On January 16, 2023 Molecular Partners AG (SIX: MOLN; NASDAQ: MOLN), a clinical-stage biotech company developing a new class of custom-built protein drugs known as DARPin therapeutics, reported 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) (Press release, Molecular Partners, JAN 16, 2023, View Source [SID1234626265]). 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.
Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:
Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing
Schedule Your 30 min Free Demo!
"AML is a notoriously difficult cancer to treat, largely due to the overlapping targets expressed on both healthy and leukemic cells. Our team has worked relentlessly over the past three 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 cytotoxic power of engaging 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 be expressed together on AML blast cells and leukemic stem cells over healthy cells. It also targets CD3 on cytotoxic T cells, which will preferentially activate when at least two of the surface proteins are bound. This novel mechanism is intended to greatly favor CD3 activation in 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, pharmacokinetics, 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 select sites within the HOVON cooperative group. Additional clinical sites are planned as well.
MP0533 preclinical data demonstrates it induces preferential T cell mediated killing of 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.