Eftilagimod alpha

Novel combination achieves 60.8% response rate and 90.2% disease control rate in first-line non-small cell lung cancer (1L NSCLC)Notably, ~92% of all evaluable patients have PD-L1 TPS <50%, including 43% with PD-L1 below 1 (TPS <1%), who represent an area of high unmet needData demonstrates significant improvement in response rates compared to historical controls, and safety continues to be favourableMulti-centre INSIGHT-003 is evaluating the same immunotherapy/chemotherapy combination used in the pivotal TACTI-004 Phase III in 1L NSCLCAdditional data from INSIGHT-003 is planned for presentation at a medical conference later this year SYDNEY, AUSTRALIA, May 15, 2025 (GLOBE NEWSWIRE) -- Immutep Limited (ASX: IMM; NASDAQ: IMMP) (“Immutep” or “the Company”), a late-stage immunotherapy company targeting cancer and autoimmune diseases, today announces that a 60.8% response rate and 90.2% disease control rate, according to RECIST1.1, has been achieved in the investigator-initiated INSIGHT-003 trial as of the data-cut off date of 06 May 2025. INSIGHT-003 is evaluating eftilagimod alpha (efti) in combination with the anti-PD-1 therapy, KEYTRUDA® (pembrolizumab) and doublet chemotherapy as first-line treatment for patients with advanced or metastatic non-squamous non-small cell lung cancer (1L NSCLC). Marc Voigt, CEO of Immutep, stated, “Our level of confidence in efti driving a new standard of care for patients with non-small cell lung cancer via our pivotal TACTI-004 trial continues to rise with the strength of the data from INSIGHT-003 and TACTI-002. Across two trials we have now efficacy data from 165 patients with 1L NSCLC who have been treated with efti and KEYTRUDA, either with or without chemotherapy. In multi-national settings, efti has generated consistent and remarkable improvements in response rates. In particular, the interim ORR data in patients with PD-L1 expression below 50% in the ongoing INSIGHT-003 trial, who represent over two-thirds of the 1L NSCLC patient population, is very encouraging.” Majority of Patients have PD-L1 TPS <50%Notably, ~92% of all evaluable patients (N=51) in the INSIGHT-003 study have PD-L1 TPS <50%. This includes 49% of patients with PD-L1 Tumour Proportion Score (TPS) of 1-49% and 43% of patients with PD-L1 TPS <1%, as shown in the table below. Strong Response Rates Across All PD-L1 Expression LevelsData from all evaluable patients demonstrates significant improvement of Overall Response Rate (ORR) according to RECIST 1.1 across all levels of PD-L1 expression compared to historical control from a registrational trial of anti-PD-1 and doublet chemotherapy in non-squamous 1L NSCLC1: 75.0% ORR versus 62.1% ORR in patients with high PD-L1 expression (TPS >50%)64.0% ORR versus 49.2% ORR in patients with low PD-L1 expression (TPS 1-49%)54.5% ORR versus 32.3% ORR in patients with negative PD-L1 expression (TPS <1%) The 60.8% response rate regardless of PD-L1 expression (TPS 0-100%) represents a substantial improvement compared to historical control of 48.0%.1 The relative outperformance is particularly strong given the registrational trial has four times as many patients with high PD-L1 expression (~32% of patients versus ~8% in INSIGHT-003), who have the highest response rates. Importantly, in patients with TPS <50% (N=47), who have a high unmet need and represent over two-thirds of the 1L NSCLC patient populaton, the triple combination with efti achieved a 59.6% response rate as compared to historical control of 40.8%.1 INSIGHT-003 Overall Response Rate & Disease Control Rate, according to RECIST1.1PD-L1 Expression LevelsTPS 0-100%(N=51)TPS <1%(N=22)TPS 1-49%(N=25)TPS <50%(N=47)TPS ≥50%(N=4)ORR %60.854.564.059.675.0DCR %90.286.492.089.4100 SafetySafety continues to be favourable for the triple combination in 1L NSCLC with no new safety signals. Next StepsAdditional data updates from this trial are expected to be presented at a medical conference in 2025 and beyond. About INSIGHT-003INSIGHT-003 is an investigator-initiated study conducted by the Frankfurt Institute of Clinical Cancer Research IKF and several other German centres. It is being run as the third arm (Stratum C) of the ongoing Phase I INSIGHT trial with Prof. Dr. Salah-Eddin Al-Batran as lead investigator. The study is evaluating a triple combination therapy in front-line non-small cell lung cancer patients consisting of efti administered subcutaneously in conjunction with an existing approved standard-of-care combination of anti-PD-1 therapy (pembrolizumab) and chemotherapy (carboplatin and pemetrexed) delivered intravenously. The trial will assess the safety, tolerability, and initial efficacy of the combination. About Eftilagimod Alfa (efti)Efti is Immutep’s proprietary soluble LAG-3 protein and MHC Class II agonist that stimulates both innate and adaptive immunity for the treatment of cancer. As a first-in-class antigen presenting cell (APC) activator, efti binds to MHC (major histocompatibility complex) Class II molecules on APC leading to activation and proliferation of CD8+ cytotoxic T cells, CD4+ helper T cells, dendritic cells, NK cells, and monocytes. It also upregulates the expression of key biological molecules like IFN-ƴ and CXCL10 that further boost the immune system’s ability to fight cancer. Efti is under evaluation for a variety of solid tumours including non-small cell lung cancer (NSCLC), head and neck squamous cell carcinoma (HNSCC), and metastatic breast cancer. Its favourable safety profile enables various combinations, including with anti-PD-[L]1 immunotherapy 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). 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. 1. 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.19.03136 KEYTRUDA® is a registered trademark of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA. 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

Eftilagimod and Keytruda\'s median overall survival data in first-line, PD-L1-negative head and neck cancer look favorable to historical data on a cross-trial comparison basis. \n Immutep believes its LAG-3 candidate eftilagimod alpha may have a path to approval in first-line head and neck cancer after reporting what one analyst deems “impressive” overall survival data.Monday, Immutep said a combination of eftilagimod and Merck & Co.’s Keytruda helped patients live a median of 17.6 months when used as first-line therapy in patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) with PD-L1 expression below a combined positive score (CPS) of 1.The overall survival result came from 31 evaluable patients enrolled in cohort B of a phase 2b trial coded Keynote-C34, or Tacti-003. The trial doesn’t have an active internal control arm. But as Immutep noted, the 17.6-month median looks better than historical data from two existing standard-of-care regimens. In a note, Jefferies analyst David Stanton, M.D., called the survival readout “impressive.”Immutep suggests that a high unmet need for first-line treatment of PD-L1-negative HNSCC could potentially pave eftilagimod a path to approval, and the Australian biotech has requested a meeting with the FDA to discuss that. Eftilagimod already boasts an FDA “fast track” designation in first-line HNSCC.“Given the strength of the efficacy and safety results generated to date with efti in combination with [Keytruda], we will meet with regulators to discuss next steps and potential paths to approval,” Immutep CEO Marc Voigt said in a statement.According to Voigt, the eftilagimod-Keytruda combo’s value proposition lies in that it offers a potential immunotherapy-only regimen, while the standards today for PD-L1-negative patients all include chemotherapy. Eftilagimod is a LAG-3 fusion protein, which activates antigen-presenting cells to boost an immune response, according to Immutep. Back in 2019, the FDA approved Keytruda in combination with chemotherapy for all patients with first-line HNSCC, including those with PD-L1-negative tumors. The approval was based on the phase 3 Keynote-048 trial showing that Keytruda plus chemo reduced the risk of death by 23% versus Eli Lilly’s EGFR inhibitor Erbitux and chemo in the overall population regardless of PD-L1 expression levels. At the time, the FDA simultaneously approved Keytruda monotherapy but only for PD-L1-positive tumors that express the biomarker at CPS score at or above 1.A post hoc analysis of Keynote-048 later showed that Keytruda-chemo didn’t demonstrate a clear overall survival benefit over Erbitux-chemo in the PD-L1-negative subgroup. The median overall survival was 11.3 months versus 10.7 months. The death risk was even 21% higher for that subgroup for the Keytruda-chemo arm, although researchers cautioned that this analysis was only descriptive and limited by the small number of patients involved.Regardless of Keytruda-chemo’s position, eftilagimod and Keytruda’s 17.6-month median overall survival length now looks better than those by the two chemo-containing regimens with the obvious caveat of a cross-trial comparison.The latest overall survival showing builds on some promising tumor response data from the Immutep regimen. Last year, Immutep reported a 35.5% objective response rate—including 12.9% complete responses—for eftilagimod and Keytruda from cohort B of Tacti-003. The numbers compare favorably to Keytruda-chemo’s 30.8% ORR—including 2.6% CR—in Keynote-048’s PD-L1-negative subgroup.“Driving durable responses that translate into clinically meaningful survival holds tremendous promise for these patients in need of more tolerable and efficacious therapies,” Voigt said in a statement Monday. Immutep looks poised to carve out a niche market from PD-L1-negative disease, which makes up about 20% of first-line HNSCC patients, according to the company. As Voigt noted, there’s a lack of competitor chemo-free trials targeting this population.Merck recently partnered with Exelixis to combine Keytruda with the latter company’s investigational tyrosine kinase inhibitor zanzalintinib in HNSCC. However, the pair’s phase 3 Stellar-305 trial is only testing that combo in PD-L1-positive patients.Similarly, Merus, with an FDA “breakthrough therapy” designation, is evaluating its EGFRxLGR5 bispecific antibody petosemtamab with Keytruda in first-line HNSCC in the phase 3 LiGeR-HN1 trial—again only in PD-L1-positive patients.