Aktis Oncology has reported the first clinical data for AKY-1189, a novel Nectin-4-targeted radiopharmaceutical that demonstrated substantial tumor uptake across multiple solid tumor types in initial human studies. The data, presented at the EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics in Barcelona, marks a significant milestone for what the company describes as the industry's only Nectin-4-directed radioligand therapy.
Novel Miniprotein Platform Shows Clinical Promise
Unlike conventional radiotherapies based on small molecules, AKY-1189 utilizes an anti-Nectin-4 "miniprotein" linked to the alpha emitter actinium-225. This miniprotein is not an antibody but a biological that can be manufactured synthetically with an efficient and scalable method, according to researchers. The compound was engineered to deliver actinium-225 directly to tumors while minimizing exposure to normal organs and tissues.
Professor Mike Sathekge from the University of Pretoria presented biodistribution and dosimetry data from studies conducted under special permission from South Africa's regulator. The analysis included 15 patients evaluable for biodistribution and tumor uptake, with eight patients receiving dosimetry assessment using a lutetium-177 version of the compound for imaging advantages.
Broad Tumor Targeting Potential
The clinical data revealed "robust" uptake of the miniprotein in tumors across various cancer types. Particularly notable was the "excellent uptake" observed in ER-positive breast cancer, suggesting potential applications beyond the current Nectin-4 therapy landscape dominated by Pfizer/Astellas's Padcev in bladder cancer. The compound also demonstrated uptake in lung and colorectal tumors.
Sathekge noted that AKY-1189 could potentially treat bladder cancer patients who had relapsed on Padcev, with imaging capable of identifying those with sufficiently high levels of Nectin-4 expression. This positioning could address an important unmet medical need in the urothelial carcinoma treatment landscape.
Favorable Safety Profile Supports Clinical Advancement
The safety analysis revealed no treatment-emergent adverse events in the eight patients who received the therapeutic dosimetry assessment. While kidneys were identified as potentially dose-limiting organs, uptake was transient with rapid clearance. Importantly, uptake in normal tissues remained well below desired clinical thresholds, suggesting a "wide safety margin" and therapeutic index for the actinium-225 version.
The dosimetry analyses demonstrated that AKY-1189 has a promising biodistribution profile in normal organs and tissues, with the data supporting progression to formal therapeutic clinical studies across several solid tumor types.
Clinical Development Timeline
Based on these encouraging results from eight patients dosed under regulatory permission, Aktis is advancing AKY-1189 into formal clinical trials. A phase 1 trial is currently under regulatory review in South Africa, while the company prepares to initiate a corresponding phase 1 US study in Nectin-4-expressing tumors in 2025.
The clinical advancement comes on the heels of significant corporate developments for Aktis, including a recent radiopharmaceutical deal with Eli Lilly worth $60 million upfront and a $175 million Series B financing round. These partnerships and funding support the company's broader miniprotein radioconjugate platform development.
First-in-Class Therapeutic Approach
Matthew Roden, President and CEO of Aktis Oncology, emphasized that AKY-1189 represents the first therapeutic product candidate discovered from the company's novel miniprotein radioconjugate platform. The data suggest the platform can achieve a favorable clinical profile and opens new pathways in radiopharmaceutical development.
The miniprotein radioconjugates are designed to maximize tumor killing through high penetration followed by internalization and retention in cancer cells, while quickly clearing from normal organs and tissues. This approach aims to maximize anticancer activity while minimizing treatment side effects. The platform is also isotope-agnostic, enabling clinicians to visualize and verify target engagement with imaging isotopes prior to therapeutic radioisotope exposure.
