Aktis Oncology (AKTS) Study update summary

Clinical development strategy for AKY-2519

• Initiated a dedicated Phase 1b trial for AKY-2519 in metastatic castration-resistant prostate cancer (mCRPC), enrolling both PLUVICTO-naive and -experienced patients.

• A second Phase 1b basket trial targeting B7H3-expressing tumors, including lung and colorectal cancers, is planned for the second half of 2026, with protocol finalized and under regulatory review.

• The two-trial approach aims to efficiently generate indication-relevant data for future pivotal studies and broader patient segments.

• Trial design is informed by clinical advisory boards and tailored to distinct needs of prostate cancer versus other solid tumors.

• Both trials are conducted under IND in the U.S. at specialized and academic centers.

Rationale and preclinical/clinical data

• B7H3 is highly expressed in multiple tumor types, including mCRPC, lung, and breast cancers, with minimal expression in normal tissues, making it an attractive radiopharmaceutical target.

• High B7H3 expression correlates with poor survival and non-responsiveness to anti-PD-1 therapy in several cancers.

• Preclinical studies showed AKY-2519 and AKY-3212 have high affinity for B7H3, strong tumor retention, and robust anti-tumor effects, with AKY-3212 outperforming PSMA-617 in resistant mCRPC models.

• Many mCRPC patients are ineligible for or have sub-optimal response to PSMA-targeted therapies, highlighting unmet needs.

• B7H3 targeting radioligand therapy could unlock new opportunities across multiple solid tumor types.

Study design and patient selection

• The mCRPC trial uses a BOIN dose escalation with three dose levels (6, 9, 12 MBq) across PLUVICTO-naive and -experienced cohorts, with expansion at selected doses.

• PLUVICTO-naive patients do not require prior chemotherapy or PSMA expression testing; eligibility is based on mCRPC and progression after at least two ARPIs.

• All patients must demonstrate tumor uptake via imaging before enrollment.

• Basket trial will focus on lung, colorectal, and other B7H3-high tumors, with protocol finalized and under regulatory review.

• Efficient data generation is expected to inform future development and clinical positioning.