Cara Therapeutics Inc Research And Development Event (Virtual) Transcript

The following is excerpted from the question-and-answer section of the transcript.

Question: Daniel G. Wolle - JPMorgan Chase & Co, Research Division - Analyst : Two questions, maybe one for the company first. In the CKD trial, what are some of the considerations besides CKD stage or excluding Stage 3 patients? You have taken empowering the study to reduce the risk of significant placebo effect we saw. And related to that, in your view, is there any scientific rationale to believe that concomitant treatment to address the underlying CKD could contribute to treatment and therefore, potentially be reflected as a high placebo response? And then I have a follow-up for the doctors.

Question: Daniel G. Wolle - JPMorgan Chase & Co, Research Division - Analyst : Great. Okay. And then for Dr. Kim and Dr. Silverberg. On the primary endpoint of the proportion of subjects with greater than or equal to 4-point improvement in worst itch NRS and the KIND 1 Part B and KIND 2, what are your expectations, I guess, for a new therapy like oral to be considered clinically meaningful? And then will there be a difference based on the severity of the itch? Dr. Jonathan Silverberg;George Washington University School of Medicine and Health Sciences;Associate Professor of Dermatology Brian, do you want to take that first or... Dr. Brian Kim;Icahn School of Medicine at Mount Sinai;Vice Chair of Research I was waiting for you, but -- yes. Well, a couple of thoughts. So the 4-point reduction on the itch being considered clinically meaningful, I think that's currently kind of the industry standard, but I don't necessarily know that that will hold up as the clinically meaningful bar in perpetuity as we start to think of itch more dynamically and also as we start to think of different populations of patients with itch, whether in atopic dermatitis or others. So for example, if we're looking at populations that generally have milder itch, it's really hard to consider 4 point as being dogmatically the most clinically meaningful improvement. So I think that's the kind of main point that I generally make lately with regard to how we think about itch. How it's going to play out in terms of the trials, I think it's an endpoint that you want to see right now, given what I've said. And I think that even in -- if I'm remembering your question correctly, I think that there's still an opportunity for that kind of improvement in effect in adjunctive settings if their itches actually still remaining significant in the patient. Dr. Jonathan Silverberg;George Washington University School of Medicine and Health Sciences;Associate Professor of Dermatology Yes, that's all excellent points. I think just for context, the 4-point reduction in itch is actually not a minimal clinically important difference. That's the way the FDA refers to it because -- just some technical numbers reasons. It's really a moderate, clinically important difference. And you can't achieve -- and this is what Brian was alluding to, you can't achieve a 4-point response if you start with an itch score of 2. So it's something that is really relevant for those who have more on the moderate to severe itch at baseline. So it's an important regulatory end point right now. But certainly, I agree with Brian. There's a lot that's evolving in our understanding of itch and the endpoints of itch.

Question: Sumant Satchidanand Kulkarni - Canaccord Genuity Corp., Research Division - Analyst : This is going to be a 2-part one question. Sorry about that. Dr. Kim, from a mechanistic perspective, at what point do we need to start worrying about potential buildup of tolerance to kappa opioid receptor agonist either in the CKD or AD setting? And on atopic dermatitis for anyone who would like to take it, given the studies will only involve Oral KORSUVA as an adjunct to topical corticosteroids. In the real world, do you expect -- how do you expect to tease out the effect of any steroid sparing that might happen with oral KORSUVA use? Dr. Brian Kim;Icahn School of Medicine at Mount Sinai;Vice Chair of Research So yes, the first question is about -- is there a tolerance to kappa opioids. I'm not aware of tolerance to kappa opioids in the way that we are well aware of tolerance to new opioids. So I'm not so sure that that is necessarily a thing. And based on some of the mechanisms that I highlighted, particularly in the periphery, it seems unlikely that those kinds of nerve fibers would actually result in tolerance. But that's to be proven, I think, if that's the case. And then I think the second question is related to -- you said with the topical corticosteroids and the additional effect of the kappa opioids, the question that you were asking was what -- I'm sorry, I'm trying to remember what exactly the concern was there.