On January 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, provides an update on its activities for the quarter ended 31 December 2024 (Q2 FY25) (Press release, Immutep, JAN 30, 2025, View Source [SID1234649968]).
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EFTI DEVELOPMENT PROGRAM FOR CANCER
TACTI-004 – Start of Phase III Trial in 1L NSCLC
In December 2024, Immutep initiated its pivotal TACTI-004 Phase III clinical trial of eftilagimod alfa ("efti") for the treatment of first-line metastatic non-small cell lung cancer (1L NSCLC). The receipt of regulatory approval from the Australian Therapeutic Goods Administration means that Immutep has transitioned into a Phase III company; a significant milestone for the Company.
Immutep has successfully completed regulatory submissions in the vast majority of the more than 25 countries that will be part of the global TACTI-004 trial. Additional approvals from multiple countries are expected in the weeks and months ahead. The Company expects to enrol the first patient in Q1 of CY2025.
TACTI-003 (KEYNOTE-C34) – Phase IIb Trial in 1L HNSCC
In December 2024, Immutep reported further positive results from Cohort B of the TACTI-003 (KEYNOTEC34) Phase IIb trial. Cohort B 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) with PD-L1 negative tumours (CPS <1) who typically do not respond well to anti-PD-1 therapy alone. The results were presented by Martin Forster, M.D., Ph.D., at the ESMO (Free ESMO Whitepaper) Immuno-Oncology (IO) Annual Congress 2024.
Adding to the high response rates and favourable safety data previously reported in July 2024, the new data showed that, encouragingly, median overall survival (OS) has not yet been reached and the 12- month OS rate is 67%. A promising progression-free survival (PFS) of 5.8 months, interim median duration of response (DOR) of 9.3 months, 35.5% objective response rate (ORR) and 58.1% disease control rate (DCR) were also reported. The complete response rate increased to 12.9% and 16.1%, according to RECIST 1.1 and iRECIST, respectively. This data compares favourably to historical results from anti-PD-1 therapy alone in 1L HNSCC patients with CPS <1. In addition, efti in combination with KEYTRUDA continues to be well-tolerated with no new safety signals. Immutep will continue to follow the maturing data from TACTI-003 and engage with regulatory authorities regarding potential paths forward.
AIPAC-003 – Phase II/III Trial in Metastatic Breast Cancer
In October 2024, Immutep completed patient enrolment in the Phase II portion of the AIPAC-003 trial. The randomised Phase II portion of the trial enrolled 65 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. 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. Data cleaning and analysis is ongoing.
INSIGHT-003 – Phase I Trial in Non-Squamous 1L NSCLC
In November 2024, first overall survival results were reported from the investigator-initiated INSIGHT003 trial evaluating efti in combination with KEYTRUDA (pembrolizumab) and doublet chemotherapy as first-line treatment for patients with advanced or metastatic non-squamous non-small cell lung cancer (1L NSCLC).
Mature data from patients with a minimum follow-up of 22 months (N=21) demonstrated results significantly exceeding historical controls and expectations. Data included a median OS of 32.9 months, median PFS of 12.7 months, and a 24-month OS rate of 81.0%. Data from all evaluable patients to date (N=40) showed a marked improvement in ORR compared to historical controls. Safety remains favourable with no new safety signals reported.
Subsequent to quarter end, patient enrolment was completed for INSIGHT-003 in January 2025. The trial reached its enrolment target of approximately 50 evaluable patients across multiple clinical sites in Germany led by the Frankfurt Institute of Clinical Cancer Research IKF. Additional data updates are expected in 2025 and beyond.
EFTISARC-NEO – Phase II Trial in Soft Tissue Sarcoma
Also in November, new 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) were presented at the Connective Tissue Oncology Society (CTOS) 2024 Annual Meeting.
Based on preliminary analysis, the triple combination therapy demonstrates significant efficacy in the neoadjuvant setting for resectable STS. The combination achieved a greater than three-fold increase in tumour hyalinization/fibrosis (median 50%) at the time of surgery as compared to a historical median of 15% from radiotherapy alone. In addition to being the primary endpoint of the EFTISARC-NEO study, the tumour hyalinization/fibrosis rate has also been identified as a predictor of overall survival for STS patients in the neoadjuvant setting.
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. Additionally, the triple combination therapy is safe with no grade ≥3 toxicities related to efti and KEYTRUDA.
IMP761 DEVELOPMENT PROGRAM FOR AUTOIMMUNE DISEASE
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.
In December 2024, Immutep reported favourable initial safety data from the placebo-controlled, double-blind first-in-human Phase I study evaluating IMP761. There have been no treatment related adverse events in the first three of five single ascending dose cohorts in healthy participants. Additional safety data and assessment of pharmacokinetic/pharmacodynamic (PK/PD) relationships to follow in the first half of CY2025.
PARTNER ACTIVITY
Collaboration with Monash University
In December 2024, new findings that resolve how human lymphocyte activation gene 3 (LAG-3) binds to its main ligand MHC Class II (MHC-II), also known as HLA Class II (HLA-II) in humans, were published in Science Immunology. The work by Monash University and Immutep, is also the first to show the crystal structure of a human LAG-3/MHC-II complex and provides a better foundation for development of blocking LAG-3 therapeutics, including Immutep’s anti-LAG-3 small molecule program.
INTELLECTUAL PROPERTY
During the quarter, Immutep was granted three new patents for efti and IMP761 in various territories. In particular, Immutep was granted a new patent for efti in combination with a PD-1 pathway inhibitor for the treatment of infection from the Brazilian Patent Office and a new patent for the same combination for the treatment of cancer or infection by the Japan Patent Office. In addition, a new patent was granted for IMP761 by the Malaysian Patent Office.
CORPORATE & FINANCIAL SUMMARY
Board & Senior Management Changes
Independent Non-Executive Director, Anne Anderson, tendered her resignation from the role, effective from 4 October 2024. The Board thanked her for her contribution to Immutep and wished her every success with her next endeavours.
As Immutep’s efti program has advanced into Phase III development, the Company has continued to grow and evolve its team. As part of this, Christian Mueller, who has been with Immutep for over eight years, most recently as SVP Regulatory and Strategy has been promoted to Chief Development Officer. In addition, Dr Florian Vogl, Immutep’s Chief Medical Officer will depart the Company in April 2025. The Company’s current Medical Affairs Advisor, who has been working in different roles closely with Immutep for over nine years, Dr Stephan Winckels, has been appointed acting CMO and taken over all related responsibilities.
Cash Flow Summary
During the quarter, Immutep continued to advance its clinical trial programs for efti and for IMP761. The Company is well funded with a strong cash, cash equivalent and term deposit balance as at 31 December 2024 of approximately A$159.26 million in total, which gives Immutep an expected cash reach to the end of CY2026. The A$159.26 million total balance consists of: 1) a cash and cash equivalent balance of $73.89 million and 2) bank term deposits totalling A$85.37 million, which have been recognised as short-term investments due to having maturities of more than 3 months and less than 12 months.
In Q2 FY25, cash receipts from customers were $8k. The net cash used in G&A activities in the quarter was $566k, compared to $961k in Q1 FY25. Payments to Related Parties (detailed in item 6.1 of the Appendix 4C) comprises Non-Executive Directors’ fees and Executive Directors’ remuneration of $344k.
The net cash used in R&D activities during the quarter was $16.2 million, compared to $9.5 million to Q1 FY25. The increase is mainly due to the increased level of clinical trial activities especially the commencement of the phase III TACTI-004 clinical trial. Payments for staff costs were $2.5 million in the quarter compared to $2.8 million in Q1 FY25.
Total net cash outflows used in operating activities in the quarter were $19.0 million compared to $8.6 million in Q1 FY25.
Total cash flow used in investing activities for the quarter was $30.4 million, mainly due to the net increase of $30.0 million in 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 invested $35.3 million in short-term investments and transferred back $5.3 million from shortterm investments that had matured to cash at bank, resulting in a net increase in short-term investments of $30.0 million.