On April 28, 2023 Immutep Limited (ASX: IMM; NASDAQ: IMMP) ("Immutep" or "the Company"), a biotechnology company developing novel LAG-3 related immunotherapy treatments for cancer and autoimmune diseases, reported an update on the ongoing development of its product candidates, eftilagimod alpha (efti) and IMP761 for the quarter ended 31 March 2023 (Q3 FY23) (Press release, Immutep, APR 28, 2023, View Source [SID1234630668]).
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EFTI DEVELOPMENT PROGRAM FOR CANCER
Immutep made strong progress during the quarter to advance its clinical development strategy to position the company, or a potential partner, to fully exploit efti’s broad potential.
AIPAC-003 — Phase II/III trial in Metastatic Breast Cancer (MBC)
In March, Immutep initiated AIPAC-003 (Active Immunotherapy PAClitaxel), its integrated Phase II/III trial evaluating efti in combination with paclitaxel for the treatment of HER2-neg/low metastatic breast cancer and triple-negative breast cancer. These two indications account for ~78% of breast cancer cases. The trial commenced following the regulatory approval in the United States and Institutional Review Board (IRB) approval in Spain. Immutep anticipates enrolling the first patient in Q2 CY2023.
As a first-in-class soluble LAG-3 protein targeting MHC Class II ligands on antigen-presenting cells (APC), efti is well positioned to improve clinical outcomes from standard-of-care chemotherapy due to its unique mechanism of action. Its activation of APC triggers a broad immune response that includes significant increases in cytotoxic CD8+ T cells armed with chemo-induced tumour antigens to target cancer.
The AIPAC-003 trial employs an integrated clinical design agreed to with the FDA to help inform a potential Biologics License Application (a request for permission to sell a biologic product) and a potential Marketing Authorisation Application with the European Medicines Agency (EMA). This trial design also allows for a risk-balanced approach with the Phase III portion dependent on the Phase II results, among other items.
TACTI-002 (also designated KEYNOTE-PN798) Phase II clinical trial
Positive final data on safety and efficacy was reported from Part B of the TACTI-002 trial in patients with 2nd line non-small cell lung cancer (NSCLC) refractory to anti-PD-(L)1 therapies in a Mini Oral presentation at ESMO (Free ESMO Whitepaper)’s European Lung Cancer Congress (ELCC) 2023. These patients have few therapeutic options, and the addition of efti to pembrolizumab may help these patients by reverting the confirmed anti-PD-(L)1 therapy resistance.
The Company reported encouraging clinical results, including an Overall Survival (OS) rate of 39% at 21 months. In addition, 83% of patients studied for Tumour Growth Kinetics showed deceleration (50%) in tumour growth or shrinkage (33%) of target lesions. Responses were confirmed and durable with responders participating in the study for more than 19 months.
The ORR, PFS, and OS were more pronounced in patients with high PD-L1 expression (N=6) or who were secondary resistant (N=25). For patients with ≥50% PD-L1 TPS expression, median OS was not yet reached, overall response rate (ORR) was 33.3%, and 6-month progression-free survival (PFS) was 50%. Efti plus pembrolizumab was well tolerated without any new safety signals, and there was no treatment discontinuation due to adverse reactions.
TACTI-003 – Phase IIb clinical trial in 1st line HNSCC
In early 2023 Immutep announced it has successfully enrolled over 50% of the planned 154 patients into the randomised Phase IIb TACTI-003 trial. Subsequent to quarter end TACTI-003 has reached 75% enrolment, and Immutep expects to complete enrolment by mid-year positioning the Company to report top-line results in H2 of CY2023.
Planned late-stage trial in 1st line NSCLC
Immutep is continuing its preparations for a late-stage trial evaluating efti in 1st line NSCLC in combination with anti-PD-1 therapy. The NSCLC program will be shaped by the maturing data from the Company’s ongoing TACTI-002 and INSIGHT-003 trials. Current activity is focused on trial design and engagement with regulatory authorities and other stakeholders. The Company obtained US FDA Fast Track designation late last year for this indication.
INSIGHT-003 – Phase I in 1st line NSCLC
In February, the investigator-initiated INSIGHT-003 trial reached its enrolment target of 20 patients with 1st line NSCLC for this first triple combination therapy study of efti with standard-of-care combination of anti-PD-1 therapy and chemotherapy. INSIGHT-003 has been now extended to include a total of 50 patients. The expansion of INSIGHT-003 will further inform planning for registrational studies.
IMP761 DEVELOPMENT PROGRAM FOR AUTOIMMUNE DISEASES
During the first quarter, our preclinical development continued for IMP761, including preparations to begin the toxicology study. As the first immunosuppressive agonist antibody to LAG-3 acting upstream on activated T cells to target the root cause of self-antigen-specific T cell induced disease, IMP761 is a potential game-changer in how autoimmune diseases are treated. The Company currently anticipates that clinical development will begin in the first half of CY2024.
INTELLECTUAL PROPERTY
During the quarter, Immutep was granted three new patents directed to efti. The first is a United States patent drawn to methods of treating cancer with a combination of efti and chemotherapy, where the efti is administered in a dose of more than 6 mg. This is the third United States patent granted from this family.
The second patent is an Indian patent that protects Immutep’s intellectual property relating to combined preparations of efti with a PD-1/PD-L1 therapy for the treatment of cancer or infection. The third patent is an Australian patent which relates to a potency assay for release testing of efti. The assay is used in Immutep’s commercial-scale (2,000L) manufacturing process. This new Australian patent follows the grant of a similar patent in South Korea in 2022.
BOARD AND MANAGEMENT CHANGES
On 11 April, Lis Boyce was appointed as Non-Executive Director replacing Lucy Turnbull, who re-joined the board after the sudden and untimely death of Grant Chamberlain in January 2022. The Board is grateful to Lucy for stepping in under such tragic circumstances and for her boundless energy and valued insights.
Ms Boyce is a highly experienced corporate lawyer and currently a partner at Piper Alderman. She has extensive experience in the Life Sciences and Healthcare sectors as well as in capital raisings, strategic collaborations, commercial contracts and mergers and acquisitions. Lis is currently deputy chair of AusBiotech’s AusMedtech Advisory Group and a member of AusBiotech’s State Committee for NSW.
On 26 April, Immutep announced that it expanded its leadership team with the appointment of Florian D. Vogl, M.D., Ph.D., MSc., as Chief Medical Officer (CMO) with effect from 1 May 2023. Dr. Vogl has over a decade of experience in the biopharmaceutical industry with extensive clinical development expertise in the field of oncology. Most recently, he was CMO of Cellestia Biotech where he focused on delivering new treatments to patients with cancer and autoimmune disorders that had limited therapeutic options. Prior to Cellestia, Dr. Vogl held senior management roles in Europe and the United States, including Head of Clinical Development Europe at Rainier Therapeutics, Senior Global Medical Leader, Oncology Development at Novartis, and as Early Development Leader, Oncology Pipeline at Amgen.
Dr. Vogl assumes the CMO role from Frédéric Triebel, M.D., Ph.D., who previously acted as both Chief Scientific Officer (CSO) and CMO of Immutep. Dr. Triebel’s foremost focus will be on his responsibilities as CSO and as a member of Immutep’s Board.
FINANCIAL SUMMARY
Immutep continued to focus on prudent cash management during the past quarter (Q3 FY23). The Company remains well funded with a cash runway extending to the end of FY24.
Cash receipts from customers in the quarter increased to $30k, compared to $8k in Q2 FY23. The net cash used in G&A activities in the quarter was $1.12million compared to $734k in Q2 FY23. Payments to Related Parties, detailed in Item 6 of the Appendix 4C cash flow report for the quarter, includes $257k in payments for Non-Executive Director’s fees and Executive Director’s remuneration.
The net cash used in R&D activities in the quarter was $11.52 million, compared to $5.87 million in Q2 FY23. The increase was mainly due to the increased clinical trial and manufacturing activities.
Total net cash outflows used in operating activities in the quarter were $14.17 million compared to $7.02 million in Q2 FY23.
Immutep’s cash and cash equivalent balance at 31 March 2023 was approximately $55.2 million, giving the Company an expected cash reach based on current estimates to June 2024. Immutep will continue to manage its solid cash balance carefully as it pursues its overall clinical development strategy.
A copy of the Appendix 4C — Quarterly Cash Flow Report for the quarter is attached.