GTP-binding proteins

The ABILITY-1 Study is evaluating MDNA11, a highly selective long-acting IL-2 Superkine, in combination with KEYTRUDA® (pembrolizumab) for treatment of patients with advanced solid tumorsMDNA11 continues to demonstrate encouraging single-agent activity from the monotherapy dose escalation portion of the ABILITY-1 StudyCompany expects to report results from both the monotherapy expansion and combination escalation and expansion arms of the Phase 2 study in H1 and H2 2024 TORONTO and HOUSTON, Feb. 13, 2024 (GLOBE NEWSWIRE) -- Medicenna Therapeutics Corp. (“Medicenna” or the “Company”) (TSX: MDNA, OTCQB: MDNAF), a clinical-stage immunotherapy company focused on the development of Superkines, today announced the first patient dosed in the combination arm of the Phase 1/2 ABILITY (A Beta-only IL-2 ImmunoTherapY) study evaluating MDNA11, a long-acting, “beta-enhanced not-alpha” interleukin-2 (IL-2) super-agonist, with KEYTRUDA® (pembrolizumab). The combination portion of the study is designed to evaluate the potential for a synergistic effect of MDNA11 with KEYTRUDA® in patients with advanced solid tumors. “Dosing the first patient in the combination arm with MDNA11 and KEYTRUDA® is a significant milestone for Medicenna and are excited with the progress of our novel IL-2 superkine," said Fahar Merchant, PhD, President and CEO of Medicenna. “By combining MDNA11 with KEYTRUDA®, we are building upon the promising data generated to date by MDNA11 as a single agent. Targeting the PD1/PD-L1 pathway in addition to MDNA11’s differentiated mechanism of action is expected to further stimulate and restore the patient’s immune system, which should result in improved antitumoral activity and patient outcomes. We are thrilled to enter this new phase of development of MDNA11 and further demonstrate its potential in combination with the world’s best-selling drug.” Solid tumors represent 90% of all cancers and although CPI therapies have shown promising advances in some types of immunosensitive cancers, more than 70% of patients do not respond to or become resistant to such therapies. MDNA11, with its uniquely differentiating ‘beta-enhanced not-alpha’ features, continues to be a potential best-in-class next-generation IL-2 super-agonist for treatment of advanced solid tumors. Pre-clinical data published in JITC in 2022 demonstrated that mice receiving both, MDNA11 and checkpoint inhibitors achieved complete and sustained tumor control even after multiple rechallenges, demonstrating the capacity for MDNA11 to sensitize solid tumors to checkpoint blockade1. The ABILITY-1 Study is actively recruiting patients with different types of recurrent or metastatic solid tumors at multiple sites in the USA, Canada, Australia, and South Korea and is expected to initiate patient enrolment in Europe. Preliminary results from both the monotherapy expansion and combination escalation and expansion arms of ABILITY-1 the study will be available in H1 and H2 2024. KEYTRUDA® is a registered trademark of Merck Sharp & Dohme Corp, a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. 1https://pubmed-ncbi-nlm-nih-gov.libproxy1.nus.edu.sg/35058325/ 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 pembrolizumab (Keytruda®). In the combination dose escalation of the Phase 2 study, approximately 6-12 patients are expected to be enrolled and administered ascending doses of MDNA11 intravenously once every two weeks 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 MDNA11 MDNA11 is an extensively engineered long-acting recombinant IL-2 “Superkine” fused with human albumin. MDNA11 has complete abrogation of IL-2 receptor alpha binding and is the only IL-2 therapy in clinical development with enhanced binding to the intermediate affinity receptor (beta-gamma). These changes enable effective expansion and activation of anti-tumor CD8+ effector and NK cells while avoiding excessive stimulation of immunoinhibitory Treg cells or side effect inducing endothelial cells, as well as ensuring retention in the tumor and tumor draining lymph nodes. These changes vastly increase efficacy and therapeutic index over the predecessor drug aldesleukin. MDNA11 is currently being evaluated in the Phase 1/2 ABILITY-1 study as both a monotherapy and in combination with the PD-1 blocking antibody pembrolizumab (Keytruda®). 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 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 that relate to the future operations of the Company, plans and projections and other statements that are not historical facts, including, without limitation, statements on the clinical development and potential of MDNA11, the ABILITY-1 Study and its enrolment and the timeline for reporting results and additional data. 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 and Annual Report on Form 20-F 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. Contacts Christina CameronInvestor Relations, Medicenna Therapeuticsir@medicenna.com(647) 953-0673

Planegg/Martinsried, September 18, 2023. Medigene AG (Medigene, the “Company”, FSE: MDG1, Prime Standard), an immuno-oncology platform company focusing on the discovery and development of T cell immunotherapies for solid tumors, announces today that it has selected its lead candidate for MDG2011, a T cell receptor engineered T cell (TCR-T) therapy targeting KRAS (Kirsten rat sarcoma viral oncogene homologue) G12V with HLA-A*11 and being developed in combination with the Company’s PD1-41BB costimulatory switch protein (CSP) technology. Medigene’s end-to-end (E2E) platform, has successfully generated not one but three KRAS G12V-HLA-A*11 TCRs, each with distinct, multiple HLA-A*11 subtype recognition patterns that exceed the Company’s selection criteria for highly specific, sensitive and potentially safer (3S) TCRs. After deploying Medigene’s proprietary algorithms for evaluation of the unique characteristics of each of the 3S TCRs, including peptide specificity, tumor cell recognition and off-target toxicity, the Company has prioritized one of the 3S TCRs as the lead to move forward to the pre-clinical stage for Medigene’s MDG2011 program. “The unique approach of our E2E platform to generate and optimize 3S TCRs, has continued to deliver above expectations and we are delighted to have been presented with the positive challenge of having to select a lead from three strong candidates for our MDG2011 program targeting KRAS G12V-A11,” said Dr. Selwyn Ho, Chief Executive Officer at Medigene. “The selection of this first mKRAS (mutant KRAS) lead TCR further validates our capabilities to generate 3S TCRs across both neoantigens and cancer-testis antigens. By combining all our TCRs with our PD1-41BB or CD40L-CD28 costimulatory switch proteins, we remain convinced that our approach will consistently deliver best-in-class TCR-T therapies leading to improved outcomes for patients suffering from difficult-to-treat solid tumors. We look forward to presenting the first pre-clinical data on MDG2011 at upcoming scientific conferences in the last quarter of 2023.” The Company’s E2E platform continues to generate 3S TCRs with unique attributes that add additional dimensions to the potential of Medigene’s TCR-T therapies as well as to confirm the Company’s discovery research efforts. One such attribute is the identification of a TCR candidate demonstrating bi-specific recognition for both the KRAS G12V and G12C mutations. Directed TCR discovery efforts in the future will enable identification of an optimal KRAS G12C-specific TCR lead. The two remaining KRAS G12V-A11 TCRs not selected for the MDG2011 program will be added to Medigene’s KRAS TCR library for potential future programs that align the product vision with the profile of each TCR. Patents have been filed for each of the three TCRs. MDG2011 is the first program of Medigene’s pipeline expansion into a library of neoantigens (also known as oncogenic driver mutations) that comprise multiple KRAS mutations and HLAs (human leukocyte antigens) including, but not limited to: KRAS G12V-HLA-A*11 (MDG2011)KRAS G12V-HLA-A*03 (MDG2012)KRAS G12D-HLA-A*11 (MDG2021) These TCRs will be combined with the PD1-41BB and/or the CD40L-CD28 costimulatory switch proteins to enhance penetration, proliferation, persistence and enhanced cytotoxic function of Medigene’s TCR-T cells while mitigating the immunosuppressive effects of the tumor microenvironment. Neoantigens are tumor-specific antigens, which play a critical role in the growth and maintenance of tumors. These mutations are found in many solid tumors and their prevalence varies depending on the cancer type. Importantly, if present, these mutations are found in each tumor cell. KRAS mutations are widely recognized as the most common oncogene mutations in difficult to treat solid tumors existing in ~30% of solid tumors, such as pancreatic, colorectal, endometrial and non-small-cell lung cancer. Global incidence of solid tumors expressing KRAS mutations is estimated to be in excess of 300,000 patients. --- end of press release --- About Medigene AG Medigene AG (FSE: MDG1) is an immuno-oncology platform company dedicated to developing T cell therapies to effectively eliminate cancer. Its end-to-end technology platform, built on multiple proprietary and exclusive TCR generation and optimization, as well as product enhancement technologies, allows Medigene to create best-in-class differentiated, T cell receptor engineered T cell (TCR-T) therapies for multiple solid tumor indications that are optimized for both safety and efficacy. This platform provides product candidates for both its in-house therapeutics pipeline and partnering. For more information, please visit www.medigene.com About Medigene’s End-to-End Platform Medigene’s immunotherapies help activate the patient’s own defense mechanisms by harnessing T cells in the battle against cancer. Medigene’s end-to-end platform combines multiple exclusive and proprietary technologies to create best-in-class TCR-T therapies. The platform includes multiple TCR generation and optimization technologies (e.g., Allogeneic-HLA (Allo-HLA) TCR Priming), as well as product enhancement technologies (e.g., PD1-41BB and CD40L-CD28 Costimulatory Switch Proteins, Precision Pairing) to aid the development of differentiated TCR-T therapies. Partnerships with multiple companies including BioNTech, 2seventy bio, and Hongsheng Sciences, continue to validate the platform’s assets & technologies. About Medigene’s TCR-T Cells T cells are at the center of Medigene’s therapeutic approaches. Medigene’s immunotherapies help activate the patient’s own defense mechanisms, and harness T cells in the battle against cancer. Medigene’s therapies arm the patient’s own T cells with tumor-specific T cell receptors (TCRs) creating TCR-modified T cells with enhanced potential to detect and efficiently kill cancer cells. Medigene’s approach to immunotherapy is designed to overcome the patient’s tolerance of cancer cells and tumor-induced immunosuppression. By activating the patient’s T cells outside the body, genetically modifying them with tumor-specific TCRs and expanding the resultant activated TCR-T cells, patients can rapidly be given large numbers of tumor-specific T cells to fight their cancer. About Medigene’s PD1-41BB Costimulatory Switch Protein Checkpoint inhibition via PD-1/PD-L1 pathway: Cells of solid tumors are sensitive to killing by activated T cells but can escape this killing activity by producing inhibitory molecules known as ‘checkpoint proteins’, such as the Programmed Death Ligand 1 (PD-L1), on their surface. When this occurs, activated T cells which express PD-1, the natural receptor for PD-L1, are inactivated. The expression of PD-L1 is an adaptive immune resistance mechanism for tumors that can help them survive and grow. The 4-1BB (CD137) costimulatory signaling pathway: Effective T cell immune responses to antigens typically require both a primary antigenic stimulation via the T cell receptor (TCR) and costimulatory signals. The intracellular signaling domains of the 4-1BB protein offer a well-characterized pathway to costimulation and enhanced T cell responses. Medigene’s PD1-41BB switch receptor turns the tumor’s attempted self-defense mechanism against the tumor by substituting the inhibitory signaling domain of PD-1 with the activating signaling domain of 4-1BB. Therefore, instead of inactivating T cells, the switch receptor delivers an activating signal to TCR-T cells. PD1-41BB-modified TCR-T cells proliferate strongly in the presence of PD-L1-positive tumor cells and kill more tumor cells upon repeated exposure. Additionally, these switch receptor signals enable TCR-T cells to function better with low levels of glucose or high levels of TGFß, two conditions characteristic of strongly hostile tumor microenvironments. About Medigene’s CD40L-CD28 Costimulatory Switch Protein The CD40L/CD40 pathway plays a major role in immune regulation and homeostasis. The CD40L (ligand) is a member of the tumor necrosis family and primarily expressed on activated T cells: CD4+ T cells, where its primary function is in the T cell-mediated activation of dendritic cells (DCs) and monocytes. CD8+ T cells thus promoting their expansion and differentiation through DCs. CD40 is also present on B cells and expressed on dendritic cells (DCs), monocytes and macrophages as well as by non-hematopoietic cells such as epithelial and endothelial cells. Expression of CD40 has been confirmed in a wide variety of solid tumors like melanoma, prostate, and lung cancers, as well as in carcinomas of the nasopharynx, bladder, cervix, and ovary. CD28 is expressed on T cells providing costimulatory signals required for T cell activation and survival. Thus, the CD40L/CD40 pathway plays a crucial role in activation of T cells. Medigene´s CD40L-CD28 costimulatory switch protein may contribute to an enhancement of cellular immune responses in several ways: CD40L expressed on activated T cells and CD40 expressed on DC transmits a signal to the antigen presenting cells that results in upregulation of costimulatory molecules and further stimulation of optimal T cell responses. CD40-expressing tumor cells can be subject to apoptosis by direct interaction with CD40L-CD28-engineered T cells independent of MHC/peptide-specific targeting. CD40 is found in the TME of the tumor endothelium, where engagement with CD40L-CD28-engineered T cells enables upregulation of adhesion molecules, thereby improving T cell infiltration into tumors. Thus, the CD40L-CD28 costimulatory switch protein acts via DCs and other non-tumor cells and may provide complementary effects to other switch receptors that exert their effects mainly via PD-1 expressing T cells. About KRAS KRAS (Kirsten rat sarcoma viral oncogene homologue) belongs to the group of small so-called Guanosine-5'-triphosphate (GTP)-binding proteins, known as RAS-like GTPases. Under physiological conditions KRAS tightly regulates cell proliferation and survival. In cancer, KRAS is found frequently altered, in a wide variety of often fatal solid cancer types like pancreatic ductal adenocarcinoma, non-small-cell lung cancer, endometrial and colorectal cancer. Mutations in the KRAS gene result in the creation of neoantigens which drive uncontrolled proliferation of cancer cells. These mutations within the KRAS gene are unique to cancer cells and absent in healthy normal tissue, making KRAS an attractive target for TCR-T therapies. T cell receptor engineered T cell therapies offer a promising approach to targeting these mutations and addressing the challenges posed by solid tumors. Unlike CAR-T cells, which require surface antigens for recognition and may have limitations in target accessibility, TCR-T cells recognize a broader range of targets including intracellular proteins like neoantigens. This unique ability makes TCR-T therapies particularly well-suited for targeting KRAS mutations and other challenging neoantigens. This press release contains forward-looking statements representing the opinion of Medigene as of the date of this release. The actual results achieved by Medigene may differ significantly from the forward-looking statements made herein. Medigene is not bound to update any of these forward-looking statements. Medigene® is a registered trademark of Medigene AG. This trademark may be owned or licensed in select locations only. Medigene Pamela Keck Phone: +49 89 2000 3333 01 E-mail: investor@medigene.com LifeSci Advisors Sandya von der Weid Phone: +41 78 680 05 38 E-mail: svonderweid@lifesciadvisors.com In case you no longer wish to receive any information about Medigene, please inform us by e-mail (investor@medigene.com). We will then delete your address from our distribution list.

Planegg/Martinsried, June 13, 2023. Medigene AG (Medigene, FSE: MDG1, Prime Standard), an immuno-oncology platform company focusing on the discovery and development of T cell immunotherapies for solid tumors, will host an R&D Event to discuss the pipeline expansion and the evolution of its end-to-end platform on Tuesday, June 20, 2023, at 10:00 am ET. A live Q&A session will follow the formal presentations and discussions. The company’s leadership team will be discussing the evolution of Medigene’s end-to-end platform and their exciting pipeline expansion into neoantigens with programs targeting multiple KRAS (Kirsten rat sarcoma viral oncogene homologue) mutations and HLAs (human leukocyte antigens), focused on developing differentiated, best-in-class T cell receptor-engineered T cell (TCR‑T) therapies for multiple solid tumor indications. Attendees are invited to listen to the presentations and discussions exploring the unmet needs in the treatment of solid tumors. Full details for the webcast and registration are as follows: Date: June 20, 2023 Time: 10:00 am ET Location: Virtual Webcast registration: https://lifescievents.com/event/medigene/ Following the call, an archived webcast will also be accessible on the Investors & Media section of the Medigene website https://www.medigene.com/investors-media/reports-presentations --- end of press release --- About MedigeneMedigene AG (FSE: MDG1) is an immuno-oncology platform company dedicated to developing T cell therapies to effectively eliminate cancer. Its end-to-end technology platform, built on multiple proprietary and exclusive product development and product enhancement technologies, allows Medigene to create best-in-class differentiated, T cell receptor engineered T cell (TCR-T) therapies for multiple solid tumor indications that are optimized for both safety and efficacy. This platform provides product candidates for both its in-house therapeutics pipeline and partnering. For more information, please visit www.medigene.com About Medigene’s End-To-End Platform Medigene’s immunotherapies help activate the patient’s own defense mechanisms by harnessing T cells in the battle against cancer. Medigene’s end-to-end platform combines multiple exclusive and proprietary technologies to create best-in-class TCR-T therapies. The platform includes multiple product enhancement technologies, (e.g., PD1-41BB Switch Receptor, CD40L-CD28 Switch Receptor, Precision Pairing) and development optimization technologies (e.g., Allogeneic-HLA (Allo-HLA) TCR Priming) to aid the development of differentiated TCR-T therapies. Partnerships with multiple companies including BioNTech, 2seventy bio, and Hongsheng Sciences, continue to validate the platform’s assets & technologies. About Medigene’s TCR-T cells T cells are at the center of Medigene’s therapeutic approaches. Medigene’s immunotherapies help activate the patient’s own defense mechanisms, and harness T cells in the battle against cancer. Medigene’s therapies arm the patient’s own T cells with tumor-specific T cell receptors (TCRs) creating TCR-modified T cells with enhanced potential to detect and efficiently kill cancer cells. Medigene’s approach to immunotherapy is designed to overcome the patient’s tolerance of cancer cells and tumor-induced immunosuppression. By activating the patient’s T cells outside the body, genetically modifying them with tumor-specific TCRs and expanding the resultant activated TCR-T cells, patients can rapidly be given significant numbers of tumor-specific T cells to fight their cancer. About KRAS KRAS (Kirsten rat sarcoma viral oncogene homologue) belongs to the group of small so-called Guanosine-5′-triphosphate (GTP)-binding proteins, known as RAS-like GTPases. Under physiological conditions KRAS tightly regulates cell proliferation and survival. In cancer, KRAS is found frequently altered, in a wide variety of often fatal solid cancer types like pancreatic ductal adenocarcinoma, non-small-cell lung cancer, and colorectal cancer. Mutations in the KRAS gene result in the creation of neoantigens which drive uncontrolled proliferation of cancer cells. These mutations within the KRAS gene are unique to cancer cells and absent in healthy normal tissue, making KRAS an attractive target for TCR-T therapies. T cell receptor engineered T cell therapies offer a promising approach to targeting these mutations and addressing the challenges posed by solid tumors. Unlike CAR-T cells, which require surface antigens for recognition and may have limitations in target accessibility, TCR-T cells recognize a broader range of targets including intracellular proteins like neoantigens. This unique ability makes TCR-T therapies particularly well-suited for targeting KRAS mutations and other challenging neoantigens. This press release contains forward-looking statements representing the opinion of Medigene as of the date of this release. The actual results achieved by Medigene may differ significantly from the forward-looking statements made herein. Medigene is not bound to update any of these forward-looking statements. Medigene® is a registered trademark of Medigene AG. This trademark may be owned or licensed in select locations only. Medigene Pamela Keck Phone: +49 89 2000 3333 01 E-mail: investor@medigene.com LifeSci Advisors Sandya von der Weid Phone: +41 78 680 05 38 E-mail: svonderweid@lifesciadvisors.com In case you no longer wish to receive any information about Medigene, please inform us by e-mail (investor@medigene.com). We will then delete your address from our distribution list.