Aktis Oncology (AKTS) Study update summary

Clinical development strategy and trial design

• Initiated a dedicated Phase 1b trial of AKY-2519 in metastatic castration-resistant prostate cancer (mCRPC), enrolling both Pluvicto-naïve and Pluvicto-experienced patients in parallel cohorts at multiple U.S. centers.

• A second Phase 1b basket trial targeting B7-H3-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, informed by advisory board insights, aims to efficiently generate indication-relevant data for future pivotal studies and address broader patient segments.

• Dose escalation in the prostate trial will use three dose levels (6, 9, and 12 MBq), with expansion for further optimization.

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

Rationale and target biology

• B7-H3 is highly expressed in multiple solid tumors, including mCRPC, lung, breast, and colorectal cancers, and is associated with poor prognosis and non-responsiveness to anti-PD-1 therapy.

• B7-H3 has low expression in normal tissues and is not expressed in salivary glands, potentially reducing off-target toxicity compared to PSMA-targeted therapies.

• 90% of mCRPC patients express B7-H3, offering a differentiated safety and efficacy profile.

Preclinical and early clinical data

• Preclinical data show AKY-2519 and its tool compound AKY-3212 have high affinity, tumor retention, and robust anti-tumor effects in xenograft and mCRPC mouse models.

• AKY-3212 demonstrated superior efficacy compared to PSMA-617 in resistant mCRPC models.