Ms. Christina Cameron reports

MEDICENNA PRESENTS UPDATED PRECLINICAL DATA ON MDNA113, A FIRST-IN-CLASS, TARGETED AND MASKED BI-FUNCTIONAL ANTI-PD1-IL2 SUPERKINE, AT THE 2024 ANNUAL MEETING OF THE AMERICAN ASSOCIATION FOR CANCER RESEARCH (AACR)

Medicenna Therapeutics Corp. today presented new preclinical data on MDNA113, the company's novel T-MASK (targeted metallo/protease activated superkine) candidate, an IL-13Ra2 (Interleukin-13 receptor alpha2) specific superkine featuring unique masking and tumour targeting characteristics, were presented at the 2024 Annual Meeting of the American Association for Cancer Research (AACR) held in San Diego, Calif., on April 9, 2024.

• MDNA113 is targeted to the tumour site where it is activated to simultaneously deliver two immunotherapies, an IL-2 superkine and anti-PD1 antibody, to the same cancer fighting immune cells in the tumour microenvironment (TME) to maximize efficacy and minimize systemic toxicity.
• MDNA113 is the company's most advanced preclinical candidate that targets IL-13Ralpha2, a tumour-associated antigen, which is overexpressed by immunologically "cold" tumours with high unmet needs in pancreatic, prostate, ovarian, breast and brain cancer affecting over two million patients every year.

"We are pleased to show preclinical data demonstrating the ability of Medicenna's first T-MASK candidate, MDNA113 to enhance tumour accumulation and tolerability of our potent bifunctional immune modulator, anti-PD1-IL-2SK," said Fahar Merchant, PhD, president and chief executive officer of Medicenna. "MDNA113 has novel features, including the tunable blockade of the IL-2R agonism, to reduce peripheral immune stimulation for enhanced tolerability, and tumour targeting to IL-13Ra2 which is linked to aggressive cancers that annually affect over two million patients world-wide. The cleavage and release of the IL-13 tumour-targeting/masking domain by matrix metalloproteases restores IL-2R signalling within the tumour microenvironment, thereby benefiting from the simultaneous and synergistic activity of IL-2R agonism and immune checkpoint blockade at the tumour site."

The company selected MDNA113, a novel, first-in-class tumour-targeted and tumour-activated bifunctional anti-PD1-IL-2 superkine with high selectivity and affinity for IL-13Ralpha2, a tumour associated antigen expressed in many aggressive solid tumours. The IL-13 superkine (MDNA213) is a highly specific tumour-targeting/masking domain which is fused via a protease sensitive linker to a bifunctional immunotherapy domain (MDNA223) containing an IL-2 superkine fused to an anti-PD1 antibody.

Key findings presented at the conference include:

• When not activated, MDNA113 shows reduced IL-2R agonism with no change to PD-1/PDL-1 blockade activity.
• Cleavage and activation of MDNA113 by cancer specific enzymes (metalloproteases) releases the T-MASK domain (MDNA213), restoring activity of the IL-2 superkine at the tumour site.
• MDNA113 shows attenuated systemic lymphocyte expansion compared with non-masked version (MDNA223), consistent with design of MDNA113.
• MDNA113 is better tolerated than non-masked counterpart (MDNA223), supporting higher and more efficacious dosing schedule.
• MDNA113 selectively binds IL-13Ra2 positive tumour cells in vitro, and durably accumulates (greater than seven days) in IL-13Ra2 positive tumours in mice.
• Cleavable MDNA113 shows similar efficacy as non-masked MDNA223 in mouse tumour models by either localized (intra-tumoural) or systemic (intra-peritoneal) delivery, consistent with proteolytic activation within TME.
• Single neoadjuvant treatment with MDNA113 in a highly invasive orthotopic 4T1.2 breast cancer model significantly increases survival by preventing metastasis.
• In summary, the T-MASK platform exemplified by MDNA113, facilitates tumour targeting and minimizes systemic toxicity while maximizing therapeutic activity at the tumour site.

The poster, "Characterization of MDNA113, a Tumor-Targeting Anti-PD1-IL-2SK Immunocytokine with Conditional Activation to Increase Tolerability and Maximize Efficacy" can be found on the AACR website for conference registrants. It will be also available on the scientific presentations page of Medicenna's website following the conclusion of the 2024 annual meeting of AACR.

About the T-MASK platform

Medicenna's novel T-MASK (targeted metallo/protease activated superkine) platform involves fusion of a dual tumour-targeting/masking domain to an immune modulator (such as a superkine or a BiSKIT) via a matrix metalloprotease (MMP) sensitive linker to (i) reduce and fine tune the potency of the immune modulator, (ii) increase its systemic tolerability (iii) prolong its retention in the TME and (iv) to maximize and restore full potency at the intended target site. The T-MASK platform offers opportunity to target and fine tune immune cell stimulation in the TME to improve the therapeutic index of Medicenna's superkine and BiSKIT platforms.

About MDNA113

MDNA113 is a novel, first-in-class tumour-targeted and tumour-activated bifunctional anti-PD1-IL-2 superkine with high affinity for IL-13Ralpha2 without binding to the functional IL-13Ra1. IL-13Ralpha2 is overexpressed in a wide range of solid tumours, including cold tumours. IL-13Ralpha2 is a tumour-associated antigen with minimal to no expression in normal tissues but is highly expressed by a wide range of tumours including cold tumours. IL-13Ralpha2 expressing tumours also have abundant MMPs in the TME that may efficiently activate MDNA113. IL-13Ralpha2 expression is associated with poor clinical outcome in multiple tumour types with an annual worldwide incidence of over two million in different tumour types including prostate cancer, pancreatic cancer, ovarian cancer, liver cancer, breast cancer and brain cancer, and among others.

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 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 (glioblastoma), 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/European Medicines Agency, respectively. Medicenna's early-stage BiSKITs (bifunctional superkine immunotherapies) and the T-MASK (targeted metalloprotease activated superkine) programs are designed to enhance the ability of superkines to treat immunologically cold tumours.

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