On November 30, 2022 Nectin Therapeutics Ltd., (Nectin) a biotechnology company developing novel targeted immunotherapies to address resistance to approved immuno-oncology (IO) treatments, reported dosing of the first patient in its Phase 1 clinical trial of NTX1088, Nectin’s first-in-class PVR (CD155) blocker, in cancer patients with locally advanced and metastatic solid tumors (Press release, Nectin Therapeutics, NOV 30, 2022, View Source [SID1234624625]). The trial is being conducted at The University of Texas MD Anderson Cancer Center (MD Anderson) with an investment from the Cancer Focus Fund, LP. The trial will include up to 90 patients treated with NTX1088 as a monotherapy and in combination with a PD-1 blocker.

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Additionally, Nectin announced that it has extended its Series A financing to over $25 million. IBF and Peregrine Ventures led the round, with participation from aMoon Fund and other existing investors. The funding will be used to support the ongoing clinical evaluation of NTX1088, and to further advance the company’s pipeline of targeted immunotherapies and Antibody Drug Conjugates (ADCs).

NTX1088 is a first-in-class high-affinity monoclonal antibody directed against PVR, a transmembrane protein expressed on cancer cells and associated with resistance to PD-1 and PD-L1 immune checkpoint inhibitors. PVR blockade by NTX1088 is the first and only therapeutic approach that aims to restore DNAM-1 (CD226) to the surface of immune cells. DNAM-1 is a cell surface glycoprotein, central to the activation of anti-cancer T and NK cells. Following interaction with PVR-expressing tumor cells, DNAM-1 is removed from the surface of immune cells. Restoring the expression and activation of DNAM-1 by blocking PVR results in increased anti-tumor activity from T and NK cells. PVR blockade additionally stimulates an anti-tumor immune response by preventing the immune-suppressing signaling of the two checkpoint receptors 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. High PVR expression is associated with poor prognosis and with resistance to PD-1 and PD-L1 blockade, making PVR an attractive therapeutic target for novel immuno-oncology therapies, both as a monotherapy and in combination with PD-1 blockers.

"PVR blockade by NTX1088, with its first-in-class differentiated mechanism of action, has demonstrated compelling preclinical anti-tumor activity both as a monotherapy and in combination with other cancer immunotherapies," said Dr. Pini Tsukerman, Co-Founder and Chief Scientific Officer of Nectin. "Importantly, NTX1088 has potent activity in ICI refractive models where TIGIT or PD-1 blockade has failed to show a benefit."

"Nectin has developed a highly innovative pipeline that has the potential to fundamentally overcome the limitations of existing IO therapies, delivering new treatment options for patients suffering from difficult-to-treat cancers, and we look forward to the results of the Phase 1 clinical trial of NTX1088," said Fabian Tenenbaum, CEO at Nectin Therapeutics. "As we continue to build on this foundation, we are delighted to welcome IBF as our new partner, joining our longstanding investors at aMoon Fund, Peregrine Ventures and Integra Holdings."

"NTX1088’s triple mechanism of action represents a unique approach to treating challenging cancers and we are excited by its potential to address a range of treatment-resistant tumors," said Ross Barrett, a founder and Managing Partner of Cancer Focus Fund. "Cancer Focus Fund was established to help finance cancer clinical trials with exceptional potential and we are delighted that this Phase 1 study of NTX1088 is underway."

The Phase 1 trial is an open-label study consisting of a dose escalation stage in up to 50 patients and an expansion stage in 40 patients. NTX1088 will be investigated as a single agent and in combination with a PD-1 blocker. 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 Piha-Paul, Associate Professor of Investigational Cancer Therapeutics at MD Anderson is the trial Principal Investigator.

About NTX1088

NTX1088 is a first-in-class monoclonal antibody directed against a key immune checkpoint, PVR, also known as CD155. NTX1088 has a triple mechanism of action. NTX1088 blocks the interaction between PVR and DNAM-1, also known as CD226, a molecule involved in the activation of anti-cancer T and NK cells. By preventing internalization and degradation of DNAM-1, NTX1088 leads to restoration of DNAM-1 expression on the surface of immune cells and results in robust antitumor activity. NTX1088 also blocks PVR interactions with TIGIT and CD96, preventing their immune inhibitory signaling. NTX1088 demonstrated superior antitumor activity compared to approved and investigational immune checkpoint inhibitors in preclinical models and had a favorable safety profile in non-human primates.