Eftilagimod alpha

Findings published in Science Immunology resolve how human LAG-3 binds to its main ligand providing a better foundation for development of blocking LAG-3 therapeutics, including Immutep’s anti-LAG-3 small molecule programData also supports eftilagimod alfa’s (efti) preferential binding to a subset of MHC Class II molecules on antigen-presenting cells leading to their activation SYDNEY, AUSTRALIA, Dec. 16, 2024 (GLOBE NEWSWIRE) -- Immutep Limited (ASX: IMM; NASDAQ: IMMP) ("Immutep” or “the Company”), a clinical-stage biotechnology company developing novel LAG-3 immunotherapies for cancer and autoimmune disease, today announces new findings published in Science Immunology that resolve how human lymphocyte activation gene 3 (LAG-3) binds to its main ligand MHC Class II (MHC-II), also known as HLA Class II (HLA-II) in humans. The publication is the first to show the crystal structure of a human LAG-3/HLA-II complex and provides a better foundation for development of blocking LAG-3 therapeutics, including Immutep’s anti-LAG-3 small molecule program. Under the oversight of Professor Jamie Rossjohn FAA FRS, at Monash University’s Biomedicine Discovery Institute (BDI), and in collaboration with Immutep, this breakthrough is an exemplar of the importance of industry-academia alliances. The LAG-3 immune control mechanism is the exclusive focus of Immutep across both cancer and autoimmunity and a clinically validated target of deep interest throughout the academic, medical, and industry sectors. Dr. Jan Petersen, first author of the study, said: “The way the PD-1 and CTLA-4 immune checkpoint molecules bind to their respective ligands has been resolved for many years. However, the resolution of the interface between another important checkpoint molecule, LAG-3, and its main ligands, HLA-II molecules, has remained elusive. Solved using data collected at the Australian Synchrotron, a structure of a LAG-3/HLA-II complex provides a structural foundation to harness rationally for future development of antibodies and small molecule therapeutics designed to block LAG-3 activity.” Dr. Frédéric Triebel, Immutep’s CSO, added: “It is thrilling to be able to see and analyze the interactions taking place at the interface between the soluble homodimeric LAG-3 protein and its main ligand. We now better understand how efti uniquely acts as an MHC-II agonist by preferentially binding to a subset of MHC-II molecules clustered in lipid raft microdomains on the surface of antigen-presenting cells. These findings add to the strong foundation of our work with Professor Rossjohn and his team to develop a deeper understanding of the structure and function of the LAG-3 immune control mechanism, particularly as it relates to our anti-LAG-3 small molecule program.” The Crystal Structure of the Human LAG-3–HLA-DR1–Peptide Complex publication details how LAG-3 engages two HLA-II molecules (see Figure 1). The data in the publication supports efti’s (soluble LAG-3) preferential binding to a subset of MHC-II molecules on antigen-presenting cells leading to their activation. Figure 1: Human LAG-3 homodimer (with domains D1, D2, D3 and D4) binding to two separate HLA-II (MHC-II) molecules on the surface of an antigen-presenting cell (APC), imposing a distinct 38° offset angle. This figure has been modified from the original Figure 1c of Petersen et al to aid visualisation. About the Monash Biomedicine Discovery InstituteCommitted to making the discoveries that will relieve the future burden of disease, the Monash Biomedicine Discovery Institute (BDI) at Monash University brings together more than 120 internationally-renowned research teams. Spanning seven discovery programs across Cancer, Cardiovascular Disease, Development and Stem Cells, Infection, Immunity, Metabolism, Diabetes and Obesity, and Neuroscience, Monash BDI is one of the largest biomedical research institutes in Australia. Our researchers are supported by world-class technology and infrastructure, and partner with industry, clinicians and researchers internationally to enhance lives through discovery. About ImmutepImmutep is a clinical-stage biotechnology company developing novel LAG-3 immunotherapy for cancer and autoimmune disease. We are pioneers in the understanding and advancement of therapeutics related to Lymphocyte Activation Gene-3 (LAG-3), and our diversified product portfolio harnesses its unique ability to stimulate or suppress the immune response. Immutep is dedicated to leveraging its expertise to bring innovative treatment options to patients in need and to maximise value for shareholders. For more information, please visit www.immutep.com. Australian Investors/Media:Catherine Strong, Sodali & Co+61 (0)406 759 268; catherine.strong@sodali.com U.S. Media:Chris Basta, VP, Investor Relations and Corporate Communications+1 (631) 318 4000; chris.basta@immutep.com ABN: 90 009 237 889

Data shows strong overall survival, progression-free survival, and durability from novel combination of efti in combination with pembrolizumab in difficult-to-treat head and neck cancer patients with PD-L1 CPS <1Positively, median overall survival (OS) has not yet been reached and the 12-month OS rate is 67%, both well above historical controlsComplete response rate increases to 12.9% and 16.1%, according to RECIST 1.1 and iRECIST, respectivelyTreatment continues to be well tolerated SYDNEY, AUSTRALIA, Dec. 12, 2024 (GLOBE NEWSWIRE) -- Immutep Limited (ASX: IMM; NASDAQ: IMMP) ("Immutep” or “the Company”), a clinical-stage biotechnology company developing novel LAG-3 immunotherapies for cancer and autoimmune disease, today announces positive clinical results from Cohort B of the TACTI-003 (KEYNOTE-C34) Phase IIb trial. This study evaluates eftilagimod alpha (efti) in combination with MSD’s (Merck & Co., Inc., Rahway, NJ, USA) anti-PD-1 therapy KEYTRUDA® (pembrolizumab) in first line recurrent/metastatic head and neck squamous cell carcinoma (1L HNSCC) patients with negative PD-L1 expression. The new promising data presented by Martin Forster, M.D., Ph.D., at the ESMO Immuno-Oncology (IO) Annual Congress 2024 includes strong overall survival, progression-free survival, and durability. This adds to the high response rates and favourable safety data previously reported on 12 July 2024. Prof. Martin Forster of the UCL Cancer Institute and University College London Hospital NHS Foundation Trust, London, UK, and TACTI-003 Investigator, stated, “The new survival and durability data, coupled with increasing complete responses, build on the strong response rates already established with this novel IO combination in head and neck squamous cell cancers with PD-L1 CPS <1. This difficult-to-treat disease places a high burden on patients who unfortunately have very limited treatment options that all include chemotherapy. Collectively, these impressive results build on the potential promise of efti to improve patient outcomes and expand populations that respond to anti-PD-1.” Results Data as of the 31 October 2024 cut-off date in evaluable 1L HNSCC patients (N=31) whose tumours express PD-L1 below 1 (Combined Positive Score [CPS] <1) and who typically do not respond well to anti-PD-1 therapy alone shows: Positively, median overall survival (OS) has not yet been reached and the 12-month OS rate is 67%Promising progression-free survival (PFS) of 5.8 monthsStrong durability with interim median duration of response (DOR) of 9.3 monthsHigh 35.5% objective response rate (ORR) and 58.1% disease control rate (DCR), as reported on 12 JulyComplete response rate increases to 12.9% and 16.1%, according to RECIST 1.1 and iRECIST, respectively1Efti in combination with pembrolizumab continues to be well-tolerated with no new safety signals This data compares favourably to historical results from anti-PD-1 therapy alone in 1L HNSCC patients with PD-L1 CPS <1 including a 7.9-month median OS, 12-month OS rate of 39%, 2.1-month median PFS, 2.6-month median DOR, 5.4% ORR and 32.4% DCR with no complete responses2-3. Marc Voigt, CEO of Immutep, noted, “Despite the significant progress of cancer immunotherapy over the past decade and the positive change in the therapeutic landscape it has brought to bear, head and neck cancer patients with PD-L1 expression of less than one continue to have limited treatment options that all include chemotherapy. We believe this data is an encouraging step in the right direction towards potentially bringing a new approach to this underserved population, representing up to 20% of patients with this difficult disease.” Next StepsPatients with PD-L1 CPS <1 is an underserved patient population with limited treatment options. Immutep will continue to follow the maturing data from TACTI-003 and engage with regulatory authorities regarding potential paths forward. The ESMO IO poster is available on the Posters & Publications section of Immutep’s website. KEYTRUDA® is a registered trademark of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA. About ImmutepImmutep is a clinical-stage biotechnology company developing novel LAG-3 immunotherapy for cancer and autoimmune disease. We are pioneers in the understanding and advancement of therapeutics related to Lymphocyte Activation Gene-3 (LAG-3), and our diversified product portfolio harnesses its unique ability to stimulate or suppress the immune response. Immutep is dedicated to leveraging its expertise to bring innovative treatment options to patients in need and to maximise value for shareholders. For more information, please visit www.immutep.com. Complete response rate was 9.6%, according to RECIST 1.1 and iRECIST, respectively, at earlier cut-off date as previously reported on 12 July 2024Burtness, B. et al. Pembrolizumab Alone or With Chemotherapy for Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma in KEYNOTE-048: Subgroup Analysis by Programmed Death Ligand-1 Combined Positive Score. Journal of Clinical Oncology 2022 40:21, 2321-2332. Note, the 5.4% ORR and 32.4% DCR are calculated from the 37 evaluable patients with CPS <1.Burtness B. et al. Abstract LB-258: Efficacy of first-line (1L) pembrolizumab by PD-L1 combined positive score <1, 1-19, and ≥20 in recurrent and/or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC): KEYNOTE-048 subgroup analysis. Cancer Res 15 August 2020; 80 (16_Supplement): LB–258. https://doi.org/10.1158/1538-7445.AM2020-LB-258 Australian Investors/Media:Catherine Strong, Sodali & Co+61 (0)406 759 268; catherine.strong@sodali.com U.S. Media:Chris Basta, VP, Investor Relations and Corporate Communications+1 (631) 318 4000; chris.basta@immutep.com