Molecular Partners Presents New Preclinical Data Supporting its MP0533 DARPin T-Cell Engager for the Treatment of AML

ZURICH-SCHLIEREN, Switzerland and CONCORD, Mass., Dec. 12, 2022 (GLOBE NEWSWIRE) — 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, presented today 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.

MP0533 engages CD3 on T cells while binding up to three tumor-associated antigens (CD33, CD70, and CD123) on AML cells. By modulating the affinity to each TAA, Molecular Partners designed MP0533 to induce T cell-mediated killing preferentially when the cancer cells express two or three of the TAAs. This avidity-driven T cell activation ensures preferential killing of AML cells, that consistently expresses two or three of the target antigens. At the same time, it reduces the damage to healthy cells, which tend to express only one of the target antigens. Such damages have been a recurrent issue with other T-cell engagers in AML.

“Our preclinical data provides a strong base for MP0533’s clinical entry. Its design strategy is to focus the proven power of CD3-mediated T-cell killing onto AML cells and eliminate the systemic toxicity that has been a challenge for CD3 T-cell engagers as a class in this disease. The ability of multi-specific DARPins to exploit the natural differentiation in antigen expression between healthy and cancerous cells supplies a powerful platform for highly targeted immuno-oncology solutions,” said Nicolas Leupin, MD, Ph.D., CMO of Molecular Partners. “We look forward to the MP0533 PhI study which, on top of the recent encouraging Phase I data presented at SITC (Society for Immunotherapy of Cancer) for MP0317 (targeting FAP and CD40, enabling tumor-localized immune activation), illustrates the strength and uniqueness of our DARPin portfolio.”

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. The unique safety profile of MP0533 was further supported by several other parameters including a lower level of cytokine release relative to benchmark mono-targeted T cell engagers, both in vitro in a whole blood assay and in vivo in the humanized mouse AML models.

These results have been disclosed at ASH 2022 in a podium presentation, which will also be made available on Molecular Partners’ website.

Presentation: “A Multispecific DARPin CD3 Engager Targeting CD33, CD123, and CD70 for the Treatment of AML and MDS Designed to Selectively Target Leukemic Stem Cells”
Session: 604
Timing: December 12, 2022: 5:45PM Central Time
Presenter: Anne Goubier, DVM

A Phase I clinical trial to evaluate safety and dose of MP0533 has been authorized to proceed by Swiss regulatory authorities’ and ethics committees. Patient enrollment is planned to initiate in the near future.