Joseph Pantginis: Hey, guys. Good afternoon. Thanks for taking the question. Brian, I want to latch on to your comment about the hyperawareness around the GLPs. And specifically, look, there’s a growing notion here about the “Emerging AE profile” of these drugs as they’re used for longer periods of time. I mean, no need to quote a lot of the studies or what have you. So I guess, can you take a moment to add a little more color or emphasis why you believe 2735 has a better AE profile? Obviously, it appears like it’s coming out right now in the studies and what you’ve disclosed. But anything you can really emphasize, I think, would be helpful for us, as well as similar to an earlier question, as this field evolves, has it changed any of your thinking with regard to how your own development plans might progress?
Brian Lian: Yes thanks, Joe. I think what we’ve seen in the Phase 1 experience with VK2735 is really encouraging on AEs. AEs, for the most part were mild to moderate. Tolerability was really outstanding. We didn’t really see a dose dependency in some of the AEs. The highest dose cohort actually looked a lot like the lowest dose cohort when it came to the GI tolerability side effects like nausea and vomiting. And it’s a small data set, so it’s hard to talk too much definitively. But there is some evidence that when GIP is activated, there is an offset to the GLP-1 induced nausea, and that might allow better tolerability with the dual agonist where GIP is part of the mechanism. Really early in our data set to say that, but if that is true, then the dual agonist should separate on tolerability over time relative to simply a high dose GLP-1 monoagonist. But really early to make those sorts of comments right now.
Joseph Pantginis: Any views on development plans? Have there been any alterations in your mind based on how the field has been evolving?
Brian Lian: No, no. We’re full steam ahead on both. The oral program is a little more slow than we’d like, but it’s pedal to the metal on both programs right now. No changes to our plans.
Joseph Pantginis: Great. Thanks, Brian.
Brian Lian: Thanks, Joe.
Operator: The next question comes from Andy Hsieh of William Blair. Please go ahead.
Andy Hsieh: Great. Thanks for taking my question. So, looking at the obesity week presentation, I’m just curious if you have thoughts regarding baseline characteristics, especially for age. Looking at the average age, 29 for placebo, 42 for the highest dose. Does that favor placebo and underestimate the effect size of 27, 35? We’ve seen some imbalances in age across, several obesity studies.
Brian Lian: Yes, I don’t know if that’s – there were some imbalances in age and also in weight, and then some of the cohorts had more men than women and more women than men, and it was really hard to discern any differences based on any of those metrics. But I think, we’ll be able to make a better call on that after the Phase 2 study. It’s a good question, though.
Andy Hsieh: Yes, okay. Great. So related to that, just curious about, expectations or how you frame expectations for liver fat reduction for the VENTURE study that we’ll read out in the first half.
Brian Lian: Well, with VENTURE, we’re looking more at body weight and not at liver fat, so we’re just looking at body weight changes. We’re not doing the MRI in the VENTURE trial. We did see really attractive reductions, although the numbers were small in the Phase 1 study, but nearly 60% relative reduction in liver fat after four doses. That was really impressive, a bit higher than we expected in just four doses, but we’re not doing the MRI in the VENTURE study.
Andy Hsieh: Got it, okay. And maybe lastly for manufacturing, obviously there’s a lot of press and attention related to the drug class. I’m just curious, you can comment on 2735’s CMC where it is, capacity for either like a Phase 2b or Phase 3 study?
Brian Lian: Yes thanks, it’s a great question and an area we’re spending a lot of time on. We don’t foresee any capacity constraints near term. If we were to be launching the drug next year, that would be different because the demands would be much higher, but for the clinical supplies, absolutely no problem we foresee today. We are looking more now than I think we probably would otherwise have looked at scalability and various approaches to enhance yields and shorten timelines for large scale syntheses. And I think we’re a place where we have several options available to us. And I don’t think by the time this compound would be available commercially, I don’t think supply constraints would be the challenge that they are today.
Andy Hsieh: Got it, great. Thanks for answering all of our questions.
Brian Lian: Thanks a lot, Andy.
Operator: The next question comes from Thomas Smith of Leerink Partners. Please go ahead.
Thomas Smith: Hey guys, good afternoon. Thanks for taking the questions. Just on 2735, I think you’ve generated quite a bit of preclinical data now for the oral form of this compound. I was wondering if there’s any plans or opportunities for you to present some of these preclinical data in the near term, maybe before we get the Phase 1 data that’s now expected in Q1.
Brian Lian: Yes thanks, Tom. We’ve been pretty quiet about the data from the oral formulation. And so we don’t have any plans at this point to present data between now, animal data between now and the Phase 1 readout in the first quarter.
Thomas Smith: Okay, got it. And another question on 2735. I know you just showed some strong liver fat reduction data at obesity week. Can you just remind us Brian, how you’re thinking about 2735 potential in NASH? And I guess whether you’re considering generating any of your own data there with 2735, either alone or in combination with 2809?
Brian Lian: Yes well, we did the MRIs here and we didn’t have a baseline requirement for an MRI in the Phase 1 study, but we did it just to see if there was some impact. We know with the GLP-1s, I think we can see 30 some percent reductions. And so we had hoped with the GIP and GLP-1 dual agonists that you’d see something in that neighborhood. And we did see that and better. But so it was kind of a sort of proof-of-concept there. We don’t have any plan today to move into NASH. It was just something that we wanted to know how does it compare to a mono agonist. And I think it compares favorably to the mono agonist that we’ve seen. And I think it also, even though the timeline’s a lot shorter it compares favorably to the triple agonist data that are out there, the much longer time treatment window with that compound. But I think we feel good about what we’ve seen so far.
