SPX-303

SPX-303 is a first-in-class bispecific antibody therapy designed to simultaneously target two crucial immune checkpoint proteins: Leukocyte immunoglobulin-like receptor subfamily B member 2 (LILRB2) and Programmed death-ligand 1 (PD-L1). This innovative therapy was developed by SparX Biopharmaceutical (also referred to as SparX Group or SparX Biotech) and received FDA clearance for its Investigational New Drug (IND) application in late 2023[4][9]. ## Mechanism of Action SPX-303 works through a dual mechanism that targets both myeloid and T-cell immune checkpoints[10]. The drug is ingeniously engineered to overcome cancer cells' exploitation of immune checkpoints as a defense mechanism against immune attacks[6]. By simultaneously inhibiting LILRB2 and PD-L1, SPX-303 aims to enhance the immune system's ability to recognize and destroy cancer cells effectively[6][10]. ## Clinical Development The first patient was dosed with SPX-303 in April 2024 at HonorHealth Research Institute[6][8]. As of May 2025, the drug is in Phase 1 clinical trials, with patients being enrolled at a dose level of 20 mg/kg[10]. The ongoing Phase 1 study is an open-label, dose-escalation, and safety expansion study evaluating SPX-303's safety, tolerability, and preliminary efficacy in patients with resistant or refractory solid tumors[3][5][8]. ## Target Indications SPX-303 is being investigated for several solid tumor indications, including: - Colorectal Cancer (Phase 1) - Renal Cell Carcinoma (Phase 1) - Squamous Cell Carcinoma of Head and Neck (Phase 1) - Other solid tumors[1][3][8] The drug represents a significant advancement in macrophage checkpoint blockade and T cell co-engagement strategies, potentially serving as a next-generation immuno-oncology therapy for patients with limited treatment options[10].

Other names

anti-ILT4/anti-PD-L1 bispecific antibody SPX-303anti-LILRB2/PD-L1 bispecific antibody