Immutep (ASX:IMM) Limited said in its quarterly activities report and Appendix 4C for the quarter ended 30 September 2026 that its Phase III TACTI-004 trial of eftilagimod alfa (efti) in first-line non-small cell lung cancer has been discontinued early after a futility outcome. The biotechnology company, which develops LAG-3-based immunotherapies for cancer and autoimmune disease, said it is now directing resources to two programmes: efti in other cancers and its autoimmune candidate IMP761.

What went wrong with TACTI-004

Immutep said a root cause analysis found structural differences, including a subtle N-glycan difference, between efti made at 2,000-litre scale for TACTI-004 and the 200-litre scale material used in earlier studies. The company said clinical and trial-execution factors do not explain the result. It has contracted a new 200-litre manufacturing run, noting that ten GMP batches at that scale were used in earlier studies including TACTI-mel, TACTI-002 and INSIGHT-003. A further update on the root cause work is due at the annual general meeting on 27 November 2026. These are the company's own findings, and the manufacturing fix has not yet been tested in a trial.

Where efti development goes next

Immutep said it will focus on registration-directed development in head and neck squamous cell carcinoma with a combined positive score below 1, and in neoadjuvant soft tissue sarcoma. It is targeting the start of those studies in the second half of calendar 2027, subject to strategy, regulatory, manufacturing, partnering and resource factors.

The company pointed to earlier data. In the Phase I INSIGHT-003 study in non-squamous first-line lung cancer, median overall survival was 30.9 months in the overall population, with a data cut-off of 27 March 2026. In the Phase II EFTISARC-NEO soft tissue sarcoma study, median tumour hyalinisation or fibrosis was 51.5 per cent in 38 patients against a 35 per cent target, meeting the primary endpoint. The US Food and Drug Administration granted orphan drug designation in April 2026. Immutep closed the AIPAC-003 breast cancer study effective 30 June 2026 and placed an investigator-initiated neoadjuvant breast cancer study on hold pending the root cause analysis. Licensing partner Dr. Reddy's Laboratories supports the new approach, and preliminary talks with other parties are continuing.

IMP761 in autoimmune disease

IMP761, an agonist anti-LAG-3 antibody, is now a co-priority with efti. In a placebo-controlled first-in-human Phase I study, the company reported favourable safety in healthy volunteers and a statistically significant inhibition of skin blood perfusion at 7 mg/kg (p equals 0.029), with pharmacokinetics supporting dosing every four weeks. A late-breaking poster is due at the ACR Convergence meeting in Orlando on 10 November 2026.

Cash, costs and runway

Net operating cash outflow fell to A$19.1m from A$38.9m in the previous quarter, with research and development payments of A$16.5m against A$22.0m, reflecting the TACTI-004 close-out. Cash and cash equivalents were A$48.41m at quarter end, and the company reports no debt or undrawn facilities. During the quarter it received a A$0.86m Australian research and development tax rebate, and after quarter end a French research tax credit of about A$2.16m (EUR 1.36m), which is not in the 30 September balance.

Management said cost reductions, including headcount and operating expense cuts, should extend its runway well into the first half of calendar 2028. The Appendix 4C, however, shows 2.53 quarters on the quarter's outflows, which include one-off trial close-out payments, and the filing says that figure does not reflect lower expected spending.

Corporate matters

Effective 28 September 2026, each American Depositary Share now represents 200 ordinary shares rather than 10, equivalent to a one-for-twenty ADS reverse split, with ASX-listed shares unaffected. Immutep said it regained Nasdaq minimum bid price compliance on 13 October 2026. Following a director's resignation, the audit and risk committee has two members and the company is not currently compliant with ASX Listing Rule 12.7; it expects to appoint another independent director by 30 June 2027.