Victor Perlroth: Well, I think, you know, we believe that it’s broadly relevant, both within the high prevalence diseases that represent the anti-VEGF market and we believe it’s highly relevant outside of that into what we call sort of that greenfield area of macular edema and inflammation or the uveitic complex. And we believe those are two different opportunities and that’s why we have two different molecules to be able to develop into both of them, right? So the KSI-101 allows us to have the protein alone, which is really a sledgehammer, highly potent on the two mechanisms at a very high formulation strength that should have a strong immediacy. So we’re excited about that. And obviously IL-6 plays a very important role in driving the macular edema in those patients and also in driving the inflammation.
Within the retinal vascular diseases, inflammation clearly plays an important role. I think the question though when you think about the drug development, what is necessary to show in a pivotal program and do you want to play around for several years in Phase 2 studies trying to explore what large subgroups within say wet AMD or what large subgroup within DME, where that inflammation is driving elements of the efficacy or the lack of efficacy in those patients. So rather than take that approach, what we’re planning to do is to run the non-inferiority pivotals to get the molecule approved in the different indications based on our expertise in running those studies. And then, work either in parallel or in smaller studies or in investigator sponsored studies or post approval to be able to really tie patients with high inflammation to the drug to be able to show some improved level of efficacy.
But we don’t think we need to do that in Phase 2 setting. We can drive these molecules for approval in the non-inferiority setting and then work with physicians to showcase the special contribution of the mechanism.
Samantha Meadows: And then just a quick follow-up for DAYBREAK, you mentioned dosing 501 every four to 24 weeks and then dosing aflibercept according to the label. What is your perspective on the recent FDA draft guidance regarding the use of a comparable dosing regimen in terms of like dosing frequency with the active comparator?
Victor Perlroth: Well, that’s a good question. I think, we’ve been in constant communication with the agency for all three clinical programs and we will confirm the study design once we have all the information necessary. And that’s really all we want to share for now in terms of the specifics. It’s needless to say what the final study design for all of our pivotals will be based on feedback from the FDA. I do think historically looking back Kodiak has driven innovation within study design with FDA successfully for ourselves and other companies have followed our example. And at this stage, we’re in discussion and we’ll see kind of where we end up.
Operator: [Operator Instructions] And our next question line of Daniil Gataulin from Chardan.
Daniil Gataulin: I have one on 501 in wet AMD specifically for the second pivotal study. Are you guiding for — with regards of any timelines when you plan on starting the trial, and will that also include tarcocimab or do you plan to generate tarcocimab data from DAYBREAK first before initiating the second study?
Victor Perlroth: We don’t — we haven’t disclosed and we don’t have a complete plan for the second study of wet AMD. We know that we need one for approval for 501 in that case. But we haven’t thought — we haven’t disclosed and we have a plan of it’s sequential or is it somewhat overlap between the two studies.
Daniil Gataulin: And I have another quick question on, what do you think are the potential consequences if tarcocimab does not succeed in the DAYBREAK study?
Victor Perlroth: Well, I guess, we believe that tarcocimab can be an important medicine for patients with wet AMD. But rather than just relying on the results of the DAYLIGHT study where we dose monthly, we’ve decided that it makes sense to demonstrate that by having a full group in DAYBREAK. So if we didn’t meet the end point in DAYBREAK then physicians would not feel excited to use it in wet AMD or presumably maybe based on having two unsuccessful studies in wet AMD, we might not be able to get approval in the indication. So it represents a bet that we’re making. We’re optimistic and we think it can drive substantial demand in wet AMD for tarcocimab and be really important. So in some way, introducing tarcocimab into the DAYBREAK study is a gamble but it’s one that’s educated based on our detailed review of our data.
And also the adjustments that we’ve made to the go-to market material and also our, I suppose expertise or lessons learned from having run six pivotal so far. So we’re excited to run tarcocimab in DAYBREAK and to see the data and hopefully to include that and to share that with the community and we think it can be really powerful.
