Bayer announced initiation of dosing in a Phase I first-in-human clinical study with 225Ac-PSMA-Trillium (BAY 3563254), a next-generation targeted alpha therapy. The investigational candidate, labeled with actinium-225 and comprising a novel PSMA (prostate-specific membrane antigen) -targeting small molecule with a customized albumin-binding moiety, is designed to potentially improve therapeutic efficacy and reduce side effects in normal organs such as salivary glands. The dose-escalation study (NCT06217822) will evaluate the safety, tolerability and efficacy of 225Ac-PSMA-Trillium in patients with advanced metastatic castration resistant prostate cancer (mCRPC).

Prostate cancer is the second most commonly diagnosed cancer in men1 and a key area of focus at Bayer. Despite significant advances in the last decade, mCRPC remains a deadly disease with a median survival of about 31 months.2 Bayer remains committed to advancing medical innovations for patients across all stages of prostate cancer. In April, Bayer introduced 225Ac-PSMA-Trillium during the New Drugs on the Horizon session at the AACR (American Association of Cancer Research) Annual Meeting.3 Along with preclinical in vitro and in vivo characterization, the results were presented for a Phase 0 clinical imaging and dosimetry study conducted in participants with prostate cancer.

Targeted alpha therapy is an emerging class of radionuclide therapy that can be used against a variety of tumors. It is designed to deliver alpha particle radiation directly to the tumor inside the body, either via its bone-seeking property (radium-223) or by combining alpha radionuclides, such as actinium-225, with specific targeting moieties. This localized delivery of the radioactive payload induces difficult to repair double-strand DNA breaks in tumor cells; damage that can cause cell cycle arrest or cell death.

At the same time, because the energy does not travel very far, there is a potential for reduced damage to nearby normal tissues.