MDNA223 / Medicenna - LARVOL DELTA

Stimulation of IL-2 signaling with highly selective IL-2R agonists enhances immune effector cell response in mouse and patient-derived glioblastomas (SITC 2024) - "Conclusions In vivo studies in mouse orthoptic GBM models and primary human GBM explants demonstrate the potential use of MDNA11 and MDNA223 for the treatment of this highly aggressive tumor indication with a high unmet need. Ongoing research focuses on further elucidating the mechanism of action of MDNA11 and MDNA223 in GBM as well as exploring potential synergy with other therapeutics and treatment modalities."

IO biomarker • Preclinical • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor • CD8 • FASLG • GZMB • IL2RA • STAT5 • STAT5AWqe

Invigorating effector immune cells with highly selective IL-2R agonists and potential synergy with tumor targeting therapeutics for treatment of glioblastomas (SNO 2024) - "There was also increased release of soluble Fas ligand and granulysin, consistent with an activated anti-tumor immune response within the TME. Ongoing studies include in depth immune profiling to further understand the mechanism of MDNA11 and MDNA223 in GBM as well as to test potential synergy with tumor targeting therapeutics and other treatment modalities capable of eliciting immunogenic cell death."

Immune cell • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor • CD8 • FAS • FASLG • GZMB • IL2 • IL2RA

Characterization of MDNA113, a tumor-targeting anti-PD1-IL-2SK immunocytokine with conditional activation to increase tolerability and maximize efficacy (AACR 2024) - "Background-MDNA113 consists of an IL-13 decoy receptor-binding domain (MDNA213) fused to anti-PD1-IL-2SK (MDNA223) immunocytokine using a matrix metalloprotease (MMP) sensitive linker (PSL). Conclusion-MDNA113 is a tumor-targeting and conditional-activatable anti-PD1/IL-2SK fusion characterized with potent PD1/PDL1 blockade and 'not-alpha, beta enhanced' IL-2R agonism. MDNA113 is better tolerated than the non-mask version while achieving similar effect on tumor control, therefore offering a much broader therapeutic index."

Clinical • IO biomarker • Oncology • Solid Tumor • CD8 • IL13 • STAT5 • STAT5AWqe

Medicenna Presents Updated Preclinical Data on MDNA113, a First-in-Class, Targeted and Masked Bi-functional anti-PD1-IL2 Superkine, at the 2024 Annual Meeting of the American Association for Cancer Research (AACR) (GlobeNewswire) - "Medicenna Therapeutics...announced new preclinical data on MDNA113, the Company’s novel T-MASK (Targeted Metallo/protease Activated SuperKine) candidate, an IL-13R⍺2 (Interleukin-13 receptor alpha2) specific superkine featuring unique masking and tumor targeting characteristics, were presented at the 2024 Annual Meeting of the American Association for Cancer Research (AACR)....MDNA113 shows attenuated systemic lymphocyte expansion compared to non-masked version (MDNA223), consistent with design of MDNA113. MDNA113 is better tolerated than non-masked counterpart (MDNA223), supporting higher and more efficacious dosing schedule. MDNA113 selectively binds IL-13R⍺2 positive tumor cells in vitro, and durably accumulates (>7 days) in IL-13R⍺2 positive tumors in mice."

Preclinical • Breast Cancer • Oncology

Characterization of a tumor-targeting and activatable T-MASK platform to enhance tumor accumulation and tolerability of potent immune modulators (SITC 2023) - "MDNA213 is fused via a PSL to MDNA11 and MDNA223, both containing a not-alpha, beta-enhanced IL-2 fused with albumin or anti-PD1 antibody respectively. Conclusions MDNA113 is a novel T-MASK construct designed to increase tolerability while leveraging the synergy between PD1/PDL-1 blockade and IL-2R agonism for immunotherapy. Ongoing studies investigate alternative tumor-targeting/masking domains and immune modulators, including other cytokines and potent therapeutic agents, to potentially broaden the utility of the T-MASK platform."

Oncology • Solid Tumor • IL13 • IL2RA • STAT5 • STAT5AWqe

Medicenna Presents Preclinical MDNA223 BiSKIT Data at the AACR Special Conference on Tumor Immunology and Immunotherapy (GlobeNewswire) - "Medicenna Therapeutics Corp...announced that new preclinical data characterizing MDNA223, an anti-PD1-IL-2 BiSKIT (Bifunctional SuperKine for ImmunoTherapy), were presented at the 2023 AACR Special Conference in Cancer Research: Tumor Immunology and Immunotherapy held from October 1 - 4, 2023, in Toronto, Canada....Demonstrated superior efficacy and survival benefit in multiple syngeneic tumor models, including 'cold' tumors compared to co-administration (combination) of anti-PD1 and IL-2 agonist, Synergized with agonist of the STING (Stimulator of Interferon Genes) pathway to enhance tumor inhibition and promote an abscopal effect as demonstrated by shrinkage of the untreated tumor on opposite flank, Synergized with STING agonist and enhanced tumor inhibition by abscopal effect, Enhanced tumor response while being well-tolerated in a step-up dosing setting."

Preclinical • Oncology

Medicenna to Present at the AACR Special Conference Cancer Research: Tumor Immunology and Immunotherapy (GlobeNewswire) - "Medicenna Therapeutics...announced that the Company will present preclinical results featuring its MDNA223 BiSKIT candidate at the 2023 AACR Special Conference in Cancer Research: Tumor Immunology and Immunotherapy to be held from October 1 - 4, 2023, in Toronto, Canada."

Preclinical • Oncology

Medicenna Presents Preclinical Data Demonstrating Anti-Tumor Activity of its Anti-PD1-IL-2 BiSKIT and Long-Acting IL-4/IL-13 Super-antagonist at Cytokines 2022 (GlobeNewswire) - "In vitro data presented at the meeting demonstrated MDNA223’s potency against the PD1/PDL1 checkpoint was similar to that of a control anti-PD1 antibody while displaying increased affinity for IL-2 receptor beta (IL-2Rβ) and no binding to IL-2 receptor alpha (IL-2Rα). This enhanced IL-2Rβ selectivity resulted in potent and preferential stimulation of anti-cancer CD8+ T cells over pro-tumor Treg cells. In vivo murine data showed MDNA223 exhibiting a prolonged pharmacodynamic response extending beyond the duration of pharmacokinetic exposure. In addition, the murine surrogate of MDNA223 showed superior efficacy compared to co-administration of anti-PD1 and long acting MDNA109FEAA in murine models of colon, skin, and breast cancer."

Preclinical • Breast Cancer • Colon Cancer • Gastrointestinal Cancer • Melanoma • Oncology • Skin Cancer • Solid Tumor