Core Insights - Molecular Partners AG is presenting updated data from a Phase 1/2a trial of its T-cell engager MP0533 for treating acute myeloid leukemia (AML) at the 67th ASH Annual Meeting [1][2] Group 1: Trial Results - The multicenter, open-label study shows that densified dosing of MP0533 is tolerable and leads to improved serum exposure with preliminary antitumor activity [2][4] - As of September 1, 2025, 54 patients have been treated with MP0533, with 8 out of 48 evaluable patients achieving a response, including 5 reaching composite complete responses [4] - The trial indicates that patients with lower disease burden are more likely to benefit from MP0533, with 6 of 8 responders presenting with less than 20% bone marrow blasts at baseline [4][7] Group 2: Expert Commentary - Prof. Courtney DiNardo expressed optimism about the clinical benefits of MP0533 in a mutation-agnostic manner for R/R AML patients, particularly those with lower disease burden [3] - Philippe Legenne highlighted the progress of the trial, noting the feasibility of the densified dosing regimen and the interest from consortia for further studies [5] Group 3: Mechanism of Action - MP0533 is a novel tetra-specific T cell-engaging DARPin that targets three tumor-associated antigens (CD33, CD123, CD70) on AML cells and the immune activator CD3 on T cells, designed to preferentially kill AML cells while minimizing damage to healthy cells [6] Group 4: Presentation Details - The poster presentation titled "Phase 1/2 study of MP0533" outlines clinical benefits with an acceptable safety profile across 9 dosing regimens, emphasizing the feasibility of accelerated step-up dosing [7][8]

Core Insights - Molecular Partners AG is presenting updated data from a Phase 1/2a trial of its T-cell engager MP0533 for treating acute myeloid leukemia (AML) at the 67th ASH Annual Meeting [1][2] Group 1: Trial Results - The multicenter, open-label study shows that densified dosing of MP0533 is tolerable and leads to improved serum exposure with preliminary antitumor activity [2][4] - As of September 1, 2025, 54 patients have been treated with MP0533, with 8 out of 48 evaluable patients achieving a response, including 5 reaching composite complete responses [4] - Six of the eight responders had less than 20% bone marrow blasts at baseline, indicating that patients with low disease burden are likely to benefit the most from MP0533 [4][7] Group 2: Expert Commentary - Prof. Courtney DiNardo expressed optimism about the clinical benefits of MP0533 in mutation-agnostic R/R AML patients, particularly those with lower disease burden, supporting further investigation in a Phase 2 setting [3][5] Group 3: Drug Mechanism and Design - MP0533 is a novel tetra-specific T cell-engaging DARPin that targets three tumor-associated antigens (CD33, CD123, CD70) on AML cells and the immune activator CD3 on T cells, designed to preferentially kill AML cells while minimizing damage to healthy cells [6][9] Group 4: Future Development - The trial is progressing well, with the densified dosing regimen showing feasibility and an acceptable safety profile, prompting interest from several consortia for further studies in both R/R and front-line AML settings [5][9]

Core Viewpoint - Molecular Partners AG is advancing its clinical-stage development of MP0533, a novel tetra-specific T cell engager for treating acute myeloid leukemia (AML), with updated data to be presented at the upcoming ASH Annual Meeting [1][2]. Group 1: Clinical Trial Details - The Phase 1/2a trial of MP0533 is a first-in-human, multicenter, open-label study focusing on relapsed/refractory AML and myelodysplastic syndrome (MDS)/AML patients [2]. - Initial results indicate that MP0533 has an acceptable safety profile across dosing regimens DR 1–9, with encouraging preliminary signs of antitumor activity [2]. - The study is currently in the dosing phase for patients in DR 10 [2]. Group 2: Mechanism of Action - MP0533 is designed to engage T cells by targeting three tumor-associated antigens (CD33, CD123, and CD70) on AML cells, as well as the immune activator CD3 on T cells [3]. - This tetra-specific approach allows MP0533 to preferentially bind to AML cells, which commonly express multiple target antigens, while minimizing binding to healthy cells [3]. Group 3: Presentation Details - The presentation at the ASH Annual Meeting will include initial results from the optimized treatment regimen of MP0533, including densified dosing and adapted premedication [4]. - The session is scheduled for December 7, 2025, from 6:00–8:00 PM ET, with the full abstracts available on the ASH website [4]. Group 4: About DARPin Therapeutics - DARPin therapeutics represent a new class of custom-built protein drugs that offer multi-target specificity and high stability, providing advantages over traditional protein-based therapeutics [5]. - The DARPin platform is designed for rapid and cost-effective drug discovery, producing candidates with optimized properties and high production yields [5]. Group 5: Company Overview - Molecular Partners AG focuses on developing DARPin therapeutics to address medical challenges that other drug modalities cannot effectively target, with oncology as its primary area of focus [6]. - The company has been operational since 2004 and maintains offices in Zurich, Switzerland, and Concord, Massachusetts, USA [6].

Core Insights - Molecular Partners AG is presenting updated data from a Phase 1/2a trial of MP0533, a novel T cell engager for acute myeloid leukemia (AML) patients, at the upcoming ASH Annual Meeting [1][2] Group 1: Clinical Trial Details - The trial is a first-in-human, multicenter, open-label study evaluating MP0533 in relapsed/refractory AML and myelodysplastic syndrome (MDS)/AML patients [2] - MP0533 demonstrates an acceptable safety profile across dosing regimens DR 1–9, with preliminary signs of antitumor activity being encouraging [2] - The study is currently administering doses to patients in DR 10 [2] Group 2: Mechanism of Action - MP0533 is a tetra-specific T cell-engaging DARPin that targets three tumor-associated antigens (CD33, CD123, CD70) on AML cells and the immune activator CD3 on T cells [3] - The design allows MP0533 to preferentially bind to AML cells over healthy cells, enhancing T cell-mediated killing while minimizing damage to healthy cells [3] Group 3: Presentation Details - The presentation will occur on December 7, 2025, during the session focused on investigational drugs and cellular therapies for acute myeloid leukemias [4] - The full abstracts will be available on the ASH website starting November 3, 2025 [4] Group 4: About DARPin Therapeutics - DARPin therapeutics represent a new class of custom-built protein drugs that offer multi-functionality and multi-target specificity [5] - The platform is designed for rapid and cost-effective drug discovery, producing candidates with optimized properties and high production yields [5] Group 5: About Molecular Partners AG - Molecular Partners AG is a clinical-stage biotech company focused on developing DARPin therapeutics, primarily in oncology [6] - The company has various programs in different stages of development and collaborates with leading pharmaceutical companies [6]

Pipeline Highlights - MP0712 (212Pb x DLL3) IND-enabling studies completed, IND filed[15] - Strategic collaboration with Orano Med expanded to ten 212Pb programs[15] - Lead candidate MP0726 targeting mesothelin (MSLN) nominated based on pre-clinical data[15] - Improved response rate and antitumor activity in low disease burden patients of ongoing Phase 1/2a reported for MP0533 at EHA 2025[15] - Study protocol approved for combo IIT with standard-of-care in cholangiocarcinoma for Switch-DARPin MP0317[15] Financial Position - The company has CHF ~105 million in cash as of September 30, 2025[8, 15] - The company is financed until 2028 through key value inflection points[8] MP0712 Radio-DARPin Therapy - MP0712 induces complete and durable tumor regression in NCI-H82 tumor model at 10 µCi injected every week[27] - Phase 1 study is expected to start in H2 2025, with initial safety and efficacy data in 2026[32] MP0533 Tetra-specific T-cell Engager for AML - In DR 8, 3 of 8 evaluable patients responded after cycle 1: 1 CR and 2 CRh as best overall response[62] - In DR 1-7, 12% (4) patients had response rate, while in DR 8, 37.5% (3) patients had response rate[69]

Core Insights - Molecular Partners AG is advancing its clinical-stage pipeline, focusing on DARPin therapeutics, with significant developments in its Radio-DARPin programs and T-cell engagers [1][2][3] Research & Development Highlights - The IND application for MP0712, a Radio-DARPin targeting DLL3 for small cell lung cancer, has been filed, with a Phase 1 trial expected to start by the end of 2025 [3][7] - Initial clinical imaging data for MP0712 will be presented in November, showcasing its application in compassionate care in South Africa [2][5] - MP0533, a multispecific T-cell engager for acute myeloid leukemia (AML), has shown promising results, with over 30% of evaluable patients achieving a clinical response [10][12] - The company is exploring further dosing strategies for MP0533 to enhance patient outcomes and is planning to present updated data at the ASH Annual Meeting in December [11][12] - MP0317, a tumor-localized agonist, is undergoing an investigator-initiated trial for advanced cholangiocarcinoma, with a focus on progression-free survival [13][14] Corporate Governance Highlights - Martin Steegmaier, Ph.D., has been appointed as Chief Scientific Officer, bringing extensive oncology drug development experience [17] Financial and Business Outlook - For 2025, the company anticipates total operating expenses of CHF 55-60 million, with sufficient cash reserves of CHF 105 million to fund operations until 2028 [18][19]

Core Insights - Molecular Partners AG is making significant progress in its clinical programs, particularly with MP0712 and MP0533, with key milestones expected in the near future [2][6] - The company has appointed Martin Steegmaier, Ph.D., as Chief Scientific Officer, enhancing its leadership team [2][15] - Financially, the company is in a strong position with cash reserves projected to last until 2028 [2][19] Research & Development Highlights - MP0533 is in a Phase 1/2a trial for acute myeloid leukemia, showing promising results with over 30% of evaluable patients achieving a clinical response [3][4] - The dosing regimen for MP0533 has been optimized to enhance patient responses, with initial data from cohort 9 expected in Q4 2025 [5][6] - MP0712, a Radio-DARPin therapy for small cell lung cancer, is preparing for an IND filing, with initial clinical data anticipated in H1 2026 [8][9] Corporate Governance Highlights - The appointment of Martin Steegmaier, Ph.D., as CSO is aimed at strengthening the company's focus on oncology drug development [15] - A strategic review led to a planned reduction of up to 40 positions, which is expected to improve operational efficiency and extend the cash runway into 2028 [16] Financial and Business Outlook - For 2025, the company expects total operating expenses between CHF 55-65 million, with a significant portion being non-cash costs [18] - As of June 30, 2025, cash and cash equivalents totaled CHF 114 million, sufficient to fund operations into 2028 [19]

Radio-DARPin Therapy & MP0712 - Molecular Partners is focused on oncology with differentiated assets like MP0533 and MP0712, addressing unmet medical needs[8] - The company has CHF ~149 million, ensuring funding into 2027[8, 110] - MP0712, a 212Pb-DLL3 targeted radiotherapeutic, addresses the critical unmet need in SCLC, where >85% of patients express DLL3[36, 39] - Preclinical data shows MP0712 induces complete tumor regression in ~70% of mice at 4x 10µCi and ~20% of mice at 8x 5µCi in the NCI-H82 tumor model at day 63[45] - MP0712 clinical development strategy includes Phase 0 imaging studies and Phase 1 dose escalation studies starting in H2 2025, with initial clinical data expected by YE[54] Next-Gen Immune Cell Engagers & MP0533 - MP0533 is a tetra-specific T-cell engager designed to kill AML cells by targeting CD33, CD123, and CD70[69, 77] - Preliminary data from the MP0533 Phase 1/2a study shows 4 responders reported in DR 1-7 with manageable safety[80] - An improved MP0533 exposure was achieved at DR 8 with a steeper and denser step-up dosing regimen[82, 86] Switch-DARPin Platform - The Switch-DARPin platform aims to overcome limitations of current T cell engagers by enabling targeted and conditional activation of immune cells[94, 101] - Preclinical data shows the EpCAM-MSLN-CD2/CD3 Switch induces tumor regression more efficiently than a MSLN-CD3 engager (Tritac)[107]

Company Overview - Molecular Partners is a clinical-stage biotech company pioneering DARPin therapeutics for patients, with operations in Switzerland and the US[8] - The company is well financed into 2027 with approximately CHF 149 million[8] (Note: The outlook section mentions CHF ~131 million[95], so there might be a slight discrepancy) - Molecular Partners has proprietary DARPin platforms, including Radio-DARPins and Switch / T cell engagers[8] Pipeline Highlights - MP0712 (Radio-DARPin Therapy targeting DLL3) is in co-development for SCLC & NECs[9] - The co-development agreement with Orano Med includes up to 10 RDT programs, including MP0712[9] - MP0533 (Next-Gen Immune Cell Engager) is being developed for r/r AML and AML/MDS[9] MP0712 (Radio-DARPin Therapy) - MP0712 is the first 212Pb-DLL3 targeted radiotherapeutic for SCLC, where >85% of SCLC patients express DLL3[25] - Preclinical studies show MP0712 induces complete and durable tumor regression in the NCI-H82 tumor model at 10µCi injected every week[28] - Phase 1 study is expected to start in H2 2025, with initial safety and efficacy data in 2026[33] MP0533 (Tetra-specific T-cell Engager for AML) - MP0533 is designed to induce T cell-mediated killing preferentially when 2 or 3 AML-associated antigens are co-expressed[66] - Preliminary data from the Phase 1/2a study shows encouraging blast reduction, particularly in patients with lower disease burden at baseline[75] - Improved MP0533 exposure was observed at DR 8 with a steeper and denser step-up dosing regimen[78]

Core Viewpoint - Molecular Partners AG announced positive updated data from a Phase 1/2a trial of its tetraspecific T-cell engager MP0533 for relapsed/refractory acute myeloid leukemia (AML) at the EHA Congress in Milan [1][2] Group 1: Trial Results - In cohort 8, 3 out of 8 evaluable patients (over 30%) achieved a clinical response after the first cycle, including 1 complete response and 2 complete responses with partial hematologic recovery [3] - Patients in cohort 8 maintained exposure to MP0533 for over 4 days within the predicted therapeutic range, with 5 out of 8 patients showing more than 50% blast reduction [4] - The safety profile of MP0533 was deemed acceptable after the adjustment of the target dose in cohort 8 [9] Group 2: Dosing Regimen - Cohort 8 implemented a higher starting dose and an additional day of dosing, reaching the target dose by day 12 instead of day 15, which contributed to improved clinical responses [3][6] - The amended protocol for cohort 9 includes further acceleration of the step-up dosing, increased frequency of dosing, and the introduction of anti-CD20 premedication to enhance therapeutic exposure and response duration [7][9] - Initial data from cohort 9, which is currently dosing patients, is expected in the second half of 2025 [8] Group 3: Company Overview - Molecular Partners AG is a clinical-stage biotech company focused on developing DARPin therapeutics, with oncology as its main area of focus [10] - The company was founded in 2004 and operates in both Zurich, Switzerland, and Concord, Massachusetts, USA [10]