Dr. Fahar Merchant reports

MEDICENNA'S MDNA11 POTENTIAL IN EARLIER LINE MELANOMA SETTING HIGHLIGHTED IN PRESENTATION OF THE NEO-CYT TRIAL AT ASCO 2026

Medicenna Therapeutics Corp.'s long-acting, beta-enhanced not-alpha IL-2 superkine, MDNA11, was featured in a poster presentation describing the investigator-sponsored NEO-CYT trial at the 2026 Annual Meeting of the American Society of Clinical Oncology (ASCO), held in Chicago from May 28 to June 2.

• NEO-CYT positions MDNA11 in a front-line neoadjuvant melanoma setting, where immunotherapy before surgery may help generate deeper and more durable anti-tumour immune responses.
• Up to 80 patients with locally advanced melanoma will be randomized in this investigator-sponsored, multicenter phase 1b NEO-CYT trial led by Prof. Paolo A. Ascierto of the Istituto Nazionale tumouri Fondazione "G. Pascale" and sponsored by Fondazione Melanoma Onlus.
• Together with the continuing phase 1/2 Ability-1 expansion cohorts in the 2L/3L Tx setting, NEO-CYT supports a broader clinical strategy to evaluate MDNA11 across select tumour types and multiple stages of disease, expanding future commercial opportunities.
• MDNA11 clinical data updates from the Ability-1 and NEO-CYT trials are anticipated in H2 2026.

Surgery has long been the first course of action in treating locally advanced melanoma. Recently, the landmark NADINA clinical trial (comprising two preoperative cycles of ipilimumab plus nivolumab) completely flipped the conventional treatment paradigm on its head by proving that giving combination immunotherapy before surgery is significantly more effective than the previous postsurgery standard, setting a new gold standard of care. However even with this regimen, 41 per cent of patients did not achieve a major pathologic response (less than 10 per cent of viable tumour). In view of the promising single agent activity of MDNA11 in patients with metastatic melanoma, the hypothesis of the NEO-CYT trial is to demonstrate if patient outcomes can be further enhanced over the gold standard of care by introducing MDNA11 in combination with nivolumab plus/minus ipilimumab.

"NEO-CYT provides an important opportunity to evaluate MDNA11, a potentially best-in-class IL-2 superagonist, in a front-line neoadjuvant setting where immune activation may be especially impactful," said Fahar Merchant, PhD, president and chief executive officer of Medicenna. "If the tumour is still present at the time of the treatment, the immune cells 'see' more of the cancer cells. This allows the most potent anti-tumour immune cells to expand and attack the tumour and can remain active in the body for many years, preventing the tumours from recurring. Importantly, this trial complements our continuing Ability-1 study, which has already demonstrated durable disease control in more advanced stages of melanoma. The Ability-1 trial is also advancing MDNA11 into earlier lines of therapy through expansion cohorts in 2L/3L melanoma, endometrial cancer, colorectal cancer, lung cancer and tumour agnostic biomarker driven cancers. We look forward to sharing updates on the Ability-1 trial and the NEO-CYT study during the second half of 2026."

NEO-CYT is a randomized, multicentre phase 1b trial evaluating MDNA11 in combination with nivolumab, with or without ipilimumab, as neoadjuvant therapy in patients with high-risk, surgically resectable Stage IIIB/C/D cutaneous melanoma. The study is sponsored by Fondazione Melanoma Onlus and led by Prof. Paolo A. Ascierto of the Istituto Nazionale Tumori Fondazione "G. Pascale" in Naples, Italy.

The trial represents an important expansion of MDNA11's clinical development into an earlier-line, curative-intent melanoma setting. Neoadjuvant immunotherapy, administered before surgery while the tumour and its immune microenvironment remain intact, has emerged as a promising strategy to generate deeper anti-tumour immune responses and improve long-term outcomes for patients with high-risk resectable melanoma. However, a meaningful proportion of patients still do not achieve a major pathologic response with checkpoint-based neoadjuvant therapy, underscoring the need for novel immune-activating approaches that may improve depth and durability of response.

The NEO-CYT poster at ASCO highlighted the scientific rationale for combining MDNA11 with checkpoint inhibitors in the neoadjuvant setting. Prior clinical and translational research has shown that lack of response to neoadjuvant checkpoint therapy may be associated with an immunologically "cold" tumour microenvironment, including IL-2-related immune features. MDNA11 was designed to selectively engage the IL-2 receptor beta pathway, promoting expansion, and activation of CD8+ T cells and NK cells that are central to anti-tumour immunity, while minimizing stimulation of immunosuppressive regulatory T cells.

The study is expected to enroll up to 80 patients across four treatment arms. The control arm will comprise of patients treated with the current gold-standard, ipilimumab plus nivolumab, while investigational arms will evaluate MDNA11 in combination with nivolumab alone, MDNA11 in combination with ipilimumab plus nivolumab, and an optional arm adding tocilizumab to MDNA11 plus ipilimumab and nivolumab following Steering committee safety review.

The primary efficacy end point is major pathologic response at surgery, defined as 10 per cent or less viable tumour in the treated tumour bed. Co-primary safety end points include the incidence, severity and duration of treatment-related adverse events, with particular focus on immune-related adverse events.

MDNA11 is also being evaluated in Medicenna's continuing phase 1/2 Ability-1 study, where it has demonstrated immune activation, including expansion of CD8+ T cells and NK cells, as well as single-agent clinical activity and a manageable safety profile in patients with advanced solid tumours. Together, NEO-CYT and Ability-1 are intended to inform Medicenna's broader development strategy for MDNA11 across multiple treatment settings, including earlier-line melanoma populations where patients may have more intact immune systems and greater potential to benefit from immunotherapy.

Clinical updates from MDNA11 studies are anticipated in the second half of 2026.

About high-risk Stage III surgically resectable melanoma

Melanoma is the fifth most common cancer in the United States and the most lethal form of skin cancer. Stage III melanoma refers to disease that has spread beyond the primary tumour to regional lymph nodes or nearby tissue, but not to distant organs. In high-risk Stage III melanoma, patients face a significant risk of recurrence even after complete surgical removal, underscoring the need for effective systemic treatment strategies. Neoadjuvant immunotherapy, administered before surgery while the tumour and its immune microenvironment remain intact has emerged as a promising approach to improve pathologic responses and long-term outcomes in this setting.

About MDNA11

MDNA11 is a 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+ 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 monotherapy and in combination with pembrolizumab.

About Fondazione Melanoma Onlus

Fondazione Melanoma Onlus is a non-profit organization based in Naples, Italy, that supports and promotes melanoma research, education, and clinical trials. It is known for organizing international conferences like the Melanoma Bridge, which bring together clinicians and researchers to discuss advancements in melanoma treatment and its related fields. The foundation also sponsors scientific awards for outstanding achievements in melanoma research.

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 first-in-class targeted PD-1 x IL-2 bispecific, MDNA113, is in development for solid tumours and was designed using the company's proprietary BiSKITs (bifunctional superkine immunotherapies) and T-MASK (targeted metalloprotease activated superkine) platforms. 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/EMA, respectively.

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