Sofpironium Bromide

Fresh Tracks Therapeutics still holds on to a sliver of hope that it won't have to dissolve, saying it would abandon dissolution plans if an offer of better value is received. Fresh Tracks Therapeutics is dissolving after spending months searching for alternatives, with the company’s board unanimously approving a liquidation plan. To lighten its load and wind down, the Colorado-based biotech is discontinuing all clinical and preclinical development programs and laying off most of its team by early October, according to a Sept. 19 release. In connection with the proposed liquidation—which still needs to be approved by shareholders—the board has let go of Fresh Tracks President and CEO Andrew Sklawer, effective Oct. 2, according to Securities and Exchange Commission documents. The company’s chief financial officer Albert Marchio II will take the top spot while also holding CFO and secretary along with director and chair of the board titles. Over the last few months, Fresh Tracks has searched for potential strategic alternatives including possible mergers, reverse mergers and acquisitions before reaching this conclusion. Over the summer, the autoimmune-focused biotech shut down R&D work to search for a potential buyer to overcome its limited resources.   Fresh Tracks also recently sold its rights to $168 million in biobucks back to Botanix Pharmaceuticals for anticholinergic drug sofpironium bromide in return for just $6.6 million upfront. Botanix had already bought the overall rights to the drug, which was in late-stage development for excessive underarm sweating, the previous year. With sofpironium bromide sold off, Fresh Track’s most advanced asset is FRTX-02, the first oral DYRK1A inhibitor to enter the clinic for an autoimmune condition. This spring, the biotech touted phase 1 results showing that the therapy is a “generally safe and well-tolerated, once-daily oral treatment for a broad range of autoimmune and inflammatory diseases.” However, all of Fresh Tracks’ efforts have come up short. The company now plans on holding a special shareholder meeting in the fourth quarter of this year to ask for approval of the liquidation and dissolution. Upon approval and the filing of the certificate of dissolution, Fresh Tracks plans to make liquidating distributions to shareholders in an aggregate amount between $5 million and $7 million, or 84 cents and $1.17 per share—figures that exclude money the company intends to save. Those estimates are based on 5,926,497 shares of outstanding common stock existing as of Sept. 19. However, the biotech added that the amount actually distributed to shareholders could “vary substantially” based on a number of factors. Before market close, the company’s stock stood at 58 cents per share. The liquidation, which was announced right after market close Sept. 19, sent the stock up to 91 cents as of 5 p.m. ET. With all that said, Fresh Tracks is still hanging on to a sliver of hope it can keep operating. If, before the dissolution is finalized, the biotech receives an offer that would provide superior value to shareholders, the liquidation and dissolution could be abandoned, the company said.

▎药明康德内容团队编辑根据PDUFA的预期目标日期，预计9月，美国FDA将对6款创新药物或疫苗的批准做出监管决定，本文将对这些疗法或疫苗进行相关介绍。▲9月有望在美国获批的新药（药明康德内容团队制图，点击可见大图）药物名称：Nedosiran适应症：原发性高草酸尿症（PH）公司名称：诺和诺德（Nova Nordisk）旗下Dicerna Pharmaceuticals原发性高草酸尿症（PH）是一种超罕见、危及生命的遗传病，根据基因突变分为三种已知亚型PH1、PH2和PH3。这些基因突变引起的代谢酶缺乏，导致草酸盐的过度产生。草酸盐的过量积累会引起复发性肾结石、肾钙质沉着症和慢性肾病，可能进展为需要透析的终末期肾病。Nedosiran是一款RNAi疗法，通过与表达肝乳酸脱氢酶（LDH）的mRNA结合，抑制该蛋白表达，这是导致草酸盐过度生成的关键代谢酶。在一项2期临床试验中，nedosiran达到主要终点，在PH1亚型患者中，与安慰剂相比，nedosiran组患者的尿液中草酸盐排泄较基线显示出统计学显著性的降低（p<0.0001）。试验也达到其关键次要终点，与安慰剂相比，在第90天后的两次或两次以上连续随访时，nedosiran组患者达到并维持正常、或接近正常草酸盐排泄（Uox）的比例显著更高（50%比0%，p=0.0025）。在接受nedosiran治疗的患者中，73%在试验期间至少发生1次达到正常化或接近正常化。药物名称：Motixafortide适应症：用于多发性骨髓瘤（MM）患者自体移植的干细胞动员（SCM）公司名称：BioLineRx多发性骨髓瘤是第二常见的血液系统恶性肿瘤，自体干细胞移植是标准治疗模式的一部分，可延长该癌症患者的生存期。尽管有可用的治疗方法，许多患者仍然无法收集充足数量的血液干细胞进行移植。Motixafortide是一款创新CXCR4抑制剂。GENESIS临床3期试验的关键结果显示，该药物达到所有主要和次要终点，支持在G-CSF的基础上加用motixafortide，以作为多发性骨髓瘤患者在移植时促进SCM的潜在新标准治疗。在试验中，在G-CSF的基础上加用motixafortide使大多数患者能够在单次给药中实现采集≥600万个造血干细胞的目标。该药物与G-CSF组合通常显示良好的耐受性以及安全性特征。药物名称：Zilucoplan适应症：全身性重症肌无力（gMG）公司名称：优时比（UCB）gMG是一种罕见的慢性自身免疫性疾病。患者自身的致病性免疫球蛋白G（IgG）抗体会破坏神经和肌肉之间的突触传递，引起虚弱和可能危及生命的肌无力。Zilucoplan以高亲和力和特异性、靶向与末端补体激活途径的组分C5结合，这可防止C5被C5转化酶裂解为补体成分C5a和C5b，进而阻止膜攻击复合物（MAC）的下游组装和活性。此外，zilucoplan与对应于C5b的C5结构域结合，从而阻断C5b与补体成分C6的结合。Zilucoplan通过抑制末端补体途径激活和MAC下游组装的双重作用机制，防止其破坏离子通道传导和神经肌肉信号传递。关键性3期RAISE试验共入组174例患者，以1：1的比例随机接受zilucoplan或安慰剂每日皮下给药，治疗持续12周。试验达到其主要终点，使用zilucoplan治疗可在关键的gMG特异性的结果方面产生具有临床意义和统计学意义的改善——在第12周时，zilucoplan组患者的安慰剂矫正的重症肌无力-日常生活活动能力量表（MG-ADL）总分平均改善了2.09分（p＜0.001）。此外，zilucoplan的安全性和耐受性良好，两组治疗后出现的治疗伴发不良反应发生率相似——zilucoplan为76.7%，安慰剂为70.5%。药物名称：Momelotinib适应症：骨髓纤维化公司名称：GSKMomelotinib具有独特的作用机制，可抑制三条关键信号通路：激活素A受体I型（ACVR1）、JAK1和JAK2。骨髓纤维化是一种由JAK-STAT信号异常导致的罕见血液肿瘤，其症状特征包括脾脏肿大、进行性贫血和其它全身性症状。在治疗骨髓纤维化患者的一项关键性3期临床试验中，momelotinib达到所有主要和关键次要终点。治疗24周时，momelotinib组达到总体症状评分（TSS）较基线改善超过50%的患者比例为25%，对照组这一数值为9%。24周时不依赖输血的患者比例：momelotinib组为31%，对照组为20%；脾脏体积减少超过35%的患者比例：momelotinib组为23%，对照组为3%。这表明momelotinib在缓解症状、脾脏应答和控制贫血方面较对照组具有统计学显著性的改善，且这一改善具有临床价值。Sierra Oncology于去年6月向美国FDA递交momelotinib治疗骨髓纤维化的新药申请（NDA）。在去年7月，GSK宣布完成对Sierra Oncology公司的收购。获得这款在研疗法的开发权益。药物名称：Sofpironium bromide适应症：原发性腋窝多汗症公司名称：Botanix PharmaceuticalsSofpironium bromide是一种抗胆碱能/抗毒蕈碱药物，通过与受体结合阻断出汗信号，从而抑制腺体出汗。该疗法设计为使用专有涂抹器将Sofpironium bromide以凝胶制剂的形式递送至腋下，使患者避免直接接触手上的药物。在3期试验当中，约85%患者在使用15% Sofpironium Bromide凝胶后病情出现具临床意义的改善。在2021年末所公布的两项Sofpironium bromide临床3期试验的积极结果显示，该药物达成所有主要和次要终点。这两项3期研究共超过700例患者入组，并有约300例患者参加一项为期48周的药物安全性研究。在所有研究中均未发生治疗相关严重不良事件，不良事件为一过性，性质为轻度至中度。药物名称：Pombiliti（cipaglucosidase alfa）适应症：庞贝病公司名称：Amicus Therapeutics庞贝病是一种由酸性α-葡萄糖苷酶（GAA）缺乏所引起的遗传性溶酶体贮积症。GAA水平的降低或缺失导致糖原在肌肉及其他组织的溶酶体中堆积，继而引发了庞贝病相关的病症（如肌无力和呼吸功能不全），甚至造成患者死亡。Pombiliti是一种独特的人源重组酸性α-葡萄糖苷酶，其化学结构经过优化后可加强细胞对药物的吸收。今年3月，欧盟委员会批准Pombiliti上市，作为长效酶替代（ERT）疗法，与miglustat联用，治疗晚发型庞贝病成人患者。Miglustat是一种口服酶稳定剂，旨在增强Pombiliti的活性。今年8月，英国监管机构亦批准该疗法上市。Pombiliti的批准是基于关键性3期临床试验PROPEL的临床数据，试验结果显示，与标准治疗方式alglucosidase alfa相比，这一组合在治疗晚发型庞贝病患者（包括已经接受过酶替代疗法但治疗需求尚未得到满足的患者）方面获得了具有临床意义的改善效果。大家都在看▲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] Motixafortide (BL-8040) in HSC mobilization. Retrieved August 31, 2023 from https://biolinerx.com/motixafortide-in-hsc-mobilization/[2] UCB announces U.S. FDA acceptance of new drug application and EMA MAA validation for zilucoplan for the treatment of generalized myasthenia gravis in adult patients. Retrieved August 31, 2023, from https://www.ucb.com/stories-media/Press-Releases/article/UCB-announces-US-FDA-acceptance-of-new-drug-application-and-EMA-MAA-validation-for-zilucoplan-for-the-treatment-of-generalized-myasthenia-gravis-in-adult-patients[3] Novel treatment for Primary Axillary Hyperhidrosis. Retrieved August 31, 2023 from https://botanixpharma.com/sofpironium-bromide/[4] Amicus Therapeutics Announces European Commission Approval for Pombiliti™ in Patients with Late-Onset Pompe Disease. Retrieved August 31, 2023, from https://ir.amicusrx.com/news-releases/news-release-details/amicus-therapeutics-announces-european-commission-approval-1[5] Dicerna Presents PHYOX™2 and Primary Hyperoxaluria Healthcare Utilization Data at American Society of Nephrology (ASN) Kidney Week 2021. Retrieved August 31, 2023 from https://www.businesswire.com/news/home/20211104006090/en[6] GSK Reaches Agreement to Acquire Late-Stage Biopharmaceutical Company Sierra Oncology For $1.9bn. Retrieved August 31, 2023 from https://www.businesswire.com/news/home/20220411006012/en[7] Hodgson, J. Drug pipeline 1Q23 — Everything everywhere all over the place. Nat Biotechnol 41, 591–593 (2023). https://doi.org/10.1038/s41587-023-01775-y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