On May 9, 2024 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 ending March 31, 2024 (Press release, Monte Rosa Therapeutics, MAY 9, 2024, View Source [SID1234643008]).
Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:
Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing
Schedule Your 30 min Free Demo!
"We’re excited by the significant advances made across our entire portfolio, including both our oncology and immunology/inflammation programs," said Markus Warmuth, M.D., Chief Executive Officer of Monte Rosa Therapeutics. "Our Phase 1/2 clinical trial evaluating MRT-2359 for MYC-driven solid tumors is on track and we plan to announce the recommended Phase 2 dose later this quarter and to report clinical data from this program in the second half of the year. We eagerly anticipate the initiation of a Phase 1 study of MRT-6160, the first of our MGD drug candidates for immune-related diseases, in mid-2024, with results from the study expected in Q1 2025. Preclinical GLP toxicology data we’ve announced today, along with data in multiple disease models, suggest the potential for a highly differentiated profile across multiple autoimmune diseases. Additionally, MRT-8102, our NEK7-directed MGD targeting diseases driven by IL-1β and the NLRP3 inflammasome, is rapidly progressing toward clinical studies. We’ve recently demonstrated strong CNS exposure and NEK7 degradation in non-human primates, supporting the potential development of MRT-8102 in neurologic indications and obesity amongst others, in addition to its potential use in gout, pericarditis, and other peripheral inflammatory conditions. We’re also very pleased to announce our discovery program for CCNE1 (Cyclin E1), a well-validated oncology target generally considered undruggable by conventional modalities. We believe our ability to degrade CCNE1 potently and selectively and to elicit anti-tumor activity in in vivo models provides further validation for the differentiation of our QuEEN discovery engine and the potential of our MGDs against a broad spectrum of targets."
Dr. Warmuth concluded, "The rapid and efficient progression of our pipeline clearly illustrates the power of our AI/ML-driven QuEEN discovery engine. Through our ongoing internal efforts as well as our research collaboration with Roche, we look forward to continuing this strong progress."
RECENT HIGHLIGHTS
MRT-2359, GSPT1-directed MGD for MYC-driven solid tumors
•
Monte Rosa continues to evaluate MRT-2359 in a Phase 1/2 clinical trial in MYC-driven solid tumors (NCT05546268). Enrollment is ongoing in backfill cohorts at clinically active doses using a 5-days-on, 9-days-off drug schedule and in dose escalation cohorts using a 21-days-on, 7-days-off drug schedule. The Company is on track to determine the recommended Phase 2 dose (RP2D) in Q2 2024 and report Phase 1 study results in H2 2024. Monte Rosa expects to initiate the Phase 2 portion of the study before year-end.
•
The Company presented preclinical data at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting demonstrating that treatment with MRT-2359 resulted in marked tumor regressions in the AR-V7- and c-MYC-expressing 22RV1 xenograft mouse model of prostate cancer associated with resistance to anti-androgen agents.
MRT-6160, VAV1-directed MGD for systemic and neurological autoimmune/inflammatory diseases
•
The MRT-6160 program is on track for an anticipated Investigational New Drug (IND) submission to the U.S. Food and Drug Administration (FDA) in Q2 2024, and initiation of a Phase 1 single ascending dose/multiple ascending dose (SAD/MAD) study in mid-2024. Phase 1 results are anticipated in Q1 2025.
•
The Company reported additional results from completed preclinical GLP toxicology studies of MRT-6160 in rats and non-human primates (NHPs). The data demonstrate a highly favorable safety profile with no significant changes in peripheral immune cell compartments.
•
Monte Rosa expects to present additional preclinical data for MRT-6160 in models of autoimmune and inflammatory diseases at the upcoming Digestive Disease Week (DDW) and European Alliance of Associations for Rheumatology (EULAR) medical meetings.
MRT-8102, NEK7-directed MGD for inflammatory diseases driven by IL-1β and the NLRP3 inflammasome
•
In March 2024, Monte Rosa announced the initiation of IND-enabling 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, critical elements of the inflammatory process. This is the first development candidate to be declared from the Company’s NEK7 development program.
•
Monte Rosa reported that MRT-8102 has demonstrated highly favorable CNS exposure and degradation in a study in cynomolgus monkeys. The data support the potential for development of MRT-8102 in diseases including Parkinson’s disease, Alzheimer’s disease, and obesity. The Company is evaluating applications across multiple inflammatory disorders.
•
Monte Rosa expects to submit an IND application for MRT-8102 in Q1 2025.
CCNE1-directed MGD program for CCNE1-amplified tumors
•
Monte Rosa reported a new discovery program for CCNE1 (Cyclin E1)-directed MGDs for the treatment of CCNE1-amplified tumors. CCNE1, a key component of the cell cycle and a known driver of many cancers, is generally considered an undruggable target by conventional modalities.
Additional corporate updates
•
In October 2023, Monte Rosa entered into a strategic collaboration and licensing agreement with Roche, a global healthcare leader, to discover and develop MGDs against targets in cancer and neurological diseases. The collaboration continues to advance research activities according to plan.
ANTICIPATED MILESTONES
•
Announce the recommended Phase 2 dose for the MRT-2359 Phase 1/2 study in Q2 2024 and report Phase 1 clinical results in H2 2024. Initiate the Phase 2 portion of the study before year-end. The Company is evaluating Phase 2 expansion cohorts in high-prevalence c-MYC-driven tumors including hormone receptor-positive breast cancer and prostate cancer, as well as tumor types and patient populations driven by L- and N-MYC including non-small cell lung cancer (NSCLC), small cell lung cancer (SCLC), and solid tumors with amplifications of L- and N-MYC.
•
Submit an IND application for MRT-6160 in Q2 2024 and initiate a Phase 1 SAD/MAD study in healthy volunteers in mid-2024; report results from the Phase 1 study in Q1 2025. Monte Rosa expects to subsequently initiate proof-of-concept (POC) studies in autoimmune/inflammatory diseases including ulcerative colitis and rheumatoid arthritis, with additional potential POC studies in dermatology, rheumatology, and neurology indications.
•
Submit an IND application for MRT-8102 in Q1 2025.
•
Nominate a development candidate for the CDK2 preclinical program in 2024.
UPCOMING PRESENTATIONS
•
Monte Rosa plans to present a poster at the Digestive Disease Week (DDW) Conference on May 21, 2024, in Washington, DC, titled, "MRT-6160, a VAV1-Directed Molecular Glue Degrader, Inhibits Disease Progression in a T-cell Transfer Mediated Murine Colitis Model Concomitant with Reduced Calprotectin Expression."
•
Monte Rosa plans to present a poster at the European Alliance of Associations for Rheumatology (EULAR) Conference on June 14, 2024, in Vienna, Austria, titled, "MRT-6160, a VAV1-Directed Molecular Glue Degrader, Reduces Joint Inflammation, Cytokine Production, and Autoantibody Levels in a Collagen-Induced Arthritis Disease Model."
FIRST QUARTER 2024 FINANCIAL RESULTS
Collaboration Revenue: Collaboration revenue for the first quarter of 2024 was $1.1 million, compared with $0 during the same period in 2023. Collaboration revenue represents revenue recorded under the Roche License and Collaboration agreement.
Research and Development (R&D) Expenses: R&D expenses for the first quarter of 2024 were $27.0 million, compared to $26.8 million during the same period in 2023. R&D expenses 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, the preparation of MRT-6160 to enter the clinic, and the continued development of the Company’s QuEEN discovery engine. Non-cash stock-based compensation constituted $2.7 million of R&D expenses for Q1 2024, compared to $2.1 million in the same period in 2023.
General and Administrative (G&A) Expenses: G&A expenses for the first quarter of 2024 were $9.0 million compared to $7.5 million during the same period in 2023. The increase in G&A expenses was a result of increased headcount, stock-based compensation expense, and fees paid to consultants in order to support our growth and operations. G&A expenses included non-cash stock-based compensation of $2.2 million for the first quarter of 2024, compared to $1.8 million for the same period in 2022.
Net Loss: Net loss for the first quarter of 2024 was $32.0 million, compared to $33.3 million for the fourth quarter of 2023.
Cash Position and Financial Guidance: Cash, cash equivalents, restricted cash, and marketable securities as of March 31, 2024, were $197.8 million, compared to cash, cash equivalents, restricted cash, and marketable securities of $237.0 million as of December 31, 2023. The decrease of $39.2 million was primarily due to operational use of cash.
The Company expects its cash and cash equivalents to be sufficient to fund planned operations and capital expenditures into the first half of 2026.
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 systemic and neurological autoimmune indications, such as multiple sclerosis, rheumatoid arthritis, inflammatory bowel disease, and dermatological disorders. Preclinical studies have demonstrated that MRT-6160 can inhibit disease progression in in vivo autoimmunity models.
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 gout, cardiovascular disease, neurologic disorders including Parkinson’s disease and Alzheimer’s disease, ocular disease, diabetes, obesity, and liver disease. 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 models following ex vivo stimulation of whole blood. MRT-8102 has shown a favorable profile in non-GLP toxicology studies.