MRT-2359 / Monte Rosa Therap - LARVOL DELTA

Monte Rosa Therapeutics Announces First Quarter 2025 Financial Results and Business Updates (GlobeNewswire) - "Share additional MRT-2359 Phase 1/2 study data in CRPC patients resistant to androgen receptor (AR) therapy and in patients with HR+ breast cancer in H2 2025....Submit an IND application for a CDK2 and/or cyclin E1-directed MGD in 2026."

IND • P1/2 data • Castration-Resistant Prostate Cancer • Hormone Receptor Positive Breast Cancer • Solid Tumor

Monte Rosa Therapeutics Announces First Quarter 2025 Financial Results and Business Updates (GlobeNewswire) - "Research and Development (R&D) Expenses: R&D expenses for the first quarter of 2025 were $32.2 million, compared to $27.0 million for the first quarter of 2024. These increases were driven by the successful achievement of key milestones in our R&D organization, including the continuation of the MRT-2359 clinical study, the progression and growth of our preclinical pipeline, including research performed in connection with our collaboration with Roche, the advancement of MRT-6160 to enter the clinic..."

Commercial • Castration-Resistant Prostate Cancer • HER2 Positive Breast Cancer • Immunology • Solid Tumor

Drug target ID and binding site mapping in complex cellular environments using LiP-MS (AACR 2025) - "This workflow bypasses the need for protein purification, mitigating risks of protein truncation or misfolding.To evaluate LiP-MS' performance on molecular glue MoAs, we performed global target ID experiments using two well-characterized models: the cyclin K degraders CR8 and SR-4835 and the GSPT1 degraders MRT-2359 and Eragidomide...Applying HR-LiP, we mapped the binding site of the BRD4 inhibitor JQ1 on full-length BRD4, a large protein challenging to study via standard methods, using a mammalian transient overexpression system. Similarly, we located binding sites for EGFR inhibitors gefitinib and afatinib on the membrane-bound EGFR protein. Additionally, we pinpointed the SMER28 binding site on the hexameric ATPase VCP, an autophagy enhancer, demonstrating the method's applicability to large protein complexes.In conclusion, LiP-MS provides a versatile toolbox for identifying drug targets and mapping binding sites within complex cellular environments."

Oncology • BRD4 • CDK12 • CRBN • DDB1 • GSPT1

Seeking new glues - Toward an E3 ligase-agnostic molecular glue degrader identification platform (AACR 2025) - "Conversely, a key challenge with cell-based screening approaches is to understand the mechanism by which the target is degraded, relying on the identification of the ubiquitin ligase or adaptor protein that is mediating the effect of the compound.Here, we demonstrate the utility of our cell-based screening platform by developing degrader assays for two separate targets, Cyclin K and GSPT1, both therapeutically relevant for oncology, and with respective MGDs in clinical trials (CT7439 for cyclin K by Carrick Therapeutics, and MRT-2359 and Eragidomide from Monte Rosa Therapeutics and Cellgene/BMS, respectively).Further, to address the challenge of deconvoluting the mechanistic basis for monovalent degrader hits from cell-based assays, we have utilized limited proteolysis coupled with mass spectrometry (LiP-MS)...This methodology allows the identification of the proteins involved in mediating degradation of a target, such as a ubiquitin ligase recruited to a target via an..."

Oncology • GSPT1

Discovery of novel, potent and orally active GSPT1 molecular glue degraders (AACR 2025) - "In fact, clinical proof of concept has been obtained with immunomodulatory drugs such as thalidomide, lenalidomide and pomalidomide, which degrade IKZF1/IKZF3...GSPT1 degrader antibody conjugates are now in clinical trials for breast cancer (ORM-5029) and AML (BMS-986497/ORM-6151)...These encouraging results have prompted us to explore a series of GSPT1 MGDs.In the present study, we describe the discovery of a series of novel, potent and orally active GSPT1 MGD targeting tumors with high GSPT1 expression...This compound demonstrates in vivo efficacy in CDX model with a favorable profile comparable to that of MRT-2359. In summary, a series of orally active GSPT1 degraders have been discovered with preclinical profile suitable for further development to manage cancers with high GSPT1 expression."

Breast Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • BCL6 • GSPT1 • IKZF1 • IKZF3 • STAT6 • VAV1

MRT-2359, GSPT1-directed MGD for MYC-driven solid tumors (GlobeNewswire) - P1/2 | N=174 | NCT05546268 | Sponsor: Monte Rosa Therapeutics, Inc | "Using the 5/9 dosing schedule, doses of 0.5 mg and 1 mg per day were generally well tolerated with mostly low-grade adverse events (AEs)...Using the 21/7 schedule, both the 0.5 and 0.75 mg doses were generally well tolerated with mostly low-grade AEs observed. The 0.5 mg dose using the 21/7 dose schedule was selected as the recommended phase 2 dose (RP2D). Optimal degradation (based on optimal PD modulation in preclinical studies) of approximately 60% was achieved in biomarker L-/N-MYC high tumor samples, as assessed by targeted mass spectrometry... there was 1 confirmed partial response (PR), and 4 patients with stable disease (SD), for a disease control rate (DCR) of 38%. Of 24 biomarker negative patients (low L-MYC and N-MYC expression), there was 1 unconfirmed PR and 3 patients with SD, for a DCR of 17%...expects to present additional results for this cohort in H2 2025."

P1/2 data • Non Small Cell Lung Cancer • Small Cell Lung Cancer

Monte Rosa Therapeutics Announces Fourth Quarter 2024 Financial Results and Provides Corporate… (GlobeNewswire) - "Submit an IND application for MRT-8102 in H1 2025. Submit an IND application for the second generation NEK7-directed MGD with enhanced CNS penetration in 2026."

IND • Immunology • Inflammation • Oncology

Monte Rosa Therapeutics to Present Pipeline Update and Release Fourth Quarter and Full Year 2024 Financial Results on March 20, 2025 (GlobeNewswire) - "Monte Rosa Therapeutics, Inc...announced that management will present a pipeline update including clinical results from its Phase 1 SAD/MAD study of the VAV1-directed MGD MRT-6160 and its Phase 1/2 study of MRT-2359 in MYC-driven solid tumors. A conference call and webcast are planned for Thursday, March 20, 2025, at 8:00 a.m. ET."

P1 data • P1/2 data • HER2 Negative Breast Cancer • Neuroendocrine Tumor • Non Small Cell Lung Cancer • Prostate Cancer • Small Cell Lung Cancer

Monte Rosa Therapeutics Provides Corporate Update and Key Anticipated Milestones for 2025 (GlobeNewswire) - "Key Anticipated Milestones for 2025: Share updated data, including biomarker and activity data, from the MRT-2359 Phase 1/2 study in Q1 2025. Report initial data from the Phase 1 SAD/MAD study of MRT-6160 in healthy volunteers in Q1 2025, including data on safety, pharmacokinetics, VAV1 protein degradation, and key downstream pharmacodynamic markers....Nominate a development candidate for the second-generation NEK7 program with enhanced CNS penetration in H2 2025. Nominate a CDK2 program development candidate in H1 2025."

New molecule • P1 data • P1/2 data • Diffuse Large B Cell Lymphoma • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer • Neuroendocrine Tumor • Non Small Cell Lung Cancer • Prostate Cancer • Small Cell Lung Cancer

Monte Rosa Therapeutics Provides Development Progress Update for Ongoing MRT-2359 Phase 1/2 Study in Patients with MYC-driven Solid Tumors (GlobeNewswire) - P1/2 | N=174 | NCT05546268 | Sponsor: Monte Rosa Therapeutics, Inc | "Results from dose escalation arms of Phase 1/2 study of MRT-2359 demonstrated a favorable safety profile and targeted levels of GSPT1 degradation using a 21 days on, 7 days off drug dosing schedule in heavily pretreated solid tumor patients; Recommended Phase 2 dose determined as 0.5 mg daily at a 21 days on, 7 days off drug dosing schedule; Additional MRT-2359 Phase 1/2 study clinical results, including biomarker and activity data, anticipated in Q1 2025."

P1/2 data • Estrogen Receptor Positive Breast Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Prostate Cancer • Small Cell Lung Cancer • Solid Tumor

Monte Rosa Therapeutics Announces Third Quarter 2024 Financial Results and Provides Corporate Update (GlobeNewswire) - "Announce the recommended Phase 2 dose and data from the Phase 1 dose escalation portion of the MRT-2359 Phase 1/2 study including safety, biomarker data, and clinical activity before the end of 2024. The Company also expects to provide guidance on Phase 2 expansion cohorts before year-end."

Clinical • P1 data • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Oncology

Monte Rosa Therapeutics Announces Second Quarter 2024 Financial Results and Provides Corporate Update (GlobeNewswire) - "ANTICIPATED MILESTONES: Announce the recommended Phase 2 dose for the MRT-2359 Phase 1/2 study and report Phase 1 clinical activity and safety results in H2 2024. The Company also plans to initiate the Phase 2 portion of the study before year-end; Submit an IND application for MRT-8102 in H1 2025. Nominate a development candidate for the CDK2 preclinical program in 2024."

IND • P1 data • Pipeline update • Trial status • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Immunology • Inflammation • Lung Cancer • Non-Hodgkin’s Lymphoma • Oncology • Solid Tumor

Monte Rosa Therapeutics Provides Development Progress Updates on MRT-2359 and MRT-6160 (GlobeNewswire) - "Monte Rosa Therapeutics, Inc...today announced progress updates for its two lead programs, MRT-2359, an MGD being developed for MYC-driven solid tumors...'We continue to successfully recruit and advance our ongoing MRT-2359 Phase 1/2 study.'...Enrollment is ongoing in the 0.75 mg, 21 days on, 7 days off dose escalation cohort."

Trial status • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lung Cancer • Neuroendocrine Tumor • Non Small Cell Lung Cancer • Non-Hodgkin’s Lymphoma • Oncology • Small Cell Lung Cancer • Solid Tumor

The GSPT1 molecular glue degrader MRT-2359 is active against prostate cancer (AACR 2024) - P1/2 | "No significant in vivo response was observed for xenografts of the insensitive cell line PC-3. These data support the clinical investigation of MRT-2359 in prostate cancer."

Genito-urinary Cancer • Lung Cancer • Neuroendocrine Tumor • Non Small Cell Lung Cancer • Oncology • Prostate Cancer • Small Cell Lung Cancer • Solid Tumor • AR • GSPT1 • MYC • MYCN

Monte Rosa Therapeutics Announces Fourth Quarter and Full Year 2023 Financial Results and Provides Corporate Update (GlobeNewswire) - "ANTICIPATED UPCOMING MILESTONES: Announce the recommended Phase 2 dose for the MRT-2359 Phase 1/2 study in Q2 2024 and report updated Phase 1 clinical results thereafter. Initiate the Phase 2 portion of the study before year-end. The Company is exploring Phase 2 expansion cohorts in high-prevalence c-MYC-driven tumors such as hormone receptor-positive breast cancer and prostate cancer, as well as tumor types and patient populations driven by L- and N-MYC including NSCLC, SCLC, and solid tumors with amplifications of L- and N-MYC."

P1 data • Trial status • Breast Cancer • Genito-urinary Cancer • Hormone Receptor Positive Breast Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Prostate Cancer • Solid Tumor

Monte Rosa Therapeutics Announces Fourth Quarter and Full Year 2023 Financial Results and Provides Corporate Update (GlobeNewswire) - "Monte Rosa plans to present a poster at the upcoming American Association for Cancer Research (AACR) Annual Meeting demonstrating that treatment with MRT-2359 resulted in marked tumor regressions in an AR-V7-expressing 22RV1 xenograft mouse model of c-MYC-driven prostate cancer associated with resistance to anti-androgen agents."

Preclinical • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

Monte Rosa Therapeutics Provides Corporate Update and Key Anticipated Milestones for 2024 (GlobeNewswire) - "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; 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."

Fast track designation • Trial status • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor

Study of Oral MRT-2359 in Selected Cancer Patients (clinicaltrials.gov) - P1/2 | N=135 | Recruiting | Sponsor: Monte Rosa Therapeutics, Inc

Trial completion date • Trial primary completion date • Diffuse Large B Cell Lymphoma • Endocrine Cancer • Hematological Malignancies • Lung Cancer • Lymphoma • Neuroendocrine Tumor • Non Small Cell Lung Cancer • Non-Hodgkin’s Lymphoma • Oncology • Small Cell Lung Cancer • Solid Tumor • MYC • MYCN

Monte Rosa Therapeutics Announces Third Quarter 2023 Financial Results and Provides Corporate Update (GlobeNewswire) - "The Company now expects to release the recommended Phase 2 dose for the MRT-2359 Phase 1/2 study in Q2 2024. On track for planned IND submission for MRT-6160 in the first half of 2024. The Company expects to nominate a development candidate for its NEK7 preclinical program in Q1 2024. The Company expects to nominate a development candidate for its CDK2 preclinical program in 2024."

IND • P1/2 data • Pipeline update • Immunology • Oncology • Solid Tumor

Monte Rosa Therapeutics Announces $25 Million Registered Direct Offering, Priced At- the-Market Under Nasdaq Rules (Monte Rosa Therap Press Release) - "Monte Rosa Therapeutics, Inc...today announced that it has raised $25 million at-the-market from a life sciences-dedicated investor....Monte Rosa intends to use the net proceeds from the offering towards its further advancement of its clinical and late preclinical pipeline, including MRT-2359, its orally bioavailable, GSPT1-directed MGD, MRT-6160, its orally bioavailable VAV1-directed MGD, and its NEK7 program, to key value inflection points."

Financing • Immunology • Oncology

Monte Rosa Therapeutics Announces Interim PK/PD and Clinical Data for MRT-2359 in Phase 1/2 Trial for MYC-Driven Solid Tumors (GlobeNewswire) - P1/2 | N=33 | NCT05546268 | Sponsor: Monte Rosa Therapeutics, Inc | "Monte Rosa Therapeutics...announced interim data from the Phase 1 dose escalation part of its ongoing Phase 1/2 open-label, multicenter study of MRT-2359 in patients with MYC-driven solid tumors, including lung cancers and high-grade neuroendocrine cancer....'We are excited to learn more about the clinical profile of MRT-2359 in our ongoing Phase 1/2 clinical study, and early next year we plan to provide further clarity on the expected timing for the full Phase 1 data disclosure in 2024'....Clinical activity was seen across all dose levels. Of the six biomarker-positive patients, two achieved a partial response (PR), one confirmed and one unconfirmed, and one patient experienced durable stable disease (SD)....Monte Rosa Therapeutics will host a conference call and webcast today at 8:00 a.m. ET to discuss the interim PK/PD and clinical data for MRT-2359."

P1 data • PK/PD data • Bladder Cancer • Genito-urinary Cancer • Lung Cancer • Neuroendocrine Tumor • Non Small Cell Lung Cancer • Oncology • Prostate Cancer • Small Cell Lung Cancer • Solid Tumor

Monte Rosa Therapeutics Announces Second Quarter 2023 Financial Results and Provides Corporate Update (GlobeNewswire) - "UPCOMING MILESTONES: On track to present initial Phase 1/2 clinical data for MRT-2359 in MYC-driven solid tumors, including pharmacokinetics (PK), pharmacodynamics (PD), safety, and available initial efficacy data, in the second half of 2023."

P1/2 data • PK/PD data • Oncology • Solid Tumor

Orphan Designation: Treatment of small cell lung cancer (FDA) - Date Designated: 06/21/2023

Orphan drug • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor • Thoracic Cancer

Monte Rosa Therapeutics Announces First Quarter 2023 Financial Results and Provides Corporate Update (GlobeNewswire) - "On track to announce initial clinical data, including pharmacokinetic (PK), pharmacodynamic (PD), safety, and available initial efficacy data from the Phase 1 part of the ongoing Phase 1/2 clinical trial evaluating MRT-2359 in MYC-driven tumors, including non-small cell lung cancer, small cell lung cancer, and other MYC-driven tumors, in the second half of 2023; On track to advance multiple preclinical programs to development candidates in immunology, inflammation, and oncology, including declaring a VAV1 development candidate in the second quarter of 2023..."

P1 data • Pipeline update • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lung Cancer • Lymphoma • Neuroendocrine Tumor • Non Small Cell Lung Cancer • Non-Hodgkin’s Lymphoma • Oncology • Small Cell Lung Cancer • Solid Tumor • Thoracic Cancer

Discovery of MRT-2359, an orally bioavailable GSPT1 molecular glue degrader, for MYC-driven cancers (AACR 2023) - P1/2 | "Similar levels of activity were also observed in neuroendocrine lung cancer PDXs and lymphoma models. Oral MRT-2359 is currently in a Phase 1/2 clinical trial in selected cancer patients with MYC-driven NSCLC, SCLC, high grade neuroendocrine cancers and diffuse large B-cell lymphoma (NCT05546268)."

Diffuse Large B Cell Lymphoma • Endocrine Cancer • Hematological Malignancies • Lung Cancer • Lymphoma • Neuroendocrine Tumor • Non Small Cell Lung Cancer • Non-Hodgkin’s Lymphoma • Oncology • Small Cell Lung Cancer • Solid Tumor • GSPT1 • MYC