Hello, and welcome to the CFT7455 phase I update investor call. All participants are in a listen-only mode. Should you need assistance, please signal a conference specialist by pressing the star key, followed by zero. After today's presentation, there will be an opportunity to ask questions. To ask a question, you may press star, then one on your telephone keypad. To withdraw from the question queue, please press star, then two. Please note, this event is being recorded. I would now like to hand the call to Courtney Solberg. Please go ahead. Good afternoon, everyone, and thank you for joining our call to discuss phase I dose escalation clinical data of CFT7455 for the potential treatment of relapsed refractory multiple myeloma. We're making forward-looking statements today, and slide two contains our legal disclaimer on this matter. Those presenting on today's call are Andrew Hirsch, our President and CEO, Stew Fisher, our Chief Scientific Officer, and Len Reyno, our Chief Medical Officer. We'll begin the opening remarks and then walk you through our preclinical and dose escalation clinical data of CFT7455 in relapsed refractory multiple myeloma. We will end today's call with a Q&A session. I will now turn the call over to Andrew Hirsch for some introductory remarks. Thank you, Courtney, and thank you all for joining our call today. I'm excited to share the update today on the phase I trial of CFT7455, our MonoDAC degrader of IKZF1 and IKZF3, for the treatment of multiple myeloma and non-Hodgkin's lymphoma. Before we jump into the data, I'll provide a quick overview of C4T for those of you who are new to the story. C4 Therapeutics is focused on delivering on the promise of targeted protein degradation science to create a new generation of medicines that have the potential to transform patients' lives. In addition to our own pipeline of drug candidates for both liquid and solid tumors, we have ongoing discovery collaborations with Roche and Biogen. Today, we announced a new collaboration with Merck to develop degrader antibody conjugates, or DACs. We're thrilled to collaborate with Merck to innovate in the growing field of antibody drug conjugates, to combine the catalytic activity, potency, target specificity, and durability of degraders with the specific binding and delivery capabilities of antibodies. As part of the collaboration, we will receive a $10 million upfront payment and are eligible to receive milestone payments totaling approximately $600 million, as well as tiered royalties on future sales for the initial target. The agreement also provides Merck with the option to extend the collaboration to include three additional targets, which could yield option exercise payments, as well as potential milestones and royalties. If Merck exercises all of its options, we would be eligible to receive up to approximately $2.5 billion in potential payments across the entire collaboration. We look forward to collaborating with Merck to innovate within the growing field of antibody drug conjugates. Turning now to our clinical pipeline, we have three clinical stage assets, including CFT7455. Our BRAF V600 degrader, CFT1946, is currently in phase I dose escalation for non-small cell lung cancer, melanoma, and colorectal cancer. Next month, we'll provide guidance on when we expect to share the first data from this trial. CFT8919 is our EGFR degrader, and our partner, Betta Pharmaceuticals, will conduct the phase I trial in non-small cell lung cancer patients with an L858R mutation in China. Last week, Betta received IND clearance from the CDE in China, and we expect the phase I trial to initiate in 2024. As you can see on slide six, we have advanced multiple oncology programs and generated necessary clinical data to make strategic decisions on the portfolio during the year. Now, turning to CFT7455, the adjustment to a 14 days on, 14 days off schedule is now yielding expected results. The totality of the data to date supports CFT7455 as a potential therapy option for multiple myeloma across multiple lines of treatment. First, CFT7455 is well-tolerated, with no DLTs resulting in discontinuations. Second, the data suggests that 14/14 is the optimal schedule for CFT7455's PK properties, which replicates the modeling data we shared in the spring of 2022. Third, we've characterized both the anti-myeloma activity and immunomodulatory effects of CFT7455 at doses up to 75 micrograms, which supports a role in combination with novel myeloma agents or as a maintenance therapy option. Finally, robust IMWG responses have been achieved when patients are treated with CFT7455 in combination with dexamethasone across the first two dose escalation cohorts. In fact, three out of the nine patients we've treated have achieved a PR or better. Importantly, while the n's are small, the best responses we've seen are in patients refractory to BCMA therapies. These patients are the ones we would likely pursue for the treatment through an accelerated approval path. Before turning to the phase I data, our CSO, Stew Fisher, will walk through the biological rationale for degrading IKZF1 and IKZF3 in multiple myeloma and some of the foundational preclinical data supporting its development. Thank you, Andrew. I'll start with a reminder on three consequences of IKZF1, IKZF3 degradation here on slide 10. IKZF1 and IKZF3 are transcription factors required for cancer cell growth and survival in myeloma, as well as NHL. Degrading IKZF1 and IKZF3 cause multiple myeloma and NHL cell death. Second, IKZF1 controls the factors required for activation of fully differentiated T-cells, and IKZF1 degradation results in T-cell activation. ... Third, neutropenia is an inevitable consequence because IKZF1 is the natural transcription factor that governs the process of early stem cell differentiation into neutrophils. Thus, degradation of IKZF1 in the bone marrow results in redirecting emerging stem cells to other hematopoietic cell lineages. Neutropenia is observed with all IKZF1/3 degraders as a result of reduced replenishment of neutrophil populations over time, rather than a direct effect on neutrophil viability. Incorporating a dosing holiday period with an IKZF1/3 degrader allows for the natural process of stem cell replenishment of neutrophils. Taken together, achieving beneficial efficacy and immune cell activation while minimizing neutropenia are accomplished through appropriate dose and schedule regimens. Based on this biology, there is a balancing act that all IKZF1/3 degrader medicines need to determine how to balance the manageable neutropenia with antitumor activity. Most IKZF1/3 degraders have a half-life of 24 hours or less, which is compatible with a dosing schedule of 21 days on for efficacy and seven days off to provide a holiday for neutrophil recovery. Additionally, adding dexamethasone helps with safety and efficacy, which is why this class of medicines have always been combined with dexamethasone, helping maintain that balance between neutropenia and efficacy. Because CFT7455 has a half-life of 48 hours, the 14/14 schedule is optimal because it allows for sufficient target coverage to ensure robust activity, but it also provides time for neutrophil recovery. Later, my colleague will share how this is translated into the clinic. The various shortcomings of the currently approved multiple myeloma and NHL IKZF1/3 degraders are described on slide 12. To overcome these shortcomings, we intentionally designed CFT7455 with these four key points. First, reducing off-target toxicity. Second, overcoming resistance that occurs with approved IKZF1/3 degraders. Third, excellent catalytic efficiency with the ability to rapidly distribute into tissues with enhanced residence time to enable deep target suppression, resulting in highly potent antitumor efficacy. And fourth, finally, one of the key complications of multiple myeloma is renal deficiency, where approximately 50% of multiple myeloma patients have renal impairment. This can be a limiting factor in patients treated by IKZF1/3 degraders that are cleared renally. CFT7455 was designed to metabolize through the liver to be better tolerated by these patients and potentially avoid kidney clearance. Slide 13 demonstrates CFT7455's differentiated preclinical PK and PD. In this experiment, CC-92480, or mezigdomide, utilizes a tenfold higher dose relative to CFT7455, and we don't see measurable concentrations of mezigdomide after four hours. In contrast, CFT7455 maintains concentrations above DC80, the concentration required to degrade 80% of the target proteins for all or nearly all of the 24-hour dosing period. Notably, both molecules achieve 100% degradation of target at these doses, but CFT7455 is more effective in sustaining target degradation in multiple myeloma tumors over time. On slide 14, we show an in vivo xenograft model with a cell line reflecting resistance to IKZF1/3 degraders due to low levels of cereblon. The exposure reflects the equivalent of 50 micrograms daily human dose for 14 days. When CFT7455 is combined with dexamethasone, there are robust tumor regressions compared to the monotherapy regimens. This data demonstrates that the 14/14 schedule is the optimal dosing schedule for CFT7455 and is predicted to be efficacious when combined with dexamethasone. This data is supportive of what we are starting to see in the clinic. I will now turn the call over to Len to review the CFT7455 clinical data for multiple myeloma. Thank you, St ew. As a reminder, when we initiated the first-in-human trial, we utilized a 21 days on, seven days off dosing schedule, which is consistent with other agents in this class. The data shared last April demonstrated that CFT7455 had a longer than predicted half-life of 48 hours. As a result, when CFT7455 was dosed for 21 days, there was not enough time for neutrophils to recover during the seven-day break from daily dosing. Again, it is important to note that neutropenia is an exposure-related, on-target side effect of all IKZF1/3 degraders. We revised our dosing strategy, taking advantage of the longer half-life to dose for 14 days on, 14 days off, to permit adequate target degradation. This also allows enough clearance time of CFT7455 from plasma to levels low enough for neutrophils to recover. Available capsule sizes led us to enroll patients at the first three dose levels, utilizing a Monday, Wednesday, Friday dosing regimen over the first 14 days. Once these exposures were declared safe, the final two monotherapy dose escalation cohorts were dosed at the optimal daily 14-day on, 14 days off schedule. Consistent with the approach of phase I trials, the goal remained to define the safety of CFT7455, determine the maximum tolerated or administered dose, as well as estimate antitumor activity. As a reminder, we will not be sharing any data from the 21/7 monotherapy multiple myeloma arm, as this was shared last April, nor will we be showing NHL monotherapy data as this dose escalation trial continues to progress. Next, I'll review the 14/14 monotherapy data for multiple myeloma. At the end of the presentation, we will share some of the emerging and promising data from the plus dexamethasone arm. As seen on slide 17, we escalated our monotherapy multiple myeloma arm from 25 micrograms Monday, Wednesday, Friday, to 75 micrograms daily dosing utilizing a 14/14 schedule. An adaptive Bayesian Logistic Regression Model, or BLRM, with overdose control to guide dose escalation and cohort size was used. Typically, three to four patients are dosed at each cohort for initial safety evaluation. DLTs are defined only in cycle one. The monotherapy arm is complete. We made the strategic decision not to escalate beyond 75 micrograms daily, as we have generated sufficient CFT7455 data to characterize exposure, safety, and pharmacodynamics over a range of relevant doses for future combinations with novel agents. We define 75 micrograms as the maximum administered dose, or MAD, and we are not exploring further monotherapy dosing refinements to declare a maximum tolerated dose. The key enrollment criteria for these multiple myeloma patients included three or more lines of prior therapy, adequate bone marrow function is required, although grade II neutropenia was permitted at baseline, disease progression on or within 60 days of the patient's last anti-myeloma therapy, and the patients had to be refractory both to lenalidomide and pomalidomide, as well as a protease inhibitor, a glucocorticoid, or a CD38 monoclonal antibody. The table on slide 18 shows the baseline patient and disease characteristics. The monotherapy patient population was multi-refractory and treated with a median of seven prior therapies, ranging from three to 21. All patients received LEN, POM, and a CD38 antibody. Notably, 55% of patients had either CAR T or T-cell engager therapies, and some of them, in fact, had both. Slide 19 describes the treatment disposition. We treated 22 patients in the monotherapy dose escalation cohorts. At the time of this data cut, November 28, 2023, we have three patients who are still ongoing and 19 have discontinued. The discontinuation due to an adverse event was related to a grade II rash in the setting of early signs of disease progression. It is worth noting that the patients that came off the trial due to physician decision and/or patient withdrawal also had early signs of early progressive disease. As seen on the table on slide 20, CFT7455 was well tolerated in all 22 heavily pretreated patients utilizing the 14/14 schedule. Grade III or greater drug-related effects were, as expected, neutropenia and other hematologic effects. We had a total of 11 patients experience grade III or higher neutropenia. As a reminder, if the patient has had grade IV neutropenia for at least seven days, or if febrile neutropenia occurs in cycle one, these are considered DLTs. In this regard, at the 75 microgram dose, one patient experienced grade IV neutropenia lasting greater than seven days, and one patient experienced febrile neutropenia. Both AEs were defined as DLTs, and both patients remained on study. We had no DLTs resulting in discontinuation across the entire monotherapy arm. The safety data speaks to the promise of CFT7455, with limited safety concerns outside of hematology, which is consistent with IKZF1/3 degraders. Other AEs include a variety of clinical and lab observations. There was one patient who had Pseudomonas-positive respiratory culture during a neutropenic episode, which was successfully managed with antibiotics, and they resumed therapy. Overall, we saw very few grade III or greater adverse events. Turning to the next slide, the clinical pharmacokinetics show that the clearance of the drug is consistent with a 48-hour half-life. At higher dose levels, we are measuring plasma concentrations greater than or equal to 0.9 ng/mL, which we predicted from our preclinical models to be associated with optimal anti-myeloma effects. The next slide shows the clinical pharmacodynamic data. On the left, you see our modeling graph for the 14/14 schedule. On the right graph, we have confirmed our hypothesis that the anti-myeloma effects with the daily 14-day schedule is associated with protein degradation over approximately 21 days. Additionally, target degradation was greater with daily dosing than with Monday, Wednesday, Friday dosing, both utilizing the 14/14 schedule. Hence, daily dosing for 14 days provides deep degradation, and the neutrophils have time to recover during the dosing holiday. Before sharing the efficacy data, I wanted to remind everyone of the IMWG criteria that establishes the response criteria for multiple myeloma patients, as seen on slide 23. Multiple myeloma patients are evaluated for response based on various measures of disease-modifying activity, depending on the specific clinical and laboratory features of the patient's disease. We use the same response criteria for the anti-myeloma activity from our plus dexamethasone arm, which we will share with you later in the presentation. The anti-myeloma monotherapy activity is presented on s lide 24. In total, we had nine patients with stable disease, two patients with a minimal response, and one patient with partial response. In this regard, at the 50 microgram daily dose, two patients experienced stable disease and one patient experienced a minimal response, while at the maximum administered dose, 75 micrograms daily, all four patients benefited, with three stable disease and one partial response. Turning to slide 25, I want to walk you through the immunotherapy clinical data we saw with CFT7455 as a monotherapy. Although novel agents such as anti-CD38 antibodies, CAR T therapies, and bispecifics have high response rates in relapsed refractory multiple myeloma, many patients still do not respond or respond and ultimately progress. Bispecifics and antibodies exhaust T-cells, which limits the durability of response. In our monotherapy dose escalation data set, we demonstrate clinical evidence of immune T-cell activation at well-tolerated clinical exposures of 25 micrograms and 50 micrograms, respectively. The safety profile, evidence of anti-myeloma activity, as well as immune cell activation, demonstrates that CFT7455 is an ideal IKZF1/3 degrader for potential combinations with novel agents, or as a maintenance therapy option when utilizing CFT7455 at doses below the maximum administered dose. On this next slide, we summarize nonclinical translational data that confirms enhanced immune cell lysis when CFT7455 is combined with daratumumab or teclistamab, providing a strong rationale for these combinations in clinic. To summarize our monotherapy clinical findings, the 14/14 schedule is optimal for CFT7455. Plasma exposure increases with dose, and the estimated half-life is 48 hours. From a safety perspective, CFT7455 is well-tolerated with no unexpected toxicity signals. CFT7455 has anti-myeloma activity in multi-refractory patients. And finally, we saw clinical evidence of immune T-cell activation at doses below the MAD. This monotherapy data set provides the necessary safety, efficacy, and immunomodulatory data to explore CFT7455 combinations with novel multiple myeloma agents in earlier lines of therapy, as well as a maintenance therapy option. Turning to slide 29, I will walk you through the early and promising interim data we have generated from the CFT7455 plus dexamethasone arm for multiple myeloma. The dose escalation arm utilizing a 14/14 schedule is ongoing, and as a reminder, we initiated this arm in January. It should be noted that the CFT7455 dose levels tested in this arm do not precisely map to the monotherapy CFT7455 dose levels we just reviewed. This reflects regulatory requirements to initially establish safety at combination doses just below the monotherapy doses that were declared safe. Cohort size is governed by the same Bayesian statistical methods that are used in the monotherapy portion of the protocol, and DLT definitions are unchanged. We have escalated through two dose cohorts, 50 micrograms Monday, Wednesday, Friday, and 37.5 micrograms daily, both cohorts with the co-administration of dexamethasone. As of the data cutoff, November 28th, we've had no DLTs. The early dose escalation data that follows is from these two cohorts. The multiple myeloma patients in the plus dexamethasone arm are heavily pretreated, and in the first two cohorts, we've enrolled nine patients. These patients received a median of six prior therapies, with a range from four to 12, including all expected standard of care regimens. Notably, 56% of patients received prior CAR T or T- cell engager therapies. The safety profile of CFT7455 administered with dexamethasone is also well tolerated. Grade III or greater drug-related effects were, as expected, consistent with the monotherapy safety signal. No AEs have led to dose reductions, discontinuations, or DLTs. Across the first two dose cohorts, the most common side effects are anemia and neutropenia. The febrile neutropenia noted on this slide at 37.5 microgram daily dosing actually occurred during cycle two in a patient with a history of recurrent respiratory infections. As seen on the table on slide 32, at low doses of CFT7455 plus dexamethasone, we've already started to see multiple promising responses, and the best responses have been with patients refractory to BCMA therapies. At our lowest dose evaluated, 50 micrograms Monday, Wednesday, Friday, we saw 1 PR. This patient had undergone five prior lines of therapy and is still ongoing. At the second dose level, 37.5 micrograms daily, 14/14, one patient experienced stable disease that came off trial for reasons not related to CFT7455. One patient experienced a PR and still ongoing, and most notably, another patient went from having a very good partial response to now having a stringent complete response... Let's examine in more detail the data from the patient with a stringent complete response at 37.5 microgram daily dosing with dexamethasone. This 65-year-old woman had progressed after five lines of prior therapy, including most recently, CAR T. Shown graphically on the middle panel, deep IKZF1 degradation is noted with each of the first three cycles. The graph on the right confirms a durable decrease in serum-free light chains. By IMWG criteria, she met the definition for a stringent complete response, including absence of clonal cells from the bone marrow biopsy. To summarize, on slide 34, CFT7455 is well-tolerated with dexamethasone, with no new safety signals. We are seeing promising anti-myeloma activity at doses that do not exceed 50% of the maximum administered monotherapy dose. These include two2 PRs and one stringent CR. The emerging data supports the potential of CFT7455 when combined with dexamethasone to improve patient outcomes for multi-refractory, multiple myeloma patients. We are now enrolling at the 62.5 microgram daily dose, as well as a phase I dose expansion cohort at the 37.5 microgram daily dose. We have seen our enrollment rates increase now that we are moving into active dose levels where there is promising efficacy. I will now review the development plan and next steps. We believe there are multiple opportunities to address unmet needs in multiple myeloma across various lines of treatment. A first-line opportunity would be in triplet combinations with Dara or proteasome inhibitors, as well as a maintenance therapy option after transplantation. Second and third-line opportunities consist of triplet combinations, as well as in combination with BCMA BiTEs, CAR Ts, and other immunotherapy options. Finally, fourth and fifth-line opportunities would be in combination with novel agents or in combination with dexamethasone or multi-refractory patients. Each of these lines of treatment has a considerable market opportunity for CFT7455 to capture. To address this market opportunity, we've outlined an appropriate path forward for a potential label on slide 37. We have always said we will need to partner this program as the studies we need to conduct to realize the full potential of this molecule, and to take it into earlier lines, is something we cannot take on with our current resources. First, it is possible to pursue accelerated approval for CFT7455 plus dexamethasone in the multi-refractory, multiple myeloma patient population. Second, we will seek a partner to initiate numerous combination studies leading to several potential label expansion opportunities. Third is a maintenance option for patients who are post-transplant. Each of these settings represents a large market opportunity and high unmet needs. I will now turn the call back over to Andrew to conclude the call. Thank you, Len. So as I said at the beginning of the call, the schedule adjustment we made is now yielding the results that we expected to see with CFT7455 combined with dexamethasone. There have been some ups and downs with this program, but the data shared to date demonstrates our confidence that this is an important molecule. We've established a safety profile that meets our expected product profile for use in multiple myeloma, and we've also established the necessary monotherapy activity for combinations with novel myeloma agents, including immunostimulatory activity. And finally, we have promising efficacy in combination with dexamethasone at the most recent dose level studied, which suggests a path to an accelerated approval in multi-refractory multiple myeloma. While the monotherapy arm is complete, we continue to dose escalate in the plus dexamethasone multiple myeloma arm, as well as the monotherapy NHL arm. We expect to present data from both of these arms in 2024. We're grateful to the patients and their families who participated in the trial to date, and thank our investigators and C4 colleagues for their continued efforts to advance CFT7455 for the benefit of patients. Operator, please open the lines for question and answers. Thank you. We will now begin the question-and-answer session. To ask a question, you may press star, then one on your telephone keypad. If you are using a speakerphone, please pick up your handset before pressing the keys. To withdraw your question, please press star then two. At this time, we will pause momentarily to assemble our roster. Today's first question comes from Etzer Darout with BMO Capital Markets. Please go ahead. Great, thanks for taking the question, and congrats here on the update, and the clinical activity that you're demonstrating with the molecule. I guess maybe the first one is maybe a little bit more color on the data that we'll see in 2024 for the phase I dose escalation combination with DEX. First, maybe what the criteria are for potentially enrolling higher doses in that cohort, and then would the data include sort of this 10 or less patients in those 37.5 microgram, 62.5 microgram QD doses, or is it just really just strictly the ex- the sort of escalation portion of that study? And then I have a follow-up. Etzer, I'll let Len address that. Thanks for your question, Etzer. The next step for the study in dose escalation is to pursue the safety declaration at 62.5 micrograms plus DEX. So the enrollment of that cohort and all the patients that actually been identified for that cohort will consist of approximately four patients who will be treated for a month, one cycle, and then evaluated to determine whether the drug is safe at that dose level. In parallel, while we enroll those patients, we'll actually also recruit patients to further expand the number of patients at 37.5 micrograms. The initial goal of bringing that cohort up to 10 patients. When we get the information on both of those cohorts, we'll make decisions regarding next steps. Those next steps could include further escalation beyond 62.5 micrograms, expanding 62.5 micrograms, at least initially to 10 patients, and also exploring a dose level between the two. All of those decisions will be data-driven. Suffice to say, the goal of those data-driven decisions will be to optimize and maximize the highest dose we can give safely with dexamethasone, because we know dose matters as it relates to efficacy, but also then to characterize multi-safety, efficacy, and tolerance. It's very difficult to say exactly how many patients will be treated in 2024 because it will follow the data, but we do anticipate at a minimum, that we'll be adding easily an additional 15 or more patients in the plus DEX cohorts. These patients will all be enrolled in the same eligibility criteria of the current protocol. Again, the exploration initially across these doses will continue to be in multi-refractory patients, of the same demographic characteristics that you saw presented earlier today. Great. No, thank you. And then just maybe on the mechanism here, kind of looking at this sort of prior refractory patient population that sort of saw the response. Is this just really speaking to the maybe the orthogonality, if you will, of IKZF1/3 degradation targeting? Is there something else about this sort of mechanism where you kind of see these highly refractory patients still seeing sort of a response and stringent complete response at that with the therapy? So just to clarify, I mean, are you asking why that patient had that response because they're multi-refractory? Yeah, yeah. Yeah, is it really just speaking to maybe how orthogonal IKZF1/3 degradation is to some of the other approaches that are being explored in multiple myeloma? Yeah, St ew, take that. Yeah, thanks, Etzer. I think that's a great point. And in fact, we're talking about completely different mechanisms here, in terms of the other therapies. As we mentioned earlier, there is an activation component of the immune system, so that could, you know, activate other therapies, but that's not really what we're really considering here. This is just showing that upon penta-refractory, you can come back and go with a very potent IKZF1/3 degrader and have an enhanced effect here that is clearly giving patient benefits. So I think you can think of these as orthogonal, but perhaps synergistic, depending on how you combine them down the line. If you remember what kind of St ew highlighted at the beginning, right? You know, we designed this to be active even with low cereblon levels, right? Because we know, at least with the BMS agents, right, as you sequence through, you know, cereblon can actually kind of degrade itself until you have lower and lower cereblon levels. So the more potent, the more catalytically active, a degrader, the more efficacy you can drive at with lower cereblon levels in the cell. So, you know, we didn't-- we don't have the data to say this patient had low cereblon levels or not, but that's sort of the theory of why this, you know, at least should work, you know, in a pom refractory setting. Great. Thank you. Congrats again. Thanks. Thank you. The next question comes from Brad Canino with Stifel. Please go ahead. Thank you, and nice to see the initial activity with this DEX combo here. I was hoping you could help me contextualize these combo data relative to Bristol's mezigdomide, really, both in terms of their experience with neutropenia and I think some of the supportive care they've used to address the neutropenia, and also in terms of the quality of response seen here relative to the total mezigdomide experience, which seems like a lot of patients to date. Thank you. This is Len Reyno. I'll try to answer that question as best we can by, by first stating that, obviously there's much more clinical data to compare to with mezigdomide, and we're still early in our plus DEX experience, and, and most of the Bristol experience through dose escalation and then in, really the 100-patient expansion cohort is all plus DEX. I will sort of reference back to their original phase I experience, where during the dose escalation phase, at the recommended, dose for expansion, they had three DLTs at 1 mg. And, and I think we're in a similar level of DLTs at our maximum administered dose. It's difficult for trust to make cross-trial comparisons, but if we look at what they've seen in total in the 100-patient cohort they presented in the New England Journal of Medicine, what we can say is in that cohort, 54% of patients had grade IV neutropenia. And in that cohort, as far as we understand, it did not preclude the use of G-CSF. So in that cohort, they ended up with 87% of patients getting growth factor. So I think the general quality of our signal is similar, but I don't think we're able to really make direct comparisons between the two datasets at this time.... What we can say with confidence is that, you know, we're really very comfortable that we have an entirely manageable and predictable neutropenia signal with mono therapy. Again, I'll circle back, that no patients came off because of neutropenic complications. And as we shifted to plus DEX, what really excites us about that is, as expected in the small number of patients, we see the same qualitative safety signal, but now emerging at doses below those, associated with true effects in monotherapy, that we're now seeing pretty dramatic, evidence of anti-myeloma effects. Yeah, I think I would add, you know, again, just to, you know, it's hard to compare given kind of the size of the data set, but, right, we did see a PR at the, you know, the very first dose level study, then a stringent complete response at the second dose level, right, of 37.5 microgram daily. Right, and when you compare that to, the mezigdomide data, right, they only really had one CR out of 76 patients studied in their dose escalation experience, and that was at the RP2D of 1 mg QD dose. I think as we saw the data coming out of ASH this past weekend, you know, one of the things I think that we noted, with interest is that, that, in different settings, they're not really going forward with that 1 mg dose, and they're still kind of working around schedule, and dose, you know, kind of even studying things down to 0.3 mg. So it, it's not clear to us that they're very comfortable at that 1 mg dose, kind of 21/7. And, and we've heard anecdotally that, you know, it, there's some, some side effects that are, that are kind of, you know, kind of, create some tolerability issues, and we've seen across some of their data, you know, dose reductions, at a somewhat high level. So, you know, again, our data is not... I'm not trying to suggest that our, you know, our data, our data is smaller, but I think that's some of the challenges that I think we've, we've heard anecdotally and seen from their data set, that, you know, if, if our data kind of plays out with, with more n, I think could give us an advantage there. But we'll have to see in a, a more complete data set. Yep, thank you. Maybe just one follow-up on the sCR that you're seeing these patients, what it tells you about the feasibility of the 14-day on, 14-day off schedule? Because when I look at most of the CELMoDs, they all had to do 21 days, 21 out of 28, like you were originally trying to do to maintain a solid response in person. Thank you. Yeah, look, I think there's nothing magic, right, about 21/7, right? The goal is you need to have enough of a break with this class of medicines, as St ew mentioned, to balance the activity of the neutropenia, and that's really driven by the drug's half-life. So, I think based on the data set we have, and there's that slide that I love in the presentation that compares the modeling data with the clinical data in monotherapy, I think it's doing exactly as we predicted on the 14/4, given that we have a twice as long half-life. So, I think for our drug, 14/4 is absolutely appropriate. We see the suppression of the target over the time period we think we need to drive efficacy, and we've seen that. We've seen anti-myeloma activity with monotherapy, but also responses in combination with DEX, and then the recovery necessary to sort of appropriately manage the neutropenia. So I think that data set that we have gets us very comfortable that given our half-life, 14/4 is the right, right schedule. All right. Thanks again. Thank you. The next question is from Derek Archila with Wells Fargo. Please go ahead. Hey, good afternoon, and, thanks for taking the question, and congrats on the data. Just two brief questions from us. I guess first off, just in terms of the prioritization around, you know, finding a partner, for the combo and looking at, you know, earlier line multiple myeloma. And then just, a more kind of clarification on the grade IV neutropenia cases. I guess, you know, I can kind of, you know, glean stuff from the footnotes, but just kind of understand, you know, kind of what the rate of grade IV, neutropenia was, and, just I think you kind of gave, the Bristol, rate, but, you know, just to put that into context in terms of comparing to, other agents. Thanks. Len, you want to tackle that one? So please go ahead. Yeah. So again, the slide summarizes grade III and IV. So, and so it includes all grade IIIs as well as grade IV. Grade IV is 500 neutrophils or below. What we can say is that at the higher dose levels of 15, 14, 14 days on, 14 days off, each of those had two grade IV neutropenias. The numbers are really small, and I think I wouldn't try to calculate a rate from those numbers and keep coming back to the same observation that the neutropenic clinical events were modest, and by clinical events, meaning the actual complications of the neutropenia were relatively rare, and uncomplicated. But I think it would be wrong to actually assign a percentage expected grade IV rate with cohorts as small as they are. And you had a question on the collaborations, partnering and priorities? What was it? Yes, in terms of the priority, prioritization around finding a partner, you know, for early line, and I guess, is that, you know, something that you would look to be like a 2024 event? Or again, yeah, just how quickly would you want to do that? Yeah, look, I think the data set we have with monotherapy is really supportive of starting those combinations, and I think it would be ideal to have a partner to do that versus us trying to start those on our own. I think, you know, our focus, at least operationally, will be completing the phase I, you know, two study that we have ongoing, and starting to think about if we were to take it ourselves, you know, how we would go forward for an accelerated approval in multi-refractory with plus DEX. But in order to start really those combination trials with some of the more novel agents. I think it would be useful to have a partner going forward. We think there's lots of different combinations that we could do that we think are of interest, where our drug would synergize. But just operationally, that'll be very... That's challenging for a small company to implement. Got it. Congrats. Thanks. Thanks, Sir. Thank you. As a reminder, to ask a question, you may press star, then one. The next question comes from Eric Joseph with JP Morgan. Please go ahead. Hi, this is Noah on for Eric. Thanks for taking our questions. Just could you characterize the synergistic nature of DEX here, just noting that dexamethasone appears more synergistic than additive relative to the monotherapy arm? And then also, just can you mind me whether the patients in the study are being managed with prophylactic meds or G-CSF? Thank you. Yeah, I'll take the first point. I think it's still unclear what the specific mechanistic basis for this synergy between dexamethasone and the IKZF1/3 degrader class. It's clearly there. It's obvious from our studies preclinically, as you saw with the preclinical data in vivo. But the actual specific mechanism for why that's working and it at the tumor level is still unclear. I think I'll follow on, this is Len speaking. From the clinical side, I think what you're seeing clinically, we can qualitatively describe. I think it's too early to sort of really describe the magnitude of the synergy. But what I will say about the patients that are treated in the plus DEX cohort is remind you, when we showed you the monotherapy anti-myeloma effects, at those exposures, they were quite modest. Stringent complete response is not a modest effect, and it's occurring at a dose level that essentially represents an exposure that's half of the maximum administered dose of monotherapy. So we're pretty excited about that because it maps so well back to the preclinical in vivo experiment that St ew shared with you during the presentation. I do think it's important to remind everybody that notwithstanding that neutropenia is the expected and inevitable side effect of degrading these targets, that the way all of the protocols, ours and everybody else's, are designed, is in that in cycle one, there is no prophylactic use of supportive care growth factors. So patients' counts are allowed to drop to what the nadir will be, and then the nadir is observed, to see how long it takes to recover. The only use of growth factors that's permitted in cycle one is a patient who actually would have a neutropenic event, meaning they have characterized, they now have duration more than seven days, or they have a febrile event, and that would then, in most cases, the physicians would add growth factor. In practice, what happens, and including in the protocol, in subsequent cycles, because safety now has already been characterized without growth factors, clinicians will use their judgment, and if they think a patient's neutropenic level is too low or might be prolonged, they can introduce growth factor as a standard practice in treating these patients in clinic. And that's why you end up, when you see presentations of larger trials, where you see growth factor used, as in the experience for Bristol and mezigdomide, in that 100-patient cohort, they reported that 87% of patients received growth factor. So again, it's only in cycle one where you're really trying to get, quite frankly, an academic understanding of the effect on neutrophils, that you don't use the growth factor. In practice, actually, neutropenia with these drugs is a manageable, expected, and not a serious clinical problem. Yeah, I'll just add, when we talk to physicians, they're not bothered at all because they know, they're used to seeing it, they're used to treating it. You know, they know how to handle it in practice, so it's not something that they're concerned about. They're concerned when it leads to infection, right, and patients get into trouble, but you know, most physicians understand how to manage it in their patients. Thank you. The next question comes from Gavin Clark -Gartner with Evercore ISI. Please go ahead. Hey, thanks for taking the questions. First, I just want to confirm that the dexamethasone combination didn't impact the, PK and the exposure at all? That's correct. It didn't. We didn't show it because it didn't impact it. Oh, correct. Yeah. Yes. No, yes. The data is very clear that we've... In the interest of time and the presentation and emerging collection of all the data, but the data as expected shows no impact of dexamethasone on 7455 exposure, and in particular, that no impact includes there's no enhancement of exposure. So the results we're seeing in clinic are not because you end up getting equivalently higher exposures at lower doses. Those clinical results are absolutely associated with the exposure that you would expect at monotherapy. Perfect. That's all. Apologies if I missed this before, but for the combination cohort, specifically, did you say in which cycle, in which patients, the febrile neutropenia and the grade III and IV neutropenia events occurred? Is that all in the first cycle, or did that some of it happen later? ... As it turns out, in the plus DEX cohort, because those tables were summarizing all events across all cycles, actually, the febrile neutropenia in the plus DEX didn't occur in cycle one. So, in particular, the one at 37.5 microgram was a patient with a long history of recurrent respiratory infections, who in cycle two actually had a bona fide infection and neutropenia that got growth factor and actually otherwise did fine. But they were not cycle one events. I think your other question was like grade III versus IV? Yeah, I think the numbers are real. Well, not, not I think. I know the numbers are really small in the plus DEX to make those determinations. And in fact, what I can say is that the patients that have actually had responses actually had only had grade II and grade III neutropenia, respectively. The febrile neutropenia was in a grade IV patient. But I think what's important about that is that, in the plus DEX cohort, there were no DLTs. Yes. Right? That's... So that, that's the important- Yes. -piece, right? What, what percentage are grade III- Yes And four is sort of irrelevant. What we care about are DLTs in that. Yes. Typically, what happens clinically is grade III neutropenia. Occasionally, a patient with grade III neutropenia will have a fever, and therefore it becomes clinically significant. Most of the grade IIIs are of no significance at all. And even grade IV neutropenia in itself is not of clinical significance in the absence of a fever. And what we know is, of course, that the duration of grade IV neutropenia is actually the risk of fever, not the actual fact that it exists. So, but again, we keep coming back to the same place, that the neutropenic signal that we're seeing is predictable and entirely manageable. Yeah, that's all helpful. Congrats on the progress. Great. Thanks, Gavin. Thank you. This concludes our question and answer session. I'd like to turn the call back to Andrew Hirsch for closing remarks. Great. Thank you, and thank you all for your attention today. As you can see, we're really pleased with the data on CFT7455, which suggests this is a real treatment option for patients with multiple myeloma. We look forward to seeing many of you next month in San Francisco. Have a good evening. Goodbye. The conference has now concluded. Thank you for your participation. You may now disconnect your lines.