Medicenna Presents Preclinical Data on IL-2 Super-Antagonist MDNA209 and Anti-PD1-IL-2 BiSKIT MDNA113
核心洞察
Medicenna (搜索)'s MDNA209, an IL-2 super-antagonist, demonstrated a 400% increase in overall survival in an animal model of graft versus host disease (搜索) (GvHD (搜索)), suggesting potential in autoimmune disease treatment.
MDNA113, a tumor-targeted anti-PD1-IL-2 BiSKIT, showed enhanced efficacy in mice with IL-13Rα2 (搜索)-overexpressing tumors, indicating promise for treating immunologically 'cold' tumors like pancreatic and ovarian cancers.
The BiSKIT approach of MDNA113 allows for conditional activation in the tumor microenvironment, potentially improving safety and efficacy compared to traditional anti-PD1 therapies.
Medicenna (搜索) Therapeutics Corp. presented preclinical results for two of its programs, MDNA209 and MDNA113, at the Promise of Interleukin-2 Conference in Paris. The data highlight the potential of these assets in treating autoimmune diseases (搜索) and solid tumors, respectively, leveraging Medicenna's IL-2 Superkine platform.
MDNA209: IL-2 Super-Antagonist for Autoimmune Diseases
MDNA209 is a first-in-class IL-2 super-antagonist designed to restore immune balance by selectively blocking IL-2Rβγc (搜索), a receptor highly expressed by effector CD8 T cells implicated in tissue damage in autoimmune disorders. Preclinical data in an aggressive animal model of graft versus host disease (搜索) (GvHD (搜索)) demonstrated that MDNA209 extended overall survival by 400%, reduced weight loss, and improved clinical scores. These results suggest its therapeutic potential for treating GvHD and other autoimmune diseases (搜索), which affect 5-10% of the global population.
MDNA209-Fc inhibits both, IL-2 and IL-15 induced p-STAT5 signaling, reduces IFNγ release and slows immune cell proliferation without reducing Treg population.
MDNA113: Tumor-Targeted Anti-PD1-IL-2 BiSKIT for Cold Tumors
MDNA113 is an IL-13Rα2 (搜索) tumor-targeted BiSKIT (Bifunctional SuperKine for ImmunoTherapy) that delivers an anti-PD1-IL-2 Superkine (anti-PD1-IL-2SK) directly to the tumor microenvironment (TME), where it is conditionally activated by tumor-associated proteases. This approach aims to enhance efficacy and reduce toxicity compared to systemic anti-PD1 therapies, which have shown limited benefit in approximately 70% of cancer patients.
In preclinical studies, MDNA113's efficacy was significantly enhanced in mice harboring tumors engineered to overexpress IL-13Rα2 (搜索), resulting in complete tumor regression in most animals. This highlights its potential to treat immunologically "cold tumors" such as pancreatic, prostate, ovarian, and breast cancers (搜索), which affect over two million patients annually. The IL-13 Superkine masks the IL-2 domain during peripheral circulation, reducing toxicity, and is cleaved by tumor-specific proteases in the TME, releasing the BiSKIT to engage with T-cells and stimulate T-cell activity while preventing T-cell exhaustion via the anti-PD1 domain.
Mice treated with MDNA113 showed reduced peripheral lymphocyte expansion compared to anti-PD1-IL-2SK due to masking by the IL-13 Superkine. MDNA113 showed greater tolerability than anti-PD1-IL-2SK following repeat dose administration in mice.
Clinical Implications
These preclinical findings support the further development of MDNA209 and MDNA113 as potential therapies for autoimmune diseases (搜索) and solid tumors, respectively. Medicenna (搜索) is leveraging its IL-2 Superkine platform to advance its pipeline of transformative medicines, addressing unmet needs in both oncology and autoimmune indications.