Cystic fibrosis related diabetes

2021年国际糖尿病联盟（IDF）公布的数据显示，全球约有5.37亿人（占全球成年群体的10.5%）患有糖尿病；到2045年，预计有7.83亿成年人（即12.2%）患有糖尿病。此外，2021年约有5.41亿人（即10.6%）患有糖耐量受损（IGT），且其患2型糖尿病的风险增加；到2045年，预计这一数字会增加至7.3亿（11.4%）。在2型糖尿病漫长的发展过程中，临床医生根据当前的诊断标准难以早期发现患者的血糖异常，这可能无意中促成了目前糖尿病前期/糖尿病患病率的快速升高。 近期，IDF在Diabetes Research and Clinical Practice上发表一份立场声明，提出75 g口服葡萄糖耐量试验（OGTT）后1小时血糖（1-h PG）检测可为一种更灵敏、更实用的方法，用于筛查高危人群的中度高血糖（IH）和2型糖尿病。具体诊断标准为：1-h PG值≥8.6 mmol/L：用于诊断IH，并应进行生活方式干预及鼓励积极参与糖尿病预防计划。1-h PG值≥11.6 mmol/L：用于诊断2型糖尿病，并应进行复查以确认诊断，然后转诊进行进一步的评估和治疗。截图来源：Diabetes Research and Clinical Practice现行诊断标准有哪些不足？文章相关社论指出，IH，有时被称为“糖尿病前期”，是一种介于正常血糖调节（NGR）和2型糖尿病之间的状态，包括空腹血糖受损（IFG）和葡萄糖耐量受损（IGT）。根据当前诊断标准的定义，许多IH患者将发展为2型糖尿病。此外，大多数有罹患2型糖尿病风险的人没有得到及时识别，从而也无法及早进行如生活方式等的干预。目前，用于高血糖和2型糖尿病诊断标准的指标有空腹血糖（FPG）、糖化血红蛋白（HbA1c）和OGTT 2小时血糖（2-h PG）等。近两年的中国指南以及世界卫生组织（WHO）1999对于糖尿病前期和糖尿病的诊断标准如下：▲中国成人糖尿病前期诊断标准（图片来源：参考资料[6]）▲中国成人糖尿病诊断标准（图片来源：参考资料[5]）▲WHO 1999关于高血糖状态分类（图片来源：参考资料[5]）文中指出，仅依靠FPG和/或HbA1c来诊断IH和2型糖尿病可能会错过早期诊断和预防的机会。而在OGTT中通过2-h PG诊断为IGT的患者，可以通过改变生活方式和/或药物治疗来预防2型糖尿病，但OGTT 2-h PG这个检查过程需要时间比较长。鉴于全球糖尿病患病率持续上升，因此需要一种更灵敏、更实用的诊断方法，来识别早期2型糖尿病风险增加的个体，以便尽早进行干预。1-h PG具有哪些优势？文章指出，OGTT 1-h PG可缩短OGTT所需时间，具有实用性等优势。OGTT 1-h PG也是比FPG、HbA1c和OGTT 2-h PG更敏感的生物标志物。在涉及不同人群的横断面和纵向研究中，1-h PG水平显示出了预测受试者进展为2型糖尿病的较好灵敏度和特异性。1-h PG水平在识别高风险儿童和青少年方面也具有较高的灵敏度。此外，一项前瞻性研究证实，1-h PG（AUC=0.75，敏感性75%，特异性68%）比FPG（AUC=0.63，敏感性55%，特异性64%）或2-h PG（AUC=0.68，敏感性56%，特异性73%）水平更准确地预测进展为2型糖尿病。此外，OGTT 1-h PG是确定未来患2型糖尿病风险的可靠预测指标。大量流行病学数据证实，在不同种族、性别和年龄人群中，OGTT 1-h PG在预测糖尿病及其相关并发症等方面优于FPG、HbA1c和OGTT 2-h PG。世界各地的许多观察性研究一致表明，OGTT 1-h PG≥8.6 mmol/L与2型糖尿病的发生直接相关；值得注意的是，与FPG或OGTT 2-h PG相比，这种关联更为明显。此外，在糖耐量正常（定义为HbA1c<5.7%或FPG<100 mg/dL或OGTT 2-h PG<140 mg/dL）的未确诊2型糖尿病或2型糖尿病高风险人群中，1-h PG≥8.6 mmol/L检测对微血管和大血管并发症、阻塞性睡眠呼吸暂停（OSA）、囊性纤维化相关糖尿病（CFRD）、代谢功能障碍相关脂肪性肝病（MASLD）和过早死亡的风险具有高度预测性。IDF立场声明建议，采用1-h PG≥8.6 mmol/L诊断IH，以及1-h PG≥11.6 mmol/L诊断2型糖尿病，可以比目前推荐的方法更早地发现高危人群，同时能及早干预。小结总的来说，相比于常规的高血糖或2型糖尿病诊断标准，采用OGTT 1-h PG进行筛查将有助于更早识别2型糖尿病高风险人群，并有助于减少糖尿病的全球影响。文章表示，OGTT 1-h PG可提供一种更为灵敏且实用的方法，以在不降低IH和糖尿病预测值的情况下提高检测的便利性。参考资料[1] Sun H, et al., (2022). IDF Diabetes Atlas: Global, regional and country-level diabetes prevalence estimates for 2021 and projections for 2045. Diabetes Res Clin Pract, https://doi.org/10.1016/j.diabres.2021.109119.[2] Bergman M, et al., (2024). International Diabetes Federation Position Statement on the 1-hour post-load plasma glucose for the diagnosis of intermediate hyperglycaemia and type 2 diabetes. Diabetes Res Clin Pract, doi: 10.1016/j.diabres.2024.111589.[3] International Diabetes Federation position statement recommending use of 1-hour plasma glucose test to diagnose intermediate hyperglycaemia and type 2 diabetes. Diabetes Res Clin Pract. 2024 Mar 30:111646. doi: 10.1016/j.diabres.2024.111646.[4] Michael Bergman et al. Current diagnostic criteria identify risk for type 2 diabetes too late. The Lancet Diabetes & Endocrinology. Doi: 10.1016/S2213-8587(23)00039-6[5] 中华医学会糖尿病学分会, 国家基层糖尿病防治管理办公室. 国家基层糖尿病防治管理指南（2022）[J]. 中华内科杂志, 2022, 61(3): 249-262.[6] 中华医学会内分泌学分会, 中华医学会糖尿病学分会, 中国医师协会内分泌代谢科医师分会. 中国成人糖尿病前期干预的专家共识（2023版）[J]. 中华糖尿病杂志, 2023, 15(6): 484-494.撰文 | 医学新视点编辑 | 阿拉斯加宝● 重磅！5次问鼎NEJM，吴一龙教授团队或将改写全球指南！ALK阳性NSCLC的辅助治疗显著提高患者生存率● 每周“洗脑”30分钟，让大脑返老还童？Nature最新：改善老年的认知能力，还能缓解阿尔茨海默症的病理！但要注意...● 重磅！DRG致医院亏损?捆绑了医生的手脚？不敢看重病？国家医保局澄清并广开言路，真理越辩越明！特病单议成讨论重点版权说明：梅斯医学（MedSci）是国内领先的医学科研与学术服务平台，致力于医疗质量的改进，为临床实践提供智慧、精准的决策支持，让医生与患者受益。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。点击下方「阅读原文」 立刻下载梅斯医学APP

vTv discovered small molecule RAGE inhibitor is being developed by Cantex under worldwide development and commercialization agreementHIGH POINT, N.C., June 16, 2023 (GLOBE NEWSWIRE) -- vTv Therapeutics Inc. (Nasdaq: VTVT), a clinical stage biopharmaceutical company focused on the development of cadisegliatin (TTP399) as an adjunctive therapy to insulin for the treatment of type 1 diabetes ("T1D"), announced today that Cantex Pharmaceuticals, Inc. recently obtained an exclusive worldwide license from Georgetown University for intellectual property related to the potential use of azeliragon to treat, prevent or alleviate cancer treatment-related cognitive decline. Azeliragon, a small molecule receptor for advanced glycation end products (RAGE) inhibitor, was originally discovered by vTv and studied as a potential treatment for Alzheimer’s disease. Prior to licensing azeliragon to Cantex, vTv produced a substantial body of clinical data supporting the safety and tolerability of azeliragon, as well as preclinical data demonstrating the potential therapeutic benefit of vTv’s RAGE antagonists on several diseases, including cancer and diabetic complications. “We once again extend our congratulations to our partners at Cantex on the continued strengthening of their IP estate for azeliragon. Already protected by a robust composition of matter patent and a variety of regulatory exclusivities, azeliragon has broad therapeutic potential which, if realized, could result in sizeable commercial opportunities in oncology and multiple other indications in which RAGE is implicated,” said Paul Sekhri, President and Chief Executive Officer of vTv Therapeutics. “We look forward to the results of Cantex's collaboration with Georgetown, which will provide greater visibility into the potential of azeliragon to alleviate cognitive decline caused by chemotherapy.” About AzeliragonAzeliragon is an orally administered small molecule drug, taken once daily, that inhibits interactions of the receptor for advanced glycation end products (known as RAGE) with certain ligands, including HMGB1 and S100 proteins in the tumor microenvironment. Azeliragon was originally under development for Alzheimer's disease by vTv Therapeutics from whom Cantex licensed it. Clinical safety data from these trials, involving more than 2000 individuals dosed for periods up to 18 months, indicate that azeliragon is very well tolerated. Cantex is also developing azeliragon for the treatment of brain metastasis, metastatic pancreatic cancer, glioblastoma, and neoadjuvant therapy of breast cancer. In addition, a phase 2/3 trial is currently enrolling hospitalized COVID-19 patients, evaluating the efficacy of azeliragon in the prevention of acute kidney injury. About vTv TherapeuticsvTv Therapeutics Inc. is a clinical stage biopharmaceutical company focused on developing oral, small molecule drug candidates. vTv has a pipeline of clinical drug candidates led by programs for the treatment of type 1 diabetes and cystic fibrosis related diabetes. vTv’s development partners are pursuing additional indications in type 2 diabetes, chronic obstructive pulmonary disease, renal disease, primary mitochondrial myopathy, and glioblastoma and other cancers and cancer treatment-related conditions. For more information, please visit www.vtvtherapeutics.com. About Cantex Pharmaceuticals, Inc.Cantex Pharmaceuticals, Inc. is a privately held, clinical stage pharmaceutical company focused on developing transformative therapies for cancer and other life-threatening medical conditions for which new treatments are urgently needed. For more information, please visit www.cantex.com. Forward-Looking StatementsThis release contains forward-looking statements, which involve risks and uncertainties, including statements regarding the potential grant of the FDA Approval. These forward-looking statements can be identified by the use of forward-looking terminology, including the terms “anticipate,” “believe,” “could,” “estimate,” “expect,” “intend,” “may,” “plan,” “potential,” “predict,” “project,” “should,” “target,” “will,” “would” and, in each case, their negative or other various or comparable terminology. All statements other than statements of historical facts contained in this release, including statements regarding the agreements and transactions described in this release are forward-looking statements. These statements involve known and unknown risks, uncertainties and other important factors, including the risk that the FDA Approval is not received on a timely basis or at all, that may cause our actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or implied by the forward-looking statements. Important factors that could cause our results to vary from expectations include those described under the heading “Risk Factors” in our Annual Report on Form 10-K and our other filings with the SEC. These forward-looking statements reflect our views with respect to future events as of the date of this release and are based on assumptions and subject to risks and uncertainties. Given these uncertainties, you should not place undue reliance on these forward-looking statements. These forward-looking statements represent our estimates and assumptions only as of the date of this release and, except as required by law, we undertake no obligation to update or review publicly any forward-looking statements, whether as a result of new information, future events or otherwise after the date of this release. We anticipate that subsequent events and developments will cause our views to change. Our forward-looking statements do not reflect the potential impact of any future acquisitions, merger, dispositions, joint ventures or investments we may undertake. We qualify all of our forward-looking statements by these cautionary statements. Contacts: Investors: Lee Roth Burns McClellan lroth@burnsmc.com Media: Selina Husain / Robert Flamm, Ph.D. Burns McClellan, Inc. shusain@burnsmc.com / rflamm@burnsmc.com

vTv discovered small molecule RAGE inhibitor being developed by Cantex under worldwide development and commercialization agreementHIGH POINT, N.C., May 24, 2023 (GLOBE NEWSWIRE) -- vTv Therapeutics Inc. (Nasdaq: VTVT), a clinical stage biopharmaceutical company focused on the development of an adjunctive therapy to insulin for the treatment of type 1 diabetes ("T1D"), today announced that the United States Patent and Trademark Office recently issued a patent to Cantex Pharmaceuticals, Inc. that covers claims related to the use of azeliragon as a potential treatment of glioblastoma multiforme (GBM). Azeliragon is a small molecule inhibitor of the receptor for advanced glycation end products (RAGE) discovered by vTv and licensed to Cantex Pharmaceuticals. Cantex has ongoing azeliragon clinical trials in metastatic pancreatic cancer, neoadjuvant therapy of breast cancer, and hospitalized COVID patients to prevent acute kidney injury, and will soon initiate FDA-approved clinical trials of azeliragon in newly diagnosed glioblastoma, and in brain metastases in combination with stereotactic radiosurgery. Earlier this year, Cantex received Food and Drug Administration Orphan Drug Designation for azeliragon for the treatment of glioblastoma. On June 22, 2021, vTv and Cantex entered into a licensing agreement under which Cantex obtained exclusive worldwide rights to develop and commercialize azeliragon. Under the terms of the agreement, the companies will allocate downstream profits under a tiered arrangement if successfully developed and launched. Prior to the Cantex agreement, vTv was developing azeliragon for the treatment of Alzheimer’s disease. Through these efforts, vTv generated a significant body of clinical data supporting the safety and tolerability profile of azeliragon. Evidence suggests that RAGE—ligand interactions play a vital role in cancer, as well as in a range of inflammatory diseases. “We would like to congratulate Cantex on receipt of this important addition to the azeliragon patent estate covering its use as a potential therapy for GBM. Coupled with the Orphan Drug Designation granted for this indication in early 2023, Cantex is building robust protections around this novel small molecule RAGE inhibitor, aimed at maximizing the commercial opportunities for azeliragon should its clinical development be successful,” said Paul Sekhri, President and Chief Executive Officer of vTv Therapeutics. “We will be closely following the ongoing GBM study as well as Cantex’s development efforts in other indications where RAGE is implicated.” About AzeliragonAzeliragon is an orally administered small molecule, taken once daily, that inhibits interactions of the receptor for advanced glycation end products (known as RAGE) with certain ligands, including HMGB1 and S100 proteins in the glioblastoma microenvironment. By preventing interaction of RAGE with these ligands, azeliragon may inhibit glioblastoma and overcome its resistance to effective treatment. Azeliragon was originally under development for Alzheimer's disease by vTv Therapeutics from whom Cantex licensed it. Clinical safety data from these trials, involving more than 2000 individuals dosed for periods up to 18 months, indicate that azeliragon is very well tolerated. Cantex is also developing azeliragon for the treatment of brain metastasis, pancreatic cancer, and breast cancer. In addition, a phase 2/3 trial is currently enrolling hospitalized COVID-19 patients, evaluating the efficacy of azeliragon in the prevention of acute kidney injury. About vTv TherapeuticsvTv Therapeutics Inc. is a clinical stage biopharmaceutical company focused on developing oral, small molecule drug candidates. vTv has a pipeline of clinical drug candidates led by programs for the treatment of type 1 diabetes and cystic fibrosis related diabetes. vTv’s development partners are pursuing additional indications in type 2 diabetes, chronic obstructive pulmonary disease, renal disease, primary mitochondrial myopathy, and pancreatic cancer. For more information, please visit www.vtvtherapeutics.com. About Cantex Pharmaceuticals, Inc.Cantex Pharmaceuticals, Inc. is a privately held, clinical stage pharmaceutical company focused on developing transformative therapies for cancer and other life-threatening medical conditions for which new treatments are urgently needed. For more information, please visit www.cantex.com. Forward-Looking StatementsThis release contains forward-looking statements, which involve risks and uncertainties, including statements regarding the potential grant of the FDA Approval. These forward-looking statements can be identified by the use of forward-looking terminology, including the terms “anticipate,” “believe,” “could,” “estimate,” “expect,” “intend,” “may,” “plan,” “potential,” “predict,” “project,” “should,” “target,” “will,” “would” and, in each case, their negative or other various or comparable terminology. All statements other than statements of historical facts contained in this release, including statements regarding the agreements and transactions described in this release are forward-looking statements. These statements involve known and unknown risks, uncertainties and other important factors, including the risk that the FDA Approval is not received on a timely basis or at all, that may cause our actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or implied by the forward-looking statements. Important factors that could cause our results to vary from expectations include those described under the heading “Risk Factors” in our Annual Report on Form 10-K and our other filings with the SEC. These forward-looking statements reflect our views with respect to future events as of the date of this release and are based on assumptions and subject to risks and uncertainties. Given these uncertainties, you should not place undue reliance on these forward-looking statements. These forward-looking statements represent our estimates and assumptions only as of the date of this release and, except as required by law, we undertake no obligation to update or review publicly any forward-looking statements, whether as a result of new information, future events or otherwise after the date of this release. We anticipate that subsequent events and developments will cause our views to change. Our forward-looking statements do not reflect the potential impact of any future acquisitions, merger, dispositions, joint ventures or investments we may undertake. We qualify all of our forward-looking statements by these cautionary statements. Contacts: Investors: Lee Roth Burns McClellan lroth@burnsmc.com Media: Selina Husain / Robert Flamm, Ph.D. Burns McClellan, Inc. shusain@burnsmc.com / rflamm@burnsmc.com