Immutep (ASX: IMM; NASDAQ: IMMP) announced receipt of FDA orphan drug designation for eftilagimod alfa in soft tissue sarcoma (STS), a rare cancer affecting fewer than 200,000 people in the United States.
The designation may provide development incentives including tax credits, user-fee exemptions, and, if ultimately approved for the indication, seven years of US orphan exclusivity.
Eftilagimod alfa is a recombinant soluble LAG-3 Ig fusion protein that functions as an MHC class II agonist, binding to antigen-presenting cells to drive CD8+ cytotoxic T-cell activation — a mechanism that distinguishes it from inhibitory anti-LAG-3 antibodies such as relatlimab. The designation was supported by data from the investigator-initiated Phase II EFTISARC-NEO trial, in which eftilagimod alfa combined with pembrolizumab and radiotherapy in the neoadjuvant setting met its primary endpoint in 38 evaluable patients, demonstrating median tumour hyalinization/fibrosis of 51.5% against a pre-specified target of 35% and a historical benchmark of approximately 15% with radiotherapy alone.
The STS designation arrives at a complicated moment for Immutep. The company recently discontinued its Phase III TACTI-004 trial evaluating eftilagimod alfa with pembrolizumab and chemotherapy in metastatic non-small cell lung cancer (NSCLC), and CEO Marc Voigt indicated the company is conducting a comprehensive review of its pipeline following that discontinuation. The STS designation, Voigt said, provides a potential direct pathway into a late-stage neoadjuvant study in the indication. A Phase II/III AIPAC-003 trial in metastatic breast cancer remains active.
In the LAG-3 target landscape, eftilagimod alfa’s agonist mechanism sets it apart from the dominant inhibitory checkpoint approach. Bristol-Myers Squibb markets relatlimab in combination with nivolumab (Opdualag) for melanoma — the only approved anti-LAG-3 therapy — while fianlimab, a Regeneron/Sanofi anti-LAG-3 antibody, is in late-stage development in melanoma and other solid tumours. Neither programme is active in STS, leaving eftilagimod alfa without a direct LAG-3 comparator in the indication.