Awesome. Hey, everyone. Thanks for attending the Jefferies New York Conference, day two, also last day. Short but sweet. I am happy to welcome the C4 Therapeutics management team. We have Andrew Hirsch, the President and Chief Executive Officer, as well as Scott Boyle, the Chief Business Officer. I'll turn it over to them for opening remarks. Great. Thanks. Thanks for having us here. We're really excited to share what we're working on at C4. Obviously, our lead program, cemsidomide, is front and center, especially in the wake of some of the exciting data in the space coming out of ASCO. Happy to join. Excellent. Well, maybe let's take a step back. You will have a good amount of data next year, right? If we think about the next 12- 14 months, what are the major catalysts you think investors should be paying attention to? As I think about our own programs, we're very excited about the data that we shared at ASH last fall around cemsidomide, which we think demonstrates a potential best-in-class profile in the IKZF1/3 degrader space. We saw really compelling signs of efficacy at our overall 36% response rate across 72 patients across all doses. At our highest doses, which are 75 micrograms and 100 micrograms, we saw a 40% and 53% response rate, respectively, across those two cohorts, which we think is very competitive with what we see as the other portfolio of IKZF1/3 degraders. Importantly, and important for the landscape, the safety profile was incredibly differentiated. We saw very low rates of neutropenic complications, low rates of discontinuations and dose reductions, which is important as you think about the myeloma space, where it's a combination treatment regimen. There are no real monotherapy treatments that are existing. There are triplets, quads, etc. Having a tolerable profile where you're able to give what we think is the optimal dose, our recommended phase II dose is 100 micrograms, but even at 75, we saw really compelling activity in combination with other agents, is critically important. I think that really tees up where we're headed. What we've done from that is started two additional studies. The first is a phase II study called the MOMENTUM Study. That's a single-arm study of cemsidomide plus dexamethasone in the fourth-line-plus patient population. That study is conducted with registrational intent, and our goal is to submit that for a late line study should the data be supportive. In addition, we've started a phase I-B combination study with elranatamab, and that's the BCMA BiTE from Pfizer. That is going to be a dose-finding study, a safety study, which will support a potential pivotal study in that combination, serving as a confirmatory study for the single arm, as well as expanding the label into a second-line or later patient population. Those are the key things for us that we're working on. We've guided to initial data in the second half of 2027 from the MOMENTUM study. That'll be the investigator-assessed endpoint. The regulatory endpoint is an independent monitoring committee endpoint, along with some durability. That won't be until mid-2028. With the phase I-B, we'll have the complete data mid-2027. We will be providing updates as we move through dose escalation cohorts, as we have done in the past with our first-in-human phase I study. Okay. Awesome. Super helpful. We've started to see CELMoDs and CELMoD-like therapies heat up, especially in the past couple of months with Bristol studies, right? We'll definitely talk about SUCCESSOR-2, which was huge. I guess you're taking on a different strategy than what Bristol is. You went over the programs you're starting, but the intent of your combination regimens, where you see cemsi fitting into the respective settings relative to Bristol's, and I guess your confidence that there could be differentiation with either your regimen or your drug on safety and efficacy. Yeah. I'll start, as we think about the landscape and how it's evolving, has really informed our development strategy. I think Bristol has been very clear about what their development strategy is in terms of replacing their current IMiD franchise with the next gen, they call them CELMoDs. That's their sort of branded names, but whether you call them IMiD, CELMoDs, all of them are IKZF1/3 degraders, including ours. They're all the same. What we see happening in the landscape is really two main shifts, and maybe a third emerging. The first is we see a lot of these new immune-directed agents, BCMA BiTEs. CAR Ts, even some tri-specifics. Those immune-directed agents are moving into earlier lines of treatment, so focused on the second-line setting, and we saw that recently with the J&J MajesTEC-9 data set that was presented at ASCO in the second-line setting. What the consequence of that is that patients now in the earlier lines are seeing more effective therapies. They're living longer, but yet they still progress. That's going to increase the size of the late fourth-line-plus patient population. That's where our first pillar of our strategy is the MOMENTUM study developing in that setting. We think that's going to grow bigger than it is today. Our estimates today are about a billion and a half dollar market opportunity. We think that will grow as more effective therapies move earlier. That's the first piece. The second is we do think those more effective therapies are going to be earlier, but we think that combining them with an IKZF1/3 degrader is really important because of the dual mechanism of IKZF1/3 degradation. Those mechanisms are as follows. The first is it actually is foundational to the biology of the disease. It stops the proliferation of plasma cells, which is the cause of the disease. The second is that it activates the immune system. What we've seen with these immune-directed agents is they lose efficacy because of T-cell exhaustion. Combining those together w e think can create a more effective combination therapy, bringing the response rates and the depth of response rates on par with what we're seeing with the current state-of-CAR T therapies, but in a more easily administered regimen. Our strategy is really going after those two trends. That we have labels in combination with where we think the market's going. The third trend that's just recently emerging is this idea of fixed duration of these highly toxic. Really effective agents. We see once a patient gets into a deep MRD negative CR, the question is, do you need to be on a BiTE or some other of a BiTE daratumumab combination forever, or can that be removed and put into a maintenance treatment? A profile like cemsidomide is perfect for that because it both gives you the best of both worlds. It's very effective but has high levels of tolerability which makes it well-suited for that maintenance treatment. We haven't started work there, but we've been engaged with in discussions with KOLs about how do we t hink about development in a either post CAR T or kind of post BiTE IKZF1/3 degrader maintenance setting. Okay. That makes a lot of sense. Then just moving on to the SUCCESSOR-2 data that was presented at ASCO. What were your major takeaways? Was there anything that was surprising from the data? As a reminder for everyone, Bristol SUCCESSOR-2, the progression-free survival was 18 months versus 8.3 months. That said, the control arm was doublet. They are running a head-to-head versus the PV pomalidomide combo regimen, and that data's going to be next year. I think that will be strategically exciting for Bristol. Given how big of a class IMiDs are, if a CELMoD like treatment of that class can show superiority in a head-to-head, I think that would change kind of the landscape as to how you consider where this fits in therapy. Your thoughts. As you said, we're not surprised that that trial had a significant impact on PFS. They sort of said that without sharing the data. Even before that, it's a triplet versus a doublet, and the triplet had three effective therapies versus two. It would've been a real problem if that didn't win. That part wasn't a surprise. Actually, nothing was a surprise, but consistent with what we saw in the phase I, right, we did see high levels of dose reductions and discontinuations due to safety, etc. I think the median relative dose intensity in that study for mezigdomide was 83%. Right. I think the average is probably lower than that, given that that's the median number. That was consistent again with what we know about the profile of the drug and what we saw from both their phase I dose escalation and their phase I 100-patient expansion in terms of how well patients are tolerated. They didn't really present all the data on safety. We don't know, for instance, what the G-CSF use was, et c. There's a little bit more, and maybe we'll see that in the forthcoming Lancet publication. That wasn't a surprise. When we think about SUCCESSOR-1, to your point, I think that is the real important study. When you triangulate, which is always risky, but cross-trial comparisons, I think looking at both the comparator arm in the MajesTEC-9 study as well as a small 52-patient study called the SELECT study, that showed about an 11-month PFS for a, I think, a PVd regimen. The comparator arm also showed about an eight-month in the MajesTEC-9 study. I think there's a good shot if they replicate the 18, that whether it's 11 or nine, that study's going to win also. That makes sense just given the improvements that both we and BMS have made from the first-generation IKZF1/3 degraders that are on the market. Okay. Awesome. Super helpful. Because you're not running any head-to-head studies, right? When you ask Bristol, they said this study they're confident about, but they don't necessarily need to file on it. It's more to. Are you planning on running a head-to-head, or do you think you would kind of benefit from physicians looking at this benefit from Bristol study and be like, Hey, this is kind of proof of concept on the efficacy? Yeah. We don't intend to run a head-to-head against any of the existing approved IKZF1/3 degraders lenalidomide and pomalidomide, because that's not really our strategy, right? Our strategy is not to try to replace those in the marketplace. Our strategy, as I articulated, is to get a label in the late-line setting with cemsidomide plus dex as a doublet, where we've already shown quite compelling efficacy. Tolerability in probably the most heavily pretreated patient population that this mechanism's been studied. We think that data is quite compelling and really de-risks the phase II MOMENTUM study. In combination with elranatamab, that's really our strategy. It's not to go head-to-head. We don't plan to do that. They do need to do that because I think they're going to need it for reimbursement, right? They're going to need it because they're trying to replace lenalidomide and pomalidomide with iberdomide and mezigdomide. Right. Awesome. Super helpful. Andrew, you alluded to this. You guys are focusing on the dose reductions and the dose intensity, right? You've said cemsi is a potentially more tolerated drug. Can you go over the data points that support this? Do you think the current regimen leaves efficacy on the table if you could dose higher and maintain higher dose intensity? Yeah. I think if I look at the data that we have, I think from the phase I w e had very few, I think 6%, dose reductions due to tolerability. We just had very low levels of G-CSF use. I think what's important is everyone focuses on the neutropenia rate. That's just really a lab value, right? What matters is, are there complications in terms of infections, dose reductions, or discontinuations, and that's really where the drug differentiates. We saw very low levels of infections compared to mezigdomide and even iberdomide. They had something like 25%. As apples to apples as you can be in cross-trial comparisons, they had 25% dose reductions in that phase I study. I think we only had 6%. Awesome. That to me is really what speaks to the tolerability and safety benefit is you don't have that. We had much lower rates of G-CSF use. I think, is it 36%, if I'm remembering the number correctly. Their numbers were kind of north of 60. Okay. Interesting, because I think people are focused on the overall rates as well as the grade 3/4s, in which I think both regimens look generally in line. You said focus on the dose discontinuations, G-CSF use. Yeah. Again, it's a lab value, right? Now certainly, if you're in grade 4 neutropenia, that increases your risk of infections, and I think what was encouraging for us is everyone reports the grade 3/4 rate. When you look at the grade 4 rate across our study, across our doses, very consistent. Only about a third of patients have grade 4 at any of our dose cohorts. What moves around a little bit is the grade 3 number. That's because these aren't random. People like to look at dose escalation and think, are these randomized for each dose? They're not randomized. I'll give you an example. In our 75 microgram cohort, 95% of patients were prior transplant. That was a huge outlier compared to some of the other dose cohorts. You can't really look at them as independent randomized studies. We did see consistency in terms of the grade 4 across all those dose cohorts. Awesome. Yeah. Maybe just talking about your prior phase I-B at the 100 microgram dose. This is with a heavily refractory population. You're seeing a 53% overall response rate in a difficult-to-treat population, granted this was very small. Do you think that will translate to a larger population? How are you thinking about the durability in a larger trial? Yeah. I would say the top line is we would expect it to translate, and if you look at the ibermez experience, and you look at their phase I. Their expansion, those numbers held pretty consistently, and that's been the case with this class of medicines. There's two caveats that I'll give is the phase I dose escalation study was conducted only in the U.S. The MOMENTUM study is going to be a global study. It'll be both U.S. and European sites. We may expect slightly different treatment patterns. We think in Europe there's less likely to be as many patients who have seen CAR T or T-cell engager treatment than we have in the U.S., but we think it's largely going to be the same patient population. Okay. That's super helpful. Then you guys are going for accelerated approval next year in the fourth-line population. Can you kind of. 2028. Sorry. 2028. Can you go over your discussions with the FDA on what the bar you need to show in order to file? Just as a practice, we don't get into the back and forth with our FDA discussions. What I can say is we have had your typical Type C meetings that one would have around development strategy, certainly around recommended phase II dose. Our development strategy takes that input into consideration as we have planned and executed that strategy. Okay. Makes sense. Then your second-line strategy, you have this supply agreement with Pfizer. Have you disclosed what the trial design is in terms of the doses for both? Is it just the commercialized dose, your go-forward dose, or is there a balance of the two components that you're considering? Yeah. Our goal in that study is not to change the elranatamab dose. Okay. Makes sense. We've disclosed the design. The way that trial works is when you enroll a patient, the patient goes through the step-up dosing regimen that is currently right in the label. If a patient doesn't get to that step-up dosing, they don't get cemsidomide. Only when that patient gets to the full dose do we then introduce cemsidomide because there are toxicities associated with elranatamab, including in the step-up dosing period. Those shouldn't be attributed to the combination. That's part of that design. We're enrolling about six patients per cohort. We're starting at 75 micrograms, which is one dose lower than our recommended phase II dose, which is pretty standard for a new combination. The trial's designed to be incredibly flexible. If we declare 75 safe in those six patients, what we can do is we can expand at 75. We can choose to escalate to 100, or we could open an expansion at 50 if we want to explore that. Depending on what we see, we may want to add patients at 75. We may want to open a safety cohort at 50. It's incredibly flexible to really explore the combination across the range of those three doses, 50, 75, and 100, and that'll be determined based on the data that comes out of that first 75 microgram combination cohort. Yeah. That makes a lot of sense. Is there a upper end of safety that you are willing to tolerate when you're thinking about the doses you want to move forward with? That's hard to say. Obviously, the goal is to not interrupt the BiTE dosing. There's no dose reduction strategy for BiTEs, right? It's you stop and hold therapy, which we don't want to do. A little bit is going to be the proof is in the pudding, and we'll see what we see. Once we do that'll help us inform next steps. It's all going to be data-driven. Okay. Makes a lot of sense. I think we kind of talked about this, but Bristol has both mezi and IBR, right? You have a potentially more tolerable drug that they want to use upfront and then less tolerable, more efficacious. How do you think of cemsi positioning? It almost sounds like you think you can get to the efficacy of mezi and then the safety of IBR, right? You said it, I didn't, but yes. Which is a high bar. I guess, how are you thinking about positioning? It seems like you said refractory setting, moving up lines of therapy, but then you are also combining with Pfizer. It seems like you're looking at how the safety profile evolves. Is there kind of an appetite to evaluate other second-line regimens over time? Yeah, absolutely. I think that's a great question. I think our goal is multiple myeloma is a combination regimen disease. We think that it will be important to establish cemsidomide as the combination agent of choice, where IKZF1-3 degradation can increase the benefit to patients. That's really what our strategy is shaped around. In fact, on our latest Q1 financial results call, we announced that we're going to start a second phase I-B to combine with an anti-CD38 antibody and a proteasome inhibitor. That doesn't mean that it's going to be a label-enabling phase III strategy, but we do think the important thing to do is really establish broad combinability with the key major agents, MOAs, in the class, and that's really the objective here. What we would love to be able to do is establish a single dose that is the combinable dose for whatever regimen you're trying to do. That's really the goal. Given what you talked about as the profile, we think we have. When we say best in class, we mean we have optimal efficacy and safety, whereas, as you pointed out. I think the other two agents in the class that are being developed sort of make a trade-off between efficacy and safety. We think given the properties of our drug and the pharmacology, we don't have to do that. Okay. That makes a lot of sense. I guess moving on to the market, can you just go over how big that market opportunity is for MOMENTUM as well as in second-line? We'll give Scott some airtime. Sure. Yeah. As Andrew said, we believe that the immune agents are going to move earlier, creating a larger fourth-line opportunity. The MOMENTUM study is intending to tackle that 4th-line patient population. We've made some assumptions, and we think it's $1 billion-$1.5 billion revenue peak opportunity in that patient cohort. As we move into the 2nd line with the others, we believe together those two can get us to about a $4 billion opportunity for cemsidomide in combination there. Obviously, if other combinations come on board, we expect that opportunity could grow for cemsidomide. Okay. Awesome. Maybe just to go over the Roche agreement that you guys had recently. In terms of the DAC agreement, can you go over You've said that you haven't disclosed what the target's, but you guys are being very smart about target selection. You want to look for targets that can actually be differentiated, right? There is also a framework that you're using when looking at prior degraders. Can you kind of walk us into your approach in the framework, and if there's anything, and then some of the target profiles you're looking at? Yeah. DACs are degrader-antibody conjugates, where it's an ADC, but replacing the cytotoxic cargo with a degrader. The concept there is that degraders have catalytic activity and then can be designed in the way that we've done in our orally designed ones to be highly selective for the greater target of interest. This new DAC modality has the potential of a highly selective one-two punch in cancer targets. We've had a long-going collaboration with Roche in designing oral degraders. When they got interested in this DAC concept, of course, we were happy to find a way to extend our relationship. As you said. We've announced a collaboration with Roche where we've gone after two targets together. The way that we think about target selection is the degrader opens up a lot broader anticancer activity than a cytotoxic agent could be. Roche was aligned with the way that we were thinking about this. There also, with a DAC, you could go after degrader targets that might not be able to be tolerated in a systemic delivery of a degrader. The antibody does the targeting to the correct cell type, and then you could imagine perhaps a less tolerable, degrader target. That being said, we haven't disclosed the DAC targets with Roche yet, but philosophically, we were aligned and happy to have them leverage our learnings in that space. Okay. Awesome. As you think about, would you want to take your DACs into an area where you've already seen? There's oral SERDs, right? Then I think the data there is starting to say there is going to be a population where you get the most benefit, and then there's going to be a population where you're not really seeing much of a benefit with the degrader approach. How are you thinking about both indication selection and target selection? Yeah. Certainly on the DAC piece, I think that it's going to be a combination of the concept upon the target of the antibody as well as the degrader. If taking a step back on C4's next generation discovery pipeline, and perhaps maybe that's where we could go, we're aimed at indications in inflammation and neurodegeneration and neuroinflammation. We took the lessons that we learned over the 10 years of targeting oncology agents as well as non-oncology targets with our collaborator, Biogen. We've made decisions to go after clinically validated pathways, but where the degrader modality is the right way to unlock a particular target, where there's a best in class, a first in class, excuse me, opportunity there. Some of those learnings we've embedded into our target selection in the next generation. I think the other thing that drove the target selection there was an insight that we and others have developed degraders over the time. Initially, the point of view was that these large heterobifunctional degraders wouldn't cross the blood-brain barrier and penetrate into the brain. I think initially the point of view was that those sorts of indications would be excluded. We demonstrated with our data and some of the other players in the degrader space is that you can actually design heterobifunctional degraders to grow into the brain. We saw that with two of our oncology programs and of course some of our collaboration programs, that opened up a larger indication class that we hadn't considered before. That's it. Putting those two pieces together, it unlocks some of those opportunities. I think the other point around target selection that is tuned to the degrader modality, as opposed to inhibitor, is you can design degraders to bottom out at a certain level of degradation. For example, you could say we only want a degrader 60% of the target. You can design degraders to do that based on the kinetics and the preclinical activities that we do. It allows the concept of normalizing levels as opposed to having to get to deep levels of degradation, which you would expect you might need in oncology. Again, I think some of those three principles dictated the target selection in our next generation portfolio. Awesome. That's super helpful. Are there any timelines you can give us on that collaboration? We've not disclosed any timelines with our Roche collaboration. Okay. Remind us again how many of these are pre-IND versus early phase I? All of our collaborations to date are still in the discovery stage. Biogen, which we had a collaboration with, has taken two molecules, degraders, into their clinical portfolio. Those have advanced it to that point. Okay. Awesome. Super helpful. I guess we have time for one last question. In closing, I'm just going to ask a generic C4 story. What do you think is the most underappreciated aspect of C4 right now? Well, I'll say the whole thing, but certainly the preclinical pipeline is underappreciated, but partially because we haven't shared data yet, mostly for competitive reasons. When we get to the right stage, we're excited to share that. That's understandable. I do think the cemsidomide story. The recent run-up in the share price is still underappreciated. This is a wholly owned post proof of concept asset that shows best in class potential, in a large and growing market, with a very differentiated development plan focused on where the market's evolving versus where it's been. I think that is something that hasn't really been appreciated. I do think it's starting to, as some of the BMS data supports what we've been saying for the last several years. Hopefully our data will follow that. I do think that's probably the biggest underappreciated part of the story. Awesome. Well, thank you so much for the time, C4 team. Thank you so much for everyone for being here. Great. Thank you. Thanks. Thank you.