Medicenna Therapeutics : 2025 Annual Information Form

Published: 2025-06-26 06:59:06 ET MDNA.TO

Published on 06/26/2025 at 06:59

ANNUAL INFORMATION FORM FOR THE YEAR ENDED MARCH 31, 2025

Unless otherwise indicated, all information in the Annual Information Form is presented as at and for the year ended March 31, 2025

June 25, 2025

TABLE OF CONTENTS

INTRODUCTION AND FORWARD-LOOKING STATEMENTS 1

CORPORATE STRUCTURE 4

GENERAL DEVELOPMENT OF THE BUSINESS 6

NARRATIVE DESCRIPTION OF THE BUSINESS 13

RISK FACTORS 37

DIVIDENDS 59

SHARE CAPITAL 59

MARKET FOR SECURITIES 60

BOARD OF DIRECTORS AND MANAGEMENT 60

CEASE TRADE ORDERS, BANKRUPTCIES, PENALTIES OR SANCTIONS 65

CONFLICTS OF INTEREST 65

LEGAL PROCEEDINGS AND REGULATORY ACTIONS 66

INTEREST OF MANAGEMENT AND OTHERS IN MATERIAL TRANSACTIONS 66

TRANSFER AGENT 66

MATERIAL CONTRACTS 66

INTEREST OF EXPERTS 66

ADDITIONAL INFORMATION 67

SCHEDULE A AUDIT COMMITTEE INFORMATION 68

APPENDIX 1 AUDIT COMMITTEE CHARTER 70

INTRODUCTION AND FORWARD-LOOKING STATEMENTS

The information contained in this Annual Information Form (this "AIF") is stated as at March 31,

2025, unless otherwise indicated.

All references in this AIF to the "Company", "Medicenna", "we", "us", or "our" and similar expressions refer to Medicenna Therapeutics Corp. and the subsidiaries through which it conducts its business, unless otherwise indicated.

All amounts are in Canadian dollars, unless otherwise indicated.

This AIF contains forward-looking statements within the meaning of applicable securities laws. Forward-looking statements are neither historical facts nor assurances of future performance. Instead, they are based on current beliefs, expectations or assumptions regarding the future of the business, future plans and strategies, operational results and other future conditions of the Company. These statements involve known and unknown risks, uncertainties and other factors which may cause the actual results, performance or achievements of the Company, or industry results, to be materially different from any future results, performance or achievements expressed or implied by such forward-looking statements. 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 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. All statements contained herein other than statements of historical fact regarding the prospects of the Company's industry or its prospects, plans, financial position or business strategy may constitute forward-looking statements and can generally be identified by the use of forward-looking words, such as "plan", "expect", "is expected", "budget", "scheduled", "estimate", "forecast", "contemplate", "intend", "anticipate", or "believe" or variations (including negative variations) of such words and phrases, or statements that certain actions, events or results "may", "could", "would", "might", "shall" or "will" be taken, occur or be achieved and similar expressions are generally intended to identify forward-looking statements.

By their very nature, forward-looking statements involve inherent risks and uncertainties, both general and specific, and risks exist that predictions, forecasts, projections and other forward-looking statements will not be achieved. The Company cautions readers not to place undue reliance on these statements as a number of important factors could cause the actual results to differ materially from the beliefs, plans, objectives, expectations, anticipations, estimates and intentions expressed in such forward-looking statements. Risks, uncertainties and other factors which may cause the actual results, performance or achievements of the Company, as applicable, to be materially different from any future results, performance or achievements expressed or implied by such forward-looking information and statements include, but are not limited to, the risks described under the heading "Risk Factors" in this AIF.

Forward-looking statements in this AIF include, but are not limited to, statements with respect to:

the therapeutic potential, clinical development and related milestones of the Corporation's Superkines and Empowered Superkines including MDNA11, the BiSKITsTMplatform, the T-MASKTMplatform and bizaxofusp (formerly MDNA55);

the timely completion of the milestones related to the MDNA11 ABILITY study;

the impact of the delay on clinical data;

the clinical trial collaboration and supply agreement ("CTCSA") with Merck (known as MSD outside the United States and Canada);

statements related to the potential extensions of the term of patents;

potential strategic partnership to facilitate bizaxofusp's further development and

commercialization; and

the use of proceeds from public equity offerings and private placements and the necessity for the Corporation to have recourse to such equity offerings.

Although the Company has attempted to identify important factors that could cause actual actions, events or results to differ materially from those described in forward-looking statements, there may be other factors that cause actions, events or results to differ from those anticipated, estimated or intended, including the following:

the lack of product revenue and inability to continue operations and research and development without sufficient funding;

the Corporation's requirements for, and the Corporation's ability to obtain, future funding

on favorable terms or at all;

the Corporation's history of losses and expectations of future losses;

the Corporation's inability to complete development of or the inability to commercialize (if

approved), its products

the Corporation's product candidates, which are in the early stages of development;

the expense, length and uncertainty of clinical drug development programs;

the inability to achieve publicly announced milestones according to schedule, or at all;

the risk that competitors may develop and market products that are more effective that the Corporation's product candidates or that the products developed by competitors may render the Corporation's product candidates obsolete or uncompetitive;

the Corporation's inability to secure a partnership for bizaxofusp (formerly MDNA55);

the costs and uncertainty associated with extensive government regulation;

the potential negative results from clinical trials or studies, adverse safety events or toxicities involving the Corporation's products used alone or in combination with other products of collaborators;

the Corporation's ability to manage the unique risks and uncertainties related to

developing biologics which could have a negative impact on future results of operations;

the risk that preliminary and interim data from the Corporation's clinical trials that the Corporation may announce or publish from time to time may change as patient data are further examined, audited or verified and more patient data become available;

the value of the "Fast Track" designation granted to bizaxofusp and that it may not actually lead to a faster development or regulatory review or approval process and could be withdrawn by the United States Food and Drug Administration ("FDA");

the value of the "Orphan Drug" designation granted to bizaxofusp and that it may not actually lead to a faster development or regulatory review or approval process, may not be granted additional market exclusivity, may not receive tax credits and could be withdrawn by the FDA or the European Medicines Agency ("EMA");

the unfavorable pharmacokinetic or pharmacodynamic properties of MDNA11 used alone or in combination with other products of collaborators;

the potential of the pre-clinical products of the Corporation;

the risk of product liability claims;

the Corporation's inability to enroll subjects in clinical trials or to enter or complete clinical

trials on a timely basis;

the failure of the Corporation's product candidates to receive the marketing approval or market acceptance necessary for commercial success or to maintain any ongoing regulatory requirements it may be subject to;

the potential for environmental exposure to hazardous or radioactive materials that are

used in the Corporation's discovery and development process;

the disruption in the availability of key components for ongoing clinical studies that could delay clinical studies, product testing and regulatory approval of the Corporation's product candidates;

the Corporation's reliance on third parties for the planning, conduct and monitoring of

preclinical and clinical trials and for the manufacture of drug product;

the Corporation's reliance on contract manufacturers over whom the Corporation has

limited control;

the loss of license rights due to breach of license agreements;

the conditions and restrictions of the Cancer Prevention and Research Institute of Texas

("CPRIT") grant;

the ability to protect the Corporation's intellectual property and proprietary technology;

the ability for the Corporation to obtain patent's term extensions;

the potential involvement in intellectual property litigation;

the risk that third parties on whom the Corporation rely for product development may not

adequately protect the Corporation's trade secrets;

the risk of product liability claims;

the limitations surrounding intellectual property rights;

the volatility in the price of the Common Shares;

the dilution of investor's voting power and reductions in earnings per share owing to future

issuances of equity or the conversion of securities into Common Shares;

the fact that future profits will likely be used for the continued growth of the Corporation's

business and not for the payment of dividends;

the Corporation's treatment as a passive foreign investment company and potential

adverse U.S. federal income tax consequences associated with such treatment;

the difficulty U.S. investors may face in bringing actions against the Corporation for violations of U.S. federal or state securities laws and challenges in enforcing the judgments of U.S. courts against the Corporation and its directors and executive officers;

changes in government regulations that could impact the Corporation's business and

operations;

failure to comply with the U.S. Foreign Corrupt Practices Act, the Canadian Corruption of Foreign Public Officials Act and other global corruption and anti-bribery laws;

failure to comply with healthcare laws;

the ability of the Corporation's significant shareholders to assert a material influence over the Corporation's operations and governance;

the adverse impact of factors outside the Corporation's control, such as global health

pandemics, natural disasters, geopolitical conflict and macroeconomic challenges;

the Corporation's ability to successfully manage its growth;

the failure of any acquired business, product, service or alliance to yield expected benefits;

the Corporation's dependence upon certain key personnel, the loss of whom could

adversely affect its ability to achieve its business objectives;

changes in government regulations that could impact the Corporation's business and

operations;

foreign currency exchange risks relating to the relative value of the United States dollar;

the failure of the Corporation's disclosure controls and procedures to detect all errors or

prevent all incidences of fraud;

the failure to maintain an effective system of internal controls;

the vulnerability of the computer and information systems of the Corporation, its consultants and contractors, and third parties on which the Corporation relies, to security breaches or failure;

the pursuit of opportunities for further research and development or additional business opportunities; and

the impact of trade barriers on the Corporation's business, operations and financial

condition.

Although the Company has attempted to identify important factors that could cause actual actions, events or results to differ materially from those described in forward-looking statements, there may be other factors that cause actions, events or results to differ from those anticipated, estimated or intended.

All forward-looking statements reflect the Company's beliefs and assumptions based on

information available at the time the assumption was made.

Although the forward-looking statements contained in this AIF are based upon what the Company's management believes to be reasonable assumptions, the Company cannot assure readers that actual results will be consistent with these forward-looking statements.

Any forward-looking statements represent the Company's estimates only as of the date of this AIF and should not be relied upon as representing the Company's estimates as of any subsequent date. The Company undertakes no obligation to update any forward-looking statement or statements to reflect events or circumstances after the date on which such statement is made or to reflect the occurrence of unanticipated events, except as may be required by securities laws.

CORPORATE STRUCTURE

Medicenna Therapeutics Corp., formerly A2 Acquisition Corp. ("A2"), is the resulting issuer following a "three-cornered" amalgamation involving A2, 1102209 B.C. Ltd., a wholly owned subsidiary of A2 incorporated pursuant to the Business Corporations Act (British Columbia) ("BCBCA"), and Medicenna Therapeutics Inc. ("MTI"), completed on March 1, 2017.

A2 was formed by articles of incorporation under the Business Corporations Act (Alberta) on February 2, 2015, and following its initial public offering, was a capital pool company ("CPC") listed on the TSX Venture Exchange ("TSXV"). As a CPC, A2 had no assets other than cash and did not carry on any operations other than identifying and evaluating opportunities for the acquisition of an interest in assets or businesses for the completion of a qualifying transaction.

On March 1, 2017, A2 completed its qualifying transaction in accordance with the policies of the TSXV by way of reverse takeover of A2 by the shareholders of MTI (the "Qualifying Transaction"). In addition, on March 1, 2017 and prior to the completion of the Qualifying Transaction, the Company amended its articles as a result of (a) implementing a consolidation (the "Consolidation") of its pre-Qualifying Transaction Common Shares (the "A2 Shares") on the basis of one new Common Share for every fourteen A2 Shares (1:14) and (b) changing its name to Medicenna Therapeutics Corp.

On August 2, 2017 Medicenna graduated to the Toronto Stock Exchange ("TSX"). On November

13, 2017, Medicenna continued under the Canada Business Corporations Act ("CBCA").

On March 30, 2021, the Company set up its wholly owned subsidiary Medicenna Australia PTY Ltd (Australia).

Medicenna's head and registered office is located at Suite 903, 2 Bloor Street W, Toronto, Ontario, M4W 3E2.

MTI is a wholly owned subsidiary of Medicenna and was incorporated pursuant to the provisions of the BCBCA on October 31, 2011. MTI has three wholly owned subsidiaries: Medicenna Biopharma Inc. (British Columbia), Medicenna Biopharma Inc. (Delaware) and Medicenna Australia PTY Ltd (Australia). MTI's head and registered office is located at 2 Bloor Street W, 7thFloor, Toronto, Ontario, M4W 3E2.

Medicenna Biopharma Inc. (British Columbia) was incorporated under the BCBCA on October 5, 2012. Its head and registered office is located 2 Bloor Street W, 7thFloor, Toronto, Ontario, M4W 3E2.

Medicenna Biopharma Inc. (Delaware) was incorporated in the State of Delaware on July 1, 2014. Its registered office is located at 1209 Orange Street, Wilmington, New Castle County, Delaware 19801 and its head office is at 1700 Post Oak Blvd, Suite 600, Houston, Texas 77056.

Medicenna Australia Pty Ltd. was incorporated in Adelaide, South Australia on March 30, 2021. Its registered office is located at Level 5, 63 Pirie Street, Adelaide, SA, 5000.

The following organizational chart demonstrates the corporate structure of the Company:

Medicenna Therapeutics Inc.

(British Columbia)

Medicenna Therapeutics Corp.

(Canada)

100%

100%

100%

Medicenna Australia Pty Ltd. (Australia)

Medicenna Biopharma Inc. (Delaware)

Medicenna Biopharma Inc. (British Columbia)

100%

Medicenna Therapeutics is a clinical-stage immunotherapy company developing engineered cytokines, called Superkines, designed to improve the specificity, function and safety profile of interleukins. Medicenna's Superkine Platform transforms Superkines into multi-functional

therapies that modulate, dampen, amplify or fine-tune the immune system. Medicenna's mission is to harness the power of directed evolution to develop novel immunotherapies that have the potential to revolutionize the treatment landscape in oncology and other immune-related diseases.

Medicenna owns diverse platforms licensed from Stanford University (Stanford) to develop a pipeline of Superkine candidates: Interleukin-2 ("IL-2") agonists, IL-2 antagonists and partial agonists of IL-2. Additional assets from Stanford also include several super-agonists of IL-4 and IL-13 and dual IL-4/IL-13 antagonists. These Superkines can be developed either on their own as short or long-acting therapeutics or fused with cell-killing proteins to generate Empowered Superkines that precisely deliver potent payloads to cancer cells without harming adjacent healthy cells. Superkines can also be fused with a large variety of proteins, antibodies, checkpoint inhibitors, and even other Superkines to incorporate two synergistic therapeutic activities into one molecule, creating novel Bi-specific SuperKine ImmunoTherapies and Targeted Metalloprotease Activated SuperKines, referred to by Medicenna as BiSKITsTMand T-MASKTM, respectively.

The Company's lead clinical program is MDNA11, a next-generation long-acting beta-enhanced not-alpha IL-2 super agonist. MDNA11 comprises a molecule of human albumin that accumulates in tumors and tumor draining lymph nodes and augments MDNA11's half-life. MDNA11 is currently being evaluated in the ABILITY-1 (A Beta-only IL-2 ImmunoTherapY) study, a Phase 1/2 clinical trial in patients with advanced and/or metastatic solid tumors. The ABILITY-1 study is a global, multi-center, open-label study that will assess the safety, tolerability and anti-tumor activity of MDNA11 as monotherapy and in combination with KEYTRUDA®(pembrolizumab) under a clinical collaboration with Merck. The Company has successfully completed a Phase 1 monotherapy dose-escalation study with MDNA11 with a favourable safety profile and demonstrated early signs of single-agent efficacy in this setting. The monotherapy recommended dose for expansion ("RDE") for MDNA11 has been established and enrollment in the dose-expansion phase 2 portion of the ABILITY-1 trial is currently underway. In addition, enrollment in the combination dose expansion portion of the ABILITY-1 trial is underway having established the MDNA11 combination recommended dose for expansion ("cRDE") at 90 µg/kg administered every 2 weeks together with KEYTRUDA administered at 400 mg every 6 weeks.

Medicenna's most advanced candidate is bizaxofusp, formerly MDNA55, a first-in-class IL-4 receptor ("IL-4R") targeted therapy for the treatment of recurrent glioblastoma ("rGBM"), the most common and uniformly fatal form of brain cancer. Bizaxofusp is a fusion of a circularly permuted version of IL-4, fused to a potent fragment of the bacterial toxin, Pseudomonas exotoxin ("PE"), and is designed to preferentially target tumor cells that over-express the IL-4R. Bizaxofusp has successfully completed a Phase 2b trial for rGBM and holds FastTrack and Orphan Drug status from the FDA and FDA/EMA, respectively.

The Company's earlier stage candidates from the BiSKITsTMand T-MASKTMplatforms, encompassing IL-2, IL-4 and IL-13 super-agonists and super-antagonists, are in pre-clinical development. Medicenna's lead pre-clinical program, MDNA113, is a novel IL-13Rα2 tumor-targeted and "masked" anti-PD-1-IL-2 Superkine (anti-PD1-IL-2SK), engineered to precisely deliver clinically validated anti-PD-1 and IL-2SKto the tumor microenvironment (TME).

GENERAL DEVELOPMENT OF THE BUSINESS

Year ended March 31, 2025 and subsequent events

On April 9, 2024, the Company presented new clinical data on MDNA113, which is a targeted and masked bi-functional anti-PD1-IL2SK, at the 2024 Annual Meeting of the American Association for Cancer Research ("AACR").

On April 9, 2024, the Company presented updated clinical results of single agent MDNA11 antitumor activity from dose escalation and ongoing dose expansion of the Phase 1/2 ABILITY-1 Study at the 2024 Annual Meeting of the AACR. Key data presented included 100% reduction of target lesions in one melanoma and one pancreatic cancer patient observed among 4 partial responses ("PR") to date which include 2 of 4 evaluable dose expansion patients and 2 of 2 MSI-H patients. In addition, the Company reported durable stable disease (SD) in 3 melanoma patients for 6 to 18 months with concomitant tumor shrinkage.

On April 26, 2024, the Company announced a $20 million investment by RA Capital Management, a multi-stage investment manager based in Boston, MA, by way of a non-brokered private placement (the "2024 Offering"). The 2024 Offering closed on April 30, 2024.

On May 14, 2024, the Company filed a Form 15-12G with the SEC to deregister its Common Shares under the U.S. Securities Exchange Act of 1934, as amended, which has the effect of suspending its U.S. SEC reporting obligations indefinitely.

On May 31, 2024, the Company presented evidence of durable single agent activity and potent immune effector response with MDNA11 in the dose escalation portion of Phase 1/2 ABILITY-1 Study at the 10th Annual Oncology Innovation Forum. The Company presented data demonstrating durable response in a pancreatic cancer patient with 100% regression of target and non-target lesions for over 104 weeks who continued to show remission four months after stopping treatment.

On June 1st, 2024, the Company presented survival follow-up and updated final study results at the 2024 ASCO Annual Meeting in Chicago. Key data showed statistically significant survival benefit in unresectable recurrent GBM patients who received a single high dose treatment of bizaxofusp in a phase 2b study compared to propensity matched external control arm. See Research & Development Update - Bizaxofusp for clinical updates.

On September 6, 2024, the Company presented preclinical data on MDNA209, a high affinity IL-2R biased IL-2/IL-15 super-antagonist, in an oral presentation at The Promise of IL-2 Therapy conference held in Paris. Key data showed significant survival benefit with a long-acting MDNA209 in a mouse model of acute graft versus host disease ("GvHD"). See Research & Development Update - MDNA209 for research updates.

On November 8, 2024, an internationally recognized academic team from the University of College London and the University of Edinburgh presented promising pre-clinical results at the 39th Annual Meeting of the Society for Immunotherapy of Cancer ("SITC") evaluating MDNA11 and anti-PD1-IL-2SKin mouse models of glioblastoma ("GBM") and patient-derived GBM explants. See Research & Development Update - Bizaxofusp for research updates.

On November 8, 2024, the Company presented data at SITC from its most-advanced preclinical BiSKITTMprogram, MDNA113, a novel IL-13Rα2 tumor-targeted and conditionally activated anti-

PD1-IL-2 superkine (anti-PD1-IL-2SK). Key data demonstrated that MDNA113 achieved complete tumor regression of IL-13Rα2 expressing tumors, highlighting its potential to treat a vast range of immunologically "cold tumors" that annually affect over two million cancer patients worldwide. See Research & Development Update - MDNA113 for research updates.

On November 11, 2024, the Company announced that data from the ongoing Phase 1/2 ABILITY-1 study were presented at the SITC, demonstrating positive single-agent activity of MDNA11 from the dose expansion cohorts and an encouraging safety profile and early anti-tumor activity in combination with Merck's KEYTRUDA. MDNA11 continued to demonstrate promising deep and durable single agent activity, with a 30% (3 of 10) objective response rate ("ORR") in the monotherapy dose expansion cohort (in checkpoint-resistant patients). See Research & Development Update - MDNA11 for clinical updates.

On November 25, 2024 the Company presented preclinical data on MDNA11 and Bizaxofusp at the 2024 Annual Meeting of the Society for Neuro-Oncology ("SNO"). Data showed that MDNA11 provided significant survival benefits in preclinical glioblastoma models and that Bizaxofusp selectively kills human tumor cells and immune-suppressive cells, enhancing anti-tumor immunity. Combination therapy with MDNA11 and bizaxofusp demonstrates synergistic tumor-killing in human GBM tumoroids.

On December 5, 2024 the Company provided clinical update to the ABILITY-1 study and announced the first complete responder in MDNA11 in combination with KEYTRUDA (pembrolizumab) combination dose escalation arm in an oral presentation at the Immunotherapy Bridge Conference held in Naples, Italy. A 70-year-old patient with advanced chemo-refractory anal cancer achieved a complete response in 8 weeks when treated with MDNA11 in combination with KEYTRUDA (pembrolizumab). See Research & Development Update - MDNA11 for clinical updates

On December 13, 2024 the Company presented preclinical data on MDNA11 as a first step to shrink tumors before surgery and prevent metastasis at the 2024 San Antonio Breast Cancer Symposium ("SABCS"). Data presented showed that a single dose of MDNA11 alone was more effective than a combination of immune checkpoint inhibitors (anti-PD1 and anti-CTLA4) in preventing metastasis and achieving long-term survival including promotion of anti-tumor specific memory, in an aggressive mouse model of triple negative breast cancer ("TNBC").

On February 25, 2025 the Company presented data at the inaugural AACR-Immuno-Oncology Conference showing that MDNA11 significantly expands a unique population of 'stem-like' CD8+T cells that leads to more persistent and effective anti-tumor activity and that MDNA11 has shown durable single agent activity, with a 30% (3 of 10) ORR in the monotherapy dose expansion cohort in checkpoint-resistant patients.

On April 28, 2025, Medicenna announced the presentation of updated clinical data from the ongoing Phase 1/2 ABILITY-1 study evaluating MDNA11 in patients with advanced solid tumors at the 2025 Annual Meeting of AACR in Chicago, Illinois, including continued anti-tumor activity and safety of MDNA11 in combination with Merck's KEYTRUDA with an ORR of 36% (5 of 14) in all tumor types enrolling in the Phase 2 expansion cohorts. Patients from the MDNA11 monotherapy dose expansion and dose escalation arms treated at ≥ 60 µg/kg achieved an ORR of 29.4% (5 of 17) in all tumor types enrolling in the Phase 2 expansion cohorts. The monotherapy arm continued to demonstrate encouraging durability with a melanoma patient and a pancreatic

cancer patient remaining tumor-free and off-treatment after entering the study 2 and 3 years ago, respectively. See Research & Development Update - MDNA11 for clinical updates.

On April 30, 2025, Medicenna announced the presentation of new pre-clinical data from MDNA113, its first candidate from the BiSKITTMplatform, at the 2025 Annual Meeting of the AACR in Chicago, Illinois. Key data demonstrated compelling anti-tumor activity in IL-13Rα2 positive tumors in mice, including signs of enhanced memory that may support durable responses. See Research & Development Update - MDNA113 for research updates.

Year ended March 31, 2024

On April 17, 2023, we announced new preclinical data characterizing the Interleukin 13 ("IL-13") Superkines, MDNA132 and MDNA213 (an improved version of MDNA132), and a series of IL-13 BiSKITs were presented at the Annual Meeting of AACR, held in Orlando, Florida. The results demonstrated that the IL-13 Superkines represent a versatile platform for engineering the next generation of precision immunotherapies for many immune-resistant IL-13Rα2 expressing tumors.

On October 3, 2023, new preclinical data characterizing MDNA223, an anti-PD1-IL-2 BiSKIT (Bifunctional SuperKine for ImmunoTherapy), including its synergy when combined with STING agonists were presented at the 2023 AACR Special Conference in Cancer Research: Tumor Immunology and Immunotherapy held in Toronto.

On October 25, 2023, Medicenna announced dosing of the first patient in the Phase 2 monotherapy dose expansion portion of the ABILITY-1 Study.

On October 27, 2023, Medicenna announced that it was delisted from the Nasdaq as the Company did not meet the listing requirements, that it would be reducing its presence in the U.S. to conserve cash, and that Jeff Caravella, Chief Financial Officer, and Brent Meadows, Chief Business Officer, departed the Company, effective October 26, 2023.

On November 2, 2023, the trading of the Common Shares on the Nasdaq was suspended as a result of the Company's failure to comply with the US$1.00 per share minimum bid price requirement of US$1.00 per share under the Nasdaq Listing Rule 5450(a)(1) after receiving notice form on April 25, 2023 from Nasdaq granting the Company's request for a 180-day extension to regain compliance with the minimum bid requirement. Subsequently, on November 2, 2023, a Form 25-NSE was filed with the United States Securities and Exchange Commission (the "SEC"), which removed the Company's securities from listing and registration on Nasdaq.

On November 3, 2023, the Company presented preclinical data on its first-in-class IL-13R2 targeted candidate, MDNA113, from its T-MASK platform, which delivers a masked bispecific anti-PD1-IL2 Superkine to IL-13R2 expressing tumors (annual incidence of over 2 million)1 where it is activated by cancer specific enzymes. This data was presented at the 38th Annual Meeting of the SITC held in San Diego. See Research & Development Update - T-MASK Platform for research updates.

On November 6, 2023, Medicenna announced encouraging single-agent activity from the dose escalation and evaluation portion of the ABILITY-1 study in advanced cancer patients receiving

‌1 https://www.wcrf.org/cancer-trends/worldwide-cancer-data/

doses  60 µg/kg of MDNA11 (N = 15) who had previously failed immune check-point inhibitor therapies. The results included ongoing partial responses with 100% and 70% reduction of target lesions in pancreatic and melanoma cancer patients, respectively, in addition to durable stable disease in 3 melanoma patients (> 20 to 80 weeks). This data was presented at the 38thAnnual Meeting of the SITC held in San Diego.

On November 17, 2023, the Company announced that a poster presentation and an oral summary highlighting longer term follow up results from the Phase 2b clinical trial of bizaxofusp, the Company's first-in-class IL-4R targeted therapy for the treatment of patients with rGBM, will be presented by Dr. Steven Brem, M.D. (Medical Director, Centre for Precision Surgery, Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania) at the SNO 2023 Annual Meeting, taking place from November 15-19, 2023, in Vancouver, Canada.

On December 19, 2023, the Company announced the commencement of trading on the OTCQB Venture Market in the United States.

On January 9, 2024, the Company announced the initiation of enrollment in the combination arm of the Phase 1/2 ABILITY study evaluating MDNA11, a long-acting, "beta-enhanced not-alpha" interleukin-2 (IL-2) super-agonist, with Merck's pembrolizumab (KEYTRUDA). The combination portion of the study is being conducted as part of the previously announced Clinical Trial Supply and Collaboration Agreement1 between Medicenna and Merck (known as MSD outside the United States and Canada) and is designed to evaluate the potential for a synergistic effect of MDNA11 with KEYTRUDA in patients with advanced solid tumors.

On January 12, 2024 the Company announced that its board of directors accepted the resignation of PricewaterhouseCoopers LLP and appointed MNP LLP as the auditor of the Company.

On February 13, 2024, the Company announced that it had dosed the first patient in the combination arm of the ABILITY-1 clinical trial, evaluating potential synergistic effect of MDNA11 when administered with KEYTRUDA (pembrolizumab). The study will evaluate the safety, tolerability, cRDE and therapeutic activity of MDNA11 when combined with pembrolizumab in the dose-escalation and dose-expansion arms of the clinical trial.

On February 14, 2024, the Company announced that Dr. Humphrey Gardner transitioned from Chief Medical Officer to consultant and that Dr. Arash Yavari, Chair of Medicenna's Development Advisory Committee, will henceforth lead the clinical activities as Director of Clinical Strategy. On February 14, 2024 the Company also announced that the Board of Directors approved the appointment of David Hyman, CA, CBV as Chief Financial Officer of the Company. Mr. Hyman is an experienced financial professional with over 25 years of experience spanning public practice, capital markets, private equity and industry. For the past five years, Mr. Hyman has provided fractional and full time CFO services to multiple public and private companies, including two early-stage pharmaceutical companies.

On February 14, 2024, the Company reported clinical data from the on-going monotherapy escalation and expansion arms of the ABILITY-1 study. In addition to previously announced tumor response data, a third patient in the study has also shown a partial response. Amongst 13 patients, all having previously failed or resistant to immune checkpoint inhibitors ("ICI"), receiving high doses of MDNA11 ( 60 g/kg) with tumor types being evaluated in the monotherapy expansion cohort, the response rate, clinical benefit rate, and tumor control rate increased to 23%

(3 PRs), 46% (3 PRs and 3 patients with stable disease for  24 weeks), and 69% (3 PRs and 6 SDs), respectively, with concomitant shrinkage of target lesions in all patients with stable disease.

Year ended March 31, 2023

On April 8, 2022, Medicenna announced new preclinical data highlighting the potent anti-tumor efficacy of the next-generation BiSKIT, anti-PD1-MDNA109FEAA, an anti-PD1 antibody fused to an IL-2 Superkine as well as on its long-acting dual IL-4/IL-13 super-antagonist, Fc-MDNA413, during poster sessions at the AACR Annual Meeting.

On May 2, 2022, Medicenna announced new clinical data from the third cohort of the Phase 1/2 ABILITY Study of MDNA11 and on May 11, 2022, Medicenna presented clinical data from the Phase 1/2 ABILITY Study during a poster presentation at the 9th Annual Frontiers in Cancer Immunotherapy Meeting, organized by the New York Academy of Sciences. These data were subsequently updated as described below.

On June 9, 2022, we announced that the U.S. Patent and Trademark Office (the "USPTO") had issued U.S. Patent No. 11,352,402 titled, "Interleukin-4 Receptor-Binding Fusion Proteins And Uses Thereof." The patent provides intellectual property ("IP") protection for composition and methods of treating degenerative diseases via administration of a fusion protein comprising an IL-4 or IL-13 Superkine and an anti-apoptotic Bcl-2 family polypeptide. The patent's term extends into at least 2038 without accounting for any potential extensions.

On July 12, 2022, the USPTO issued U.S. Patent No. 11,117,943, titled "Superagonists and Antagonists of Interleukin-2." The patent provides IP protection for methods of treating leukemia using IL-2 muteins that have an increased binding capacity for IL-2R and a decreased binding capacity for IL-2Rc.

On July 27, 2022, Medicenna announced new clinical data on safety, PK, PD and anti-tumor activity from the Phase 1/2 ABILITY Study of MDNA11, which were presented at the Cytokine Based Drug Development Summit, held in Boston. These data were subsequently updated and are described below.

On August 10, 2022, we raised gross proceeds of US$20.0 million ($25.6 million) pursuant to an underwritten public offering of units, with each unit consisting of one Common Share and one Common Share purchase warrant. Each Common Share purchase warrant entitles the holder to purchase one Common Share at an exercise price of US$1.85 until expiration of the warrants on August 9, 2027.

On September 13, 2022 we entered into a CTCSA with Merck (known as MSD outside the United States and Canada) to evaluate MDNA11 in combination with KEYTRUDA (pembrolizumab), Merck's anti-PD-1) therapy, in the ongoing Phase 1/2 ABILITY Study.

On September 22, 2022, Medicenna announced presentation of data demonstrating the anti-tumor activity of the MDNA223 and MDNA413. The data were featured in two separate poster presentations at the 10th Annual Meeting of the International Cytokine & Interferon Society, which took place both virtually and in-person in Big Island, Hawaii.

On September 28, 2022, Medicenna announced new clinical data on anti-tumor activity from the Phase 1/2 ABILITY study of MDNA11. These data were subsequently updated and are described below.

On November 10, 2022, the Company announced new safety, PK, and PD data from the first four dose escalation cohorts of the Phase 1/2 ABILITY Study of MDNA11, the Company's "beta-only" long-acting IL-2 super-agonist. The data were featured in two posters presented at the SITC's 37th Annual Meeting, which took place from November 8, 2022 until November 12, 2022.

On January 5, 2023, Medicenna announced that the USPTO had issued U.S. Patent No. 11,542,312 titled "IL-2 Superagonists in Combination with Anti-PD-1." The patent provides IP protection for methods of treating cancer with an IL-2 Superkine such as MDNA11 and a PD1 (for example, pembrolizumab), PDL1 or CTLA-4 checkpoint inhibitor in combination, as planned in the on-going ABILITY Study, or as a single agent using our BiSKIT™ platform. The patent's term extends into at least 2039, without accounting for any potential extensions.

In January 2023, the full results of a single-arm Phase 2b trial of bizaxofusp in patients with recurrent glioblastoma were published in the peer-reviewed journal Neuro-Oncology. Results showed the trial met its primary endpoint, with median overall survival ("mOS") in the primary and supportive analysis populations exceeding the trial's pre-defined success criteria and the mOS historically achieved with currently approved therapies.

On February 17, 2023, Medicenna announced that it had entered into a sales agreement with Oppenheimer & Co. Inc. acting as sales agent, pursuant to which the Company may, from time to time, sell through an "at-the-market" ("ATM") offering on the Nasdaq such number of Common Shares that would have an aggregate offering price of up to US$10 million under the ATM prospectus supplement. Medicenna will determine, in its sole discretion, the time, minimum price and maximum number of Common Shares to be sold under the ATM offering. The ATM was terminated in 2023 as a result of the Nasdaq delisting.

On March 15, 2023, we announced the publication of an abstract at the 2023 AACR Annual Meeting which described preclinical studies characterizing a long-acting version of MDNA132 and BiSKITs™, comprising MDNA132 fused to an IL-2 super-agonist or anti-PD1 antibody. MDNA132 is an IL-13 Superkine designed to enable targeted delivery of immunotherapies to the tumor microenvironment. MDNA132 exhibits high affinity and selectivity for the IL13Rα2, which is highly overexpressed in various tumors such as pancreatic, prostate, bladder, colorectal, breast and lung cancer but minimally expressed in healthy tissues.

On March 30, 3023, we announced updated data from the Phase 1/2 ABILITY Study. These data include the most recent antitumor activity data from the trial's first four dose escalation cohorts and initial PK/PD data from the fifth dose escalation cohort.

MDNA11

A Potential Best-in-Class 'β-Enhanced Not-α' Interleukin 2 Super Agonist

MDNA11 is the only long-acting 'beta-enhanced not-alpha' interleukin 2 (IL-2) super agonist in clinical development, designed to preferentially activate anti-cancer immune cells (CD8+ T and NK cells) over immunosuppressive (pro-cancer) Tregs. Fusion with human albumin augments MDNA11's half-life and promotes its accumulation in tumors and tumor draining lymph-nodes. MDNA11 is currently being evaluated in the Phase 1/2 ABILITY-1 Study (NCT05086692) in patients with various advanced solid cancers. The ABILITY-1 Study is a global, multi-center, open-label clinical trial that assesses the safety, tolerability, and anti-tumor activity of MDNA11 as monotherapy and in combination with Merck's KEYTRUDA. The figure below describes the ABILITY-1 Study.

On April 28th, 2025, at the AACR conference held in Chicago, Illinois, Medicenna reported updated clinical results from the ABILITY-1 study among patients who progressed on prior immune checkpoint inhibitor ICI therapy:

Deep and Durable Anti-Tumor Activity with Single-Agent MDNA11 in ICI-Resistant Patients

ORR of 40% in the monotherapy dose escalation (treated at ≥ 60 μg/kg) and expansion arm (1 confirmed CR, 1 confirmed PR and 2 unconfirmed PRs) among 10 patients with tumor types currently enrolling in the Phase 2 monotherapy expansion cohort. All patients had previously failed ICI therapy and had advanced and/or metastatic cutaneous melanoma with secondary resistance to ICI or MSI-H/dMMR tumors. Note that the non-melanoma skin cancer cohort is not recruiting as it was replaced with a new cohort of virally-derived cancers subsequent to a protocol amendment.

The ORR is 29.4% from a total of 17 patients when including patients with cancers planned for Phase 2 expansion cohort and patients with primary ICI resistant melanoma who received at least 60 µg/kg of MDNA11 (Q2W).

Overall, objective responses in ICI-resistant patients include 1 CR and 4 PRs:

2 PRs among 4 MSI-H patients (ORR of 50%) with both responders having metastatic pancreatic ductal adenocarcinoma (PDAC).

1 CR and 1 PR among 6 patients with ICI secondary resistant melanoma (ORR of 33.3%).

1 PR among patients with ICI primary resistant melanoma.

Complete resolution of all target and non-target lesions in two patients with on-going remission following end-of-treatment:

Cutaneous melanoma patient achieved a durable response exceeding 12 months during the study with complete resolution of target and non-target metastatic lesions and continues to remain off anti-cancer therapy for more than 6 weeks.

Pancreatic cancer patient (MSI-H) achieved a durable response for 20 months during the study with complete resolution of target and non-target metastatic lesions in the liver including a new lesion treated with MDNA11 following a single cycle of radiation and continues to remain off anti-cancer therapy for more than 12 months.

Stable disease (SD in 6 patients for a disease control rate (DCR = CR+PR+SD) of 65% including 2 with duration > 6 months, yielding a clinical benefit rate of 41% (7/17).

Continued Anti-Tumor Activity in Heavily Pre-treated Patients in MDNA11 Combination Dose Escalation with KEYTRUDA

Enrollment in the combination dose expansion portion of the ABILITY-1 study is underway having established the MDNA11 cRDE at 90 µg/kg administered every 2 weeks together with KEYTRUDA administered at 400 mg every 6 weeks.

Encouraging anti-tumor activity continues to be observed with MDNA11 in combination with KEYTRUDA in patients enrolled in the dose escalation portion of the study:

5 objective responses (1 CR and 4 PRs) among heavily pre-treated patients, including two previously reported objective responses in historically low immunotherapy responders:

70-year-old male with anal squamous cell carcinoma (SCC) who previously progressed on two prior lines of chemotherapy achieved a CR on the first study evaluable imaging scan (week 8); patient continues on combination treatment following a confirmed CR.

52-year-old female with TMB-H/MSS colorectal cancer who previously progressed on two prior lines of chemotherapy achieved a confirmed PR. While off-study for 4 months, the patient continues to show deepening of the tumor response in the absence of any treatment.

ORR of 31% (4 of 13) in patients with cancers planned for the Phase 2 combination expansion cohort, including cutaneous melanoma, MSI-H/dMMR, and TMB-H tumors, and an ORR of 36% (5 of 14) when including the virally-derived cancers.

SD in 3 patients for a disease control rate (DCR = CR+PR+SD) of 57% (8/14).

Desirable Safety Profile

MDNA11 continues to demonstrate a desirable safety profile both as a single agent and in combination with KEYTRUDA and was generally well tolerated across all dose levels:

No dose limiting toxicities (DLTs) observed with MDNA11 at doses up to 120 µg/kg (Q2W) in monotherapy and in combination with KEYTRUDA (400 mg, Q6W).

Majority of treatment related adverse events (TRAEs) were grade 1 or 2 (> 92%) and resolved within 48 hours.

Grade 3 TRAEs mainly constituted transient liver functions test (LFT) elevations based on laboratory tests and were clinically asymptomatic.

Grade 3 hypotension was observed in monotherapy patients with baseline adrenal insufficiency with existing risk of blood pressure drop.

One isolated single case of asymptomatic grade 4 hepatic enzyme increase that resolved within 72 hours without intervention (MDNA11 monotherapy).

Robust Pharmacodynamic Response Consistent with Anticipated MDNA11 Pharmacology

Pharmacodynamic data on effector immune cells support the mechanistic rationale for MDNA11's promising

anti-tumor activity. Key pharmacodynamic data included:

Robust expansion of immune effector cells in monotherapy and combination with KEYTRUDA with notable increases in effector (DNAM), 'stemness-like' (TCF-1) and memory CD8+ T cells, which are critical for sustained anti-tumor responses.

Robust, dose-dependent lymphocyte expansion in combination with KEYTRUDA, sustained with repeat MDNA11 dosing, and plateauing at the 90 µg/kg MDNA11 dose level.

MDNA11 preferentially expands peripheral effector immune cells (CD8+ T and NK cells) over Tregs with CD8+ T cells remaining as the major cytotoxic immune population.

Analysis of paired biopsies showed increased tumor infiltration of CD25+ activated CD8+ T cells and NK cells post-MDNA11 monotherapy treatment.

MDNA11 Administration Prior to Surgery

On December 13th, 2024, Medicenna announced the presentation of new preclinical data at the 2024 San Antonio Breast Cancer Symposium ("SABCS"), the world's largest breast cancer conference which took place from December 10-13, 2024, in San Antonio Texas. The presentation highlighted the potential of MDNA11 to improve treatment outcomes of triple negative breast cancer ("TNBC"), an area of high unmet need, when administered prior to surgery (neoadjuvant therapy). Key conclusions from the presentation included:

Single neoadjuvant treatment with MDNA11 provided significant survival benefit in an orthotopic model of TNBC by preventing metastasis.

MDNA11 promotes tumor infiltration of cytotoxic (Granzyme B+) CD8+ T cells with no increase in immune suppressive Tregs.

Neoadjuvant MDNA11 promotes development of antigen-specific memory response that protects against tumor rechallenge.

Neoadjuvant MDNA11 monotherapy is more effective than the combination of anti-mPD1 + anti-mCTLA4 in prevention of metastasis and extending survival.

MDNA11 Anticipated Milestones for H2/2025

The consolidated safety profile, robust pharmacodynamic data, and anti-tumor activity of MDNA11 as a single-agent and in combination with KEYTRUDA underscore its best-in-class potential in advanced solid tumors.

Medicenna anticipates completing monotherapy expansion and combination dose escalation enrolment, and to initiate the combination expansion portion of the Phase 1/2 ABILITY-1 Study in the first half of calendar 2025. Additionally, the Company anticipates providing further clinical updates at medical conferences in the second half of 2025.

Bizaxofusp (formerly MDNA55) for the Treatment of Recurrent Glioblastoma

Unmet Need in Glioblastoma

Glioblastoma is one of the most complex, deadly, and treatment-resistant cancers. Nearly all patients relapse following standard of care. It is expected that annually there will be at least 15,000 new diagnoses of GBM in United States and Canada and more than 300,000 new cases worldwide. Nearly all GBM patients relapse following standard of care ("SOC"). rGBM is universally fatal with a median survival of 6-9 months. Approved treatments have failed to significantly extend survival beyond a few months, therefore development of novel approaches for treating GBM and rGBM remains a great unmet need.

Medicenna's Bizaxofusp

Medicenna's phase 3 ready asset for rGBM, bizaxofusp, is a genetically engineered fusion of a circularly permuted version of IL-4 to a potent catalytic component of the bacterial Pseudomonas exotoxin which effectively arrests protein synthesis leading to cell death. The IL-4 component is engineered to selectively target cells that express IL-4, including GBM and immune suppressive cells occupying the TME surrounding GBM to protect anti-tumor immune defense. Bizaxofusp is infused into the tumor using a minimally invasive enhanced convection delivery technique to bypass the blood-brain barrier. Bizaxofusp holds both FastTrack and Orphan Drug status from the FDA and FDA/EMA, respectively.

Bizaxofusp, to-date, has been tested in 118 patients with high grade gliomas (including 112 patients with rGBM) and most recently completed a successful Phase 2b (N=44) trial for nonresectable rGBM where it demonstrated a doubling of median overall survival ("mOS") to 13.5 months in the high-dose population compared to SOC mOS of 6-9 months. The Phase 2b clinical trial was conducted in a multi-center, open-label, single-arm study in patients with first or second recurrence or progression of GBM after surgery or radiotherapy ± adjuvant therapy or other experimental therapies. Preliminary results were published in June 2023 issue of NeuroOncology (doi: 10.1093/neuonc/noac285).

A separate analysis collected rGBM survival and prognostic data from 81 eligibility matched patients who had contemporaneously received treatment at major clinical centres using current SOC. These data from patient registries were used to establish a matched External Control Arm ("ECA"). Blinded survival data from propensity score ("PS") balanced ECA (established by matching with bizaxofusp-treated population based on 10 different prognostic factors using propensity scoring methods) were then used as a control arm versus survival data from the Phase 2b bizaxofusp trial.

Statistically Significant Survival Benefit from a Single Dose of Bizaxufusp in Unresectable rGBM

On June 1st, 2024, the Company presented survival follow-up and updated final study results at the 2024 ASCO Annual Meeting in Chicago. Key findings from the presentation are shown in the figure below and include:

In the Phase 2b study, a single treatment with high dose bizaxofusp in unresectable rGBM patients achieved significant survival benefit (mOS of 13.5 vs. 7.2 months, p=0.009) and reduced risk of death by almost half (hazard ratio: 0.54, 95% confidence interval: 0.34-0.83) versus a PS balanced ECA.

Bizaxofusp significantly increased median overall survival (mOS) by 88% (p = 0.009) and improved overall survival at 1 and 2 years by 180% and 290%, respectively when compared to the PS balanced ECA.

Tumor control was associated with a significant increase in mOS following treatment with bizaxofusp and consequently, may be an early surrogate of survival benefit in future studies.

TRAEs were primarily neurological or aggravation of pre-existing neurological deficits expected with rGBM. There were not laboratory abnormalities nor any systemic toxicities.

The TME of GBM is highly abundant in immune suppressive cells which act to constrain the anti-tumor activity of key anti-tumor effector immune cells. These immune suppressive cells also express IL-4R and therefore are susceptible to the cell killing potency of bizaxofusp.

On November 25, 2024 the Company presented preclinical data on bizaxofusp and MDNA11 at the 2024 Annual Meeting of the SNO in Houston Texas. Key data from the presentation included:

MDNA11 showed significant survival benefit in an orthotopic model of GBM.

Single treatment with bizaxofusp induced tumor shrinkage and stimulated durable anti-tumor immune response in the TME of rGBM patients.

Bizaxofusp kills immune suppressive MDSC and Tregs, leading to stimulation of CD8+ T cells.

Combination of bizaxofusp and MDNA11 shows synergy in inducing tumor cell killing in patient derived GBM tumoroids.

Phase 3 Partnering and Regulatory Milestones

Following the end of Phase 2 ("EOP2") meeting with the FDA, an innovative open-label hybrid Phase 3 registration trial that allows the use of a substantial number of patients (two-thirds) from a propensity matched ECA to support marketing authorization of bizaxofusp for rGBM, was accepted by the FDA.

Medicenna is pursuing strategic partnerships to assist with additional clinical development of bizaxofusp, as well as preparing the program for commercialization and its subsequent launch in various countries where marketing authorization is granted. Medicenna estimates that the total cost of completing a pivotal registrational trial, associated regulatory and manufacturing activities and preparing bizaxofusp for commercial launch to be approximately $60 to $80M USD.

Confidential primary market research conducted for the Company has estimated that bizaxofusp has peak revenue potential of more than $800M USD for unresectable rGBM alone and an additional ~$3B USD potential in other brain cancers in adults such as newly diagnosed GBM, metastatic brain tumors and various pediatric brain cancers known to express the IL-4R.

Pre-Clinical Assets

BiSKITsTM(Bi-functional SuperKine ImmunoTherapies) Platform

Our BiSKITsTM platform allows us to develop designer IL-2, IL-4 and/or IL-13 Superkines by fusing them to other proteins, checkpoint inhibitors, antibodies or cytokines in order to combine two distinct and yet synergistic mechanisms of action into a single multi-functional molecule: a BiSKITTM.

T-MASKTM(Targeted Metallo/protease Activated SuperKine) Platform

Medicenna's novel T-MASKTM (Targeted Metallo/protease Activated SuperKine) platform involves fusion of a dual tumor-targeting/masking domain to an immune modulator (such as a Superkine or a BiSKITTM) via a matrix metalloprotease ("MMP") sensitive linker to (i) fine-tune the potency of the immune modulator, (ii) increase its systemic tolerability (iii) prolong its retention in the TME and (iv) to maximize its full potency at the intended target site where the masking domain is removed by design. In summary, the T-MASKTM platform offers opportunity to target and fine-tune immune cell stimulation in the TME to further improve the therapeutic index of Medicenna's Superkine and BiSKITTM platforms.

MDNA113: A Tumor-targeting and Activatable 'Masked' Anti-PD-1-IL-2 BiSKITTMfor Cancer

MDNA113, is our most advanced pre-clinical asset encompassing both, the T-MASKTM and BiSKITTM platforms. It is a novel first-in-class tumor targeted and activatable bifunctional anti-PD1-IL-2 superkine in which the tumor targeting/masking domain is an engineered IL-13 superkine with exceptionally high affinity and specificity for IL-13Rα2, a tumor associated antigen overexpressed in diverse tumors but not normal tissues. The IL-13 superkine also provides a 'masking' domain to partially reduce the immune stimulatory activity of MDNA113 to reduce risk of systemic toxicity due to immune stimulation. Within the TME where there is abundant MMPs, the IL-13 masking domain is released and the activity of the core anti-PD1-IL-2SK is fully restored to activate cytotoxic CD8+ T cells (by inducing IL-2R) while at the same time preventing these anti-tumor T cells from exhaustion by the PD-(L)1 blockade.

On April 30, 2025, Medicenna announced the presentation of new pre-clinical data from MDNA113, its first candidate from the BiSKITTM platform, at the 2025 AACR Annual Meeting in Chicago, Illinois. Key highlights from the presentation included:

Cis-binding maximizes synergy between immune checkpoint blockade and IL-2R activation on the same CD8⁺ T effector cells for optimal tumor cytotoxicity.

MDNA113 retains PD-(L)1 blockade while exhibiting attenuated IL-2R signaling that is restored upon cleavage by tumor-specific proteases in the TME.

Preferential tumor localization and retention of MDNA113 in the TME for at least 72 hours in mice implanted with tumors expressing IL-13R2.

IL-13SK masking of IL-2SK in MDNA113 enhances tolerability and attenuates IL-2SK induced peripheral lymphocyte expansion in mice.

MDNA113 inhibits MC38/IL-13Rα2 tumor growth in mice and promotes memory response against

tumor rechallenge with 100% protection observed with complete responders.

MDNA113 enhances infiltration of functionally active CD8+ T cells over NK cells & Tregs in different tumor models.

The combination of MDNA113's tumor targeting and conditional activation represents a uniquely differentiated and potentially superior alternative to other anti-PD-1-IL-2 bispecific therapies currently in development.

On November 8, 2024, the Company presented preclinical data on MDNA113 at the 39th SITC Annual Meeting in San Diego, CA. Data were also highlighted in an oral presentation at the Promise of IL-2 Therapy on September 7, 2024 (Paris, France) and at the Annual Meeting of AACR on April 9, 2024 (San Diego, CA). Key data presented at these conferences included:

When not activated, MDNA113 shows reduced IL-2R agonism with no change in PD-1/PDL-1 blockade activity.

Cleavage and activation of MDNA113 by cancer specific enzymes (metalloproteases) releases the IL-13 masking domain, restoring activity of the IL-2 Superkine at the tumor site.

MDNA113 shows reduced systemic lymphocyte expansion, resulting in increased tolerability.

MDNA113 achieves anti-tumor response as 'non-mask' control in mouse models with IL-13Rα2

tumors, including durable and complete tumor regression in vast majority of cases.

Analysis of tumors harvested from MDNA113 treated mice shows enrichment of Granzyme B expressing CD8+ T cells, consistent with their active cytotoxic function within the TME.

Single neoadjuvant treatment with MDNA113 in a highly invasive orthotopic 4T1.2 breast cancer model significantly increases survival by preventing metastasis, underscore the broad potential of MDNA113 in immuno-oncology.

In summary, MDNA113 has the potential to make a meaningful impact on a broad range of IL-13Rα2 expressing tumors, including immunologically "cold" tumors (e.g., pancreatic, prostate, ovarian, breast and brain tumors), affecting over two million patients every year world-wide.

MDNA209: An IL-2/IL-15 Pathway Super-Antagonist

MDNA209 binds with exceptional affinity to IL-2Rβ but has reduced binding to the common IL-2γc receptor. Therefore, MDNA209 occupies IL-2Rβ and blocks downstream effect and in doing so effectively prevents activation of effector CD4+ and CD8+ T cells and NK cells. As a result, we believe that MDNA209 can provide effective therapy against diseases such as autoimmune (e.g., multiple sclerosis) and graft-versus-host (e.g., transplant rejection) diseases (Mitra et al., 2015).

At the Promise of Interleukin-2 Therapy Conference held in Paris, France, from September 4th-7th, 2024, Medicenna reported pre-clinical results on MDNA209. Key data from the presentation included:

MDNA209 is a potent antagonist that blocks the ability of wild-type IL-2 and IL-15 to induce immune cell proliferation and secretion of pro-inflammatory cytokines (interferon-), which contribute to aberrant inflammation and auto-immune conditions.

In an aggressive animal model of acute GvHD, MDNA209 was able to extend overall survival by 400 percent, reduce weight loss and improve clinical scores.

The presentation outlined the potential of MDNA209 to treat autoimmune diseases, including high grade GvHD which has a 1-year survival rate of only 40%. Transplant patients with GvHD experience significant morbidity and mortality with limited therapeutic options to prolong survival.

MDNA413: An IL-4/IL-13 Super-Antagonist

Medicenna's IL-4 and IL-13 Superkines, licensed from Stanford, are engineered cytokines which possess enhanced affinity and selectivity for either the Type 1 or Type 2 IL-4 receptor or dedicated IL-13 receptor such as IL-13R2. Receptor selectivity is achieved by engineering mutations into the IL-4 or IL-13 cytokines to enhance binding to specific IL-4R or IL-13R subunits. These mutations also modulate the bioactivity of

IL-4 or IL-13, resulting in Superkines with enhanced signalling (super-agonists) or capacity to block signalling (super-antagonists).

Our promising IL-13 Superkine antagonist is MDNA413. Compared to wild-type IL-13, MDNA413 has been engineered to have a 2,000-fold higher selectivity for the Type 2 IL-4R and potently blocks both IL-4 and IL-13 signalling (Moraga et al., 2015). Blocking of Type 2 IL-4R by MDNA413 potentiates anti-tumor response by reversing Th2 condition (tumor-promoting) of the TME to a Th1 condition which supports and promotes anti-tumor immune cells. We believe that MDNA413's capacity to block IL-4/IL-13 signalling has the potential to address a significant unmet medical need for effective therapies against immunologically cold tumors which are often resistant to approved checkpoint inhibitors and other immunotherapies.

Additionally, Th2 skewing also underlies non-oncology conditions such as asthma and atopic dermatitis as well as other allergic diseases. MDNA413 has the potential to make a meaningful impact on the treatment of these allergic conditions which can be reformulated to provide options for nasal (for asthma) and topical administration (for atopic dermatitis).

The development of next-generation IL-2 agonists for cancer immunotherapy is an area of intense interest within the biotechnology industry. The Company is aware of several IL-2 agonists and bi-specifics in various stages of development, due to the number of competitors only those with a monofunctional approach and in the clinical stage of development are noted in the table below.

Developer

Name

Stage

Cue Biopharma

CUE101/102

Phase 1/2

AsherBio

AB248

Phase 1/2

BioNTech

BNT152/153

Phase 1/2

Ascendis Pharma

Transcon IL-2

Phase 1/2

Aulos

AU-007

Phase 1/2

Synthekine

STK-012

Phase 1/2

Werewolf

WTX-124

Phase 1/2

Many of the programs in development are engineered variants of IL-2 that each attempt to reduce CD25 binding and extend the therapeutic window of native IL-2. To our knowledge, MDNA11 is the only IL-2 product in development where a significantly reduced CD25 binding and an increased CD122 binding have been observed while maintaining greater than 95% sequence homology to native IL-2. In addition to these findings, MDNA11 relies on an albumin binding designed to increase its half-life to allow for dosing every 2 or 3 weeks rather than PEGylation as many of its competitors. Albumin is known to accumulate in tumors providing MDNA11 with enhanced targeting capabilities. MDNA11 remains competitive being the only not-α, β-enhanced IL-2 in clinical development with sustained deep and durable single-agent activity demonstrated thus far in a Phase 1/2 trial for advanced solid tumors.

The Company anticipates that its current level of cash and cash equivalents and marketable securities, will be sufficient to execute its current planned expenditures through mid 2026. This estimate assumes continuation of the MDNA11 Phase 1/2 ABILITY study, and that any further development of bizaxofusp will be completed by a partner.

The Company does not earn any revenues from its drug candidates and is therefore considered to be in the development stage. As required, the Company will continue to finance its operations through the sale of equity or pursue non-dilutive funding sources available to the Company in the

future. The continuation of research and development activities for bizaxofusp, MDNA11 and the BiSKITsTMplatform and the commercialization of bizaxofusp is dependent upon the Company's ability to successfully finance and complete its research and development programs through a combination of equity financing and revenues from strategic partners. The Company has no current sources of revenues from strategic partners.

We rely on third parties as for the controlled use of hazardous and radioactive materials including with respect to their manufacture, storage, handling and disposal. As such, the compliance by the Company with environmental federal, provincial, state and local laws and regulations does not and will not, to the knowledge of the Company, have any significant impact on our capital spending, profits or competitive position within the normal course of our operating activities. There can be no assurance, however, that the Company will not be required to incur significant costs to comply with environmental laws and regulations in the future or that its operations, business or assets will not be materially adversely affected by current or future environmental laws or regulations.

Medicenna regards its intellectual property rights as one of the foundation blocks upon which it continues to build a successful biopharmaceutical development company. Medicenna has established a strong and defensive intellectual property position to protect its proprietary technologies. To date, Medicenna has 19 patent families providing patent protection in the US and in contracting states to the Patent Corporation Treaty. The Company has a total of 136 patents issued or filed of which 81 patents have been granted or allowed, and the remaining patent applications are pending in the United States and other countries.

Patent families owned or licensed by Medicenna related to bizaxofusp (U.S. cases listed):

Targeted Cargo Protein Combination Therapy (U.S. Patent No. 9,629,899)

IL-4 Fusion Formulations for Treatment of Central Nervous System (CNS) Tumors (U.S. Patent No. 12,274,735)

Combination Therapy of MDNA55 and a Vascular Endothelial Growth Factor A (VEGF-A) (pending U.S. Patent Application No. 18/248,601; published)

Expiry dates for the above patents and related family members range from 2029 to 2040.

In addition to the above patent protection, bizaxofusp has been granted Orphan Drug Designation in the United States and Europe for the treatment of GBM, which would result in seven and 10 years of orphan drug exclusivity in the U.S. and Europe, respectively. Additionally, upon approval, bizaxofusp as a biologic, is expected to be eligible for 12 years Reference Product Exclusivity in the United States, eight years data exclusivity plus two years market exclusivity in Europe, six years data exclusivity plus two years market exclusivity in Canada and other markets where similar means of exclusivity are available.

Patent families owned or licensed by Medicenna related to the Superkine and Empowered Superkine platforms (granted/allowed U.S. cases listed / representative PCT listed):

IL-2 Superagonists in Combination with Anti-PD-1 Antibodies (U.S. Patent No.

11,542,312 granted, U.S. Patent App. No. 17/816,823 allowed)

Interleukin-4 Receptor-Binding Fusion Proteins and Uses Thereof (Pro-apoptotic Fusions) (U.S. Patent Nos. 10,093,708 and 11,084,856)

Interleukin-4 Receptor Binding Fusion Proteins and Uses Thereof (Anti-apoptotic Fusions) (U.S. Patent Nos. 10,106,592 and 11,352,402) (U.S. Patent App. No. 17/738,620; published)

Interleukin-2 Fusion Proteins and Uses Thereof (U.S. Patent Nos. 10,781,242 and 11,680,090) Targeted cargo protein combination therapy (U.S. Patent No. 9,629,899)

Il-4-fusion formulations for treatment of central nervous system (CNS) tumors (U.S. Patent No. 12,274,735)

Uses and Methods for Oncolytic Virus Targeting of IL-4/IL-13 and Fusions Thereof (U.S. Patent App. No. 15/733,815; allowed)

Combination therapy of MDNA55 and a vascular endothelial growth factor a (VEGF-a) (U.S. Patent App. No. 18/248,601; published)

Bifunctional Superkines and Uses Thereof (U.S. Patent App. No. 18/002,824; published)

Uses and Methods for IL-2, IL-13, and IL-4 Cytokine Bifunctional Molecules (U.S. Patent App. No. 18/840,261; pending)

IL-2 Superantagonists Constructs, Methods and Uses Thereof (U.S. Patent App. No. 19/110,294; pending)

IL-2 Fusion Proteins (PCT/IB2024/000480; unpublished)

Use of Immunomodulation Methods in Combination with Cytokine Fusions for Disease Treatment (PCT/IB2024/053637; published)

Superagonists and Antagonists of Interleukin-2 (U.S. Patent Nos. 9,428,567; 10,183,980; 11,117,943; and 12,006,347)

Superkines and Synthekines: Repurposed Cytokines with New and Enhanced Signaling Activities (U.S. Patent No. 9,738,696; 10,738,096; 12,187,771)

Superagonists, Partial Agonists and Antagonists of Interleukin-2 (U.S. Patent Nos. 10,150,802; 10,654,905; 11,384,131; 12,202,873)

Therapeutic IL-13 Polypeptides (U.S. Patent Nos. 9,512,194; 9,732,133; 10,227,389;

11,084,858 and 11,993,639)

IL-13/IL-4 Superkine: Immune Cell Targeting Constructs and Methods of Use Thereof (U.S. Patent App. No. 17/059,937; published)

Disclaimer

Medicenna Therapeutics Corp. published this content on June 26, 2025, and is solely responsible for the information contained herein. Distributed via Public Technologies (PUBT), unedited and unaltered, on June 26, 2025 at 10:58 UTC.