NP-137

We are delighted to receive this Horizon Europe grant, which is a further validation of both our scientific approach and our development strategy in head and neck cancer” — Patrick Mehlen, CEO and Co-founder NETRIS Pharma LYON FRANCE AND GENEVA , SWITZERLAND, May 28, 2026 / EINPresswire.com / -- NETRIS Pharma, a clinical-stage oncology company targeting the netrin-1 / epithelial-to-mesenchymal transition (EMT) axis, today announced that it has secured €7.25 million in funding under the European Union’s Horizon Europe programme to conduct a Phase 2b randomized clinical trial of NP137 in head and neck squamous cell carcinoma (HNSCC). The trial will be led by Principal Investigator Dr. Jérôme Fayette, MD, PhD, a medical oncologist at Centre Léon Bérard (Lyon, France), and conducted in partnership with GORTEC (Groupe Oncologie Radiothérapie Tête Et Cou), the leading French cooperative oncology group in HNSCC led by Professor Jean Bourhis and TTCC group, the Spanish group for the treatment of head and neck tumors, chaired by Dr. Ricard Mesia. “Head and neck squamous cell carcinoma remains a disease with significant unmet need, particularly with a large portion of patients relapsing under immunotherapy. The scientific rationale for targeting netrin-1 in HNSCC to alleviate resistance to immunotherapy and thus extend the survival of patients is compelling,and the clinical outcomes from the Phase2 ImmunoNET study confirms the potential of NP137 to deliver meaningful clinical benefit for our patients,” said Dr. Jérôme Fayette, MD, PhD, Principal Investigator and Medical Oncologist at Centre Léon Bérard. Patrick Mehlen, PhD, Chief Executive Officer of NETRIS Pharma, said: “We are delighted to receive this Horizon Europe grant, which is a further validation of both our scientific approach and our development strategy in head and neck cancer. NP137 is the only clinical-stage anti-netrin1 therapy, and HNSCC is a key indications given the resistance to current treatment. Conducting this Phase 2b study in partnership with GORTEC, the most experienced cooperative group in this field, and under the leadership of Dr. Fayette, provides the ideal framework to generate the high-quality clinical evidence needed to advance NP137 toward regulatory discussions. This funding reinforces our commitment to bringing truly differentiated therapies to patients with limited options.” “GORTEC is proud to partner with NETRIS Pharma on this innovative Phase 2b programme. Head and neck cancer is a field where new mechanistic approaches are urgently needed. The netrin-1 / EMT axis represents a clinically actionable target, and we look forward to generating robust data in the context of this well-designed Horizon Europe-funded trial,” said Professor Jean Bourhis, Chief Executive Officer and Chief Medical Officer of GORTEC. The Horizon Europe programme is the European Union’s key funding mechanism for research and innovation. « Following the positive outcome of the immunonet study, this funding reflects the high value of NP137 in oncology », said Christophe Guichard, Chief Financial Officer of NETRIS Pharma. The funding will support the design, conduct and analysis of the Phase 2b randomized trial in HNSCC, building on the clinical evidence supporting the role of netrin-1 in driving treatment resistance in this indication. The project will be conducted through a consortium led by NETRIS Pharma with GORTEC, Grupo Español de Tratamiento de Tumores de Cabeza y Cuello - TTCC and Université Libre de Bruxelles. About the Phase 2b HNSCC Trial The Phase 2b trial is a randomized, multi-center study evaluating NP137 in patients with head and neck squamous cell carcinoma. The study will be conducted across multiple centers in France and Spain under the sponsorship of GORTEC, with Dr. Jérôme Fayette of Centre Léon Bérard serving as Principal Investigator. The trial design will incorporate translational endpoints aimed at further characterizing the role of netrin-1 and its receptors as predictive biomarkers of response to NP137, consistent with NETRIS Pharma’s precision oncology development strategy. Full details of the trial design, including patient population, primary and secondary endpoints, and treatment schedule, will be disclosed at the time of trial initiation. About GORTEC GORTEC (Groupe Oncologie Radiothérapie Tête Et Cou) is the leading French cooperative oncology group dedicated to the clinical development of innovative treatments for head and neck cancers. GORTEC has conducted numerous landmark clinical trials in HNSCC and is widely recognized as one of the most prolific and scientifically rigorous cooperative groups in this field in Europe. The group is led by Professor Jean Bourhis, a world-leading expert in head and neck oncology and radiation oncology. About Horizon Europe Horizon Europe is the European Union’s flagship research and innovation programme, with a budget of €95.5 billion for the period 2021–2027. It aims to strengthen the EU’s scientific and technological base and boost its innovation capacity. Funding from Horizon Europe is highly competitive and awarded on the basis of scientific excellence and societal impact. About NP137 NP137 is NETRIS Pharma’s lead investigational asset, a first-in-class humanized monoclonal antibody (mAb) that blocks netrin-1, a developmental secreted protein re-expressed by cancer cells as a survival mechanism. By targeting netrin-1, NP137 is designed to block epithelial-to-mesenchymal transition (EMT), a process implicated in tumor progression, metastasis, and resistance to chemotherapy, targeted therapy, and immunotherapy. NP137 is currently in clinical development across multiple solid tumor indications including pancreatic ductal adenocarcinoma (PDAC), hepatocellular carcinoma (HCC), and head and neck squamous cell carcinoma (HNSCC). About NETRIS Pharma NETRIS Pharma (www. netrispharma .com) is a clinical-stage biotechnology company focused on developing therapies targeting the netrin1 / dependence receptor axis to overcome cancer treatment resistance. The company was co-founded by scientists who pioneered the biology of netrin1 and dependence receptors. Its lead programme NP137 is currently in clinical development across multiple solid tumor indications including pancreatic cancer, hepatocellular carcinoma, and head and neck squamous cell carcinoma. For further information, please contact: NETRIS Pharma Christophe Guichard CFO and IR christopheguichard@netrispharma.com Forward-Looking Statements: This press release contains forward-looking statements based on current expectations and projections. These statements involve inherent risks and uncertainties, including the outcome of regulatory interactions, the results of future clinical trials, and market conditions. Actual results may differ materially from those anticipated. Readers are cautioned not to place undue reliance on these statements. Christophe GUICHARD NETRIS Pharma email us here Legal Disclaimer: EIN Presswire provides this news content "as is" without warranty of any kind. We do not accept any responsibility or liability for the accuracy, content, images, videos, licenses, completeness, legality, or reliability of the information contained in this article. If you have any complaints or copyright issues related to this article, kindly contact the author above.

撰文 | 阿童木 胰腺导管腺癌（PDAC）是侵袭性最强、预后最差的实体瘤之一，长期缺乏突破性治疗进展。其中，局部进展期胰腺癌（LAPC）约占新诊断病例的30%。这类患者尚未发生远处转移，却常因肿瘤包绕或侵犯腹腔干、肠系膜上动脉等关键血管而失去手术机会，处于“未转移但不可切除”的治疗困境【1】。由于既不同于可切除胰腺癌，也不同于转移性疾病，LAPC在临床上长期处于夹层地带：往往难以纳入转移性试验，也不符合围手术期研究条件。目前，LAPC一线治疗仍主要依赖mFOLFIRINOX或吉西他滨联合方案，生存获益有限。如何提高转化切除率，并在局部控制之外进一步改善系统治疗效果，仍是该领域的核心挑战。 近年来，人们逐渐认识到，胰腺癌治疗失败并不完全源于药物杀伤不足，还与肿瘤细胞高度可塑性有关。上皮-间质转化（EMT）被认为是其中关键机制之一。进入EMT状态的肿瘤细胞会降低上皮特征，获得更强迁移能力、侵袭性及耐药性，从而削弱化疗效果【2】。已有研究提示，FOLFIRINOX治疗过程中本身即可诱导部分胰腺癌细胞进入EMT状态，这可能构成继发耐药的重要来源。 Netrin1原本是一种胚胎发育阶段的分泌型糖蛋白，参与轴突导向、血管生成及细胞存活调控。在成人组织中，其表达通常较低，但多种肿瘤会重新激活这一发育程序。既往研究显示，Netrin1不仅促进肿瘤生长和转移，也参与EMT早期启动，使癌细胞维持更强的适应能力和恶性表型【3】。针对Netrin1的单克隆抗体NP137此前已在临床前研究中表现出抑制EMT、诱导肿瘤“再上皮化”的潜力(详见BioArt报道：Nature背靠背 | Netrin-1单抗NP137能够抑制肿瘤EMT过程)，因此被视为一种有望提高化疗敏感性的全新策略【4】。 近日，里昂第一大学Patrick Mehlen和Gael Roth实验室等在Nature杂志发表了题为Netrin1 blockade alleviates resistance to chemotherapy in pancreatic cancer的研究文章，研究显示，抗Netrin1抗体NP137联合mFOLFIRINOX用于局部进展期胰腺癌具有良好耐受性，并显示积极疗效信号：中位无进展生存期（PFS）10.85个月，中位总生存期（OS）16.43个月，23%患者获得后续转化手术机会。机制分析进一步表明，该联合方案显著抑制EMT相关转录程序，提示阻断肿瘤可塑性可能是增强化疗反应的重要路径。 该研究共纳入43例LAPC患者，中位年龄65岁，超过半数患者基线评估为明确不可切除。治疗方案为NP137联合mFOLFIRINOX，每2周给药一次，最长12个周期。安全性结果显示，3/4级治疗相关不良事件发生率为37%，总体与既往mFOLFIRINOX单药数据相近。NP137相关不良事件以轻中度输液反应及血液学异常为主，未明显增加联合治疗负担。 疗效方面，41例可评估患者中客观缓解率（ORR）为29%，疾病控制率（DCR）达95%，88%的患者肿瘤体积出现缩小。中位缓解持续时间为9.02个月。进一步随访显示，中位PFS为10.85个月，中位OS为16.43个月。肿瘤标志物CA19-9方面，69%的可评估患者下降超过50%。更值得关注的是，43例患者中有10例接受后续手术切除，整体转化手术率达到23%，多数实现R0切除。对于原本缺乏手术机会的LAPC患者而言，这一结果具有明确临床意义。 为了回答“为什么联合治疗有效”，研究团队对治疗前穿刺标本及治疗后手术标本进行了激光捕获显微切割，分离肿瘤细胞后实施RNA测序。结果显示，联合治疗后最显著下调的生物学通路之一正是EMT。研究者进一步提炼出由45个基因组成的核心EMT特征集，用于评估肿瘤可塑性状态。与既往公开数据中mFOLFIRINOX单独治疗导致EMT上升不同，加入NP137后这一趋势被逆转。也就是说，NP137并非单纯叠加一种抗体药物，而是在分子层面有效克服了EMT介导的化疗耐药程序。 作者还观察到，在联合治疗队列中，无论患者肿瘤原本属于经典型还是基底样分型，预后差异均不明显。传统上，基底样或EMT偏高型胰腺癌往往预后更差、对治疗反应更弱。而在本研究中，这种分层差异被削弱，提示NP137可能部分打破了EMT相关高危生物学特征带来的治疗壁垒。 进一步分析发现，Netrin1受体Neogenin（NEO1）的表达水平与治疗获益密切相关。在历史对照队列中，接受mFOLFIRINOX治疗的Neogenin高表达患者往往预后更差；但在联合NP137后，这一趋势出现逆转。Neogenin高表达患者中位PFS达到15.65个月，而低表达组为10.22个月，延长超过5个月；中位OS尚未达到，且40%的患者获得转化手术机会。RNA测序与免疫组化结果高度一致，提示Neogenin有望成为筛选NP137获益人群的伴随诊断标志物。 体外实验进一步提供了机制支持。研究者在Panc02胰腺癌细胞中敲低Neogenin后发现，NP137抑制细胞迁移的作用明显减弱，说明其抗肿瘤效应具有Neogenin依赖性。同时，MAPK-ERK通路抑制剂可影响这一过程，提示Netrin1-Neogenin轴可能通过MAPK信号促进肿瘤恶性行为。 总体而言，这项研究的意义并不仅在于提供了一种新的联合治疗方案，更重要的是提出了一个值得重视的治疗理念：胰腺癌化疗失败，部分原因可能来自治疗过程中被激活的肿瘤可塑性程序。若能同步阻断EMT等适应机制，传统化疗的疗效或可被重新释放。 然而，本研究样本量有限，尚不能替代随机对照证据，NP137是否真正优于现有标准治疗，Neogenin检测如何标准化，以及该策略能否拓展至转移性胰腺癌，仍需后续Ⅱ期和Ⅲ期临床试验验证。即便如此，本研究为长期停滞的胰腺癌治疗领域提供了一个清晰方向：未来的突破，也许不仅来自更强的杀伤药物，更来自对肿瘤“变形能力”的精准限制。 原文链接： https://doi.org/10.1038/s41586-026-10436-4 制版人： 十一 参考文献 1. Sally, Á, McGowan, R., Finn, K. & Moran, B. M. Current and future therapies for pancreatic ductal adenocarcinoma. Cancers 14, 2417 (2022). 2. Lengrand, J. et al. Pharmacological targeting of netrin-1 inhibits EMT in cancer. Nature 620, 402–408 (2023). 3. Mehlen, P., Delloye-Bourgeois, C. & Chédotal, A. Novel roles for slits and netrins: axon guidance cues as anticancer targets? Nat. Rev. Cancer 11, 188–197 (2011). 4. Cassier, P. A. et al. Netrin-1 blockade inhibits tumour growth and EMT features in endometrial cancer. Nature 620, 409–416 (2023). 学术合作组织 （*排名不分先后） 战略合作伙伴 （*排名不分先后） · 转载须知 【原创文章】BioArt原创文章，欢迎个人转发分享，未经允许禁止转载，所刊登的所有作品的著作权均为BioArt所拥有。BioArt保留所有法定权利，违者必究。 BioArt Med Plants 人才招聘 点击主页推荐活动 关注更多最新活动！