Dr. Fahar Merchant reports

MEDICENNA PRESENTS COMPELLING RESULTS FROM THE ABILITY-1 CLINICAL TRIAL AT THE 2025 AACR ANNUAL MEETING

Medicenna Therapeutics Corp. has presented updated clinical data from the continuing phase 1/2 Ability-1 study evaluating MDNA11 in patients with advanced solid tumours at the 2025 annual meeting of the American Association for Cancer Research in Chicago, Ill. MDNA11, a long-acting beta-enhanced not-alpha interleukin-2 superagonist, is being evaluated as a monotherapy or in combination with the Merck (known as MSD outside of the United States and Canada) anti-PD-1 therapy, Keytruda (pembrolizumab).

"We are encouraged by the anti-tumour activity and safety of MDNA11 in both the monotherapy and combination setting, including the three recent responders, particularly in patients who have shown resistance to checkpoint inhibitors or with tumour types with historically low responses to immunotherapies and addressing a vastly underserved cancer population," commented Fahar Merchant, PhD, president and chief executive officer of Medicenna. "Today's efficacy and immunodynamic data have provided the foundation to commence the dose expansion portion for MDNA11 in combination with Keytruda. In the monotherapy setting, we continue to see deep and durable single-agent activity of MDNA11 with two patients remaining in complete remission and off therapy. Together, these data reinforce the best-in-class potential for MDNA11 as a potent and safe immunotherapy that is poised to transform the existing treatment paradigm for patients with difficult-to-treat tumours. We look forward to sharing additional clinical data from the Ability-1 study at future medical conferences this year."

Key findings from the continuing Ability-1 study (data cut-off as of April 15, 2025) include the following.

Safety profile:

• MDNA11 continues to demonstrate an acceptable safety profile both as a single agent and in combination with Keytruda. Over 90 per cent of treatment-related adverse events were Grade 1 and 2 and transient, with no dose limiting toxicities observed with MDNA11 at doses up to 120 micrograms per kilogram (Q2W) in monotherapy and in combination with Keytruda (400 mg, Q6W).

Immunodynamics:

• Robust expansion of immune effector cells in monotherapy and combination with Keytruda with notable increases in effector (DNAM), stemness-like (TCF-1) and memory CD8-plus T-cells, which are critical for sustained anti-tumour responses;
• Robust, dose-dependent lymphocyte expansion in combination with Keytruda, sustained with repeat MDNA11 dosing, and plateauing at the 90 micrograms per kg MDNA11 dose level.

Clinical activity of MDNA11 in combination with Keytruda during dose escalation

Enrolment in the combination dose expansion portion of the Ability-1 study is under way having established the MDNA11 combination recommended dose for expansion at 90 micrograms per kg administered every two weeks together with Keytruda administered at 400 mg every six weeks.

Encouraging anti-tumour activity continues to be observed with MDNA11 in combination with Keytruda in patients enrolled in the dose escalation portion of the study:

• Five objective responses (one CR and four PRs) among heavily pretreated patients, including two previously reported objective responses in historically low immunotherapy responders:
  • 70-year-old male with anal squamous cell carcinoma who previously progressed on two prior lines of chemotherapy achieved a CR on the first study evaluable imaging scan (week eight); patient continues on combination treatment following a confirmed CR;
  • 52-year-old female with TMB-H/MSS colorectal cancer who previously progressed on two prior lines of chemotherapy achieved a confirmed PR; while off-study for four months, the patient continues to show deepening of the tumour response in the absence of any treatment.
• Objective response rate of 31 per cent (four of 13) in patients with cancers planned for the phase 2 combination expansion cohort, including cutaneous melanoma, MSI-H/dMMR and TMB-H tumours, and an ORR of 36 per cent (five of 14) when including the virally derived cancers;
• Stable disease in three patients for a disease control rate (DCR equals CR plus PR plus SD) of 57 per cent (eight out of 14).

Monotherapy tumour response in immune checkpoint inhibitor-resistant patients

MDNA11 continues to demonstrate encouraging deep and durable single-agent anti-tumour activity among patients who progressed on prior immune checkpoint inhibitor therapy:

• ORR of 40 per cent in the monotherapy dose escalation (treated at equal or greater than 60 micrograms per kg) and expansion arm (one confirmed CR, one confirmed PR and two unconfirmed PRs) among 10 patients with tumour types currently enrolling in the phase 2 monotherapy expansion cohort. All patients had previously failed ICI therapy and had advanced and/or metastatic cutaneous melanoma with secondary resistance to ICI or MSI-H/dMMR tumours. Note that the non-melanoma skin cancer cohort is not recruiting as it was replaced with a new cohort of virally derived cancers subsequent to a protocol amendment.
• The ORR is 29.4 per cent from a total of 17 patients when including patients with cancers planned for phase 2 expansion cohort and patients with primary ICI resistant melanoma who received at least 60 micrograms per kg of MDNA11 (Q2W).
• Over all, objective responses in ICI-resistant patients include one CR and four PRs:
  • Two PRs among four MSI-H patients (ORR of 50 per cent) with both responders having metastatic pancreatic ductal adenocarcinoma (PDAC);
  • One CR and one PR among six patients with ICI secondary resistant melanoma (ORR of 33.3 per cent);
  • One PR among patients with ICI primary resistant melanoma.
• Complete resolution of all target and non-target lesions in two patients with continuing remission following end-of-treatment:
  • Cutaneous melanoma patient achieved a durable response exceeding 12 months during the study with complete resolution of target and non-target metastatic lesions, and continues to remain off anti-cancer therapy for more than six weeks;
  • Pancreatic cancer patient (MSI-H) achieved a durable response for 20 months during the study with complete resolution of target and non-target metastatic lesions in the liver including a new lesion treated with MDNA11 following a single cycle of radiation, and continues to remain off anti-cancer therapy for more than 12 months.
• SD in six patients for a disease control rate (DCR equals CR plus PR plus SD) of 65 per cent including two with duration greater than six months, yielding a clinical benefit rate of 41 per cent (seven out of 17).

A copy of the poster and related slide deck has been posted on the scientific presentations page of Medicenna's website.

Keytruda is a registered trademark of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co. Inc., Rahway, N.J., United States.

About MDNA11

MDNA11 is an intravenously administered, long-acting, beta-enhanced not-alpha IL-2 superkine specifically engineered to overcome the shortcomings of aldesleukin and other next-generation IL-2 variants by preferentially activating immune effector cells (CD8-plus T- and NK-cells) responsible for killing cancer cells, with minimal or no stimulation of immunosuppressive tregs. These unique proprietary features of the IL-2 superkine have been achieved by incorporating seven specific mutations and genetically fusing it to a recombinant human albumin scaffold to improve the pharmacokinetic profile and pharmacological activity of MDNA11 due to albumin's natural propensity to accumulate in highly vascularized sites, in particular tumour and tumour draining lymph nodes. MDNA11 is currently being evaluated in the phase 1/2 Ability-1 study as both monotherapy and in combination with Keytruda.

About the Ability-1 study

The Ability-1 study (NCT05086692) is a global, multicentre, open-label study that assesses the safety, tolerability, pharmacokinetics, pharmacodynamics and anti-tumour activity of MDNA11 as monotherapy or in combination with Merck's anti-PD-1 therapy, Keytruda (pembrolizumab). In the combination dose escalation portion of the phase 2 study, patients have been enrolled and administered ascending doses of MDNA11 intravenously in combination with Keytruda. This portion of the study includes patients with a wide range of solid tumours with the potential for susceptibility to immune modulating therapeutics. The combination recommended dose for expansion has been established, and the study has commenced combination dose expansion.

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 a monotherapy and in combination with Merck's anti-PD-1 therapy, Keytruda (pembrolizumab). 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/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 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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