On May 8, 2025 Monte Rosa Therapeutics, Inc. (Nasdaq: GLUE), a clinical-stage biotechnology company developing novel molecular glue degrader (MGD)-based medicines, reported business highlights and financial results for the first quarter ended March 31, 2025 (Press release, Monte Rosa Therapeutics, MAY 8, 2025, View Source [SID1234652752]).

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"We’ve made significant progress across our entire portfolio in the development of our only-in-class and first-in-class molecular glue degrader therapeutics, targeting diseases poorly addressed by conventional pharmaceutical approaches," said Markus Warmuth, M.D., Chief Executive Officer of Monte Rosa Therapeutics. "As highlighted in our recent pipeline update, our MRT-6160 Phase 1 study results support the broad potential application of this molecule as a novel treatment approach for immune-mediated diseases, and we are working diligently to advance the program into Phase 2 studies alongside our collaborators at Novartis. For our GSPT1 program, based on encouraging preliminary data from our ongoing Phase 1/2 study of MRT-2359 in MYC-driven solid tumors, we are focused on castration-resistant prostate cancer, an exciting opportunity in a population with widespread c-MYC expression. Study enrollment is ongoing, and we expect to report additional clinical data in H2 2025. Lastly, we continue to make excellent progress with our earlier stage programs. Our NEK7 program, targeting inflammatory diseases driven by IL-1β and the NLRP3 inflammasome, is on track, and we plan to file an IND submission for MRT-8102 in the first half of this year. Recent preclinical data for our CDK2-directed MGD highlight the substantially greater tumor regression achieved with our MGD combined with standard of care therapies compared to standard of care alone. We look forward to an IND submission for our CDK2 and/or CCNE1 cell cycle programs next year."

RECENT HIGHLIGHTS

MRT-6160, VAV1-directed MGD for immune-mediated conditions

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In March 2025, Monte Rosa announced clinical results from its MRT-6160 Phase 1, single ascending dose / multiple ascending dose (SAD/MAD) study in healthy volunteers (clinicaltrials.gov identifier NCT06597799). The results support a clear path into anticipated Phase 2 studies and broad potential applications in multiple immune-mediated diseases. Further development of MRT-6160 toward Phase 2 studies is ongoing, in collaboration with Novartis.
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Monte Rosa has a global exclusive development and commercialization license agreement with Novartis to advance VAV1 MGDs including MRT-6160. Monte Rosa is eligible to receive up to $2.1 billion in development, regulatory, and sales milestones, beginning upon initiation of Phase 2 studies. Monte Rosa will co-fund any Phase 3 clinical development and will share any profits and losses associated with the manufacturing and commercialization of MRT-6160 in the U.S., and is also eligible for tiered royalties on ex-U.S. net sales.

MRT-2359, GSPT1-directed MGD for MYC-driven solid tumors

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In March 2025, Monte Rosa provided updated clinical results in evaluating the safety, pharmacodynamics, and clinical activity of MRT-2359 in various tumor types. The Company has determined castration-resistant prostate cancer (CRPC) to be the primary MRT-2359 development focus. The Company continues to enroll and evaluate patients with CRPC, with the potential to expand enrollment to 20-30 patients if a positive efficacy signal continues to be observed, and expects to present additional results in H2 2025. Monte Rosa also continues to enroll and evaluate patients with HR+ breast cancer and expects to present additional results for this cohort in H2 2025.

NEK7-directed MGDs for inflammatory and CNS diseases driven by IL-1β and the NLRP3 inflammasome

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Monte Rosa has successfully completed GLP tox studies for MRT-8102, a first-in-class, NEK7-directed MGD for the treatment of inflammatory diseases driven by interleukin-1β (IL-1β) and the NLRP3 inflammasome, supporting a considerable safety margin. The Company is on track to submit an IND application for MRT-8102 in H1 2025 and plans to initiate Phase 1 healthy volunteer and proof-of-concept studies in individuals with high levels of C-reactive protein (CRP) and in cardio-immunology indications. The Company continues to evaluate future Phase 2 proof-of-concept studies in gout, pseudogout (calcium pyrophosphate deposition disease), and osteoarthritis.

Cyclin E1 and CDK2-directed MGD programs for treatment of solid tumors

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In April 2025, Monte Rosa presented preclinical data on the potential of its highly selective CDK2-directed molecular glue degrader, MRT-51443, to treat HR-positive/HER2-negative breast cancer at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2025. MRT-51443 demonstrated superior anti-tumor activity in HR-positive/HER2-negative breast cancer models when combined with CDK4/6 inhibition and anti-estrogen therapy as compared to the standard-of-care combination of CDK4/6 inhibition and anti-estrogen therapy. Results also showed that MRT-51443 displayed superior selectivity compared to clinical-stage CDK2 inhibitors.

QuEEN (Quantitative and Engineered Elimination of Neosubstrates) discovery engine

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Monte Rosa is advancing novel discovery programs for immunology and inflammation targets that the Company believes have the potential for highly differentiated, oral MGDs degrading undruggable targets in critical I&I pathways. These may include programs with the potential to improve upon the clinical profile of cell therapies, such as CAR-T, or biologics, such as FcRn inhibitors.

ANTICIPATED UPCOMING MILESTONES AND DEVELOPMENT PRIORITIES

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Continue advancement of MRT-6160 toward Phase 2 initiation, in collaboration with Novartis.
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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.
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Submit an IND application for MRT-8102 in H1 2025.
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Submit an IND application for the second-generation NEK7-directed MGD with enhanced CNS penetration in 2026.
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Submit an IND application for a CDK2 and/or cyclin E1-directed MGD in 2026.

FIRST QUARTER 2025 FINANCIAL RESULTS

Collaboration revenue: Collaboration revenue for the first quarter of 2025 was $84.9 million and $1.1 million for the quarter ended March 31, 2024. Collaboration revenue represents amounts earned from our collaboration and license agreements with Roche and Novartis, primarily revenue recognized from the Novartis $150 million upfront payment in the fourth quarter of 2024 based on progress made on our performance obligations defined in the Novartis License Agreement.

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, and the continued development of the Company’s QuEEN discovery engine. Approximately $1.0 million included in R&D expenses are to be reimbursed pursuant to our license agreement with Novartis. Non-cash stock-based compensation constituted $3.1 million of R&D expenses for Q1 2025, compared to $2.7 million in the same period in 2024.

General and Administrative (G&A) Expenses: G&A expenses for the first quarter of 2025 were $8.7 million compared to $9.0 million for the first quarter of 2024. G&A expenses included non-cash stock-based compensation of $2.2 million for the first quarter of 2025, compared to $2.2 million in the same period in 2024.

Net Income (Loss): Net income for the first quarter of 2025 was $46.9 million, compared to a net loss of $32.0 million for the first quarter of 2024.

Cash Position and Financial Guidance: Cash, cash equivalents, restricted cash, and marketable securities as of March 31, 2025, were $331 million, compared to cash, cash equivalents, restricted cash, and marketable securities of $377 million as of December 31, 2024. The decrease of $46 million was primarily due to the operational use of cash and one-time payments not recorded in operating expenses, including $12.2 million of value-added tax (VAT) collected from Novartis in the fourth quarter of 2024 in connection with the Novartis $150 million upfront payment and remitted to the Swiss Federal Tax Administration in the first quarter of 2025.

Based on current cash, cash equivalents, restricted cash, marketable securities, the Company expects its cash and cash equivalents to be sufficient to fund planned operations and capital expenditures into 2028.

About MRT-6160
MRT-6160 is a potent, highly selective, and orally bioavailable investigational molecular glue degrader of VAV1, which in preclinical studies has shown deep degradation of its target with no detectable effects on other proteins. VAV1 is a key signaling protein downstream of both the T- and B-cell receptors. VAV1 expression is restricted to immune cells, including T and B cells. MRT-6160 has shown promising activity in preclinical models of multiple immune-mediated conditions. In a Phase 1, single ascending dose / multiple ascending dose (SAD/MAD) study in healthy subjects (clinicaltrials.gov identifier NCT06597799), MRT-6160 demonstrated sustained, dose-dependent VAV1 degradation in peripheral blood T and B cells after single and multiple dose administration. MRT-6160 also substantially inhibited secretion of inflammatory cytokines from whole blood derived T and B cells following ex vivo stimulation. Under the terms of an agreement announced in October 2024, Novartis has exclusive worldwide rights to develop, manufacture and commercialize MRT-6160 and other VAV1 MGDs. Monte Rosa is eligible to receive up to $2.1 billion in development, regulatory, and sales milestones, beginning upon initiation of Phase 2 studies. Monte Rosa will co-fund any Phase 3 clinical development and will share any profits and losses associated with the manufacturing and commercialization of MRT-6160 in the U.S., and is also eligible for tiered royalties on ex-U.S. net sales.

About MRT-2359
MRT-2359 is a potent, highly selective, and orally bioavailable investigational molecular glue degrader (MGD) of GSPT1. 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. MRT-2359 is being investigated in an ongoing Phase 1/2 study (clinicaltrials.gov identifier NCT05546268) in solid tumors, including castration-resistant prostate cancer (CRPC). In CRPC patients resistant to AR therapy, a patient group characterized by widespread expression of c-MYC, MRT-2359 demonstrated encouraging early signals of clinical response.

About MRT-8102
MRT-8102 is a potent, highly selective, and orally bioavailable investigational molecular glue degrader (MGD) that targets NEK7 for the treatment of inflammatory diseases driven by IL-1β and the NLRP3 inflammasome. NEK7 has been shown to be required for NLRP3 inflammasome assembly, activation and IL-1β release both in vitro and in vivo. Aberrant NLRP3 inflammasome activation and the subsequent release of active IL-1β and interleukin-18 (IL-18) has been implicated in multiple inflammatory disorders, including cardiovascular disease, gout, osteoarthritis, neurologic disorders including Parkinson’s disease and Alzheimer’s disease, and metabolic disorders. In a non-human primate model, MRT-8102 was shown to potently, selectively, and durably degrade NEK7, and resulted in near-complete reductions of IL-1β and caspase-1 following ex vivo stimulation of whole blood. MRT-8102 has demonstrated a considerable safety margin (>200-fold exposure margin over projected human efficacious dose) in GLP toxicology studies.