Monte Rosa Therapeutics, Inc. · NASDAQ:GLUE
Monte Rosa Therapeutics — Investor Presentation (October 2026)
86 slides from Monte Rosa Therapeutics's investor presentation, October 2026
Slide 1: Degrading Proteins, Making Medicines
Degrading Proteins, Making Medicines Innovating Beyond New Heights | October 2026
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: Monte Rosa Therapeutics – A Leader in Targeted Protein Degradation
Monte Rosa Therapeutics – A Leader in Targeted Protein Degradation Building the Future • Potential multi-billion-dollar market opportunities with only-in-class molecular glue degraders (MGDs) • Leader in AI-driven protein-protein interaction (PPI) Delivering Value prediction and rational design of n
Slide 4: Most Disease-driving Biology Remains Inaccessible With Conventional Modalities
Most Disease-driving Biology Remains Inaccessible With Conventional Modalities ~15% • Many disease-driving proteins are not addressable “druggable” with existing therapeutic modalities, including small-molecule inhibitors, antibodies, and even other targeted protein degraders, because they lack enzy
Slide 5: Monte Rosa MGDs: Opportunity for Paradigm-Changing Medicines
Monte Rosa MGDs: Opportunity for Paradigm-Changing Medicines • MGDs are small molecules that remove the entire disease-causing protein rather than partially suppressing its activity, eliminating both enzymatic and non-enzymatic functions Exquisite selectivity • Protein elimination enables catalytic
Slide 6: Next-Gen MGD-Based Therapeutics Delivering Meaningful Clinical Results
Next-Gen MGD-Based Therapeutics Delivering Meaningful Clinical Results • VAV1 is an upstream T- and B-cell signaling node, enabling broad cytokine and autoantibody suppression with a single oral agent First-in-class VAV1 MGD MRT-6160/ • Phase 1 demonstrated >90% VAV1 degradation with robust for dive
Slide 7: Monte Rosa Pipeline and Upcoming Milestones
Monte Rosa Pipeline and Upcoming Milestones Next Target Compound Indication(s) Preclinical Phase 1 Phase 2 Phase 3 Anticipated Milestone Sjögren's disease Immunology & Inflammation VAV1 MRT-6160 Additional Licensed to Novartis* (DDY391) Ph 2 initiations Psoriatic arthritis Coronary artery disease, M
Slide 8: Creating Value through Strategic Collaborations
Creating Value through Strategic Collaborations Global license for VAV1 molecular glue Strategic collaboration to develop Collaboration for degraders to treat Scope degraders, including MRT-6160 (DDY391) MGDs for cancer and neurological immune-mediated diseases (Sep. 2025) (Oct. 2024) diseases (Oct.
Slide 9: I&I Pipeline
Therapeutics I&I Pipeline Monte Rosa
Slide 10: Beyond Biologics-in-a-Pill: Potential for Next-Generation I&I Drugs
Beyond Biologics-in-a-Pill: Potential for Next-Generation I&I Drugs Degrading previously undruggable signaling nodes to modulate multiple cytokines VAV1 (Adaptive NEK7 (Innate Immunity) Immunity) MRT-6160 (DDY391) MRT-8102 • Most current biologics inhibit single downstream cytokines, often leaving P
Slide 11: VAV1 Program (MRT-6160/DDY391)
VAV1 Program (MRT-6160/DDY391) Licensed to Novartis
Slide 12: MRT-6160 (DDY391) At a Glance
MRT-6160 (DDY391) At a Glance First-in-class VAV1 MGD for diverse T and B-cell driven diseases VAV1 Rationale Opportunity • VAV1 is an upstream T- and • Large potential immunology B-cell signaling node, opportunities, with biological enabling broad cytokine and relevance across multiple major autoan
Slide 13: MRT-6160: Upstream Immune Modulation via Targeted VAV1 Degradation
MRT-6160: Upstream Immune Modulation via Targeted VAV1 Degradation Oral MGD delivering coordinated suppression of pathogenic T- and B-cell signaling MRT-6160 Reduces Multiple Pathogenic Cytokines (IL-2, IL-6, IL-17) and Secreted Antibodies (sIgG) • MRT-6160 is an oral molecular glue degrader that se
Slide 14: VAV1: Upstream Targeting Node Controlling Clinically Validated Pathways
VAV1: Upstream Targeting Node Controlling Clinically Validated Pathways Clinically validated pathway in VAV1 signaling is associated with several T and B cell immunologic outcomes autoimmune/inflammatory disease T cell activation B cell activation/Plasma cell differentiation (Antibody production) Th
Slide 15: VAV1: Unique Mechanism with Broad Potential Applications
VAV1: Unique Mechanism with Broad Potential Applications Potential to address multiple autoimmune diseases with a safe, oral therapy T-cell mediated T/B-cell mediated 2030E Drug Class Sales Example Drugs (I&I indications only) TNF Humira, Enbrel $9B Evidence of VAV1 mechanistic overlap IL17A Taltz,
Slide 16: Preclinical Data Support Broad Potential Application of MRT-6160
Preclinical Data Support Broad Potential Application of MRT-6160 T-cell transfer-induced colitis model MRL-Faslpr spontaneous autoimmune disease model of inflammatory bowel disease (e.g., SLE, Sjögren’s) 6 6 Lymphadenopathy score CD45RBlow non-pathogenic control Vehicle Vehicle 5 Upadacitinib, 10 mg
Slide 17: Summary of Phase 1 Data
Summary of Phase 1 Data • Pharmacodynamic and functional ex vivo studies performed during Phase 1 suggest significant effects on cytokine production can be achieved following marked and sustained degradation of VAV1 in humans • Demonstrated levels of VAV1 degradation consistent with levels of degrad
Slide 18: MRT-6160 Phase 1 Healthy Volunteers Study: Design and Objectives
MRT-6160 Phase 1 Healthy Volunteers Study: Design and Objectives All cohorts randomized & placebo controlled SAD cohorts MAD cohorts Study Endpoints One oral dose 7 daily oral doses SAD DL5 Primary • Safety and tolerability SAD DL4 SAD DL3 MAD DL3 Secondary & exploratory • Pharmacokinetics SAD DL2 M
Slide 19: MRT-6160 Achieved Dose-Dependent VAV1 Degradation >90%
MRT-6160 Achieved Dose-Dependent VAV1 Degradation >90% in Peripheral Blood T Cells After Single and Multiple Dose Administration SAD MAD 60 Placebo 40 Placebo DL1 DL1 DL2 DL2 VAV1 Protein in Peripheral Blood T cells VAV1 Protein in Peripheral Blood T cells 40 DL3 20 DL3 DL4 DL5 (% Change from Predos
Slide 20: VAV1 Degradation Resulted in Functional Inhibition of T and B Cells
VAV1 Degradation by MRT-6160 Resulted in Significant Functional Inhibition of T and B Cells following a Single Dose Administration SAD 60 MRT-6160 treatment: 40 • Significantly attenuated CD69 upregulation (% Change from Predose at 24h) 20 on T and B cells following TCR stimulation, Placebo DL1 refl
Slide 21: MRT-6160 Sustained Suppression of TCR-mediated Cytokine Production
MRT-6160 Resulted in Sustained Suppression of TCR-mediated Cytokine Production following Single or Multiple Dose Administration SAD IL-2 IL-17A IFN-γ MAD IL-2 IL-17A IFN-γ Placebo Placebo Placebo Placebo Placebo Placebo MRT-6160 MRT-6160 MRT-6160 MRT-6160 MRT-6160 MRT-6160 60 120 80 40 40 (% Change
Slide 22: Safety Summary
Safety Summary • MRT-6160 was well tolerated with no serious adverse events (SAE) • Observed treatment-emergent adverse events (TEAE) were mild (82%) or moderate (18%) and self-limiting • Overall TEAE frequency was similar between MRT-6160 and placebo • TEAE observed in 2 or more subjects treated wi
Slide 23: Strategic Agreement to Accelerate and Broaden MRT-6160 Development
Strategic Agreement to Accelerate and Broaden MRT-6160 (DDY391) Development Global license agreement with Novartis to advance VAV1-directed molecular glue degraders including MRT- Scope 6160 (DDY391), in development for immune-mediated conditions (announced Oct. 2024) • $150M upfront payment • Eligi
Slide 24: NEK7 Program (MRT-8102)
Mp. Monte Rosa Therapeutics NEK7 Program (MRT-8102)
Slide 25: MRT-8102 At a Glance
MRT-8102 At a Glance First-in-class NEK7 MGD for NLRP3 inflammasome driven diseases NEK7 Rationale Opportunity • NEK7 is essential for NLRP3 • Large cardiometabolic and inflammasome assembly, inflammatory markets with limited oral, enabling upstream blockade of upstream anti-inflammatory options IL-
Slide 26: NEK7 Enables Pathogenic NLRP3 Activation to Drive Disease Biology
NEK7 Enables Pathogenic NLRP3 Activation to Drive Disease Biology NEK7/NLRP3 activating stimuli • Multiple metabolic and genetic factors can promote NEK7/NLRP3 activators directly NEK7-mediated NLRP3 inflammasome complex assembly stimulate pathway in a kinase-independent manner or enhance DAMPs Meta
Slide 27: NEK7/NLRP3 Pathway Elevated Across Multiple Indications
Members of the NEK7/NLRP3 Downstream Signaling Cascade are Elevated Across Multiple Indications with High Unmet Need ASCVD, HS and gout have highest Upregulation of pathogenic cascade downstream of pyroptosis pathological NEK7/NLRP3 activity scores is conserved across the top NEK7/NLRP3-active indic
Slide 28: Large Market Opportunities Supported by Strong Biological Rationale
Large Market Opportunities Supported by Strong Biological Rationale Coronary artery disease Gout Hidradenitis suppurativa • Central role of NEK7/NLRP3 in • Canonical NEK7/NLRP3-pathway • Highest NEK7/NLRP3-pathway plaque biology and atherogenic disease: MSU crystals trigger NEK7- activity score of a
Slide 29: MRT-8102 is Highly Differentiated Over Other NLRP3/IL-1/IL-6 Pathway Modalities
NEK7-directed MGD MRT-8102 is Highly Differentiated Over Other NLRP3/IL-1/IL-6 Pathway Modalities Neosubstrate- MGD available for MGD directed MGD additional targeting degradation Intact cell NEK7 POI POI CRBN Pyroptosis POI NLRP3 Complex Neosubstrate CRBN degradation formation Calprotectin Canakinu
Slide 30: NEK7 Is Critical for a Broad Set of NLRP3-mediated Inflammatory Diseases
20 NEK7 Is Critical for a Broad Set of NLRP3-mediated Inflammatory Diseases Joint Swelling (mm) 15 In Preclinical Models 10 Mouse: MRT-8102 reduced heart damage Rabbit: MRT-8102 5 reduced in two cardiovascular disease models MSU-induced gout flare 0 Prophylactic treatment in acute Prophylactic treat
Slide 31: NEK7 MGD Drove Preferential Abdominal Fat Loss in Cyno Obesity Model
NEK7 MGD, Alone or in Combo with Semaglutide, Drove Preferential Abdominal Fat Loss While Sparing Lean Mass in a Cyno Obesity Model Cynomolgus monkey: NEK7 MGD promoted body Preferential decrease of fat mass Percent fat weight loss alone and with semaglutide over lean massc (relative to whole body)c
Slide 32: The Role of the NEK7/NLRP3 Pathway in ASCVD
The Role of the NEK7/NLRP3 Pathway in ASCVD
Slide 33: Pathogenic Role of NEK7/NLRP3 Pathway in Plaque Biology and Atherogenic Progression
The Multifaceted Pathogenic Role of the NEK7/NLRP3 Pathway in Plaque Biology and Atherogenic Progression DAMPs, crystals, metabolic factors Genetic (NLRP3 SNPs, CHIP mutations) NEK7/NLRP3 effectors IL-1β | IL-18 | DAMP release | Oxidative stress Endothelial Cell dysfunction Increased uptake of oxLDL
Slide 34: DAMPs, Including Calprotectin, Potently 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 Plaque burden Plaque inflammation Plaque instability Foam cell Neutrophil Calprotectin S100A9 S100A
Slide 35: MRT-8102 Potently Inhibits Pyroptosis and Release of DAMPs and IL-1β
MRT-8102 Potently Inhibits Pyroptosis and Release of DAMPs and IL-1β Anti-IL-1/IL-6 biologics Pyroptosis Pyroptosis - SYTOX Green IL-1β IL-1b 150 150 MRT-8102 cytokines Rilonacept SYTOX Green IL-1 100 100 Ziltivekimab % of Vehicle % of Vehicle NLRP3 IL-1/IL-6 IL-1β NEK7 IL-1 IL-6 blocking biologic
Slide 36: Clinical Experience Supports Upstream Targeting of NEK7/NLRP3 Pathway
Clinical Experience Supports Upstream Targeting of NEK7/NLRP3 Pathway as a Superior Approach to Impact MACE TET2 ChIP Thrombosis Metabolic Cholesterol Fibrinogen IL-1/IL18/ IL-6 Genetic DAMPs/ CRP Thrombogenic factors NLRP3 SNP LoDoCo2 COLCOT CANTOS ZEUS NEK7/NLRP3 pathway modulation IL-1β neutrali
Slide 37: NLRP3 Activating Variants Increase Signaling and Cardiovascular Risk
NLRP3 Activating Variants Increase Signaling and Cardiovascular Risk NLRP3 variant associated with strong risk of CVD; NLRP3 risk variant shows larger effect on inflammatory IL-6(R) benefit restricted to CHIP+ subgroup cytokines and CRP compared to IL-6(R) variant NLRP3 risk variants in all comers C
Slide 38: 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 Cumulative CV risk associated with are significantly increased in unstable plaques NEK7/NLRP3-relevant cytokines, lipids, and DAMPs NEK7/NLR
Slide 39: GFORCE-1 Clinical Study Results
GFORCE-1 Clinical Study Results As disclosed on October 1, 2026
Slide 40: GFORCE-1: A Phase 1 Study of MRT-8102 in Subjects with Elevated CVD Risk
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 w
Slide 41: 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 Study population MRT-8102 (5 mg) n ~ 27 • Obesity, elevated CRP >3 and <15 mg/L Primary endpoint Randomization • Safety and tolerability of 28 days MRT-8102 (20 mg) n ~ 27 dosing with 28 days follow u
Slide 42: MRT-8102 Achieved Robust and Sustained NEK7 Degradation
MRT-8102 Achieved Robust and Sustained NEK7 Degradation SAD MAD GFORCE-1 Robust and sustained degradation of NEK7 noted in peripheral blood T cells (~80 - 90%) 42 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)
Slide 43: GFORCE-1: Summary of Unblinded Safety Data
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%)
Slide 44: GFORCE-1 Population: Probing ASCVD Pathogenic Drivers in CVD Risk Subjects
GFORCE-1 Population: Probing ASCVD Pathogenic Drivers in CVD Risk Subjects 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 atheroscler
Slide 45: Key ASCVD Pathogenic Drivers and Markers of Systemic Inflammation Assessed in GFORCE-1
Key ASCVD Pathogenic Drivers and Markers of Systemic Inflammation Assessed in GFORCE-1 NEK7/NLRP3 pathway activation in plaque Cytokines and DAMPs IL-1, calprotectin, HMGB1, S100A12, SAA Localized effects Systemic effects Macrophage / EC / SMC Plaque destabilization / Plaque rupture & Acute phase r
Slide 46: MRT-8102 Reduced Plasma Calprotectin to Healthy Volunteer Levels
MRT-8102 Reduced Plasma Calprotectin to Healthy Volunteer Levels Calprotectin is elevated in subjects Treatment reduced Calprotectin to levels associated with elevated CVD risk with low risk of future CV events (week 4) -56%* 2000 40 Placebo (n=27) MRT-8102 (n=74) 800 Median Calprotectin (ng/mL) (%C
Slide 47: MRT-8102 Reduced Plasma S100A12 and Serum SAA to Healthy Volunteer Levels
MRT-8102 Reduced Plasma S100A12 and Serum SAA to Healthy Volunteer Levels MRT-8102 reduces S100A12 to levels in HVs MRT-8102 reduces SAA to levels in HVs -51%* -46%* 200 20 80 12 150 60 Median S100A12 (ng/mL) 100 40 10 Median SAA (mg/L) S100A12 (ng/mL) 60 15 30 8 SAA (mg/L) 40 10 20 6 4 20 5 10 2 0
Slide 48: Pathological Crosstalk between HMGB1 and IL-1β Downstream of NEK7/NLRP3
Pathological Crosstalk between HMGB1 and IL-1β Downstream of NEK7/NLRP3 Reinforces Plaque Progression and Instability in ASCVD Biological crosstalk between HMGB1 and IL-1β influences HMGB1 and IL-1β baseline levels strongly correlate, multiple aspects of vessel and plaque biology reinforcing biologi
Slide 49: MRT-8102 Treatment Reduced HMGB1 and IL-1β Levels
MRT-8102 Treatment Reduced HMGB1 and IL-1β Levels MRT-8102 treatment resulted in meaningful HMGB1 MRT-8102 treatment resulted in meaningful IL-1β reduction in subjects with higher baseline levels reduction in subjects with higher baseline levels > 4.7 (ng/mL) > 170 (fg/mL) 40 1000 1000 30 900 900 20
Slide 50: MRT-8102 Treatment Led to Reductions in Fibrinogen
MRT-8102 Treatment Led to Reductions in Fibrinogen Fibrinogen baseline is elevated Treatment significantly reduced fibrinogen to normal physiological levels in GFORCE-1 population -28%* 800 20 Placebo (n=27) MRT-8102 (n=74) 500 Median Fibrinogen (mg/dL) (%Change from Predose) 10 400 Fibrinogen (mg/d
Slide 51: MRT-8102 Induced 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 hsCRP and IL-6 reduced to levels associated after 4 weeks of dosing with low risk of future CV events 40 Placebo (n=27) 20mg QD (n=26) 10 -85%* 8 -54%* 5mg QD (n=27) 40mg QD (n=21) (%Change From Predose
Slide 52: NLRP3 Risk Alleles Correlate to Baseline Increase of ASCVD Drivers
NLRP3 Risk Alleles Correlate to Baseline Increase of ASCVD Drivers Elevated levels in NLRP3 risk allele carriers • Two high-priority NLRP3 risk SNPs, rs10754555 and rs10754558, have been linked to increased NLRP3 pathway activation S100A12 +66 and cardiovascular risk. HMGB1 +54 • In line with publis
Slide 53: MRT-8102 for Coronary Artery Disease
MRT-8102 for Coronary Artery Disease
Slide 54: CAD: Large Opportunity to Address Atherosclerotic Risk with a Safe, Oral Treatment Targeting NEK7
CAD: Large Opportunity to Address Atherosclerotic Risk with a Safe, Oral Treatment Targeting NEK7 CAD Market High Unmet Medical Need in CAD MRT-8102 Opportunity Overview Potential to complement existing lipid and metabolic therapies >30% ‣ Targeting NEK7/NLRP3 pathway could CAD patients suffer from
Slide 55: A Phase 2b Study in Patients with Coronary Artery Disease
: A Phase 2b Study in Patients with Coronary Artery Disease MRT-8102 5 mg daily Population MRT-8102 10 mg daily ~160 patients with stable coronary R artery disease and residual MRT-8102 15 mg daily inflammation Placebo Enrollment 6-month treatment Outcome measures Exploratory endpoints • Change in l
Slide 56: MRT-8102 for Treatment and Prevention of Gout Flares
MRT-8102 for Treatment and Prevention of Gout Flares
Slide 57: MRT-8102 Has Potential to Resolve and Prevent Gout Flares
MRT-8102 Has Potential to Resolve and Prevent Gout Flares MSU-driven activation Resolution of inflammation MRT-8102 reduces MSU-induced inflammasome of NLRP3/NEK7 pathway and gout tophi via NEK7 MGD activation and gout flare in a preclinical model - NEK7 MGD + NEK7 MGD In vitro MSU stim 150 MRT-8102
Slide 58: Short-term Increase in Gout Flares Following ULT Treatment Driven by NEK7/NLRP3-IL-1 Axis
Short-term Increase in Gout Flares Following ULT Treatment is Largely Driven by the NEK7/NLRP3-IL-1 Axis Urate lowering therapies can trigger Prophylaxis with canakinumab treatment prevents the short-term a short-term increase in gout flares increase in gout flares following Pegloticase treatment C
Slide 59: Gout: Large Market With High Unmet Need For New Prophylactic Therapies
Gout: Large Market With High Unmet Need For New Prophylactic Therapies Gout Market Significant unmet medical need in gout Overview MRT-8102 Opportunity >55% Gout-treating physicians surveyed are not satisfied Strong efficacy potential for flare with current prophylaxis options management and long-te
Slide 60: A Phase 2 Study in Gout Flare Prevention Following Acute Flare Management
A Phase 2 Study in Gout Flare Prevention Following Acute Flare Management WHY MRT-8102 FOR GOUT GEMINI-1 STUDY • Gout is a canonical NEK7/NLRP3 pathway Population Goals MRT-8102 DL1 disease: MSU crystals trigger • Dose exploration NEK7-mediated NLRP3 • ~ 60 pts • Safety and efficacy complex assembly
Slide 61: MRT-8102 for Hidradenitis Suppurativa
MRT-8102 for Hidradenitis Suppurativa
Slide 62: MRT-8102 Significantly Suppresses NLRP3 Activity in Ex Vivo HS Lesions
MRT-8102 Significantly Suppresses NLRP3 Activity in Ex Vivo HS Lesions NLRP3:NLRP1 ratio increases MRT-8102 suppresses NLRP3 activity in NLRP3 score highest in HS lesions during disease progression human HS lesions NLRP3* 14x 4x NLRP3 activity correlates with Hidradenitis Suppurativa ASCVD 250 80 di
Slide 63: HS: Significant Unmet Need for New Oral Therapies
HS: Significant Unmet Need for New Oral Therapies HS Market Large unmet medical need in HS Overview MRT-8102 Opportunity 55% Potential for robust clinical activity in Of HS patients are not well-managed with SOC, both biologic-naïve and refractory patients even with anti-TNF and anti-IL-17 biologic
Slide 64: A Phase 2 Randomized Study in Moderate to Severe Hidradenitis Suppurativa
A Phase 2 Randomized Study in Moderate to Severe Hidradenitis Suppurativa WHY MRT-8102 FOR HS GALAXY-1 STUDY • HS ranks highest in NEK7/NLRP3 pathway score of MRT-8102 DL1 any indication we studied, Population with consistent upregulation Goals of NLRP3, IL-1β, and DAMPs • Dose exploration in lesion
Slide 65: Oncology Pipeline
Mp. Monte Rosa Therapeutics Oncology Pipeline
Slide 66: Degrading Undruggable and Difficult-to-Drug Oncology Targets
Degrading Undruggable and Difficult-to-Drug Oncology Targets Therapy-resistant mCRPC is characterized by increased CCNE1 and CDK2 are highly validated targets for solid MYC, E2F, AR and other oncogenic pathway activity tumors that drive multiple hallmark cancer mechanisms M G1 eIF4E, Cyclin D1, AR A
Slide 67: GSPT1 Program (MRT-2359)
Mp. Monte Rosa Therapeutics GSPT1 Program (MRT-2359)
Slide 68: MRT-2359 At a Glance
MRT-2359 At a Glance First-in-class oral GSPT1 MGD for AR-mutant metastatic castration-resistant prostate cancer (mCRPC) GSPT1 Rationale Opportunity • GSPT1 degradation exploits a • Focused entry into a defined, synthetic-lethal vulnerability in high-unmet-need AR-mutant mCRPC MYC/AR-driven tumors b
Slide 69: Potential to Address Key Unmet Need for mCRPC Patients With AR Mutations
Potential to Address Key Unmet Need for mCRPC Patients With AR Mutations mCRPC Market Unmet Need of mCRPC AR-mutant Population Overview MRT-2359 Opportunity in • AR mutations in mCRPC patients have been reported to Poor prognosis, have significantly shorter overall survival AR Mutant mCRPC easy to i
Slide 70: Clinical Data Summary
Clinical Data Summary • MRT-2359 in combination with enzalutamide achieved compelling clinical activity in a subset of heavily pre-treated metastatic castration resistant prostate cancer (mCRPC) patients with androgen receptor (AR) mutations. • Of the 5 patients with AR mutations: • 5 patients showe
Slide 71: MRT-2359 Phase 1/2 Clinical Study Design
MRT-2359 Phase 1/2 Clinical Study Design Phase 1: Dose Escalation Phase 2: Expansion Cohort Combination of MRT-2359 with enzalutamide in Monotherapy of MRT-2359 in lung cancer, high-grade neuroendocrine heavily-pretreated metastatic castration tumors and solid tumors with N-/L-MYC amplification resi
Slide 72: Patient Demographics, Clinical Characteristics and Prior Therapies
Patient Demographics, Clinical Characteristics and Prior Therapies: MRT-2359 Compared to Mevrometostat Phase I Trial MRT-2359 + Enzalutamide Mevrometostat + Enzalutamide Patient Characteristics Total (N=23) Phase I total (N=47)1 Age, median (range), years 71 (54-83) 70 (53 – 87) Race, N (%) White 14
Slide 73: Combination of MRT-2359 and Enzalutamide was Well Tolerated
Combination of MRT-2359 and Enzalutamide was Well Tolerated and May be Favorable over EZH2 Inhibitors Treatment-Related AEs Occurring in >20% Patients MRT-2359 0.5mg and Enzalutamide MRT-2359 0.75mg and Enzalutamide Total Dose Level 160mg 160mg N=23 N=17 N=6 CTC AE V5 Grade G1 (%) G2 (%) G3 (%) G4 (
Slide 74: MRT-2359 and Enzalutamide Achieved High PSA Response Rate in AR Mutant mCRPC
MRT-2359 and Enzalutamide Achieved High PSA Response Rate in AR Mutant mCRPC 100 50 • MRT-2359 + enzalutamide achieved 100% Best % PSA change PSA response rate; PSA response in 5 of 5 heavily pretreated patients with AR 0 mutations -50 • PSA50 (n=3) • PSA90 (n=2) -100 • PSA response rate in overall
Slide 75: MRT-2359 plus Enzalutamide Achieved Tumor Regressions in AR Mutant mCRPC
MRT-2359 plus Enzalutamide Achieved Tumor Regressions in AR Mutant mCRPC 80 MUT 60 Best % change in RECIST1.1 MUT 40 MUT MUT 20 MUT WT 0 V7 -20 V7 V7 -40 V7 -60 V7 WT -80 V7 AR status WT WT V7 V7 V7 V7 V7 WT V7 Mut V7 Mut Mut Mut Mut V7 RECIST PD PD SD PD SD SD PD SD PD SD SD SD SD PR PR Response WT
Slide 76: Compelling Activity in Heavily Pretreated Patients with AR Mutations
Compelling Activity in Heavily Pretreated Patients with AR Mutations Best % change in PSA Best % change in RECIST Best % change in ctDNA Best % change in CTC counts 0 0 0 0 N/A * Best % change in mutant ctDNA ** Best % change in CTC counts Best % change in RECIST 1.1 -20 -20 -20 -20 Best % change in
Slide 77: MODeFIRe-1 MRT-2359 Phase 2 Study in CRPC
MODeFIRe-1 MRT-2359 Phase 2 Study in CRPC (up to 25 pts) Study Population Treatment • Enrollment completion ~12 months Simon’s 2-Stage Design MRT-2359 0.5mg (21/7) + after initiation (up to 25 pts) 2nd gen AR inhibitor apalutamide mCRPC with AR mutations • Endpoints include PSA response, PSA +/- REC
Slide 78: CCNE1 Program
Therapeutics Mp. Monte Rosa CCNE1 Program
Slide 79: CCNE1 (Cyclin E1) is a Target for Solid Tumors with Deregulated Cyclin E1
CCNE1 (Cyclin E1) is a Target for Solid Tumors with Deregulated Cyclin E1 Cyclin E drives multiple hallmark cancer mechanisms M Therapeutic hypothesis: CDT1 G1 MCMs G2 • CCNE1 (Cyclin E1) is a well-recognized human oncogene that drives multiple hallmarks of cancer, and has been G0 – S progression S
Slide 80: Potent and Highly Selective CCNE1-directed MGDs
Potent and Highly Selective CCNE1-directed MGDs MRT-55811 induced tumor regression in CCNE1 amplified ovarian model • MRT-55811 is a potent and highly selective CCNE1 molecular glue degrader that drives robust G1/S cell-cycle arrest in CCNE1-amplified Ovarian cancer cells. 1000 • CCNE1 degradation l
Slide 81: CDK2 Program
Therapeutics Mp. Monte Rosa CDK2 Program
Slide 82: CDK2 is a Key Driver of Cell Cycle Progression in Cancer
CDK2 is a Key Driver of Cell Cycle Progression in Cancer CDK2: a key cell cycle regulator Therapeutic hypothesis: • CDK2 is a key driver of cancers with cyclin dependent kinase pathway alterations • MGDs will achieve greater selectivity against other CDKs and kinases in general, as well as more sust
Slide 83: Differentiated CDK2 Selectivity Supports Combination Strategies
Differentiated CDK2 Selectivity Supports Combination Strategies MRT-51443 triple combination substantially reduced tumor growth vs. ribo + fulv in MCF7 model • MRT-51443 selectively degrades CDK2, leading to G1 arrest and inhibition of proliferation in CDK2-dependent cancer cells 50 • CDK2 degradati
Slide 84: Team
Therapeutics Mp. Monte Rosa
Slide 85: World-Class Leadership
World-Class Leadership Deep expertise in molecular glue discovery, drug development and precision medicine Markus Warmuth, M.D. Sharon Townson, Ph.D. John Castle, Ph.D. Magnus Walter, DPhil Chief Executive Officer Chief Scientific Officer Chief Data and Information Chief Technology Officer Officer F
Slide 86: Thank you
Thank you Mp. Monte Rosa Therapeutics
Monte Rosa Therapeutics — Investor Presentation (October 2026) on 6ix