NP137 / NETRIS Pharma - LARVOL DELTA

LAP-NET1: Phase 1b study investigating the association of NP137 with mFOLFIRINOX in locally advanced pancreatic ductal adenocarcinoma. (ASCO-GI 2026) - P1 | "Funded by Netris Pharma, Fondation ARC Clinical Trial Registration Number: NCT05546853 The full, final text of this abstract will be available on Jan 05 at 05:00 PM EST."

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

IMMUNONET: A proof of concept phase II evaluating NP137 as add on therapy in solid tumors under standard immunotherapies: Interim analysis of primary and secondary refractory cohorts (ESMO 2025) - P2 | "Table: 966P PFR 12W PRF N=18 evaluable pts SRF N=17 evaluable pts N, % 2, 11.1% 9, 52.9% 95% unilateral confidence interval [2.0%; -[ [31.1%; -[ Conclusions This first encouraging data especially in HNSCC and NSCLC in SRF cohort supports the inclusion of 11 and 5 additional pts in PRF and SRF cohort, respectively. BulkRNAseq and spatial transcriptomic performed on pre/12-week biopsies linking EMT, tumor infiltrate and clinical response will be presented."

P2 data • Head and Neck Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • NTN1

Netrin-DCC Inhibition Suppresses Neuroendocrine Neoplasms Growth in vivo. (PubMed, Endocr Relat Cancer) - "We examined the effect of netrin on cell viability using DCC knockdown and NP137, a netrin-inhibiting antibody...TCGA analysis showed a negative correlation between NTN3 expression and survival. In conclusion, our data suggest that NTN-3, NTN-1, and DCC have interdependent oncogenic roles in PNENs, which can be reversed by blocking NTN binding to DCC."

Journal • Preclinical • Endocrine Cancer • Lung Cancer • Neuroblastoma • Neuroendocrine Carcinoma • Neuroendocrine Tumor • Oncology • Pancreatic Cancer • Small Cell Lung Cancer • Solid Tumor • DCC • NTN1

NETRIS Pharma to Present Clinical Results of NP137 in Combination with Immune Checkpoint Inhibitors at ESMO 2025 (EIN Presswire) - "In cohort 3 (secondary refractory) where a majority of NSCLC and HNSCC patients were enrolled, the primary endpoint of Progression-Free Rate at 12 weeks (PFR-12W) was met ahead of stage 2. These results strongly suggest the efficacy of combining NP137 with anti–PD-1/PD-L1 therapy in this difficult-to-treat population and warrant further controlled studies to confirm these findings...the combination of NP137 with ICI was very well tolerated."

P2 data • Non Small Cell Lung Cancer • Squamous Cell Carcinoma of Head and Neck

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