GLP-2 (Entera Bio)

JERUSALEM, June 07, 2023 (GLOBE NEWSWIRE) -- Entera Bio Ltd. (NASDAQ: ENTX), (“Entera” or the “Company”) a leader in the development of orally delivered peptides and therapeutic proteins, today announced that it has appointed Haya Taitel, Head of Sanofi’s Global Transplant Franchise as an independent director to the Company’s Board of Directors. "We are thrilled that Haya has joined our Board," said Miranda Toledano, Chief Executive Officer of Entera. "With more than 30 years of experience building industry-leading commercial organizations across big pharma and biotech, Haya brings a veteran and unique perspective to Entera’s Board of Directors. We believe that Haya’s track record shepherding late-stage products through regulatory approval to commercial readiness, implementing payor and channel strategies for blockbusters, including products in women’s health, will be invaluable as we continue to prepare our global strategy related to EB613’s phase 3 program and our future pipeline. We are humbled that Haya, in addition to our existing clinical and regulatory advisory board, recognizes the potential for EB613 and its unique positioning to potentially alter the paradigm for post-menopausal women with osteoporosis. These champions are paramount to adequately preparing the success of our programs.” "Entera is looking to make a real difference with its platform technology and core products across major disease areas with significant unmet need, especially with EB613 for women at high risk of fracture, there are over 100 million women globally who could become candidates for this important therapy,” said Haya Taitel. “I have been following Entera’s regulatory development and the progress of this program closely and am looking forward to working with the Board and management team as Entera enters this pivotal stage for EB613. I am also excited for the pipeline candidates selected where Entera’s platform appears to provide a breakthrough simple mini tablet format for patients to better actively manage their health, such as GLP-2 and PTH for hypoparathyroidism.” Ms. Taitel has over 30 years of global C-level biopharma commercial and strategic executive experience. Ms. Taitel currently serves as the Head of Sanofi’s Global Transplant Franchise where she is responsible for increasing franchise growth and profitability. Prior to her role at Sanofi, Ms. Taitel served as the Chief Commercial Officer of Kadmon Pharmaceuticals, LLC, where she contributed to the launch of Rezurock®, from 2013 until the company was acquired by Sanofi for $1.9 billion in November 2021. Ms. Taitel also led Kadmon Board’s Executive Commercial Committee. Beginning in 1997, Ms. Taitel had held various commercial leadership positions of increasing seniority at Johnson and Johnson in multiple therapeutic areas, including oncology, immunology, neurology and women’s healthcare. Ms. Taitel holds a Master of Science, Pharmacology, (PharmD equivalence) from Temple University and a Bachelor of Science, Pharmacy and Biology from the Hebrew University School of Pharmacy in Jerusalem, Israel. About Entera Entera is a leader in the development of orally delivered macromolecules, including peptides and other therapeutic proteins. The Company focuses on significant unmet medical needs where a daily mini tablet form of a peptide treatment or replacement therapy holds the potential to transform the standard of care. The Company’s most advanced product candidates, EB613 for the treatment of high risk, post-menopausal osteoporosis and EB612 for the treatment of hypoparathyroidism, are in clinical development. EB613 is the first oral, once daily mini tablet presentation of synthetic hPTH (1-34), (teriparatide), consisting of the exact same 34 amino acid sequence as daily subcutaneous teriparatide injection, Forteo®, which requires daily SC injections. A placebo controlled, dose ranging Phase 2 study of EB613 tablets (n= 161) met primary (PD/biomarker) and secondary endpoints (BMD) in a dose dependent manner and was presented at the ASBMR 2021 Annual Conference. A phase 1 PK study of novel PTH formulations is planned for H1 2023 to ascertain feasibility of a new hypo candidate (a prior formulation had positive Phase 2a data announced in 2015 and published in JBMR 2019) and for another potential indication. For more information on Entera Bio, visit . Cautionary Statement Regarding Forward Looking Statements Various statements in this press release are “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995. All statements (other than statements of historical facts) in this press release regarding our prospects, plans, financial position, business strategy and expected financial and operational results may constitute forward-looking statements. Words such as, but not limited to, “anticipate,” “believe,” “can,” “could,” “expect,” “estimate,” “design,” “goal,” “intend,” “may,” “might,” “objective,” “plan,” “predict,” “project,” “target,” “likely,” “should,” “will,” and “would,” or the negative of these terms and similar expressions or words, identify forward-looking statements. Forward-looking statements are based upon current expectations that involve risks, changes in circumstances, assumptions and uncertainties. Forward-looking statements should not be read as a guarantee of future performance or results and may not be accurate indications of when such performance or results will be achieved. Important factors that could cause actual results to differ materially from those reflected in Entera’s forward-looking statements include, among others: changes in the interpretation of clinical data; results of our clinical trials; the FDA’s interpretation and review of our results from and analysis of our clinical trials; unexpected changes in our ongoing and planned preclinical development and clinical trials, the timing of and our ability to make regulatory filings and obtain and maintain regulatory approvals for our product candidates; the potential disruption and delay of manufacturing supply chains; loss of available workforce resources, either by Entera or its collaboration and laboratory partners; impacts to research and development or clinical activities that Entera may be contractually obligated to provide; overall regulatory timelines; the size and growth of the potential markets for our product candidates; the scope, progress and costs of developing Entera’s product candidates; Entera’s reliance on third parties to conduct its clinical trials; Entera’s expectations regarding licensing, business transactions and strategic collaborations; Entera’s operation as a development stage company with limited operating history; Entera’s ability to continue as a going concern absent access to sources of liquidity; Entera’s ability to obtain and maintain regulatory approval for any of its product candidates; Entera’s ability to comply with Nasdaq’s minimum listing standards and other matters related to compliance with the requirements of being a public company in the United States; Entera’s intellectual property position and its ability to protect its intellectual property; and other factors that are described in the “Cautionary Statements Regarding Forward-Looking Statements,” “Risk Factors” and “Management’s Discussion and Analysis of Financial Condition and Results of Operations” sections of Entera’s most recent Annual Report on Form 10-K filed with the SEC, as well as the company’s subsequently filed Quarterly Reports on Form 10-Q and Current Reports on Form 8-K. There can be no assurance that the actual results or developments anticipated by Entera will be realized or, even if substantially realized, that they will have the expected consequences to, or effects on, Entera. Therefore, no assurance can be given that the outcomes stated or implied in such forward-looking statements and estimates will be achieved. Entera cautions investors not to rely on the forward-looking statements Entera makes in this press release. The information in this press release is provided only as of the date of this press release, and Entera undertakes no obligation to update or revise publicly any forward-looking statements, whether as a result of new information, future events or otherwise, except to the extent required by law. Contact: Entera Bio: Ms. Miranda Toledano Chief Executive Officer Entera Bio Email: miranda@enterabio.com

关注并星标CPhI制药在线5月22日，医药行业发生了一笔“微不足道”的并购。当日，Ironwood以10亿美元的价格收购了VectivBio，获得后者核心管线GLP-2药物。耗资10亿美金买下一款GLP-2药物，Ironwood的举措可以说是剑走偏锋，因为同样作为胰高血糖素样肽，GLP-1（胰高血糖素样肽-1）才是市场的热门。GLP-1可增强胰岛素的分泌，减少食物摄入，抑制胃排空和消化道分泌，以及抑制胰高血糖素分泌，对于糖尿病和肥胖患者都有很好的疗效。诺和诺德、辉瑞、礼来等多家公司为其争得不可开交，有数据统计显示，目前全球在研GLP-1药物总和已超过300，没有最卷只有更卷。而GLP-2（胰高血糖素样肽-2）则不同，它主要的作用在于刺激肠道粘膜的细胞生长，防止细胞凋亡，抑制胃排空和胃酸分泌，以及增强肠道营养吸收和血流量，目前主要的应用方向是短肠综合症。由于唯一应用场景为罕见病，市场空间有限，患者招募都是困难，因此全球在研药物数量不足20款，可以说相当冷门。巨大的差距让人不禁发问：作为同源姐妹，在GLP-1撑起2家药王的同时，GLP-2真的只值10亿美金吗？/ 01 /分道扬镳的同源姐妹作为同源姐妹，GLP-1、GLP-2缘何分道扬镳？可以说，出生决定命运。GLP-1可以促进人体胰岛素的分泌，起到降低血糖的功效；而GLP-2的核心作用，则是调节胃肠道细胞的生长、增殖。显而易见，二者对血糖浓度的影响完全相反，GLP-1可以抑制胰高血糖素分泌，降低血糖；而GLP-2能够增加血糖，并且促进肠道生长。医学研究人员甚至将GLP-1和GLP-2称之为是肠道脂蛋白产生的“阴阳”分子，两者起到互补作用。机制的不同，两者的治疗领域也截然相反。GLP-1将用于治疗二型糖尿病和减肥，GLP-2当前唯一的适应症是用于治疗短肠综合症，帮助患者吸收营养物质。短肠综合症主要病因是大规模小肠切除手术导致的肠道面积减少，从而引发营养吸收不良，造成其他综合症状。目前，已有的治疗方式是通过肠外营养技术，为患者直接提高营养物质；或通过肠道修复增加对营养物质的吸收。GLP-2药物恰好能够达成这一目标，其能够增加肠道上皮细胞，扩大接触面积，同时抑制肠胃蠕动，延长胃排空时间，从而增加肠道吸收。自此，二者的道路彻底分道扬镳。与GLP-1药物的主要适应症糖尿病相比，短肠综合症并不是常见的疾病。首先来看GLP-1的崛起。不管是糖尿病患者，还是肥胖患者，全球基数都不小，这也促进了GLP-1类药物的开发。再来看GLP-2的落寞。短肠综合症是一种罕见疾病，根据VectivBio财报，全球创新药支付环境最发达的国家地区中，美国短肠综合症患者年新增数量只有约9000人，欧洲为7500人左右，日本只有1000人左右。新药的开发与研究总是离不开巨大的市场需求，不同适应症患者数量规模造成的市场需求差异，使得GLP-2必然无法超过它的同源姐妹GLP-1。/ 02 /潜力巨大的冷门赛道当然，这并不意味着，GLP-2未来不能翻身。当前，GLP-2应用极为狭窄，核心在于医学界对其认知不够，并不能够完全阐述其作用机制。未来，这一切有可能得到改变。就现有研究来看，GLP-2虽然主要由肠道粘膜肠内分泌L细胞释放，主要存在于胃肠道中；但在大脑中也有合成，可以通过神经元影响分泌系统，从而实现在不同环境中的作用。也就是说，GLP-2的研究有两大方向。第一是在胃肠道领域，例如VectivBio将其应用在预防和治疗严重胃肠道急性移植物抗宿主病（GvHD）疾病，目前来看进展不错。随着对GLP-2研究的进一步深入，在短肠综合症的应用不过是冰山一角，最新的文献表明，研究者正试图将GLP-2药物用于肥胖、糖尿病、营养不良、急性移植物抗宿主病（aGVHD）、肾功能衰竭、骨脆等领域。今年4月，Zealand一款GLP-1/GLP-2双靶点药物Dapiglutide治疗肥胖症的研究也进入Ⅱ期临床。Dapiglutide是基于GLP-1在葡萄糖稳态方面的作用以及GLP-2对神经元抑制产生饱腹感的代偿机制开发的新药，在临床前的实验阶段数据表现良好，Ⅱ期临床结果预计在明年公布。未来，随着医学界对GLP-2的机制认识更加清晰，其在胃肠道疾病领域，必然能够发挥更大的作用。第二则是分泌系统导致的不同疾病。因为GLP-2能够影响分泌系统，因此具有治疗诸多该类疾病的潜力，例如热门赛道NASH（非酒精性脂肪性肝炎）。NASH被认为与肠肝轴功能障碍密切相关，而诸多研究显示，GLP-2似乎能够通过多种机制，达到治疗效果。阿尔兹海默症海默症甚至也有可能被GLP-2治疗。一些研究显示，在海马体中，GLP-2能促进神经元细胞增殖，被认为可以用于阿尔兹海默症的治疗。另外，在骨质疏松症领域，GLP-2似乎也是潜力选手。一些研究显示，GLP-2可以抑制破骨细胞，使得骨密度增加。当然，这些研究都处于极早期阶段。GLP-2究竟能否满足市场期待，还需要医学界努力探索。/ 03 /必须改善的依从性在适应症探索之前，GLP-2还要一个明确的问题亟待解决：增加依从性。GLP-2极容易在人体内被降解，因此与人体高度同源的GLP-2药物性极差，需要改变响应的分子结构，以延长半衰期。然而，这一过程并不容易，导致GLP-2药物的研究一直进展缓慢，直到GLP-2R激动剂Teduglutide获批上市，才再次吸引了人们的兴趣。Teduglutide最早于2012年在欧盟获批，随后在美国、日本相继获得批准，用于治疗成人短肠综合症，之后扩大适应症用于1岁及以上的短肠综合征患儿，于2022年6月23日在我国申请上市。Teduglutide 与天然GLP-2的不同之处在于N末端的第二个位置的丙氨酸被甘氨酸取代。这阻止了蛋白水解酶二肽基肽酶IV（DDP-IV）的对GLP-2及其类似物的水解作用，从而延长其半衰期。天然GLP-2的半衰期只有7分钟，Teduglutide半衰期约为3-5小时。半衰期延长可以有效增强GLP-2对神经元的作用效果，从而发挥更好的治疗作用。对于短肠综合症患者而言，Teduglutide能够帮助肠上皮细胞增长，同时增加对营养物质的吸收。作为第一代药物，Teduglutide独自享有整个蛋糕。在2022年，它的销售额为7.5亿美元。之后，关于GLP-2药物的研究开始增加，首先研究的方向是提高患者依从性，不少企业纷纷布局，Zealand、派金生物、VectivBio等公司均开展了临床试验。其中率先脱颖而出的正是VectivBio公司的Apraglutide。Apraglutide取代了天然GLP-2的四个氨基酸，使得其对DPP-IV抗性提高，与血浆蛋白的结合率降低，半衰期达到了30个小时，是Teduglutide十倍，这让它有了极大的优势。简单来说，Teduglutide需要每天注射给药，而Apraglutide只需每周注射给药一次就可以达到疗效，对于需要长效用药的患者无疑是个好消息。明显的差异让人们预计Apraglutide将取代Teduglutide的市场地位，销售峰值达到10亿美元以上。现在，回看文章开篇Ironwood的这笔交易，确实是目的明确。公司聚焦于胃肠道疾病，如果有了Apraglutide这员猛将，可以说是如虎添翼。在短肠综合症治疗方向上，Ironwood已经近水楼台，但其他公司也不会就这样将蛋糕拱手相让。GLP-2的广阔前景我们尚不能一探究竟，但可以预见的是，GLP-2狂想曲才刚刚开始演奏。文／徐林卓【企业推荐】智药研习社近期课程报名来源：氨基观察声明：本文仅代表作者观点，并不代表制药在线立场。本网站内容仅出于传递更多信息之目的。如需转载，请务必注明文章来源和作者。投稿邮箱：Kelly.Xiao@imsinoexpo.com▼更多制药资讯，请关注CPHI制药在线▼点击阅读原文，进入智药研习社~