Good morning, and thank you, everyone, for joining the virtual UBS Global Healthcare Conference. I'm Colin Bristow, 1 of the biotech analysts here at UBS, and it's my pleasure to have our top pick C4 here with us today. So speaking on behalf of the company, we have Andrew Hirsch, CEO Stu Fischer, CSO and Adam Crystal, CMO. So 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 Meat system.
But alternatively, feel free to email me at colin.bristowbs.com, and I'm happy to fill the question for you. So with that, I'll hand it over to Andrew. Please go ahead.
Yes. 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. And 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. But we're happy to answer any questions we can. Obviously, we didn't have any data today. That data is going to be presented at the Keystone meeting. And we'll have an investor event around that to go through a lot of the data and that's in our press release we issued this morning.
So I'll turn it back to you, Colin, and fire away.
Super. And thanks for timing that program advancement with our confidence. Appreciate it. So let's just start high level on a from a platform perspective. There's obviously numerous regulated companies out there now.
It's a hot space. How is C4's approach and platform differentiated versus your peers?
Yes, it's a great question, 1
we get a lot. And 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. And I know what you know and it's publicly available about the others. But what I'll really do is focus on what makes our platform unique and there are really 4 key elements to that. And first is really central for us.
We focus on optimizing the entire degradation cycle rather than a single step in the process. And so for those of you kind of new to the degrader space, 1 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 sort of cycle. And that can range anywhere from 300 to 3000 times a minute. And so we believe though that optimal degraders do this towards 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. And so that's our lead program is an example of this. If you look at the potency and the catalytic the improved catalytic efficiency of our lead programs 7, 455 versus pomalidomib, for example, we actually see we induce apoptosis in our in vivo models and you don't see that. And so that's where really optimizing that Calytic cycle can really make the best of raters.
And our entire approach is really designed to accomplish this. And 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. And those tools allow us to really move quickly and with confidence to get to a drug candidate nomination. I'd say the 3rd key feature of our platform is that we really focus deeply on cerablon.
It's a decision that company made very early on. It's 1 of the E3 ligases that are in the body. And we chose it for 2 reasons. 1, 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, CerroBLON is going to be there to do the work. And secondly, it's the only really clinically validated ligase since it's the ligase of the image drugs, which have been on the market. There's a long track record, and we know what those do. And the other 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 Cerablon.
So we haven't seen the need to do that. And then we've also made a deep investment there. We've got about 15 distinct chemical series of cereblon binders, and that really enables us to optimize degraders. And then I would say the last key feature is that we have the capability to do what we call Monodax or for the generic term molecular glues and bideac or hetero bifunctional degraders. And both can deliver viable clinical candidates.
For example, our lead program is a mono Dac and then the EGFR program, for example, we announced this morning, as well as the BRD-nine program, those are buybacks. And what that enables us to do is really match the target selection with the discovery optimization process. So there are certain targets that lend themselves to 1 or the other. And so we have that flexibility given what targets we want to go after. So I think that those are the key 4 elements that are really important to how we think about differentiating and what's important for optimizing our integrators.
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 greater companies. And so I think there's really a 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. And so, I mean, 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. And can you talk about some of the complexities and technological challenges of developing a monodac versus a Vidaac?
Yes, I mean, sure. I mean, 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 don't 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 de greater performance.
But I'll let Stu get into some of the technical details.
Yes, I think Andrew has really highlighted that these 2 approaches are truly complementary. And it's not that we see fundamental differences between the 2 and 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 BDAX and a monoDAC to drug candidate status. So I think it really comes down to target selection, which of these 2 approaches lends itself best to get a good to greater hit that we can then utilize our platform to optimize against. So, we don't really see any kind of challenge or benefit to either approach, but they do require subtly different med chem approaches, but both of those are certainly well within our capabilities.
Okay, great. And some of your peers are using tissue specific fly gazes. Just how do you think about that conceptually? Is it something that's attractive to you guys at some point?
Yes, I'll fill that 1. 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. I think the because 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 to reduce that to practice.
On the 1 hand, 1 should ask what kind of targets would lend themselves to that to get maximum benefit of a tissue specific ligase. And on that front, I think if you're by and large, I think most of this, there's a value in this approach lies in having a more safe profile. That is that you don't have to worry about off target or off tissue mechanistic tox, that's what that targets tissue specific ligase would bring. I think that opens up targets that would otherwise be pan essential or toxic to other tissues. So 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, because then if you use those kind of targets, then you're going to lose that benefit of that selectivity.
On the other hand, and so and I would say 1 of the challenges I see with the ligase the ligome as it is, most of these ligase 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. So, 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. And so that's what we focus on in our first phase of C4. But 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. And then maybe moving to some more specifics of 7, 455. What is do you foresee a potential benefit in an asset that could preferentially target Ikaros versus AROS in treating multiple myeloma?
I can field this, if you like, Andrew.
Yes. Adam, why don't you take care of this 1?
It's hard to say with confidence that, that will be the case. And I point to data in really multiple myeloma, where maximum sales 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. And to some extent, this is true in the NHLs as well. So 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 IKCF1 and IKCF3. It's possible that it could be achieved, but I think certainly a challenge and we see no benefit doing so.
So just remind us, does 7, 455 have equivalent potency and degradation kinetics on both the targets?
That's right.
Okay. And then I know this is a question you get a lot, but could you just run us through how 745 is differentiated versus Bristol, Salmod's iberdomide 9, 2480?
Yes, absolutely. So we really optimized CFT-seven thousand 455 for potency on target being AKZF13 as well as catalytic activity. It is a fast molecule. And we really believe this molecule has the opportunity to differentiate on 2 things. 1 would be simply efficacy.
And what I point to is the in vivo data we've shared before demonstrating that we achieved equal efficacy as DC92, 480 at oneone 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. And 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. So what I mean by that is that historically, IMIDs, as well as the experimental cell mods have been developed and explored in combination with dexamethasone. And the primary reason for this is because dexamethasone boosts the overall response rate and efficacy of LEN and PAM in presumably 2020.
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 PAM, dex that we may well be best served by moving it forward in the absence of dexamethasone. And our first in human study enables us to find a dose of 7, 455 both as single agent as well as in parallel in combination with dexamethasone and move either or both of those forward into expansion.
Okay, great. Just 1 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 has had at active doses or clinically achievable doses. And I'm speaking vaguely now, I'll clarify. What I mean by effect on cells is spaces versus apoptosis. And to reach the conclusion I'm getting to really is that with these slower molecules, what's achieved is largely stasis.
And with the faster molecules, what's achieved is largely apoptosis. And I believe to achieve a maximal or optimal antineoplastic effect, you really want to be killing those cells and apoptosis certainly achieves that.
Great. Now this is something we've talked a lot about, but at AACR, you presented some data on 745's activity in cerebron down regulated or partially depleted H949 cell lines. Could you just could you walk us through these data and what should we take away from it and why is it important?
Yes, absolutely. So effectively, the model we created there was a model of resistance to LEN and POM, where you take H-29s, you grow them up in LEN, seroglond levels drop, they become resistant to LEN, then you switch into POM, seroglond levels drop a little bit further and they're resistant to POM. And then what you have is a cell line, which has resistance to HER2MID molecules we just discussed and down regulation of Seraflin. 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 down regulation of CerroBlind.
And to some extent, that correlates with resistance. I don't want to say to reach a conclusion to what degree it causes resistance, but it's certainly a reasonable mechanism of resistance. Despite that down regulation of Sarafon and the active resistance to lenin palm, our molecule retains activity and that's it. And this makes sense, right? 1 could hypothesize that the cells have learned to survive LENNPOM by down regulating cereblon to the point that LENIN POM can't drive enough IKZF13 degradation to kill the cells.
But our molecule is more potent and faster, effectively meaning it requires less cereblon around to do the job, so it retains activity. And in my mind, what this translates to is the very real possibility that our molecule would be active in an analogous setting.
Okay, great. Do you have or have you established in a preclinical model a theoretical threshold of serogron depletion that would render 7, 455 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. And 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 the 24 hour dosing cycle.
But I think to what degree down regulation of CerroBlanc would confer resistance is a really hard question to answer. The literature is actually challenging, meaning 1 can look at baseline levels of cerablon before patient ever gets an IMBIT and see whether or not that predicts responsiveness to an IMBIT. And the short answer is that the literature is mixed. So even that sort of simple first pass question with clinical data is very challenging.
Okay. Now a question we get a lot, I'm sure you do too, but Perkin trials, your the Phase 1 trial initiated in mid April in your press release today, you said sites are open and rolling. 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. And now playing these timelines forward, I guess kind of like a 2 part question. When would you reasonably expect to be able to provide us with a data set from that trial? Then 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. And this is really based on 2 important pieces of data that drive this. 1 is the timing. If we dose our 1st patient in the next month or so, we'll have 6 months until the end of the year.
In my mind, that is not enough to put together a story of a data set. 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. And we're just too low to have confidence that it was representative of the true data. And so I think ideally what we would like to put forward is instead of representing the RP2D of 1 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.
And I think that would be the ideal to have a dose. But 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 forward at that time with the aim of presenting it at a medical meeting.
Okay, great. And then as we think about that readout and the trial design, how many patients' worth of data should we expect to get at that Phase 2 go forward dose?
Sure. So there are a few ways to answer that and they're all straightforward, but they're different. So it depends on whether we're talking about the 3 basic doses that will determine potentially, right, a dose in NHL, a dose in myeloma as So each So each of those I would imagine would have in the range of 12 to 15 patients if we do this well. And in some cases, the data feeds into each other. So 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.
And it depends on whether or not we present the entire data set, right? 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. And 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. So and we don't know until we know.
Absolutely, fair.
And again, something we talked about before, but can you remind us what are you hoping to see in terms of efficacy on the at the Phase 2 dose?
At the Phase 2 dose, yes. So I think this is 1 of the most critical questions for this study. How are we benchmarking efficacy? And I think the trial is intentionally designed both to so that the patient population in myeloma mirrors that in the Phase 1 with CC92, 480. This is for 2 reasons.
1, scientifically, we think it's the right population to go into. And second is that it allows us to use that data as a reasonable benchmark. Obviously, Phase 1 uncontrolled data, not perfect, but the best we can do. That data set is still emerging, but what CC92, 480 published in ASCO 2020 was at their RP2D, which was 1 milligram plus dexamethasone, 3 weeks on, 1 week off, in about 20 patients and overall response rate of about 50%. And that is PR's RAVIK.
So effectively, we want to compare ourselves to that. Now that number is challenging by something that all such numbers are challenged by low end, right? I don't know if that 50% is really 35%, 70% or 50%. But what we're aiming to be is at our single agent RP2D, just CFT-seven thousand 455, I'd like to see us be as good or better than 9, 240 and 80 plus dex. And with our molecule 9, 455 plus dexamethasone, the goal is to be better than the activity achieved with 9, 200, 000, 000, 000, 000, 000, 000, 000, 000, 000, 000, 000, 000, 000, 000, 000, 000, 000, 000, 000
And let me just add though, right, that the data we're talking about sharing in 2022 is dose escalation data. So you're likely to see a mix of patients, right, at different doses versus the data Adam referred to with 9, 200, 000, 000, 000, 000, which was 20 patients at a single dose. So I think that's the other caveat to just be careful of when folks will inevitably compare the data we release next year.
Sure. And actually, another question on the trial design, but how are you guys managing cytopenias, etcetera? And how does this contrast to the Bristol program?
Yes. 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 1 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 the toxicity. But after that TLC evaluation period, we do allow support for cytopenias to be given really in line with non institutional standard of care.
Okay. Okay, great. Maybe we can switch gears now to 8919. So, obviously, the talk of today And 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 giving you confidence to take this forward?
Sure.
Adam, you want to tackle that?
Yes. I mean, 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 L858 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 to either 1st, 2nd or 3rd generation inhibitors such as the T790M gatekeeper mutation, the C797S mutation, which destroys the covalent binding site of Usimarin. 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.
And 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. 1 of the things 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. But 2 things I would point out are that, overall, the PFS is 17 months. So while the overall response rate is stunning 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. And I think that a de greater approach might provide the opportunity to sort of break through that, let's call it 17 month barrier that you see with osimeridine that I think would be very challenging to do by improving with the better kinase.
There are reasons to believe a degrader could do it. The other thing that I would point out is that this is a specific an allosteric degrader which specifically targets the LA58R mutation. And that LA85R mutation is something of a liability for osimerinib. While the overall PFS in the frontline study, which resulted in the approval of osimertinib is 17 months, It's different for LA5R and the activating L mutation. Really in LA5R, it goes down to about 14 months in comparison to about 21 months for exon19 deletion, which is to say the bar for this molecule, even in the frontline setting, isn't the overall 17 months plus but lower on 14 months.
And we believe that creates a real medical unmet need that our molecule has the potential to address.
I would add 1 other thing too, because it's an allosteric binder. It doesn't compete with the inhibitors. So we'll see what the data looks like, but there is the potential, it doesn't compete. So that could be used in combination with a kinase inhibitor if that was warranted based on the data and based on the treatment approach.
Okay. And timelines for this program, I mean, can you help us think through to when we could potentially see some clinical data?
I mean, I think it's easiest to follow the press release on this 1, which really points to IND filing mid next year. And I think that following from there, I would apply sort of to your standard timelines from IND filing the first patient in. And then I would expect something in the range of a year before we had the same sort of 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. So this is a target that's not really been clinically validated. What do you foresee as some of the potential risks to this program?
Sure. So I think it's a very fair question that any target, which has not previously been pursued clinically with risk that tried to improve 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. And 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 SMARCB1 bleed tumors, that susceptibility is specific or particular to the tumor cell. By virtue of the genetic lesions that make them susceptible to BRD9 by virtue of the genetic lesions would drive the tumor, they're susceptible to BRD9 that the SSAT and S section translocation and synovial on some RP-one will be the tumor and the other And normal cells don't have that, creating that therapy.
I think the other real piece of data that increases our confidence that BRD-nine degradation will be tolerable is data that recently was released at cash in abstract form by Inouye et al. Along with Omar Abdelahab and others. And 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 tolerable, there's a little bit of a myeloid shift, there's thrombocytopenia, there's a little bit of upregulation of hemoglobin, but these mice were relatively unaffected by that. And so 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 the dependency on BRP-nine and exciting for the target and the reason we like it so much or 1 of them is that you need to degrade it.
What I mean by that in a straightforward manner is that, for example, synovial sarcoma cell don't care about BRD-nine inhibition. 1 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 complete the target, basically replicating what's seen when you air pin out or knock out the target, you see a real effect on cell viability and in vivo we have demonstrated really nice regressions in single agent with them. So in short, any novel target has risk, but there are very real reasons to believe that going after this good molecule like ours as well as an appropriate therapeutic index.
Okay, great. And so obviously, cyanobelzalkane 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 BFD9 integrator? And help us think about what do you think you need to show in a potentially Phase 2 registrational setting? Absolutely.
So I'll
be clear, we have yet to finalize our clinical trial design, though I think I know what it's going to be. I think it will frankly be straightforward. An escalation of single agent finding the dose and then an expansion in an unlimited number of patients, let's say, 20 to 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 would put downward pressure on the number required in that additional expansion. And I think further speculation is also challenging because it will depend on both the data that we have, the degree of efficacy, which is seen, as well as interactions with health authorities.
So I think, in short, find a dose, expand in a smaller number and a smallish number of patients to get a better sense of 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 BRD-nine could lend itself to?
Absolutely. So there is a population of patients who will have SMARCB1 deletion, which biologically creates this dependence to MBRP9 as followed by a very similar mechanism. This includes things like ATRT and rhabdomor and a biliary sarcoma. And 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.
And 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. And 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 prostate cancer that suggests a role. So we keep very close tabs on this and are hopeful that with time, there will emerge very clear opportunities to use here at United Greater
Great. Thank you. Maybe we can move on to the BRAF and REP programs. Can you just similar line of questioning, could you walk us through what you've seen there that got you excited and then the sort of development timelines and plan there?
Sure. So I'll speak to BRAF and then perhaps I'll pass the baton to Stu to speak to Red. I think BRAF is extraordinarily exciting for us, really for 2 reasons. 3, I would say. The first is the rationale.
This molecule effectively degrades type 1 BRAF mutant 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 RAP inhibitors by virtue of paradoxical activation. So it really overcomes the potential liability of all of those approved Type 1 RAF inhibitors, all of the approved RAF inhibitors, which may indeed limit their efficacy in the emergence of resistance. And I think that translates to other things that we're excited about, which is really deep.
And the data that has been particularly excited to put this into patients, the data that we have made public before in the S1 and elsewhere, which demonstrates that our molecules are in comparison to approved RAP inhibitors, able to achieve a deeper and more durable regression and what I think fair to say is a model of the upfront setting, and that it retains activity in the resistance. So in particular, what we did was we knocked in NRAS261, a clinically bonafide mechanism of resistance to rapid inhibition in melanoma into an A375 melanoma model, Chesapeake 600E. And in that setting, as you would predict, those models are insensitive to rapid headcounts. However, our molecule retains activity in that setting, suggesting that really could have the activity in the relapse setting that we've been hypothesizing. So strong rationale, deeper and more durable in the upfront setting than approved graft inhibitors pre clinically and activity in the persistent setting.
Great, thanks. And then Stu,
do you want to tackle RET?
Yes, I'll tackle the RET program. So we remain very excited about the RET program potential. But we're also quite aware that this is a competitive space. Praseltinib and sepracatinib 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 from mutation and that is emerging in clinical data.
So, the goal for our program is to have a degrader that covers all the potential mutants that are that can emerge both gatekeeper and solvent front mutations, in addition to covering the fusions that cause the disease as well. So 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 with within a 10 fold potency range, all of those mutants and the frontline sort of fusions that drive the disease. But we want to make sure that any molecule we put forward is going to have the profile that can be best in class.
So we're taking not our time, but we're taking great care and making sure that those compounds that we do advance have all the features of the best in class molecule.
Okay. That's great. Maybe just a quick taking different assets into multiple myeloma versus NHL. What do you think the reason is for this? And what gives you the confidence that 7, 455 is kind of 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' strategy. And so 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, IKZF1 and IKZF3. So 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. And then maybe just as we're going 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?
Yes, Cheryl, I can tackle that. So as we reported in our latest filing, we ended the quarter with $346, 000, 000 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, but don't have an update for you on runway today.
Okay. That's great. And 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?
Yes. So I'll say on the partner programs, obviously, we have very 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 3 of our collaboration partners and the programs within that. And hopefully, as we get closer to moving them, moving those into the clinic, we'll be able to share more.
But until then, I really wouldn't expect any communicate beyond BRAF, obviously, which is the lead in the Roche collaboration. There's not really much we're allowed to say. And so I wouldn't expect there to be much there. And then, similarly, I think we have some really exciting targets that we're working on across both mono DAC and buyback 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 and timing is, we'll share more. But for now, not much to say. Stu, do you want to add anything about how we're thinking about some of these targets maybe at a high level?
Yes. I mean, I think what we're at the highest level, we it goes back to where we started this conversation and that we have capabilities both for buybacks and mono DACs. 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 buybacks that we've been demonstrating to date. So I'd say, going forward, what you'll see is C4 continue to expand on its existing platform, but grow most heavily in the Monodact capability, because that's what we feel we can truly provide complementary approaches to some of the most challenging targets out there. That's really our vision.
Okay. And then just I guess as a continuation from the partnership discussion, as you think about moving towards commercialization 7, 455, even maybe sooner 8, 634, would you look to partner these on a commercial basis or is this something you want to go out alone?
Yes. So let me talk about 7, 455 first. I think that we're very comfortable as a small company taking that program through kind of the Phase onetwo 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 lymphomas. But we recognize that moving this program forward into second line, 3rd line, etcetera, is going to require large global studies with comparator arms against the combination regimens that are the mainstains of myeloma treatment today.
And that's something that we're probably unlikely to be able to execute kind of well and would be best served doing that with a partner. So likely for that, we would, we'd obviously want to keep some obviously, keep some role in the program. It's an important program for us. We think has really, really large potential. So we're not looking to out license it.
But 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. BRD-nine 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 focused markets. And so that's something we'll get there, we'll likely consider doing.
That's great. And I think that brings us to the end of time. So 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 paulin.brissoubsdot com. Thank you everyone for dialing in. And have a great day. Thanks guys.
Yes. Thanks for having us.
Thank you. Thank you, Colin.
Have a good day, everyone.