netrin-1

A new scientific finding is the foundation for the first clinical trial in the U.S. to study an experimental drug's ability to fight pancreatic cancer with metastasis to the liver.   Pancreatic cancer is tricky to manage because it spreads easily and early, and the tumors have a unique biological makeup. But, researchers made a breakthrough by learning about the genetic changes that occur during tumor migration -- and also found a drug that can obstruct the process. The next step is a groundbreaking clinical trial at the University of Rochester's Wilmot Cancer Institute, planned for early in 2024, to test the drug from their laboratory discovery, said senior investigator Darren Carpizo, MD, PhD, co-leader of Wilmot's Genetics, Epigenetics and Metabolism research program, and chief of Surgical Oncology at the University of Rochester Medical Center. "We will be the first institution in the U.S. to study the safety and effectiveness of the experimental drug, known as NP137, on pancreatic cancer that has spread to the liver," Carpizo said. Carpizo and several collaborators recently published the results of their bench science investigation in the journal Cell Reports, and Carpizo will lead the Wilmot clinical trial with Aram Hezel, MD, chief of Hematology/Oncology at Wilmot, and Nabeel Badri, MBChB, a medical oncologist at Wilmot. The five-year survival rate for pancreatic cancer is only 12 percent, which is a slight increase in 2023 compared to previous years. The number of cases is rising worldwide, however, and by 2030, pancreatic cancer is predicted to be the second leading cause of cancer deaths. Why is pancreatic cancer deadly? First, because it spreads (metastasizes) very early during its development. In 85 percent of patients, the cancer has already spread outside of the pancreas at diagnosis. Even when the cancer is localized to the pancreas and surgical removal is possible, the majority of patients face a recurrence of their cancer. The metastasis causes these patients to eventually succumb to the disease, which is why researchers are focused on understanding the biology of metastatic pancreatic cancer. Second, although pancreatic cancer cells do not have to travel far to reach the liver, along the way they genetically reprogram themselves and become stronger. The result: newly seeded cancer cells in the liver have a distinctly different biology from the primary tumor in the pancreas, and are able to resist standard treatment, Carpizo said. In their latest work, Wilmot researchers built on what was already known about a key gene, Netrin-1, involved in pancreas, breast and colon cancers. They discovered, for the first time, the complex mechanisms that allow Netrin-1 to drive the lethal, genetic changes as pancreatic cancer cells migrate to the liver. They also showed how Netrin-1 activates hepatic stellate cells, which are involved in liver fibrosis, a serious chronic disease, priming the liver as a host for cancer. In mice and in tissue studies, when researchers suppressed Netrin-1 with the anti-cancer drug (NP137), cancer was less likely to spread and cancer cell death occurred. The team includes scientists from Rutgers University, where Carpizo worked as a surgeon-scientist before joining Wilmot in 2020, Fox Chase Cancer Center in Philadelphia, and a laboratory in France. The Wilmot clinical trial will likely require eligible patients to take two cycles of NP137 before surgery, undergo surgery to remove the cancer, and then take more of the experimental medication along with chemotherapy after surgery for up to six months, Carpizo said. He noted that NP137 is made by Netris Pharma, of Lyon, France, and is currently being tested in clinical trials in that country. The Pancreatic Cancer Action Network (PanCAN) funded much of the work through a grant to Carpizo; Wilmot also provided pilot funding. PanCAN has emphasized that the recent, small uptick in survivorship rates for pancreatic cancer is due to transformative research and clinical trials, and strongly recommends that patients talk to their oncologists about clinical trials at every stage of their disease. Carpizo's study is part of a larger collaborative effort at Wilmot aimed at pancreatic cancer. Others, including URMC Surgery Chair David Linehan, MD., and Wilmot investigator Scott Gerber, PhD., and members of the Cancer Microenvironment research program, are also conducting studies on new, targeted treatments. The goal is to use newly discovered drugs in combination with immunotherapy, radiation therapy, and chemotherapy to attack pancreatic cancer.

ImmunoNET Study Aims to Expand Patient Response to Immunotherapies LYON, France--(BUSINESS WIRE)-- NETRIS Pharma, a clinical-stage private biopharmaceutical company developing a new class of drugs based on dependence receptor biology, today announced dosing of the first patient in the ImmunoNET trial. ImmunoNET is a multicenter, open-label, proof of concept phase II trial designed to assess the clinical and biological activity of NETRIS Pharma’s first drug candidate, NP137, as add-on therapy in patients with advanced/metastatic solid tumors treated by standard immunotherapies. “The enrollment of the first patient in ImmunoNET is a new clinical milestone for NETRIS Pharma. Immune-checkpoint inhibitors have revolutionized the treatment of cancer, yet the vast majority of patients do not respond or transiently respond to these immunotherapies. Based on a unique mode of action of NP137 and biomarker studies conducted in Phase 1, we believe we can enlarge the fraction of responding patients and potentially prevent resistance,” said Patrick Mehlen, CEO of NETRIS Pharma. “ImmunoNET has been specifically designed by clinicians to provide new solutions for patients suffering from resistance to immune-checkpoint inhibitors.” The study will enroll up to 90 patients suffering from solid-tumor cancers, including Head and Neck, Melanoma, Non-Small Cell Lung Cancer, Urothelial and other tumor types. These patients will be classified according to their responses to immunotherapy, in 3 arms: (1) patients under stable disease after 12 weeks under standard PD-1/PD-L1 therapy; (2) patients with radiological progression; and (3) patients with radiological progression following an initial objective response according to RECIST V1.1, with clinical benefit according to RECIST. “Despite some remarkable results with the use of immunotherapy, which have become the new standard of care in various oncology indications, many patients are experiencing an absence of response or immune resistance,” said Jérome Fayette, clinical oncologist at Centre Léon Bérard and Principal Investigator of this Investigator Initiated Trial conducted in collaboration with several key clinical centers in France. “We look forward to measure the potential benefit of NP137 on patients partially or not responding from immunotherapy.” “NETRIS Pharma is thankful to the EU Innovation Council and SME’s Executive Agency (EISMEA) to participate to the funding of this trial after having been selected as one of the most innovative project in Europe in December 2021 under the EIC accelerator Instrument program,” added Christophe Guichard, CFO of NETRIS Pharma. About NETRIS Pharma NETRIS Pharma, a clinical-stage company designs and develops anti-cancer therapeutic molecules, particularly monoclonal antibodies, to block the interaction between dependence receptors and their ligands. NETRIS Pharma, based in Lyon, is the world most advanced biopharmaceutical company targeting netrin-1. Further information can be found at: . About NP137 NP137 is a humanized monoclonal antibody of isotype IgG1 directed against netrin-1. Most types of tumors produce an abnormal amount of dependence receptors’ ligands, which prevents cells from apoptosis. Netrin-1 is overexpressed in a large percentage of human cancers. Expression of netrin-1 often correlates with disease severity and no therapy has ever been tested against this new pathway. Pre-clinical studies show NP137 to have an anti-cancer effect as a monotherapy as well as synergistic effects in combination with chemotherapy or immune checkpoint inhibitors. Further to the confirmation of the excellent safety pro human, NETRIS Pharma is simultaneously actively recruiting up to 240 patients in a separate randomized Phase 2 GYNET trial, in uterine cancer indications, in combination with chemotherapy and immunotherapy. About Centre Léon Bérard Centre Leon Berard is among the top 3 Comprehensive Cancer Center in France and an integrated cancer research site (SIRIC), with a high level of excellence in basic, translational and clinical research in oncology. It is accredited by the Organization of European Cancer Institutes (OEIC) and hosts the Cancer Research Centre of Lyon (CRCL – U1052 – UMR5286), with more than 500 collaborators involved in all domains of cancer research. Further information can be found at: ; . About EIC Accelerator The EIC Accelerator supports individual Small and Medium Enterprises (SMEs), in particular Startups and spinout companies to develop and scaleup game-changing innovations. ImmunoNET is co-funded by the European Union. Views and opinions expressed are however those of the author(s) only and do not necessarily reflect those of the European Union or NETRIS Pharma. Neither the European Union nor NETRIS Pharma can be held responsible for them. View source version on businesswire.com: Contacts NETRIS Pharma Patrick MEHLEN, CEO, patrickmehlen@netrispharma.com Christophe GUICHARD, CFO and IR, christopheguichard@netrispharma.com Mike Sinclair, Halsin Partners (for NETRIS Pharma) msinclair@halsin.com Centre Léon Bérard Press Office: +33 (0) 4 69 85 61 85 julie.colomb@lyon.unicancer.fr Source: NETRIS Pharma View this news release online at:

Aims to combine NETRIS Pharma’s mAb with selected radioisotopes LYON, France--(BUSINESS WIRE)-- NETRIS Pharma SAS, a private clinical-stage biopharmaceutical company, announced today that it has entered into a scientific collaboration agreement with Orano and the Centre Léon Bérard (CLB) to develop novel Antibody Radio-Conjugates for the treatment of cancer. Initially, the parties intend to conduct a preclinical proof-of-concept efficacy study with new radio-conjugate targeting Netrin-1, combining Netris’ monoclonal antibody (mAb) NP137 with undisclosed radioelement from Orano. “Based on strong preclinical evidence showing the potential of linking NP137, our proprietary mAb, with approved radioelements for both imaging and therapy purposes, this collaboration with Orano and CLB has the potential to develop novel radio-conjugate that provide significant clinical benefits to patients,” said Patrick Mehlen, Founder and Chief Executive Officer of NETRIS Pharma. Both NETRIS Pharma and Orano have entered into this collaboration with Centre Léon Bérard based on the potential opportunities brought by novel radioisotope conjugates in oncology. Under the terms of the agreement, planned to be completed within one year, NETRIS Pharma, Orano and CLB will contribute their unique respective expertise in anti-netrin-1 biology and mode-of-action, radioisotope and nuclear based products, and preclinical and clinical oncology expertise to develop new compounds for clinical use. “For Orano, it is a real opportunity to couple a new radioisotope with NP137developed by NETRIS Pharma thanks to the know-how of the Léon Bérard Comprehensive Cancer Center, in order to create a highly effective compound,” declared Guillaume Dureau, Orano’s Director of Research & Development and Innovation. “With this collaboration, we hope to lay the foundation of a long-term partnership driven by the significant complementary expertise of the three partners.” “The vectorized radiotherapy practice of the Léon Bérard Comprehensive Cancer Center is among the most innovative ones in Europe,” said Jean-Yves Blay, General Director of CLB. “New technologies using original cargoes to deliver radioelement are key to provide more effective treatments to patients. With the collaboration leveraging our strong clinical practice, we look forward to the future developments of this project.” About NP137 NP137, a humanized monoclonal antibody of isotype IgG1 directed against netrin-1, is the first drug candidate developed by NETRIS Pharma. Most types of tumors produce an abnormal amount of dependence receptor ligands, which prevents cells from dying. Netrin-1 is overexpressed in a large percentage of human cancers. Expression of netrin-1 often correlates with disease severity and no therapy has ever been tested against this new pathway. Preclinical studies show NP137 to have an anti-cancer effect as a monotherapy as well as synergistic effects in combination with chemotherapy or immune checkpoint inhibitors. NP137 has been so far administered to more than 140 patients and confirmed its excellent safety pro in monotherapy and combination with chemotherapy and immunotherapy. The company is currently actively recruiting up to 240 patients in its Phase 2 trial in uterine cancer indications. About NETRIS Pharma NETRIS Pharma, a clinical-stage company designs and develops anti-cancer therapeutic molecules, particularly monoclonal antibodies, to block the interaction between dependence receptors and their ligands. NETRIS Pharma, founded in 2008 and based in Lyon, is the world most advanced biopharmaceutical company targeting netrin-1. Further information can be found at: . About Orano As a recognized international operator in the field of nuclear materials, Orano delivers solutions to address present and future global energy and health challenges. Its expertise and mastery of cutting-edge technologies enable Orano to offer its customers high value-added products and services throughout the entire fuel cycle. Every day, the Orano group’s 16,500 employees draw on their skills, unwavering dedication to safety and constant quest for innovation, with the commitment to develop know-how in the transformation and control of nuclear materials, for the climate and for a healthy and resource-efficient world, now and tomorrow. Orano, giving nuclear energy its full value. Orano looks continuously at opportunities to value material derived from its core nuclear energy activities in a sustainable approach. Nuclear medicine therapy is one of the currently explored strand realized with the production of lead-212 (a rare radioisotope used for targeted alpha therapy) and clinical studies underway. Orano aims to further strengthen its development in the medical field and complete its pipeline with new promising radioisotopes. Further information can be found at: About Centre Léon Bérard Centre Leon Berard is among the top 3 Comprehensive Cancer Center in France and an integrated cancer research site (SIRIC), with a high level of excellence in basic, translational and clinical research in oncology. It is accredited by the Organization of European Cancer Institutes (OEIC). It hosts the Cancer Research Centre of Lyon (CRCL – U1052 – UMR5286), with more than 500 collaborators involved in all domains of cancer research (immune system, tumor genesis and microenvironment, EMT, cancer escape and drug resistance, epidemiology, etc.). The CRCL operates a wide variety of state of the art technology platforms designed to foster the development of innovative therapies and accelerate technology transfer from bench to bedside. CLB is also one of the few preclinical facility in the world able to develop a “theranostic” approach based on the radiolabeling of antibodies, with process, technologies and regulatory compliance for handling of radioelements in the healthcare environment. Further information can be found at: ; View source version on businesswire.com: Contacts NETRIS Pharma Investor Relations : Christophe Guichard christopheguichard@netrispharma.com Orano Press Office: +33 (0)1 34 96 12 15 press@orano.group Investor relations: Marc Quesnoy investors@orano.group Centre Léon Bérard Press Office: +33 (0) 4 69 85 61 85 julie.colomb@lyon.unicancer.fr Source: NETRIS Pharma View this news release online at: