Mr. Daniel Scarr reports

MEDICENNA PRESENTS ABILITY-1 DATA AT SITC 2026 SHOWING 40% ORR IN GASTROINTESTINAL CANCER PATIENTS WITH BIOMARKER ENRICHED TUMORS RESISTANT TO APPROVED THERAPIES

Medicenna Therapeutics Corp. has released new clinical data from the phase 1/2 Ability-1 study of MDNA11 presented during an oral session at the Society for Immunotherapy of Cancer 2026 annual meeting.

The presentation, titled "MDNA11 Demonstrates Clinical Activity as Monotherapy and in Combination with Pembrolizumab in Biomarker-Enriched Gastrointestinal Malignancies, Including ICI-Refractory Disease," was delivered by Prof. Paolo Ascierto, MD, director of Department of Skin Cancers, Cancer Immunotherapy and Development Therapeutics, National Cancer Institute IRCCS, Fondazione G. Pascale, Naples, Italy.

As previously announced on Nov. 4, 2026, the company will host a KOL webinar on Nov. 10, 2026, at 9 a.m. ET, with Dr. Tawbi and Dr. Mansinho to discuss the results and their clinical implications. In addition, the webinar will include a presentation of new data from the ICI-resistant cutaneous melanoma and MSS endometrial cancer cohorts.

The SITC presentation highlighted durable anti-tumour activity with MDNA11 alone and in combination with Merck's (known as MSD outside of the United States and Canada) anti-PD-1 therapy, Keytruda (pembrolizumab), in patients with MSI-H or MSS TMB-H gastrointestinal cancers, including patients whose disease had progressed following prior ICI therapy.

Among 20 efficacy-evaluable patients with protocol-defined MSI-H or MSS TMB-H GI cancers, MDNA11 plus or minus pembrolizumab achieved a 40-per-cent ORR (eight out of 20) and 80 per cent DCR (16 out of 20). Responses were observed across multiple GI tumour types, including colorectal cancer, pancreatic ductal adenocarcinoma, cholangiocarcinoma and anal squamous cell carcinoma. The cohort was heavily pretreated, with a median of three prior systemic treatment lines, including adjuvant therapy (range one to 10); 65 per cent had received prior ICI therapy, 45 per cent had received at least four prior systemic treatment lines and 35 per cent had active liver metastases at baseline.

"The 40-per-cent response rate observed in this 20-patient cohort of MSI-H or MSS/TMB-H gastrointestinal cancers is very promising, particularly because we are seeing responses in patients whose cancers have already progressed on immunotherapy and for whom effective treatment options are limited," stated Prof. Paolo Ascierto, recipient of the 2026 SITC lifetime achievement award. "What stands out even more is the activity of MDNA11 monotherapy in patients with active liver metastases -- a population that is difficult to treat and typically responds poorly to checkpoint inhibitors."

"The Ability-1 data presented at SITC strengthens our conviction that MDNA11 can address a meaningful unmet need after checkpoint inhibitor failure in many different cancers," said Fahar Merchant, PhD, president and chief executive officer of Medicenna. "We are particularly encouraged by the single-agent activity of MDNA11 in ICI-refractory GI cancers and the durability of these responses across multiple tumour types. Results from the melanoma and endometrial cancer cohorts, all refractory to immune checkpoint inhibitors, are similarly promising, positioning MDNA11 for potential registrational studies as we strengthen evidence to confirm durability of tumour control."

Key findings in MSI-H/TMB-H gastrointestinal cancers:

• Combined cohort: 40-per-cent ORR (eight out of 20) and 80-per-cent DCR (16 out of 20); five out of eight responses were confirmed; and ORR includes unconfirmed and continuing responses.
• Median duration of response was not reached with responses continuing.
• MDNA11 monotherapy: 36-per-cent ORR (four out of 11) and 82-per-cent DCR (nine out of 11).
• MDNA11 plus pembrolizumab: 44-per-cent ORR (four out of nine) and 78-per-cent DCR (seven out of nine).
• ICI-refractory subset: 31-per-cent ORR (four out of 13), including 33-per-cent ORR (three out of nine with MDNA11 monotherapy and 25-per-cent ORR (one out of four) with MDNA11 plus pembrolizumab.
• Tumour regression was observed in 55 per cent of evaluable patients (11 out of 20).

Published post-ICI, data sets in MSI-H/dMMR GI cancers have reported limited activity with available salvage approaches, including ORRs of approximately 11 per cent with ICI rechallenge and approximately 12 to 13 per cent with chemotherapy plus or minus targeted therapy. Emerging salvage programs have reported ORRs in the approximately 7- to 22-per-cent range. These cross-trial comparisons are descriptive; and patient populations, prior treatment exposure and response assessment differ across studies.

Single-agent activity in patients with liver metastases

Liver metastases are associated with lower response rates and shorter progression-free survival following checkpoint inhibition in MSI-H/dMMR GI cancers. In Ability-1, MDNA11 showed single-agent activity in patients with active liver metastases:

• All four evaluable MSI-H GI patients with measurable liver target lesions treated with MDNA11 monotherapy experienced regression of their liver lesions.
• All eight measurable hepatic target lesions (100 per cent) regressed in patients with PDAC, CRC and cholangiocarcinoma.

"The activity observed in patients whose cancers had already progressed on checkpoint therapy is clinically important, particularly the consistent regression of active liver lesions with MDNA11 monotherapy," said Andre Mansinho, MD, a principal investigator in the Ability-1 study and director of clinical research at Start Lisbon. "These patients often have limited effective treatment options, and liver metastases are associated with poorer outcomes even with checkpoint inhibition. The durability and breadth of activity suggests differential activity likely driven by the unique beta-enhanced design and albumin directed localization supporting the potential of MDNA11 to address unmet needs in cancer immunotherapy."

Clinical activity in ICI-resistant cutaneous melanoma and MSS endometrial cancer

Ability-1 also demonstrated durable activity with MDNA11 alone and in combination with pembrolizumab in heavily pretreated, Stage 4 cutaneous melanoma. In the protocol defined expansion cohorts (N equals 18), 100 per cent had Stage 4 disease, 90 per cent had prior exposure to both PD-1 and CTLA-4 therapy, and 30 per cent had liver metastases.

• In patients with secondary ICI resistance treated with MDNA11 monotherapy (n equals 10), ORR was 30 per cent, and DCR was 60 per cent.
• In patients with primary ICI resistance treated with MDNA11 plus pembrolizumab (n equals eight), ORR was 38 per cent, and DCR was 38 per cent.

MDNA11 plus pembrolizumab also showed efficacy signals in MSS endometrial cancer:

• In an expansion cohort comprising patients with secondary resistance to prior immune checkpoint inhibitor therapy (including multiple patients who had progressed following prior pembrolizumab plus lenvatinib), MDNA11 in combination with pembrolizumab achieved a confirmed objective response rate of 28.6 per cent (two out of seven).

Additional data on melanoma and endometrial cancers will be shared during the KOL event.

Manageable safety profile

Across the pooled monotherapy and combination cohorts of the Ability-1 safety population (N equals 69 monotherapy; N equals 73 combination), MDNA11 continued to demonstrate a manageable safety profile:

• No dose-limiting toxicities were observed through 120 micrograms per kilogram.
• More than 90 per cent of treatment-related adverse events were Grade 1 or Grade 2 and were predominantly transient, with a median duration of one to two days.
• Approximately 65 per cent of greater than or equal to Grade 3 TRAEs were laboratory abnormalities, mostly asymptomatic.
• Grade 4 TRAE were exceedingly rare, comprising 0.3 per cent of all TRAE events in both treatment groups, and all but one were asymptomatic laboratory abnormalities.
• One transient Grade 4 cytokine release syndrome event occurred in a patient with baseline low blood pressure and resolved within four days.
• No Grade 5 treatment-related adverse events were reported.
• No new safety signals were observed with the addition of pembrolizumab.
• Treatment-related dose reductions in monotherapy and combination were 2.9 per cent and 5.5 per cent, respectively. Treatment-related permanent discontinuation were 0 per cent and 4 per cent in the monotherapy and combination arms, respectively.

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

KOL event

Medicenna will host a KOL event on Nov. 10, 2026, from 9 a.m. to 10 a.m. ET featuring Hussein A. Tawbi, MD, PhD, professor of melanoma medical oncology and director of personalized cancer therapy at the University of Texas MD Anderson Cancer Center, and Andre Mansinho, MD, MSc, director of clinical research at Start Lisbon, to discuss the SITC data, the new melanoma and endometrial cohort data, and the clinical development potential for MDNA11. Please register.

About MDNA11 and the Ability-1 study

MDNA11 is an investigational, long-acting IL-2 superkine engineered to preferentially activate and expand cancer-fighting CD8+ T-cells and natural killer cells, with minimal stimulation of immunosuppressive regulatory T-cells.

Ability-1 (NCT05086692) is an open-label, multicentre phase 1/2 dose escalation and expansion study evaluating the safety, tolerability, pharmacokinetics, pharmacodynamics and anti-tumour activity of MDNA11 alone and in combination with pembrolizumab in patients with advanced solid tumours. The study is being conducted in collaboration with Merck Sharp & Dohme, a subsidiary of Merck & Co., Rahway, N.J., United States.

About Medicenna Therapeutics Corp.

Medicenna is a clinical-stage immunotherapy company developing engineered cytokine therapies designed to selectively engage the immune system to treat cancer and autoimmune diseases. Medicenna is advancing MDNA11, a long-acting IL-2 superkine designed to selectively activate cancer-fighting immune cells, which is currently being evaluated in the phase 1/2 Ability-1 study and the phase 1b NEO-CYT study. The company is also developing MDNA113, a targeted PD-1 by IL-2 bifunctional immunotherapy for solid tumours, and MDNA209, an antagonist of CD122 blocking IL-2/IL-15 signalling, using its proprietary BiSKIT and T-MASK platforms. The company's most advanced program, bizaxofusp (formerly MDNA55), is a targeted IL-4 empowered superkine that has been evaluated in more than 130 patients across five clinical trials, including a phase 2b study in recurrent glioblastoma. Bizaxofusp has received fast-track designation from the Food and Drug Administration, orphan drug designation from the FDA, and orphan designation in the European Union.

We seek Safe Harbor.