Nature publishes Phase 1b data showing NETRIS Pharma’s NP137 improves survival and surgery conversion in locally advanced pancreatic cancer.

NETRIS Pharma has reported encouraging Phase 1b results for its anti-netrin-1 antibody NP137 in locally advanced pancreatic ductal adenocarcinoma (LAPC), with data from the LAPNET-01 study published in Nature and previously presented at AACR.

The study evaluated NP137 in combination with modified FOLFIRINOX (mFOLFIRINOX) as a first-line treatment in patients with unresectable LAPC, a disease area where current standard chemotherapy delivers limited long-term survival benefit and low surgical conversion rates.

Across 41 evaluable patients, the combination achieved an overall response rate of 29%, with 88% of patients experiencing tumour shrinkage. Median progression-free survival (PFS) reached 10.85 months and median overall survival (OS) was 16.43 months, with 62% of patients alive at 12 months.

One of the most notable signals came from a biomarker-defined subgroup. Patients with high tumour expression of neogenin, a netrin-1 receptor linked to epithelial-to-mesenchymal transition (EMT), showed markedly improved outcomes. In this group, median PFS reached 15.65 months compared with 10.22 months in the low-expression group, while the 12-month OS rate reached 100% at data cut-off. Conversion to surgery also increased substantially, reaching 40% in the neogenin-high subgroup.

Professor Gael Roth, professor in GI oncology at CHU Grenoble Alpes and first author of the Nature paper, said: “Achieving this early clinical efficacy in pancreatic ductal adenocarcinoma is very promising for patients who have limited options. The group of neogenin-high patients, where we saw dramatically extended PFS and OS is unprecedented and opens a path for personalised and potentially more effective treatment of this group of pancreatic cancer patients,” adding: “The LAPNET-01 data amply justify further development in pancreatic ductal adenocarcinoma.”

NETRIS Pharma chief executive officer Patrick Mehlen said: “While this is only a Phase 1b trial, we are thrilled to observe the strong PFS and OS being achieved in the neogenin-high PDAC patients in LAPNET-01; we are eager to confirm these results in a larger study.” He added: “This marks the third Nature publication outlining the compelling scientific and mechanistic rationale for our anti-netrin1 strategy. LAPNET-01 data strongly support the clinically meaningful potential of targeting the netrin-1 / EMT axis to overcome the development of treatment resistance by PDAC, especially in neogenin-high patients.”

The company said it plans to initiate a randomised, potentially registrational Phase 2 trial in first-line metastatic pancreatic cancer, with a companion diagnostic approach using neogenin immunohistochemistry to identify patients most likely to benefit.

Safety findings were broadly consistent with expectations for the chemotherapy backbone, with a 37% rate of grade 3 or higher adverse events and no unexpected safety signals attributed to NP137.

From a clinical development perspective, the data position netrin-1 pathway inhibition as a novel resistance-targeting strategy rather than a direct cytotoxic approach. NETRIS is also exploring NP137 in additional solid tumour indications, including hepatocellular carcinoma and head and neck squamous cell carcinoma.

Pancreatic ductal adenocarcinoma remains one of the most difficult solid tumours to treat, with limited conversion-to-surgery rates and median survival typically measured in the low teens in months even under modern chemotherapy regimens.

If validated in later-stage trials, the neogenin signal could become an early example of biomarker-driven stratification in EMT-targeted therapy, an area that has so far lacked approved pharmacological interventions.