Monte Rosa Therapeutics, Inc. · NASDAQ:GLUE
Monte Rosa Therapeutics — FY2024 Earnings Presentation
48 slides from Monte Rosa Therapeutics's earnings presentation, Mar 20, 2025
Slide 1: Q4 and Full Year 2024 Earnings Call and Pipeline Update
Q4 and Full Year 2024 Earnings Call and Pipeline Update Proteome Editing Through Molecular Glue Degraders Innovating Beyond New Heights | March 2025
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: Today's Update
Today’s Update 1. MRT-6160: Results from Phase 1 HV trial support clear path into Immunology & Inflammation broad Phase 2 development 2. NEK7: Progress towards IND filing, clinical development plan 3. QuEEN : Building future “only-in-class” I&I opportunities 4. MRT-2359: Encouraging activity support
Slide 4: VAV1 Program (MRT-6160)
Mp. Monte Rosa Therapeutics VAV1 Program (MRT-6160)
Slide 5: VAV1 is a Key Regulator of T- and B-cell Activity
VAV1 is a Key Regulator of T- and B-cell Activity …plays a critical role across multiple VAV1 signaling is associated with several T and B cell immunologic clinically validated pathways in immune- outcomes and… mediated disease T cell B cell TCR BCR Cytokine CD69 CD69 receptor TYK2 BTK VAV1 VAV1 JAK
Slide 6: Strategic Agreement to Accelerate and Broaden MRT-6160 Development
Strategic Agreement to Accelerate and Broaden MRT-6160 Development Basel Global license agreement with Novartis to advance VAV1-directed molecular glue Scope degraders including MRT-6160, in development for immune-mediated conditions (announced Oct. 2024) • $150M upfront payment • Eligible for up to
Slide 7: Safety, PK and PD Data from SAD and MAD Healthy Volunteers Phase 1 Trial
Safety, PK and PD Data from SAD and MAD Healthy Volunteers Phase 1 Trial of VAV1 MGD MRT-6160
Slide 8: 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 Study Endpoints SAD cohorts MAD cohorts One oral dose 7 daily oral doses Primary • Safety and tolerability SAD DL5 SAD DL4 Secondary & exploratory • Pharmacokinetics SAD DL3 MAD DL3 • Pharmac
Slide 9: MRT-6160 Displayed a Dose-Dependent Human Pharmacokinetic Profile
MRT-6160 Displayed a Dose-Dependent Human Pharmacokinetic Profile Plasma concentration vs time Pharmacokinetic data (AVE ± SEM) 1000 DL1 Dose T1/2 Cmax AUC0-24 Level (hr) (ng/mL) (hr*ng/mL) DL2 Plasma Concentration DL3 1 24.1± 2.6 18.3 ± 1.0 300.3 ± 16.4 100 DL4 2 26.8 ± 1.9 32.6 ± 2.2 527.0 ± 30.3
Slide 10: In Vitro Assay Validation of PD and Immune Cell Functional Testing
In Vitro Assay Validation of PD and Immune Cell Functional Testing Degradation assessment Ex vivo stimulation of whole blood to monitor T- & B-cell functions TCR BCR CTRL IL-17A IFN-γ T cell IL-2 IL-6 B cell T cell 37°C / Overnight TCR = T-cell receptor (α-CD3/α-CD28) BCR = B-cell receptor (α-IgD +
Slide 11: MRT-6160 Achieved Dose-Dependent VAV1 Degradation >90% in T Cells
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 DL3 20 DL4 DL5 (% Change from Predos
Slide 12: VAV1 Degradation Resulted in Significant 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 MRT-6160 treatment: 60 • Significantly attenuated CD69 upregulation 40 on T and B cells following TCR stimulation, reflecting functional inhibition (% Change from Pr
Slide 13: Sustained Suppression of TCR-mediated CD69 Activation
MRT-6160 Resulted in Sustained Suppression of TCR-mediated CD69 Activation following Single or Multiple Dose Administration SAD CD69 on T cells CD69 on B cells MAD CD69 on T cells CD69 on B cells Placebo Placebo Placebo Placebo 60 MRT-6160 MRT-6160 120 MRT-6160 MRT-6160 CD69 Activation in Peripheral
Slide 14: 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 15: 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 16: Conclusions
Conclusions • Pharmacodynamic and functional ex vivo studies suggest significant effects on cytokine production can be achieved following marked and sustained degradation of VAV1 • Demonstrated levels of VAV1 degradation consistent with levels of degradation required to induce efficacy in preclinica
Slide 17: NEK7 Programs (MRT-8102 and CNS optimized)
NEK7 Programs (MRT-8102 and CNS optimized)
Slide 18: NEK7 is a Key Regulator of NLRP3 Inflammasomes, IL-1 and IL-18
NEK7 is a Key Regulator of NLRP3 Inflammasomes, IL-1 and IL-18 NLRP3 NEK7 NEK7 enables NLRP3 assembly in a + kinase-independent manner Inactive Active Wheel-like pro-IL-1 Activated NLRP3 NEK7 NLRP3 oligormerization pro-IL-18 NLRP3 complex IL-1 IL-18 NEK7-deficient macrophages are severely impaired
Slide 19: Lowering of CRP Levels Anticipated as a Result of NEK7 Degradation
Lowering of CRP Levels Anticipated as a Result of NEK7 Degradation C-reactive protein (CRP) is an acute-phase protein downstream of NLRP3/NEK7 inflammasome NLRP3/NEK7 activation in chronic inflammation Canakinumab (anti-IL-1β) leads to reductions in CRP Ridker et al., 2012 • In addition, several NLR
Slide 20: IL-1/NLRP3 Signaling is a Clinically Validated Pathway for Inflammatory Diseases
IL-1/NLRP3 Signaling is a Clinically Validated Pathway for Inflammatory Diseases Cardio-immunology Rheumatology Neurology Neuroinflammation Recurrent pericarditis Gout Epilepsy Rilonacept (IL-1α/β) – approved for Canakinumab (IL-1β) – approved for Belnacasan (CASP1) – reduction in recurrent pericard
Slide 21: MRT-8102: Efficient Development Path in Peripheral Inflammatory Diseases
MRT-8102: Efficient Development Path in Peripheral Inflammatory Diseases Anticipated Studies Goal/Objective • Safety, tolerability, and pharmacokinetics in healthy volunteers Phase 1 HV • NEK7 degradation in blood after single and multiple daily doses • Changes in levels of inflammatory cytokines •
Slide 22: MRT-8102 Induced Durable Pharmacodynamic Modulation In Vivo
MRT-8102, a Potent and Highly Selective NEK7-directed MGD, Induced Durable Pharmacodynamic Modulation In Vivo MRT-8102 induces highly selective MRT-8102 exposure results in MRT-8102 potently degrades NEK7 NEK7 degradation prolonged PD effect 150 1000 MRT-8102 exposure 150 Plasma concentration (ng/ml
Slide 23: Preclinical GLP Tox Study Suggests Considerable Safety Margin
Preclinical GLP Tox Study Suggests Considerable Safety Margin In vivo NEK7 degradation leads to inhibition of Caspase-1 Toxicology summary in rats and cynos (28d GLP tox) activity and IL-1β release in ex vivo stimulation assay percent relative to predose 150 in vivo dosing Average Casp-1 activity, (
Slide 24: MRT-8102 Reduced MSU Crystal-driven Effects in Rabbit Gout Model
MRT-8102 Reduced MSU Crystal-driven Effects in Rabbit Gout Model Joint swelling MSKUS pathologic findings Histopathology score 20 8 8 Histopathology score Joint Swelling (mm) pathologic findings Number of MSKUS 15 6 6 10 4 4 *** *** 5 2 2 *** *** 0 0 0 -1 6h 8h 0h 2h D1 D2 D3 D4 D5 6 e e kg e D kg e
Slide 25: CNS-Optimized NEK7 Program
CNS-Optimized NEK7 Program
Slide 26: CNS-Optimized NEK7 MGD Demonstrated Profound NEK7 Degradation in Cynomolgus Monkey
CNS-Optimized NEK7 MGD Demonstrated Profound NEK7 Degradation and Pathway Inhibition In Vivo Over Several Days in Cynomolgus Monkey NEK7 in cyno PBMC NEK7 in cyno CSF IL-1β post-ex vivo stimulation 150 150 150 in vivo dosing in vivo dosing in vivo dosing percent relative to predose percent relative
Slide 27: Building Future Opportunities in I&I
Building Future Opportunities in I&I
Slide 28: MGD Strengths Align with I&I Requirements
MGD Strengths Align with I&I Requirements High degradation in immune and blood cells Catalytic MOA drives sustained PD effect T cell MRT-8102 Plasma concentration (ng/ml) 1000 150 B cell exposure relative to predose (%) Macrophage Bladder 100 MGD catalytic action NEK7/β-actin 100 Brain CRBN is expre
Slide 29: Degrading Undruggable Targets in Critical I&I Disease Pathways
Degrading Undruggable Targets in Critical I&I Disease Pathways Inflammatory & auto-inflammatory Neutrophil NK cell Apoptotic cell pDC Neutrophil Immune Monocyte ADAPTIVE B-cell complex Type I IFN modulation INNATE mDC Autoantibodies Immune Oral IL-1 drugs Complement “FcRn in a Pill” complex T cell B
Slide 30: Today's Update
Today’s Update 1. MRT-6160: Results from Phase 1 HV trial support clear path into Immunology & Inflammation broad Phase 2 development 2. NEK7: Progress towards IND filing, clinical development plan 3. QuEEN : Building future “only-in-class” I&I opportunities 4. MRT-2359: Encouraging activity support
Slide 31: GSPT1 program (MRT-2359)
Mp. Monte Rosa Therapeutics GSPT1 program (MRT-2359)
Slide 32: Targeting MYC-driven Tumors Through GSPT1 Degradation
Targeting MYC-driven Tumors and Their Addiction to Protein Translation Through GSPT1 Degradation 1 Genes involved in protein synthesis Addiction e.g., eIF4E, 4EBP1 and 4EBP2 MYC To sustain growth, MYC-driven tumors are addicted to protein translation DNA P 1 4EBP1 P P P 2 Dependency mTOR 4EBP1 Prote
Slide 33: MYC-Driven Pathologies Explored in MRT-2359 Phase 1/2 trial
MYC-Driven Pathologies Explored in MRT-2359 Phase 1/2 trial N-MYC SCLC N-MYC High L/N-MYC high Neuroendocrine tumors and/or Heme NSCLC L-/N-MYC amplified L-MYC High N-MYC high tumors SCLC/NE transformation L-MYC Neuroendocrine lung cancer Indication Size c-MYC High Prostate cancer Breast cancer AR p
Slide 34: MRT-2359-001 Phase 1/2 Clinical Study Design
MRT-2359-001 Phase 1/2 Clinical Study Design Phase 1: Dose Escalation Phase 2: Possible Expansion Lung cancer, high-grade neuroendocrine tumors Cohorts and solid tumors with N-/L-MYC amplification NSCLC* 2mg 5/9 SCLC** 1.5mg 5/9 RP2D N-MYC/L-MYC amplified tumors 1mg 5/9 0.75mg 21/7 HR+/Her2- Breast
Slide 35: Patient Demographics and Clinical Characteristics in Dose Escalation
Patient Demographics and Clinical Characteristics in Dose Escalation Patient Characteristic Total (N=59)* Age, median (range), years 63 (30-80) Female, N (%) 30 (51) Race, N (%) White 48 (81) Black 4 (7) Asian 3 (5) Other 4 (7) ECOG performance status, N (%) 0 or 1 58 (98) 2 1 (2) Cancer type, N (%)
Slide 36: MRT-2359 Treatment-Related AEs in > 10% patients
MRT-2359 Treatment-Related AEs in > 10% patients (N=59) Dose Level 0.5 mg 5/9 (N=9) 1 mg 5/9 (N=13) 1.5 mg 5/9 (N=5) 2 mg 5/9 (N=5) 0.5 mg 21/7 (N=18) 0.75 mg 21/7 (N=9) CTC AE V5 Grade G1-2 G3 (%) G4 (%) G1-2 G3 (%) G4 (%) G1-2 G3 (%) G4 (%) G1-2 G3 (%) G4 (%) G1-2 G3 (%) G4 (%) G1-2 G3 (%) G4 (%)
Slide 37: Biomarker Status and PD modulation in L-/N-MYC Amplified Tumors
Biomarker Status and PD modulation in L-/N-MYC Amplified Tumors, NSCLC, SCLC and High-Grade NE Tumors 100 GSPT1 (% of pre-dose) Biomarker negative (N=12) Biomarker positive (N=5) 50 0 Screening C1D19 Mean +/- SEM • L-MYC and N-MYC expression in tumor tissue obtained at • Paired, tumor containing bio
Slide 38: Summary of Activity in SCLC, NSCLC, NE Tumors and MYC Amplified Tumors
Summary of Activity in SCLC, NSCLC, high-grade Neuroendocrine Tumors and L- and N-MYC Amplified tumors • L-MYC and N-MYC expression in tumor tissue obtained at baseline or known L-MYC or N-MYC amplification in the absence of tissue was available in 48 patients and 37 were evaluable for response asse
Slide 39: Current Data for MRT-2359 and Enzalutamide in CRPC
Current Data for MRT-2359 and Enzalutamide in Castrate-Resistant Prostate Cancer • As of 10 March 2025, RECIST 1.1 is available for 3 patients showing: • 1 PR (confirmed, -57%; heavily pretreated CRPC with AR LBD mutation H875Y) • 2 SDs (both CRPC with AR-V7 transcripts, multiple prior treatments in
Slide 40: Confirmed PR in Refractory CRPC with AR H875Y Mutation
Confirmed PR in Refractory CRPC with AR H875Y Mutation Patient continues on study (C5) Baseline After 2 cycles After 4 cycles -46% -57% 40
Slide 41: Summary
Summary • Encouraging early data in CRPC: 1 PR and 2 SD in first 3 evaluable, heavily pretreated patients with either AR mutations or AR-V7 expression • Opportunity to enroll 20 - 30 patients if positive efficacy signal continues to be observed • Large, high unmet need indication not requiring bioma
Slide 42: CCNE1 (Cyclin E1) and CDK2 Programs
CCNE1 (Cyclin E1) and CDK2 Programs
Slide 43: CCNE1 and CDK2 are Critical Drivers of Cancer Cell Cycle
CCNE1 and CDK2 are Critical Drivers of Cancer Cell Cycle Cyclin E1 and CDK2 drive multiple hallmark cancer mechanisms • CCNE1 and CDK2 are key drivers of cancers with cyclin dependent kinase CDT1 MCMs pathway alterations • CCNE1 not druggable by G0 – S progression conventional modalities • CCNE1 and
Slide 44: MRT-50969 Inhibits Tumor Growth in CCNE1 Amplified Gastric and Breast Cancer Models
MRT-50969 Inhibits Tumor Growth in CCNE1 Amplified Gastric and Breast Cancer Models In Vivo MRT-50969 inhibits tumor growth MRT-50969 inhibits tumor growth in CCNE1 amplified gastric cancer model in CCNE1 amplified breast cancer model Tumor Volume (mm3) 1500 1200 Tumor volume (mm3) Mean +/- SEM 1000
Slide 45: CDK2 MGD Demonstrates Activity in Combination with CDK4/6 Inhibitor and Fulvestrant
CDK2 MGD Demonstrates Activity in Combination with CDK4/6 Inhibitor and Fulvestrant in ER+ Breast Cancer Model MRT-51443 induces robust tumor regression in combination MRT-51443 triple combination substantially with CDK4/6 inhibition and fulvestrant reduces tumor growth vs. ribo + fulv Vehicle MRT-5
Slide 46: Summary and Concluding Remarks
Summary and Concluding Remarks
Slide 47: Monte Rosa Pipeline and Upcoming Milestones
Monte Rosa Pipeline and Upcoming Milestones Next Target Compound Indication(s) Discovery IND-Enabling Clinical Anticipated Ownership Milestone Immunology & Inflammation Immune-mediated * VAV1 MRT-6160 Phase 2 initiation Diseases IND submission MRT-8102 IL-1β/NLRP3-driven in H1 2025 NEK7 Inflammatory
Slide 48: Monte Rosa Therapeutics
Mp. Monte Rosa Therapeutics
Monte Rosa Therapeutics — FY2024 Earnings Presentation on 6ix