I'll start. Okay. Okay, welcome back, everyone. For those listening in the room and on the webcast, I'm Yigal Nochomovitz, biotech analyst here at Citi. This is the second day of our BioPharma Back to School Conference, so everyone's back to school, including the biotech people. It's my pleasure to have the senior management of Lexicon Pharmaceuticals here with me, Mike Exton, CEO, Craig Granowitz, CMO. Thank you, both of you, for joining.
Pleasure.
Appreciate it. Obviously, a lot going on at Lexicon. The company's evolved a lot. New programs, new data. So, Mike, you want to start, set the scene for us?
Yeah.
A lot of people just want to hear the basics. You know, what are the programs and what are the key catalysts coming?
Yeah, no, absolutely. It's been a busy two-thirds of the year, and now that the kids are back at school, it's going to be a very busy back third, I'd say. Yeah, look, it's been a very interesting year for us as we started the year pivoting back towards a pure R&D company to focus on the pipeline. As a result of that, we've made great progress, I believe, across the main three assets that we have in the pipeline. Taking them somewhat chronologically, in the first quarter of the year, we licensed LX9851, which was a preclinical asset for obesity and related conditions. We signed an exclusive worldwide license to Novo Nordisk for that particular asset. We're delighted to be able to have done that and that they see the value in that asset.
As everyone's aware, one of the world leaders in obesity, and we can talk a little bit more about that program. We read out the PROGRESS phase 2b study in diabetic peripheral neuropathic pain for pilavapadin, a novel non-opioid medicine for neuropathic pain, as well as other related conditions that we're also investigating preclinically. We've spent the last four or five months really digging into that dataset and looking now across the platform of the phase II program to see and analyze all of that data moving towards an end-of-phase II meeting late this year.
We feel, having analyzed all of that data, and we'll talk about that, obviously, that the 10 mg dose is fully endorsed by us and the Scientific Advisory Board and others to move into phase III, which we can start in early next year, potentially the very first non-opioid oral medicine in diabetic peripheral neuropathic pain to be approved in 20 years or so. That's an exciting program. In fact, now that school's back, September will be an incredibly busy month of data rollouts at various medical meetings. Everyone will get an opportunity to really see eventually the full dataset across the platform that gives us confidence moving into phase III. Last but not least, with sotagliflozin, we continue to sell INPEFA in the marketplace for heart failure.
Actually, we're selling about the same this year as we did last year with a skeleton resource that's going very well. For Zynquista, we continue the end-of-review engagement with the FDA. Perhaps most importantly, certainly coming out of the European Society of Cardiology meeting, where there was a lot of great data, both from us and others, that I think has significant read-through to our HCM program, hypertrophic cardiomyopathy. So that gives us a lot of confidence in the SONATA trial, which is really enrolling very well, looking for completion of all patient enrollment in 2026. Really a lot of great things that have been done and a lot more to look forward to over the next quarter or so.
Okay, well, maybe let's start with the cardio and HCM, considering that was the weekend's big news in biotech. And you had a pooled analysis SCORED and SOLOIST, correct? Can you talk about that? Because obviously, those were the heart failure studies, but I'm curious what you drew out of that new analysis that may be helpful or interesting with regard to HCM.
Yeah. I'll let Craig take you through the data, the age breakdown. But not only did we see that data, but also, Craig, maybe you can comment on DAPA Act, which was in recent or worsening heart failure, which really showed that SOTA is the premier medicine amongst the SGLT inhibitors for that particular condition, so.
Yeah, I'll start, Yigal, with the data that we presented, as you referenced, is that we did an analysis of the pooled 12,000-plus patients in the heart failure program, both the recent or worsening heart failure and the chronic and at-risk for patients for heart failure. What we found was a consistent response across that age group, even up to and beyond age 75, which, as you know, HFpEF is a group largely of more elderly rather than younger patients, unlike HFrEF, which is generally five to 10 years younger in age of onset. What we found is that there was a consistent response. The overall risk is higher the older you get, but the relative risk reduction was consistent across all of the age groups that we looked at. I think also importantly, two other key points.
The first is that there was also a consistent reduction in MACE events, which we continually see, which is unique to SOTA in the SGLT class, and the other is that the safety was similar, again, across all age groups, including even the very elderly in that study, so we thought that this analysis was important on a number of levels as we continue to move into the heart failure space. Mike did mention, and this might be a follow-up question, but I'll just touch upon it, is that, as you know, one of the key trials of that meta-analysis, the SOLOIST trial, is a trial in recent and worsening heart failure.
The population and the endpoints were almost identical to the 2,000-plus patient TIMI-sponsored trial that was done with dapagliflozin in recent and worsening heart failure, which missed its endpoint, showed about a 10%-15% reduction at 60 days post-release from the hospital. We have a 50% reduction in hospital readmission at that time point. So again, and they put this as part of the meta-analysis in that study. If you look at the three key trials that have been done in the SGLT class in recent and worsening heart failure study with empagliflozin called EMPULSE, dapagliflozin called DICTATE-AHF, and SOLOIST, we have a 50% reduction in hospital readmissions and cardiovascular death at either 30 days, 60 days, or 90 days.
If you look at the data that was presented by the investigators from TIMI, there is no difference in response with the SGLT2 inhibitors at 30 days, a statistically non-significant reduction at 60 days, and in EMPULSE, really not even a meaningful difference until day 90.
To what do you attribute this? I mean, obviously, yours is the dual mechanism, SGLT1, SGLT2. Is that the driver, or are there other aspects of the trial design or entry criteria that may have impacted how they missed and you did not miss?
I think the trial designs are actually quite similar. These are stabilized patients with a hospitalization for heart failure. Once they are stabilized and in the hospital, they are then switched over to therapy prior to leaving the hospital. So these groups are all roughly the same in terms of patient characteristics and underlying other medications. I think you touched on it, which is why we continue to be so bullish on our value in HFpEF and in HCM, is that there are direct effects that the SGLT1 blocking mechanism has above and beyond those of the SGLT2 inhibitors, because there are also SGLT1 receptors on the myocardium.
As was in a review article by Eugene Braunwald on HCM in the New England Journal of Medicine this week, it talks about cardiac energetics, which I think we've touched upon a little bit, and we expect more data will be coming, is that there are unique and differentiated effects of sotagliflozin on the cardiac energetics, which is particularly important in HCM.
Now, I mean, the SCORED and the SOLOIST data, you've had that for some time. I'm just curious on the timing of the pooled, this pooled analysis, this was just a new way to look at the dataset? Just explain how this happened now versus because I would imagine you had this data for some time, or no?
It's a great question, Yigal, and I think as we continue to probe more deeply into HFpEF, and again, going back to the myocardial effects, and as you know that with the SGLT2 inhibitors, the effect size minimizes over time, over ejection fraction, as you're getting close to normal ejection fraction, as has been published by both DAPA and EMPA. There is a mitigation, in fact, no benefit at those with higher ejection fractions, if you look at KCCQ score, six-minute walk test with either EMPA or DAPA, and with SOTA, one of the areas we think, again, with these SGLT1 effects, that we have consistent risk reduction across the entire range of ejection fraction, so as there is a bias towards the more elderly patients, and people have asked us about an age effect, that we thought this was something that was meaningful.
I think ESC felt the same way, having it presented as an oral presentation at the meeting.
I think as we look at that commercially, maybe this is also a good segue into HCM. It is for a patient that's turning up into an office, cardiology office in the community, and that physician is looking at the patient either potentially with HFpEF and/or with non-obstructive HCM. By demonstrating the efficacy of sotagliflozin in HFpEF, together with our data that we'll soon see in SONATA in non-obstructive HCM, it's nearly a one-stop shop for treatment of either of those patients, which until you do further testing and diagnoses, that patient could be presenting with. So it allows a physician, a cardiologist to prescribe with confidence a medicine that could be applicable in both disease states.
It's a specialized area. I mean, it's a big area, obviously, a lot of patients, but it's still specialized, and not a lot of, even a lot of knowledgeable investors don't necessarily know exactly the, can you just explain the difference, HFpEF versus the non-obstructive? What are the telltale signs of each one? And is it easily muddled? And how do you make the differential diagnosis? Or can it be both? Or how does that all work?
So if you think about the overall disease, clinically, if you look at a patient, there's no difference between a non-obstructive HCM patient and a HFpEF patient. They present the same way. It's a person with normal ejection fraction, but has heart failure, symptoms of heart failure, and radiography consistent with that, a big thick left ventricle. So those are, in a sense, from a clinical standpoint, grossly the same disease. It's sort of like.
So there's a reason to be confused sometimes. Okay.
Sure. Yeah, absolutely, and I think one of the reasons why there's been such a dramatic underdiagnosis of non-obstructive HCM is, unlike obstructive HCM, where you see a big outflow tract obstruction and you have a large gradient across the aortic outflow, is in non-obstructive, it's not so easy to tell. I think there are a number of diagnostic criteria that are becoming more aware, particularly if you look at EKGs and you do more sophisticated testing looking at cardiac energetics. There are genetic diseases that are associated with HCM, particularly the overactivity of the actin and myosin that you don't see in sort of run-of-the-mill HFpEF. But the first reason why we started looking at HCM is we did an analysis of those patients that had HFpEF, had left ventricular hypertrophy without hypertension.
Because the major reason why people have left ventricular hypertrophy in the United States and Europe is due to hypertension. The heart is pumping against this big pressure gradient for decades, and the heart gets thicker. And as the heart gets thicker, eventually it gets so thick it outruns its blood supply, and you end up with heart failure. So if you exclude the patients with hypertension, that group is enriched for a group that looks very much and probably had occult HCM in it in our own clinical heart failure program. We saw a 50% reduction in heart failure events and MACE in that subgroup. We've published that subgroup. It was about 500 patients. That was when we started really looking seriously about SOTA as a unique agent in the SGLT class for HCM.
Collectively, Yigal, again, just to sort of bring this back strategically where we're seeing it, because as you said, we've had the SCORED and SOLOIST data for a long time. We've looked to launch that in heart failure against the SGLT class in general, which makes it difficult from a payer perspective. But as we look forward to HCM being hopefully positive with the SONATA trial, there's a real opportunity for us, particularly in HFpEF, for sotagliflozin to be the drug of choice, the first drug of choice for both HFpEF and HCM, for which clinically, as Craig said, essentially a community cardiologist sees them present as exactly the same. They can use this medicine because it's safe, it's well-known, and it's efficacious and more efficacious than other SGLTs in the class.
Okay, well, that's a very good review of the landscape. Can we just go through then just the mechanics of the SONATA trial? What exactly are the endpoints? What is the progress of the study? You said, I think it's reading out next year?
Yeah, we'll finish enrollment next year.
Next year, okay.
But maybe, Yigal, if you don't mind, before we get to SONATA, it's worthwhile touching on MAPLE and ODYSSEY that read out at ESC. So ODYSSEY was from Bristol Myers, which was the very first readout of a trial in non-obstructive HCM. As you know, mavacamten, or CAMZYOS, is indicated in obstructive because it reduces the outflow tract obstruction, as Craig said. And I'll let Craig describe the study and the outcome. And then the other one was MAPLE, which was a study of aficamten from Cytokinetics, where it compared aficamten versus a beta blocker, which is the typical first-line agent in HCM. In this case, it was in obstructive HCM. And both of those sets of data, I think, have incredibly useful read-throughs to the HCM program for sotagliflozin in SONATA. So maybe let us touch on that data first, and then we'll move into the mechanics of SONATA.
Yeah, so thank you for the question, Yigal. The ODYSSEY trial was very important because it was the first CMI readout in non-obstructive HCM. It did not hit either of its two pre-specified endpoints, which was peak VO2, which is a standard metric for the CMIs in HCM, or the KCCQ, which is really the primary endpoint. They split the alpha. I don't want to get into too many technical details statistically, but they put most of the weighting of the endpoint on the KCCQ, and they missed on both those endpoints. There's a question of, will the class of CMIs work as well in non-obstructive HCM as they do in obstructive HCM? Because I sort of look at the CMIs as kind of a medical septal reduction surgery. They are very effective, both afi and mava, at lowering the outflow tract obstruction in obstructive HCM.
The issue is, though, that the underlying disease process, and this gets to why our trial design is what it is, the underlying dysfunction between obstructive and non-obstructive HCM on the myocardium and the heart muscle itself is similar. And we believe that sotagliflozin, and uniquely sotagliflozin in the SGLT class, and very differently than CMIs, are working to address that metabolic disorder of the myocardium in HCM. That is the unifying hypothesis in HCM, which is the fundamental physiologic problem. And you see that because if you do septal reduction therapy in symptomatic HCM patients, 10%-20% of those patients within a few years go on to develop heart failure. So they are converted from an obstructive HCM patient to a non-obstructive HCM patient.
And again, one of the reasons we have the quality of investigators and the interest in the field is that we are addressing that underlying fundamental pathophysiology. So that's sort of the ODYSSEY trial. The MAPLE trial.
So just to clarify, so have we had a CMI ever work in non-HCM? Or that's never?
Non-obstructive.
Non-obstructive.
Not in a large randomized controlled trial. ODYSSEY was the first, and it was not successful. There's a trial that is being run right now by Cytokinetics called ACACIA, which is fully enrolled. And I think, as you heard, or your listeners heard yesterday from Cytokinetics, that that trial, I believe, will be reading or finishing next year.
Okay. Okay, now, but then you want to talk about MAPLE.
So MAPLE, I think, is a very important study. And Mike and I were talking about this. I think we didn't realize just how meaningful it was to the field because what it was was a first-line therapy of a CMI, in this case, aficamten, against a beta blocker. And beta blockers have been used for decades, really, since beta blockers and HCM were identified, without much clinical evidence to support their use. I think one of the takeaways from MAPLE, as much as aficamten was successful, it also highlighted that beta blockers might actually cause harm. So I think there's a rethink now, or will be a rethink after the meeting, of what is the role of a beta blocker in HCM at all, because the outcomes in that were arguably worse than the baseline after the patients were on a beta blocker for the duration of the study.
So not only did aficamten improve many of the endpoints, but that the beta blocker, actually, the endpoints were worse at the end of the trial than the beginning.
And so one could conclude from that data that potentially aficamten could be used as a first-line agent in obstructive HCM. That is practically unlikely, mainly because of cost, access, the logistics involved in getting a patient on and maintaining them on a CMI. And so our take-home for sotagliflozin is that, in fact, beta blockers potentially cause harm. They're the go-to first-line agent in HCM. And now there'll be a rethink in the cardiac community. And in fact, SOTA is well-positioned to be that first-line treatment, so long as SONATA is positive, with following use of a CMI should it be needed for worsening or more symptomatic HCM further down the track. So really position SOTA to take that first-line therapy option in both obstructive and non-obstructive HCM.
So the point of MAPLE is that because you were running the beta blocker versus the novel therapy, this exposed the weakness of the beta blocker because you just didn't have a randomized study to do this before.
Exactly.
Is that correct?
Yeah, that's exactly right. No one who was going to run that trial, right?
This was sort of an unintended consequence.
Yeah, it's been, in a way, just a natural thing for clinicians to do. Beta blockers are very effective medicines for a range of different conditions, and so it made sense for them to try it, but without any evidence, and now, really, for the first time, and kudos to Sido for running this study, it really showed that that is a false assumption, and they need to rethink.
Not to distract too much from the Lexicon discussion, but in MAPLE, so did the study work because aficamten worked or because beta blockers failed?
Both.
Both.
Yeah. So again, the issue is if you compare to baseline, aficamten was successful in their endpoints. And again, I don't want to overspeak for Cytokinetics, but the beta blocker also was worse. So when you look at, compared to the active arm, it made the results look even better.
Yeah, okay. All right, so that brings us to your study.
So I think long windup for the pitch. I'm looking at the clock. I have to get to.
We're good. We're good. We've got time.
But I think that really highlights your original question way back when on the importance of the trial design of our study, the SONATA-HCM trial. I think all this background is very important because we thought about this as we designed the trial. So there's a number of very different attributes in the trial design. The first is that it is the only trial that's looked at both obstructive and non-obstructive in the same trial. And the primary endpoint of KCCQ, which is symptom relief, which is really what the CMIs are approved for, is symptom relief, is the primary endpoint in the trial. And by including both obstructive and non-obstructive, we believe since the fundamental mechanism underlying the both is the same, that's why we put them together.
Just like we were the first to do in heart failure, a HFrEF and a HFpEF study together in the same trial. So that's one attribute. The second is, I think you're aware, is that one of the big concerns with CMIs is potentially causing heart failure. That the major issue and the reason for the REMS is that EFs drop below 50%. And that was clearly a major problem in the ODYSSEY trial for BMS, is 20% of the patients had an EF drop below 50. We are allowing patients.
That's interesting. What's the reason? I mean, because I thought the whole idea was improving the myocardial, the contractility, right?
Well, actually, it's the opposite. It is reducing the force of the overcontractility. So the whole idea is correcting overcontractility. And again, I don't want to speak for those that are expert in this area, but my understanding is that one of the issues is that you are, in a sense, making the actin and myosin less overactive than the disease state causes. And the underlying pathophysiology and the way that the CMIs are working is they're working to change the interaction between actin and myosin, which results in excessive oxygen consumption. In fact, most early patients with HCM have an overdynamic ejection fraction. The heart is too active. The flip side of that is that in a percentage of patients, you actually have their ejection fraction drop below 50. So in a sense, we're an agent, and we're indicated to prevent and reduce heart failure.
These are agents that the REMS are put in place because they result in heart failure. So we also, in our entry criteria, if the patient's not on a CMI, and I'll get to that in a minute, the ejection fraction inclusion criteria is 50%. The CMIs are at 60%. If the patient is on a CMI and we allow patients to be on CMIs, that inclusion criteria is 55%. But again, we are allowing patients in the trial with a lower baseline EF than the CMIs because we don't have a heart failure issue with our drug. We prevent heart failure. The third point I already touched upon is that we're allowing any patient on any therapy that has symptomatic heart failure by KCCQ at baseline.
So they can be on a beta blocker, they can be on a calcium channel blocker, they can be on disopyramide, they can be on a CMI, they can be on any of those therapies. The key inclusion criteria is a diagnosis of HCM, whether obstructive or non-obstructive, and have a KCCQ score below 85. That's it. The other important point during the therapy, for example, if you look at a trial like ACACIA, there are about nine echoes that need to be done during that treatment. We have three. So again, the burden of monitoring, the burden of the endpoint is far different than the CMI trials have been and are currently running.
So there are a lot of moving parts to the study because you've got the obstructive, the non-obstructive, you've got whether they're on the CMI, not on the CMI. I guess there's some stratification, so it's all balanced out. And then how do you win? I mean, you can win on everything. Do you have sub-analysis? So if you hit it on the HCM, it's one. If you can get a label, if you hit it on non, it's a label. What is the hierarchy of analysis? How much of that have you talked about publicly? I don't know.
We haven't discussed a lot. I mean, we have talked about the fact that the endpoint is powered for the overall group. Again, just go back to what we did with SOLOIST-WHF in heart failure. So what the FDA generally does, and they did in the case of SOLOIST-WHF, is the study, and what we've agreed with the FDA already, because we did go down to the agency before we started this trial, and we agreed on endpoints and statistical methodology and a statistical analysis plan, is that the study is powered for the overall group, and the patients are randomized one-to-one. So it's 250 patients with obstructive, 250 patients with non-obstructive in the trial. The study is powered based on the overall result. We will look at an interaction p-value between obstructive and non-obstructive.
But as I've said, and I think we feel very confident about this based on our interactions with the KOLs, since we're addressing an underlying physiologic issue, there probably is not going to be a major effect size based on whether they're obstructive or non-obstructive.
The comparison is what?
Placebo.
Placebo. Okay. And so was there a thought that you would do beta blockers, or that was never the discussion?
Remember, beta blockers were allowing them to be ob or non-ob.
Oh, so they're on them in the background on both sides.
Correct.
Oh, beta blockers.
Calcium channel blockers or CMI. Remember, the key inclusion criteria is symptomatic disease, whatever their underlying therapy, right? We're just enrolling patients based on symptoms.
But then obviously, once they're enrolled, I mean, then they must stay on their whatever background they're on. They're forced to stay on.
Yeah, there are certainly elements in the protocol because with CMIs, there are dose adjustments. But one of the inclusion criteria is that they're on a stable dose of their CMI for a period of time.
I think it's an assumption, and obviously, we don't see the data yet in the enrollment, but I wouldn't expect too many patients in SONATA to be on a CMI. The penetration is relatively small so far in mavacamten. So we'll certainly see patients with background beta blocker, calcium channel blockers. Maybe we get some CMIs, but I wouldn't necessarily predict that there'd be a massive group that is on the CMI.
But that's on the results of MAPLE, which I didn't know until because I hadn't looked at it closely, but you would want more people on a beta blocker in the control arm. I mean.
Maybe why they're symptomatic.
Practically speaking.
Yeah.
They're effectively all on beta blockers. I mean, that's sort of like every patient that comes in, they're on a beta blocker. Again, I don't know exactly what the numbers are, but my guess is 80%-90% or more will be on a beta blocker. Now, that might change over time, but I think that will take some time to diffuse into the field of changing medical practice to not put patients on beta blockers, especially outside the United States.
Okay, so just one more on HCM. So your enrollment is finishing next year, and then data is when?
Again, one of the advantages of this is it's a relatively short study with a relatively short follow-up. Unlike the CMIs, where these are new agents and a totally new class, and they have a long follow-up period, we don't need to do that because these are proven drugs that are already indicated and on the market. So we will have data, I think we've talked about, beginning of 2027.
Okay, for the KCCQ.
Q.
Okay. All right. At that point, I guess, would you know the outcome? I guess that's a psychoanalytic question, though. Would they know the outcome of ACACIA by then?
From what they've said, yes.
Oh, okay. All right. Let's shift gears then.
$5. That's some money we've ever spent on SOTA. That's really impressive, Yigal.
At least it's the topic du jour.
Exactly.
Okay. All right, well, let's talk about pilavapadin. So you did some work with the dose, and there was some discussion around 10 or 20, right? And then you picked 10.
Yeah.
You had the end of phase II meeting, or that's coming up?
It'll be at the end of the year.
That's coming up. And what do you want to lock down in that meeting?
We want to lock down the design for phase III and the dosing, which, as we said, we feel very good about. And we're just getting into the final throes of putting all the information together right now for submission to the FDA. So it's really the clinical design of the phase III program that's important. The dose, ensuring, as we've said before, that we believe single arm, single active, single placebo study, so two arms in each phase III study is the way to go. And we just need that confirmed by the FDA.
So you mean two identicals? How does it work?
Yeah, we've already had a pretty thorough meeting with the FDA before we've started the PROGRESS trial, which is now completed, and I think what we've seen with a couple of other companies that are also now trying to work in the pain space, you need two well-designed trials that are run in this area with a positive outcome. We believe, based on the effect size and the variance of the data, that about 350 patients per group, so 700 patients in a two-arm study, and two of those trials run in parallel, would be adequate for approval. We've heard that from the FDA, and I think we've seen other companies now talking about phase III programs in neuropathic pain, and they came to the same conclusion in that regard, so we feel quite good about the design, the size, the powering.
Because remember, we have three studies that we've run in phase II with pilavapadin in different neuropathic pain states. We have now a very good understanding with well over 700 patients treated, over 650 of which were in DPNP and another 50 or so that were treated with PHN, that we have a good understanding of this drug and the population PK in terms of exposure and response. We have a very large phase II database on this molecule. I think we want to reaffirm with the FDA our assumptions going in, the dose, the size of the trials, the number of trials, and then all the other studies that FDA would like to see that would support the registration.
There are a number of trials we've already run that are non-pivotal trials, but very important for final approval and labeling, and just want to reaffirm that with the agency.
I mean, it doesn't sound like to me. It sounds like it should be fairly clear and straightforward, essentially, with this. I mean, you're not proposing anything too far afield, right? I mean, it's just versus placebo, two studies. Well, you've done the powering calculations. It's just more do you expect any pushback from them, or is it just?
I mean, I think the value of having run two phase II studies and then having the PHN study and then all the other data we've run is that a lot of the questions, I think, have already been addressed. Running pain studies is hard enough. There are enough variables. Particularly, the placebo effect is a huge issue in this. The issue around concurrent medications is a big issue in this. Patient adherence, the PRO endpoint. So one of the approaches we took was the more that we could do in phase II to simplify the design, simplify the primary endpoint, the better. Because when you add arms and you add complexity of endpoints, you increase variability and questions. So we did a thorough phase II program compared to what has been done historically in the pain space.
But we did that specifically to reduce some of the variability and some of the questions that you would have going into a phase III discussion or pre-phase III discussion with the FDA.
Did you consider any of these crossover designs where you switch and you put the pill of patients on placebo and placebo on pill at the end? I mean, that sounds more complex, but it's not necessarily because actually it can increase the power in terms of the crossover.
I think those are great studies for phase II. I think a variation of that, which some people do if they're worried about rebound effects, is to do sort of a withdrawal type study where you have a response and do a blinded withdrawal study. We don't feel that either one of those is relevant, right? We've already had two studies where we had a blinded runoff period. And I think very importantly, we saw there was no sort of liking potential for the drug, right? Because in all these drugs, essentially acting agents, there's an issue of potential addiction potential. There's also an issue of rebound pain, which is commonly seen in this, in part due because many of the other drugs have very short half-lives. We have now demonstrated that there are neither of those in our blinded runoff period.
That the necessity for looking at off-drug effects, and we've also demonstrated and we presented on the RELIEF trial, the first phase II trial, that the benefits of this drug persist for weeks after you stop dosing, certainly because of the long half-life, but maybe we're beginning to do some rewiring of the pain circuitry as well. I mean, I think that's purely speculative on my part. But as you know, neuropathic pain is both an issue of physiology and psychology. Pain is very much a learned and reinforced behavior with people. I'm not saying that in any pejorative way. It's just that when you establish the circuits of pain, you have to rewire the brain with chronic pain to minimize some of that pain state.
Okay. And then the power, and so if you would, if you get these numbers that you got in the phase II, the 1.7 or thereabouts and the 1.3, that would work. That would win, right? If you got those numbers again with your powering, you'd be in good shape.
That would be a statistically significant difference. I think there's a drug that was just recently approved in a pain state for chronic fatigue syndrome that basically was what they achieved, and they were labeled.
Okay.
With two studies, yep.
With two studies. Right. Okay. And those are, well, so you get the sign-off from the FDA later in the year. And I guess this is more of like a financing question, but do you have the capital to do these studies? Because these are not 1,400 patients, I think, right?
No, right. The phase III trials are relatively inexpensive because they're short duration and there's not a lot of fancy testing, etc. So they're relatively inexpensive. Having said that, it's our intention to partner this program. We're deep into that process at the moment, working towards the end of phase II meeting, which will obviously be important for some potential partners to get the outcome of that meeting, even though, as you said, it is pretty straightforward. Having the outcome confirmed post-meeting could be important for some partners. And we're really focused on finding, as we did for 9851, the best partner that not only can bring the potential pain program forward and invest in the phase III program, but importantly, look at the overall expansion of potential indications across not only indications in neuropathic pain, but spasticity.
Potentially, there's other neuroscience types of indications for which we have some preclinical data and making sure we take advantage of the breadth of the implication of AAK1.
And you're looking for what type of a deal? I mean, is it like a region-specific deal or something multi-net, like multi-region?
No, I think it will be worldwide. I think there's various options as to the depth of involvement of Lexicon, depending on who the partner could be. I think the most important thing that we're focused on now is, like as we've seen with both Novo and with Viatris, in each case, these partners are fully invested and believing in the mechanism and want to do a very significant broad program in both of those cases. So I think we're a little bit agnostic to the type of player. And indeed, we're talking to different types of players on different scales, but it's making sure that we truly have someone that's invested in this program for the long term.
All right. Awesome. All right, well, great. Thank you both very much. We look forward to finishing the enrollment and then be a little while for the data, but certainly be very exciting to see that.
Great, Yigal. If I could just sort of finally point everyone's attention to the Arrowhead meeting, which is at the beginning of October, I believe, which we obviously have a number of data readouts and presentations at medical meetings in September. The Arrowhead meeting is the one where we will really cover the breadth of the data across all of our phase II program. I think that will really form the basis that people will see as we take into the end of phase II meeting.
And that's a medical meeting? And where is that?
San Diego.
San Diego. Okay, and that's a neuro meeting. What exactly? What type of meeting is it?
Yeah, it's a pain meeting.
Pain medicine. Okay. Okay. Excellent. Thanks.
Great.
All right.
Thanks so much. Appreciate it, Yigal. Thank you.
Thank you, Yigal.