공고 • Apr 23
Medicenna Therapeutics Corp Presents Positive Data Demonstrating Superior Safety and Efficacy Potential of Its First-In-Class Anti-Pd-1 X Il-2 Bifunctional Superkine Mdna113 At Aacr
Medicenna Therapeutics Corp. presented new positive preclinical data from MDNA113, its first-in-class tumor-anchored and conditionally activated anti-PD-1 x IL-2 bifunctional Superkine, at the American Association for Cancer Research Annual Meeting 2026 in San Diego, California. The data demonstrate that MDNA113’s architecture delivers on the promise of a truly differentiated and highly tolerable PD-1 x IL-2 bifunctional. In a head-to-head non-human primate study, MDNA113 was well tolerated at doses up to 50 mg/kg while a representative anti-PD-1 x IL-2a-biased bispecific could not be administered a second dose at a fraction of that exposure due to severe toxicity, including evidence of vascular leak syndrome. MDNA113 was well tolerated at doses up to 50 mg/kg in non-human primates with pharmacokinetics consistent with approved anti-PD-1 therapies, supporting advancement toward an Investigational New Drug submission expected in the second half of 2026. PD-1 bispecifics have emerged as a leading next-generation approach to enhancing the efficacy of PD-1 inhibitors, the best-selling class of oncology drugs in the world. The commercial potential of PD-1 x IL-2 bispecifics specifically has been validated by recent multi-billion-dollar transactions. MDNA113 is built on the Company’s IL-2 and IL-13 Superkine platforms. The ß-enhanced not-a IL-2 Superkine at the core of MDNA113 is shared with MDNA11, the Company’s clinical-stage IL-2 Superkine, which has demonstrated durable single-agent anti-tumor activity and a manageable safety profile in the ongoing Phase 1/2 ABILITY-1 study in patients with advanced solid tumors. Unlike competing PD-1 x IL-2 programs that utilize proprietary anti-PD-1 antibodies, MDNA113 incorporates variants of commercially validated, approved human anti-PD-1 antibodies. MDNA113 is designed to address the safety and dosing limitations that have constrained first-generation molecules in this class by combining a commercially validated anti-PD-1 antibody with Medicenna’s clinically validated IL-2 Superkine, the only next-generation IL-2 with demonstrated durable single-agent anti-tumor activity, in a tumor-targeted, conditionally activated architecture. MDNA113’s masking architecture achieved greater than 10,000-fold attenuation of IL-2R agonism relative to the non-masked parent molecule while preserving full PD-1/PD-L1 blockade, and the masking domain demonstrated stability in serum for at least 8 days, confirming that IL-2 Superkine is effectively shielded from systemic exposure until activated within the tumor microenvironment. MDNA113 demonstrated two independent mechanisms of conditional activation: tumor-associated matrix metalloprotease cleavage fully restored IL-2R signaling at the tumor site, and proximity-dependent unmasking upon engagement with PD-1-expressing T cells provided a second activation pathway independent of protease expression, a key differentiator versus competing masked programs that rely solely on matrix metalloprotease cleavage. MDNA113’s IL-13Ra2 tumor-targeting domain drove selective accumulation and prolonged residence at the tumor site for at least 3 days in IL-13Ra2-expressing tumors, with clearance from non-expressing tissue, a tumor-anchoring capability not incorporated by any other PD-1 x IL-2 bispecific in development. In syngeneic mouse tumor models, MDNA113 demonstrated significant tumor growth inhibition with preferential expansion of CD8+ T cells expressing Granzyme B over NK cells and regulatory T cells, and efficacy was compromised with an uncleavable version, confirming conditional activation within the tumor microenvironment is required for therapeutic effect. MDNA113 was well tolerated at doses of 10, 30 and 50 mg/kg in non-human primates with pharmacokinetics consistent with approved anti-PD-1 antibodies, expanded CD8+ T cells without significant regulatory T cell increase, and did not produce dose-limiting adverse findings at any dose level tested. In a head-to-head non-human primate comparison at molar-equivalent doses, an anti-PD-1 x IL-2a-biased bispecific (1.4 mg/kg) exhibited severe toxicity after a single dose, including evidence of vascular leak syndrome, significant body weight loss, decreased serum albumin, elevated blood urea and liver enzymes, and increased white blood cell counts, and could not receive a second dose due to ongoing adverse events. By contrast, MDNA113 was well tolerated at exposures more than 30-fold higher than the single tolerated dose of the a-biased comparator and received repeat dosing without treatment-limiting findings, demonstrating a fundamentally wider therapeutic window than competing first-generation anti-PD-1 x IL-2a-biased bispecifics. MDNA113 is a novel, first-in-class tumor-targeted and tumor-activated bifunctional anti-PD-1x IL-2 Superkine with exceptionally high affinity for IL-13Ra2 without binding to the functional IL-13Ra1. IL-13Ra2 is overexpressed in a wide range of solid tumors, including “immunologically cold” tumors, with minimal to no expression in normal tissues. IL-13Ra2-expressing tumors also have abundant matrix metalloproteases in the tumor microenvironment that may efficiently activate MDNA113. IL-13Ra2 expression is associated with poor clinical outcomes in multiple tumor types including prostate, pancreatic, ovarian, liver, breast and brain cancer, with an annual worldwide incidence of over 2 million.