Dr. Fahar Merchant reports

MEDICENNA COMPLETES MDNA11 DOSE ESCALATION AND COMMENCES MONOTHERAPY DOSE EXPANSION IN THE PHASE 1/2 ABILITY STUDY

Medicenna Therapeutics Corp. has provided a clinical update on the monotherapy dose escalation portion of the first-in-human, phase 1/2 Ability study in patients with advanced solid tumours, as its drug candidate MDNA11, a beta-only, long-acting IL-2 superagonist, advances to the monotherapy dose expansion phase.

"We are pleased to see that MDNA11 continues to demonstrate durable single-agent activity in patients with advanced, treatment-refractory cancer, together with a manageable safety profile, and preserving its differentiated pharmacodynamic (PD) qualities, even though the phase 1 Ability study was not specifically designed to demonstrate efficacy," said Dr. Fahar Merchant, PhD, president and chief executive officer of Medicenna. "The promising therapeutic activity observed in patients who have progressed on multiple prior anti-cancer therapies, including a patient with a particularly aggressive form of cancer -- pancreatic ductal adenocarcinoma -- fuels our enthusiasm for initiating the dose expansion phase of the study. The PD data supports 90 grams/kilogram dose as the recommended dose for expansion (RDE), which will be evaluated in selected cancers that are most likely to benefit from MDNA11 monotherapy. We look forward to the upcoming readouts from the monotherapy dose expansion phase later this year and commencing the combination portion of the trial, where MDNA11 will be evaluated with Keytruda, as part of our clinical collaboration with Merck."

The main objectives of the dose escalation stage of the phase 1/2 Ability study were to evaluate MDNA11's safety, tolerability, pharmacokinetics and pharmacodynamics (PK/PD), and preliminary anti-tumour activity to inform RDE selection in patients with advanced cancers that were refractory to up to four different lines of systemic therapy. A total of six dose escalation cohorts (MDNA11 dose ranging from three g/kg to 120 g/kg) constituting 20 patients were evaluated, with the majority (75 per cent) having also received at least one line of immunotherapy.

Key findings from the dose escalation portion of the study include:

1. Favourable safety profile -- MDNA11 was generally well tolerated across cohorts, with the majority of adverse events (AEs) being grade 1 or 2, with no grade 4 or 5 AEs.
2. Promising single-agent activity and durable tumour control -- several patients exhibited encouraging evidence of single-agent activity with tumour control observed in seven of 19 evaluable patients (37 per cent):
   • Confirmed partial response to single-agent MDNA11 in a highly aggressive tumour type: A patient in cohort 4 (60 g/kg dose) with metastatic pancreatic ductal adenocarcinoma (PDAC), who had failed to respond to multiple prior systemic therapies, continues to show tumour shrinkage of all metastatic lesions in the liver after each successive scan. The most recent scan showed an 80-per-cent decrease in total tumour size (sum of tumour diameters of the target lesions) with complete regression of two out of three lesions. This patient continues on study treatment with MDNA11;
   • Prolonged stable disease in metastatic melanoma progressed on prior immune checkpoint inhibition: A patient in cohort 2 (commenced on 10 g/kg dose and subsequently increased to 30, 60 and 90 g/kg), having failed prior immunotherapy, experienced stable disease for 84 weeks.
3. Pharmacodynamic data on effector anti-tumour immune cells continue to support the mechanistic rationale for MDNA11's promising anti-tumour activity, with MDNA11 inducing robust expansion of a population of potent activated CD8+T cells and increasing NK cells, but with limited expansion of Tregs which can suppress anti-tumour immunity. More details are described in today's call and the presentation available on Medicenna's website.
4. Based on the totality of the dose escalation data, an RDE of 90 g/kg given every other week by IV infusion has been chosen for the monotherapy expansion phase of the trial.
5. Selection of specific cancers for evaluation in the monotherapy dose expansion phase was determined based on clinical data available from the Ability study, discussions with Medicenna's clinical advisory board and other expert key opinion leaders, and an understanding of the immunobiology of the selected tumour types and the potential for MDNA11 monotherapy in the postcheckpoint inhibitor setting. The following tumour types will be recruited in the dose expansion phase of the study:
   • Melanoma;
   • Non-melanoma skin cancers;
   • Microsatellite instability-high (MSI-H) or deficient DNA mismatch repair (dMMR) cancers. This population was selected to determine if the response achieved in the PDAC patient may have been due to the MSI-H profile. The PDAC patient unequivocally progressed on Keytruda, which is approved for MSI-H cancers.

Medicenna expects to report initial results from Ability's monotherapy dose expansion in the fourth quarter of 2023. Plans are to commence the combination phase of the trial evaluating MDNA11 with Keytruda in the fourth quarter of 2023, with initial results expected in early 2024.

About the phase 1/2 Ability study

The Ability (a beta-only IL-2 immunotherapy) study is designed to assess the safety, pharmacokinetics, pharmacodynamics and anti-tumour activity of various doses of intravenously administered MDNA11 in patients with advanced, treatment-refractory solid tumours. The trial includes an MDNA11 monotherapy phase, as well as a combination phase designed to evaluate MDNA11 with Keytruda (pembrolizumab). Approximately 104 patients are expected to be enrolled into the Ability study. Following establishment of the RDE in the study's monotherapy dose escalation phase, Medicenna plans to conduct a dose expansion phase that will enroll patients with melanoma and other selected solid tumour types in the monotherapy and combination settings.

About Medicenna Therapeutics Corp.

Medicenna is a clinical-stage immunotherapy company focused on the development of 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 GBM (glioblastoma multiforme), 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 (FDA) and the FDA/EMA (European Medicines Agency), respectively. Medicenna's early-stage BiSKITs program (bifunctional superkine immunotherapies) is designed to enhance the ability of superkines to treat immunologically cold tumours.

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