David Clark: Happy to do that. So in the CANAL study, in the IPF cough subjects, what we basically looked at post-hoc analysis looking at those baseline cough frequency affect the efficacy signal and there was not a relationship. So even those subjects who fell into the lower baseline cough frequencies had the same efficacy signal as the higher baseline cough frequency subjects. That was one of the rationales when we were looking at the enrichment strategy that we’ve just disclosed for the RCC RIVER study, why we’re going for the 1:1 enrichment, so that we can, in essence, assess both the moderate cough frequency population of 10 to 19 and the high cough frequency that are being focused on with the P2X3 programs equally. We really want to get a good look. And that lack of baseline cough frequency to efficacy effect in CANAL, we think, is supportive of that approach.
Jennifer Good: And we think because the drug works centrally at the brainstem, which mediates coughing and breathing, that it really should work across cough counts as long as you get to some minimum level where there’s not so much variance.
Rohan Mathur: Thanks so much.
Jennifer Good: Thank you, Rohan.
Operator: The next question comes from Thomas Smith of Leerink Partners. Please go ahead. Hello, Thomas. Are you there? The next question comes from Sean Kim of JonesTrading. Please go ahead.
Sean Kim: Hi. Thank you for taking my questions. I guess the first question that I have is on the RCC trial. So given that you are stratifying for moderate versus severe, just curious to hear the potential statistical plan for those two groups, whether you’re going to be seeking statistical significance in moderate and also severe individually and also combined. And beyond the statistical significance, what do you think will be clinically meaningful reduction, especially for the moderate group? Thank you.
Jennifer Good: Yes. David?
David Clark: Thank you for that question. So with the end of 60 that we’re studying in RIVER, we have powered it for a 45% treatment effect with nalbuphine, okay? So a 25% effect greater than our anticipated placebo effect, which we expect to be — we’ve assumed to be 20% in that study. So that’s for the total population of 60 subjects. We think that is appropriately conservative. Clearly, we saw a much greater than a 25% separation from placebo. We saw double that in the CANAL study, as you know, in the IPF population. So we think we’ve been conservative. What that means is if we get an effect size, which is larger than 25% versus placebo, we would actually have 80% power in both subgroups. So if we increase more than our conservative 25% versus placebo effect size, and we would be powered in both of the groups of approximately 30 subjects each. Does that address your question?
Sean Kim: Yeah, definitely.
Jennifer Good: And David he also asked about clinical meaningfulness, what was defined as clinical meaningfulness.
David Clark: Yes. And that really sets about — as you know 20% to 30% is believed by the majority of experts to be the sort of range that is clinically significant if you’re looking at these reductions in cough frequency. And that was one of the reasons that we’ve set this, the ability to power the 60 subjects with a — detect a 25% effect size because that is clinically relevant to patients or is believed to be by experts in the field.
Sean Kim: Okay. Great. Thank you very much.
Jennifer Good: Thank you, Sean.
Operator: The next question comes from Serge Belanger from Needham & Company. Please go ahead.
Serge Belanger: Hi. Good afternoon. Thanks for taking the questions. I have two. I guess first, on the cough program. Can you maybe talk about the pathology differences between IPF cough and refractory chronic cough and whether you think Haduvio’s mechanism of action to be more effective in one disease or another? And then on the PN program, just curious if you’ve had any discussions about partnering and how you would describe the level of interest for that program. Thanks.
