Avelumab

Media Release Entered into strategic collaboration with Dr. Reddy’s for commercialisation of eftilagimod alfa (efti) in all countries outside North America, Europe, Japan, and Greater ChinaIn January 2026, Immutep received ~A$30 million upfront payment from Dr. Reddy’s and is eligible to receive up to ~A$528 million in potential milestones, plus royalties on commercial sales of eftiStrong operational progress reported for TACTI-004 (KEYNOTE-F91) Phase III trial evaluating efti in first line non-small cell lung cancer (1L NSCLC), with completion of the futility analysis on track for the first quarter of CY2026Data from INSIGHT-003 at ESMO Congress 2025 show combination of efti with KEYTRUDA® and chemotherapy generates strong response rates across all PD-L1 expression levels in 1L NSCLC, including 61.7% ORR in low & no PD-L1 (TPS <50%), well above 40.8% from historical controlsPrimary endpoint met in EFTISARC-NEO Phase II evaluating neoadjuvant efti in soft tissue sarcoma detailed in Proferred Paper oral presentation at ESMO Congress 2025Translational data from EFTISARC-NEO shared in an oral presentation at CTOS 2025 demonstrate efti’s strong immune system activation with statistically-significant increases in multiple cytokines / chemokines and correlation between key immune proteins and pathologic responsesPositive feedback received from the FDA regarding the successful completion of Project Optimus requirements and agreement on 30 mg as the optimal biological dose for eftiStrong response rates and immune activation in heavily pretreated metastatic breast cancer patients from AIPAC-003 Phase II presented at 2025 San Antonio Breast Cancer SymposiumIMP761, a first-in-class LAG-3 agonist antibody for autoimmune diseases, completed 2.5 and 7 mg / kg dosing levels in a Phase I study; dose dependent immunosuppressive effect against a strong foreign antigen observed with continued favourable safety profileImmutep received A$4.6 million R&D tax incentive from the French government to support the ongoing and planned global clinical development of efti and IMP761Strong cash, cash equivalent and term deposit position of A$99.1 million as at 31 December 2025. Receipt of the ~A$30 million upfront payment subsequent to the quarter’s end leading to a pro-forma balance of A$129.3 million which extends Immutep’s cash reach well into Q2 CY2027, not including any potential milestone payments from the Dr. Reddy’s agreement. SYDNEY, AUSTRALIA, Jan. 29, 2026 (GLOBE NEWSWIRE) -- Immutep Limited (ASX: IMM; NASDAQ: IMMP) (“Immutep” or “the Company”), a late-stage immunotherapy company targeting cancer and autoimmune diseases, provides an update on its activities for the quarter ended 31 December 2025 (Q2 FY26). EFTI DEVELOPMENT PROGRAM IN ONCOLOGY IMMUTEP AND DR. REDDY’S STRATEGIC COLLABORATION Most significantly, in December, Immutep and Dr. Reddy’s announced that their respective wholly-owned subsidiaries, Immutep SAS and Dr. Reddy’s Laboratories SA, entered into a strategic collaboration and exclusive licensing agreement for the development and commercialisation of eftilagimod alfa (efti) in all countries outside North America, Europe, Japan, and Greater China. Efti is Immutep’s first-in-class novel immunotherapy that directly activates the immune system to fight cancer, which is under evaluation in a Phase III trial, TACTI-004 (KEYNOTE-F91). As per the agreement, and after the quarter’s end, Immutep has received from Dr. Reddy’s the upfront payment of USD 20 million (~AUD 30.2 million). It is also eligible to receive potential regulatory development and commercial milestone payments of up to USD 349.5 million (~AUD 528.4 million), plus royalties on commercial sales in these markets. Immutep holds the global manufacturing rights to the product across all markets and will supply the product to Dr. Reddy’s in the licensed markets. Immutep retains all rights to the product in the key pharmaceutical markets, including North America, Europe, and Japan. LUNG CANCER TACTI-004 (KEYNOTE-F91) – Ongoing Phase III Trial in 1L NSCLC In December, Immutep reported strong operational progress in the TACTI-004 (KEYNOTE-F91) Phase III trial evaluating 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), one of the largest indications in oncology. The combination of efti with KEYTRUDA and chemotherapy has the potential to establish a new standard of care in 1L NSCLC 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. As of mid-December, the registrational TACTI-004 trial had enrolled 289 patients (over 38% of the trial’s targeted enrolment of 756 patients), and enrolment continues at a robust pace. Additionally, the number of activated clinical sites exceeded 120 and 27 countries had received full regulatory approvals. As announced in October 2025, TACTI-004 had enrolled the necessary number of patients to conduct the futility analysis that remains on track for the first quarter of CY2026. Immutep anticipates reaching 50% of the patient enrolment target for TACTI-004 soon. Additionally, with the completion of Project Optimus as discussed below, TACTI-004 has started to open sites in the United States. INSIGHT-003 – Phase I Trial in Non-Squamous 1L NSCLC In October, Immutep announced promising data from the investigator-initiated INSIGHT-003 trial, which is evaluating the same immunotherapy/chemotherapy combination used in TACTI-004 (KEYNOTE-F91), was detailed in a poster presented by Dr. med. Akin Atmaca, Head of the Thoracic Oncology, Krankenhaus Nordwest, UCT-University Cancer Center, Frankfurt, Germany at the ESMO Congress 2025. In this multi-centre study, the novel combination of efti with KEYTRUDA and chemotherapy (carboplatin/pemetrexed) has generated strong objective response rates (ORR) and disease control rates (DCR) in 51 evaluable patients with advanced or metastatic non-squamous 1L NSCLC across all PD-L1 expression levels. Notably, the ORR and DCR reported in INSIGHT-003 outperforms historical controls irrespective of PD-L1 levels (e.g., TPS <1%, TPS 1-49%, and TPS >50%). This is particularly important for patients with low and no PD-L1 (TPS <50%), who represent over two-thirds of the 1L NSCLC patient population and for whom PD-(L)1 inhibitors typically perform suboptimally. In patients with TPS <50% (N=47), the combination with efti has achieved a strong and improved 61.7% ORR compared to historical control of 40.8%.1,2 Further to the strong efficacy data from INSIGHT-003, the combination with efti continues to have a favourable safety profile. SOFT TISSUE SARCOMA EFTISARC-NEO – Phase II Trial in Soft Tissue Sarcoma In October, Immutep announced that positive data from the EFTISARC-NEO Phase II investigator-initiated trial evaluating efti with radiotherapy plus KEYTRUDA in the neoadjuvant setting for resectable soft tissue sarcoma (STS) was shared in a Proffered Paper oral presentation by Katarzyna Kozak, M.D., Ph.D., Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland at the ESMO Congress 2025 in Berlin, Germany. The EFTISARC-NEO trial met the primary endpoint and significantly exceeded the study’s prespecified 35% tumour hyalinization/fibrosis with a median 51.5% tumour hyalinization/fibrosis (p<0.001) in the evaluable patient population (N=38).3 This may hold significance in terms of future outcomes as tumour hyalinization/fibrosis serves as an early surrogate endpoint correlated with improved survival in STS patients.4 Disease-free survival and overall survival data are immature at this stage and will be presented in the future. In November, early translational data from the EFTISARC-NEO trial were detailed in an oral presentation by Paweł Sobczuk, M.D., Ph.D., Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland, at the Connective Tissue Oncology Society (CTOS) 2025 Annual Meeting held in Boca Raton, Florida. Results from the initial twenty patients who underwent surgery in the trial show a strong immune system activation in line with efti’s mode of action, with statistically significant increases in the expression of key cytokines and chemokines in peripheral blood — specifically CXCL9, CXCL10, IL-23, and IFN-γ. The increase on treatment of immune response biomarkers like IFN-γ correlated with pathologic responses in this study, meaning patients with a biomarker increase during treatment also had a higher probability of a good clinical response at surgery. Additionally, during the quarter, the EFTISARC NEO trial was awarded second place in the distinguished Golden Scalpel Award competition in Poland. This competition recognises the most innovative solutions in Polish medicine and is presented by independent experts to initiatives that set new standards in advancing healthcare. EFTISARC-NEO was the only oncology project to receive this accolade, underscoring its leadership and breakthrough potential in cancer treatment. BREAST CANCER AIPAC-003 – Phase II/III Trial in Metastatic Breast Cancer Immutep continues to execute the AIPAC-003 trial, which has enrolled 71 metastatic hormone receptor positive (HR+), HER2-negative/low patients resistant to endocrine therapy including cyclin-dependent kinase 4/6 (CDK4/6) inhibitors or triple-negative breast cancer patients. Immutep completed patient enrolment in the randomised Phase II portion of the AIPAC-003 trial in late 2024. Patients across 22 clinical sites in Europe and the United States have been randomised 1:1 to receive either 30 mg or 90 mg dosing of efti in combination with paclitaxel to determine the optimal biological dose consistent with the FDA’s Project Optimus initiative and prior regulatory interaction with FDA. In October, Immutep announced that positive feedback had been received from the US Food and Drug Administration (“FDA”) regarding the successful completion of Project Optimus requirements and agreement on 30 mg as the optimal biological dose for efti. The agreement with the FDA on efti’s optimal biological dosing carries strategic importance in the ongoing and future clinical development of efti, including the global TACTI-004 (KEYNOTE-F91) Phase III trial. In December, Immutep announced that new data from the AIPAC-003 trial was presented by Dr. Nuhad Ibrahim, Professor, Department of Breast Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center at the 2025 San Antonio Breast Cancer Symposium (SABCS) taking place in San Antonio, Texas. The data presented shows that both efti dosing levels on top of weekly paclitaxel in heavily pretreated metastatic breast cancer patients, who received a median of three prior lines of systemic therapy, led to strong objective response rates (ORR) and disease control rates (DCR) of 41.9% and 87.1% (30 mg efti) and 48.5% and 78.8% (90 mg efti), respectively, in the evaluable population (N=64). New Investigator-Initiated Phase II Trial for Neoadjuvant Efti in HR+/HER2-negative Breast Cancer Immutep continues to progress with a new investigator-initiated Phase II trial evaluating neoadjuvant efti as monotherapy and in combination with chemotherapy prior to surgery in early-stage HR+/HER2-negative breast cancer patients. The trial aims to assess pathological complete response (pCR) after neoadjuvant efti treatment and neoadjuvant chemotherapy (NAC). The study will treat up to 50 evaluable patients in a two-stage design and will be primarily funded by grants and The GW University Cancer Center. Immutep will provide efti at no cost, technical support, and limited funding that falls within its existing budget. UROTHELIAL CANCER INSIGHT-005 The investigator-initiated INSIGHT-005 Phase I study, conducted by the Institute of Clinical Cancer Research, Krankenhaus Nordwest (IKF) to evaluate the safety and efficacy of efti in combination with avelumab in up to 30 patients with metastatic urothelial cancer, was discontinued by IKF after the end of the quarter. This decision was made, as significant changes in the treatment landscape created challenges with patient recruitment. Only 3 patients were recruited in total. IMP761 DEVELOPMENT PROGRAM FOR AUTOIMMUNE DISEASE IMP761 – Phase I Trial In December, Immutep announced a positive update from the placebo-controlled, double-blind first-in-human Phase I study in healthy participants evaluating IMP761, a first-in-class LAG-3 agonist antibody for autoimmune diseases. The single-ascending dose escalation portion of the trial successfully completed the 2.5 and 7 mg / kg dosing levels of IMP761 with continued positive safety and efficacy data. IMP761 was tolerated well with no treatment-related adverse reactions beyond mild intensity. Additionally, evidence of dose dependent immunosuppressive effects with IMP761 was observed with significant, long-lasting inhibition of the three T-cell-mediated intradermal reactions to a strong foreign antigen on day 2, 9 and 23. Given the encouraging efficacy and safety to date, the trial will continue as planned and additional updates are anticipated in the first half of CY2026 including a planned presentation of data at a major medical conference. INTELLECTUAL PROPERTY During the quarter, Immutep was granted four patents. The New Zealand Patent Office granted a new patent protecting Immutep’s intellectual property for a binding assay for determining MHC Class II binding activity of LAG-3 protein. The assay is used in the characterisation of efti in GMP-grade manufacturing. Three new patents directed to IMP761 were also granted. Two were granted in Brazil and one in Japan. CORPORATE & FINANCIAL SUMMARY Annual General MeetingImmutep successfully held its Annual General Meeting (AGM) during the quarter, with all resolutions put forward to shareholders strongly approved. The Company appreciates the continued support and engagement of its shareholders as it advances its strategic and operational objectives. Cash Flow Summary During the quarter, Immutep continued to exercise prudent cash management as it advanced its clinical trial programs for efti and for IMP761. The Company is well funded with a strong cash and cash equivalent, and term deposit balance as at 31 December 2025 of approximately A$99.1 million, which is in line with budget as at the beginning of FY2026, while progressing our clinical programs within announced timeframes. The total balance consists of 1) a cash and cash equivalent balance of A$72.7 million and 2) bank term deposits totaling A$26.4 million, which have been recognised as short-term investments due to having maturities of more than 3 months and less than 12 months. This amount is topped up by the upfront payment (~A$30.2 million) from Dr. Reddy’s received in January 2026, leading to a pro-forma balance of A$129.3 million at the time of preparing this report. In Q2 FY26, cash receipts from customers were A$4k. The net cash used in G&A activities in the quarter was A$1.3 million, compared to A$578k in Q1 FY26. During the quarter, Immutep received EUR2.59 million (~ A$4.6 million) R&D tax incentive payment in cash from the French Government under its Crédit d’Impôt Recherche scheme (CIR) to support the ongoing and planned global clinical development of efti and IMP761. The cash used in R&D activities during the quarter was A$9.9 million, compared to A$15.8 million in Q1 FY26. The higher figure in the prior quarter was primarily due to the large prepaid clinical trial expenses and higher milestone‑based manufacturing payments made in Q1 FY26. Payment for staff costs was A$2.6 million in the quarter, compared to A$3.4 million in Q1 FY26. Total net cash outflows used in operating activities in the quarter were A$9.4 million compared to A$19.0 million in Q1 FY26. Payments to Related Parties comprises Non-Executive Directors’ fees and Executive Directors’ remuneration of A$474k. Total cash outflow used in investing activities for the quarter was A$144k, which is mainly for the acquisition of office and lab equipment. Furthermore, during the quarter, a long-term vendor* agreed to defer payment of ~A$30 million which would be payable by Immutep for future services related to Biologics License Application (BLA) readiness by up to 30 months. This provides strong external validation of Immutep’s development strategy and long-term value creation potential. The current funds available to the Company at the time of this report provide an expected cash reach well into Q2 CY2027, not including receipt of any future potential milestone payments to be received. About ImmutepImmutep is a late-stage biotechnology company developing novel immunotherapies for cancer and autoimmune disease. The Company is a pioneer in the understanding and advancement of therapeutics related to Lymphocyte Activation Gene-3 (LAG-3), and its diversified product portfolio harnesses LAG-3’s 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. Shirish Gadgeel et al. Updated Analysis From KEYNOTE-189: Pembrolizumab or Placebo Plus Pemetrexed and Platinum for Previously Untreated Metastatic Nonsquamous Non–Small-Cell Lung Cancer. JCO 38, 1505-1517 (2020). DOI:10.1200/JCO.19.03136Immutep’s Efti with KEYTRUDA® (pembrolizumab) & Chemotherapy Achieves High Response Rates in First-Line Non-Small Cell Lung Cancer - May 2025 press releaseESMO Congress 2025 Proffered Paper presentation, “EFTISARC-NEO: A phase II study of neoadjuvant eftilagimod alpha, pembrolizumab and radiotherapy in patients with resectable soft tissue sarcoma”Rao SR et al. Extent of tumor fibrosis/hyalinization and infarction following neoadjuvant radiation therapy is associated with improved survival in patients with soft-tissue sarcoma. Cancer Med. 2022 Jan;11(1):194-206. doi: 10.1002/cam4.4428. Epub 2021 Nov 27. PMID: 34837341; PMCID: PMC8704179. Australian Investors/Media:Eleanor Pearson, Sodali & Co.+61 2 9066 4071; eleanor.pearson@sodali.com U.S. Investors/Media:Chris Basta, VP, Investor Relations and Corporate Communications+1 (631) 318 4000; chris.basta@immutep.com ------------------------------------ *Immutep does not consider the arrangement with or the identity of the vendor to be information that a reasonable person would expect to have a material effect on the price or value of the entity’s securities and considers that this disclosure contains all materially relevant and accurate information in assessing the impact on the value of Immutep’s securities. The long-term vendor is recognised internationally as one of the leaders in its sector, supporting a broad portfolio of biotechnology and pharmaceutical companies across multiple regions. The vendor operates multiple state-of-the-art facilities across Asia, North America, and Europe and is recognised for its strong financial position, robust global infrastructure, and industry-leading quality systems. It is publicly listed on a major international exchange.

点击蓝字 关注我们 TGF-β（transforming growth factor β）是一种多效性细胞因子，在细胞增殖、分化和组织纤维化等多种生物过程中发挥关键作用。 TGF-β超家族成员包括TGF-β1/2/3、BMP、Activin 等；其受体主要为I型和II型丝氨酸/苏氨酸激酶受体（TβRI，TβRII）。TGF-β信号通路的功能取决于细胞和组织微环境，其调节机制十分复杂。 TGF-β信号传导可分为Smad依赖的经典途径和非Smad依赖性的途径： 1. 经典途径 Smad 依赖通路是TGF-β 信号转导的核心通路，从信号启动到基因调控形成闭环，每一步都精准可控。其中Smad4是该通路的核心因子。 2. 非Smad依赖途径 除了经典 Smad 通路，TGF-β 还能通过多种非 Smad 依赖途径传递信号，应对不同生理需求，其通路主要包括：MAPK通路；PI3K-AKT通路；Rho GTP通路。 TGF-β 信号通路主要在以下一些领域发挥重要作用： 免疫应答调节：通过 Smad 通路抑制 T细胞和B 细胞的活化与增殖、减少炎症因子（如 IL-2、IFN-g）的分泌，避免自身损伤；TGF-β也是调节性T细胞（Treg）分化过程中的重要因子，可预防各类自身免疫性疾病。 促进损伤修复及组织纤维化：TGF-β是组织损伤后修复反应的核心因子。在伤口愈合初期，TGF-β通过诱导炎症细胞的趋化、促进肉芽组织形成、刺激成纤维细胞的增殖、并促进胶原等细胞外基质蛋白的合成，对于组织重建不可或缺。然而，当TGF-β信号持续过度活化时，会导致细胞外基质的过度沉积和正常组织结构的破坏，从而引发病理性纤维化。TGF-β信号通路与多种器官纤维化的病理发展密切相关，如特发性肺纤维化、肝纤维化/肝硬化、肾间质纤维化和心肌纤维化等，是抗纤维化药物研发的核心靶点。 在肿瘤微环境（TME）中的双重作用： 在癌症发生的早期阶段，TGF-β 更多地展现出其作为肿瘤抑制因子的一面，能够激活一系列细胞内的信号通路，通过抑制癌细胞的增殖、诱导癌细胞凋亡，来阻止肿瘤的形成和发展。 在TME中，肿瘤细胞及肿瘤相关基质细胞常常大量分泌TGF-β。在肿瘤晚期，这种高水平的TGF-β创造了一个强烈的免疫抑制微环境：抑制细胞毒性T细胞和NK细胞的抗肿瘤功能，促进Treg和髓源性抑制细胞（MDSC）等抑制性免疫细胞的募集与功能，从而帮助肿瘤实现免疫逃逸，抵消其他免疫疗法（如PD-1抗体疗法）的效果。 TGF-β的药物开发： 该通路最著名的药物当属默克研发的PD-L1/TGF-b双功能抗体M7824。其结构包括完整的PD-L1抗体端（avelumab）和TGF-bRII胞外结构域（trap），理论上可同时阻断PD-1及TGF-b信号通路，从而打造免疫疗法2.0产品。 从临床前研究来看，M7824在多个肿瘤模型中表现出优异的抗肿瘤疗效。 在早期临床试验中，M7824同样在多种肿瘤中显示疗效，尤其是PD-L1阳性患者的响应率非常高，显著优于PD-1抗体的历史数据。 然而，好景不长。2021年开始，M7824接连在多种适应症上遭遇临床失利。2021年1月，M7824在微卫星高度不稳定/错配修复缺陷实体瘤II期临床试验以及NSCLC III期临床试验中失败；2021年3月，M7824单药二线治疗局部晚期或转移性胆道癌的II期临床试验失败；2021年8月，M7824联合吉西他滨和顺铂一线治疗局部晚期或转移性胆道癌患者的研究也宣告失败。 在2022年默克的年报中，M7824的研发管线已经消失无踪。 小结： 作为一种多效细胞因子，TGF-b的生物学机制非常复杂。这种复杂性不仅表现在配体受体的表达和发布、以及因此传导的下游信号通路；同时表现在TGF-b在疾病的不同阶段可能发挥截然不同的功效，这也给药物开发带来了极大的挑战。靶向TGF-b通路的研发任重而道远。 Reference： Rik Derynck et al., Nature Reviews Clinical Oncology, 2021, 18(1): 9-34. TGFβ biology in cancer progression and immunotherapy. Robert J Salmond et al., Biology, 2023, 12(2): 297. Regulation of T Cell Activation and Metabolism by Transforming Growth Factor-Beta. Xueke Shi et al., Biomolecules, 2020, 10(12): 1666. Transforming Growth Factor-β Signaling in Fibrotic Diseases and Cancer-Associated Fibroblasts. Joshua M Moreau et al., Science Immunology, 2022, 7(69): eabi4613. Transforming growth factor–β1 in regulatory T cell biology. Yan Lan et al., Science Translational Medicine, 2018, 10(424): eaan5488. Enhanced preclinical antitumor activity of M7824, a bifunctional fusion protein simultaneously targeting PD-L1 and TGF-β. Luis Paz-Ares et al., Journal Thoracic Oncology, 2020, 15(7): 1210-1222. Bintrafusp Alfa, a Bifunctional Fusion Protein Targeting TGF-β and PD-L1, in Second-Line Treatment of Patients With NSCLC: Results From an Expansion Cohort of a Phase 1 Trial.