Good morning, ladies and gentlemen, and welcome to Monte Rosa Therapeutics MRT-2359 Interim Phase 1 Data Release and Corporate Update conference call. All participants are now in a listen-only mode. There will be a question-and-answer session at the end of this call. Please be advised that this call is being recorded at the company's request. I would now like to turn the call over to Andrew Funderburk, Investor Relations at Monte Rosa Therapeutics. Thank you, operator. Good morning, everyone, and welcome to our MRT-2359 Interim Phase 1, 2 Data Release and Corporate Update conference call. Joining me on the call are Markus Warmuth, Chief Executive Officer, Filip Janku, Chief Medical Officer, and Owen Wallace, Chief Scientific Officer. Earlier this morning, we issued press releases highlighting our interim PK/PD and clinical data for MRT-2359 and our strategic collaboration with Roche. We have also posted slides on the Monte Rosa website that will accompany management's remarks. A replay of today's call will be available on the investor section of our website approximately 2 hours after its completion. After our prepared remarks, we will open the call for Q&A. As a reminder, various remarks that we make during this call about the company's future expectations, plans, and prospects constitute forward-looking statements for purposes of the safe harbor provisions under the Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by these forward-looking statements as a result of various important factors, including those discussed in the Risk Factors section of our most recent annual report on Form 10-K, which is on file with the SEC, as updated by our subsequent filings. In addition, any forward-looking statements represent our views only as of today and should not be relied upon as representing our views as of any subsequent date. Except as required by law, we specifically disclaim any obligation to update or revise any forward-looking statements, even if our views change. Now, I will turn the call over to our CEO, Markus Warmuth. Thank you, Andrew. I'm turning now to slide 3. This is an extremely exciting day for Monte Rosa. We have just announced multiple positive updates that further establish us as a leading molecular glue degrader company. First, we've released interim data from our phase 1 dose-escalation study of MRT-2359, our GSPT1-directed molecular glue degrader, or MGD. We believe the data represents the first-ever evidence of clinical activity of a rationally designed molecular glue degrader in a solid tumor setting. The data also is the first demonstration of clinical activity of an agent designed to address MYC-driven cancers, an area of vast unmet medical need. The data demonstrated optimal levels of GSPT1 degradation at all dose levels tested, and the level of degradation achieved clinically is consistent with degradation levels associated with efficacy in our preclinical studies. Second, we've announced a strategic collaboration with Roche to discover novel molecular glue degraders targeting undruggable targets in cancer and neurological diseases. The partnership substantially expands the reach of our clean discovery engine and builds on the potential of this platform to design exquisitely selective molecular glue degraders. This deal provides Monte Rosa with a $50,000,000 upfront payment and meaningful potential near-term and long-term economics. Lastly, we are now projecting that our cash runway will carry us into Q3 of 2025. This will enable us to develop MRT-2359, as well as our VAV1 programs, through major anticipated clinical milestones. Now, let me start with a few highlights of our Roche collaboration outlined on slide five. We're thrilled to partner with an industry leader in oncology and neuroscience on this strategic collaboration and licensing agreement to discover and develop MGDs against currently undruggable cancer and neurological disease targets. This collaboration has the potential to accelerate the application of our platform into neuroscience and additional areas of oncology, leveraging Roche's deep development and commercial expertise in these areas. The agreement is focused on a limited number of targets. For each of these targets, our platform has the potential to create an MGD with highly specific target protein degradation, resulting in the opportunity for meaningful therapeutic advance. Under the deal terms, Monte Rosa will lead early discovery activities against specified targets up to a defined point, and then Roche would lead any further preclinical and clinical development. Monte Rosa will receive an upfront payment of $50,000,000 and is eligible for potential preclinical, clinical, and commercial and sales milestones that could exceed $2,000,000,000, as well as tiered royalties. Roche has the option to expand the partnership to additional targets for additional nomination fees, as well as potential preclinical, clinical, and commercial and sales milestones, as well as tiered royalties. Importantly, we retain full ownership over all our existing pipeline programs. This agreement does not encumber any programs we're working on internally, including currently undisclosed programs. Further, we are free to pursue disease targets outside of those specified in the agreement, including targets in oncology and neuroscience. In conjunction with our just-released MRT-2359 clinical data, we view this collaboration as important additional validation by an industry leader of our clean discovery engine and its unique capabilities, and it certainly underscores the tremendous progress the company has made since its inception. We believe we have a great partner in Roche that ideally complements our capabilities and shares our vision and drive to develop transformative therapies. Let's now turn to MRT-2359 and an interim update on our phase 1 study in MYC-driven tumors. Featured on Slide 7, MYC family transcription factors, including c-MYC, L-MYC, and N-MYC, are well-established drivers of human cancers that maintain high levels of protein translation necessary to support uncontrolled cell proliferation and tumor growth, at least in some tumor types. They are some of the most frequently altered and activated oncogenic drivers, implicated in a significant fraction of solid tumors, including subsets of non-small cell lung cancer, small cell lung cancer, prostate, breast, and colorectal cancer, as well as neuroendocrine tumors. To date, however, MYC has been very challenging to drug. The ability to drug MYC transcription factors, directly or indirectly, could open up a large new therapeutic opportunity. We believe we have initial evidence for such an approach by degrading GSPT1 using MRT-2359. So to briefly outline the therapeutic hypothesis, our extensive in vitro and preclinical work demonstrates that GSPT1 is a synthetic lethal target in the context of MYC-driven tumors. This is true for all three MYC family members. MYC-driven tumor cells require extremely high levels of translational throughput for these cells to be transformed and survive. We believe this addiction to protein synthesis creates a dependency on the translation termination factor, GSPT1. Translation needs to be efficiently and accurately terminated, and we have shown preclinically, that when GSPT1 is degraded by MRT-2359, that process no longer takes place efficiently, thus decreasing growth and survival of tumor cells. Now, let's turn to MRT-2359 itself. On Slide 8, we highlight some of the key properties of the molecule. Importantly, MRT-2359 is highly selective, and as you can see in Western blot images, it does not degrade any of the known cereblon neosubstrates. It's also extremely selective in proteomic studies. As shown in the volcano plot on the right, MRT-2359 only engages GSPT1 and GSPT2. Additionally, we have shown that MRT-2359 has a great overall ADME profile with no observed CYP or hERG issues, and good oral bioavailability across species. To validate the in vivo activity of MRT-2359, and to inform levels of protein degradation required to achieve tumor reduction, we conducted a very large study with primary human xenografts, as shown on Slide 9. In this PDX study, we honed in on lung cancer, where we are focused in our current clinical trial, and included models of non-small cell adenocarcinoma, small cell lung cancer, and neuroendocrine lung cancer. The red bars here indicate MYC-activated tumors. Blue bars are MYC negative. You can see that the responses are quite strong in MYC-activated tumors, with little efficacy in MYC-negative tumors. Importantly, we took 7 representative models from this study and performed targeted mass spectrometry, which is the assay we are actually using in the clinic to measure GSPT1 levels. As you can see, at a dose that leads to significant tumor shrinkages in the models, we achieve approximately 60% GSPT1 degradation, and degradation did not further increase at higher doses. As a reminder, and you can find additional data in our public corporate slide deck posted on our website, MRT-2359 was designed to plateau out at optimal depth of degradation to lead to tumor growth inhibition and cell death in MYC-driven tumor cells, without causing unacceptable toxicities in other cells. Consistent with what we saw in the PDX study, the optimal level of degradation in our in vitro work was also determined to be approximately 60% by targeted mass spectrometry. So in conclusion, approximately 60% degradation is what we were targeting to achieve in the clinic. The clinical trial itself is a phase 1/2 study of MRT-2359 in patients with MYC-driven tumors, such as non-small cell lung cancer, small cell lung cancer, high-grade neuroendocrine tumors of any primary tumor type, L or N-MYC amplified solid tumors, all of these being tumor types with enrichment for high L and N-MYC expression. Slide 10 provides an overview of the phase 1 part of the study and the objectives of this interim data disclosure, which are to demonstrate dose-dependent PK, to demonstrate that we can get optimal levels of GSPT1 degradation in PBMCs in tumor tissues. It's safe dose levels and without the toxicity seen for some agents in this class, and then finally, to share any preliminary efficacy signals. I now provide a summary on Slide 11 of the interim clinical data as of the September 7 cutoff date, and then we'll go into some details. As of the data cutoff date, we completed 3 dose levels, 0.5, 1, and 2 mg, and a total of 21 patients have been enrolled. Patients have been dosed on a 5 days on, 9 days off, or 5 and 9 schedule. First, we saw dose proportional pharmacokinetics after all dosing across the 3 dose levels without food effect. Second, on pharmacodynamics or PD, clinical data supports that, as predicted, based on preclinical modeling, the 0.5 milligram starting dose was pharmacodynamically fully active, and that is based on PD assessment in both PBMCs as well as tissue biopsies. PD modulation was optimal across all dose levels, so around 60% degradation of GSPT1 was reached from the starting dose, and a similar level of PD modulation was observed at the 1 and 2 milligram dose levels as well. Turning now to clinical activity, it's important to keep in mind that this was a heavily pretreated, heterogeneous phase 1 study population that was not preselected for biomarker status. With that said, we see clinical activity across all dose levels, and we regard these results as very promising for this early stage of development. So of the 21 patients enrolled, 15 were evaluable for efficacy as of the cut-off date. Of these, six were biomarker positive, five were biomarker negative, and four patients did not have biomarker data available. Of the six biomarker-positive patients, two had a partial response, one confirmed and one unconfirmed, and one patient experienced a durable stable disease. The confirmed partial response patient and the small cell lung cancer patient with durable stable disease currently remain on treatment. There was an additional durable stable disease in a non-small cell lung cancer patient, where biomarker status was not available because of a pretreatment biopsy or any archival tissue not available to us. It is worth noting also that, as anticipated, we did not observe clinical activity in any of the biomarker-negative patients. Lastly, turning to safety and tolerability, we have identified what we believe to be a favorable dose range for the 5 and 9 dosing schedule. The adverse event profile at 0.5 and 1 milligram was very favorable, with only grade 1, 2 toxicities observed and not requiring any dose interruptions or reductions. At 2 milligram, in line with the findings from our preclinical GLP toxicology studies, we started to see some hematological toxicities, including grade 4 thrombocytopenia. This was manageable with dose reduction or dose interruptions, and patients experiencing a grade 4 adverse event continued dosing on the drug. Most importantly, we did not see some of the toxicities characteristic for other agents in this class. There was no evidence for cytokine release syndrome, no hypertension, hypotension, and no clinically significant changes in calcium, as had been reported by BMS/Celgene for their molecule CC-90009. In summary, we are very encouraged by these data. With optimal PD modulation across all dose levels, initial signs of clinical activity, and evidence that the toxicities that have affected other GSPT1 agents have been dialed out. So I now hand the call over to Filip to review additional details of the clinical data. Thank you, Markus. On slide 12, you can see our pharmacokinetic and pharmacodynamic data. Starting on the left, we see dose proportional pharmacokinetics across all three dose levels in line with preclinical models. We did not observe any food effects. On the right, looking at pharmacodynamics in PBMCs in terms of GSPT1 degradation based on target mass spectrometry, we observed degradation of around 60%, which was consistent across all dose levels. These levels of degradation are what the molecule was optimized towards and are in line with maximal degradation observed in preclinical studies that Markus discussed earlier. This level of degradation is what we believe to be optimal for achieving synthetic lethality in MYC-expressing tumor tissues without triggering toxicities in other tissues. On slide 13, looking at tumor biopsies, we assess GSPT1 degradation from pre-treatment screening biopsies and on-treatment biopsies. We had 11 patients across the 3 cohorts for whom we were able to obtain matched samples, where GSPT1 protein levels were assessed with target mass spec. We saw consistent GSPT1 degradation at these dose levels, matching what we have seen with PBMCs on the prior slide. The data are highly encouraging, and we think they demonstrate that MRT-2359 is exerting the desired optimal depth of degradation within the tumor at all dose levels. Turning to the safety data shown on slide 14, we believe that MRT-2359 demonstrates a favorable overall safety profile supportive of continued development. As Markus noticed, there was no hypotension, no cytokine release syndrome, and no clinically significant hypocalcemia seen at any dose, and I'd highlight that no patient discontinued therapy due to adverse events. Dose levels of 0.5 milligram and 1 milligram showed only modest, mostly grade 1, gastrointestinal treatment-related adverse events and no grade 3 or worse toxicities while achieving optimal levels of GSPT1 degradation. At these doses, no hematological toxicity was observed. As shown in table, at 2 milligrams, we observed dose-limiting toxicity of grade 4 thrombocytopenia, and we saw non-dose limiting grade 4 neutropenia and leukopenia. Both of these were reversible and did not result in treatment discontinuation. Now, let's turn to activity. As Markus pointed out, we see evidence of clinical activity across all dose levels, consistent with the optimal GSPT1 degradation observed across these cohorts. Also, despite the early stage of the study, we observed that MRT-2359 can induce significant and rapid tumor shrinkage. I'd now like to share a couple of patient case studies. On Slide 15, we present a case study of a patient with metastatic high-grade neuroendocrine bladder cancer with high expression of N-MYC, based on the tumor biopsy analysis. This patient was heavily pretreated with 4 prior lines of therapy, including chemotherapy and immunotherapy. The patient started at 2 milligrams, but required dose reduction for hematological toxicity. The lower dose has been well-tolerated without any safety issues. The patient demonstrated a notable response to therapy. CT imaging after 4 weeks of treatment demonstrated 34% reduction in sum of target lesions compared to baseline, which then improved to 59% reduction on the subsequent CT. Representative CT images show the continuing reduction in the size of the lung lymph node on the upper panel, and the right liver lesion on the lower panel. Moving to slide 16, this case study presents a heavily pretreated patient with metastatic non-small cell adenocarcinoma of the lung, who was found to have small cell neuroendocrine transformation on the baseline tumor biopsy. The patient was also heavily pretreated with 4 prior lines of therapy, including chemotherapy and several lines of immunotherapy. The patient started at the lowest dose, 0.5 mg. CT imaging after several weeks of MRT-2359 demonstrated 41% reduction in the sum of target lesions per RECIST. When you look at the baseline scan, you can see multiple liver lesions, dark areas, some of them circled, and you can see that these were essentially resolved in the follow-up scan, which was conducted while the patient was on treatment. The patient experienced frequent dose interruptions due to symptoms from bowel obstruction, not related to MRT-2359, which made it impossible for the patients to continue scheduled oral dosing. We believe this has, at very least, contributed to the response, not confirming on a subsequent CT scan. Slide 17 shows the summary of our preliminary efficacy data seen in biomarker-positive patients. Overall, a data cutoff on September 7, of 21 patients treated, 15 were evaluable for efficacy, and six of these 15 patients were classified as biomarker positive based on N-MYC or L-MYC expression or neuroendocrine status in lung cancer. Of these six patients, which are depicted in the waterfall plot, there was one confirmed partial response and one unconfirmed partial response. In addition, a patient with small cell lung cancer with N-MYC and L-MYC expression showed stable disease with no change in sum of target lesions. It's very unusual for small cell lung cancer not to show any growth, as it's typically a rapidly advancing disease, so we believe this is a meaningful outcome. Both, the patient with high-grade neuroendocrine bladder cancer and the small cell lung cancer patient with stable disease remain on treatment post their latest scan. We also observed durable stable disease in a patient with non-small cell lung adenocarcinoma, who has been on therapy for more than seven months. However, the biomarker status of this patient remains unknown because of the lack of available tumor tissue for testing at baseline. Overall, four of 15 evaluable patients did not have biomarker status available, mostly because of a lack of screening, biopsy, and archival tissue, and in one case, the data is not yet available. Five patients were evaluable and biomarker negative, and in line with our therapeutic hypothesis, we have not seen activity in these patients. Lastly, the six unevaluable patients, either withdrew consent for non-drug related reasons, had not reached their first scan as of the data cutoff, or experienced early clinical progression. None, except the patient that withdrew the consent, was biomarker positive. We are very pleased with these initial findings from the study and eager to continue enrolling patients. I'll now turn the call back to Markus. Thank you, Filip. We believe this interim clinical data is highly encouraging. Even at this early stage of development, we have seen what we believe is compelling PK, PD, and safety, as well as encouraging signals of clinical activity, including one confirmed and one unconfirmed partial response. Let's discuss the next steps of the program, as shown on slide 18. We are currently dosing 1.5 milligram on the 5 and 9 schedule. In addition, we are planning to explore a 21 days on, 7 days off, or 21/7 dosing schedule. Given the limited toxicities we have seen at the 0.5 and 1 milligram dose levels, we believe the 21/7 schedule could further improve drug activity by maintaining an acceptable safety profile by achieving longer target coverage. From there, we plan to select a recommended phase 2 dose, and we are planning to report on full phase 1 data in 2024, with further clarity on the expected timing of the disclosure to be provided early next year. Let's turn to slide 20, which shows our pipeline. All our programs address undruggable or inadequately drugged proteins with high levels of target validation. In addition, we believe each of our programs has the opportunity for rapid clinical proof of concept with a biomarker-based patient selection strategy, and notably, each has broad market opportunities. So let me go through a few highlights and milestones coming up. First, and we've discussed extensively the interim clinical data for MRT-2359. We plan to select and initiate phase 2 expansion cohorts after we select a recommended phase 2 dose next year. In addition to the tumor types in the phase 1 dose escalation cohorts, I'd note that we've seen very promising preclinical results in other common tumor types, including c-MYC-positive prostate and breast cancer, which could be considered for expansion cohorts as well. We believe the collective opportunity for therapy targeting MYC-driven tumors is substantial. Second, MRT-6160 is our highly selective VAV1 development candidate going through IND-enabling studies as we speak. VAV1 is a currently undruggable target involved in both T and B-cell biology, and it's important to relay signals downstream of the T-cell and B-cell receptors. We expect to file an IND in the first half of next year and then plan to progress into a phase 1 SAD/MAD study in healthy volunteers. We believe this program has wide potential applications in autoimmune diseases, including both large indications like rheumatoid arthritis, multiple sclerosis, and psoriasis, as well as niche indications. In addition, our NEK7 program for inflammatory diseases, currently in lead optimization, is advancing quickly behind MRT-6160. We have identified a molecule we are currently profiling towards development candidate selection. In our preclinical work, we've seen strong and very selective in vivo degradation of NEK7, with potent inhibition of the NLRP3 inflammasome. We believe this program could have substantial advantages over NLRP3 small molecule inhibitors due to the differentiated role in of NEK7 in the inflammasome, the actual depth and duration of pathway inhibition achievable, as well as an emerging role of NEK7 in mast cell degranulation. Lastly, our CDK2 program, currently in lead optimization, has potential for greater selectivity against this target than ATP site inhibitors. CDK2 has been recognized as a promising but challenging target for ovarian and breast cancer. So while today's call focused on our most advanced program, MRT-2359, we are now a multi-asset company. Moving to slide 21. In conclusion, we believe Monte Rosa has the industry-leading platform for molecular glue degraders, and we have shown this by advancing multiple highly differentiated programs, each of them with an exquisitely selective molecule. Our MGDs have the potential to solve many of the limitations of other modalities by selectively degrading therapeutically relevant proteins considered undruggable or inadequately drugged at this point. Today's announcements mark a major milestone in the progression of our company. We've demonstrated clinical activity of a rationally designed MGD in solid tumors for the first time, opening the door for a large potential opportunity in MYC-driven solid tumors. Our discovery collaboration with Roche in oncology and neurological diseases further validates the power of our discovery engine and expands our reach into new therapeutic areas. Our Roche collaboration cements the financial position of the company, providing cash runway into Q3 2025 to enable us to advance our internal pipeline to key value inflection points. Thank you very much for joining us today. I'll now turn the call over to questions. Thank you. Ladies and gentlemen, to ask a question, you will need to press star one one on your telephone and wait for your name to be announced. To withdraw your question, press star one one again. Please stand by while we compile the Q&A roster. Our first question coming from the line of Derek Archila with Wells Fargo. Your line is open. Great. Good morning, and congrats, team, on the data. Just a couple questions from us. I guess, first off, you know, do you think you're safely out of the window of seeing any side effects associated with CC-90009? You know, have we seen enough data to kind of confirm, you know, that we, we aren't going to see CRS and, you know, kind of hypocal and some things like that. I guess the second question would be just your expectations of moving from the 5 + 9 schedule to the 21 and 7. Just thoughts on how that switch might, you know, change the, the overall profile of the drug, and whether you've tested that preclinically. Thanks. Yeah, thanks, Derek. So, on your first question, again, very pleased with the safety and tolerability profile that we're seeing so far. Clearly identified two dose levels here. We're not seeing any of these toxicities that have been reported for the BMS/Celgene molecule. There's really no hints of cytokine release syndrome associated with hypotension, no hypocalcemia either. So, I think we feel really good about what we've seen so far. Obviously, something we had expected from all our preclinical data, but good to actually have that reconfirmed in the clinical setting. And then on 21-7, you know, again, obviously, as I said, encouraged by the safety and tolerability profile we have seen. Obviously, also actually quite pleased with the pharmacodynamic modulation, but keep in mind, it's a 5 and 9 schedule. And there is a bit of a blind spot in our sample collection, meaning, of course, it is quite possible that after day 8, leading to the next round of treatment, GSPT1 levels come back. And so we do think that longer coverage of GSPT1 degradation can be beneficial. We have sure done all the preclinical work to enable that 21-7 schedule. As a fact, we are enabled to go to daily dosing if we wanted to. Obviously, again, the clinical trial needs to be done first, or expanded to that schedule. But all the preclinical work that we have done, we believe is extremely encouraging. Excellent. Well, congrats again on the data. Thanks for taking the questions. Thank you. Our next question coming from the line of Ellie Merle from UBS. Your line is open. Hi, this is Sarah on for Ellie. Thanks so much for taking the question. Just looking for, moving forward into phase 2, how are you thinking about the recommended phase 2 dose, given, the degradation similar across the profile? Thanks. Yeah, excellent question. Obviously, too early in the trial to completely answer it. We are, as I said before, extremely pleased with what we've seen at the 0.5 and 1 milligram dose level. I'm clearly seeing saturated PD modulation there, with a very favorable tolerability profile now going into 21-7. As you might remember, our study design actually allows us, even before we go into expansion, to recruit a substantial number of patients into each cohort, actually into the sort of safety cohorts, but then also into backfills. I think what you should expect to see moving into next year and a recommended phase 2 dose is, once we have tried that additional schedule, to explore further within the phase 1 portion on the right dose level and then declare a recommended phase 2 dose from there. Great. Thank you. Thank you. One moment for our next question. Our next question coming from the line of Edward Tenthoff from Piper Sandler. Your line is open. Great, thank you. And, congratulations both on the data and on the Roche collaboration. I'm particularly pleased to see MRT-2359 behaving so well with initial signs of activity. I wanted to ask, since a lot of questions were asked on MRT-2359, just with respect to the Roche collaboration, you know, have you had any conversations about the declared candidates? Or was this really just a deal where you were looking to do discovery? And I know it hasn't been disclosed, but can you give us a sense for how many limited targets were included? Thank you. Yeah, so, not in a position to talk about the number of targets at this point. Again, super excited about this, this collaboration. You know, obviously, when you have an office in Basel, then- Yeah ... almost in walking distance, to, to Roche, it's almost natural for, at some point, these conversations to, to happen. There, there's many other reasons, of course, not just like the, the short commute- Sure -why we are excited about talking with those. But, naturally, you start to talk. It's a small town, right? And so it is a true discovery collaboration. You know, I'll point out that, yeah, I mean, we still wholly own our entire publicly disclosed portfolio. And I think each of these programs certainly has the opportunity for future partnerships, just based on the commercial opportunity, the breadth of- Sure diseases that we can cover. But again, not in a position today to give you any more details. Well, congratulations across the board. Thanks. Thanks, Ed. Thank you. And our next question coming from the line of Michael Schmidt with Guggenheim. Your line is open. Hey, guys. Thanks for taking my questions. I was wondering if you could talk a bit more about your thoughts around the biomarker selection, I suppose. Can you talk a bit about the criteria used to determine patients as biomarker positive? Have seen any correlation in the responses with expression levels, and how do you think about utilizing biomarkers in the phase 2, potentially? Yeah, great question, Michael. And so, you know, as, as you know, I mean, extensive work that went into this, uh, preclinically, and obviously some of that shown today, but even more of it obviously in, in some of our prior presentations. Again, why, why this mechanism technically works, in the context of all three MYC transcription factors, early on, just in order to not cast too wide a net, we honed in on, on L- and N-MYC, and in particular in lung cancer and in neuroendocrine tumors. And so the biomarker strategy here is essentially high expression of L- and N-MYC, with one exception, and that is neuroendocrine lung cancer, where we actually have seen preclinically efficacy even, when L- and N-MYC is expressed at lower levels. We think that is just based on additional wiring that leads to activation of the MYC transcription factor network. But then anywhere else, we're looking for high levels of L- and N-MYC expression. Again, it's expression, not amplification, and we're determining that using a qPCR assay. We have not disclosed the actual thresholds to call a tumor L- or N-MYC positive versus negative or high versus low. But of course, there is a predefined cutoff level, and predefined based on preclinical data. And so there is a little bit of data in the efficacy summary slide, right where we're labeling which of these tumors were high for L-MYC, high for N-MYC, and whether or not they had neuroendocrine status. And so this is how we're going after. And again, I'm very pleased to see that the clinical activity that we have is limited to the biomarker-positive subset. Not seeing any clinical activity in the biomarker-negative subset in this trial so far, except this one patient, where unfortunately we didn't have that screening biopsy or any archival tissue available. Great. Thank you. Thank you. And our next question coming from the line of Eric Joseph with JP Morgan. Your line is open. [audio distortion] Sorry, Eric, you were breaking up quite a bit. Sorry. [audio distortion] Yeah, so we still only get every third or fourth word. Maybe let's move to the next question in the meantime, see if Eric can get better reception later. Certainly. One moment, please, for our next question. Our next question coming from the line of Kelly Shi with Jefferies. Your line is open. Congrats on the great progress. I have two questions. First, are there any signals that could suggest a certain tumor types or tissues to be more responsive to GSPT1 degradation than others, from both preclinical and the clinical evidence? And then the second question is, for the six unevaluable patients, how many of them are biomarker positive, and also treated at, which those levels? Thank you. Yes, so to your question on degradation and any preference per tumor type, I'd say we're not necessarily expecting that for as long as these tumors are MYC-positive. I would say probably too small a sample set at this point to derive solid conclusions. But again, at least for now, what we're seeing across the different biomarker positives, there's no significant difference in degradation. And then the second one on the unavailables. Filip, do you want to answer that question? Yeah, sure. So the patients who were unavailable, they were actually kind of relatively equally distributed across all those levels. Yeah, again, they were all biomarker negative, except one patient, who was positive, but had to withdraw consent, for actually non-drug related reasons. Thank you. Thank you. Our next question coming from the line of Christopher Liu with Leerink Partners. Your line is now open. Hey, guys. Thanks for the question. I just had a follow-up on the biomarkers. In terms of the non-small cell lung cancer patient, where you guys got a partial response. On that chart on slide 17, it looks like they were negative on both. So just kind of wondering, you know, what the cutoff was for that low N-MYC expression that you guys had? Mm-hmm. Yeah, so, this patient for L- and N-MYC was actually under the cutoff level, so determined biomarker negative. But again, as mentioned before, because of what we had seen pre-clinically, in small cell lung cancer, and also in neuroendocrine lung cancer, for just lung cancer, we're considering neuroendocrine positivity, and we're actually using pathology and our own signature for that. So, neuroendocrine status in that tumor type is considered to be within the biomarker positive definition of the trial. Right. So that patient, super interesting, as Filip pointed out, because was a non-small cell lung cancer patient, but then on treatment, and again, multiple rounds of prior treatments, transformed into small cell lung cancer and was clearly of neuroendocrine differentiation, both by pathology and our own signature. Okay, got it. And then if there needed to be, like, a panel or something where, you know, physicians were looking at high levels of N-MYC or L-MYC, but in the case of non-small cell lung cancer with neuroendocrine, that would kind of be the criteria to look at? Is that, is that what I'm understanding? Yeah. I wasn't able to understand your, your, the last part of your question. I'm trying to answer it, but if I'm completely off, let me know. So yes, for neuroendocrine, we're using pathology for that. But, as mentioned, we also, at least sort of in this early portion of the trial are reconfirming this, on mRNA level with our own new endocrine signature. And that's an assay using the nCounter platform. Okay. And just one more question. In terms of the data readout that you guys have guided for next year, does that include the new dosing regimen? Yes, that would include the new dose regimen. Okay. Thank you very much. Thank you. Our next question coming from the line of Marc Frahm with TD Cowen. Your line is open. Hey, thanks for taking my questions and congrats on the data. I know the kind of biomarker positivity, you know, was predefined based on some preclinical data, but I believe the plan was, you know, in the clinic to kind of refine that over time. Just any insights you've gained so far that may lead you to kind of move the line as to where what you're calling MYC positive? And then also, just any plans that as you're starting to maybe backfill and expand out some of the dose levels to get towards selecting a dose, just any plans right now to narrow enrollment to just biomarker positive patients? A great question, and so, on your first question, we're very pleased to see how the preclinical work has translated here into the clinical setting across the board, but in particular on biomarkers. And so, at this point, no adjustments. As you might remember, even the expansion arms in phase 2 would allow us to modify those cutoffs. But I'd say so far, what we're seeing, yeah, very much in line with what we have for preclinically. But again, sure, it's still a small sample number, of course, that we're basing this on. And then the second question, enriching for more biomarker positives. Yes, absolutely. Obviously, in the backfill cohorts, you know, we can actually through the protocol, at least by tumor type, enrich to give us a higher chance. It's obviously not preselected, right? So I think even if we say, "Hey, let's have more small cell," there's always a possibility that there is a small cell lung cancer patient that turns out to be biomarker positive. But there's certainly strategies for us to further enrich. That said, I think we've landed exactly where we wanted to land in regards to biomarker positive, Ryan. I'm assuming, before we started the trial, that in those escalation, about a third of the patients would turn out to be biomarker positive. Great. Thank you. Thank you. And as a reminder, to ask a question, please press star one, one. And our next question coming from the line of Eric Joseph with JP Morgan. Your line is now open. Hi, thanks. Hopefully, you can hear me now. Much better. Great. Good. In fact, so most of my questions were just sort of answered in the follow-up. I guess any measure here of CNS exposure with MRT-2359 so far in the trial? I guess, what are your expectations about the compound being active in cases of Mm. Yeah, NET progression. Thank you. You know, a great question, and, unfortunately, no conclusion at this point, Ryan. I don't think there were enough cases here for us to solidly conclude one way or another. Okay, great. Thanks for taking the question. Thank you. I see no further questions in the Q&A queue at this time. I will now turn the call back over to Mr. Warmuth for any closing remarks. Sounds great. Yeah, so, again, thanks, everyone, for joining this morning's call. Thanks for the questions, and unless there is another question, would actually like to close the call. Thank you. Ladies and gentlemen, that ends our conference for today. Thank you for your participation. You may now disconnect.