Collagen

CLEVELAND, Oct. 29, 2024 (GLOBE NEWSWIRE) -- Abeona Therapeutics Inc. (Nasdaq: ABEO) today announced that the Company has resubmitted its Biologics License Application (BLA) to the U.S. Food and Drug Administration (FDA or Agency) for prademagene zamikeracel (pz-cel), its investigational autologous cell-based gene therapy, as a potential new treatment for patients with recessive dystrophic epidermolysis bullosa (RDEB). “We have worked closely with the FDA in preparing for the pz-cel BLA resubmission and thank the Agency for their ongoing guidance,” said Vish Seshadri, Chief Executive Officer of Abeona. “We have incorporated the Agency’s feedback and are confident that our resubmission package addresses all the Chemistry Manufacturing and Controls items identified in the Complete Response Letter, including observations from the completed Pre-License Inspection of our manufacturing facility. Upon acceptance of the BLA, we look forward to assisting the FDA in the completion of its review.” The BLA resubmission follows the Company’s Type A meeting in August 2024, where Abeona aligned with the FDA on the content of the resubmission, including additional information to satisfy all Chemistry Manufacturing and Controls (CMC) requirements outlined in the Complete Response Letter (CRL) received in April 2024. In the CRL, the FDA required that certain additional information needed to satisfy CMC requirements be provided before the application could be approved. The CRL did not identify any deficiencies related to the clinical efficacy or clinical safety data in the BLA, and the FDA did not request any new clinical trials or clinical data to support the approval of pz-cel. The BLA resubmission is supported by clinical efficacy and safety data from the pivotal Phase 3 VIITAL™ study (NCT04227106) and a Phase 1/2a study (NCT01263379). Upon acceptance of the BLA resubmission, Abeona expects the FDA to set a new Prescription Drug User Fee Act (PDUFA) target action date for pz-cel. The review period for a resubmitted BLA is either two or six months from the resubmission date depending on the FDA's classification of a resubmission as Class 1 or Class 2, respectively. The FDA’s decision on acceptance of a BLA resubmission is typically made within 14 calendar days following the resubmission. About prademagene zamikeracel (pz-cel) Prademagene zamikeracel (pz-cel), Abeona’s investigational autologous, COL7A1 gene therapy, is currently being developed for the treatment of recessive dystrophic epidermolysis bullosa (RDEB), a rare genetic skin disease caused by a mutation in both copies of the COL7A1 gene. As a result of this defect, cells are unable to express functional collagen VII protein which is needed to form anchoring fibrils that bond the epidermis to the dermis. Lack of anchoring fibrils leads to fragile skin that blisters easily and patients suffer from years of painful wounds, itch and increased risk of infection and squamous cell carcinoma. Pz-cel is made from patients' own skin cells that are genetically corrected with a functional COL7A1 gene integrated into the skin cells’ genome to express collagen VII. These gene-corrected cells are expanded to form keratinocyte sheets to cover wound areas in a single surgical application. Pz-cel has been granted Regenerative Medicine Advanced Therapy, Breakthrough Therapy, Orphan Drug and Rare Pediatric Disease designations by the U.S. FDA. About Abeona Therapeutics Abeona Therapeutics Inc. is a clinical-stage biopharmaceutical company developing cell and gene therapies for serious diseases. Prademagene zamikeracel (pz-cel) is Abeona’s investigational autologous, COL7A1 gene-corrected epidermal sheets currently in development for recessive dystrophic epidermolysis bullosa. The Company’s fully integrated cell and gene therapy cGMP manufacturing facility served as the manufacturing site for pz-cel used in its Phase 3 VIITAL™ trial, and is capable of supporting commercial production of pz-cel upon FDA approval. The Company’s development portfolio also features AAV-based gene therapies for ophthalmic diseases with high unmet medical need. Abeona’s novel, next-generation AAV capsids are being evaluated to improve tropism profiles for a variety of devastating diseases. For more information, visit www.abeonatherapeutics.com. Forward-Looking Statements This press release contains certain statements that are forward-looking 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, and that involve risks and uncertainties. We have attempted to identify forward-looking statements by such terminology as “may,” “will,” “believe,” “anticipate,” “expect,” “intend,” “potential,” and similar words and expressions (as well as other words or expressions referencing future events, conditions or circumstances), which constitute and are intended to identify forward-looking statements. Actual results may differ materially from those indicated by such forward-looking statements as a result of various important factors, numerous risks and uncertainties, including but not limited to, the timing and outcome of the FDA’s review of our BLA resubmission for pz-cel; the FDA’s grant of a Priority Review Voucher upon pz-cel approval; continued interest in our rare disease portfolio; our ability to enroll patients in clinical trials; the outcome of future meetings with the FDA or other regulatory agencies, including those relating to preclinical programs; the ability to achieve or obtain necessary regulatory approvals; the impact of any changes in the financial markets and global economic conditions; risks associated with data analysis and reporting; and other risks disclosed in the Company’s most recent Annual Report on Form 10-K and subsequent periodic reports filed with the Securities and Exchange Commission. The Company undertakes no obligation to revise the forward-looking statements or to update them to reflect events or circumstances occurring after the date of this press release, whether as a result of new information, future developments or otherwise, except as required by the federal securities laws.

OTC2024类器官前沿应用与3D细胞培养论坛圆满落幕，点击图片可查看会后报告，咨询OTC2025类器官论坛请联系：王晨 180 1628 8769 引言：要说起这几年来自免领域，什么适应症的交易最火，那非IBD（炎症性肠病）莫属！ 针对IBD，我们之前的文章中写过TNF-α、JAK、TL1A等靶点（感兴趣的朋友可点相关蓝字观看）！ 今天这篇我们要写一个自免领域一个非常牛掰的靶点：α4β7！ 它的牛掰之处在于，横跨自免和抗感染两大领域！绝对有爆款潜质！ 针对此靶点开发的维多珠单抗已经成为IBD领域的一颗明珠，同时近几年也有公司另辟蹊径，针对此靶点开发了治疗HIV的产品，且已进入临床二期，不过最重要的事情先说在前面：这个靶点目前还不卷！ 图注：现有自免靶点、靶向药物和作用机制(MOA)。 01 α4β7 靶点介绍 整合素α4β7是一种异二聚体的I型跨膜糖蛋白，由α4和β7亚基组成，也是由这两个亚基而得名。 α4β7作为在淋巴细胞表面表达的归巢受体，在T细胞、B细胞、NK细胞及其他免疫细胞上表达。通过与粘膜地址蛋白细胞粘附分子-1（MAdCAM-1） 的相互作用，介导淋巴细胞运输到肠道相关淋巴组织（GALT）。 MAdCAM-1作为α4β7的主要天然配体，表达在肠粘膜高内皮小静脉（HEV）的管腔表面。 除MAdCAM-1外，动物细胞中大多数细胞外基质蛋白（包括胶原蛋白、纤连蛋白和层粘连蛋白）的主要受体也是整合素。整合素以较低的亲和力和他们结合，除发挥粘附作用外，也具有将细胞外信号向细胞内传递的作用。 02 α4β7在IBD和HIV发病中的病理作用 淋巴细胞归巢是指在正常生理条件下，淋巴细胞选择性地迁移到某些淋巴器官。这种迁移由粘附分子（包括整合素α4β7、整合素LFA-1和L-选择素）之间的级联相互作用介导。 在病理条件下，淋巴细胞不受控地迁移到炎症部位，产生自身免疫疾病等病症。在这种情况下，淋巴细胞首先附着在内皮细胞上，然后沿着内皮细胞滚动。最终，粘附稳定下来，并实现向HEV的迁移。这种病理过程主要由整合素α4β7和MAdCAM-1的相互作用介导。 2.1 IBD  慢性炎症性肠病（IBD），包括克罗恩病和溃疡性结肠炎，是由自身免疫反应引起的肠道疾病。 克罗恩病主要累及回肠和结肠, 且整个小肠和大肠的任意位置都有可能发生病变，患者的典型症状是肛周病变、瘘管和组织学肉芽肿。 溃疡性结肠炎则主要累及直肠和部分结肠。此外, 溃疡性结 肠炎患者的典型特征为血性腹泻, 并伴随着腹痛、体重减轻、 呕吐等症状。 IBD的免疫学病理特征是肠系膜血管中淋巴细胞粘附和迁移受阻，导致淋巴细胞不受控制地聚集在肠道。 如上文所述，α4β7与高内皮小静脉（HEV）的AdCAM-1间的相互作用在此过程中起着关键作用。因此，靶向α4β7和MAdCAM-1成为了开发IBD药物的策略之一。 2.2 HIV  肠道相关淋巴组织(GALT)是HIV-1复制的主要部位。在感染的急性期，GALT 中的CD4+ T细胞是HIV-1的主要靶标。 高表达α4β7的CD4+ T细胞更容易受到HIV-1的生产性感染。HIV-1包膜蛋白gp120可与α4β7结合，导致CD4+T细胞LFA-1快速激活，从而促进HIV-1的高效细胞间传播。 艾伯维开发的ABBV-382可以通过干扰α4β7与其配体MAdCAM-1和gp120之间的相互作用来阻断CD4+ T细胞刺激和HIV-1感染。另外，ABBV-382还可以与HIV-1 形成免疫复合物，增强抗原的免疫原性，从而潜在地诱导HIV-1特异性免疫反应。目前，ABBV-382与抗PD-1单抗Budigalimab联合使用，正在进行一项二期研究（NCT06032546）。 03 已上市的大单品——维多珠单抗 维多珠单抗是武田开发的，靶向α4β7的，异二聚体单抗药物。2014年5月20日被FDA批准上市，随后在全球不同领域获得批准，获批的适应症为中度至重度活动性溃疡性结肠炎和活动性克罗恩病。 作为肠道选择性的α4β7整合素拮抗剂，维多珠单抗通过选择性阻断α4β7整合素与其天然配体 MAdCAM-1间的相互作用，抑制T淋巴细胞进入肠道固有层和肠道相关淋巴组织（GALT），减轻肠道炎症，而不损害全身免疫反应。 维多珠单抗是武田的主要资产之一，为公司的整体收入带来了巨大的利润。2022年，Entyvio（商品名）的总销售额为$5364M，2018年-2022年的五年销售情况见下图。 04 有哪些玩家？ 因为这个靶点的“通吃”特点，其前景那是非常无法估量的，虽然目前只有一个药物获批，但胖猫认为，将来这个靶点肯定能在药物江湖中掀起“腥风血雨”！ 除武田外，其实布局该靶点的管线并不多。这样一个已经被验证有效性且横跨两个大的治疗领域的靶点，为啥就没有人卷呢？值得立项的团队深思！ 目前处于后期的管线如下表所示： 除此外，我们还人肉整理了自免适应症领域的上市药物，请大家自行参考。其中，标黄的一栏为维多珠单抗。 END 免责声明：本文仅作知识交流与分享及科普目的，不涉及商业宣传，不作为相关医疗指导或用药建议。文章如有侵权请联系删除。 OTC2024类器官前沿应用与3D细胞培养论坛圆满落幕，点击图片可查看会后报告，咨询OTC2025类器官论坛请联系：王晨 180 1628 8769

Oct. 07, 2024 -- Ultragenyx Pharmaceutical Inc. (NASDAQ: RARE), a biopharmaceutical company focused on the development of novel products for rare and ultra-rare diseases, today announced that it has received Breakthrough Therapy Designation from the U.S. Food and Drug Administration (FDA) for setrusumab (UX143) as a treatment to reduce the risk of fracture associated with osteogenesis imperfecta (OI) Type I, III, or IV in patients 2 years of age and older. "FDA designation of setrusumab as a Breakthrough Therapy emphasizes the seriousness of osteogenesis imperfecta and the impact of this disease on people and their families affected by this disorder,” said Eric Crombez, M.D., chief medical officer at Ultragenyx. “The designation is also recognition of the significant clinical benefit observed in the Phase 2 portion of the Orbit study and supports our work to expeditiously bring this investigational therapy to patients who currently have no approved treatment option.” The FDA’s decision is based on preliminary clinical evidence including the positive 14-month results from the Phase 2 portion of the Orbit study, which demonstrated a rapid and clinically meaningful decrease in fracture rate in patients, and from the completed Phase 2b ASTEROID study. Breakthrough Therapy Designation aims to expedite the development and review of drugs that are intended to treat serious or life-threatening diseases and whose preliminary clinical evidence indicates that the drug may demonstrate substantial improvement on one or more clinically significant endpoints over existing therapies. Setrusumab was granted Orphan Drug Designation in the United States and EU, rare pediatric disease designation in the United States, and accepted into the European Medicine Agency’s Priority Medicines program (PRIME). Osteogenesis Imperfecta (OI) includes a group of genetic disorders impacting bone metabolism. Approximately 85% to 90% of OI cases are caused by genetic variants in the COL1A1 or COL1A2 genes, leading to either reduced or abnormal collagen and changes in bone metabolism. The collagen mutations in OI can result in increased bone brittleness, which contributes to a high rate of fractures. Patients with OI also exhibit inadequate production of new bone and excess bone resorption, resulting in decreased bone mineral density, bone fragility and weakness. OI can also lead to bone deformities, abnormal spine curvature, pain, decreased mobility, and short stature. No treatments are globally approved for OI, which affects approximately 60,000 people in commercially accessible geographies. Setrusumab is a fully human monoclonal antibody that inhibits sclerostin, a negative regulator of bone formation. Blocking sclerostin is expected to increase new bone formation, bone mineral density and bone strength in OI. In mouse models of OI, the use of anti-sclerostin antibodies was shown to increase bone formation, improve bone mass to normal levels, and increase bone strength against fracture force testing to normal levels. In 2019, Mereo BioPharma completed the Phase 2b dose-finding study (ASTEROID) for setrusumab in 112 adults with OI. The ASTEROID study demonstrated treatment with setrusumab resulted in a clear, dose-dependent and statistically significant effect on bone formation and bone density at multiple anatomical sites among adult participants with OI. Ultragenyx and Mereo BioPharma are collaborating on the development of setrusumab globally based on the collaboration and license agreement between the parties. The companies have developed a comprehensive late-stage program to continue development of setrusumab in pediatric and young adult patients across OI sub-types I, III and IV. Ultragenyx is a biopharmaceutical company committed to bringing novel therapies to patients for the treatment of serious rare and ultrarare genetic diseases. The company has built a diverse portfolio of approved medicines and treatment candidates aimed at addressing diseases with high unmet medical need and clear biology, for which there are typically no approved therapies treating the underlying disease. The company is led by a management team experienced in the development and commercialization of rare disease therapeutics. Ultragenyx’s strategy is predicated upon time- and cost-efficient drug development, with the goal of delivering safe and effective therapies to patients with the utmost urgency. The content above comes from the network. if any infringement, please contact us to modify.