Sirolimus

外周血管疾病（PVD）主要分为外周动脉疾病、外周静脉疾病以及淋巴管疾病。仅以外周动脉疾病（PAD）的患者人数来看，弗若斯特沙利文就曾预测中国PAD患者数量将从2021年的0.52亿人增长至2030年的0.62亿人；手术量也将从2021年约16.3万台增长至2030年约60.2万台，复合年增长率约为15.6%。 外周介入市场比起冠脉介入来说有着更为庞大的患者基数，增长动力强劲。同时外周介入术式多样，专用治疗器械的种类也更加丰富，市场空间同样广阔。据IQVIA研究数据，2022年中国外周介入市场已经达到120亿人民币，未来5年预计仍将以15%的复合增长率持续增长。 从市场参与者来看，虽然跨国企业在外周介入领域拥有丰富的产品线基础，但近年来中国本土血管介入医疗器械选手也凭借政策扶持、创新环境和资本市场优势迅速崛起，已成为外周介入市场中的有力竞争者。 上海畅德医疗科技有限公司（以下简称：畅德医疗）成立于2021年11月，公司致力于在外周介入器械领域高效打造一整套完整的解决方案，在下肢动脉狭窄介入治疗、血栓管理、静脉疾病介入治疗及慢性疾病管理等治疗领域持续发力。 上市公司前总裁领衔， 布局十余款产品并迎来收获期  作为一家初创企业，畅德医疗自成立以来先后启动了用于外周动脉狭窄与血栓、静脉曲张与血栓以及其他周围血管疾病治疗的球囊、支架、血栓抽吸设备、导管等十余个项目的研发和注册。 截至2024年上半年，公司已收获其中四款产品的注册证，并有三款外周介入产品已完成上市前临床试验并将于近期陆续递交NMPA注册申请。 畅德医疗董事长兼总经理苗铮华对此表示：“公司能取得现在的成果主要基于三个方面的优势。首先，虽然畅德医疗是一家初创企业，但公司在团队配置上已经比较成熟和完善，包括我在内的团队核心成员均在血管介入领域拥有深厚的技术沉淀、经验积累以及敏锐的市场洞察。” “第二是我们在规划产品管线之前，对市场规模、未来增量以及竞争对手的集中度等要素都做了深入调研，利用对行业的深刻认知寻找突破口，聚焦于渗透率不足且发展迅速的血管及相关领域；第三，除了丰富的介入器具研发经验外，畅德团队还拥有成熟的临床注册和商业化经验，能够合力带动项目高效、稳定地推进。” 据悉，苗铮华作为行业老匠，在血管介入领域拥有超20年从业经验，创办畅德医疗之前，苗铮华还曾任心血管介入领域上市公司总裁一职，并成功带领这家企业成为首批登陆科创板的25家企业之一。 凭借创始团队在血管介入领域的经验积累与行业洞察，畅德医疗实现了从外周动脉到外周静脉疾病，从疾病治疗到慢病管理，从me too、me better到me only的多元化产品布局。 2024年2月，畅德医疗自主研发的Pearl-Flow®间歇脉冲加压理疗仪正式获批上市。自体动静脉瘘被称为透析患者的生命线，是血液透析患者首选的血管通路类型。在临床实践中，自体动静脉瘘在术后一般需等待1-3个月才能成熟，且有较高的成熟失败率，可能会严重影响患者透析的质量。因此，一款可以缩短内瘘成熟时间的有效方法，对血透患者而言具有重要的临床意义。 Pearl-Flow®是一款针对自体动静脉内瘘（AVF）的促成熟提供解决方案，通过袖带间歇加压的方式压迫患者肢体，增加治疗区域的血液流速及血流量，从而促进AVF成熟，提高造瘘手术的成功率。 Pearl-Flow®间歇脉冲加压理疗仪 Pearl-Flow®的成功获批一方面为透析患者促进AVF术后成熟，提供了一款更为高效、安全、舒适的解决方案；另一方面也凸显了畅德医疗打造完整解决方案的战略布局。 “随着医药集采和DRGs支付制度在中国的不断推进，医疗器械领域已很难再出现像冠脉药物支架一样的‘爆品’，靠一个产品养活一家企业的时代已经结束。畅德医疗希望通过提供完整的产品包、高毛利和低毛利的多产品协同，更好地分摊研发、生产和销售成本，在未来快速实现盈利。”苗铮华介绍道。 在加速成果转化的过程中，畅德医疗也收获了来自资本的青睐，先后完成由君联资本、华杰高景、礼来亚洲基金、晨兴创投投资的天使轮和A轮融资。 两款药物球囊与一款静脉闭合胶完成临床试验，年内启动注册  畅德医疗先后完成EF-Yangtze®药物洗脱膝下球囊扩张导管和EF-Don®药物高压分流球囊扩张导管这两款外周介入新器具的上市前临床，预计将于年内提交注册申请。 血管狭窄是血透患者血管通路最常见的并发症之一，也是导致动静脉内瘘丧失了透析功能的重要原因。内瘘球囊扩张术（PTA）是目前血液透析患者治疗动静脉内瘘狭窄的首选选择。其中药物涂层球囊作为外周动脉介入领域的创新产品，因其独特的药物涂层设计可以有效减少血管再狭窄的风险，提高治疗效果。 在6月8日刚结束的2024新血管大会上，专家对畅德医疗EF-Yangtze®膝下药物球囊的前瞻性、多中心、随机对照研究成果进行分享。本次上市前临床试验由首都医科大学宣武医院郭连瑞教授担任首席研究者，共纳入221名患者，目前正在6个月随访中。会上分享的两个入组病例显示，手术后病变血管均血流通畅，并且EF-Yangtze®膝下药物球囊表面药物分布均匀、紧致，没有发生脱落，输送系统通过性能良好。 EF-Yangtze®药物洗脱膝下球囊扩张导管 这是因为EF-Yangtze®膝下药物球囊采用了无载体重结晶工艺技术。该技术既能增强雷帕霉素在球囊表面的粘附力，确保安全性和有效性，又能在球囊扩张后通过均匀大小的针状结晶体实现药物快速进入血管壁的内膜、中膜及外膜，并在血管壁表面形成一个药物薄层，利于药物在组织中的持续存留。 从差异化优势来看，目前国内仅有一款紫杉醇膝下药物球囊获批，而EF-Yangtze®采用的是雷帕霉素药物。相比紫杉醇，雷帕霉素已被证实是安全且有效的细胞抑制作用药物，并且其抗再狭窄能力和安全系数优于紫杉醇也已在冠脉载药支架得到了充分验证。但雷帕霉素为弱脂溶性药物，在血液中的停留时间和药物有效时间较短。对此，畅德医疗研发团队着力研究药械结合，有效延长其在组织中的停留时间。 同时，畅德医疗也在开发一款采用紫杉醇的药物球囊——EF-Don®药物高压分流球囊扩张导管。EF-Don®的前瞻性、多中心、随机对照研究由上海中医药大学附属龙华医院施娅雪教授和重庆医科大学附属第一医院赵渝教授共同担任首席研究者，旨在评估EF-Don®在治疗血液透析患者自体动静脉瘘透析通路狭窄病变的安全性和有效性。目前，EF-Don®同样在临床随访中。 EF-Don®药物高压分流球囊扩张导管 动静脉内瘘狭窄病变的病理不同于动脉粥样硬化，狭窄段静脉致密的纤维化或穿刺部位的疤痕增生组织，使部分病变难以用普通压力的球囊完全扩张开。EF-Don®提供了一种融合“高压扩张+药物治疗”于一体的解决方案：通过高压有效扩张顽固狭窄病变的同时，利用球囊表面喷涂的紫杉醇药物直接作用于治疗区域的血管壁，从而显著降低再狭窄的发生概率。 除了上述两款药物球囊产品外，畅德医疗自主研发的治疗下肢静脉曲张的EF-Volga™静脉闭合系统目前已递交注册资料。苗铮华对此表示，“目前国内市场上暂无同类静脉胶产品获批，但其技术本身契合静脉曲张手术更微创化的发展趋势，有望成为未来国内主流治疗方式之一。” EF-Volga™静脉闭合系统 “自研+合作”双轮驱动，中国市场与国际市场同步开发  从市场来看，外周介入赛道广而大，从裸支架和裸球囊到药物涂层球囊（DCB）、血管减容器械和药物支架，外周动脉介入领域的产品不断升级换代，为医生和患者提供了更多的治疗选择。为了进一步加快产品线的搭建，为医疗机构提供更多元化的诊疗产品和服务，畅德医疗除了自主研发外，还通过外部合作加速公司发展。 2022年，畅德医疗就与美国Control Medical达成战略合作，共同推进机械血栓抽吸套件进口产品在中国的商业化推广和临床应用。苗铮华对此介绍道，“畅德医疗目前有两款血栓抽吸类产品。一款是与Control Medical合作的Control™血栓清除系统；一款是团队自研的负压吸引泵及抽吸导管系统。这两款产品均将于2024年下半年获批上市。” Control™血栓清除系统 具体而言，Control™血栓清除系统主要适用于外周血管和冠状动脉的血栓清除，并已获美国FDA批准上市，已帮助数千名患者安全有效地清除心脏、腿部、手臂、腹部和脑部血栓。 Control™血栓清除系统利用创新型手动操控血栓抽吸器实现强劲抽吸力，帮助术者更高效可控、灵活便捷地完成血栓抽吸过程。此外，产品具有齐全的规格型号选择，可满足不同场景下的血栓清除需求。 “通过此次国际合作，一方面，团队对行业前沿创新技术和产品有了更多认知，；另一方面，Control Medical的血栓清除系统为无源类产品，而畅德医疗研发的为有源类产品，两者在适应症和目标客户等方面均存在差异，这使得双方产品形成了良好的优势互补，助力畅德医疗打造血管疾病微创伤治疗一体化解决方案。”苗铮华说到。 秉持着开放合作的态度，畅德医疗还积极与外周血管介入器械行业产业链上下游探索融合创新。据透露，目前公司正在与上海高校团队合作加强在部分领域工艺水平的提高与突破，进一步优化产品性能，并维护供应链的稳定。 “针对海外市场，我们也有一款产品已经启动了CE认证工作。未来，畅德医疗将坚持以盈利为目的出海，通过自主研发及与全球合作伙伴的深层协同，深度挖掘未被满足的临床痛点，持续提升产品及服务的可及性和友好性，为患者提供投入-获益的最佳解决方案。”苗铮华表示。 令人印象深刻的是，在2024新血管大会的讨论环节上，多位三甲医院教授纷纷表示，国产器械公司在下肢动脉腔内治疗的技术和理念上已经在迅速追赶国际潮流的路上，看到这些创新型新器具令人振奋。同时，作为临床医生，专家也期待畅德医疗®的产品能够尽快上市，并以强有力的临床数据为支撑，为临床提供更安全、有效的治疗选择。 近 期 推 荐 声明：动脉网所刊载内容之知识产权为动脉网及相关权利人专属所有或持有。未经许可，禁止进行转载、摘编、复制及建立镜像等任何使用。 动脉网，未来医疗服务平台

June 24, 2024 Biodexa Pharmaceuticals PLC Biodexa Announces Positive Phase 2 Clinical Trial Results of eRapa™ at 12 months in Familial Adenomatous Polyposis (FAP) Overall 75% Non-progression Rate at 12 Months Median Decrease in Overall Polyp Burden at 12 Months of 17% Cohort 2 Non-progression Rate at 12 months of 81% and Median Decrease in Poly Burden of 29% Informs Phase 3 Dosage Regimen Data Reported in Oral Presentation at 2024 Bi-Annual InSIGHT Meeting (DATELINE) JUNE 24 -- Biodexa Pharmaceuticals PLC (“Biodexa” or the “Company”) (Nasdaq: BDRX), an acquisition-focused clinical stage biopharmaceutical company developing a pipeline of innovative products for the treatment of diseases with unmet medical needs, announced that 12 month results of a Phase 2 clinical trial of eRapa™ in Familial Adenomatous Polyposis (“FAP”) (NCT04230499) were reported in an oral presentation at the prestigious 2024 InSIGHT bi-annual meeting in Barcelona by Carol Burke, M.D., a specialist gastroenterologist at the Cleveland Clinic and a leading authority in FAP, a mostly genetic disease of precancerous polyps for which the only current remedy is surgical removal of the colon and/or rectum. The Phase 2 study was partially supported by $3 million in grant funding from the Cancer Prevention and Research Institute of Texas (CPRIT) under product development awards DP22053 and DP190069. The Phase 3 study of eRapa in FAP is supported by a $17 million grant from CPRIT. Dr. Burke is the Principal Investigator for the both the Phase 2 study and the upcoming Phase 3 registrational study. Stephen Stamp, CEO of Biodexa, said, “The promising Phase 2 results, if confirmed in a registrational Phase 3 study, may delay or potentially obviate the need for resection of the colon and/or rectum in FAP patients. The six-month, and now 12-month, data together with its apparent tolerability suggest longer term use of eRapa may be possible, with the potential to forestall resection and substantially increase the quality of life of patients with this devastating pre-cancerous condition impacting up to 40,000 patients in the U.S. and up to 60,000 in Europe.” Design of the Phase 2 study The open-label study was conducted in seven U.S. centers of excellence in 30 adult patients with median age of 43 years with intact colon (n=6) or post-colectomy and ileo-rectal anastomosis and at least 10 adenomas in the rectal remanent (n=24). Patients were sequentially enrolled into three dosing cohorts of 10 patients each for a 12-month treatment period: 0.5mg every other day (Cohort 1), 0.5mg daily every other week (Cohort 2), and 0.5mg daily (Cohort 3). Upper and lower endoscopic surveillance occurred at baseline and after six months. Although the primary endpoints were safety and tolerability of eRapa and percentage change from baseline in polyp burden at six months, as measured by the aggregate of all polyp diameters, patients continued to receive treatment and monitoring for 12 months (secondary endpoint). Results of the Phase 2 study at 12 months Overall, 21 of 28 (75%) patients were deemed to be non-progressors at 12 months with a median reduction in polyp burden of 17%. In Cohort 2, eight of nine (89)% of patients were deemed non-progressors at 12 months with a median reduction in polyp burden of 29%. Over the course of 12 months, there were four related Grade 3 or higher and one related Serious Adverse Event reported during the trial and 95% compliance rate at 12 months. One patient was removed from the trial due to non-compliance. In summary, eRapa appeared safe and well-tolerated with a median 17% reduction in the total polyp burden at 12 months compared with baseline and an overall 75% non-progression rate. The 89% non-progression rate and 29% median reduction in polyp burden in Cohort 2 is likely to be the preferred dosage regimen for Phase 3. Polyp burden data at six months compared with baseline was presented at the Digestive Disease Weekly scientific conference in Washinton D.C. on May 21, 2024. Planned Phase 3 registrational study of eRapa in FAP The Phase 3 registrational study is planned to be a double-blind placebo-controlled design recruiting approximately 140 high risk patients diagnosed with germline or phenotypic FAP. The primary clinical endpoint is likely to be the first progression free survival event which will include major surgery (or referral thereto), polypectomy for advanced neoplasia, advancement of Spigelman stage, diagnosis of high-grade dysplasia or cancer and death from any cause. A $17 million grant from CPRIT will support this study. About eRapa eRapa is a proprietary oral tablet formulation of rapamycin, also known as sirolimus. Rapamycin is an mTOR (mammalian Target Of Rapamycin) inhibitor. mTOR has been shown to have a significant role in the signalling pathway that regulates cellular metabolism, growth and proliferation and is activated during tumorgenesis1. Rapamycin is approved in the US for organ rejection in renal transplantation as Rapamune®(Pfizer). Through the use of nanotechnology and pH sensitive polymers, eRapa is designed to address the poor bioavailability, variable pharmacokinetics and toxicity generally associated with the currently available forms of rapamycin. eRapa is protected by a number of issued patents which extend through 2035, with other pending applications potentially providing further protection beyond 2035. eRapa in FAP FAP is characterized as a proliferation of polyps in the colon and/or rectum, usually occurring in mid-teens. There is no approved therapeutic option for treating FAP patients, for whom active surveillance and surgical resection of the colon and/or rectum remain the standard of care. If untreated, FAP typically leads to cancer of the colon and/or rectum. There is a significant hereditary component to FAP with a reported incidence of one in 5,000 to 10,000 in the US2 and one in 11,300 to 37,600 in Europe3. eRapa has received Orphan Designation in the US with plans to seek such designation in Europe. Importantly, mTOR has been shown to be over-expressed in FAP polyps – thereby underscoring the rationale for using a potent and safe mTOR inhibitor like eRapa to treat FAP. About the Cancer Prevention and Research Institute of Texas CPRIT was created by the Texas Legislature and approved by a statewide vote in 2007 to lead the Lone Star State’s fight against cancer. In 2019, Texas voters again voted overwhelmingly to continue CPRIT with an additional $3 billion for a total $6 billion investment in cancer research and prevention. To date, CPRIT has awarded over $3 billion in grants to Texas research institutions and organizations through its academic research, prevention and product development research programs. CPRIT has also recruited more than 281 distinguished researchers to Texas, supported the establishment, expansion or relocation of 51 companies to Texas and generated over $7.66 billion in additional public and private investment. CPRIT funding has advanced scientific and clinical knowledge and provided over 8.1 million life-saving cancer prevention and early detection services to Texans in all 254 counties. Learn more at 1. Tian et al., mTOR Signalling in Cancer and mTOR Inhibitors in Solid Tumor Targeting Therapy, Int J Mol Sci. 2019 Feb; 20(3): 755 2. 3. For more information, please contact: Biodexa Pharmaceuticals PLC Stephen Stamp, CEO, CFO Tel: +44 (0)29 20480 180 About Biodexa Pharmaceuticals PLC Biodexa Pharmaceuticals PLC (listed on NASDAQ: BDRX) is a clinical stage biopharmaceutical company developing a pipeline of innovative products for the treatment of diseases with unmet medical needs. The Company’s lead development programs include eRapa, under development for Familial Adenomatous Polyposis and Non-Muscle Invasive Blader Cancer: tolimidone, under development as a for the treatment of type 1 diabetes; and MTX110, which is being studied in aggressive rare/orphan brain cancer indications. eRapa is a proprietary oral tablet formulation of rapamycin, also known as sirolimus. Rapamycin is an mTOR (mammalian Target Of Rapamycin) inhibitor. mTOR has been shown to have a significant role in the signalling pathway that regulates cellular metabolism, growth and proliferation and is activated during tumorgenesis. Tolimidone is an orally delivered, potent and selective inhibitor of Lyn kinase. Lyn is a member of the Src family of protein tyrosine kinases, which is mainly expressed in hematopoietic cells, in neural tissues, liver, and adipose tissue. Tolimidone demonstrates glycemic control via insulin sensitization in animal models of diabetes and has the potential to become a first in class blood glucose modulating agent. MTX110 is a solubilised formulation of the histone deacetylase (HDAC) inhibitor, panobinostat. This proprietary formulation enables delivery of the product via convection-enhanced delivery (CED) at chemotherapeutic doses directly to the site of the tumor, by-passing the blood-brain barrier and potentially avoiding systemic toxicity. Biodexa is supported by three proprietary drug delivery technologies focused on improving the bio-delivery and bio-distribution of medicines. Biodexa’s headquarters and R&D facility is in Cardiff, UK. For more information visit . Forward-Looking Statements Certain statements in this announcement may constitute “forward-looking statements” within the meaning of legislation in the United Kingdom and/or United States. Such statements are made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995 and are based on management’s belief or interpretation. All statements contained in this announcement that do not relate to matters of historical fact should be considered forward-looking statements. In certain cases, forward-looking statements can be identified by the use of words such as “plans”, “expects” or “does not anticipate”, or “believes”, or variations of such words and phrases or statements that certain actions, events or results “may”, “could”, “would”, “might” or “will be taken”, “occur” or “be achieved.” Forward-looking statements and information are subject to various known and unknown risks and uncertainties, many of which are beyond the ability of the Company to control or predict, that may cause their actual results, performance or achievements to be materially different from those expressed or implied thereby, and are developed based on assumptions about such risks, uncertainties and other factors set out herein. Reference should be made to those documents that Biodexa shall time to time or announcements that may be made by Biodexa in accordance with the rules and regulations promulgated by the SEC, which contain and identify other important factors that could cause actual results to differ materially from those contained in any projections or forward-looking statements. These forward-looking statements speak only as of the date of this announcement. All subsequent written and oral forward-looking statements by or concerning Biodexa are expressly qualified in their entirety by the cautionary statements above. Except as may be required under relevant laws in the United States, Biodexa does not undertake any obligation to publicly update or revise any forward-looking statements because of new information, future events or events otherwise arising.