Dr. Fahar Merchant reports

MEDICENNA REPORTS MDNA11'S COMPELLING ANTI-CANCER ACTIVITY IS ASSOCIATED WITH SIGNIFICANT EXPANSION OF 'STEM-LIKE' CANCER FIGHTING IMMUNE CELLS AT THE INAUGURAL AACR-IMMUNO-ONCOLOGY CONFERENCE AND PROVIDES ABILITY-1 STUDY UPDATE

Medicenna Therapeutics Corp. has presented new clinical data from its continuing Ability-1 study evaluating MDNA11 alone or in combination with Merck's (known as MSD outside of the United States and Canada) anti-PD-1 therapy, Keytruda (pembrolizumab) in patients with advanced solid tumours. The data were presented in a late-breaking abstract at the inaugural American Association for Cancer Research Immuno-Oncology Conference (AACR-IO), taking place in Los Angeles, Calif., from Feb. 23 to Feb. 26, 2025.

Highlights:

• MDNA11 significantly expands a unique population of stem-like CD8+ T cells that leads to more persistent and effective anti-tumour activity.
• MDNA11 has shown durable single-agent activity, with a 30-per-cent (three of 10) objective response rate (ORR) in the monotherapy dose expansion cohort in checkpoint-resistant patients (as of Dec. 5, 2024).
• Disease control rate (DCR) of 78 per cent (seven of nine) in combination with Merck's (known as MSD outside of Canada and the United States) anti-PD-1 therapy, Keytruda (pembrolizumab), includes one complete response, one partial response and five stable disease (as of Dec. 5, 2024).
• The safety review committee cleared the dosing of 120 micrograms per kilogram MDNA11 every two weeks in combination with Keytruda as no dose-limiting toxicities (DLTs) have been observed to date.
• To improve patient convenience, dosing of 120 micrograms per kilogram MDNA11 every three weeks as a monotherapy or in combination with Keytruda is currently in progress.
• Additional tumour types are to be evaluated as part of Ability-1 study in monotherapy and combination dose expansion cohorts, with combination dose expansion expected to initiate mid 2025.
• Updated safety and efficacy results of MDNA11 as a monotherapy and in combination with Keytruda are to be presented at medical conferences in the first half of 2025.

Cancer often leaves the immune system in a state of exhaustion, where its front line defenders -- CD8+ T cells -- lose their ability to function effectively. Checkpoint inhibitors, such as anti-PD-1, have been shown to reinvigorate exhausted T cells and improve the outcome in patients with cancer. Unfortunately, only a fraction of the patients with cancer respond to PD-1 blockade, thus prompting a vigorous search for other pathways that can improve the efficacy of immunotherapies. A rare type of immune cells, called stem-like CD8+ T cells, holds the key to maintaining powerful, long-term immune responses. Stem-like T cells have the remarkable ability to resist burnout and have the ability to renew themselves, to proliferate and remain in battle mode until all tumour cells are eliminated.

"To the best of our knowledge, these are the first reported human clinical data to demonstrate the ability of any type of IL-2 to dramatically boost the population of stem-like T cells that subsequently result in durable tumour control," said Dr. Fahar Merchant, president and chief executive officer of Medicenna. "Stem-like T cells are like the superheroes of the immune system. They can renew themselves, multiply and keep fighting cancer over time. What's exciting about these pharmacodynamic data is that they provide us with a potential road map for how we might further reinvigorate the immune system with MDNA11 to leverage stem-like T cells, the immune system's secret power, to improve health outcomes for people living with cancer, further demonstrating MDNA11's best-in-class potential."

Dr. Arash Yavari, director of clinical strategy at Medicenna, added: "The combination of MDNA11 with Keytruda in Ability-1 has shown consistent pharmacokinetic and pharmacodynamic profiles with repeated dosing. Combined with preliminary evidence of clinical activity in less immunologically responsive tumour types observed to date during combination dose escalation, these findings highlight the potential of MDNA11 to enhance both the efficacy and scope of immune checkpoint inhibition. We have also announced the addition of several new tumour types in the Ability-1 trial. We are confident about the potential of the combination of MDNA11 with Keytruda to improve outcomes for patients with a range of difficult-to-treat cancers."

Key highlights from the presentation

Pharmacokinetics:

• MDNA11 exhibits consistent pharmacokinetic profiles with repeat administration as both single agent and when combined with Keytruda.

Pharmacodynamics:

• MDNA11 associated with dose-dependent expansion of CD8+ T and NK cells, which is sustained over repeat dose cycles as both single agent and when combined with Keytruda;
• Significant expansion of activated effector CD8 + T cells, effector memory T cells and central memory T cells with MDNA11, key immune cell subsets associated with durable anti-tumour response; MDNA11 promotes the expansion of a unique subset of cancer-fighting CD8 + T cells with stem-like properties: MDNA11 significantly expands a unique progenitor population of stem-like TCF1+ CD8+ T cells, which possess remarkable self-renewal capabilities and have the ability to differentiate into potent effector cells upon encountering tumour antigen to promote sustained anti-tumour immune responses; these cells are regarded as critical for maintaining long-lasting anti-tumour immunity and have been positively linked to immunotherapy responses such as immune checkpoint blockade;
• Greater expansion of stem-like CD8 + T cells was significantly associated with clinical responses to MDNA11 (pooled monotherapy and combination therapy data).

Other Ability-1 study updates:

• Additional tumour types to be evaluated as part of MDNA11 monotherapy and Keytruda combination dose expansion cohorts: MSI-H/dMMR, TMB-H, cutaneous melanoma, virally associated tumours (monotherapy portion only) and gynecological tumours (combination portion only);
• Completion of monotherapy expansion and combination dose escalation enrolment anticipated in the middle of calendar 2025;
• Combination dose expansion expected to initiate in the middle of calendar 2025.

A copy of the presentation has been posted on the scientific presentations page of Medicenna's website.

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. MDNA11 is being evaluated in the phase 1/2 Ability-1 study (NCT05086692) as monotherapy and in combination with Keytruda. 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 FDA (U.S. Food and Drug Administration) and the FDA/European Medicines Agency, respectively. Medicenna's early-stage, high-affinity, IL-2beta-biased IL-2/IL-15 superantagonists, from its MDNA209 platform, are being evaluated as potential therapies for autoimmune and graft-versus-host diseases. Medicenna's early-stage Biskits (bifunctional superkine immunotherapies) and T-Mask (targeted metalloprotease-activated superkine) programs are designed to enhance the ability of superkines to treat immunologically cold tumours.

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