the other thing about the study that's important to point out is that we -- patients went through a single-blind placebo run-in. So it certainly eliminates a lot of patients who were placebo responders and that may have dampened some of the effect on the pain scoring side as well.

Yes. And you've also commented on the use of the rescue medication, the use of the baseline DPNP medication. Could you comment on that, how that might have affected the ADPS?

I'm sorry. Ask that one more time.

The fact that the patients use more rescue medication in the placebo group and the fact that more than half of the patients were on an underlying DPNP medication.

Yes, I think that just kind of speaks to what I just said, which is basically even on concomitant medications, those patients were significantly having significant amount of pain that nudge them towards utilizing rescue medication, but it just speaks to how those patients could benefit from even a point or 2 drop would be meaningful to those patients.

Good. Could you comment a bit on what are the most commonly perceived complaints from patients? I know that I've heard sleep is important, the quality of the pain, the -- how patients describe the pain itself.

Yes, absolutely. I mean I mentioned previously that the burning element specifically seems to be a very common characteristic. There seems to be a very significant impact of those symptoms at night. And so there's significant difficulty with initiating sleep and maintaining sleep. And so when you can significantly chip away at those 2 elements of DPN, I think it has a pretty significant clinical impact.

The one last question before turning it over to the operator for questions, is the tolerability of treatment. Again, many have asked about how does the tolerability of this agent compare to other existing therapies.

I think a lot of it boils down to how the medication is prescribed to the patient and how they're educated on what expectations are. So clinically, when we're prescribing gabapentin or Lyrica, we go through a great deal of education with the patient about how to gradually escalate the dose, what kind of side effects to expect that those side effects maybe calibrate and then maybe an equilibrium reached where patients no longer experience those side effects. So I think it's important to point out that it's -- those AEs documented are consistent with the current drugs available on the market. And I think if patients had better education, it may have actually led to better retention as patients kind of realize that those symptoms would resolve, especially in relationship possibly to that loading dose.

Right. And I think you saw in your own site during the course of treatment, as you and the staff became more familiar with the study drug and the type of situations that the patients faced in their dosing that your retention rates actually improved.

Absolutely. And I think you have to also consider the fact that patients are participating in a trial, so they are even more very and more inclined to consider any side effect they experience to be through the drug and have a lower threshold for stopping. So I think once we kind of [ can ] and the fact that it was likely related to the loading dose and that these symptoms would likely resolve once stable state -- once the steady state was reached, it was easier to kind of create or retain patient inline.

Terrific. So now I'm going to turn it over to the operator for questions from those who are on the line.

[Operator Instructions] Our first question comes from Yigal Nochomovitz from Citi.

On for Yigal. We have a few for Dr. Patel. I guess, first, can you speak a little bit further to the clinical meaningfulness of the 1.4 point absolute change on ADPS seen with the low dose and about 0.7 point change on a placebo-adjusted basis. I guess, is there any way to maybe benchmark the data to other medications approved for DPN? Or is it just too difficult to compare since as you highlighted, about half of these patients were on some sort of background therapy?

Do you want to finish asking all the questions? Or how do you want to go through it?

I'll just -- I could just start with that one, maybe, and then I'll have a follow-up.

Okay. Sure.

I can comment on that. I think, as I mentioned previously, the level of efficacy being achieved by what's currently on the market is underwhelming. I think we saw a lot of patients in the study who were on common medications and continue to site high pain scores. So I think that there is certainly room for at least adjuvant therapy. I think that these medications can certainly coexist potentially. And although a point or 1.5 might not seem like a lot, I think clinically, it's still meaningful to these patients. I mean every tool we can offer to these patients to reduce their pain is meaningful to them. So it's all relative, and I think that it certainly has a role.

Okay. Great. That's helpful. And then can you just talk a little bit about how you would like to see a registrational study designed for this indication? What are the sort of key elements that you would want to see? And then maybe for the company, just on the Phase III design, do you believe that you need to do additional dose-finding work or do you expect to take the 100 milligram, followed by the 10 milligram dose into the Phase III?

Great. So Dr. Patel, do you want to answer the first part...

I'll offer my 2 sets on that. So -- and I'm speaking from a clinical standpoint, having run the trial. If you look at just the numbers, it looks like the results plateau with the high dose arm, but I don't know if that's necessarily accurate or true. I think part of the reality is that some of those patients experienced AEs and maybe previously withdrew from the study and that may have affected the pain scoring. I also question whether a loading dose is really needed. I think the drive to have a loading dose was driven by wanting to achieve drug signal quickly and that -- I certainly can have appreciation for that. It's a short treatment period and a short study. But I'll comment on it again, if you create patient by in the clinical scenario and you dose-wise escalate patients or you say, hey, this will take some time to gain efficacy, then I think that maybe the next study design may have lower loading doses, but may not even need a loading dose. And I guess I can let Craig also comment on that as well.

Thank you, Dr. Patel. I'll make a few comments as well from the company standpoint. We believe we have an effective dose. We believe that the low dose -- the loading dose of 100 milligram with the 10-milligram daily maintenance dose is a dose that has achieved the benchmarks and then some for this proof-of-concept study. I think you also know that we have Fast Track designation already with the FDA for painful diabetic neuropathy. And we are really moving with speed and efficiency into larger pivotal trials to demonstrate definitive efficacy. The final design of which we are really seeking input from our advisers, like Dr. Patel as well as from the FDA. Operator, next question?

Your next question comes from Joseph Stringer for Needham & Company.

First one is for Dr. Patel. Just curious, given the inclusion/exclusion criteria and the criteria around background meds, how representative are the patients in this Phase II trial with the broader or the typical DPN patients that you would see? And then I have a follow-up.

Sure. I can answer that. I mean I don't have exact numbers for you, but I think that it's a fair representation of the current landscape in the clinical scenario. So I think patients are on treatment defined by whether the primary doctor or treating physician takes action, whether the drug has efficacy whether it's the patient that the patient still remain on the drug. So I think that it does reflect actually the current landscape for treatment and what patients are taking in the real world.

Yes. Joey, maybe I'll just provide a little more context. Dr. Patel, I think, laid out very well the demographics. The average age in the early 60s is a group of patients with long-standing significant diabetes and neuropathic pain. If anything is skewed to a group of patients that had very significant pain, which was a higher threshold. The fact that we had a very good gender distribution of 40-60. The fact that there was nearly 20% representation of African Americans, I think, is highly unusual, and I think a very demographically representative sample. The fact that their body weight was in the low 30s from a BMI. I mean, to me, this really was quite typical of what you would see of a group of patients with painful diabetic neuropathy of long-standing duration in the United States. And as a reminder, there are about 40 total sites that participated, all of them were U.S. based. So I think when we have had discussions with other advisers, they've been very complementary of the fact that this is a highly representative sample, if anything, as Dr. Patel said during his prepared remarks, skewed towards more significant pain. Most of the entry criteria on these studies has a minimal pain score of 4. The difference between 4 and 5 for baseline is significant. And this was a group of patients with really moderate to severe pain of long-standing, consistent duration.

Very helpful. And then just 2 more quick ones for me. One for Dr. Patel just in terms of the tolerability profile, just given that you see sort of a dose-dependent increase in AEs, how does this compare to other DPN medications? And would you need to see that those rates be attenuated before you feel comfortable using the drug in patients or -- and then a question for the company would be around -- just can you remind us when the AE occurred? Was it sort of early on in the dosing perhaps due to the loading dose? And then if I understood you correctly, you're plan is to move directly into a pivotal program? Or would you need to do more dose ranging trials or to sort of tune the loading dose.

Okay. I can handle the first one and this is Dr. Patel. So clinically, when we're prescribing, let's say, for example, a medication like gabapentin, the goal is not to establish efficacy as quick as possible. These patients have been in pain for a long time. The goal is to first establish tolerability, find an appropriate dose and then slowly gauge efficacy over time as you build that patient up and either evaluate for side effects or let them learn to tolerate the side effects that they dissipate. So this drug would not necessarily be the way we would prescribe it clinically in terms of the way it's schemed out. So I think that it's reasonable to say if this drug were available clinically, I would probably start at a relatively low dose. I'd let it build up and it slowly achieved a steady state and educate the patient that this could take up to 4 to 8 weeks to find a therapeutic efficacious range. So it's a little bit different. That's why I don't know it necessarily translates but I would have no hesitation using a drug like this, I've seen. I see potential in it. I think as we've likely discussed, I just think the dosing portion needs to be worked out.

Joey, I'll just provide a little more context around that. I think if you look at the clinical experience and the labeling for other agents, whether it's gabapentin or some of the others, they have significant liabilities that were not seen in this trial, things like weight gain, hyperphagia, disordered dreams, rebound, loss of efficacy or pain and dependency or potential dependency are all issues that we did not see at all in this study. And I think they are important differentiators. I think some of the slides that Dr. Patel showed which to me why that 5-week follow-on period was so important is the adverse events that were occurring at the end of therapy mitigate very quickly once patients stop. There was no rebound. And actually, the efficacy continued for weeks afterward. As you know, many of the other agents that are being used today have very short half lives. And if the patients miss even a couple of doses, their pain returns or anticipatory pain return. So what I've heard described by many clinicians is that there is this almost fear of missing a dose because they're going to lose their efficacy both from a combination of the rebound pain and rapid loss of efficacy because of rapid loss of drug levels. So what we've heard from a number of sources is that there are a number of very interesting and beneficial effects of this agent. I'll answer the next question you had around the timing of onset. And all of the adverse events, particularly in the low-dose arm that led to dropouts really occurred within the first couple of weeks. After week 3, there was no difference in the dropout rate between the low-dose arm and the placebo arm. To me, that's a really important point is that we believe that there is an opportunity to further optimize the tolerability, as Dr. Patel already mentioned, patient education is an issue. Looking at the loading dose is an issue which we believe we can study in Phase III. And then also the time of day of dosing, we picked the time of day of dosing in a proof-of-concept Phase II that was going to maximize the safety observation window where the patients took the dose, particularly the loading dose in the morning at the site with observed treatment, whereas most of these agents are administered in the evening to minimize some of the side effects that are associated. So we also, for an evidence of caution and to really make sure we have an accurate picture of the safety profile, we dosed the drug probably in the least effective manner that would be dosed in the real world. So we believe that there are a number of opportunities to further improve the dosing. And to your third question, we believe that we can manage these all within a pivotal trial because the feedback we've gotten from many experts is that you have an effective dose. There are some things that you can study, but they can be studied in the context of a pivotal trial. So as I mentioned, we are really working to finalize the trial design with some advisers, taking into account some of the topics that I just touched upon and in close collaboration with the FDA to move very rapidly into our first pivotal study.

Your next question comes from Yasmeen Rahimi from Piper Sandler.

Congrats on the presentation. My questions are directed to Dr. Patel. Maybe the first place to start off would be, could you maybe comment on whether the placebo rate across the pain measures as well as sleep in the new burning pain that was reported were in line with other historical pain studies in this population. Two, if you could comment on the onset of action. We saw a remarkable drop in pain as quickly as week 1. Are there other agents in this population that delivers such a rapid onset of action? And then the third question for Dr. Patel, given what you know about this drug as well as the mechanism of action, are there other types of pain studies that you would encourage the company to pursue given -- based on your understanding of the product as well as its mechanism of action.

Sure. If I recall, your first question was focusing on how the current market drugs impact sleep interference and burning pain in comparison or how this drug would fit in. I don't think that's really been vetted out completely. I think that we know that some of those drugs can make patients drowsy and that it may make them feel sedated and sleep better, but I don't think that's really been studied as a reported benefit. And I think that part of the problem with sleep in this population isn't that they need to be sedated so that they are on pain, it actually is tolerating the pain in a better degree, especially that burning pain that kind of eats them as they're trying to fall seep or as they stay asleep. So I don't know how it compares to current market agents, but I definitely think it hits a major unmet need regarding that patient population, their specific pain. The second question...

Timing of onset of the efficacy, the week one, how different it that.

Yes. And again, like it's different from how we would typically dose a drug like gabapentin or Lyrica. If we wanted to go for a really peak effect, we could certainly give them like a really heavy dose. I think the benefit of this drug is that, that it has achieved steady -- dosing at that way that it achieve steady state very quickly, and then you can see that signal occur. So I -- I think it's speaks to the efficacy of the drug that as quickly as we wanted that drug peaks and they maintain their dose, the daily maintenance dose. That drug signal is already there.

And other pain states.

Yes, that's a good question. So I think the next frontier for Lexicon if I understand, they currently have a study that's just completed enrollment for PHN. And so certainly, there's opportunity in the world neuropathic pain in general, whether it's chemotherapy-induced pain, peripheral neuropathy, post-surgical pain and there's plenty of patients that would benefit from having better treatment options for neuropathic pain. So there's -- I think there's tons of runway.

And then if I may ask one last question. I was wondering what you thought of the placebo responses across the 3 in -- across the 2 pain measures, whether they were in line with other pain studies that you have conducted in this population.

I think pain studies inherently are difficult because patients -- there's a significant percentage of placebo responders that enroll in study. So I think what happened with this particular study is that the single-blind placebo run-in has actually eliminated a lot of placebo responders. And I'm not sure that other studies have really done a strong enough job of eliminating that noise from the data results. So I think it further highlights the importance of the study results.

I'll turn it back over to Jeff to close.

Yes. Thank you, Dr. Patel for joining us today and for the presentation of the data. We're happy to be able to share that with our shareholders. And with the broader audience that what you presented here today. And thanks, Craig as well for the questions and the answer session. We appreciate that. We're really excited about this opportunity. There not very often that you have a success in painful diabetic neuropathy, and this is a chance to have a really pioneering new medicine, which we're excited about the opportunity, and we're committed to bringing forward and we're working towards, as Craig mentioned, finding a path to get this into Phase III quickly, which has been something that we've been strongly encouraged to do by our advisers and to bring this to patients as quickly as possible. One of the things that I think is particularly notable is that this is on top of standard of care. And that standard of care included gabapentin and pregabalin in a lot of patients and that's a different environment than a lot of other pain studies have been conducted. And one of the things we've done a little bit of market assessment and market research is that, that is highly valued. The ability to use this on its own or in combination with existing therapies is something that health care providers and payers have told us is important and valuable. So we're excited about that as well. We're looking forward to sharing more data with you as we go forward and to giving you new updates on as we get regulatory feedback and get prepared to go into late-stage development with LX9211. So with that, thank you for everyone for joining us today, and we'll look forward to providing you with further updates. We will close out the call.

Ladies and gentlemen, this concludes your conference call for today. We thank you for participating and ask that you please disconnect your lines.