Core Insights - Immutep Limited has successfully dosed the first patient in its pivotal TACTI-004 Phase III trial, evaluating eftilagimod alfa in combination with KEYTRUDA and chemotherapy for advanced non-small cell lung cancer (NSCLC) [1][2] Company Overview - Immutep is a late-stage biotechnology company focused on developing immunotherapies for cancer and autoimmune diseases, particularly leveraging LAG-3 to stimulate or suppress immune responses [7] Trial Details - TACTI-004 is a randomized, double-blind, controlled Phase III study that will enroll approximately 756 patients across more than 150 clinical sites in over 25 countries [5][6] - The trial's dual primary endpoints are progression-free survival and overall survival, with patients randomized 1:1 to receive either the treatment combination or a control [6] Market Context - Lung cancer is the leading cause of cancer-related deaths, with an expected increase in incidence to approximately 3 million cases worldwide by 2030; NSCLC accounts for about 80-85% of lung cancer diagnoses [3] - There is a significant unmet need for new treatment options for NSCLC, as less than 30% of patients survive five years post-diagnosis [3] Regulatory and Recruitment Status - Recruitment for TACTI-004 is ongoing, with approvals from various regulatory authorities including Australia, Canada, and several European countries; further approvals are anticipated [2][5]

Core Insights - Immutep Limited is set to present a poster on the pivotal TACTI-004 Phase III trial at the European Lung Cancer Congress (ELCC) 2025, highlighting its focus on immunotherapy for cancer treatment [1][2] Group 1: Trial Overview - The TACTI-004 Phase III trial evaluates Immutep's MHC Class II agonist, eftilagimod alfa (efti), in combination with Merck's anti-PD-1 KEYTRUDA® and chemotherapy for first-line treatment of advanced or metastatic non-small cell lung cancer (1L NSCLC) [2][3] - The global trial aims to enroll approximately 750 patients across over 150 clinical sites in more than 25 countries, regardless of PD-L1 expression [2] Group 2: Presentation Details - The poster presentation is titled "TACTI-004: a double-blinded, randomized phase 3 trial in patients with advanced/metastatic non-small cell cancer receiving eftilagimod alfa (MHC class II agonist) in combination with pembrolizumab (P) and chemotherapy (C) versus placebo + P + C" [4] - The presentation is scheduled for March 26, 2025, at 13:50 CET, with the poster to be made available on Immutep's website following the event [4] Group 3: Eftilagimod Alfa (efti) Profile - Efti is a proprietary soluble LAG-3 protein and MHC Class II agonist that stimulates both innate and adaptive immunity, enhancing the immune response against cancer [5][6] - Efti is under evaluation for various solid tumors, including NSCLC, head and neck squamous cell carcinoma, and metastatic breast cancer, and has received Fast Track designation from the FDA for first-line treatments in HNSCC and NSCLC [6] Group 4: Company Background - Immutep is a late-stage biotechnology company focused on developing novel immunotherapies for cancer and autoimmune diseases, leveraging its expertise in Lymphocyte Activation Gene-3 (LAG-3) [7] - The company aims to provide innovative treatment options while maximizing shareholder value [7]

[Results for Announcement to the Market](index=2&type=section&id=Results%20for%20Announcement%20to%20the%20Market) [Financial Performance Summary](index=2&type=section&id=Financial%20Performance%20Summary) The company's total revenue and other income rose 77% to A$7.28 million, though net loss increased 5% to A$22.38 million due to higher R&D expenses Key Financial Metrics (Half-Year Ended 31 Dec 2024 vs 31 Dec 2023) | Metric | Change | Value (A$) | | :--- | :--- | :--- | | Other Income | up 77% | 7,276,004 | | Total revenue and other income | up 77% | 7,276,004 | | Loss after tax attributable to members | up 5% | (22,377,429) | Net Tangible Assets per Share | Date | Cents | | :--- | :--- | | As at 31 December 2024 | 11.30 | | As at 31 December 2023 | 8.99 | - The increase in net loss was primarily driven by a **A$4.89 million rise in R&D and intellectual property expenses**, partially offset by increased interest and grant income[4](index=4&type=chunk) [Directors' Report](index=4&type=section&id=Directors'%20Report) [Principal Activities](index=4&type=section&id=Principal%20Activities) The company is a clinical-stage biotechnology firm developing novel immunotherapies related to the LAG-3 protein for cancer and autoimmune diseases - The company's core focus is on developing **LAG-3 related immunotherapies** for both cancer and autoimmune diseases[10](index=10&type=chunk) [Review of Operations](index=4&type=section&id=Review%20of%20Operations) The company initiated its TACTI-004 Phase III trial, reported positive data from other trials, and advanced its autoimmune disease program [TACTI-004: Phase III trial in 1L NSCLC](index=5&type=section&id=TACTI-004%3A%20Phase%20III%20trial%20in%20first%20line%20non-small%20cell%20lung%20cancer%20(1L%20NSCLC)) Immutep commenced its registrational TACTI-004 Phase III trial for efti in combination with KEYTRUDA® and chemotherapy for 1L NSCLC patients - The TACTI-004 trial is a global, randomized, double-blind Phase III study with dual primary endpoints of progression-free survival and overall survival, enrolling **~750 patients**[15](index=15&type=chunk) [TACTI-003: Phase IIb trial in 1L HNSCC](index=5&type=section&id=TACTI-003%3A%20Phase%20IIb%20trial%20in%20first%20line%20head%20and%20neck%20squamous%20cell%20carcinoma%20(1L%20HNSCC)) The TACTI-003 trial reported positive new data, showing superior performance for the efti and KEYTRUDA combination in both PD-L1 positive and negative patients - In PD-L1 positive (CPS ≥1) patients, the combination showed a **durable response of 17.5 months**, with the largest outperformance in the CPS ≥20 subgroup[16](index=16&type=chunk) - In PD-L1 negative (CPS <1) patients, the combination achieved a **35.5% ORR**, a **12.9% complete response rate**, and a 12-month OS rate of 67%[18](index=18&type=chunk)[19](index=19&type=chunk) [AIPAC-003: Phase II/III trial in Metastatic Breast Cancer](index=6&type=section&id=AIPAC-003%3A%20Integrated%20Phase%20II%2FIII%20trial%20in%20Metastatic%20Breast%20Cancer) Patient enrollment was completed for the randomized Phase II portion of the AIPAC-003 trial evaluating efti with chemotherapy in metastatic breast cancer - Patient enrollment was completed in October 2024 for the **65-patient randomized Phase II portion** of the trial, which is evaluating two doses of efti (30mg vs 90mg) with chemotherapy[21](index=21&type=chunk) [Other Phase I and II Studies with Eftilagimod Alpha](index=7&type=section&id=Other%20Phase%20I%20and%20II%20Studies%20with%20Eftilagimod%20Alpha) Other efti studies continued to yield positive results, including impressive overall survival in NSCLC and significant efficacy in soft tissue sarcoma - In the TACTI-002 trial (Part A), median OS reached **35.5 months** in 1L NSCLC patients with PD-L1 expression (TPS ≥1%)[23](index=23&type=chunk) - The EFTISARC-NEO trial in soft tissue sarcoma demonstrated a median **50% tumor hyalinization/fibrosis**, a threefold increase over the historical median from radiotherapy alone[24](index=24&type=chunk) [IKF INSIGHT Clinical Trial Platform](index=8&type=section&id=Institute%20of%20Clinical%20Cancer%20Research%20(IKF)%20INSIGHT%20Clinical%20Trial%20Platform) The investigator-initiated INSIGHT platform generated promising data, with the INSIGHT-003 trial showing significant survival benefits in NSCLC - Mature data from the INSIGHT-003 trial (N=21) in NSCLC showed a median OS of **32.9 months**, median PFS of 12.7 months, and a 24-month OS rate of **81.0%**[32](index=32&type=chunk) - The INSIGHT-003 trial completed its enrollment target of approximately **50 evaluable patients** in January 2025[30](index=30&type=chunk) [Autoimmune Disease Clinical Development](index=8&type=section&id=Autoimmune%20Disease%20Clinical%20Development) The company advanced its autoimmune pipeline by initiating a Phase I trial for IMP761 and regaining all rights to IMP731 from GSK - The Phase I trial for **IMP761**, a first-in-class LAG-3 agonist for autoimmune diseases, began dosing in August 2024 with favorable initial safety data[34](index=34&type=chunk) - All development and commercialization rights for the LAG-3 depleting antibody **IMP731** have been restored to Immutep from GSK[35](index=35&type=chunk) [Intellectual Property](index=10&type=section&id=Intellectual%20Property) Immutep strengthened its intellectual property portfolio by securing ten new patents across various territories for its key product candidates - The company was granted **ten new patents** for its key assets: efti, IMP761, and the out-licensed LAG525 (licensed to Novartis)[46](index=46&type=chunk)[47](index=47&type=chunk)[49](index=49&type=chunk)[50](index=50&type=chunk) [Corporate Summary & Financial Performance](index=10&type=section&id=Corporate%20Summary%20%26%20Financial%20Performance) The company joined the S&P/ASX 300 index and maintained a strong financial position with A$159.26 million in cash, ensuring a runway to late 2026 - The company was added to the **S&P/ASX 300 index**, recognizing its growth and increasing market visibility[52](index=52&type=chunk) Financial Performance Highlights (A$) | Metric | H1 FY25 | H1 FY24 | | :--- | :--- | :--- | | Total Revenue & Other Income | 7.28 million | 4.11 million | | R&D and IP Expenses | 25.33 million | 20.44 million | | Corporate Administrative Expenses | 4.23 million | 4.80 million | | Loss After Tax | (22.38 million) | (21.23 million) | - The company is well-funded with a cash, cash equivalent, and term deposit balance of approximately **A$159.26 million**, providing an expected cash runway to the end of calendar year 2026[59](index=59&type=chunk) [Outlook](index=11&type=section&id=Outlook) The company's focus is on advancing the TACTI-004 Phase III trial for efti, which provides a clear path to potential marketing approval - The initiation of the **TACTI-004 Phase III trial** has transformed Immutep, providing a visible pathway to marketing approval for its lead product, efti[60](index=60&type=chunk) [Auditor's Independence Declaration](index=12&type=section&id=Auditor's%20Independence%20Declaration) [Declaration](index=12&type=section&id=Declaration) The lead auditor confirmed no contraventions of auditor independence requirements under the Corporations Act 2001 - The auditor, PricewaterhouseCoopers, declared that there were **no contraventions of auditor independence requirements** or any applicable code of professional conduct during their review[64](index=64&type=chunk)[66](index=66&type=chunk) [Half-Year Financial Report](index=13&type=section&id=Half-Year%20Financial%20Report) [Consolidated Statement of Comprehensive Income](index=13&type=section&id=Consolidated%20Statement%20of%20Comprehensive%20Income) The company reported a net loss of A$22.38 million for the half-year, an increase from the prior period's A$21.23 million loss Consolidated Statement of Comprehensive Income (A$) | Line Item | 31 December 2024 | 31 December 2023 | | :--- | :--- | :--- | | Total revenue and other income | 7,276,004 | 4,110,397 | | R&D and IP expenses | (25,330,664) | (20,436,458) | | Corporate administrative expenses | (4,233,642) | (4,802,183) | | **Loss for the half-year** | **(22,377,429)** | **(21,228,191)** | | Other comprehensive income/(loss) | 5,074,247 | (600,632) | | **Total comprehensive loss** | **(17,303,182)** | **(21,828,823)** | | Basic and diluted loss per share (Cents) | (1.54) | (1.79) | [Consolidated Balance Sheet](index=14&type=section&id=Consolidated%20Balance%20Sheet) The company's balance sheet reflects a strong liquidity position with A$173.76 million in current assets and net assets of A$172.47 million Consolidated Balance Sheet Summary (A$) | Line Item | 31 December 2024 | 30 June 2024 | | :--- | :--- | :--- | | Cash and cash equivalents | 73,886,442 | 161,790,147 | | Short-term investments | 85,374,520 | 20,086,308 | | **Total current assets** | **173,764,061** | **191,350,442** | | **Total assets** | **182,328,516** | **201,579,281** | | **Total liabilities** | **9,856,310** | **12,057,539** | | **Net assets** | **172,472,206** | **189,521,742** | [Consolidated Statement of Changes in Equity](index=15&type=section&id=Consolidated%20Statement%20of%20Changes%20in%20Equity) Total equity decreased to A$172.47 million, primarily due to the period's net loss, partially offset by positive foreign currency translation Movement in Total Equity (A$) | Description | Amount | | :--- | :--- | | Balance at 1 July 2024 | 189,521,742 | | Loss for the half-year | (22,377,429) | | Other comprehensive income | 5,074,247 | | Employee Share based payments | 253,646 | | **Balance at 31 December 2024** | **172,472,206** | [Consolidated Statement of Cash Flows](index=16&type=section&id=Consolidated%20Statement%20of%20Cash%20Flows) Net cash outflow from operations was A$28.55 million, with cash and equivalents decreasing to A$73.89 million after investing activities Consolidated Statement of Cash Flows Summary (A$) | Line Item | 31 December 2024 | 31 December 2023 | | :--- | :--- | :--- | | Net cash outflows from operating activities | (28,546,264) | (18,450,440) | | Net cash outflows in investing activities | (62,815,234) | (419,121) | | Net cash outflows in financing activities | (427,170) | (431,859) | | **Net increase in cash and cash equivalents** | **(91,788,668)** | **(19,301,420)** | | Cash and cash equivalents at end of period | 73,886,442 | 103,734,981 | [Notes to the Consolidated Financial Statements](index=17&type=section&id=Notes%20to%20the%20Consolidated%20Financial%20Statements) The notes confirm the company's going concern status, its single operating segment, and details of an outstanding convertible note - The financial statements have been prepared on a **going concern basis**, as the directors believe the Group's total cash and short-term investment balance of **A$159.26 million** is sufficient to pay its debts for at least the next 12 months[83](index=83&type=chunk)[84](index=84&type=chunk) - The Group operates in a single operating segment: **Cancer Immunotherapy**[88](index=88&type=chunk) - As of the reporting date, a 2015 convertible note with a notional amount of **A$1.10 million** remains outstanding, maturing on August 4, 2025[99](index=99&type=chunk)[100](index=100&type=chunk) [Directors' Declaration](index=28&type=section&id=Directors'%20Declaration) [Declaration Statement](index=28&type=section&id=Declaration%20Statement) The directors declared the financial statements provide a true and fair view and that the company can meet its financial obligations - The directors declared that the financial statements give a **true and fair view** of the group's financial position and performance, and that the company is a **going concern**[125](index=125&type=chunk) [Independent Auditor's Review Report](index=29&type=section&id=Independent%20Auditor's%20Review%20Report%20to%20the%20Members) [Auditor's Conclusion](index=29&type=section&id=Auditor's%20Conclusion) The auditor's review found no matter suggesting the financial report does not comply with the Corporations Act 2001 - The auditor's review concluded that nothing came to their attention to suggest the half-year financial report does not comply with the Corporations Act 2001, including giving a **true and fair view** of the Group's financial position and performance[126](index=126&type=chunk)[127](index=127&type=chunk) - The auditor clarified that a review is **substantially less in scope than an audit** and, accordingly, they do not express an audit opinion[132](index=132&type=chunk)

Core Viewpoint - Immutep Limited has made significant advancements in its clinical programs, particularly with the initiation of the Phase III trial for eftilagimod alfa (efti) in first-line metastatic non-small cell lung cancer (1L NSCLC), marking its transition into a Phase III biotechnology company [3][4][8]. Clinical Development Updates - The TACTI-004 Phase III trial for efti in 1L NSCLC commenced in December 2024, following regulatory approval from the Australian Therapeutic Goods Administration [3][4]. - Positive results from the TACTI-003 (KEYNOTE-C34) Phase IIb trial were reported, showing a 67% 12-month overall survival (OS) rate and a promising progression-free survival (PFS) of 5.8 months for patients with PD-L1 negative tumors [5][6]. - The AIPAC-003 trial in metastatic breast cancer completed patient enrollment in October 2024, with 65 patients randomized to receive different doses of efti in combination with paclitaxel [7][9]. - The INSIGHT-003 trial reported a median OS of 32.9 months and a 24-month OS rate of 81.0% for patients with advanced or metastatic non-squamous NSCLC [10][11][12]. - The EFTISARC-NEO trial demonstrated a greater than three-fold increase in tumor hyalinization compared to historical data, indicating significant efficacy in soft tissue sarcoma [13][14][15]. Product Development and Research - IMP761, a first-in-class agonist LAG-3 antibody for autoimmune diseases, reported favorable initial safety data from its Phase I study [16][17]. - Collaboration with Monash University led to new findings on the binding of LAG-3 to MHC Class II, enhancing the understanding of LAG-3 therapeutics [18]. Intellectual Property - Immutep was granted three new patents for efti and IMP761 in various territories, including Brazil and Japan, enhancing its intellectual property portfolio [19][20]. Financial Overview - As of December 31, 2024, Immutep reported a strong cash position of approximately A$159.26 million, expected to fund operations until the end of CY2026 [23]. - The net cash used in R&D activities during Q2 FY25 was A$16.2 million, reflecting increased clinical trial activities [25]. - Total cash flow used in investing activities for the quarter was A$30.4 million, primarily due to an increase in short-term investments [26].

Core Insights - The article emphasizes the importance of understanding the science behind biotech investments to avoid pitfalls in the industry [1]. Group 1 - The author has a PhD in biochemistry and extensive experience in analyzing clinical trials and biotech companies [1]. - The mission is to educate investors on the scientific aspects of biotech businesses to facilitate informed decision-making [1].

Core Insights - Immutep Limited has completed patient enrolment in the EFTISARC-NEO trial, which evaluates eftilagimod alpha in combination with radiotherapy and KEYTRUDA® for patients with resectable soft tissue sarcoma [1][2][4] Group 1: Trial Details - The Phase II trial, conducted by the Maria Skłodowska-Curie National Research Institute of Oncology, has successfully enrolled 40 patients [2] - Positive data from the trial was presented at the CTOS Annual Meeting in November 2024, showing a greater than three-fold increase in tumour hyalinization/fibrosis (median 50%) compared to a historical median of 15% from radiotherapy alone [3] - The treatment has shown safety with no grade ≥3 toxicities related to efti and pembrolizumab [4] Group 2: Future Expectations - Data updates from the EFTISARC-NEO trial are anticipated in 2025 [4][8]

Core Insights - Immutep Limited has completed patient enrolment in the INSIGHT-003 trial, which is evaluating the combination of eftilagimod alpha (efti) with KEYTRUDA® and doublet chemotherapy for advanced non-squamous non-small cell lung cancer [1][7] - The Phase I trial has successfully enrolled approximately 50 evaluable patients across multiple clinical sites in Germany [2] - Initial Overall Survival results from INSIGHT-003 indicate a median Overall Survival of 32.9 months and a 24-month Overall Survival rate of 81.0%, which is significantly better than the 22.0-month median OS and 24-month OS rate of 45.5% from a registrational trial of anti-PD-1 and doublet chemotherapy [3][6] - Additional data updates from INSIGHT-003 are anticipated in 2025 and beyond [3][7] Company Overview - Immutep is a clinical-stage biotechnology company focused on developing novel LAG-3 immunotherapies for cancer and autoimmune diseases [5] - The company is recognized for its pioneering work in LAG-3 therapeutics, aiming to provide innovative treatment options and maximize shareholder value [5]

Core Insights - Immutep Limited has announced favorable initial safety data for IMP761, the world's first LAG-3 agonist, with no treatment-related adverse events reported in the first three cohorts of a Phase I study [1][2] - The study aims to assess the safety and immunosuppressive efficacy of IMP761 in healthy participants, with additional safety data and pharmacokinetic/pharmacodynamic assessments expected in the first half of CY2025 [2][3] Company Overview - Immutep is a clinical-stage biotechnology company focused on developing LAG-3 immunotherapies for cancer and autoimmune diseases, leveraging its expertise in LAG-3 to create innovative treatment options [6] - The company is conducting a Phase I trial of IMP761 at the Centre for Human Drug Research in the Netherlands, involving up to 49 participants [2] Product Details - IMP761 is designed to enhance the "brake" function of LAG-3 on T cells, aiming to restore immune system balance and address the root causes of various autoimmune diseases [1][3] - Preclinical studies have shown that IMP761 significantly decreases inflammatory cytokines and effectively suppresses antigen-specific T cell-mediated immune responses [3][5] Future Developments - The company is eager to generate more data from the ongoing study, which is crucial for derisking this promising asset in the context of autoimmune diseases [2] - Additional safety data and assessments of pharmacokinetic and pharmacodynamic relationships are anticipated in the first half of CY2025 [1][2]

Group 1 - Immutep Limited has published findings in Science Immunology that clarify how human LAG-3 binds to its main ligand MHC Class II, providing a foundation for developing blocking LAG-3 therapeutics, including its anti-LAG-3 small molecule program [1][3] - The study reveals the crystal structure of a human LAG-3/HLA-II complex, which is significant for future therapeutic developments targeting LAG-3 [1][3] - Eftilagimod alfa (efti) has been shown to preferentially bind to a subset of MHC Class II molecules on antigen-presenting cells, leading to their activation [1][3] Group 2 - The research was conducted under the supervision of Professor Jamie Rossjohn at Monash University's Biomedicine Discovery Institute, highlighting the importance of industry-academia collaborations in advancing LAG-3 research [2] - The findings contribute to a deeper understanding of the LAG-3 immune control mechanism, which is a clinically validated target of interest across various sectors [2][3] - The study emphasizes the unique action of efti as an MHC-II agonist, which preferentially binds to specific MHC-II molecules clustered in lipid raft microdomains on antigen-presenting cells [3]

Core Insights - The article highlights positive clinical results from Immutep Limited's TACTI-003 Phase IIb trial, demonstrating the efficacy of eftilagimod alpha (efti) in combination with pembrolizumab for treating difficult-to-treat head and neck cancer patients with PD-L1 CPS <1 [1][4][5] Group 1: Clinical Results - Median overall survival (OS) has not yet been reached, with a 12-month OS rate of 67%, significantly higher than historical controls [1][4] - Promising progression-free survival (PFS) of 5.8 months and strong durability with an interim median duration of response (DOR) of 9.3 months [4] - The objective response rate (ORR) is 35.5%, and the disease control rate (DCR) is 58.1%, with complete response rates increasing to 12.9% and 16.1% according to RECIST 1.1 and iRECIST, respectively [4][5] Group 2: Treatment Tolerance and Safety - The combination treatment continues to be well-tolerated, with no new safety signals reported [4][5] - This data compares favorably to historical results from anti-PD-1 therapy alone, which showed a median OS of 7.9 months and a 12-month OS rate of 39% [4] Group 3: Market Implications - The results indicate a potential new treatment option for the underserved population of head and neck cancer patients with PD-L1 expression of less than one, representing up to 20% of patients [5][6] - The company plans to continue monitoring the maturing data from TACTI-003 and engage with regulatory authorities regarding potential paths forward [6]