Vudalimab (PD1 x CTLA4)

Ongoing Phase 2 clinical study for the treatment of patients with metastatic castration-resistant prostate cancer (mCRPC)

Tumor infiltrating lymphocytes express multiple immune checkpoints and co-stimulatory receptors. Xencor’s bispecific tumor microenvironment (TME) activators seek to more effectively reactivate these tumor-killing T cells by engaging multiple T-cell targets simultaneously. This approach eliminates the need for the multiple antibodies and allows for more selective targeting of T cells with high checkpoint expression, which may potentially improve the therapeutic index of combination immunotherapies.

Vudalimab is a bispecific antibody that simultaneously targets immune checkpoint receptors PD-1 and CTLA-4 and is designed to promote tumor-selective T-cell activation. Xencor’s XmAb® Bispecific Fc Domain serves as the scaffold for these two antigen binding domains and confers long circulating half-life, stability and ease of manufacture on vudalimab. XmAb bispecific Fc domains have been engineered to eliminate Fc gamma receptor (FcγR) binding, with the intent to prevent activation and/or depletion of T cells via engagement by FcγR-expressing cells. In preclinical studies, dual blockade of PD-1 and CTLA-4 with vudalimab significantly enhanced T cell proliferation and activation, and anti-tumor activity in vivo.

Xencor has initiated a Phase 2 clinical study of vudalimab in patients with mCRPC, as a monotherapy or in combination depending on molecular subtype, and a Phase 2 clinical study in patients with advanced gynecologic and genitourinary malignancies, as well as clinically defined high-risk mCRPC.

Each of Xencor’s bispecific TME activators tests a distinct mechanism of TME activation. XmAb104 (PD-1 x ICOS) is being evaluated in Phase 1 clinical studies.

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