Slide 1: MRT-2359 Phase 1/2 Clinical Data Update
Degrading Proteins, Making Medicines MRT-2359 Phase 1/2 Clinical Data Update December 16, 2025 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: 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 4 patients with AR mutations: 4 patients showed a PSA response, including
Slide 4: Therapeutic Rationale in mCRPC
Therapeutic Rationale in mCRPC
Slide 5: MRT-2359 Exploits Key Therapeutic Vulnerabilities in Therapy-Resistant CRPC
mRNA eIF4E eIF4E complex Initiation Termination GSPT1 STOP eRF1 Ribosome with growing peptide chain eIF4E Ribosome stalling, translation reduction MRT-2359 eRF1 eRF1 Therapy-resistant mCRPC is characterized by increased MYC, E2F, AR and other oncogenic pathways activity MRT-2359 + enzalutamide suppr
Slide 6: Pharmacogenomic Profiling Identified AR/MYC-positive Prostate Cell Lines as Sensitive to MRT-2359
Pharmacogenomic Profiling Identified AR/MYC-positive Prostate Cancer Cell Lines as Exquisitely Sensitive to MRT-2359 Unbiased pharmacogenomic analysis identified prostate lineage as highly sensitive to MRT-2359 Selective sensitivity noted in MYC/AR+ lines; minimal sensitivity in AR negative lines AR
Slide 7: Proteomics Analysis Revealed Modulation of AR and MYC/E2F Pathway by MRT-2359
Proteomics Analysis Revealed Modulation of AR and MYC/E2F Pathway by MRT-2359 VCaP model (AR-V7 low) 22RV1 model (AR-V7 high) log2FC (MRT-2359) log2FC (enzalutamide) log2FC (MRT-2359) log2FC (enzalutamide) AR-independent proteins AR pathway-relevant proteins CRPC-relevant oncoproteins MRT-2359 treat
Slide 8: MRT-2359 in Combination with Enzalutamide or Pluvicto Increased Activity in Xenograft Models
MRT-2359 in Combination with Enzalutamide or Pluvicto Demonstrated Increased Activity Over Monotherapies In Xenograft Models LNCaP AR Mutant (Mut), AR-V7 negative VCAP AR amplified, AR-V7 low MRT-2359 + enzalutamide drove tumor regressions in CDX models of CRPC with various AR alterations including
Slide 9: MRT-2359 Clinical Data Update
MRT-2359 Clinical Data Update
Slide 10: MRT-2359 Phase 1/2 Clinical Study Design
0.5mg 5/9 Phase 2: Expansion Cohort Phase 1: Dose Escalation 1.5mg 5/9 1mg 5/9 MRT-2359 Phase 1/2 Clinical Study Design Monotherapy of MRT-2359 in lung cancer, high-grade neuroendocrine tumors and solid tumors with N-/L-MYC amplification 2mg 5/9 | 5/9 = 5 days on drug, 9 days off drug | 21/7 = 21 da
Slide 11: Biomarker Profiling of Tumor and Liquid Biopsies
Biomarker Profiling of Tumor and Liquid Biopsies Identify key AR alterations in tumor biopsies, ctDNA, and CTCs, including AR mutations and AR-V7 transcripts Verify non-neuroendocrine histology through RNAseq Tissue biopsy L702H T877A/S H875Y AR mutations Tumor tissue CTCs ctDNA Liquid biopsy Sequen
Slide 12: Patient Demographics, Clinical Characteristics and Prior Therapies
Patient Demographics, Clinical Characteristics and Prior Therapies: MRT-2359 Compared to Mevrometostat Phase I Trial Patient Characteristics MRT-2359 + Enzalutamide Total (N=20) Mevrometostat + Enzalutamide Phase I total (N=47)1 Age, median (range), years 72 (54-83) 70 (53 – 87) Race, N (%) White 12
Slide 13: 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 Dose Level MRT-2359 0.5 mg and Enzalutamide 160 mg N=14 MRT-2359 0.75 mg and Enzalutamide 160 mg N=6 Total N=20 CTC AE V5 Grade G1 (%) G2 (%) G3 (%) G4 (%) G1 (%) G2 (%) G3 (%) G4 (%) All grades Fat
Slide 14: 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 AR status V7 V7 V7 WT WT V7 V7 WT V7 V7 Mut Mut* Mut Mut RECIST Response PD PD SD PD SD SD SD PD SD PD SD SD PR PR RECIST % 0 -13 0 +29 -9 +12 -2 +67 -16 -7 -20 0 -62 -61 abi + - + - + + + - + - + + + + 2nd gen ARi + + + +
Slide 15: MRT-2359 plus Enzalutamide Achieved Tumor Regressions in AR Mutant mCRPC
MRT-2359 plus Enzalutamide Achieved Tumor Regressions in AR Mutant mCRPC Best % change in RECIST in patients spanning AR alterations Durable disease control noted in mutant and ARi naïve patients AR status WT WT V7 V7 V7 Mut V7 V7 WT V7 V7 Mut Mut Mut RECIST Response PD PD SD PD SD SD SD PD SD PD SD
Slide 16: Compelling Activity in Heavily Pretreated Patients with AR Mutations
Compelling Activity in Heavily Pretreated Patients with AR Mutations Best % change in ctDNA Best % change in RECIST Best % change in CTC counts Best % change in PSA Response SD SD* PR PR RECIST % -20 0 -62 -61 Abiraterone + + + + 2nd gen ARi + - - + Docetaxel + + + + Pluvicto - + + + N/A N/D 0 -20 -
Slide 17: Analysis of Tumor Biopsies Supports MRT-2359 Mode of Action
Analysis of Tumor Biopsies Supports MRT-2359 Mode of Action – Correlation of Activity with and Modulation of MYC, E2F and AR Pathway Unbiased Post-Hoc Analysis of RNAseq from tumor biopsies identified MYC, E2F and AR Activity as key predictors of tumor shrinkage* Treatment reduced multiple key pathw
Slide 18: Confirmed PR and PSA90 Response in mCRPC with Activating AR Mutation
Confirmed PR and PSA90 Response in mCRPC with Activating AR Mutation Baseline After 2 cycles After 4 cycles Treatment cycle -46% -57% -56% -56% -62% AR H875Y VAF 33% <LoQ <LoQ 1% 6% 26% Months on treatment PSA (ng/mL) % change in sum of target lesions Data cut-off December 03, 2025
Slide 19: Confirmed SD and PSA50 in mCRPC Patient with Activating AR Mutation
Confirmed SD and PSA50 in mCRPC patient with Activating AR Mutation AR L702H VAF 11.7% <LoQ <LoQ 6.3% 2.4% Baseline After 4 cycles -13% -16% -20% -18% -18% Data cut-off December 03, 2025 Months on treatment PSA (ng/mL) % change in sum of target lesions
Slide 20: Next Steps
Next Steps
Slide 21: MODeFIRe-1 Phase 2 Study of MRT-2359 in CRPC
MODeFIRe-1* Phase 2 MRT-2359 Phase 2 Study in CRPC (up to 25 pts) * MODeFIRe-1 Trial: Molecular Degrader For Inhibitor Resistance Enrollment Simon’s 2-Stage Design (up to 25 pts) mCRPC with AR mutations PSA +/- RECIST measurable Treatment MRT-2359 0.5mg (21/7) + 2nd gen ARi (apa, daro, or enza) 28-d
Slide 22: Summary
Summary
Slide 23: Summary
MRT-2359 in combination with enzalutamide achieved compelling clinical activity (100% PSA response) in a subset of heavily pre-treated metastatic castration resistant prostate cancer (mCRPC) patients with androgen receptor (AR) mutations. Overall disease control rate (DCR) of 64% in a total of 14 ev
Slide 24: Monte Rosa Pipeline and Upcoming Milestones
Monte Rosa Pipeline and Upcoming Milestones GSPT1 Castration-resistant Prostate Cancer IL-1β/NLRP3-driven Inflammatory Diseases VAV1 Licensed to Novartis* Immune-mediated Diseases Discovery Target Indication(s) Phase 2 initiation in 2026 Next Anticipated Milestone IND-Enabling Clinical Phase 1 inter
Slide 25: Q&A
Q&A
Slide 26: Thank you
Thank you Mp. Monte Rosa Therapeutics