- First-in-class monoclonal antibody targeting KIR3DL3, the inhibitory receptor for HHLA2, designed to reverse immune suppression in the tumor microenvironment

- The study will assess safety, tolerability and inform dosing strategy

NextPoint Therapeutics, a clinical-stage biotechnology company developing precision immuno-oncology therapeutics targeting the novel HHLA2 pathway, announced today that the first patient has been dosed with NPX267 in a Phase 1 first-in-human clinical trial for the treatment of patients with solid tumors known to express HHLA2, a tumor antigen strongly upregulated in many human tumors independently of PD-L1.

The Phase 1a/1b open-label, multi-center study (NCT05958199) consists of a dose escalation and an expansion stage to evaluate the tolerability, pharmacokinetics, immunogenicity and biomarker strategy of NPX267 in patients with metastatic solid tumors including epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) and other indications.

Killer cell immunoglobulin-like receptor 3DL3 (KIR3DL3) is expressed on effector T cells and natural killer (NK) cells in the tumor microenvironment and is an inhibitory receptor for the tumor antigen HHLA2, expressed on a range of solid tumors. Binding of KIR3DL3 to HHLA2 is believed to allow tumors to cloak themselves and hide from immune cells.

“Many cancers hijack the HHLA2 pathway to evade the immune system, whose signaling mechanisms were independently co-discovered by NextPoint’s scientific co-founders, Dr. XingXing Zang and Dr. Gordon Freeman,” said Detlev Biniszkiewicz, PhD, Chief Executive Officer of NextPoint Therapeutics. “Because HHLA2 is expressed independently of PD-L1 and is often highly expressed in PD-L1-negative cancers, targeting the HHLA2-KIR3DL3 interaction is a promising new approach for patients with cancer.”

“We are excited to launch the clinical evaluation of NPX267, our lead therapeutic program targeting the HHLA2 pathway,” said Leena Gandhi, MD, PhD, Chief Medical Officer of NextPoint Therapeutics. “This study will provide important data on the therapeutic activity of NPX267 as well as the mechanism of HHLA2-mediated immunosuppression via KIR3DL3 and inform our clinical strategy for developing precision immunotherapeutic treatments for patients.”

About NPX267

NPX267 is a first-in-class monoclonal antibody targeting KIR3DL3, the inhibitory receptor for the HHLA2 pathway (B7-H7), and is designed to prevent immune escape in solid tumors. By blocking the binding of KIR3DL3 on exhausted T and NK cells to HHLA2 expressed on tumor cells, NPX267 may be able to reactivate tumor antigen-primed immune cells in HHLA2-expressing solid tumors. Preventing KIR3DL3-mediated immune suppression may enhance anti-tumor immune responses for patients with HHLA2-positive cancers – a tumor antigen expressed independently of PD-L1. To learn more, visit www.clinicaltrials.gov (NCT05958199).

About NextPoint Therapeutics

NextPoint is advancing the field of immuno-oncology through its leading scientific work on the novel HHLA2 pathway. Our innovative approach integrates foundational science with a defined clinical biomarker to deliver a new class of monotherapies for patients who will not benefit from PD-1/L1 inhibitors. Our team of proven drug developers is working closely with our renowned scientific founders to launch a new world of precision immuno-oncology. To learn more, visit nextpointtx.com.

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