C4 Therapeutics, Inc. (CCCC) Earnings Call Transcript & Summary

Okay. Good morning, and welcome again to the 40th Annual JPMorgan Healthcare Conference. I'm Eric Joseph, senior biotech analyst for the firm. Our next presenting company is C4 Therapeutics, and to talk to us a little bit about the company, it's my pleasure to introduce CEO, Andrew Hirsch. There will be a Q&A session after the presentation. Feel free to submit questions by clicking the Ask A Question icon. With that, Andrew, thanks so much for sharing some of your time with us this morning.

Great. Thanks, Eric. Good morning, everyone, and thanks for joining our presentation. Before I begin, I'd like to thank JPMorgan for inviting us to participate in the conference, and I'm pleased to share an update on C4 Therapeutics today. You should all have access to the slides, that I'll indicate which slide number I'm on as I progress through the presentation. I'll be making forward-looking statements today as part of the presentation, and Slide 2 contains our legal disclaimer on this matter. I'll start the presentation on Slide 3. C4 Therapeutics is focused on making medicines that use a novel approach called targeted protein degradation, which we believe has the potential to transform the treatment of disease. For most of our industry's history, the focus has been on small molecule medicines that inhibit the activity of disease-causing proteins. This approach has been successful and has led to meaningful improvements in patient outcomes. However, it's been limited to the 15% or less of the proteome where we can find ways to bind to active sites to effectively inhibit activity. And further, for those targets for inhibitors have been approved, selective pressure ultimately results in resistance that renders inhibitor approaches ineffective over time. By harnessing the body's natural process for destroying unwanted proteins, targeted protein degradation offers a novel method to treat disease and replicate the benefits of genetic knockdowns with a small molecule approach. Since our company's founding in 2015, we've invested in our research platform, which we called TORPEDO, with the goal of creating degrader medicines that can overcome resistance, tackle currently undruggable targets and ultimately improve treatment options for patients. Slide 4 highlights the key elements of our TORPEDO platform that enable us to do this. First, we focus our optimization efforts on making the most catalytically efficient degraders that optimize the overall degradation process instead of individual steps in that process. What's unique about degraders is that once they enable the destruction of a target protein molecule, they can go back and do it again and again. We call this the calalytic cycle, and we believe that optimized degraders complete this cycle as fast as possible. This is important because our data shows that degraders with these properties are the most potent degrader medicines. Second, we've made a significant investment in computational methods and tools that enhance our ability to rationally design degraders. These in silico models allow us to design degraders with enhanced potency and selectivity across our pipeline. Our cellular degradation assays provide volumes of high-quality data, which we analyze using a proprietary and unique framework based on fundamental enzymology principles. These models allow us to robustly predict both the depth and duration of target degradation at any dose. A third important feature of our platform is our decision to focus on Cereblon as our ligase of choice for all of our key drug discovery efforts. This was a strategic decision that the company made very early on that was driven by 2 key factors: First, Cereblon's the only E3 ligase that's clinically validated. As if the ligase used by the IMiD drugs, we have a rich and successful clinical history with these agents that demonstrate that it can be safe and effective in the clinical setting. Second and probably most important, Cereblon is universally distributed across all tissues and cellular compartments in the body. This wide distribution provides great latitude in targeted selection and disease indication. We've made a deep investment in at least 15 distinct chemical series of proprietary Cereblon binders. This is important because subtle differences in the Cereblon binding portion of a degrader can have fairly large impacts on the catalytic efficiency of a degrader. Since our founding, we've worked on over 50 different targets. We've had a greater than 90% success rate with Cereblon. So in fact, we really haven't found the need to move beyond it either. And finally, our platform has the ability to utilize MonoDAC degraders, sometimes called molecular glues and BiDAC degraders, which are generically referred to as heterobifunctional degraders, depending on the features of the protein we're targeting for destruction. This gives our chemists additional tools to target various classes of disease-causing protein. While the hit IB approach is different for each of these degrader types, once we have a confirmed hit, we can leverage the same platform to optimize each. As Slide 5 shows, C4 Therapeutics is well positioned as a leader in targeted protein degradation, with world-class medicinal chemistry capabilities and a validated platform to efficiently and rationally develop degrader medicines. We've developed a robust pipeline with multiple oncology programs either in or soon to be in the clinic. These programs demonstrate the opportunity with targeted protein degraders and have the potential to address unmet need in larger groups of patients. I'll review each of these programs later on in the presentation. In addition, we have a strong foundation to support this growth for our experienced team across discovery and clinical, our strategic partnerships and strong balance sheet. Slide 6 describes the early portfolio strategy the company embarked on. With our initial programs, we sought to establish the potential of our platform by first focusing on validated targets where despite well-understood biology and approved medicines providing benefit to patients, there remains an unmet medical need. We saw degrader targets that were clinically derisked with a strong rationale for degrader approach, where genetics are a clear driver of disease and there is a defined clinical development path. These first 4 high-potential programs are now all progressing in and toward the clinic, with preclinical data from each supporting the discovery capabilities of our TORPEDO platform. Slide 7 captures how we're preparing to advance the next phase of our strategy, where we'll leverage the experience we now have with TORPEDO to tackle higher risk, more novel targets, where there is a potential to transform patient care. This next wave of oncology programs will address historically difficult to drug targets that cannot be addressed by other modalities. Ultimately, we believe this will deliver first-in-class molecules, both MonoDAC and BiDAC degraders, with potential to unlock the full patient impact of targeted protein degradation oncology and together with collaborators across other therapeutic areas. Our initial target selection strategy has led to the robust pipeline of degrader medicines shown on Slide 8. I'll go into detail in a moment on each of our 4 most advanced programs. In addition to those programs, we have a broad discovery effort of both wholly owned oncology programs and programs with our 3 platform collaboration partners. With Roche, we're working on developing degraders for various cancers. Roche is our longest collaboration and was entered into in early 2016, just after the company was founded. In this 6-target deal, we've delivered DCs on 2 of the targets, which now live in our pipeline, and there are 4 remaining targets to be developed in the collaboration. Biogen is an exciting collaboration because it expands our platform into neurologic conditions across 5 targets of interest. And lastly, our Calico collaboration was recently extended with respect to 1 target through March of 2023. Let's now turn to our most advanced wholly owned programs. Our lead program, CFT7455, can be thought of as a next-generation IMiD as it targets the same targets, IKZF1/3 as lenalidomide and pomalidomide. It's well known that depletion of IKZF1/3 kills myeloma cells, but because the marketed medicines weren't known to be degraders when they were developed, we believe they aren't potent enough to achieve maximal efficacy in these patient populations. Slide 10 provides an overview of both the patient population and the areas of remaining unmet need despite the use of IMiDs as a backbone therapy for multiple myeloma patients. Based on the preclinical data that I'll share, we believe there's a transformative opportunity for this program. Slide 11 provides an overview of non-Hodgkin's lymphoma, which is a diverse group of cancers in which lymphocytes grow abnormally. IKZF1/3 are key drivers of malignancies in many NHLs, but the approved IKZF1/3 degraders have limited activity in this setting. Because of the improved potency of CFT7455 over the approved IMiDs, we're exploring its effectiveness in treating different types of non-Hodgkin's lymphoma with the goal of improving upon some of the patient outcomes shown here. On Slide 12, we display some of our foundational in vivo data for CFT7455. On the left panel are results from our study in the H929 xenograft model, which is the workhorse of multiple myeloma translational research. There are 3 key takeaways from the study. First, 7455 is markedly more active than pomalidomide at the clinically relevant dose. Second, treatment with 7455 results in deep regression at doses as low as 30 micrograms per kilogram as a single agent. And third, in comparison to CC-92480, BMS' most potent in clinical stage IKZF1/3 degrader, 7455 achieves comparable efficacy at 1 100 for the dose. On the right panel is data from the same experiment but at the 100-microgram per kilogram dose level. This is plotted on a per mouse basis over an extended period of time. While we see the same tumor regression during the dosing period, after dosing stopped, those CRs were durable in all but 1 mouse out of 50-plus days. Slide 13 outlines the Phase I/II trial design for CFT7455. This trial was initiated in mid-2021 and allows us to accomplish 3 objectives. First, it will allow the identification of a discrete dose in both multiple myeloma and non-Hodgkin's lymphoma, which is critical because historically, these 2 patient populations have tolerated different doses of IMiDs. Second, by including Cohort B1 and B2, it allows us to explore CFT7455 with and without dexamethasone, which is typically given with IMiD therapy to boost limited monotherapy activity. Given the potency of our degrader, we believe that we have the potential to drive meaningful efficacy as a monotherapy. Lastly, it allows us to collect early efficacy data in the expansion cohorts, albeit in a small number of patients in the indication of interest. We've made meaningful progress in this study, and I'm pleased to share that enrollment in Cohort A is complete, and we expect to present data from this cohort at a medical meeting in the first half of this year. Cohorts B1 and C are now enrolling patients, and will continue to progress the strong trial throughout 2022. The next program I'll highlight is our BRD9 degrader, CFT8634. Slide 15 provides an overview of synovial sarcoma, which is the primary disease focus for our BRD9 program. BRD9 is a target you may be less familiar with. It's a member of the BAF complex, which is responsible for chromatin remodeling. Mutations in discrete subunits of the BAF complex result in specific tumor types. One such mutation, the SS18-SSX translocation, results in BRD9 dependency and is a hallmark of synovial sarcoma. Additionally, the lesions of SMARCB1 are seen in other solid tumors and result in the same BRD9 dependency. As a result, these tumor types are of interest for this program as well. These tend to be a collection of rare tumor types, but the overall size is consistent with that of synovial sarcoma. Synovial sarcoma is an area of high unmet need. First-line therapy provides a median progression-free survival of about 7 months. Median survival is approximately 18 months, and there are no effective second-line therapies. BRD9 is a target that can only be drug with a degrader approach, and the reason is outlined in the cartoon on Slide 16. Inhibitors of BRD9 have been shown to be pharmacologically inactive in synovial sarcoma models. This is because existing BRD9 inhibitors address only the bromo domain of BRD9, while the oncogenicity of BRD9 depends on sub-domains not addressed by traditional inhibitors. As a result, inhibiting the bromodomain has no effect on synovial cell viability as shown in the left image. By contrast, our degrader eliminates the entire protein as shown on the right image, thus replicating the potent antitumor effect we see in BRD9 knockout models. This is demonstrated on Slide 17. We've been able to design a potent and selective oral degrader of BRD9, which has demonstrated robust dose-dependent responses in the Yamato xenograft model and in patient-derived xenograft models. Today, we announced that the IND for CFT8634 has been cleared by FDA, and we're in the process of initiating our Phase I dose escalation study, which will evaluate single agent CFT8634, in synovial sarcoma and SMARCB1 deleted tumors. Slide 18 contains the trial schema for this study. And I'm sure everyone's first question is going to be when can we expect to see data, and as is our practice, once we have all sites activated and have a sense of the pace of enrollment, we'll be able to provide some high-level guidance at that time. I'll next turn to our BRAF V600X program, which we recently received full rights to from Roche. Slide 20 contains a summary of a target, which is mutated in approximately 15% of all cancers, including non-small cell lung cancer, melanoma, colorectal cancer and several other tumor types as depicted on this slide. The vast majority of BRAF mutations are classified as V600X and we've developed a degrader CFT1946 to target disputation and overcome the liabilities of approved BRAF inhibitors. Inhibition of BRAF causes paradoxical RAF activation, which can result in diminished efficacy of the inhibitors. In addition, resistance to BRAF inhibition occurs over time, often driven by the mechanisms which drive BRAF dimerization and capitalize on this paradoxical activation, such as BRAF amplification or the BRAF slight variant. By degrading the target instead of inhibiting it, as shown on Slide 21, we can prevent the paradoxical RAF activation and allow for a deeper elimination of mutant BRAF signaling to create deeper and more durable responses. Slide 22 demonstrates this benefit with CFT1946. On the left panel, we show improved and more durable efficacy of CFT1946 compared to encorafenib, which is an approved small molecule BRAF inhibitor. And on the right panel, we show the tolerability of CFT1946 again compared to encorafenib. We look forward to sharing additional preclinical data from this program at a medical meeting in the first half of this year. We also expect to submit an IND and initiate a Phase I study in non-small cell lung cancer, melanoma and colorectal cancer harboring the BRAF V600X mutation in the second half of the year. Before I wrap up, I'd like to cover 1 more program that we're advancing towards the clinic. CFT8919 was designed as a selective degrader of EGFR L858R, which is a common mutation found in non-small cell lung cancer. Slide 24 captures the treatment landscape. I'd like to call your attention to a few areas. First, non-small cell lung cancer comprises approximately 85% of all U.S. lung cancers with 195,000 patients diagnosed in 2020. Of these cases, 10% to 15% is driven by the EGFR mutation, and this percentage rises to 40% in the Asian population. The EGFR LR mutation is the second most common EGFR mutation, and patients with this mutation experience a less durable response to improved EGFR inhibitors, including osimertinib. What's exciting about CFT8919 is that our team has designed this degrader to bind to an allosteric site that's uniquely created by the L858R activating mutation. You can see this on Slide 25. This brings 2 distinct advantages over inhibitors that bind to the orthosteric binding site. First, it will avoid known mutations in the orthosteric binding site and does not require covalent binding through C797S, which will enable the degrader to be effective, independent of secondary EGFR mutations. Second, because we're binding to an allosteric site created by the LR mutation, we're able to achieve exquisite selectivity for this mutation. This is demonstrated on Slide 26 in a BaF3 model. On the left panel, you can see the effect of our degrader on cell lines with the LR driver mutation, including those with the most common resistance causing secondary mutations. Importantly, the black line represents wild-type EGFR which shows no activity of the degrader. On the right panel, you can see this in a more quantitative fashion, with the relative potency of CFT8919 compared to osimertinib and erlotinib across multiple relevant resistant mutations. As expected, osimertinib and erlotinib are inactive in the setting of resistant mutations in EGFR while CFT8919 retains activity. Lastly, on Slide 27 on the left panel, we show that in vivo, CFT8919 achieved near complete tumor regression that's comparable to osimertinib in a model of first-generation EGFR inhibitor resistant tumors. On the right panel, we demonstrate near complete tumor regression in a model resistant osimertinib, demonstrating the potential of this molecule. Previously, we guided to having this program in the clinic by the end of this year. But some of the required CMC work has taken a bit longer than anticipated. And so we plan to have all IND-enabling activities complete by year-end. We now expect to start a clinical trial in 2023. So as you can see, there's quite a lot of activity planned at C4T this year, and Slide 28 summarizes our key 2022 milestones for our 4 most advanced programs. By the end of the year, we expect to have 2 additional programs in the clinic in addition to CFT7455. We're planning to present new preclinical data on all 3 of these programs in the first half of this year, demonstrating the power of our TORPEDO platform. In addition, we plan to present the first clinical data from Cohort A of the CFT7455 Phase I trial in the first half of the year. These milestones, coupled with our ongoing discovery efforts, well-positioned C4T to progress degrader medicines to patients and continue our leadership in the evolving targeted protein degradation space. On behalf of all the employees at C4T, thank you for your time and attention this morning. And I look forward to updating you on our progress throughout the year. I'll now ask Adam Crystal, our Chief Medical Officer; Stew Fisher, our Chief Scientific Officer; and Lauren White, our Chief Financial Officer, to join us for the breakout session.

Okay, great. Thanks, Andrew, for that presentation. First question, I think I should focus on CFT7455, where you're anticipating initial data mid-year, if I heard correctly. This is a category that we've seen validated multiple times over. Again, can you just speak a little bit to what you view as the unmet need still in multiple myeloma that could be addressed by a better or best-in-class IMiD? And I guess kind of guide us a little bit around sort of what that initial market opportunity might be, assuming that the development course is going to start from kind of last line and move up?

Yes, and I'll turn it over to Adam in a second to talk about that in more detail, but I think the point and our goal here with this program would be to sort of replace the current set of IMiDs as a backbone of multiple myeloma therapy. We think there's key advantages to a more potent degrader like CFT7455 versus some of the other or less potent less call it the active degraders. Adam, do you want to sort of expand on that?

Sure, thank you for the questions. Clear to ask that there remains a very large opportunity in this space. Andrew spoke to lenalidomide and pomalidomide being entrenched backbone therapies in the earlier lines as well as relapsed setting, really for a total addressable market of about $50 million. We believe that our molecule preclinically looks differentiated from all of the BMS molecules out there and see opportunities to become a backbone therapy. Initially, our path, we believe, is to play in mind using the relapsed refractory setting. But ultimately, we believe that there is a path to full approvals in combination with it being triple or otherwise to gain in earlier lines of therapy, ultimately displacing the standards of care and currently there, the image, and competing with or beating the emerging cell mods, which also have designs in development there.

So I guess looking to the initial readout coming in Cohort A, this is a Cohort A being the dose escalation portion. Can you just sort of speak to sort of the composition of patients in that study you're looking at, or at least both patients with myeloma and as well as NHL, I believe are eligible to participate. Can you sort of guide us a little bit in terms of anticipated patient numbers there? And also, if I remember correctly, you're also looking at both monotherapy and dex combination use in this early portion. Can you -- is that the case? And can you get kind of guide to patient numbers on both regimens?

Sure. So at this point, we're not going to comment on sort of specific patient numbers that will be in the study. You'll have to see that when we maybe present that. Just to remember, Cohort A is monotherapy only. That's -- and it's mixed in myeloma and non-Hodgkin's lymphoma, and we started off escalating in the mix group early on. And then as I said in our prepared remarks, we split into cohorts B1 and C, which are now enrolling to be indication-specific because we know from the history with IMiDs that patients tolerate dose to -- different doses of IMiDs with different indications. And so those are enrolling now. So Cohort A is the data that we'll be presenting, which is that early escalation cohort.

Okay, great. Thanks, that you clarified. So I guess 1 aspect that is differentiated here is the dispensation of dexamethasone at least or at least kind of identifying the opportunity for a monotherapy therapeutic regimen without the use of dexamethasone. Can you just sort of speak to sort of what, I guess, the burden for patients currently where dexamethasone is pretty much part of all standard of care where IMiDs are used. What does that mean for patients potentially being able to dispense with that part of standard of care today?

Yes, sure. Adam, you want to tackle that one?

Sure. So I certainly agree entirely that dexamethasone administration is standard of care with existing and investigational molecules of this class. But it comes with very real toxicity including susceptibility of infection, friable skin, weight gain, insomnia, mood, sexual dysfunction, abnormal hair growth. It is a nontrivial burden of changes, which emerge in patients who take chronic dexamethasone. In short, we believe that because of the differentiated preclinical activity this molecule has seen, there is an opportunity to develop as a dexamethasone sparing agent and spare patients from this list of very considerable adverse events.

Okay. Okay. The -- in NHL, right, IMiDs have struggled to some extent thus far. Preclinically, you're showing a differentiated activity profile. What do you think mechanistically is contributing to that? Is it the depth of transcription factor, targeted done regulation? Is it the mix? I guess, mechanistically what do you think is contributing to that? And -- then I guess from a clinical standpoint, what level of activity do you think would be compelling to advance the program forward either as monotherapy or as part of a combination?

Sure. Adam, why don't you cover that one as well.

Absolutely. So I think your point is well taken that use in the NHL space. It's worth noting that lenalidomide is approved in 3 indications, mantle cell, marginal zone lymphoma and follicular lymphoma. They are active. Indeed, activity has been shown with lenalidomide in peripheral T-cell lymphoma albeit limited as well as to diffuse large B-cell lymphoma really large Phase III study is just no registration in diffuse large B-cell lymphoma. We believe that this molecule has the potential to deliver transformative care for those diseases. And your question as to why really comes down to the data which demonstrates that this molecule CFT7455 has such market increase in potency in other futures for lenalidomide as well as pomalidomide. IKZF1/3 are key drivers of malignancy in NHL. And so the improvement of the molecule does result in market improvement [Technical Difficulty] translate [Technical Difficulty] brings me to the next part of your question in terms of what we hope to see in terms of clinical activity in NHL. And of course, this depends on the subtype of NHL for peripheral T-cell lymphoma, we really see a clear opportunity with a relatively low bar in an area of true unmet medical need and are looking and hoping to achieve an overall response rate of about 35% just an exciting path forward to an accelerated approval. For MCL in the post-BTK inhibitor space, we're aiming for an overall response rate greater than 50%. And I think it's worth noting that we're also interested in exploring other indications, including BPL. Those patients are eligible for the escalation portion of the study, though not yet with the expansion.

Okay. As you've alluded to, I'm sure a lot of investors can appreciate, right? Combinations are going to be part of the -- most likely going to be part of the development path forward. With Bristol's cell mod agent, you've actually seen them look at combinations pretty early on in its development cycle. Here with 7455, like where, I guess, do you anticipate sort of exploring that combination potential and pursuing that strategically?

Yes, sure. I mean combinations are clearly on our development path. Myeloma and lymphoma are combination regimen kind of indications. So I think the key is to get through to kind of recommended Phase II doses near that as we start to think about what are the combination regimens. There's the common standard ones that are used in each of those indications. And those will happen as we get further into development, but there's certainly a lot of planning going on now around which ones to move forward to. Adam, do you want to add anything there?

The only thing that I would add is that, there is a clear path to the standard of care regimens, particularly in myeloma, speaking of prednisone inhibitors and CD38 antibodies. I think it's also fair to say we're interested in seeing how the potential to combine 7455 with new or novel agents such as biospecifics, would work out and I think time and data will tell.

Okay. Maybe shifting targets a little bit here and picking up on 8919, the EGFR degrader. If I'm correct, this is among the main candidates, the TPD space kind of unique in that it's a membrane-bound target. So I'm just kind of curious to know whether developing a degrader for a membrane-bound protein, is it any more or less challenging than it is for a cytosolic or nuclear presenting target.

Sure. Great question. I'll ask Stew to address that one.

Yes, thanks, Eric. Actually, EGFR, you're right, it's a membrane-bound protein. We actually found multiple series of actives there. So finding degraders there was not necessarily any more difficult than other proteins. And we've seen that in other membrane-bound proteins as well. It was a challenging program, but it wasn't, I think, due to target locations. So that's not really as far as we can tell, as indicator of target challenge or not.

Okay. Okay. The CNS penetration of the drug that you're highlighting is also promising and certainly relevant for metastatic -- sorry, non-small cell lung cancer as a common part of progression there. I guess can you kind of contact -- at this point, kind of provide some context around the level of CNS distribution you're seeing with 8919? And to the extent possible to may contrast with osimertinib?

Yes, sure. Stew, do you want to handle that one?

Yes. Similarly, I think that it sort of continues on your last question, what we found in optimizing 8919 was making sure it was highly catalytically efficient. And once we have that, we saw very large disconnects between the PK and the PD and efficacy as we see with all of our degrader programs, that's why we spent the time optimizing it. As a result, CNS penetration is a component of that. That's a PK question. What we're finding is it's not easy to compare, and it's actually coming out appropriate to compare head-to-head exposure requirements for inhibitors, even covalent inhibitors like osimertinib and the degrader modality. In general, and specifically for 8919, we need far less exposure in any compartment, including CNS. So we're still working through exactly how to scale those expectations to human dosing. But it's actually not easy or maybe even appropriate to compare the 2. So we don't really have an ability to put that in context.

Okay. It was -- is L858R mutation requisite for the activity of 8919? And I ask because I'm just wondering whether some of the other noncanonical mutations, the exon 21 mutants might also be in scope with that compound.

Yes, sure. Adam, do you want to answer that?

Sure. So CFT8919 was specifically designed to creating GFR L858R and to retain activity in the setting of secondary mutations. It's an allosteric degrader and it doesn't bind the active site, obviously. Clinically, the allosteric site, which it binds is created by the LR mutation. So this is to say it's not present in wild-type EGFR. It's not present in exon 19 deletion, nor in other kinases. This affords excellent selectivity, really of LR doses this time with the spare toxicity. Now you mentioned some noncanonical exon 21 mutations. In our presentation in the sort of the ANDA profile, there are 2 mutants which are picked up at L858R. One is L858R and the other is a noncanonical mutant at 861 to a lesser degree. But I think it's most fair to think of this molecule as LR specific sparing exon 20, sparing exon 19, though sparing wild-type.

A couple of submitted questions here, I'm going to try and probably combine them, and they speak to the platform, it's competitive space. What are the -- I guess, what limitations of the competing targeted protein degrader platforms are addressed by TORPEDO? And can you speak to points of differentiation and kind of speak to the rationale also of focusing explicitly or exclusively, I should say, on Cereblon where competitors, to some extent, might be looking beyond just Cereblon? Yes, and I guess, a, maybe related to that, Cereblon is ubiquitously expressed. How should one be thinking about the potential toxicity profile from associated with degraders leveraging Cereblon exclusively.

Yes, Eric. So it's a good question, it's one we get a lot, it's hard for us to sort of speak to any great detail around competitive platforms because we're not -- we don't work there, we don't know the details of where those limitations are. I can certainly speak to and I highlighted in the presentation, the key elements of our platform that we think enable us to develop the most healthy integrators. I talked about those sort of being our focus on catalytic activity, right, the tools and computational methods we have, our focus on Cereblon and the ability to do both MonoDAC degraders and BiDAC degraders. So I think we're quite comfortable that the platform we've put together is enabling us to do the work we need to do. And as I mentioned, we've worked on over 50 targets as a company and have a greater than 90% success rate. With regard to the specific question around Cereblon, I'll maybe turn it over to Stew and have him answer that question.

Yes. I think -- so in terms of other novel E3 ligase. We have actually worked on novel E3 ligases characterized -- now that we express characterized and actually found some hits to those. But what we found was there's risks to a lack of knowledge on the ligases themselves, which presents some risk to any clinical program, which again, to get back to Andrew's point, Cereblon being validated. We understand that there isn't much tox risk with that ligase itself. So I'd say we actually like the profile for Cereblon. And we've also found that -- and that's one of the reasons why we focused so early on in Cereblon. I'll add 1 more point. The fact that we've invested so deeply in Cereblon gives us a tremendous toolkit that enables all of our programs for us to move quickly and with degraders, which are extremely catalytically efficient. And I think that also underscores to us anyway that to get into a ligase, any ligase, you really need to have built it out and understand it thoroughly. Not only its biology, but also the chemical toolkit that is worthy of moving molecules quickly and with the best profile into the clinic.

And maybe I'll just add 1 thing in terms of the comment around tox. We certainly know the known targets that drive common toxicity with Cereblon SALL4, GSPT1, for example. In our screens, those are anti-targets, right? So we actually look to ensure that either in the MonoDAC side that we don't have any activity against those or even with a BiDAC that the Cereblon linking portion of that BiDAC degrader doesn't have activity against those targets because we know that those are toxicity driven targets.

Maybe 1 last question, not that you don't have a lot tackle already in the existing pipeline, but how -- I guess how should investors be thinking about additional pipeline expansion, either internally or through your collaborative efforts with your partners, is maybe the first overarching question. And just kind of picking back up on this capabilities on both the MonoDAC and also the BiDAC side. The MonoDAC, I guess, currently is the IMiD as we think about pipeline development or pipeline expansion, I guess, would we see additional MonoDACs being named, I guess, in the midterm.

Yes. So at a high level, right, we continue to invest in the discovery platform, both in terms of new program development, as well as advancing with the platform and making modifications as we see and see opportunities. So we don't -- we're not providing guidance on sort of DCs per se. From what I would say is from an internal perspective and an internal program perspective. Its sized to give about a DC every other year. I think you've seen a kind of vast productivity wave come through that's resulted in the 4 programs that we've talked about. But we don't expect that to necessarily continue, especially as we start to work on harder and harder targets that are more difficult to drug. But -- so we don't have any guidance there. I'll ask Stew to address the question you had with respect to sort of MonoDAC versus BiDAC approaches. I think at a high level, we're agnostic that we're really focused on the targets and then driving the right modality within the degrader space that we think is optimal for that target.

Yes, I think, Andrew, you've put it well. We -- I think the way we look at it is that having both capabilities and it allows us the degraders latitude to go after targets either that have chemical buying ways or not, BiDAC versus MonoDAC at the most extreme bookends. But you're right, we have -- the IMiD, our best-in-class IMiD in CFT7455 is an example of our ability to deliver dose types to the clinic and then the rest of the pipeline is BiDACs. I remain very excited about our MonoDAC platform. It is founded on that Cereblon toolkit that I mentioned that drives all of our programs. We've got a large, diverse set of binders now, greater than 4,000 members of that, probably over 200 scaffolds exemplified in there. And I think when you have a tool set of that size, and you can start to ask questions around other targets and whether you can get hits, I think we're seeing some promising data in there and degrons that are not currently known. And that is going to feed a pipeline in the future, but it's very early days, and so we're dealing with actives, not hits and not lead series and DCs. But I remain very optimistic, but it's going to be some time before you see that maturing.

And then with our collaboration, obviously, we're limited to what we can say but I'd love to share all the exciting work we're doing because it really is quite interesting. But we'll have to be driven by their willingness to let us share that.

We'll certainly stay tuned. We'll have to leave it there for time for now. So thanks, Andrew, and the C4T team. We really appreciate it. Everybody, have a great morning -- a great meeting.

Great, yes.