Bizaxofusp

Single-agent MDNA11 shows a 30% objective response rate (3 of 10) in the monotherapy dose expansion cohort among patients with advanced and/or metastatic solid tumors who had disease progression with immune checkpoint inhibitor (ICI) therapy Among ICI-resistant, high-dose MDNA11, phase 2-eligible patients in the monotherapy escalation and expansion cohorts (N=20), the response rate is 25% (5/20) including 1 complete response (CR) and 4 partial responses (PR) Treatment responses have been observed in 2 of 3 microsatellite instability-high (MSI-H) patients, both with pancreatic cancer, and in 3 of 11 patients with cutaneous melanoma including one CR With no dose limiting toxicities (DLTs) or new safety signals observed in combination with Merck’s (known as MSD outside of the US and Canada) anti-PD-1 therapy, KEYTRUDA® (pembrolizumab) to date, the combination dose escalation is enrolling patients at the highest dose of MDNA11 evaluated in monotherapy (120 µg/kg) 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 TORONTO and HOUSTON, Nov. 11, 2024 (GLOBE NEWSWIRE) -- Medicenna Therapeutics Corp. (“Medicenna” or the “Company”) (TSX: MDNA, OTCQX: MDNAF), a clinical-stage immunotherapy company focused on the development of Superkines, presented updated clinical results from the ongoing monotherapy dose expansion and combination dose escalation portions of the Phase 1/2 ABILITY-1 (A Beta-only IL-2 ImmunoTherapY) study evaluating MDNA11, a long-acting ‘beta-enhanced not-alpha’ interleukin-2 (IL-2) super-agonist, as monotherapy or in combination with Merck’s (known as MSD outside of the US and Canada) anti-PD-1 therapy, KEYTRUDA® (pembrolizumab), in patients with advanced solid tumors, at the 39th Annual Meeting of the Society for Immunotherapy of Cancer (SITC), held in Houston, Texas, on November 9th, 2024. “We are thrilled to share promising results from the Phase 1/2 ABILITY-1 study, with MDNA11 continuing to show deep and durable single-agent activity in patients resistant to checkpoint therapy including 2 patients with metastatic, treatment-refractory pancreatic cancer,” said Fahar Merchant, Ph.D., President and CEO of Medicenna. “We are especially pleased to see that MDNA11 in combination with KEYTRUDA® is demonstrating a favorable safety profile, robust pharmacodynamics and early signs of anti-tumor activity in heavily pre-treated patients allowing us to bolster the dose of MDNA11 to 120 µg/kg every 2 weeks and begin to evaluate dosing at a more convenient frequency of once every three weeks. We look forward to sharing additional clinical updates from the monotherapy and combination arms at medical conferences in the first half of 2025.” Key findings from the on-going monotherapy and combination dose escalation portions of the ABILITY-1 study at the time of data cut-off (i.e. October 15th, 2024) include: 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: An objective response rate (ORR) of 30% in the monotherapy dose expansion arm with 3 PRs among 10 patients who had all previously failed ICI therapy and had advanced and/or metastatic melanoma, non-melanoma skin cancer or MSI-H/dMMR tumors irrespective of tumor origin.The ORR is 25% (1 CR, 4 PR) from a total of 20 patients when including 10 phase 2 eligible patients from the MDNA11 monotherapy dose escalation arm who received at least 60 µg/kg.Objective responses included: 2 PRs among 3 MSI-H patients (ORR of 66.7%) with both responders having pancreatic ductal adenocarcinoma (PDAC). One patient with MSI-H PDAC was initially misclassified as MSI-H small bowel cancer with metastases in the pancreas.1 CR and 2 PRs among 11 patients with cutaneous melanoma (ORR of 27.3%).SD in 6 patients including 3 with duration > 24 weeks, yielding a clinical benefit rate of 40% (8/20). Monotherapy Safety Profile Key findings from the monotherapy dose escalation and ongoing monotherapy expansion arms of the ABILITY-1 study demonstrate MDNA11’s favorable safety profile: As previously reported, DLT or vascular leak syndrome were not observed during monotherapy dose escalation with a majority (94%) of treatment-related adverse events (TRAEs) being either grade 1 or 2 and resolving within 48 hours; grade 3 TRAEs mainly constituted asymptomatic transient LFT elevations; one isolated 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 analyses showed potent and durable systemic immune responses following MDNA11 administration with clear evidence of immune activation in the tumor microenvironment: MDNA11 showed significant increases in markers of stemness, central and effector memory and enhanced effector function in circulating CD8+ T and NK cells.Analysis of paired biopsies showed increased tumor infiltration of CD25+ activated CD8+ T cells and NK cells post-MDNA11 treatment. Combination Dose Escalation Safety Profile No DLTs, grade 4 or 5 TRAEs were observed in combination dose escalation cohorts 1 or 2 (60 µg/kg Q2W or 90 µg/kg Q2W MDNA11 with 400 mg Q6W KEYTRUDA®) during the DLT observation period. The Safety Review Committee approved enrollment of the next higher-dose cohorts as follows: Cohort 3: 120 µg/kg Q2W MDNA11 and 400 mg Q6W KEYTRUDA®Cohort 4: 120 µg/kg Q3W MDNA11 and 400 mg Q6W KEYTRUDA® Combination Dose Escalation Pharmacodynamics Early pharmacodynamic analyses demonstrated robust lymphocyte expansion which was sustained with repeat dosing at both 60 µg/kg and 90 µg/kg Q2W MDNA11 in combination with 400 mg Q6W KEYTRUDA®. Combination Dose Escalation Tumor Response Encouraging preliminary signs of anti-tumor activity were observed with MDNA11 in combination with KEYTRUDA® (400 mg Q6W) in dose escalation cohorts 1 (60 µg/kg Q2W MDNA11) and 2 (90 µg/kg Q2W MDNA11). Among 5 heavily pre-treated efficacy-evaluable patients, tumor control (PR or SD) was observed in 4 patients including a PR in a microsatellite-stable (MSS) colon cancer patient. A copy of the poster and a related slide deck have been posted on the “Scientific Presentations” page of Medicenna’s website. 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 KEYTRUDA®. In the combination dose escalation portion of the Phase 2 study, approximately 6-12 patients are expected to be 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. Upon identification of an appropriate dose regimen for combination, the study will proceed to a combination dose expansion cohort. 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. MDNA11 is being evaluated in the Phase 1/2 ABILITY-1 Study (NCT05086692) as a monotherapy and in combination with pembrolizumab. 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. Medicenna’s early-stage high-affinity IL-2β biased IL-2/IL-15 Super-antagonists, from its MDNA209 platform, are being evaluated as potential therapies for autoimmune and graft-versus host diseases. Medicenna’s early-stage BiSKITs™ (Bifunctional SuperKine ImmunoTherapies) and the T-MASK™ (Targeted Metalloprotease Activated SuperKine) programs are designed to enhance the ability of Superkines to treat immunologically “cold” tumors. For more information, please visit www.medicenna.com, and follow us on Twitter and LinkedIn. KEYTRUDA® is a registered trademark of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA. Forward-Looking Statements This news release contains 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 potential and safety profile of MDNA11 (both as monotherapy and in combination with KEYTRUDA®), 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. 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. 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. 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/Media Contact: Christina CameronInvestor Relations, Medicenna Therapeutics(647) 953-0673ir@medicenna.com

MDNA113 is a novel IL-13Rα2 tumor-targeted and “masked” BiSKIT (Bifunctional SuperKine for ImmunoTherapy), engineered to deliver an anti-PD1-IL-2 Superkine (anti-PD1-IL-2SK) to the tumor microenvironment (TME), where it is conditionally activated by tumor-associated proteases MDNA113 treatment achieved complete tumor regression of IL-13Rα2 expressing tumors, highlighting its potential to treat a vast range of malignancies, including immunologically “cold tumors” that annually affect over two million cancer patients worldwide Internationally recognized academic teams in the UK showed promising pre-clinical results with a long-acting IL-2SK (MDNA11) and anti-PD1-IL-2SK BiSKIT, in mouse models of glioblastoma (GBM) and patient-derived GBM explants Updated MDNA11 clinical results from the ABILITY-1 study will be presented tomorrow at SITC TORONTO and HOUSTON, Nov. 08, 2024 (GLOBE NEWSWIRE) -- Medicenna Therapeutics Corp. (“Medicenna” or the “Company”) (TSX: MDNA, OTCQX: MDNAF), a clinical-stage immunotherapy company focused on the development of Superkines, announced that new preclinical data from its BiSKIT (MDNA113) and IL-2 super agonist (MDNA11) programs will be presented today at the 39th Annual Meeting of SITC being held in Houston, Texas. In addition, as announced previously, updated clinical results from the MDNA11 Phase 1/2 ABILITY-1 study will be presented tomorrow, Saturday November 9, 2024 at SITC. “We are excited to demonstrate our ability to generate novel therapeutics such as MDNA113, to address unmet needs in oncology, by smartly leveraging both our IL-2 and IL-13 Superkine platforms in one molecule,” said Fahar Merchant, Ph.D., President and CEO of Medicenna. “Today’s data demonstrates the effectiveness of MDNA113 to inhibit tumor growth, particularly in IL-13Rα2 positive tumors, and showcase its potential to completely protect and prevent metastasis in an aggressive breast cancer model when administered just once prior to surgery. In a separate presentation, independent work from our academic collaborator in the UK demonstrated the capacity of MDNA11 and anti-PD1-IL-2SK BiSKIT to significantly extend overall survival in an aggressive GBM mouse model and stimulate activity of resident effector immune cells in fresh human GBM explants.” MDNA113 is based on the Company’s IL-2 and IL-13 Superkine Platforms, the former being used to develop MDNA11, a long-acting IL-2 super agonist, currently being evaluated in the Phase 1/2 ABILITY-1 study for the treatment of advanced and/or metastatic solid tumors. Key highlights from the presentations are: MDNA113 is a conditionally activatable anti-PD1-IL-2SK with a cleavable IL-13SK dual masking/tumor-targeting domain to limit systemic immune stimulation while maximizing anti-tumor response Mice treated with MDNA113 showed reduced peripheral lymphocyte expansion without impacting anti-PD1/PDL1 blockade, and better tolerability when compared to unmasked anti-PD1-IL-2SK.Cleavage by tumor-specific proteases removes the IL-13SK targeting and masking domain of MDNA113, restoring the synergy between IL-2R agonism and anti-PD1 blockadeEfficacy of MDNA113 is substantially enhanced in mice harboring MC38 tumors that have been engineered to overexpress IL-13Rα2, resulting in complete tumor regression in a vast majority of animalsSingle neoadjuvant treatment (pre-surgery) with MDNA113 in a highly invasive orthotopic 4T1.2 model of triple negative breast cancer resulted in 100% survival by preventing metastasis and enrichment of cytotoxic GrzB-positive CD8+T cells within the tumor microenvironment. Stimulation of IL-2 signaling with highly selective IL-2R super-agonists enhances immune effector cell response in mouse and patient-derived glioblastomas Long-acting IL-2SK (i.e., MDNA11) and anti-PD1-IL-2SK (i.e., therapeutic core of MDNA113) significantly extended the survival of mice bearing aggressive orthotopic GBMs when compared to control mice or mice treated with native IL-2 or anti-PD1.GBMs from anti-PD1-IL-2SK treated mice showed higher frequency of infiltrating CD8+T and NK cells with no change in immune suppressive Tregs.Ex-vivo primary patient-derived fresh GBM explants treated with IL-2SK or anti-PD1-IL-2SK showed increased CD8+ T and NK cell populations concomitant with reduced tumor cell burden. Copies of the two presentations will be available on the “Scientific Presentations” page of Medicenna’s website after the conference. About MDNA113 MDNA113 is a novel, first-in-class tumor-targeted and tumor-activated bi-functional anti-PD1-IL2 Superkine with exceptionally high affinity for IL-13Rα2 without binding to the functional IL-13R⍺1. IL-13Rα2 is overexpressed in a wide range of solid tumors, including cold tumors with minimal to no expression in normal tissues. IL-13Rα2 expressing tumors also have abundant matrix metalloprotease in the tumor microenvironment that may efficiently activate MDNA113. IL-13Rα2 expression is associated with poor clinical outcome in multiple tumor types including prostate cancer, pancreatic cancer, ovarian cancer, liver cancer, breast cancer and brain cancer, with an annual world-wide incidence of over 2 million. 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 (NCT05086692) as both monotherapy and in combination with pembrolizumab. 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 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. Medicenna’s early-stage high-affinity IL-2β biased IL-2/IL-15 Super-antagonists, from its MDNA209 platform, are being evaluated as potential therapies for autoimmune and graft-versus host diseases. Medicenna’s early-stage BiSKITs™ (Bifunctional SuperKine ImmunoTherapies) and the T-MASK™ (Targeted Metalloprotease Activated SuperKine) programs are designed to enhance the ability of Superkines to treat immunologically “cold” tumors. For more information, please visit www.medicenna.com, and follow us on Twitter and LinkedIn. Forward-Looking Statements This news release contains 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 potential and safety profile of MDNA11 and MDNA113. 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. 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. 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. 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/Media Contact: Christina CameronInvestor Relations, Medicenna Therapeutics(647) 953-0673ir@medicenna.com