Greetings and welcome to Monte Rosa Therapeutics' Conference Call to discuss the company's Interim Clinical Results from the ongoing phase I study of MRT-8102. At this time, all participants are in a listen-only mode. A question-and-answer session will follow the formal presentation. As a reminder, this conference is being recorded. It is now my pleasure to introduce Andrew Funderburk, Senior Vice President, Investor Relations and Strategic Finance at Monte Rosa. Thank you, Andrew. You may begin. Thank you. Good morning, everyone. Thank you for joining our conference call today to discuss the interim clinical results from the ongoing phase I study of our NEK7-directed molecular glue degrader, MRT-8102, in healthy volunteers and subjects at elevated cardiovascular disease risk. With us on today's call are Markus Warmuth, Chief Executive Officer, and Filip Janku, Chief Medical Officer. A copy of the presentation materials is also available on our IR website. Before we begin, I would like to remind everyone that any statements we make or information presented on this call that are not historical facts are forward-looking statements that are based on our current beliefs, plans, and expectations, and are made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Please refer to our annual report and other filings we make with the SEC for our risk factors and other information. With that, I'll turn the call over to Markus. Thank you, Andrew, and thank you, everyone, for joining us this morning. Today, we're thrilled to provide an update on the interim results from our phase I study of our NEK7-directed molecular glue degrader, MRT-8102. In brief, the interim results have exceeded our already high expectations and speak to the potential of MRT-8102 to transform the treatment of atherosclerotic cardiovascular disease, as well as other cardiovascular, cardiometabolic, and inflammatory conditions. Most notably, MRT-8102 induced rapid and compelling reduction in hsCRP across all doses tested in both healthy volunteers and high CVD risk subjects, a total of 112 subjects. I'll highlight a few key findings from our interim data. The single ascending dose, or SAD, and multiple ascending dose, or MAD, cohorts have been completed with no safety concerns as of the data cut-off date of December 23rd. During SAD and MAD, MRT-8102 was dosed from 5 milligrams to 400 milligrams, and the data suggest that we're seeing maximum activity even at the lowest dose level, so 5 milligrams, consistent with the high potency and catalytic mechanism of action of MRT-8102. Importantly, even after just a single dose, as well as after seven days of dosing, we saw a 78% reduction in high sensitivity CRP in subjects with elevated baseline CRP levels. The interim analysis of 24 subjects who have completed four weeks of dosing in part 3, the cohort recruiting subjects at high risk of developing CVD, was, if anything, even more remarkable. We observed an 85% sustained reduction of hsCRP through the end of week four. A striking 94% of subjects achieved reduction of hsCRP to under 2 milligrams per liter after four weeks of dosing. These results are even more pleasing in light of the high median baseline hsCRP level of 6.3 milligrams per liter across subjects treated with MRT-8102. Lastly, we also observed a 31% reduction in fibrinogen, an independent atherosclerotic risk factor, after four weeks of dosing. Both the total drop in hsCRP as well as the rate of reduction of hsCRP to under 2 milligrams per liter are matched, if at all, only by high doses of IL-6 targeting antibodies in cross-trial comparisons. And I will show you some of the data in a second. Based on these striking results, we are expanding our phase I CRP proof of concept study in elevated CVD risk subjects. This study, now named GFORCE-1, will include additional dose levels, which we believe will enable us to accelerate development in ASCVD. Data from the expanded GFORCE-1 study are expected in the second half of 2026. Now, as promised, let's put these results into context. As you can see on slide 4, on the left side, the reduction of hsCRP after just four weeks of dosing at 40 milligrams of MRT-8102 is consistent with those achieved with the higher doses of IL-6 biologics after three months of dosing at the high doses and numerically better than an IL-1 beta antibody or an IL-1 alpha inhibitors based on cross-trial comparisons. In the graph on the right, we look at the percent of subjects achieving CRP reduction to less than 2 milligrams per liter across different agents. Similar to the analysis on the left side, MRT-8102's 94% rate compares quite favorably to other agents, with results consistent with those observed with IL-6 biologics after three months of dosing at the higher dose levels. Importantly, we believe that upstream targeting of NEK7 has significant advantages over downstream targeting of IL-6, notably through MRT-8102's ability to suppress pyroptosis, the pathological event responsible for secretion of multiple disease-promoting cytokines that later leads to IL-6 secretion and CRP production. So let me talk about these advantages and others on the next slide in more detail. This slide five is dedicated to mapping out the biological rationale for degrading NEK7 and why we believe it's highly differentiated over other compounds and modalities targeting the NLRP3, IL-1, and IL-6 pathway. MRT-8102 is an oral molecular glue degrader that selectively and catalytically degrades NEK7 to suppress NLRP3 inflammasome activity. As compared to small molecule inhibitors, MRT-8102 induces catalytic NEK7 degradation, leading to long-lasting inflammasome disassembly and sustained inhibition of cytokine release, most importantly, without the on-off pathway inhibition characteristic of inhibitors. Moreover, and as will be discussed later by our CMO, Filip Janku, MRT-8102 is exquisitely selected for NEK7, as confirmed by our proteomics work, minimizing the risk of off-target effects. Given that MRT-8102 prevents inflammasome assembly and activation, it is highly effective at suppressing pyroptosis, the pathological event that is ultimately responsible for secretion of disease-promoting cytokines such as IL-1 alpha, IL-1 beta, and IL-18, as well as damage-associated molecular patterns or DAMPs, which are known to be important drivers of inflammatory processes. Although various mono and bispecific biologics currently under investigation can robustly target one or more of the cytokines downstream of pyroptosis, ultimately, these classes of therapeutics may be limited by their inability to suppress the full spectrum of disease-relevant cytokines and, more importantly, the release of DAMPs. Furthermore, whereas MRT-8102 selectively reduces the pool of cytokines driven by NLRP3 inflammasome activation, biologics like IL-1 and IL-6 targeting antibodies may indiscriminately inhibit this pool of cytokines irrespective of their source and thus potentially elevate infection risk by impacting immune pathways beyond the NLRP3 inflammasome pathway. The role of NLRP3 and IL-1 beta in ASCVD has been well established through various approaches. As an example, slide 6 highlights the key findings of a landmark clinical trial called CANTOS. In this study published by Ridker and colleagues, canakinumab, a monoclonal antibody targeting IL-1 beta, was dosed in over 10,000 patients with prior myocardial infarction and hsCRP levels of greater than 2 milligrams per liter, a threshold above which there is higher risk of cardiovascular events and mortality. Treatment led to a significant reduction in hsCRP, with the median reduction from baseline being 37 percentage points greater in the 150 milligram group than in the placebo arm at the 48-month time point. Consistent with the reduction in hsCRP, treatment led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid lowering. Despite the significant efficacy noted, Canakinumab was also associated with a higher incidence of fatal infection than was placebo, which ultimately yielded an unfavorable risk-benefit profile. The higher risk of infection is likely due to the above-mentioned indiscriminate and deep suppression of an NLRP3 independent pool of IL-1 beta, a cytokine that plays a critical role in host protective immunity. Importantly, MRT-8102 is unlikely to share this risk, as treatment is expected to only impact the NLRP3 relevant pool of IL-1 beta, and as you will hear later, so far, we have not seen any elevated infection risk in our clinical study. Now, let's take a moment to detail the biology of ASCVD and why we believe that upstream targeting of NEK7 and NLRP3 may have greater potential than downstream IL-6 biologics in ASCVD. The illustration on the left on slide seven shows how monocytes, upon uptake of oxidized LDLs, become the initiator and driver of disease through chronic activation of NLRP3 inflammasomes and consequential pyroptosis. This pathological activation of NLRP3 promotes plaque destabilization and downstream CVD events through contribution of cellular debris, lipids, and further recruitment of bone marrow-derived macrophages to the growing plaques. Given the involvement of the NLRP3 inflammasome, we believe that MRT-8102 treatment-induced suppression of pyroptosis could be an effective means by which to stabilize plaques and hence reduce cumulative incidence of major adverse cardiac events. As shown in the top right graph, an unbiased analysis using an in-house generated NLRP3 activity signature across thousands of data sets, spanning hundreds of diseases, indeed identified ASCVD as one of the top-ranking conditions with strong NLRP3 activation. As expected, CAPS, a group of rare and hereditary autoinflammatory disorders, also scored highly in our analysis. CAPS is known to be driven by constitutively active NLRP3 mutants, providing a positive control to this analysis and adding validity to our approach. Interestingly, in addition to CAPS and ASCVD, we also noted other diseases that scored comparably to ASCVD and CAPS, which are currently being explored as additional indications that MRT-8102 or next-generation molecules could move into in the future. Consistent with the transcriptomic study, an unbiased genetic association analysis shown on the bottom right found an NLRP3 gain-of-function single nucleotide polymorphism, or SNP, to be significantly associated with increased downstream CVD events, including stroke, coronary artery disease, and peripheral artery disease, further supporting the role of the NLRP3 inflammasome in driving disease pathology. By comparison, although IL-6 signaling was also associated with CVD outcomes, the effects were weaker than that observed for NLRP3, implying that upstream targeting of NLRP3 activity may have the potential for greater efficacy than targeting downstream cytokines such as IL-6. In summary, these data strongly support an opportunity for MRT-8102 in the treatment of CVD indications. Slide 8 highlights the substantial market opportunity in ASCVD. While LDL cholesterol-lowering agents are well established as a part of the treatment paradigm, nearly 40% of patients have achieved their LDL-C targets but still experience life-threatening CVD events. This demonstrates the substantial residual risk not fully addressed by LDL-C lowering and speaks to the promise and importance of complementary approaches such as targeting the NEK7 NLRP3 pathway. I'd now like to turn the call over to Filip to discuss the interim results of our phase I study of MRT-8102 in more detail. Thank you, Markus. Before I get into the clinical study, I want to briefly discuss why we think the MRT-8102 preclinical profile points to its best-in-class potential, as we illustrate on slide 10. In short, we believe the potency, selectivity, and long-lasting pharmacodynamics of MRT-8102 differentiated from IL-1 and NLRP3 inflammasome approaches such as inhibitors or biologics. MRT-8102 is highly potent with a DC50 of 2.5 nanomolar, as illustrated on the middle panel with our proteomic analysis. It's monoselective for NEK7, with no measurable degradation of other proteins, including other NEK family members. Finally, as shown on the right, the catalytic mechanism of action results in prolonged pharmacodynamic effects even after a single dose, with about 80%-90% degradation of NEK7 in situ that translates into substantial inhibition of IL-1 beta secretion after ex vivo stimulation, as we have shown in earlier disclosures. We think all these properties have translated quite well in the clinical data I'm now about to discuss. Slide 11 details the design of our phase I study. In the single ascending dose, or SAD cohort, we had 48 participants across five dose levels ranging from 40 milligrams to 400 milligrams. In the multiple ascending dose, or MAD cohorts, we had 40 participants across five dose levels ranging from 5 milligrams to 200 milligrams. The ongoing part 3 of the study that evaluates MRT-8102's activity at 40 milligrams for 28 days in subjects with elevated cardiovascular disease risk will enroll approximately 36 subjects, of which a portion, 24 subjects, had completed four weeks of dosing and assessment of CRP levels as of the data cut-off date. The primary endpoint was safety and tolerability. Key secondary and exploratory endpoints included pharmacokinetics and inflammatory markers, including assessment of NEK7 degradation in peripheral blood cells, changes of the acute phase reactants, hsCRP and fibrinogen, levels of endogenous IL-6 in blood and cerebrospinal fluid, and IL-1 beta levels following ex vivo stimulation. The data cut-off date we are using for this interim readout and the totality of the data presented today is December 23, 2025. Slide 12 shows NEK7 degradation in peripheral blood T cells after single and multiple dose administration. Consistent with preclinical studies, we noted rapid and marked degradation of NEK7 in peripheral blood T cells even after a single administration of MRT-8102. Approximately 80% to 90% degradation was noted at six hours post a single dose of MRT-8102, a level that was sustained following multiple administrations ranging from seven days in the MAD portion of the trial to up to four weeks in the part 3 portion of the study. As expected, based on the catalytic mechanism of action of MRT-8102, even a dose as low as 5 milligrams achieved approximately 80% NEK7 degradation following seven daily administrations and 24 hours after the last dose. These results were in line with preclinical data from our cyno PK/PD studies that suggest that the pathway inhibition can be achieved at these levels of degradation. In light of achieving optimal NEK7 degradation across all those levels, we were able to analyze downstream inflammatory markers, including hsCRP in aggregate across all SAD cohorts. Through this analysis, we observed a significant reduction in high-sensitivity CRP even after just a single dose, as shown on slide 13. Across all subjects treated with a single dose of MRT-8102, of which the majority had normal CRP levels at baseline, we observed 52% reduction in CRP at 96 hours post-dose. As expected, the reduction in CRP was greater in subjects with higher median baseline CRP, with a median CRP reduction at 96 hours of 72% and 78% in the subset of subjects with baseline CRP equal to or greater than 1 milligram per liter and equal to or greater than 2 milligrams per liter, respectively. Again, comparable activity was noted across all SAD dose levels ranging from 40 milligrams to 400 milligrams, suggesting a wide range of doses available for future development. We obtained similarly encouraging results from the seven-day multiple dose administration cohorts detailed on slide 14. Similar to the SAD part of the study, we were able to analyze all MAD dose levels in aggregate in light of comparable NEK7 degradation levels from 5 to 200 milligrams. Through this analysis, we observed a 61% reduction in CRP in all subjects treated with MRT-8102 and greater reductions in subjects with higher baseline median CRP levels, approaching nearly 80% in subjects with median baseline CRP of equal to or greater than one, equal to or greater than two, or equal to or greater than 3 milligrams per liter. Of note, as mentioned previously by Markus, individuals with elevated CRP equal to or greater than 2 milligrams per liter are at greater risk of cardiovascular events. Thus, reducing CRP levels below this threshold is crucial for reducing cardiovascular morbidity and mortality risks. Based on only seven days of treatment, seven of nine or 78% of subjects with baseline CRP of equal to or greater than 2 milligrams per liter achieved suppression of hsCRP to less than 2 milligrams per liter, indicative of potential to lower cardiovascular risk. I'll return to this important metric when we discuss the results from our high cardiovascular disease risk part 3 of the study. To gain a deeper mechanistic understanding of MRT-8102's profound impact on CRP, we monitored plasma levels of the pro-inflammatory cytokine IL-6, a well-characterized stimulator of CRP production and secretion from the liver, as detailed on slide 15. Consistent with the reduction in CRP noted previously, MRT-8102 treatment significantly reduced IL-6 by 55% in the 14 MAD subjects with a median baseline CRP equal to or greater than 1 milligram per liter. Importantly, the absolute levels of IL-6 were reduced below the threshold of 1.65 pg/mL, defined by the previously mentioned CANTOS study as a level below which there is a significant decrease in risk of cardiovascular events and mortality. Knowing that the NLRP3 IL-1 beta axis is a stimulator of IL-6 production, we next investigated the impact of MRT-8102 on IL-1 beta production and secretion in ex vivo stimulation experiment of whole blood. Consistent with the strong reduction in CRP noted in subjects with elevated baseline CRP, and despite relatively modest induction levels under the assay conditions used, we noted a comparable close to 80% inhibition in IL-1 beta secretion in whole blood ex vivo assays from these subjects following multiple administrations of MRT-8102. Importantly, we observed a near-perfect correlation between NEK7 degradation and IL-1 beta levels throughout the dosing period, as shown here for a representative subject that displayed about 80% degradation and close to 90% inhibition of IL-1 beta. In summary, MRT-8102 during the MAD portion of our phase I study effectively inhibited the entirety of the NLRP3 IL-1 beta IL-6 CRP axis, reducing critical biomarkers to levels associated with significantly reduced risk for cardiovascular events and mortality. Slide 16 shows one additional important readout from the MAD cohorts. We performed cerebrospinal fluid, or CSF, collection at a single dose level, 100 milligrams, and then analyzed samples for levels of MRT-8102 as well as multiple inflammatory markers, including CRP and IL-6. MRT-8102 CSF levels were consistent with levels needed to be active against NEK7. Importantly, in two subjects with elevated IL-6 in cerebrospinal fluid at baseline, MRT-8102 treatment reduced IL-6 levels in the CSF consistent with CNS penetration. Plasma IL-6 levels at baseline for these two subjects were low, suggesting a CNS-CSF-driven effect for both elevation as well as suppression of CSF IL-6 levels. I'll now move to the part 3 cohort, a proof-of-concept study of MRT-8102 in subjects with elevated cardiovascular disease risk. The study design shown on slide 17 is for 36 subjects randomized 3:1 to MRT-8102 at a dose of 40 milligrams once daily or placebo. Subjects are defined as having elevated cardiovascular disease risk based on measures of obesity and elevated plasma CRP levels. The primary endpoints are safety and tolerability, with secondary endpoints being change in CRP levels and pharmacokinetics. Endpoints for hsCRP include absolute reduction as well as reduction to less than 2 milligrams per liter, a threshold level that defines lower cardiovascular disease risk, as we discussed earlier. We also measure pharmacodynamic markers, including NEK7, IL-6, IL-18, and fibrinogen. I'll now turn to some of the key results from the interim analysis from the CRP proof-of-concept study. This analysis included data from 24 subjects, both placebo and MRT-8102, who have completed four weeks of dosing as of the data cut-off date, as shown on slide 18. The data show that MRT-8102 dosed at 40 milligrams once daily induced rapid and deep reductions of hsCRP and fibrinogen. The panel on the left shows that median CRP declined by 80% after one week, consistent with our observation from the MAD portion of the phase I study, and by 85% after four weeks of dosing. Also, a remarkable 94% of subjects reached hsCRP levels of below 2 milligrams per liter. So the hsCRP values returned to levels associated with lower cardiovascular disease risk, as shown in the middle panel. Lastly, there was a 31% reduction in fibrinogen, an independent atherosclerotic risk factor, observed during the treatment period. Slide 20 shows the summary of blinded safety data, meaning that we are still blinded as to which subjects were on MRT-8102 versus placebo. As of the data cut-off, 112 subjects had completed dosing across the SAD, MAD, and part 3 portions of the study. Across this sample of patients, MRT-8102 was well tolerated with a favorable safety profile with no serious adverse events. Treatment-emergent adverse events were mild to moderate. There was no evidence of increased infection risk and no dose dependency of AEs. The evaluation and data collection are ongoing for part 3 of the study. Of note, one participant in part 3 was diagnosed as asymptomatic acute infectious hepatitis A while on study. As the data is blinded, we don't know yet if that participant received MRT-8102 or placebo. The participant experienced a transient ALT elevation equivalent to a grade 3 that improved while continuing on treatment for a couple of days. Turning to slide 20, based on these highly encouraging initial data, we are expanding our phase I study, which has now been named GFORCE-1, to include additional dose exploration of MRT-8102 in subjects with elevated cardiovascular disease risk. We will be enrolling subjects in three-dose cohorts, still randomized 3:1 active drug to placebo, for a total of approximately 108 subjects. The ongoing cohort at 40 milligrams will be one of the three dose levels. The additional dose levels will be disclosed at a later time. As we have shown today, the effects on CRP levels are induced early and are then maintained. Therefore, our 28-day study can provide valuable information for dose levels necessary to lead to therapeutic benefit and can therefore help to streamline and accelerate our subsequent GFORCE-2 phase II study on atherosclerotic cardiovascular disease. Lastly, and importantly, our expanded GFORCE-1 study will also allow us to draw important conclusions for additional indications. As shown on slide 21, we do indeed see multiple attractive opportunities for MRT-8102 across a wide range of indications. I won't go into details, but to summarize, there is both high unmet medical need and strong biological rationale for a NEK7-directed molecular glue degrader in MASH, as well as in indications with acute and recurrent flares of NLRP3-driven inflammation like recurrent pericarditis, gout, and osteoarthritis, and last but not least, also in allergic diseases like asthma. We are exploring opportunities to expand our NEK7 program into these indications, and we plan to provide further details on our approach as we complete the GFORCE-1 study. I'll now turn the call back to Markus for some concluding remarks. Thank you, Filip. We couldn't be more excited by these promising interim results from our phase I study of MRT-8102. The SAD and MAD cohorts have been completed with no safety concerns and demonstrated deep and sustained NEK7 degradation at all dose levels tested, along with compelling reductions in hsCRP in subjects with elevated baseline CRP levels. An interim analysis of the part 3 cohorts in high-risk CVD subjects demonstrated 85% sustained reduction of hsCRP through the end of week four. 94% of subjects achieved reduction of hsCRP levels to below 2 milligrams per liter after four weeks of dosing, so down to levels of CRP that are associated with lower CVD risk. Furthermore, we observed 31% reduction of fibrinogen, an important and independent risk factor for atherosclerosis, after four weeks of dosing. The study now named GFORCE-1 will be expanded, and additional dose levels will be explored to accelerate development in ASCVD and inform development in other indications. Data from this expanded study is expected in the second half of 2026. Furthermore, we plan to initiate a phase II study named GFORCE-2 of MRT-8102 in ASCVD in 2026. Monte Rosa will expand its NEK7 program to next-generation MGDs with attractive properties supporting a range of indications. We believe our second-generation NEK7 program could provide greater strategic optionality as we potentially pursue multiple indications with various patient populations and price points. Beyond ASCVD, we are evaluating moving MRT-8102 or next-generation MGDs into multiple other indications, including those Filip has already discussed. Finally, on slide 24, I briefly highlight the great progress across our entire pipeline. Our VAV1-directed MGD program, MRT-6160, licensed to Novartis, is progressing towards initiation of multiple phase II studies in immune-mediated diseases this year. Monte Rosa is eligible for milestone payments beginning upon initiation of phase II studies. VAV1 is a previously undruggable target that functions as a key signaling protein downstream of both the T and B cell receptors. Our phase I study results and extensive preclinical work support the potential of MRT-6160 to treat multiple immune-mediated conditions, and we are excited for our partner, Novartis, to begin patient studies of this novel therapy. Also, we recently provided a detailed clinical update on the results of our phase I study of MRT-2359 in patients with castration-resistant prostate cancer. We'll be presenting an update on those clinical data at the upcoming ASCO GU meeting in late February. Based on the compelling clinical activity of MRT-2359 in combination with Enzalutamide in heavily pretreated metastatic castration-resistant prostate cancer patients with androgen receptor mutations, we plan to initiate a phase II study called Modifier One in this population this year. We also look forward to an IND submission for our CDK2 program by the end of the year. Finally, we look forward to announcing one or several additional of our highly differentiated programs stemming from our QuEEN discovery engine in the immunology and inflammation space, specifically for targets related to Th1, Th2, Th17, and myeloid pathways. Results such as what we've shared today help validate the ability of QuEEN and our scientists to deliver compelling clinical MGD candidates targeting novel biology and previously undruggable targets, in particular in the inflammasome area. Thank you all for your attention today and your interest in Monte Rosa. With that, I would like to open the call up for questions. Operator. Thank you. To ask a question, please press star 11 on your telephone and wait for your name to be announced. To withdraw your question, please press star 11 again. The first question will come from Marc Frahm with TD Cowen. Your line is open. Hey. Yes, thanks for taking my questions. Congrats on the data. Maybe to start off with just a kind of a higher-level strategic question, just Marcus, with the range of indications here that this is applicable to and some of the timelines that would be associated to kind of translating these impressive CRP reductions and pathway engagement into kind of clinical endpoints, just how do you think about prioritizing indications, partnerships to help support kind of things in parallel? Just can you kind of walk through that strategic viewpoint? I'm happy to. I mean, we're obviously super excited about the results we're presenting today. Certainly game-changing at the very least for NEK7 as a target, if not for the NLRP3 signaling space. And that said, we're certainly quite eager to continue to push this program, not just 8102, the entire program. We feel well-positioned to execute on this on our own. Obviously, we've prioritized ASCVD because that is becoming an exciting but also somewhat competitive space. I think, again, with the data today, we're well-positioned there, and we don't want to lose any time. But certainly from there, over the next months, quarters, we'll continue to work on additional indications. We will look carefully sort of what the attractiveness of these are. There's obviously still potential readouts coming from other companies this year as well. So again, overall, big focus now on this targeting program. And as I said, certainly feel confident that we can keep pushing this on our own. Thanks. That's helpful. And then maybe appreciating some of the safety data is still blinded to you, and you obviously know no significant infection risk coming out yet. But just anything else kind of lower level, particularly for some of these that may be indications where this could be chronic, very long-term therapy for very broad populations, just anything more of kind of like the annoyance level types of AEs, headaches, things like that, kind of popping up that's worth noting. Filip, do you want to answer that? Yeah. Marc, I mean, as I actually pointed out, I mean, the data is still blinded, so we don't know who is on MRT-8102 and who is on placebo. I mean, in general, we see a very mild profile with mostly grade one treatment-emergent adverse events, obviously typical for the phase I studies. So far, actually, the frequency and the grade of adverse events is actually very favorable. It's a very well-behaved compound. Okay. Thank you. Congrats again on the data. Thank you. The next question will come from Edward Tenthoff with Piper Sandler. Your line is open. Great. Thank you, guys. I mean, out of the park. Incredible. My question kind of has to do with cardiovascular indications. I think this makes a ton of sense here. But these are big and can be expensive studies to run. So do you think there's a way that you could either sub-stratify patient populations with biomarkers to either accelerate, and do you ultimately anticipate you'd have to do a cardiovascular outcome study? Congrats on the data. No, thanks. Thanks, Thanks, Ed. I mean, great question. Obviously, it's alluding a little bit to our work on the genomic bioinformatics side. I think there's certainly subpopulations we could possibly identify. I think it's probably too early to sort of talk much about it today, but certainly something we're intensely looking into. With that said, sure, the size of a trial is always defined by the effect size. And clearly, at the very least today, we can say that the four-week data suggesting from a CRP modulation point of view, this can be superior to kind of canakinumab. I'm trying to say that I do not have to treat 10,000 patients to get to a positive outcome on MACE. But again, it's super early. Let's see what we get through the rest of GFORCE-1 and then GFORCE-2. But again, I'm super keen to push this as far into development as we possibly can on our own. Yeah. Excellent. Great point. And congrats on the data, guys. Thank you. Our next question will come from Brian Cheng with JP Morgan. Your line is open. Hey, guys. Thanks for taking our question this morning. Can you talk about the doses that you have picked in the expansion risk subject part 3? It seems that the 5 mg-10 mg, when you look back at the MAD portion, is already getting you pretty close to the maximum output in terms of NEK7 degradation. So should we assume a lower dosage than the 40 mg that you have already tested in the risk subject part 3? And I guess, ultimately, what level of NEK7 degradation do you want, and at what time point? And then we have a quick follow-up. Thank you. I mean, great question. And as we pointed out in our presentation, I mean, the 80%-90% degradation are really optimal, right? I mean, it's essentially the floor of that assay, I mean, it's a flow cytometry assay in T cells. As you pointed out, really no reason to believe that there's any dose response. We didn't actually show the breakdown in CRP reduction across the different dose levels, but even from there, it was equivalent, obviously, with fewer subjects per group. It becomes a little bit more noisy, so long story short, part of the expansion will likely be going to lower doses, but I think there's also an opportunity to go to higher doses because the safety obviously allows that. I think that would give us information on the onset of CRP reduction, which might not matter so much for ASCVD, but certainly can inform us how good and fast this molecule will also work in indications like gout, where it's all about, obviously, managing acute flares. Got it. Then just on the safety side, can you elaborate a little bit more on the grade 3 ALT elevation that you saw? Was that a treatment-related event? And did that event happen in the MAD portion or the CVD risk portion? And then any color on the timing of the event as well? Thank you. Okay, I think the CRP part of the subpart 3 of the protocol, we report the treatment-emergent adverse events. So essentially, any adverse events recorded during the study are reported. Again, it is still blinded. So we do not know who is on MRT-8102, who is on placebo. So this participant was actually diagnosed with acute infectious hepatitis at this time while on the study and was completely asymptomatic. The timing suggests that the subject contracted hepatitis prior to study participation. If the study continues to be blinded, as I said, we cannot really say, is it placebo or MRT-8102? But of interest, the ALT actually improved while on study treatment. Great. Thank you, guys. And congrats on the data. Thank you. And the next question will come from Clara Dong with Jefferies. Your line is open. Hi. Good morning. Congrats on the data. Very interesting findings here. So maybe just a follow-up question, Brian's question. So for the doses, have you identified any kind of downstream markers like IL-6 fibrinogen? The The dose separation, even when you saw pretty flat NEK7 degradation across those doses. And maybe a follow-up is from a safety standpoint, given fibrinogen's role in coagulation, how are you thinking about kind of the lower bound of acceptable suppression? Is there kind of a theoretical threshold below which we should think about bleeding might be a concern there? Thank you. A great question. I'll start with your last one on fibrinogen. At this point, really no concern whatsoever, right? I mean, all these subjects obviously start with elevated fibrinogen levels, so they're above the normal range. We didn't expand too much on it today, hopefully in a future presentation. But we did actually then bring those individuals down into the normal range, but certainly not anywhere near to a range where you would be subnormal. So at this point, no concern. Again, certainly, the fibrinogen data we presented today, yet again, is better than what was seen for kind of Canakinumab. I would say extremely encouraging, again, from a future sort of management of cardiovascular events. In regards to dose response to any of the biomarkers, there's absolutely nothing there, right? Sure, as I said, the error bars become a little bit bigger as you go through the groups and you have smaller n's per group. But for CRP, for IL-6, like endogenous and plasma, or for whole blood stimulation of IL-1 beta, no dose response throughout. So again, 5 milligram, from our point of view, still more or less a fully active dose level as far as we can tell with the information we have in hand today. That is super helpful. And congrats again. Sounds good. Thanks. Thank you. Our next question comes from Derek Archila with Wells Fargo. Your line's open. Hey, good morning, and congrats on the data. Just two from us. I guess first, and you alluded to it a little bit on 8102's onset of action. I mean, it seems like a real advantage here in terms of how quick and how potent the drug is. But I guess maybe can you expand on how that's going to inform potential indications for selection beyond cardiovascular disease? And then just secondly, in cardiovascular disease, I presume that we probably see a lot of patients on other types of drugs like statins and combos there. So I guess, how do you think about the safety and drug-drug interactions with those potential therapies? And I guess in part 3, were any of those patients on any sort of background therapy? Thanks. Good, Jonathan. So essentially, as far as the background therapies, I mean, they were healthy volunteers. So these were not expected to be on any background therapies. When it comes to the CRP study, there were some limited number of background therapies which were allowed. We are not really much concerned about it because from the data which we have, essentially, the drug-drug interaction potential is not really affected from the studies which we have done preclinically and so far clinically as well. Very helpful. And then on the onset of action and kind of indication selection? So the onset of action is pretty rapid. I mean, as we just presented. So that essentially gives you a lot of optionalities for the future development. So obviously, as Markus mentioned the diseases in which we can manage the frequency and occurrence of flares, whether it's gout, which obviously has a huge potential for innovation. It's a large patient population in the U.S. and elsewhere, as well as maybe the more niche indications such as pericarditis. But simply, once it's in indication, it's actually quite rapid. There is a potential for acute indications as well. I actually think that this data really kind of expands the potential to the broad spectrum of acute and chronic inflammatory conditions. Understood. And then maybe oh, go ahead. Sorry. No, you also mentioned actually what is the potential for combination. It kind of is a build-up on what I already said in my first part of the answer. I actually think that the potential for combinations with a variety of agents, I think that might be relevant for indications such as MASH. I definitely don't see any limitations in terms of ease of safety or drug-drug interaction, definitely given the very favorable safety profile. Got it. Understood. And I just wanted to follow up. Just in terms of the enrollment criteria from part 3 to the GFORCE-1 study, they look pretty similar, but any notable differences or anything that you'd be changing between the populations there? Thank you. So essentially, the difference progression between the part 3 and GFORCE-1 is essentially the expanded number of dose levels and patient sample size. Otherwise, it's a study which is designed in terms of enrollment criteria, actually exactly the same. So we started on this part 3, which was three-to-one randomization, 36 subjects, 36 subjects, one dose level. And given that we see such an early and sustained suppression of the CRP, we actually think that we can very efficiently do quite a bit of dose exploration work as far as the efficacy on CRP is concerned, which would actually allow us to streamline and be more nimble and faster in the phase two CRP study, which we will have inevitably to make. Excellent. Thank you very much. And congrats again. Sounds good. Yeah. Thanks. Thank you. And the next question will come from Michael Schmidt with Guggenheim. Your line is open. Hey, guys. Good morning. Thanks for taking my questions. Yeah, really nice data. Just a couple of follow-ups. Could you just clarify whether 8102 is active in the CNS? It seems to have some CNS penetration. And have you seen some early effects, perhaps, on body weight or other outcomes in that area? Yeah, just bigger picture-wise, how do you see differentiation versus direct NLRP3 inhibitors in terms of the scope of development and the opportunities that perhaps can be most differentiated by targeting NEK7 directly? Certainly, very convinced with what you have shown today on potential CNS penetration. I'm saying potential because, sure, CSF is always just a surrogate of having drug in the brain. That said, these two individuals with elevated IL-6 in their CSF and how we were actually able to bring those levels down are really great indication that we have enough there. That's why we're also now paying a little less attention in our ongoing MedChem for next-generation molecules to CNS penetration. We believe we have enough there and are looking more for other differentiated profiles. In regards to weight loss, again, it's still blinded. So yes, obviously, we're keeping track of weight. But at this point, obviously, I can't comment on whether there's any 8102-specific effect on weight. And then just in terms of development scope, perhaps relative to NLRP3 inhibitors, I guess, in which areas do you think the differentiated mechanism could be most differentiated? I mean, I think in general, what we're seeing here, and hopefully, that came across as very sustained PD modulation. I think that has translated really well to data that suggests that this modality, this mechanism of action, might be superior to NLRP3 inhibitors. I think the 85% reduction and 94% for the lack of a better term normalization of CRP speak for itself. So I think we're very well positioned vis-à-vis NLRP3 inhibitors literally wherever we want to go, hence sort of the push into ASCVD. I also want to reiterate that we're seeing this effect. Though we picked a dose in the mid-range, we didn't have to go all the way up and be pretty much at the top of our MAD. It was 40 mg versus 200 being the highest in MAD. And as I pointed out, 5 milligrams, at least based on what you have seen in MAD, we like to also work. That gives us a lot of opportunity in regards to, obviously, carving out manageable doses and ideally, of course, superior safety as well vis-à-vis some of the other agents. Great. Thanks. Congrats on the data. Really nice update. Sounds great. Thanks. Thank you. And the next question comes from Robert Driscoll with Wedbush. Your line is open. Great. Thanks. Good morning, guys. Thank you for taking the question here. Just a quick follow-up on Michael's question. I just wonder if there's anything to note around those two patients on the CSF IL-6, just in terms of their baseline characteristics, just kind of given their plasma IL-6 was normal. And then just any thoughts you might have or maybe insights from preclinical data into the durability of the effect here, kind of maybe past four weeks. Thanks. Yeah. I mean, durability past four weeks, I can't get very specific, but we have done experiments across various different species that obviously go longer than four weeks. And again, there's really no reason to believe that these effects at some point would start to retreat. As a fact, in some of these experiments, we see them continue to improve way beyond week four. I think we should be in pretty good shape there based on preclinical data. But obviously, we'll know more once we start to have data from the phase two study. I think you had a second question that I now can't remember. Yeah. It was on the two patients. I mean, I start, but I mean, there's nothing we offered. I mean, again, this was a healthy volunteer population. These were not individuals that were diagnosed prior to entering the study with any sort of neuroinflammatory or neurodegenerative disease. It was just sort of luck in some ways, right, to have that finding. And as I said, convinced us that not just do we have the exposure in the CSF, there's probably pharmacological activity in the brain. But yeah, nothing more known about these two individuals. Great. Thanks, guys. Very exciti ng. Sounds good. Yeah. Thanks, Robert. Thank you. And the next question will come from Oliver McCammon with LifeSci Capital. Your line's open. Congrats on the data. And thanks for taking my questions. Just looking at the CVD cohort, it appears that you have pretty consistent hsCRP reductions without evidence of a rebound. Keeping in mind that this is an early dataset, can you walk us through the potential clinical significance of these data in your view, particularly relative to some competitor readouts we've seen in this space, and then also curious when we could expect data from GFORCE-2 and ASCVD. Thanks again. Yeah. Thanks, Olivier. I mean, we are super excited about it because one of the things which has been seen consistently with several NLRP3 IL-1 targeting agents is that while the CRP reduction can be rapid, maybe to some extent similar, you see after a few weeks and sometimes within the very short timeframe, you see a little bit of rebound, that the CRP reduction is kind of retreating a little bit, and we don't seem to see it at all, right? I mean, if anything, the over time during the four weeks of study, the CRP reduction has actually keep building on up to this 85%, which we see in the second half of the study, including the week four. So obviously, there is a well-established evidence that the higher is your CRP, the higher is your cardiovascular disease risk. I mean, it's a very kind of, in some extent, linear thing from whether you are under 1 milligram or 2 milligram or 3 milligram. So actually having sustained inhibition of CRP should translate into higher efficacy in terms of reducing cardiovascular morbidity and mortality. Thanks again. Really appreciate it. Thank you. I show no further questions at this time. I will now turn the call back over to management for closing remarks. It sounds great. I want to use the opportunity to thank you all again for your attention today and your interest in Monte Rosa. With that, I'm happy to close the call. This concludes today's conference call. Thank you for participating. You may now disconnect.