Medicenna Updates MDNA11 Clinical Trial Results at the ESMO-IO Congress 2025, Further Bolstering its Anti-Tumor Activity in Advanced Solid Tumors

Rhea-AI Summary

Medicenna (OTCQX: MDNAF) presented updated Phase 1/2 ABILITY-1 data for MDNA11 at ESMO-IO Congress on Dec 10, 2025. Key findings at the Biological Effective Dose Range (60–120 µg/kg Q2W/Q3W) include monotherapy ORR of 42% and DCR of 83% in patients treated after progression on immune checkpoint inhibitors, ORR of 38% in checkpoint-resistant melanoma, and ORR of 22% in MSI-H tumors. Combination with KEYTRUDA showed ORR/DCR of 50%/75% in MSS endometrial cancer and 25%/88% in TMB-H tumors. Median OS was longer in patients achieving disease control (monotherapy mOS 120.2 vs 28.6 weeks; combination mOS not reached vs 26 weeks). Safety was manageable with >90% Grade 1–2 TRAEs and no DLTs up to 120 µg/kg.

Positive

• ORR 42% in post‑ICI patients at BEDR
• DCR 83% in monotherapy post‑ICI cohort
• ORR 50% for MDNA11 + KEYTRUDA in MSS endometrial cancer
• Monotherapy mOS 120.2 weeks for patients with disease control
• No DLTs observed up to 120 µg/kg

Negative

• Several subgroup results from small cohorts (e.g., N=4, N=8, N=9)
• Survival analyses described as exploratory (not definitive)
• Grade 3–4 laboratory abnormalities reported despite clinical resolution

News Market Reaction

-13.01%

1 alert

-13.01% News Effect

On the day this news was published, MDNAF declined 13.01%, reflecting a significant negative market reaction.

Data tracked by StockTitan Argus on the day of publication.

Key Figures

Monotherapy ORR post-ICI: 42% Monotherapy DCR post-ICI: 83% Melanoma ORR: 38% +5 more

8 metrics

Monotherapy ORR post-ICI 42% Phase-2 eligible BEDR patients; next line after immune checkpoint inhibitors

Monotherapy DCR post-ICI 83% Phase-2 eligible BEDR patients after progression on checkpoint inhibitors

Melanoma ORR 38% Monotherapy expansion cohort in checkpoint-resistant cutaneous melanoma

MSI-H ORR 22% Monotherapy expansion cohort in MSI-H tumors

MSS endometrial ORR 50% Combination MDNA11 + KEYTRUDA in MSS endometrial cancers

TMB-H DCR 88% Combination MDNA11 + KEYTRUDA in TMB-H tumors

Monotherapy median OS (disease control) 120.2 weeks Patients with CR/PR/SD vs 28.6 weeks without disease control

p-value (monotherapy OS) p=0.002 Association between disease control and overall survival

Market Reality Check

Price: $0.6000 Vol: Volume 327,920 is about 2...

high vol

$0.6000 Last Close

Volume Volume 327,920 is about 2.54x the 20-day average of 129,132, indicating elevated trading interest ahead of/around the data. high

Technical Shares at $0.86 are trading above the 200-day MA of $0.77 but sit 41.18% below the 52-week high and 50.03% above the 52-week low.

Peers on Argus

Peers in Biotechnology show mixed, mostly modest moves (e.g., ACHFF -3.72%, MSCL...

Peers in Biotechnology show mixed, mostly modest moves (e.g., ACHFF -3.72%, MSCLF -4%, NRXBF -1.91%, BSEM +0.23%, HOPHF flat), suggesting MDNAF’s -13.01% move is more stock-specific than sector-driven.

Historical Context

5 past events · Latest: Nov 13 (Positive)

Pattern 5 events

Date	Event	Sentiment	Move	Catalyst
Nov 13	Earnings and update	Positive	-2.8%	Quarterly results, MDNA11/MDNA113 timelines, cash runway to at least mid-2026.
Nov 06	Clinical collaboration	Positive	-1.9%	Announcement of NEO-CYT neoadjuvant MDNA11 melanoma trial collaboration.
Oct 23	Clinical data preview	Positive	+44.7%	Planned ESMO-IO presentation of updated MDNA11 ABILITY-1 clinical data.
Oct 20	Investor conferences	Neutral	+6.7%	Upcoming investor and industry conference participation through late 2025.
Oct 01	Investor conference	Neutral	-1.7%	Participation in ROTH healthcare conference with investor meetings.

Pattern Detected

Clinical and strategic updates have often produced mixed price reactions, with one strong rally on MDNA11 data but several modest declines following otherwise constructive news.

Recent Company History

Over recent months, Medicenna highlighted multiple milestones around its Superkine pipeline. Clinical updates for MDNA11 from the ABILITY-1 trial and preclinical data for MDNA113 were presented at major meetings, with one ABILITY-1 update on Oct 23, 2025 coinciding with a 44.74% move. The company also announced the melanoma NEO-CYT trial and participated in several investor conferences. An earnings update on Nov 13, 2025 reaffirmed cash of $15.7M and runway into at least mid-2026. Today’s detailed ABILITY-1 results extend this clinical narrative.

Market Pulse Summary

The stock dropped -13.0% in the session following this news. A negative reaction despite encouraging...

Analysis

The stock dropped -13.0% in the session following this news. A negative reaction despite encouraging efficacy metrics fits a pattern where prior positive updates sometimes met selling pressure, as seen after earlier news with constructive clinical or strategic content. Today’s detailed ABILITY-1 data, including ORRs such as 42% post-ICI and survival separation with median OS of 120.2 weeks vs 28.6 weeks, contrasted with a -13.01% move, highlighting how valuation, risk appetite, or profit-taking can overshadow data strength.

Key Terms

objective response rate (ORR), disease control rate (DCR), microsatellite stable (MSS), MSI-H, +4 more

8 terms

objective response rate (ORR) medical

"in each case exceeding objective response rate (ORR) benchmarks in these difficult"

The objective response rate (ORR) is the percentage of patients in a clinical trial whose tumors shrink by a pre-set amount for a minimum time, counting both complete disappearance and meaningful partial shrinkage. Investors watch ORR because it gives an early, quantitative signal that a treatment is having a direct effect on disease—like the percent of people whose fever drops after taking a medicine—which can influence expectations for later trial success, regulatory approval, and market potential.

disease control rate (DCR) medical

"had an ORR of 42% and a disease control rate (DCR) of 83% underscoring"

The disease control rate (DCR) is the share of patients in a clinical trial whose cancer either shrinks, disappears, or does not get worse for a predefined period after treatment. For investors, DCR is a practical measure of a drug’s ability to halt disease progression — akin to counting how many cars in a fleet are kept running or fixed after a repair — and can influence a therapy’s regulatory prospects, market potential, and perceived risk.

microsatellite stable (MSS) medical

"for MSS endometrial cancer while MSS TMB-H tumors demonstrated ORR and DCR"

Microsatellite stable (MSS) describes a tumor whose short, repeating DNA sequences remain unchanged during cell division, meaning the cancer’s DNA repair system is functioning normally. For investors this matters because MSS status is a common biological test result used to predict how well certain therapies—especially some immunotherapies—will work, influence clinical trial design and enrollment, and affect regulatory decisions and commercial prospects for new cancer treatments.

MSI-H medical

"MSS endometrial cancer, MSI-H and TMB-H cancers, in each case exceeding"

MSI‑H stands for microsatellite instability‑high, a tumor feature where repeated stretches of DNA accumulate many small “typos” because the cell’s repair machinery is broken — imagine a spell-checker that's failed and lets repeated words and mistakes pile up. It matters to investors because MSI‑H both guides the use and development of specific cancer drugs and diagnostics and can determine patient eligibility for trials, influencing the commercial size and regulatory path for therapies and tests.

TMB-H medical

"MSS endometrial cancer, MSI-H and TMB-H cancers, in each case exceeding"

TMB-H stands for “tumor mutational burden–high,” a medical test result showing a cancer has a large number of DNA mutations. Investors care because tumors with many mutations are more likely to respond to certain immune-based cancer drugs, so a TMB-H result can expand the pool of patients for a therapy, influence clinical trial success, and affect regulatory approvals and market value. Think of it like a product with many visible flaws that makes it easier for a fixer tool to find and repair it.

immune checkpoint inhibitors (ICI) medical

"following progression on immune checkpoint inhibitors (ICI), had an ORR of 42%"

Immune checkpoint inhibitors (ICI) are a class of cancer drugs that help the body’s immune system recognize and attack tumor cells by removing molecular “brakes” that normally limit immune responses. They matter to investors because their clinical trial results, regulatory approvals, safety profiles and patent status can drive large changes in drug sales, company valuations and partnership or acquisition activity, similar to how a blockbuster product can reshape a company’s revenue outlook.

overall survival (OS) medical

"disease control (CR, PR and SD) and overall survival (OS) in both monotherapy"

Overall survival (OS) is the length of time from the start of a treatment or clinical study until death from any cause, essentially measuring how long patients live after a therapy begins. Investors watch OS because it is the most direct evidence a treatment extends life; stronger OS results can drive regulatory approvals, wider use and higher revenue expectations, much like sales figures proving a product actually works.

interleukin-2 (IL-2) medical

"a long-acting ‘beta-enhanced not-alpha’ interleukin-2 (IL-2) super-agonist"

Interleukin-2 (IL-2) is a naturally occurring protein that acts like a signal or switch to activate and grow certain immune cells; in medicine it is used or mimicked to boost the body’s immune response against infections and cancers. For investors, IL-2 matters because drugs based on it can drive clinical trial outcomes, safety profiles, regulatory decisions and potential market value, much like a key ingredient that determines whether a new recipe succeeds or fails.

AI-generated analysis. Not financial advice.

MDNA11 demonstrates durable anti-tumor activity in phase-2 eligible expansion cohorts, enriched for immune checkpoint resistant melanoma, MSS endometrial cancer, MSI-H and TMB-H cancers, in each case exceeding objective response rate (ORR) benchmarks in these difficult to treat populations 

In the monotherapy expansion cohorts, irrespective of tumor type, patients treated with MDNA11, as the next treatment following progression on immune checkpoint inhibitors (ICI), had an ORR of 42% and a disease control rate (DCR) of 83% underscoring potential of MDNA11 in earlier lines of treatment

Monotherapy expansion cohorts demonstrate ORRs of 38% in melanoma and 22% in MSI-H corresponding to DCR of 75% and 78%, respectively

MDNA11 in combination with KEYTRUDA (pembrolizumab) shows ORR and DCR of 50% and 75%, respectively, for MSS endometrial cancer while MSS TMB-H tumors demonstrated ORR and DCR of 25% and 88%, respectively

Monotherapy and combination treatment achieve durable responses in multiple advanced metastatic tumors, including pancreatic, breast, colorectal, endometrial, bladder, anal cancer and melanoma

Tumor control (responders and those with stable disease) was associated with significantly prolonged median overall survival (mOS) in both monotherapy and combination cohorts

Medicenna will host a webinar with its management team and the presenting Principal Investigator along with commentary from key opinion leaders to discuss the updated data

TORONTO and HOUSTON, Dec. 10, 2025 (GLOBE NEWSWIRE) -- Medicenna Therapeutics Corp. (“Medicenna” or the “Company”) (TSX: MDNA, OTCQX: MDNAF), a clinical-stage immunotherapy company focused on the development of Superkines targeting cancer and autoimmune diseases, today presented updated clinical data from the ongoing Phase 1/2 ABILITY-1 study evaluating MDNA11 in patients with advanced solid tumors at the European Society of Medical Oncology (ESMO) Immuno-Oncology Congress 2025. MDNA11, a long-acting ‘beta-enhanced not-alpha’ interleukin-2 (IL-2) super-agonist, is being evaluated as a monotherapy or in combination with Merck’s (known as MSD outside of the US and Canada) anti-PD-1 therapy, KEYTRUDA^® (pembrolizumab).

A live webinar will be hosted this morning with Medicenna’s management team, the presenting investigator, and additional commentary from key opinion leaders. Participants may register at: [Link]. A replay of the webinar will also be available on Medicenna’s website following the event.

“The most important message from today’s data is that they absolutely add to the differentiation of MDNA11’s mechanism relative to other next-generation IL-2s and reinforce the consistency of its anti-tumor activity in late stage cancers refractory to checkpoint inhibitors,” said Fahar Merchant, Ph.D., President and CEO of Medicenna. “With durable responses in multiple late stage metastatic tumors, including pancreatic, breast, colorectal, endometrial, bladder, anal cancer and melanoma, it is difficult for us not to conclude that MDNA11 demonstrates meaningful efficacy. The recent announcement of the NEO-CYT trial sponsored by Fondazione Melanoma, in pre-surgery patients with high-risk melanoma, provides external validation of our approach and adds to our conviction that MDNA11 is potentially a de-risked drug candidate for earlier stage cancer patients harbouring healthier immune systems. We look forward to sharing new and mature data in the coming weeks and months from the ABILITY-1 study, new data from the NEO-CYT study and non-human primate data with MDNA113, our targeted and conditionally activated anti-PD1-IL-2 BiSKIT which is anticipated to enter its first in human study later next year.”

Dr. André Mansinho, Principal Investigator and Presenting Author, commented: “I am encouraged by the durability of responses and the immune activation profile we observed with MDNA11, both as a single agent and combined with pembrolizumab. The clinical activity in checkpoint-resistant cohorts, together with prolonged remissions suggest a meaningful therapeutic signal that merits further evaluation in broader and earlier patient populations.”

Key findings from the ABILITY-1 study (data cut-off as of December 1, 2025) include:

Safety Profile

• MDNA11 continues to demonstrate a manageable safety profile both as a single agent and in combination with KEYTRUDA. Over 90% of treatment-related adverse events (TRAEs) were Grade 1-2 and transient, typically resolving within 48 hours. No dose-limiting toxicities (DLTs) were observed with MDNA11 at doses up to 120 µg/kg in monotherapy or in combination with KEYTRUDA and Grade 3-4 events were mainly laboratory abnormalities without clinical sequelae.
  
  

Biological Effective Dose Range (BEDR)

• The preliminary recommended dose for expansion for both monotherapy and combination arms was established at 90 µg/kg Q2W with the BEDR set at 60 to 120 µg/kg (Q2W and Q3W).
  
  

Monotherapy Tumor Response in Immune Checkpoint Inhibitor (ICI) Resistant Patients

Amongst Phase-2 Eligible Patients treated at the BEDR (60 to 120 µg/kg) with Single-Agent MDNA11 (N=22):

• ORR of 42% (5 of 12) and DCR of 83% (1 CR, 4 PR, 5 SD) amongst patients who were treated with MDNA11 as the next treatment line following progression on a checkpoint inhibitor, highlighting the potential of MDNA11 in earlier treatment settings.
  
  
• ORR in 2° checkpoint-resistant cutaneous melanoma was 38% (3 of 8) with a disease control rate of 75% (1 CR, 2 PR, 3 SD).
  
  
• ORR in MSI-H tumors was 22% (2 of 9) with a disease control rate of 78% (2 PR, 5 SD).
  
  
• Two monotherapy patients with long-term remission include a pancreatic MSI-H patient (>21 months off-treatment) and a melanoma patient (>7 months off-treatment).
  
  

Clinical Activity of MDNA11 in Combination with KEYTRUDA

Encouraging anti-tumor activity was also observed with MDNA11 in combination with KEYTRUDA in patients who either progressed on checkpoint therapy or were ineligible for ICI therapy.

Amongst phase-2 eligible patients treated at the BEDR with MDNA11 (60 to 120 µg/kg) and KEYTRUDA (400 mg Q6W) (N=30):

• In microsatellite stable (MSS) endometrial cancers with secondary resistance to immune checkpoint inhibition, the ORR was 50% (2 of 4) with a DCR of 75% (2 PR, 1 SD)
  
  
• In TMB-H tumors, the ORR was 25% (2 of 8) with a DCR of 88% (2 PR, 5 SD) and tumor regression observed in 6 of 8 patients (75%)
  
  
• In addition, a patient with cutaneous melanoma and primary resistance to a standard of care combination of two immune checkpoint inhibitors (nivolumab + ipilimumab), including hepatic tumor involvement, achieved a PR with MDNA11 + KEYTRUDA at the first on-study scan.
  
  

Significant Improvements to Overall Survival Amongst Those with Disease Control

MDNA11 demonstrated a significant association between disease control (CR, PR and SD) and overall survival (OS) in both monotherapy and combination cohorts among patients treated within the BEDR of MDNA11 with or without KEYTRUDA:

• In the monotherapy cohorts, patients with disease control (N=24) had a median OS of 120.2 weeks compared with 28.6 weeks in those without disease control (N=24) (p=0.002; HR 0.29 [95% CI: 0.13-0.66]).
  
  
• In the combination cohorts, patients with disease control (N=27) had a median OS that was not yet reached compared with 26 weeks in those without disease control (N=18) (p=0.014, HR 0.28 [95% CI: 0.02-0.85]).
  
  

Although these survival data are exploratory, they provide additional support for the clinical relevance of MDNA11-mediated disease control.

A copy of the poster and related slide deck has been posted on the “Scientific Presentations” page of Medicenna’s website.

KEYTRUDA^® is a registered trademark of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.

About MDNA11

MDNA11 is an intravenously administered, 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 tumor and tumor draining lymph nodes. MDNA11 is currently being evaluated in the Phase 1/2 ABILITY-1 study as both monotherapy and in combination with KEYTRUDA.

About the ABILITY-1 Study

The ABILITY-1 study (NCT05086692) is a global, multi-center, open-label study that assesses the safety, tolerability, pharmacokinetics, pharmacodynamics and anti-tumor activity of MDNA11 as monotherapy or in combination with Merck’s anti-PD-1 therapy, KEYTRUDA (pembrolizumab). In the combination dose escalation portion of the Phase 2 study, patients have been enrolled and administered ascending doses of MDNA11 intravenously in combination with KEYTRUDA. This portion of the study includes patients with a wide range of solid tumors with the potential for susceptibility to immune modulating therapeutics. The combination Recommended Dose for Expansion (cRDE) has been established and the study has commenced combination dose expansion.

About Medicenna Therapeutics

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 tumors 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 5 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 FastTrack and Orphan Drug status from the FDA and FDA/EMA, respectively.

For more information, please visit www.medicenna.com, and follow us on X and LinkedIn.

Forward-Looking Statements

This news release may contain forward-looking statements within the meaning of applicable securities laws. Forward-looking statements include, but are not limited to, express or implied statements regarding the future operations of the Company, estimates, plans, strategic ambitions, partnership activities and opportunities, objectives, expectations, opinions, forecasts, projections, guidance, outlook or other statements that are not historical facts, such as statements on the therapeutic treatment potential and safety profile of MDNA11 (both as monotherapy and in combination with Merck’s anti-PD-1 therapy, KEYTRUDA [pembrolizumab]) and the timing and/or release of any additional clinical updates. Drug development and commercialization involve a high degree of risk, and only a small number of research and development programs result in commercialization of a product. Results in early-stage pre-clinical or clinical studies may not be indicative of full results or results from later stage or larger scale clinical studies and do not ensure regulatory approval. You should not place undue reliance on these statements, or the scientific data presented.

Forward-looking statements are often identified by terms such as “will”, “may”, “should”, “anticipate”, “expect”, “believe”, “seek”, “potentially” and similar expressions. and are subject to risks and uncertainties. Forward-looking statements are based on a number of assumptions believed by the Company to be reasonable at the date of this news release. Although the Company believes that the expectations reflected in such forward-looking statements are reasonable, there can be no assurance that such statements will prove to be accurate. These statements are subject to certain risks and uncertainties and may be based on assumptions that could cause actual results and future events to differ materially from those anticipated or implied in such statements. Important factors that could cause actual results to differ materially from the Company’s expectations include the risks detailed in the latest annual information form of the Company and in other filings made by the Company with the applicable securities regulators from time to time in Canada.

The reader is cautioned that assumptions used in the preparation of any forward-looking information may prove to be incorrect. Events or circumstances may cause actual results to differ materially from those predicted, as a result of numerous known and unknown risks, uncertainties, and other factors, many of which are beyond the control of the Company. The reader is cautioned not to place undue reliance on any forward-looking information. Such information, although considered reasonable by management, may prove to be incorrect and actual results may differ materially from those anticipated or implied in forward-looking statements. Forward-looking statements contained in this news release are expressly qualified by this cautionary statement. The forward-looking statements contained in this news release are made as of the date hereof and except as required by law, we do not intend and do not assume any obligation to update or revise publicly any of the included forward-looking statements.

This news release contains hyperlinks to information that is not deemed to be incorporated by reference in this new release.

Investor and Company Contact:

Shushu Feng
Investor Relations, Medicenna Therapeutics
(416) 964-5442
ir@medicenna.com

FAQ

What efficacy did Medicenna (MDNAF) report for MDNA11 at ESMO-IO on Dec 10, 2025?

At the BEDR (60–120 µg/kg) MDNA11 showed an overall monotherapy ORR of 42% and DCR of 83% in patients treated after checkpoint inhibitor progression.

How did MDNA11 perform with KEYTRUDA in MSS endometrial cancer in the ABILITY-1 study?

The combination produced an ORR of 50% and a DCR of 75% in MSS endometrial cancer (N=4) at the BEDR.

What safety profile did Medicenna report for MDNA11 in the Dec 1, 2025 data cut?

MDNA11 had a manageable safety profile with >90% of TRAEs Grade 1–2, no DLTs up to 120 µg/kg, and mainly transient lab abnormalities for Grade 3–4 events.

What overall survival difference was seen for patients with disease control on MDNA11 (MDNAF)?

In monotherapy cohorts patients with disease control had mOS of 120.2 weeks versus 28.6 weeks without disease control (p=0.002).

What dose did Medicenna set as the preliminary recommended expansion dose for MDNA11?

The preliminary recommended dose for expansion was set at 90 µg/kg Q2W with a BEDR of 60–120 µg/kg.