NP137 / NETRIS Pharma - LARVOL DELTA

LAPNet1: Phase 1b study investigating the association of NP137 with mFOLFIRINOX in locally advanced pancreatic ductal adenocarcinoma. (ASCO 2025) - P1 | "The primary endpoint is the proportion of patients experiencing adverse events (AEs) of any grade and grade 3/4 AEs (CTCAE v 5.0) related to the experimental treatment at 6 months. Secondary endpoints are best overall objective response according to RECIST 1.1, 12-month progression-free survival (PFS-12m), 12-month overall survival (OS-12m), surgical resection rate, quality of life (EORTC QLQ-C30), time to deterioration and ancillary outcomes based on spatial transcriptomic and classic bulk RNA sequencing."

Metastases • P1 data • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • NTN1

IMMUNONET: A multicenter, open-label, proof-of-concept phase II trial evaluating NP137 as add-on therapy in advanced/metastatic solid tumors treated with standard immunotherapies. (ASCO 2025) - P2 | "Prespecified goals for the first stage were met, stage 2 enrolment is underway. Cohort 2 has enrolled 21 patients, and cohort 3 has enrolled 19 of 23 planned evaluable patients."

Clinical • IO biomarker • Metastases • P2 data • Oncology • Solid Tumor • NTN1

Sonic hedgehog medulloblastomas are dependent on Netrin-1 for survival. (PubMed, Nat Commun) - "In line with these data, a monoclonal netrin-1 blocking antibody (anti-netrin-1 mAb/NP137) has been preclinically developed and netrin-1 blockade has recently been investigated in phase 1 and 2 clinical trials in several adult cancers...In line with that, we next show that netrin-1 blockade potentiates the efficacy of SMO inhibitor therapy in vivo. Together, our data indicate that, netrin-1 blockade, used as monotherapy or in combination with SMO inhibitors, is a promising therapeutic strategy in SHH medulloblastomas."

Journal • Brain Cancer • Medulloblastoma • Oncology • Pediatrics • Solid Tumor • NTN1

Pre-Clinical Validation of a Novel Immunotherapeutic Treatment for Endometriosis and Associated Chronic Pain (WCE 2025) - "This study strongly supports NP137 as a feasible, non-invasive therapeutic strategy and an effective treatment for endometriosis growth and associated CP. Ongoing studies aim to elucidate mechanisms underlying our findings."

Preclinical • Endometriosis • Gynecology • Pain • Women's Health • NTN1

LAP-NET1: Study Investigating the Association of NP137 With mFOLFIRINOX in Locally Advanced Pancreatic Ductal Adenocarcinoma (clinicaltrials.gov) - P1 | N=43 | Active, not recruiting | Sponsor: University Hospital, Grenoble | Trial completion date: Mar 2027 ➔ Jun 2025 | Trial primary completion date: Mar 2026 ➔ Dec 2024

Trial completion date • Trial primary completion date • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • CA 19-9

AML-NET: Acute Myeloid Leukemia Treated With With NETrin Abs in Combination With [AZACITIDINE + VENETOCLAX] (clinicaltrials.gov) - P1/2 | N=1 | Terminated | Sponsor: Centre Leon Berard | N=35 ➔ 1 | Trial completion date: Nov 2027 ➔ Feb 2025 | Recruiting ➔ Terminated | Trial primary completion date: Mar 2027 ➔ Feb 2025; low recruitment rate

Enrollment change • Trial completion date • Trial primary completion date • Trial termination • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology

LAP-NET1: Study Investigating the Association of NP137 With mFOLFIRINOX in Locally Advanced Pancreatic Ductal Adenocarcinoma (clinicaltrials.gov) - P1 | N=52 | Active, not recruiting | Sponsor: University Hospital, Grenoble | Recruiting ➔ Active, not recruiting

Enrollment closed • Metastases • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma

GYNET: GYNecological Cancers Treated with NETrin MAbs in Combination with Chemotherapy and /or Pembrolizumab (clinicaltrials.gov) - P1/2 | N=240 | Active, not recruiting | Sponsor: NETRIS Pharma | Recruiting ➔ Active, not recruiting

Combination therapy • Enrollment closed • Metastases • Cervical Cancer • Endometrial Cancer • Gynecologic Cancers • Oncology • Solid Tumor

LAP-NET1: Study Investigating the Association of NP137 With mFOLFIRINOX in Locally Advanced Pancreatic Ductal Adenocarcinoma (clinicaltrials.gov) - P1 | N=52 | Recruiting | Sponsor: University Hospital, Grenoble | Trial completion date: Nov 2025 ➔ Mar 2027 | Trial primary completion date: Nov 2024 ➔ Mar 2026

Metastases • Trial completion date • Trial primary completion date • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma

Liver-NET1: Study Investigating the Association of NP137 With Atezolizumab-Bevacizumab Combination in First Line in Unresectable HCC (clinicaltrials.gov) - P1 | N=52 | Recruiting | Sponsor: University Hospital, Grenoble | Trial completion date: Nov 2025 ➔ Mar 2027 | Trial primary completion date: Nov 2024 ➔ Mar 2026

Trial completion date • Trial primary completion date • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • Solid Tumor • AFP

AML-NET: Acute Myeloid Leukemia Treated With With NETrin Abs in Combination With [AZACITIDINE + VENETOCLAX] (clinicaltrials.gov) - P1/2 | N=35 | Recruiting | Sponsor: Centre Leon Berard | Initiation date: Dec 2023 ➔ Dec 2024

Combination therapy • Trial initiation date • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology

Study of Perioperative NP137 and FOLFIRINOX in Resectable Pancreatic Cancer (clinicaltrials.gov) - P1 | N=25 | Not yet recruiting | Sponsor: Nabeel Badri | Initiation date: Jul 2024 ➔ Jan 2025

Trial initiation date • Gastrointestinal Cancer • Hepatology • Oncology • Pancreatic Cancer • Solid Tumor

Anti-Netrin-1 decorated nanoparticles combined with chemotherapy for the treatment of triple-negative breast cancer. (PubMed, Biomater Adv) - "In this work, we developed a docetaxel-loaded nanoemulsions (NEs) binding an anti-netrin-1 monoclonal antibody (NP137) to selectively target the netrin-1 protein overexpressed in many different tumors. To validate our treatment strategy in vivo, the 4T1 murine breast cancer model was used. As a result, the comparison of active-targeted and non-targeted NEs revealed that only active-targeted NE could decrease the tumor growth rate."

Journal • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • NTN1

GYNET: GYNecological Cancers Treated With NETrin mAbs in Combination With Chemotherapy and /or Pembrolizumab (clinicaltrials.gov) - P1/2 | N=240 | Recruiting | Sponsor: NETRIS Pharma | Trial completion date: Jul 2025 ➔ Jul 2026 | Trial primary completion date: Oct 2024 ➔ Oct 2025

Combination therapy • Metastases • Trial completion date • Trial primary completion date • Cervical Cancer • Endometrial Cancer • Gynecologic Cancers • Oncology • Solid Tumor

Targeting of netrin-1 by monoclonal antibody NP137 inhibits the EMT in cancer. (PubMed, J Immunother Cancer) - No abstract available

Journal • Oncology • NTN1

Study of Perioperative NP137 and FOLFIRINOX in Resectable Pancreatic Cancer (clinicaltrials.gov) - P1 | N=25 | Not yet recruiting | Sponsor: Nabeel Badri

New P1 trial • Gastrointestinal Cancer • Hepatology • Oncology • Pancreatic Cancer • Solid Tumor

LAP-NET1: Study Investigating the Association of NP137 With mFOLFIRINOX in Locally Advanced Pancreatic Ductal Adenocarcinoma (clinicaltrials.gov) - P1 | N=52 | Recruiting | Sponsor: University Hospital, Grenoble | Not yet recruiting ➔ Recruiting | Trial completion date: Nov 2024 ➔ Nov 2025

Enrollment open • Metastases • Trial completion date • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma

AML-NET: Acute Myeloid Leukemia Treated With With NETrin Abs in Combination With [AZACITIDINE + VENETOCLAX] (clinicaltrials.gov) - P1/2 | N=35 | Recruiting | Sponsor: Centre Leon Berard | Not yet recruiting ➔ Recruiting

Enrollment open • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology

AML-NET: Acute Myeloid Leukemia Treated With With NETrin Abs in Combination With [AZACITIDINE + VENETOCLAX] (clinicaltrials.gov) - P1/2 | N=35 | Not yet recruiting | Sponsor: Centre Leon Berard

New P1/2 trial • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology

GYNET: GYNecological Cancers Treated With NETrin mAbs in Combination With Chemotherapy and /or Pembrolizumab (clinicaltrials.gov) - P1/2 | N=240 | Recruiting | Sponsor: NETRIS Pharma | Trial completion date: Nov 2024 ➔ Jul 2025

Trial completion date • Cervical Cancer • Endometrial Cancer • Gynecologic Cancers • Oncology • Solid Tumor

Liver-NET1: Study Investigating the Association of NP137 With Atezolizumab-Bevacizumab Combination in First Line in Unresectable Hepatocellular Carcinoma (clinicaltrials.gov) - P1 | N=52 | Recruiting | Sponsor: University Hospital, Grenoble | Not yet recruiting ➔ Recruiting | Trial completion date: Nov 2024 ➔ Nov 2025

Enrollment open • Trial completion date • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • Solid Tumor

Blocking Netrin-1 Slows Cancer Progression. (PubMed, Cancer Discov) - "Preclinical and early clinical data demonstrate that treating endometrial cancer with the netrin-1 inhibitor NP137 helps arrest the epithelial-to-mesenchymal transition and disease progression. Additional research is needed to understand the mechanism of action between the monoclonal antibody and chemotherapy, as well as determine whether this treatment could help patients with other cancers."

Journal • Endometrial Cancer • Oncology • Solid Tumor • NTN1

Pharmacological targeting of netrin-1 inhibits EMT in cancer. (PubMed, Nature) - P1 | "Pharmacological inhibition of netrin-1 by administration of NP137, a netrin-1-blocking monoclonal antibody currently used in clinical trials in human cancer (ClinicalTrials.gov identifier NCT02977195 ), decreased the proportion of EMT tumour cells in skin SCC, decreased the number of metastases and increased the sensitivity of tumour cells to chemotherapy...Netrin-1 inhibition decreased EMT in these transplanted A549 cells. Together, our results identify a pharmacological strategy for targeting EMT in cancer, opening up novel therapeutic interventions for anti-cancer therapy."

Journal • Non-melanoma Skin Cancer • Oncology • Squamous Cell Carcinoma • Squamous Cell Skin Cancer • Transplantation • NTN1 • TGFB1

Netrin-1 blockade inhibits tumour growth and EMT features in endometrial cancer. (PubMed, Nature) - "Given the importance of EMT in resistance to current standards of care, we show in the EC mouse model that a combination of NP137 with carboplatin-paclitaxel outperformed carboplatin-paclitaxel alone. Our results identify netrin-1 blockade as a clinical strategy triggering both tumour debulking and EMT inhibition, thus potentially alleviating resistance to standard treatments."

Journal • Endometrial Cancer • Oncology • Solid Tumor • NTN1

UNC5B promotes EMT and metastasis of pancreatic adenocarcinomas and expresses different isoforms that impact sensitivity to Netrin-1 blockade (AACR 2023) - "ARID1A mutations caused cell lines to become mesenchymal, but the cells returned to an epithelial phenotype upon knockout of UNC5B. In current and future clinical trials, NP137 may particularly benefit patients with tumors that harbor mutations in ARID1A or ARID1B, focal amplifications of UNC5B, and/or high expression of the caspase-3-containing isoform of UNC5B."

Gastrointestinal Cancer • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • ARID1A • ARID1B • CASP3 • NTN1 • YAP1