Monte Rosa Therapeutics, Inc. · NASDAQ:GLUE
Monte Rosa Therapeutics — Corporate Update (October 2023)
22 slides from Monte Rosa Therapeutics's corporate update, Oct 17, 2023
Slide 1: From Serendipity to Rational Design: Taking Molecular Glue Degraders to New Heights
From Serendipity to Rational Design Taking Molecular Glue Degraders to New Heights | October 2023
Slide 2: Forward-Looking Statements
Forward-Looking Statements These materials include 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 i
Slide 3: Monte Rosa Therapeutics – Call Highlights
Monte Rosa Therapeutics – Call Highlights Updated cash runway into Q3 2025 Interim analysis of data from our Phase I dose escalation study of MRT-2359, providing evidence of optimal PD modulation, clinical activity and a favorable tolerability profile Partnership with Roche to develop MGDs for oncol
Slide 4: Monte Rosa Therapeutics – Roche Partnership
Monte Rosa Therapeutics – Roche Partnership
Slide 5: Monte Rosa Tx – Roche Partnership: Summary
Monte Rosa Tx – Roche Partnership: Summary Discovery partnership on targets in oncology and neurological disease Leverages synergies between Monte Rosa Tx – a leading molecular glue degrader company – and Roche – a leading global health care company Monte Rosa Tx performs preclinical drug discovery
Slide 6: GSPT1 Program – Phase I Interim Update
GSPT1 Program – Phase I Interim Update
Slide 7: Targeting MYC-driven Tumors and Their Addiction to Protein Translation
Targeting MYC-driven Tumors and Their Addiction to Protein Translation Addiction To sustain growth, MYC-driven tumors are addicted to protein translation Dependency Therapeutic vulnerability 1 2 3 This addiction creates a dependency on the translation termination factor GSPT1 GSPT1 is a therapeutic
Slide 8: MRT-2359 is a Potent and Selective GSPT1 Degrader
MRT-2359 is a Potent and Selective GSPT1 Degrader in vitro data CRBN binding, Ki 113 nM Ternary complex, EC50 < 7 nM Degradation, DC50 (in disease relevant cell lines) 1 - 20 nM MRT-2359 induced selective GSPT1 degradation and showed favorable ADME/DMPK profile MRT-2359 is a potent GSPT1 degrader AD
Slide 9: Activity of MRT-2359 in NSCLC, SCLC and Lung NE Patient-derived Xenograft Models
Activity of MRT-2359 in NSCLC, SCLC and Lung NE Patient-derived Xenograft Models Collection of PDX models 9 SCLC Adeno NSCLC NE-LC biomarker negative biomarker positive Targeted mass spectrometry in 7 representative models PD modulation 100 50 0 -50 -100 N-Myc (qPCR) Best % TV change 100 50 0 -50 -1
Slide 10: MRT-2359-001 Phase 1/2 – Phase 1 Interim Update
Dose level 1 Phase 1: Dose Escalation Backfill slots for additional patients for each dose level Backfill Dose level 2 Dose level 3 Dose level X Backfill Backfill Lung cancer (NSCLC & SCLC), DLBCL, high-grade neuroendocrine tumors, and N-/L-MYC amplified solid tumors MRT-2359-001 Phase 1/2 – Phase 1
Slide 11: Executive Summary
Executive Summary As of September 7th, 2023, 3 dose levels (0.5 mg, 1 mg, 2 mg) have been completed with 21 patients enrolled (including backfill patients) Observed dose dependent PK after oral dosing Clinical data support that 0.5 mg starting dose was fully active based on pharmacodynamic (PD) asse
Slide 12: MRT-2359 displayed dose dependent plasma exposure
MRT-2359 displayed dose dependent plasma exposure Summary of Pharmacokinetics and Pharmacodynamics MRT-2359 displayed deep GSPT1 degradation in PBMCs at all dose levels GSPT1 expression assessed using targeted mass spectrometry PD modulation in PBMCs observed across all dose levels; level of degrada
Slide 13: GSPT1 Degradation by Targeted Mass Spectrometry in Tissue Biopsies
GSPT1 Degradation by Targeted Mass Spectrometry in Tissue Biopsies MRT-2359 reduced GSPT1 expression in human tissue biopsies GSPT1 degradation assessed from pre-treatment screening biopsies and biopsies taken at day 19 Matched biopsies obtained from 11 patients across the 3 cohorts analyzed GSPT1 e
Slide 14: MRT-2359: Treatment-Related AEs
MRT-2359: Treatment-Related AEs Occurring in > 2 patients# No observed clinically significant hypocalcemia or hypotension/cytokine release syndrome AE Preferred Term 0.5 mg (N=9)## 1 mg (N=7)## 2 mg (N=5) ## Overall (N=21) Any Grade Grade > 3 Any Grade Grade > 3 Any Grade Grade > 3 Any Grade Grade >
Slide 15: Confirmed PR in High Grade Neuroendocrine Bladder Cancer
Confirmed PR in High Grade Neuroendocrine Bladder Cancer Baseline 8 weeks 4 weeks High Grade (HG) neuroendocrine bladder cancer Baseline tumor biopsy demonstrated high N-MYC expression 4 prior lines of therapy including chemotherapy and pembrolizumab Patient initiated on 2 mg for first 5/9 regimen,
Slide 16: Unconfirmed PR in NSCLC with SCLC/NE Transformation
Unconfirmed PR in NSCLC with SCLC/NE Transformation Baseline 3 weeks NSCLC (adenocarcinoma) Baseline tumor biopsy demonstrated SCLC/NE transformation, low N- and L-MYC expression Multiple lines of prior therapy including chemotherapy, pembrolizumab and atezolizumab Patient initiated on 0.5 mg CT on
Slide 17: MRT-2359-001 – Preliminary Efficacy Data
MRT-2359-001 – Preliminary Efficacy Data As of September 7th, 2023, 15/21 evaluable patients treated across 3 cohorts, 6/15 patients were identified as biomarker positive Of these 6 biomarker positive patients, 2 have experienced a PR (1 confirmed, 1 unconfirmed) and 1 patient has SD PR (-59%) – HG
Slide 18: Summary and Next Steps
Summary and Next Steps Clinical data support that 0.5 mg starting dose was active based on PD assessment (PBMC and tissue), with optimal PD modulation across dose levels tested Encouraging initial clinical activity at all dose levels: 2 PRs (1 confirmed, 1 unconfirmed) and 1 SD in 6 evaluable, heavi
Slide 19: Portfolio
Portfolio
Slide 20: Monte Rosa Pipeline
Monte Rosa Pipeline Oncology Inflammation Immunology Genetic diseases MRT-2359 (GSPT1) NSCLC, SCLC and other MYC-driven Malignancies NEK7 Inflammatory Diseases MRT-6160 (VAV1) Autoimmune Disease Discovery Program/ Target Indication(s) Full Phase 1 data (update on timing in early 2024) Multiple SCD t
Slide 21: Monte Rosa Therapeutics - Highlights
Monte Rosa Therapeutics - Highlights Taking molecular glue degraders (MGDs) to new heights Rationally designed MGDs with potential to solve many of the limitations of other modalities by selectively degrading therapeutically relevant proteins considered undruggable or inadequately drugged Highly pro
Slide 22: Mh. Monte Rosa
Mh. Monte Rosa Therapeutics
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