Announcement • May 24
Aktis Oncology Inc Reports First-In-Human Clinical Imaging and Dosimetry Data for AKY-2519 Demonstrating Robust Tumor Uptake And Limited Normal Tissue Exposures In Patients With B7-H3 Expressing Tumors
Aktis Oncology, Inc. reported first-in-human clinical imaging and dosimetry data for AKY-2519, a miniprotein radioconjugate targeting B7-H3 expressing tumors. The data from two separate assessments of AKY-2519 – a clinical imaging and dosimetry assessment in patients with metastatic castration-resistant prostate cancer (mCRPC) and a clinical imaging assessment in patients with various solid tumor types – demonstrated robust tumor uptake and limited normal tissue exposure. These findings, which supported the advancement of a broad clinical development program for AKY-2519, will be presented in two poster presentations at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting, being held May 29 – June 2, 2026, in Chicago. These data informed the design of an ongoing Phase 1b clinical trial in patients with mCRPC and a second Phase 1b trial of AKY-2519 in various B7-H3 expressing tumor types, which are expected to initiate in the second half of 2026. The broad development opportunity for AKY-2519, the second clinical-stage program for multiple tumor types, exemplifies the vision to bring targeted radiopharmaceuticals to large patient populations with significant unmet need. These first-in-human clinical imaging and dosimetry data suggest the potential of AKY-2519 to expand targeted radiopharmaceuticals to broader patient populations while also offering a potentially important new radiopharmaceutical option for the mCRPC patient population. The robust tumor uptake and retention and low normal tissue uptake consistently seen with AKY-2519 in these assessments gives an initial understanding of its potential to kill cancer cells while minimizing normal-tissue radiation exposure. Moreover, the low predicted dose in salivary glands suggests AKY-2519’s unique potential as a B7-H3-targeted agent for mCRPC versus PSMA-targeting agents. B7-H3 is highly expressed in mCRPC, lung, colorectal and various other solid tumor types, with limited expression in normal tissues. High tumor expression of B7-H3 has been shown to be associated with poor prognosis and lack of response to certain therapies in multiple tumor types. AKY-2519 is the second clinical-stage targeted miniprotein radioconjugate discovered and developed from Aktis’ proprietary platform. The program includes [64Cu]Cu-AKY-2519 for imaging with copper-64 (64Cu) and [225Ac]Ac-AKY-2519 for therapeutic use with actinium-225 (225Ac). Aktis is currently enrolling patients in an mCRPC-dedicated Phase 1b trial of AKY-2519 in PLUVICTO®-naïve and PLUVICTO®-experienced patients, with preliminary data anticipated in 2027. The company is on track to initiate a second Phase 1b trial of AKY-2519 in other B7-H3 expressing solid tumors in the second half of 2026. Aktis’ lead program, AKY-1189, a miniprotein radioconjugate targeting Nectin-4 expressing tumors, is currently being evaluated in a Phase 1b trial, with preliminary data expected in the first quarter of 2027. Conducted at the Nuclear Medicine Research Infrastructure (NuMeRI) at the University of Pretoria and Steve Biko Academic Hospital, South Africa, the assessment evaluated the biodistribution and dosimetry of AKY-2519, using [68Ga]Ga-AKY-2519 and low dose, non-therapeutic [177Lu]Lu-AKY-2519 as imaging surrogates in 16 patients with mCRPC. In the first part of the assessment, patients were given [68Ga]Ga-AKY-2519 and imaged using PET/CT at 30, 60, and 90 - 150 minutes to evaluate normal tissue distribution, tumor uptake and comparison with uptake of FDA-approved diagnostic PSMA-11. In the second part of the imaging assessment, patients were given low-dose, non-therapeutic [177Lu]Lu-AKY-2519 and imaged using SPECT/CT at 3, 24, and 144 hours to evaluate dosimetry (mean absorbed dose) and to estimate predicted [225Ac]Ac-AKY-2519 absorbed doses, at a therapeutic administration schedule of 8 MBq x4, in normal tissues and tumors. Administration of AKY-2519 was generally well tolerated, with no adverse events or infusion-related reactions reported with either [68Ga]Ga-AKY-2519 or [177Lu]Lu-AKY-2519. Predicted absorbed doses of AKY-2519 in key normal tissues (bone marrow, liver, kidneys, salivary glands) were estimated to be favorable when compared to reference clinical benchmarks. Notably, the predicted absorbed dose of AKY-2519 to the salivary glands was lower compared to approved radiopharmaceuticals. AKY-2519 demonstrated robust tumor uptake and retention in tumors for at least 6 days after administration. Predicted absorbed doses of AKY-2519 to prospectively selected tumors, including involved prostate and seminal vesicles and nodal and bony metastases, were within expected therapeutic ranges for approved radiopharmaceuticals. The combined findings of predicted absorbed doses in tumors and normal tissues suggest a wide therapeutic index and a favorable profile for AKY-2519 compared to approved radiopharmaceuticals. Distribution of tumor uptake appears comparable between [68Ga]Ga-AKY-2519 and [68Ga]Ga-PSMA-11 at the standard 60 minutes measurement time point, with tumor uptake with [68Ga]Ga-AKY-2519 increasing over time. Conducted by the Department of Nuclear Medicine, University of Duisburg-Essen and German Cancer Consortium (DKTK), Universitätsklinikum Essen (University Hospital Essen), Essen, Germany, the assessment evaluated the biodistribution and tumor uptake of [68Ga]Ga-AKY-2519 in patients with advanced or metastatic disease in a variety of solid tumors, including prostate, lung, colorectal, and other tumor types (n=18). Following intravenous administration of [68Ga]Ga-AKY-2519 patients were imaged with PET/CT and SUV (standardized uptake value) measurements were taken to assess tumor uptake and normal tissue distribution at 15, 60 and 120 minutes. Administration of [68Ga]Ga-AKY-2519 was generally well tolerated, with no adverse events or infusion-related reactions reported. Robust uptake of [68Ga]Ga-AKY-2519 as measured by SUVmax was observed across multiple tumor types, including prostate, non-small cell lung cancer (NSCLC), small cell lung cancer (SCLC), and rectal cancer at various time points out to 120 minutes with representative patients showing: Prostate cancer: SUVmax = 33.9-37.4; NSCLC: SUVmax = 17.5-21.5; SCLC: SUVmax = 15.4; and Rectal cancer: SUVmax = 15.3. In prostate cancer, high [68Ga]Ga-AKY-2519 tumor uptake was consistently observed across metastatic disease sites with the most intense uptake observed in bone and visceral metastases. PET/CT imaging 120 min after [68Ga]Ga-AKY-2519 injection showed low uptake in critical normal tissues.