Monte Rosa Therapeutics, Inc. · NASDAQ:GLUE
Monte Rosa Therapeutics — Keystone 2026
15 slides from Monte Rosa Therapeutics's conference presentation, Jan 21, 2026
Slide 1: MRT-6160, a highly selective and first-in-class VAV1-directed molecular glue degrader
MRT-6160, a highly selective and first-in-class VAV1-directed molecular glue degrader, demonstrates activity in multiple immune- mediated disease models Dr. Adam N.R. Cartwright | 21 January 2026 | Keystone
Slide 2: Disclosures
Disclosures I have the following relevant financial relationships to disclose: • Employee for Monte Rosa Therapeutics • Stock options for Monte Rosa Therapeutics (GLUE) Monte Rosa Therapeutics has a global exclusive license agreement with Novartis to advance VAV1 MGDs including MRT-6160 2
Slide 3: Summary: MRT-6160, a VAV1-Targeting MGD for the Treatment of Multiple Immune-Mediated Diseases
Summary: MRT-6160, a VAV1-Targeting MGD for the Treatment of Multiple Immune-Mediated Diseases • MRT-6160 is a highly selective, first-in-class molecular glue degrader of VAV1, a key T/B cell signaling protein • In preclinical studies, oral administration of MRT-6160 attenuates disease progression a
Slide 4: VAV1 Possesses GEF-Dependent and –Independent Functions
VAV1 Possesses GEF-Dependent and –Independent Functions GEF-dependent enzymatic functions GEF-independent scaffolding function T cell receptor B cell receptor T cell receptor B cell receptor VAV1 SH2N BLNK LAT Rac1 VAV1 BTK Actin SH2C SH3 polymerization Immune synapse PLCɣ formation Gads VAV1 Cell m
Slide 5: VAV1 is a Highly Validated Target for Attenuating T- and B-cell Activity
VAV1 is a Highly Validated Target for Attenuating T- and B-cell Activity VAV1-/- mice are viable, fertile, and display Multiple CRISPR screens identified VAV1 loss-of-function T- and B-cell phenotypes as key player in primary human T-cell function VAV1-/- mice Primary human T cells T-cell function B
Slide 6: MRT-6160, A Molecular Glue Degrader Drugging the Undruggable
MRT-6160, A Molecular Glue Degrader Drugging the Undruggable Molecular glues reprogram E3 ubiquitin ligases MRT-6160 enables the targeting of VAV1 to induce degradation of target ‘neosubstrate’ proteins for proteasomal degradation VAV1 MRT-6160 Cereblon CRBN Ubiquitin MGD, e.g. chain MRT-6160 Ubiqui
Slide 7: Demonstrates Exquisite Potency and Selectivity for VAV1 In Human and Mouse
MRT-6160 Demonstrates Exquisite Potency and Selectivity for VAV1 In Human and Mouse MRT-6160 demonstrates high selectivity and potency MRT-6160 demonstrates high selectivity and potency for human VAV1 in PBMCs for mouse Vav1 in splenocytes 125 125 p-value (-log10) Normalized to DMSO p-value (-log10)
Slide 8: Reduces TCR- and BCR-Mediated Effector Functions In Vitro
MRT-6160 Reduces TCR- and BCR-Mediated Effector Functions In Vitro MRT-6160 inhibits TCR-mediated T-cell activation, MRT-6160 inhibits BCR-mediated proliferation, and pro-inflammatory cytokine production B-cell activation, effector functions and differentiation CD69 IL-6 CD69 Proliferation 120 120 1
Slide 9: Inhibits Disease Progression and Cytokine Production in a Collagen-Induced Arthritis Model
MRT-6160 Inhibits Disease Progression and Pro-inflammatory Cytokine Production in a Collagen-Induced Arthritis Model MRT-6160 inhibited disease progression MRT-6160 reduced secretion and disease severity of a CIA model of key disease-associated serum cytokines 7 Vehicle ✱✱ ✱✱✱✱ 6 Anti-TNF, 10 mg/kg
Slide 10: Inhibits Disease Progression, Cytokine Production, and Neuroinflammation in an EAE Model
MRT-6160 Inhibits Disease Progression, Pro-inflammatory Cytokine Production, and Neuroinflammation in an EAE Model MRT-6160 reversed disease progression resulting MRT-6160 reduced expression of cytokines, tissue in lower overall disease burden than standard of care damage, and T cell pathway express
Slide 11: Inhibits Disease Progression, Cytokine Production, and Colon Damage in a T Cell Transfer Colitis Model
MRT-6160 Inhibits Disease Progression, Pro-inflammatory Cytokine Production, and Colon Damage in a T Cell Transfer Colitis Model MRT-6160 inhibited disease progression MRT-6160 reduced expression of key disease-associated and colon weight:length ratio cytokines and tissue damage in the colon ✱✱ ✱✱✱
Slide 12: Inhibits Disease Progression, Autoantibody Production, and Nephritis in the MRL-Faslpr Model
MRT-6160 Inhibits Disease Progression, Autoantibody Production, and Nephritis in the MRL-Faslpr Lymphoproliferative Autoimmune Model MRT-6160 inhibits disease progress across MRT-6160 reduces kidney histopathology multiple metrics in the MRL-Faslpr autoimmune model including lupus and interstitial n
Slide 13: VAV1 Degradation by MRT-6160 Exceeds 90% with Significant Functional Inhibition of T and B Cells
VAV1 Degradation by MRT-6160 Exceeds 90% with Significant Functional Inhibition of T and B Cells following a Single Dose Administration Dose-dependent degradation of Attenuation of immune cell activation (CD69 expression) VAV1 in peripheral blood T cells and cytokine production in T and B cells 60 6
Slide 14: VAV1 is an Upstream Targeting Node Associated with Clinically Validated Pathways
VAV1 is an Upstream Targeting Node Associated with 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 produ
Slide 15: Thank you
Thank you i a= ae. y} ’ MonteRosa Therapeutics