Medicenna Therapeutics Corp. announced new preclinical data demonstrating proof of concept for the Company?s novel T-MASK (Targeted Metallo/protease Activated SuperKine) platform technology with the Company?s development candidate, MDNA113, at the 38th Annual Meeting of the Society for Immunotherapy of Cancer (?SITC?) held in San Diego, CA, from November 1-5, 2023. The Company selected MDNA113, a novel, first-in-class tumor-targeted and tumor-activated bi-specific antiPD1-IL-2 Superkine as its first development candidate using the T-MASK platform.

MDNA113 has high selectivity and affinity for the IL-13 decoy receptor IL-13Ra2, a tumor associated antigen expressed by many aggressive solid tumors. MDNA113 is fused via a protease sensitive linker (?PSL?) to MDNA223, containing a not-alpha, beta-enhanced IL-2 Superkine fused to anti-PD1 antibody. Key findings include: T-MASK platform integrates tumor targeting and prolonged tumor retention with conditional activation to maximize anti-tumor efficacy and minimize systemic toxicity MDNA113 shows reduced IL-2R agonism with no change to PD1/PDL-1 blockade MDNA113 reduces systemic lymphocyte expansion showing dampening of systemic activity Cleavage of MDNA113 by tumor associated metalloproteases restores IL-2R signaling.

MDNA113 is as effective as non-masked MDNA223 (a bispecific antiPD1-IL-2 superkine) in tumor models. Unlike other conditionally activated immunotherapies, the T-MASK platform has the following unique features: The IL-13 Superkine, engineered to bind with high affinity to the tumor associated antigen IL-13R?2, is used both as a tumor targeting component and a masking agent. The level of masking is tunable and avoids complete blockade of the immune-modulator thereby retaining good tolerability while achieving adequate systemic activity during its transit to the tumor micro-environment (TME) Upon delivery to the TME, the IL-13 Superkine traps the immune-modulator within the tumor for a prolonged period, allowing adequate time for metalloproteases to cleave the protease sensitive linker (?PSL?) and activate the long-acting immune-modulator Combining modest systemic immune simulation with potent immune activation within the TME, could provide better outcomes for patients with immunosuppressive tumors.

Title: Characterization of a tumor-targeting and activatable T-MASK platform to enhance tumor accumulation and tolerability of potent immune modulators Poster Number: 1071 Presentation Date: Friday, November 3, 2023, 9:00 am to 7:00 pm PDT.