First thing to see whether you see any weight loss, with our compound, obviously have weight loss from semaglutide, that’s been published many times. It was published in the competitor compound data that you saw. Next thing is to understand effect of weight loss, effect of food intake. And then once that study is completed, what happens to other parameters, lipid parameters, what happens to diabetes parameters like glucose, insulin, OGTT, HOMA-IR, what’s happening to steatosis. So, as we know, obesity or reduction in obesity results in benefit on a number of parameters, so we look for that. In the combo study, obviously, we would look for not just effects of monotherapy, but what is the effect of NLRP3 inhibition on weight loss vis-à-vis semaglutide alone or a GLP-agonist alone, is it additive, is it synergistic.
Eventually, we would like to understand that this mechanism is orthogonal. So, again, the mouse studies are really a way to build like the in vitro studies, a lot of links in understanding this pathway, right. So, we have built – we have done some work in the microbial cells, we will get data from the mouse studies. And then obviously, we are committed to doing the human study, but pretty exciting stage in this part of the NLRP3 pathways. Always been interested in Parkinson’s, but this has opened a whole new area. And I think we are sort of in the forefront of this with our molecule to be able to sort of connect the dots, and looking forward to sharing the mouse data with you guys in a few weeks, end of the second quarter. I think your third question was…
Martin Auster: Potential for 2735 in HS.
Raju Mohan: Potential for 2735 in HS, yes, so we think there is potential – clear potential for a 2735 mechanism in HS. I will just caution you that the results from the AbbVie study were very, very encouraging, but there isn’t a real one-to-one correspondence between a IL-1 beta antibody such as canakinumab NLRP3 mechanism versus the AbbVie, it’s an IL-1 alpha/beta antibody as well as, for example, an IL-1 alpha/beta trap, such as rilonacept, right. So, there is a little bit of area there that has to be explored. But yes, certainly, there is enough rationale for looking at analog PC molecule in HS.
Operator: Thank you. We will take our next question from Derek Archila with Wells Fargo.
Derek Archila: Hi there. [Technical Difficulty] Thanks for taking our questions. I guess just a couple on [Technical Difficulty]. Given what you have seen in your Phase 1 data in your NT-0796 positive outcome in their Phase 1b/2a, do you think getting to Phase 2b trial is now de-risked? And then also, do you expect 3232 to differentiate from NT-0796 in Parkinson’s?
Raju Mohan: Yes. So, if I – sorry, you were fading a little bit. So, your question was, has the data from NodThera in their Parkinson’s Phase 2a de-risked our trial, is that was the question. Yes, so let me assume that’s the question. So, it’s always good to see data from any drug in the class where there hasn’t been a lot of data out there showing effects on biomarkers in the study, right. But again, for us, we believe from our Phase 1 study, everything we have seen, this is an extremely well-behaved compound. It’s suitable for QD dosing at low doses. We expect to have coverage of IC90 at doses starting at 10 milligrams to 12 milligrams. And it’s a real clean single-order kinetics dosing profile. So, we are looking forward to this 28-day study and generate our own data.
Like I said, I don’t have any doubts that we will see effects on IL-1 beta downstream markers NLRP3. Again, IL-1 beta, IL-6, hsCRP, and we will establish our own biomarker profile both in blood and in CSF, with respect to things like neurofilament light chain and other biomarkers as well. And there was some data from NodThera. But our compound is so well behaved because we hit the target so hard, that we will have to set our own calibration for the Phase 2a before we go into a longer Phase 2 study.
Operator: Thank you. We will take our next question from Sam Slutsky with Life Science.
Sam Slutsky: Hi. Good afternoon everyone. I hopped on a tad late, so if you answered any of my questions previously, just let me know. On the obesity preclinical study with 3232, just kind of generally speaking, how similar or different is the methodology to what NodThera did in their preclinical study? And then do you anticipate that there will be any bigger conclusions that were drawn from it other than just kind of the binary of it looks good or not on weight loss?
Raju Mohan: Yes. Good to hear from you, Sam, and happy to repeat the answers for you. I don’t think I ever in my 30 years spent so much time talking about mice studies, but happy to do so. It’s – so there is really no learnings from the mouse study that the competitor did. Again, it was a pretty standard IL study, so you have obese mice. In olden days, you had to generate these mice by feeding them a high-fat diet for 15 weeks or longer. Nowadays, these are off the shelf. You can buy obese mice diet in these obese mice. In terms of – so we have done these trials before, perhaps looking at different endpoints. In this case, the primary endpoint, obviously, is weight loss, and we look at secondary end points, as I mentioned before, the effects on liver weight, body weight, body skin.
We have – we are also doing dexa in the study to look at lipids, we look at liver steatosis. We do staining in the liver. So, everything that you would want to read out post the weight loss there as well. Really, again, like I said before, you need to look at individual readings from the study to understand how it translates or potentially translates into what you expect in humans. It’s not a one-to-one correlation. These models are used for a number of things. You will see them being used for developing drugs for diabetes. They have been used for DPP-4 inhibitors. They have been used for SGLT2. They have been used for GLP-1 agonist. Now, we are looking at NLRP3. So, it’s really a broad model, and you can take individual pieces on this model and then reconstruct what you would want to see in a human study, right.
And again, we are excited about not just this model. This model is just a path for us to go into the humans. And so we will complete the models. We will get you the data in a few weeks and then on to the human study. And in the meantime, our biologists are actively trying to link the dots in understanding hypothalamic interaction with NLRP3 and effects on downstream, so just trying to build a picture.
Sam Slutsky: Okay. That’s helpful. And just real quick on 2735 on the potential prevention of MACE in pericarditis study, you think about just that landscape unmet need currently in paradigm, where do you see the profile of 2735 kind of best slotting in?
Raju Mohan: Yes. Let me have Marty. We have talked a lot about it. Let Marty articulate this for you. Marty?
Martin Auster: Yes, sure, Sam. So, obviously, there is some evolution in some of the management of cardiovascular disease. And so that will sort of mature over the time course that we are developing 2735. I think on the recurrent pericarditis side, you have a pretty classic sort of niche orphan indication with limited therapeutic options. Currently, rilonacept’s really your sort of your go-to for difficult to manage refractory patients. It’s obviously may be less than perfect for some patients due to its nature is an injectable therapeutic. It’s also a very expensive therapeutics. There is some opportunity certainly to, I think put forth an oral option for patients who are suffering with recurrent pericarditis symptoms.
And I think that disease is often managed now with sort of a bit more of a scattered approach without necessarily a lot of consistency in treatment guidelines and people use things like aspirin and steroids and prednisolone [ph] and things like that. And I think a very nice targeted NLRP3 inhibitor, such as 2735 could play an important role. And obviously, the clinical pathway is heavily de-risked by the success of IL-1 driven biologics in the setting. So, excited to kind of develop that and find the right filing for that in the treatment paradigm.
Sam Slutsky: Got it. Alright. Thanks everyone.
Operator: Thank you. We have no further questions at this time. I will now turn the presentation back over to Dr. Raju Mohan for any additional or closing remarks.
Raju Mohan: Yes. Thank you everybody. Thank you to all on the call. So, we thank you for your continued interest in Ventyx, obviously, a very exciting period for us. We look forward to connecting with you at the investor conference in the coming months, connecting with you on the mice data. We are looking forward to talking about our efforts with 002 partnerships, moving towards the Phase 3 trial, and then hopefully reporting on – and coming back and reporting on the ongoing Crohn’s trial. So, a lot to talk about, but again, for today, thank you all and thank you to the team.
Operator: Thank you everyone. This concludes today’s teleconference. We appreciate your participation. You may disconnect.
