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Degrading Proteins, Making Medicines MRT-8102 Phase 1 Clinical Data Update January 7, 2026
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2 2 Forward-Looking Statements This communication includes express and implied “forward-looking statements,” including forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Forward-looking statements include all statements that are not historical facts and, in some cases, can be identified by terms s uch as “may,” “might,” “will,” “could,” “would,” “should,” “expect,” “intend,” “plan,” “objective,” “anticipate,” “believe,” “estimate,” “predict,” “potential,” “continue,” “ongoing,” or the negative of these terms, or other comparable terminology intended to identify statements about the future. Forward-looking statements contained herein include, but are not limited to, statements about our a bility to grow our product pipeline, our ability to successfully complete research and further development and commercialization of our drug candidates in current or future indications, incl uding the timing and results of our clinical trials and our ability to conduct and complete clinical trials, statements regarding our progress and speed of development of only-in-class and first-in-class molecular glue degrader therapeutics, statements around the Company's QuEEN discovery engine, its advancement and the broad potential applications of the platform and the Company's ability to create lo ng-term value through focused pipeline execution and strategic collaborations, as well as to expand the targetable protein space for MGD drug discovery, unlocking new opportu nities to address previously undruggable therapeutic targets, statements related to the expected potential clinical benefit of any of our candidates, statements regarding the positive int erim Phase 1 data and potential benefits of MRT-8102, our expectations regarding the potential of MRT-8102 to transform the treatment of ASCVD and other cardiovascular and cardiometabolic diseases, o ur belief that our data supports the potential of MRT-8102 to be an oral best-in-class therapeutic among agents targeting the NRLP3/ IL-1/IL-6 pathway and establish the significant potential of MRT-8102 in multiple chronic inflammatory diseases, including ASCVD, our statements regarding the expansion of our proof-of-concept GFORCE-1 study in subjects with elevated CVD risk and acceleration of the anticipated Phase 2 (GFORCE-2) study of MRT- 8102 in ASCVD patients, our expectations regarding the timing for sharing data from the GFORCE -1 study of MRT-8102 and timing of initiation of a Phase 2 GFORCE-2 study of MRT-8102 in ASCVD, our statements and expectations regarding our evaluation of additional Phase 2 proof of concept studies in MASH, gout, and re current pericarditis, conditions strongly linked to NLRP3 pathway activation, statements regarding our expectations that our collaborator, Novartis, will initiate multiple Phase 2 studies of VAV1-directed MGD MRT-6160 in immune-mediated diseases in 2026, our expectations regarding the submission of an IND application for a next-generation NEK7-directed MGD and timing thereof, our expectations to initiate a MODeFIRe-1 Phase 2 study of MRT-2359 in combination with a second-generation androgen receptor inhibitor in CRPC in 2026, as well as to present updated data from the on going Phase 1/2 study of MRT-2359 at the ASCO Genitourinary Cancers Symposium in February 2026, our expectations regarding the submission of an IND application for a CDK2 and/or cyclin E1-directed MGD and timing thereof, statements regarding the clinical significance of the clinical data read-out at upcoming scientific meetings and timing thereof, statements around our ability to capitalize on and potential benefits resulting from our research and translational insights, , including announcements related to preclinical programs, as well as our the ability to optimize collaborations with industry partners on our development programs, statements regarding regulatory filings for our development programs, including the planned timing of such regulatory filings , such as IND applications, and potential review by regulatory authorities, statements around our expectations of success for our programs, strength of collaboration relationships, among o thers. By their nature, these statements are subject to numerous risks and uncertainties, including those risks and uncertainties set forth in our most recent Annual Report on Form 10 -K for the year ended December 31, 2024 filed with the U.S. Securities and Exchange Commission on March 20, 2025, most recent Quarterly Reports on Form 10 -Q and any subsequent filings, that could cause actual res ults, performance or achievement to differ materially and adversely from those anticipated or implied in the statements, as well as the risk that outcomes of preclinical studies may n ot be predictive of clinical trial results and the risk that initial or interim results from a clinical trial may not be predictive of the final results of the trial or the results of future trials. You should not rely upon forward-looking statements as predictions of future events. Although our management believes that the expectations reflected in our statements are reasonable, we cannot guarantee that t he future results, performance, or events and circumstances described in the forward-looking statements will be achieved or occur. Recipients are cautioned not to place undue reliance on t hese forward-looking statements, which speak only as of the date such statements are made and should not be construed as statements of fact. We undertake no obligation to publicly update any forward-looking statements, whether as a result of new information, any future presentations, or otherwise, except as required by applicable law. Certain information contained in t hese materials and any statements made orally during any presentation of these materials that relate to the materials or are based on studies, publications, surveys and other data obtained from thir d-party sources and our own internal estimates and research. While we believe these third-party studies, publications, surveys and other data to be reliable as of the date of these materials, we hav e not independently verified, and make no representations as to the adequacy, fairness, accuracy or completeness of, any information obtained from third-party sources. In addition, no independent source has evaluated the reasonableness or accuracy of our internal estimates or research and no reliance should be made on any information or statements made in these materials relating to or based on such internal estimates and research. These materials remain the proprietary intellectual property of Monte Rosa Therapeutics and should not be distributed or repr oduced in whole or in part without the prior written consent of Monte Rosa Therapeutics.
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3 3 • MRT-8102, a NEK7-directed molecular glue degrader (MGD), induced rapid and compelling reduction in hsCRP across all doses testedin both healthy volunteers and high-CVD risk subjects (112 subjects in total) • SAD (48 healthy volunteer subjects) and MAD (40 healthy volunteer subjects) cohorts completed with no adverse safety signals • MRT-8102 was dosed from 5 – 400mg (SAD: 40 – 400mg; MAD: 5 – 200mg) and data suggest maximum activity achieved from lowest dose level (5mg MAD) • ~80-90% NEK7 degradation noted in T cells at all dose levels tested • 78% reduction in hsCRP achieved in subjects with elevated baseline CRP levels after both single and multiple dose administration • Favorable AE profile with no adverse safety signal observed as of data cut off date of 12/23/25 • Part 3 (CRP PoC) of Phase 1 study exploring 40 mg MRT-8102 in high-risk CVD subjects (obesity/elevated CRP) is ongoing and 24 subjects have been evaluated up to end of week 4. Preliminary data for these subjects showed: • 85% sustained reduction of hsCRP through end of week 4 • 94% subjects achieved reduction of hsCRP levels to <2 mg/L* after 4 weeks of dosing (baseline hsCRP level of 6.3 mg/L) • 31% reduction of fibrinogen after 4 weeks of dosing • No SAEs, no severe AEs as of data cut off date of 12/23/25, evaluation ongoing • Study (now named GFORCE-1) will be expanded and additional dose levels will be explored to accelerate development in ASCVD; data expected in H2 2026 • Early hsCRP results continue to support MRT-8102 development across chronic inflammatory diseases such as ASCVD and MASH • hsCRP reduction data compares favorably to previously reported third party data on NLRP3 inhibitors in development and canakinumab (IL-1 antibody) and is on par with IL-6 biologics** Summary hsCRP, high-sensitivity C-reactive protein *hsCRP levels of >2 mg/L are associated with elevated CVD risk **Comparison not based on head-to-head studies
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4 4 0 20 40 60 80 100 88% 83% 77% 96% 82% 67% 55% 69% 75% 94% Proportions of Subjects Achieving on-treatment hsCRP <2 mg/L NEK7 MGD NLRP3i IL-1 biologic IL-6 biologic IL-6 biologic -80 -89%-85% -70% -92%-88% -77% -59% -64% -55%-51% -85% hsCRP (% Change From Predose) -20 -40 -60 -100 0 MRT-8102 shows favorable reduction of hsCRP compared to other inflammasome and IL-6 targeted agents in development MRT-8102 achieves favorable rates of hsCRP <2 mg/L compared to other inflammasome and IL-6 targeted agents MRT-8102 – Beyond an Oral IL-1/IL-6 Modality MRT-8102 data compares favorably to data reported for NLRP3 inhibitors and appears on par with data reported for IL-6 antibodies MRT-8102 provides convenience of oral route of administration MRT-8102 may also provide potential advantage of inhibiting pyroptotic cell death and hence have a superior effect on local inflammation and plaque stabilization in ASCVD NT-0796 – Clarke N et al. Anti-Neuroinflammatory and Anti-Inflammatory Effects of the NLRP3 Inhibitor NT -0796 in Subjects with Parkinson’s Disease. Movement Disorders 2025; Nodthera Press Release June 2024 for Obese Subjects with Cardiovascular risk; V T3232 – Ventyx Corporate Presentation August 2024 for HV and Ventyx Press Release October 2025 for Subjects with Obesity and Cardiovascular Risk Factor (CRP reduction from FAS, CRP <2 mg/L from MAS); Canakinumab - Ridker PM et al. Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease. NEJM 2017; Ridker PM et al. Relationship of C-reactive protein reduction to cardiovascular event reduction following treatment with canakinumab: a secondary analysis from the CANTOS randomized controlled trial. Lancet 2018; Ziltivekimab - Ridker PM et al. IL-6 inhibition with ziltivekimab in patients at high atherosclerotic risk (RESCUE): a double-blind, randomized, placebo-controlled, phase 2 trial. Lancet 2021; Pacibekitug - Tourmaline Bio Phase2 TranQuility Trial Topline Results May 2025. W –week; M –month; D –day. Note: Comparisons between MRT-8102 and other therapies represented herein are based on post-hoc analyses comparing MRT-8102 clinical information with publicly available information for other therapies. Any comparisons use information from different clinical trials, conducted by different parties, at different points in time, with differences in trial designs and patient populations. No head -to-head clinical trials have been conducted, cross-trial comparisons should not be made, and this information is provided only for illustrative purposes. MRT-8102 MRT-8102 MRT-8102 40 mg QD NT-0796 150 mg BID VTX3232 40 mg QD VTX3232 30 mg QD Canakinumab 150 mg Ziltivekimab 7.5 mg Q4W Ziltivekimab 15 mg Q4W Ziltivekimab 30 mg Q4W Pacibekitug 25 mg Q90D Pacibekitug 50 mg Q90D Pacibekitug 15 mg Q30D W2 W12 M3 W12 W12 W12 D90 D90 D90W4 W4 MRT-8102 40 mg QD NT-0796 undisclosed dose VTX3232 30 mg QD Canakinumab 150 mg Ziltivekimab 7.5 mg Q4W Ziltivekimab 15 mg Q4W Ziltivekimab 30 mg Q4W Pacibekitug 25 mg Q90D Pacibekitug 50 mg Q90D Pacibekitug 15 mg Q30D W12 M3 W12 W12 D90 D90 D90W4 W4 W12 >
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5 5 In contrast to small molecule inhibitors (SMIs), MRT-8102 induces catalytic NEK7 degradation, long-lasting inflammasome disassembly, and sustained inhibition of cytokine release MRT-8102 is Highly Differentiated over Other NLRP3/IL-1/IL-6 Pathway Modalities Due to inhibition of NLRP3 assembly, MRT-8102 prevents pyroptotic cell death-mediated release of inflammatory cytokines and DAMPs known to drive disease pathology. Mono- and bispecific biologics fail to inhibit pyroptosis, leading to incomplete blockage of the pathological drivers of disease MAS825 CRBN CRBN POI POI POI Neosubstrate- directed MGD MGD available for additional degradation Complex formation Neosubstrate degradation Pathway signaling following SMI treatment Time 0 100 Target abundance & pathway signaling following MGD treatment Target abundance following SMI treatment
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6 6 Improving inflammatory status — independent of changes in lipid profile — reduced cumulative incidence of CV events and confirmed the role of inflammation in atherosclerotic disease CANTOS Study Established Role of Inflammation in Cardiovascular Disease 50-60% reduction in CRP noted across dose groups following Canakinumab treatment for 48 mo Significant reduction in recurrent CV events noted at 150 mg dose Ridker PM et al. NEJM (2017) 0 10 20 25 5 15 Cumulative Incidence of Primary End Point (%) 0 1 2 3 4 5 Years Hazard ratio, 0.85 (95% CI, 0.74-0.98) P=0.021 0 3 6 9 12 24 36 48 Months 10 0 -10 -20 -30 -40 -50 -60 -70 Percent Change from Baseline
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7 7 Upstream Targeting of NLRP3/NEK7 Pathway May Have Greater Potential than Downstream IL-6 Biologics in ASCVD NLRP3 activation promotes plaque growth, destabilization and CV events MRT-8102 has potential to stabilize plaques preventing thrombosis MRT-8102 ox-LDL Monocyte Foam cells NLRP3 activation Plaque destabilization CV events Statins ASCVD ranks amongst top NLRP3 activated indications Indication 1 ASCVD CAPS Indication 2 Indication 3 Indication 4 Indication 5 Indication 6 NLRP3 activity score 0 3 6 Human genetics* supports causal relationship between NLRP3 and ASCVD Peripheral artery disease Odds ratio (95% CI) for CV risk Ischemic stroke Coronary artery disease 1.0 2.0 3.0 * Analysis based on Georgakis et al. Circ Genom Precis Med (2020); Zhu Z et al. Cell Mol Neurobiol (2016); Zhang K et al. Research Square (2021); Zhou D et al., BioMed Research International (2016). Odds ratios were directionally harmonized (OR = 1/OR) to display consistent benefit vs harm. Monocyte Mutation/SNP within pathway:
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8 8 ASCVD Presents a Substantial Market Opportunity for MRT-8102 Source: Arnett et al. Circulation (2019); Pesce et al. Front Cardiovasc Med. (2025); Alanaeme et al. Am Heart J Plus (2022); Mazhar et al. Eur Heart J. (2024) Additional interventions: lifestyle change, surgical procedures (angioplasty, endarterectomy, bypass, etc.) LDL-C lowering ASCVD Market Overview 18.7M Patients in the U.S. ~60% Patients have a CRP level above 2 mg/L Antiplatelet drug (aspirin, prasugrel, ticagrelor) Ezetimibe, or bempedoic acid PCSK9 inhibitors Statins Statins Statins Opportunity Treatment Paradigm Anti-platelet drug (aspirin, prasugrel, ticagrelor) Anti-platelet drug (aspirin, prasugrel, ticagrelor) 1L 2L 3L + + + + + Anti-platelet Address residual cardiovascular risk ‣ Even among patients who achieve their LDL-C targets, up to 40% still experience life-threatening cardiovascular events, demonstrating substantial residual risk not fully addressed by LDL-C lowering
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MRT-8102 Profile and Interim Results of Phase I Study
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10 10 MRT-8102 potently degraded NEK7 MRT-8102 induced highly selective NEK7 degradation MRT-8102: Preclinical Profile Points to Best-in-Class Potential MRT-8102 exposure resulted in prolonged PD effect 0 24 48 72 96 120 0.1 1 10 100 1000 0 50 100 150 Time post-dose (h) Plasma concentration (ng/ml) NEK7/β-actin relative to predose (%) 20 10 PK NEK7 Cyno @ 10 mg/kg single dose MRT-8102 exposure prolonged PD effect Human PBMC @ 24h treatment 0.01 0.1 1 10 100 1000 10000 0 20 40 60 80 100 MRT-8102 (nM) NEK7 protein % of DMSO control DC50 = 2.5 nM No degradation of other known CRBN neosubstrates Potency, selectivity, and long-lasting pharmacodynamics differentiate from other IL-1/NLRP3 inflammasome approaches MRT-8102 has potential to avoid on-off pharmacodynamics and off-target toxicities of NLRP3 inhibitors
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11 11 MRT-8102 Phase I Study – Dose Levels and Endpoints All cohorts randomized, placebo controlled (6+2) 200 mg 100 mg** 40 mg 5 mg 10 mg SAD cohorts (Part 1) One oral dose 48 participants MAD cohorts (Part 2) 7 daily oral doses 40 participants 400 mg 300 mg 200 mg* 40 mg 100 mg CRP PoC in elevated CVD risk subjects (Part 3) 28 daily oral doses ~36 participants 40 mg Cohort randomized 3:1 treatment vs placebo Primary endpoint • Safety and tolerability Key secondary & exploratory endpoints • PK (blood +/- CSF) • NEK7 degradation • Change in CRP level • IL-6 (blood and CSF) • Fibrinogen • Ex-vivo: IL-1β Data cutoff December 23, 2025 * Additional subjects included in 200mg cohort due to sample processing issues; hence a total of 16 subjects have been enrolled in 200mg SAD dose level **CSF collection Completed Ongoing
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12 12 Day 8 100 mg QD Placebo 40 mg QD 200 mg QD 5 mg QD 10 mg QD Wk 2 Wk 4 Placebo 40mg QD 6h 24h -100 -80 -60 -40 -20 0 20 40 60 NEK7 Protein in Peripheral Blood T cells (% Change From Predose) 100 mg SD Placebo 40 mg SD 200 mg SD 300 mg SD 400 mg SD MRT-8102 Achieved 80 – 90% NEK7 Degradation in Peripheral Blood T Cells After Single and Multiple Dose Administration Rapid and robust degradation of NEK7 noted in peripheral blood T cells (~80 - 90%) across all dose levels, consistent with preclinical findings CRP PoCMADSAD SAD – 48 subjects (placebo + MRT-8102); MAD - 40 subjects (placebo + MRT-8102); CRP PoC – 16 subjects (placebo + MRT-8102), data delivery pending for remaining 8 subjects. Data are shown as Mean ± SEM. Day 8, week 2 and week 4 values shown are determined 24h post last dose. Time Post Treatment Initiation
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13 13 Day 2 Day 4 -100 -80 -60 -40 -20 0 -52% -25% Median CRP (% Change From Predose) (n=36) Day 2 Day 4 -100 -80 -60 -40 -20 0 -78% -44% (n=7) Day 2 Day 4 -100 -80 -60 -40 -20 0 -72% -45% (n=13) Baseline CRP ≥2 mg/L Single Dose of MRT-8102 Led to Significant Reduction in Serum hsCRP Baseline CRP ≥1 mg/LAll subjects Maximum activity achieved at all SAD dose levels (40 – 400mg) (n=36) Baseline median CRP – 0.70 mg/L (n=7) Baseline median CRP – 3.96 mg/L (n=13) Baseline median CRP – 2.80 mg/L
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14 14 0 20 40 60 80 100 67% 50% 78% 67% Proportion of Participants (3/6) (4/6) hsCRP <1 mg/L hsCRP <2 mg/L (6/9) (7/9) All (n=30) ≥1 mg/L (n=14) ≥2 mg/L (n=9) ≥3 mg/L (n=6) -100 -80 -60 -40 -20 0 -78%-74%-78% -61% Median hsCRP (% Change From Predose) Predose On-treatment 0 2 4 6 8 (n=14) hsCRP (mg/L) 40 mg QD 100 mg QD 10 mg QD 5 mg QD 200 mg QD MRT-8102 induced significant reduction in serum hsCRP during multiple dose administration* Multiple Daily Doses of MRT-8102 Led to Significant and Sustained Reduction of Serum hsCRP Significant proportion of subjects achieved hsCRP reduction to <2 mg/L* * Values correspond to the best response of hsCRP of day 6, 7, 9 and 14 combined across all MAD dose levels Baseline CRP ≥1 mg/L Baseline CRP ≥2 mg/L ≥3 mg/L 61% drop in hsCRP across all subjects regardless of CRP level at baseline; data consistent with maximum MRT-8102 activity achieved at all dose levels Up to 78% decrease in hsCRP noted in subjects with elevated CRP levels at baseline 78% of subjects with elevated baseline CRP of >2 mg/L achieved suppression of hsCRP to <2 mg/L 0.92 2.33 4.75 6.46Baseline CRP (mg/L)
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15 15 0h 6h D5 D8 D9 D10 -100 -80 -60 -40 -20 0 Time Post Treatment Initiation NEK7 and IL-1β (% Change From Predose) NEK7 IL-1β Multiple Daily Doses of MRT-8102 Led to Reductions of IL-6 and IL-1β * Ridker PM et al. European Heart Journal (2018) Significant reduction in median IL-6 levels to below CV risk threshold noted in subjects with elevated CRP ~80% inhibition in IL-1β secretion noted in subjects with elevated CRP at baseline at doses ranging from 5 – 200 mg Suppression in IL-1β secretion correlates with NEK7 degradation across all time points Predose On-treatment 0 1 2 3 4 (n=14) Median IL-6 (pg/ml) Low CV Risk* -55% 55% reduction of endogenous IL-6 plasma levels Baseline CRP ≥1 mg/L Predose On-treatment 0 200 400 600 800 (n=12) IL-1β (pg/mL) 40 mg QD 100 mg QD 10 mg QD 5 mg QD 200 mg QD Overlay of representative subject -77% Rapid and sustained reduction of IL-1β after ex-vivo stimulation Baseline CRP ≥1 mg/L On-treatment Off-treatment High CV Risk*
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16 16 MRT-8102 Treatment Reduced IL-6 Levels in CSF Consistent with CNS Penetration Predose D7 0 5 10 15 20 25 30 Plasma IL-6 (pg/mL) Predose D7 0 5 10 15 20 25 30 CSF IL-6 (pg/mL) Cerebrospinal fluid (CSF) • Predose • Day 7 75% reduction of CSF IL-6 in 2 subjects with elevated levels at baseline Cerebrospinal fluid (CSF) collection (100 mg QD) Dotted line indicates median established with CSF and plasma samples derived from healthy volunteers (n=20) Astrocytes Microglia Pro-inflammatory cytokines 100 mg dose achieved levels of MRT-8102 in CSF consistent with pharmacologically active concentrations Significant decrease in CSF IL-6 noted in two subjects with elevated baseline levels following 7d administration Plasma IL-6 levels at baseline for these two subjects were low suggesting CNS/CSF-specific effects CSF IL-6 Plasma IL-6
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17 17 CRP PoC (Part 3) Study of MRT-8102 in Subjects with Elevated CVD Risk Double blind period - CRP endpoint: absolute reduction and reduction to <2 mg/L - CRP measurements: pre-dose, D1, D7, D14, D21, D28, D35 Placebo n ~9 MRT-8102 (40 mg) n ~27 Randomization Day 56Day 28Day 1 Safety follow up Study population • Obesity (waist > 40” for men or > 35” for women and/or BMI > 30) • Elevated CRP >3 and <15 mg/L Primary endpoint • Safety and tolerability of 28 days dosing Secondary endpoints • Change in CRP levels • PK Exploratory endpoints • PD (NEK7, IL-6, IL-18, Fibrinogen, SAA) • Body weight • Other markers of CV risk
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18 18 1 2 3 4 0% 20% 40% 60% 80% 100% 56% 83% 89% 94% 33% 44% 50% 56% Time Post Randomization (Weeks) Proportion of Participants hsCRP <1 mg/L hsCRP <2 mg/L 0 1 2 3 4 -40 -20 0 20 Time Post Randomization (Weeks) Mean Fibrinogen (%Change From Predose) Placebo MRT-8102 0 1 2 3 4 -100 -80 -60 -40 -20 0 20 Time Post Randomization (Weeks) Median hsCRP (%Change From Predose) Placebo MRT-8102 85% decrease of hsCRP after 4 weeks of dosing 94% of subjects show suppression of hsCRP to <2 mg/L* Interim Analysis of CRP PoC Cohort Suggests MRT-8102 Induced Rapid Reductions of hsCRP and Fibrinogen -80% -82% -85% -85% 85% reduction in CRP noted after 4 weeks of dosing that correlated well with sustained NEK7 degradation during the treatment period 94% of subjects show suppression of hsCRP to <2 mg/L after 4 weeks of dosing Up to 31% reduction in fibrinogen, an independent atherosclerotic risk factor**, noted during treatment period * Baseline median CRP: Placebo - 4.0 mg/L; MRT-8102 - 6.3 mg/L; Baseline mean Fibrinogen: Placebo - 394 mg/dL; MRT-8102 – 431 mg/dL ** Meade TW et al. Lancet (1986); Kannel WB et al. JAMA (1987); Fibrinogen Studies Collaboration, JAMA (2005) Up to 31% reduction in fibrinogen after 4 weeks of treatment -19% -30% -30% -31% (n=24)(n=24) (n=24)
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19 19 Summary of Blinded Safety Data As of data cutoff of December 23, 2025, 112 subjects completed dosing: • SAD/MAD completed, 88 HV participants enrolled • Part 3 (CRP PoC) ongoing, 24 participants with elevated CVD risk and high CRP levels have concluded hsCRP assessment and are included in the analysis Safety Profile: • Well tolerated with favorable safety profile with no SAEs • Treatment-emergent AEs were mild to moderate • No evidence of increased infection risk • No dose dependency • Evaluation and data collection ongoing for Part 3* * One participant in Part 3 was diagnosed with asymptomatic, acute infectious hepatitis A while on study (unknown if particip ant received MRT-8102 or placebo). Participant experienced a transient ALT elevation equivalent to a Gr 3 that improved while on treatment.
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20 20 GFORCE-1 Study: Dose Exploration of MRT-8102 in Subjects with Elevated CVD Risk Double blind period CRP endpoint: absolute reduction and reduction to <2 mg/L CRP measurements: pre-dose, D1, D7, D14, D21, D28, D35 Expanded dose exploration to accelerate Phase 2 ASCVD study: Ph 2 initiation planned in 2026 Placebo n ~ 27 MRT-8102 (DL1)* n ~ 27 Randomization Day 56Day 28Day 1 Safety follow up Study population • Obesity (waist > 40” for men or > 35” for women and/or BMI > 30) • Elevated CRP >3 and <15 mg/L Primary endpoint • Safety and tolerability of 28 days dosing Secondary endpoints • Change in CRP levels • PK Exploratory endpoints • PD (NEK7, IL-6, IL-18, Fibrinogen, SAA) • Body weight • Other markers of CV risk MRT-8102 (DL2)** n ~ 27 MRT-8102 (DL3)** n ~ 27 GFORCE, Glue for CRP Elimination * DL of 40 mg (n=27) with corresponding placebo (n=9) completed enrollment ** Two additional DLs with corresponding placebo to be included in the next amendment
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21 21 Additional Attractive Opportunities Exist for MRT-8102 Rheumatology Gout • ~3M U.S. addressable population, representing the approximately one-third of gout patients with stage 3+ CKD • Gout SOC therapies are contradicted or lack safety data in CKD patients, imposing a major treatment challenge • High unmet need among chronic refractory patients, who often suffer from breakthrough flares Metabolic dysfunction- associated steatohepatitis • ~7-9M U.S. addressable population • Large and rapidly-growing market; development effort mainly focuses on reducing steatosis • Growing scientific evidence that targeting inflammation could provide additional clinical benefit Cardio-Immuno-Metabolic *SYSADOA: symptomatic slow-acting drugs for osteoarthritis, such as chondroitin sulfate, glucosamine, hydrochloride, diacerin Source: Clarivate; Alanaeme et al. (2022); Mazhar et al. (2024); Hagstrom et al. (2024); Zhu et al. (2012); Mohammed et al. (2019); Settipane et al. (2019); Pollack et al. (2022); Hinks et al. (2021); Esteban-Gorgojo et al. (2018); MRTx interviews, survey, and analysis Allergic Diseases Osteoarthritis Asthma • ~1-3M U.S. addressable population, with non-Type 2 disease representing 30-50% of severe asthma • High NLRP3 inflammasome activity in non-type 2 inflammatory subtype • Non-type 2 presents lack of response to corticosteroid therapy, responsive to anti- TSLP • Potential to expand to Type 2 inflammatory subtype • ~3-4.5M U.S. addressable population • Canakinumab decreased rates of knee and hip replacement • A safe, novel anti-inflammatory option for long-term management • 4-5L treatment option for patients refractory to SYSADOA* and NSAIDs Recurrent pericarditis • ~40K U.S. addressable population • Significant unmet need for therapies with improved safety and tolerability profile given typically long duration of treatment • Strong preference for oral treatments among patients
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Summary and Pipeline Update
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23 23 • SAD (48 healthy volunteer subjects) and MAD (40 healthy volunteer subjects) cohorts completed with no adverse safety signals, ~80-90% NEK7 degradation noted in T cells at all dose levels tested, and compelling reduction in hsCRP in subjects with elevated baseline CRP levels • Part 3 (CRP PoC) of Phase 1 study exploring 40 mg MRT-8102 in high-risk CVD subjects (obesity/elevated CRP) is ongoing and 24 subjects have been evaluated up to end of week 4. Preliminary data for these subjects showed: • 85% sustained reduction of hsCRP through end of week 4 • 94% subjects achieved reduction of hsCRP levels to <2 mg/L* after 4 weeks of dosing (baseline hsCRP level of 6.3 mg/L) • 31% reduction of fibrinogen after 4 weeks of dosing • No SAEs, no severe AEs as of data cut off date of 12/23/25, evaluation ongoing • Study (now named GFORCE-1) will be expanded and additional dose levels will be explored to accelerate development in ASCVD; data expected in H2 2026, with plans to initiate Phase 2 GFORCE-2 study 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 • Monte Rosa considering to advance MRT-8102 or next-generation MGD into multiple other indications Summary and Next Steps *hsCRP levels of >2 mg/L are associated with elevated CVD risk
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24 24 Monte Rosa Pipeline and Upcoming Milestones GSPT1 Castration-resistant Prostate Cancer IL-1β/NLRP3-driven Inflammatory Diseases VAV1 Licensed to Novartis* Immune-mediated Diseases PreclinicalTarget Indication(s) Phase 2 initiation in 2026 Next Anticipated MilestonePhase 1 Phase 2 Phase 1 data and Phase 2 initiation in 2026 Multiple Phase 2 initiations in 2026 Multiple Targets Includes those licensed/optioned to Roche and Novartis I&I, Oncology, Genetic and Neurological Diseases Announce additional targets NEK7 Compound MRT-2359 MRT-6160 MRT-8102 Discovery IND submission in 2026 Next Generation CCNE1/ CDK2 CCNE1 Amplified Tumors ER+ Breast Cancer IND submission in 2026Discovery Immunology & InflammationOncologyVarious * Novartis has exclusive worldwide rights to develop, manufacture and commercialize MRT-6160 and other VAV1 MGDs. Monte Rosa is eligible for up to $2.1B in development, regulatory, and sales milestones, beginning upon initiation of Phase 2 studies, and is also eligible for 30% US P&L share and ex-US tiered royalties. Notes: IND = investigational new drug. ER = endocrine receptor. I&I = immunology and inflammation. Phase 3
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Q&A
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Thank you