Medicenna Shares Preclinical Data on Anti-PD1-IL-2 BiSKIT and IL-2 Super Agonist at SITC Annual Meeting

Medicenna Therapeutics Corp., a clinical-stage immunotherapy company, recently presented new preclinical data from its BiSKIT (MDNA113) and IL-2 super agonist (MDNA11) programs at the 39th Annual Meeting of SITC in Houston, Texas. MDNA113 is a novel IL-13Rα2 tumor-targeted and "masked" BiSKIT engineered to deliver an anti-PD1-IL-2 Superkine to the tumor microenvironment, where it is activated by tumor-associated proteases. This treatment achieved complete tumor regression in IL-13Rα2 expressing tumors, showcasing its potential to treat various malignancies, including immunologically "cold tumors" affecting over two million cancer patients worldwide.

Internationally recognized academic teams in the UK demonstrated promising pre-clinical results with MDNA11 and anti-PD1-IL-2SK BiSKIT in mouse models of glioblastoma (GBM) and patient-derived GBM explants. Updated clinical results from the MDNA11 ABILITY-1 study were also set to be presented at SITC.

Fahar Merchant, Ph.D., President and CEO of Medicenna, expressed excitement about the new therapeutics such as MDNA113, highlighting its ability to inhibit tumor growth, especially in IL-13Rα2 positive tumors. MDNA113 showed potential to protect against and prevent metastasis in an aggressive breast cancer model when administered once prior to surgery. In separate presentations, academic collaborators in the UK highlighted the capacity of MDNA11 and anti-PD1-IL-2SK BiSKIT to significantly extend survival in aggressive GBM mouse models and stimulate the activity of resident effector immune cells in fresh human GBM explants.

MDNA113 is based on Medicenna's IL-2 and IL-13 Superkine Platforms. MDNA11, a long-acting IL-2 super agonist, is currently being evaluated in the Phase 1/2 ABILITY-1 study for advanced and/or metastatic solid tumors. Key highlights from the presentations include the conditionally activatable nature of MDNA113, which has a cleavable IL-13SK dual masking/tumor-targeting domain that limits systemic immune stimulation while maximizing anti-tumor response. Mice treated with MDNA113 showed reduced peripheral lymphocyte expansion without impacting anti-PD1/PDL1 blockade and better tolerability compared to unmasked anti-PD1-IL-2SK. Tumor-specific proteases remove the IL-13SK targeting and masking domain of MDNA113, restoring synergy between IL-2R agonism and anti-PD1 blockade. The efficacy of MDNA113 is significantly enhanced in mice harboring MC38 tumors engineered to overexpress IL-13Rα2, resulting in complete tumor regression in most animals. A single neoadjuvant treatment with MDNA113 in a highly invasive orthotopic model of triple-negative breast cancer resulted in 100% survival by preventing metastasis and enriching cytotoxic GrzB-positive CD8+ T cells within the tumor microenvironment.

Stimulation of IL-2 signaling with highly selective IL-2R super-agonists enhances immune effector cell response in mouse and patient-derived glioblastomas. Long-acting IL-2SK (MDNA11) and anti-PD1-IL-2SK (the therapeutic core of MDNA113) significantly extended survival of mice bearing aggressive orthotopic GBMs compared to control mice or mice treated with native IL-2 or anti-PD1. GBMs from anti-PD1-IL-2SK treated mice showed higher frequencies of infiltrating CD8+ T and NK cells with no change in immune suppressive Tregs. Ex-vivo primary patient-derived fresh GBM explants treated with IL-2SK or anti-PD1-IL-2SK showed increased CD8+ T and NK cell populations along with reduced tumor cell burden.

MDNA113 is a novel, first-in-class tumor-targeted and tumor-activated bi-functional anti-PD1-IL-2 Superkine with high affinity for IL-13Rα2. IL-13Rα2 is overexpressed in a wide range of solid tumors, including cold tumors, with minimal expression in normal tissues. Its expression is associated with poor clinical outcomes in multiple tumor types, such as prostate, pancreatic, ovarian, liver, breast, and brain cancer, affecting over two million individuals annually.

MDNA11 is an intravenously administered, long-acting 'beta-enhanced not-alpha' IL-2 Superkine specifically designed to overcome the limitations of aldesleukin and other next-generation IL-2 variants by preferentially activating immune effector cells (CD8+ T and NK cells) responsible for killing cancer cells, with minimal stimulation of immunosuppressive Tregs. This has been achieved by incorporating seven specific mutations and genetically fusing it to a recombinant human albumin scaffold to improve the pharmacokinetic profile and pharmacological activity due to albumin's natural propensity to accumulate in highly vascularized sites, such as tumors and tumor-draining lymph nodes. MDNA11 is currently being evaluated in the Phase 1/2 ABILITY-1 study as both monotherapy and in combination with pembrolizumab.

Medicenna is dedicated to developing novel, highly selective versions of IL-2, IL-4, and IL-13 Superkines and first-in-class Empowered Superkines. Their long-acting IL-2 Superkine, MDNA11, is a next-generation IL-2 with superior affinity toward CD122 (IL-2 receptor beta) and no CD25 (IL-2 receptor alpha) binding. This preferentially stimulates cancer-killing effector T cells and NK cells. Bizaxofusp (formerly MDNA55), an IL-4 Empowered Superkine, has been studied in five clinical trials including a Phase 2b trial for recurrent GBM. Bizaxofusp has obtained FastTrack and Orphan Drug status from the FDA.

Medicenna's early-stage high-affinity IL-2β biased IL-2/IL-15 Super-antagonists from the MDNA209 platform are being evaluated as potential therapies for autoimmune and graft-versus-host diseases. Their early-stage BiSKITs (Bifunctional SuperKine ImmunoTherapies) and T-MASK (Targeted Metalloprotease Activated SuperKine) programs are designed to enhance Superkine treatments for immunologically "cold" tumors.