Focused on developing the next Superkines
Preclinical and discovery programs
Leveraging the broad capabilities and potential of interleukins, the Medicenna Superkine platform is geared towards identifying and engineering interleukins (abbreviated as IL) for a variety of indications.
IL-2 Superkine Antagonist
MDNA209: Immune Off Switch
MDNA209 is an IL-2 Superkine that has a 200 times higher affinity to the IL-2Rβ, similar to MDNA11. Where MDNA11 boosts the immune system into action, MDNA209 suppresses it by blocking the immune-activating signal. The mechanism of MDNA209 is suited for diseases such as autoimmune disorders where aberrant T cells are overactive and attack healthy tissue.
IL-2Rβ can prove to be an effective target for fine-tuning the immune responses. Read more about this receptor here.
IL-4 and IL-13 Superkines
Th2 cells, a subgroup of T helper (Th) cells that mediate the activity of the adaptive immune system, are responsible for long-term protection against pathogens. IL-4 and IL-13 are critical to the development of Th2 immune responses. However, when imbalanced, they can lead to allergy, asthma, fibrosis and even aggressive forms of cancer.
In some cancers, the tumor twists the function of Th2 cells to help it grow and protect itself, instead of fighting it. Both IL-4 and IL-13, which have overlapping functions, participate in perpetuating tumor-associated immune cells and the tumor microenvironment, both of which aid the cancer.
Blunting the ability of these two interleukins through our Superkine platform offers the opportunity to benefit patients suffering from cancer and other Th2-mediated diseases. Our IL-4 and IL-13 Superkines are designed to disrupt the undesirable signals that the tumors have co-opted to protect themselves. In doing so, it creates the possibility to attack them using checkpoint inhibitors or other forms of immunotherapy.
MDNA413 is another IL-13 Superkine. In this case, it has an increased affinity for the IL-13 receptor subunit alpha-1 (IL-13Rα1). This is a Type 2 receptor that is shared between IL-4 and IL-13, and is expressed on the immunosuppressive cells of the TME, as well as effector cells associated with Th2 diseases. MDNA413 has a 52-fold greater affinity for IL-13Rα1 — and is 391 times less likely to bind the IL-13Rα2 dummy receptor — compared to normal IL-13. Additionally, it prevents the receptor from initiating its usual signaling events.
MDNA132 is a modified IL-13 Superkine that is 16 million times more likely to bind the “dummy” IL-13 receptor subunit alpha-2 (IL-13Rα2). This receptor is not normally expressed on healthy cells, but is highly expressed on tumors such as glioblastoma, breast, colorectal, gastric, thyroid, prostate, lung and pancreatic cancer — but not in healthy tissue. Because of this selectivity and differentiation, IL-13Rα2 can prove to be a viable drug target.