Dr. Fahar Merchant reports

MEDICENNA ANNOUNCES PROMISING SINGLE-AGENT RESPONSE AND DURABILITY OF MDNA11 IN THE PHASE 1/2 ABILITY STUDY DURING DOSE ESCALATION AT THE 38TH ANNUAL MEETING OF THE SOCIETY FOR IMMUNOTHERAPY OF CANCER (SITC)

Medicenna Therapeutics Corp. presented new clinical data from the phase 1 monotherapy dose escalation/evaluation portion of the phase 1/2 Ability-1 (a beta-only IL-2 immunotherapy) study evaluating MDNA11 at the 38th annual meeting of the Society for Immunotherapy of Cancer (SITC) held in San Diego, Calif., on Nov. 4, 2023. MDNA11 is the only long-acting, beta-enhanced, not-alpha, interleukin-2 (IL-2) super-agonist in clinical development, in patients with advanced solid tumours.

"We are very encouraged by two partial responses and three durable stable diseases in patients with advanced cancer who had progressed on multiple prior therapies, reinforcing MDNA11's promising single-agent activity," said Fahar Merchant, PhD, president and chief executive officer of Medicenna. "These data add to the growing body of evidence demonstrating the clinical effectiveness of MDNA11 with highly favourable underlying immune response, characterized by robust expansion and activation of CD8+ T cells with minimal impact on immune-suppressive Tregs. MDNA11, with uniquely differentiating beta-enhanced not-alpha features, continues to be a potential best-in-class next-generation IL-2 super-agonist for treatment of advanced solid tumours. We look forward to reporting results from the monotherapy expansion and combination escalation arms of the phase 2 study in the first half of 2024."

Key findings from the phase 1 monotherapy dose-escalation portion of the Ability-1 study at time of data cut-off (Oct. 26, 2023) include:

• Favourable safety profile: No dose-limiting toxicity (DLT) reported and no evidence of vascular leak syndrome (VLS). Vast majority (95.6 per cent) of treatment-related adverse events (TRAEs) were of grade 1 to 2 severity and resolved within 48 hours. Grade 3 TRAEs mainly constituted transient LFT elevations and no grade 4 or 5 events were reported.
• Encouraging single-agent anti-tumour activity at doses of 60 ug/kg (micrograms per kilogram) (N equals 15):
  • Partial response reported in two patients with aggressive tumour types:
    • A patient with metastatic pancreatic ductal adenocarcinoma (PDAC, MSI-H), who had previously failed on multiple systemic therapies, and exhibited primary resistance to immune checkpoint inhibitors, experienced remarkable response to MDNA11 (60 ug/kg) with baseline target lesions and non-target lesions showing deepening shrinkage on successive imaging scans. Following return from a seven-week vacation, a single new lesion was observed and MDNA11 treatment was resumed. Prior to receiving one cycle of radiotherapy for the new lesion, complete resolution of initial two targets and one non-target lesions was achieved. Patient continues on MDNA11 postradiotherapy.
    • A patient with cutaneous melanoma, who progressed on prior line of dual checkpoint inhibitors, treated with MDNA11 (90 ug/kg dose), showed a 70-per-cent reduction of the target lymph node lesion at week 12.
  • Durable stable disease in three metastatic melanoma patients with concomitant reduction in tumour burden: Two patients with SD of greater than 20 (acral melanoma) and more than 24 weeks (cutaneous melanoma) are continuing MDNA11 treatment in the 120 ug/kg cohort. One patient with cutaneous melanoma had SD for more than 1.5 years, having started MDNA11 at the 10 ug/kg dose with subsequent intrapatient dose escalations of 30, 60 and 90 ug/kg.
  • Potent proliferation of effector immune populations: Pharmacodynamic data showed robust and durable activation of effector immune cells, particularly CD8+ T cells (CD25+, OX40+), with minimal impact on the immunosuppressive Treg population.
  • Recommended dose for expansion (RDE): Target dose of 90 ug/kg (following two step-up doses of 30 and 60 ug/kg) Q2W IV infusion was chosen for monotherapy expansion portion of the Ability-1 study.
  • Monotherapy expansion part of Ability-1 is enrolling patients with metastatic melanoma, non-melanoma skin cancers (CSCC, MCC and BCC) and MSI-H/dMMR tumours.

The main objectives of the monotherapy dose escalation part of the phase 1/2 Ability-1 study (Clinicaltrials website ID: NCT05086692) were to assess MDNA11's safety, tolerability, PK (pharmacokinetics), PD (pharmacodynamics) and anti-tumour activity to inform on the RDE in an all-comer solid tumour population with advanced cancers refractory to prior systemic therapies. A total of six dose escalation cohorts (MDNA11 dose ranging from three ug/kg to 120 ug/kg) were evaluated, with the majority of patients (73 per cent) having also received at least one prior line of immunotherapy with or without primary resistance to immune checkpoint inhibitors.

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

About MDNA11

MDNA11 is an intravenously administered, long-acting beta-enhanced not-alpha interleukin-2 (rIL-2) superkine, specifically engineered to overcome the shortcomings of aldesleukin and other next-generation IL-2 variants by preferentially activating immune effector cells (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 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 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, 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 U.S. Food and Drug Administration (FDA) and the FDA/EMA (European Medicines Agency), respectively. Medicenna's early-stage Biskits (bifunctional superkine immunotherapies) program is designed to enhance the ability of superkines to treat immunologically cold tumours.

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