Aspa Therapeutics, Inc.

声明：因水平有限，错误不可避免，或有些信息非最及时，欢迎留言指出。本文仅作医疗健康相关药物介绍，非治疗方案推荐（若涉及）;本文不构成任何投资建议。 2024年9月10日，专注于遗传性疾病的BridgeBio Pharma宣布了公司在研的AAV5基因疗法BBP-631用于治疗先天性肾上腺皮质增生症（CAH）的1/2期开放标签ADventure研究的初步结果。鉴于试验结果未达到目前需要追加资本投资的门槛，公司表示将不会继续推进该试验，此外将继续监测于2021年开始的这项研究中的八名入组患者，目前没有与治疗相关的严重不良事件报告。 这项1/2期开放标签ADventure研究旨在评估BBP-631在典型CAH成人患者中的安全性、耐受性和药效学活性。迄今为止，该研究的主要结果包括： 所有患者在服用较大剂量时，内源性皮质醇分泌均有所增加。在两个最高剂量水平的ACTH刺激试验后，与基线相比的最大变化分别为4.7 μg/dL 和 6.6 μg/dL，皮质醇水平高达11μg/dL。 11-脱氧皮质醇（21-羟化酶的产物）的大量持久增加和17-羟孕酮（17-OHP）（21-羟化酶的底物）的减少为BBP-631转基因的持久活性提供了令人信服的证据：在最高剂量水平，持续的11-脱氧皮质醇与基线相比平均增加了55倍，与基线相比最大增加了99倍。这意味着平均最大值是正常值上限的23倍。17-羟孕酮大幅降低，大多数患者的降幅≥50%，最大降幅达95%。 BBP-631 的耐受性良好，仅有轻度至中度的治疗突发不良事件 (TEAE)，未报告与治疗相关的 SAE。 BridgeBio首席执行官兼创始人Neil Kumar博士说：“虽然迄今为止的数据还不能说明问题，但这项研究首次表明，CAH 患者确实可以自己制造皮质醇，而且基因疗法可以在这一患者群体中安全应用。我们将继续致力于为 CAH 群体寻找合适的合作伙伴，并对预筛选研究和 ADventure 研究的参与者和表示有兴趣的人表示感谢。我们还要感谢ADventure研究的调查人员和工作人员、CAH患者权益组织以及更广泛的CAH社区。" BridgeBio首席财务官、特许金融分析师、博士Brian Stephenson表示："鉴于试验结果未达到目前需要追加资本投资的门槛，BridgeBio将按照我们的资本分配原则，削减基因疗法预算超过5000万美元，并将基因疗法保留给我们无法以其他方式治疗的优先靶点。我们相信基因疗法有可能满足尚未得到满足的巨大需求，我们渴望与 FDA 和卡纳文社区密切合作，目标是尽快将我们的疗法带给卡纳文病患者家庭。” BridgeBio将不再致力于开发BBP-631用于治疗CAH ，但公司仍在积极寻求合作机会，以支持 BBP-631或用于治疗CAH 的下一代基因疗法的未来开发。该公司2个产品已处于商业化阶段，目前有8条研发管线，包括Acoramidis在内的3个候选产品处于3期临床试验阶段。 BridgeBio公司目前的主要工作是为其转甲状腺素蛋白淀粉样变性心肌病（ATTR-CM）药物acoramidis可能获得批准做准备，美国FDA将于11月29日对该药物做出决定。Acoramidis是一种口服、强效、高选择性小分子转甲状腺素蛋白（TTR）稳定剂，用于治疗ATTR-CM。BridgeBio已授予拜耳（Bayer）公司在欧洲商业化acoramidis用于治疗ATTR-CM的独家权利。 Acoramidis作用机制（图片来源：公司官网） 公司管线中还有一款用于治疗卡纳万病的在研静脉注射（IV）AAV9基因疗法BBP-812。2024年9月10日，BridgeBio Pharma宣布美国FDA已授予BBP-812再生医学高级疗法（RMAT）称号，RMAT指定是在美国FDA对研究BBP-812的CANaspire 1/2期临床试验的临床数据进行审查后授予的，BBP-812是一种潜在的疗法，可满足卡纳万病患者尚未得到满足的医疗需求。 据联邦试验数据库显示，BridgeBio的子公司Aspa Therapeutics正在一项1/2期开放标签研究中测试这种代号为BBP-812的疗法，该研究将于2026年10月结束。 图片来源：https://clinicaltrials.gov 此外，BridgeBio正与National Resilience合作，生产候选药物及其管线中的其他基因疗法。BridgeBio公司也表示目前正在 “积极寻求合作机会”，以开发基因疗法或治疗遗传病的潜在后续候选药物。该公司称，CAH影响着美国和欧盟约75,000人。 参考资料：公司公告

BridgeBio said Tuesday night it won’t move forward with a gene therapy for a group of genetic disorders that impair adrenal glands and cause disruptions in producing cortisol. The California biotech made the decision because Phase 1/2 data were “not yet transformational,” CEO Neil Kumar said in a company-issued statement. BridgeBio’s subsidiary Adrenas Therapeutics was testing the AAV5 gene therapy, dubbed BBP-631, in adults with classic congenital adrenal hyperplasia, or CAH. With the move, BridgeBio will lower its gene therapy budget by $50 million, dealing another blow to the field, which has struggled with high-profile negative readouts , a major dip in investor interest , and falling interest from some pharma giants. BridgeBio was working with biomanufacturer National Resilience to produce the candidate and other gene therapies in its pipeline. BridgeBio is now “actively seeking partnership opportunities” for the gene therapy or potential follow-up candidates for the genetic disease, it said Tuesday. The company said CAH impacts about 75,000 people in the US and EU. A BridgeBio spokesperson didn’t immediately respond to an Endpoints News inquiry about whether the moves will impact the company or its subsidiary’s workforce. The drugmaker said trial investigators will continue monitoring the eight patients who enrolled in the study, which began in 2021. There were no reports of treatment-related serious adverse events, BridgeBio said. Much of BridgeBio’s focus currently is on preparing for a potential approval of its ATTR-CM drug acoramidis, which is up for an FDA decision date of Nov. 29. In recent months, the company has offloaded certain chunks of its pipeline to an oncology-focused spinout and rare disease assets to another new venture, called GondolaBio . “The Adrenas Therapeutics team acknowledges that this is disappointing news,” the subsidiary wrote in a Sept. 10 post on its website. “We are assured that our combined efforts during the past six years have contributed to improved understanding and greater hope for what is possible for people living with CAH.” The gene therapy delivered a functional copy of the 21-hydroxylase gene through a one-time IV infusion. The company said it hoped the treatment would help CAH patients produce their own cortisol and aldosterone so that they no longer needed daily glucocorticoid and mineralocorticoid doses, or at least limit the number of doses needed. Going forward, BridgeBio is “reserving gene therapy for priority targets that we cannot treat any other way,” according to a statement from CFO Brian Stephenson. That means focusing on a different gene therapy for a rare inherited disorder known as Canavan disease, which leads to progressive destruction of nerve cells and neurodevelopmental delays. Stephenson said the company is “eager to work closely with the FDA and the Canavan community” on getting the treatment to patients. BridgeBio’s subsidiary Aspa Therapeutics is testing the therapy, codenamed BBP-812, in a Phase 1/2 open-label study slated to wrap up in October 2026, according to a federal trials database.

- Following treatment, the N-acetylaspartate (NAA) levels of CANaspire participants are consistent with levels seen in individuals with milder Canavan disease based on findings from the Company’s natural history study and reports in the scientific literature - Sustained reductions in NAA were measured in the urine, cerebrospinal fluid (CSF), and brain of all participants and have been observed for over a year in the earliest dosed participants - After dosing, brain magnetic resonance imaging (MRI) of participants demonstrated robust improvements in the formation of myelin, or white matter, which is essential for brain development - Positive changes in sitting ability and head control have also been observed using multiple assessments including the Gross Motor Function Measure-88 (GMFM-88), a standardized clinical outcome measure used by physical therapists to assess movement function in children - If successful, BridgeBio’s gene therapy for Canavan disease could be the first therapeutic option for children born with this devastating and fatal neurodevelopmental disorder PALO ALTO, Calif., May 22, 2023 (GLOBE NEWSWIRE) -- BridgeBio Pharma, Inc. (Nasdaq: BBIO) (“BridgeBio” or the “Company”), a commercial-stage biopharmaceutical company focused on genetic diseases and cancers, presented promising positive data from six participants dosed in CANaspire, its Phase 1/2 clinical trial of BBP-812, an investigational intravenous (IV) adeno-associated virus serotype 9 (AAV9) gene therapy for the treatment of Canavan disease. “Canavan disease is a rapidly progressive, rare neurological disease that affects children from birth and has no treatment options beyond supportive care. The changes in key biomarkers, brain myelination and – critically – clinical function observed in children receiving BBP-812 in our study are compelling, and as we continue to advance our program we are hopeful that we will see outcomes that make a meaningful difference in the lives of children with Canavan disease and their families,” said Genevieve Laforet, M.D., Ph.D., vice president of clinical development at Aspa Therapeutics, the BridgeBio affiliate that is developing BBP-812 for Canavan disease. “We are beyond grateful to the children and their families who are participating in CANaspire as well as the study investigators, who together are making it possible to explore the potential of BBP-812 as a therapy for Canavan disease. We intend to work with the FDA to move our program forward as rapidly as possible, including exploring available expedited programs such as accelerated approval.” As of March 23, 2023, findings from the trial include: All participants showed a rapid and lasting decrease in levels of NAA, a key chemical marker elevated in children with Canavan disease, after dosing with BBP-812 The duration of individual participant follow-up ranged from 1 to 15 months post-treatment The most recent data continue to show reductions in NAA in all participants and all compartments tested. Across individual participants, percent decreases in NAA from baseline ranged between 70% and 95% in cerebrospinal fluid (CSF), 29% and 88% in urine, and 8% and 75% in brain (by magnetic resonance spectroscopy) All participants in the CANaspire trial had urine NAA levels consistent with typical Canavan disease prior to receiving BBP-812. After receiving BBP-812, urine NAA levels in all participants fell to what can be considered less severe Canavan disease as reported in the scientific literature and observed in the Company’s natural history study MRI scans indicated the presence of improved myelination, which is essential for brain development, in the brainstem and cerebellum of all participants These findings have been noted as early as 3 months after BBP-812 administration and were present at post-dosing Month 12 in the participant who has been followed the longest in the trial In contrast to the natural history of typical Canavan patients in which already-limited functional abilities are lost over time, no trial participants have lost function and there have been incremental improvements in achievement of developmental milestones Improvement in the GMFM-88 sitting dimension (measuring upright head control and sitting ability) has been shown to varying degrees in all participants who have been evaluated post-treatment, including one participant who has developed the ability to walk with a mobility aid and has a score on the GMFM-88 sitting dimension consistent with that of unaffected children BBP-812 has been shown to be generally well-tolerated to date, with a safety pro with other systemically administered AAV9 gene therapies The Data and Safety Monitoring Committee (DSMC), an independent panel of expert physicians and clinical trial experts, has conducted a thorough evaluation of the CANaspire trial safety data and have endorsed the Company’s plan for advancement to the next dosing level Florian Eichler, M.D., director of the leukodystrophy service at Massachusetts General Hospital, Center for Rare Neurological Disease and principal investigator of the CANaspire gene therapy clinical trial for Canavan disease, reflects on the progress of the trial: "The reduction in NAA to levels consistent with less severe Canavan disease, MRIs indicating potential improvement of myelin in the brainstem, and the measurable functional gains observed among participants, together are unlike any findings I have seen in children with Canavan disease." About CANaspire CANaspire is a Phase 1/2 open-label study designed to evaluate the safety, tolerability, and pharmacodynamic activity of BridgeBio’s AAV9 gene therapy candidate, BBP-812, in pediatric patients with Canavan disease. Each eligible patient will receive a single intravenous (IV) infusion of BBP-812. The primary outcomes of the study are safety, as well as change from baseline of urine and central nervous system N-acetylaspartate (NAA) levels. Motor function and development will also be assessed. For more information about the CANaspire trial, visit TreatCanavan.com or ClinicalTrials.gov (NCT04998396). About BBP-812 BBP-812 is an investigational AAV9 gene therapy for Canavan disease. Using AAV gene therapy, BridgeBio seeks to deliver functional copies of the ASPA gene throughout the body and into the brain, potentially correcting the disease at its source. Preclinical proof-of-concept results have shown the approach restores survival and normal motor function in Canavan disease models. BBP-812 was granted Fast Track Designation, Rare Pediatric Drug Designation, and Orphan Drug Designation by the U.S. Food and Drug Administration. BBP-812 was also granted Orphan Drug Designation by the European Medicines Agency. About Canavan Disease Affecting approximately 1,000 children in the United States and European Union, Canavan disease is an ultra-rare, disabling and fatal disease with no approved therapy. Most children are not able to meet developmental milestones, are unable to crawl, walk, sit or talk, and die at a young age. The disease is caused by an inherited mutation of the ASPA gene that codes for aspartoacylase, a protein that breaks down a compound called N-acetylaspartate (NAA). Deficiency of aspartoacylase activity results in accumulation of NAA, and ultimately results in toxicity to myelin in ways that are not currently well understood. Myelin insulates neuronal axons, and without it, neurons are unable to send and receive messages as they should. The current standard of care for Canavan disease is limited to supportive therapy. About BridgeBio Pharma, Inc. BridgeBio Pharma Inc. (BridgeBio) is a commercial-stage biopharmaceutical company founded to discover, create, test and deliver transformative medicines to treat patients who suffer from genetic diseases and cancers with clear genetic drivers. BridgeBio’s pipeline of development programs ranges from early science to advanced clinical trials. BridgeBio was founded in 2015 and its team of experienced drug discoverers, developers, and innovators are committed to applying advances in genetic medicine to help patients as quickly as possible. For more information visit bridgebio.com and follow us on LinkedIn and Twitter. BridgeBio Pharma, Inc. Forward-Looking Statements This press release contains forward-looking statements. Statements BridgeBio makes in this press release may include statements that are not historical facts and are considered forward-looking within the meaning of Section 27A of the Securities Act of 1933, as amended (the “Securities Act”), and Section 21E of the Securities Exchange Act of 1934, as amended (the “Exchange Act”), which are usually identified by the use of words such as “anticipates,” “believes,” “estimates,” “expects,” “intends,” “may,” “plans,” “projects,” “seeks,” “should,” “will,” and variations of such words or similar expressions. BridgeBio intends these forward-looking statements to be covered by the safe harbor provisions for forward-looking statements contained in Section 27A of the Securities Act and Section 21E of the Exchange Act. These forward-looking statements, including statements relating to the expectations, plans, prospects and potential benefits of BBP-812 for the treatment of Canavan disease gene therapy program, the ability of BBP-812 to be the first therapeutic treatment option for children born with Canavan disease, the safety and efficacy pro the investigational gene therapy, the intention of BridgeBio to work with the FDA to move its program forward as rapidly as possible, including exploring accelerated approval and other expedited review pathways, and the statement in Dr. Florian Eichler’s quote regarding the potential and benefits of the gene therapy program, reflect our current views about our plans, intentions, expectations, strategies and prospects, which are based on the information currently available to us and on assumptions we have made. Although we believe that our plans, intentions, expectations and strategies as reflected in or suggested by those forward-looking statements are reasonable, we can give no assurance that the plans, intentions, expectations or strategies will be attained or achieved. Furthermore, actual results may differ materially from those described in the forward-looking statements and will be affected by a number of risks, uncertainties and assumptions, including, but not limited to, BridgeBio’s ability to advance BBP-812 in clinical development according to its plans, the ability of BBP-812 to treat Canavan disease, the ability of BBP-812 to retain Fast Track Designation, Rare Pediatric Drug Designation, and Orphan Drug Designation from the U.S. Food and Drug Administration and Orphan Drug Designation from the European Medicines Agency, initial and ongoing data from our preclinical studies and clinical trials not being indicative of final data, the potential size of the target patient populations our product candidates are designed to treat not being as large as anticipated, the design and success of ongoing and planned clinical trials, future regulatory filings, approvals and/or sales, despite having ongoing and future interactions with the FDA or other regulatory agencies to discuss potential paths to registration for our product candidates, the FDA or such other regulatory agencies not agreeing with our regulatory approval strategies, components of our filings, such as clinical trial designs, conduct and methodologies, or the sufficiency of data submitted, uncertainty regarding any impacts due to COVID-19, such as delays in regulatory review, manufacturing and supply chain interruptions, adverse effects on healthcare systems and disruption of the global economy, the impacts of current macroeconomic and geopolitical events, including changing conditions from hostilities in Ukraine, increasing rates of inflation and rising interest rates, on business operations and expectations, as well as those risks set forth in the Risk Factors section of our Annual Report on Form 10-K for the year ended December 31, 2022 and our other filings with the U.S. Securities and Exchange Commission. Moreover, we operate in a very competitive and rapidly changing environment in which new risks emerge from time to time. These forward-looking statements are based upon the current expectations and beliefs of our management as of the date of this press release and are subject to certain risks and uncertainties that could cause actual results to differ materially from those described in the forward-looking statements. Except as required by applicable law, we assume no obligation to update publicly any forward-looking statements, whether as a result of new information, future events or otherwise. BridgeBio Media Contact: Vikram Bali contact@bridgebio.com (650)-789-8220