Eftilagimod alpha

Media Release Efti in combination with pembrolizumab and radiotherapy demonstrates significant efficacy in the neoadjuvant setting in patients with soft tissue sarcomaOver three-fold increase in tumour hyalinization, the primary endpoint of the study and an important predictor of overall survival, as compared to historical results from radiotherapy alone SYDNEY, AUSTRALIA, Nov. 14, 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 the presentation of new data from EFTISARC-NEO, a Phase II investigator-initiated trial of eftilagimod alpha (efti) in combination with radiotherapy plus KEYTRUDA® (pembrolizumab) for patients with soft tissue sarcoma (STS), at the Connective Tissue Oncology Society (CTOS) 2024 Annual Meeting. Based on preliminary analysis among 21 patients available for primary endpoint assessment, the triple combination therapy demonstrates significant efficacy in the neoadjuvant setting for resectable STS. Katarzyna Kozak, M.D., Ph.D., and Paweł Sobczuk, M.D., Ph.D., medical oncologists at the Department of Soft Tissue/Bone Sarcoma and Melanoma at MSCNRIO (Warsaw) and the trial’s principal investigators, stated: “Our belief in efti’s unique mechanism of action to complement radiotherapy and pembrolizumab in order drive better outcomes for patients with this rare aggressive disease was the foundation of the EFTISARC-NEO trial. These very encouraging results we are presenting today build our confidence in the synergistic effects of this new therapeutic approach and its potential to treat these patients in dire need of more effective therapies. In particular, the high level of hyalinization/fibrosis achieved with this novel combination therapy, three-times above historical results from standard radiotherapy, demonstrates remarkable efficacy in patients with resectable soft tissue sarcomas.” In the neoadjuvant setting for patients with resectable STS, the combination achieved a greater than three-fold increase in tumour hyalinization/fibrosis (median 50%) at the time of surgical resection as compared to a historical median 15% from standard radiotherapy alone. In addition to being the primary endpoint of the EFTISARC-NEO study, the tumour hyalinization/fibrosis rate has also been identified as an important predictor of overall survival for STS patients.1,2 The EFTISARC-NEO trial, with a data cut-off of 20 October 2024, also showed 71.4% of patients achieved a pathologic response defined as ≥35% of hyalinization/fibrosis and 9.5% of patients achieved a complete pathologic response. The triple combination therapy is safe with no grade ≥3 toxicities related to efti and pembrolizumab. Dr. Frédéric Triebel, CSO of Immutep, said: “We are pleased with the strength of these preliminary results in this difficult-to-treat cancer. To see 71.4% of soft tissue sarcoma patients achieving a pathologic response defined as ≥35% of hyalinization/fibrosis combined with low viable tumour cells at 8% is very promising, especially as strong efficacy has been observed in different STS subtypes. We look forward to further evaluation of efti’s potential as neoadjuvant immunotherapy to help drive improved clinical outcomes.” The ongoing open-label EFTISARC-NEO Phase II study, conducted by the Maria Skłodowska-Curie National Research Institute of Oncology (MSCNRIO) in Warsaw, is expected to reach the planned enrolment of 40 patients in Q1 CY2025. The trial is primarily funded with an approved grant from the Polish government awarded by the Polish Medical Research Agency program. For more information, visit clinicaltrials.gov (NCT06128863). The CTOS poster is available on the Posters & Publications section of Immutep’s website. 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 Schaefer IM, Hornick JL, Barysauskas CM, Raut CP, Patel SA, Royce TJ, Fletcher CDM, Baldini EH. Histologic Appearance After Preoperative Radiation Therapy for Soft Tissue Sarcoma: Assessment of the European Organization for Research and Treatment of Cancer-Soft Tissue and Bone Sarcoma Group Response Score. Int J Radiat Oncol Biol Phys. 2017 Jun 1;98(2):375-383. doi: 10.1016/j.ijrobp.2017.02.087. Epub 2017 Feb 24. PMID: 28463157.Rao SR, Lazarides AL, Leckey BL, Lane WO, Visgauss JD, Somarelli JA, Kirsch DG, Larrier NA, Brigman BE, Blazer DG, Cardona DM, Eward WC. 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.

Positive feedback received from US FDA regarding the planned TACTI-004 Phase III in first-line non-small cell lung cancer successfully concluding regulatory preparations for the trial designEfti in combination with MSD’s KEYTRUDA® reports positive efficacy and favourable safety in first-line head and neck cancer in TACTI-003 Phase IIb trialFirst participant successfully dosed in the first-in-human Phase I trial of IMP761, a novel LAG-3 agonist antibody designed to treat autoimmune diseasesImmutep added to the S&P ASX300 Index, recognising its considerable growth and enhancing market visibilityImmutep has a strong aggregate cash, cash equivalent and term deposit position of A$172.3 million as at 30 September 2024 with an expected cash reach to the end of CY2026. SYDNEY, AUSTRALIA, Oct. 29, 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, provides an update on its activities for the quarter ended 30 September 2024 (Q1 FY25). EFTI DEVELOPMENT PROGRAM FOR CANCER TACTI-004 (KEYNOTE-PNC91) – 1L NSCLC Phase III Clinical Collaboration with MSD In July, Immutep received positive feedback from the US Food and Drug Administration (FDA) regarding its planned TACTI-004 Phase III trial of eftilagimod alfa (efti) in combination with KEYTRUDA® (pembrolizumab), MSD’s (Merck & Co., Inc., Rahway, NJ, USA) anti-PD-1 therapy, and histology-based platinum doublet chemotherapy for the treatment of first-line metastatic non-small cell lung cancer (1L NSCLC), regardless of PD-L1 expression. The FDA feedback builds on previously received guidance from the Paul-Ehrlich-Institut and the Spanish Agency for Medicines and Health Products, successfully concluding the preparatory regulatory interactions for the design of this registrational trial. The study will enrol ~750 patients regardless of PD-L1 expression in order to address the entire 1L NSCLC market eligible for anti-PD-1 therapy. TACTI-003 (KEYNOTE-C34) – Phase IIb clinical trial in 1L HNSCCTACTI-003 is evaluating efti in combination with MSD’s anti-PD-1 therapy KEYTRUDA® (pembrolizumab) as first-line treatment of recurrent or metastatic head and neck squamous cell carcinoma patients (1L HNSCC). The randomized Cohort A portion of the study is evaluating efti in combination with KEYTRUDA as compared to KEYTRUDA monotherapy in patients with PD-L1 positive (Combined Positive Score [CPS] ≥1) tumours, whereas Cohort B is evaluating efti in combination with KEYTRUDA in patients with PD-L1 negative tumours (CPS <1). In July, Immutep reported updated positive efficacy and safety results from Cohort B of the TACTI-003 Phase IIb trial at an ESMO Virtual Plenary session. In patients with negative PD-L1 expression (CPS <1) in Cohort B, efti in combination with KEYTRUDA® achieved a 35.5% objective response rate (ORR). This is among the highest recorded for a treatment approach not containing chemotherapy in patients with CPS <1. The immuno-oncology combination with efti also attained a high complete response rate of 9.7%, which compares favourably to a historical control of 0% from anti-PD-1 monotherapy in 1L HNSCC patients with a CPS <1. Additionally, durability of responses was tracking well. In September, further data was reported from Cohort A of the TACTI-003 trial in a late-breaking abstract and prestigious Proffered Paper oral presentation at ESMO Congress 2024. At ESMO, late-breaking abstracts are generally reserved for high-quality, new research findings from randomised phase II or phase III trials with implications for clinical practice or understanding of disease processes. Proffered Papers are oral presentations of original data of superior quality, followed by expert discussion and perspectives. In patients with PD-L1 positive tumours (CPS ≥1), efti in combination with KEYTRUDA outperformance was largest in CPS ≥20 with 31.0% ORR (34.5% ORR including a partial response recorded after data cut-off date) versus 18.5% ORR for KEYTRUDA monotherapy. Efti in combination with KEYTRUDA led to a high durability of response of 17.5 months in patients with CPS ≥1 and the combination continues to have favourable safety profile. Additionally, a statistically significant increase in absolute lymphocyte count, measured as an exploratory biomarker, was seen in the efti with KEYTRUDA arm indicating an effective efti-induced immune response in this randomised setting. Immutep will continue to follow the maturing data from TACTI-003, with the most relevant endpoint of Overall Survival expected in 2025 and engage with regulatory authorities regarding potential paths forward. TACTI-002 (KEYNOTE-PN798) – Phase II clinical trial in 1L NSCLCImmutep continues to follow patients with first-line non-small cell lung cancer (1L NSCLC), in Part A of the TACTI-002 trial, where excellent median Overall Survival (mOS) rates were seen across all levels of PD-L1 expression. Immutep has previously reported final data from the other parts of the TACTI-002 trial. AIPAC-003 – Integrated Phase II/III trial in MBCSubsequent to quarter end, Immutep completed patient enrolment in the randomised Phase II portion of the AIPAC-003 trial in October. The Phase II portion enrolled 65 metastatic hormone receptor positive (HR+), HER2-negative/low or triple-negative breast cancer patients who had exhausted endocrine therapy including cyclin-dependent kinase 4/6 (CDK4/6) inhibitors. The patients have been enrolled across 22 clinical sites in Europe and the United States and have been randomised 1:1 to receive either 30mg or 90mg dosing of efti in combination with paclitaxel to determine the optimal biological dose of efti consistent with the FDA’s Project Optimus initiative. Further updates will be provided after data collection, data cleaning and analysis. INSIGHT-003 – Phase I in non-squamous 1L NSCLCThe investigator-initiated INSIGHT-003 trial continued to enrol patients throughout the quarter and they have been safely dosed across six sites in Germany. Further updates from the trial are anticipated in Q 4 CY2024. INSIGHT-005 – Phase I trial in Urothelial CarcinomaThe INSIGHT-005 trial is evaluating efti and the anti-PD-L1 therapy BAVENCIO® (avelumab) in up to 30 patients with metastatic urothelial cancer. The study is jointly funded with Merck KGaA, Darmstadt, Germany. EFTISARC-NEO – Phase II Trial in Soft Tissue SarcomaNew data from the EFTISARC-NEO Phase II investigator-initiated trial of efti in combination with radiotherapy plus KEYTRUDA® (pembrolizumab) for patients with soft tissue sarcoma (STS) will be presented on 14 November at the Connective Tissue Oncology Society (CTOS) 2024 Annual Meeting taking place in San Diego, California. IMP761 DEVELOPMENT PROGRAM FOR AUTOIMMUNE DISEASEIn August, Immutep successfully dosed the first participant in the first-in human Phase I trial of IMP761 after receiving regulatory clearance from the ethics and competent authority in the Netherlands to initiate the study. Safety data from this first-in-human study is anticipated by the end of the calendar year 2024, with pharmacokinetics and pharmacodynamics data in first half CY2025. IMP761 is a first-in-class agonist LAG-3 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. INTELLECTUAL PROPERTY During the quarter, Immutep was granted seven new patents for efti, IMP761 and LAG525 (ieramilimab) in various territories. Two patents were granted for efti in combination with a PD-1 pathway inhibitor in South Korea and Brazil and one patent was granted in Mexico for a binding assay for determining MHC Class II binding activity. The assay is used in the characterisation of efti in GMP-grade manufacturing. New patents were also granted for IMP761 in India and Israel. For LAG525, which is exclusively licensed to Novartis by Immutep, two new patents were granted in Australia and Taiwan. CORPORATE & FINANCIAL SUMMARY Immutep enters the ASX300Following the September quarterly review of the S&P Dow Jones Indices, Immutep was added to the S&P/ASX 300 index. Joining the ASX300 recognises the Company's considerable growth over the years, enhances its market visibility and supports investor confidence. Cash Flow SummaryDuring the quarter, Immutep continued to advance its clinical trial programs for efti and preclinical program for IMP761 to create value for shareholders. The Company is well funded with a strong cash and cash equivalent balance as at 30 September 2024 of approximately A$120.3 million. In addition to this cash balance, Immutep has an A$52.0 million bank term deposit, which has been recognised as a short-term investment due to the maturity date of 5-12 months. This aggregate position of A$172.3 million as at 30 September 2024 gives Immutep an expected cash reach to the end of CY2026. Cash receipts from customers in Q1 FY25 were $20k. During the quarter, Immutep received a €2,194,918 (~A$3,602,362) research and development (R&D) tax incentive payment in cash from the French Government under its Crédit d’Impôt Recherche scheme and $549k from the Australian government R&D tax rebate. The net cash used in G&A activities in the quarter was $961k, compared to $1.9 million in Q4 FY24. Payments to Related Parties comprises Non-Executive Directors’ fees and Executive Directors’ remuneration of $576 k. The net cash used in R&D activities during the quarter was $9.5 million, compared to $3.8 million to Q4 FY24. The increase is mainly due to the increased level of clinical trial activities. Payment for staff costs was $2.8 million in the quarter compared to $2.0 million in Q4 FY24. Total net cash outflows used in operating activities in the quarter were $8.6 million compared to $7.4 million in Q4 FY24. For the cash flow used in investing activities, the company invested $32.4 million in bank term deposits with maturity between 5 and 6 months which has been recognised as a short-term investment. Net cash outflow from financing activities for the quarter was approximately $373 k including $254k for the payment of capital raising cost. 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. Investors/Media:Chris Basta, VP, Investor Relations and Corporate Communications+1 (631) 318 4000; chris.basta@immutep.com