Nectin Therapeutics Advances Ongoing Clinical Trial and Expands Sites to Israel

On December 26, 2023 Nectin Therapeutics Ltd., (Nectin), a biotechnology company developing novel targeted immunotherapies that address resistance to approved immune oncology treatments, reported that it has progressed its Phase 1 clinical trial of NTX1088 to include a combination therapy arm with the immune-oncology drug KEYTRUDA (pembrolizumab), MSD’s anti-PD-1 therapy, and expanded the trial to four additional global sites to include Sheba Medical Center, Hadassah Medical Center, Ochsner Health, and City of Hope along with flagship site, MD Anderson Cancer Center (Press release, Nectin Therapeutics, DEC 26, 2023, View Source [SID1234638798]).

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NTX1088 is Nectin’s First-in-Class lead candidate – a highly potent monoclonal antibody directed against PVR (CD155), a transmembrane protein expressed on cancer cells and associated with resistance to PD1 and PDL1 immune checkpoint inhibitors. PVR blockade by NTX1088 is the first and only therapeutic approach aimed at restoring the antitumor immune activity of DNAM1 (CD226). DNAM1 is a cell surface glycoprotein, central to the function of T and NK cells, that is degraded by PVR on tumor cells. Restoring the expression and activation of DNAM1 by blocking PVR results in increased antitumor activity from T and NK cells. PVR blockade by NTX1088 further stimulates an antitumor immune response by preventing the suppressing signaling of several immune checkpoint receptors, including TIGIT and CD96. NTX1088 is currently being clinically evaluated as a monotherapy and in combination with KEYTRUDA (pembrolizumab).

"We are very pleased to treat Israeli patients as part of NTX1088’s clinical trial," said Dr. Raanan Berger, Director of the Cancer Center at the Sheba Medical Center. "We are impressed by the pre-clinical data and the novel mechanism of action of PVR blockade and are looking forward to collaborating with Nectin Therapeutics to evaluate the impact of this first-in-class therapy for cancer patients."

"Nectin’s innovative pipeline holds a therapeutic promise for patients with hard-to-treat cancers. This transformational potential is proudly driven by dedicated research efforts in Israel, making it very compelling for Nectin to establish trial sites close to home," said Dr. Keren Paz, Chief Development Officer of Nectin Therapeutics. "We are encouraged by the rapid progress of our NTX1088 clinical program and are excited to expand it globally."

About NTX1088

NTX1088 is a first-in-class monoclonal antibody directed against a key immune checkpoint, PVR (CD155), currently in a Phase I clinical trial. NTX1088 blocks the interaction between PVR and DNAM1(CD226), a transmembrane molecule, involved in the activation of anti-cancer T and NK cells. By preventing internalization and degradation of DNAM1, NTX1088 leads to restoration of DNAM1 expression on the surface of immune cells, resulting in robust antitumor activity. NTX1088 also blocks PVR interactions with its other ligands, such as TIGIT and CD96, preventing their immune inhibitory signaling. NTX1088 demonstrates superior antitumor activity compared to approved and investigational immune checkpoint inhibitors in preclinical models and had a favorable safety profile in non-human primates. NTX1088 is currently being clinically evaluated as a monotherapy and in combination with KEYTRUDA (pembrolizumab).