SGT-001

— Received Rare Pediatric Disease and Orphan Drug Designation for Duchenne muscular dystrophy (Duchenne) gene therapy candidate SGT-003 with patient dosing in Phase 1/2 trial expected Q2 2024 — — Company entered into non-exclusive licensing agreement for use of its proprietary, muscle- targeted AAV-SLB101 capsid — — Company ends first quarter 2024 with approximately $206.1 million in cash and investments. Solid has anticipated cash runway into 2026 — CHARLESTOWN, Mass., May 15, 2024 (GLOBE NEWSWIRE) -- Solid Biosciences Inc. (Nasdaq: SLDB), a life sciences company developing precision genetic medicines for neuromuscular and cardiac diseases, today reported financial results for the first quarter ended March 31, 2024, and provided a business update. “In the first quarter of 2024, we continued our focus on executing across our pipeline and we remain on track to initiate patient dosing in our SGT-003 trial in the second quarter of 2024. We anticipate providing a topline readout of safety, microdystrophin expression and functional benefit by year end,” said Bo Cumbo, President and CEO, Solid Biosciences. “Supported by the $108.9 million capital raise completed in January 2024, our strong cash position of $206.1 million provides us with both anticipated runway into 2026 and the resources to execute across our portfolio, including bringing SGT-003 for Duchenne muscular dystrophy into the clinic, advancing SGT-501 for catecholaminergic polymorphic ventricular tachycardia (CPVT) towards IND submission and continuing to progress the rest of our diversified pipeline of neuromuscular and cardiac gene therapy candidates.” Company Updates Solid expects to initiate dosing in the Phase 1/2 trial of SGT-003 in pediatric patients with Duchenne in the second quarter of 2024. Initial safety, microdystrophin expression and functional benefit data from the first 3-4 patients enrolled in the trial is expected by the fourth quarter of 2024. Solid expects to Investigational New Drug Application (IND) for its first cardiac gene therapy candidate, SGT-501 for the treatment of catecholaminergic polymorphic ventricular tachycardia (CPVT), in the first quarter of 2025. Solid continues to advance the rest of its therapeutics portfolio with ongoing preclinical studies in BAG3, mouse studies in TNNT2 and preclinical work in RBM20. Platform enabling work in both capsids (NHP, mouse and pig studies) and portfolio wide CMC process development work is ongoing. Recent Company Highlights On April 1, 2024, Solid announced that the FDA granted Rare Pediatric Disease Designation for its Duchenne gene therapy candidate SGT-003. This designation encourages development of new drugs for the prevention and treatment of rare pediatric diseases. If a new biologics license application (BLA) is approved for SGT-003, the Company may be eligible to receive a priority review voucher. This voucher could be redeemed to obtain priority review for any subsequent marketing application for a different product and may be sold or transferred. On March 7, 2024, Solid announced that it entered into a non-exclusive licensing agreement for use of its proprietary, muscle-targeted AAV-SLB101 capsid in the development of an RNAi therapy to treat FSHD (Facioscapulohumeral muscular dystrophy). The Company aims to license AAV-SLB101 broadly to both companies and academic institutions pursuing treatments for rare diseases. On January 16, 2024, Solid announced that the FDA granted Orphan Drug Designation for SGT-003. This designation provides certain benefits, including specified financial incentives, to support clinical development and the potential for up to seven years of market exclusivity in the U.S. upon regulatory approval. On January 8, 2024, Solid announced a $108.9 million private placement with new and existing investors. The Company expects to use net proceeds of approximately $103.7 million from the private placement to fund ongoing pipeline development programs, business development activities, working capital and other general corporate purposes. First Quarter 2024 Financial Highlights There were no collaboration revenues for the first quarters of 2024 or 2023. Research and development expenses for the three months ended March 31, 2024, were $18.9 million, compared to $24.6 million for the three months ended March 31, 2023. The decrease of $5.8 million in research and development expenses was primarily due to a $7.2 million decrease in manufacturing and research related costs for SGT-003 and $2.3 million decrease in costs for SGT-001 primarily related to our decision to prioritize SGT-003, partially offset by a $3.8 million increase in manufacturing and research related costs for SGT-501. General and administrative expenses for the three months ended March 31, 2024, were $8.0 million, compared to $7.4 million for the three months ended March 31, 2023. The increase of $0.6 million was primarily related to a $0.4 million increase in legal fees, and a $0.2 million increase in corporate and business development costs. Net loss for the first quarter of 2024 was $24.3 million, compared to $30.1 million for the first quarter of 2023. The decrease in net loss was the result of lower research and development costs and an increase in yields on cash, cash equivalents, and available-for-sale securities. Solid had $206.1 million in cash, cash equivalents, and available-for-sale securities as of March 31, 2024, compared to $123.6 million as of December 31, 2023. The Company expects that its cash, cash equivalents, and available-for-sale securities as of March 31, 2024, will enable it to fund key strategic priorities into 2026. About Solid Biosciences Solid Biosciences is a life sciences company focused on advancing a portfolio of gene therapy candidates including SGT-003 for the treatment of Duchenne muscular dystrophy (Duchenne), SGT-501 for the treatment of catecholaminergic polymorphic ventricular tachycardia (CPVT), AVB-401 for the treatment of BAG3-mediated dilated cardiomyopathy, and additional assets for the treatment of fatal cardiac diseases. Solid is advancing its diverse pipeline across rare neuromuscular and cardiac diseases, bringing together experts in science, technology, disease management, and care. Patient-focused and founded by those directly impacted, Solid’s mandate is to improve the daily lives of patients living with these devastating diseases. For more information, please visit . Forward-Looking Statements This press release contains “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995, including statements regarding future expectations, plans and prospects for the company; the ability to successfully achieve and execute on the company’s priorities and achieve key clinical milestones; the company’s SGT-003 program, including expectations for initiating dosing and availability of clinical trial data; the company’s expectations for submission of an IND for SGT-501; Solid’s plans to license AAV-SLB101 broadly to both companies and academic institutions; the anticipated use of proceeds from the January 2024 private placement; the potential benefits of Rare Pediatric Disease Designation and Orphan Drug Designation; the cash runway of the company and the sufficiency of the Company’s cash, cash equivalents, and available-for-sale securities to fund its operations; and other statements containing the words “anticipate,” “believe,” “continue,” “could,” “estimate,” “expect,” “intend,” “may,” “plan,” “potential,” “predict,” “project,” “should,” “target,” “would,” “working” and similar expressions. Any forward-looking statements are based on management’s current expectations of future events and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in, or implied by, such forward-looking statements. These risks and uncertainties include, but are not limited to, risks associated with the ability to recognize the anticipated benefits of Solid’s acquisition of AavantiBio; the company’s ability to advance SGT-003, SGT-501, AVB-401 and other preclinical programs and capsid libraries on the timelines expected or at all; obtain and maintain necessary approvals from the FDA and other regulatory authorities; replicate in clinical trials positive results found in preclinical studies of the company’s product candidates; obtain, maintain or protect intellectual property rights related to its product candidates; compete successfully with other companies that are seeking to develop Duchenne and other neuromuscular and cardiac treatments and gene therapies; manage expenses; and raise the substantial additional capital needed, on the timeline necessary, to continue development of SGT-003, SGT-501, AVB-401 and other candidates, achieve its other business objectives and continue as a going concern. For a discussion of other risks and uncertainties, and other important factors, any of which could cause the company’s actual results to differ from those contained in the forward-looking statements, see the “Risk Factors” section, as well as discussions of potential risks, uncertainties and other important factors, in the company’s most recent filings with the Securities and Exchange Commission. In addition, the forward-looking statements included in this press release represent the company’s views as of the date hereof and should not be relied upon as representing the company’s views as of any date subsequent to the date hereof. The company anticipates that subsequent events and developments will cause the company's views to change. However, while the company may elect to update these forward-looking statements at some point in the future, the company specifically disclaims any obligation to do so. Solid Biosciences Investor Contact: investors@solidbio.com Media Contact: Glenn Silver FINN Partners glenn.silver@finnpartners.com

近日，据一家致力于解决杜氏肌肉营养不良症（DMD）的社区性非营利机构PPMD报道，一名参与辉瑞公司杜氏肌营养不良症（DMD）II期临床试验的男孩已经死亡。报道内容来源于辉瑞提交给该非营利机构的信件，根据这封信描述的信息来看，该男孩参与了辉瑞名为Daylight的临床试验，并于2023年年接受了该公司的AAV9（腺相关病毒）基因疗法fordadistrogene movaparvovec的治疗。（研发代码：PF-06939926，我们这里简称926）。辉瑞在社区信中表示，它尚未掌握有关该男孩发生的所有信息，目前正在与试验现场调查员合作以了解更多信息。有鉴于患者死亡，目前辉瑞已经停止了与III期临床CIFFREO交叉部分相关的给药。这其实不是该药物的第一次死亡事件，在2021年12月时辉瑞公司就报道了一名年轻患者在临床中死亡。本文将对926的临床问题和DMD领域的开发背景进行简单汇总。难以攻克的DMD堡垒在DMD领域使用AAV的尝试，其实先行者几乎都碰了壁，对于DMD这一疾病缺乏足够了解是一方面：因为DMD这一疾病主要涉及心脏，而不同突变类型DMD导致情况更加复杂；AAV技术还有很多不成熟的地方是另外一方面：如AAV的免疫原性，人体对AAV的先天免疫效果先行者辉瑞，Sarepta，Solid biosciences均在这一领域上栽了跟头，第二梯队的安斯泰来等企业也在这一过程中遭遇了众多问题，后续采用AAV递送的CRISPR基因编辑甚至也导致了死亡案例。1.Solid biosciencesSolid可能是前三家中最惨的一个，技术上他们的SGT-001采用的是与辉瑞相似的AAV9将合成dystrophin的基因（microdystrophin）递送给DMD患者身体。但很快就受困于AAV剂量限制毒性，19年临床就被FDA叫停，虽然后来工艺迭代一度解除临床暂停，但公司方面最终还是选择放弃，不得不迭代AAV新衣壳去开发SGT-003来解决问题。2.Sarepta而Sarepta/罗氏的AAV疗法Elevidys采用的是AAVrh74，虽然成功上市，但其实有一定争议，Elevidys在研究中其实没有达到临床终点，只是依靠积极的次要终点才成功上市。3.辉瑞当时Sarepta临床终点没有达到时，辉瑞的CSO兼研发总监Mikael Dolsten称，这使得他们的926在某种程度上成为了 the main game in town（美国俚语：无可奈何的选择）。也确实是无可奈何的选择，辉瑞方面的问题同样很多，之前I期临床时926就出现过涉及非典型溶血性尿毒症综合征(aHUS)样补体激活的急性肾损伤，使得患者后续需要血液透析和补体抑制剂eculizumab进行治疗。而接下来就是三起严重不良事件，三名患者接受926治疗后出现严重肌无力，其中两起涉及了心肌炎，而对这一问题的持续探索（由三家先行者共同发起的探索）导致新的临床研究方案将排除具有外显子9至13突变（外显子缺失，复制，插入或点突变）或外显子29和30缺失的DMD患者。似乎这些特定的缺失患者完全不适用AAV基因治疗……紧接着就是2021年12月时，一名高剂量组患者因为针对AAV的先天免疫，累及心脏，导致心力衰竭和心源性休克。4.安斯泰来而后续跟进的安斯泰来则直接连续砍去三款管线：AT702，AT751，AT753，本来安斯泰来是通过收购基因疗法公司Audentes来获得AAV技术的，他们采用的方法是利用经过修饰的AAV载体来提供反义序列来靶向有问题的DMD蛋白，但来自Audentes的技术却先后出现严重问题，在AT132在2020年到2021年被先后不断被曝死亡事件，且被暂停临床后，这三款DMD的临床管线也遭到了裁去。安斯泰来曾经试图用Cartesian Therapeutics的蛋白酶来针对AAV问题中的中和抗体，但他们后来显然放弃了。5.CRISPR而CRISPR的死亡案例也令人深思。2022年10月一名27岁的DMD患者在接受rAAV9递送的CRISPR疗法后第六天就发生了严重的心肺毒性，后续对该患者的尸检也表明该名患者不仅仅出现了补体激活，还因为AAV9导致的强烈先天免疫累及多器官衰竭。总结总的来说，在DMD领域的AAV开发不易，有些病情严重的患者有些时候也很难有更好的选择，这可能是相当难抉择的。例如出现事故的CRISPR-AAV疗法公司，那是哥哥为弟弟治病开发的AAV治疗公司，不愿意失去亲人的尝试谁都会去做。只能期望未来通过对AAV各方面的改进，能够使其更加安全可靠。参考来源：https://www-nejm-org.libproxy1.nus.edu.sg/doi/full/10.1056/NEJMoa2307798心脏AAV基因治疗临床转化的思考https://www.fiercebiotech.com/biotech/after-sarepta-miss-pfizers-cso-says-its-dmd-gene-therapy-main-game-townhttps://www.fiercebiotech.com/biotech/pfizer-reports-death-young-boy-dmd-who-participated-gene-therapy-trial仅交易一年就退货？主要终点未达到，却支持提交疗效补充申请FDA受理DMD基因治疗的疗效补充申请DMD基因治疗进行首位商业患者给药首款DMD基因治疗报上市，来自Sarepta/罗氏死亡不良事件嫌疑打消，辉瑞DMD基因疗法重启Ⅲ期临床https://www.parentprojectmd.org/news/本周好文推荐如需转载请联系佰傲谷并在醒目位置注明出处········