Astellas Pharma Inc. (TSE: 4503) and Vir Biotechnology, Inc. (Nasdaq: VIR) signed a global strategic collaboration deal that will see Astellas gain global rights to VIR-5500, a prostate-specific membrane antigen (PSMA)-targeted PRO-XTEN dual-masked T-cell engager (TCE) for the treatment of prostate cancer.
Under the deal terms, Astellas is set to take on global development activities once Vir’s Phase I study for the molecule has been completed. Astellas will will lead future commercialization in the United States and hold exclusive commercial rights outside the US, while Vir has the option to co-promote VIR-5500 in the US market. Vir stands to receive USD 335 million in the near term, divided into a USD 240 million upfront cash payment, USD 75 million in equity investment, and another USD 20 million near-term milestone. Global development costs for VIR-5500 will be shared, with Astellas responsible for 60% and Vir Biotechnology responsible for 40% of all costs. US profits will be split equally, while Vir is eligible for tiered double-digit royalties on ex-US market sales. Finally, Vir is also eligible for up to USD 1.37 billion in development, regulatory, and sales milestones.
VIR-5500 is a bispecific T-cell engager designed to bind PSMA on tumor cells and CD3 on T cells, redirecting cytotoxic T-cell activity toward PSMA-expressing cancer cells. The molecule is built on Vir’s PRO-XTEN platform, which incorporates dual masking domains that block the active binding arms of the bispecific while in systemic circulation. These masks are designed to be cleaved by proteases enriched in the tumor microenvironment, enabling conditional activation at the tumor site.
The dual-masked design seeks to address therapeutic index limitations that have constrained T-cell engager development in solid tumors. PSMA is expressed not only on prostate cancer cells but also at lower levels in normal tissues such as salivary glands, lacrimal glands, and the small intestine, contributing to on-target, off-tumor toxicity and cytokine release syndrome (CRS) observed with conventional PSMA-directed T-cell engagers.