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

All right. Thanks. Good afternoon. I'm Eric Joseph, senior biotech analyst with JPMorgan. Our next presenting company is C4 Therapeutics, and presenting for the company is CEO, Andrew Hirsch. There'll be a Q&A after the presentation. Just raise your hand, we'll bring a mic over to you before asking a question. And to folks tuning in online, feel free to submit a question via the portal. So with that, Andrew, thanks for joining us.

Great. Thanks, Eric, and thank you to JPMorgan for having us here today. Good afternoon. Thanks, all of you, for joining us. I'm really excited to provide an overview and an update of all that's been going on at C4 over the past year and, in fact, what's exciting about the upcoming year as we continue to advance our portfolio. But before I do, some legal business to attend to. My presentation will contain forward-looking statements, and Slide 2, that you see here, contains our legal disclaimer on this matter. So turning to the next slide. C4 Therapeutics is a clinical-stage company, and we're really focused on delivering on the promise of targeted protein degradation to develop the next generation of medicines to help transform patients' lives. And in doing that, we developed a portfolio of high-value investigational medicines, all of which pursue targets that we think benefit from a degrader approach, where there's a strong degrader rationale, in addition to an internal discovery pipeline, focusing again on targets where we have a strong conviction that a degrader can provide a differential activity and improve patient outcomes in that setting. I'll go through each of these programs in detail in a bit once I summarize where we are as a company. The next slide really shows where we've been and that we're entering our 10th year as a company. And since our founding, we've really led the way in this new modality of targeted protein degradation science to the point where, over the last 4 years, we've put 4 programs into the clinic, 3 of which are currently active today, in addition to delivering 2 development candidates to a collaboration partner. We've also demonstrated that these large heterobifunctional degraders that we can develop, which have a great drug-like properties, including blood-brain barrier penetration. And as we look forward to 2025 and beyond, we continue to advance the company with the goal of develop -- becoming a fully integrated biotech company as we continue to advance our clinical portfolio as well as continue to invest in our very productive discovery platform. The next slide gives a quick snapshot of our 3 clinical assets, which we will go into detail in a bit. First is cemsidomide, this is our most advanced and derisked program. Last month, we had 2 clinical presentations at ASH that really reinforce the potential that this asset is a best-in-class degrader of IKZF1 and 3, which is a key -- which is really important in the pathogenesis of both multiple myeloma and non-Hodgkin's lymphoma. Cemsidomide is a top priority for C4T, and I'll talk in a minute about the data, what supports that and then the path forward. We're really excited to have announced that we're going to be advancing this program into the next phase of development, and I'll outline in a bit what that looks like. Our next program is CFT1946. This is the only clinical stage degrader targeting BRAF V600 mutations. We quickly advanced this program into the clinic, which is a testament to the strong investigator interest and unmet need, and that culminated in an oral presentation at ESMO in the fall of last year, where we've shared an interim look at the Phase I data. The data demonstrated proof of mechanism. We showed that we could deliver the drug safely, degrade the target, and we saw promising signs of antitumor activity, although early. We also demonstrated that this drug has blood-brain barrier penetration, which is important for patients with CNS metastases. We continue to enroll patients in the Phase I, and I'll outline how that will play out over the course of the year and enable some decision-making around this program. And then the last program, which was most recently entered the clinic late last year, is CFT8919. That's an allosteric degrader of EGFR L858R. That's being done in collaboration with our partners in China, Betta Pharmaceuticals. They're running the Phase I dose escalation study. We're very excited about this, and I'll talk more in a little bit about the degrader rationale and where we see the opportunity is for a degrader of this target versus inhibiting it, which is a more common approach to this target. So that tees up a very exciting 2025 for the company. And Slide 6 highlights the milestones that we communicated in our press release yesterday morning. I think the first thing, again, as I mentioned earlier, we're excited to advance cemsidomide into the next phase of clinical development, both in multiple myeloma and in PTCL. And we're working to plan and get these studies up and running, and we expect to initiate those in early 2026. In parallel, we'll be completing the Phase I dose escalation study and plan to present that data. In addition, as part of that protocol, we'll be explaining the PTCL cohort under that Phase I protocol. And then with 1946, again, the goal there is to complete our Phase I dose escalation, and then we have a number of tumor-specific cohorts, both as monotherapy in melanoma and in combination in CRC and also in melanoma. And that will be generating data from those cohorts that will really define and inform the next phase of development for this program, and we plan to present that data in the second half of the year. And then as I mentioned, in 8919, that's currently in dose escalation. We're not guiding to data presentations on that program for 2025, but we will be sharing and seeing data generated from China by our partner, Betta, and that is going to enable us to make decisions on the next phase of development. And then on the discovery front, we will continue to present and publish data from our internal pipeline as well as advancing programs, both internally as well as with our collaboration partners. So turning to cemsidomide, I'm going to walk you through both the myeloma and NHL plans for cemsidomide. But before I do that, I thought it would be important to reground everybody in the biology of IKZF1 and 3 degraders since it's something that is not top of mind, given that these therapies have been around for quite a long while. What's important is IKZF1/3 are transcription factors that are upstream of IRF4 and really regulate myeloma and lymphoma cell growth, both T-cell and B-cell lymphoma. And that's important in that degrading those targets has really 2 consequences of biology. The first is it leads directly to cell death. But the second is it also has some T-cell activation, and that becomes important as we think about therapeutic strategies in the emerging myeloma landscape. The other consequence of degrading IKZF1/3, and this is consistent across all classes, is it does block neutrophil maturation. And so you do see neutropenia associated as an on-target toxicity with this class. And as we think about the therapeutic profile, the real goal of what we're trying to do here is degrade the target enough that we can stop myeloma activity, but also have a tolerable -- have levels of neutropenia that are acceptable and tolerable that we can continue therapy, and that's traditionally done with the break-in in treatment therapy. Based on that biology, we started a Phase I study across multiple myeloma and non-Hodgkin's lymphoma, and I'll give you a brief update on that. We've completed the monotherapy melanoma arm in relapsed/refractory melanoma -- sorry, myeloma, too many M diseases. So we've completed that. That data was presented in December of 2023, and I'll share a little bit about that. The clear evidence there was the T-cell activation and that becomes important as we think about therapeutic strategies with immune-based agents. The data we presented at ASH just a month ago is from the highlighted cohorts you see here in blue and green. So that's a plus dex combo in multiple myeloma. That dose escalation is ongoing. The highest dose we shared is 75 micrograms, but we're currently enrolling at 100 micrograms. And clearly, we've not exceeded the maximum tolerated dose, and we'll continue to escalate until we achieve that. And then we also presented data in monotherapy in NHL. That study enrolled all types of NHL, although you'll see it's concentrated in PTCL, which given -- shows the unmet need there. And then we have additional dose-finding ongoing. We're currently enrolling at 75 micrograms as a monotherapy. So as we look to the myeloma landscape, it's evolving, and it's been evolving quite rapidly over the last several years as we see the advent of CAR-T therapies as well as bispecific T-cell engagers that have really revolutionized the landscape in multiple myeloma. Now that -- you may ask the question, is there a role for a best-in-class degrader of IKZF1 and 3? And the answer is yes, because what's important is the biology that I referred to earlier is really continues to be relevant across all lines of therapy, but it is fundamental to the driver of disease. And so we see the opportunity for cemsidomide to really play across all lines of therapy in combination with multiple different agents. As many of you know, multiple myeloma is a combination agent therapy with both triplets and quad regimens. And so we think an important profile is to try to maximize the activity of the drug while providing a safe and tolerable profile that doesn't add to toxicities of existing agents. This is a snapshot of the T-cell activation data. I'm on Slide 11, for those of you on the webcast. And what we showed at doses of 25, 50 and 75 micrograms is that we're able to increase effector memory T-cell populations by dosing monotherapy cemsidomide. And that's important because as we've seen advent of T-cell therapies for myeloma, they have really impressive response rates. But one of the challenges that we see is T-cell exhaustion, and so the patients continue to progress. And so we think combining this biological effect with a T-cell engager can help both deepen the durability and increase the durability of those responses Slide 12 is a summary, a snapshot summary of the data that we presented at ASH just a month ago. And what you can see in the left panel is both by dose and, overall, the response rate. And so what we demonstrated at the highest dose presented, which is 75 micrograms plus dex, a 36% overall response rate, which is very competitive, as well as a 45% clinical benefit rate, which includes the marginal responses. And so that is competitive with the next-generation class of these degraders from BMS. And then if you look on the right panel, this is truly where I think the drug differentiates, and I mentioned this is important in the combination landscape. You can see the safety or, call it, caveats of cross-trial comparisons, and what we're comparing here is the safety profile of cemsidomide plus dex in the sort of the left sub-panel. And you can see fairly low levels of Grade 3, 4 neutropenia as well as low levels of the consequences of that, which is febrile neutropenia and infection against the very low backdrop of G-CSF use. That contrasts with the BMS' most advanced drug, mezigdomide, where if you look at the data in the New England Journal, both from their Phase I dose escalation as well as in their expansion cohort at their recommended Phase II dose of 1 mg, you see quite high rates of Grade 3 and 4 neutropenia as well as febrile neutropenia and infections. And this occurred against the backdrop of very high rates of G-CSF use; 77% of patients received G-CSF, and still, they have that safety result. And so I think as we continue to look at the emerging landscape, we really see this profile of cemsidomide as establishing really the potential for a best-in-class profile, where we have excellent activity and much improved safety, which really positions it nicely to be the combination agent of choice in the emerging myeloma landscape. So based on that, we've outlined the next set of studies that we are currently working to operationalize, and really, that is highlighted here on Slide 13. And you can see 2 combinations here with more novel agents. So cemsidomide plus dex plus an anti-CD38 antibody as well as cemsidomide plus a BCMA bispecific. That's going to leverage both that T-cell activation data that I shared as well as the direct myeloma cell kill data that we also shared at ASH. And then in addition, we expect to start a single arm cemsidomide plus dex Phase II study that we think has the potential for accelerated approval. That's the current patient population that we've studied. And what's interesting is, as you see the newer therapies move forward and patients have longer survival, that only increases the pool of patients in that 5th and plus line setting as patients have responses but don't -- are not cured and they continue to progress. And so we think that, that opportunity is quite meaningful and growing as we continue to see newer therapies move into earlier and earlier lines of treatment. Turning quickly to NHL. We think there's also a potential here based on the biology. You can see that lenalidomide has been approved across multiple types of B-cell lymphomas, and we think cemsidomide has the opportunity to actually drive better usage in those classes, especially where there's a high unmet need. Slide 15 is summarizing the data we shared at ASH, and I'm focusing here on PTCL. And what we've seen here is really compelling response rates as a monotherapy. You see a 44% ORR with a complete metabolic response rate of 25% in this heavily pretreated patient population and then associated with a very well-tolerated safety profile with manageable rates of on-target neutropenia. So this really supports its development, both in PTCL, where there's a huge unmet need, as well as the potential in other non-Hodgkin's lymphomas. And so a plan here is a little simpler, just given the landscape. Again, we think there's a potential for a single agent monotherapy in second-line and later PTCL and then focusing on a randomized Phase III in an earlier line of therapy, combining with standard of care, depending on the patient's CD30 status. So taken together, we see a really exciting path forward for cemsidomide, starting off with early labels in late line, both myeloma and PTCL, and then moving into earlier lines of therapy in combination with more novel agents in myeloma and standard of care agents in PTCL. And then ultimately, as we think about broader development, really establishing cemsidomide as the backbone therapy across all lines of multiple myeloma, including the potential for maintenance as well as expanding it into additional NHL indications. But our focus to begin with is going to be the plan that I just outlined. So turning quickly to CFT1946. That's our degrader for BRAF V600 mutants. The degrader rationale here is quite simple. BRAF inhibition has proved to be a very valuable treatment pattern for cancers, driven by mutant V600 BRAF. There are a few liabilities though. The first is that there are resistance mechanisms that occur based on a scaffold function. So the inhibited monomer blocks monomer signaling, but that inhibited monomer can dimerize and then lead to signaling through the MAPK pathway, which we're trying to stop. And so by removing the protein, what that does is not only blocks its activity but the protein is not there to dimerize and completely block signaling. The other reliability we see with BRAF inhibition is inhibition of wild type, and that leads to some skin toxicity that leads to some tolerability issues. So 1946, we think, is a really advantage in treatment of BRAF cancer. It's just because of the deep elimination of the protein. The specificity we've engineered into the molecule avoids wild-type activity, and so we don't expect to see AEs associated with wild-type inhibition. And as well, we have CNS penetration. We presented data with Kp,uu values of 0.34 to 0.88, suggesting robust brain penetrants, which is important for patients in -- with brain mets. In CRC, the resistance mechanisms are slightly different. There's an intrinsic resistance for down-regulation of the MAPK pathway that leads to upregulation of EGFR, and so we expect to see a need to combine with an EGFR blockade agent like cetuximab. So we're conducting the Phase I/II study. You can see here the ongoing portions are enrolling in green. The data we presented at ESMO last year was really the monotherapy dose escalation with, I think, 7 patients of PD. So in addition to the traditional escalation portion, we had cohorts where we're taking baseline in cycle 1 day 15 samples to understand degradation. And then we've expanded into tumor-specific cohorts, as you can see here, both in melanoma as a monotherapy as well as in CRC in combination with cetuximab and in melanoma in combination with trametinib. And that's the data that will inform the future development path that we expect to generate this year and share throughout the course of the year. As a refresher, the data we presented at ESMO demonstrated proof of mechanism. You can see in the panel on the left, both through IHC and H-scores, showing nice degradation of the target at early doses. And in addition, the safety profile was as expected. We didn't see any DLTs across all doses that we've studied. And most of the treatment-related adverse events were mild to moderate, and we did not see any skin-related toxicities that would suggest wild-type activity. And then from an efficacy perspective, we saw early evidence of antitumor activity across doses and tumor types. And so we expect, now that as we move into the tumor-specific cohorts, to really share that data during the course of this year, which we think will really help us identify how and where to do further development. As we think about further development, there's multiple paths, we think, to a label, both in melanoma and CRC in the left panel. We highlight the path forward in melanoma. Depending on the data set that comes out of the monotherapy or plus MEK inhibitor cohorts, we see starting in BRAF-exposed patients and then moving into earlier lines in naive patients, either with or without that MEK inhibitor, but then also looking at frontline in combination with immune checkpoint inhibitors, which are beginning to be standard of care in the frontline treatment. And then in colorectal cancer, combination with cetuximab is the path forward, and we expect that to elucidate itself as we complete that cetuximab combination cohort. In the few minutes I've got left, I may come a little bit over, I'll talk about our CFT8919, our EGFR L858R degrader. This is a program that just started clinical development toward the end of last year. 8919 is an interesting molecule in that it binds to an allosteric site that is uniquely created by the L858R mutation, and that confers a number of benefits over inhibition. The first is a safety issue. We know that binding to the orthosteric site, which exists in wild-type EGFR, can lead to wild-type toxicities. But because that binding pocket that the degrader binds to does not exist, we don't see any degradation of wild-type EGFR, which think -- which would increase its tolerability. Secondly, while all the inhibitors do well, mutations of the orthosteric binding pocket couldn't create resistance mechanisms. We don't have that problem because we're binding to a different site, and so we think the ability to overcome those resistance mechanisms is a clear benefit. And what's interesting is when we look at the data set from osimertinib, for example, which is a fantastic drug, we see that L858R patients do less well, and that's consistent with other inhibitors of this target. And there was data presented at AACR in 2025 by another party that clearly elucidated why this is. And if you look at the far left panel, you can see there's existing early co-mutations pretreatment that are impacting the binding pocket that the inhibitor binds to. By binding to the allosteric site, we avoid those. And so we think for the LR population, we can improve the durability of response versus the current class of inhibitors. Just sharing some preclinical data, you can see in the kinome map here on the left, highly specific to EGFR L858R and active in a setting of a model of osimertinib resistance with a C797S mutation. In addition, we've done a luciferase brain metastases model, where we've shown excellent brain penetration and efficacy in these models, suggesting activity, which is important for these patients with CNS metastases. The development path here is, while complicated, fairly straightforward. We would take an earlier approval in the second-line setting in patients who've progressed due to secondary mutation in EGFR and then moving into the frontline setting, where we think we can improve, as I mentioned, the outcome for early frontline patients with L858R mutation. The dose escalation study, as I mentioned, just started in China with our partner, Betta Pharmaceuticals. And while we're not guiding to data presentations during the year, we expect to have that data throughout the course of the year, which will help inform future development. So just in closing, taken together, I think 2025 is going to be an exciting year for C4 Therapeutics. We have a number of important milestones across the portfolio, including with the platform, which really puts us on pace to become a fully integrated biotech company, focusing on oral bioavailable degraders, which is our goal. Before I close, I just want to thank all the employees of C4 Therapeutics for all their hard work in making all the results you see here happen, as well as the patients, the physicians and the caregivers on our clinical study. So with that, I think we have some time for questions. I want to ask Len Reyno, our Chief Medical Officer; and Kendra Adams, our Chief Financial Officer, to come up and join me for the Q&A session. Thank you.

All right. So we have some time for questions and I can start. Actually, keen to get a sense of really the unmet need in myeloma with patients that are treated with anti-CD38 antibodies, whether usually in some kind of combination regimen there, right? As that combo expansion cohort gets underway, what would be viewed as sort of a differentiated clinical profile relative to, let's say, DARZALEX plus an IMiD?

Yes. So let me tackle that. So let's reshape the question. It's a great question, but let's reshape it in terms of the clinical question at hand and that is notwithstanding the profound and incredibly important improvements in myeloma care, there are a group of patients that currently show up in oncologist offices this afternoon, tomorrow, yesterday and they've received these incredibly powerful drugs, and they still relapse and progress. So they have -- they come to the clinic with a problem, and that problem is progressive myeloma notwithstanding the effective use of these agents. So the first path of the unmet need is to address that, and we're doing that uniquely in our current first-in-human study that's really never been shown before. So what gets lost in the mix here is, if you look at who we treated in the ASH data set, it's a unique data set. Fully 66% of the patients on that study have had a CAR-T or a T-cell engager. And if you drill down, most of them has also actually seen CD38-directed therapy. So by showing efficacy in that group, which we've now done, you have actually got a permission slip to actually move across that thing and if you -- across the lines of therapy or the lines of mechanisms. And what you'll see embedded in the plan that Andrew just shared, is the first step to do that is to say, let's nail down the signal in plus dex, in what we're going to call multi-refractory, and let's begin to explore then novel combinations. And we think 2 key novel combinations to explore are CD38 plus dex plus cemsidomide and, in particular, explored in BCMA-exposed patients and then, separately, to also simultaneously explore and try to address the unmet need that's inherent in BCMA-directed therapies. And that unmet need is notwithstanding the very high response rate. Patients are still progressing that relatively quickly by myeloma standards and there's an opportunity to improve the quality of that response. So to take a patient from a PR to a CR or a CR to a MRD-negative CR. And the way to do that is to exploit the immune-enhancing effect of cemsidomide, which we also demonstrated in our 2023 disclosure, losing track of years. So we're basically methodology -- or sequentially building the building blocks to do what is ultimately the best value creating for the asset, and that is that cemsidomide is the best-in-class degrader that has a role across multiple mechanistic partners and multiple lines of therapy.

I think the other thing, Eric, too, is that you people remember that the approved IMiDs, lenalidomide, pomalidomide, weren't -- no one knew they were degraders when they were developed. And as a result, they're not optimized degraders. They're not nearly as potent as cemsidomide. And so by increasing the potency, we think we can do better than in combination with those, given combining a CD38 with a much more potent optimized degrader.

I guess if you are looking at -- not optimized degraders, nevertheless, fairly commonly used. And...

Yes, exactly.

This is true.

There is the point.

You're not going to [indiscernible] but that's a good thing because...

And yes, yes -- and that use does -- is accompanied by a very challenging or a pretty challenging tolerability profile on the neutropenia side, right? And this has been one of the points of differentiation where you can make comparisons. There are limits to that with cemsidomide versus the IMiD. So I'm wondering just in terms of managing patients on a CD38 plus an IMiD today to the extent to which sort of that neutropenia is a problem for maintaining dose intensity and being gentler on that side could be an opportunity for additional clinical benefit?

Most absolutely. And I think the really important principle here and that is that in order to effectively penetrate into established drugs that are used in earlier lines of therapy, we have to do that without compromising the ability to deliver the established agent. And the way that gets you in trouble where you start to compromise that equation is if you introduce new toxicities that are not manageable. And so I think while people appropriately always look at the top line summary of our data, that's a starting point. But the differentiating part of our data is, in fact, just how clean the safety signal is and recognizing that, notwithstanding we've been treating a multi-refractory late line population of patients, we've not had a patient come off drug because of drug-related toxicity. That's a really important benchmark as we do these combinations. And what we want to be able to do is to justify the introduction without compromising the standard of care that's already there. So I think we're well positioned for those activities, and I think the differentiation of those activities potentially become clarified in clinic pretty quickly that you'll be able to share data from trials like that, that show that information.

Yes. And I think when you contrast that, when you looked at -- there's a lot of data coming out at ASH with mezigdomide, and I think one of the things, while there were some impressive top line results, when you look under the hood at some of the safety data, I think in the Phase II bortezomib study, combo study, 98% of patients had dose reductions due to toxicities. And so that's something that, obviously, you want to avoid. Our drug, we think, has a great therapeutic range. But I think when you have to dose reduce to a suboptimal efficacious dose, that's not great for patients.

You're -- in the presentation, you seem to be leaning in -- giving a little more forthright about your first registration program, a late-line multiclass refractory single-arm pivotal potentially. What are the gating steps perhaps to launching that trial? Anything that is contingent upon completing -- well, probably completing the -- that probably is the case, right, completing the Phase I study? Maybe talk a little bit about that and probably a follow-up to that as well.

Yes. Let's be really clear. We think it's important in the current Phase I study to define the upper margin of how much of this drug you can give, and that's just good drug development. But none of the planning of these studies that are on the menu here are gated on that. So yes, we may swap in. Right now, we know the dose is at least 75. We might, at the end, as we develop the protocol, swap in a different dose that's higher. But the other piece of information that we already know from our Phase I experience, which is perhaps not surprising but it's really important to emphasize, that as we have increased exposure with patients, we've seen clear evidence of increasing anti-myeloma effect. And so it just behooves us to give the maximum exposure or maximum dose that gets us there. But this is not the kind of situation where we need to say, "Wait until we have a certain data point to design the study and operationalize the plans for it." Similarly, the study that's in combining with a BiTE, that BCMA, we have all the data we need for that. That's monotherapy data that we actually [indiscernible] there's no gating on it. It's simply that in good drug development, we want to have a data set that allows us to understand the total range of exposures in drug doses you can get safely while building and developing these next trials that move towards label-developing activities.

Yes. And I would say that the important piece is operational. Our current trial is at Phase I sites in the U.S., and we would like this to be -- the next study is to be more global at more treatment sites where you have a different profile of patient. And so that requires a lot more ClinOps activity of getting those sites vetted up and running and active in the study. So when we talk about an early 2026 start, that's talking about dosing a patient. Certainly, all the work behind getting the trial up and running and sites activated to enroll patients will happen during 2025.

As part of that trial, patients will hope -- seems the setting is going to be in the post-BCMA setting, right, or patients will have to -- sorry, seen prior anti-BCMA therapy. Does their response to therapy or the duration of response to therapy, is that a qualifying factor or an entry criteria whether they're refractory or relapse of that?

No, not as an entry criteria. Obviously, we'll be very aware of -- one of good drug development states that answer the clinical problem, the clinical problem patients have had those drugs and have progressive disease that they will succumb to if it's not controlled. That's it, to your point, which I agree with, it's always interesting to know are there groups of patients that do better or benefit more, and the way to do that is to make sure you get that data collected and then, in due course and at the right time, see if there are differences in subgroups, et cetera. But the core clinical problem is the patient themselves doesn't care what -- whether they're relapsed, refractured. They care that my myeloma is not controlled, and I need a therapeutic intervention at this point in time to hopefully get it back under control or the outcome is going to be death. And so we'll have those conversations. The other thing that's important to note is while you would state the patients should have been exposed to certain lines of therapy, as you go into a more global study, there's, of course, regional differences as to what conventional therapies are given routinely, et cetera. So you need to make sure one of the things we want to do is broadly define multi-refractory because it should also include patient choice and things patients may choose because my earlier career in clinical practice, not all patients choose all the things. And so we want to make sure that, yes, the patients have had standard of care that clearly is known to alter their outcome, but we also have broadly asked the question is, are these the kind of patients that would benefit? So again, we'll have dialogue both with investigators and, ultimately, the agency around those definitions, but the goal is to create the value in as many patients as possible where appropriate.

And Eric, just a reminder, the current study, we have enrolled patients who have seen prior BCMA. So we do have some sense for what's cemsidomide [indiscernible] look like.

Yes. We have no doubt that we can give the drug safely there and get efficacy. There's -- that's core part of our thesis.

Just thinking about what the market looks like in 3 -- 2, 3 years, let's say, right, if the BMS franchise with mezigdomide and iberdomide are successful, where -- when you talk to physicians, where do the legacy IMiDs remain within the treatment paradigm also as it kind of increasingly become generic?

I'm not going to stab at it.

I don't think we know.

Yes, I don't think we know. But I think if you look at the labeling strategy that BMS is taking with both iberdomide and mezigdomide, it's very clear that their strategy is to replace their franchise lenalidomide and pomalidomide, and that's sort of how the Phase III registrational studies that they have underway are designed, right? Whether that's successful or not, that's future prediction. But I think that's a tough bar, right? I think what we have outlined in the development strategy is a little bit of kind of the Wayne Gretzky, where's the puck going, right? And so I think -- I don't know what the future of the generic IMiDs is going to be. But I do know that from our strategy, we're trying to identify where do we think the landscape is going. And we've outlined that earlier uses of immune-based agents, and so we want to combine our drug there in a way that has its use in where the more contemporaneous treatment patterns are.

And I guess if I could add one point, our success in creating value for patients with cemsidomide is not predicated on those outcomes, because we're making the case that we combine with the state of our partners, that the bulk of the sort of disease-modifying care is going to be focused on that. So they can be successful and there can be generic use of now off-patent drugs, et cetera. That will or won't happen to the degree that the data supports. But that's why we're building a clinical thesis that's value for patients and ultimately investors that's independent of those activities because we really think that the idea that you rigorously must go through line 1 versus line 2 and they all find is actually going to change to what are the menu of mechanism of actions you've seen, how did you do with that MOA, what would be the opportunity for you at this point in the natural history of your disease based on your preferences and your tolerance for safety risks and so on and so forth? So we're trying to build a future-proof strategy that exploits the fundamental thing that remains true here. And I came to this 1.5 years ago after a lot of time in solid tumors. What's really unique about IKZF1 and 3, and it's really important to emphasize, is that no matter what treatment therapy you get, what line, how many you've gotten, the underlying biology remains relevant. And tackling and, therefore, modifying the underlying biology always remains a arguable valuable set therapeutic strategy. So lots of unknowns, but I think we're really positioned strongly to play in that space.

Okay. Well, good. On that note, we'll leave it there. Thanks, everybody, for tuning into the session, and thanks to the C4 team for joining us.

Thank you, Eric.

Thank you.