SLC6A19

「  本文共：16条资讯，阅读时长约：3分钟 」今日头条恒瑞MOR靶向镇痛药获批上市。恒瑞医药1类新药富马酸泰吉利定注射液（SHR8554）获国家药监局批准上市，适用于腹部手术后中重度疼痛。SHR8554可激活μ阿片受体（MOR），选择性地激活G蛋白偶联通路，具有中枢镇痛效果的同时，可减轻胃肠道不良反应和减少呼吸抑制不良反应的发生率。今年1月，CDE已受理该新药提交的“骨科手术后镇痛”新适应症上市申请。国内药讯1.和黄「呋喹替尼」获批香港上市。和黄医药VEGFR抑制剂呋喹替尼（fruquintinib）获香港监管部门批准上市，用于治疗既往接受过氟尿嘧啶类、奥沙利铂和伊立替康为基础的化疗，以及既往接受过或不适合接受抗VEGF治疗、抗EGFR治疗（RAS野生型）的转移性结直肠癌患者。在国际III期试验 (MRCT) FRESCO-2研究中，与安慰剂相比，呋喹替尼治疗组的mOS延长2.6个月，mPFS延长1.9个月。2.科笛引进非那雄胺喷雾剂报产。科笛集团从Polichem公司引进的外用非那雄胺喷雾剂CU-40102的新药上市申请（NDA）获CDE受理，用于治疗雄激素性脱发。与口服非那雄胺不同，CU-40102可直接精确地涂抹在头皮表面，保持用药部位高浓度并减少药物全身暴露。在Ⅲ期临床中，CU-40102治疗组24周时患者的顶部秃发目标区域内的总毛发计数及终毛计数的统计较安慰剂显著改善。3.辉瑞CD3/BCMA双抗中国报产。辉瑞CD3/BCMA双抗Elranatamab（Elrexfio,PF-06863135）的上市申请获CDE受理，用于治疗复发或难治性多发性骨髓瘤（R/R MM）。在II期研究MagnetisMM-3（NCT04649359）研究中，elranatamab在既往至少接受过四种治疗的患者中达到61%的客观缓解率以及56.1%的非常好的部分缓解率。去年8月，该产品已获FDA加速批准上市，成为第二款在美获批的CD3/BCMA双抗。4.驯鹿BCMA靶向CAR-T见刊PNAS。驯鹿生物靶向BCMA的CAR-T产品伊基奥仑赛注射液（CT103A）在研究者发起的一项针对免疫介导坏死性肌病（IMNM）的探索性研究（NCT04561557）中获积极结果。CT103A回输18个月后，患者徒手肌力检查（MMT-8）评分从基线的96分，改善至137分；血清肌酸激酶水平从4778 IU/L降至260 IU/L，肌红蛋白水平从837 ng/mL降至66.2 ng/mL；临床中未发现新的安全性风险。详细结果发表在《美国国家科学院院刊》（PNAS）上。5.荣昌预计2023年营收10.8亿元。荣昌生物发布2023年年度业绩预告，预计2023年度营业收入约108,000万元，较上年同期将增加收入约31,000万元，同比增加约40%;预计实现归属于母公司所有者的净亏损约155,000万元，较上年同期将增加亏损约55,200万元，同比亏损增加约55%；预计归属于母公司所有者扣除非经常性损益后的净亏损约158,000万元，较上年同期将增加亏损约46,400 万元，同比亏损增加约42%。6.中国生物制药南方总部开业运营。1月31日，中国生物制药南方总部在广州国际生物岛正式开业。南方总部目前已引入包括治疗非酒精性脂肪性肝炎的拉尼兰诺、软雾吸入药械平台Softhale和新一代肿瘤免疫疗法等海外临床项目。未来，中国生物制药将通过南方总部和海外子公司invoX，引进全球领先的药品管线，并在广州实现临床转化和产业化。国际药讯1.BMS靶向CD19自体CAR-T报两项sBLA。FDA受理百时美施贵宝CD19靶向CAR-T疗法Breyanzi（Liso-cel）两项补充生物制品许可申请（sBLA），用于治疗复发或难治性滤泡性淋巴瘤（FL）和套细胞淋巴瘤（MCL）经治患者。FDA同时授予它们优先审评资格，PDUFA日期分别为今年5月23日和5月31日。在临床试验中，Breyanzi在复发/难治性FL患者中达到97%（p<0.0001）总缓解率（ORR）；在MCL患者达到86.5%的ORR。2.强生CD38单抗皮下注射制剂报新适应症。强生CD38抗体皮下注射制剂Darzalex Faspro（daratumumab）已向FDA提交补充生物制品许可申请（sBLA），联合硼替佐米、来那度胺和地塞米松（D-VRd）用于适合接受自体干细胞移植（ASCT）的新诊断多发性骨髓瘤成人患者的诱导和巩固治疗，以及之后联合来那度胺（D-R）用于维持治疗。在III期PERSEUS研究中，47.5个月随访数据显示，daratumumab联合方案使疾病进展风险降低58%。3.NaV1.8抑制剂两项止痛Ⅲ期临床积极。Vertex公司选择性NaV1.8抑制剂VX-548用于术后（腹部整形手术和拇囊炎切除手术）中重度急性疼痛治疗的两项Ⅲ期临床均达到主要终点。与安慰剂相比，VX-548组患者48小时内疼痛强度差异的时间加权总和评分（SPID48）显著降低，SPID48的平均差异分别为48.4（P<0.0001）和29.3（P=0.0002）；但与羟考酮/对乙酰氨基酚（HB/APAP）组合相比，VX-548组SPID48的改善没有达到优效标准。VX-548总体耐受性良好。4.新型反义RNA疗法治疗DMD的Ⅱ期临床积极。Sarepta公司多肽磷酰二胺吗啉寡聚体（PPMO）疗法SRP-5051（vesleteplirsen）治疗适于使用外显子51跳跃治疗的杜氏肌营养不良（DMD）患者的国际Ⅱ期临床MOMENTUM（SRP-5051-201研究）结果积极。在28周时，SRP-5051（30mg/kg，每4周一次）可使抗肌萎缩蛋白的平均表达水平达到5.17%（较基线提高4.53%，P<0.0001）；平均外显子跳跃率达到11.11%（较基线提高10.07%）。此外，患者在预防性地接受补充镁治疗后，未发生与治疗相关的停药。5.SLC6A19别构抑制剂PKU早期临床积极。Jnana公司靶向苯丙氨酸（Phe）转运蛋白SLC6A19的潜在“first-in-class”小分子抑制剂JNT-517，在治疗苯丙酮尿症（PKU）患者的Ⅰ期临床获积极结果。与安慰剂相比，JNT-517组第28天患者的平均血液Phe水平显著降低51%（p=0.0019）；患者临床应答率达到88%；药物安全性良好。Jnana计划在今年下半年与监管机构沟通，寻求明年直接将JNT-517推进至关键Ⅲ期临床。6.赛诺菲布局IL-10R激动剂。赛诺菲宣布与Synthekine公司达成合作许可协议，获得后者专有蛋白质工程平台优化的多种IL-10R激动剂的临床前、开发和商业化权益，用于治疗炎症性疾病。工程化蛋白分子可选择性地激活特定细胞上的细胞因子信号传导，从而最大限度地提高疗效并降低毒性。根据协议，Synthekine将获得4000万美元的预付款，临床前、开发、监管和商业里程碑潜在付款，以及产品的分级特许权使用费。7.司美格鲁肽2023年大卖212亿美元。1月31日，诺和诺德发布2023年Q4及全年业绩。2023年总销售额为2322.61亿丹麦克朗（约337.01亿美元），同比增长31%。司美格鲁肽全年总销售额达到约211.58 亿美元：司美格鲁肽注射液Ozempic（2型糖尿病）收入957.18亿丹麦克朗（139.17亿美元，+60%）；司美格鲁肽片剂Rybelsus（2型糖尿病）收入187.50亿丹麦克朗（27.26亿美元，+66%）；司美格鲁肽注射液Wegovy（肥胖）收入313.43亿丹麦克朗（45.57亿美元，+407%）。医药热点1.南京鼓楼医院互联网医院服务再升级。近日，南京鼓楼医院互联网医院线上复诊医保在线支付开通，旨在解决患者因时间、空间无法到线下医院复诊开药的问题，同时医保报销节省看病费用。患者授权医保电子凭证后，即可享受“在线复诊—续方开药、开检查—医保支付—药品配送”的一体化医疗服务，线上复诊的挂号费及后续药费、检查费均可医保线上支付，切实给患者带来便利。2.浙江报告1例H3N2与H10N5混合感染死亡病例。据国家疾控局30日通报，浙江省发现一例H3N2与H10N5混合感染病例。患者，女，63岁，安徽宣城人，既往有多种基础性疾病。2023年11月30日出现咳嗽、咽痛、发热等症状；12月2日因病情加重收入当地医疗机构救治；12月7日，转至浙江省医疗机构住院治疗，后因病情严重于12月16日死亡。专家评估认为，此次疫情为一次偶发的禽到人的跨种属传播。该病毒感染人的风险低，未发生人传人的情况。评审动态  1. CDE新药受理情况（01月31日) 2. FDA新药获批情况（北美01月29日）股市资讯上个交易日 A 股医药板块 -4.66%涨幅前三     跌幅前三欧康医药+2.48%  之江生物-10.54%赛托生物+2.10%  景峰医药-10.12%健友股份+1.96%  海正药业-10.04%[荣丰控股]预计2023年年度实现归居于上市公司股东的净利润亏损2300万元-3700万元，同比增长39.36%-2.46%;扣除非经常性损益后的净利润亏损3186万元-4586万元，同比增长61.77%-44.97%;营业收入1.1亿元-1.2亿元。[片仔癀]预计2024年第一季度，公司可实现归属于上市公司股东的净利润同比增长不低于25%。[华东医药]发布业绩预告，预计2023年年度实现归属于上市公司股东的净利润盈利28.12亿元-28.62亿元，同比增长12.50%-14.50%;归属于上市公司股东的扣除非经常性损益后的净利润盈利27.35亿元-27.84亿元，同比增长13.50%-15.50%。- The End -戳“阅读原文”，了解更多医药研发及股市资讯。

▎药明康德内容团队编辑Jnana Therapeutics公司今天宣布，在研疗法JNT-517在治疗苯丙酮尿症（PKU）患者的1期临床试验中获得具有统计学意义的积极中期结果。JNT-517是一款潜在“first-in-class”小分子抑制剂，针对苯丙氨酸（Phe）转运蛋白SLC6A19。基于这些积极的中期结果，Jnana已调整其1b期临床试验设计，以支持JNT-517在2025年上半年开始关键性3期临床试验。JNT-517正在一项随机双盲、含安慰剂对照的1期临床试验中接受评估，对象为轻度至重度PKU患者。预定的中期分析基于13名参与者的数据，其中8人接受JNT-517治疗，5人接受安慰剂治疗，持续28天，试验结果显示：与安慰剂相比，JNT-517组患者在第28天的平均血液Phe水平降低了51%（p=0.0019），具有统计学意义。观察到高应答率，JNT-517组88%（7/8）参与者血液Phe水平从基线降低>30%；63%（5/8）降低>45%；25%（2/8）降低>65%。不论基线血液Phe水平如何，接受JNT-517治疗的参与者均显示出稳定的应答。JNT-517起效快速，治疗7天后即实现了显著的血液Phe降低，并在整个28天的给药期内持续。JNT-517安全且耐受性良好，没有严重不良事件，也没有临床上显著的实验室参数变化，与1a期健康志愿者研究中展示的安全性特征一致。基于这些中期结果，Jnana已调整正在进行的试验方案。公司预计将在2024年中公布第二剂量队列的顶线数据，并计划在2024年下半年的科学会议上提交两个剂量队列的完整数据。Jnana计划在2024年下半年与监管机构展开讨论，并寻求在2025年上半年直接将JNT-517推进到关键性3期临床研究中。▲JNT-517作用机理（图片来源：Jnana Therapeutics公司官网）PKU由苯丙氨酸羟化酶（PAH）缺乏引起。苯丙氨酸是存在于所有含蛋白质食物中的一种氨基酸，而PAH是分解Phe所必需的酶。当PAH缺乏或功能缺陷时，Phe将在血液中积累至异常高的毒性水平。如果不及时治疗，血液中的Phe可导致进行性和严重的神经功能损伤和神经心理并发症。而SLC6A19是一种转运蛋白，负责肾脏对Phe的重吸收，让Phe重新回到血液中。因此，抑制SLC6A19为治疗PKU提供了一种新的途径。SLC转运蛋白的结构和细胞内位置具有高度多样性，通常难以表达和纯化，不容易使用生物物理方法进行分析，并且可能没有已知的配体。Jnana的化学蛋白质组平台RAPID仅根据小分子结合蛋白的能力来发现候选化合物，它为处理具有挑战性的SLC靶标提供了一种有前景的方法。该公司通过生成SLC6A19与小分子配体复合物的冷冻电镜结构，揭示了Jnana专有的小分子抑制剂结合在SLC转运体上的一个隐秘别构位点。JNT-517通过这一新颖的隐藏别构位点阻断肾脏对Phe的重吸收，提供了一种减少血液Phe水平的新策略。大家都在看药明康德为全球生物医药行业提供一体化、端到端的新药研发和生产服务，服务范围涵盖化学药研发和生产、生物学研究、临床前测试和临床试验研发、细胞及基因疗法研发、测试和生产等领域。如您有相关业务需求，欢迎点击下方图片填写具体信息。▲如您有任何业务需求，请长按扫描上方二维码，或点击文末“阅读原文/Read more”，即可访问业务对接平台，填写业务需求信息▲欲了解更多前沿技术在生物医药产业中的应用，请长按扫描上方二维码，即可访问“药明直播间”，观看相关话题的直播讨论与精彩回放参考资料：[1] Jnana Therapeutics Announces Positive Clinical Proof of Concept Achieved with JNT-517, a Potential First-in-Class Oral Treatment for PKU. Retrieved January 30, 2024, from https://www.jnanatx.com/jnana-therapeutics-announces-positive-clinical-proof-of-concept-achieved-with-jnt-517-a-potential-first-in-class-oral-treatment-for-pku/?pag=1免责声明：药明康德内容团队专注介绍全球生物医药健康研究进展。本文仅作信息交流之目的，文中观点不代表药明康德立场，亦不代表药明康德支持或反对文中观点。本文也不是治疗方案推荐。如需获得治疗方案指导，请前往正规医院就诊。版权说明：本文来自药明康德内容团队，欢迎个人转发至朋友圈，谢绝媒体或机构未经授权以任何形式转载至其他平台。转载授权请在「药明康德」微信公众号回复“转载”，获取转载须知。分享，点赞，在看，聚焦全球生物医药健康创新

Treatment with JNT-517 demonstrated a statistically significant mean blood phenylalanine reduction of 51% versus baseline JNT-517 was safe and well tolerated with no serious adverse events Jnana has adapted the ongoing trial to accelerate the program and aims to advance JNT-517 directly into a pivotal study in early 2025 BOSTON, Jan. 30, 2024 (GLOBE NEWSWIRE) -- Jnana Therapeutics, a clinical-stage biotechnology company leveraging its next-generation chemoproteomics platform to discover medicines for challenging-to-drug targets, today announced positive, statistically significant interim results from its ongoing clinical study of JNT-517 in individuals with phenylketonuria (PKU). JNT-517, a small molecule inhibitor of the phenylalanine (Phe) transporter SLC6A19, is being evaluated as a potential first-in-class oral treatment for PKU across all ages and genotypes. On the basis of these positive interim results, Jnana has adapted the Phase 1b trial design to support the potential for accelerated progression of JNT-517. “There is an urgent need for an oral, safe, and efficacious therapy for the more than 60% of individuals with PKU not currently on therapy. Across the spectrum of mild to severe disease, our results demonstrate a robust, sustained reduction in blood Phe levels, the registrational endpoint for PKU, giving us high confidence in the path forward for JNT-517,” said George Vratsanos, M.D., Chief Medical Officer and Head of R&D at Jnana Therapeutics. “We are also encouraged by this validation of the power of our RAPID platform to discover small molecules with compelling clinical benefit against challenging-to-drug targets.” JNT-517 is being studied in a randomized, double-blind, placebo-controlled trial in individuals with mild to severe PKU. Following a 28-day screening period focused predominantly on ensuring an average blood Phe level of >600µM, study participants were randomized with no run-in period to 75mg of JNT-517 twice daily (BID) or placebo. The planned interim analysis was based on 13 participants, eight dosed with JNT-517 and five dosed with placebo over 28 days, and demonstrated the following results: JNT-517 led to a statistically significant (p=0.0019 vs. placebo) mean blood Phe reduction from baseline of 51%, measured per-protocol at day 28. A high response rate was seen where seven of eight (88%) treated participants achieved >30% reduction in blood Phe from baseline; five of eight (63%) achieved >45% reduction; and two of eight (25%) achieved >65% reduction. A robust response was seen across participants treated with JNT-517 irrespective of baseline blood Phe levels, which ranged from 593µM to 1,526µM with a mean of 1,124µM. A rapid onset of effect was observed with significant blood Phe reduction achieved within seven days after commencing dosing, which was sustained through the full 28 days of dosing. JNT-517 was safe and well tolerated with no serious adverse events and no clinically significant changes in laboratory parameters, consistent with the safety pro in the Phase 1a healthy volunteer study. “JNT-517 represents a completely new therapeutic approach that could transform the current treatment paradigm in PKU, in particular for individuals with severe, or classical, PKU where there is the highest unmet medical need,” said Cary O. Harding, M.D., study investigator and Professor of Molecular and Medical Genetics at Oregon Health and Science University School of Medicine. “I am encouraged by the clinical results to date and look forward to working with Jnana and the PKU community to continue to advance this program.” Based on these interim results, Jnana has adapted the protocol of the ongoing trial to include dose exploration. Jnana expects topline data from the second dose cohort in mid-2024 and plans to submit full data from the two dose cohorts for presentation at a scientific meeting in the second half of 2024. Jnana anticipates the company will engage regulators in the second half of 2024 and seek to advance JNT-517 directly into a pivotal Phase 3 study in the first half of 2025. JNT-517Phase 1b Clinical Trial The ongoing clinical program includes a randomized, double-blind, placebo-controlled trial evaluating the safety, tolerability, pharmacokinetics, and effect on blood and urinary Phe of JNT-517 dosed over a four-week period in individuals diagnosed with PKU. The study dosed its first participant with PKU in August 2023 and is enrolling individuals aged 18 to 65 at clinical sites in the United States and Australia. For more information about the study, please see clinicaltrials.gov (NCT05781399). About JNT-517 JNT-517 is a selective small molecule inhibitor of the Phe transporter SLC6A19 that has the potential to be a first-in-class oral therapy used to treat any person with PKU, regardless of age or genotype. JNT-517 acts at a novel, cryptic allosteric site to block kidney reabsorption of Phe and offers a promising new approach to reduce blood Phe levels. The U.S. Food and Drug Administration granted JNT-517 Rare Pediatric Disease Designation in late 2022. About PKU PKU is a rare inherited metabolic disorder caused by a deficiency of the enzyme phenylalanine hydroxylase (PAH). This enzyme is required for the breakdown of phenylalanine (Phe), an amino acid found in all protein-containing foods. When PAH is deficient or defective, Phe accumulates to abnormally high levels in the blood. If left untreated, toxic levels of Phe in the blood can result in progressive and severe neurological impairment and neuropsychological complications. The SLC transporter SLC6A19 is responsible for kidney reabsorption of Phe back into the bloodstream, and the inhibition of SLC6A19 offers a novel, oral approach for the treatment of PKU by facilitating urinary excretion of excess Phe. About Jnana Therapeutics Jnana Therapeutics is a clinical-stage biotechnology company leveraging its next-generation RAPID chemoproteomics platform to discover medicines for highly validated, challenging-to-drug targets to treat diseases with high unmet needs. Jnana is focused on developing first- and best-in-class therapies to treat a wide range of diseases, including rare diseases and immune-mediated diseases. Jnana’s wholly owned lead program, JNT-517, which targets an allosteric site on the phenylalanine transporter SLC6A19, is a potential first-in-class oral approach for the treatment of PKU, a rare genetic metabolic disease. Located in Boston, Jnana brings together scientific leaders in small molecule drug discovery and development, a highly experienced management team, and the backing of leading life science investors Bain Capital Life Sciences, RA Capital Management, Polaris Partners, Versant Ventures, Avalon Ventures, Pfizer Ventures, and AbbVie Ventures. For more information, please visit and follow us on Twitter/X and LinkedIn. Media Contact Adam Silverstein Scient PR media@jnanatx.com Investor Relations Josh Rappaport Stern IR ir@jnanatx.com