Okay, I think we're gonna get started. Good morning, and welcome to the end of the first morning of our first day at the Cantor Healthcare Conference. My name is Eric Schmidt, delighted to have you all here with us, and particularly delighted to introduce our next presenting company, Kymera. We've got with us the company's CMO, Jared Gollob, and we have next to Jared on his right, the company's CFO, Bruce, and then Justine Koenigsberg here also from the company. Bruce Jacobs, excuse me, and Justine Koenigsberg, IR, as well. Guys, thanks for coming.
Thanks for having us.
For those of us less familiar with the story, maybe just start with a kinda quick high-level overview of state of the organization.
Yeah, sure. Just to start, so, you know, we were founded, eight years ago, to start from the beginning. You know, we essentially, you know, currently, intend to be a sort of fully integrated biotech company, taking drugs all the way from discovery through to registration and commercialization. You know, we essentially see ourselves as leader in the targeted protein degradation space, really by virtue of the fact that, you know, we have advanced, you know, and developed drugs against multiple undruggable and difficult to drug targets. We essentially have evolved a very robust, drug discovery engine that's allowing us to more, rapidly and efficiently develop degraders against, high priority undruggable targets. And we've been, I think, very aggressive in moving our programs into the clinic.
We've moved four programs into the clinic over the last three and a half years, and have shown actually translation of safety, PK/PD, and even efficacy across all four of those programs. Right now, if you look at our pipeline, we have five programs in our pipeline, you know, including three immunology programs and two oncology programs. We have one immunology program in the clinic, two oncology programs in the clinic, three immunology programs on deck. We had announced earlier this year that we had sort of pivoted more toward immunology, and that was really based on positive data we were seeing in phase one for the IRAK4 program that's partnered with Sanofi, as well as our strong conviction that our ability to develop oral degraders against high priority targets like STAT6 and TYK2 could really be transformative in the I& I space.
You know, for STAT6, we think of this as potential for Dupixent in a pill. We think this could be transformative in the treatment of Th2 diseases, and for TYK2, we think we're the only approach that can really replicate, you know, a human TYK2 loss-of-function phenotype, and therefore be transformative in IL-12/23 interferon-driven diseases and differentiate from the inhibitors, so right now in terms of where we are with those programs, you know, we actually reported a positive result for IRAK4 this summer, where Sanofi did a blinded interim analysis of efficacy and safety that led to their expanding our ongoing phase two studies to allow us to further accelerate the path to phase three. We think it was a very positive development.
You know, for, you know, STAT6, at this point, you know, we've completed our IND-enabling studies without seeing any safety findings in GLP tox, and we're poised to dose our first subjects, you know, in this half, and have data readouts, in the first half of next year. And then for TYK2, our plan is to be in the clinic in the first half of next year and to have data, in the second half. You know, for oncology, we're actually very pleased with the progress we've made in oncology as well. We have two programs, our STAT3 and MDM2 programs. Both of those have shown that we can dose escalate to doses that are giving a strong target knockdown and pathway inhibition at doses that are safe and well-tolerated, and we've seen clinical activity in liquid and solid tumors.
So I think our aim right now, we've finished dose escalation in STAT3. We're gonna continue to enroll lymphoma patients and present an update, especially on Hodgkin's lymphoma patients, where we've seen very nice activity later this year, probably at a medical meeting like ASH. And then for MDM2, we're still dose escalating and envision maybe having a next update, you know, probably in the early part of next year. But both of those programs, I think are on track and doing well. Importantly, we have, you know, funding to allow us to get through multiple key inflection points for those programs and for other programs in our pipeline. Maybe Bruce can speak to where we are from a financing standpoint.
Yeah, so we ended the September quarter with... Actually, we'll be presenting the September quarter. But we ended June, post our financing, if you just heard financing, about $930 million. So that takes us into the middle part of 2027, and as Jared said, will take us through many of these key events for this, the immunology pipeline that you'll see in the coming quarters and years.
Okay, so a lot going on. Maybe let's start high level and just, protein degradation as a platform. For those of us who may be a little bit less familiar with the field, you know, how have things progressed? Where are we today, overcoming some of the challenges that maybe were initially present here?
I think, you know, when we think about protein degradation, we see the two main sort of challenges are around target selection, and also just around the chemistry that's applied to finding ligands to hard-to-ligand, you know, protein targets. I think target selection, it's very interesting. You know, every TPD company appears to have sort of a different pipeline, which is nice, with relatively little overlap. You know, we have some very important guiding principles for how we think about targets, you know, at Kymera. For us, first of all, it's very important for us to be going after either undruggable targets, like transcription factors, or multifunctional protein targets that have scaffolding functions that cannot be addressed with small molecule inhibitors. It's very important for us that we're going after pathways that are very well-validated clinically and genetically.
We don't wanna take a lot of biologic risk. We're willing to take technical risk, but not biologic risk, and so that's very important for us to go after these clinically validated pathways. It's important for us to be able to show differentiation from small molecule inhibitors early in clinical development, to show the real degrader advantage, and it's important for us, we at Kymera are very interested in larger commercial opportunities where there's very high unmet need, where there are programs that can be essentially, you know, pipelines in a product. You know, STAT6, TYK2, IRAK4, these are all, I think, you know, representative of that, so I think that that's one dimension. The other dimension really is, you know, in addition to target selection, is around chemistry, and I think we've brought a lot of capabilities in-house over the past three, four years.
Our ability to really understand protein chemistry, protein, you know, biology, protein structure, to really be able to develop, efficiently develop ligands that are highly selective and potent, you know, against, you know, undruggable transcription factors and other targets. You know, you've seen this with STAT6, you'll see it with TYK2, you'll see it with other programs that we haven't disclosed yet, but that will be coming out, you know, in the next one to two years. I think our ability to do this more rapidly and efficiently is a real plus. We think we're sort of best in industry in our ability to prosecute undruggable proteins and targets and to find novel ligands, you know, with our in-house capabilities.
I think this is really, you know, fueling our pipeline and allowing us to go after truly high-priority targets, and we think there are multiple ones that are right behind STAT6 and TYK2 that are at least as exciting as those programs.
So is it more just internal know-how and experience that's allowed you to be successful relative to, you know, versus some new technology that you feel like you invented or rely upon?
I think a lot of it is internal know-how. A lot of it is, you know, we've created thousands, if not tens of thousands, of degraders across multiple programs now. Part of it is an iterative process, right? Learning how to make degraders, not just how to make ligands, but how to make the linkers, how to, you know, alter the chemistry so that we can have oral drugs that have desirable PK properties, make these highly potent and selective. I think this is our own proprietary chemistry, which I think is unique to Kymera and is representative of the quality of the chemists, you know, that we have working at our company. I think it's really about that.
Now, I think it's also true to say that even though we've focused a lot on heterobifunctional degraders, we're also interested in other ways to degrade proteins, including molecular glues, and we have ongoing extensive efforts there, and I think frankly, our ability to ligand undruggable proteins opens up even other ways for us to drug targets that don't have to necessarily rely on degradation.
There, you know, there's unquestionably a learning curve, and while we don't typically disclose programs until they've at least reached DC or close to, at least a line of sight on IND, the speed at which we can achieve those steps, if you will, along the development of a molecule, has dramatically changed over the years. You know, again, STAT6, we won't get into all the details on that, but if you look at how quickly we've been able to move with that program, there's no doubt that our learnings from all the work that we did in IRAK4 played a important role there.
Bruce, maybe for you on the business side, you're playing in some big boy ballparks with regard to these I& I opportunities and indications. What role might partnerships play in future, development and strategy?
Right. So currently as most of you probably know, we have an ongoing partnership with Sanofi around our IRAK4 program. We ran the phase I study. They took over and are running phase II. We do have the ability to elect to opt in. We can opt in before the start of the first phase III, so that's an important right to you know, share the economics in the US. But partnerships, you know, we obviously consider them all the time. Frankly, a lot of the interest is inbound inquiries and we've at this point, though, made it clear that our focus, at least for our immunology program, is to keep those programs wholly owned. We think there's tremendous value creation potential that we can achieve.
We've shown we know how to advance a program through clinical studies with our IRAK4 program, so we're planning to get to some of these really important value creation points on our own. You know, down the road, we'll see if it makes sense, but at this point in time, I think we have the capital and we have the capabilities, which are the two key ingredients to advance these programs on our own.
Where do you guys wanna start? You wanna start with IRAK4 or STAT6?
You know, we love both of those programs, so whichever one you wanna start with.
IRAK4 is first alphabetically. So, maybe let's just start as the target, Jared. What makes this a good target from a human genetic evidence, whether it maybe also supports safety?
Yeah, I think there are several dimensions there. You know, one, from an efficacy standpoint, you know, we know that IRAK4 is a key signaling node in the Myddosome pathway that is essentially controlling signaling through all the Toll-like receptors and through all of the different IL-1 receptors. So IL-1 family receptors signaling through IL-33, IL-18, IL-1 alpha, IL-1 beta, all of those. So it really has the potential to, you know, have a very broad pleiotropic effect in inflammation. We know that the pathways have been validated, especially the IL-1R pathways, through drugs that are targeting IL-18, IL-1 alpha, IL-1 beta, IL-33, across multiple different, you know, derm and respiratory indications, so there's the clinical validation there. I think importantly, there's also genetic validation for safety, and I think that's really essential.
You know, there are human IRAK4 knockouts who, as adolescents and adults, have no phenotype. They don't get infections. There are really no other manifestations. That tells us we can knock this target down hard chronically in adults without there being infectious complications. And so I think that de-risking on the, on the efficacy side and on the safety side is what makes IRAK4 such an interesting target. It also... It classically gives us that degrader advantage. We know that inhibitors are only partially able to block myddosome signaling. That's one reason why the Pfizer and Bayer inhibitors have not been successful in the clinic in diseases like HS and AD. You know, our experience so far, at least small experience with HS and AD in phase I, was that we were seeing activity that was tied to target knockdown and pathway modulation.
And so we think that the greater is the way to go if you're gonna try to drug this pathway, and there are other companies that are now sort of following suit. If you look at Gilead and Nurix and their collaboration, they're trying to develop an IRAK4 degrader. There are other companies doing that. I think people are starting to see the light, that if you wanna really, you know, hit this target and hit this pathway, which I think people believe can be transformative, and Sanofi believes that, we believe that, you have to use a degrader.
The choice of indication here, HS, I guess that comes from the IL-1R activity, or what-
It does from both actually. You know, HS is a disease that's very, very heavy inflammatory burden. There have been a number of papers showing that cytokines like IL-1 alpha, IL-1 beta, IL-36, are driving that disease. Toll-like receptors also are very important. These patients have lesions that are colonized and/or infected with bacteria, so they're activating toll-like receptors like crazy. If you activate toll-like receptors and IL-1 receptors, you're getting the elaboration of IL-17, of TNF, of interferon gamma, all these various cytokines. So I think mechanistically, you know, hitting IRAK4 has real potential, we think, in this disease. It's exciting that, you know, the AbbVie IL-1 alpha/beta antibody showed activity in HS in a randomized placebo-controlled trial recently.
We've shown activity in HS in our small phase I uncontrolled study, but not just against lesions, but also very, I think, robust activity against pain, which is really the main symptom that these patients suffer from.
With a degrader like this, how do you think about measuring selectivity? How do you know that, you know, you're not wiping out other proteins in the patient?
This is a very important part of, you know, how we vet and develop our degraders and develop, you know, our final candidates who go into the clinic. Selectivity is king, as well as potency, and we get the selectivity through the ligand, but also through formation of ternary complex with E3 ligase target protein of interest in our drug. And so we always look very closely at, you know, very, very sensitive proteomics assays, where we can look at 11-15 thousand proteins at a time across multiple cell types using very high concentrations of our drug. Those proteomics are what show us that exquisite selectivity. You know, the KT-474 only hits IRAK4. STAT6 only hits STAT6, doesn't hit other STATs. TYK2, likewise.
And so for us to be able to have confidence that these drugs can go into the clinic, that we can push the doses that are gonna give us maximal round-the-clock knockdown, pharmacologic inhibition, and not run into off-targets or safety issues, selectivity is really critical, and that's why we're very confident in the safety profiles of these drugs.
What evidence do you have, either preclinically or maybe from the phase I experience, that you are getting good, potent knockdown of IRAK4 degradation?
I think preclinically, you know, if you go back to our phase I study, you know, we started off at a dose of 25 milligrams as a single dose, and even there, we were seeing more than 50% degradation that was lasting for at least several days. You know, in the multi-dose portion for IRAK4, 25 milligrams given daily for 14 days was giving us 90+% degradation of the target. We got more than 98% degradation at doses of 50 milligrams and above. So we're getting... The potency is really translating. I think what I want to emphasize is that what we've seen preclinically in terms of selectivity and potency of our drug, and even clinical activity, has right now translated with high fidelity across all of our programs, four programs that have moved into the clinic, and we think that read-through is essential.
That's why we can point to STAT6 and say, "Look at the potency, look at the preclinical activity against the target, look at the preclinical activity versus Dupi in AD models and asthma models." You know, we have high expectations that that's gonna translate into the clinic now based on what we've shown you for IRAK4, for STAT3, for MDM2, for IRAKIMiD previously.
You mentioned earlier that the small molecules just weren't potent enough here. Why do we think 90% or maybe even above 90% degradation is gonna do the trick? How much do you... Where do we think we need to go?
I think, you know, I think in, on the immunology, and I think we really believe that we have, you know, and will continue to have, we think, probably the best in the industry oral immunology pipeline. [It's] all about, can an oral small molecule achieve biologics-like activity? I think to this point, you know, the biologics, right, they're injectables, and the injectables can only reach relatively small fractions of patients, and many patients don't want injectables, and many patients want to switch, if they are on injectables, to orals. But you have to be able to match the activity. You know, oral small molecule inhibitors like Sotyktu for TYK2, they're always compromising either activity or safety for an oral drug. We believe that we've shown that not just 95% degradation, but round-the-clock 95%.
That means that at trough level between doses, you're maintaining 90-95% degradation. That's complete pharmacologic inhibition of that pathway with an oral small molecule. Only degraders can do that, and that's the only way you're gonna be able to match the activity of an injectable antibody, and we believe we can do that for STAT6, for TYK2, and for other programs coming up behind it.
Can we compare that inhibition activity to what we saw with the small molecule inhibitors in terms of the amount of inhibition that they gave? I'm not-
Yes.
Yeah.
Yeah, if you look at the small molecule, TYK2 as an example, if you look at Sotyktu, BMS's compound, if you look at Takeda's compound, if you look at the sort of activity they're seeing in psoriasis, for example, you know, they're probably getting maybe 60%-70% of most engagement of the target round the clock, and that's sort of reflected in their PASI 75 scores that are considerably below what you see for drugs like Skyrizi, you know, the IL-23 biologics. The only oral drug that we've seen that's come close to biologics has been the J&J IL-23 peptido-mimic. So I think that, what that's telling us is that, you know, the oral biologics are not giving you that, that round-the-clock, full blockade of the pathway, not just because of the pharmacology, but because they're not addressing both the scaffolding and kinase functions of the protein.
Whereas we believe TYK2, for example, can do that. You know, we believe STAT6 will do that. Even IRAK4, right, is the only modality capable of doing it for that particular target. So I think that really is the, is the objective here, is to get that level of target engagement, if you wanna have an oral drug that's gonna have biologics-like activity, and we feel that's going to change the treatment paradigm in immuno- in, I and I diseases.
Okay, so what. Let's review the decision by Sanofi about a month or two ago with regard to their change of phase two design and readout. What, maybe Bruce, you want to chime in here? What exactly was Sanofi able to see, and-
Yeah.
What was the rationale for?
Yeah, sure. So, Sanofi we announced that Sanofi took an interim look, safety and efficacy data, made the decision to expand the study, and I know you and I have talked about this. It sounds counterintuitive that it's expanding the study, but also faster to ultimately registrational activities, and that's as a result of the fact that the way the phase two was initially designed, there was gonna be an initial phase two study and then a period of time to look at that data and then a subsequent phase two that would allow us to move in, you know, kind of a phase two B type construct that would allow us to move into registrational studies. We've effectively, you know, combined those. So, what is happening is there'll be some additional doses that will be explored.
So it'll be, I guess, a true dose range finding study, and at the conclusion of that, we think we'll be in a position to embark on the phase three pivotal studies. Thus far, we haven't been able to share the exact impact on near-term timing for the phase two dataset. The initial guidance was that we would share that data in the first half of 2025. So far, we've only said that it'll be later than that. There will be a ClinicalTrials.gov posting in the very near term, at which point it'll be clear what the updated trial design is and also the primary completion dates, and we'll be able to talk more about that.
But ultimately, the critical point is it will meaningfully, we think, reduce the time between now and when we are able to enter phase three studies for the program.
Any sense of how large a study this will be, with the changes?
I think, you know, I mean, the end will increase. You know, the aim is to add additional dose levels just to do full dose range finding. That's the regulatory requirement for being able to go from a phase 2b to a phase 3. We don't yet know what the magnitude of that will be, but that'll get posted on clinical trials, so everybody will see, you know, what that N is gonna be. They'll see the number of dose levels, and they'll also see the primary estimated completion dates.
Is it now powered for a certain effect size?
We really can't get into those details, but I do think that, you know, the aim of this study is for it to be a definitive study for understanding ultimately efficacy and safety relative to placebo, so that this can be the one study that FDA can look at and say, "Now you're ready to go on to phase three." That's how this will accelerate the program, by having just one study that takes us into phase three.
What do you or Sanofi need to see in order to, you know, be confident in a phase 3, either in HS or AD or limited?
I think, you know, it's a good question 'cause some people have asked us: Well, do you need to be like an HS as good as an IL-17, or do you need an AD to be as good as Dupixent? And I think what we've said is, look, the aim here is, you know, to be clearly active and better than placebo. Do we have the possibility of being as active as an IL-17 in HS or as a Dupixent in AD? Yes, but do we need to be that active for this to be a viable drug? I think the answer is no.
I think that, you know, if you have a drug that is safe and well-tolerated, it's an oral drug, and it's clearly active relative to placebo, I think there's amazing potential for that drug, especially across a broad, array of indications, you know, that go beyond HS and AD, that go into IBD and lupus and respiratory indications like asthma, COPD. So I think, you know, the bar isn't that high for efficacy, but I think that this mechanism, you know, may allow us to see, you know, quite substantial efficacy across different indications.
Okay, I think we better move to STAT6 in the interest of time and your other loved child. First, just again, about the target, talk to us about how STAT6 relates as a target relative to, say, IL-4.
I think, you know, everybody can acknowledge the primacy of the IL-4 and IL-13 pathways in Th2 inflammation, and then all the diseases that stem from Th2 inflammation. I think Dupixent has been a tremendous drug, not just 'cause it has helped so many patients, but because it has validated those pathways as best as you can clinically validate pathways. So I think for the past decade or more, people have been interested in finding an oral drug that can also drug those IL-4 and IL-13 pathways as effectively as Dupixent. That's been the Holy Grail, and the one target that's been of greatest interest is STAT6. The STAT6 is the obligatory transcription factor controlling signaling through IL-4 and IL-13, and it is also highly selective for those pathways. It does not serve other pathways. It only serves IL-4 and IL-13.
There are human genetics that support, you know, its role here. STAT6 gain-of-function mutations, these patients get Th2 diseases, no other phenotype, just Th2 diseases. STAT6 knockout mice, you know, are fertile, healthy, well, so it should be safe to knock down STAT6. The problem has been, can you find an approach, a ligand to STAT6, and can you pharmacologically block STAT6 24/7, round the clock, 90-95% if you wanna match the activity of a biologic? Our belief has been only a degrader can do that. So we spent years, you know, investing in the chemistry to find a degrader that was highly potent, highly selective. We now have a degrader. Our best degrader so far, KT -621, has, you know, low single- to low double-digit picomolar potency, highly selective for STAT6.
And now we've shown preclinically that we can match the activity of Dupixent against IL-4 and IL-13 in vitro and match its activity in vivo and AD and asthma models, as long as we can achieve 90+% degradation of STAT6. We believe that STAT6 small molecule inhibitors are gonna suffer from the limitations of occupancy-based approaches, which is that you're not gonna be able to get that round-the-clock pharmacological inhibition of the target. You know, these STAT6 inhibitors, you know, rely on SH2 domain ligands that are highly conserved among STATs. And so even if you claim to have a specific molecule against, say, STAT6, if it's against an SH2 domain, if you have to push the dose high to get full blockade, you're probably gonna start running into off-targets.
Whereas we are not gonna see that with degraders. In our hands, we've actually compared our degrader to inhibitors and have shown superiority in terms of blocking the pathway. The only approach in our hands that matches what biologics can do is a degrader. So that's why we're very excited about this approach. We think it can really be a Dupixent in a pill and be transformative in the field.
So is that the target product profile, Dupixent in a pill?
Potentially.
Does the degrader activity have any implications for safety? Is there any need to have scaffolding function for STAT6?
That's an important question, and if you scour the literature, you know, with the exception of maybe an occasional one-off paper that might implicate STAT6 in a something other than IL-4, IL-13, none of those have been corroborated with follow-up papers. You know, I think all the data point to this only being IL-4 and IL-13 serving. I mentioned earlier that the gain of function, STAT6 mutations, the only phenotype is TH2 inflammation. If this was serving other pathways, you would expect to see something there. We mentioned the STAT6 knockout mice that are well and have no phenotype. In our own preclinical data, in our tox studies that have gone as long as...
Our in vivo studies that have gone as long as sixty days, our tox studies that have been up to four weeks in monkeys, dogs, and we've also done tox studies, you know, in rats and in mice. Our four-week GLP tox studies were in rats and in non-human primates, and we have not seen, you know, any adverse events. We've not seen any in- life issues, any chemistry or heme issues, any gross histopath or microscopic histopath findings. Our NOAELs and our GLP tox are essentially the top doses. And so I think all of that together points to, you know, STAT6 being a good target to sort of be able to hit hard chronically with our very selective degraders.
The next milestone for KT-621?
Yeah, so we announced on our quarterly call in early August that we had completed our IND-enabling work, meaning all the preclinical work was done. So the steps from there were to assemble that, get the IND on file, get that cleared, and get the first patient dose. So we're somewhere between that announcement of completing IND-enabling and dosing the first patient. The next public announcement will be when we have done that, so you should expect it-
When you dose the first patient.
When we dose the first patient.
Okay.
Exactly. So we typically have an announced IND clearance, so it'll likely be that first patient dosage is our next press release, and you know, we've said second half, so we're obviously well into the second half, so you should expect that in the foreseeable future.
That'll be a healthy volunteer study?
Yes.
Maybe just talk a little bit about the phase I design.
Yes. So the phase I study will be healthy volunteer. If you look at our KT-474 IRAK4 program, or at least the SAD/MAD healthy volunteer portion, this will, you know, bear a great resemblance to that. So single ascending dose, the MAD will be 14 daily doses. And, you know, we will be focused really on, obviously, safety and PK, but also on STAT6 degradation. The number one objective of that phase I study is to show that we can fully degrade STAT6 by more than 90-95% in skin and blood, and do it at doses that are safe and well-tolerated.
Given that 90% threshold, where we've shown activity comparable to Dupixent in our preclinical models, if we show that, you know, in healthy volunteers, you know, full degradation of STAT6, that's safe and well-tolerated, we think that will be a huge de-risking event for the program. We also plan on looking at some Th2 biomarkers in healthies, 'cause you can see modest elevations of TARC and IgE in these healthy subjects, and Dupixent has shown some modest impact on those biomarkers, and we think we probably will see something similar, so we will be looking at those, but our number one aim here is to show, you know, full degradation of STAT6, comparable to what we've seen preclinically.
Again, if the read-through from our other programs is indicative of what we think we'll see, I think we're very confident in being able to see that level of degradation that's gonna be safe and well-tolerated.
Is there a first indication for clinical proof of concept that you've got in your mind?
We have that planned out. We haven't revealed it publicly yet. I think we'll be able to talk more about that once we're in the clinic in phase I. But I will say that if we look at the Dupixent blueprint, in terms of where they've gone, where they've been approved, that's where we're going initially. I think we're interested, in particular, in the larger indications, starting there anyway. So AD, asthma, COPD, you know, there are tens of millions of patients, right, in those indications, only a fraction of which are actually, you know, on Dupixent. So I think that's where we would start.
Okay. And I didn't mean to shortchange the TYK2 inhibitor, KT-294 but maybe just in the last minute that we have, you can give us a quick rationale for why degradation of TYK2 makes more sense than inhibition.
Yeah, I think the key is that, you know, only a degrader can phenocopy the human TYK2 loss of function phenotype, where they get loss of IL-12/23 interferon signaling and protected against autoimmune disease. The small molecule inhibitors are not able to phenocopy that. The small molecule inhibitors suffer from lacking the depth and breadth that TYK2 degradation can give. They don't pharmacologically around-the-clock block the pathway, and they don't fully block IL-12/23 and Type I interferon because they're not affecting the scaffolding function. And so we believe that we can show in a phase I healthy volunteer study, that we can get that critical round-the-clock, twenty-four seven, 90% degradation of the target, and also show our activity against IL-12/23 and Type I interferon, and importantly, sparing IL-10, which is important for treating IBD.
That's the main liability with Sotyktu. And that the next step after that would be a proof of concept study in patients. We haven't decided which set of patients. It could be psoriasis, but there, we want to show that we have biologics like activity. I think for us to advance the program beyond a phase II proof of concept, we have to be able to show we have, like, Skyrizi-like activity, for example, in psoriasis or biologics-like activity. We don't want to just have incremental activity over and above what small molecule inhibitors have shown.
Okay, we're out of time, but, Jared, Bruce, thank you so much for joining us today. Appreciate it.
Thanks, Jared.
Yeah, thanks so much, Jared.