ROCK1

SEATTLE, CAMBRIDGE, Mass. & TOKYO--(BUSINESS WIRE)-- Aurion Biotech, whose mission is to restore vision to millions of patients with life-changing regenerative therapies, today announced several presentations during the 2024 American Society of Cataract and Refractive Surgery (ASCRS) Annual Meeting to be held April 5-8, 2024 in Boston, Massachusetts. At Eyecelerator and ASCRS 2024, data will be presented from the Company’s Escalón and IOTA studies, which treated subjects with its combination cell therapy product (biologic/drug) comprised of neltependocel (allogeneic human corneal endothelial cells [CECs]) and Y-27632 (an inhibitor of Rho-associated, coiled-coil containing protein kinase [ROCK]). “We are delighted to share additional insights into these clinical studies, in multiple sessions at the Eyecelerator and ASCRS 2024 meetings,” said Michael Goldstein, M.D., president and chief medical officer, Aurion Biotech. “We believe these presentations will be of significant interest to the ophthalmology community, as they highlight the exciting potential of our cell therapy to treat patients with corneal endothelial disease.” The schedule of presentations includes: Corneal Endothelial Cell Therapy for Corneal Endothelial Disease Thursday, April 4, 2024 1:00 p.m. EST Eyecelerator, Omni Boston Hotel at the Seaport, Level 2 Marquis room Presenter: Greg Kunst, Chief Executive Officer, Aurion Biotech Comparison of Subjects with Corneal Edema Receiving Corneal Endothelial Cells with ROCK Inhibitor in One Eye vs. Cells Alone in the Fellow Eye Sunday, April 7, 2024 2:00 p.m. EST ASCRS Boston Convention & Exhibition Center (BCEC) - Level 2 Presenters: Michael Goldstein, M.D., President & Chief Medical Officer, Aurion Biotech; Nysha Blender, O.D., Senior Director Medical Affairs, Aurion Biotech Human Corneal Endothelial Cell Transplantation Combined with Cataract Extraction and PCIOL in Subject with Corneal Edema Monday, April 8, 2024 8:45 a.m. EST ASCRS Boston Convention & Exhibition Center (BCEC) - Meeting Level 2, Room 259A Presenter: Elizabeth Yeu, M.D., President, ASCRS; Virginia Eye Consultants Aurion Biotech recently opened a Phase 1 / 2 clinical trial (ABA-1 / CLARA), a prospective, multi-center, randomized, double-masked, parallel-arm cell dose-ranging study in subjects with corneal edema secondary to corneal endothelial dysfunction. The study will evaluate three different doses of neltependocel used in combination with Y-27632. Approximately 100 subjects will be randomized in sites in the U.S. and in Canada. The ABA-1 / CLARA trial is designed to assess the safety, tolerability, and efficacy of AURN001 for the treatment of corneal edema secondary to corneal endothelial dysfunction. The primary endpoint is the percentage of subjects who gain 3 lines of vision at 6 months. Aurion Biotech’s combination cell therapy recently received regulatory approval from Japan’s Pharmaceuticals and Medical Devices Agency (PMDA), for the treatment of bullous keratopathy, marking the first-ever regulatory approval in the world for an allogeneic cell therapy to treat corneal endothelial disease. About Aurion Biotech With offices in Seattle, Cambridge and Tokyo, Aurion Biotech is a clinical-stage biotech company, whose mission is to restore vision to millions of patients with life-changing regenerative therapies. Aurion Biotech is the recipient of the prestigious Prix Galien award for best start-up in biotech. The Company’s first candidate is for the treatment of corneal edema secondary to corneal endothelial disease, and is the first off-the-shelf, clinically validated cell therapy for corneal care, having received regulatory approval in Japan. The Company has initiated clinical trials in the U.S. and Canada. Privately held, Aurion Biotech is backed by leading investors that include Deerfield, Alcon, Petrichor, Flying L Partners, Falcon Vision / KKR, and Visionary Ventures. To learn more about Aurion Biotech, visit .

Allogeneic Cell Therapy for the Treatment of Corneal Edema Secondary to Corneal Endothelial Dysfunction SEATTLE & CAMBRIDGE, Mass. & TOKYO--(BUSINESS WIRE)-- Aurion Biotech, whose mission is to restore vision to millions of patients with life-changing regenerative therapies, today announced that it has dosed the first Canadian subject in its Phase 1 / 2 clinical trial (ABA-1, CLARA) of AURN001, a cell therapy for the treatment of corneal edema secondary to corneal endothelial dysfunction. “We are very pleased to have begun dosing subjects in this trial in Canada,” said Michael Goldstein, MD, MBA, President and Chief Medical Officer of Aurion Biotech. “Treating subjects in both the United States and Canada in our CLARA trial is an important milestone in our clinical development program. We believe that our cell therapy has the potential to revolutionize the treatment of corneal patients throughout the world.” AURN001 is a combination cell therapy product (biologic/drug) comprised of neltependocel (allogeneic human corneal endothelial cells [CECs]) and Y-27632 (an inhibitor of Rho-associated, coiled-coil containing protein kinase [ROCK]). AURN001 is intended to be administered to the eye as a one-time, intracameral injection. The Phase 1 / 2 clinical trial (ABA-1, CLARA) is a prospective, multi-center, randomized, double masked, parallel-arm cell dose-ranging clinical trial in subjects with corneal edema secondary to corneal endothelial dysfunction. The study will evaluate three different doses of neltependocel used in combination with Y-27632. Approximately 100 subjects will be randomized in sites in the U.S. and in Canada. This trial is designed to assess the safety, tolerability, and efficacy of AURN001 for the treatment of corneal edema secondary to corneal endothelial dysfunction. The primary endpoint is the percentage of subjects who gain 3 lines of vision at 6 months. About Corneal Endothelial Dysfunction Corneal edema secondary to endothelial dysfunction is a sight-threatening and debilitating condition affecting millions of people throughout the world. When corneal endothelial cells die or degrade, they do not regenerate. If left untreated, corneal endothelial cell loss can cause corneal edema (swelling) and loss of vision. Although corneal transplants are effective, there are disadvantages with these procedures – PKP/DMEK/DSAEK – including limited donor organ supply. Transplants require a supply of donor corneas in a 1:1 ratio (one healthy donor cornea to treat each diseased one), yet it’s estimated that there is only one donor cornea available for every 70 diseased eyes.1 In addition, post-operative recovery for corneal transplant patients requires that they lie flat on their backs for up to three days, in order for the transplant to adhere to the corneal stroma. About Aurion Biotech With offices in Seattle, Cambridge and Tokyo, Aurion Biotech is a clinical-stage biotech company, whose mission is to restore vision to millions of patients with life-changing regenerative therapies. Aurion Biotech is the recipient of the prestigious Prix Galien award for best start-up in biotech. The Company’s first candidate is for the treatment of corneal edema secondary to corneal endothelial disease, and is the first off-the-shelf, clinically validated cell therapy for corneal care, having received regulatory approval in Japan. The Company has initiated clinical trials in the U.S. and Canada. Privately held, Aurion Biotech is backed by leading investors that include Deerfield, Alcon, Petrichor, Flying L Partners, Falcon Vision / KKR, and Visionary Ventures. To learn more about Aurion Biotech, visit . _______________ 1

引言恶病质影响50-80%的癌症患者，占癌症相关死亡的20%，但驱动恶病质的潜在机制尚不清楚。2024年3月18日，北京大学肖瑞平及胡新立共同通讯在Nature Metabolism 在线发表题为“Activation of GPR81 by lactate drives  tumour-induced cachexia”的研究论文，该研究发现在患有癌症恶病质的男性和女性患者以及临床相关的小鼠模型中，循环乳酸水平与体重减轻程度呈正相关。乳酸输注本身足以在无肿瘤小鼠中以剂量依赖的方式触发恶病质表型。此外，还证明脂肪特异性G蛋白偶联受体(GPR)81消融，与全局GPR81缺乏类似，可以改善雄性小鼠乳酸诱导或肿瘤诱导的脂肪和肌肉消耗，揭示脂肪GPR81是乳酸分解代谢作用的主要介质。在机制上，乳酸/GPR81诱导的恶病质发生独立于已建立的蛋白激酶A分解代谢途径，但它是由信号级联顺序激活Gi-Gβγ-RhoA / ROCK1-p38介导的。这些发现突出了靶向GPR81治疗这种危及生命的癌症并发症的治疗潜力。恶病质的特点是体重迅速减轻，约占癌症相关死亡的20%。癌症恶病质患者会出现虚弱、厌食、贫血和疲劳，导致生活质量下降，对癌症治疗的耐受性差。虽然癌症恶病质例证了一个突出的未满足的医疗需求，其潜在的机制知之甚少。脂肪和肌肉的减少是恶病质的主要表现。几种炎症细胞因子，如肿瘤坏死因子(TNF)、白细胞介素(IL)-6、转化生长因子-β和干扰素(IFN)-γ，都与刺激脂肪和肌肉重构有关，这些脂肪和肌肉重构是由癌细胞的旺盛生长引起的。它们被认为是癌症恶病质发病的主要驱动因素。然而，多项抗炎治疗的临床试验结果令人失望，这表明靶向炎症细胞因子不足以治愈癌症恶病质。迄今为止，在肿瘤生物学和医学领域仍然存在一个基本的知识缺口，即肿瘤与宿主代谢失调之间的联系。模式图（Credit: Nature Metabolism）综上所述，该研究揭示了乳酸对GPR81的慢性激活可以通过Gαi/ o-Gβγ-RhoA / ROCK1-p38信号级联促进脂肪褐变和脂肪分解，从而促进肌肉营养不良和全身高分解代谢。因此，靶向GPR81及其关键信号成分有望对抗癌症恶病质代谢损伤，从而改善恶病质患者的生活质量和寿命。原文链接https://www-nature-com.libproxy1.nus.edu.sg/articles/s42255-024-01011-0责编|探索君排版|探索君文章来源|“iNature”End往期精选围观一文读透细胞死亡(Cell Death) | 24年Cell重磅综述（长文收藏版）热文Nature | 破除传统：为何我们需要重新思考肿瘤的命名方式热文Nature | 2024年值得关注的七项技术热文Nature | 自身免疫性疾病能被治愈吗？科学家们终于看到了希望热文CRISPR技术进化史 | 24年Cell综述