Purple Biotech IM1240 Shows 8-Fold Longer Half-Life and Activity in PD-1–Resistant Tumors
PPBT•Purple Biotech’s IM1240 demonstrated an eight-fold longer half-life and 16-fold greater exposure than its non-capped variant in primate toxicology, with minimal IL-6 and TNF-α induction at 10 mg/kg supporting a widened therapeutic window. IM1240 induced apoptosis and tertiary lymphoid structure formation in PD-1 and chemotherapy-resistant head and neck, bladder, NSCLC explants.
1. Primates Toxicology and Pharmacokinetics
In a non-GLP study in non-human primates, IM1240 exhibited an approximately eight-fold longer half-life and 16-fold greater systemic exposure than the non-capped variant IM1222. At a 10 mg/kg dose, IM1240 induced minimal IL-6 and TNF-α, demonstrating a broad therapeutic window and mitigation of cytokine release risks.
2. Anti-Tumor Activity in Patient-Derived Explants
IM1240 triggered apoptosis across six PD-1–resistant head and neck squamous cell carcinoma lymph node samples and a chemotherapy-resistant bladder cancer biopsy. In NSCLC explants, it drove formation of mature tertiary lymphoid structures, increased CD8 T and NK cells, and reduced regulatory T cells and tumor burden.
3. Essential Contribution of NKG2A Arm
Comparisons with the NKG2A loss-of-function variant IM1340 showed that both the CD3 and NKG2A arms are required for full anti-tumor activity. Loss of NKG2A function abolished TLS formation and immune remodeling, underscoring NKG2A’s role in IM1240’s differentiated mechanism.
4. Clinical Advancement Plans
The preclinical results validate the CAPTN-3 masking strategy and support advancing IM1240 toward a first-in-human clinical study in 2027. The data position IM1240 as a next-generation immunotherapy candidate for patients with PD-1 and chemotherapy-resistant tumors.
