Kezar Life Sciences, Inc. (NASDAQ:KZR) Q3 2019 Earnings Conference Call - Final Transcript
Nov 12, 2019 • 08:30 am ET
Certainly. [Operator Instructions] Our first question today is coming from Maury Raycroft from Jefferies. Your line is now live.
Hi. This is Rob Nolan [Phonetic] for Maury. Congrats on the update, and thank you for taking the questions. A couple for us. So, can you provide any additional perspective on how the step-up dosing is helping reducing the tolerability concerns?
So from a mechanistic standpoint, we are unaware of what is actually driving at the molecular level, the first-dose nausea and vomiting that we see, most predominantly at 60 milligrams, though we -- I must note that we have seen it either at a much lower rate even in cohorts 2a and 2b with the first step-up dose of our first dose of 30 milligrams. In our healthy volunteer study we're presenting here, we did look for inflammatory cytokine that might be driving this response and we were unable to see with subcu administration of 616. A cytokine response that could explain this first-dose effect, so that doesn't provide a mechanism for us.
But given that we are very consistently showing the mitigation, reduced rates with the step-up dosing both in healthy volunteers and in patients and we can point to the precedent data with KYPROLIS, a related molecule from a chemistry standpoint, we see this path forward. We know from the data with VELCADE that this is not due to target inhibition, since VELCADE is not associated with first-dose nausea and vomiting, either with subcu or IV administration. We think it has more to do with non-specific reactions to the chemistry, meaning peptide epoxyketones that underlie KZR-616 and KYPROLIS.
That's helpful. Thank you. And then one more question. So you mentioned that the discontinuations decreased from 38% to 20%. So just wanted to confirm that the cause of the discontinuation will seem before and after the step-up dosing or were there any other factors that led to reduced dropout?
Great question. Not all discontinuations, by the way I should be clear due to the nausea and vomiting. And in fact what is included in that discontinuation were discontinuations due to adverse events, which were consistent between the first two cohorts, cohorts 1 and 2 and cohorts 2a and 2b. In addition, there are -- were a number of withdrawal of consents that did not have which comes as a discontinuation, which did not have a reason for withdrawal of consents listed. So we don't have complete accurate reasons as to why that is. But I would like to point out that much of this may be due to proper education of both patient and physician at the site to keep patients on study. And this is not uncommon for first-in-patient studies like ours, and I'm very heartened by the fact that in Cohort 2b we have enrolled patients with -- and gotten the majority through one month of dosing without any discontinuations thus far and quite frankly, we don't anticipate any further discontinuations in this cohort suggesting that with continued