Medicenna Therapeutics : Q2 2024 Management's Discussion and Analysis

Published: 2025-02-25 15:13:05 ET MDNA.TO

Management's Discussion and Analysis

For the Three and Six Months Ended

September 30, 2024

DATE OF REPORT: November 14, 2024

MANAGEMENT'S DISCUSSION AND ANALYSIS

The following management's discussion and analysis ("MD&A") has been prepared as at November 14, 2024 for the three and six months ended September 30, 2024 and should be read in conjunction with the unaudited interim condensed consolidated financial statements of Medicenna Therapeutics Corp. for the three and six months ended September 30, 2024 and September 30, 2023, and the audited annual consolidated financial statements and accompanying notes for the year ended March 31, 2024 (the "Annual Financial Statements"), which have been prepared in accordance with International Financial Reporting Standards ("IFRS") as issued by the International Accounting Standards Board ("IASB"). Our IFRS accounting policies are set out in note 2 of the Annual Financial Statements and all dollar amounts are expressed in Canadian dollars unless otherwise noted.

All references in this MD&A 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.

This MD&A 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 "seek", "plan", "expect", "is expected", "continue", "predict", "potential", "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", "should", "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. There can be no assurance that such statements will prove to be accurate and actual results and future events could differ materially from those anticipated in such 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 "Risks and Uncertainties" in this MD&A and the Company's Annual Information Form ("AIF") for the fiscal year ended March 31, 2024 filed on SEDAR+ on June 26, 2024.

Forward-looking statements in this MD&A include, but are not limited to:

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:

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 MD&A 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 MD&A 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.

COMPANY OVERVIEW

Medicenna Therapeutics is a clinical-stage immunotherapy company developing engineered cytokines, called Superkines, designed to improve the specificity, function and safety profile of unmodified 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: 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 BiSKITsTM and T-MASKTM, respectively.

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 interleukin 4 receptor ("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.

Our second 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 (the "ABILITY-1 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 or in combination with KEYTRUDA® (pembrolizumab) under a clinical collaboration with Merck (known as MSD outside the United States and Canada). The Company has successfully completed a Phase 1 monotherapy dose- escalation study with MDNA11 with a favourable safety profile and demonstrated early signs of 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, dose escalation study of MDNA11 in combination with KEYTRUDA® is currently in progress.

Our earlier stage candidates from the BiSKITsTM and T-MASKTM platforms, encompassing IL-2, IL-4 and IL- 13 super-agonists and super-antagonists, are in pre-clinical development.

RECENT ACHIEVEMENTS & HIGHLIGHTS

The following are highlights for the three and six month periods ending September 30, 2024 through the date hereof:

FINANCING UPDATE

Six months ended September 30, 2024

Private Placement

On April 30, 2024, the Company closed a $20 million financing through a private placement (the "2024 Offering") with RA Capital Management ("RA"). Pursuant to the terms of the 2024 Offering, RA subscribed for 5,141,388 Common Shares at a price of $1.95 per share and, in lieu of common shares, pre-funded warrants to purchase 5,141,388 Common Shares at a purchase price of $1.94 per pre-funded warrant, for total net proceeds to the Company of $20 million. The Company intends to use the net proceeds from the

2024 Offering for further development of its MDNA11 program, advancement of its preclinical programs and general corporate purposes.

Warrants

During the six months ended September 30, 2024, 1,037,250 warrants with a strike price of $1.20 were exercised for proceeds of $1.2 million On July 31, 2024, there were 65,750 warrants with a strike price of $1.20 that expired unexercised. In addition, 369,017 warrants with a strike price of $1.75 were exercised for proceeds of $0.6 million.

Subsequent to quarter end, an additional 1,089,650 warrants with a strike price of $1.75 were exercised for proceeds of $2.0 million. The remaining 90,385 warrants with a strike price of $1.75 expired unexercised on October 17, 2024.

Six months ended September 30, 2023

2023 At-The-Market Facility

On February 17, 2023, the Company entered into a sales agreement with Oppenheimer & Co. Inc., acting as sales agent (the "2023 ATM Agreement"), pursuant to which the Company may, from time to time sell, through at-the-market offerings on the Nasdaq such number of Common Shares as would have an aggregate offering price of up to US$10.0 million (the "2023 ATM Facility"). During the six months ended September 30, 2023, the Company did not issue any Common Shares pursuant to the 2023 ATM Facility.

Further to the Nasdaq Delisting, the 2023 ATM Agreement was terminated.

Warrants

During the six months ended September 30, 2023, no warrants were exercised.

RESEARCH & DEVELOPMENT UPDATE

Our Pipeline of Superkines

MDNA11

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 promote 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 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 or in combination with Merck's KEYTRUDA®. The figure below describes the ABILITY-1 Study.

ABILITY-1 Study Schema: MDNA11 Monotherapy and in Combination with KEYTRUDA®

Deep and Durable Anti-tumor Activity with Single-Agent MDNA11 in Immune Checkpoint Inhibitor ("ICI") Resistant Patients: 30% Response Rate in Monotherapy Expansion Cohort (3 of 10) and 25% Response Rate Among All High-dose Phase 2 Eligible Patients (5 of 20)

On November 9th, 2024, at the 39th Annual Meeting of the SITC, Medicenna reported positive, updated clinical results from the ongoing monotherapy expansion and combination escalation portions of the Phase 1/2 ABILITY-1 Study. Comprehensive clinical updates were also presented on April 9th, 2024, at the 2024 Annual Meeting of the AACR and on May 31st, 2024, just prior to the 2024 American Society of Clinical Oncology ("ASCO") Annual Meeting.

The updated results at SITC demonstrated that the ORR was 30% in the monotherapy dose expansion cohort (3 of 10) among ICI resistant patients with advanced and/or metastatic solid tumors. The ORR was 25%, including 1 CR and 4 PRs, among all ICI resistant high dose (≥ 60 µg/kg MDNA11) phase 2-eligible patients (5 of 20).

Two PRs were observed among 3 microsatellite instability high ("MSI-H") ICI resistant patients (ORR 66.7%) with both responders having pancreatic ductal adenocarcinoma ("PDAC"). ORR in patients with ICI resistant cutaneous melanoma was 27% (3 of 11), with one patient achieving a complete response at week 52 who remains on treatment at week 63.

Combination Escalation with KEYTRUDA®: Encouraging Safety Profile and Early Signs of Anti- tumor Activity in Heavily Pre-treated Patients, including a PR in a Microsatellite Stable ("MSS") Colorectal Cancer Patient

In the combination portion of the study with KEYTRUDA® no dose limiting toxicities were observed at the 90 µg/kg dose level, and the next 2 cohorts have started enrollment at the higher dose of 120 µg/kg administered either once every 2 weeks or once every 3 weeks, with 400 mg KEYTRUDA® administered once every 6 weeks.

Among 5 efficacy-evaluable patients in the combination dose escalation arm, tumor control (PR or SD) was observed in 4 patients including a PR in a microsatellite-stable (MSS) colon cancer patient, a tumor-type which has failed to demonstrate efficacy in response to checkpoint inhibitor therapy in previous clinical trials.

Key, consolidated findings on MDNA11 from the data presented at SITC, prior to ASCO, and at AACR included:

Monotherapy Tumor Response in Checkpoint Resistant Patients

MDNA11 continues to demonstrate encouraging deep and durable single-agent anti-tumor activity among patients who progressed on prior ICI therapy:

30% Response Rate in Monotherapy Expansion Cohort and 25% Response Rate Amongst All High Dose Phase 2 Eligible Patients who Failed Checkpoint Therapies:

Monotherapy Safety

MDNA11 demonstrated a favorable safety profile and was generally well tolerated across all dose cohorts, with no dose limiting toxicities ("DLT") or vascular leak syndrome reported, and a majority of treatment related adverse events (TRAEs) being grade 1 or 2 (94%) and resolving within 48 hours; grade 3 TRAEs mainly constituted asymptomatic transient LFT elevations; one isolated laboratory based grade 4 TRAE was observed with asymptomatic transient LFT elevation in the monotherapy dose expansion arm which resolved within 72 hours without intervention. Repeat administration of MDNA11 at the target doses continues to improve tolerability.

Monotherapy Pharmacodynamics

Pharmacodynamic data on effector anti-tumor immune cells continue to support the mechanistic rationale for MDNA11's promising anti-tumor activity:

Disclaimer

Medicenna Therapeutics Corp. published this content on February 25, 2025, and is solely responsible for the information contained therein. Distributed by Public, unedited and unaltered, on February 25, 2025 at 20:12:07.904.