NP137 / NETRIS Pharma - LARVOL DELTA

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 • First-in-human • 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

First-in-human • New P1/2 trial • 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 | Recruiting | Sponsor: Centre Leon Berard | Initiation date: Dec 2023 ➔ Dec 2024

First-in-human • Trial initiation date • 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=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 • First-in-human • Trial completion date • Trial primary completion date • Trial termination • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology

IMMUNONET: NP137 Clinical and Biological Activities Assessment in Patients With Advanced/Metastatic Solid Tumors Treated by Standard Anti PD-1/PD-L1 Immunotherapies (clinicaltrials.gov) - P2 | N=87 | Recruiting | Sponsor: Centre Leon Berard | Not yet recruiting ➔ Recruiting

Enrollment open • IO biomarker • Oncology • Solid Tumor

IMMUNONET: NP137 Clinical and Biological Activities Assessment in Patients With Advanced/Metastatic Solid Tumors Treated by Standard Anti PD-1/PD-L1 Immunotherapies (clinicaltrials.gov) - P2 | N=87 | Not yet recruiting | Sponsor: Centre Leon Berard

IO biomarker • New P2 trial • Oncology • Solid Tumor

IMMUNONET: NP137 Clinical and Biological Activities Assessment in Patients With Advanced/Metastatic Solid Tumors Treated by Standard Anti PD-1/PD-L1 Immunotherapies (clinicaltrials.gov) - P2 | N=57 | Active, not recruiting | Sponsor: Centre Leon Berard | Recruiting ➔ Active, not recruiting | N=87 ➔ 57

Enrollment change • Enrollment closed • Solid Tumor

IMMUNONET: NP137 Clinical and Biological Activities Assessment in Patients With Advanced/Metastatic Solid Tumors Treated by Standard Anti PD-1/PD-L1 Immunotherapies (clinicaltrials.gov) - P2 | N=57 | Active, not recruiting | Sponsor: Centre Leon Berard | Trial primary completion date: Feb 2026 ➔ Jan 2027

Trial primary completion date • Oncology • Solid Tumor

Netrin1 blockade alleviates resistance to chemotherapy in pancreatic cancer. (PubMed, Nature) - P1 | "Here we report the results of a phase 1b study that assesses the combination of NP137 with modified FOLFIRINOX (mFOLFIRINOX) in first line patients with locally advanced pancreatic cancer (ClinicalTrials.gov: NCT05546853 )...Moreover, survival outcomes were extended for patients with tumour cells that expressed high levels of the netrin1 receptor neogenin-median PFS 15.65 months in neogenin-high versus 10.22 months in neogenin low. Our results support the idea that netrin1 blockade alleviates resistance to chemotherapy by inhibiting EMT, particularly in neogenin-high pancreatic cancer."

Journal • Oncology • Pancreatic Cancer • Solid Tumor • NTN1

LAP-NET1: Results of a phase 1b evaluating NP137, an inhibitor of the epithelial-to-mesenchymal transition, in combination with mFOLFIRINOX for the first-line treatment of locally advanced pancreatic ductal adenocarcinoma. (ASCO 2026) - P1 | "NP137 in combination with mFOLFIRINOX demonstrates a favorable safety profile, promising clinical activity and a mechanistically distinct mode of action supported by translational analyses. These results warrant further investigation of netrin-1 blockade in randomized trials and provide a rationale for biomarker-driven development of NP137 in PDAC. Further work is ongoing to better characterize the distribution of NEO1 in first-line unresectable PDAC."

Clinical • Combination therapy • Metastases • P1 data • Oncology • Pancreatic Ductal Adenocarcinoma • NTN1

A self-amplifying nerve-fibroblast circuit drives colorectal cancer progression. (PubMed, Cancer Cell) - "In human CRC, high NTN1 expression is associated with a mesenchymal-like subtype and poor patient outcomes. These findings suggest that the neuro-mesenchymal interaction is central to CRC progression and could be therapeutically targeted with a CHRM3 antagonist or NTN1-blocking antibody."

Journal • Colorectal Cancer • Oncology • Solid Tumor • CAFs • CHRM3 • NTN1

Netrin Pathway Activation in Pseudohypoxic Neuroendocrine Tumors: Mechanistic Characterization and Targeted Therapy (ENDO 2026) - "These combined findings position the Netrin pathway as a critical driver in hypoxic neuroendocrine neoplasms. Disruption of Netrin-receptor binding by NP137 represents a promising novel therapeutic strategy for patients with advanced PPGL."

Endocrine Cancer • Gastrointestinal Neuroendocrine Tumor • Neuroendocrine Tumor • Oncology • Solid Tumor • Von Hippel-Lindau Syndrome

Liver-NET1: Study Investigating the Association of NP137 With Atezolizumab-Bevacizumab Combination in First Line in Unresectable HCC (clinicaltrials.gov) - P1 | N=43 | Active, not recruiting | Sponsor: University Hospital, Grenoble | Trial completion date: Mar 2027 ➔ Mar 2029 | Suspended ➔ Active, not recruiting

Enrollment closed • Trial completion date • Hepatocellular Cancer • Oncology • Solid Tumor

Unraveling a new ECM stiffening function of the axon guidance molecule Netrin-1 (AACR 2026) - "This stiffening effect was reversed by NP137, a monoclonal antibody targeting NTN1...Ongoing structural analyses are being conducted on fibroblast-derived matrices, with and without endogenous Netrin-1 expression, to evaluate its potential remodeling effects on collagen IV and fibronectin networks. In parallel, these matrices are utilized in functional assays to investigate how Netrin-1 ECM impact, influences cellular behaviours and transcriptional activity, using a range of experimental approaches."

Oncology • NTN1

LAPNET-01: Translational results of a Phase 1b evaluating NP137, an inhibitor of the epithelial-to-mesenchymal transition in combination with mFOLFIRINOX for the first-line treatment of locally advanced pancreatic ductal adenocarcinoma (AACR 2026) - "NP137 in combination with mFOLFIRINOX demonstrates a favorable safety profile, promising clinical activity, and a mechanistically distinct mode of action supported by translational analyses. These results warrant further investigation of netrin-1 blockade in randomized trials and provide a rationale for biomarker-driven development of NP137 in pancreatic cancer."

Clinical • Combination therapy • Metastases • P1 data • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • NTN1

Netrin-1/UNC5B-TFF3 axis modulates cancer stem cells self-renewal and chemoresistance in metastatic colorectal cancer (AACR 2026) - "Netrin-1 sustains mCRC CSC self-renewal through an UNC5B-dependent, TFF3-mediated paracrine survival mechanism. Pharmacologic inhibition of netrin-1 with NP137 induces CSC apoptosis and enhances chemotherapy efficacy, identifying the netrin-1/UNC5B/TFF3 axis as a promising therapeutic target to overcome stemness-driven resistance in metastatic colorectal cancer."

Cancer stem • Metastases • Colorectal Cancer • Oncology • Solid Tumor • LGR5 • NTN1 • PROM1 • SOX4 • TFF3

Novel Netrin-1-Targeted Radiotheranostics for Managing Advanced Solid Tumors (TAT-Alpha 2026) - "Conclusion These findings highlight NP137 as a promising radioimmunoconjugate for netrin-1–positive advanced solid tumors, with potential applications in both molecular imaging and RLT. Its high tumor specificity and uptake, combined with the strong therapeutic efficacy of this first alpha- and beta-emitting monoclonal antibody, support further evaluation and rapid clinical translation."

Metastases • Breast Cancer • Lung Cancer • Oncology • Solid Tumor • NTN1

Liver-NET1: Study Investigating the Association of NP137 With Atezolizumab-Bevacizumab Combination in First Line in Unresectable HCC (clinicaltrials.gov) - P1 | N=43 | Suspended | Sponsor: University Hospital, Grenoble | Recruiting ➔ Suspended

Trial suspension • Hepatocellular Cancer • Oncology • Solid Tumor

LAP-NET1: Study Investigating the Association of NP137 With mFOLFIRINOX in Locally Advanced Pancreatic Ductal Adenocarcinoma (clinicaltrials.gov) - P1 | N=43 | Completed | Sponsor: University Hospital, Grenoble | Active, not recruiting ➔ Completed

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

Study of Perioperative NP137 and FOLFIRINOX in Resectable Pancreatic Cancer (clinicaltrials.gov) - P1 | N=25 | Not yet recruiting | Sponsor: Aram Hezel | Trial completion date: Dec 2027 ➔ Sep 2032 | Trial primary completion date: Dec 2027 ➔ May 2027

Trial completion date • Trial primary completion date • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor

Deciphering netrin-1 implication in pancreatic cancer (LCC 2026) - "Using PDAC-derived organoids and in vivo mouse models, we investigated NTN-1 expression and identified a significant effect of NP137 treatment on tumour growth when combined with Folfirinox chemotherapy, that was not detected with NP137 or chemotherapy alone. These findings are currently investigated in the treated mouse samples described above and could also partially explain NP137 mode of action. Altogether, this study investigated the role and the biological effects of NTN-1 in PDAC and identified it as an interesting target to overcome chemotherapy resistance and improve patient outcomes."

Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • NTN1

LAP-NET1: Phase 1b study investigating the association of NP137 with mFOLFIRINOX in locally advanced pancreatic ductal adenocarcinoma. (ASCO-GI 2026) - P1 | "NP137 plus mFOLFIRINOX was well tolerated, without additional toxicity beyond chemotherapy, and demonstrated promising efficacy in LAP. These results support further evaluation in randomized trials. Correlative biomarker and transcriptomic analyses are ongoing and will be presented."

Metastases • P1 data • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • CA 19-9 • NTN1

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