Norovirus bivalent vaccine(LigoCyte Pharmaceuticals, Inc.)

创新药物的研发总是充满失败的可能，本文统计了2024年5款临床试验失败的疫苗，涉及Transgene、GSK、HilleVax、Ultimovacs ASA、Barinthus Biotherapeutics这5家企业。从所处临床阶段看，基本都处于临床2期。下面为具体信息，如有错漏，欢迎留言补充。 1、公司：Transgene 疫苗：TG4001 临床阶段：2期 10月14日，Transgene公布了其治疗性癌症疫苗Tipapkinogen sovacivec（TG4001）最新的2期临床研究结果，与PD-L1抑制剂阿维鲁单抗（Avelumab）联用治疗HPV16阳性宫颈和肛门生殖器肿瘤未达到主要终点——改善无进展生存期。 TG4001是一款基于重组修饰牛痘病毒（MVA）为载体的疫苗，被设计表达HPV-16 E6/E7和佐剂（IL-2）。TG4001通过刺激免疫系统识别HPV-16 E6/E7，以攻击HPV阳性肿瘤细胞。TG4001已在超过350人中进行试验。 不过值得注意的是，虽然该疫苗的2期试验未达到主要终点，但据其预先计划的亚组分析显示，接受TG4001联合治疗方案的宫颈癌患者显示出积极的治疗趋势。但这还需要通过其他分析（包括PD-L1状态）进一步确认并评估。 2、公司：GSK 疫苗：GSK3943104 临床阶段：2期 9月11日，葛兰素史克（GSK）宣布其首款单纯疱疹病毒（HSV）疫苗GSK3943104在2期临床试验中未能达到试验的主要疗效目标，公司将不再推进到3临床，但会继续完成2临床的安全性数据随访和分析，这些数据可以为复发性生殖器疱疹提供有价值的见解，并为未来的研究工作提供参考。 GSK3943104是一款生殖器疱疹的治疗性疫苗，研发目的是减少复发性生殖器疱疹患者的病变。它通过诱导已经感染病毒的患者产生抗病毒免疫力，以限制疱疹的活跃和复制并减少复发。 3、公司：HilleVax 疫苗：HIL-214 临床阶段：2b期 7月8日，HilleVax公司发表声明称，由于2b期NEST-IN1试验未能达到主要或次要疗效终点，公司将停止为婴儿进一步开发HIL-214诺如疫苗。不过，公司会继续探索HIL-214在成人中开发的可能性。 HIL-214是一种诺如病毒二价GI.1/GII.4病毒样颗粒（VLP）疫苗，用于预防由诺如病毒感染引起的中度至重度急性胃肠炎。NEST-IN1是一项2b期随机、双盲、安慰剂对照临床试验，目的是评估HIL-214在美国和拉丁美洲部分地区为约5个月大婴儿首次接种疫苗时的有效性、安全性和免疫原性，涉及约2800名受试者。 在NEST-IN1研究中，有51个主要终点事件，其中疫苗组25个（n=1425），安慰剂组26个（n=1399），疫苗效力为5%（95%置信区间：-64%，45%）。该研究未达到其主要终点，即未能证明对由GI.1或GII.4诺如病毒基因型引起的中度或重度急性胃肠炎（AGE）事件具有疗效。在次要终点方面也未观察到任何临床益处。HIL-214的安全性和免疫原性特征与NEST-IN1中前200名受试者的预设分析以及之前报告的研究中观察到的一致。公司认为，在该试验中多种新兴GII.4毒株的出现可能影响了疫苗在婴儿中的疗效。 4、公司：Ultimovacs ASA 疫苗：UV1 临床阶段：2期 8月6 日，Ultimovacs ASA宣布其UV1治疗头颈部鳞状细胞癌（HNSCC）患者的FOCUS 2期临床试验（NCT05075122）的顶线结果。数据显示，该研究未能达到其主要和次要终点。 UV1是一款肿瘤疫苗，由三种长合成肽组成，表达人类端粒酶（hTERT）逆转录酶亚基的 60 个氨基酸，其作用机制是通过诱导针对 hTERT 的特异性T细胞反应。皮内注射UV1后，皮肤中的抗原呈递细胞（APC）将对这些肽进行处理并激活T细胞。活化的疫苗特异性T细胞进入循环，在HLA复合物背景下搜索显示其同源抗原的细胞，激活免疫系统级联反应，从而增强抗肿瘤反应。 值得注意的是，UV1正在进行5项2期研究，针对5个不同的适应症——黑色素瘤、间皮瘤、卵巢癌、头颈癌、非小细胞肺癌，包括约670名患者。然而，除了间皮瘤外，目前针对黑色素瘤和头颈癌的研究都显示失败了。今年3月，Ultimovacs宣布UV1联用Ipilimumab+nivolumab治疗不可切除或转移性黑色素瘤的2期临床试验INITIUM主要终点和次要终点均未达到。 目前，Ultimovacs公司将重心转移到UV1治疗卵巢癌上，相关的2期数据预计将于2025年上半年公布。 5、公司：Barinthus Biotherapeutics 疫苗：VTP-200 临床阶段：1b/2期 4月18日，Barinthus Biotherapeutics宣布其在研的高危人瘤病毒（hrHPV）相关宫颈癌的疗法VTP-200的1b/2期试验（APOLLO）已达到主要终点，数据表明其对高危人瘤病毒（hrHPV）相关宫颈癌的治疗是安全的。但是，由于未能证明该疗法确实有效，这家生物技术公司正在考虑如何进一步开发候选药物。 VTP-200是一种免疫治疗组合方案，涉及患者使用ChAdOx载体接受初始剂量，使用MVA载体接受第二剂量。两种剂量都编码相同的HPV抗原，目的是产生针对HPV的抗原特异性T细胞免疫反应。 APOLLO试验是一项随机、安慰剂对照的1b/2期多中心试验，在英国和欧盟招募了108名参与者，旨在评估VTP-200在25-55岁患有持续高危（hr）HPV感染和低度宫颈病变的女性中的安全性、耐受性和免疫原性。结果显示，该试验达到主要安全终点，VTP-200总体耐受性良好，无治疗相关的3级或更高级别的不良事件（AE）或严重的AE（SAE）；在接受最高ChAdOx 剂量的组中观察到高危（hr）HPV（60%，第 2 组）和宫颈病变（67%，第2组和第5组） 的清除率呈阳性趋势；来自五个不同活性剂量组的汇总数据显示，与安慰剂组相比，hrHPV 或宫颈病变清除率没有统计学意义改善。 参考资料： [1]汇总|2024年全球值得关注的79个临床试验失败案例.法迈医讯.2024年12月26日. [2]63项失败临床研究汇总|2024 H1.生物药大时代.2024年07月07日. [3]II期失败的实体瘤疫苗.佰傲谷BioValley.2024年10月15日. [4]生殖器疱疹疫苗：GSK宣布失败，但Moderna和BioNTech仍有机会！.艾坦汀官方.2024年12月03日. [5]癌症疫苗 UV1 新数据！头颈鳞癌 II 期临床结果未达终点.Insight数据库.2024年08月06日. [6]接连失败的肿瘤疫苗.生物制药小编.2024年08月09日. [7]安全但无效？！Barinthus正在评估HPV相关癌症疗法的未来.一度医药.2024年04月22日. 识别微信二维码，可添加药时空小编 请注明：姓名+研究方向！

$189.3 million of cash, cash equivalents and marketable securities as of September 30, 2024 The company is exploring the potential for continued development of its norovirus vaccine candidates in adults as well as business development related activities and other strategic alternatives BOSTON, Nov. 07, 2024 (GLOBE NEWSWIRE) -- HilleVax, Inc. (Nasdaq: HLVX), a clinical-stage biopharmaceutical company focused on developing and commercializing novel vaccines, today reported financial results for the quarter ended September 30, 2024. Third Quarter 2024 Financial Results As of September 30, 2024 and December 31, 2023, the company had cash, cash equivalents and marketable securities totaling $189.3 million and $303.5 million, respectively. Research and development expenses for the third quarter 2024 were $20.2 million, compared to $27.3 for the third quarter 2023. The decrease was primarily due to lower clinical development costs. General and administrative expenses for the third quarter 2024 were $6.2 million, compared to $6.6 million for the third quarter 2023. The decrease was primarily due to lower professional service costs. Other income for the third quarter 2024 was $0.6 million, compared to $2.1 million for the third quarter 2023. The decrease was primarily driven by interest expense incurred on the repayment of the term loan facility during the third quarter of 2024. Net loss for the third quarter 2024 was $25.8 million, compared to $31.8 million for the third quarter 2023. About HilleVax HilleVax is a clinical-stage biopharmaceutical company focused on developing and commercializing novel vaccines. Its initial programs, HIL-214 and HIL-216, are virus-like particle (VLP) based vaccine candidates in development for the prevention of moderate-to-severe acute gastroenteritis (AGE) caused by norovirus infection. Globally, norovirus is estimated to result in over approximately 700 million cases of AGE and 200,000 deaths per year, resulting in over $4 billion in direct health system costs and $60 billion in societal costs per year. The burden of norovirus falls disproportionately on young children and older adults. For more information about HilleVax, visit the company’s website at http://www.HilleVax.com. Forward-Looking Statements The Company cautions you that statements contained in this report regarding matters that are not historical facts are forward-looking statements. The forward-looking statements are based on the Company’s current beliefs and expectations and include, but are not limited to: the timing and scope of any workforce reductions, the amount and timing of the related charges and costs, and intended objectives and benefits of a workforce reduction; and the Company’s plan to explore the potential for continued development of its norovirus vaccine candidates as well as business development-related activities for these vaccine candidates. Actual results may differ from those set forth in this report due to the risks and uncertainties inherent in the Company’s business, including, without limitation: the preliminary nature of the Company’s estimates of the charges and cash expenditures to be incurred in connection with the recent workforce reduction; the Company may not realize the benefits expected from the workforce reduction, including the Company’s ability to conserve cash; the Company’s ability to retain key personnel; to date the Company has depended primarily on the success of HIL-214, and the Company may be unable to identify a viable development path forward for its vaccine candidates; the Company may be unable to secure partnerships or other strategic collaborations on acceptable terms or at all; and other risks described in the Company’s filings with the Securities and Exchange Commission (SEC), including under the heading “Risk Factors” in the Company’s annual report on Form 10-K and any subsequent filings with the SEC. You are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof, and the Company undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date hereof. All forward-looking statements are qualified in their entirety by this cautionary statement, which is made under the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Contact: Shane MaltbieIR@hillevax.com+1-617-213-5054 HilleVax, Inc. Condensed Consolidated Statement of Operations Data(in thousands, except share and per share data)(unaudited) Three Months Ended Nine Months Ended September 30, September 30, 2024 2023 2024 2023 Operating expenses: Research and development $20,165 $27,308 $72,744 $73,425 In-process research and development — — 15,325 — General and administrative 6,215 6,603 22,836 19,629 Impairment charges — — 8,235 — Total operating expenses 26,380 33,911 119,140 93,054 Loss from operations (26,380) (33,911) (119,140) (93,054)Total other income 557 2,096 5,820 6,448 Net loss $(25,823) $(31,815) $(113,320) $(86,606)Net loss per share, basic and diluted $(0.52) $(0.81) $(2.31) $(2.26)Weighted-average shares of common stock outstanding, basic and diluted 49,382,277 39,039,553 49,008,614 38,252,981 HilleVax, Inc. Condensed Consolidated Balance Sheet Data(in thousands)(unaudited) September 30,2024 December 31,2023 Cash, cash equivalents and marketable securities $189,310 $303,483 Total assets 220,622 344,434 Total liabilities 36,349 78,909 Total stockholders’ equity 184,273 265,525 Total liabilities and stockholders’ equity 220,622 344,434