Dr. Fahar Merchant reports

MEDICENNA 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 2026

Medicenna Therapeutics Corp. today presented new positive preclinical data from MDNA113, its first-in-class tumour-anchored and conditionally activated anti-PD-1 x IL-2 bifunctional superkine, at the American Association for Cancer Research (AACR) annual meeting 2026 in San Diego, Calif.

• New in vivo data demonstrate exceptional selectivity, localization and potency of MDNA113 in the tumour and tumour microenvironment while enhancing the systemic tolerability profile.
• Head-to-head non-human primate comparison against an anti-PD-1 x IL-2alpha-biased bispecific demonstrates MDNA113's superior tolerability and significantly wider therapeutic window.
• MDNA113 was well tolerated at doses up to 50 milligrams/kilogram in non-human primates with pharmacokinetics consistent with approved anti-PD-1 therapies, supporting advancement toward an investigational new drug (IND) submission expected in the second half of 2026.

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-2alpha-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.

"Taken together, these data demonstrate that MDNA113 is a first-in-class PD-1 x IL-2 bifunctional with exquisite design that delivers superior tolerability and a significantly wider therapeutic window compared with first-generation approaches," said Dr. Fahar Merchant, PhD, president and chief executive officer of Medicenna. "This is exactly the kind of data we had hoped for on our design thesis: by combining tumour anchoring, dual conditional activation and a beta-enhanced not-alpha IL-2 superkine, we can dose at levels comparable to approved anti-PD-1 therapies without the systemic toxicity that has forced competitors to compromise on potency by lowering the dose and attenuating activity of IL-2. With MDNA113, we have fused a blockbuster anti-PD-1 with our IL-2 superkine, which has already demonstrated promising single-agent activity in immunotherapy-resistant patients, significantly derisking clinical development. We look forward to advancing MDNA113 toward an IND submission later this year."

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 multibillion-dollar transactions.

MDNA113 is built on the company's IL-2 and IL-13 superkine platforms. The beta-enhanced not-alpha 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-tumour activity and a manageable safety profile in the continuing phase 1/2 Ability-1 study in patients with advanced solid tumours. 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-tumour activity, in a tumour-targeted, conditionally activated architecture.

Key highlights from the presentation

• 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 eight days, confirming that IL-2 superkine is effectively shielded from systemic exposure until activated within the tumour microenvironment.
• MDNA113 demonstrated two independent mechanisms of conditional activation: tumour-associated matrix metalloprotease (MMP) cleavage fully restored IL-2R signaling at the tumour 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 MMP cleavage.
• MDNA113's IL-13Ralpha2 tumour-targeting domain drove selective accumulation and prolonged residence at the tumour site for at least three days in IL-13Ralpha2-expressing tumours, with clearance from non-expressing tissue, a tumour-anchoring capability not incorporated by any other PD-1 x IL-2 bispecific in development.
• In syngeneic mouse tumour models, MDNA113 demonstrated significant tumour 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 tumour 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-2alpha-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 continuing adverse events.
• By contrast, MDNA113 was well tolerated at exposures more than 30-fold higher than the single tolerated dose of the alpha-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-2alpha-biased bispecifics.

A copy of the poster is available on the "Scientific Presentations" page of Medicenna's website.

About MDNA113

MDNA113 is a novel, first-in-class tumour-targeted and tumour-activated bifunctional anti-PD-1x IL-2 superkine with exceptionally high affinity for IL-13Ralpha2 without binding to the functional IL-13Ralpha1. IL-13Ralpha2 is overexpressed in a wide range of solid tumours, including "immunologically cold" tumours, with minimal to no expression in normal tissues. IL-13Ralpha2-expressing tumours also have abundant matrix metalloproteases in the tumour microenvironment that may efficiently activate MDNA113. IL-13Ralpha2 expression is associated with poor clinical outcomes in multiple tumour types including prostate, pancreatic, ovarian, liver, breast and brain cancer, with an annual worldwide incidence of over two million.

About Medicenna Therapeutics Corp.

Medicenna is a clinical-stage immunotherapy company focused on developing novel, highly selective versions of IL-2, IL-4 and IL-13 superkines, and first-in-class empowered superkines. Medicenna's 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, thereby preferentially stimulating cancer-killing effector T cells and NK cells. Medicenna's first-in-class targeted PD-1 x IL-2 bifunctional, MDNA113, is in development for solid tumours and was designed using the company's proprietary BiSKITs (bifunctional superkine immunotherapies) and T-MASK (targeted metalloprotease activated superkine) platforms. Medicenna's IL-4 empowered superkine, bizaxofusp (formerly MDNA55), has been studied in five clinical trials enrolling over 130 patients, including a phase 2b trial for recurrent GBM, the most common and uniformly fatal form of brain cancer. Bizaxofusp has obtained fast-track and orphan drug status from the Food and Drug Administration and FDA/EMA, respectively.

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