Yasmeen Rahimi: Thank you so much.
Operator: The next question is from Yigal Nochomovitz with Citi. Please go ahead.
Carly Kenselaar: Hi team. This is Carly on for Yigal. Can you hear me okay.
Lonnel Coats: Yes, we can.
Craig Granowitz: Yes, we can.
Carly Kenselaar: Okay, awesome. Thank you. So for LX9211, in the plot you shared from RELIEF-DPN-1 and the RELIEF-PHN-1, I just wanted to kind of get your perspective on the overlapping error bars between drug and placebo. Obviously, you hit stat sig, but there seems to be a fair amount of overlap in the error bar. So just curious your thoughts on that. And as you think about the design for a Phase 3, are there any additional steps you can take to minimize the placebo response?
Lonnel Coats: Great question, Carly. Let me turn it over to Craig.
Craig Granowitz: Thank you, Carly, for the question. The error bars are really a reflection of the variability of the data and the size of the study. And that’s why we did not achieve significance for example, in the PHN-1 study because while the magnitude of the effect size was even larger than we had forecasted to achieve statistical significance. And as a reminder, the reduction was 0.8 points in the ADPS score, which was greater than we had powered the study. The variability was also somewhat larger than we had anticipated. We took a number of steps in the trial to minimize some of the variability. And one of the reasons why these studies in neuropathic pain are so difficult is patient variability, and we actually received quite a bit of positive feedback in the medical and scientific community for the design of the trial with prequalifying the patients with the run-in period, which as we’ve shared with this group before, actually undercuts the overall efficacy because by reducing variability, you are starting the patients already on placebo, which actually lowers their pain score because there is a strong placebo effect.
So again, for full transparency and integrity of the data we’re showing the error bars, but the data are statistically significant. And I think it is a reflection of the population that is being studied that there is that degree of variability.
Lonnel Coats: And as for €“ as you start thinking about Phase 3, we’ve learned quite a bit about how best to set up the Phase 3 study as well as you want to talk a little bit about the parameters.
Craig Granowitz: Yes. Thank you, Lonnel. So again, what we believe is that we’re going to be having a program, not just a single study for Phase 3, which is very consistent with other clinical trials. The feedback we’ve had is some of the questions that have been asked, the 12-week study is probably the duration of the trials and to continue to look at these run-in periods to further refine the patient population to minimize those patients that have significant day-to-day variability in their pain score and to better harmonize the ability of patients to accurately complete these forms. As a reminder, the primary endpoint is what’s called a visual analog scale. You are asking the patient to remember back during the course of that day what is their average pain score measured on a scale of 0 to nine.
So as you can imagine, it is a very qualitative endpoint. It’s not a lab value, it’s not a diagnostic test. It’s a very subjective endpoint. So we want to make sure that we have patients that having consistent pain, significant or moderate to severe pain and a minimum of variability on day-to-day pain as well as consistent ability to effectively comprehend and complete the forms. But we’ve learned a lot in our Phase 2 program to be sure we’re getting the right patient population that can give a consistent, accurate reflection of their pain state.
