Monte Rosa Therapeutics AG

Dive Brief:Sanofi will advance an experimental inflammatory disease drug into Phase 2 clinical testing after its biotechnology company partner KymeraTherapeutics reported Wednesday what it described as encouraging results from a small study.The trial was designed to test whether Kymeras drug would be processed in the bodies of people with one of two inflammatory skin conditions in the same way as it had in healthy volunteers. Not only did the drug meet that goal, but study data suggested clinical improvements such as clearing skin and lessened itching.Kymera described these early results as important for the science behind its drug, a pill designed to degrade harmful proteins. We believe that, for the first time, we have demonstrated clinical impact of a degrader, KT-474, outside of oncology and in complex inflammatory diseases, said Kymera CEO Nello Mainolfi in a statement.Dive Insight:Kymera is one of several biotech companies working on protein-degrading drugs, along with Arvinas, C4 Therapeutics, Nurix Therapeutics, Monte Rosa Therapeutics and Lycia Therapeutics.The startups have raised significant funding from venture and public investors, as well as drawn the attention of large pharmaceutical companies like Pfizer, Roche, Vertex Pharmaceuticals and Sanofi.Their basic idea is to use small molecule drugs to degrade or destroy disease-causing proteins, rather than finding ways to bind to them and thereby block their activity.Arvinas, C4 and Nurix have each made their way into clinical testing with protein-degrading drugs, but their programs are focused on cancers.While Kymera is working in oncology, too, it is further along with its inflammatory disease drug, dubbed KT-474. Two years ago, Sanofi paid Kymera $150 million to access KT-474 and an earlier-stage program, which are aimed at a protein known as IRAK4 thats thought to play a role in diseases like hidradenitis suppurativa, atopic dermatitis and rheumatoid arthritis.The data released Wednesday are the most tangible sign of the drugs potential, suggesting it could work as intended in hidradenitis suppurativa or atopic dermatitis and potentially curb some of patientssymptoms. A Phase 2 study, which Sanofi intends to start in 2023, would be a much higher hurdle of whether KT-474 can actually benefit patients in a significant way, however.Still, Kymera is encouraged and views the data it generated as clinical validation for targeting IRAK4 with a protein degrader. Data showed that its drug knocked down IRAK4 levels in both the blood and skin.Treatment was also generally well tolerated. No serious side effects or drug-related infections were reported, and no patients discontinued the drug or lowered its dose due to adverse events. Kymera did note modest, non-adverse changes in heart rhythm, known as QTcF prolongation, between days 7 and 14 in the study, which later resolved spontaneously.The HS and AD patient data are encouraging as they highlight the broad potential of KT-474 and continue to validate Sanofis commitment to the target and to [targeted protein degradation]s unique ability to unlock this critical pathway, said Naimish Patel, Sanofis head of global development for immunology and inflammation, in a statement.Shares in Kymera rose by as much as 32% Wednesday, before falling back to trade up 20%.Also on Wednesday, Kymerasaid testing of two of its protein degraders in cancer continue to advance and that it would share additional data next year. '

– Initiated Patient Dosing in Phase 1/2 Clinical Trial Evaluating MRT-2359, a GSPT1-directed Molecular Glue Degrader, for Treatment of MYC-driven Tumors – – Progressed VAV1 Molecular Glue Degrader Program into Lead Optimization – BOSTON, Nov. 10, 2022 (GLOBE NEWSWIRE) -- Monte Rosa Therapeutics, Inc. (NASDAQ: GLUE), a biotechnology company developing novel molecular glue degrader (MGD)-based medicines, today reported business highlights and financial results for the third quarter, ended September 30, 2022. “Throughout 2022, we have made important strides in advancing our QuEEN™ platform and our portfolio of MGDs derived from it, including our GSPT1 degrader MRT-2359. The FDA’s clearance of our first investigational new drug application, along with the recent initiation of patient dosing of MRT-2359 in our clinical trial in MYC-driven tumors, serve as strong validation of our platform, the quality of our team and the level of innovation we are bringing to the field,” said Markus Warmuth, M.D., CEO of Monte Rosa. “We are continually progressing toward our goal of discovering and developing MGDs into a new generation of precision medicines for patients who currently have no real alternatives. With a strong cash position and investor support, we are well positioned to continue to execute on our first clinical program, as well as advance additional discovery programs through lead optimization.” THIRD QUARTER 2022 & RECENT HIGHLIGHTS Received a Study May Proceed Letter from the U.S. Food and Drug Administration (FDA) to begin a Phase 1/2 clinical trial for MRT-2359, a potent, selective and orally bioavailable GSPT1-directed MGDRecently initiated patient dosing with MRT-2359, evaluating the treatment of MYC-driven solid tumors, including lung cancerAdvanced VAV1 degrader program into lead optimization; VAV1 plays a key role in T-cell and B-cell development and activation and is a highly validated target for multiple autoimmune diseases, as well as several types of lymphomaContinued progress of CDK2 and NEK7 programs toward development candidate nominationsEntered into collaboration with Professor Sereina Riniker, Ph.D., (ETH Zürich) to integrate molecular dynamics into Monte Rosa’s AI/ML engine for target identification and virtual screeningGave multiple presentations at the 5th Annual Targeted Protein Degradation Summit in October in Boston, which included new and updated preclinical data supporting development of MRT-2359 in MYC-driven lung cancer, and novel AI applications for the discovery of MGDsPresented overview of development of MRT-2359 as a GSPT1-directed MGD to target MYC-driven malignancies at the 34th EORTC-NCI-AACR Symposium on Oct. 28 in Barcelona, Spain UPCOMING INVESTOR EVENTS Monte Rosa will be participating in the following upcoming investor conferences: Jefferies 13th Annual Global Healthcare Conference, Nov. 15-17, LondonPiper Sandler 34th Annual Healthcare Conference, Nov. 29-Dec. 1, New York41st Annual J.P. Morgan Health Care Conference, Jan. 9-12, 2023, San Francisco THIRD QUARTER 2022 FINANCIAL RESULTS Research and Development (R&D) Expenses: R&D expenses for the third quarter of 2022 were $21.3 million, compared to $15.1 million for the third quarter of 2021. These increases were due to the expansion of R&D activities, including the advancement of MRT-2359 toward clinical development and the development of the company’s QuEEN™ platform and its preclinical programs, as well as increased headcount and laboratory-related expenses due to the company’s continued growth as an R&D organization. R&D expenses for the third quarter of 2022 included non-cash stock-based compensation of $1.7 million and non-cash lease expense of $1.5 million due to a rent holiday on the company’s Harrison Avenue facility lease. The same period in 2021 included non-cash stock-based compensation expense of $1.1 million. General and Administrative (G&A) Expenses: G&A expenses for the third quarter of 2022 were $7.0 million, compared to $4.8 million for the third quarter of 2021. The increase in G&A expenses was a result of additional expenses incurred in support of the company’s growth and operations as a public company. G&A expenses included non-cash stock-based compensation of $1.5 million for the third quarter of 2022, compared to $1.0 million for the same period in 2021. Net Loss: Net loss for the third quarter of 2022 was $27.3 million, compared to $19.8 million for the third quarter of 2021. Cash Position and Financial Guidance: Cash, cash equivalents, restricted cash and marketable securities as of September 30, 2022, were $277.4 million, compared to cash, cash equivalents and restricted cash of $299.5 million as of June 30, 2022. The decrease is primarily related to cash used to fund operations of $20.6 million and cash used for fixed assets of $1.4 million, partially off-set by proceeds from the exercise of stock options of $0.1 million. The company expects that its cash and cash equivalents will be sufficient to fund planned operations and capital expenditures into late 2024. About Monte RosaMonte Rosa Therapeutics is a biotechnology company developing a portfolio of novel molecular glue degrader (MGD) medicines. These medicines are designed to employ the body’s natural mechanisms to selectively eliminate therapeutically relevant proteins. The company has developed a proprietary protein degradation platform, called QuEEN™ (Quantitative and Engineered Elimination of Neosubstrates), that enables it to rapidly identify protein targets and MGD product candidates that are designed to eliminate therapeutically relevant proteins in a highly selective manner. The company’s drug discovery platform combines diverse and proprietary chemical libraries of small molecule protein degraders with in-house proteomics, structural biology, AI/machine learning-based target selection, and computational chemistry capabilities to predict and obtain protein degradation profiles. For more information, visit www.monterosatx.com. Forward-Looking StatementsThis 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 in herein include, but are not limited to, statements about our product development activities, including our expectations around MRT-2359 and the ongoing development of our QuEEN™ platform, and the advancement of our pipeline and the various products therein, , our expectations of timing for of our clinical trial for MRT-2359, our ability to initiate and the timing of initiation of additional lead optimization programs, and our expectations regarding our ability to nominate and the timing of our nominations of additional development candidates. By their nature, these statements are subject to numerous risks and uncertainties, including the impact that the current COVID-19 pandemic will have on our development activities and operations, as well as those risks and uncertainties set forth in our most recent Quarterly Report on Form 10-Q and Annual Report on Form 10-K for the year ended December 31, 2021 filed with the US Securities and Exchange Commission, and any subsequent filings, that could cause actual results, performance or achievement to differ materially and adversely from those anticipated or implied in the statements. You should not rely upon forward looking statements as predictions of future events. Although our management believes that the expectations reflected in our statements are reasonable, we cannot guarantee that the future results, performance or events and circumstances described in the forward-looking statements will be achieved or occur. Recipients are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date such statements are made and should not be construed as statements of fact. We undertake no obligation to publicly update any forward-looking statements, whether as a result of new information, any future presentations or otherwise, except as required by applicable law. Certain information contained in these materials and any statements made orally during any presentation of these materials that relate to the materials or are based on studies, publications, surveys and other data obtained from third-party sources and our own internal estimates and research. While we believe these third-party studies, publications, surveys and other data to be reliable as of the date of these materials, we have not independently verified, and make no representations as to the adequacy, fairness, accuracy or completeness of, any information obtained from third-party sources. In addition, no independent source has evaluated the reasonableness or accuracy of our internal estimates or research and no reliance should be made on any information or statements made in these materials relating to or based on such internal estimates and research. Consolidated Balance Sheets(in thousands, except share and per share amounts)(unaudited) September 30, December 31, 2022 2021 Assets Current assets: Cash and cash equivalents $112,394 $346,071 Marketable securities 159,755 — Proceeds receivable from common stock sale 13,507 — Other receivables 4,050 — Prepaid expenses and other current assets 4,569 2,595 Current restricted cash 960 — Total current assets 295,235 348,666 Property and equipment, net 19,384 12,325 Operating lease right-of-use assets 38,534 — Restricted cash, net of current 4,302 5,338 Other long-term assets 148 — Total assets $357,603 $366,329 Liabilities and stockholders’ equity Current liabilities: Accounts payable $9,753 $6,558 Accrued expenses and other current liabilities 8,972 10,080 Current portion of operating lease liability 3,065 — Total current liabilities 21,790 16,638 Defined benefit plan liability 2,128 2,176 Operating lease liability 42,593 — Total liabilities 66,511 18,814 Commitments and contingencies Stockholders’ equity Common stock, $0.0001 par value; 500,000,000 shares authorized, 48,528,247 shares issued and 48,372,781 shares outstanding as of September 30, 2022; and 500,000,000 shares authorized, 46,794,295 shares issued and 46,535,966 shares outstanding as of December 31, 2021 5 5 Additional paid-in capital 493,443 471,566 Accumulated other comprehensive loss (2,602) (2,021)Accumulated deficit (199,754) (122,035)Total stockholders’ equity 291,092 347,515 Total liabilities and stockholders’ equity $357,603 $366,329 Consolidated Statement of Operations(in thousands, except share and per share amounts)(unaudited) Three months endedSeptember 30, 2022 2021 Operating expenses: Research and development $21,342 $15,115 General and administrative 7,020 4,753 Total operating expenses 28,362 19,868 Loss from operations (28,362) (19,868) Other income: Interest income, net 997 13 Foreign currency exchange gain, net 63 18 Loss on disposal of fixed assets (16) — Total other income 1,044 31 Net loss $(27,318) $(19,837) Net loss per share attributable to common stockholders—basic and diluted $(0.58) $(0.43) Weighted-average number of shares outstanding used in computing net loss per common share—basic and diluted 46,732,353 45,987,866 Contacts: InvestorsShai Biran, Monte Rosa Therapeuticsir@monterosatx.com MediaDan Budwick, 1ABdan@1abmedia.com

BOSTON, Nov. 01, 2022 (GLOBE NEWSWIRE) -- Monte Rosa Therapeutics, Inc. (NASDAQ: GLUE), a biotechnology company developing novel molecular glue degrader (MGD)-based medicines, today announced the company has dosed the first patient in its Phase 1/2 clinical trial evaluating MRT-2359 for the treatment of MYC-driven solid tumors, including lung cancer. MRT-2359 is a potent, selective and orally bioavailable GSPT1-directed MGD, designed to disrupt protein synthesis in MYC-driven tumors, and lead to anti-tumor activity. “MYC transcription factors are well-defined drivers of human cancers, and disrupting protein translation has emerged as a promising path to address this highly prevalent disease pathway. Dosing the first patient is a significant milestone in developing MRT-2359 as a therapeutic option for MYC-driven cancers,” said Filip Janku, M.D., Ph.D., Chief Medical Officer of Monte Rosa. “We have designed our Phase 1 trial to move efficiently through dose escalation and, by focusing on tumor types where MYC expression is prevalent, to improve our chances of seeing early signals of clinical activity. We are encouraged by the strong preclinical data and hope that MRT-2359 will make a meaningful difference in the lives of patients.” The Phase 1/2, open-label, multicenter study will primarily assess the safety, tolerability, pharmacokinetic (PK), pharmacodynamic (PD) and preliminary clinical activity of MRT-2359 in patients with previously treated selected solid tumors, including non-small cell lung cancer (NSCLC), small cell lung cancer (SCLC), high-grade neuroendocrine cancer of any primary site, diffuse large B-cell lymphoma (DLBCL) and solid tumors with L-MYC or N-MYC amplification. In the Phase 1 portion of the study, patients will receive escalating doses of MRT-2359 to determine the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D). Once the RP2D is determined, the anti-tumor activity of MRT-2359 will be assessed as part of the Phase 2 portion of the study, which includes molecular biomarkers for stratification and selection. To learn more about the MRT-2359 clinical trial, visit clinicaltrials.gov (Identifier: NCT05546268). About MRT-2359 MRT-2359 is a potent, selective and orally bioavailable molecular glue degrader (MGD) that induces the interaction between the E3 ubiquitin ligase component cereblon (CRBN) 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. Our preclinical studies have shown that this addiction to MYC-induced protein translation creates a dependency on GSPT1. MRT-2359 exploits this vulnerability by inducing degradation of GSPT1, disrupting protein synthesis preferentially in MYC-driven cell lines and leading to anti-tumor activity in MYC-driven tumor models. Our ongoing Phase 1/2 clinical study aims to evaluate the safety, tolerability and anti-tumor activity of MRT-2359. About Monte Rosa Monte Rosa Therapeutics is a biotechnology company developing a portfolio of novel molecular glue degrader (MGD) medicines. These medicines are designed to employ the body’s natural mechanisms to selectively eliminate therapeutically relevant proteins. The company has developed a proprietary protein degradation platform, called QuEEN™ (Quantitative and Engineered Elimination of Neosubstrates), that enables it to rapidly identify protein targets and MGD product candidates that are designed to eliminate therapeutically relevant proteins in a highly selective manner. The company’s drug discovery platform combines diverse and proprietary chemical libraries of small molecule protein degraders with in-house proteomics, structural biology, AI/machine learning-based target selection, and computational chemistry capabilities to predict and obtain protein degradation pro For more information, visit . 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 in herein include, but are not limited to, statements about our product development activities, including our expectations around MRT-2359, the ongoing development of our QuEEN™ platform and the advancement of our pipeline and the various products therein, our expectations of timing of our clinical trial for MRT-2359, our ability to initiate and the timing of initiation of additional lead optimization programs, and our expectations regarding our ability to nominate and the timing of our nominations of additional development candidates. By their nature, these statements are subject to numerous risks and uncertainties, including the impact that the current COVID-19 pandemic will have on our development activities and operations, as well as those risks and uncertainties set forth in our most recent Quarterly Report on Form 10-Q and Annual Report on Form 10-K for the year ended December 31, 2021 filed with the US Securities and Exchange Commission, and any subsequent filings, that could cause actual results, performance or achievement to differ materially and adversely from those anticipated or implied in the statements. You should not rely upon forward looking statements as predictions of future events. Although our management believes that the expectations reflected in our statements are reasonable, we cannot guarantee that the future results, performance or events and circumstances described in the forward-looking statements will be achieved or occur. Recipients are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date such statements are made and should not be construed as statements of fact. We undertake no obligation to publicly update any forward-looking statements, whether as a result of new information, any future presentations or otherwise, except as required by applicable law. Certain information contained in these materials and any statements made orally during any presentation of these materials that relate to the materials or are based on studies, publications, surveys and other data obtained from third-party sources and our own internal estimates and research. While we believe these third-party studies, publications, surveys and other data to be reliable as of the date of these materials, we have not independently verified, and make no representations as to the adequacy, fairness, accuracy or completeness of, any information obtained from third-party sources. In addition, no independent source has evaluated the reasonableness or accuracy of our internal estimates or research and no reliance should be made on any information or statements made in these materials relating to or based on such internal estimates and research. Contacts: Investors Shai Biran, Monte Rosa Therapeutics ir@monterosatx.com Media Dan Budwick, 1AB dan@1abmedia.com