On April 22, 2026 NETRIS Pharma, a clinical-stage oncology company targeting the netrin-1 / epithelial-to-mesenchymal transition (EMT) axis, reported that positive results from « LAPNET-01 » its phase 1b trial (NCT05546853) of NP137, were published in Nature (DOI: 10.1038/s41586-026-10436-4) :
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The data show that in patients with pancreatic ductal adenocarcinoma (PDAC) with locally advanced PDAC (LAPC), treatment with NP137, the first-in-class anti-netrin1 monoclonal antibody, in combination with modified FOLFIRINOX (mFOLFIRINOX) as a first-line therapy achieved a median progression free survival (PFS) of 10.85 months, median overall survival (OS) of 16.43 months and a 23% conversion-to-surgery rate. In addition, a subset of patients with high tumor netrin-1 receptor neogenin expression showed a median PFS of 15.65 months, a 40% conversion-to-surgery rate and a 12-months OS rate of 100%.
« 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 personalized and potentially more effective treatments of this group of pancreatic cancer patients » said Gael Roth, MD, PhD, Professor in GI Oncology at Grenoble Alpes University Hospital, LAPNET-01 lead investigator and first author of the paper in Nature. « The LAPNET-01 data amply justify further development in pancreatic ductal adenocarcinoma ».
Patrick Mehlen, PhD, Chief Executive Officer of NETRIS Pharma, 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. 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. These exciting positive data will accelerate further development of NP137, the first-in-class anti-netrin1 monoclonal antibody. We are engaging with US and EU regulatory authorities as we design the development pathway for NP137 to treat PDAC and other solid tumors.
The next steps for NETRIS include initiation of a randomized, potentially registrational, phase 2 trial of NP137 in first-line metastatic PDAC, incorporating a neogenin IHC assay to help validate this test as a potential companion diagnostic. The development of NP137 is advancing in several other oncology indications including HCC and HNSCC.
About LAPNET-01
LAPNET-01 (NCT05546853) was a multicenter, open-label, phase 1b study promoted by Grenoble Alpes University Hospital and conducted across nine centers in France. Between March 2023 and June 2024, 43 patients with LAPC were enrolled to receive 14 mg/kg of NP137 administered every two weeks in combination with mFOLFIRINOX, for up to 12 cycles. The study population was representative of LAPC. At baseline, all patients were considered unresectable, including 2 with metastatic disease.
The LAPNET-01 trial was designed around the specific hypothesis that mFOLFIRINOX drives EMT-mediated resistance in LAPC and that concurrent netrin1 blockade with NP137 could mitigate this effect, thereby augmenting the depth and durability of response to chemotherapy.
Response and Disease Control
Among 41 evaluable patients assessed by RECIST 1.1, 12 achieved a confirmed partial response (ORR 29%; 95% CI 0.16–0.46), with a median duration of response of 9.02 months (95% CI 5.84–NR). 88% of patients experienced tumor shrinking.
Progression-Free and Overall Survival
Median PFS was 10.85 months at a median follow-up of 13.1 months (95% CI 10.03–15.61), with 6-month and 12-month PFS rates of 88% and 45%, respectively. Notably, patients with high tumor neogenin expression treated with mFOLFIRINOX+NP137 achieved a markedly superior median PFS of 15.65 months versus 10.22 months in the neogenin-low group (p=0.003).
Median OS was 16.43 months (95% CI 12.75–NR), with 6-month and 12-month OS rates of 91% and 62%, and 21 patients still alive at the data cut-off. Median OS was not yet reached in the neogenin-high group with a 12-months OS rate of 100% at the time of data cut-off.
These outcomes compare favorably to benchmark data from the NEOPAN trial, which reported median PFS of approximately 9.7 months and median OS of approximately 15.7 months with FOLFIRINOX alone in LAPC.
Conversion to Surgery
Ten of 43 intention-to-treat patients (23%) and four of 10 (40%) of neogenin-high patients underwent post-therapy R0 resection — a rate that is substantially higher than benchmark conversion rates from prospective LAPC trials.
Neogenin, Candidate Companion Diagnostic
Pre-planned exploratory analyses examined components of the netrin1 signaling pathway for associations with outcomes in LAPNET-01. NEO1, encoding neogenin — a netrin1 receptor previously shown to mediate the netrin1-driven epithelial-to-mesenchymal transition (EMT) and tumor progression in pancreatic cancer preclinical models — emerged as the most strongly correlated gene with improved efficacy outcomes in the non-refractory patient subset (n=21) with available transcriptomic data.
Clinical Safety
Safety was assessed in all 43 patients who received at least one dose of NP137 plus mFOLFIRINOX. While 100% of patients experienced at least one adverse event (AE) with a grade 3 and above adverse event rate of 37%, this profile was comparable to what is anticipated with the chemotherapy backbone alone.
Full details of the LAPNET-01 data are available in the Nature paper :
The aggregated body of evidence — spanning two prior Nature publications (Cassier et al. and Lengrand et al., see links below), the NETRIS AACR (Free AACR Whitepaper) 2026 posters (Poster #2445, #7489 and #0822, presented this week, on April 20), and today’s Nature 2026 manuscript — supports a coherent mechanistic hypothesis : netrin1, re-expressed by cancer cells as a survival mechanism, is a master upstream regulator of epithelial-to-mesenchymal transition (EMT), a central mechanism for the development of acquired resistance in many tumor types.
The absence of a pharmacological EMT inhibitor in the approved oncology arsenal — a gap explicitly noted by the Nature editors in the clinical briefing accompanying the 2023 publications — positions NP137 as a potential first-in-class agent addressing a mechanism of resistance that is orthogonal to debulking agents such as checkpoint inhibition, KRAS targeting, and antibody-drug conjugate strategies.
About LAPC
Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal malignancies, ranking as the fourth leading cause of cancer-related death globally, with a five-year survival rate below 5%. LAPC — a subset representing roughly 30% of PDAC cases at diagnosis — occupies a particularly difficult clinical niche because tumors at this stage are predominantly unresectable, yet lack distant metastases, rendering patients ineligible for both metastatic and curative-intent surgical protocols.
The current standard of care, FOLFIRINOX or gemcitabine-based combinations, yields a median PFS of 6–10 months and a median OS of approximately 12–17 months in LAPC (LAP-07, NEOPAN trials). Conversion-to-surgery rates under these regimens are low: prospective data from the NEOPAN and CONKO-007 trials report R0 resection rates of 6% and 18%, respectively, while PANOVA-3 reported 10.8% under gemcitabine/nab-paclitaxel.
(Press release, Netris Pharma, APR 22, 2026, View Source [SID1234664683])