Monte Rosa Therapeutics Inc. (NASDAQ:GLUE) shared interim data from an ongoing Phase 1/2 clinical study evaluating MRT-2359 in combination with enzalutamide in heavily pretreated patients with metastatic castration-resistant prostate cancer (mCRPC).The Phase 1/2 study evaluated 0.5 mg and 0.75 mg of MRT-2359 administered orally on a 21-days-on, 7-day-off drug schedule in combination with Pfizer Inc. (NYSE:PFE) and Astellas Pharma Inc.’s (OTC:ALPMF) (OTC:ALPMY) Xtandi (enzalutamide).The study population, as ...

Summary of Monte Rosa Therapeutics Conference Call Company Overview - **Company**: Monte Rosa Therapeutics (NasdaqGS:GLUE) - **Focus**: Development of MRT-2359, a GSPT-1-directed molecular glue degrader for treating metastatic castration-resistant prostate cancer (CRPC) Key Industry Insights - **Target Market**: Heavily pretreated metastatic castration-resistant prostate cancer patients, particularly those with androgen receptor (AR) mutations - **Market Opportunity**: Up to 30% of metastatic CRPC patients in later lines of therapy carry AR mutations, indicating a substantial market potential for MRT-2359 [6][25] Core Findings from Clinical Trials - **Clinical Activity**: In a small phase II expansion arm, MRT-2359 combined with enzalutamide showed a 100% PSA response rate in four patients with AR mutations, with two patients achieving PSA 90 responses and two achieving PSA 50 responses [5][17] - **Disease Control Rate**: The overall disease control rate was 64% across 14 patients, with two RECIST partial responses and several patients showing stable disease [6][18] - **Safety Profile**: The combination was well tolerated, with mild to moderate gastrointestinal adverse events being the most common, suggesting a favorable safety profile compared to other therapies [6][17] Mechanism of Action - **MRT-2359 Mechanism**: Acts as a molecular glue degrader of GSPT-1, leading to the degradation of MYC and other oncoproteins, which is critical for the growth of prostate cancer cells [7][9] - **Preclinical Evidence**: Prostate cancer cell lines with high MYC expression showed greater sensitivity to MRT-2359, supporting its therapeutic rationale [10][11] Future Directions - **Next Steps**: Plans to initiate a signal-confirming phase II study in 2026, focusing on AR mutant patients and potentially expanding to earlier line settings [24][25] - **Study Design**: The upcoming study will utilize a Simon's two-stage design, enrolling up to 25 patients with metastatic CRPC and AR mutations, with endpoints including PSA response and safety [24] Pipeline Updates - **Other Programs**: Progress on MRT-6160, a VAV1-directed MGD program licensed to Novartis, and MRT-8102, a NEK7-directed MGD, with plans for multiple phase II studies in immune-mediated diseases and cardiovascular conditions, respectively [26][27] Additional Insights - **Comparative Analysis**: The PSA response rate of 29% in the overall population is comparable to other combination therapies, indicating competitive positioning in the market [17][25] - **Patient Demographics**: The study population was heavily pretreated, with 75% having prior treatment with second-generation AR inhibitors and 80% with chemotherapy, highlighting the challenging nature of the patient cohort [16][18] Conclusion - **Encouraging Data**: The results from the phase I-II study of MRT-2359 demonstrate compelling clinical activity in a high unmet need population, with plans for further studies to confirm its efficacy and safety in treating metastatic CRPC [25][26]

Clinical Trial Results of MRT-2359 - MRT-2359 combined with enzalutamide demonstrated a 100% PSA response rate in heavily pre-treated mCRPC patients with AR mutations[5, 38, 59] - Among the 4 patients with AR mutations, 2 patients showed PSA90 responses and 2 patients showed PSA50 responses[5, 38] - Two patients with AR mutations achieved RECIST partial responses (1 confirmed, 1 unconfirmed), and two had stable disease, resulting in a 100% disease control rate in the AR mutant population[5] - An overall disease control rate (DCR) of 64% was observed in 14 evaluable patients, including 5 patients without AR mutations who had stable disease[5, 59] Safety and Tolerability - The combination of MRT-2359 and enzalutamide was well-tolerated, with the most frequent adverse events (AEs) being mild or moderate manageable GI symptoms[5, 33, 59] - Treatment-related AEs occurring in >15% patients included fatigue (50%), diarrhea (45%), nausea (35%), arthralgia (30%), decreased appetite (30%), vomiting (30%), neutropenia (25%), and muscular weakness (20%)[31, 32] Future Plans - The company plans to initiate a signal-confirming 2-stage Phase 2 study (MODeFIRe-1) of MRT-2359 in combination with a 2nd generation AR inhibitor in 2026, targeting AR-mutated mCRPC[2, 56, 59] - Updated data from the Phase 1/2 study is expected to be presented at the ASCO Genitourinary Cancers Symposium in February 2026[59]

In mCRPC patients with androgen receptor (AR) mutations, treatment with MRT-2359 in combination with enzalutamide led to a 100% PSA response rate (4 of 4 patients) and a 100% disease control rate, including 2 patients with RECIST responses and 2 with stable disease Combination of MRT-2359 and enzalutamide was generally well-tolerated with primarily Grade 1-2 adverse events Company plans to initiate a new, signal-confirming Phase 2 study of MRT-2359 targeting AR mutant and AR signaling-dependent patients i ...

Conference call and webcast to be held at 8 a.m. ET on December 16, 2025BOSTON, Dec. 15, 2025 (GLOBE NEWSWIRE) -- Monte Rosa Therapeutics, Inc. (Nasdaq: GLUE), a clinical-stage biotechnology company developing novel molecular glue degrader (MGD)-based medicines, today announced that management will host a live conference call and webcast on Tuesday, December 16, 2025, at 8:00 a.m. ET. The webcast presentation will highlight interim clinical results from the ongoing Phase 1/2 study of the GSPT1-directed MGD ...

Monte Rosa Therapeutic (NasdaqGS:GLUE) FY Conference December 02, 2025 01:30 PM ET Company ParticipantsMarkus Warmuth - CEOConference Call ParticipantsTed Tenthoff - Senior Biotech AnalystTed TenthoffGreat. Good afternoon, everyone. My name is Ted Tenthoff. I'm a senior biotech analyst at Piper Sandler. And before I begin, I'm required to point out certain disclosures regarding the relationship between our next presenting company, Monte Rosa, and Piper, which are listed at the back of the room and also at t ...

Core Insights - The individual has a B.Tech degree in Mechanical Engineering and nearly twenty-five years of experience in the oil and gas sector, primarily in the Middle East [1] - The investment strategy is informed by traits of efficiency, carefulness, and discipline, developed through extensive industry experience [1] - There is a sustained interest in U.S. equity markets, focusing on technology, energy, and healthcare sectors [1] - The investment approach has evolved from growth investing to a blend of value and growth, emphasizing the understanding of business economics and competitive advantages [1] - The individual believes in the importance of allowing time and compounding to enhance investment returns, particularly in high-quality businesses [1] - A moderately conservative orientation is adopted, with a focus on minimizing downside risk as retirement approaches [1] - Recent rebalancing towards income-generating assets such as dividend-paying equities and REITs reflects a shift in investment priorities [1] - Investing is viewed as a means to achieve peace of mind, not just high returns [1] - The individual aims to engage with a community of investors interested in the intersection of business fundamentals and intelligent investing [1] - There is a commitment to investing in ecologically sensitive businesses, highlighting a focus on sustainability [1]

Summary of Monte Rosa Therapeutics Conference Call Company Overview - **Company**: Monte Rosa Therapeutics (NasdaqGS:GLUE) - **Focus**: Targeted protein degradation using molecular glue degraders, which selectively bind to ubiquitin ligases to degrade disease-driving proteins [3][4] Core Insights - **Molecular Glue Technology**: - Differentiates from traditional protein degradation technologies by not requiring druggable targets, allowing for the targeting of undruggable proteins [5][7] - The platform has shown success with three molecules currently in clinical trials, demonstrating exquisite selectivity [4] - **VAV1 Program**: - Partnership with Novartis to develop MRT6160, targeting the undruggable VAV1 protein, with plans to move into Phase II trials [9][11] - Recent healthy volunteer data indicates effective degradation of VAV1 and potential for addressing multiple indications in autoimmune diseases [12][13] - Selection criteria for Phase II trials focus on Th17 biology, leveraging Novartis' experience with autoimmune treatments [15][16] - **NEX-seven Program**: - Targets NAC7, a crucial component of the NLRP3 inflammasome, aiming for deeper and longer-lasting inhibition of inflammatory pathways [20][21] - Initial data expected next year, with a focus on achieving around 80% to 90% degradation for optimal efficacy [27] - **Jazz PT1 Program**: - MRT2359 targets GSPT1, relevant in castration-resistant prostate cancer driven by MYC transcription factors [33] - Early data from a small patient cohort shows promising results, leading to an expansion of the study to 20-30 patients [35][36] Additional Programs - **CDK2 and CCNE1 Degraders**: - CDK2 degradation is expected to be effective in ER-positive breast cancer, while CCNE1 is suited for cyclin E amplified tumors [38][39] - Both programs are on track for future development [39] Financial Position - **Cash Runway**: Current guidance indicates a cash runway through 2028, supporting multiple Phase II proof of concept studies [40] Other Important Points - **Collaboration with Novartis**: The partnership has expanded to include licensing on additional preclinical programs, indicating a strong collaborative relationship [17][19] - **Clinical Development Strategy**: Emphasis on rigorous biomarker assessments and imaging to evaluate treatment efficacy rather than relying solely on PSA responses in prostate cancer [36][37] - **Potential Combination Therapies**: Consideration of combining therapies with GLP-1 for cardiometabolic diseases, indicating a strategic approach to broaden treatment applications [28] This summary encapsulates the key points discussed during the conference call, highlighting Monte Rosa Therapeutics' innovative approaches, ongoing programs, and financial health.

Summary of Monte Rosa Therapeutics Conference Call Company Overview - **Company**: Monte Rosa Therapeutics (NasdaqGS:GLUE) - **Focus**: Development of molecular glue degraders in the protein degradation space, targeting inflammation, immunity, and oncology [2][3] Key Programs - **MRT-6160**: First-in-class degrader of guanine nucleotide exchange factor Vav1, licensed to Novartis, expected to enter phase two [3] - **MRT-8102 (NEK7 degrader)**: In clinical trials targeting inflammation and IL-1 signaling [3] - **MRT-2359 (GSPT-1 degrader)**: Currently being tested in prostate cancer in combination with enzalutamide [3] NEK7 Degrader Insights - **Mechanism**: NEK7 is a kinase essential for NLRP3 inflammasome assembly; degrading NEK7 prevents inflammasome assembly, differing from traditional NLRP3 inhibitors [5] - **Safety Profile**: Initial studies indicate low risk associated with NEK7 degradation, with no relevant findings in toxicology studies up to doses significantly above human exposure [7][8] - **Selectivity**: Molecular glue degraders show selectivity by interacting through protein-to-protein interactions, minimizing off-target effects [9][10] Clinical Development - **Phase One Trial Design**: Includes standard safety and tolerability assessments, with endpoints focusing on NEK7 degradation and CRP levels as a pharmacodynamic marker [20][21] - **CRP as a Marker**: CRP reduction is linked to efficacy in targeting IL-1 and NLRP3, with historical data supporting its relevance [15][16] Future Directions - **Phase Two Plans**: Potential indications include ASCVD, MESH, pericarditis, and gout, with a focus on exploring different doses for each condition due to varying inflammation levels [22][24][26] - **Oncology Updates**: Upcoming data on MRT-2359 in prostate cancer, with a focus on patient demographics and response rates [28][30] Additional Considerations - **Market Potential**: Gout affects approximately 10 million people in the US, indicating a significant unmet need for effective treatments [24] - **Regulatory Expectations**: Different doses may be required for various indications, aligning with regulatory agency requirements [26] This summary encapsulates the key points discussed during the conference call, highlighting Monte Rosa Therapeutics' strategic focus, clinical programs, and future development plans.

Summary of Monte Rosa Therapeutics FY Conference Call Company Overview - **Company**: Monte Rosa Therapeutics (NasdaqGS:GLUE) - **Industry**: Biotechnology, specifically focusing on molecular glue degraders Key Points and Arguments Molecular Glue Degraders - Molecular glue degraders engage the cell's intrinsic protein destruction machinery by binding to ubiquitin ligase, reshaping proteins to target undruggable proteins [3][4] - This technology has historical precedents with drugs like lenalidomide and pomalidomide, which were not initially recognized as molecular glue degraders [3] Pipeline and Drug Targets - **VAV1 Program**: - Targeted by a partnership with Novartis, VAV1 is considered well-validated through mouse genetic data, showing protection from autoimmune diseases [5] - The program is focused on autoimmune diseases driven by T and B cell components [5] - Safety profile appears clean with no off-target toxicities reported [6][7] - Potential market opportunities include diseases like arthritis, lupus, and inflammatory bowel disease (IBD) [8] - **NEK7 Program (MRT-8102)**: - Targets NEK7 to inhibit the NLRP3 inflammasome, providing deeper and prolonged pathway inhibition compared to direct NLRP3 inhibitors [14][15] - Potential indications include gout and pericarditis, with a focus on conditions driven by crystal formation [17][18] - Phase I study includes a part assessing the impact on CRP levels in individuals with elevated CRP due to obesity [19][20] Clinical Data and Future Steps - Phase I data for VAV1 showed a clean safety profile and effective dose linearity, with degradation observed across multiple dose levels [10] - Upcoming phase II studies will be guided by Novartis' expertise in TH17 biology, with further indications to be added [11][12] - For NEK7, expectations for data disclosure include proof of concept for the pathway early on, with a focus on achieving 70-80% NEK7 degradation for efficacy [21] Partnerships and Development Strategy - Monte Rosa has partnerships with Novartis and Roche, which have been beneficial for revenue generation [25] - The company feels capable of carrying the NEK7 clinical development program forward independently, although larger trials may require future partnerships [25] GSPT1 Degrader Program - Focused on prostate and breast cancer, with enrollment going well and initial efficacy data expected by the end of the year [26][27] - The program aims to explore combinations with other therapies, such as enzalutamide, in metastatic castration-resistant prostate cancer (CRPC) [28] Early Stage Pipeline - The CDK2 cyclin E1 package is closest to IND filings, with a focus on targeting undruggable proteins and multiple cytokine signaling pathways [31][32] Additional Important Insights - The company emphasizes the potential of its technology to address previously undruggable targets, positioning itself as a leader in the molecular glue degrader space [3][32] - The focus on immune modulation rather than suppression suggests a strategic advantage in developing therapies for autoimmune diseases [7]