Good morning, and thank you everyone for joining the UBS Global Healthcare Virtual conference. I'm Colin Bristow, the biotech analyst here at UBS, and it's my pleasure to have our top pick, C4, here with us today. Speaking on behalf of the company, we have Andrew Hirsch, CEO, Stu Fisher, CSO, and Adam Crystal, CMO. Andrew and team, thank you for joining us today. Before we start, if anyone has a question, there is a question function in this global meet system. Alternatively, feel free to email me at colin.bristow@ubs.com and I'm happy to field the question for you. With that, I'll hand it over to Andrew. Please go ahead. Thanks, Colin, and thanks for UBS for hosting us. I did want to note that we have some exciting news that we announced this morning. As many of you know, we have been evaluating whether or not to take our EGFR program forward into the clinic. This morning, we're really pleased to announce and excited about this program that we are going to move that forward into the clinic. I'm sure we'll talk about that as we get through your list of questions through the chat. We're happy to answer any questions we can. Obviously, we didn't have any data today. That data's going to be presented at the Keystone meeting. We'll have an investor event around that to go through a lot of the data. That's in our press release we issued this morning. I'll turn it back to you, Colin, and fire away. Super. Thanks for timing that program advancement with our conference. Appreciate it. Let's just start high level from a platform perspective, there's obviously numerous degrader companies out there now, it's a hot space. How is C4's approach and platform differentiated versus your peers? Yeah, it's a great question, one we get a lot. I think there are clearly differences in approach across the companies. It's really hard for me to compare since I'm intimately focused on our platform. I know what you know, and what's publicly available about the others. What I'll really do is focus on what makes our platform unique, and there are really four key elements to that. First is really central for us. We focus on optimizing the entire degradation cycle rather than a single step in the process. For those of you new to the degrader space, one of the key differentiation features of a degrader versus inhibitors is that, once they've done their job of enabling the destruction of a single protein molecule, target protein molecule, they can actually go back and do it again, and we call this the catalytic cycle. That can range anywhere from 300 to 3,000 times a minute. We believe, though, that optimal degraders do this toward the 3,000 times per minute part of the range, and that's where you get maximal efficacy, you get the real benefits of degraders, and you can see differential biology. Our lead program is an example of this. If you look at the potency and the improved catalytic efficiency of our V programs, CFT7455, versus pomalidomide, for example. We induce apoptosis in our in vivo models. You don't see that. That's where really optimizing that catalytic cycle can really make the best degraders. Our entire approach is really designed to accomplish this. As I said, it's really fundamental to how we think about optimizing degraders. Secondly, kind of following along that, we've developed a framework of assays, methods, and tools that we use to really translate the kinetic properties of our degraders that we see in vitro into highly predictive models for in vivo performance. Those tools allow us to really move quickly and with confidence to get to a drug candidate nomination. I'd say the third key feature of our platform is that we really focus deeply on cereblon. It's a decision the company made very early on. It's one of the E3 ligases that are in the body. We chose it for two reasons. One, it's widely expressed in all tissues and compartments, so it gives us quite wide target latitude. We know that whatever target we want to go after, cereblon's going to be there to do the work. Secondly, it's the only really clinically validated ligase since it's the ligase of the IMiD drugs which have been on the market. There's a long track record, and we know what those do. The last reason is we haven't actually seen the need to go beyond that, because we've worked on about 45 targets over the history of the company. We've had about a 95% success rate with cereblon. We haven't seen the need to do that. We've also made a deep investment there. We've got about 15 distinct chemical series of cereblon binders. That really enables us to optimize degraders. I would say the last key feature is that we have the capability to do what we call MonoDACs or for the generic term, molecular glues in BiDACs or heterobifunctional degraders. Both can deliver viable clinical candidates. For example, our lead program is a MonoDAC. The EGFR program, for example, we announced this morning, as well as the BRD9 program, those are BiDACs. What that enables us to do is really match the target selection with the discovery optimization process. There are certain targets that lend themselves to one or the other. We have that flexibility given what targets we want to go after. I think those are the key four elements that are really important to how we think about differentiating and what's important for optimizing our degraders. At the end of the day, we think that our peer companies, their approaches are complementary to ours and given the breadth of degrader opportunities, I think there's room for everyone given that there's very little target overlap across the degrader companies. I think it's a wide-open space as you mentioned earlier, it's really exciting, and we're really happy to be a leader in the space. Great. Thank you. It's a good segue actually to the fact that your lead program is a MonoDAC, which is I think fairly unique amongst your peers. Can you talk about some of the complexities and technological challenges of developing a MonoDAC versus a BiDAC? Yeah, sure. I think there's a number of different ones, and I'll let Stu go into some of the technical details. I think for us, we're really flexible. We're not challenged either way. Once we get to sort of hit ID, all the tools and processes that I talked about earlier are really the same in terms of optimizing the degrader performance. I'll let Stu go into some of the technical details. Yeah, I think Andrew's really highlighted that these two approaches are truly complementary. It's not that we see fundamental differences between the two in our ability to optimize them to drugs. That's clearly been the case as exemplified by our pipeline. We've been able to advance both BiDACs and a MonoDAC to drug candidate status. I think it really comes down to target selection and which of these two approaches lends itself best to get a good degrader hit that we can then utilize our platform to optimize against. We don't really see any kind of challenge or benefit to either approach, but they do require subtly different medicinal chemistry approaches, but both of those are certainly within our capabilities. Okay, great. Some of your peers are using tissue-specific ligases. Just how do you think about that conception? Is it something that's attractive to you guys at some point? Yeah, I'll field that one. I think the vision of a tissue-specific ligase is quite attractive, and it's something we have talked about quite a bit at C4. In that vision, you can see perhaps the most precise medicine available, where you'd be able to target a specific indication with a ligase that's expressed in that particular tumor. I think the challenge comes, at least at this point in the field, on how do we do that to practice. On the one hand, one should ask what kind of targets would lend themselves to that to get maximal benefit of a tissue-specific ligase. On that front, by and large, I think most of the value in this approach lies in having a more safe profile, and that is that you don't have to worry about off-target or off-tissue mechanistic tox. That's what that tissue-specific ligase would bring. I think that opens up targets which would otherwise be pan-essential or toxic to other tissues. It opens up more landscape for targets, but I think that does put a lot of pressure then to ensure that that ligase is only expressed in those tissues. If you use those kind of targets, then you're going to lose that benefit of that selectivity. On the other hand, I would say one of the challenges I see with the ligase, the ligome as it is most of these ligases are generally very poorly characterized. We don't really understand their biology. We don't really understand their location and their expression levels or cycling within a different cellular differentiation state. I think that there's risk in trying to understand that and then deploy it at this stage. I do believe in the long run we will do this, but I think there's a lot of fundamental biology and chemistry needed to lift those ligases off the ground and deploy them as druggable entities. We're interested in participating in that effort, but it's not something we see that actually can be reduced to practice in the near term to deliver medicines to patients. That's what we focus on in our first phase of C4. I think in our future vision, certainly it does include downstream efforts and additional ligases to incorporate, include other applications such as tissue-specific ligases. Okay, great. Maybe moving to some more specifics of CFT7455, do you foresee a potential benefit in an asset that could preferentially target Ikaros versus Aiolos, in treating multiple myeloma? I can field this if you like, Andrew. Yeah. Why don't you take care of this one? It's hard to say with confidence that would be the case. I point to data in really multiple myeloma where maximum cell of those myeloma cells requires knockout of both IKZF1 and IKZF3. Knocking out either has some effect on cell viability, but maximal effect requires knockout of both. To some extent, this is true in the NHLs as well. We believe that our molecule is really optimized for both the multiple myeloma and NHL spaces. Furthermore, I think it's fair to say in our hands, the SAR is really inseparable in targeting IKZF1 and IKZF3. It's possible that it could be achieved, but I think certainly a challenge, and we see no benefit in doing so. Just to run us through, CFT7455 have equivalent potency and degradation kinetics on both the targets? That's right. Okay. I know this is a question you get a lot, could you just run us through how 745 is differentiated versus Bristol's, CELMoDs, iberdomide, 92480? Yeah, absolutely. We really optimized CFT7455 for potency on targeting IKZF1 through three, as well as catalytic activity. It is a fast molecule. We really believe this molecule has the opportunity to differentiate on two things. One would be simply efficacy. What I'd point to is the in vivo data we've shared before demonstrating that we achieve equal efficacy as CC-92480 at one one-hundredth the dose. We believe this positions us well clinically to translate those to efficacy which may be superior to anything that is currently available, whether approved or experimental. The second is that really on the back of this exquisite potency in terms of in vivo activity, we believe there's a differentiating opportunity to develop this molecule as a Dexamethasone-sparing agent. What I mean by that is that historically, IMiDs, as well as the experimental CELMoDs, have been developed and explored in combination with Dexamethasone. The primary reason for this is because Dexamethasone boosts the overall response rate and efficacy of Len and Pom and presumably 220. However, the feedback that we've gotten that we agree with entirely from KOLs is that our molecule is so active as a single agent, meaning no Pom, I'm sorry, meaning no Dex, that we may well be best served by moving it forward in the absence of Dexamethasone. Our first-in-human study enables us to find a dose of seven four five five, both as single agent as well as in parallel in combination with Dexamethasone, and move either or both of those forward into expansion parts. Okay, great. Just one question in my email, actually. How important is the rapidity of degradation in terms of realizing a clinical benefit? I think it's critically important, and I think that the data that speaks to that clearly is actually in the literature as well as data we've generated internally, which demonstrates the effect on cells which is had at active doses or clinically achievable doses. I'm speaking vaguely now, I'll clarify. What I mean by effect on cells is stasis versus apoptosis. To reach the conclusion I'm getting to really is that with these slower molecules, what's achieved is largely stasis. With the faster molecules, what's achieved is largely apoptosis. I believe to achieve a maximal or optimal anti-neoplastic effect, you really want to be killing those cells, and apoptosis certainly achieves that. Great. This is something we've talked a lot about, but at AACR, you presented some data on CFT7455's activity in Cereblon downregulated or partially depleted H929 cell lines. Could you walk us through these data and what should we take away from it and why is it important? Yeah, absolutely. Effectively, the model we created there was a model of resistance to lenalidomide and pomalidomide, where you take H929s, you grow them up in lenalidomide, Cereblon levels drop, they become resistant to lenalidomide. You switch them to pomalidomide, Cereblon levels drop a little bit further, and they're resistant to pomalidomide. What you have is a cell line which has resistance to either IMiD molecules we just discussed and downregulation of Cereblon. It's important to note that this model is potentially clinically relevant. It's published in the literature that patients who are on IMiDs do demonstrate downregulation of Cereblon. To some extent, that correlates with resistance. I don't want to reach a conclusion to what degree it causes resistance, but it's certainly a reasonable mechanism of resistance. Despite that downregulation of Cereblon and the active resistance to lenalidomide and pomalidomide, our molecule retains activity in that setting. This makes sense, right? One could hypothesize that the cells have learned to survive lenalidomide and pomalidomide by downregulating Cereblon to the point that lenalidomide and pomalidomide can't drive enough IKZF3 degradation to kill the cells. Our molecule is more potent and faster, effectively meaning it requires less Cereblon around to do the job, so it retains activity. In my mind, what this translates to is the very real possibility that our molecule would be active in an analogous setting in a blood cancer. Okay, great. Do you have, or have you established a preclinical model, a theoretical threshold of Cereblon depletion that would render seven four five five inactive? That's a super great question. I haven't actually thought about it quite in that way before. To be honest, we've looked at the flip side of it, which is to what degree do we need to degrade target for it to be maximally active. I think there, we do want to have greater than 80% target degradation. What we've modeled is for a portion of the 24-hour dosing cycle, though I'm confident we'll be able to obtain that for the entirety of a 24-hour dosing cycle. I think to what degree downregulation of Cereblon would confer resistance is a really hard question to answer. The literature is actually challenging, meaning one can look at baseline levels of Cereblon before a patient ever gets an IMiD and see whether or not that predicts responsiveness to an IMiD. The short answer is that the literature is mixed. Even that sort of simple first pass question with clinical data is very challenging to answer. Okay. A question we get a lot, I'm sure you do too, but in PERKIN trials, the phase I trial initiated in mid-April. In your press release today, you said sites are open enrolling. We still not had or confirmation of a patient dose. Have there been any delays? Can you just confirm on here that we're on track? Can you talk us through that? It's super fair question. It's an exciting milestone for us. We are on track. There have been no delays, certainly no significant delays. We are active and ready to enroll, and we are confident that we will meet our goal of achieving first patient first dose, in the first half of this year. Okay. Now playing those timelines forward, I guess kind of like a two-part question. When would you reasonably expect to be able to provide us with a data set from that trial? The second part of that question, again, is something we get a lot, I'm sure you do, is what is the potential for us to see something from you guys before year-end? Very important question. We have consistently been guiding to 2022 for the release of clinical data. This is really based on two important pieces of data that drive this. One is the timing. If we dose our first patient in the next month or so, we'll have six months until the end of the year. In my mind, that is not enough to put together a story of a dataset. It's enough time to put together a few data points, which would have a tremendous amount of error bars, in all of those points. The N would just be too low to have confidence that it was representative of the true data. I think ideally what we would like to put forward is a set of data representing the RP2D of one of the cohorts in our study, along with the PK and PD and safety data and hopefully efficacy data. I don't know how many dose levels it will take to achieve that. I think that would be the ideal to have a dose. I think that at some point next year, it is fair to expect us to have what we would consider a publishable unit, and we would put it forward at that time with the aim of presenting it at a medical meeting. Okay, great. As we think about that readout and the trial design, how many patients worth of data should we expect to get at that phase II go-forward dose? Sure. There are a few ways to answer that, and they're all straightforward, but they're different. It depends on whether we're talking about. There are three basic doses that will determine potentially, right. A dose in NHL, a dose in myeloma as single agent, and a dose in myeloma with Dexamethasone. Each of those, I would imagine, would have in the range of 12 to 15 patients if we do this well. In some cases, the data feeds into each other. It really depends. I would say something in the range of 12 to 15 at each of those dose levels, maybe a little bit lower in some cases. It depends on whether or not we present the entire data set. These are the doses for all of these conditions or if we're simply going to publish single agent in myeloma, single agent in NHL. Okay. Just I'll add to some of it depends on how many escalation cohorts we go through, right? I mean, that's obviously the big driver here. Right. We don't know until we know. Absolutely fair. Again, something we've talked about before, but can you remind us what are you hoping to see in terms of efficacy at the phase II dose? At the phase II dose? Yeah. I think this is one of the most critical questions for this study. How are we benchmarking efficacy? I think the trial is intentionally designed, so that the patient population in myeloma mirrors that in the phase I with CC-92480. This is for two reasons. One, scientifically, we think it's the right population to go into. Second is that it allows us to use that data as a reasonable benchmark. Obviously, phase I uncontrolled data, not perfect, but the best we can do. That data set's still emerging, but what CC-92480 published in ASCO 2020 was at their RP2D, which was one milligram plus Dexamethasone, three weeks on, one week off in about 20 patients and an overall response rate of about 50%. That is PRs or better. Effectively, we want to compare ourselves to that. Now, that number is challenging by something that all such numbers are challenged by, low N, right? I don't know if that 50% is really 35%, 70%, or 50%. Right. What we're aiming to be is at our single agent RP2D, just CFT7455, I'd like to see us be as good or better than 92480 plus Dex. With our molecule 7455 plus Dexamethasone, the goal is to be better than the activity achieved with 92480 plus Dexamethasone. Great. Let me just add, though, that the data we're talking about sharing in 2022 is dose escalation data. You're likely to see a mix of patients at different doses versus the data Adam referred to with 92480, which was 20 patients at a single dose. I think that's the other sort of caveat to just be careful of when folks will inevitably compare the data we release next year. Sure. Actually, another question on the trial design, but how are you guys managing Cytopenias, et cetera, and how does this contrast to the Bristol program? Yeah. I have to say, of course, I don't know the details of how the Bristol program is managing it. There are constraints that any phase I trial has in terms of what supportive care, meaning growth factor, can be given during cycle 1. If it's given during cycle 1, it effectively becomes challenging, if not impossible, to identify the appropriate dose and dose-limiting toxicity. After that DLT evaluation period, we do allow support for Cytopenias to be given really in line with additional standard care. Okay, great. Maybe we can switch gears now to CFT8919, obviously the talk of today. Just take us a step back and walk us through this program, how we got to where we are, what you have seen that's now given you confidence to take this forward. Stewart, do you want to tackle that? Yeah. I think it's fair to say we're extraordinarily excited to move this forward. Really, the idea of the molecule frames this out, and what we're putting forward is an orally bioavailable allosteric degrader, which specifically targets EGFR L858R, the driver mutation in something like 40% of EGFR positive non-small cell lung cancer, and also covers the secondary mutations which occur in EGFR, which often cause resistance by the first, second, or third-generation inhibitors, such as the T790M gatekeeper mutation or the C797S mutation, which destroys the covalent binding site of Osimertinib. We think there's a very clear path to develop this molecule in the setting of resistance to Osimertinib in patients who have such mutations. I think it's fair to say that we also think there's a very viable path if the clinical data reads out as we hope it will, to identifying a role for this molecule in that upfront space. There are a few things that are different about this molecule than all other kinase inhibitors that are out there in the clinical realm, and I think a couple worth pointing out, obviously, it's a degrader. This comes with potential advantages. I think it's fair to say osimertinib is a wonderful molecule. It's a wonderful kinase inhibitor, potent, selective inhibition of mutant EGFR activity and tolerability. Two things I would point out are that overall, the PFS is 17 months. While the overall response rate is sitting about 80%, 17 months is something that I think we as a community should aim to do better for in the first-line setting for EGFR mutant lung cancer. I think that a degrader approach might provide the opportunity to sort of break through that, let's call it 17-month barrier that you see with Osimertinib, that I think would be very challenging to do by improving with a better kinase inhibitor. There are reasons to believe a degrader could do it. The other thing that I would point out is that this is an allosteric degrader which specifically targets the L858R mutation. That L858R mutation is something of a liability for Osimertinib. While the overall PFS in the frontline study, which resulted in the approval of Osimertinib, is 17 months, it's different for L858R and the activating Del19 mutation. Really, in L858R, it goes down to about 14 months in comparison to about 21 months for exon 19 deletion. Which is to say the bar for this molecule, even in the front-line setting, isn't the overall 17 months plus, but lower, 14 months, and we believe that creates a real medical unmet need that our molecule has potential to address. I would add one other thing, too, because it's an allosteric binder, it doesn't compete with the inhibitors. We'll see what the data looks like. There is the potential. It doesn't compete, so they could be used in combination with a kinase inhibitor if that was warranted based on the data and based on the treatment approach. Okay. Timelines for this program? Can you help us think through to when we could potentially see some clinical data? I think it's easiest to follow the press release on this one, which really points to IND filing mid-next year. I think that following from there, I would apply sort of to your standard timelines from IND filing the first patient in, then I would expect something in the range of a year before we had the things for a complete story that we just articulated referring to publish rather than a few data points. Okay, great. Maybe let's talk about the BRD9 program now. This is a target that's not really been clinically validated. What do you foresee are some of the potential risks to this program? Sure. I think it's a very fair question in that any target which has not previously been pursued clinically comes with risks that tried and true clinical targets do not. I think that for this particular molecule, there is a strong scientifically based rationale to believe that effectively therapeutic index will be there. That's really based on the concept of synthetic lethality, meaning that in cancers which are susceptible to depletion of this target, such as synovial sarcoma or SMARCA4-mutant tumors, that susceptibility is specific or particular to the tumor cell by virtue of the genetic lesions which drive the tumor, they're susceptible to BRD9, FUS-SS18 translocation in synovial sarcoma if you want deletion two part for the other two. Normal cells don't have that dependency, creating that therapeutic window. I think the other real piece of data that increases our confidence that BRD9 degradation would be tolerable is data that recently was released at ASH in abstract form by Inouye et al, along with Omar Abdel-Wahab and others. Really what this showed, which was of note to us, is that conditional knockout of BRD9 in the hematopoietic compartment really results in these mice that are tolerable. There's a little bit of a myeloid shift. There's thrombocytopenia. There's a little bit of upregulation of chemokine, these mice were relatively unaffected by that. I think there is very real reason to believe that it would be tolerable. I think in terms of efficacy, the data is extraordinarily strong, meaning there's a dependency on BRD9, and exciting for the target, and the reason we like it so much, or one of them, is that you need to degrade it. What I mean by that, in a straightforward manner, is that, for example, synovial sarcoma cells don't care about BRD9 inhibition. One can take a bromodomain inhibitor, put it on synovial sarcoma cells, and they simply don't care. There's no effect on cell viability. Instead, if you deplete the target, basically replicating what's seen when you hairpin out or knock out the target, you see a real effect on cell viability, and in vivo we have demonstrated really nice regressions with single agent with our molecule. In short, any novel target has risks, but there are very real reasons to believe that going after this with a molecule like ours will result in efficacy as well as an appropriate therapeutic index. Okay, great. Obviously, synovial sarcoma is a very tough to treat tumor, nothing out there, and potentially lending itself to a faster market strategy. Can you outline what that looks like from the development path for your BRD9 degrader and help us think about what do you think you need to show in a potentially phase II registrational setting? Absolutely. I'll be clear, we have yet to finalize our clinical trial design, though I think I know what it's going to look like. I think it'll frankly be straightforward. An escalation of single agent finding the dose and then an expansion in a limited number of patients, let's say 20-30, to see whether or not we achieve a predetermined signal which would allow us to open up that expansion further to a number of patients which would allow us to achieve that accelerated approval. I don't want to speculate exactly on what that number is, but I think the fact that it is a relatively rare indication will put downward pressure on the number required in that additional expansion. I think further speculation is also challenging because it will depend on both the data that we have, the degree of efficacy which is deemed, as well as interactions with health authorities. I think, in short, find a dose, expand in a smallish number of patients to get a better sense of the signal, and then determine the minimal number of patients we need to further enroll to get to that accelerated approval. Great, thank you. Any other indications that you think targeting BRD9 could lend itself to? There is a population of patients who have SMARCB1 deletion, which biologically creates this dependence on BRD9 as well by a very similar mechanism. This includes things like ATRT and rhabdoid tumor and epithelioid sarcoma. Together, they are a meaningful number of patients. We think that the best path to initial registration is in synovial sarcoma, but the data says that if it works there, it should work in these other tumors as well. Then beyond that, I think it's fair to say that there's a large literature supporting that BRD9 does play a role in other malignancies. At present, it's not exactly clear the best way to use that in other indications, but there's data in AML, there's data published in ovarian cancer, there's data published in prostate cancer that suggests a role. We keep very close tabs on this and are hopeful that with time, there will emerge very clear opportunities to use BRD9 degrader in other indications. Great, thank you. Maybe we need to move on to the BRAF and RET programs. Similar line of questioning. Can you walk us through what you've seen there that got you excited and then the development timelines and plan there? Sure. I'll speak to BRAF, and then perhaps I'll pass the baton to Stu to speak to RET. I think BRAF is extraordinarily exciting for us, really for two reasons. Three, I would say. The first is the rationale. This molecule effectively degrades type 1 BRAF mutants, such as the V600E mutant. What this means is that this monomer is degraded. It cannot incorporate into the dimer and can't be active in that dimer setting, which occurs with the approved RAF inhibitors by virtue of paradoxical activation. It really overcomes the potential liability of all of the approved type 1 RAF inhibitors, which may indeed limit their efficacy and the emergence of resistance. I think that translates to two other things that we're excited about, which is really deep. The data that has me particularly excited to put this into patients is data that we have made public before in the S1 and elsewhere, which demonstrates that our molecules are, in comparison to approved RAF inhibitors, able to achieve a deeper and more durable regression in what I think fair to say is a model of the upfront setting, and that it retains activity in the resistant setting. In particular, what we did was we knocked in NRAS Q61K, a clinically bona fide mechanism of resistance to RAF inhibition in melanoma, into an A375 melanoma model, BRAF V600E. In that setting, as you would predict, those models are dead insensitive to RAF inhibitors. Our molecule retains activity in that setting, suggesting that it really could have the activity in the relapse setting that we've been hypothesizing. Strong rationale, deeper and more durable in the upfront setting than approved RAF inhibitors, pre-clinically, and activity in the resistant setting. Great. Thanks. Stu, you want to tackle RET? Yeah, I'll tackle the RET program. We remain very excited about the RET program potential. We're also quite aware that this is a competitive space. Pralsetinib and selpercatinib are really excellent drugs, and that is playing out in the clinic. They have limitations for sure, and that is that they're prone, both of them, to solvent front mutation, and that is emerging in clinical data. The goal for our program is to have a degrader that covers all the potential mutants that can emerge, both gatekeeper and solvent front mutations, in addition to covering the fusions that cause the disease as well. We're looking for a molecule that is really truly best in class. What I would say is that we're making great strides on that. We've actually got molecules which do cover within a tenfold potency range, all of those mutants and the frontline sort of fusions that drive the disease. We want to make sure that any molecule we put forward is going to have the profile that can be best-in-class. We're taking, not our time, but we're taking great care in making sure that those compounds that we do advance have all the features of a best-in-class molecule. Okay, that's great. Maybe just a quick question, switching back to CFT7455. Because Bristol's instead of differentiate strategy in terms of taking different assets into multiple myeloma versus NHL. What gives you the confidence that CFT7455 is the right hammer for both those nails? Sure. I think I would say that we don't have any particular insight into what's driving BMS's strategy. I'm very reluctant to speculate on that. I think that we are driven by the data that we have as well as our understanding of the biology, which we discussed earlier, really that for these indications, you really want to be crushing IKZF1 and IKZF3. We designed a molecule to do that. We believe we've achieved it. It has the opportunity to be best in class, and as such, it's really appropriate, if not optimized, for both of those indications. Okay, great. Then maybe just, as we're drawing to the end of time, can you talk a little bit about just your cash position and burn rate and the runway that gives you? Yeah, sure. I can tackle that. As we reported in our latest filing, we ended the quarter with $346 million in cash. Obviously, with the announcement this morning moving the EGFR program into the clinic, that's going to increase our spend a little bit. It's really skewed toward late 2022 and 2023 as the clinical trial ramps up. Today, we're not really providing an update on runway guidance. We're excited to really move this program forward, we don't have an update for you on runway today. Okay, that's great. Anything you can tell us about beyond the assets we've talked about, I know you're working on some sort of transcriptional control, you have partnered programs. Anything we should be watching out for there? Yeah. I'll say on the partner programs, obviously, we're not really allowed to talk about many of those. We're excited about the progress we've made. We've made really excellent progress across all three of our collaboration partners in the programs within that. Hopefully, as we get closer to them moving those into the clinic, we'll be able to share more, but until then, I really wouldn't expect any communication beyond BRAF, obviously, which is the Roche collaboration. There's not really much we're allowed to say, and so I wouldn't expect there to be much there. Similarly, we have some really exciting targets that we're working on across both MonoDAC and BiDAC approaches that are earlier in our pipeline. At this point, we don't really want to share anything about them, including what the targets are or timelines. As we get closer and have kind of line of sight to develop a candidate and think about what that. Clinical program timing is, we'll share more. For now, not much to say. Stu, you want to add anything about how we're thinking about some of these targets, maybe at a high level? I think at the highest level, it goes back to where we started this conversation, that we have capabilities both for BiDACs and MonoDACs. I will say this, we're investing heavily in the MonoDAC approach to further expand our capabilities there and really complement the strength that we have in the BiDACs that we've demonstrated to date. I'd say, going forward, what you'll see is C4 continue to expand on its existing platform, but grow most heavily in the MonoDAC capability. That's where we feel we can truly provide complementary approaches to some of the most challenging targets out there. That's really our vision. Okay. Then just, I guess, as a continuation from the partnership discussion, as you think about moving towards commercialization CFT7455, even maybe sooner CFT8634, would you look to partner these on a commercial basis, or is this something you want to go at alone? Let me talk about CFT7455 first. I think that we're very comfortable as a small company taking that program through the phase I/II that we've outlined and through potential accelerated approval based on what the data looks like. Obviously, this program we think has greater potential than just that in penta-refractory myeloma or relapsed refractory non-Hodgkin's lymphoma. We recognize that moving this program forward into 2nd line, 3rd line, et cetera, is going to require large global studies, with comparator arms against the combination regimens that are the mainstays of myeloma treatment today. That's something that we're probably unlikely to be able to execute well, and it would be best served doing that with a partner. Likely for that, we would. We'd obviously want to keep some role in the program. It's an important program for us. We think has really large potential. We're not looking to out-license it. Certainly, we would want to have someone to collaborate with and help really maximize the value of this asset to patients across all lines of therapy and all indications where we think the drug will have utility. BRD9 is a very different story, as well as frankly, I think EGFR. I think that those are indications where a company of our size can move that forward on our own and frankly, commercialize ourselves, in targeted focus markets. That's something, when we get there, we'll likely consider doing. That's great. I think that brings us to the end of time. This has been fantastic. Thank you. Thank you, Andrew, Adam, Stu. This is super insightful. If anyone has any follow-ups, feel free to email me at colin.bristow@ubs.com. Thank you everyone for dialing in and have a great day. Thanks, guys. Yeah, thanks for having us. Thank you. Have a good day, everyone.