Medicenna Presents Preclinical IL-13 Superkine Data at the AACR Annual Meeting
-- IL-13 Superkines provide a versatile strategy for targeted delivery of anti-cancer agents to IL-13Rα2, which is overexpressed in many solid tumors but minimally expressed in normal tissues
-- MDNA132 and MDNA213 are novel IL-13 Superkines that are highly specific and preferentially accumulate in the microenvironment of IL-13Rα2-expressing tumors
--IL-13 Empowered Superkines™ act synergistically in combination with IL-2 Superkines in aggressive models of immunologically “cold” tumors
“Our IL-13 Superkines have been engineered to target the IL-13 decoy receptor, IL-13Rα2, which is overexpressed in several solid tumors but minimally expressed in normal tissues, making it an attractive target for immunotherapies,” said
The AACR poster includes data demonstrating that both MDNA132 and MDNA213 exhibit highly selective binding to the IL-13 decoy receptor (IL-13Rα2) and, in a murine model, selectively accumulate in the tumor microenvironment (TME) for several days. The presentation also characterizes a series of next generation IL-13 Superkines, which are described below:
Anti-mCD3-MDNA132: A first-in-class IL-13 directed Cell Engager (ICE – Making Cold Tumors Hot™) comprised of MDNA132 fused to an anti-CD3 antibody. In vitro data demonstrate the molecule retains strong binding affinity to both IL-13Rα2, expressed on tumors, and CD3, expressed by cancer fighting immune cells. The ICE™ platform is designed to overcome cancer cells’ immune escape by recruiting the patients’ own immune cells to directly target immunologically “cold” tumors.
MDNA19-MDNA213: A first-in-class BiSKIT™ (Bifunctional SuperKines for ImmunoTherapy) comprised of MDNA213 fused to MDNA19, the Fc version of our IL-2 Superkine MDNA11. In vitro data demonstrate that the BiSKIT retains strong binding affinity and selectivity to both the IL-13Rα2 and CD122 (IL-2Rβ) receptors and stimulates cancer killing effector T cells and NK cells without stimulating cells associated with toxicity or pro-tumor immune suppression. This BiSKIT enables localization and retention of our IL-2 Superkines in the TME.
Anti-mPD1-MDNA213: A first-in-class BiSKIT comprised of MDNA213 fused to an anti-PD1 checkpoint inhibitor. In vitro data demonstrate that this BiSKIT retains strong binding affinity for both IL-13Rα2 and PD1, effectively blocks the PD1/PD-L1 interaction with similar potency as the native anti-PD1 antibody, allowing its activity to be localized in the TME.
MDNA213-PE: A novel Empowered Superkine™ comprised of MDNA213 fused to the PE cytotoxin. In vitro data demonstrate that this molecule exhibits selective and potent cytotoxic activity towards human and murine cancer cells that express IL-13Rα2. Additionally, in a murine, checkpoint inhibitor-refractory, triple-negative breast cancer model, MDNA213-PE inhibited tumor growth as a single agent and synergized with an IL-2 Superkine (MDNA19) to significantly enhance therapeutic efficacy.
The poster, “Characterization of MDNA132, an IL-13 Decoy Receptor Selective Superkine for Targeted Delivery of Immunotherapies to the Tumor Microenvironment,” can be found on the AACR website for conference registrants. It will be available on the Events and Presentations page of Medicenna’s website following the conclusion of the meeting.
Medicenna is a clinical stage immunotherapy company focused on the development of novel, highly selective versions of IL-2, IL-4 and IL-13 Superkines and first in class Empowered Superkines. Medicenna’s long-acting IL-2 Superkine, MDNA11, is a next-generation IL-2 with superior CD122 (IL-2 receptor beta) binding without CD25 (IL-2 receptor alpha) affinity thereby preferentially stimulating cancer killing effector T cells and NK cells. Medicenna’s early-stage BiSKITs™ program, (Bifunctional SuperKine ImmunoTherapies) is designed to enhance the ability of Superkines to treat immunologically “cold” tumors. Medicenna’s IL-4 Empowered Superkine, bizaxofusp (formerly MDNA55), has been studied in 5 clinical trials including a Phase 2b trial for recurrent GBM, the most common and uniformly fatal form of brain cancer. Bizaxofusp has obtained FastTrack and Orphan Drug status from the FDA and FDA/EMA, respectively.
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Source: Medicenna Therapeutics Corp.