Monte Rosa Therapeutics, Inc. · NASDAQ:GLUE
Monte Rosa Therapeutics — Technical Presentation (October 2026)
44 slides from Monte Rosa Therapeutics's technical presentation, Oct 1, 2026
Slide 1: MRT-8102 GFORCE-1 Clinical Study Results
Degrading Proteins, Making Medicines MRT-8102 GFORCE-1 Clinical Study Results October 1, 2026 Exhibit 99.2
Slide 2: Forward-Looking Statements
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 an
Slide 3: GFORCE-1: A Phase 1 Study of MRT-8102 in Subjects with Elevated CVD Risk
MRT-8102, a selective first-in-class NEK7 MGD, demonstrated a favorable safety and tolerability profile, sustained NEK7 degradation, and broad normalization of elevated pathogenic drivers of ASCVD Study design: 108 subjects with elevated CVD risk; 8-week study, randomized to MRT-8102 at 5, 20, and 4
Slide 4: Therapeutic Rationale for Degrading NEK7
Therapeutic Rationale for Degrading NEK7
Slide 5: NEK7 Enables Pathogenic NLRP3 Activation to Drive Disease Biology
NEK7 Enables Pathogenic NLRP3 Activation to Drive Disease Biology Multiple metabolic and genetic factors can promote NEK7-mediated NLRP3 inflammasome complex assembly in a kinase-independent manner NEK7/NLRP3 pathway activation causes pyroptotic cell death, leading to release of IL-1α/β, IL-18, and
Slide 6: NEK7/NLRP3 Downstream Signaling Elevated Across Multiple Indications
Members of the NEK7/NLRP3 Downstream Signaling Cascade are Elevated Across Multiple Indications with High Unmet Need Upregulation of pathogenic cascade downstream of pyroptosis is conserved across the top NEK7/NLRP3-active indications ASCVD, HS and gout have highest pathological NEK7/NLRP3 activity
Slide 7: The Role of the NEK7/NLRP3 Pathway in ASCVD
The Role of the NEK7/NLRP3 Pathway in ASCVD
Slide 8: Pathogenic Role of NEK7/NLRP3 in Plaque Biology and Atherogenic Progression
The Multifaceted Pathogenic Role of the NEK7/NLRP3 Pathway in Plaque Biology and Atherogenic Progression Endothelial Cell dysfunction enhances adhesion molecules and vascular leakage Increased uptake of oxLDL and retention of oxidized cholesterol in foam cells VSMC proliferation or phenotypic transf
Slide 9: Upstream Targeting of NEK7/NLRP3 Pathway to Impact MACE
Clinical Experience Supports Upstream Targeting of NEK7/NLRP3 Pathway as a Superior Approach to Impact MACE Clinical efficacy achieved NLRP3 SNP TET2 ChIP Metabolic Genetic Cholesterol LoDoCo2 COLCOT CANTOS ZEUS NEK7/NLRP3 pathway modulation IL-1β neutralization IL-6 neutralization 5,522 pts with ch
Slide 10: NLRP3 Activating Variants Increase Signaling and Cardiovascular Risk
NLRP3 Activating Variants Increase Signaling and Cardiovascular Risk NLRP3 risk variant shows larger effect on inflammatory cytokines and CRP compared to IL-6(R) variant NLRP3 variant associated with strong risk of CVD; IL-6(R) benefit restricted to CHIP+ subgroup NLRP3 risk variants in all comers I
Slide 11: Mediators of NLRP3 Pathway Driven Atherosclerosis are Cumulative Cardiovascular Risk Factors
Mediators of NLRP3 Pathway Driven Atherosclerosis/-thrombosis are Established Cumulative Cardiovascular Risk Factors NLRP3, relevant cytokines, and DAMP levels are significantly increased in unstable plaques NEK7/NLRP3 pathway DAMPs & thrombogenic factors Data from PMIDs 24026779, 29957458, 21435605
Slide 12: Results of GFORCE-1 Study
My. Monte Rosa Therapeutics Results of GFORCE-1 Study
Slide 13: GFORCE-1 Study: Dose Exploration of MRT-8102
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 Placebo n ~ 27 MRT-8102 (40 mg) n ~ 27 Randomization Day 56 Day 28 Day 1 Safety follow
Slide 14: GFORCE-1 Participants Baseline Characteristics
GFORCE-1 Participants Baseline Characteristics Baseline Characteristics Placebo (n=27) MRT-8102 5 mg (n=27) MRT-8102 20 mg (n=27) MRT-8102 40 mg (n=27) Total (n=108) Median age, years (IQR) 45 (30 - 53) 38 (34 - 50) 40 (34 - 55) 41 (37 - 52) 41 (34 - 52) Male, n (%) 12 (44.4) 8 (29.6) 11 (40.7) 13 (
Slide 15: MRT-8102 Achieved Robust and Sustained NEK7 Degradation
MRT-8102 Achieved Robust and Sustained NEK7 Degradation Robust and sustained degradation of NEK7 noted in peripheral blood T cells (~80 - 90%) across all dose levels at week 4, consistent with preclinical findings Data are medians (IQR). SAD (n=48); MAD (n=40); GFORCE-1 (n=101) SAD MAD GFORCE-1
Slide 16: GFORCE-1: Summary of Unblinded Safety Data
Safety data were collected over 8 weeks for 108 participants (MRT-8102, n=81; placebo, n=27) No SAEs were reported Frequency of treatment-emergent AEs (TEAEs) was similar between MRT-8102 (33% participants) and placebo (30% participants) Most (86%) of MRT-8102 TEAEs were grade 1* The most frequent T
Slide 17: Favorable Safety and Tolerability Profile Over 8 Weeks
MRT-8102 Demonstrated a Favorable Safety and Tolerability Profile Over the Period of 8 Weeks Treatment-Emergent Adverse Events (AE) Placebo (n=27) MRT-8102 5 mg (n=27) MRT-8102 20 mg (n=27) MRT-8102 40 mg (n=27) Participants with any AE, n (%) 8 (30) 7 (26) 8 (30) 12 (44) Participants with any AE le
Slide 18: Clinical Activity of MRT-8102 on Key Pathogenic Drivers of ASCVD
Clinical Activity of MRT-8102 on Key Pathogenic Drivers of ASCVD
Slide 19: GFORCE-1 Enrolled a Population at Risk of CVD
GFORCE-1 enrolled a population at risk of CVD and a biomarker profile that is informative of established ASCVD Population: Obese subjects at elevated CVD risk, reflecting a population with a high ratio of silent atherosclerosis; established ASCVD diagnosis not required Based on REACT study, prevalen
Slide 20: Key ASCVD Pathogenic Drivers and Markers Assessed in GFORCE-1
Macrophage / neutrophil activation Plaque destabilization / vessel wall alterations Plaque rupture & thrombus formation Acute phase response EC / SMC dysfunction Vulnerable plaque Immune cell recruitment Plaque initiation Ruptured plaque Fibrinogen CRP + Lp(a) Key ASCVD Pathogenic Drivers and Marker
Slide 21: NEK7/NLRP3 Related Markers Elevated at Baseline in GFORCE-1
IL-1β, DAMPs, and thrombogenic factors NEK7/NLRP3 Pathway Related Cytokines, DAMPs and Thrombotic Markers were Elevated at Baseline in GFORCE-1 Subjects Calprotectin (ng/mL) HMGB1 (ng/mL) IL-6 (pg/mL) hsCRP (mg/L) SAA (mg/L) IL-1β (fg/mL) (n=67) (n=101) (n=64) (n=101) (n=66) (n=101) (n=40) (n=101) (
Slide 22: NLRP3 Risk Alleles Correlate to Baseline Increase of ASCVD Drivers
NLRP3 Risk Alleles Correlate to Baseline Increase of ASCVD Drivers Two high-priority NLRP3 risk SNPs, rs10754555 and rs10754558, have been linked to increased NLRP3 pathway activation and cardiovascular risk. In line with published data, nearly 1 in 3 subjects (29%) carry a highest-risk genotype (GG
Slide 23: Modulation of Molecular Drivers of Plaque and Vascular Biology
Modulation of Molecular Drivers of Plaque and Vascular Biology
Slide 24: DAMPs, Including Calprotectin, Activate NEK7/NLRP3 in Neighboring Cells
DAMPs, Including Calprotectin, Potently Activate NEK7/NLRP3 in Neighboring Cells to Amplify Plaque Burden and Instability Calprotectin levels correlate with plaque burden, inflammation and instability Croce et al., Circulation, 2009. Data from Peng et al., Cardiovasc Diabetol, 2011, Cheng et al., Fr
Slide 25: MRT-8102 Potently Inhibits Pyroptosis and Release of DAMPs and IL-1β
MRT-8102 Potently Inhibits Pyroptosis and Release of DAMPs and IL-1β Pro-IL-1a Pro-IL-1b Pyroptosis Cytokine release Anti-IL-1/IL-6 biologics Pyroptotic Cell Intact Cell NLRP3 NEK7 IL-1a IL-18 IL-1b NEK7 MRT-8102 DAMP release calprotectin NEK7 MGD IL-1/IL-6 blocking biologics Do not inhibit pyroptos
Slide 26: MRT-8102 Reduced Plasma Calprotectin to Healthy Volunteer Levels
Calprotectin is elevated in subjects with elevated CVD risk Treatment reduced Calprotectin to levels associated with low risk of future CV events (week 4) MRT-8102 Reduced Plasma Calprotectin to Healthy Volunteer Levels Median reduction of 56% in plasma calprotectin to levels comparable to those obs
Slide 27: Calprotectin Equally Reduced Across All Dose Levels
Plasma Levels of Calprotectin were Equally Reduced Across all Dose Levels in Response to MRT-8102 5mg QD 57% reduction 40mg QD 52% reduction 20mg QD 54% reduction Data are Tukey box-and-whisker plots; HV: SAD and MAD part; * p<0.002 compared to predose (MRT-8102 treated); p-value from Wilcoxon test
Slide 28: MRT-8102 Reduced Plasma S100A12 and Serum SAA
MRT-8102 Reduced Plasma S100A12 and Serum SAA to Healthy Volunteer Levels Median reduction of 46% and 51% in plasma S100A12 and serum SAA, respectively, to levels comparable to those observed in healthy volunteers after 4 weeks of dosing MRT-8102 reduces S100A12 to levels in HVs Data are medians (IQ
Slide 29: Biological Crosstalk Between HMGB1 and IL-1β
Biological crosstalk between HMGB1 and IL-1β influences multiple aspects of vessel and plaque biology HMGB1 and IL-1β baseline levels strongly correlate, reinforcing biological proximity Pathological Crosstalk between HMGB1 and IL-1β Downstream of NEK7/NLRP3 Reinforces Plaque Progression and Instabi
Slide 30: MRT-8102 Treatment Reduced HMGB1 and IL-1β Levels
MRT-8102 treatment resulted in meaningful HMGB1 reduction in subjects with higher baseline levels MRT-8102 Treatment Reduced HMGB1 and IL-1β Levels (n=64) (n=101) > 4.7 (ng/mL) (n=20) -40%* (n=67) (n=101) (n=17) > 170 (fg/mL) MRT-8102 treatment resulted in meaningful IL-1β reduction in subjects with
Slide 31: MRT-8102 Treatment Led to Reductions in Fibrinogen
Treatment significantly reduced fibrinogen to normal physiological levels MRT-8102 Treatment Led to Reductions in Fibrinogen Fibrinogen baseline is elevated in GFORCE-1 population Median reduction of 28% in fibrinogen to levels comparable to those observed in healthy volunteers after 4 weeks of dosi
Slide 32: Markers of Systemic Inflammation
Markers of Systemic Inflammation
Slide 33: Rapid and Sustained Reductions in hsCRP and IL-6 Levels
MRT-8102 Induced Rapid and Sustained Reductions in hsCRP and IL-6 Levels Robust decrease of hsCRP after 4 weeks of dosing Data are medians (IQR); * p<0.0001 compared to predose; p-value from Wilcoxon test; HV: SAD and MAD part % Change from predose in hsCRP at week 4 per cohort: 5mg QD -86%, 20mg QD
Slide 34: Update on Development Plans
Update on Development Plans
Slide 35: GFORCE-2: A Differentiated Phase 2 Approach
: A Differentiated Phase 2 Approach Proposed trial design subject to review by FDA Inform an innovative & efficient Phase 3 study design focused on the patient population with the most modifiable disease ASCVD drivers and systemic biomarkers Imaging Genetics DAMPs (calprotectin, S100A12, HMGB1), cyt
Slide 36: GFORCE-2: A Phase 2b Study in Patients with Coronary Artery Disease
: A Phase 2b Study in Patients with Coronary Artery Disease Outcome measures Change in levels of key pathogenic ASCVD drivers including atherogenic, thrombogenic mediators and lipids Change in local cardiac imaging, from baseline to 6 months Exploratory endpoints Cardiac imaging Establish pharmacoge
Slide 37: Planned Phase 2 Studies for Gout and HS
Ph2 Study in Gout Flare Prevention Following Acute Flare Management Initiation planned Q4 2026 / Q1 2027 Trial ~ 60 pts w/recurrent gout flares 12 weeks Outcome Measures and PoC expectation Reduction in pain VAS by 72 hours Frequency of new flares Ph2 Study in Moderate to Severe Hidradenitis Suppura
Slide 38: MRT-8102 Opportunities and Pipeline Update
MRT-8102 Opportunities and Pipeline Update
Slide 39: CAD: Large Opportunity with a Safe, Oral Treatment Targeting NEK7
CAD: Large Opportunity to Address Atherosclerotic Risk with a Safe, Oral Treatment Targeting NEK7 MRT-8102 Opportunity Potential to complement existing lipid and metabolic therapies Targeting NEK7/NLRP3 pathway could provide broader suppression of atherogenic and thrombotic pathways Oral administrat
Slide 40: Large Market Opportunities Supported by Strong Biological Rationale
Large Market Opportunities Supported by Strong Biological Rationale Hidradenitis suppurativa Highest NEK7/NLRP3-pathway activity score of any indication studied, with consistent upregulation of NLRP3, IL-1β, and DAMPs in lesional tissue ~400-450K U.S. addressable population Significant unmet need wi
Slide 41: Summary and Next Steps
Summary and Next Steps WHAT GFORCE-1 SHOWED Favorable safety profile across all dose levels tested: no SAEs, no infection signal Robust, sustained target engagement: ~80–90% NEK7 degradation at all dose levels Broad normalization of ASCVD pathogenic drivers: markers of local plaque progression, thro
Slide 42: Monte Rosa Pipeline and Upcoming Milestones
Monte Rosa Pipeline and Upcoming Milestones GSPT1 Castration-resistant Prostate Cancer NEK7/NLRP3-driven Diseases VAV1 Licensed to Novartis* Sjögren's disease Preclinical Target Indication(s) Ph 1/2 update in 2026; Ph 2 update in 2027 Next Anticipated Milestone Phase 1 Phase 2 Multiple Ph 2 initiati
Slide 43: Q&A
Q&A
Slide 44: Thank you
Thank you Mp. Monte Rosa Therapeutics
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