Aktis Oncology (AKTS) Status update summary

Program and Clinical Development Updates

• AKY-2519, a novel miniprotein radioconjugate targeting B7-H3, is advancing through two phase I-B trials: one in metastatic castration-resistant prostate cancer (mCRPC) and another basket trial for B7-H3-expressing solid tumors, including lung and colorectal cancers.

• The prostate cancer trial enrolls both PLUVICTO-naive and PLUVICTO-experienced patients, with preliminary data expected in 2027; the basket trial is set to begin dosing in the second half of 2026.

• AKY-2519 is designed for high tumor penetration, rapid plasma clearance, and minimal normal tissue exposure, aiming to address unmet needs in multiple tumor types.

• Ongoing and upcoming trials aim to expand AKY-2519's use across multiple solid tumors, with imaging and dosimetry data presented at ASCO 2026.

• GMP manufacturing suite expected to be operational in the second half of 2026.

Imaging, Dosimetry, and Efficacy Insights

• Imaging and dosimetry studies in 34 patients showed robust tumor uptake and retention, with low normal tissue exposure, supporting a favorable therapeutic index.

• Tumor doses were substantially higher than those to normal tissues, with predicted absorbed doses for nodal metastases reaching 141–268 Gy over four cycles, while kidneys and salivary glands received much lower doses.

• PET-CT imaging with AKY-2519 consistently identified lesions also seen with PSMA-11, suggesting B7-H3 as a promising target for prostate cancer and other solid tumors.

• The agent was well tolerated, with no adverse events or infusion reactions reported in the imaging studies.

• AKY-2519 demonstrates a wide therapeutic index, robust tumor targeting, and favorable safety profile.

Expert Perspectives and Competitive Landscape

• Key opinion leaders highlighted the strong tumor retention, minimal kidney and bone marrow exposure, and rapid clearance as differentiators from other radiopharmaceuticals and antibody-drug conjugates (ADCs).

• B7-H3 is considered a clinically de-risked, broadly actionable target, with high expression in prostate, lung, colorectal, head and neck, and pediatric tumors.

• ADCs targeting B7-H3 have shown limited efficacy and notable toxicity, while T-cell engagers and radioligand therapies (RLTs) like AKY-2519 are seen as more promising.

• The low salivary gland exposure of AKY-2519 could address a key limitation of PSMA-targeted therapies, such as xerostomia.

• Results support broad clinical development in multiple tumor types and inform ongoing and future trials.