Nectin Therapeutics Ltd., a biotechnology company developing novel targeted immunotherapies, and Cancer Focus Fund, LP, a unique investment fund established in collaboration with The University of Texas MD Anderson Cancer Center (MD Anderson) to provide funding and clinical expertise to advance promising cancer therapies, have announced a Cancer Focus Fund investment of $5.4 million to finance a Phase 1 clinical trial of Nectin‘s PVR (Polio Virus Receptor) blocker, NTX1088, in cancer patients with locally advanced and metastatic solid tumors.
The Poliovirus receptor (PVR, CD155) has recently been gaining significant interest as a therapeutic target in the field of tumor immunology due to its prominent endogenous and immune functions. In contrast to healthy tissues, PVR is expressed at high levels in several human malignancies and seems to have protumorigenic and therapeutically attractive properties that are currently being investigated in the field of recombinant oncolytic virotherapy. PVR participates in a considerable number of immunoregulatory functions through its interactions with activating and inhibitory immune cell receptors. These functions are often modified in the tumor microenvironment, contributing to tumor immunosuppression. Indeed, increasing evidence supports the rationale for developing strategies targeting these interactions, either in terms of checkpoint therapy (i.e., targeting inhibitory receptors) or in adoptive cell therapy, which targets PVR as a tumor marker.
NTX1088 is a high-affinity monoclonal antibody directed against PVR, an immune checkpoint ligand, NTX1088 blocks the signaling of the immune checkpoint receptors TIGIT and CD96 while restoring the expression and immune function of DNAM1 (CD226), resulting in increased anti-tumor immune effects from activated T cells and natural killer (NK) cells in the tumor microenvironment. 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 PD1 blockade, making PVR an attractive therapeutic target for novel immuno-oncology therapies, both as a monotherapy and in combination with PD1 blockers.
The Cancer Focus Fund investment will support a Phase 1 clinical study at MD Anderson, assessing NTX1088 in the treatment of locally advanced and metastatic solid tumors. Cancer Focus Fund is receiving a combination of equity and future payments from Nectin based on the achievement of certain clinical and commercial milestones.
“The Cancer Focus Fund is committed to advancing the clinical development of novel cancer therapies with the potential to have a significant impact on patients,” said Ross Barrett, a founder and Managing Partner of the Cancer Focus Fund. “Despite their early promise, the majority of cancer patients do not respond to, or eventually acquire resistance to, current immunotherapies. NTX1088 has a unique mechanism of action that works in three ways to suppress the immune inhibitory effects of tumors while also promoting direct anti-tumor activity. We are delighted to help fund this first-in-human clinical trial at MD Anderson, our collaborator in leading Cancer Focus Fund-financed clinical trials.”
The Phase 1 trial is an open-label study in 90 patients that will be conducted in two stages – a dose-escalation stage and an expansion stage. NTX1088 will be investigated as a single agent and in combination with a PD1 blocker. The primary objectives of the dose-escalation stage are to assess safety and tolerability and to select a recommended safe and effective dose. In the expansion stage of the trial, NTX1088‘s safety and tolerability will be further evaluated, along with initial efficacy measures and exploratory assessments of pharmacodynamic and predictive biomarkers, which will assist in stratifying patients moving forward. Sarina A. Piha-Paul, MD, an Associate Professor in the Department of Investigational Cancer Therapeutics at MD Anderson, will serve as the Principal Investigator.
“Nectin Therapeutics is developing a portfolio of innovative anticancer compounds directed at highly differentiated targets within the nectin family of immune checkpoints,” said Fabian Tenenbaum, Chief Executive Officer of Nectin Therapeutics. “The upcoming initiation of our first-in-human clinical trial is a major milestone for the company. We welcome the financial support from the Cancer Focus Fund and the clinical expertise of MD Anderson in facilitating the Phase 1 study for this promising new approach to helping patients mount an effective immune response to their cancer.”
The Phase 1 trial is expected to begin enrolling patients around mid-year 2022.
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. It binds PVR with high affinity and blocks its interactions with TIGIT and CD96, preventing their immune inhibitory signaling. NTX1088 also blocks the interaction between PVR and DNAM1, also known as CD226, a molecule that is an immune checkpoint receptor involved in the activation of anti-cancer T cells and NK cells. By preventing internalization and degradation of DNAM1, NTX1088 leads to restoration of DNAM1 expression on the surface of immune cells and results in robust antitumor activity. NTX1088 demonstrated superior antitumor activity compared to approved and investigational immune checkpoint inhibitors in preclinical models and revealed a favorable safety profile in non-human primates.
About Cancer Focus Fund
The Cancer Focus Fund LP is a unique investment fund established in collaboration with The University of Texas MD Anderson Cancer Center. The fund provides investment support to advance promising cancer therapies that are close to being tested in humans or are in early clinical development, as well as the clinical trial expertise and infrastructure of MD Anderson and strategic partners Ochsner Health System Precision Cancer Therapies Program New Orleans and the LSU Feist Weiller Cancer Center Shreveport. The Fund’s objective is to leverage this unique combination to provide investors with superior risk-adjusted returns. In collaboration with partner MD Anderson, the Cancer Focus Fund provides both capital and translational research expertise with the goal of accelerating the development of novel cancer therapies that result in better outcomes for patients while generating returns for investors.
About Nectin Therapeutics Ltd.
Nectin Therapeutics was founded in 2017 by Dr. Pini Tsukerman, Co-Founder and Chief Scientist; Prof. Ofer Mandelboim from the Immunology & Cancer Research Center at the Hebrew University; and Prof. Stipan Jonjic from the Department of Histology and Embryology/Center for Proteomics, Faculty of Medicine, University of Rijeka. It was initially funded by the Hebrew University of Jerusalem tech fund Integra Holdings. Nectin is based on technology developed by Hebrew University researcher Prof. Ofer Mandelboim from the Immunocology and Cancer Research Center and Prof. Stipan Jonjic from the Department of Histology and Embryology Center for Proteomics at the Faculty of Medicine in the University of Rijeka in Croatia. Nectins are families of cellular adhesion molecules involved in Ca2+-independent cellular adhesion.
Nectin Therapeutics is a biotechnology company devoted to transforming the lives of cancer patients by leveraging unique insights into the nectin pathway to develop the next generation of immune-oncology (IO) therapies, through a diverse pipeline of novel monoclonal antibodies (mAbs) and antibody-drug-conjugates (ADCs). Its 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, Integra Holdings, and Cancer Focus Fund.
Source: March 7, 2022 PRNewswire
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