Good morning, everyone. Thanks for joining us for another session at the 44th J.P. Morgan Healthcare Conference. I'm Brian Chang. I'm one of the senior biotech analysts here at the firm. On stage, we have the CEO from Kymera Therapeutics, Nello Mainolfi. I'll now pass the mic to their CEO for a short presentation, followed by a live audience Q&A. Nello, the stage is yours.
Thanks, Brian. Thanks, everybody, for joining us. Hopefully, the sound is good. Always great to be at J.P. Morgan in a new room this year. So in the next 20 to 30 minutes, I want to take the opportunity to tell you a little bit about Kymera, where we're going in 2026, and probably more importantly, where we're going in the next three to five years. So if you look back, so actually this year, in May, will be the 10th year anniversary since we founded Kymera. And we spent the past 10 years building strategy, capabilities, and team to deliver a whole new generation of medicines. What we're trying to build is something that has actually never been done before: oral drugs with biologics-like activity.
And what we've done in the past 10 years, and we'll take a quick look at last year, is taking us a step and a step closer to our vision and our goal. So if we just look for a minute on what we've accomplished, 2025 was really a pivotal year for the company. About two years ago, around this conference, we presented for the first time our STAT6 program. We showed with preclinical studies that if you degrade STAT6, you can deliver activity, a blockade of IL-4 and IL-13, in cells, in vivo models that can mimic, if not being numerically superior to what has been seen with a mega blockbuster drug like dupilumab.
So last year, actually in two portions, in June and December, we have been able to complete the early clinical translation of KT-621 and demonstrate that actually if you degrade STAT6 in humans, either in healthy volunteers and later in patients, you can actually deliver a full pathway blockade of IL-4 and 13 and impact both biomarkers and clinical endpoints at least as effectively as upstream biologics. So we'll talk about that. But that was a really exciting, important part of our 2025. We initiated a Phase 1 study. We'll talk about a new study that we started recently. We also presented a new program, our IRF5 degrader KT-579, another transcription factor in highly validated pathways where there are effective biologics but no effective oral convenient drug. And that's what 579 will deliver.
Last year, we not only presented the program but also completed all IND-enabling work to being able to go into the clinic soon this year. We also had a lot of important corporate updates. We continue to collaborate with Sanofi on our IRAK4 degrader and decided to advance the second-generation degrader in the clinic this year. We entered the collaboration with Gilead on this novel first-in-class CDK2 molecular glue for oncology. We were able to raise almost $1 billion last year, which gives us about now $1.6 billion that will fund the company through at least into 2029. Importantly, it allows us to take several of our programs through proof of concept, phase two studies, and for KT-621 in several phase three studies. This is a snapshot of 2024 as the foundational pivot of the year for what Kymera is trying to do.
And we can only do this thanks to both the team, the strategy, and the capabilities that we built, as I mentioned a few minutes ago. And maybe it's worth highlighting just a few of the things that I think make Kymera really unique in biotech. One is our target selection strategy. Our target selection strategy was defined about 10 years ago and actually has not changed. We go after undrugged targets that have never been drugged before, either fully or at all, in pathways that have been validated by usually injectable biologics, where we know our oral intracellular degraders can deliver a completely differentiated profile. Again, the concept of oral drugs with biologics-like activity. We have decided about five years ago to focus almost solely on immunology. We believe this is the time to advance a whole new generation of oral therapies in immunology.
Obviously, we're not the only ones, but we believe we're leading the transformation of how patients with immune-inflammatory diseases will be treated in the next decade. We can only do this thanks to the team and the capabilities that we've built. We understand the specificity of our degraders at the molecular level, at the atom level. We know how to make them behave like pharmaceutical agents, selective-specific, safe, and well-tolerated. And importantly, we're rediscovering, redefining these new rules of discovery and development. What does it mean to develop oral drugs that match the activity of biologics? They're a whole new concept that we're pioneering at Kymera. And we can only do it thanks to the team in our translational development organization that have been able to build very creative early clinical studies that not only de-risk but also validate our mechanisms and allow us to accelerate late development.
And you'll see the work that we're doing with STAT6, how it speaks to this particular point. So this is the problem statement. And this is the problem statement that we're very passionate about at Kymera. We're just going to talk about order of magnitude and not individual accurate numbers. But if you look at the 10 most common immune-inflammatory diseases, they're written very small in the slide, but you can imagine go from AD, asthma, RA, SLE, etc. There are about, let's say, more than 100 million patients in the seven major markets. The patients that access advanced systemic therapy are about five million patients. So we have lots of effective therapies, but we have two problems: how the system prescribes advanced systemic therapy, so treatment paradigms, and again, how patients can access advanced systemic therapy.
We believe strongly that if we develop drugs that have the activity, the safety, the efficacy of these advanced biologics, but the convenience of oral drugs and the access that we can deliver for patients, we can transform how patients are treated. This is not about the convenience over a biologic. It's about where patients are going to be accessing our drugs. Our vision here is to be our drugs the first option for all patients with immune-inflammatory diseases. How can we accomplish that? This is probably the only technical slide of today, so bear with me, but at least on the, let's say, chemistry discovery part. We know, obviously, how biologics work. You inject the drug. They have generally a long half-life, and you can cover the target for an extended period of time.
And this allows you to have an extended saturating effect on the target and obviously an extended effect on the clinical manifestation of that disease. Traditional small molecules, let's say in the past 50, 30, 20 years, have tried to get close or replicate that type of pathway blockade. The problem is that for every copy of protein, you can see on the left of the slide, you need one molecule. So you have a stoichiometric inhibition of your target that requires for targets that are expressed usually in the nanomolar to micromolar levels, you need a large amount of drug for a long period of time, usually for 24 hours. And that's generally extremely difficult to accomplish, if not impossible, with a once-a-day oral drug. In fact, I don't remember of a small molecule inhibitor, traditional small molecule inhibitor, that covers the target more than 95% for 24 hours.
So the reason why degraders can accomplish this is because one molecule of our degrader can degrade hundreds, if not thousands, of copies of protein. We can only fit five on this slide, but believe me, we can do more than that. And so this allows us to have a catalytic mechanism. So a small amount of drug for a short amount of time can degrade the protein completely and fully. So when we dose once a day, we can accomplish sustained complete pathway inhibition. I would say in some cases, if you take a drug every day, you will probably accomplish more pathway inhibition than a saturating dose of an injectable biologic. So we are landing here on our pipeline just to give you a quick sense of where we are, where we're going.
I think it's fair to say that the KT-621 and STAT6 program is probably in the top three. I would say the first or the most compelling program in biopharma, but let's say in the top three, given the breadth of opportunity, the validation that is behind it, and also the stage of development. We just started two phase 2b studies. We started the AD phase 2b study late last year. Actually, we dosed our first patient in, I believe, late October. And then recently, we said we were going to start the asthma phase 2b study in Q1. We actually ended up starting in week one of the year. And both of these studies will have data in 2027. So we'll have about 500 patients' worth of data for KT-621 in 2027. We'll talk more about these studies soon.
Exciting year for KT-579. We are shortly initiating our phase one study, and we'll have phase one data in the second half of the year. We're also planning to start a patient study, hopefully also this year, after the healthy volunteer study. We also have, as you know, two programs in collaboration, one with Sanofi. We're on track to initiate our phase one study with the second-generation IRAK4 degrader, KT-485. And then we have the exciting partnership with Gilead on this really unique CDK2 molecular glue, which I don't have any time to go into the details of, but hopefully we'll be able to share more data this year and in the future.
I thought it makes sense to use KT-621, our strategy, our discovery, our data, and our development strategy to simplify how we think about both the drug discovery and development principles at Kymera, our strategy, and more importantly, how we believe we're going to change how patients are treated with our drugs. This introduction slide has been used by myself multiple times. Nonetheless, I think for being comprehensive, it's worth highlighting two key pieces of information here. One, IL-4 and IL-13 is the most validated biology in type 2 inflammation. Type 2 inflammation, or one could say allergic inflammation, is the most common type of inflammation in the Western world with more than 150 million patients suffering from a series of diseases, eight diseases in which dupilumab has been approved, but there is actually more.
There are food allergies and other diseases that have not yet been treated with a type 2 drug. So the drug that is most successful at blocking IL-4 and IL-13 biology is dupilumab. This is a monoclonal antibody that blocks IL-4 receptor alpha and in doing so blocks the signaling of IL-4 and IL-13. We have found that if you degrade STAT6, the selective and obligate transcription factor for IL-4 and IL-13 signaling, you're able to block the pathway as well as an upstream biologic like dupilumab. And this is not only our work, but also if you look at human genetics data, it points to the fact that STAT6 is the key transcription factor for allergic diseases. There are many drugs in this pathway, but there is no oral drug that targets this pathway intracellularly. And that's really what we're trying to transform.
This slide contains a lot of information. I just want to guide you through the two important ones. You can see the diseases on the right. These are indications in which dupilumab has been approved. We're talking about more than 100 million patients. The penetration of upstream biologics into this patient population is in the single-digit %. You would ask yourself, how is this possible? The challenge is, again, as I said earlier, some diseases are treated not thinking about the underlying inflammation in the proper way. Actually, they're just treating the symptoms. Lots of patients and prescribers think twice before prescribing an injectable biologic.
When we talk about the type 2 drugs, dupilumab and others being a $20- to soon $30 billion drug, while this is obviously an important statement and it's actually a fact, what we're trying to do is not necessarily competing with these agents in that $20 billion market. We're trying to expand by multiple of that market the number of patients that we can access. So that's the opportunity that is in front of us. So maybe to spend a couple of minutes on what's stopping the penetration of many of these medicines to even just moderate to severe patients. So obviously here, we're using asthma and AD. About 60% of patients do not have adequate control of their disease. We have topical drugs that only or inhaled drugs only target mild patients. Current oral therapies either are not active enough or have safety challenges.
Biologics, again, they're associated with high treatment burden. So patients go through a needle fear, fatigue. Often you need to go through several injections before you reach steady state. Complex treatment initiation for some drugs, you need blood testing. So we've done a market analysis. Many companies have done this market analysis. I think the data is absolutely consistent. What patients want is first rapid onset of relief of their symptoms, convenience of an oral pill, no treatment initiation requirement, so no blood tests, and obviously a good safety and tolerability profile. So the data that we've generated so far on KT-621 fulfills exactly what patients want. And so this is a drug for all patients. We believe if you have a type 2 disease, moderate to severe disease initially, KT-621 should be the first option for these patients.
This is why we believe we can expand this $20 billion market to a multiple of that number. Let's go through some exciting data. This is my favorite slide because it was my idea, but we'll see if it works out with the audience. This was a way to try and summarize everything that we learned on KT-621 in a single slide. On the left, we have the preclinical data obviously highlights extremely potent degrader that blocks IL-4 and IL-13 in vitro and in vivo completely and at least as well as dupilumab. In many cases, even better. In terms of safety, all the studies that we've run, four weeks, four months, we're actually about to complete six- to nine-month tox. We even have completed embryo fetal development studies in all species, and we've seen no findings, no adverse events.
So the most compelling safety profile that I've seen in my career. In humans, we've learned a lot. Some of it is summarized. Deep, complete degradation in blood and skin of STAT6, impact on lesions of AD patients on skin, impact on itch of AD patients, impact on FeNO as well as relief of asthma symptoms in comorbid asthma, impact on allergic rhinitis. So with 200 humans between healthy volunteers and patients, we have basically de-risked the biology of STAT6 and KT-621. And now I'm going to take you through some data. So in this phase 1b study that we reported last year in December, these were 22 patients with moderate to severe AD. We looked at a series of biomarkers in blood, in skin, and actually in lungs.
We saw really robust reduction, all these type 2 cytokines, TARC, about 74% in patients that had elevated TARC at baseline, at least as well as what has been seen with upstream biologics. Eotaxin, which is a cytokine right downstream of IL-4 and 13, we've seen really robust reduction into the 70%, superior to even what has been seen with biologics in this pathway. IgE that requires much longer time to see an effect for biology reasons. We still saw a measurable effect even at four weeks. IL-31, which is the most important pruritogenic cytokine, Kymera was the first company to demonstrate you can actually see a reduction, a robust reduction even after 28 days in the blood of AD patients. Then again, another creative idea from the team, not from me, was actually looking at FeNO. So this is fractional exhaled nitric oxide.
It's a biomarker of lung inflammation. So we actually learned that even AD patients have a ton of inflammation in their lungs. We're able to reduce that Th2 tone in lungs of AD patients for the first time. So again, just looking at biomarkers effect of KT-621 shows that we have an extremely compelling profile to treat patients with type 2 inflammation in blood and skin and in lungs. So let's look at some of the efficacy data. So one thing maybe I'll start by saying, obviously we don't have time today to go through all the data, but the important thing about KT-621, that these two doses, that 100 mg and 200 mg that had the same degradation profile, gave the same effect on both biomarker or similar effect on biomarkers and clinical endpoints.
KT-621 had the same effect whether you had very severe disease or if you had less severe disease. So if you had high EASI at baseline or low EASI at baseline, high TARC at baseline or low TARC at baseline, we had exactly the same type of impact on disease endpoint. And this is why it goes back to the point I made earlier, a drug for everybody. This is why this drug is so compelling because of the fact that it works just as well regardless of your disease at baseline. And also works just as well whether you were previously on type 2 biologics like dupilumab or you were naive to type 2 biologics. So that's very important because we want to be able to offer for people that are on injectable biologics an oral option.
So here we're looking at changes of lesions, whether you measure by EASI or SCORAD, 60% and about 50%. This is again in line, if not numerically superior to what has been seen with injectable biologics at day 28. We also had robust effect on categorical endpoints like EASI 50, EASI 75. Itch, which is the critical effect that the critical symptoms that AD patients have to deal with every day. We have a really robust effect. Whether you measured it with peak pruritus NRS or you measured through SCORAD Itch, we're able to see between 40%-45% reduction. You can see in both EASI and itch, very quick impact on symptoms already at day eight. And importantly, in both cases, I'm actually going back here and forth, we see no apparent plateauing of this response.
This leads us to believe that there is much more efficacy to be seen as we continue to dose this drug. What we're trying to treat, obviously we're trying to treat the manifestation of the disease, but importantly, we're trying to make patients' lives better. This slide, together with each slide, is actually the most important slide. If you look at the left, this is the measure of sleeplessness. How many times do you wake up at night for scratching? That is what changes people's lives. If you cannot sleep at night, you can't work, you cannot function. I believe there isn't a lot of data with other agents with this particular endpoint, but I believe we're outperforming many other drugs from this point of view.
Even at day eight, we have really robust reduction of sleeplessness and at day 28 to 29, almost 80%. Also other quality of life like the DLQI and POEM, really robust responder rates. So this has enabled us to accelerate the development of KT-621, and we initiated this broad Phase 2 study. So phase 2b, this is moderate to severe patients, the criteria on the left, 200 patients, 16 weeks of dosing, 52 weeks of open label extension, three doses of KT-621, one placebo, one to one to one to one. Primary endpoint and secondary endpoint are traditionally used for AD. Importantly, we have recently started to also enroll adolescents on this study. Again, it goes back to the drug for everybody.
This is a disease of children, so we want to try and bring children into our development and into our label as quickly as possible. So we expect data for this program by middle of next year. So we weren't happy with obviously measuring AD in AD patients. We looked beyond that, and we were able to validate the effect of KT-621 also in lower and upper respiratory inflammation. So we had four patients, small number. We had four patients that had comorbid asthma, and we looked at FeNO, again, fractional exhaled nitric oxide. If you remember, when we looked at all patients, we had about 33% reduction. Now we have uncontrolled mild asthma, so the baseline of FeNO was around 50, so it was actually quite elevated, and we were able to reduce it between 50%-60% very rapidly.
At day eight already, we're close to actually above 50%, so this is really telling you that our drug distributes to the lung effectively and has an effect that is as robust, if not superior, to upstream biologics. Not only we measured FeNO, which is a biomarker, we actually measured at four weeks again, also impact on a clinical measure of asthma, which is this ACQ-5 questionnaire, and here we saw all patients have a reduction of ACQ-5 that was superior than a minimum clinically important difference, which led to 100% responder rate, meaning all patients had a response to our drug, so beyond asthma, so lungs, we also looked at allergic rhinitis. This is a very common comorbidity for patients with atopic dermatitis. Here we had between six and seven patients that were evaluable for this particular comorbidity.
Also here we had high responder rate, again in line with what has been seen with upstream biologics. This has, again, emboldened us and gave us the confidence and the excitement to initiate our phase 2b study. Today, actually, we're describing for the first time the design of the study. We've started the study, as I mentioned, about a week ago. This is a moderate to severe eosinophilic asthma. We're looking at patients with high EOS 300 and high FeNO 25. This is because we know based on the development of other drugs in this pathway like dupilumab; this is the patient population where we expect to see the biggest treatment effect.
This is a dose ranging study, about 264 patients for 12 weeks, again, three doses of KT-621, the same three doses that we're using for the AD study and one placebo, and we're looking at FEV1 as the primary endpoint. This allows us to actually differentiate doses versus placebo in a short amount of time to allow us to move into a registrational phase three study as quickly as possible, also for this study, we expect to have data next year, so this concludes, as I said earlier, really the early translation of clinical translation of KT-621 and STAT6 targeting in patients, in humans, I should say.
So we have so much data starting with human genetics saying that if you target STAT6, you should block type 2 inflammation and potentially deliver this dupilumab in a pill kind of profile that we like to use for simplicity's sake. We've shown in preclinical data our ability to robustly block the pathway again completely. In healthy volunteers, we were able to show that we can degrade the target exceptionally well and have impact on biomarkers and type 2 biomarkers even in healthy volunteer with an absolutely pristine safety profile. And then now in AD patients, again, we've shown that we can degrade the target in blood, in skin, in lungs, obviously given the effect on this biomarker. We have impact on these biomarkers broadly. We have impact on clinical endpoints in both AD asthma and allergic rhinitis. We have pristine safety, no treatment-related adverse events in this study.
And all the numbers that you've seen today really are in line, if not in some cases numerically superior to biologics in this pathway, just telling you that we can block out 4 and 13 exceptionally well. And so we're excited about, obviously, these phase two B studies and what we can do for patients with these diseases. So here's where we are today. And I think the important aspect that I want to kind of highlight is that from these phase two B studies, let's start with the one on top, our AD study. The goal is out of these three doses to select one that will go into phase three campaigns.
We expect to initiate multiple phase 3 campaigns in parallel, and hopefully we can use the same dose without repeating phase 2b studies for multiple other skin indications using the phase 3 dose that we select in the AD study. Similarly, for asthma, we hopefully will select a dose to go into phase 3 with asthma, and the same dose we can potentially use for asthma, CRS, and other respiratory indications, so in order for us to be able to go into phase 3 studies directly in parallel in multiple indications. That's really our strategy that we obviously continue to vet and validate as we get closer to initiation of our first phase 3 study, which is actually quite soon, relatively quite soon. Kymera is obviously not just about KT-621 and STAT6.
I like this slide because it gives us an opportunity to look at the programs and the impact. At the end of the day, that's what we're trying to do. And we divide it across, let's say, disease areas. So KT-621, I think, is the best type 2 drug. So that treats all these indications you see in the left part of the slide. IRF5, which is a program, again, will generate data this year, is really in the rheumatology space. So IBD, RA, SLE, Sjögren's, etc. We have a partnership with Sanofi and IRAK4. This is more Th1, Th17. And here we're just giving a preview of a couple of programs that are close to disclosure time. Hopefully, at least one of them will be able to disclose.
So just to give you a sense of the areas that we're going to be looking into developing these drugs. I would say one is more focused on type one inflammation and one is, let's say, more focused if you look on the right side of the slide on autoantibody-driven diseases. Again, these are all oral drugs, again, targets that have never been drugged with oral molecules. So this is, I believe, my last slide. So 2026, busy year. The goal is to complete enrollment of the AD study with KT-621, continue to enroll the asthma study to generate data by 2027, initiate and complete and release the data for the phase 1 study of KT-579. As I just mentioned earlier, we hopefully will be in the position to disclose a new program in immunology that will be going into IND-enabling studies later this year.
And then again, continue to advance our partner program to important inflection points. So I wouldn't be able to do anything that I've shown you today without the amazing team that is in Watertown, Massachusetts. So I want to thank them for everything that they've done. The team here, for inviting me, and all of you, for taking the time out of your busy schedule to listen to this presentation.
Thanks, Nello.
I think it's too long.
No, no, no, no, not at all. Let's start the Q&A. For those of you who are in the audience, if you have any questions, feel free to raise your hand. And for those joining us virtually, you can submit questions on the portal. I'll just start off with more of a broader picture question. Can you put 621's data from last month into a bigger context? I think as we think about your portfolio overall, do you see a read-through to your next work and so on? And overall, how does that de-risk the underlying technology to roll out the next degrader?
Yeah, great question, Brian. I think this, I believe, I should know this. I believe this is our sixth program that goes into the clinic. And in all the programs that we've advanced in the clinic, we've shown an absolute amazing fidelity of translation between the data we had generated preclinically and how we've seen safety, target engagement, early clinical impact. And so I think obviously we've also learned a ton in the past 10 years. I always say that KT-621, KT-579, KT-485, and others that you'll see, these are I like to call them second-generation degraders, meaning they're benefiting from years of learnings that we've had with the first programs that we discovered and then advanced into the clinic.
I think the data, the 621 data, which I think for many ways that you look at it is as good as you could ever hope for, just speaks to the fact that we have a really absolute control on how we design these degraders and how they behave clinically. So yes, the short answer is I think it validates the work that we're doing with 579 with the second-generation IRAK4 degrader and all the future programs that we're bringing forth because all programs are following this type of strategy of high specificity, high potency, and good physicochemical properties and the right targets.
We'll take a question from the audience.
Thank you. I actually have two questions. The first one is you explained the logic of choosing a PROTAC compared to the inhibitor very well. But I want to ask, what is the clinical consequence of the PROTAC? Is it leading to a stronger efficacy, or is it leading to a less frequent dosing? That's the first question. And then second question is we all know the Dupixent is doing very well with the AD and asthma. So did we try to compare maybe the efficacy on the animal test or whatever, like compared to Dupixent?
Yeah. So the first question is, what can degraders offer? So many things. First, as I said, there are no small molecules that can block a target completely 24/7 because the PK and the PD relationship is one to one. And it's extremely difficult to have enough drug on board 24/7 to block the target. So it allows you to actually have maximal target inhibition, which should lead to blockade, which should lead to superior clinical benefits. I would also say that in many cases, not in all cases, proteins have more than one function. So when you remove the protein, you can actually benefit from removing all function of the protein and not the catalytic function that the small molecule is able to block. And then your second question is about, so we've done plenty of preclinical studies comparing KT-621 to dupilumab.
I'm always very careful to claim superiority because dupilumab is such an exceptionally effective and successful drug. I cannot use a few preclinical studies to claim that we're a better drug. All I can say is that in these preclinical studies, when we degrade the target 90% or more, we see an effect that is at least as good as what you see with the saturating dose of dupilumab in these models. We're so close to generating robust placebo-controlled clinical data. I would love to use that data to delve more into these comparisons. I like it. We have audience. I never get audience questions in this presentation. Thank you.
Thank you for your presentation. So I have two questions. The first one is we noticed that you have a QD, but I also noticed that you're emphasizing the lasting effect, especially for asthma, it's a QW-like efficacy. So do you have a plan to do QW dosing?
So a great question. Actually, you also asked a similar question. I forgot to answer. So the question is, yes, sorry, I'm so used to repeat questions. I apologize. You guys have all heard the question. So QD is what we believe to be the most commercially viable dosing paradigm that we believe, based on analysis, will allow for maximal compliance. We know if you look at our data in phase 1, we know that actually one dose of KT-621 is able to retain maximal degradation for multiple days. So it is possible that you could dose less frequently. It's not something we're exploring clinically today, but it's something that could be explored at some point.
Thank you. So second point is just my curiosity because degrader and the PROTAC and the molecular glue, notice that the first one is PROTAC and CDK2 is molecular glue. So what's your basic criteria, some technology to you? Which one you would choose for which target?
Yeah. Excellent question. So very simple answer. It's really, really driven by the problem we're trying to solve. If we want to degrade a target that we can find a small molecule binder for selectively, there is no better technology than heterobifunctional degraders. You have complete control of specificity and of the mechanism. If we cannot find a specific binder to protein X, or for example, for CDK2, we cannot find the specific binder that is specific for CDK2, as you know, there is high homology between CDK2 and CDK1. So we choose this protein-protein interaction enabling technology, which many call molecular glues. So that's how we separate the two.
Well, thank you so much for your time. And that's all the time we have. Thanks for coming.
Thank you, everybody.
Thank you.