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

Great. Good afternoon, everyone. My name is Jess Fye. I'm a senior biotech analyst at JPMorgan. And we're continuing the 2021 Health Care Conference today with Lexicon. Quick housekeeping note before we get started. Unlike in years past, this year is a little different. So we can't just go across the hall for a breakout session. You can use that blue Ask a Question button on your screen. That'll send me questions over the portal. I can ask them to management during Q&A after the presentation. So with that out of the way, let me turn it over to Lexicon's CEO, Lonnel Coats.

Jessica, thank you, and good afternoon, everyone, for joining us on this call today. As always, when I start this presentation, I start off by thanking all the extraordinary men and women here at Lexicon that work tirelessly every day to advance our science into the hands of patients. Today, I'll be making forward-looking statements, and some of those statements certainly will contain risks. Our risks are identified in our SEC filings, and you certainly are free to look at that. Let me jump right in. For the first 10 years of Lexicon's existence, for those who are new to the Lexicon story, we spent looking at the physiology and behavior of 5,000 genes. And from that, we try to find the most druggable targets. And from that, we found the best way to advance compounds into the clinic across a swath of many different areas. So everything you hear us talk about would have come from that discovery effort. So when you look at Lexicon's pipeline, the first product I'll talk to you about is the first dual inhibitor of SGLTs, which is SGLT1 and SGLT2, called sotagliflozin. Sotagliflozin was approved in Europe for type 1 diabetes. We're very pleased about that. And for those who have followed the story, you know that we continue to work with the FDA to find a clear pathway forward here in the United States for type 1 diabetes. But today, my efforts will be focused on sotagliflozin for heart failure. We have completed 2 long-term studies that have shown tremendous benefit that I must spend most of today's conversation on those 2 trials. The second product I want to talk to you about, there's a tremendous innovation that came out of a discovery alliance with Bristol-Myers Squibb that is wholly owned now by Lexicon is LX9211, which is what I consider to be one of the most elegant products I've had the opportunity to work on. Right now, LX9211 is in the clinic with 2 Phase II trials, one for diabetic peripheral neuropathic pain and the second one is postherpetic neuralgia. And then there's other compounds that we continue to work on and we'll be characterized, and we'll talk a lot more about in the future. It also is important to note that to telotristat ethyl, which is also known as XERMELO. XERMELO was the first compound that we advanced from discovery all the way to market, and we sold the rights to XERMELO last year to TerSera. However, Lexicon still has a vested interest in the work that TerSera is doing for biliary tract cancer. And should they have success there, Lexicon will share on the upside of that product. So let me talk about sotagliflozin as well as LX9211, which will be the focus of my conversation today. Both of these are first-in-class innovations. If I start with sotagliflozin. It is the first SGLT1 and SGLT2 combination product for areas of heart failure as well as diabetes. We have completed 2 large Phase III trials called SCORED and SOLOIST, which I'll talk to you a little bit about later. Both of these studies, because of the findings, were presented in The New England Journal of Medicine. Why? Because we believe there are class distinguishing characteristics that came from these studies. First and foremost, for the first time in a long time, you have a compound that have shown benefit for patients with preserved ejection fraction. Secondly, we saw outstanding benefit in myocardial infarction as well as stroke. Thirdly, we took a significant risk with the SOLOIST program by administering sotagliflozin within the hospital setting. For patients who were hemodynamically stable, they went on the sotagliflozin. And it gave us an opportunity to see what happens in following those patients in the first 30 days. And last but not least, we believe that SGLT1 continues to contribute significantly to the benefits we see with sotagliflozin, and therefore, we saw a significant benefit in severe chronic kidney disease. As a result of that, we took this information to the FDA. And as we reported out this morning, we got clearance from the FDA that these 2 trials are enough for us to file an NDA seeking a broad indication for heart failure. We believe this now will lead to more earnest discussions for -- with the partners we've already talked to and certainly, any future discussions we'll have for any potential new partners as we've now gotten this question off the table. Let me shift over LX9211 as a quick summary. LX9211 target is AAK1. It is an innovative approach to treating neuropathic pain. In the preclinical and the Phase I studies, benefits in multiple models of neuropathic pain were certainly substantiated. The -- we avoid the opioid pathway, which we think is a good thing. And the once-daily dosing was substantiated as well as a wonderful clinical safety profile. That's why I call this a very elegant program. There are now 2 Phase II studies, which will read out in Q4 of this year, both for diabetic peripheral neuropathic pain as well as postherpetic neuralgia. So let me jump right into heart failure. There's a lot of numbers on this slide. I'm just simply going to say there's a large market. But there's one number we're going to focus on, on Slide 7. And the reason that we focus on this number is why we took the risk with the SOLOIST program. There is about 1 million patients that are admitted into the hospital in the United States every year for heart failure. About 40% of those patients will have type 2 diabetes. That is a significant marketplace that is building and growing every year. So let me talk to you about the impact, what we consider the dual mechanism offers that others do not. We all know that SGLT2s are extraordinary compounds, and they've shown remarkable benefits in things like type 2 diabetes as well as what remarkable results that we see in HFrEF or reduced ejection fraction that was seen by the class has been nothing short of remarkable. As well as we've seen moderate benefit in chronic kidney disease when you look at the SGLT2 mechanism. However, when you add the SGLT1, which lowers glycemic variability, we believe the results that we have now seen in these 2 long-term studies where we are now seeing a significant benefit in HFpEF or preserved ejection fraction is coming from the SGLT1. We also believe we're seeing significant benefits in myocardial infarction as well as stroke as a result of the SGLT1. As well as we see severe chronic kidney disease being absolutely impactful leveraging sotagliflozin as a result of the SGLT1. Why do I say that? Because I believe there is a growing body of evidence that SGLT1 inhibition contributes to CV benefits. Here, you see on the left side on Slide 9 in cardiovascular diabetology. When you lower glycemic variability, you have less ventricle dysfunction, less myocardial infarction and stroke risk. In a second and different study that was presented in the Journal of the American College of Cardiology, when you look at genetic variance of SGLT1 where the SGLT1 is absent, you see decreased postprandial glucose, which we believe leads to less heart failure and also less death. In the third independent study looking at SGLT1, looking at the preclinical mechanistic data that was printed in a cardiovascular diabetology, we showed that in the rats model, sotagliflozin was able to impact and have a significant impact on HFpEF again and preserved ejection fraction where benefit was seen. So the evidence is starting to collect that the SGLT1 could be what is contributing to the benefits that I'm about to show you. Now both of these studies were published in The New England Journal of Medicine. The SOLOIST program was patients who were admitted into the hospital, that had worsening heart failure. And the SCORED program where patients -- all of the patients in that program had diabetes and chronic kidney disease. So let me show you the results. Sotagliflozin achieved in the SOLOIST program a 33% risk reduction and the primary endpoint of total cardiovascular death, also for hospitalization for heart failure and urgent heart failure visits. You can see that the separation started early and continued throughout the program. Most important, you see a p-value of 0.0009. Added to that, the treatment patient years to avoid 1 event is 4, which is significantly low. On the next slide, Slide 12, you see the sotagliflozin achieved significance in the primary endpoint in less than 30 days. This was important because we enrolled patients who were in the hospital setting or who immediately left the hospital setting, and you start to see the separation. This is a unique benefit because we know that hospitals are -- their payment systems are impacted by re-admission. This gives a clear example that patients can start on sotagliflozin in the hospital and leave on sotagliflozin as they leave the hospital. Great finding. Now when we look across HFrEF or reduced ejection fraction as well as preserve ejection fraction, you can see across both there are significant benefit that sotagliflozin is providing. In the cases of HFpEF, which is a left ventricle ejection fraction greater than 50, you see a hazard ratio of 0.48. That is quite remarkable. Now what's also remarkable about this slide, it does not matter about the subgroups. What is geographical subgroups? It is it is gender, it is age, eGFR. Sotagliflozin continued to provide a benefit with a substantial hazard ratio. Next slide. On Slide 14. When we look at the SCORED program, sotagliflozin achieved a 26% risk reduction in the primary endpoint of total cardiovascular death, hospitalization for heart failure and urgent hospital -- excuse me, urgent heart failure visits. Once again, you see a p-value of 0.004, very low p-value, substantial outcome. Also in a SCORED program, we look very closely at MI and stroke. And clearly, you can see here for fatal and nonfatal, you see a 0.68 hazard ratio. And for fatal and nonfatal stroke, you see a hazard ratio of 0.66. When you pull this all together, you see a hazard ratio of 0.77, and you see a p-value of 0.002. This is indeed a significant differentiating finding. This slide certainly is -- Slide 16 shows a reduction in A1c across moderate and severe categories in the SCORED program. This is important because when you reduce the glucose variability, we think that is what also contributes to the benefit we're seeing in heart failure. So as patients lose eGFR, you are still seeing the benefit being administered by sotagliflozin. This is quite a remarkable finding in a study as large as this was. This slide is quite remarkable. On Slide 17, sotagliflozin demonstrated efficacy across the entire spectrum of left ventricle ejection fraction. So whether you start to the left and go to the right, to the left, when you look below 50, that is reduced ejection fraction. And to the right, as you go above 50, that is preserved. And you can see that straight blue line. You can see that the hazard ratio continued to be quite extraordinary. And then when you add in the confidence intervals, you continue to get a substantial benefit across the entire ejection fraction curve. This is quite remarkable. This is a quite remarkable finding. And again, we believe you are seeing this because there's a contribution that the SGLT1 may be making here that's leading us to this outcome. With that, we put together a proposed label and we sent it to the FDA and had conversations that basically, sotagliflozin will be indicated to reduce the risk of CV death, hospitalization for heart failure and urgent visits for heart failure and adopt patients with type 2 diabetes with either worsening heart failure or risk factors for heart failure. This is significant because in this, should we be successful, ultimately, this will encompass both patients with reduced ejection fraction as well as patients with preserved ejection fraction. That will be a first. Secondly, the rapid benefit we saw in patients with worsening in heart failure, we expect also to make it into the label because this will be important given that you administer the drug inside of the hospital and saw such a substantial benefit. Last but not least, we saw a substantial reduction in MI and stroke. We believe it will make its way into the label. But ultimately, to maximize that value, we do believe additional work would have to be done there, but it will make its way into the label. Let me move into neuropathic pain, my favorite product. With LX9211, the market overall for neuropathic pain, we think, is quite substantial. So I won't run into all of these numbers other than to say you have a worldwide market for DPNP somewhere around $12 million in 2026. We know the current therapies are limited by lack of efficacy side effects and potential for abuse. What I love about this innovative approach is it's highly selective. It's an oral molecule and Lexicon holds the exclusive development and commercialization rights, and we just recently received Fast Track designation for diabetic peripheral neuropathic pain from the FDA. So we have an innovative approach to treat neuropathic pain without the addictive potential. Why is that the case? And why we were excited about it? When the scientists first looked at this, they did this formalin paw model. And when you look to the -- on Slide 22, when you look to the numbers 2 phase or the second phase of this, it clearly showed that the knockout mice were resistant to pain. We then did the spinal nerve ligation model. And once again, what you clearly show, the knockout were more resistant to pain. This certainly excited our folks in discovery, and it gave us confidence to go further into development. This model on Slide 23 shows, again, neuropathic pain behavior and rats in the DPNP model where these rats had diabetes and they -- on the purple side of the curve, these are nondiabetic mice. On the brown are the diabetic mice. And what you see in the green and the blue is when you had to take the knockout, you see the knockout behave to pain almost similar to those who are without neuropathic pain. Quite a substantial finding. I'm going to, for the sake of time, I'm going to move to the preclinical Phase I results. The preclinical data demonstrated excellent CNS penetration, a reduction in pain behavior. The MOA is independent of the opioid pathway. In the single and multiple dose Phase I studies and supported preclinical profile, once-a-day dosing in a favorable clinical safety profile. Again, we believe we have an innovative approach to treat neuropathic pain without the addictive potential and without some of the effects we see with gabapentinoids. So we went into 2 proof-of-concept studies for DPNP and PHN. For diabetic peripheral neuropathic pain is a double-blind placebo-controlled parallel group, multicenter study with 3 arms. Placebo in 1 arm. Another arm will be 100-milligram loading dose and then 10 milligrams thereafter. In the second arm, it will be a 200-milligram dose with 20 milligrams thereafter. The primary endpoint will be changed from baseline to week 26 using the average daily pain score. There will be approximately 300 patients at 30 U.S. sites. And patient enrollment and dosing is now ongoing. We expect results in Q4. And as I said before, we now have -- we have Fast Track designation from the FDA. We've also put into clinic for PHN, a double-blind placebo-controlled parallel group multi-center study with 2 arms, placebo and a 200-milligram dose of active drug plus a 20 -- excuse me, 200-milligram loading dose followed by 20 milligrams daily. The primary endpoint, again, is changed from baseline to week 6 in the average daily pain score and approximately 74 patients at up to 30 sites globally. The patient enrollment and dose is ongoing. And again, we believe we will have results in Q4 of this year. The outlook for Lexicon. We are in a strong financial position with 2 years of cash. Our objectives is to: find a collaboration for sotagliflozin for heart failure; then advance an NDA in the heart failure indication here in the United States; pay very close attention to our 2 POC results that we'll call out at the end of this year for LX9211; and then you can expect additional publications for sotagliflozin, and I would pay very close attention to those additional publications as we continue to stratify this data. There will be a lot more to say about sotagliflozin as we go forward. There will be additional publications that we'll start putting out into the marketplace around LX9211 in terms of the preclinical findings that we have so that everyone can be clear about what we have on hand. Last but not least, we will expect a call out from TerSera late this year around the biliary tract cancer results. And again, we expect some upside should we be successful there from the outcome of that work. With that, I'll stop there.

Great. Thanks, Lonnel, and we'll just give it a moment for your colleagues' video to come back on. And while we're doing that, I would just remind folks that if you want to ask a question, you can use the blue button on your screen to send questions to the portal, and I can ask them from management. But maybe first, just to start out, just for a little context, how does the potential indication that the FDA says that SCORED and SOLOIST will support, how does that indication compare to the -- for Farxiga label and the Jardiance label?

Yes. Well, the label that we're trying to get is a broader one that will encompass both the patients who will have reduced ejection fraction as well as those patients with preserved ejection fraction. The second thing that will be different is that we administered sotagliflozin in the hospital setting, and so we'll expect to get the worst in heart failure component in the label as well. Those are 2 very differentiating components that at this point, we have the data that we think we can advance and have a differentiating label. I will ask my colleague, Praveen, if there's anything else he would add other than what I just said.

Well, I think one of the main things, Jessica, is that the closest label which comes to proposed sotagliflozin label happens to be with dapagliflozin. However, it is restricted to cardiovascular death and hospitalization for heart failure and reduced ejection fraction only, and they recently obtained that in 2020. Our proposed label, as Lonnel had mentioned in his slide, happens to not only contain cardiovascular death, hospitalization for heart failure, but also urgent heart failure visits in type 2 diabetes with worsening heart failure or additional risk factor for heart failure, which -- and across the spectrum of ejection fraction. So ours should be very, very broad label when granted by FDA.

Okay. Great. Now you talked about in your 2021 objectives, both the collaboration and the NDA filing for sotagliflozin in heart failure. Will you file on your own? Or will you wait for a partnership before doing that?

Well, Jessica, great question. We've started to work on the NDA. We got the guidance that we needed from the FDA. And a good deal of the work is done, particularly in areas like CMC as we file for type 1 before. So we will continue to do the work and prepare the NDA so we do not lose time. So when we get a partnership, that partnership or collaborator will certainly have some input on how we complete the NDA. But we will most likely be in a position where we would not have lost time in preparing that NDA for filing.

All right. And what type of deal structure would you be most interested in as you think about a potential partnership?

It's a great question. For us, we're looking for being able to participate in the upside. Because we do think we have a differentiated label. We do think we're seeing things that, quite frankly, is going to be very difficult for others to replicate. And therefore, what's most important to us is to make sure we get value over time from this asset. And therefore, we'll put more emphasis on value on the upside of this asset versus typically, when you go in, you try to get as much of the upfront as you can. Now we don't get -- we expect to get our respectable upfront. But by the same token, it's extremely important, I think, for us to get and participate in the upside of this compound. So the structure will be, I think, more focused on the upside more so than the upfront.

Great. And to be clear, while you're -- today, announcing a feedback on your ability to file for a heart failure indication. Is there any reason to think you would not be able to secure an approval for improving glycemic control in type 2 diabetes?

Well, the way we think about sotagliflozin has shifted, right? We have not filed -- we have a ready to file a type 2 label we could have done it at any time. But we made a decision that the first way we want to go into market is to present sotagliflozin as a drug for heart failure for patients living with type 2 diabetes. Not the other way around, a diabetes drug that's being presented for patients who have heart failure. And so it's a nuance, but it's an important nuance in terms of how you bring this drug to market and how you position it. So for us, it is not our intent to seek a glycemic control label. But if a partner wants to do that, then they're free to do it. But for our purposes, we believe the best way to advance sotagliflozin at this point is to utilize the heart failure indication for patients live with type 2 diabetes.

Lonnel, if I may add. I think it is obvious, Jessica, that if we wanted a type 2 label or glycemic control label, we could get that easily. I mean, we have all the studies and the dossiers almost complete. It was -- all the studies were completed 1 year, 1.5 years ago. So it's not a question of if we can get. Yes, we can get it if we wanted to.

Good point. Thanks for the clarification, Praveen.

Thanks.

Got it. And if a partner wanted to also get a label in type 2 diabetes, would the regulatory review for each of those indications have to happen in sequence or can it happen concurrently?

Yes, it's a good question. I would assume it will happen in sequence. I would strongly encourage it happens in sequence and go out to heart failure first. I just believe these data that we just -- that I just presented, it hasn't been seen before. And so you're better off going out to the heart failure indication for patients who have type 2 diabetes than trying to get caught up in the glycemic control marketplace. So our focus will continue to be on the heart failure area. And if a partner, again, wants to pursue a broader label, then that's something we certainly can talk about in the negotiations.

Okay. Got it. And I was noticing that the other -- that the SGLT2 labels kind of specifically say not for treatment of type 1 diabetes as a limitation [ of use ]. Have you heard any more or talked any more to the FDA about the path forward in type 1?

Jessica, you and I have talked about this quite a bit. Maybe I'm stubborn, so I'm never giving up type 1 unless I'm driven out of town. We have had some more dialogue -- and when we get to our earnings call, I think we'll have more clarity on what approach we take with the agency. I think all we're simply asking from this agency is a clear pathway to approval for patients living with type 1 diabetes, where an adjunct to insulin can provide substantially increased benefit, improvements in the overall quality of life and the risk can be managed, and we believe that thoroughly. And therefore, we need a clear pathway forward from the FDA, and we're going to keep pushing until we get it.

Great. You also talked about the -- some of the epidemiology data as it relates to heart failure and the kind of potential indication you could secure with sotagliflozin. Can you put some dollars around that? So what do you see as the peak sales opportunity? And/or launching with kind of the cardiovascular angle first, do you think of pricing is potentially different relative to the products that were originally approved for glycemic lowering?

I won't get into the peak sales stuff because that's all part of what we discuss in potential collaborations. But I will say, yes. If you can approach the heart failure market and you can get the proper label and indication, you should go after heart failure, you should be talking to cardiologists. That's where you should start. And if you start there, then you compare this to what you see with ENTRESTO for reduced ejection fraction. What do you see from ENTRESTO for preserved ejection fraction. And this is the -- these are the programs you should be comparing yourself to. If we get caught up in a diabetes market, then it's not a proper comparison relative to the results we just saw. It needs to be compared to the programs that we see in heart failure. And therefore, that's where we will push, and I think that's where we'll have our greater success. In terms of the payers, yes, I've never launched a product where payers said, "Yes, come on in, let's give you some money." So it's always going to take some effort to position the product properly, engage with the payers, educate them on what you have here, make sure they understand what the results are, make sure they understand that the uniqueness that we've seen in this compound has not been replicated so far. And therefore, it deserves reimbursement relative to patients deserving having choice. Today, a patient who has preserved ejection fraction has very few choices. In fact, we witnessed a couple of ad coms with Novartis and ENTRESTO and the top cat that happened at the end of this year. And you saw the struggle with the ad com trying to find a way forward because there's nothing. There's not very much in the arm alternative too, to offer patients for -- that have preserved ejection fraction. So you've got a great vote, but the data was fairly convoluted. There were some challenges around what was actually shown. And what is the cutoff point? Well, here with sotagliflozin, you don't have to argue about the cutoff point. Whether you start at reduced or you go all the way to preserved, you see a statistical significant and you see a uniqueness in the hazard ratio where you are reducing risk, period. And that hasn't been seen before. So I also believe that is why the FDA was able to get back to us quickly and gave us the encouragement to go forward to filing this compound.

Okay. Maybe we can switch to your favorite product. Is it still your favorite product?

It is still my favorite product. This is my [indiscernible]

All right. So as we think about these Phase II readouts coming up, talk to me about what represents a win in those trials? What's the bar you want to hit on a placebo-adjusted basis for the change from baseline in average daily pain score?

Dr. Tyle, you want me to take that or you want to take it?

I mean, obviously, the win here is that we show statistically significant results between placebo and active. That -- I don't think we have disclose, Jessica, as to what that delta is in the average daily pain score between active and placebo on which the statistics is based. But it is a meaningful difference. Less than 1 point on a scale of 10, but statistically significant will make us win the game.

Yes. Listen, this program, I've said this before at this conference, this is a high-risk program. But that's what I like about it. It's a high-risk program because if you win, you win. If you win on DPNP, you're going to win. If you win on postherpetic neuralgia, you win. If you went on both, my goodness. So I think we're taking the proper shot on goes here. What's critical for us is to mine these studies to be sure that we are looking at these studies, that the right patients are enrolled and randomizing these programs. And that Praveen's team is having direct contact with every site. We're just not leaving it to the CRO. I came from my previous company, ASI, we had lots of CNS programs. I look at what happened with Aricept and the uniqueness of that drug, which is very elegant, small, oral molecule in terms of small pill, 5 to 10 milligrams, very little safety issues that you had any concern about but had very dynamic benefits. I believe this is the same type of program, which is what excites me. But we're going to have to watch very carefully the enrollment, patient selection, education and compliance. If we do that well, then I'm very confident we're going to win on one or both of these programs.

Okay. And just to go back, did you say your power to detect less than a 1 point difference?

It is. Yes.

And is that clinically meaningful to have less than a 1 point difference?

I think our investigators and KOLs have told us that 0.5 point difference is clinically meaningful.

This is a phase -- these are Phase II trials. So what you're trying to get is the level of activity that informs you of Phase III. And so what you're going to -- how you're going to construct the Phase III program is going to be somewhat different than what your expectations of trying to find signals in a Phase II program with 300 patients.

Can you talk a little bit more about the mechanism of action for this product? And whether it addresses centralized pain that might be driving this symptomatology in patients with more advanced DPN?

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

Yes. So the mechanism of action or the site of action is the central nervous system site. It's the spinal dorsal horn is where the site of action is. So it's centrally mediated. So we feel pretty confident that we're going to be able to address those types of issues given the mechanism. It's tied into -- there's some evidence that ties it into alpha to adrenoreceptor pathways. It's clearly not on the opioid pathway. So there are a number of different elements of the mechanism of action that we're continuing to define. But it is a centrally mediated site of action and in the CNS.

Okay. Got it. And I know placebo response is frequently an issue in pain studies. Can you talk a little bit more about your strategies for controlling the placebo response here? Lonnel, you were emphasizing kind of patient selection. But maybe specifically, what elements of patient selection and what other strategies are you using to avoid a high placebo response?

Well, you want to make sure you have patients that are not naive to their conditions. So you want to make sure you have patients who actually experienced it for a period of time. Secondly, you don't want patients who, quite frankly, that may be depressed because they respond very differently in your clinical programs. And you don't want also the patient who are the extreme patient that comes into your program that doesn't respond to anything. So you want to make sure that you get the patient who is excited to be part of the program, looking for the right drug or remedy for them and that will be compliant. So part of the design of our study is to test and challenge whether patients are going to be compliant. Because we're going to be relying on their score that will be coming through electric diaries, electronic diaries. So we really got to make sure that patients are coming into the program will be compliant. So those are some of the things that I can tell you that we're doing. Some of the others, I would say, a little bit more proprietary.

What about things like concomitant medications?

Praveen, I'll let you talk about the concomitant medications.

So Jessica, we are allowing all the conmeds provided they are stable on it. So we don't allow patients who have started, let's say, gabapentin or pregabalin within the last week or 2. We want them stable on those. And same thing on the analgesics or over-the-counter products. They can take over-the-counter products as and when needed. We want to see the effect of 9211 on top of these medications because we believe that 9211 will provide benefit on top of gabapentin or pregabalin or even concomitant use of any over-the-counter medicines.

Got it. And it looks like on clinicaltrials.gov, one of the inclusion criteria is pain from DPN present for at least 6 months. Is 6 months long enough to be sort of not naive to their condition?

We believe so.

Yes. I think the time line came from a lot of consultation with some of our advisers that are in this space and what we have to look for and look out for. And some of it have also just come from my own experience of how you manage these trials to make sure you do everything you can to give yourself a fighting chance to reduce that placebo response that's going to happen. And I think #1 to that is really compliance. You need patients that are going to be compliant with how this is going to lay out. I think the second thing is you really need physicians that are all in looking for the right patients and make sure they're trained adequately, which is why Dr. Tyle and his team are working directly with these sites along with TerSera to make sure training is adequate and follow through and follow-up is also appropriate.

Right. So with these measures that you're taking on enrollment, is the greenfield rate tracking in line with your expectations?

Yes. Yes. I mean, we expected a certain percent screen failure, and we are actually slightly above that.

Yes. I don't get mad about that because what we have put in place to try to get the right kind of patient and get the right kind of outcome and result is going to lead to a higher screen failure rate. This is not a matter of just getting the study done on a certain time frame. This is a matter of getting a successful trial. And therefore, you have to set up the engineering process to make sure that's what's going to happen. So yes, we're running a little bit higher on the screen failure rate, but I'm not mad at that at all. That still keeps us on track on the current track that we're on. And if it moves a little bit, I can tell you the reason it's moving is that we're going to take the time to make sure that we are getting the right patients into this program.

Okay. Got it. So we're just about out of time, so we'll wrap it up there. But thanks, everyone, for tuning in and thanks to the Lexicon team.

Thank you. Thank you very much.

Good to see you, Jessica.

Thanks, Jess.