MP0533 / Molecular Partners - LARVOL DELTA

UPDATED RESULTS FROM THE ONGOING PHASE 1/2A STUDY OF MP0533, A TETRA-SPECIFIC DESIGNED ANKYRIN REPEAT PROTEIN (DARPIN; CD33 X CD123 X CD70 X CD3), IN PATIENTS WITH RELAPSED/REFRACTORY AML OR MDS/AML (EHA 2025) - P1/2 | "MP0533 shows an acceptable safety profile across all cohorts after adjustment of the TD in DR8. Preliminary antileukemic activity, safety, and PK/PD data from DR8 support further dose optimization to enhance MP0533 exposure and maximize its therapeutic benefit."

Clinical • P1/2 data • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • CD123 • CD27 • CD33 • CD70 • CXCL10 • IFNG • IL3 • IL3RA • TNFA

MP0533-CP101: Study of MP0533 in Patients Acute Myeloid Leukemia or Myelodysplastic Syndrome (clinicaltrials.gov) - P1/2 | N=249 | Recruiting | Sponsor: Molecular Partners AG | N=70 ➔ 249 | Trial completion date: Dec 2027 ➔ Dec 2029 | Trial primary completion date: Dec 2025 ➔ Dec 2027

Enrollment change • Trial completion date • Trial primary completion date • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology

Molecular Partners Reports Financial Results and Highlights from Q1 2025 (GlobeNewswire) - "Data from dosing cohort 8 in Phase 1/2a trial of MP0533 demonstrate increased rates and depth of responses; study protocol amendment now approved, and dosing cohort 9 enrollment initiated, additional data expected in 2025."

P1/2 data • Trial status • Acute Myelogenous Leukemia

Molecular Partners Outlines Clinical Expansion Plans and Strengthens Radiopharma Strategic Focus for 2025 at 43rd Annual J.P. Morgan Healthcare Conference (GlobeNewswire) - "Dialogue with the U.S. Food and Drug Administration (FDA) is ongoing and Molecular Partners and Orano Med anticipate submitting the IND application for MP0712 in H1 2025, with the first-in-human study to start following regulatory clearance....Molecular Partners has submitted an amendment to the study protocol to improve the exposure profile of MP0533 and to further deepen and expand responses being observed in cohort 8. Data on the amended dosing scheme are expected in 2025."

Clinical protocol • IND • Acute Myelogenous Leukemia • Myelodysplastic Syndrome • Small Cell Lung Cancer

MP0533 (CD33 x CD123 x CD70 x CD3), a Tetra-Specific CD3-Engaging Darpin for the Treatment of Patients with Relapsed/Refractory AML or MDS/AML: Results of an Ongoing Phase 1/2a Study (ASH 2024) - P1/2 | "SUMMARY/CONCLUSION : MP0533 dosed weekly showed an acceptable safety profile in the first 7 DRs of this ongoing phase 1/2a study. Preliminary antileukemic activity and pharmacodynamics data are encouraging, with 4 responders and evidence of target engagement and T-cell activation."

Clinical • IO biomarker • P1/2 data • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • CD123 • CD27 • CD33 • CD4 • CD69 • CD70 • CD8 • CXCL10 • CXCL9 • GZMB • IFNG • IL2RA • IL3RA • TNFA

Molecular Partners Announces Upcoming Poster Presentations at the 65th ASH Annual Meeting and Exposition (GlobeNewswire) - "The poster to be presented at ASH 2024 will provide a clinical update of the ongoing first-in-human dose-escalation phase 1/2a study of MP0533 in patients with relapsed/refractory acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS)/AML. MP0533 showed an acceptable safety profile in the first 7 dose cohorts, with the majority of adverse events reported being infusion-related reactions and cytokine release syndrome; The poster to be presented at ASH 2024 builds on the data presented earlier this year at the European Haematology Association 2024 Congress and provides further preclinical in vivo proof-of-mechanism data, demonstrating that MP0621 could be an efficient next-generation conditioning regimen for autologous HSCT."

P1/2 data • Preclinical • Acute Myelogenous Leukemia • Hematological Malignancies • Myelodysplastic Syndrome • Oncology

Molecular Partners Reports H1 2024 Corporate Highlights and Financials (Molecular Partners Press Release) - "MP0712: Molecular Partners will present additional data in an oral presentation at the 2024 Congress of the European Association of Nuclear Medicine (EANM) in October 2024, and plans to initiate a first-in-human clinical trial of MP0712 in 2025; MP0533: MP0533...is currently being evaluated in a Phase 1/2a clinical trial for patients with relapsed/refractory acute myeloid leukemia (r/r AML) and myelodysplastic syndrome/AML...Molecular Partners plans to present a clinical update on the program in H2 2024, and on the amended dosing scheme for MP0533 in 2025."

Clinical • New P1 trial • Preclinical • Acute Myelogenous Leukemia • Myelodysplastic Syndrome • Oncology

MOLECULAR PARTNERS ANNOUNCES PUBLICATION IN CANCER IMMUNOLOGY RESEARCH OF PRECLINICAL DATA SUPPORTING MP0533’S PROPOSED MECHANISM OF ACTION (Molecular Partners Press Release) - "MP0533 led to tumor-localized T-cell activation and efficacious tumor regression in an antigen-dependent manner across different in vivo models. Notably, when compared to other T cell engagers that target single antigens, MP0533 led to lower levels of cytokine release, findings that were confirmed through in vitro, in vivo, and ex vivo studies. This included IL-6, a cytokine known as a primary driver of cytokine release syndrome, a systemic toxicity that has so far limited the development of T cell engagers as potential treatment options of AML....MP0533 is currently being evaluated in a Phase 1/2a trial in patients with relapsed/refractory AML or myelodysplastic syndrome (MDS/AML)....The Company expects to present an update from the study in H1 2024."

P1/2 data • Preclinical • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

The CD33xCD123xCD70 Multispecific CD3-Engaging DARPin MP0533 Induces Selective T Cell-Mediated Killing of AML Leukemic Stem Cells. (PubMed, Cancer Immunol Res) - P1/2 | "These studies show that the multispecific-targeting strategy used with MP0533 holds promise for improved selectivity towards LSCs and efficacy against clonal heterogeneity, potentially bringing a new therapeutic option to this group of patients with high unmet need. MP0533 is currently being evaluated in a dose-escalation phase 1 study in patients with relapsed or refractory AML (NCT05673057)."

Journal • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • Transplantation • CD123 • CD33 • CD70 • IL3RA

MOLECULAR PARTNERS REPORTS CORPORATE HIGHLIGHTS FROM Q4 2023 AND KEY FINANCIALS FOR FULL YEAR 2023 (Molecular Partners Press Release) - "Data from the Phase 1/2a trial of MP0533, including safety and efficacy, to be presented in H1 2024; expansion of enrollment to higher dose cohorts planned in H2 2024; Initial preclinical data from first Switch-DARPin program cKIT x CD16a x CD47 expected in H1 2024; preclinical proof-of-concept studies expected in H2 2024, which should provide strong translational efficacy data; The full dataset from the MP0317 Phase 1 dose-escalation trial expected in H1 2024."

P1/2 data • Preclinical • Trial status • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology

MOLECULAR PARTNERS PROVIDES UPDATES AT 42ND ANNUAL J.P. MORGAN HEALTHCARE CONFERENCE (Molecular Partners Press Release) - "Data from projected therapeutically active doses of MP0533 from the Phase 1/2a trial, including safety and efficacy, to be presented in H1. Lead RDT candidate (DLL3) to be advanced into IND-enabling studies in H1, and nomination of additional targets and lead candidates for the RDT pipeline. Initiation of clinical studies and first-in-human data are expected in 2025. Initial data from the first program of the company’s Switch-DARPin platform – a cKIT x CD16a x CD47 multispecific DARPin for targeted immune cell activation against HSCs as next-generation conditioning regimen for HSCT in AML patients – to be presented in H1. The full dataset from the MP0317 Phase 1 dose-escalation in H1."

Clinical data • New trial • P1 data • P1/2 data • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • Solid Tumor

MP0533, a CD3-Engaging Darpin Targeting CD33, CD123, and CD70 in Patients with Relapsed/Refractory AML or MDS/AML: Preliminary Results of a Phase 1/2a Study (ASH 2023) - P1/2 | "The results of this ongoing phase 1/2a study indicated an acceptable safety profile of MP0533 monotherapy in 5 patients up to DR 3 with weekly infusions. Preliminary response data are encouraging, with one response observed in 1 of 2 patients evaluable for response in DR 3 to date."

Clinical • IO biomarker • P1/2 data • Acute Myelogenous Leukemia • Fatigue • Hematological Disorders • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • CD123 • CD33 • CD70 • IL3RA • TP53

Molecular Partners Presents Positive Initial Data from First Four Dosing Cohorts of Ongoing Phase 1/2a Trial of MP0533 for Patients with Relapsed/Refractory AML and AML/MDS at ASH Annual Meeting (Yahoo Finance) - P1/2a | N=70 | NCT05673057 | Sponsor: Molecular Partners AG | "Molecular Partners AG...presented positive initial clinical data from its ongoing Phase 1/2a trial of MP0533, a novel tetra-specific T cell engager, in a poster at the 65th American Society of Hematology (ASH) Annual Meeting and Exposition....Two responders have been observed to date, including a patient achieving complete response (CR) in DR 4 and another patient with morphological leukemia-free state (MLFS) in DR 3 (initially identified as CRi at the time of abstract submission, data cutoff July 2023). These responses are particularly notable for having occurred at dose levels below those predicted for therapeutically relevant activity."

P1/2 data • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology

Molecular Partners to Present on DARPin Oncology Innovations at Protein & Antibody Engineering Summit Europe (PEGS) (GlobeNewswire) - "Molecular Partners AG...will present on several of its programs at the 15th Annual Protein & Antibody Engineering European Summit (PEGS Europe), which runs November 14-16 in Lisbon, Portugal....The presentation consists of a review of several differentiated mechanisms of action that leverage the DARPin platform...MP0317, a CD40 agonist, is designed to activate immune cells specifically within the tumor microenvironment by anchoring to fibroblast activation protein (FAP), which is highly expressed on tumor cells....MP0533, a novel tetra-specific DARPin for the treatment of patients with relapsed/refractory acute myeloid leukemia (AML) and myelodysplastic syndrome (AML/MDS), engages CD3 on T cells and targets three tumor-associated antigens (TAAs) CD33, CD123, and CD70."

Clinical data • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • Solid Tumor

Molecular Partners to Present Initial Data from Ongoing Phase 1/2a Trial of MP0533 for Patients with Relapsed/Refractory AML and AML/MDS at the 65th ASH Annual Meeting and Exposition (GlobeNewswire) - P1/2a | N=70 | NCT05673057 | Sponsor: Molecular Partners AG | "Molecular Partners AG...will present preliminary data from its ongoing Phase 1/2a trial of MP0533...at the 65th American Society of Hematology (ASH) Annual Meeting and Exposition being held from December 9–12 in San Diego, California. MP0533 is in development for the treatment of patients with relapsed/refractory acute myeloid leukemia (r/r AML) and myelodysplastic syndrome (AML/MDS)...As of data cut-off (20 July 2023) of the abstract published today, five patients across three dosing regimens had been treated. The preliminary data reported indicate an acceptable safety profile, with no dose-limiting toxicity or Grade ≥3 adverse reactions. Grade 1/2 events considered related to MP0533 included infusion-related reactions and cytokine release syndromes....The Company anticipates to present data including from the fourth dose cohort at the ASH Annual Meeting and Exposition in December this year."

P1/2 data • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology

MOLECULAR PARTNERS INTERIM MANAGEMENT STATEMENT Q3 2023: CONTINUED VALIDATION SEEN ACROSS THE DARPIN PORTFOLIO (Molecular Partners Press Release) - "Recruitment in the MP0533 Phase 1/2a trial in patients with relapsed/refractory acute myeloid leukemia (AML) and myelodysplastic syndrome/AML (MDS/AML) is on track, with patients presently being treated at dose regimen five. Initial safety and activity data from this ongoing clinical trial will be presented at the American Society of Hematology (ASH) Annual Meeting and Exposition in December 2023. Additional data are expected to be presented in H1 2024....The Company has completed patient recruitment of the ongoing MP0317 dose escalation portion of the Phase 1 trial in patients with advanced solid tumors at the highest planned doses and will present latest results from this ongoing trial at the Society for Immunotherapy of Cancer (SITC) Annual Meetings on November 3, 2023....Final data of this Phase 1 study are anticipated in H1 2024."

Enrollment status • P1 data • P1/2 data • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • Solid Tumor

Molecular Partners Reports H1 2023 Corporate Highlights and Financials (GlobeNewswire) - "Recruiting and dose-escalation are ongoing with seven sites open across Europe, presently dosing patients in the fourth cohort. Preliminary results from this clinical trial are expected in Q4 2023 and additional data in H1 2024."

P1/2 data • Trial status • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology

Therapeutic Applications Based on the DARPin Platform – From Small Size Single Domain to Hexavalent and Multi-Specific Binding Molecules (PEGS 2023) - "The DARPin technology enables the exploration of new therapeutic designs on multiple disease pathways. Based on DARPin properties (small size, high affinity, excellent stability), we can generate single-domain DARPin agents for fast-in/fast-out radio ligand therapies (RLT) with high tumor accumulation – OR – generate multi-specific DARPin therapeutics such as MP0533, a half-life extended CD3-based T cell engager targeting simultaneously CD33, CD123, and CD70 to selectively target malignant AML cancer cells."

Acute Myelogenous Leukemia • Oncology • CD123 • CD33 • CD70

MOLECULAR PARTNERS REPORTS CORPORATE HIGHLIGHTS FROM Q4 2022 AND KEY FINANCIALS FOR FULL YEAR 2022 (Molecular Partners Press Release) - "MP0533: initial clinical results of the Phase 1 trial in AML anticipated in Q4 2023; MP0317: completion of patient recruitment in the dose escalation of Phase 1 trial anticipated in H1 2023."

Enrollment status • P1 data • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

Molecular Partners Initiates Clinical Study of Trispecific Candidate MP0533 for the Treatment of Acute Myeloid Leukemia (GlobeNewswire) - "Molecular Partners AG...announced today that the first patient has been treated in a Phase 1 first-in-human study evaluating the safety, tolerability, and efficacy of MP0533, the company’s candidate for acute myeloid leukemia (AML)....The Phase 1 open-label dose escalation study will enroll patients with relapsed/refractory AML and higher-risk myelodysplastic syndromes (MDS). It is designed to assess the safety, tolerability, and efficacy of MP0533 in addition to a range of secondary endpoints, such as the effect on LSCs, pharmacodynamics, T-cell activation, and cytokine release. Between 20-45 patients are expected to be enrolled across five sites in Switzerland and the Netherlands in collaboration with certain sites within the HOVON cooperative group. Additional clinical sites are planned as well."

Trial status • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology

Molecular Partners Provides Updates at 41st Annual JPM Healthcare Conference (GlobeNewswire) - "The company expects milestones in 2023 to include: Q1 2023: The recruitment of the first patient in the company’s phase 1 study of MP0533 (CD33 X CD123 X CD70 X CD3), a novel tri-specific t-cell engager for the treatment of AML and High Risk MDS; 1H 2023: Complete recruitment in the dose escalation of the Phase 1 trial of the company’s MP0317 (FAP X CD40) program for the treatment of solid tumors."

Trial status • Acute Myelogenous Leukemia • Hematological Malignancies • Myelodysplastic Syndrome • Oncology • Solid Tumor

Molecular Partners Provides Updates at 41st Annual JPM Healthcare Conference (GlobeNewswire) - "The company expects milestones in 2023 to include...H1 2023: Scientific presentations of DARPin radioligand therapies and their potential differentiation as tumor targeting moiety; Formal selection of DLL3 DARPin RLT clinical candidate; Q4 2023: A first data readout from the Phase 1 study of MP0533."

Clinical data • P1 data • Pipeline update • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology

Study of MP0533 in Patients With Relapsed or Refractory Acute Myeloid Leukemia or Myelodysplastic Syndrome (clinicaltrials.gov) - P1/2 | N=70 | Recruiting | Sponsor: Molecular Partners AG

New P1/2 trial • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology

MP0533: A Multispecific Darpin CD3 Engager Targeting CD33, CD123, and CD70 for the Treatment of AML and MDS Designed to Selectively Target Leukemic Stem Cells (ASH 2022) - "We generated a multi-specific avidity-driven CD3 engaging DARPin molecule with tailored affinities towards different TAAs showing high efficacy and with the potential for better LSC selectivity and lower cytokine release compared with mono-specific TCE approaches. Further, our approach to achieve systemic half-life extension could ensure a more convenient Q1W IV therapy. A Phase I clinical trial to evaluate safety and dose of MP0533 in humans is imminent."

Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • CD123 • CD33 • CD34 • CD70

Molecular Partners Presents New Preclinical Data Supporting its MP0533 DARPin T-Cell Engager for the Treatment of AML (PipelineReview) - "IMolecular Partners AG...new preclinical data showing its DARPin T-cell engager MP0533 can induce preferential killing of cells expressing two or three tumor-associated antigens (TAAs) compared to cells expressing a single TAA. The data was disclosed in an oral presentation at the 64th Annual American Society of Hematology Meeting in New Orleans....As presented today, MP0533 was able to activate T-cells and destroy AML cells in samples from newly diagnosed and previously treated AML patients with different TAA expressions. Humanized mouse models confirmed MP0533’s ability to activate intra-tumoral T-cells and control tumor growth. The research also showed that MP0533 was able to directly target and kill LSCs while sparing a variety of healthy cells including hematopoietic stem cells."

Preclinical • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology