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 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].

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]