Announcement • Jul 13
Immutep Limited Provides Positive Update on INSIGHT-003 Phase I Trial and Discontinues TACTI-004 Phase III Trialin 1 Line Non-Small Cell Lung Cancer Immutep Limited announced a significant positive update of the investigator-initiated INSIGHT-003 Phase I trial evaluating eftilagimod alfa (efti) in combination with MSD’s anti-PD-1 therapy KEYTRUDA (pembrolizumab) and chemotherapy as 1 line therapy for advanced/metastatic non-small cell lung cancer in 51 evaluable non-squamous patients. Approximately 92% of patients enrolled in INSIGHT-003 had no or low PD-L1 expression (Tumour Proportion Score: TPS <50%), representing a population with significant unmet medical need. With a minimum of 30 months of follow-up, median Overall Survival was 30.9 months in the overall population regardless of PD-L1 expression (N=51), with the same median Overall Survival observed in patients with TPS <50% (N=47) and 37.8 months in TPS>=50% (N=4). These mature results continue to compare favourably to the 22.0 month median Overall Survival from a registrational trial of anti-PD-1 and doublet chemotherapy in non-squamous 1 line non-small cell lung cancer regardless of PD-L1 expression. Notably, patients with TPS <50%, for whom PD-L1 inhibitor-based therapies typically perform suboptimally, were overrepresented in INSIGHT-003 compared with historical benchmarks (~92% versus ~68%). No new safety signal was identified since the previous data cut-off. In March 2026, following a planned interim futility analysis, Immutep Limited announced that it would discontinue the TACTI-004 Phase III trial in 1 line non-small cell lung cancer based on a recommendation from the Independent Data Monitoring Committee. In the TACTI-004 futility analysis (N=173), the objective response rate in the overall patient population receiving standard of care plus efti was 42.9% compared with 55.1% in patients receiving standard of care plus placebo. The difference was observed across both squamous and non-squamous histologies, and the efti arm did not demonstrate superiority in any TPS subgroup. By comparison, the objective response rate in INSIGHT-003 has been 62.7%, despite the high proportion of patients with TPS <50%. Pending a final analysis of all patients, to date no new safety signals have been observed in TACTI-004. Preliminary immune monitoring data generated from TACTI-004 indicate that patients treated with efti exhibited a markedly different immune activation profile compared with that observed in previous studies. This assessment is based on analyses of absolute lymphocyte counts and circulating monocyte counts in blood. These findings contrast with observations from almost 600 patients treated with efti in five earlier studies (AIPAC, AIPAC-003, TACTI-mel, TACTI-002 and TACTI-003), which were presented at ASCO 2026, and also contrast with observations from INSIGHT-003. The TACTI-004 analysis, which includes all recruited and evaluable patients who received a minimum of 12 weeks of treatment, remains ongoing, with additional results expected in Third Quarter Calendar Year 2026. The company will continue to analyse this data as part of its ongoing root cause analysis of a range of potential factors, including manufacturing, and will share the outcome of that analysis as soon as it becomes available. Immutep Limited is being assisted in this process by its partners, including Dr. Reddy’s and WuXi Biologics. Additional results from the root cause analysis related to TACTI-004 are expected in Third Quarter Calendar Year 2026. Announcement • Jun 04
Immutep Presents Positive Interim Phase I Data for IMP761, A First-In-Class Lag-3 Agonist Antibody Immutep Limited announced it will present first-in-human clinical data for its lead autoimmune candidate, IMP761, at the European Alliance of Associations for Rheumatology (EULAR) Congress, in London, UK on 4th June 2026 at 1.30 pm UK time in a poster session. The data is from the ongoing Phase I, randomized, placebo-controlled, double-blind first-in-human study (NCT06637865) being conducted by the Centre for Human Drug Research (CHDR) in Leiden, the Netherlands, evaluating IMP761 in healthy volunteers using CHDR’s keyhole limpet haemocyanin (KLH) challenge model. The KLH challenge is a validated human immune response model that enables insights into IMP761’s pharmacological activity early in clinical development. Initial clinical findings showed significant and clinically relevant pharmacodynamic activity, including reduction of local inflammatory responses and attenuated T-cell activity compared to placebo across cohorts ranging from 0.9 mg/kg to 7 mg/kg, with 7 mg/kg being statistically significantly better in terms of skin blood perfusion compared to placebo (p = 0.029). IMP761 was safe and very well tolerated at all dose levels tested and the study successfully reached its primary endpoint for the single ascending dose part of the study. The pharmacokinetics of single ascending doses of IMP761 support once per 4-week dosing. The results highlight the potential of IMP761 to treat multiple autoimmune diseases driven by T-cell mediated inflammation and support further evaluation in a Phase II setting. The poster will be available on the Posters & Publications section of Immutep’s website following the presentation. IMP761 is a first-in-class immunosuppressive LAG-3 agonist antibody and the only LAG-3 agonist currently in clinical development. It is designed to selectively target activated T cells at sites of inflammation, with the aim of reducing pathological immune responses while preserving systemic immune function. Preclinical data supporting IMP761’s mechanism have been published in the Journal of Immunology, with additional supporting data in oligoarticular juvenile idiopathic arthritis (o-JIA) published in Pediatric Research. The program builds on Immutep’s expertise in the LAG-3 pathway and is being developed as a potential mechanism-based therapy across multiple autoimmune indications driven by T-cell-mediated inflammation. Announcement • May 31
Immutep Limited Announces Results from Systematic Evaluation of Eftilagimod Alfa in Combination with Standard-Of-Care Therapies in Late-Stage Cancer Patients Immutep Limited announced results from a systematic evaluation of 5 clinical trials of eftilagimod alfa ("efti") an antigen-presenting cell (APC) activator in combination with standard-of-care (SOC) therapies in late-stage cancer patients. In these trials, treatment with 30 mg subcutaneous (SC) efti plus SOC resulted in a significant increase in circulating absolute lymphocyte count (ALC), a blood-based measure of immune activity, compared to SOC alone where this effect was not seen. Increased ALC was significantly associated with improved clinical outcomes in the E+SOC group. A clinically meaningful and significant median overall survival (OS) improvement (median +7.7 months; p=0.00171) was seen in ALC responders compared to ALC non-responders in the efti + SOC group. No corresponding association between ALC response and OS was observed in the SOC alone group. The analysis included 5,922 patients across five independent clinical studies (TACTI-mel, TACTI-002, TACTI-003, AIPAC, AIPAC-003) spanning four cancer indications (NSCLC, HNSCC, MBC, melanoma), correlating the pharmacological effects of efti in combination with SOC treatments with clinical efficacy. Effects were observed across the different tumor types and were independent of the combination partner that is, chemotherapy or immunotherapy such as PD-1 antagonists. In addition, treatment with efti plus SOC was associated with a rapid and significant increase in circulating TH1-related biomarkers, which correlated with clinical response. Gene expression profiling further demonstrated enhanced T-cell function scores in responding patients. Collectively, these data suggest that efti induced broad immune activation, including circulating immune cells, cytokine responses and gene expression, and that this activation was associated with improved clinical benefit in late-stage cancer patients across multiple tumor types. The data will be presented in a poster at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting. Efti has been tested in multiple clinical trials, including the TACTI program (TACTI-mel, TACTI-002, TACTI-003 and TACTI-004). In March 2026, following a planned interim futility analysis, Immutep discontinued the TACTI-004 Phase III trial in first-line non-small cell lung cancer based on a recommendation from the Independent Data Monitoring Committee, and Immutep continues to review available data to understand factors behind the futility outcome and to evaluate implications for the broader eftilagimod alfa development program. The data presented in this explorative analysis does not include data from the TACTI-004 study, as immune data collection for that trial had not been completed at the time of the analysis. All data presented were generated from earlier clinical trials. Announcement • Mar 19
Immutep Limited Reports Progress From Phase I Study Of LAG-3 Agonist IMP761 For Autoimmune Diseases Immutep Limited reported that the single ascending dose (SAD) portion of its IMP761 study has been successfully completed, with dosing up to 14 mg/kg. IMP761 was well tolerated across all dose levels, and no safety concerns or dose-limiting toxicities were observed to date. The study is currently progressing in the multiple ascending dose (MAD) portion, which is evaluating pharmacokinetics and safety across two dose levels. Completion of the MAD portion is expected in the third quarter of 2026. IMP761 continues to show a clear immunosuppressive effect in healthy participants challenged with a foreign antigen in an intra-dermal reaction, with durable inhibition of T-cell–mediated responses after a single administration. These first-in-human findings support our mechanistic aim of selectively silencing pathogenic, self-antigen–specific memory T cells via LAG-3 agonism and provide the basis for dose levels to be tested in a future phase II trial in patients with autoimmunity. IMP761 data, including Phase I results, will be presented at the European Alliance of Associations for Rheumatology (EULAR) annual congress in London, UK on 4th June 2026 at 1.30 pm UK time in a poster view session. A LAG-3 agonist represents a novel therapeutic approach aimed at restoring immune tolerance by modulating T-cell activity, with potential applications across a range of autoimmune diseases, including rheumatoid arthritis, Type 1 diabetes, and multiple sclerosis. IMP761 is the first LAG-3 agonist antibody developed to potentially treat these large, increasingly prevalent disorders, each of which represent multi-billion-dollar markets. By enhancing the physiological “brake” function of LAG-3 to silence dysregulated self-antigen-specific memory T cells, IMP761 is designed to target the cause of autoimmune diseases and restore balance to the immune system. LAG-3 expression on activated T cells demonstrates high specificity for disease sites, especially in tissues characterised by chronic inflammation. This distinct characteristic of the LAG-3 immune checkpoint suggests IMP761 may enable a more targeted therapeutic approach with fewer adverse effects compared to other treatments. IMP761, a first-in-class immunosuppressive lymphocyte-activation gene-3 (LAG-3) agonist antibody, has the potential to address the root cause of many autoimmune diseases by specifically silencing autoimmune memory T cells that accumulate at disease sites and restoring balance to the immune system. Encouraging pre-clinical in vivo and in vitro studies show IMP761 inhibits peptide-induced T cell proliferation, activation of human primary T cells, and an antigen-specific delayed-type hypersensitivity (DTH) reaction. Additional preclinical data in oligoarticular juvenile idiopathic arthritis details how IMP761 led to a decrease in 48 hours in a broad spectrum of effector cytokines in coculture experiments where patients T cells are mixed with autologous synoviocytes. Similarly, IMP761 decreased IFN?, interleukin-4, and tumor necrosis factor a levels in supernatants from cocultures of T cells from patients with systemic sclerosis with their autologous dermal fibroblasts. Announcement • Mar 13
Immutep Limited Discontinues TACTI-004 Phase III Study in First Line NSCLC Following Futility Analysis Immutep Limited announced that the Independent Data Monitoring Committee (IDMC) for the TACTI-004 Phase III study evaluating eftilagimod alfa (efti) in patients in first line non-small cell lung cancer has recommended the discontinuation of the trial following a planned interim futility analysis in accordance with the study protocol. Based on its review of the available safety and efficacy data, the IDMC recommended that the trial be discontinued for futility. In response to the IDMC’s recommendation, enrolment in the study will be halted and the Company will implement an orderly wind down of the study, including appropriate patient follow up and site close out in accordance with regulatory and ethical obligations. Immutep now anticipates its cash runway will be extended well beyond the previously guided timeframe of Second Quarter calendar year 2027, which was set prior to the trial's cessation. The Company will provide an updated outlook on its revised cash runway and will reassess capital allocation priorities once operational assessments and a full analysis of the study data have been finalised. TACTI-004 (Two ACTive Immunotherapies) is a randomised, double-blind, controlled Phase III study evaluating eftilagimod alfa (efti), a first-in-class MHC Class II agonist, in combination with MSD’s anti-PD-1 therapy, KEYTRUDA (pembrolizumab), and chemotherapy as first line therapy for patients with advanced or metastatic non-small cell lung cancer with no EGFR, ALK or ROS1 genomic tumour aberrations. The global trial was to enrol approximately 756 patients regardless of PD-L1 expression and with non-squamous or squamous tumours at over 150 clinical sites in over 25 countries. Patients were being randomised 1:1 to receive either efti in combination with pembrolizumab and chemotherapy in the treatment arm or pembrolizumab in combination with chemotherapy and placebo in the control arm. The study’s dual primary endpoints were progression-free survival and overall survival. Efti is a novel immunotherapy that directly activates antigen-presenting cells or APCs (e.g. dendritic cells, monocytes) via the MHC Class II pathway to fight cancer. As an MHC Class II agonist, its activation of APCs engages the adaptive and innate immune system to initiate a broad anti-cancer immune response. This includes priming and activating cytotoxic T cells as well as generating important co-stimulatory signals & cytokines that further boost the immune system’s ability to combat cancer. Efti is under evaluation for a variety of solid tumours including non-small cell lung cancer (NSCLC), as well as head and neck squamous cell carcinoma (HNSCC), soft tissue sarcoma, and breast cancer. Its favourable safety profile has enabled various combinations like with anti-PD-[L]1 immunotherapy, radiotherapy, and/or chemotherapy. Efti has received Fast Track designation in first line HNSCC and in first line NSCLC from the United States Food and Drug Administration (FDA). Announcement • Feb 06
Immutep Limited Achieves 50% Enrolment in Global TACTI-004 (KeyNOTE-F91) Phase III Trial in 1L NSCLC Immutep Limited announced it has achieved 50% of the patient enrolment target in the TACTI-004 (KEYNOTE-F91) Phase III trial evaluating eftilagimod alfa (efti) in combination with MSD's (Merck & Co. Inc., Rahway, NJ, USA) anti-PD-1 therapy, KEYTRUDA (pembrolizumab), and chemotherapy as first line therapy for advanced/metastatic non-small cell lung cancer (1L NSCLC). The combination of efti with KEYTRUDA and chemotherapy has the potential to establish a new standard of care in 1L NSCLC, one of the largest and deadliest indications in oncology, by expanding the number of patients who respond to anti-PD-1 therapy., across all PD-L1 expression levels, along with enhancing clinical outcomes and extending patients' survival. The registrational TACTI-004 Phase III has enrolled 378 patients globally and enrolment continues its robust pace. Additionally, over 140 clinical sites are now activated across 27 countries. The futility analysis and completion of patient enrolment remain on track for the first quarter and the third quarter of CY2026, respectively. KEYTRUDA is a registered trademark of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co. Inc.,Rahway, NJ, USA. TACTI-004 (Two ACTive Immunotherapies) is a randomised, double-blind, controlled Phase III study evaluating efti, a first-in-class MHC Class II agonist, in combination with MSD's ("Merck & Co. Inc. ("Merck & Co. Ltd., Rahway, NJ,USA) anti-PD-1 Therapy, and chemotherapy as first line therapy For patients with advanced or metastatic non-small cell lung Cancer with no EGFR, ALK or ROS1 genomic tumour aberrations. As an MHC Class II agonist., its activation of APCs engages the adaptive and innate immune system to initiate a broad anti-cancer immune response. This includes priming and activating cytotoxic T cells as well as generating important co-stimulatory signals & cytokines that further boost the immune system's ability to combat cancer. Efti is under evaluation for a variety of solid tumours including non-small cell lung cancer ("NSCLC") in a pivotal Phase III trial called TACTI-004 (KEYNOTE-F91), as well as head and neck squamous cell carcinoma (HNSCC), soft tissue sarcoma, and breast cancer. Its favourable safety profile enables various combinations like with anti-PD-[L1 immunotherapy, radiotherapy, and/or chemotherapy. Efti has received Fast Track designation in first line HNSCC and in first line NSCLC from the United States Food and Drug Administration (FDA). 
