Dr. Fahar Merchant reports

MEDICENNA PRESENTS PRECLINICAL DATA ON MDNA113, ITS TARGETED METALLOPROTEASE ACTIVATED SUPERKINE (T-MASK) AT THE 38TH ANNUAL MEETING OF THE SOCIETY FOR IMMUNOTHERAPY OF CANCER (SITC)

Medicenna Therapeutics Corp. has released new preclinical data demonstrating proof of concept for the company's novel T-MASK (targeted metalloprotease-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, Calif., from Nov. 1 to 5, 2023.

"We are pleased to show preclinical data demonstrating the ability of our T-MASK platform to enhance tumour-specific accumulation, increased anti-tumour activity while improving the safety profile of potent immune modulators such as Medicenna's bispecific IL-2-AntiPD1 superkine," said Dr. Fahar Merchant, PhD, president and chief executive officer of Medicenna. "The results presented today demonstrates proof of concept with MDNA113, our first T-MASK candidate specifically designed to deliver bispecific IL-2-antiPD1 superkine to cancers that express the tumour associate antigen, IL-13Ra2. This is an important advance for cancer immunotherapy as the IL13Ra2 target is linked to aggressive cancers that annually affect over two million patients worldwide."

The company selected MDNA113, a novel, first-in-class tumour-targeted and tumour-activated bispecific 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-13Ralpha2, a tumour-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 tumour targeting and prolonged tumour retention with conditional activation to maximize anti-tumour 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 tumour associated metalloproteases restores IL-2R signalling.
• MDNA113 is as effective as non-masked MDNA223 (a bispecific anti-PD1-IL-2 superkine) in tumour 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 tumour-associated antigen IL-13Ra2, is used both as a tumour-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 tumour microenvironment (TME).
• Upon delivery to the TME, the IL-13 superkine traps the immune-modulator within the tumour 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 tumours.

A copy of the poster will be posted to the events and presentations page of Medicenna's website following the conclusion of the meeting. Details on the in-person poster presentation are shown below.

Title: Characterization of a tumour-targeting and activatable T-MASK platform to enhance tumour accumulation and tolerability of potent immune modulators

Poster No.: 1071

Presentation date: Friday, Nov. 3, 2023, 9 a.m. to 7 p.m. PDT

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 CD122 (IL-2 receptor beta) binding without CD25 (IL-2 receptor alpha) affinity, 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, including a phase 2b trial for recurrent glioblastoma, the most common and uniformly fatal form of brain cancer. Bizaxofusp has fast-track and orphan drug status from the Food and Drug Administration and FDA/European Medicines Agency, respectively. Medicenna's BiSKITs (bifunctional superkine immunotherapies) and T-MASK (targeted metalloprotease-activated superkines) programs are in preclinical development designed to enhance the ability of superkines to treat immunologically cold tumours.

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