MRT-2359, a molecular glue degrader (MGD) being developed for MYC-driven solid tumors, advancing in ongoing Phase 1/2 clinical trial; determination of recommended Phase 2 dose expected in Q2 2024; Phase 1 clinical data anticipated in H2 2024
MRT-6160, a VAV1-directed MGD in development for systemic and neurological autoimmune diseases, on track toward expected IND submission in Q2 2024 and initiation of Phase 1 SAD/MAD study mid-year; Phase 1 clinical data expected in Q1 2025
MRT-8102, a first-in-class NEK7-directed MGD and NLRP3/IL-1β pathway inhibitor, demonstrated efficient blood-brain barrier penetration and CNS activity in non-human primates (NHPs); IND submission on track for Q1 2025
New discovery program unveiled for CCNE1-directed MGDs; first to directly drug important, previously undruggable solid tumor oncology target
Strong cash position expected to fund operations into H1 2026, enabling advancement of MRT-2359, MRT-6160, and MRT-8102 programs through clinical milestones
“We’re excited by the significant advances made across our entire portfolio, including both our oncology and immunology/inflammation programs,” said
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) 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 today announced 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) andEuropean 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 today announced 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 today announced 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 onMay 21, 2024 , inWashington, 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 onJune 14, 2024 , inVienna, 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
Research and Development (R&D) Expenses: R&D expenses for the first quarter of 2024 were
General and Administrative (G&A) Expenses: G&A expenses for the first quarter of 2024 were
Net Loss: Net loss for the first quarter of 2024 was
Cash Position and Financial Guidance: Cash, cash equivalents, restricted cash, and marketable securities as of
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.
About Monte Rosa
Forward-Looking Statements
This communication includes express and implied “forward-looking statements,” including forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Forward-looking statements include all statements that are not historical facts and in some cases, can be identified by terms such as “may,” “might,” “will,” “could,” “would,” “should,” “expect,” “intend,” “plan,” “objective,” “anticipate,” “believe,” “estimate,” “predict,” “potential,” “continue,” “ongoing,” or the negative of these terms, or other comparable terminology intended to identify statements about the future. Forward-looking statements contained herein include, but are not limited to, statements about our ability to grow our product pipeline, statements around the Company’s QuEEN™ discovery engine and the Company’s view of its potential to identify degradable protein targets and rationally design MGDs with unprecedented selectivity, statements around the power and differentiation of the QuEEN discovery engine and the potential of the Company’s MGDs against a broad spectrum of targets, statements about the advancement and timeline of our preclinical and clinical programs, pipeline and the various products therein, including (i) our product development activities, our ongoing clinical development of MRT-2359, our expectations to announce the recommended Phase 2 dose later in the second quarter of 2024, the timing for our disclosure of any initial data from our Phase 1 clinical trial of MRT-2359 in the second half of 2024, and our plans to initiate the Phase 2 portion of the study before year-end, (ii) the ongoing development of MRT-6160, and the planned submission of an IND to the FDA for MRT-6160 in the second quarter of 2024, our expectations of timing for initiation of a Phase 1 SAD/MAD study mid-2024 and the timing for our disclosure of Phase 1 clinical data of MRT-6160 in the first quarter of 2025, as well as our expectation to present additional preclinical data in models of autoimmune and inflammatory diseases at the upcoming DDW and
Consolidated Balance Sheets | ||||||||
(in thousands, except share amounts) | ||||||||
(Unaudited) | ||||||||
2024 | 2023 | |||||||
Assets | ||||||||
Current assets: | ||||||||
Cash and cash equivalents | $ | 99,752 | $ | 128,101 | ||||
Marketable securities | 93,140 | 104,312 | ||||||
Other receivables | 601 | 505 | ||||||
Prepaid expenses and other current assets | 5,543 | 3,294 | ||||||
Total current assets | 199,036 | 236,212 | ||||||
Property and equipment, net | 34,036 | 33,803 | ||||||
Operating lease right-of-use assets | 28,422 | 28,808 | ||||||
Restricted cash | 4,863 | 4,580 | ||||||
Other long-term assets | 389 | 352 | ||||||
Total assets | $ | 266,746 | $ | 303,755 | ||||
Liabilities and stockholders’ equity | ||||||||
Current liabilities: | ||||||||
Accounts payable | $ | 6,828 | $ | 11,152 | ||||
Accrued expenses and other current liabilities | 10,713 | 14,600 | ||||||
Current deferred revenue | 20,407 | 17,678 | ||||||
Current portion of operating lease liability | 3,345 | 3,162 | ||||||
Total current liabilities | 41,293 | 46,592 | ||||||
Deferred revenue, net of current | 28,529 | 32,323 | ||||||
Defined benefit plan liability | 2,568 | 2,713 | ||||||
Operating lease liability | 41,837 | 42,877 | ||||||
Total liabilities | 114,227 | 124,505 | ||||||
Commitments and contingencies | ||||||||
Stockholders’ equity | ||||||||
Common stock, | 5 | 5 | ||||||
Additional paid-in capital | 553,063 | 547,857 | ||||||
Accumulated other comprehensive loss | (2,693 | ) | (2,724 | ) | ||||
Accumulated deficit | (397,856 | ) | (365,888 | ) | ||||
Total stockholders’ equity | 152,519 | 179,250 | ||||||
Total liabilities and stockholders’ equity | $ | 266,746 | $ | 303,755 |
Consolidated Statement of Operations and Comprehensive Loss | ||||||||
(in thousands, except share and per share amounts) | ||||||||
(unaudited) | ||||||||
Three months ended | ||||||||
2024 | 2023 | |||||||
Collaboration revenue | $ | 1,064 | $ | — | ||||
Operating expenses: | ||||||||
Research and development | 27,026 | 26,755 | ||||||
General and administrative | 8,985 | 7,504 | ||||||
Total operating expenses | 36,011 | 34,259 | ||||||
Loss from operations | (34,947 | ) | (34,259 | ) | ||||
Other income (expense): | ||||||||
Interest income, net | 2,442 | 2,437 | ||||||
Foreign currency exchange (loss) gain, net | 620 | (85 | ) | |||||
Loss on sale of marketable securities | — | (131 | ) | |||||
Total other income | 3,062 | 2,221 | ||||||
Net loss before income taxes | (31,885 | ) | (32,038 | ) | ||||
Provision for income taxes | (83 | ) | — | |||||
Net loss | $ | (31,968 | ) | $ | (32,038 | ) | ||
Net loss per share—basic and diluted | $ | (0.53 | ) | $ | (0.65 | ) | ||
Weighted-average number of shares outstanding used in computing net loss per common share—basic and diluted | 60,156,187 | 49,347,473 | ||||||
Comprehensive loss: | ||||||||
Net loss | $ | (31,968 | ) | $ | (32,038 | ) | ||
Other comprehensive loss: | ||||||||
Provision for pension benefit obligation | 35 | 14 | ||||||
Unrealized gain (loss) on available-for-sale securities | (4 | ) | 345 | |||||
Comprehensive loss | $ | (31,937 | ) | $ | (31,679 | ) |
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Source:
2024 GlobeNewswire, Inc., source