Dr. Fahar Merchant reports

MEDICENNA PRESENTS UPDATED RESULTS OF SINGLE AGENT MDNA11 ANTI-TUMOR ACTIVITY FROM DOSE ESCALATION AND ONGOING DOSE EXPANSION OF THE PHASE 1/2 ABILITY-1 STUDY AT THE 2024 ANNUAL MEETING OF THE AMERICAN ASSOCIATION FOR CANCER RESEARCH (AACR)

Medicenna Therapeutics Corp. presented updated clinical results from the monotherapy dose-escalation and continuing expansion portions of the phase 1/2 Ability-1 (a beta-only IL-2 immunotherapy) study evaluating MDNA11, a long-acting beta-enhanced not-alpha interleukin-2 (IL-2) super-agonist, in patients with advanced solid tumours, at the 2024 Annual Meeting of the American Association for Cancer Research (AACR) held in San Diego, Calif., on April 9, 2024.

"Although early, we have been impressed with MDNA11's single-agent activity demonstrating a response rate of 29 per cent and clinical benefit rate of 50 per cent in patients with advanced solid tumours who have all failed prior immunotherapies," said Fahar Merchant, PhD, president and chief executive officer of Medicenna. "We are very encouraged by a new partial response in a 85-year-old MSI-high patient with small bowel cancer, and are particularly pleased with 100-per-cent reduction of all baseline target lesions in two of the four partial responders, which includes a pancreatic cancer and a melanoma patient. MDNA11 continues to demonstrate its best-in-class potential. To further expedite the study, new sites in the U.S. and Korea have started enrolment in the ongoing monotherapy expansion and combination escalation arms of the Ability-1 study, as we look forward to reporting additional data at a medical conference in the first half of 2024."

Key findings from the monotherapy dose-escalation and continuing expansion portions of the Ability-1 study at the time of data cut-off (that is, March 22, 2024) include:

• Acceptable safety profile: No dose-limiting toxicity (DLT) reported and no evidence of vascular leak syndrome (VLS). The vast majority (95 per cent) of treatment-related adverse events (TRAEs) were of grade 1 to grade 2 and resolved within 48 hours; grade 3 TRAEs mainly constituted asymptomatic transient LFT elevations; no grade 4 or grade 5 events were reported.
• Encouraging single-agent anti-tumour activity at doses of greater than or equal to 60 micrograms/kilogram (kg) in phase 2 eligible patients (N equals 14), who were all resistant to immune checkpoint inhibitors:
  • Partial response reported for four patients with aggressive tumour types who had progressed on prior checkpoint inhibitors:
    • A pancreatic ductal adenocarcinoma (MSI-H) patient with primary resistance to pembrolizumab who was treated with MDNA11 (60 microg/kg) showed 100 per cent resolution of all baseline lesions at week 66. A new lymph node lesion developed during a eight-week MDNA11 treatment break (vacation) was treated with a single course of radiotherapy prior to resumption of MDNA11. All baseline lesions remained completely resolved and the new lymph node lesion was less than 10 millimetres (mm) (considered physiological per RECIST version 1.1), and MDNA11 treatment ended at week 90, while follow-up continues.
    • A patient with cutaneous melanoma progressed on dual checkpoint inhibitors, was treated with MDNA11 (90 microg/kg), and showed 100 per cent resolution of the target lesion at weeks 28 and 36, with continuing reduction of the non-target lesions. Patient remains on MDNA11 treatment.
    • A second checkpoint-resistant cutaneous melanoma patient (nivolumab and rechallenge) showed partial response on MDNA11 (90 microg/kg) with a 31.25 per cent reduction of target lesion at week 12 following pseudo-progression at week 8. A new lymph node lesion developed at week 16, while baseline target and non-target lesions remained stable or decreased. Patient remains on MDNA11 treatment.
    • An 85-year-old small bowel cancer (MSI-H) patient with secondary resistance to pembrolizumab showed partial response on MDNA11 (90 microg/kg) at week 20 with 37-per-cent reduction in target lesions. Patient remains on MDNA11 treatment.
  • Durable stable disease (SD) for greater than or equal to 24 weeks with shrinkage of target lesions observed in three metastatic melanoma patients:
    • Two patients (acral and cutaneous) with SD for more than 24 weeks on MDNA11 (120 microg/kg).
    • A third patient (cutaneous) with SD for more than 1.5 years started on MDNA11 at 10 microg/kg dose, and was subsequently dose escalated to 30 microg/kg, 60 microg/kg and 90 microg/kg.

MDNA11 continues to exhibit potent effector immune profile with sustained peripheral expansion of cytotoxic CD4+ T, CD8+ T and NK cells with minimal impact on immunosuppressive Tregs. CD8/Treg ratio and activation markers (CD25+ and OX40+) showed peak increase in CD8+ T cells at the recommended dose for expansion (RDE) (90 microg/kg Q2W IV (intravenous)). OX40 on Tregs also peaked at the RDE but, in contrast to CD8+ T cells, it leads to impairment of their immune suppressive function.

Monotherapy expansion is continuing to enroll patients with metastatic melanoma, non-melanoma skin cancers (cSCC, MCC and BCC) and MSI-H/dMMR tumours. Combination dose escalation has also commenced.

A copy of the poster and a related slide deck have been posted to the scientific presentations page of Medicenna's website.

About MDNA11

MDNA11 is a long-acting beta-enhanced not-alpha interleukin-2 superkine specifically engineered to overcome the shortcomings of aldesleukin and other next-generation IL-2 variants by preferentially activating immune effector cells (CD4+ T, CD8+ 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 (PK) 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 a monotherapy and in combination with pembrolizumab (Keytruda).

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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