VDAC

LONDON, UK I January 29, 2024 I Vidac Pharma Holdings Plc. (Hamburg and Stuttgart: T9G; ISIN:GB00BM9XQ619; WKN: A3DTUQ), a clinical-stage oncology biopharmaceutical company pioneering a groundbreaking new way of treating cancer, today announces favorable findings from a Phase 2a interim analysis of its lead drug candidate VDA-1102 in Mycosis Fungoides (MF), a form of Cutaneous T-Cell Lymphoma (CTCL) and a rare “orphan” disease which might command fast-track regulatory processing . The data provide further signs of the efficacy and safety of Vidac Pharma’s family of non-toxic small molecules in treating cancer. The interim analysis of 50% of subjects showed an Objective Response Rate (ORR) of 56%, with 22% complete response (CR), and 34% partial response. Responses were observed between 8 and 12 weeks. These results compare favorably to the standard of care of mechlorethamine, which has a 13% CR and a much longer median response time of 26 weeks. Side-effects were local and mild in severity, except in one case, which was moderate. All patients recovered, however, and the disease did not progress in any of the patients during the 4 months of the study. “These interim results are another important confirmation that Vidac Pharma’s approach of attacking cancer at its core has substantial therapeutic potential. Our drug candidates reverse the abnormal metabolism that is a characteristic of all cancer cells, halting tumor proliferation and immune-resistance. What we are seeing bears the promise of applying these drugs across a wide range of cancers,” said Vidac Pharma Chief Executive Officer Max Herzberg. The interim results come from more than 50% of planned patients - 9 out of 16 – in an open-label within-subject placebo-controlled study into the efficacy and safety of VDA-1102 as a topical ointment treatment for 12 weeks in adult subjects with relapsed stage-1 MF. Next milestones are full-population interim results, expected in the second quarter, and final results in Q4. Vidac Pharma is developing a breakthrough new technology which reverses the abnormal metabolism of cancer cells – known as the Warburg effect - by preventing the Hexokinase 2 (HK2) enzyme from blocking the VDAC mitochondrial relay channels. Clinical data have shown the powerful effects this can have in halting cancer cell proliferation and restoring programmed cell death. Vidac’s lead drug candidate VDA-1102 is also at the clinical development stage for patients with actinic keratosis (AK), for which the company will soon launch a second Phase 2b study. 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 was proven effective against advanced Actinic Keratosis (AK) and Cutaneous T-cell Lymphoma (CTCL) in Phase 2 trials in humans. www.vidacpharma.com SOURCE: Vidac Pharma

12月24日的《热心肠日报》，我们解读了 10 篇文献，关注：发酵食品，心血管，n-3脂肪酸，时间营养学，素食，糖尿病，脂肪肝，生酮饮食，热量限制，3D打印，环保。 Nature Reviews：发酵食品与胃肠健康（综述） Nature Reviews Gastroenterology and HEPAtology——[65.1] ① 发酵食品（FF）对人体健康的各个方面，尤其是胃肠道健康都有益影响，FF中的发酵过程可以产生新的化合物，例如生物活性肽和胞外多糖；② 发酵可以帮助从食物基质中去除潜在的有毒或有害化合物，将FF中的活的或死的微生物或其成分引入肠道可以带来健康益处；③ FF中有益微生物和生物活性化合物的独特组合可以通过多种方式促进胃肠道健康；④ 充分了解FF的治疗和临床潜力，需要进一步研究，包括随机对照试验和采用基于组学的方法的跨学科研究。 【主编评语】 虽然发酵最初可能是作为保存食物底物的一种手段而发展起来的，但许多发酵食品及其成分被认为对人类健康的各个方面特别是胃肠道健康具有有益的影响。近期发表于Nature Reviews Gastroenterology and Hepatology的一篇综述重点讨论了发酵食品促进肠道健康潜力的机制。（@注册营养师陈彬林） 【原文信息】 Fermented foods and gastrointestinal health: underlying mechanisms 2023-12-11, doi: 10.1038/s41575-023-00869-x 增加EPA或DHA摄入，对有心血管病家族史者或有益 Circulation——[37.8] ① 本研究纳入来自10个不同国家且基线时无心血管疾病（CVD）的40,885名成年人，用血液或组织测定的多不饱和脂肪酸作为饮食摄入的替代标志；② 与无EPA/DHA摄入低且无CVD家族史的人群相比，EPA/DHA摄入低且有CVD家族史的CVD总相对危险度（HR）为1.41，而仅有家族史的HR为1.25，仅EPA/DHA低摄入的HR为1.06（但无统计学意义）；③ 总之，血液或组织的n-3多不饱和脂肪酸的低水平（反映了油性鱼类的低摄入量）增加了与CVD家族史相关的CVD风险。 【主编评语】 目前尚不清楚膳食摄入多不饱和脂肪酸（PUFA）是否会改变与心血管疾病（CVD）家族史相关的CVD风险。近期Circulation发表了一项研究，评估了低PUFA摄入量的生物标志物与长期心血管疾病风险相关的家族史之间的相互作用。观察到低二十碳五烯酸或二十二碳六烯酸（EPA/DHA）摄入量的生物标志物与家族史之间存在显著的相互作用，而其他PUFA则没有。本研究结果提示，有必要强调食用油性鱼类对有心血管疾病家族史的个体的好处。（@注册营养师陈彬林） 【原文信息】 Role of Polyunsaturated Fat in Modifying Cardiovascular Risk Associated With Family History of Cardiovascular Disease: Pooled De Novo Results From 15 Observational Studies 2023-12-04, doi: 10.1161/CIRCULATIONAHA.123.065530 Nature子刊：早晚餐吃得晚，或增加心血管病风险 Nature Communications——[16.6] ① 纳入超10.3万名成人，分析进餐、禁食时间与心脑血管疾病发病率间的关系，在平均随访7.2年间，共发生2036例CVD和988例脑血管疾病事件；② 早餐每延迟1小时，患CVD风险增加6%，但早餐时间与脑血管疾病风险无关，晚餐每延迟1小时，患脑血管疾病风险增加8%，但晚餐时间连续变量与CVD风险无显著关联；③ 夜间禁食时间与脑血管疾病风险间负相关，夜间禁食时间每增加1小时，其患病风险会降低7%；④ 早餐、晚餐吃得早，还可大幅降低糖尿病的发生。 【主编评语】 食物摄入在调节昼夜节律中起关键作用，参与心血管系统、血糖稳态的调节。目前，尚不清楚进餐时间与心脑血管疾病发病率间的关系。近日，法国巴黎北索邦大学研究人员在Nature Communications发表最新研究，纳入超10万人的数据，发现早餐、晚餐吃得晚，与心脑血管疾病风险增加相关，这种关联在女士中更明显。此外，夜间禁食时间每增加一小时，患脑血管疾病的风险降低7%，值得关注。（@九卿臣） 【原文信息】 Dietary circadian rhythms and cardiovascular disease risk in the prospective NutriNet-Santé cohort 2023-12-14, doi: 10.1038/s41467-023-43444-3 JAMA子刊：纯素饮食可改善心血管健康——来自同卵双胞胎的临床试验证据 JAMA Network Open——[13.8] ① 该研究纳入了22对双胞胎进行随机分配，接受纯素或杂食饮食；② 与杂食饮食参与者相比，纯素饮食参与者在8周后的平均低密度脂蛋白胆固醇水平和平均空腹胰岛素下降；③ 纯素食者在8周时空腹高密度脂蛋白胆固醇、甘油三酯、维生素B12、葡萄糖和氧化三甲胺水平相对于基线的绝对中位数下降幅度较大，但不显著；④ 该试验结果表明，与健康的杂食性饮食相比，健康的植物性饮食具有显著的保护性心脏代谢作用。 【主编评语】 越来越多的证据表明，与杂食性饮食相比，纯素饮食可以通过改善饮食质量（即增加蔬菜、豆类、水果、全谷物、坚果和种子的摄入量）带来潜在的心血管益处。为了控制可能改变饮食对心脏代谢影响的遗传差异，JAMA Network Open最新公布一项随机临床对照试验，随机分配同卵双胞胎遵循纯素或杂食饮食8周来比较健康纯素饮食和健康杂食饮食对心脏代谢的影响，数据表面纯素饮食有益于心血管健康。（@RZN） 【原文信息】 Cardiometabolic Effects of Omnivorous vs Vegan Diets in Identical Twins - A Randomized Clinical Trial 2023-11-30, doi: 10.1001/jamanetworkopen.2023.44457 亚硝酸盐、亚硝胺摄入较多，可增加糖尿病风险（综述） Nutrition Reviews——[6.1] ① 本系统综述最终纳入6项观察性研究，共有108615名参与者；② 亚硝酸盐摄入量最高组相比最低组的糖尿病发生风险更高（OR=1.61，95%CI 1.08–2.39）；③ 较高的亚硝胺摄入量倾向于增加糖尿病风险（OR=1.52，95%CI 0.76–3.0），且与1型糖尿病的相关性（OR=1.79，95%CI 0.76–3.0）强于2型糖尿病（OR=1.42，95%CI 0.76–3.0）；④ 此外，亚硝酸盐的摄入量与两种糖尿病表型都有剂量依赖性正相关；⑤ 未发现糖尿病风险与高硝酸盐摄入量之间的联系。 【主编评语】 糖尿病是一个全球性的健康问题，饮食是导致糖尿病的一个因素。关于硝酸盐、亚硝酸盐和亚硝胺与糖尿病风险之间关系的研究结果并不一致。近期发表于Nutrition Reviews的一项系统综述发现，饮食中摄入更多的亚硝酸盐与患1型和2型糖尿病的风险更高有关，而亚硝胺的摄入也可能增加患糖尿病的风险，但硝酸盐和糖尿病之间没有明显的联系。总体而言，应注意避免食用含亚硝酸盐的食物。（@注册营养师陈彬林） 【原文信息】 Dietary nitrate, nitrite, and nitrosamine in association with diabetes: a systematic review and meta-analysis 2023-11-25, doi: 10.1093/nutrit/nuad148 厦门大学：小心纳米塑料加剧脂肪肝！ Journal of Hazardous Materials——[13.6] ① 纳米塑料（NP）通过上调Fatp2促进脂质摄取，加重HFD诱导的肝脏脂肪变性；② NP通过稳定Ip3r1促进肝细胞中内质网-线粒体接触（MAMs）的组装，导致线粒体Ca2+过载和氧化还原失衡；③ Nrf2通过与其启动子结合下调miR26a，增加肝脏中多个miR26a靶基因表达，导致Vdac1等NASH相关基因上调；④ 上调的Vdac1通过促进NF-κB P65和Keap1的核易位使Nrf2失活，MAM-系链与Nrf2和miR26a形成反馈调节回路，感知肝细胞氧化还原稳态，调节NAFLD向NASH的转变。 【主编评语】 生活方式、遗传和环境因素影响非酒精性脂肪肝病（NAFLD）向非酒精性脂肪性肝炎（NASH）的发展，纳米塑料（NP）作为一种新的环境代谢干扰物，其在肝脏中的积累可能会增加患NAFLD的风险，但其在NAFLD向NASH转变过程中的作用仍不清楚。厦门大学林怡、申河清与团队近期发表于Journal of Hazardous Materials上的文章，发现NP从胃肠道吸收后可转运至肝脏，并作为诱导剂，与HFD一起驱动NASH进展，氧化还原传感器miR26a是NAFLD向NASH转变的关键分子开关。（@RZN） 【原文信息】 Nanoplastic propels diet-induced NAFL to NASH via ER-mitochondrial tether-controlled redox switch 2023-11-30, doi: 10.1016/j.jhazmat.2023.133142 Nature子刊：重症患者可采用肠内生酮喂养 Nature Communications——[16.6] ① 29名接受机械通气的多器官功能衰竭重症患者被随机分配接受生酮和标准（葡萄糖）肠内喂养；② 干预10天，生酮组低血糖事件较少（0.0%vs1.6%），需较少的外源胰岛素（0vs78IU）；③ 生酮组腹泻比例较高（76.9%vs53.3%），但每日腹泻比例差异不太明显（53.5%vs42.9%）；④ 生酮组获得83.3%和84.4%的能量和蛋白质目标，RQ（呼吸商）为0.78，对照达90.4%和79.3%，RQ为0.83；⑤ 生酮喂养安全可行，耐受性良好，可能是重症患者能源衰竭的解决措施。 【主编评语】 在危重症中，葡萄糖和脂肪酸利用受损导致的生物能量衰竭会导致多个组织的器官功能障碍。酮体可能形成一种替代的底物来源，但在生理不稳定的患者中诱导生酮状态的可行性和安全性尚不清楚。Nature Communications近期发表的文章，报道了一项对比生酮和标准肠内喂养的双中心试点开放标签试验，结果显示肠内生酮喂养安全可行，耐受性良好，可能是重症患者能源衰竭的解决措施。（@章台柳） 【原文信息】 A pilot study of alternative substrates in the critically Ill subject using a ketogenic feed 2023-12-15, doi: 10.1038/s41467-023-42659-8 老了再开始少食，也能减缓果蝇衰老 PNAS——[11.1] ① 在生命的不同时期将雄性果蝇从高热量 (H) 饮食转向低热量 (L) （HL）饮食或LH饮食，这些转变即使发生在晚年，也会立即改变果蝇的衰老速度；② HL转变迅速降低果蝇死亡率，使其略低于恒定L饮食，并延长寿命；③ H饮食中衰老的果蝇应激反应增强，并导致HL转换后死亡率迅速下降，相反LH变化会增加死亡率并缩短寿命；④ LH导致更丰富的转录组变化，包括核糖体生物发生、应激反应和生长增加，这些可能导致更高的死亡率。 【主编评语】 老年人的肥胖率正在增加，并导致与年龄相关的退化。热量限制（CR）可以缓解肥胖表型，延缓与年龄相关的变化。但老年人如何从高热量（H）饮食转变为低热量（L）饮食中受益尚不清楚。PNAS近期发表的文章，发现将雄性果蝇从H饮食转变为L饮食，可减缓衰老速度、增加寿命，即使这种转变发生在老年期。（@章台柳） 【原文信息】 Late-life shift in caloric intake affects fly metabolism and longevity 2023-12-08, doi: 10.1073/pnas.2311019120 食品3D打印技术用于封装生物活性化合物（综述） Critical Reviews in Food Science and Nutrition——[10.2] ① 3D食品打印可通过将生物活性化合物（BC）封装到三维基质中来帮助保护BC活性和生物利用率；② 基于挤压的3D食品打印可提高BC的稳定性和生物利用率，水凝胶是基于3D食品打印的封装技术的理想材料；③ 封装和3D打印技术是两项革命性技术，可提供多种优势和健康益处，两者结合可助力未来开发个性化功能食品；④ 但这些方法大多是实验室规模的成熟技术，它们的实际应用尚未得到解决，未来的研究需解决与工艺优化和标准程序有关的挑战。 【主编评语】 生物活性化合物（BCs）主要来源于植物，部分来源于动物。包括多酚、维生素、类胡萝卜素、生育酚、有机酸和omega-3脂肪酸在内的天然BCs已被证明可以通过降低患心血管疾病、糖尿病和癌症的风险来促进健康。但大多数BCs的生物可及性和生物利用度较低，阻碍了它们潜在的健康促进作用。食品3D打印技术是一种具有定制特定形状、实现个性化营养、开发新型资源等功能的未来食品加工技术。近期发表于Critical Reviews in Food Science and Nutrition的一篇综述重点介绍了基于3D打印的食品封装方法的进步。（@注册营养师陈彬林） 【原文信息】 Designing future foods: Harnessing 3D food printing technology to encapsulate bioactive compounds 2023-10-26, doi: 10.1080/10408398.2023.2273446 Nature：第一个关于食品的全球气候协议对减少温室气体排放有用吗？（新闻） Nature——[64.8] ① 第28届联合国气候变化大会开幕之际，134个国家签署了一份宣言，承诺减少与食品生产和消费相关过程的温室气体排放；② 肉类、乳制品和其他动物产品比水果和蔬菜等其他食物产生的排放量更多；③ 在肉类高消费国家，减少动物产品的消费应该成为优先事项，例如通过在财政上支持严重依赖畜牧业的国家；④ 然而，由于在全球范围内改变人们的饮食方式很复杂，减少食物碳排放并不简单，实现这些目标涉及复杂的政治决策。 【主编评语】 近期在迪拜举行的COP28气候大会开幕之际，134个国家签署了一份宣言，承诺减少与食品生产和消费相关过程中的温室气体排放。Nature对此发表了一篇新闻稿，讨论了关于减少食品生产中温室气体排放的第一个全球宣言，表达了对此宣言肯定的一面，但指出其回避了一些最具争议的问题，如要改变人们饮食习惯是非常复杂的。（@注册营养师陈彬林） 【原文信息】 Eat less meat: Will the first global climate deal on food work? 2023-12-08, doi: 10.1038/d41586-023-03960-0 感谢本期日报的创作者：湖人总冠军，九卿臣，Jadon，注册营养师陈彬林，orchid，Sunflower，Jenny 点击阅读过去10天的日报： 12-23 | 肠脑轴前沿：10文一览肠道与脑健康的紧密关系 12-22 | 《自然·综述》领衔，10文聚焦微生态干预 12-21 | 今日Nature：线粒体如何影响肠道脂代谢？ 12-20 | Nature重磅：从微生物暗物质中挖掘40万个新基因家族 12-19 | 周文/贺艳娟/贾伟/陈翔Cell子刊：从肠菌入手，改善多发性骨髓瘤治疗 12-18 | 《自然·综述》年度回顾：晚期大肠癌治疗的新选择 12-17 | Lancet子刊双文齐发：维生素D对心血管病和骨折的预防效果存疑 12-16 | 肠道细胞知多少？多文聚焦小细胞中的大学问 12-15 | 今日Science：菌群如何“排挤”病原体？生态学原理探究竟 12-14 | 今日Nature和Cell齐发，肠道菌群研究再掀小高潮

A critical milestone completed on the mission path of commercializing Itraconazole in numerous oncology indications. TAMPA, Fla., Dec. 13, 2023 /PRNewswire/ -- Inhibitor Therapeutics, Inc. ("Inhibitor") (OTCQB: INTI) has entered into an exclusive, worldwide licensing agreement (the "License") with Johns Hopkins University (JHU) for their U.S Patent 8,980,930 (Canada Patent 2,572,223) "New Angiogenesis Inhibitors". Angiogenesis Inhibitors, as described by the National Cancer Institute, are unique cancer fighting agents as they block the growth of blood vessels that support tumor growth rather than blocking the growth of the tumor cells themselves. Inventors affiliated with JHU developed this patent, listing Itraconazole as an Active Pharmaceutical Ingredient (API) that has anti-angiogenic properties. The License notes field of use is for use in Prostate Cancer, Basal Cell Carcinoma including Basal Cell Carcinoma Nevus Syndrome (an orphan oncology disease), and Lung Cancer, all of which emphasize a significant unmet need. Inhibitor believes the License is a mutually beneficial agreement, yielding a modest annual royalty rate with milestone payments typical to such a license. Within the literature Head et al1 explains the long-term recognition that angiogenesis is a requirement for tumor growth and metastasis and that growing tumors can promote angiogenesis by secreting proangiogenic factors such as VEGF, basic FGF, EGF and others. These proangiogenic factors stimulate the proliferation, migration, and differentiation of the endothelial cells that make up the inner layer of all blood vessels, causing them to form new vessels that grow towards the source of these factors, this process termed "tumor angiogenesis". It is identified that the major target of itraconazole in endothelial cells is VDAC1. VDAC1 knockdown profoundly inhibits mTOR activity and cell proliferation in HUVEC revealing a previously unknown connection. Inhibition of VDAC1 by itraconazole leads to an increase in cellular AMP:ATP ratio and activation of the AMP-activated protein kinase (AMPK), an upstream regulator of mTOR. VDAC1-knockout cells are resistant to AMPK activation and mTOR inhibition by itraconazole, demonstrating that VDAC1 is the mediator of this activity. In their testing it was found that by using a phenotypical approach starting with the effect of itraconazole the G1-S cell cycle transition of the endothelial cells, itraconazole specifically inhibited the mTOR signaling pathway by downregulating the kinase activity of mTORC1. Chow Et Al2 completed a study utilizing RNA sequencing to decipher the biological pathway propelling BCC growth. From the assay results, it was observed that BCCs exhibited a considerable amplification in the expression of the mTOR pathway. This pathway plays an essential role in regulating angiogenesis, the growth of new blood vessels from pre-existing ones. Thus, this indicates that it is the heightened activity of the mTOR pathway, and the consequent enhancement of angiogenesis, that stimulates the growth. Data from Inhibitor's completed Phase 2b SCORING Trial complements the literature with reference to the Lesion Response of the study which shows that across the 477 target lesions the investigators reported reductions of any size from baseline for 399 (83.65%) lesions, 64 (13.42%) had no change and 14 increased in size. A pre-determined reduction of 30% or greater was seen in 275 of the 477 (57.7%) target lesions, including 130 lesions which resolved completely (27.3%). A total of 13 new 'surgically eligible' lesions across 8 of the 38 patients developed over the duration of the study. For more information about Inhibitor and our mission please visit us on our website () and for any further or specific queries you may have please visit our contact us page, submit your details/query, and a representative will be happy to get in touch. Forward-Looking Statements This press release contains projections and other forward-looking statements regarding future events and our future financial performance. All statements other than present and historical facts and conditions contained in this release, including any statements regarding future results of operations and financial positions, business strategy and plans, expectations for future product sales, our ability to convert our pipeline to revenue and our objectives for future operations, are forward-looking statements (within the meaning of the Private Securities Litigation Reform Act of 1995, Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended). These statements are only predictions and reflect our current beliefs and expectations with respect to future events and are based on assumptions and subject to risk and uncertainties and subject to change at any time. We undertake no obligation to update the information made in this release in the event facts or circumstances subsequently change after the date of this press release. We operate in a very competitive and rapidly changing environment. New risks emerge from time to time. Given these risks and uncertainties, you should not rely on or place undue reliance on these forward-looking statements. Actual events or results may differ materially from those contained in the projections or forward-looking statements. SOURCE INHIBITOR Therapeutics, Inc.