Key Takeaways:
Actinium Pharmaceuticals' first-in-class radioconjugate ATNM-400 shrank KRAS-mutant lung tumors by as much as 135% in preclinical models and achieved complete responses in all mice when combined with osimertinib in EGFR-mutant models, data presented at SNMMI 2026 show.
Actinium Pharmaceuticals' ATNM-400, an Actinium-225 antibody radioconjugate, drove tumor regression of 135% in KRAS-mutant non-small cell lung cancer models and achieved complete responses in 100 percent of mice when combined with osimertinib in EGFR-mutant models, data presented June 2 at the Society of Nuclear Medicine and Molecular Imaging 2026 Annual Meeting in Los Angeles show.
"These data further strengthen our conviction that ATNM-400 represents a fundamentally different approach to treating NSCLC solid tumors," Sandesh Seth, Actinium's Chairman and CEO, said. "The consistency of activity we have now demonstrated across both EGFR- and KRAS-driven NSCLC supports our vision for ATNM-400 as a potential mutation-agnostic backbone therapy."
In KRAS G13D models, a single dose of ATNM-400 produced 124% and 135% tumor growth inhibition at two dose levels with full body-weight recovery. Treatment with approved KRAS inhibitors sotorasib and adagrasib increased ATNM-400's target expression up to 3.5- and 3.8-fold, respectively, reaching statistical significance at every dose. Combining ATNM-400 with either inhibitor deepened tumor-cell killing beyond either agent alone. In EGFR-mutant models, ATNM-400 monotherapy achieved 75% tumor growth inhibition versus 40% for osimertinib, while the combination reached 107% inhibition with complete cures in all treated mice.
The KRAS inhibitor class in NSCLC is projected to exceed $5 billion in peak sales, and the EGFR-mutant segment has peak sales estimates over $15 billion, led by osimertinib which generated $7.3 billion in 2025. NSCLC accounts for roughly 85 percent of the more than 2 million lung cancer cases diagnosed globally each year, a market more than twice the size of prostate cancer. ATNM-400's target is expressed in approximately 98 percent of NSCLC tumors and is conserved across EGFR-, KRAS-, and other driver-defined subgroups, with expression increasing as resistance emerges.
How ATNM-400 Differs From Targeted Inhibitors
Unlike mutation-specific drugs such as sotorasib, adagrasib, and osimertinib that block a particular mutant protein, ATNM-400 delivers a high-linear-energy-transfer alpha-particle payload that induces dense, irreversible double-strand DNA breaks and tumor-cell death independent of a tumor's driver mutation or signaling pathway. This mechanism underpins its mutation-agnostic activity. The target antigen is present in approximately 98 percent of NSCLC tumors and highly expressed in approximately 70 percent, and it is further increased in tumors that have become resistant to EGFR, KRAS, and immune-checkpoint therapies.
Combination Strategy and Commercial Opportunity
The data show that KRAS G12C inhibitors raise ATNM-400's target expression dose-dependently, building a rationale for combining the radioconjugate with these therapies. The same synergy-enabling biology was previously shown with osimertinib, which increased target expression and produced 107% tumor growth inhibition when combined with ATNM-400. Actinium estimates this positions ATNM-400 to participate in established markets by enhancing the standard of care while also reaching the broader NSCLC population beyond any single mutation. The company holds approximately 250 patents and patent applications, including intellectual property related to cyclotron-based production of Ac-225.
Actinium shares trade on the NYSE American under the ticker ATNM. The company is advancing ATNM-400 toward the clinic and expects to share additional data across its solid tumor programs in the coming months.
This article is for informational purposes only and does not constitute investment advice.
