CPI RSV F Vaccine (Blue Lake Biotechnology)

▎药明康德内容团队编辑本期看点1. 靶向Clever-1的单克隆抗体bexmarilimab治疗复发或难治性（r/r）高危（HR）骨髓增生异常综合征（MDS）患者，在1期临床试验中的总缓解率（ORR）为87.5%，患者的中位总生存期（mOS）有望高于接受当前标准治疗的患者。2. 潜在“first-in-class”的小分子p53再激活剂rezatapopt（PC14586）的早期临床结果积极，15例携带TP53 Y220C突变的晚期卵巢癌患者中有14例达到了部分缓解（PR）或疾病稳定（SD）。3. 用于治疗由PKP2基因突变引起的致心律失常性右室心肌病（ARVC）的候选基因疗法TN-401在临床前研究中将小鼠的中位寿命延长了超过10倍，即将开展1b期临床试验。药明康德内容团队整理Bexmarilimab：公布1期临床试验数据Faron Pharmaceuticals公司公布了其靶向Clever-1的单克隆抗体bexmarilimab的1期研究的积极临床进展。Bexmarilimab是Faron公司全资拥有的研究性免疫疗法，旨在通过靶向髓系细胞功能和激活免疫系统，克服对现有疗法的耐药性并优化临床疗效。Bexmarilimab能与巨噬细胞上的免疫抑制受体Clever-1结合，该受体有助于肿瘤生长和转移（即帮助癌症躲避免疫系统）。通过靶向巨噬细胞上的Clever-1受体，bexmarilimab可改变肿瘤微环境，将巨噬细胞从免疫抑制（M2）状态重编程为免疫刺激（M1）状态，上调干扰素的产生，启动免疫系统攻击肿瘤，使癌细胞对标准治疗敏感。此前公布的结果显示，bexmarilimab治疗去甲基化药物（HMA）治疗失败的HR MDS患者的ORR为100%（5/5）。此次公布的结果显示，这5名患者中有4名在8个月后依然存活。通常，复发或难治性HR MDS患者的mOS小于6个月。尽管该试验中接受治疗的患者的mOS尚未公布，但根据目前的数据，研究人员估计它将高于当前标准治疗（或当前已批准的治疗）的水平。在首批5名患者之后，研究人员继续招募了3名患者，目前的ORR为87.5%（7/8），这些患者中有1例达到了完全缓解（CR）、3例达到骨髓完全缓解（mCR）、1例达到PR、2例达到血液学改善和1例因无关的严重不良事件而提前退出的疾病稳定的患者。去年美国血液学会（ASH）年会上报告的r/r AML患者队列的规模更大（n=18）且随访更成熟（中位随访时间为6个月），目前估计的mOS超过8个月。该人群的历史mOS约为6个月，这意味着当前的数据将支持以mOS作为该人群的终点进行注册试验。Rezatapopt（PC14586）：公布1/2期临床试验数据PMV Pharmaceuticals公司公布了其潜在“first-in-class”的小分子p53再激活剂rezatapopt（PC14586）用于治疗实体瘤患者的1/2期临床试验的最新结果。该候选疗法旨在选择性地与p53 Y220C突变蛋白的口袋结合，从而恢复野生型或正常的p53蛋白结构，抑制肿瘤的功能。此前，美国FDA授予了PC14586快速通道资格，用于治疗携带p53 Y220C突变体的局部晚期或转移性实体肿瘤患者。此次公布的数据针对的是携带TP53 Y220C突变的晚期卵巢癌患者亚组。截至2023年9月5日的数据，15例接受PC14586治疗的卵巢癌患者的疗效可评估，7例患者达到了确认的PR，7例患者达到了SD，1例患者的疾病发生了进展。患者的中位缓解持续时间为7个月。在基线时血清CA-125可测量的15例患者中，有6例有CA-125缓解。其中，5例患者达到了影像学的PR，1例患者为SD。在可评估的患者总人群（包括卵巢癌患者）中，治疗相关不良事件大多为1-2级，最常见（>20%）的是恶心（51%）、呕吐（43%）和血肌酐升高（27%）。与总人群相比，卵巢癌患者中治疗相关不良事件的发生频率和严重程度相似。此外，当PC14586与食物一起给药时，其胃肠道毒性有所改善。TN-401：即将启动1b期临床试验Tenaya Therapeutics公司的候选基因疗法TN-401旨在通过AAV9将PKP2基因的功能拷贝靶向递送至心肌细胞，来恢复PKP2蛋白的产生，从而治疗由PKP2基因突变引起的致心律失常性右室心肌病。在临床前研究中，TN-401可恢复PKP2基因的表达，从而恢复桥粒和间隙连接的细胞结构，阻止左心室射血分数的下降，阻止或逆转右心室的扩张，改善室性心律失常的发生频率和严重程度，并防止不良的纤维重塑，显著延长模型小鼠的寿命。接受TN-401预防性治疗的小鼠的中位寿命至少为58周，较对照组小鼠（4.7周）的中位寿命延长超过10倍。基于这些积极的临床前研究数据，2023年10月，美国FDA批准了TN-401的IND申请，可以启动TN-401在PKP2相关ARVC患者中的首次人体1b期临床试验。Tenaya Therapeutics公司计划在2024年下半年为这项研究中的首位患者进行给药。Deltacel（KB-GDT-01）：公布1期临床试验中第二例患者的数据Kiromic BioPharma公司公布了其在研γ-δ T细胞（GDT）疗法Deltacel（KB-GDT-01）用于治疗IV期转移性非小细胞肺癌（NSCLC）患者的1期临床试验的积极早期疗效数据。Deltacel是一种同种异体细胞治疗产品，由未经修饰的供体来源GDT组成。Deltacel旨在利用GDT的天然效力靶向实体瘤，最初的临床开发重点是NSCLC（约占肺癌病例的80%至85%）。两项临床前研究的数据表明，Deltacel与低剂量放射治疗相结合具有良好的安全性和有效性。从治疗开始六周后获得的初步结果显示，Deltacel在控制肿瘤生长方面具有有效性，以及良好的安全性和耐受性。此前公布的首例患者在治疗前三天被确诊为病情进展活跃。接受Deltacel治疗六周后，CT扫描证实了此患者的病情稳定，初步的无进展生存期为一个半月。此次公布的是第二例患者的初步疗效结果。该患者在治疗开始前进行了核磁共振（MRI）扫描，发现了新的转移灶，这些新病灶在治疗后第六周的MRI复查中被发现已完全消退。Lonigutamab：公布1/2期临床试验数据ACELYRIN公司公布了其皮下注射（SC）的人源化IgG1单克隆抗体lonigutamab用于治疗甲状腺眼病（TED）的1/2期试验的积极数据。Lonigutamab靶向胰岛素样生长因子-1受体（IGF-1R），其皮下给药的特点有望实现长期给药，并有可能最大限度地减少相对于静脉注射疗法的暴露，该公司认为这有望提高临床缓解的深度和持久性。此次公布的结果显示，在首次测量（首次给药后的第3周）时，lonigutamab迅速改善了突眼和临床活动评分（CAS）。在队列1中，在接受lonigutamab治疗的患者中，50%患者的眼球突出较基线减少≥2 mm，所有患者的CAS均降低≥2个百分点，25%患者实现了>1 Bahn-Gorman评分的改善。而在队列2中，67%患者的眼球突出较基线减少≥2 mm，83%患者的CAS降低≥2个百分点，40%患者实现了>1 Bahn-Gorman评分的改善。▲Lonigutamab的1/2期临床试验的结果（图片来源：参考资料[10]）VX-407：IND申请获得FDA许可Vertex Pharmaceuticals公司宣布，美国FDA已经批准了VX-407的IND申请，用于治疗常染色体显性多囊肾病（ADPKD）。VX-407是一种潜在“first-in-class”的小分子校正剂，旨在通过校正有缺陷的多囊蛋白1（PC1）折叠来恢复功能，从而治疗ADPKD患者中的PKD1变体亚群（估计约占整个ADPKD患者中的10%）。VX-407旨在阻止肾囊肿的生长，减少肾脏体积，从而防止发展为肾衰竭。Vertex公司计划于今年3月启动针对健康受试者的1期临床试验。Briquilimab：公布近期临床进展Briquilimab（原名JSP191）是Jasper Therapeutics公司开发的一种靶向性糖基化单克隆抗体，可阻止干细胞因子与细胞表面受体c-Kit（又称CD117）结合，从而抑制通过受体发出的信号。该公司于近期公布了briquilimab作为治疗范可尼贫血（Fanconi Anemia）预处理剂的积极1b/2a期临床试验结果。结果显示，所有接受briquilimab治疗的患者（6例）均实现了完全供体植入和全血细胞计数恢复。此外，briquilimab的安全性和耐受性良好。该公司还宣布，其皮下注射的briquilimab用于治疗慢性自发性荨麻疹和慢性诱发性荨麻疹的1b/2a期临床试验已完成了首例患者给药。BLB201：公布1/2a期临床试验的初步数据Blue Lake Biotechnology公司公布了其RSV候选疫苗BLB201的1/2a期临床试验前两个队列的初步数据。BLB-201旨在表达RSV F蛋白，其专有的PIV5载体可以通过鼻腔给药诱导体液免疫和细胞免疫。这种给药方式可以提高儿科患者和害怕打针的患者的接受度。临床前研究结果显示，BLB-201在各类动物模型中均能对RSV引起的感染起预防作用。此前，BLB-201已获得FDA的快速通道资格，用于预防老年人（>60岁）和儿科人群（<2岁）的RSV相关急性疾病。此次公布的数据显示，BLB201的免疫原性和耐受性良好。截至目前，在18-59个月大的RSV血清阳性儿童（n=10）中，单次鼻内剂量接种BLB201未出现重大安全事件。在接种高剂量BLB201的5名受试者中，研究人员在接种后的第四周观察到RSV中和抗体（nAb）显著增加，其中80%患者的nAb比基线时增加了3.6-57倍。此外，还观察到RSV特异性粘膜IgA抗体和细胞免疫反应。目前的试验正在继续招募RSV血清阳性和RSV血清阴性的儿童，年龄最小的只有8个月大。大家都在看药明康德为全球生物医药行业提供一体化、端到端的新药研发和生产服务，服务范围涵盖化学药研发和生产、生物学研究、临床前测试和临床试验研发、细胞及基因疗法研发、测试和生产等领域。如您有相关业务需求，欢迎点击下方图片填写具体信息。▲如您有任何业务需求，请长按扫描上方二维码，或点击文末“阅读原文/Read more”，即可访问业务对接平台，填写业务需求信息▲欲了解更多前沿技术在生物医药产业中的应用，请长按扫描上方二维码，即可访问“药明直播间”，观看相关话题的直播讨论与精彩回放参考资料（可上下滑动查看）[1] Lantern Pharma Announces Initial Patients Dosed in First-In-Human Clinical Trial for AI-Guided Drug-Candidate, LP-284. Retrieved March 18, 2024, from https://www.businesswire.com/news/home/20240315803823/en/[2] New Positive Data Presented on Briquilimab Conditioning in Patients with Fanconi Anemia. Retrieved March 18, 2024, from https://ir.jaspertherapeutics.com/news-releases/news-release-details/new-positive-data-presented-briquilimab-conditioning-patients[3] PMV Pharmaceuticals PYNNACLE Phase I Data of Rezatapopt in Advanced Ovarian Cancer Featured in Late-Breaking Oral Presentation at 2024 SGO Annual Meeting on Women’s Cancer. Retrieved March 18, 2024, from https://www.globenewswire.com/news-release/2024/03/18/2848140/0/en/PMV-Pharmaceuticals-PYNNACLE-Phase-I-Data-of-Rezatapopt-in-Advanced-Ovarian-Cancer-Featured-in-Late-Breaking-Oral-Presentation-at-2024-SGO-Annual-Meeting-on-Women-s-Cancer.html[4] Inside Information: Additional Positive Data from the Phase 1 Part of the BEXMAB Study in Both Higher-Risk HMA-Failed MDS and r/r AML. Retrieved March 18, 2024, from https://www.globenewswire.com/news-release/2024/03/18/2847836/0/en/Inside-Information-Additional-Positive-Data-from-the-Phase-1-Part-of-the-BEXMAB-Study-in-Both-Higher-Risk-HMA-Failed-MDS-and-r-r-AML.html[5] TENAYA THERAPEUTICS ANNOUNCES PUBLICATION OF TN-401 GENE THERAPY PRECLINICAL DATA IN NATURE COMMUNICATIONS MEDICINE. Retrieved March 18, 2024, from https://investors.tenayatherapeutics.com/news-releases/news-release-details/tenaya-therapeutics-announces-publication-tn-401-gene-therapy[6] Early Efficacy Results Show Primary Lung Tumor Stabilization and Complete Disappearance of Brain Metastases in Second Patient in Kiromic BioPharma’s Deltacel-01 Clinical Trial. Retrieved March 20, 2024, from https://www.businesswire.com/news/home/20240319287248/en[7] Jasper Therapeutics Announces First Patient Dosed in Phase 1b/2a SPOTLIGHT Clinical Study of Briquilimab in Chronic Inducible Urticaria. Retrieved March 20, 2024, from https://ir.jaspertherapeutics.com/news-releases/news-release-details/jasper-therapeutics-announces-first-patient-dosed-phase-1b2a[8] DepYmed Receives Clearance from U.S. Food and Drug Administration to Initiate Phase 1 Clinical Trial for DPM-1003 for the Treatment of Rett Syndrome. Retrieved March 20, 2024, from https://www.globenewswire.com/news-release/2024/03/19/2848739/0/en/DepYmed-Receives-Clearance-from-U-S-Food-and-Drug-Administration-to-Initiate-Phase-1-Clinical-Trial-for-DPM-1003-for-the-Treatment-of-Rett-Syndrome.html[9] Antennova Completes First Dosing Cohort for Anti-CD24 mAb, ATN-031, in the Phase I PERFORM Study. Retrieved March 20, 2024, from https://www.prnewswire.com/news-releases/antennova-completes-first-dosing-cohort-for-anti-cd24-mab-atn-031-in-the-phase-i-perform-study-302094397.html[10] ACELYRIN, INC. Announces Positive Phase 1/2 Proof-of-Concept Data for Lonigutamab, First Subcutaneous Anti-IGF-1R to Demonstrate Clinical Responses in Thyroid Eye Disease. Retrieved March 20, 2024, from https://investors.acelyrin.com/node/7661/pdf[11] 23andMe Initiates Phase 1 Clinical Trial for its Dual Mechanism Antibody, 23ME-01473, Targeting ULBP6. Retrieved March 20, 2024, from https://investors.23andme.com/news-releases/news-release-details/23andme-initiates-phase-1-clinical-trial-its-dual-mechanism[12] Vertex Announces FDA Clearance of Investigational New Drug Application for VX-407 for the Treatment of Autosomal Dominant Polycystic Kidney Disease (ADPKD). Retrieved March 22, 2024, from https://www.businesswire.com/news/home/20240321788878/en[13] Blue Lake Biotechnology reports positive interim clinical data in children for its RSV vaccine candidate. Retrieved March 22, 2024, from https://www.bluelakebiotechnology.com/news/blue-lake-biotechnology-reports-positive-interim-clinical-data-innbspchildren-for-its-rsv-vaccine-candidatenbsp[14] CAMP4 Therapeutics Announces Dosing of First Participant in Phase 1 Clinical Study of CMP-CPS-001. Retrieved March 22, 2024, from https://www.globenewswire.com/news-release/2024/03/21/2850154/0/en/CAMP4-Therapeutics-Announces-Dosing-of-First-Participant-in-Phase-1-Clinical-Study-of-CMP-CPS-001-a-Potential-First-in-Class-Therapeutic-for-Urea-Cycle-Disorders.html[15] Public Health Vaccines Announces the Initiation of the First Clinical Trial Evaluating Its Nipah Virus Vaccine. Retrieved March 22, 2024, from https://www.prnewswire.com/news-releases/public-health-vaccines-announces-the-initiation-of-the-first-clinical-trial-evaluating-its-nipah-virus-vaccine-301478712.html免责声明：药明康德内容团队专注介绍全球生物医药健康研究进展。本文仅作信息交流之目的，文中观点不代表药明康德立场，亦不代表药明康德支持或反对文中观点。本文也不是治疗方案推荐。如需获得治疗方案指导，请前往正规医院就诊。版权说明：本文来自药明康德内容团队，欢迎个人转发至朋友圈，谢绝媒体或机构未经授权以任何形式转载至其他平台。转载授权请在「药明康德」微信公众号回复“转载”，获取转载须知。分享，点赞，在看，聚焦全球生物医药健康创新

ATHENS, Ga. & SAN JOSE, Calif.--(BUSINESS WIRE)-- Blue Lake Biotechnology, Inc., a clinical-stage intranasal vaccine company developing parainfluenza virus 5 (PIV5)-vectored vaccines that harness the full breadth of the immune system to protect against serious infectious diseases, today announced preliminary data from the first two cohorts of a Phase 1/2a clinical trial studying BLB201, the company’s investigational vaccine against severe respiratory syncytial virus (RSV) disease. The data show that BLB201 is immunogenic and well tolerated, with no significant safety events reported to date following a single intranasal dose in RSV seropositive children 18-59 months of age. The ongoing trial is currently enrolling both RSV seropositive and RSV seronegative children as young as eight months of age. “Given the challenges of developing an RSV vaccine for children, it is highly encouraging that BLB201, our intranasal RSV vaccine candidate, has been well tolerated in this age group so far,” said Biao He, Ph.D., founder and CEO of Blue Lake Biotechnology. “It is also very exciting to see RSV-specific immune responses to our vaccine in children who have previously been exposed to RSV. We are eager to generate more data in younger children, including infants who have not had prior exposure to RSV, and to develop a highly effective and safe vaccine to protect this vulnerable population from RSV.” Among the initial 10 participants ages 18-59 months who received BLB201 study vaccine in this Phase 1/2a study (NCT05655182), there have been no serious vaccine-related safety signals reported to date. In the five participants who received the higher dose of 107 PFU of BLB201, prominent increases in RSV neutralizing antibody (nAb) responses were observed at four weeks post-vaccination, with 80% having a 3.6- to 57-fold rise in nABs over baseline. RSV-specific mucosal IgA antibody and cellular immune responses were also observed. “For the first time, an RSV vaccine candidate has been shown to generate increases in anti-RSV antibody responses in RSV-seropositive children, suggesting that BLB201 could be effective even in infants who have pre-existing anti-RSV antibodies,” continued Dr. He. “This is particularly encouraging given that the target population of our vaccine includes infants under eight months old who may already have passive immunity to RSV from maternal antibodies or exogenously administered anti-RSV antibodies.” About RSV Respiratory syncytial virus (RSV) is a highly contagious and common respiratory virus and one of the leading causes of acute respiratory disease, infecting more than 64 million people worldwide per year. For most people, it causes symptoms similar to the common cold, but for infants, the immunocompromised, people with chronic heart or lung disease, and older adults, it can cause severe illness and be life-threatening. Repeat infections with RSV are believed to be common, so even people who contracted RSV when they were younger adults and healthy can be at risk from RSV infection later in life. According to the Centers for Disease Control, up to 80,000 children under five years old and up to 160,000 older adults are hospitalized per year because of RSV infection in the US, with up to 10,000 deaths each year. While there are approved antibody drugs and a maternal RSV vaccine that can provide passive immunity against RSV to infants, there is no approved vaccine for generating prophylactic immunity against RSV in infants and children. Such a vaccine is needed to fully protect young populations at significant risk from severe RSV disease. About BLB201 BLB201 is an RSV vaccine candidate that is currently in Phase 1/2a clinical testing in children ages eight to 59 months of age. It has received Fast Track designation from the US Food and Drug Administration for the prevention of RSV-associated acute respiratory disease in adults (>60 years) and pediatric populations (<2 years). BLB201 encodes the RSV F protein and uses a proprietary PIV5 vector, which is not known to cause human disease. PIV5 has been commonly administered to dogs as part of combination distemper/kennel cough vaccines for decades. Blue Lake Biotechnology is developing BLB201 as an intranasal vaccine to prevent acute and severe disease associated with RSV infection. Phase 1 clinical trial results demonstrate BLB201's safety and ability to induce antibody and cell-mediated immune responses, positioning it as a promising candidate in the fight against RSV. About CyanVac and Blue Lake Biotechnology CyanVac LLC and its affiliate, Blue Lake Biotechnology, Inc., are developing intranasal vaccines that harness the full breadth of the immune system to keep people healthy, prevent serious infectious diseases, and protect the health of vulnerable populations. Our platform uses a proprietary parainfluenza virus 5 vector into which a foreign gene from a targeted pathogen is inserted. We have generated a robust clinical-stage pipeline of best-in-class vaccines designed to overcome the limitations of existing vaccine technologies. Our lead product candidates have demonstrated potential for high efficacy and durability with few vaccine-related side effects. Learn more at Blue Lake Biotechnology.