Nectin Therapeutics to Collaborate With Merck on Clinical Trial of Anti-PVR Antibody in Combination with KEYTRUDA in Patients With Locally Advanced & Metastatic Solid Tumors

Nectin Therapeutics Ltd. recently announced it has entered into a clinical trial collaboration agreement with Merck. Under this collaboration, Nectin will evaluate the safety, tolerability, and antitumor activity of its novel anti-PVR antibody, NTX1088, in combination with KEYTRUDA (pembrolizumab), Merck’s anti-PD1 therapy, in patients with locally advanced and metastatic solid tumors.

NTX1088 is a First-in-Class and 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 aiming 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 suppressed 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.

PVR is overexpressed in many solid tumors across different cancer indications, including lung, colorectal, liver, ovarian, breast, adrenal, pancreatic, uterine, head and neck, gastric and esophageal cancers. High PVR expression is associated with poor prognosis and with resistance to PD1 and PDL1 blockade, making PVR an attractive therapeutic target for novel immuno-oncology therapies, both as a monotherapy and in combination with PD1 blockers.

Phase 1 of the clinical trial with NTX1088 was initiated in November 2022. KEYNOTE-E92 NCT05378425 is an open label study consisting of a dose escalation stage, followed by an expansion stage in 90 patients. NTX1088 will be investigated as a single agent and in combination with KEYTRUDA. The primary objectives of the dose escalation stage are to assess safety and tolerability and to select a recommended safe and effective Phase 2 dose. In the expansion stage, NTX1088’s safety and tolerability will be further evaluated, along with efficacy measures and exploratory assessments of pharmacodynamic and predictive biomarkers. Dr. Sarina Phia-Paul, Associate Professor of Investigational Cancer Therapeutics at MD Anderson Cancer Center, is the trial’s Principal Investigator.

“We are very pleased to partner with Merck as we explore the therapeutic potential of NTX1088 in combination with KEYTRUDA,” said Dr. Keren Paz, Chief Development Officer of Nectin Therapeutics. “This collaboration represents an important milestone for Nectin, and a promising new therapy for cancer patients. Our preclinical studies have shown that PVR blockade by NTX1088, as a monotherapy, and in combination with PD1 inhibitors, can significantly enhance antitumor immunity. We look forward to advancing the clinical trials for NTX1088 as we pursue the development of new treatment options for patients who do not respond to existing therapies.”

NTX1088 is a first-in-class monoclonal antibody directed against a key immune checkpoint, PVR, also known as CD155 currently in its Phase I clinical trial. NTX1088 blocks the interaction between PVR and DNAM1, also known as 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, 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.

Nectin Therapeutics is a clinical-stage biotechnology company devoted to transforming the lives of cancer patients by leveraging unique insights into the nectin pathways to develop the next generation of immuno-oncology (IO) therapies. The company’s differentiated therapies have the potential to set new standards for efficacy and patient response rates across various difficult-to-treat cancers. Nectin’s technology addresses major escape mechanisms of current IO therapies through a diverse pipeline of novel monoclonal antibodies and antibody-drug-conjugates. It has a world-class scientific and management team with deep experience in oncology drug development and a successful track record in building biotechnology companies and developing innovative therapies. Nectin Therapeutics is a venture-backed, privately held company, funded by aMoon Fund, Peregrine Ventures, IBF, Integra Holdings and Cancer Focus Fund.