On January 8, 2024 Monte Rosa Therapeutics (Nasdaq: GLUE), a clinical-stage biotechnology company developing novel molecular glue degrader (MGD)-based medicines, reported anticipated 2024 milestones ahead of its participation in the 42nd Annual J.P. Morgan Healthcare Conference (Press release, Monte Rosa Therapeutics, JAN 8, 2024, View Source [SID1234639090]). The company’s presentation, taking place on Wednesday, January 10, 2024, at 3:00 p.m. PT, will focus on strategic priorities for 2024, including anticipated progress with the ongoing Phase 1/2 clinical trial of MRT-2359 in MYC-driven solid tumors as well as future development plans for MRT-2359 and MRT-6160, its VAV1-directed MGD for autoimmune diseases.

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"2023 was an exciting and highlight-filled year for Monte Rosa Therapeutics, including encouraging interim Phase 1/2 MRT-2359 clinical results, advancement of our VAV1-targeted MGD into IND enabling studies, and initiation of a strategic collaboration with Roche," said Markus Warmuth, M.D., Chief Executive Officer of Monte Rosa Therapeutics. "Building on last year’s successes, this year we look forward to announcing the RP2D for our MRT-2359 program and initiating multiple Phase 2 expansion cohorts in tumors characterized by high L- and N-MYC expression, with the potential to consider indication expansion into c-MYC-driven tumor types such as ER+ breast cancer and castration-resistant prostate cancer. Our highly selective VAV1-directed MGD MRT-6160 is anticipated to enter a Phase 1 healthy volunteer study this year with the aim to move efficiently into early proof-of-concept studies in patients across multiple autoimmune indications. Lastly, we also expect to nominate additional development candidates in 2024 for programs in both oncology and inflammation/immunology. Our strong balance sheet and cash runway into 1H 2026 positions us to advance our programs through important clinical milestones."

Recap of 2023 Achievements

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Presented interim data from the Phase 1/2 clinical trial of MRT-2359 demonstrating tumor reductions in patients with biomarker-positive cancers and favorable pharmacokinetic (PK), pharmacodynamic (PD), and tolerability profiles.
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Announced development candidate MRT-6160, a VAV1-directed MGD, for the treatment of autoimmune diseases, and presented preclinical data demonstrating that MRT-6160 attenuates autoimmune disease progression.
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Entered into a strategic collaboration and licensing agreement with Roche to discover and develop novel molecular glue degraders targeting cancer and neurological diseases, with a $50 million upfront payment and eligibility to receive future preclinical, clinical, commercial and sales milestone payments exceeding $2 billion, as well as tiered royalties.

Corporate Updates and Key Anticipated Milestones

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Monte Rosa announced today that it has received U.S. Food & Drug Administration Fast Track Designation for MRT-2359 for the treatment of patients with previously treated, metastatic small cell lung cancer (SCLC) with L-MYC or N-MYC expression.
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Monte Rosa expects to announce the RP2D for the MRT-2359 Phase 1/2 clinical trial in MYC-driven solid tumors in Q2 2024. Enrollment is ongoing in backfill cohorts at clinically active doses using a 5 days on drug, 9 days off drug schedule. The Company has simultaneously started dose escalation of higher dose density cohorts using a 21 days on, 7 days off schedule.
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The Company expects to submit an IND for MRT-6160, a VAV1-targeted MGD, in the first half of 2024 and to initiate a Phase 1 single ascending dose / multiple ascending dose study in healthy volunteers in mid-2024.
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The Company expects to nominate a development candidate for the NEK7 preclinical program in Q1 2024.
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The Company expects to nominate a development candidate for the CDK2 preclinical program in 2024.

J.P. Morgan Healthcare Conference Presentation

Dr. Warmuth will present Monte Rosa’s pipeline and business updates during a presentation at the 42nd Annual J.P. Morgan Healthcare Conference on Wednesday, January 10, 2024, at 3:00 p.m. PT. A webcast of the presentation will be accessible via the "Events & Presentations" section of Monte Rosa’s website at ir.monterosatx.com, and an archived version will be made available following the presentation.

About MRT-2359

MRT-2359 is a potent, highly selective and orally bioavailable investigational molecular glue degrader (MGD) that induces the interaction between the E3 ubiquitin ligase component cereblon and the translation termination factor GSPT1, leading to the targeted degradation of GSPT1 protein. The MYC transcription factors (c‑MYC, L-MYC and N-MYC) are well-established drivers of human cancers that maintain high levels of protein translation, which is critical for uncontrolled cell proliferation and tumor growth. Preclinical studies have shown this addiction to MYC-induced protein translation creates a dependency on GSPT1. By inducing degradation of GSPT1, MRT-2359 is designed to exploit this vulnerability, disrupting the protein synthesis machinery, leading to anti-tumor activity in MYC-driven tumors.

About MRT-6160

MRT-6160 is a potent, highly selective, and orally bioavailable investigational molecular glue degrader of VAV1, which in our in vitro studies has shown deep degradation of its target with no detectable effects on other proteins. VAV1, a Rho-family guanine nucleotide exchange factor, is a key signaling protein downstream of both the T-and B-cell receptors. VAV1 expression is restricted to blood and immune cells, including T and B cells. Preclinical studies have shown that targeted degradation of VAV1 protein via an MGD modulates both T- and B-cell receptor-mediated activity. This modulation is evident both in vitro and in vivo, demonstrated by a significant decrease in cytokine secretion, proteins vital for maintaining autoimmune diseases. Moreover, VAV1-directed MGDs have shown promising activity in preclinical models of autoimmune diseases and thus have the potential to provide therapeutic benefits in multiple autoimmune indications, such as multiple sclerosis, rheumatoid arthritis, and dermatological disorders. Preclinical studies demonstrate MRT-6160 inhibits disease progression in in vivo autoimmunity models.