On November 9, 2023 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 quarter ended September 30, 2023 (Press release, Monte Rosa Therapeutics, NOV 9, 2023, View Source [SID1234637403]).

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!

"This has been a pivotal time for Monte Rosa as we announced both our first clinical data and our first major strategic collaboration," said Markus Warmuth, M.D., Chief Executive Officer of Monte Rosa Therapeutics. "We’re very excited about the clinical data for MRT-2359, our GSPT1-directed molecular glue degrader, and in particular the early signs of clinical activity in MYC-driven solid tumors. We’re equally excited to partner with Roche to enable and accelerate expansion of our QuEEN discovery engine to discover and develop molecular glues against targets previously considered impossible to drug for cancer and neurological diseases. We also completed a registered direct offering that, together with our ongoing pipeline prioritization efforts, is expected to extend our cash runway into the first half of 2026. We look forward to continuing to execute on our pipeline, including delivering Phase 2 interim data for MRT-2359 and Phase I healthy volunteer data for our immunology and inflammation-directed VAV1 and NEK7 programs."

THIRD QUARTER 2023 AND RECENT HIGHLIGHTS

•
Announced interim clinical data from the ongoing MRT-2359 Phase 1/2 study demonstrating favorable pharmacokinetic (PK), pharmacodynamic (PD), and tolerability profiles in heavily pre-treated patients with MYC-driven solid tumors, including lung cancers and high-grade neuroendocrine tumors. MRT-2359 showed evidence of tumor size reductions, including partial responses, in heavily pretreated patients with biomarker-positive tumors. Optimal PD modulation of GSPT1 in peripheral blood mononuclear cells and tumor tissue biopsies was observed at all dose levels, consistent with its designed activity based on preclinical studies.
•
Entered into a strategic collaboration and licensing agreement with global healthcare leader Roche to discover and develop MGDs against targets in cancer and neurological diseases. Under the terms of the agreement, Monte Rosa Therapeutics will receive an upfront payment of $50 million, and is eligible to receive future preclinical, clinical, commercial and sales milestone payments that could exceed $2 billion, as well as tiered royalties.

•
Completed a $25 million registered direct offering, priced at-the-market under Nasdaq rules, with a life sciences-dedicated investor.
•
Presented preclinical data at the American College of Rheumatology (ACR) Convergence Annual Meeting demonstrating the potential of MRT-6160, a VAV1-targeting MGD, to treat immunological and inflammatory diseases. The data show that MRT-6160 attenuated disease progression in a murine collagen-induced arthritis (CIA) model.
•
Appointed Anthony M. Manning, Ph.D., to the Company’s Board of Directors. Dr. Manning is a highly accomplished drug discovery leader in the field of autoimmune and inflammatory diseases.
•
Discontinued sickle cell disease program to prioritize internal efforts on ongoing clinical-, Investigational New Drug (IND)- and lead optimization-stage programs.

UPCOMING MILESTONES

•
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.

THIRD QUARTER 2023 FINANCIAL RESULTS

Research and Development (R&D) Expenses: R&D expenses for the third quarter of 2023 were $28.3 million, compared to $21.3 million for the third quarter of 2022. These increases were driven by the successful achievement of key milestones in our R&D organization, including the advancement of MRT-2359 in the clinic, the progression of our preclinical pipeline, and the continued development of the Company’s QuEEN platform for discovery efforts. The increase in R&D expenses was driven by increased headcount and laboratory-related expenses to achieve these milestones. Non-cash stock-based compensation constituted $2.3 million of R&D expenses for Q3 2023, compared to $1.7 million in the same period in 2022.

General and Administrative (G&A) Expenses: G&A expenses for the third quarter of 2023 were $8.7 million compared to $7.0 million for the third quarter of 2022. The increase in G&A expenses was a result of increased headcount and expenses in support of the company’s growth and operations. G&A expenses included non-cash stock-based compensation of $2.2 million for the third quarter of 2023, compared to $1.5 million for the same period in 2022.

Net Loss: Net loss for the third quarter of 2023 was $34.9 million, compared to $27.3 million for the third quarter of 2022.

Cash Position and Financial Guidance: Cash, cash equivalents, restricted cash, and marketable securities as of September 30, 2023, were $183.0 million, compared to cash, cash equivalents, restricted cash, and marketable securities of $207.6 million as of June 30, 2023. The decrease of $24.6 million was primarily related to cash used to fund operations. The September 30, 2023, cash and equivalents balance does not include the $50 million upfront payment from Roche or the approximately $25 million proceeds from the registered direct offering, which were received after the end of Q3 2023.

The company expects its cash and cash equivalents, including proceeds from the Roche collaboration, will be sufficient to fund planned operations and capital expenditures into the first half of 2026.

About MRT-2359

MRT-2359 is a potent, 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 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.