On October 29, 2024 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 activitiesfor the quarter ended 30 September 2024 (Q1 FY25) (Press release, Immutep, OCT 29, 2024, View Source [SID1234647455]).
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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 HNSCC
TACTI-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 (Free ESMO Whitepaper) 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 (Free ESMO Whitepaper) Congress 2024. At ESMO (Free ESMO Whitepaper), 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 NSCLC
Immutep 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 MBC
Subsequent 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 NSCLC
The 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 Carcinoma
The 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 Sarcoma
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) 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 DISEASE
In 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 ASX 300
Following the September quarterly review of the S&P Dow Jones Indices, Immutep was added to the S&P/ASX
300 index. Joining the ASX 300 recognises the Company’s considerable growth over the years, enhances its
market visibility and supports investor confidence.
Cash Flow Summary
During 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 (detailed in item 6.1 of the Appendix 4C) comprises Non-Executive Directors’ fees and Executive Directors’ remuneration of $576k.
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.
A copy of the Appendix 4C -Quarterly Cash Flow Report for the quarter is attached.