Medicenna Shares Preclinical Results on IL-2 Super-Antagonist and Anti-PD1-IL-2 BiSKIT at IL-2 Therapy Conference

Medicenna Therapeutics Corp., a clinical-stage immunotherapy company, has shared new preclinical data that underscore the potential of its two innovative treatments, MDNA209 and MDNA113, at the Promise of Interleukin-2 Conference in Paris. This development signals significant advancements in addressing both autoimmune diseases and certain types of cancer which currently lack effective therapy options.

MDNA209 is described as a first-in-class “beta-enhanced” IL-2 Super-antagonist intended for the treatment of autoimmune diseases. These diseases stem from an immune system imbalance, affecting up to 10% of the global population. MDNA209 works by selectively blocking IL-2Rβγc, a receptor abundantly expressed by CD8 T cells involved in tissue damage within autoimmune diseases. In a rigorous animal model of graft versus host disease (GvHD), MDNA209 demonstrated an ability to extend overall survival by 400%, curb weight loss, and enhance clinical scores, showcasing its therapeutic promise for GvHD and autoimmune diseases.

MDNA113, on the other hand, is a targeted BiSKIT (Bifunctional SuperKine for ImmunoTherapy) designed to deliver an anti-PD1-IL-2 Superkine directly to the tumor microenvironment (TME). This Superkine becomes active through tumor-associated proteases. In experiments on mice with tumors engineered to overexpress IL-13Rα2, MDNA113's efficacy improved significantly, indicating its potential use for treating "cold tumors" like pancreatic, prostate, ovarian, and breast cancers, which affect millions globally each year.

According to Dr. Fahar Merchant, President and CEO of Medicenna, the promising Phase 1/2 clinical results from the ABILITY-1 trial of MDNA11 inspired the company to use the same IL-2 Superkine platform for developing new treatments for cancer and autoimmune diseases. The preclinical data for MDNA209 and MDNA113 validate the broad applicability of their IL-2 Superkines beyond oncology, presenting new opportunities for treating GvHD and other diseases.

The first presentation at the conference highlighted MDNA209's potential to treat autoimmune diseases, including severe GvHD, which typically has a low one-year survival rate. Patients suffering from GvHD after transplants face significant health challenges and limited treatment options. Preclinical data on MDNA209 illustrates its ability to extend survival, mitigate weight loss, and improve clinical outcomes in an animal model of acute GvHD.

The second presentation centered on MDNA113, a novel, targeted, and bifunctional anti-PD1-IL-2 Superkine. Despite the success of anti-PD1 therapies in some cancer treatments, about 70% of cancer patients do not benefit from such therapies. MDNA113 aims to address this gap by using an IL-13 Superkine to direct and localize the BiSKIT to the tumor site while minimizing its toxicity in peripheral circulation. Upon reaching the TME, specific proteases activate MDNA113, which then engages T-cells, stimulating their activity and preventing exhaustion.

Key findings from the presentations include:
- MDNA209, having a high affinity for IL-2Rβ but not engaging the γc subunit, acts as a receptor clamp to prevent IL-2 and IL-15 signaling, reduces immune cell proliferation, and preserves Treg populations.
- In an aggressive animal model of acute GvHD, MDNA209 significantly extended survival, reduced weight loss, and improved clinical scores.
- MDNA113, in contrast, showed reduced IL-2R signaling during testing compared to a non-masked version in cell assays and human T cells, without interfering with PD1/PDL1 blockade.
- The proteolytic activation of MDNA113 restored its IL-2R signaling capabilities, enhancing its therapeutic efficacy.
- Mice treated with MDNA113 saw lower peripheral lymphocyte expansion compared to the non-masked version, due to the IL-13 Superkine masking.
- MDNA113 demonstrated better tolerability in multiple dosages, and its efficacy was notably increased in tumors engineered to overexpress IL-13Rα2.

These advancements suggest that Medicenna's innovative platforms may offer new, effective therapies for both autoimmune diseases and challenging cancers, addressing substantial unmet medical needs.