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Unique NP137 mechanism targeting netrin-1 could alleviate anti-PD-1 resistance

Lyon, France – May 5, 2020

NETRIS Pharma SAS, a private clinical-stage biopharmaceutical company developing therapeutics based on dependence receptor biology, today announced that it has entered into a clinical collaboration agreement with MSD to investigate the safety, clinical and biological activity of NP137 with MSD’s anti-PD-1 therapy, KEYTRUDA® (pembrolizumab), in patients with locally advanced/metastatic uterine tumors. NP137 targets netrin-1, which is overexpressed in over two-thirds of uterine tumors.

The companies have entered this collaboration based on promising clinical data obtained from a phase 1 trial investigating NP137 monotherapy in patients with advanced solid tumors and the growing evidence that resistance to an anti-PD-1 therapy, such as KEYTRUDA, can be alleviated when combined with blocking netrin-1.

Under the terms of the agreement, NETRIS will sponsor a large phase 1b/2 study, which will be conducted in collaboration with the Centre Léon Bérard and with support of the specialist French oncology group of clinicians, GINECO (Groupe d’Investigateurs National des Etudes des Cancers Ovariens). The study will investigate the safety and efficacy of NP137 combined with KEYTRUDA in patients with advanced/metastatic endometrial carcinoma or cervix carcinoma.

“We are excited to collaborate with MSD, an established leader in cancer immunotherapy, on our proof-of-concept phase1b/2 study as we work to improve the lives of cancer patients,” said Patrick Mehlen, Founder and Chief Executive Officer of NETRIS Pharma. “Immunotherapies are revolutionizing the treatment of patients in several cancer indications, but there remain many other tumor types in which existing immunotherapies have not demonstrated sufficient efficacy. Based on our preclinical and clinical data demonstrating the role of netrin-1 in promoting tumor progression and modulating tumor plasticity and microenvironment, we believe NP137’s effect in combination with KEYTRUDA will lead superior patient response to immunotherapy.”

“The preliminary safety data and anti-tumor activity observed in the Phase 1a trial, together with the unique mode of action of NP137, are very exciting and clearly support evaluating a combination with KEYTRUDA,” said Isabelle Ray Coquard, MD, Ph.D. and Principal Investigator of the trial. “We anticipate starting the study summer 2020.”

KEYTRUDA® is a registered trademark of Merck Sharp & Dohme Corp, a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

The Phase 1b/2 clinical trial will enroll up to 240 patients and be divided into a Ph1b part to evaluate the safety, tolerability, and pharmacokinetics/pharmacodynamics of the NP137 KEYTRUDA combination and/or chemotherapeutic agents. The Phase 2 part will assess via randomization the clinical activity of the combination in both tumor types.

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 receptors’ ligands, which prevents cells from dying. Netrin-1 is overexpressed in a large percentage of human cancers, including over two thirds of gynecologic cancers.

In preclinical studies, NP137 inhibited tumor growth and had a significant impact on tumoral plasticity, which potentiates the efficacy of chemotherapies and immune checkpoint inhibitors. In the phase 1 dose-escalation study, NP137 was found to be safe and very well tolerated up to 20mg/kg, with no dose limiting toxicity (DLT). In addition, patients with advanced uterine cancers exhibited encouraging signs of anti-tumor activity, including prolonged stable disease and objective responses.


GINECO (Groupe d’Investigateurs National pour l’Etude des Cancers de l’Ovaire et du sein) is the French Cooperative Group in Oncology labelled by INCA (National Cancer Institute in France) developing and conducting gynecological and metastatic breast cancer clinical trials at the national and international level. The network comprises more than 700 specialized investigators representing more than 150 public or private oncology units.

About NETRIS Pharma

NETRIS Pharma, a clinical-stage biopharmaceutical 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 first company to progress this innovative approach into the clinic.


Patrick Mehlen, CEO
Tel : +33 (0)4 78 78 28 70
Email: patrickmehlen@netrispharma.com


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