This is a Phase 2 clinical study in patients with actinic keratosis involving daily application of 1 of 2 strengths of VDA-1102 topical ointment for approximately 12 weeks (84 days). This study has no placebo and the subjects enrolled in the study will know exactly what they are receiving. The objectives of the study are to evaluate the safety and benefit of these two strengths.

开始日期2018-05-23

申办/合作机构

Vidac Pharma Ltd.

[+3]

NCT02844777

/ Completed临床2期

Randomized, Double-Blind, Placebo-Controlled, Parallel-Cohort Study to Evaluate the Efficacy, Safety, Tolerability, and Pharmacokinetics of Once-Daily Application of Topical VDA-1102 Ointment for 28 Days in Subjects With Actinic Keratosis

This Phase 2 clinical trial is a multi-center, randomized, double-blind, placebo-controlled, multiple-dose, parallel-cohort study to assess the efficacy, safety and tolerability of VDA-1102 in the treatment of actinic keratosis (AK) on the head of male and female adult subjects.

开始日期2016-07-15

申办/合作机构

Vidac Pharma Ltd.

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项与 Vidac Pharma Ltd. 相关的文献（医药）

2018-12-01·Journal of Investigative Dermatology1区 · 医学

A Hexokinase 2 Modulator for Field-Directed Treatment of Experimental Actinic Keratoses

1区 · 医学

Article

作者: Kozminsky-Atias, Adi ; Herzberg, Max ; Arbel, Nir ; Becker, Oren M ; Loeb, Emmanuel ; Behar, Vered ; Pahima, Hadas

Overexpression of hexokinase 2, and its binding to VDAC1 on the outer mitochondrial membrane of cancer cells, is key to their metabolic reprogramming to aerobic glycolysis, which enables them to proliferate. We describe Comp-1, an allosteric small molecule that selectively detaches hexokinase 2 from the mitochondria. Detachment of hexokinase 2 reduces glycolysis and triggers apoptosis in cancer cells, without affecting hexokinase 1-expressing normal cells. The anti-cancer activity of Comp-1 was demonstrated in the UVB-damaged skin model in SKH-1 mice. Topical treatment with Comp-1 led to 70% reduction in lesion number and area. This in vivo efficacy was obtained without local skin reactions or other safety findings. Mechanism-related pharmacodynamic markers, including hexokinase 2 and cleaved caspase 3 levels, are affected by Comp-1 treatment in vivo. Good Laboratory Practice toxicology studies in minipigs for 28 days and 13 weeks established no systemic toxicities and minimal dermal reaction for once-daily application of up to 20% and 15% ointment strengths, respectively. Thus, Comp-1 may address a significant unmet medical need for a non-irritating efficacious topical actinic keratosis treatment.

2018-07-01·Cancer Research

Abstract 1725: A bi-functional mechanism of action: Activating the NLRP3 inflammasome and triggering apoptosis in cancer via a HK2-VDAC modulator

作者: Becker, Oren M. ; Dor-On, Eyal ; Hamo, Reut Yosef ; Behar, Vered

AbstractIntroduction: Cancer cells undergo metabolic reprogramming to enable the efficient conversion of glucose needed for massive cell growth and proliferation, a well-documented phenomenon known as the Warburg effect. A key enzyme in this process is hexokinase 2 (HK2), which catalyzes the first step of glucose metabolism. Unlike HK1, which is ubiquitously expressed in normal cells, high levels of HK2 are found in cancer where it is required for cancer initiation and transformation. HK2 in cancer cells is attached to the outer mitochondrial membrane via the VDAC1 channel. VDAC1/HK2 association blocks pro-apoptotic signals as well as allows a continuous flux of mitochondrial ATP to HK, leading to apoptosis prevention and a high rate of glycolysis.Temporal high HK2 expression, and binding to VDAC, is also found in a variety of activated immune cells to support their changing metabolic needs. It has been recently published that detachment of HK2 from VDAC is one of the first events leading to the NLRP3-inflammasome activation, resulting in IL-1β and IL-18 secretion from macrophages (Cell 166:624 (2016)).Methods: A novel small molecule VDAC/HK2 modulator, VDA-1102, is being developed as a bi-functional drug for the treatment of solid tumors – triggering apoptosis in cancer cells while simultaneously activating the NLRP3-inflammasome in macrophages to induce an anti-tumoral immune response.Results: In vitro studies established that VDA-1102 selectively detaches HK2, but not HK1, from VDAC leading to cancer cell apoptosis, glycolysis inhibition, and prevention of cancer cell proliferation. VDA-1102 treatment of mouse primary bone marrow-derived macrophages and of human macrophage cell line, THP-1 cells, established a dose-dependent NLRP3-inflammasome activation and cytokine secretion. In vivo efficacy studies demonstrated significant tumor growth delay in syngeneic solid tumor models.Analysis of tumor-associated macrophages indicated a treatment-induced change in these macrophage phenotype from M2 to M1. This change was associated with a notable increase in spleen size, an increase ratio of naïve T cell in the spleen, and a significant increase in CD8+ and CD4+ tumor-infiltrating T cells.Conclusions: This data supports the notion that VDA-1102 is a bi-functional drug that targets both cancer and the innate immune system. In cancer cells it induces apoptosis, whereas in macrophages it activates the NLRP3-inflammasome machinery and stimulates an anti-tumor immune response. Our findings support further development of VDA-1102 to evaluate its potential as an anti-cancer therapy, either as a monotherapy or in combination with checkpoint inhibitors in high HK2-expressing solid tumors.Citation Format: Vered Behar, Reut Yosef Hamo, Eyal Dor-On, Oren M. Becker. A bi-functional mechanism of action: Activating the NLRP3 inflammasome and triggering apoptosis in cancer via a HK2-VDAC modulator [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1725.

A novel chemical entity, that reverses Warburg metabolism by disrupting VDAC1/HK2 interaction through “Toposteric Effect” in Cancer

作者: Becker, Oren M. ; Yosef, Reut ; Herzberg, Max ; de Conto, Veronique ; Pahima, Hadas ; Behar, Vered ; Sagiv, Yuval ; Maubon, Nathalie ; Dor-On, Eyal

Abstract

Background Acidic pH and low oxygen levels Due to the Warburg effect have been shown to impart resistance to certain anti-cancer therapies for solid tumors, such as radiation and a variety of chemotherapeutic drugs. Cancer immunotherapy represents one of the most exciting advancements in recent cancer therapy. However, despite these achievements, the numbers of patients with effective cure are very low for patients with solid tumors. Recent studies pointed out that the main cause for this low efficiency is the Tumor microenvironment (TME), with metabolic changes, and immune evasion that renders solid tumor eradication a real challenge. Drugs targeting the inhibitory TME are urgently needed in combination with Immunotherapy, as well as other conventional therapies like chemotherapy and cancer targeted growth blockers. Methods In this study we used an inhibitor of Hexokinase-2 binding to the mitochondrial VDAC1 channel (VDA-1275), that is shown to block cancer cell proliferation, induce apoptosis in cancer cells, and change TME from a protumor to a pro-immunological environment. Our studies demonstrate a significant tumor growth inhibition and survival prolongation, combined with a strong safety profile in-vivo. In addition, a powerful synergistic anti-cancer effect was demonstrated, using a 3D cell culture with human hepatic cancer cell organoids, when VDA-1275 was combined with low levels of Cisplatin or Sorafenib, as examples for chemotherapy and targeted therapy treatments, respectively. Results Our results suggest that VDA-1275 is a novel compound that effect cancer cells directly and indirectly by changing the TME to a pro-immunogenic environment. Conclusion VDA-1275 may be used as a standalone drug, or in combination therapy that will allow more effective and safe treatment of patients with solid tumors. We coined the word and concept of “Toposteric” effect as the use of small molecules or peptides which interact with a receptor or ligand binding site avoiding the possibility of a pro-pathological harmful anchoring without affecting its active site.

项与 Vidac Pharma Ltd. 相关的新闻（医药）

2024-11-07

·Pharmaceutical Technology

Vidac secures funding to advance skin cancer trials of novel ointment

Actinic keratosis is a pre-cancerous area of thick, scaly, or crusty skin. Credit: Douglas Cliff via Shutterstock. Vidac Pharma has secured €600,000 ($645,651) in additional funding to support the clinical development of its two lead cancer candidates. The funding from existing investors, announced at the company’s recent shareholder meeting, will enable Vidac to initiate a new Phase IIb trial for its lead candidate VDA-1102 (tuvatexib) ointment. The hexokinase 2 inhibitor is being investigated in advanced cases of actinic keratosis, a skin condition that can progress to cutaneous squamous cell carcinoma (SCC). Alongside VDA-1102, the UK-based biotech continues preclinical studies of VDA-1275. Both candidates target the metabolic pathways of cancer cells by disrupting hexokinase 2 interactions with mitochondrial channels, aiming to reverse the high-energy demands of tumours and promote cancer cell death. VDA-1275 is being developed as a systemic drug for the treatment of solid tumours. Interim data from a Phase IIa study (NCT02844777) released in January 2023 showed a 56% objective response rate (ORR), with 22% complete responses (CR), observed between eight and 12 weeks. This compares to the standard-of-care treatment mechlorethamine, which has a 13% CR and a longer median response time of 26 weeks. Final results are expected in Q4 2024. Vidac has also completed a Phase IIb clinical trial (NCT03538951) for VDA-1102 in actinic keratosis. In a post-hoc analysis, the therapy demonstrated a 40% complete clearance of lesions and an 80% overall reduction in lesion count. The study also indicated that patients with advanced actinic keratosis responded more favourably to the treatment than those with less severe forms. Based on these findings, the upcoming Phase IIb trial will focus specifically on patients with advanced actinic keratosis. Unlike conventional actinic keratosis treatments that directly destroy abnormal cells, through topical therapies, cryotherapy, or photodynamic therapy, VDA-1102 works by reprogramming cancer cell metabolism. This selective approach aims to spare healthy cells, and in the Phase IIa trial, resulted mostly in mild, localised side effects, with one moderate case. Standard actinic keratosis treatments, by contrast, can cause skin inflammation, scaling, or burning, and are often invasive. In the announcement accompanying the funding, Vidac’s CEO Max Herzberg said: “I want to thank our board, advisers, team and shareholders for their support for our entirely new approach in oncology, with drugs that reverse the supercharged metabolism of cancer cells.” In June 2024, Almirall ’s Klisyri (tirbanibulin) secured FDA-expanded approval to treat larger actinic keratosis areas to up to 100cm² from the previous maximum of 25cm². Klisyri works by blocking cell division and killing abnormal cells. The most common side effects are local skin reactions, including erythema (reddening of the skin), flaking/scaling, crusting, swelling and the formation of sores and ulcers. Innovations in the pharma and medical device landscape are looking to expedite the diagnosis of skin cancers. In July 2023, the National Cancer Institute (NCI), part of the US National Institutes of Health (NIH), awarded $2m in funding to Enspectra Health through the Small Business Innovation Research (SBIR) programme. The grant will fund the development of deep learning algorithms that can predict which actinic keratosis skin lesions are likely to turn into SCC.

临床2期临床结果上市批准

2024-05-28

·药时代

强生公布「核药」I期临床数据，4名受试者死亡！

正文共：1815字 4图预计阅读时间：10分钟2024年5月21日，礼来掷重金与Aktis Oncology——一家拥有新型微型蛋白技术放射性药物平台的biotech，达成合作协议。据新闻稿披露，双方协议金额最高可达11亿美元，礼来将获得一系列明确靶标的放射性药物和诊断产品的权利。在此之前，包括诺华、拜耳、强生、BMS、阿斯利康、默沙东、强生等一众MNC均通过并购、引进、股权投资等方式入局核药。MNC再次出手核药，正是应了之前文章中提到的一个观点：核药已成MNC管线布局新风向（点击查看原文）。不过平心而论，核药并非易得的果实，MNC布局核药，能不能上市还真不一定。014名受试者死亡近日，强生在ASCO会议上首次公布了其放射性配体疗法JNJ-69086420（JNJ-6420）用于转移性去势抵抗性前列腺癌（mCRPC）的I期研究数据。JNJ-6420 是首款靶向hK2的放射性配体疗法。其中，hK2指的是人组织激肽释放酶2（human kallikrein 2）——一种在前列腺组织中表达的蛋白，在前列腺癌细胞中表达水平较高，在其他部位的表达受到限制。借助hK2抗体的靶向功能，JNJ-6420 能够特异性地与前列腺癌细胞表面的hK2蛋白结合，向前列腺癌细胞发射高能短程α粒子225Ac。根据ASCO官网口头摘要信息，此次公布的这项I期剂量爬坡试验的受试者均为经大量预处理、但未经生物标志物筛选的mCRPC患者，且这些患者在入组前至少接受过一种雄激素受体途径抑制剂治疗。试验通过静脉注射的方式，剂量探索范围从50毫居里(mCi)递增到400μCi，每8-12周给药一次。截至2024年1月5日，在这项I期临床试验中共有67名患者接受了≥1次 JNJ-6420的治疗。但从此次披露数据来看，JNJ-6420的安全性并不如意。据悉，在整个试验中，共有9名患者因治疗相关不良事件(TRAEs)放弃治疗，并有4名患者因TRAE导致死亡。完整数据显示，其中两名患者的死亡与间质性肺病（ILD）有关，一例与COVID-19引起的呼吸衰竭有关，另一例与食欲减退及低血压有关。ILD是肿瘤治疗中常见的不良事件，它会导致肺组织逐渐疤痕化。患者初步表现为呼吸困难、咳嗽、疲劳等症状，严重时危及生命。摘要中提到，目前有9%的受试者出现了ILD，且所有ILD的情况均发生在实施肺功能监测之前累积剂量达到或超过500 μCi的患者中。另外，在初步研究中，研究人员对57名接受过≥150μCi JNJ-6420患者的治疗效果进行了分析。其中，约2/3的患者经历了3级或更高级别的因治疗导致的不良事件(TEAEs，包括血小板减少症、间质性肺病、淋巴细胞减少症、白细胞减少症），且有近1/3的患者经历了严重TEAE。从积极的角度来看，目前JNJ-6420已经初显有效性，并展现出显著且持久的生化和影像学反应。根据摘要披露信息，在所有57名接受≥150μCi JNJ-6420的患者中，有一半患者被观察到前列腺特异性抗原水平下降50%。在中期分析时，客观缓解率（PR）为12.5%，且有1例患者表现出完全缓解，疾病控制率（DCR）达到28.1%。02JNJ-6420：潜在FIC安全性是一款药品上市的重要门槛之一，JNJ-6420在当下试验方案中的表现显然不达标，需要进一步调整试验方案。在之后的ASCO会议现场，强生将继续公布更多关于JNJ-6420相关试验数据。回到JNJ-6420这款药本身，上文提到过，JNJ-6420为靶向hK2的α放射性配体疗法。从靶点上看，hK2是实实在在的小众靶点。根据智慧芽数据库，目前并未有相应靶点产品上市。处于临床阶段的，除了JNJ-6420外，就仅有由Vidac Pharma Ltd.研发的一款小分子药物，目前处于临床II期阶段。此外，这款药的同位素为锕-225 （225Ac），属于α放射性核素。在核药的研发历史上，β放射性核素一直处于领先地位，包括诺华的Pluvicto和Lutathera均选择了177Lu——β放射性核素。直至2013年，全球首个α放射性核素药物（氯化镭223）才获FDA批准上市，用于治疗前列腺癌骨转移。从物理特性上讲，α放射性核素在治疗上优于β放射性核素。因为相比之下，α粒子的穿透力较弱，射程通常在几细胞直径范围内，因此对周围正常组织的损伤较小。但短射程也决定了这种核素在治疗中，很难对深部或广泛转移肿瘤起到好的治疗作用。同时相应的，生产和处理也较β放射性核素高。在近期的几笔核药相关交易中，α放射性核素频繁出现。2023年12月，BMS以36亿美元（扣除被收购方账面现金后价格）收购RayzeBio，RayzeBio的核心管线RYZ101使用的也是锕基载荷，正在开发用于胃肠道胰腺神经内分泌肿瘤和小细胞肺癌。此外，2024年3月，阿斯利康最高24亿美元收购到手的Fusion的核心管线FPI-2265也属于锕基候选药物，同样用于治疗mCRPC患者。小结核药这颗果子不好摘。从研发过程来看，因涉及药学、辐射剂量学、辐射生物学等多个学科，对科研人才经验积累要求相对高。同时，因含有放射性同位素，其生产、使用及配送都受到十分严格的政策监督，进一步成本和研发难度也随之上涨。目前一众MNC纷纷押宝，谁又能拿下一个核药上市产品？参考资料：1.Targeted Alpha-Particle Therapy: A Review of Current Trials2.各公司官网3.ASCO官网4.其他公开资料封面图来源：pixabay版权声明/免责声明本文为药时代原创文章。本文仅作信息交流之目的，不提供任何商用、医用、投资用建议。文中图片、视频、字体、音乐等素材或为药时代购买的授权正版作品，或来自微信公共图片库，或取自公司官网/网络，部分素材根据CC0协议使用，版权归拥有者，药时代尽力注明来源。如有任何问题，请与我们联系。衷心感谢!药时代官方网站:www.drugtimes.cn联系方式:电话:13651980212微信:27674131邮箱:contact@drugtimes.cn12周仅减重4.3%！GLP-1/GLP-2双靶点能否走通？「周制剂」降糖时代，GLP-1仍有“盲区”一款药物撑起4笔BD，三个经手药企均被并购！点击阅读原文，了解更多！

临床结果临床1期ASCO会议并购

2024-03-27

·GlobeNewswire-Health Care

Vidac Pharma receives Japanese Patent Office Notice of Allowance for VDA-1275 cancer drug candidate

Vidac Pharma receives Japanese Patent Office Notice of Allowance for VDA-1275 cancer drug candidate London (UK), March 27, 2024 (07:30 CET) – Vidac Pharma Holdings Plc. (Hamburg and Stuttgart: T9G; ISIN:GB00BM9XQ619; WKN: A3DTUQ), a clinical-stage oncology biopharmaceutical company pioneering a novel class of cancer treatments, today announces it has received a Notice of Allowance from the Japanese Patent Office for the composition and methods of use for its VDA-1275 drug candidate, which has shown multiple promising effects in preclinical studies. “Receiving this notice from the Japanese authorities adds to our excitement about VDA-1275, Vidac’s next and powerful anti-cancer drug candidate. In recent preclinical studies, this new molecule has shown effects, both directly against a variety of tumors in animal trials, and through powerful synergistic effects in combination with two widely used types of chemotherapy in human liver organoids,” Vidac Pharma Chief Executive Officer Max Herzberg said. Last month, Vidac announced results showing that VDA-1275 statistically significantly increased survival in a murine colorectal cancer model as a stand-alone treatment, with a survival benefit similar to Opdivo in a head-to-head comparison. In a 3-D organoid model of human liver cancer, it reduced the concentrations of sorafenib and cisplatin needed to achieve IC50 cancer cell viability by 50% and 95%, respectively. Finally, VDA-1275 triggered an immune response through several mechanisms. The company will publish these results in a peer-reviewed publication. Both VDA-1275 and the more advanced VDA-1102, which is in separate Phase 2 testing of advanced actinic keratosis and of cutaneous T cell lymphoma, disrupt the interaction between hexokinase 2 (HK2) and the voltage-dependent anion channels (VDACs) in mitochondria. Cancer cells overexpress HK2, which catalyzes the first step of the glucose metabolism necessary to fuel tumor growth. HK2 blocks VDACs, which prevents apoptosis, supports cancer cell proliferation, and suppresses immune responses. Clinical data for Vidac’s first-generation metabolic checkpoint modulator candidates have shown powerful effects in halting cancer cell proliferation and restoring immune-sensitivity and apoptosis. For more information please contact: Vidac Pharma Holding PlcDr Max Herzberg20-22 Wenlock RoadLondon N1 7GUUnited Kingdomhttp://www.vidacpharma.com/investors@vidacpharma.com+972-54-4257381+972-77-9300647Cohesion BureauGiovanni Ca’ ZorziInvestor Relationsgiovanni.cazorzi@cohesionbureau.comSophie BaumontMedia Relations sophie.baumont@cohesionbureau.com About Vidac Pharma Vidac Pharma is a clinical-stage biopharmaceutical company dedicated to discovering and developing first-in-class medicines to help people suffering from a range of oncologic and onco-dermatologic diseases. Vidac develops first-in-class anti-cancer drugs by modifying the hyper glycolytic tumor microenvironment, targeting the overexpression and wrong anchoring of the Hexokinase 2 metabolic checkpoint (HK2) in cancer cells, to renormalize tumor microenvironment and selectively provoke their programmed death without affecting surrounding normal tissue. VDA-1102, a first drug candidate of Vidac Pharma has shown to be effective against advanced Actinic Keratosis (AK) and interim results in Cutaneous T-cell Lymphoma (CTCL) gave positive effect in Phase 2 trials in humans.www.vidacpharma.com Important information The information in this press release does not constitute a public offer to sell or a solicitation to submit an offer to buy or subscribe to shares of Vidac Pharma Holding PLC, but is for informational purposes only. The contents of this announcement include statements that are, or may be deemed to be, "forward-looking statements". These forward-looking statements can be identified by the use of forward-looking terminology, including the words "believes", "estimates," "anticipates", "expects", "intends", "may", "will", "plans", "continue", "ongoing", "potential", "predict", "project", "target", "seek" or "should", and include statements the Company makes concerning the intended results of its strategy. By their nature, forward-looking statements involve risks and uncertainties and readers are cautioned that any such forward-looking statements are not guarantees of future performance. The Company's actual results may differ materially from those predicted by the forward-looking statements. The Company undertakes no obligation to publicly update or revise forward-looking statements, except as may be required by law. Attachment 20240327 - VIDAC PR Japan patent VDA1275

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药物(靶点)	适应症	全球最高研发状态

Tuvatexib ( HK2 x VDAC1 )	皮肤T细胞淋巴瘤更多	临床2期
VDA-1275 ( HK2 )	实体瘤更多	临床前
VDA-1214 ( HK2 )	实体瘤更多	终止
VDA-1270 ( HK2 )	实体瘤更多	终止