Kymera Therapeutics, Inc. (KYMR) Earnings Call Transcript & Summary

Hello, everyone, and welcome. My name is Chris Shibutani. I'm a member of Goldman Sachs Biotech Equity Research team. We're thrilled that you can join us for the 42nd Annual Goldman Healthcare Conference. Our second virtual, hopefully, will be live pretty soon. I'm joined by my colleague, hardworking CJ Zopf. CJ, wave to your fans, who does all the smart work. I make sure, as all the clients know and make sure to hire really smart people to address my many shortcomings. But we are super excited to have Kymera Therapeutics join us today for the presentation. I think the targeted protein degradation space has just become so much more visible, especially to the public equity investors. So we're really going to look forward to diving into understanding some of the setting that you guys are pursuing and understanding specifically about the company. We're thrilled to have the entire C-suite basically join us here. Nobody is doing any work back in Cambridge since you're here for the next hour, the CEO, Nello Mainolfi. Nello, you've come with a tremendous background from Novartis. And I think one of the keys to these young companies is having people who've been there and done that and management talent is so, so, so important. Bruce Jacobs, CFO. Some of you who are 100 years old like me know that Bruce and I go way back from your Wall Street days. I think people often think about hiring strategic CFOs from Wall Street. But in your case, you really have been on both sides, sell side, buy side and bring that to bear, which is terrific. And then Jared Gollob and I go back way too far. We were classmates at Columbia PNS. Jared was -- you were like the valedictorian or something, right? I think I barely passed internal medicine rotation. So I think what's so important about these companies in the innovative spaces, the management teams and the gathering of folks, and it really gives us so much confidence to be able to talk to you guys and think about the company. So with that introduction, welcome. Thank you for joining us.

Thanks, Chris.

Thanks, Chris.

Thanks, Chris.

So I think let's level set a little bit. I think people who are joining us have some sense, but targeted protein degradation, TPD, right? It's many things. And I think investors are still trying to understand a little bit what the landscape is. As if we have this map, and there's different zones within this map, both in terms of approaches, targets, the versatility is awesome, obviously, the science has been progressing for a very long time, but it's really been the last couple of years. And now investors have been able to find ways to express themselves with a series of companies that have gone in IPO. So who would like to take a stab at just sort of like explaining TPD and then from their understanding where you guys are within the landscape?

Great question, Chris. So maybe I'll take a stab at that. Maybe to do so, if you allow me, I just want to go maybe a few years back to contextualize why targeted protein degradation came about and what problem the space and we are trying to solve. So if you look in the past probably 20-plus years since the so-called genomic revolution, our goal has been to identify the right technologies to go after this plethora of undrugged proteins to change and transform quality of life. I would say countless companies have been built with this goal and many have been successful. But after 20 years and several super impactful technologies going from antibodies to oligo-based therapeutics to gene therapy, we are still dragging about 20 -- probably 20% of the proteome. So now this is where -- this is the landscape in which protein degradation comes in. So you have now a technology that has been around for actually just about that long. But only very recently has been able to really take a step change into the therapeutic modality world, thanks to advancement made in chemistry, we can go to that if you want to get really into the details. But anyway, with this landscape, what is the opportunity here? So the reason why actually we founded Kymera 5 years ago, and we just celebrated actually the 5 years of the company, was now we have a unique opportunity to expand beyond this 20%, a 15% to 20% of the proteome. Why and how? So the limitation of recent technologies that are technically able to really address many targets and Jared in his days in Alnylam can tell you that for probably a long time today, but we've been limited by either the permeability of some of these technologies like antibodies over the delivery, the ability to permeate through tissues and organs in the human body. And for some of these oligo-based therapeutics, we've been restricted to either liver targeting or tissue direct injection in most cases. So now with protein degradation, you can overcome this, and you can embrace this new technology that brings the power of genetic-like knockdown with the flexibility of the small molecule. Now obviously, no technology is perfect, and I'm sure we can talk about some of the challenges there, but that's the backdrop. So the opportunity for the first time in history to have a new small molecule-based modality to go after undruggable protein or undrugged protein. That for me is like my life mission, like I consider myself lucky to have had this opportunity because this does not happen often in the life of a scientist or a former scientist. I don't know who I am anymore. So this is the landscape. So the ambition here is to be to kind of own, both the challenges and the opportunity and to make Kymera the company that, in a few years, we'll look back and say, we've solved the challenges and we're now producing these transformative therapies.

That's very helpful context. And so I think -- I'm trying to think about so many different directions we can take this conversation. But I know that amongst investors, they're still trying to understand where each company is distinct and how they differentiate in their approach. You introduced the concept of being able to drug what's undruggable, which is one of the most significant kind of statements that you could make. And what's terrific about the opportunity with TPD is that just because there may be 3 or 5 companies that we're increasing to become aware of, this is not a zero-sum game. This is not a single pie and people are competing. This is almost like the establishment of the therapeutic modality at a tool to go in so many different directions. So talk to us about -- a little bit about what distinguishes Kymera's approach and then we'll go a little bit more in detail about the indications you're going in immunology and oncology, but what characterizes the Kymera approach?

I just want to -- maybe just for a second, also double-click on the concept of, this is a nonzero-sum game. I mean, again, we've had -- the whole biopharma industry has focused for the past, let's say, 50 years, on the same kind of 20% of the proteome. So it makes a lot of sense that if you have now companies that can expand it, it can't be a zero-sum game because you're actually opening a broader opportunity set that is in a way technically almost limitless. So what is Kymera about? And maybe just to go to the fundamental kind of founding thesis that we had 5 years ago, we founded the company to build a company that would own protein degradation as a new therapeutic modality to become a successful fully integrated biotech. And just to know some of this, for us, success, meaning having the ability to take several multiple drugs through development into the marketplace as a fully integrated biotech and with the expanding opportunity set in diseases well beyond the ones that we have today. So we're going to think about the opportunity and what we're trying to do, and I'll get into the details in a second. I go back and look at other game-changing technologies. And then you can easily point to the companies that decided to actually go fully try to solve the problems and actually come at the end of that process as the company that personified their technology and the success of it. And so that's what we're trying to build here. You can point to companies in RNAI, in antibody therapies, in ADC. I don't want to mention names here in front of everyone, but I think we can quickly get to that. And so the level of commitment that we have is not to be the best, but is to be the company that it feels the responsibility and not just the opportunity to solve some of the challenges and to provide broader therapeutic options. So the areas that we invested in what we believe makes Kymera unique and we believe will prepare Kymera to be that company in the next few years are areas that we believe are fundamental to understanding and evolving the technology. This is an E3 ligase-based technology where we use E3 ligases as the catalytic machinery to degrade protein. We only have clinically really only demonstrated activity with one E3 ligase cereblon. Preclinically, I think we've seen probably 3, 4, 5 being -- having some level of success. But there are 600 E3 ligases with unique expression profile that can enable the biology of the target that you're going after to be best pursued in matching, again, the right E3 with the right targets. So an area that we've committed a lot of time, and to be honest, money, is how do we select the right E3 ligase for the right target biology of interest from a translational medicine approach. So expressional organization and function matching between target and E3. The second area, which I think our team has done a great job starting to talk about at different conferences, and we have some publications that we're writing is the fundamental, technical, most important aspect of this technology, which is also the biggest strength of the technology, which is the ability to have an inherent biomarker when you run clinical studies, which is protein levels and the ability to understand how a degrader is absorbed, impact protein level in the presence of clearance mechanism and resynthesis rate across diverse sets of tissues of interest. What we, at the end of the day, called PK/PD is a fundamental understanding of this technology. And if you reduce it to 1 cell type and you say, I know how much degradation I'm having in my tumor sample, I think you're reducing the understanding of protein degradation. It's something that has been overly simplified. And the reason why we've invested in immunology is because we knew that, that signs and that biology allows us to look at different cell types, different tissue types, different organs, all contributing to the fundamental biology. And so understanding the PK/PD across these different contexts will allow us to kind of, again, own the challenge and own the solution very early on in the life of the company. We'll get to that hopefully later. Our Phase I study, which has never been done, has never been designed as such, in protein degradation before, a lot of it is obviously for developing KT-474 in what we believe it to be potentially a huge drug. But a lot of it is also to validate our approach in understanding this PK/PD parameters across the body that I think would be kind of first-in-class data and enabling data. And so the last one that I want to mention, so again, going back, E3 ligase toolbox, PK/PD across different issues. And the last one, this is, at the end of the day, a chemistry-based technology, where the magic will always come from the talent of the chemistry, the discovery and the biology team to make these drugs. And this comes with level of commitment that we have to 2 areas of the so-called chemistry. One is if you want to go after undrugged protein, you got to be able to find these ligands to design undrugged proteins. So for us, we are committed to a multi-pronged approach there where we use different technologies, chemoproteomics, their libraries, fragment screen in silico. So we don't go in fully in on one, but we have a comprehensive approach. And then the second part is our chemistry commitment is to actually developing drugs. So what are these molecules need to look like to be drugs that would be easily developed through the phases of clinical development. So I'll stop here. I apologize if I took too long of the time here, but so those are the 3 fundamental investment areas that we believe would propel Kymera to the place where we need it to be in a few years.

No, that's very helpful. I think I really wanted to understand landscape and strategy and then you're always very thoughtful about sharing that information. We do want to talk about the specific assets, 474 and 413. Since I took the pains to introduce the rest of the folks who are on this so Bruce, I will spare you, you can think about what your answer is, but I'll ask the exact same question to Jared. Obviously, I referenced you had such a tremendously successful medical career. You spent time at another blue-chip at Alnylam. What was the compelling reason? I'm kind of asking this because our audience is sort of thinking why should I own shares? And you voted with your feet as did you Bruce. And sort of like what is the answer to the question of like, why Kymera?

Well, I mean, Alnylam was a tremendous opportunity to work on a to being a platform-based company to be part of the sort of RNAI experience and really be involved in developing one of the first drugs, first approved drugs in that field. And it was that experience at Alnylam, the people that were there, the science that were there, the business plan that helped me to stay there for 11 years and enabled me to learn a lot about drug development, but also about platform-based technologies and how you really bring those to the fore and create actual drugs from that technology. And so Kymera was an amazing new parallel opportunity that I saw. It was obviously earlier in this development, but really had a very similar mindset, very science-driven, platform-based targeted protein degradation as another way to sort of go after undruggable targets, but with even more versatility because now you can do it with small molecules. And we're not so restricted in terms of being able to deliver RNAI therapeutics, for example, only to the liver. So you have to be part of a new technology that has such potential for developing an extensive pipeline in a disease-agnostic way, using small molecules to drug the undruggable. And being part of a very motivated, science-based group of individuals, obviously being led by Nello and really understanding what the mission of the company was really to develop drugs, to really be very patient-oriented and to use this technology, to really go into multiple different disease areas to do it quickly and efficiently in a very science-based manner. That's what really attracted me to Kymera. And I've been here now over 2.5 years. And it's really been a tremendous place to work. I think the potential here for developing drugs is really quite incredible. And I really see us having a similar trajectory, if not better, or maybe even faster than what happened at the [ lab ].

That's terrific. And so Bruce, I mean, you're going to know so many people who are in our virtual audience, right? And everyone contemplates this is like, oh, let's go industry or whatever. What was the driving force for you to find that release of the inertia, that trajectory, let's give this a try, why Kymera for you?

So for me, really, it was about the breadth of the opportunity. I think if you look out there and think about what are truly enabling technologies, right now, protein degradation is at the top of the list or at least certainly near the top, if not at the top. And for me, that was what was most exciting. And then next really comes what one does with that, right? You can have enabling technology, but what do you enable and that kind of leads me to what also got me excited. And hopefully, it will be a good segue for where you're going next, which is target selection. I think the company has been incredibly thoughtful about how it has approached target selection. And I think the potential there for what we've -- where we've chosen to focus our efforts is incredible and what really got me excited, ultimately at the end of the day.

Terrific. That's helpful. I will turn it off -- over to my colleagues, C.J. Zopf. Attack, 474.

Maybe before 474, just to segue off of Bruce's comment, can you guys give us a sense of the higher-level arc, not only target selection, but also disease area and how we should think about Kymera's focus, both in the near term and the long term?

Thanks, C.J. So we have committed early on in the life of the company, as you guys know, to working in oncology and immunology as our internal focus. And there are many arguments that can be made, why there is almost a continuum between the 2 inflammation is probably fundamental to many pathologies across many diseases. So we wanted to also use inflammation as a way to then eventually grow and expand in other disease areas. So that's how the company started. We then, thanks to our collaboration with Vertex, have evolved to be, at this point, I would say, disease-agnostic platform company, given that we're lucky to now work on 5 other different diseases outside of these 2. That -- go back to what I was saying to Chris before, which is how much -- the more complex and the more challenging the area is, the more learnings you are going to have. And for us, Vertex allowed us to learn other diseases, other pathophysiologies, other tissue types, other E3 ligases, other organs in a financially and operationally derisk manner. But it's fundamental learning that is allowing us to actually get more sophisticated also about target selection and disease expansion. So I would say that in the next probably 2 years, we are very focused on accomplishing proof-of-concept -- clinical proof-of-concept across some of these programs that have or about to enter the clinic. And I would presume that around that time, we will be more likely moving into other disease areas, either as an internal full focus or potentially with other collaborators. But I think it's important right now that we're focused on an exciting clinical pipeline. And actually, what we don't talk about, we have several programs behind these that actually are not that far away from these and so we want to continue to generate value because these therapies have all -- in all of our programs, we have transformative potential. We want to make sure that they actually do have transformative potential in patients, but that's what we're very focused on right now.

Great. So you certainly set apart -- you set up your immunology focus as being differentiating from others in this space with IRAK4, KT-474. Can you give us a sense of what is it about the underlying biology of IRAK4 that you think makes it so key for the immunological indications you're going after? And what are your pharmacological goals there?

So maybe I'll kind of try and put a few pieces together. So first of all, why did we invest in IRAK4. So again, our target selection hypothesis that continues to be valid to the date is we want to be working in pathways, where there is a high degree of validation, but we're key nodes. So meaning that we have human genetics, we have human pharmacologies in other nodes of the pathway. But the key nodes has not been derived or fully derived. But any other technology where if you use protein degradation, you are able to fully capitalize on that biology. And I always tell my team, if you cannot articulate the greater advantage in a simple sentence, we're not going to work on that program. Because this is -- the challenges here are not common with other technologies. And so you don't want to be spending time and money and resources on something that has the potential impact in the clinic over existing therapies. We want to be very confident the reason. So with this pathway, how everything came together is human genetics, very strong human genetic. I would say, in terms of immunology, there is no probably stronger human genetics that the IRAK4 nor phenotype, both in terms of efficacy being kind of protected from activation of TLR and IL-1, but also in terms of safety, there is no more benign phenotype of no -- of lack of protein with IRAK4 than there is for other continuous pathways for agents that are actually in the clinic or approved. So human genetics, then human pharmacology, many drugs that have even been approved or are post parked in the clinic in this pathway. You think about the IL-1 family antibodies, IL-1, 18, 33, 36 and IRAK4 kinase inhibitor from Pfizer that is showing positive Phase II data, but none of those can actually block this pathway fully. And so that's the opportunity that we saw and the opportunity to have a single daily oral small molecule that can have [indiscernible] antinflammatory effect. So that's the foundation for that program.

Got it. So there's obviously a lot of potential different ways you can go with this. You talked a lot about Hidradenitis Suppurativa, atopic dermatitis, rheumatoid arthritis that this can play a role in. Jared, obviously, these are somewhat crowded areas, maybe HS less so, but it's certainly getting more interest in investment. How do you think about potentially positioning this sort of mechanism there and within the treatment paradigms?

Well, I think one of the real value propositions around IRAK4 targeting is that you can have very specific selective targeting of a single protein at a very broad anti-inflammatory effect. Because of the important role, the gatekeeper role that IRAK4 plays in signaling through IL-1 receptors and [indiscernible] receptors. And so that really opens up numerous development opportunities. You've mentioned AD and HS and RA. That's really almost the tip of the iceberg. If you think about the large sort of constellation of autoimmune and autoinflammatory diseases that are driven by various IL-1 inflammatory cytokines or by toll-like receptor activation, it goes even well beyond those particular indications. And the fact that you can have this very broad anti-inflammatory effect targeting a single protein is in really counter distinction to, say, what individual monoclonal antibodies can do. So Dupixent, which is the only approved drug in AD was really targeting essentially signaling through the IL-4 receptor. Adalimumab is targeting TNF-alpha specifically for HS, the only approved drug there. So the competitive landscape in terms of approved drugs is fairly slender there, but also the advantage that we think we have over those agents is that by having a broader anti-inflammatory effect in these diseases, which are very [indiscernible] in terms of the mediators of inflammation, and we think we can have a real advantage in terms of clinical impact over just a monoclonal antibody going after TNF or an antibody that is going after the IL-4 receptor alpha. And even in RA, there are more drugs approved there, but I think there's the same limitation in terms of effectiveness of drugs that are approved there that are really going after single cytokines, where, again, we think we could have a more impactful effect by going after IRAK4 and having this broad anti-inflammatory effect. And so I think in terms of positioning, I think, for diseases like HS and AD, going after moderate to severe patients and really being able to have a drug that, number one, can be given orally. So that's a real advantage over the parenterally administered drugs that are available for those diseases as well as for RA. Having a drug that could be considerably safer referred to the IRAK4 NOL phenotype effective adults who lack IRAK4 have no susceptibility to infections. And so that could be a real advantage for being able to get the target hard, but to be able to do it safely relative to other therapeutics. So being able to have an orally administered drug, being able to have a better safety profile. And frankly, having the potential to be more effective because of this broader effect across multiple different mediators of inflammation, I think can really position KT-474 as a first-in-class drug for these indications, AD, HS and RA, but also for other indications, whether it be lupus or psoriasis or inflammatory bowel disease, all these other indications that are also driven by IL-1 inflammatory cytokines and by total receptors.

So your initial clinical work so far has been a noninterventional study. Looking at HS and AD to try to elucidate the role of IRAK4. Can you give us a sense of what you've seen there and how it's influencing your Phase I work that's also ongoing? And how has that led to sort of HS kind of coming to the fore in terms of indications?

Well, I think the IRAK4 for noninterventional study, I think, is a great example of the fact that we really want to understand as best we can, the central role of the targets and the pathways that we're going after in the pathophysiology of the diseases where we intend to develop. In order to do that, noninterventional studies could be an additional way of really doing that, especially when there hasn't really been previously much characterization of that target in certain diseases. So the noninterventional study data that we presented on HS last month at the Society for Investigator Dermatology meeting really showed that in the skin of HS patients compared to healthy subjects, you really see overexpression of IRAK4 protein, both in the dermis and the epidermis and you see it in active inflamed lesions, but you can also even see it in unaffected skin that's actually near those active lesions. And we actually show not only that the IRAK4 is overexpressed in these active lesions in HS, but that expression is correlated with overexpression of inflammatory transcripts that are central to the biology of HS. And so they can have a connection between mediators of inflammation in the skin and overexpression of IRAK4 is a really powerful way we think of showing that IRAK4 plays a central role in this disease and that targeting IRAK4 effectively with a degrader to really be able to impact this disease. We were also able, in this noninterventional study, to really beta test a number of assays that we're now using and employing in our Phase I interventional study. So assays to measure IRAK4 and skin and blood using mass spec, for example, assays to measure inflammatory gene transcripts, using nanostring gene expression profiling. All of these assays that we've used in our noninterventional study, we've now beta tested them and have even greater confidence that they're going to be effective and useful for us in our Phase I study, which will involve both healthy volunteers, but also patients with HS and AD as we get toward the latter part of that study. We have data that are being generated. We had finished our accrual of HS faster than AD, analyzing the data in AD, both the skin and blood data in the coming months and presenting those data probably as we get in the fall at an appropriate meeting.

And so I guess one of the questions is what questions will be answered for us in terms of the mechanism in that initial data set or whatever data we will see this year. And then I believe there's a clinical hold on the multiple ascending dose portion of this study. Again, what was the rationale you think for that? And what data is going to be necessary for the discussions to let that part of the study open? And what's the time line for that?

So maybe, Jared, if you don't mind, I'll take this one. So maybe the second question first. So the clinical hold on the MAD. So just to go back a bit. So our study design that Jared put together was to initiate, and I say the stage where we're looking at different doses in an escalating manner to achieve -- to accomplish the understanding of safety, PK and initial understanding of degradation. I'll go into that in a second. And then upon analyzing the first few cohorts of data, we were planning to then decide based on the data in hand, which would be the starting dose for our MAD study. And so the feedback from FDA was actually for them to be part of their process to basically let us run the SAD, let us figure out what is the data set that we believe is sufficient to them, make the case to initiate a MAD portion of the Phase I study and then basically run it by them to make sure that we're only agreement with how we both interpret the data and more importantly, how we plan to use the data for the second part of the study. So in terms of what kind of data we expect to generate. I mean, as I said earlier, the reason -- one of the reasons why we're so excited is because the data set, this will be probably up to 80, if not more, subjects worth of data, just the SAD/MAD in healthy volunteer, which probably has never been done in protein degradation, also we've never done a placebo-controlled randomized study in protein degradation. So the ability to actually have control data set, where, for example, in the SAD, you will see, obviously, the PK, the safety and the understanding of is this a once-a-day oral drug or do we need a different dose in parallel. Our expectation is still once-a-day oral drug. Then what is the level of degradation that we see in the SAD, often, we actually need a multi-dose to reach maximum degradation. But so the initial degradation in the SAD, which, again, we expect to be lower, will allow us to actually model what it will look like upon repeat dosing. And this is why it's important for us to run a few SAD cohorts first. Importantly, understanding for the first time in human, what is the kinetics of degradation. We've never seen what happens if you give a drug to humans that degrade protein, what is the time component of degradation in the presence of a single dose. So how long does that knock down last? What is the protein resynthesis in vivo? What is the dose dependency of degradation? And because we have broad biomarker, the data set will be very rich. So this is just the SAD. Then the MAD will be -- so I would call it these proof of mechanism. And we actually call it proof of platform or platform proof-of-concept, just showing all the kinetics of degradation, the PK and the PD. Then in the MAD, where it's going to be more relevant to the later translation, we expect and our goal is to reach 85% degradation upon repeat dosing. This is a 14-day study. Because we know that based on preclinical models that, that degradation is sufficient to drive profound inhibition of the pathway that gives us kind of best-in-class effect in preclinical models. But importantly, not only we're going to be able to measure degradation and knockdown in blood, but we're going to look at actually knockdown in skin, which is another key relevant issue. These are not surrogate issues. These are actually disease-relevant issues. Both clear skin and blood. And we're also going to be not only detecting protein levels, but also downstream disease-relevant cytokines. So cytokines that we know the blockade of which is therapeutically relevant by antibodies or other technologies. And also, we're going to be monitoring C-reactive protein, which is a systemic biomarker of inflammation, even that is detectable also in healthy volunteer. So the data set at the end of the SAD, MAD in healthy volunteer only, we believe, will be the major derisking event for the later clinical development of this asset because, again, we will understand safety. PK knockdown and what the knockdown does to biomarkers that are disease relevant.

Great. And we'll certainly look forward to those day later this year. I want to give some time to KT-413. In the press release this morning about some upcoming preclinical data in lymphoma models in mice. I'm curious, can you explain the rationale for combining an IRAK4 degradation activity within immune activity? How does this differ from ways others are attacking IRAK4 and oncology? And how do you plan on kind of carving out a clinical role for this?

Jared, do you want to take this one?

Sure. So for KT-413, which is our so-called IRAKIMiD that has, as you've mentioned, this dual IRAK4 degrader activity along with the IMiD activity. We're developing this specifically for a subset of diffuse large B-cell lymphoma. These patients who have an activating mutation in MYD88, which you see in about 1/4 of DLBCL patients. And this mutation, we know confers a worst prognosis, worse survival first-line R-CHOP therapy. So we know that there's a very high unmet need for this very aggressive lymphoma. What happens when you have this MYD88 mutation is that you activate 2 pathways that are really driving the malignant phenotype in this disease. You're activating the sort of IRAK4, NF-kB pathway, but you're also activating the IRAK4 pathway, which suppresses the type 1 interferon response. And that's what renders these cancers so resistant to treatment and so aggressive in their behavior. The IRAKIMiD, by targeting both IRAK4 as well as the invaded substrates, we're able to simultaneously actually block both of these pathways, block the NF-kB pathway and actually restore the type 1 interferon response with a single compound. And by doing both of those 2 things together, mechanistically, there's a synergy that leads to profound antitumor effects, where we've seen really transformative antitumor activity in xenograft models and in patient-derived xenograft models. So really, that's -- the value proposition here is, in this particular MYD88-driven lymphoma, where both of these pathways are activated simultaneously, this approach allows us to block both of these pathways with a single compound. That's very different from other approaches, even just trying to go after IRAK4 alone, for example, with an IRAK4 kinase inhibitor, for example, which Ikaros has been doing in this type of lymphoma. The reason why they haven't seen major responses in DLBCL, we think, is because targeting IRAK4 by itself is insufficient to affect the biology of these cells. You really have to be able to again shut off the NF-kB pathway and also turn back on the type 1 interferon response. To do that, you need the IMiD activity together with the IRAK4 targeted activity, and the degrader is the best way to hit IRAK4, we believe. And then having this IMiD activity on top of that, we've devised the way to do that with a single compound.

So I think we have 3 minutes left. A lot of interesting things that you guys are going after and sort of strategically. And Bruce, I'll turn this to you a little bit. You remember the days sitting on this side of it and sort of kind of understanding what companies are keeping wholly owned, what they're partnering out, you're trying to figure out what the balance sheet looks like. What -- how you're thinking about resourcing different efforts, certainly for a younger company, going after autoimmune indications, certainly, the partnership with Sanofi seems to be really valuable for you, right? I mean, absolutely, blue-chip enterprise in that realm, it makes sense financially for you guys operationally as well. Talk to us a little bit about how you think the investment community needs to have a better appreciation. And then I pose this to you, in particular, you can be a little bit pejorative in terms of like this is what I never got before what you guys should have a better appreciation for. And now that I'm sitting in this seat, I think I want to highlight this kind of parenthetical response. But talk to us about how you're thinking about the strategy behind partnerships and how you're going to best resource the projects that you have going forward because there's so many directions you can go. You've made some decisions. What's that strategy?

Yes, sure. Happy to do that. I don't know. Do you want to -- I'm happy to chip in my thought.

Go ahead. I talked plenty.

Okay. Good. So yes, Chris, I appreciate the question. We've tried to be, over time, I think, have been very thoughtful and purposeful in the approach we've taken to the collaborations. They've all, as we mentioned, serve different purposes. Sanofi is really going to allow us to power up the immunology franchise, particularly with 474, and we're excited about what that brings. And Vertex, as Nello mentioned, has allowed us really to become disease agnostic as a company. I think looking forward, we'll take that same exact approach. We feel very strongly that we have the capabilities and the resources to drive our nonpartnered programs, both into and through the clinic, and that's very much our intention. That said, I think we have the luxury of really having a lot of optionality with respect to future partnerships. And so we'll keep that in mind. But with really a very lengthy cash runway at this point, I think access to capital is not likely to be the driver of any decisions. It will be more strategic in nature. So I think that's the best way I would answer that. And I don't know if you want to add anything.

Sounds good.

No, that's very helpful. Obviously, we're coming off an incredible team, you guys did your IPO during a period of incredible strength. We now have like a like 100 IPOs in the last 18 months or something crazy like that, right? And now here we sit actually in June of '21, and we're kind of in a relative bear market. And I think you guys are in a nice catbird position to have the strength of your balance sheet and also have existing partnerships there and not be dependent. By the way, in the Goldman Sachs investor survey that we put out this morning in terms of what people are expecting, the subsector within health care that is expected to do the most outperformance from the most people in the second half of the year was mid biotech. So we're coming back, baby. So we will be optimistic. This was the clients who are responding to that survey. So I think that will be helpful. One final note of people who want to learn so much more about this company, you can download, your guys are very good about putting up your corporate deck. But seriously members, 63 pages, that's you're like haunting people like C.J. and I. It's just like how would an initiation report exceed this. It's very like Genentech 2.0, where it's like we're not getting bored, just can refer you to the website in the corporate deck. So feeling very challenged here, but tremendous depth of detail and information and science there. So I think it's very helpful. So a lot to learn, a lot of exciting stuff that's going on in the space. Thank you, all of you for taking the time to join us for this presentation, and we certainly will look forward to all the progress that you'll have going forward. We appreciate it. Thanks very much.

Thank you, Chris.

Thanks, Jared.

Thanks, C.J.

Thank you, guys.