Molecular Partners Initiates Clinical Study of Trispecific Candidate MP0533 for the Treatment of Acute Myeloid Leukemia
- Category: Proteins and Peptides
- Published on Monday, 16 January 2023 15:07
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- Unique avidity driven mechanism engages CD3 on T cells when binding either two or three tumor-associated antigens to enhance selectivity for AML cells
- Preclinical data demonstrated that MP0533 can selectively target and kill both leukemic blast cells and stem cells, while sparing healthy cells
ZURICH-SCHLIEREN, Switzerland and CONCORD, MA, USA I January 16, 2023 IMolecular Partners AG (SIX: MOLN; NASDAQ: MOLN), a clinical-stage biotech company developing a new class of custom-built protein drugs known as DARPin therapeutics, 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). MP0533 is designed to focus an immune attack against AML in a new way that preferentially spares healthy cells, which has been a historic challenge for CD3-targeting therapeutics.
“AML is a notoriously difficult cancer to treat, in large part due to the overlapping targets which are expressed on both healthy, and leukemic cells. Our team has worked relentlessly over the past 3 years to develop a molecule intended to target these cancerous cells, while avoiding healthy cells. MP0533’s mechanism represents a new level of precision targeting in complex cancers that may permit greater use of the immunostimulatory power of CD3,” said Nicolas Leupin, M.D., Ph.D., Chief Medical Officer of Molecular Partners. “We are grateful to our team and our collaborators for reaching this milestone and look forward to learning more about the potential of MP0533 to help these patients.”
MP0533 simultaneously targets three surface proteins, CD33, CD123, and CD70, that are vastly more likely to appear together on AML blast cells and leukemic stem cells over healthy cells. It also targets an immunostimulatory protein, CD3, on cytotoxic T cells, which will only activate when at least two of the surface proteins are bound. This novel mechanism is intended to greatly favor CD3 activation in proximity to leukemic stem cells rather than the systemic activation seen in previous CD3-based T cell engagers.
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.
MP0533 preclinical data demonstrates its greatly increased avidity for cells expressing two or three of the tumor associated antigens (TAAs) compared to cells expressing a single TAA. MP0533 also demonstrated an ability to induce T cell activation and killing of AML cells in samples from newly diagnosed and previously treated patients. 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, endothelial cells, and T cells.
About Molecular Partners’ Oncology Product Candidates
Molecular Partners is developing several candidates designed to activate the immune system to fight cancer while reducing damage to healthy cells. These candidates use multiple novel DARPin technologies potentially applicable against a wide range of tumor types, including DARPin candidates with the ability to restrict immune activation to the tumor microenvironment, the ability to target intracellular disease-associated proteins, and multiple novel control mechanisms for immune activation designed to direct immune attack to the right cells, at the right place, and at the right time. These capabilities can be combined during candidate design through the inherent modularity of the DARPin platform, to provide precise control over immune activation and potentially enable more effective cancer therapies.
About Molecular Partners AG
Molecular Partners AG is a clinical-stage biotech company developing DARPin therapeutics, a new class of custom-built protein drugs designed to address challenges current modalities cannot. The Company has formed partnerships with leading pharmaceutical companies to advance DARPin therapeutics in the areas of ophthalmology, oncology, and infectious disease, and has compounds in various stages of clinical and preclinical development across multiple therapeutic areas. www.molecularpartners.com; Find us on Twitter - @MolecularPrtnrs
SOURCE: Molecular Partners