GT-201

来源：药渡撰文：天际微步    编辑：哦呼2023年11月中旬，全球首款CRISPR基因编辑疗法在英国获批上市，代表基因编辑技术在疾病治疗上成功实现破冰。经过十多年的发展，最初由2位科学家在2012年突破的CRISPR技术，目前已经应用到基因编辑细胞治疗地中海贫血、基因编辑育种、基因编辑器官移植等多个场景，而首款基因编辑疗法的获批上市，标志着CRISPR基因编辑技术实现了从原创基础研究到临床转化应用的突破，是其发展史上的一个重要里程碑。值得注意的是，目前很多重磅药物都是国外药企率先上市，而国内药企的进展如何，到底谁将能率先实现突破？01基因编辑治疗赛道迎来商业化，谁将拿下国产首款CRISPR基因编辑疗法？美国福泰制药（Vertex Pharmaceuticals）与瑞士CRISPR Therapeutics合作开发的CRISPR基因编辑疗法Casgevy，先后在英国和美国获批上市，首先是2023年11月获得英国药监部门批准有条件上市，用于治疗镰状细胞病（SCD）和输血依赖性β地中海贫血（TDT），随后在12月8日，再获得美国食品药品监督管理局（FDA）批准上市。此次获批的疗法是“里程碑式进展”，标志着基因疗法的新突破，为地中海贫血、镰状细胞血症这种难以治愈的遗传性疾病提供一种新型治愈方式。基因编辑疗法与百万一针的CAR-T疗法类似，属于个性化定制药物：由患者自身的造血干细胞制成，经过基因编辑改造后，以造血干细胞移植方法，通过单次注射输回到患者体内。因此注定了其成本和价格也比较高昂。02为什么是Vertex和CRISPR两家公司？CRISPR Therapeutics是CRISPR技术的诺奖获得者之一，瑞典于默奥大学的Dr. Emmanuelle Charpentier所创立，最早应用CRISPR于临床治疗的公司之一。Vertex Pharmaceuticals是一家成立于1989年的美国药企，总部位于马萨诸塞州，是一家上市公司。该公司的主要业务是生产和销售用于治疗肺部疾病、肾脏疾病、血液系统疾病等疾病的药物。在2023年《财富》美国500强排行榜中，还以8930.7（百万美元）营收排名第427位。可见发展时间悠久，资金实力雄厚，在药物研发、生产、临床应用和销售渠道等环节积累了充足的经验。因此，通过合作，拥有CRISPR专利技术但却缺乏药物产业化经验的CRISPR Therapeutics生物技术公司借助大型药企的力量，加快将其管线推向临床和上市。其实，从两者的早期合作就可见一斑。早在2023年3月27日，Vertex公司和CRISPR Therapeutics已就使用CRISPR Therapeutics的基因编辑技术CRISPR/Cas9达成一项非排他性许可协议，以获得CRISPR技术的非独家权利，用于开发T1D的低免疫基因编辑细胞疗法。基因编辑的核心技术专利基本掌握在两位女科学家和张峰所创立的公司，包括Dr. Emmanuelle Charpentier创立的CRISPR Therapeutic，Dr. Jennifer A. Doudna创立的Intellia Therapeutics，张峰创立的Editas Medicine。因此这几家公司的基因编辑管线进展也是相对较快的，但是目前仅有CRISPR Therapeutics是通过与传统药企合作的方式去推进药物的研发。CRISPR Therapeutic：由Emmanuelle Charpentier联合Rodger Novak 和 Shaun Foy于2013年创办。Charpentier在2012年因发现CRISPR/Cas9新一代基因编辑工具获得了诺贝尔化学奖，基于其专有的 CRISPR/Cas9 平台开发针对严重疾病的基因药物，获批全球首款CRISPR基因编辑疗法Casgevy。Intellia Therapeutics：另一位基因编辑技术诺奖获得者Jennifer A. Doudna 创立，成立于2014年5月。其NTLA-2001是创新性的体内编辑疗法，通过脂质纳米颗粒(LNP)包装靶向TTR基因的CRISPR基因编辑系统，用于治疗由转甲状腺素蛋白淀粉样变性(ATTR)造成的神经疾病和心肌疾病，目前进入了临床三期。Editas Medicine：张峰参与创立的第一家基因编辑疗法公司，张峰拥有CRISPR-Cas9技术应用于真核细胞、CRISPR-Cas12a等多项基因编辑专利。其用于治疗遗传性失明疾病Leber氏先天性黑蒙症的AGN-151587基因编辑疗法已进入临床二期。03国内基因编辑疗法企业管线进展除了首款获批上市的产品，全球还有十余款CRISPR基因编辑疗法已经进入临床试验阶段，其中包含了多款中国公司开发的产品。据数据，国内基因编辑疗法进展比较快的主要为新兴的生物科技公司，如本导基因、沙砾生物、禾沐基因、邦耀生物、博雅辑因等，相关的公司目前管线均处于1/2的阶段。表1.全球基因编辑治疗药物研发进展（截至2024.3.31，数据来源：根据药渡数据库整理。）   本导基因 BD-111BD111注射液是上海本导基因技术有限公司自主研发的新型体内基因编辑抗病毒药物，属于全球First-in-Class产品。它利用原创技术类病毒体（VLP）递送CRISPR基因编辑工具，直接靶向切割1型单纯疱疹病毒（HSV-1）的基因组以清除病毒。是继美国Editas与Intellia的体内基因编辑治疗管线之后，全球第3个进入临床阶段的体内基因编辑治疗候选药物，也是全球首个CRISPR抗病毒基因编辑药物。其核心技术优势在于其全球首创的递送载体技术，将慢病毒载体进行改造，递送表达CRISPR基因编辑工具的mRNA，在体内表达CRISPR剪刀进行病毒基因切割。   邦耀生物BRL-101BRL-101是一款依托邦耀生物自主研发的造血干细胞平台（ModiHSC）开发的基因治疗产品，适应症为输血依赖型β-地中海贫血。该产品通过CRISPR/Cas9介导的BCL11A红细胞增强子的突变，导致BCL11A表达的减少，以诱导胎儿γ-血红蛋白的表达。BRL-101已于2022年10月正式在中国启动多中心1/2期注册性临床试验。其优势在于使用非病毒载体，安全性和成本上要优于使用病毒载体递送的产品。   沙砾生物GT201GT201是沙砾生物基于自研TIL扩增、编辑等平台研发的下一代TIL（肿瘤浸润淋巴细胞）管线，是国内首款进入注册临床试验的基因编辑型TIL药物。通过从患者体内获取肿瘤组织并提取TIL，经过沙砾生物特有的高效的TIL基因敲除体系将特定的基因敲除，再通过沙砾生物自研的逆转录病毒系统StaViral，可实现在多批次、不同瘤种来源的TIL细胞稳定表达目标基因，扩增后输注回患者体内以对抗妇科肿瘤。其优势在于基因编辑+免疫细胞疗法的结合，将基因编辑技术用到TIL的基因改造中，提高了免疫细胞疗法开发的效率。总体上，从竞争角度来看，同样针对β地中海贫血的邦耀生物、博雅辑因（广州子公司）、禾沐基因等三家企业的进度较快，国产首款地贫的基因编辑治疗药物有望在这三者中诞生。而在新的适应症上，本导基因的BD-111（疱疹性角膜炎）、沙砾生物的GT-201（女性生殖器官肿瘤）也进入了临床1/2期，亦有望在国内率先上市。(END)*声明：本文仅是介绍医药疾病领域研究进展或简述研究概况或分享医药相关讯息，并非也不会进行治疗或诊断方案推荐，也不对相关投资构成任何建议。内容如有疏漏，欢迎沟通指出！《2023年度中国生物医药投融资蓝皮书》重磅发布！本土Biotech与MNC合作进入2.0时代：汇总分析３起医药并购案例【药企裁员风波不断】三月汇总点击蓝字 | 关注我们

Company continues to evaluate strategic options to maximize shareholder valueMALVERN, Pa., March 28, 2024 (GLOBE NEWSWIRE) -- Galera Therapeutics, Inc. (Nasdaq: GRTX), a biopharmaceutical company focused on developing a pipeline of novel, proprietary therapeutics that have the potential to transform radiotherapy in cancer, today announced financial results for the fourth quarter and year ended December 31, 2023 and provided recent corporate updates. "As a result of last year’s FDA request for a second Phase 3 trial to support the avasopasem NDA, we have implemented key measures to extend our cash runway and assess strategic alternatives," said Mel Sorensen, M.D., Galera’s President and CEO. “Among these measures, we recognize that the decision to discontinue our GRECO trials was challenging for our team and our clinical investigators, but we believe it was the appropriate decision, following the negative futility analysis in the pancreatic trial. We are continuing to explore strategic options to maximize value to our shareholders, including a potential development path for avasopasem. This process could ultimately result in the dissolution of the Company.” Recent Corporate Updates General Corporate Updates In August 2023, the Company announced a reduction in force, which reduced the Company’s workforce by approximately 70%, as of August 9, 2023 (Workforce Reduction). The decision was made to reduce operational costs as part of broader cost-saving measures.In October 2023, the Company announced it had engaged Stifel, Nicolaus & Company, Inc., as its financial advisor, to assist in reviewing strategic alternatives with the goal of maximizing value for its stockholders. Radiotherapy-Induced Severe Oral Mucositis (SOM) In February 2023, the Company announced that the U.S. Food and Drug Administration (FDA) accepted for filing and granted priority review to the New Drug Application (NDA) for avasopasem manganese (avasopasem) for radiotherapy-induced SOM in patients with head and neck cancer (HNC) undergoing standard-of-care treatment. The Prescription Drug User Fee Act (PDUFA) target date assigned by the FDA for the NDA was August 9, 2023.In August 2023, the FDA issued a Complete Response Letter (CRL) for the NDA for avasopasem. In the CRL, the FDA communicated that the data from the Phase 2b GT-201 and Phase 3 ROMAN trials were not sufficient for approval and that an additional clinical trial will be required for an NDA resubmission.In September 2023, a Type A meeting was held with the FDA to understand the FDA’s rationale for its decision and discuss next steps to support an NDA resubmission.In October 2023, the Company received official meeting minutes from the Type A meeting in which the FDA reiterated the need for an additional Phase 3 trial to support resubmission. The Company continues to explore potential options for the development of avasopasem. Cisplatin-Related Chronic Kidney Disease (CKD) In November 2023, the Company presented the prospectively collected cisplatin-related CKD data from the Phase 3 ROMAN trial at the American Society of Nephrology (ASN) Kidney Week 2023 meeting, which took place November 2-5 in Philadelphia, PA. The oral presentation, titled "Effects of Avasopasem on Rates of Cisplatin-Induced Acute Kidney Injury and Chronic Kidney Disease," reported significant preservation of kidney function across cisplatin dosing schedules, including a 50% reduction in the avasopasem arm in the incidence of CKD one year following treatment with cisplatin compared to placebo. During the treatment phase, lower incidences of acute renal adverse events were also observed in the avasopasem arm compared to placebo. Locally Advanced Pancreatic Cancer (LAPC) In May 2023, the FDA granted Orphan Drug Designation for rucosopasem for the treatment of pancreatic cancer.In October 2023, the Company decided to halt the Phase 2b GRECO-2 trial of rucosopasem manganese (rucosopasem) in patients with LAPC, following an early futility analysis of the trial which indicated that the trial was unlikely to succeed as designed. Non-Small Cell Lung Cancer (NSCLC) In October 2023, following the futility analysis of the GRECO-2 trial, the Company decided to halt the randomized, placebo-controlled Phase 1/2 GRECO-1 trial of rucosopasem in patients with NCSLC. Fourth Quarter 2023 Financial Highlights Research and development expenses were $3.2 million in the fourth quarter of 2023, compared to $8.1 million for the same period in 2022. The decrease was primarily attributable to a decrease in avasopasem development costs and lower personnel-related expenses due to the Workforce Reduction.General and administrative expenses were $2.0 million in the fourth quarter of 2023, compared to $5.0 million for the same period in 2022. The decrease was primarily attributable to lower personnel-related expenses due to the Workforce Reduction and the halting of avasopasem commercial preparation efforts following the receipt of the CRL from the FDA for the avasopasem NDA for radiotherapy-induced SOM in August 2023.Galera reported a net loss of $(5.6) million, or $(0.10) per share, for the fourth quarter of 2023, compared to a net loss of $(16.2) million, or $(0.58) per share, for the same period in 2022.As of December 31, 2023, Galera had cash and cash equivalents of $18.3 million. Galera expects that its existing cash and cash equivalents will enable Galera to fund its operating expenses and capital expenditure requirements into the second quarter of 2025. Full Year 2023 Financial Highlights Research and development expenses were $24.1 million for the year ended December 31, 2023, compared to $31.0 million for the year ended December 31, 2022. The decrease was primarily attributable to a decrease in avasopasem development costs and lower personnel-related expenses due to the Workforce Reduction, partially offset by an increase in rucosopasem development costs.General and administrative expenses were $22.8 million for the year ended December 31, 2023, compared to $20.2 million for the year ended December 31, 2022. The increase was primarily attributable to avasopasem commercial preparations in 2023, partially offset by a decrease in personnel-related expenses driven by the Workforce Reduction.As a result of the Workforce Reduction, the Company incurred restructuring-related charges of $2.3 million in the third quarter of 2023, primarily consisting of severance payments, employee benefits and related costs.Galera reported a net loss of $(59.1) million, or $(1.33) per share, for the year ended December 31, 2023, compared to a net loss of $(62.2) million, or $(2.30) per share, for the year ended December 31, 2022. About Galera Therapeutics Galera Therapeutics, Inc. is a biopharmaceutical company focused on developing a pipeline of novel, proprietary therapeutic candidates that have the potential to transform radiotherapy in cancer. Galera’s selective dismutase mimetic product candidate avasopasem manganese (avasopasem) has been developing for radiation-induced and cisplatin-related toxicities. The FDA has granted Fast Track and Breakthrough Therapy designations to avasopasem for the reduction of severe oral mucositis induced by radiotherapy. The Company’s second product candidate, rucosopasem manganese (rucosopasem), has been in development to augment the anti-cancer efficacy of stereotactic body radiation therapy in patients with non-small cell lung cancer and locally advanced pancreatic cancer. Rucosopasem has been granted orphan drug designation and orphan medicinal product designation by the FDA and EMA, respectively, for the treatment of pancreatic cancer. Galera is headquartered in Malvern, PA. Forward-Looking Statements This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. All statements contained in this press release that do not relate to matters of historical fact should be considered forward-looking statements, including without limitation statements regarding: Galera’s pursuit of strategic alternatives and the ability of any such strategic alternative to provide shareholder value, including a potential development path for avasopasem; the potential safety and efficacy of Galera’s product candidates and their regulatory and clinical development; Galera’s ability to fund its operating expenses and capital expenditure requirements into the second quarter 2025; and Galera’s ability to achieve its goal of transforming radiotherapy in cancer treatment with its selective dismutase mimetics. These forward-looking statements are based on management’s current expectations. These statements are neither promises nor guarantees, but involve known and unknown risks, uncertainties and other important factors that may cause Galera’s actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or implied by the forward-looking statements, including, but not limited to, the following: Galera’s limited operating history; anticipating continued losses for the foreseeable future; needing substantial funding and the ability to raise capital; Galera’s dependence on avasopasem manganese (GC4419); uncertainties inherent in the conduct of clinical trials; difficulties or delays enrolling patients in clinical trials; the FDA’s acceptance of data from clinical trials outside the United States; undesirable side effects from Galera’s product candidates; risks relating to the regulatory approval process; failure to capitalize on more profitable product candidates or indications; ability to receive or maintain Breakthrough Therapy, Orphan Drug or Fast Track Designations for product candidates; failure to obtain regulatory approval of product candidates in the United States or other jurisdictions; ongoing regulatory obligations and continued regulatory review; risks related to commercialization; risks related to competition; ability to retain key employees; risks related to intellectual property; inability to maintain collaborations or the failure of these collaborations; Galera’s reliance on third parties; the possibility of system failures or security breaches; liability related to the privacy of health information obtained from clinical trials and product liability lawsuits; environmental, health and safety laws and regulations; Galera may not be able to enter into any desired strategic alternative or partnership on a timely basis, on acceptable terms, or at all; if Galera is unable to secure additional funding or enter into any desired strategic alternative or partnership, it may need to cease operations; risks related to ownership of Galera’s common stock; the possibility of Galera’s common stock being delisted from The Nasdaq Global Market; and significant costs as a result of operating as a public company. These and other important factors discussed under the caption “Risk Factors” in Galera’s Annual Report on Form 10-K for the year ended December 31, 2023 filed with the U.S. Securities and Exchange Commission (SEC) and Galera’s other filings with the SEC could cause actual results to differ materially from those indicated by the forward-looking statements made in this press release. Any forward-looking statements speak only as of the date of this press release and are based on information available to Galera as of the date of this release, and Galera assumes no obligation to, and does not intend to, update any forward-looking statements, whether as a result of new information, future events or otherwise. Galera Therapeutics, Inc.Consolidated Statements of Operations(in thousands, except share and per share data) Three Months Ended December 31, Year Ended December 31, 2023 2022 2023 2022 Operating expenses: Research and development$3,189 $8,137 $24,115 $31,012 General and administrative 1,987 5,021 22,836 20,214 Restructuring costs - - 2,309 - Loss from operations (5,176) (13,158) (49,260) (51,226)Other income (expense), net (411) (3,100) (9,822) (11,066)Loss before income tax benefit (5,587) (16,258) (59,082) (62,292)Income tax benefit - 70 - 70 Net Loss$(5,587) $(16,188) $(59,082) $(62,222) Net loss per share of common stock, basic and diluted$(0.10) $(0.58) $(1.33) $(2.30)Weighted average common shares outstanding, basic and diluted 54,385,017 27,942,210 44,549,285 27,086,664 Galera Therapeutics, Inc.Selected Consolidated Balance Sheet Data(in thousands) December 31, December 31, 2023 2022 Cash, cash equivalents, and short-term investments$18,257 $31,597 Total assets 26,141 44,036 Total current liabilities 4,957 13,379 Total liabilities 157,326 153,217 Total stockholders' deficit (131,185) (109,181) Investor Contacts:Christopher DegnanGalera Therapeutics, Inc.610-725-1500cdegnan@galeratx.com William WindhamSolebury Strategic Communications646-378-2946wwindham@soleburystrat.com Media Contact:Timothy BibaSolebury Strategic Communications646-378-2927tbiba@soleburystrat.com