Let's do this. All right, so welcome to the second day of the Citi Global Healthcare Conference. So I'm Jeff Beach. I'm the senior biopharma analyst, and my team's here in front too. So we're thrilled today to have Kymera Therapeutics. We have Bruce Jacobs, CFO. We have Jared Gollob. So welcome, guys. Good to have you. We got some questions here, but maybe you want to give sort of just a real quick, like, you know, kind of couple-minute overview, and then we can get into some of the detail.
Sure, sure, Jeff. Thanks so much for having us. It's always great to be at your conferences. So this has been a busy and active year for Kymera. As I think most of you hopefully know by this point, you know, we're one of the leaders in the targeted protein degradation field. We're actually coming up upon the 10-year anniversary of Kymera's founding, which will be next May. And I think it's amazing from where I sit to look at how the company has evolved in terms of our capabilities and obviously in terms of how that's manifested itself in our pipeline. But we've taken that focus on protein degradation.
We've, over time, narrowed our focus to the immunology space, where we think there's a tremendous opportunity to develop drugs that, using this really powerful modality, have, we think, the ability to deliver, as you've heard us say many times, biologic-like efficacy with a similar safety profile of some of these biologic drugs, which are incredibly powerful in their efficacy but have some drawbacks, which we think make oral options a compelling alternative. So at this point, we've developed a pipeline that we think is quite exciting. I'm sure we'll talk about our two wholly owned programs, our STAT6 program, which is on the cusp of some data, as you all know, and I'm sure we'll talk about that as well, and our IRF5 program, which we introduced earlier this year and is poised to enter the clinic next year as well.
We'll have some data next year on that program also, and we've got a couple of partnered programs as well, if we have time to talk about them. We partnered with Sanofi on our IRAK4 program. They've focused on our next-generation IRAK4 degrader, and we'll be entering the clinic next year in 2026, and also, just recently, actually, it was June now, but feels recent, we announced a collaboration with Gilead around a CDK2 molecular glue, and we'll hopefully have news on that molecule's progression next year, so it's been an exciting time for Kymera, and we've got a lot to discuss, I'm sure, so I'll turn it back to you for some specific questions.
Awesome. Yeah, thanks, Bruce. Yeah, so let's talk about pipeline first so we can get into strategy and kind of the longer-term outlook. So the 621 data in atopic dermatitis, you know, coming up, there's obviously a category where there's a lot of innovation. There's a lot of competition, but you guys have a really unique platform technology and the potential to have really a very exquisite potency. So talk a little bit about what maybe a win looks like there in terms of differentiation, how you're thinking about this data set as you look to mid- to late-stage trials.
Great. Yeah, thank you. Maybe I'll start. You know, essentially, you know, the 621 program has been through phase I- A, healthy volunteers, right? We think impressive data there in terms of safety, knockdown, and biomarker effect. And now we have this readout coming this month for phase I- B. I think we've been very clear upfront from the very beginning of the study that for us, a win was to meet multiple objectives with that particular phase one B study in 80 patients. You know, one of the main objectives was to show translation of safety, PK, and PD from healthy volunteers to patients.
Another important objective for us was to show, or to allow us actually to confirm the doses that we had already really selected for phase II-B based on our phase I-A healthy volunteer data, but with translation, hopefully, between healthy volunteers and patients to be able to confirm those doses for phase II-B. We've talked about biomarkers being an important objective, wanting to show a Dupi-like effect on various TH2 biomarkers, probably TARC in blood being one of the main biomarkers that many focus on in AD because it's so elevated, but other biomarkers as well in blood and in skin, and to be able to show a Dupi-like effect at 28 days. And then, you know, finally, being able to look at a variety of different AD clinical endpoints.
You know, again, if you look at 28 days and what Dupi showed across their phase three studies at 28 days on various endpoints, that provides you with a ballpark for where we'd like to be with 621 with regard to those endpoints in our phase I- B study, so for us, you know, that would be a success, being able to sort of hit those various objectives, and for us, I think, you know, we see ourselves right now as being obviously sort of farthest along in the space with regard to certainly degraders.
Even with inhibitors, even though Pfizer recently announced that they are moving into a phase II-B, they haven't shown any phase I data. We feel as though we're quite ahead of the pack with regard to either any degraders that might be out there of STAT6 or any inhibitors by at least a year or two, you know, now having very quickly over the last year or so moved through healthy volunteers, patients in I-B, and even just recently initiated our phase II- AD study dosing our first patient just over the past couple of weeks and plans to start our phase II-B asthma study in the first quarter of next year.
That's super helpful, Jared. Yeah, when you think about the 28 days for Dupi, I guess the comps, how would you think about further differentiation? Is it sort of depth of response? Is it speed of response? What are the opportunities, I think, to really separate from this study for 621?
I mean, I think we've said all along that based on our mechanism of action, you know, blocking the IL-4/13 pathway through a different mechanism, but to the same extent as what Dupi can do and what we've seen in our preclinical models is that we expect, you know, in the best case scenario, to be similar to Dupi with regard to both efficacy and safety. So when we look at 28-day results, for example, we've been a little more granular around TARC in the blood just because this is not a placebo-controlled study, but biomarkers don't tend to change much in placebo. So if you look at the Dupi data at 28 days and you see a 70%-80% reduction in TARC, that's sort of the ballpark we'd like to be.
And if you want to say that we're Dupi-like on biomarkers at 28 days, we've been a bit more reluctant to sort of land on a specific number for clinical endpoints in the absence of a placebo control. But I think, again, if you look at those, like the SOLO-1, SOLO-2, phase three data, and you draw a line at 28 days, and you look at what they saw for EASI, pruritus, and other endpoints, you'll get a sense for that's the ballpark that we'd like to be in with regard to 621. You know, from a kinetic standpoint, I think we're going to sort of learn about our kinetics for the first time in phase I- B, again, remembering that this is a four-week study. So we're not looking over the entire 16 weeks where the phase two and registration phase three studies are usually run.
That also usually include even a longer extension period of one year beyond that. So I think we'll get our first sense of kinetics with this four-week study, but it won't be the final word.
Okay. And then looking broader at biomarkers, you mentioned TARC, Jared, but also the eotaxin. Maybe talk about predictive biomarkers that maybe aren't as FDA or regulatory validated, but are a very good indicator of your mechanism and deployment. What are the potential learnings from that as you look to phase II-B?
I mean, I think, you know, from the phase I-A healthy volunteer study, we looked at TARC, but we also looked at Eotaxin, which had not been looked at by Dupi in healthy volunteers and showed a very robust effect on both. So I think in phase I-B in patients, we expect these biomarkers to be elevated to a greater extent, obviously, compared to healthy volunteers. Actually, with regard to TARC, it's known, if you look at the published data with Dupi, that the sort of percent change that you see in TARC is a function of the baseline level of TARC. So if you look at some Dupi studies outside of AD where TARC levels are lower to begin with, you see less of a percent reduction, even though it's hitting the pathway hard.
And then if you look at some of the AD studies where 10 years ago, TARC levels were very high, you see much greater % reduction in TARC. So TARC changes are a function of where you start. But in addition to TARC, which we're obviously looking at and is important, you mentioned Eotaxin in the blood. There are other Th2 biomarkers there, but also in the skin. So we have the opportunity here to biopsy skin lesions in AD patients and look at the Th2 transcriptome and other AD sort of disease-relevant genes. These have been published by Sanofi previously. So we know what the benchmarks are for seeing effects at even four weeks on the skin transcriptome.
I think the totality of those biomarker data, I think, you know, hopefully will give us a sense of whether we're in that sort of Dupi ballpark even after four weeks.
Yep. And I guess the one question is, if you look at the, you have a lot of Dupi prior data that can kind of give you a sense for the transcriptomics, the profile. But when you look to larger studies, is there less evidence when Dupi, you know, refractory Dupi patients are non-responsive? How do these biomarkers trend? And would you guys be looking to study that in larger studies, you know, more mature clinical trials, like some of the more special populations in atopic dermatitis?
Yeah, it's an interesting question. I'll answer first, and if Bruce has more information, he can answer as well. I think there hasn't been a lot of work done on understanding mechanisms in patients who don't respond as well to Dupi. It turns out that many patients do have a good response to Dupi. So there aren't really many Dupi refractory patients in either AD or asthma. But it's a very important question around, are there certain features, biomarker features in either blood or skin that might predict for better or worse responses to a drug like Dupi? And therefore, could those by extension also potentially predict responses to our drug targeting STAT6? Those sorts of things might be out there, and that might be something that we look at in the future.
I think right now, it's important that we're really focusing on looking at activity of our drug, not in Dupi refractory patients. That's not where we're going with the drug. We want to go to patients who are Dupi naive because only a very small percentage of AD and asthma patients are even getting Dupi. So that's where we intend to go with our drug. Even on our phase I-B study, we do allow prior Dupi, but only in patients who have responded previously to Dupi and then had a washout. And that'll also be the case in our phase II-B. I don't know, Bruce, if you want to add to that.
No, I would just add, and Jared alluded to this. If you look at the AD population today in the developed markets, it's over 40 million some odd patients diagnosed. And the number of patients treated with Dupi are on the order of a million or less. And so, you know, I guess the way we have looked at this opportunity set is that there's clearly various reasons why that penetration isn't higher, despite the fact that it's a $20-ish billion run rate drug. There's some drawbacks from biologics. There's some people who have issues accessing them, paying for them. So I think when you think about the opportunity set for 621, or you think about even the long-acting agents, I think there's a big pie here, if you will, that is frankly just underserved.
I mean, Dupi is a fantastic drug, but it doesn't reach nearly as broad of a population as we think it's possible that an effective and comparably effective and safe oral drug could reach, and that's really the opportunity set, so as Jared mentioned, you know, if we have any Dupi experienced patients, we'll be able to share that when we have data, but clearly, you would expect there will probably be some on the phase II-B for sure, where we'll have larger numbers overall to really do some of that analysis by different patient types.
Yeah, I guess Bruce has a follow-up to that, or Jared as well. But when you look at the investments you're making in 621 in just atopic derm, how are you thinking about maximizing the commercial opportunity? Is it really to have more of a commercial partner, perhaps like in Europe? Is it to grow eventually the indication base that you're studying from atopic derm to respiratory IBD? How do you see this playing out from maybe a mechanism, but also from a commercial?
Yeah, that's a great question, Jeff. I'll maybe start, and Jared can add in. One of the aspects that I think makes this opportunity so unique for Kymera, for STAT6 targeted agents is the playbook is out there, right? We know where Dupi is approved and where it's been effective, safe and effective. And so we have in front of us, if you will, a menu of potential indications that we could pursue that if our thesis is right, that a STAT6 agent will act on the pathway similarly to Dupilumab, we ought to be able to show similar results in a multitude of indications. So the question then becomes, from a company standpoint, how does that drive our regulatory strategy and ultimately our commercial strategy?
The approach we've taken to this point is to initially focus for our phase II-B studies on the two largest markets, AD and asthma. Those are, as I said, obviously, they represent the lion's share of Dupi sales, I think somewhere upwards of maybe as much as 80% of revenue. But they also can become what we think of almost as like sentinel type phase II-B studies for us, one in dermatology with AD and one in respiratory with asthma. So the AD trial phase II-B is underway. We've initiated the sites and we've dosed the first patient. Asthma will be off and running in the first quarter. And I think over time, as we develop this data, we'll be able to refine and share more about our development strategy and frankly, our partnering strategy for the drug as well.
To this point, anyway, we've made the very clear strategic decision that we're not interested in partnering the program despite, as you might imagine, some pretty strong interest that has come our way. We have the team and we have also the capital to fully execute on these phase II-B studies. We don't see any scenario where any partnership could improve upon how effective we are in operating these studies and also the timeliness of how quickly we run them. So I think the question about our development strategy becomes obviously much more pressing and real when we get to the phase II-B data, which we expect the first of that would be by the middle of 2027.
At that point, I think we can start to really contemplate whether there's a scenario where working together with a partner could expedite the trajectory of this path to multiple indications and how we would prioritize them. The scale and scope of pursuing everything where Dupi is today would be almost unprecedented in biotech. There would be on the order of 20 phase III studies just to target the eight or nine indications that are the first group of Dupi indications. So I think even with a partner, there would have to be some level of prioritization. But I think those are some of the discussions that we'll have when we get to that point, if it makes sense. I should say we're building this company to take this through ourselves, and that's our anticipation and expectation.
The bar to partnering for this program for us is exceptionally high because we would have to, it would have to be proven to us that we could develop this faster and more effectively and most importantly, more broadly with a partner than we could on our own, and right now, we have a very clear pathway to some very, very large markets. We have two phase II studies that will be incredibly informative, I think, in our opportunity set there, and we're building right now. We've frankly already built the development capabilities. We're already now focusing on the phase III studies and the commercial side of the organization, which we need to build as well, but I think talk to us maybe a year, year and a half, and we'll have more to report.
But right now, it's all systems go and getting through these phase II-B studies rolling.
Just a follow-up to that, Bruce. So I think one of the capital with respect to growing the indications that are in development is probably pretty reasonable that you guys have access to that. But when you think about the down-the-road commercial investments on a global basis, geographic basis, don't get the impression that's a big priority now, but maybe we'll have to see based on data, right? Is that?
Yeah, no, I think that's fair. I mean, I think clearly the size and scale of this opportunity is commensurate with the investment that will be required on our part to capitalize on that. Right now, the company is very fortunate to have had a very committed, engaged, strategically aligned group of investors who have supported us along the way. We have $980 million of cash. We have a runway into the second half of 2028. That runway pays for both of the phase II-B studies. It gets us started on at least the first phase III study for STAT6 and then also pays for IRF5 and everything else we have in our pipeline. I think we have multiple inflection points along the way to look to how we might capitalize the company to, again, further advance the program.
I think the question of commercialization is a very good one, irrespective of what we do from a development standpoint. There'll also be a time at which we ask the question, are we the right company solely to take this into the market? Are the dynamics, and you know as much as well as anyone about the competitive dynamics, rebate environment, et cetera, what's the right model for that? And that's something that we're already thinking about today, but we've got a little time before we have to make some of the most important decisions there.
Yeah, and Jared, you're right. We say that, I mean, the penetration rate of Dupi in the atopic derm is very, very low. But from a mechanism standpoint, when you guys run the analysis of all the biomarkers and maybe outside of an atopic derm, is there an indication that maybe stands out that you feel like you could really separate versus Dupi on some of the more like a respiratory biomarker or a biomarker that's more prevalent in IBD? I'm just trying to think of like maybe a non-intuitive kind of next step in terms of indications.
Yeah, that's a good question. I mean, I think at this point, we still view sort of all the places where Dupi has gone and been approved or has been shown to be active really is the landscape where we should also be able to go with 621. In terms of how we prioritize, if there's a reason to prioritize above and beyond what Bruce was referring to in terms of market size, so yes, prioritizing AD and asthma because that's 80% of the Dupi market. Eventually, COPD is also going to become more and more a market. Eosinophilic esophagitis is going to be important in others. I think those are all places that we think it will be important for us to go. I should also mention that diseases like AD, asthma, and EOE, there are substantial pediatric populations there as well.
Those represent a sizable part of not just the market opportunity, but also the urgency of really providing drugs for these young patients who are not accessing them now. You can imagine that giving injections to young children as young as six months of age is very difficult, both for parents and for children. So to be able to have oral drugs that can now access pediatric patients within these big indications, I think that's also going to be an important imperative for the company in terms of if we see this, which we do as a transformative medication now for Th2 allergic diseases and now it can be given orally, you can imagine being able to access and provide unmet need for these pediatric patient populations as well as for adults and adolescents.
I mean, I'm sure everybody's got their own market studies and there's many of them out there, but most that we have seen clearly indicate that there's a strong preference when given a choice between an effective and safe oral medication and an injection, and particularly, as Jared mentioned, when you get to the pediatric population, some of these injections can be very painful. There's a large volume of drug. Oftentimes, there's induction regimens. I think particularly for parents who have to inject their own children, you can imagine that this would be a very compelling alternative, so we think about the opportunity set not just across different indications, but also these different populations. It becomes a very interesting value proposition.
Yeah, no, that makes sense. So looking to the phase II-B study, you guys have talked about a super pharmacologic dose based on all your PK/PD analysis. Just give us the background, the context for that and why that gives you kind of confidence.
Sure, yeah. So I think for a phase II-B dose range finding study, what FDA is going to want to see is that you're looking across a range of doses that are giving you different degrees of pharmacology, potentially different degrees of efficacy, and also allows you to look at safety across these different doses where you can now sort of connect safety to what you're seeing with regard to pharmacodynamics. So I think a classic dose range finding study, you want to be able to look across a range of doses that's going to accomplish that. I think fortunately for us, because from a degradation standpoint, our target is STAT6 and we can measure the impact of the drug on STAT6 and have done that, for example, in our phase 1 healthy volunteer study.
We know sort of what range of doses are going to give us sort of super maximal degradation versus sort of maybe clinically optimal maximal degradation versus submaximal degradation, and that's the dose range that we want to be at in a phase II-B study in order to do that properly. We're probably not going to end up revealing what those doses are for the phase II-B study, just given the competitive landscape. We will obviously reveal the doses for phase I-B when we present those data this month.
I think for phase II-B, I think we're going to be keeping it at a high level and thinking of it in those three different sort of buckets, but not actually providing what the doses are, other than to say that the doses selected for phase II-B are among the doses that we did look at in our phase I-A healthy volunteer study.
That's helpful. Yeah. So yesterday, we had a chat with Marty Makary, who was talking about novel technologies, novel approaches, and the opportunity for certain diseases to be fast-tracked or certain drugs.
Did you get us a voucher?
Yeah, exactly. I was working it.
Thank you.
So talk about your accelerated development plan. Is there an opportunity in your view to maybe help speed up even more? I know you move pretty quickly from phase I-A to phase II-B, but there's a further opportunity to kind of put this on a bit of a faster track.
Yeah, no, that's a great point. And I think aspirationally, that is what we want to do. It's important for us. One of the reasons we want to maintain control of development is to be able to do just that, to accelerate development so we can get this drug to patients as quickly as possible. Our strategy right now is to have only two phase II-B studies. I think Bruce mentioned this earlier, two sentinel phase II- Bs that would then allow us to drive the phase III doses for multiple phase III indications. So you could go from two sentinel phase II-Bs in AD and asthma right into multiple phase IIIs across multiple cutaneous, GI, and respiratory indications. So I think that's one way that we'd like to accelerate.
Of course, that's going to require a discussion with FDA, for example, and European regulators once we have phase II-B data to get buy-in. But we think there's a good chance that that could happen. Likewise, we talked earlier about getting into pediatric patients. If there are innovative ways of getting the drug to pediatric patients faster, given our novel mechanism of action, given what's already been de-risked in terms of Dupi across IL-4, IL-13 in both pediatric patients, adolescents, and adults, that's something that we're also going to want to be able to explore. Again, in the spirit of if we have a transformative drug that hopefully is not just convenient, but also potentially as safe and effective as Dupi, we want to make sure we're getting that drug to the right patients as quickly as possible.
I was just going to add a couple of small points. I mean, those who know Kymera know that we move very quickly, and we've only gotten faster in how we develop drugs and move through the clinic. And that's always our aspiration, always will be. The one point I wanted to make is with respect to at least the II- B studies, patient quality is absolutely critical. And obviously, there's been plenty of examples, unfortunately, of trials that have not achieved objectives because of the patients that were admitted to those trials. And so we're going to be moving as quickly as possible. But I will also say that for these II- B trials, we will certainly be over-indexing to getting the right patients on the study. And that's going to be our central focus. We believe we can do both.
We can move quickly and get the right patients, but that will be a key focus of us for these II- B studies.
And maybe also, Jeff, just to add one last thing is we don't want there to be much white space between finishing phase one and going to phase II, finishing phase two, going into phase three. So we're constantly looking at the next phase of development, making sure we're building out our development group and capabilities and being prepared to start that next phase of development as soon as we complete the prior phase. And that's another part of the, I think, overall philosophy of being efficient here and accelerating our development program.
That's one thing that Marty kept on bringing up is idle time, right? Trying to minimize that from a review perspective. But when you look at the body of data from a pure safety, tolerability to do the two phase II- Bs, is there an end or an exposure or maybe even preclinically?
Is there something that the FDA wanted to have as sort of a foundational safety tolerability kind of database that before you can pursue multiple phase II-Bs?
Yeah, I think that's also an important question. It may not be so much the size of the safety database, just as much as the conviction that whatever doses you've chosen for, say, AD and asthma can be applicable across other indications that might be related, but not the same. So that's probably more of the issue. I think hopefully we will have a robust safety dataset coming out of these phase II- B studies with 200 plus patients in each of these studies that will support moving on to phase three. And then, of course, the sort of safety database that one needs to get initial approvals in these indications, I'm not sure there's a whole lot of flexibility there, the need for multiple phase threes.
But again, it's about being able to execute on those phase IIIs, not to have a lot of white space between your phase IIs and your phase IIIs, and to be prepared to execute on those phase IIIs by building up your development group and having the right sites working with us. I think that's going to be what's most important.
I think you know this, but for the phase II-Bs, in addition to the four months of treatment, patients will be eligible to move on to a 12-month OLE. So that's both an important attraction to those entering the study, but it also is a big part of helping us build that safety database as we move forward towards registration.
Yep. To what degree are you guys using AI or using any sort of language model to maybe help with accelerate the database or maybe translate your biomarkers to checking the box more profoundly on the safety tolerability?
Yeah, no, I think it's an important question. I'll let Bruce answer as well. I think we're starting to think about AI with regard to clinical operations and with regard to trying to maximize efficiency within our clinical trials to make sure we're getting the right patients onto our trials to make sure that sites are performing the way they need to perform as we closely monitor and supervise those sites. So I think AI does have a role there, and we've been exploring sort of how we can incorporate it there. I'm sure there are other places where we can also use AI to increase efficiency. I think as a company, we're still looking into that. We're already using AI and have been using AI on the research side, on the chemistry side.
And so I think that continues to help us with our hit finding and all the evolution of our platform that's really allowed us to go after targets like STAT6 and other IRF5 and other high priority targets. But Bruce, do you want to add?
No, I think you covered most of it. I think certainly another part of AI will be in the data analysis side of the world, so obviously, for a 20-ish patient study, that's less relevant than a 200-patient phase ii study, but you could envision there is an area where we have some investments as well as we start to generate more data to help us understand that, and I think down the road, there's some arguments that the way pharmaceuticals are sold could well be impacted by these AI agents, if you will, and so those are all areas where we're focused right now.
Yeah. No, it was just such a big part of the conversation yesterday with Marty about using more technology and early in development.
No, and I think it's really important that we're aware of what's out there and that we're looking into how we would use it as a company, and I think you're right. I mean, the future is there, and we're starting to use it in select areas within the company, but I think it's going to be important to continue to maximize so that we are as efficient as we can be in our clinical development and how we go about that.
Yep. Yeah. So let's switch gears to the IRAK4, IRF5 program. So this could be maybe even broader beyond just IBD into maybe more autoimmune. Give us kind of the framing of how you guys position this. And obviously, it's a high priority. But what would you say is the kind of first bit of kind of de-risking that we'll see that gives you confidence to grow this indication base pretty broadly?
This is for IRF5 in particular?
Yeah.
Yeah, this is for the IRF5 program. So this is another program that we're really very excited about, another one of our solely owned immunology programs in our pipeline. This has been a target that's been in the sights of many different pharma companies for years. Nobody's been able to drug it. There are many different IRFs. There are many different isoforms of IRF5. So being able to only hit IRF5 and hit all the isoforms of IRF5 has been very challenging. We're fortunate to now have a degrader that is very selective for IRF5, gets all the isoforms of IRF5. We have a very potent selective oral drug that can be used at relatively low doses. So we're very excited. IRF5, the reason why it's so interesting is because it sits at the crossroads of essentially signaling from all the toll-like receptors as well as other innate immune receptors.
It's really critical for activation of B cells, B cell autoantibody production, activation of myeloid cells like plasmacytoid dendritic cells that are producing pro-inflammatory cytokines, and also for the type I interferon response. So by hitting one target, you can hit all those different pathways that are important across diseases like lupus and other interferonopathies, across IBD, rheumatoid arthritis. So there's a plethora of diseases that can be treated if you can really hit all those pathways with one target. And I think it's also important that IRF5 is not ubiquitously expressed. Its expression is restricted to B cells, certain myeloid cell types, and it's only activated really predominantly in the disease context. So you can hit IRF5 hard, as we've shown in knockout models, for example, and not have infectious complications. So very attractive from that standpoint.
And we presented very strong preclinical data at ACR just last month in multiple models of lupus where our IRF5 degrader is more active than any of the other drugs out there, either approved or active in lupus. We've shown very profound activity in RA. We're currently doing models in IBD and other interferonopathies. So I think this drug really has the potential to be transformative in these types of diseases where there are very limited therapeutic options. And so our plan, we've completed IND enabling studies now for IRF5. We're planning on moving it into phase one early next year. So there will be a phase one readout from healthy volunteers next year. And then the plan will then be to, right on the heels of that, move into patients. And on the patient side, we're thinking about different possibilities, but certainly lupus is high up on the list.
Because I forgot to mention that IRF5, there's a very strong genetic association with IRF5 polymorphisms in lupus. In particular, that's number one. Also, RA and IBD, but that's another reason, in addition to our preclinical data, why lupus has been sort of rising to the top for us.
Are there lessons from 621 sort of early development and kind of de-risking going into an IND that you could deploy for IRF5, or is it you just look at them as separate platforms within the TPD kind of?
I mean, they are separate platforms. I think all the learnings that went into developing 621, all the chemistry learnings, certainly went into IRF5 and certainly helped us be successful in developing an amazing drug for IRF5. I think from a, in terms of IND enabling studies and moving into phase I, I think we always have learnings from our prior programs that hopefully help us be even more efficient and better with our next program. I think our 621 development so far, this is kudos to our Kymera 621 team, has been amazingly efficient in terms of how we've gone through phase one healthy volunteers, phase i-b AD patients, and now into phase ii-b already. So if we can be as efficient as that with IRF5, and hopefully we will be, that would be great.
Yep. Yeah, I think when you look at the, say, atopic derm, the probability in the known mechanism, probability of success, and the market is there, there's not really a track record. There's a pretty successful track record of assets that have moved from phase I- phase II- phase III . But in lupus, obviously, it's been a bit of a scorched earth kind of approach. So how do you consider, I guess, risk in terms of the indications that you could pick for IRF5?
Yeah, that's a really great point. Again, Lupus, whether it's scorched earth or third rail or something, whatever your metaphor is going to be. I think what's important in deciding where to go with the drug, look, for 621 and STAT6, there's much more of a linear relationship, right? You can look at de-risking of IL-4, IL-13 by dupilumab, and that provides amazing clinical de-risking in addition to genetic de-risking for that program. We don't have that degree of sort of clinical de-risking for IRF5. There's the genetic de-risking that I just mentioned. The clinical de-risking is more indirect. You have to look at drugs that are targeting the type I interferon pathway, like Saphnelo, drugs that are targeting B cells, like the BAFF inhibitors, or other drugs that are targeting pro-inflammatory cytokines, like IL-12, IL-23.
Those provide, I guess, indirect clinical validation for IRF5, which is important in all of those pathways. But because there's not a drug that blocks IRF5 right now specifically, there's probably a little more biologic risk there. So I think what's important for us is to think very carefully about the genetics, about our preclinical data, and to be very strategic in how we go about what indications we're going to prosecute first and what we're going to learn from those initial studies in patients about the pathways we're affecting in addition to the clinical activity that will then help to inform exactly where we go with the drug.
I mean, it's not terribly surprising that STAT6 gets the lion's share of the attention right now, particularly given upcoming data and the status of the program. But IRF5 is a very exciting program. And if you talk to your pharma coverage, you'll probably find that that target is on their top 10, if not top five list in immunology across many of the companies. So we're really excited about it. Next year will be a big year for that program, entering the clinic and then sharing data as well. And we'll be able to also give you more details around the development strategy for IRF5. And we didn't get to it yet. Maybe it was on your list, but we have a goal of one program introduction per year. So we've got a couple few that are vying to take center stage in 2026.
So hopefully, we'll be able to talk about a new program next year as well, which is the plan.
Yeah. And that begs a broader question, Bruce. I mean, when you look at the TPD as a mechanism, pharma has always talked about it, and they're very interested in it, but it doesn't seem like they'd want to build it from the ground up. So as there's more interest in TPD and E3 ligases, et cetera, how do you view your competitive moats? Are they sort of widening? Do you look at your body of knowledge as probably deeper than anybody's? But there are many more companies that are going after this as a mechanism.
Yeah. Look, I think every pharma, I would imagine, has a protein degradation effort. The inherent problem is you can have efforts in lots of different areas. If you don't have the commensurate level of focus that's required to be a leader, it's hard to really execute. And there's plenty of companies, and I won't name names, who have multitudes of multiples of the number of people we have focused on this that have generated very little in terms of development candidates, whereas Kymera has taken five programs into the clinic and hopefully will have another five over the next however many years. So I think we've tried to build a company that is obviously dedicated to harnessing the power of this modality, which we think has huge potential. And we've gotten very good at it.
I think we've built lead discovery efforts and a group that is best in class that is finding these novel ligands to historically undrugged targets. We've got an incredibly deep chemistry team, most all of which has been with us from the beginning, that has been able to translate those hits into potent and selective molecules, which is the name of the game, and I think what we've showed so far is just the beginning of what we think is potential for this platform and what we've built.
Okay. Awesome. Okay, guys. Thank you very much.
Thanks, Jeff.
Thanks, Jeff.