MDNA55 Our Lead Program– A Meaningful Medicine Supporting a Broad Pipeline
Our lead candidate MDNA55 is a first-in-class, Interleukin-4 Empowered Cytokine™ that specifically targets the Interleukin-4 Receptor (IL4R). The IL4R is over-expressed by 20 different cancers, cancer stem cells and immunosuppressive cells of the tumor micro-environment (TME). MDNA55 has the potential to not only purge the tumor but can also un-blind the immune system to cancer altering the treatment paradigm for a large majority of cancer patients.
MDNA55 is a novel first in class Interleukin-4 Empowered Cytokine (IL4-EC). This proprietary targeted Molecular Trojan Horse is designed to harness the exceptional specificity and affinity of Superkines™ (engineered cytokines) to selectively and simultaneously deliver cell killing Payloads to the bulk tumor, tumor microenvironment (TME) and cancer stem cells (CSC).
A Powerful Molecular Trojan Horse
Tumor Targeting Domain
Circularly Permuted Interluken-4 (cpIL-4)
Tumor Killing “Cytotoxic” Domain
Catalytic domain of Pseudomonas Exotoxin A (PE)
MDNA55 is an engineered circularly permuted interleukin-4 (cpIL-4) genetically fused to the catalytic domain of the bacterial pseudomonas exotoxin A (PE). The resulting fusion protein is designed such that the exotoxin is only active in the cytoplasm of the target cell following receptor-mediated endocytosis via the IL-4/IL-4R axis.
WHY TARGET THE IL4R
The interleukin-4 receptor (IL4R) is an attractive target for the development of cancer therapeutics, because it is frequently and intensely expressed on a wide variety of human carcinomas. The determination of a pivotal role for IL4R in the emergence and advancement of the malignant phenotype, overexpression on CSCs and its dominant role in the TME validates our approach of pursuing with the IL4R as an important cancer target.
Components of the TME, such as Tumor Associated Macrophages (TAMs), Myeloid Derived Suppressor Cells (MDSCs) and a Th2>>Th1 profile, are each attributed to a robust IL-4/IL-4R bias and generally associated with highly aggressive forms of cancer and poor survival outcomes.
Analysis of over 2,000 cancer biopsies, shows that the IL-4R is over-expressed in 20 different types solid and hematological cancers corresponding to an annual incidence rate of over a million IL4R positive cancers providing many future indications to pursue.
Examples of IL-4R Over Expression
An Initial Focus on rGBM and Brain Tumors
In the United States, nearly 23,000 primary malignant tumors of the brain will be diagnosed and cause over 15,000 deaths. 170,000 new cases of primary cancers originating in the lung, breast, colon and other organs metastasize to the brain. At metastasis, the median survival of untreated patients is 1-2 months and is extended to less then 9 months in patients treated with surgery, chemotherapy, and radiation. Analysis of over 300 brain tumor biopsies, from primary adult and pediatric brain tumors as well as adult metastatic brain tumors, consistently show that over 75% of brain cancer patients over-express the IL4R.
On a Fast Track to Make a Difference
MDNA55 was previously studied in 3 clinical trials in 72 patients with rGBM, a uniformly fatal form of brain cancer, in which it has shown compelling indications of superior efficacy to the current standard of care. MDNA55 has been granted both Fast Track (FDA) and Orphan Drug Status (FDA and EMA) for the treatment of rGBM.
Medicenna has completed patient enrollment in the Phase 2 clinical trial for MDNA55 in up to 52 rGBM patients at clinical sites throughout the U.S, and expects to complete the study in early 2020.