NTX2R13 / Nectin Therap - LARVOL DELTA

First-in-class anti-PVR mAb NTX1088 advancing through Phase I: Safe and potent in restoring DNAM1 expression to enhance antitumor immunity (AACR 2024) - P1 | "NTX1088 is investigated as a single agent and in combination with the anti-PD1 mAb, pembrolizumab (Keytruda) in patients with advanced solid malignancies...Synergy was obtained when NTX1088 was combined with PD1 blockers, or with the anti-CD112R mAb, NTX2R13.Syngeneic models of PVRK.O, demonstrated a complete immune-mediated tumor regression...First-in-human (FIH) trial is currently ongoing and biomarker analysis is showing initial mechanistic proof of concept for NTX1088 mode of action, including the restoration of DNAM1 surface expression on patients' immune cells. This is the first case of surface DNAM1 elevation in clinical settings."

IO biomarker • Oncology • Solid Tumor • CD96 • IFNG • PVR • TIGIT • TNFRSF9

Phase I trial of first-in-class anti-PVR mAb NTX1088: Restoration of DNAM1 expression as MOA for enhanced antitumor immunity (AACR 2023) - P1 | "NTX1088 will be investigated as a single agent and combined with the anti-PD1 mAb, pembrolizumab (Keytruda) in patients with locally advanced and metastatic solid malignancies.NTX1088 is a humanized, IgG4-S228P mAb that binds PVR with sub-nM affinity and blocks all known interacting receptors with a single nM EC50...Synergy was observed when NTX1088 was combined with PD1 blockers, or with the anti-CD112R mAb, NTX2R13, in line with the restoration of DNAM1 expression.Numerous humanized murine xenograft models were investigated...In conclusion, PVR blockade by NTX1088 has a remarkable pre-clinical efficacy, suggesting a potential clinical breakthrough, based on the ability of simultaneously overcome multiple tumor escape mechanisms. First-in-human (FIH) trial is currently ongoing and biomarker data is analyzed to assess clinical impact of the drug and prepare for patient stratification."

IO biomarker • P1 data • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • CD96 • IFNG • PVR • TIGIT • TNFRSF9

First-in-class anti-PVR mAb NTX1088 restores expression of DNAM1 and augments antitumor immunity (SITC 2022) - P1 | "Synergy was observed when NTX1088 was combined with PD1 blockers or with the anti-CD112R mAb, NTX2R13, in line with the restoration of DNAM1 expression. Tumor-infiltrating lymphocytes, harvested from NTX1088-treated mice, demonstrated a significantly higher prevalence of CD137+, DNAM1+, CD8+ T cells compared to all other interventions. Conclusions These promising preclinical findings, together with a clean safety profile in cynomolgus monkeys, paved the way to a Ph1 clinical study in which NTX1088 is tested as a monotherapy and in combination with pembrolizumab, in patients with locally advanced and metastatic solid tumors ( NCT05378425 )."

IO biomarker • Oncology • Solid Tumor • CD8 • CD96 • IFNG • PVR • TIGIT • TNFRSF9

First-in-class anti-PVR mAb NTX1088 restores DNAM1 expression and enhances antitumor immunity (AACR-NCI-EORTC 2022) - P1 | "Synergy was observed when NTX1088 was combined with PD1 blockers or with the anti-CD112R mAb, NTX2R13, in line with the restoration of DNAM1 expression. Moreover, the ability of NTX1088 to induce non-specific cytokine release was ruled out when tested in vitro. NTX1088 has an open IND, enrolling patients with locally advanced and metastatic solid tumors NCT05378425 No"

IO biomarker • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CD8 • CD96 • IFNG • PVR • TIGIT • TNFRSF9

NTX-1088, a first-in-class anti-PVR mAb mediates DNAM1-dependent antitumor immunity (AACR 2022) - "Synergistic effect was obtained when NTX-1088 was combined with the anti-CD112R mAb, NTX-2R13...Furthermore, NTX-1088 in combination with pembrolizumab, was superior to the combination of pembrolizumab with tiragolumab...This is a step change in antitumor immune activation that provides a remarkable and differentiated addition to the armamentarium available to patients and their treating oncologists. An IND will be open during 2Q2022."

IO biomarker • Oncology • Solid Tumor • CD8 • IFNG • PVR • TIGIT • TNFRSF9

NTX-1088, A POTENT ANTI-PVR MAB INDUCES DNAM1-MEDIATED ANTITUMOR IMMUNITY (SITC 2021) - "When tested in combination with pembrolizumab, NTX-1088 further increased all measured activation parameters, suggesting a potential synergistic effect. A synergistic effect was obtained when NTX-1088 was combined with the anti-CD112R mAb, NTX-2R13, superior to TIGIT-CD112R combinations. When compared to anti-TIGIT mAb (tiragolumab), NTX-1088 demonstrated clear superiority in activating T and NK cells as stand-alone agent...NTX-1088 shows, for the first time, exclusive triple mechanism of action, whereby simultaneous and effective blockade of TIGIT and CD96 is complemented by the efficient restoration of DNAM1. This is a step change in antitumor immune activation, which will be validated in the clinic starting early 2022."

IO biomarker • Oncology • Solid Tumor • CD8 • IFNG • TIGIT • TNFRSF9