Bilateral Vestibulopathy

FRAMINGHAM, Mass.--(BUSINESS WIRE)-- Variantyx, a leader in genomic precision medicine, today announced that the set of short tandem repeat (STR) expansions detected by its Genomic Unity® line of whole genome-based tests has been expanded. With these additions, Variantyx becomes one of the first laboratories to offer testing for two recently characterized ataxia variants: the biallelic AAGGG expansion in RFC1 that causes cerebellar ataxia, neuropathy, vestibular areflexia syndrome (CANVAS) and the monoallelic, deep intronic GAA expansion in FGF14 that causes spinocerebellar ataxia 27B (SCA27B). “Short tandem repeat gene analysis and interpretation has always been challenging in clinical diagnostics,” said Christine Stanley, PhD, FACMG, Chief Director of Clinical Genomics at Variantyx. “Because the entire genome is sequenced, Genomic Unity® testing has the ability to detect a broader range of STRs from a single sample compared to targeted technologies utilized by other laboratories. At Variantyx we’re committed to continually extending the detection capabilities of our whole genome-based platform and are pleased to now be able to provide extended analysis and interpretation of STRs which is expected to result in additional diagnostic answers for patients.” The product line now analyzes an industry-leading 37 repeat expansions, collectively enabling the genetic diagnosis of late-onset neuropathies, neuromuscular disorders and movement disorders - particularly ataxias - as well as early-onset disorders, including those with symptoms of epilepsy and intellectual disability. The additional detection capabilities are automatically included in all Genomic Unity® comprehensive analyses and relevant targeted analyses. About Variantyx Variantyx is an award-winning, technology-driven precision medicine company providing disruptive solutions for the genetic disorders, reproductive health, and precision oncology markets. The proprietary whole genome analysis platforms developed by Variantyx allow clinicians and patients to better understand a person’s genetic makeup, leading to unmatched diagnostic capabilities and improved personalized treatment recommendations. For more information, please visit . View source version on businesswire.com: Contacts Haim Neerman Haim.neerman@variantyx.com (617) 209-2090 Source: Variantyx View this news release online at:

听力损失是医学上未满足需求的最大领域之一，影响着全球约 4.66 亿人。听力损失可以追溯到多种原因，包括噪音损害、遗传、顺铂等化疗药物的耳毒性以及正常的衰老过程。 听力损失是医学上未满足需求的最大领域之一，影响着全球约 4.66 亿人。听力损失可以追溯到多种原因，包括噪音损害、遗传、顺铂等化疗药物的耳毒性以及正常的衰老过程。 过去一年里，大型药企达成的收购合作中，包括多个听力损失药物开发商，或被整体收购，或被收购部分资产。如礼来以高达 6.1 亿美元价格收购 Akouos；Korro Bio 与 Frequency Therapeutics 反向合并上市，后者拥有针对获得性感音神经性听力损失的候选药物。 有机构预测，听力损失药物市场规模将从去年的 127.1 亿美元跃升至 2030 年的 186.6 亿美元，增幅达 47%。 在与听力损失药物开发商 Decibel Therapeutics 合作 6 年后，再生元于近日豪掷 2.13 亿美元将其纳入麾下。根据交易条款，再生元将预付每股 4 美元，如果 Decibel 的主要研究候选药物达到特定里程碑则额外支付每股至多 3.50 美元，即约 1.09 亿美元预付款，以及 1.04 亿美元里程碑付款。 再生元表示，其对 Decibel 的收购既将扩大买方的耳部疾病治疗产品线，又将与 Decibel 的产品线一起深化其基因治疗产品，其大部分产品是再生元通过六年的合作共同开发的。 对于此次收购，Decibel 的投资者尤为看好，其股价从 2.79 美元/股上涨至 5.06 美元/股。 另外，此次收购交易似乎还在解决 Decibel 因临床试验、研究和人员成本上升而面临的持续现金持有挑战。截至 3 月 31 日，Decibel 第一季度末现金、现金等价物和可供出售证券为 8794.1 万美元，较该公司截至 2022 年 12 月 31 日报告的 1.04561 亿美元下降了 16%。 知名团队创立，最快管线至临床 I 期 Decibel 成立于 2013 年，并于 2021 年在纳斯达克上市。其创始人包括哈佛医学院耳科和喉科 Schuknecht 教授兼马萨诸塞州眼耳科伊顿-皮博迪实验室主任 Charles Liberman；密歇根大学克雷斯吉听力研究所所长 Gabriel Corfas；约翰·霍普金斯大学彭博杰出教授 Ulrich Mueller，以及哈佛医学院耳科和喉科教授兼马萨诸塞州眼耳科蒂洛森细胞生物学中心主任 Albert Edge。另外该公司还拥有多位来自哈佛医学院、密歇根大学、斯坦福大学等知名机构的专家作为科学顾问。 在成立之初，Decibel 就获得了 Third Rock Ventures 、葛兰素史克 SR One 风险投资部门加注的 5200 万美元 A 轮融资。 柯蒂氏器又称螺旋器，是听觉的感受器，位于哺乳动物的耳蜗内，可以将声音振动从中耳传输到听觉神经的神经末梢。噪音对耳蜗中近 15,000 个微小毛细胞和神经元或听觉神经造成的损害是迄今为止所谓的感音神经性听力损失的主要原因，其占到病例的90％。 为了开发出精确靶向听觉神经或毛细胞的药物，Decibel 的研究人员研究了内耳的结构，深入到细胞水平。其方式是采用手术方式将基因引入内耳。 2017 年，Decibel 首次和再生元联手，通过价值未公开的合作“发现和开发新的潜在疗法来保护、修复和恢复听力”。当时，除了能够利用再生元的研究工具外，Decibel 也受益于其财务支持，并保留了管线开发和商业化权利。 2021 年，双方延长了合作关系。为此，再生元在 2022 年第四季度支付了 1000 万美元的合作延期费用。 Decibel 的主要听力损失候选药物是 DB-OTO，再生元正与其合作开发。这是一种细胞选择性、腺相关病毒 (AAV) 双载体基因疗法，旨在为因 otoferlin 突变而患有严重听力损失的人提供持久的听力恢复（OTOF）基因。Decibel 去年获得 FDA 批准其 I/II 期 CHORD™ 试验（NCT05788536），该研究截至 7 月 17 日正在招募患者，预计招募 22 名患者。 ▲图 | Decibel 部分管线（来源：公司官网） 此外，再生元和 Decibel 正在合作开发两种临床前候选药物，包括针对 GJB2 相关听力损失的临床前项目 AAV.103，旨在恢复 GJB2 缺陷患者的听力，GJB2 缺陷是先天性听力损失的最常见原因；针对 STRC 相关听力损失患者的 AAV.104，旨在恢复缺乏 STRC 的个体的听力。 除了基因治疗产品组合外，Decibel 的产品线中还有 DB-020，这是一种硫代硫酸钠制剂，正在 1b 期测试中，用于治疗因顺铂化疗引起的听力损失患者。2022 年 6 月，Decibel 提供的数据显示，该疗法可以保护患者的接受治疗的耳朵免受听力损失。该公司还正在开发两种毛细胞再生项目，用于治疗平衡障碍双侧前庭病和感音神经性听力损失。 内耳疗法和听力损失之战 感音神经性听力损失是最常见的听力损失类型，占到了病例的 90％。感音神经是指内耳成千上万细小毛细胞的感觉能力。内耳（又称耳蜗）入口处的毛细胞将高频率的声音传递给大脑，所有的声波振动进入内耳都会经过这些毛细胞。感音神经性听力损失的主要原因是向大脑传递声音信号的毛细胞受损。 尽管学术研究中心、初创公司和老牌制药公司经过 20 多年的努力，但目前还没有 FDA 批准的用于治疗感音神经性听力损失的内耳疗法。主要原因是难以进入内耳的脆弱结构进行研究和药物应用。 听力损伤药物开发取得重大突破至少取决于三个关键研究方向的融合：了解基本病理生理机制，识别疾病靶点、开发候选药物或其他治疗剂，以及开发递送系统。 ▲图 | 内耳治疗药物开发的系统性障碍（来源：Frontiers） 药物开发与耳科和听力学领域之间的新颖性接口也是一种限制。“由于听力领域的药物开发很少，听力专家对药物开发了解相对较新，而具有药物开发经验的科学家往往是第一次了解听力领域，”Akouos 创始人、总裁兼首席执行官 Manny Simons 表示，在这两个领域之间建立跨学科的努力正在成为迫切需要。 作为 Decibel 的竞争对手，Akouos 公司的主导项目 AK-OTOF 使用基于腺相关病毒 (AAV) 载体的基因疗法来治疗由 otoferlin 基因突变引起的感音神经性听力损失。Otoferlin 是一种跨膜蛋白，参与钙介导的内毛细胞突触小泡响应声音的胞吐作用，这一过程对于将电信号传输到大脑至关重要。 2022 年，该公司获得 FDA 批准 AK-OTOF 的 IND 申请，并计划启动儿科 1/2 期临床试验，以评估该疗法治疗 OTOF 介导的听力损失。同年，该公司被礼来收购，扩大了礼来在基因药物领域的业务，将 Akouos 用于治疗内耳疾病的潜在一流 AAV 基因疗法产品组合纳入其中。 但也有不少公司在开发候选药物的道路上折戟。 由于 FX-322 未能达到人体研究目标，总部位于圣地亚哥的 Frequency Therapeutics 终止了感音神经性听力损失项目 FX-322 的开发，并正在裁员。FX-322 在获得性 SNHL 患者中进行的安慰剂对照 IIb 期研究，招募了 142 名患有突发性或噪音诱发的感音神经性听力损失的患者，但未能达到改善言语感知的主要疗效终点。数据显示，第 90 天时，接受 FX-322 治疗的患者与接受安慰剂的患者之间，言语感知有所改善的个体比例没有统计学意义的差异。 该公司科学创始人包括 Robert Langer。目前，Frequency 已经同意与 Korro Bio 通过反向合并上市，将于第四季度完成。 Otonomy 也在经历一系列临床失败后，宣布关闭并解雇了所有员工。其候选药物 OTO-413 在高剂量条件下，并未出现有临床意义的改善。

While Regeneron has been working with Decibel Therapeutics for some time, the deal underscores a trend as major pharmaceutical companies look to hearing loss biotechs to pad their pipelines. Regeneron, listening to the call for more gene therapies, has added hearing loss specialist Decibel Therapeutics to its playlist in a deal valuing the biotech at $109 million at closing. Regeneron and Decibel were already working together through a 2017 collaboration for three gene therapies for different forms of congenital, monogenic hearing loss. Decibel’s lead hearing loss candidate is DB-OTO, which is currently moving through a phase 1/2 trial called CHORD for individuals with hearing loss caused by mutations of the otoferlin gene. Other assets include preclinical programs AAV.103 for GJB2-related hearing loss and AAV.104 for people with stereocilin-related hearing loss. The biotech also specializes in balance. The deal has a total equity value of $213 million including contingent value rights (CVRs) if certain enrollment, dosing and regulatory milestones for DB-OTO are met. Decibel will come under Regeneron’s wing for $4 per share with the additional non-tradeable CVRs for $3.50 apiece. One of those milestones is the acceptance of a regulatory application in a number of countries by the end of 2028. Regeneron, most well known for its antibody work, sees big opportunity in gene therapy and hearing loss specifically. The company noted that while otoferlin hearing loss itself is rare, most congenital hearing loss diagnosed in developed countries results from a single gene defect. That means these patients could be targeted with gene therapy. George Yancopoulos, M.D., Ph.D., Regeneron’s chief scientific officer and president, said DB-OTO will soon be administered to patients in the early-stage trial and could provide the proof-of-concept needed to advance future gene therapies for more common types of hearing loss. In addition to the gene therapy portfolio, Decibel also has DB-020 in its pipeline, a formulation of sodium thiosulfate being tested in a phase 1b for patients with hearing loss caused by the chemotherapy cisplatin. In June 2022, Decibel presented data showing that the therapy protected patients from hearing loss in the treated ear. The company is also developing two hair cell regeneration programs for the balance disorder bilateral vestibulopathy and for sensorineural hearing loss. While Regeneron has been working with Decibel for some time, the deal underscores the accelerating interest in hearing loss biotechs. In October 2022, Eli Lilly picked up Decibel’s lead rival, Akouos, for $487 million upfront. That company is also using gene therapy to target otoferlin hearing loss. And just a month before that, Fennec Pharmaceuticals got a chemotherapy-induced hearing loss treatment approved by the FDA after decades in development.  Decibel launched its hearing loss mission in 2015 and is led by Laurence Reid, Ph.D., who joined the company in 2020. “After full consideration, the Decibel board has determined that this transaction is the best way to maximize shareholder value and ultimately benefit patients,” Reid said in a statement. “We have collaborated with our colleagues at Regeneron for the past six years and have huge respect for their research and development capabilities. We have full confidence that with Regeneron’s expertise and resources the Decibel pipeline can be optimally developed, and our team is committed to enabling that long-term success.” Decibel had cash and equivalents of $87.9 million as of March 31, which was expected to last into the first half of 2024. The biotech's shares were up 71% to $4.78 compared to a prior close of $2.79 in premarket trading Wednesday, suggesting investors like the tune of the Regeneron deal.