Operator: The next question comes from Andy Hsieh of William Blair. Please go ahead.
Andy Hsieh: Great. Thanks for taking the question and congratulations on all the progress in 2023 and look forward to a very productive 2024. A question about the oral administration. If you look at the Rybelsus label, there are some restrictions about timing of the fill, volume of water. I’m just curious about the gastric absorption technology baked into the oral formulation. Do you think that there is a potential that you can engineer away these restrictions?
Brian Lian: Yes. Thanks, Andy. We haven’t disclosed the technology or anything regarding patient behaviour in their subject behaviour in the study. We will discuss that when we disclose the data but I’ll just say now, per many Phase 1 trials, these people are fasted as they — when they take their doses in the morning, but we haven’t disclosed any additional requirements or suggestions.
Andy Hsieh: Got it. Okay. And then staying in the same obesity field, obviously, there is an increase in interest and perhaps the valuation of clinical assets that could boost lean body mass, looking at the Bersani [ph] deal recently. So in your pipeline, 5211, obviously, that has demonstrated potential for that. So I’m curious about potentially any change in prioritization or perhaps increased external inbounds on that asset that you can share with us?
Brian Lian: Yes. Thanks, Andy. It’s an interesting question. And you’re right, the VK5211 is the most potent oral agent, I believe that we’ve ever seen. I mean, certainly, to our knowledge, there’s nothing more potent on the oral side. In the hip fracture study, we saw very significant increases in lean body mass at all doses and a beautiful dose response. We reported those data in 2017 and ’18. And it’s — to the extent, a loss of muscle from these agents is clinically relevant than maybe adding muscle building agents could be a reasonable approach. It’s not clear that it is clinically relevant, the change in lean body mass. I know it sounds great, and it’s an easy clean story to tell but we do have some experience in muscle drugs, and we have experience with what the FDA considers is important, and it’s not just increase in muscle mass. So it is an interesting area. We have got a very potent compound, but the medical necessity is a little bit murky to us.
Andy Hsieh: That’s fair. Thank you very much. And maybe last quick one in terms of R&D, a little uptick this quarter. Just thinking about how do you foresee that trend going forward?
Greg Zante: Andy, I think our R&D will go up a bit this year versus last year, not radically, but it will be up a bit, focused on advancing all of our programs and assuming success. So I think you could think about it increasing a bit, but not way, way up, for sure.
Andy Hsieh: Great, appreciate it. Thank you.
Brian Lian: Thanks Andy.
Operator: The next question comes from Thomas Smith of Leerink Partners.
Thomas Smith: Hi, good afternoon. Thanks for taking the question. Maybe one, just a big picture. We’ve seen obviously, a very active environment, and it seems like there’s a lot of strategic interest in the obesity space. Can you just comment on what you’re seeing on the business development front in terms of partnership, interest on our programs, both obesity and NASH. And just remind us how you’re thinking about next steps of development across those programs.
Brian Lian: Thanks, Tom. We can’t comment too much on that. I would just say, you’re correct in saying that it’s an active area and an area of high awareness, I’d say, across the industry, based on the magnitude of the success we’re seeing and the clinical benefit that these therapies provide. So makes sense that there would be interest from potential partners, and we would be happy to engage in those discussions.
Thomas Smith: Got it. That’s helpful. And then maybe just one on VOYAGE. You mentioned having just completed the last patient biopsies recently. Maybe you could just remind us how you’re thinking about evaluating those biopsies in VOYAGE, whether you’re using a single pathologist or multipath review and just kind of walk us through the gating factors there to reporting the top line data set.
Brian Lian: Yes. Thanks. So the biopsies are the slower element there. It is a single reader that we’re using. And the single reader goes to a second reader when there’s a patient whose biopsy is right on the cusp of something like F2 or F3 fibrosis or an NAFLD activity score of 4, things like that go to a second reader. And then the first and second reader must reach a consensus before the final assessment of the slide is made. So I think we started the study really before the 3 reader approach had become more widely used. And so that’s why we have the single reader.
Thomas Smith: Got it. That’s helpful. Thanks for taking the questions.
Brian Lian: Thanks Tom.
Operator: The next question comes from Yale Jen of Laidlaw & Company. Please go ahead.
Yale Jen: Yeah. Good afternoon and thanks for taking the question. Just about 2 quick ones here. The first is that, given the reason Lilly reporting about the synergy, NASH data, and you guys actually mentioned earlier that in terms of 2735 had impact on the liver fat. I wonder whether there’s additional thoughts or any other things you guys were thinking of in your overall strategic planning or thinking.
Brian Lian: Thanks. Not really. We have a NASH program already and not interested at this point and really pursuing NASH with the VK2735 program. I do think it’s encouraging to see that the dual agonist mechanism appears to be effective at NASH resolution. I think that’s exciting. But we’re going to stick with obesity for the time being with that program.
Yale Jen: Okay. Maybe one more follow-up here, which is that Amgen recently published their AMG133 Phase 1 data. Was there any — is there any comment and thoughts that will in the fourth quarter your program as well?
Brian Lian: Yes. That was good question. We haven’t had a chance to really get into the evaluation of those data, is pretty fresh. But yes, I guess we’ll evaluate those data moving forward. But good question for Amgen.
Yale Jen: Well, thanks a lot and congrats on the progress and look for all the data this half of the year.
Brian Lian: Thanks a lot, Yale.
Operator: Next question comes from Joe Pantginis of HC Wainwright.
Joe Pantginis: Hey, guys. Good afternoon. Thanks for taking the question. So, Brian first, I just wanted to start at the back end of your question-and-answer commentary, maybe push the envelope a little bit on business development. You said you’d be happy to engage in discussions. And I was just curious, if I may. Are you able to discuss the level maturities of any potential discussions that may be ongoing?
Brian Lian: Yes, Joe, I wouldn’t want to mischaracterize that statement or mislead or anything. We’ve always been open to partnering discussions since day 1. So we’re always opportunistically evaluating whatever is presented to us. So I can’t really characterize any discussions.
Joe Pantginis: Got it. Got it. And then to the earlier question, a very earlier question was asked about VENTURE. I’ll ask the same regarding the oral study, and that is what do you consider the benchmark to success?
Brian Lian: For the oral study, yes. We’ve always considered if it could look on — well, obviously, it’s a safety and PK and tolerability study. So we look for safety, tolerability and a clean, predictable PK profile. On body weight, if we could look like an injectable GLP-1 after a month, that would be, I think, encouraging. And so what’s the magnitude there? It’s a little bit variable, but we look at 1% to 2% as being something that would probably warrant further development.
Joe Pantginis: Okay. Very fair. And then my last question, obviously, this goes into later 2024 and beyond. Are you willing to take any first passes now with regard to pivotal study plans or even designs?
Brian Lian: For obesity?
Joe Pantginis: For obesity, for NASH, in general for the company, yes.
Brian Lian: Yes, yes, yes. Yes, with both of these programs, we plan to speak with the FDA following the data analysis. So we’d like to have a Type C meeting with the FDA on the VK2735 program and outline potential next steps there. And then with the NASH program, have an end of Phase 2 meeting. And we know what the guidance is for both indications, but it would be nice to talk with the FDA to learn any recommendations or new comments that they have regarding trial design. But we do have a pretty good idea on what those trials will look like.
