A$48.50 million cash and a 200 L efti run define Immutep’s Q1

Manufacturing Differences Reframe TACTI-004 Failure

Immutep Limited (ASX:IMM; NASDAQ:IMMP) is treating a manufacturing discrepancy as the leading explanation for the unexpected outcome of its failed TACTI-004 Phase III lung cancer trial, although the investigation is not finished and has not established a conclusive cause. The company says it has identified structural differences, including a subtle difference in N-glycan structure, between efti made at 2,000 L scale for TACTI-004 and efti produced at 200 L scale for earlier successful studies.

The finding matters because Immutep says the immune activation profile observed in TACTI-004 was markedly different from previous trials. It has also said the available analysis does not point to clinical factors such as treatment-arm imbalance or safety findings, nor to trial execution issues. The company will provide a further update at its annual general meeting on 27 November, leaving the central question of whether the product can be reliably reproduced unresolved for now.

New 200 L Efti Batch Planned for Future Studies

Immutep has contracted a new manufacturing run at 200 L, the scale used for 10 previous GMP batches in Phase I and Phase II studies including TACTI-mel, TACTI-002 and INSIGHT-003. The company’s reset follows the September manufacturing findings, which first narrowed the potential registration pathway and flagged differences between the manufacturing scales.

The intended registration-directed focus is now HNSCC in patients with CPS below 1 and the neoadjuvant setting of soft tissue sarcoma. Immutep says preparations have begun, but it is targeting study starts in the second half of calendar 2027 only subject to final strategy and trial design, regulatory discussions, manufacturing timelines, partnering and available resources. Dr. Reddy’s Laboratories, its licensing partner, has been consulted and supports the approach, while preliminary discussions with other parties are also underway.

Clinical Assets Offer Partial Offset

The narrower efti strategy rests partly on results from smaller or investigator-initiated studies. In EFTISARC-NEO, 38 evaluable soft tissue sarcoma patients recorded median tumour hyalinization or fibrosis of 51.5%, exceeding the prespecified 35% target with p<0.001. Patients are still being followed for disease-free survival. Separately, health-related quality of life remained stable during neoadjuvant treatment, with several measures improving after surgery, although those findings came from a secondary endpoint.

INSIGHT-003 has also completed, with median overall survival of 30.9 months among the overall study population. The result came from 51 evaluable patients with advanced or metastatic non-squamous first-line NSCLC and is being compared by the company with historical benchmarks. No new safety signal was identified in the latest update, but these data do not reverse the discontinuation of TACTI-004.

IMP761 Moves Alongside Efti

Immutep is giving its autoimmune program a more prominent role, making IMP761 a co-priority alongside efti. The first-in-human Phase I study’s single ascending dose component met its primary endpoint in healthy volunteers, with favourable safety and tolerability across the tested doses and pharmacodynamic effects including reduced local inflammatory responses.

A late-breaking IMP761 poster is scheduled for the American College of Rheumatology Convergence in November. The candidate is being evaluated for potential use in T-cell-mediated autoimmune diseases such as rheumatoid arthritis or type 1 diabetes, but the available data remain early clinical evidence rather than proof of efficacy in patients with those diseases.

Cash Runway Extends as Trial Spending Falls

Immutep ended September with A$48.50 million in cash and term deposits, including A$48.41 million in cash and cash equivalents and about A$0.09 million in term deposits. Net operating cash outflow fell to A$19.1 million in the quarter from A$38.9 million in the previous quarter, largely because TACTI-004 close-out activity reduced clinical spending. Research and development cash use was A$16.5 million.

The company has implemented headcount and operating-cost reductions and expects TACTI-004 payments to decline significantly in subsequent quarters. It forecasts cash reach into the first half of calendar 2028, although the Appendix 4C’s formula-based calculation shows 2.53 quarters of funding when based on the unusually high Q1 outflow. A$0.86 million from the Australian R&D tax incentive and approximately A$2.16 million from France’s CIR program provide non-dilutive support, but the runway estimate remains dependent on spending falling as forecast and on future development plans.

That financial reset comes after the failed Phase III trial reshaped the pipeline and cost base. Immutep also regained compliance with Nasdaq’s minimum bid price requirement after changing its ADS ratio, while a separate governance issue remains: the board is searching for an additional independent director with financial and accounting expertise after its Audit and Risk Committee fell below the ASX Listing Rule 12.7 requirement.