NETRIS Pharma SAS

A new scientific finding is the foundation for the first clinical trial in the U.S. to study an experimental drug's ability to fight pancreatic cancer with metastasis to the liver.   Pancreatic cancer is tricky to manage because it spreads easily and early, and the tumors have a unique biological makeup. But, researchers made a breakthrough by learning about the genetic changes that occur during tumor migration -- and also found a drug that can obstruct the process. The next step is a groundbreaking clinical trial at the University of Rochester's Wilmot Cancer Institute, planned for early in 2024, to test the drug from their laboratory discovery, said senior investigator Darren Carpizo, MD, PhD, co-leader of Wilmot's Genetics, Epigenetics and Metabolism research program, and chief of Surgical Oncology at the University of Rochester Medical Center. "We will be the first institution in the U.S. to study the safety and effectiveness of the experimental drug, known as NP137, on pancreatic cancer that has spread to the liver," Carpizo said. Carpizo and several collaborators recently published the results of their bench science investigation in the journal Cell Reports, and Carpizo will lead the Wilmot clinical trial with Aram Hezel, MD, chief of Hematology/Oncology at Wilmot, and Nabeel Badri, MBChB, a medical oncologist at Wilmot. The five-year survival rate for pancreatic cancer is only 12 percent, which is a slight increase in 2023 compared to previous years. The number of cases is rising worldwide, however, and by 2030, pancreatic cancer is predicted to be the second leading cause of cancer deaths. Why is pancreatic cancer deadly? First, because it spreads (metastasizes) very early during its development. In 85 percent of patients, the cancer has already spread outside of the pancreas at diagnosis. Even when the cancer is localized to the pancreas and surgical removal is possible, the majority of patients face a recurrence of their cancer. The metastasis causes these patients to eventually succumb to the disease, which is why researchers are focused on understanding the biology of metastatic pancreatic cancer. Second, although pancreatic cancer cells do not have to travel far to reach the liver, along the way they genetically reprogram themselves and become stronger. The result: newly seeded cancer cells in the liver have a distinctly different biology from the primary tumor in the pancreas, and are able to resist standard treatment, Carpizo said. In their latest work, Wilmot researchers built on what was already known about a key gene, Netrin-1, involved in pancreas, breast and colon cancers. They discovered, for the first time, the complex mechanisms that allow Netrin-1 to drive the lethal, genetic changes as pancreatic cancer cells migrate to the liver. They also showed how Netrin-1 activates hepatic stellate cells, which are involved in liver fibrosis, a serious chronic disease, priming the liver as a host for cancer. In mice and in tissue studies, when researchers suppressed Netrin-1 with the anti-cancer drug (NP137), cancer was less likely to spread and cancer cell death occurred. The team includes scientists from Rutgers University, where Carpizo worked as a surgeon-scientist before joining Wilmot in 2020, Fox Chase Cancer Center in Philadelphia, and a laboratory in France. The Wilmot clinical trial will likely require eligible patients to take two cycles of NP137 before surgery, undergo surgery to remove the cancer, and then take more of the experimental medication along with chemotherapy after surgery for up to six months, Carpizo said. He noted that NP137 is made by Netris Pharma, of Lyon, France, and is currently being tested in clinical trials in that country. The Pancreatic Cancer Action Network (PanCAN) funded much of the work through a grant to Carpizo; Wilmot also provided pilot funding. PanCAN has emphasized that the recent, small uptick in survivorship rates for pancreatic cancer is due to transformative research and clinical trials, and strongly recommends that patients talk to their oncologists about clinical trials at every stage of their disease. Carpizo's study is part of a larger collaborative effort at Wilmot aimed at pancreatic cancer. Others, including URMC Surgery Chair David Linehan, MD., and Wilmot investigator Scott Gerber, PhD., and members of the Cancer Microenvironment research program, are also conducting studies on new, targeted treatments. The goal is to use newly discovered drugs in combination with immunotherapy, radiation therapy, and chemotherapy to attack pancreatic cancer.

DOYLESTOWN, Pa., Aug. 24, 2023 (GLOBE NEWSWIRE) -- Aprea Therapeutics, Inc. (Nasdaq: APRE) (“Aprea”, or the “Company”), a clinical stage biopharmaceutical company focused on precision oncology through synthetic lethality, today announced it has appointed Dr. Jean-Pierre Bizzari to its Board of Directors and is naming Dr. Richard Peters as its new Chairman of the Board. Dr. Bizzari will replace Mr. Christian Schade, who is stepping down from the Board. “We warmly welcome Dr. Jean-Pierre Bizzari to our Board of Directors. Jean-Pierre is an esteemed industry thought leader and was the Group Head Clinical Development Oncology at Celgene where he was responsible for developing some of the most significant and successful oncology therapeutics,” said Dr. Oren Gilad, President and Chief Executive Officer of Aprea. “Jean-Pierre joins our Board as Chris Schade retires from his role as Chairman and member of the Board to focus on his other commitments. Dr. Richard Peters has served as independent Director of Aprea since June 2020 and Chair of the Compensation Committee since November 2020. Dr. Peters will now also assume the role of Chairman, and we welcome his leadership as he guides our diverse and experienced Board.” Dr. Jean-Pierre Bizzari joins the Aprea Board having led a remarkable and distinguished career in oncology. He has been responsible for numerous global approvals of several billion-dollar therapies, including: Fotomustine, Taxotere, Revlimid, Abraxane, Vidaza, PTCL, Eloxatin, CPT-11, Gliadel, Rasburicase, and Pomalidomide to name a few. He has been involved in acquisition and licensing agreements with several major pharmaceutical companies. Dr. Bizzari is a member and leader on many scientific committees and is currently a member of the Scientific Advisory Board for the National Cancer Institute in France; a Board member of the European Organization of Research and Treatment of Cancer (EORTC) and Chairman of the EORTC New Drug Advisory Committee. He currently is on the Boards of Halozyme, ADC Therapeutics, NETRIS Pharma, and Oxford BioTherapeutics. Most recently, Dr. Bizzari was the Group Head Clinical Development Oncology at Celgene. He led global clinical development conducting over 25 Phase 3 trials, was responsible for global operations of over 950 people and was chairman of the Hematology Oncology development committee. Prior to Celgene, Dr. Bizzari was the VP of clinical development oncology at Sanofi-Aventis where he was responsible for the worldwide clinical development and approvals. He also served as VP of clinical development oncology at Rhone-Poulenc Rorer where he shepherded a deep pipeline of oncology candidates. Dr. Bizzari holds a degree in mathematics, and completed his medical studies in Nice, France. He completed his residency in oncology at Pitie Salpetriere Hospital in Paris. Dr. Bizzari said, “I am excited to join this dedicated Board, and look forward to contributing to the success of their very promising therapeutics at the center of synthetic lethality and DNA Damage Repair drug development.” Mr. Christian Schade noted, “It has been an honor to serve on this dynamic Board. I leave knowing that the Board and Company are in good hands, and that everyone involved is committed to realizing the tremendous potential of this company.” Dr. Richard Peters added, “I thank Chris for his years of service to the Board and astute leadership as we successfully navigated the company through several challenges. I look forward to working closely with our Board and terrific management team as we move towards several meaningful Company milestones.” About ApreaAprea Therapeutics, Inc. is a clinical stage biopharmaceutical company headquartered in Doylestown, Pennsylvania, focused on precision oncology through synthetic lethality. The Company’s lead program is ATRN-119, a clinical-stage small molecule ATR inhibitor being developed for solid tumor indications. Our WEE1 inhibitor is being advanced to IND submission. For more information, please visit the company website at www.aprea.com. The Company may use, and intends to use, its investor relations website at https://ir.aprea.com/ as a means of disclosing material nonpublic information and for complying with its disclosure obligations under Regulation FD. Forward-Looking Statement Certain information contained in this press release includes “forward-looking statements”, within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended related to our study analyses, clinical trials, regulatory submissions, and projected cash position. We may, in some cases use terms such as “future,” “predicts,” “believes,” “potential,” “continue,” “anticipates,” “estimates,” “expects,” “plans,” “intends,” “targeting,” “confidence,” “may,” “could,” “might,” “likely,” “will,” “should” or other words that convey uncertainty of the future events or outcomes to identify these forward-looking statements. Our forward-looking statements are based on current beliefs and expectations of our management team and on information currently available to management that involve risks, potential changes in circumstances, assumptions, and uncertainties. All statements contained in this press release other than statements of historical fact are forward-looking statements, including statements regarding our ability to develop, commercialize and achieve market acceptance of our current and planned products and services, our research and development efforts, including timing considerations and other matters regarding our business strategies, use of capital, results of operations and financial position, and plans and objectives for future operations. Any or all of the forward-looking statements may turn out to be wrong or be affected by inaccurate assumptions we might make or by known or unknown risks and uncertainties. These forward-looking statements are submits to risks and uncertainties including, without limitation, risks related to the success, timing and cost of our ongoing clinical trials and anticipated clinical trials for our current product candidates, including statements regarding the timing of initiation, pace of enrollment and completion of the trials, futility analyses, presentations at conferences and data reported in an abstract, and receipt of interim or preliminary results )including, without limitation, any preclinical results or data), which are not necessarily indicative of the final results of our ongoing clinical trials, and the other risks, uncertainties, and other factors described under “Risk Factors,” “Management’s Discussion and Analysis of Financial Condition and Results of Operations” and elsewhere in the documents we file with the U.S. Securities and Exchange Commission. For all these reasons, actual results and developments could be materially different from those expressed in or implied by our forward-looking statements. You are cautioned not to place undue reliance on these forward-looking statements, which are made only as of the date of this press release. We undertake no obligation to update such forward-looking statement for any reason, except as required by law. Investor Contact: Mike MoyerLifeSci Advisorsmmoyer@lifesciadvisors.com

转移和对化疗的抵抗性是癌症患者治疗失败和死亡的主要原因。上皮-间质转化（epithelial-mesenchymal transition, EMT）是癌细胞脱离邻近细胞并获得浸润特性的过程，在转移灶的形成和抗癌治疗抵抗性的产生中起着关键作用。迄今为止，还没有靶向癌症 EMT 的疗法。在一项新的研究中，来自法国里昂大学和瑞士布鲁塞尔自由大学等研究机构的研究人员发现不同类型癌症中肿瘤细胞表达的一种称为netrin-1的分子会刺激肿瘤细胞中的EMT，而一种靶向netrin-1的药物可以阻断癌症中的EMT。相关研究结果于2023年8月2日在线发表在Nature期刊上，论文标题为“Netrin-1 blockade inhibits tumour growth and EMT features in endometrial cancer”。这些作者发现发现出现 EMT 的癌细胞表达高水平的 netrin-1 及其受体 UNC5B。他们发现，增加 netrin-1 会促进 EMT，而靶向 netrin-1则会减少 EMT。这些作者与NETRIS Pharma公司合作开发了一种治疗性抗体，专门阻断netrin-1与其受体UNC5B之间的相互作用。他们的研究结果表明给送这种治疗性抗体不仅能减少肿瘤的形成，还能阻断这些肿瘤中的EMT，从而降低肿瘤的转移能力，并使肿瘤细胞对化疗敏感。靶向netrin-1减少皮肤鳞状细胞癌的转移并使肿瘤细胞对化疗敏感。图片来自Nature, 2023, doi:10.1038/s41586-023-06367-z。论文第一作者Justine Lengrand解释说，“我们非常高兴和兴奋地发现了第一种可以在体内靶向EMT的药物，从而减少了转移的形成和对化疗的抵抗性。”在动物模型中证明了抗netrin-1抗体预防EMT的有效性后，这些作者研究了这种药物对子宫内膜癌患者体内EMT的影响。在第二项新的标题为“Pharmacological targeting of netrin-1 inhibits EMT in cancer”的研究中，他们在法国的临床试验中为患者注射了抗netrin-1抗体。他们的研究表明，患者对这种治疗性抗体的耐受性良好，没有出现毒性反应。更重要的是，他们在给药前后的肿瘤活检中发现，这种疗法减少了子宫内膜癌患者体内的EMT。这些作者说，“这是一项重大的世界首创；我们发现了一种新药，可以在临床前模型中减少 EMT、减少转移并刺激对化疗的反应。在第二项研究中，我们为我们的基本发现在医学上的应用提供了原理证明，并表明给送抗netrin-1抗体可抑制癌症患者体内的 EMT。”项目负责人Cédric Blanpain教授评论说，“我们现在要评估的是，给送抗netrin-1抗体和减少EMT是否会使癌症患者对化疗和免疫疗法产生更好的临床反应。”这些作者确定了新的创新疗法组合，以提高肿瘤对化疗的敏感性，防止肿瘤恶化、转移和对抗癌疗法的抵抗性。Blanpain评论道，“从长远来看，有必要确定这种新疗法对子宫内膜癌患者生存的有效性，并评估这种新药物组合治疗其他类型的出现EMT的癌症（如肺癌或乳腺癌）的疗效。” 文章来源“生物谷”责编|文竞择校对|文竞择End往期精选围观历史性突破！不需卵子和精子就可以合成人类胚胎热文富豪用儿子血浆“回春”科学吗？Science：血液牛磺酸缺乏驱动衰老热文世界首例！35岁的她，通过机器人操刀移植的子宫，成功诞下宝宝热文为了避免心脏骤停，53岁的他成为“第一个”植入开创性除颤器的心脏病患者热文首次披露！175家生物制药公司的薪资数据：薪资中位数达20万美元点击“阅读原文”，了解更多~