Verbrinacogene Setparvovec

2023年10月18日，Freeline Therapeutics Holdings plc（以下简称Freeline）的大股东Syncona提交了一份Schedule 13D，以每股美国存托股份5美元现金收购Freeline的非约束性提案。根据报道，本次拟议收购的总价值为2440万美元。一度濒临绝境Freeline公司成立于2015年，位于英国斯蒂夫尼奇，是一家研究罕见病基因治疗的先驱企业，专注于开发下一代AAV基因治疗。Syncona是Freeline的大股东，目前持有Freeline 57.9%的股份。在前两年，全球经济市场低迷，Freeline公司也受到相当影响，现金流一度见底，为了节省开支，维持运营到2024年。Freeline公司在2022年，宣布了一系列大动作：出售德国子公司Freeline将子公司Freeline Therapeutics GmbH以2500万美元的价格出售给Ascend Gene and Cell Therapies。同时，作为交易的一部分，Freeline将获得开发其实验性治疗所需的权利，并在18个月内向Ascend支付至少790万美元，这是服务协议的一部分，其中包括获得某些功能和人员的访问权。很难不看出，Freeline这笔交易属于是弃车保帅。删减管线Freeline停止了B型血友病基因疗法FLT180a的研发。事实上，B型血友病基因治疗是Freeline公司最领先的管线，但是由于未来的市场竞争激烈（包括CSL/UniQure的Hemgenix和辉瑞潜在的产品等），Freeline选择将重点放在了针对戈谢病的FLT201和针对法布里病的FLT190。裁员距离2021年12月裁员25%不到一年，Freeline选择再次裁员，预计只保留100名员工。绝地翻盘停止最领先的管线，保留针对戈谢病的FLT201和针对法布里病的FLT190——这一策略在现在看来，无疑是正确的。2023年10月4日，Freeline公司公布了其核心管线FLT201治疗戈谢病的1/2期GALILEO-1试验的初步临床数据：数据显示，FLT201的安全性和耐受性良好。接受FLT201治疗的前两名患者，已经成功摆脱先前的治疗。安全性和耐受性：截至患者1给药后13周和患者2给药后6周，无输液反应和严重不良事件。所有与治疗相关的不良事件均为1级，无需干预即可解决；同一时间段内，肝转氨酶水平没有升高；两名患者的丙氨酸转氨酶（ALT）和天冬氨酸转氨酶（AST）水平均保持在正常范围内。血浆GCase水平显著增加：患者1在给药12周，血浆GCase酶活性比基线提高近700倍，超过70 μmol/L/h；患者2在给药4周，比基线提高300倍，约30 μmol/L/h；正常血浆GCase水平为0.3 ~ 1.2 μmol/L/h。此外，患者1的白细胞GCase活性在接受治疗4周后恢复到正常水平，并在最后一次测量时保持正常，患者2的白细胞GCase活性也在给药4周内达到正常水平，表明细胞从血浆中摄取了GCase。小结在Freeline公布了前两名患者的数据后，Syncona便提出收购的计划，跟了Freeline多年的Syncona无疑是对数据十分看好的。目前，Freeline公司还未对Syncona的提议做出决定，但是无论怎么说，Freeline公司看起来已经从朝不保夕中缓过神来了。参考资料：1.https://freeline.gcs-web.com/static-files/941f1b23-f79e-4cd8-a7f2-33a5fb0683c72.https://freeline.life/freeline-reports-positive-initial-clinical-data-from-first-cohort-of-phase-1-2-galileo-1-trial-of-flt201-its-novel-gene-therapy-candidate-in-gaucher-disease/3.药融圈《Freeline：停止B型血友病基因疗法，出售子公司，裁员》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﹀‍‍ ········

Completed dosing in first cohort of Phase 1/2 GALILEO-1 trial of FLT201 in Gaucher disease; expect to report initial clinical data in third quarter of 2023 Extending impact of its novel GCase variant with research program for GBA1-linked Parkinson’s disease Management to host conference call at 8:00 a.m. ET today LONDON, Aug. 15, 2023 (GLOBE NEWSWIRE) -- Freeline Therapeutics Holdings plc (Nasdaq: FRLN) today reported financial results for the second quarter of 2023 and provided a business update. “FLT201 is a potential first- and best-in-class gene therapy for Gaucher disease Type 1, the most common type of the disease,” said Michael Parini, Chief Executive Officer of Freeline. “Advancing the program is our top strategic priority, and we are extremely pleased with our recent progress and the momentum in the trial. The completion of dosing in the first cohort of our GALILEO-1 trial of FLT201 represents a significant milestone for the program, for Freeline and for the Gaucher community. We believe FLT201 has the opportunity to dramatically reduce the disease and treatment burden for people with Gaucher disease. We look forward to reporting initial clinical data in the third quarter of this year.” “In the second quarter, we also unveiled our lead research program in GBA1-linked Parkinson’s disease, which leverages the same longer-acting GCase variant as FLT201,” Parini continued. “As in Gaucher disease, GBA1 mutations lead to a deficiency of the GCase enzyme and an accumulation of pathological substrates. Approximately 200,000 people with Parkinson’s disease in the US, UK and four major European markets have GBA1 mutations, making it the most common genetic risk factor for the disease. Our GBA1-linked Parkinson’s disease program is a natural extension of our work in Gaucher and an opportunity to extend the therapeutic potential of our longer-acting GCase variant into a genetically defined patient population with a serious unmet need.” Anticipated Clinical Data for FLT201 Initial clinical data, with a focus on assessments of safety and enzyme activity, from the first cohort of the GALILEO-1 Phase 1/2 trial of FLT201 is expected in the third quarter of 2023. GALILEO-1 is a first-in-human, international, multicenter Phase 1/2 dose-finding study assessing the safety, tolerability, and efficacy of a single intravenous dose of FLT201, the company’s adeno-associated virus (AAV) gene therapy candidate for Gaucher disease Type 1. Recent Corporate Highlights Today, Freeline announced the dosing of the second patient in its GALILEO-1 trial of FLT201, marking the completion of dosing in the first cohort. In June, the company announced the dosing of the first patient in its GALILEO-1 trial. Also in June, Freeline unveiled its research program in GBA1-linked Parkinson’s disease. The program builds on its work in Gaucher disease, leveraging the same rationally engineered longer-acting GCase variant as used in FLT201 to develop a gene therapy candidate for a subset of Parkinson’s disease patients with mutations in the GBA1 gene. In preclinical studies, Freeline’s GCase variant has demonstrated at least 20-fold greater activity levels compared to wildtype enzyme in various cell lines, including brain epithelial and neuroblastoma cells. Q2 2023 Financial Results Cash Position: As of June 30, 2023, unrestricted cash and cash equivalents were $38.8 million, compared to $55.4 million as of March 31, 2023. Freeline expects its current level of cash and cash equivalents will enable the company to fund its planned operations into the second quarter of 2024. Research and Development (R&D) Expenses: R&D expenses were $19.7 million for the six months ended June 30, 2023, as compared to $38.8 million for the same period in 2022. The $19.1 million decrease was primarily attributable to a decrease in expenditures related to the company’s deprioritized FLT180a and FLT190 programs, including CMC costs and capacity fees, and reduced headcount-related costs, including share-based compensation expense. General and Administrative (G&A) Expenses: G&A expenses for the six months ended June 30, 2023, were $17.6 million, as compared to $16.3 million for the same period in 2022. The increase of $1.3 million was driven by $2.2 million in costs associated with the sale of Freeline Therapeutics GmbH and $2.0 million associated with the ADS depositary fees in connection with the ADS ratio change. These increases were offset by reduced G&A headcount-related costs, including share-based compensation expense. Gain on Settlement Agreement: The company recorded a gain of $2.2 million due to the mutual release and settlement agreement with Brammer Bio MA, LLC announced in May, which included the release of approximately $4.5 million of discharged net liabilities offset by a settlement payment of $2.3 million. Net Loss: Net loss was $14.8 million, or $0.23 per ordinary share, for the six months ended June 30, 2023, as compared to a net loss of $51.1 million, or $0.95 per ordinary share, in the same period in 2022. About Freeline Therapeutics Freeline is a clinical-stage biotechnology company focused on developing transformative gene therapies for chronic debilitating diseases. Freeline uses its proprietary, rationally designed AAV vector and capsid (AAVS3), along with novel promoters and transgenes, to deliver a functional copy of a therapeutic gene into human liver cells, thereby expressing a persistent functional level of the missing or dysfunctional protein into a patient’s bloodstream. The company is currently advancing FLT201, a highly differentiated gene therapy candidate that delivers a novel transgene, in a Phase 1/2 clinical trial in people with Gaucher disease type 1. Freeline has additional programs in research, including one focused on GBA1-linked Parkinson’s disease that leverages the same novel transgene as FLT201. Freeline is headquartered in the UK and has operations in the United States. For more information, visit or connect with Freeline on LinkedIn and Twitter. Forward-Looking Statements This press release contains statements that constitute “forward looking statements” as that term is defined in the United States Private Securities Litigation Reform Act of 1995, including statements that express opinions, expectations, beliefs, plans, objectives, assumptions or projections of Freeline Therapeutics Holdings plc (the “Company”) regarding future events or results, in contrast with statements that reflect historical facts. Examples include, among other topics, statements regarding the potential of FLT201 to be a first- and best-in-class gene therapy for Gaucher disease; the opportunity to extend the therapeutic potential of the Company’s longer-acting GCase variant into a genetically defined patient population with a serious unmet need; the Company’s expectations regarding its use of cash and cash runway; and the timing of data readouts from the Company’s GALILEO-1 Phase 1/2 clinical trial. In some cases, you can identify such forward-looking statements by terminology such as “anticipate,” “intend,” “believe,” “estimate,” “plan,” “seek,” “project,” “expect,” “may,” “will,” “would,” “could” or “should,” the negative of these terms or similar expressions. Forward-looking statements are based on management’s current beliefs and assumptions and on information currently available to the Company, and you should not place undue reliance on such statements. Forward-looking statements are subject to many risks and uncertainties, including the Company’s recurring losses from operations; the uncertainties inherent in research and development of the Company’s product candidates as well as risks associated with preclinical and clinical data, including the possibility of unfavorable new preclinical, clinical or safety data and further analyses of existing preclinical, clinical or safety data; the Company’s ability to design and implement successful clinical trials for its product candidates; whether the Company’s cash resources will be sufficient to fund the Company’s foreseeable and unforeseeable operating expenses and capital expenditure requirements for the Company’s expected timeline in light of management’s substantial doubt regarding the Company’s ability to continue as a going concern for at least 12 months from the issuance date of this press release; the Company’s failure to demonstrate the safety and efficacy of its product candidates; the Company’s ability to enroll patients in clinical trials for its product candidates; the possibility that one or more of the Company’s product candidates may cause serious adverse, undesirable or unacceptable side effects or have other properties that could delay or prevent their regulatory approval or limit their commercial potential; the Company’s ability to obtain and maintain regulatory approval of its product candidates; the Company’s limited manufacturing experience, which could result in delays in the development of its product candidates; and the Company’s ability to identify or discover additional product candidates, or failure to capitalize on programs or product candidates. A further list and description of risks, uncertainties, and other matters can be found in the Company’s Annual Report on Form 20-F for the fiscal year ended December 31, 2022, and in subsequent reports on Form 6-K, in each case including in the sections thereof captioned “Cautionary Statement Regarding Forward-Looking Statements” and “Item 3.D. Risk factors.” Many of these risks are outside of the Company’s control and could cause its actual results to differ materially from those it thought would occur. The forward-looking statements included in this press release are made only as of the date hereof. The Company does not undertake, and specifically declines, any obligation to update any such statements or to publicly announce the results of any revisions to any such statements to reflect future events or developments, except as required by law. For further information, please reference the Company’s reports and documents filed with the U.S. Securities and Exchange Commission (the “SEC”). You may review these documents by visiting EDGAR on the SEC website at . Unaudited Condensed Consolidated Statements of Operations (in thousands of U.S. dollars, except per share data) For the Six Months Ended June 30, 2023 2022 License revenue $ 617 $ — OPERATING EXPENSES: Research and development 19,720 38,785 General and administrative 17,581 16,278 Gain on legal settlement (2,227 ) — Restructuring expense 1,276 — Total operating expenses 36,350 55,063 LOSS FROM OPERATIONS: (35,733 ) (55,063 ) OTHER INCOME (EXPENSE) NET: Gain on sale of Freeline Therapeutics GmbH 20,279 — Other (expense) income, net 73 2,973 Interest income, net 240 335 Benefit from R&D tax credit 464 721 Total other income, net 21,056 4,029 Net loss before income taxes (14,677 ) (51,034 ) Income tax expense (168 ) (46 ) Net loss $ (14,845 ) $ (51,080 ) Net loss per share attributable to ordinary shareholders—basic and diluted $ (0.23 ) $ (0.95 ) Weighted average ordinary shares outstanding—basic and diluted 65,140,334 53,587,167 Unaudited Condensed Consolidated Balance Sheets (in thousands of U.S. Dollars) June 30, December 31, 2023 2022 ASSETS CURRENT ASSETS: Cash and cash equivalents $ 38,797 $ 47,279 License receivable 631 — Prepaid expenses and other current assets 6,385 6,235 Assets held for sale — 14,113 Total current assets 45,813 67,627 NON-CURRENT ASSETS: Property and equipment, net 9,284 9,007 Operating lease right of use assets 4,792 6,014 Other non-current assets 2,764 3,993 Total assets $ 62,653 $ 86,641 LIABILITIES AND SHAREHOLDERS’ EQUITY CURRENT LIABILITIES: Accounts payable $ 6,875 $ 10,058 Accrued expenses and other current liabilities 8,963 7,908 Operating lease liabilities, current 2,842 2,663 Liabilities related to assets held for sale — 10,337 Total current liabilities 18,680 30,966 NON-CURRENT LIABILITIES: Operating lease liabilities, non-current 1,957 3,261 Total liabilities 20,637 34,227 SHAREHOLDERS’ EQUITY: Deferred shares 137 137 Additional paid-in capital 502,861 500,781 Accumulated other comprehensive (loss) gain (784 ) (3,151 ) Accumulated deficit (460,198 ) (445,353 ) Total shareholders’ equity 42,016 52,414 TOTAL LIABILITIES AND SHAREHOLDERS’ EQUITY $ 62,653 $ 86,641 Media and Investor Contact: Naomi Aoki naomi.aoki@freeline.life Senior Vice President, Head of Investor Relations & Communications + 1 617 283 4298