On July 30, 2025 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, reported an update on its activities for the quarter ended 30 June 2025 (Q4 FY25) (Press release, Immutep, JUL 30, 2025, View Source [SID1234654646]).
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EFTI DEVELOPMENT PROGRAM IN ONCOLOGY
LUNG CANCER
TACTI-004 (KEYNOTE-F91) – Ongoing Phase III Trial in 1L NSCLC
Immutep’s pivotal TACTI-004 Phase III trial is on track and continues to build momentum and is recruiting patients at a growing number of activated clinical sites and countries, with now 78 sites and 23 countries having received regulatory approval, following the successful dosing of the first patient at Calvary Mater Newcastle Hospital in Australia in March 2025.
The TACTI-004 trial evaluates eftilagimod alfa (efti), a first-in-class MHC Class II agonist, in combination with MSD’s (Merck & Co., Inc., Rahway, NJ, USA) anti-PD-1 therapy KEYTRUDA and chemotherapy as first line treatment for patients with advanced or metastatic non-small cell lung cancer (1L NSCLC). The global Phase III trial with efti will randomize approximately 756 patients at more than 150 clinical sites and trial results will inform a potential marketing approval application in non-small cell lung cancer, one of the largest indications in oncology.
In late May, Immutep presented a Trial-in-Progress poster for TACTI-004 at the 2025 American Society for Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting in the United States. We have observed encouraging support from the investigators participating in the study in our meetings to date including those held at ASCO (Free ASCO Whitepaper) 2025, ELCC 2025, and an investigator meeting in Budapest, Hungary. Consistent feedback has been that the efficacy and the safety data collected thus far from the TACTI-002 and INSIGHT-003 trials are impressive and address the unmet medical needs seen by many key opinion leaders.
INSIGHT-003 – Phase I Trial in Non-Squamous 1L NSCLC
In May, Immutep announced a high 60.8% response rate and 90.2% disease control rate (N=51), according to RECIST1.1, had been achieved in the investigator-initiated INSIGHT-003 trial as of the data cut-off date of 6 May 2025. INSIGHT-003 is evaluating efti in combination with the anti-PD-1 therapy, KEYTRUDA and doublet chemotherapy as first-line treatment for patients with advanced or metastatic non-squamous non-small cell lung cancer (1L NSCLC).
In patients with TPS <50% (N=47), who represent a high unmet need and over two-thirds of the 1L NSCLC population, the triple combination with efti achieved a 59.6% response rate as compared to historical control of 40.8% from KEYTRUDA and chemotherapy.3 Safety continues to be favourable with no new safety signals. Data from this trial are expected to be presented at a medical conference later in CY2025.
HEAD AND NECK CANCER
TACTI-003 (KEYNOTE-C34) Cohort B – Phase IIb Trial in 1L HNSCC with CPS <1
In May, Immutep announced an excellent median Overall Survival (OS) of 17.6 months had been achieved in Cohort B of the TACTI-003 (KEYNOTE-C34) Phase IIb trial. This part of the Phase II study evaluates efti in combination with KEYTRUDA as first line therapy in recurrent/metastatic head and neck squamous cell carcinoma (1L HNSCC) patients with PD-L1 expression below one (Combined Positive Score [CPS] <1).
The mature 17.6-months median OS in evaluable patients (N=31) with a data cut-off of 31 March 2025 compares favourably to historical results from the two current standard-of-care approaches in the United States for 1L HNSCC patients with CPS <1 including 10.7-months from cetuximab + chemotherapy and 11.3-months from anti-PD-1 therapy + chemotherapy, as well as 7.9-months from anti-PD-1 monotherapy.1,2
Immutep requested a meeting with the U.S. Food and Drug Administration (FDA) to discuss next steps including potential paths to approval for 1L HNSCC with PD-L1 CPS <1.
SOFT TISSUE SARCOMA
EFTISARC-NEO – Phase II Trial in Soft Tissue Sarcoma
In May, Immutep announced the investigator-initiated EFTISARC-NEO Phase II trial evaluating efti with radiotherapy plus KEYTRUDA in the neoadjuvant setting for resectable soft tissue sarcoma (STS) has met its primary endpoint. The novel combination significantly exceeded the study’s prespecified median of 35% tumour hyalinization/fibrosis versus 15% for historical data from radiotherapy alone in patients with resectable STS.
The EFTISARC-NEO study is primarily funded with a grant from the Polish government awarded by the Polish Medical Research Agency program.
The trial’s investigators at the Maria Skłodowska-Curie National Research Institute of Oncology (MSCNRIO) in Warsaw, the national reference centre for STS in Poland, plan to present results from the study at a medical meeting later in CY2025.
BREAST CANCER
AIPAC-003 – Phase II/III Trial in Metastatic Breast Cancer
Immutep is continuing the AIPAC-003 trial, which enrolled 71 metastatic hormone receptor positive (HR+), HER2-negative/low or triple-negative breast cancer patients who exhausted endocrine therapy including cyclin-dependent kinase 4/6 (CDK4/6) inhibitors.
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 30mg or 90mg 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. Patient follow up, data cleaning and analysis is ongoing and an update is anticipated later in CY2025.
IMP761 DEVELOPMENT PROGRAM FOR AUTOIMMUNE DISEASE
IMP761 – Phase I Trial
Immutep is progressing with the ongoing Phase I trial of its autoimmune candidate IMP761. IMP761 is a first-in-class LAG-3 agonist antibody designed to restore balance to the immune system by enhancing the "brake" function of LAG-3 to silence dysregulated self-antigen-specific memory T cells that cause many autoimmune diseases.
In June, Immutep announced positive initial efficacy data and continued favourable safety data from the first-in-human Phase I study. Through the highest dosing level of IMP761 to date (0.9 mg/kg), there have been no treatment-related adverse events in healthy participants. Additionally, pharmacodynamic data at this dosing level show that the inhibition of T cell infiltration in the skin at day 10 following a neoantigen rechallenge has already reached 80%. The substantial reduction in T cell activity highlights the potential efficacy of IMP761 in treating autoimmune diseases.
Immutep is continuing with single ascending dose levels of 2.5, 7 and 14 mg/kg. Additional data from the Phase I is expected to follow later in CY 2025.
INTELLECTUAL PROPERTY
During the quarter, Immutep was granted four new patents. Immutep was granted two new patents for efti in combination with a PD-1 pathway inhibitor by the New Zealand Intellectual Property Office. In addition, two new patents were granted for IMP761, one by the Intellectual Property Office of the Philippines and the other by the Korean Intellectual Property Office.
CORPORATE & FINANCIAL SUMMARY
Senior Management Changes
Immutep’s Acting Chief Medical Officer, Stephan Winckels M.D, Ph.D., has been appointed to the permanent position of Chief Medical Officer. Stephan has over 15 years of experience in oncology drug development and has been working on efti trials as Medical Monitor or Data Monitoring Committee member for more than nine years.
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 30 June 2025 of approximately A$129.69 million, which is greater than budgeted as at the beginning of FY2025, while progressing our clinical programs within announced timeframes. The total balance consists of: 1) a cash and cash equivalent balance of A$67.41 million and 2) bank term deposits totalling A$62.28 million, which have been recognised as short-term investments due to having maturities of more than 3 months and less than 12 months.
In Q4 FY25, cash receipts from customers were A$6k. The net cash used in G&A activities in the quarter was A$1.44 million, compared to A$704k in Q3 FY25. Payments to Related Parties comprises Non-Executive Directors’ fees and Executive Directors’ remuneration of A$307k.
The net cash used in R&D activities during the quarter was A$15.66 million, compared to A$13.6 million in Q3 FY25. The increase is in line with increased clinical trial activities.
Payment for staff costs was A$2.5 million in the quarter, the same as for Q3 FY25. Total net cash outflows used in operating activities in the quarter were A$18.92 million compared to A$16.26 million in Q3 FY25.
Total cash outflows used in investing activities for the quarter was A$8.16 million, mainly due to the net increase of short-term investments. The short-term investments are comprised of term deposits with maturities of greater than 3 months and less than 12 months. During the quarter, the company transferred back A$12.92 million from short-term investments that had matured to cash at bank and invested A$21.05 million in short-term investments.
In July, US-based Ridgeback Capital Investments L.P. exercised its last remaining convertible notes and warrants in the Company. The cashless exercise resulted in the issuance of 7,475,208 ordinary shares. The Company is now free of any convertible debt, warrants or options.