A Phase 1 Open-label, Non-randomized, Clinical Trial to Evaluate the Safety and Immunogenicity of Hiltonol, Poly-ICLC-adjuvanted CD40.HIVRI.Env (VRIPRO) in Adult Participants Who Previously Participated in the HVTN706/MOSAICO Study and Remain Without HIV

The clinical schedule will consist of 3 injections of CD40.HIVRI.Env (VRIPRO) at weeks 0, 4, and 24.40 volunteers without HIV and in overall good health, aged 18 to 60 years, who previously participated in the HVTN 706/MOSAICO trial.

开始日期2025-02-04

申办/合作机构

National Institute of Allergy & Infectious Diseases

NCT04842682 / Active, not recruiting临床1期IIT

A Phase I Multicenter Double-blind Placebo Controlled Dose Escalation Trial of an Adjuvanted Anti-CD40 mAb Fused to Env GP140 HIV Clade C ZM-96 (CD40.HIVRI.Env) Vaccine Combined or Not With a DNA-HIV-PT123 HIV-1 Vaccine in Healthy Participants

Multicenter double-blind placebo controlled phase I dose-escalation trial that will be conducted in France and Switzerland to evaluate different dose levels of CD40.HIVRI.Env (adjuvanted with Hiltonol) alone and in co-administration with DNA-HIV-PT123.
A total of 72 eligible healthy participants will be recruited into 6 groups. Within each group, participants will be randomized in a double blind manner to active intervention or placebo in a 5:1 ratio. Enrolment into a given group (other than group "Solo 0.3") will open sequentially depending on the " go-criterion " based on the safety data of the preceding group(s).
The primary objective is to assess the safety of three dose levels of CD40.HIVRI.Env (0.3; 1; 3 mg) adjuvanted with Poly-ICLC (Hiltonol®), alone and in combination with DNA-HIV-PT123, administered at weeks 0, 4 and 24 in healthy participants.
Secondary objectives are to assess the capacity of poly-ICLC-adjuvanted CD40.HIVRI.Env alone and in combination with DNA-HIV-PT123 to elicit immune responses against HIV (immunogenicity):
* Humoral (antibody) responses ;
* B-cell responses ;
* T-cell responses.

开始日期2021-03-29

申办/合作机构

ANRS, Emerging Infectious Diseases

100 项与 CD40.HIVRI.Env vaccine( ANRS/INSERM/Baylor Research Institute) 相关的临床结果

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100 项与 CD40.HIVRI.Env vaccine( ANRS/INSERM/Baylor Research Institute) 相关的转化医学

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100 项与 CD40.HIVRI.Env vaccine( ANRS/INSERM/Baylor Research Institute) 相关的专利（医药）

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项与 CD40.HIVRI.Env vaccine( ANRS/INSERM/Baylor Research Institute) 相关的文献（医药）

2017-05-01·Journal of virology2区 · 医学

Superiority in Rhesus Macaques of Targeting HIV-1 Env gp140 to CD40 versus LOX-1 in Combination with Replication-Competent NYVAC-KC for Induction of Env-Specific Antibody and T Cell Responses

2区 · 医学

Article

作者: Roederer, Mario ; Self, Steve ; Cristillo, Anthony ; Jacobs, Bertram ; Tomaras, Georgia D. ; Gottardo, Raphael ; LaBranche, Celia ; Fulp, William ; Kao, Shing-Fen ; Salazar, Andres ; Galmin, Lindsey ; Zurawski, Sandra ; Yates, Nicole L. ; Montefiori, David C. ; Stanfield-Oakley, Sherry ; Kibler, Karen ; Yu, Xuesong ; Lacabaratz, Christine ; Zurawski, Gerard ; Pantaleo, Giuseppe ; Wang, Zhiqing ; Levy, Yves ; Klucar, Peter ; Foulds, Kathryn E. ; Ferrari, Guido ; Weiss, Deborah ; Shen, Xiaoying ; Sato, Alicia

ABSTRACT:

We compared the HIV-1-specific immune responses generated by targeting HIV-1 envelope protein (Env gp140) to either CD40 or LOX-1, two endocytic receptors on dendritic cells (DCs), in rhesus macaques primed with a poxvirus vector (NYVAC-KC) expressing Env gp140. The DC-targeting vaccines, humanized recombinant monoclonal antibodies fused to Env gp140, were administered as a boost with poly-ICLC adjuvant either alone or coadministered with the NYVAC-KC vector. All the DC-targeting vaccine administrations with poly-ICLC increased the low-level serum anti-Env IgG responses elicited by NYVAC-KC priming significantly more (up to a P value of 0.01) than in a group without poly-ICLC. The responses were robust and cross-reactive and contained antibodies specific to multiple epitopes within gp140, including the C1, C2, V1, V2, and V3, C4, C5, and gp41 immunodominant regions. The DC-targeting vaccines also elicited modest serum Env-specific IgA responses. All groups gave serum neutralization activity limited to tier 1 viruses and antibody-dependent cytotoxicity responses (ADCC) after DC-targeting boosts. Furthermore, CD4 + and CD8 + T cell responses specific to multiple Env epitopes were strongly boosted by the DC-targeting vaccines plus poly-ICLC. Together, these results indicate that prime-boost immunization via NYVAC-KC and either anti-CD40.Env gp140/poly-ICLC or anti-LOX-1.Env gp140/poly-ICLC induced balanced antibody and T cell responses against HIV-1 Env. Coadministration of NYVAC-KC with the DC-targeting vaccines increased T cell responses but had minimal effects on antibody responses except for suppressing serum IgA responses. Overall, targeting Env to CD40 gave more robust T cell and serum antibody responses with broader epitope representation and greater durability than with LOX-1. IMPORTANCE An effective vaccine to prevent HIV-1 infection does not yet exist. An approach to elicit strong protective antibody development is to direct virus protein antigens specifically to dendritic cells, which are now known to be the key cell type for controlling immunity. In this study, we have tested in nonhuman primates two prototype vaccines engineered to direct the HIV-1 coat protein Env to dendritic cells. These vaccines bind to either CD40 or LOX-1, two dendritic cell surface receptors with different functions and tissue distributions. We tested the vaccines described above in combination with attenuated virus vectors that express Env. Both vaccines, but especially that delivered via CD40, raised robust immunity against HIV-1 as measured by monitoring potentially protective antibody and T cell responses in the blood. The safety and efficacy of the CD40-targeted vaccine justify further development for future human clinical trials.

PLoS pathogens1区 · 医学

TLR-9 agonist and CD40-targeting vaccination induces HIV-1 envelope-specific B cells with a diversified immunoglobulin repertoire in humanized mice

1区 · 医学

ArticleOA

作者: Mouquet, Hugo ; Milpied, Pierre ; Tcherakian, Colas ; Li, Guangming ; Godot, Véronique ; Zurawski, Gerard ; Pantaleo, Giuseppe ; Su, Lishan ; Cardinaud, Sylvain ; Cheng, Liang ; Fenwick, Craig ; Lelièvre, Jean-Daniel ; Ortonne, Nicolas ; Gil, Laurine ; Cervera-Marzal, Iñaki ; Zurawski, Sandra M ; Lévy, Yves ; Centlivre, Mireille

The development of HIV-1 vaccines is challenged by the lack of relevant models to accurately induce human B- and T-cell responses in lymphoid organs. In humanized mice reconstituted with human hematopoietic stem cells (hu-mice), human B cell-development and function are impaired and cells fail to efficiently transition from IgM B cells to IgG B cells. Here, we found that CD40-targeted vaccination combined with CpG-B adjuvant overcomes the usual defect of human B-cell switch and maturation in hu-mice. We further dissected hu-B cell responses directed against the HIV-1 Env protein elicited by targeting Env gp140 clade C to the CD40 receptor of antigen-presenting cells. The anti-CD40.Env gp140 vaccine was injected with CpG-B in a homologous prime/boost regimen or as a boost of a NYVAC-KC pox vector encoding Env gp140 clade C. Both regimens elicited Env-specific IgG-switched memory hu-B cells at a greater magnitude in hu-mice primed with NYVAC-KC. Single-cell RNA-seq analysis showed gp140-specific hu-B cells to express polyclonal IgG1 and IgG3 isotypes and a broad Ig VH/VL repertoire, with predominant VH3 family gene usage. These cells exhibited a higher rate of somatic hypermutation than the non-specific IgG+hu-B-cell counterpart. Both vaccine regimens induced splenic GC-like structures containing hu-B and hu-Tfh-like cells expressing PD-1 and BCL-6. We confirmed in this model that circulating ICOS+memory hu-Tfh cells correlated with the magnitude of gp140-specific B-cell responses. Finally, the NYVAC-KC heterologous prime led to a more diverse clonal expansion of specific hu-B cells. Thus, this study shows that CD40-targeted vaccination induces human IgG production in hu-mice and provides insights for the development of a CD40-targeting vaccine to prevent HIV-1 infection in humans.

项与 CD40.HIVRI.Env vaccine( ANRS/INSERM/Baylor Research Institute) 相关的新闻（医药）

2024-10-02

·GlobeNewswire-Health Care

Results from a Phase I clinical trial of a dendritic cell targeting prophylactic HIV vaccine published in the Journal eClinical Medicine

PRESS RELEASE Results from a Phase I clinical trial of a dendritic cell targeting prophylactic HIV vaccine published in the Journal eClinical Medicine Provides important validation of the safety and immunogenicity of EnnoDC’s technology The ANRS VRI06 trial, carried out by Inserm, ANRS MIE and the VRI, shows that the CD40.HIVRI.Env vaccine, is safe and induces early and sustained humoral and cellular immune responses against HIVThe first clinical trial results in humans with this novel type of vaccine, which consists of a monoclonal antibody fused to the HIV envelope, targeting the CD40 molecule expressed at the surface of dendritic cellsResults were published in the Journal eClinical Medicine, an open access clinical journal, published by The Lancet Paris, France, 2 October 2024 – EnnoDC* (or “the Company”), a clinical-stage biotech company pioneering the development of first-in-class dendritic cell-targeting immunotherapies, today notes the publication of positive results from a Phase I trial of its novel Dendritic Cell (DC) targeting prophylactic HIV vaccine in the Journal eClinical Medicine, an open access clinical journal, published by The Lancet. The multicentre, double-blind placebo-controlled dose-escalation trial was conducted at clinical sites in France and Switzerland. The results, published by scientists from the Vaccine Research Institute of Inserm and the Université Paris-Est Créteil, the CHUV in Lausanne and the University of Bordeaux, show that the vaccine, CD40.HIVRI.Env, is safe and induces early and sustained humoral and cellular immune responses against HIV. No serious side effects were observed. General and local reactions at the injection site were mainly mild to moderate. Two severe adverse events were reported, which were found to be unrelated to vaccination after analysis. EnnoDC’s first-in-class approach combines the power of vaccines and immunotherapies to provide targeted immune responses for both cancer and infectious diseases. CD40.HIVRI.Env combines a humanized anti-CD40 monoclonal antibody fused with HIV envelope antigens to stimulate DCs through CD40 and deliver a targeted immune response. Pr. Yves Lévy, co-founder, Chief Medical and Scientific Officer at EnnoDC and Principal Investigator of the trial commented: “These are exciting results for EnnoDC from the first clinical study using our novel dendritic cell targeting technology. The results show that this vaccine is safe and well tolerated and that humoral and cellular immune response were activated against HIV. The results support further development of the program. In addition, the results show that this type of treatment, which specifically targets antigens to the dendritic cells via the CD40 molecule, may be potent in inducing protective immunological responses in prime-boost vaccination strategies.” Christophe Hubert, Chief Executive Officer of EnnoDC, added: “These are very encouraging results which provide further validation of our technology with positive read across to our new immunotherapies, in development for HPV-induced cancers, prostate cancer and infectious diseases.” Last week EnnoDC unveiled the next generation of DC-targeting immunotherapies supported by new leadership and an evolved strategy. EnnoDC has an extensive pipeline of clinical and preclinical stage assets in HPV-induced cancers, prostate cancer and in infectious diseases. Further information on the ANRS VRI06 trial is available in a press release issued by the Vaccine Research Institute (VRI) of Inserm and the Université Paris-Est Créteil (Unit 955 Mondor Institute for biomedical research), the CHUV in Lausanne and the University of Bordeaux through the link below:Preventive vaccine against HIV: promising results in healthy volunteers with a new vaccine technology – Vaccine Research Institute (vaccine-research-institute.fr) The full paper, published in the October 2024 issue of eClinical Medicine, can be accessed through the following link: https://doi.org/10.1016/j.eclinm.2024.102845. Further details about the trial can be found online at https://clinicaltrials.gov/study/NCT04842682. *EnnoDC is the trading name of LinKinVax Europe SAS. -Ends- For more information please contact: EnnoDC Christophe Hubert, CEOinfo@EnnoDC.com ICR Consilium Ashley Tapp / Jonathan Edwards / Kumail Waljee EnnoDC@consilium-comms.comTel: +44 (0) 20 3709 5700 About EnnoDC EnnoDC, the trading name of LinKinVax, is a clinical-stage biotech company pioneering the development of first-in-class Dendritic Cell (DC)-targeting immunotherapies. Through our versatile DC-targeting immunotherapy platform we are developing CD40-specific monoclonal antibodies fused with pathogenic antigens to induce a highly specific, safe, broad, and long-lasting immune response to combat diseases like cancer and infectious diseases. The Company currently has three active clinical trials in various stages of clinical development, addressing oncology and infectious disease indications. Its lead asset, CD40HVac is currently in a Phase I/IIa clinical trial for HPV16+ oropharyngeal cancer patients. EnnoDC is a spin out from the Vaccine Research Institute (VRI), an institute of INSERM (the French National Institute of Health and Medical Research) and is supported by longstanding investors and internationally renowned key opinion leaders who contribute their expertise in the clinical development of EnnoDC’s assets and help explore the expansive therapeutic potential of its innovative platform. Find out more online at: http://www.EnnoDC.com Follow us on X and LinkedIn About ANRS MIEANRS Emerging Infectious Diseases is an autonomous agency of Inserm (the French National Institute for Health and Medical Research). Its mission is to facilitate, evaluate, coordinate and fund research into HIV/AIDS, viral hepatitis, sexually transmitted infections, tuberculosis and emerging and re-emerging infectious diseases. For more information: https://anrs.fr/en/ About the VRI and Inserm The Vaccine Research Institute (VRI), Laboratory of excellence, was established by Inserm (French National Institute of Health and Medical Research) and the University of Paris-Est Créteil (UPEC) to conduct research to accelerate the development of effective vaccines against HIV/AIDS and (re)-emerging infectious diseases. The VRI's structure strengthens the links between basic research and translational research, patient associations and the socio-economic world. The VRI extends a network of internationally renowned scientists and research teams with multidisciplinary expertise in system biology and clinical immunology, a network of clinical centres, and shared platform.For more information: https://vaccine-research-institute.fr/ Founded in 1964, Inserm is a public scientific and technological institute dedicated to biomedical research and human health and is involved in the entire range of activities from the laboratory to the patient’s bedside. It also partners with the most prestigious research institutions in the world that are committed to scientific challenges and progress in these fields.For more information: https://www.inserm.fr/en/home/ About Université Paris-Est Créteil: With 14 faculties, schools and institutes, 1 observatory and 32 research laboratories, Université Paris-Est Créteil has been active in all fields of knowledge since 1970. Each year, UPEC trains over 42,000 students and working professionals of all ages. A major player in the dissemination of academic, scientific and technological knowledge, the university offers more than 500 training courses in all disciplines and at all levels. UPEC offers personalized support for all successes, thanks to undergraduate and graduate training, recognition of prior learning and lifelong learning opportunities. Furthermore, the university runs a growing number of apprenticeship programs in order to stimulate entrepreneurship and ease professional integration. Université Paris-Est Créteil has built its strategic plan around three strategic orientations: UPEC is an engaged university that aims to match academic excellence with societal relevance. It encourages and supports all paths of students’ success with dedicated programs. UPEC masters its trajectory and is a university open to the world and its diversity. For more information: https://www.en.u-pec.fr/ About the University of Bordeaux With more 54,000 students, 3,200 researchers and teachers, and 2,800 staff members, the University of Bordeaux is one of the leading French public research and higher education institutions, located in a dynamic and culturally rich, fast-developing region. Ranked among the top universities in France, the University of Bordeaux is renowned for the quality of its academic courses and research. It is a multi-disciplinary, research-focused institution with a strong ambition to develop as a leading, international campus. The University of Bordeaux is leading an ambitious, competitive development program in partnership with local higher education institutes and national research organizations, in order to promote Bordeaux as a “Campus of Excellence”. For more information: https://www.inserm.fr/en/home/

免疫疗法临床1期疫苗

2023-07-11

·PRNewswire

Less than half of endocrinologists are impressed with Tzield's ability to delay T1D (MARKETVUE® REPORT)

Sanofi/formerly Provention's Tzield (teplizumab), a CD3 mAb, is the only FDA-approved disease-modifying therapy that delays progression of Stage 2 T1D in patients 8 years and older. However, less than half of U.S. clinicians are impressed with the drug's ability to delay T1D onset, according to findings from REACH Market Research. NEWTON, Mass., July 11, 2023 /PRNewswire/ -- Type 1 Diabetes (T1D) is a life-long autoimmune disease where the immune system destroys the insulin-producing islet cells in the pancreas until they no longer produce insulin. To date, insulin replacement therapy has been the backbone of T1D treatment but has a significant treatment burden on patients. Recently, clinical development appears to be shifting towards therapies that could delay the need for insulin and preserve beta cell function. To access REACH's MarketVue® Report on Type 1 Diabetes, visit or contact us at [email protected]. The launch of Tzield is an important milestone in T1D disease management in that patients in the pre-diabetic stage now have an option to delay T1D onset by ~2 years, thereby delaying insulin use. Further, the approval has increased interest and awareness around screening patients who may be at risk for the disease. While the approval of Tzield has created excitement amongst clinicians, the response to its efficacy and dosing is underwhelming; less than 30% of interviewed doctors reported that they found the dosing impressive, according to REACH Market Research 's MarketVue® assessment. Endocrinologist, U.S.: "What are the potential benefits of a drug like teplizumab in a person who has stage 2 diabetes? It is not a magical bullet, but it's a good start." The current T1D pipeline consists largely of insulin-based treatments with few therapies in development to delay T1D and insulin use in recent-onset patients, including: Sanofi's teplizumab label extension for patients 0-7 yrs and recent-onset T1D NIDDK's anti-thymocyte globulin and granulocyte colony-stimulating factor Diamyd Medical AB's Diamyd, an anti-IL5 mAb Dompe Farmaceutici S.p.A's ladarixin, an anti-IL-8, CXCR1 and CXCR2 inhibitor Novartis' iscalimab, an anti-CD40 mAb Endocrinologists interviewed by REACH are eager for preventative treatments that offer a longer time to T1D progression and more convenient dosing than Tzield. Meghana Pandit, REACH Analyst: "Tzield as a concept is viewed favorably by physicians, however, there are concerns around its dosing, and efficacy profile which is reported as marginal." About MarketVue® MarketVue® reports are a rare disease focused, fresh alternative to traditionally long and outdated market research reports. MarketVue® reports cover rare disease epidemiology and key market dynamics based on research from key opinion leader interviews, physician surveys, and secondary data. About REACH Market Research REACH is an independent pharmaceutical market research company focused on rare and niche diseases. With decades of experience in pharmaceutical market research and life sciences consulting, REACH fills an important gap in the market – accessible market research solutions for rare and niche diseases. SOURCE REACH Market Research

上市批准

2023-02-26

·药明康德

多款基因疗法使患者获益长达数年、HIV疫苗组合疗法展现积极疗效... | 一周盘点

▎药明康德内容团队编辑本期看点1. 用于治疗粘多糖病II型患者的基因疗法RGX-121使患者持续获益已达三年，有望明年递交上市申请。2. 疫苗组合疗法在治疗HIV的临床试验中展现积极疗效，使正在接受抗逆转录病毒治疗的HIV感染者无需接受抗逆转录病毒治疗（ART）治疗的时间延长。3. 安斯泰来用于治疗迟发型庞贝病的基因替代疗法积极数据公布，患者停用酶替代疗法51周时的功能检测结果依然保持稳定。4. 治疗法布里病的基因疗法ST-920早期临床数据公布，观察到关键生物标志物α-半乳糖苷酶A活性的持续升高，最长的已持续超过两年。药明康德内容团队整理RGX-121：公布1/2/3期临床试验数据REGENXBIO公司宣布了其候选基因疗法RGX-121用于治疗19岁以下的II型黏多糖贮积症（MPS II）患者的1/2/3期试验的积极数据。MPS II是一种罕见的神经退行性溶酶体贮积症，由溶酶体酶艾杜糖酸-2-硫酸酯（I2S）酶缺乏引起。这种关键酶活性的降低或丧失会导致糖胺聚糖（GAG）在溶酶体的积累，从而引起溶酶体功能障碍和神经退行性病变。目前该病的标准疗法为酶替代疗法。RGX-121是一种一次性的基因疗法，旨在使用AAV9载体将编码I2S酶的人艾杜糖酸-2-硫酸酯酶（IDS）基因递送至中枢神经系统（CNS）。此次公布的结果显示，RGX-121在3种剂量水平下均具有良好的耐受性，没有药物相关的严重不良事件（SAEs）。一次性给予RGX-121后，患者脑脊液（CSF）中GAGs呈剂量依赖性的减少令人鼓舞。其中，队列3（使用关键计划剂量水平）患者的CSF GAGs的降幅最大，在给药后第48周时已接近正常水平。此外，在RGX-121给药三年后，患者的神经发育和日常活动技能也获得了持续的改善。该公司表示计划在2024年递交生物制品许可申请（BLA）。HTI：公布1/2a期临床试验数据AELIX Therapeutics公司公布了其与吉利德科学（Gilead Sciences）合作开展的一项名为AELIX-003的临床研究的数据。该研究旨在评估接受ART的HIV感染者使用含有AELIX的HTI T细胞疫苗和吉利德科学的Toll样受体7（TLR7）激动剂vesatolimod治疗方案的安全性、耐受性、免疫原性和疗效。Vesatolimod是一种在研强效选择性口服TLR7激动剂，可直接激活浆细胞样树突状细胞。在这项研究中，vesatolimod会激活体内HIV的表达，增强疫苗诱导的免疫反应，从而消除病毒感染的细胞。T细胞疫苗的HTI免疫原含有特异性HIV抗原区域，那些具有“控制器表型”（controller phenotypes）的患者对于该区域有丰富的T细胞免疫反应，这意味着它们可以在不使用抗逆转录病毒药物的情况下极大程度地控制HIV。HTI疫苗旨在将免疫反应重新聚集于HIV中特别易受攻击的部位，包括从潜伏病毒库中激活的病毒。在这项研究中，所有受试者接受疫苗/vesatolimod治疗后将在仔细监测下暂停使用抗逆转录病毒药物，以确定干预措施是否能有效控制HIV水平。结果显示，该研究达到了安全性、耐受性和免疫原性的主要和次要终点。HTI疫苗与vesatolimod联用可诱导高水平的HTI特异性T细胞反应，使HIV感染者无需ART的时间延长。病毒库高的疫苗接种者能够在没有ART的情况下维持病毒缓解24周，而所有病毒库高的安慰剂组受试者在前12周内就需要开始ART治疗。AT845：公布1/2期临床试验数据安斯泰来（Astellas Pharma）更新了其正在进行的1/2期临床试验FORTIS的初步安全性和疗效数据，该试验评估了其在研腺相关病毒（AAV）基因替代疗法AT845在迟发型庞贝病（LOPD）成人患者中的安全性、耐受性和疗效。庞贝病是由于缺乏酸性α-葡萄糖苷酶（GAA）引起的遗传性溶酶体储存障碍，GAA的水平降低或缺失导致肌肉和其他组织溶酶体中底物糖原的积累，因此又称为2型糖原累积病。这是一种会造成骨骼肌与心肌失能、通常为致命性的罕见疾病。目前，酶替代疗法（ERT）是该病唯一的获批疗法，这是一种慢性治疗，每两周需输注一次，完全依赖于组织从血浆中摄取GAA。此次公布的数据显示，4名受试者中有3名在AT845给药后停止使用ERT，在停用ERT 19、44和51周时，他们的功能检测结果保持稳定。对接受过治疗的受试者（包括中止ERT的受试者）的持续评估显示，疾病功能终点（包括用力肺活量和6 min步行测试）持续保持稳定。所有受试者对AT845输注的耐受性良好，大多数治疗中出现的不良反应为轻度（1级），并被认为与治疗无关。ST-920：公布1/2期临床试验的新数据Sangamo Therapeutics公司于近日公布了其用于治疗法布里病（Fabry disease）患者的基因疗法ST-920的1/2期临床试验STAAR的最新初步结果。法布里病是一种溶酶体贮积症，由α-半乳糖苷酶A基因（GLA）突变引起，从而导致α-Gal A活性缺乏，无法正常代谢鞘氨醇三聚己糖苷（Gb3）。Gb3在体内的积聚可以对许多重要器官造成破坏，例如肾脏、心脏、神经、眼睛、肠道以及皮肤。ST-920是一款一次性输注、肝脏靶向的基因疗法。此疗法通过AAV向患者肝脏递送功能性GLA基因拷贝，从而使细胞恢复生产α-Gal A。此次更新的数据截至2022年10月20日，在13名患者中观察到α-Gal A活性的持续升高，最长的已持续超过两年。在6个月时接受首批肾脏活检的患者中，其中1名患者的Gb3的清除率达78%，肾小球足细胞损失减少77%。所有剂量递增试验中的患者均不用再接受ERT，至今不需要恢复ERT治疗。身体健康状况SF-36评分显示，患者的平均一般健康评分在临床意义和统计学意义上均有显著增加。该公司计划将于2023年针对该疗法开展3期试验。FBX-101：公布1/2期临床试验的新数据Forge Biologics公布了其新型基因疗法FBX-101在Krabbe病患者中开展的1/2期临床试验RESKUE的初步数据。Krabbe病是由一种负责分解某类脂质（如psychosine）的溶酶体酶半乳糖甘油糖苷酶（GALC）的基因功能缺失突变引起的。如果GALC功能缺失，psychosine在细胞中的毒性积累会导致大脑和周围神经系统的髓鞘细胞死亡，进而引起患者运动功能的丧失。目前，骨髓移植是治疗中枢神经系统性Krabbe病患者的标准治疗，但患者依然会发展为周围神经系统疾病，并最终导致死亡。FBX-101是一种腺相关病毒血清型rh10（AAVrh10）基因疗法，通常在造血干细胞移植后进行。FBX-101能够向中枢和外周神经系统中的细胞递送GALC基因的功能拷贝，已被证明能在功能上纠正中枢和周围神经病变和与Krabbe病相关的行为障碍，并显著提高该病动物模型的寿命。之前公布的1/2期试验结果显示，接受FBX-101治疗6个月时，患者白细胞中GALC的活性显著提高，运动功能得到改善，且大脑正常发育。Forge公司此次公布了患者接受治疗12个月时的随访数据，研究人员在患者的血浆和CSF中观察到GALC转基因的持续高表达，且患者的运动功能和大脑发育保持正常。此外，尚未观察到与治疗相关的SAE、肝酶升高或抗AAVrh10抗体的产生。IMC-M113V：公布1期临床试验数据Immunocore公司公布了其在研TCR疗法IMC-M113V的安全性和活性数据。这是一种双特异性可溶性TCR疗法，用于治疗HIV病毒感染者。IMC-M113V建立在Immunocore公司旗下ImmTAX技术基础上，旨在消除持续被艾滋病毒感染的CD4+细胞（“储库”）。IMC-M113V的靶点是Gag蛋白的肽段，该蛋白由被HIV感染的细胞表面HLA*A02递呈。减少这些细胞的数量是在没有抗逆转录病毒药物的情况下可能达到病毒抑制状态的一种方法，有望实现功能性治愈。此次公布的是一项开放标签的1/2期临床试验，旨在确定IMC-M113V治疗HIV感染者的安全性和生物活性的剂量，这些患者的HLA-A*02:01呈阳性、接受抑制性抗逆转录病毒疗法不超过7年。结果显示，所有的3种剂量下的IMC-M113V均表现出良好的耐受性，没有严重的不良事件，没有血液学或化学方面的明显变化，也没有出现细胞因子释放综合征（CRS）或神经毒性。在整个用药和随访过程中，血浆病毒载量保持抑制。在接受15 mg剂量的患者中有一半达到了预先设定的药效学活性指标。Allocetra：获西班牙药品和医疗器械管理局批准开展1/2期临床试验Allocetra是Enlivex Therapeutics公司正在开发的一种通用的现货型细胞疗法，旨在将巨噬细胞重新编程为稳态状态。将非稳态的巨噬细胞重编程为稳态状态对于重新平衡免疫系统和解决危及生命的疾病至关重要。在临床前研究中，使用Allocetra联用免疫检查点抑制剂（PD-1抑制剂或CTLA-4抑制剂）使患有卵巢癌的小鼠及患有腹膜间皮瘤的小鼠获得了具有统计学意义的生存获益。此前，Allocetra已在美国和以色列获批开展临床试验。DNL310：公布1/2期临床试验的新数据Denali Therapeutics公司公布了其针对MPS II开展的在研酶替代疗法DNL310的1/2期临床试验的新中期数据。DNL310是一款由IDS蛋白与Denali的酶转运载体（ETV）结合的融合蛋白药物。Denali的转运载体平台含有可与天然转运受体结合的工程化Fc片段，通过与在血脑屏障上表达的天然转运受体结合，借着转胞作用（transcytosis）能够将大分子递送到大脑。DNL310被设计为可以递送IDS蛋白至包含脑部的全身细胞与组织的溶酶体中，以对GAG进行分解。此次更新的数据显示，在接受超过49周的DNL310治疗后，研究人员观察到患者在多个量表评分上的积极变化，包括Vineland适应行为量表第二版（VABS-II）、用于评估认知能力的贝利婴幼儿发展量表（BSID-III）以及总体印象量表。听觉脑干反应测试的结果显示，DNL310能够改善患者的听力。其他生物标志物数据表明，DNL310能够使脑脊液中的硫酸乙酰肝素快速并持续正常化至正常健康水平，并改善溶酶体功能相关的生物标志物。目前，使用DNL310治疗的数据已长达两年，其安全性依旧与标准护理保持一致。BXQ-350：公布1期临床试验数据Bexion Pharmaceuticals公司公布了其S1P激活剂BXQ-350在患有复发性实体瘤（包括复发性恶性脑肿瘤）的儿童和年轻人中的1期临床试验数据。BXQ-350是一种由多功能、溶酶体激活蛋白Saposin C和磷脂酰丝氨酸组成的制剂，在体外和体内显示出临床前抗肿瘤作用，特别是在结直肠、脑和其他实体瘤中。Bexion公司已完成两个针对成人和儿科人群的单药1期试验。BXQ-350在这些项目中表现出强大的安全性，并证明了BXQ-350单药在一系列肿瘤中具有活性，包括多形性胶质母细胞瘤（GBM），结直肠癌和阑尾癌。此外，其他临床和非临床数据表明，BXQ-350在化疗诱导的周围神经病变中同样具有活性。BXQ-350在此次公布数据的研究中达到了安全性和最大计划剂量的目标，支持Bexion公司在新诊断的弥漫性内源性脑桥胶质瘤（DIPG）和弥漫性中线胶质瘤（DMG）中开展儿科1期研究。BA3182：IND申请获得FDA许可BA3182是BioAtla公司开发的条件激活的生物（CAB）EpCAM/CD3双特异性T细胞接合抗体，包含两个EpCAM结合位点和两个CD3ε结合位点，用于治疗晚期腺癌。EpCAM在实体瘤中的高水平表达使其成为抗体分子治疗上皮癌，特别是腺癌的有吸引力的靶标。然而，EpCAM在正常细胞中也非常普遍，传统的EpCAM/CD3双特异性抗体的使用会面临剂量限制毒性问题。体外研究表明，CAB双特异性抗体BA3182与靶蛋白人EpCAM和人CD3结合，在肿瘤微环境（TME）的特征性酸性条件下具有高特异性和亲和力，而在正常细胞的碱性生理条件下（pH 7.4）的结合力大大降低。体内研究表明，BA3182相比于非CAB变体的治疗指数提高了100倍以上。在获得了FDA的IND批准后，BioAtla公司将进行一项首次人体1期研究，以评估BA3182在晚期腺癌患者中的安全性、药代动力学（PK）和有效性。AL01211：公布1期临床试验的初步数据AceLink Therapeutics公司公布了其用于治疗法布里病的新型GCS抑制剂在健康受试者中的1期试验的初步数据。AL01211具有优秀的效力（个位数纳摩尔半抑制浓度IC50）、高选择性和其他良好的、可支持每日一次口服的药物特性，为目前需频繁静脉注射ERT的法布里病患者提供了口服小分子疗法的潜在选择。此次公布的结果显示，AL01211在健康受试者中的安全性和耐受性良好，并能使血浆药效学生物标志物呈剂量依赖性的降低。BX004：公布1b/2a期临床试验数据BiomX公司公布了其噬菌体鸡尾酒疗法BX004用于治疗铜绿假单胞菌引起慢性肺部感染的囊性纤维化（CF）患者的安全性和有效性数据。铜绿假单胞菌是引起CF患者肺部感染和死亡的主要因素。BX004旨在靶向和破坏铜绿假单胞菌。研究结果显示，BX004治疗在所有患者和剂量水平上均安全且耐受性良好。研究人员还观察到了初步的疗效信号，相比于安慰剂组，接受BX004治疗的CF患者的细菌负荷显著减少。CDX-7108：公布1期临床试验数据Codexis公司与Nestlé Health Science公司共同公布了一项1期临床试验的数据，该试验旨在评估其候选产品CDX-7108的安全性，耐受性，PK和药效学。CDX-7108是一种脂肪酶变体，专门设计用于克服现有胰酶替代疗法（PERT）的局限性。PERT是胰腺外分泌功能不全（EPI）的主要治疗方法，这是一种使人衰弱的胃肠道疾病，由损害胰腺功能的疾病引起，例如胰腺炎、胰腺癌、克罗恩病、乳糜泻和囊性纤维化。CDX-7108对胃中的酸性条件高度稳定，并对上肠中的蛋白酶具有抗性。此次公布的初步数据显示，与安慰剂相比，接受CDX-7108的患者的脂质吸收有所改善。此外，在参与单次剂量递增和多次剂量递增研究的48名受试者中没有发现安全问题。Sevuparin：公布1b期临床试验数据Modus Therapeutics公司公布了其创新专有多糖药物sevuparin用于治疗败血症的早期临床试验的积极数据。Sevuparin具有多模式的作用机制，包括抗炎，抗粘附和抗聚集作用，是一种具有明显减弱的抗凝血特征的类肝素，与常规类肝素相比，可以给予高几倍的剂量，而没有相关的出血副作用风险。此次公布的试验结果显示，在脂多糖（LPS）诱导产生短暂炎症反应的健康受试者中，所有3种剂量水平下的sevuparin都是安全的，且耐受性良好。此外，sevuparin治疗使受试者的某些白细胞群水平呈剂量依赖性增加，在统计学上具有显著性，并能使LPS诱导的呼吸频率增加呈剂量依赖性的抑制。这些发现表明sevuparin有潜力作为全身炎症（包括败血症和感染性休克）的治疗方法。CD40.HIVRI.Env：公布1期临床试验的中期数据LinKinVax公司公布了其靶向树突状细胞的候选疫苗CD40.HIVRI.Env在健康受试者中的1期安全性和免疫原性结果。树突状细胞是免疫系统的关键激活剂，CD40.HIVRI.Env是一种将HIV包膜蛋白与特异性靶向树突状细胞表面CD40受体的单克隆抗体结合而成的候选疫苗，旨在预防艾滋病毒感染。此次公布的数据显示，该候选疫苗的安全性和耐受性良好，且能够诱导早期、显著和持续的免疫反应。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] LinKinVax Welcomes Interim Results of the ANRS VRI06 Phase I Trial Evaluating a Novel HIV Vaccine Candidate. Retrieved February 24, 2023, from https://www.businesswire.com/news/home/20230222005313/en/[2] BiomX Announces Positive Results from Part 1 of the Phase 1b/2a Study Evaluating BX004 for Treatment of Chronic Pulmonary Infections in Patients with Cystic Fibrosis. Retrieved February 24, 2023, from https://www.globenewswire.com/news-release/2023/02/22/2612975/0/en/BiomX-Announces-Positive-Results-from-Part-1-of-the-Phase-1b-2a-Study-Evaluating-BX004-for-Treatment-of-Chronic-Pulmonary-Infections-in-Patients-with-Cystic-Fibrosis.html[3] AELIX has presented promising top-line results from the clinical study AELIX-003 at the 2023 Conference on Retroviruses and Opportunistic Infections (CROI). Retrieved February 24, 2023, from https://www.aelixtherapeutics.com/aelix-therapeutics-presents-positive-results-from-randomized-placebo-controlled-phase-iia-therapeutic-hiv-vaccine-and-immune-modulator-combination-clinical-trial/[4] Immunocore announces initial Phase 1 safety and pharmacodynamic activity data with first soluble TCR therapy for people living with HIV，Retrieved February 2rd, 2023 from https://ir.immunocore.com/news-releases/news-release-details/immunocore-announces-initial-phase-1-safety-and-pharmacodynamic[5] Modus Therapeutics announces positive topline data from its Phase 1b LPS provocation study evaluating the potential of sevuparin for treatment of sepsis. Retrieved February 2rd, 2023 from https://www.modustx.com/press-release?releaseIdentifier=bef7616d-cdc3-4eae-830e-01a83e23f4af[6] Astellas Announces Update on Preliminary Safety and Efficacy Data from FORTIS Study of Investigational AT845 in Adults with Late-Onset Pompe Disease. Retrieved February 24, 2023, from https://www.prnewswire.com/news-releases/astellas-announces-update-on-preliminary-safety-and-efficacy-data-from-fortis-study-of-investigational-at845-in-adults-with-late-onset-pompe-disease-301750884.html[7] Additional Positive Interim Data from Phase I/II/III CAMPSIITE™ Trial of REGENXBIO's RGX-121 for the Treatment of MPS II (Hunter Syndrome) Presented at 19th Annual WORLDSymposiumTM. Retrieved February 24, 2023, from https://www.prnewswire.com/news-releases/additional-positive-interim-data-from-phase-iiiiii-campsiite-trial-of-regenxbios-rgx-121-for-the-treatment-of-mps-ii-hunter-syndrome-presented-at-19th-annual-worldsymposiumtm-301753564.html[8] Sangamo Therapeutics Announces Evidence of Clinical Benefit in Phase 1/2 STAAR Study in Fabry Disease. Retrieved February 24, 2023, from https://www.businesswire.com/news/home/20230222005671/en[9] Denali Therapeutics Announces New Interim Data from DNL310 Phase 1/2 Study for MPS II and DNL126 Preclinical Data for MPS IIIA at WORLDSymposium™. Retrieved February 24, 2023, from https://www.denalitherapeutics.com/investors/press-release?id=9226&type=api[10] Codexis and Nestlé Health Science Announce Interim Results from Phase 1 Clinical Trial of CDX-7108 for Exocrine Pancreatic Insufficiency. Retrieved February 25, 2023, from https://www.globenewswire.com/news-release/2023/02/23/2614809/24825/en/Codexis-and-Nestl%C3%A9-Health-Science-Announce-Interim-Results-from-Phase-1-Clinical-Trial-of-CDX-7108-for-Exocrine-Pancreatic-Insufficiency.html[11] Bexion Pharmaceuticals, Inc. Announces Publication of Pediatric Phase 1 (KOURAGE) Results. Retrieved February 25, 2023, from https://www.prnewswire.com/news-releases/bexion-pharmaceuticals-inc-announces-publication-of-pediatric-phase-1-kourage-results-301754621.html[12] BioAtla Announces FDA Clearance of Investigational New Drug Application for BA3182, a CAB-EpCAMxCAB-CD3 Bispecific T-Cell Engager for the Treatment of Advanced Adenocarcinoma. Retrieved February 25, 2023, from https://ir.bioatla.com/news-releases/news-release-details/bioatla-announces-fda-clearance-investigational-new-drug-0[13] AceLink Presents Phase 1 Study of AL01211 to Treat Fabry Disease at WORLD Symposium. Retrieved February 25, 2023, from https://www.businesswire.com/news/home/20230223005278/en/[14] Enlivex Receives Clearance From Spanish Agency of Medicines and Medical Devices For Treatment of Patients with Advanced Solid Malignancies in the Ongoing Allocetra Phase I/II Clinical Trial. Retrieved February 25, 2023, from https://enlivex.com/investor-relations/#latest-news[15] Forge Biologics Reports Positive FBX-101 Clinical Updates for Patients with Krabbe Disease at WORLDSymposium. Retrieved February 25, 2023, from https://www.businesswire.com/news/home/20230223005450/en/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

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