GPR119

CAMBRIDGE, Mass., April 30, 2024 /PRNewswire/ -- NeuroBo Pharmaceuticals, Inc. (Nasdaq: NRBO), a clinical-stage biotechnology company focused on the transformation of cardiometabolic diseases, today announced the acceptance of poster presentations for its promising cardiometabolic assets, DA-1241 and DA-1726, at the EASL Congress 2024 and the American Diabetes Association (ADA) 84th Scientific Sessions in June. "Having multiple posters selected for presentation at two of the most esteemed scientific forums emphasizes the scientific community's recognition of the compelling pre-clinical data that we have generated for DA-1241 and DA-1726," stated Hyung Heon Kim, President and Chief Executive Officer of NeuroBo. "We have completed enrollment for Part 1 of our Phase 2a clinical trial of DA-1241, a novel G-Protein-Coupled Receptor 119 (GPR119) agonist for the treatment of metabolic dysfunction-associated steatohepatitis (MASH). Additionally, we have recently dosed the first patient in the single ascending dose (SAD) Part 1 of our Phase 1 trial of DA-1726, a novel, dual oxyntomodulin (OXM) analog agonist that functions as a glucagon-like peptide-1 receptor (GLP1R) and glucagon receptor (GCGR) for the treatment of obesity. DA-1726 has consistently shown, in our preclinical data, to sustain weight loss in diet-induced obese models by decreasing food consumption and boosting energy expenditure. Both programs are progressing well, and we have been able to significantly accelerate the clinical timelines for DA-1726. We currently expect to both dose the first patient in the multiple ascending dose (MAD) Part 2 and read-out top-line data from the SAD Part 1 in the third quarter of 2024, with top-line data from the MAD Part 2 expected in the first quarter of 2025." June 5-8: EASL Congress 2024. Members of the Dong-A ST Research Center and DA-1241 Phase 2 trial Contract Research Organization (CRO), Gubra, will present pre-clinical data on DA-1241, in two poster presentations at this congress in Milan, Italy. Abstract Title: DA-1241, a GPR119 Agonist, Combined with Semaglutide Synergistically Improved Liver Fibrosis in Mice with CCl4-Induced Liver Fibrosis Authors: Il Hoon Jung, Tae Hyoung Kim, Sujin Lee, Yuna Chae, Hyung Heon Kim, Mi-Kyung Kim Presenter Name: II Hoon Jung, Dong-A ST Research Center Abstract Number: 117 Session: Poster - Fibrosis / Stellate cell biology Session Date: Thursday, June 6, 2024 Session Time: 8:30 am – 6:00 pm CET Abstract Title: Additive Hepatoprotective Effects of DA-1241, a Novel GPR119 Agonist, in Combination with Semaglutide in the GAN Diet-Induced Obese and Biopsy-Confirmed Mouse Model of MASH Authors: Monika Lewinska, Malte H. Nielsen, Susanne Pors, Henrik B. Hansen, Il Hoon Jung, Hyung Heon Kim, Michael Feigh, Mi-Kyung Kim Presenter Name: Dr. Michael Feigh, Vice President Scientific Research, Gubra Abstract Number: 1950 Session: Poster - MASLD: Experimental and pathophysiology Session Date: Thursday, June 6, 2024 Session Time: 8:30 am – 6:00 pm CET June 21-24: American Diabetes Association (ADA) 84th Scientific Sessions. A member of the Dong-A ST Research Center will present pre-clinical data on DA-1726 in a poster presentation at this scientific session in Orlando, FL. Abstract Title: DA-1726, a GLP1R/GCGR Dual Agonist, A Promising Approach in Obesity Treatment and Lipid Management Presenter Name: Yuna Chae, DA-1726 Project Manager, Dong-A ST Research Center Authors: Il-Hun Jung, Tae-Hyoung Kim, Su Jin Lee, Hyung Heon Kim, Mi-Kyung Kim, Yuna Chae Abstract Number: 2024-LB-5728 Poster Presentation Number: 2058-LB Session: 23-A Obesity-Animal Session Date: Saturday, June 22, 2024 Session Time: 12:30 pm – 1:30 pm ET After the presentations, the posters will be accessible within the "Presentations" section of NeuroBo's website at: . About NeuroBo Pharmaceuticals NeuroBo Pharmaceuticals, Inc. is a clinical-stage biotechnology company focused on transforming cardiometabolic diseases. The company is currently developing DA-1241 for the treatment of Metabolic Dysfunction-Associated Steatohepatitis (MASH) and Type 2 Diabetes Mellitus (T2DM), and is developing DA-1726 for the treatment of obesity. DA-1241 is a novel G-protein-coupled receptor 119 (GPR119) agonist that promotes the release of key gut peptides GLP-1, GIP, and PYY. In preclinical studies, DA-1241 demonstrated a positive effect on liver inflammation, lipid metabolism, weight loss, and glucose metabolism, reducing hepatic steatosis, hepatic inflammation, and liver fibrosis, while also improving glucose control. DA-1726 is a novel oxyntomodulin (OXM) analogue that functions as a glucagon-like peptide-1 receptor (GLP1R) and glucagon receptor (GCGR) dual agonist. OXM is a naturally-occurring gut hormone that activates GLP1R and GCGR, thereby decreasing food intake while increasing energy expenditure, thus potentially resulting in superior body weight loss compared to selective GLP1R agonists. For more information, please visit . Forward Looking Statements Certain statements in this release may be considered forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Words such as "believes", "expects", "anticipates", "may", "will", "should", "seeks", "approximately", "intends", "projects," "plans", "estimates" or the negative of these words or other comparable terminology (as well as other words or expressions referencing future events, conditions or circumstances) are intended to identify forward-looking statements. Forward-looking statements are predictions, projections and other statements about future events that are based on current expectations and assumptions and, as a result, are subject to risks and uncertainties. Many factors could cause actual future events to differ materially from the forward-looking statements in this release, including, without limitation, those risks associated with NeuroBo's ability to execute on its commercial strategy; the timeline for regulatory submissions; ability to obtain regulatory approval through the development steps of NeuroBo's current and future product candidates, the ability to realize the benefits of the license agreement with Dong-A ST Co. Ltd., including the impact on future financial and operating results of NeuroBo; the cooperation of our contract manufacturers, clinical study partners and others involved in the development of NeuroBo's current and future product candidates; potential negative interactions between our product candidates and any other products with which they are combined for treatment; NeuroBo's ability to initiate and complete clinical trials on a timely basis; our ability to recruit subjects for its clinical trials; whether NeuroBo receives results from NeuroBo's clinical trials that are consistent with the results of pre-clinical and previous clinical trials; impact of costs related to the license agreement, known and unknown, including costs of any litigation or regulatory actions relating to the license agreement; effects of changes in applicable laws or regulations; effects of changes to NeuroBo's stock price on the terms of the license agreement and any future fundraising; and other risks and uncertainties described in our filings with the SEC. Forward-looking statements speak only as of the date when made. NeuroBo does not assume any obligation to publicly update or revise any forward-looking statements, whether as a result of new information, future events or otherwise, except as required by law. Contact: NeuroBo Pharmaceuticals Marshall H. Woodworth Chief Financial Officer +1-857-299-1033 [email protected] Rx Communications Group Michael Miller +1-917-633-6086 [email protected] SOURCE NeuroBo Pharmaceuticals, Inc.

Full Data Readout Expected in the Second Half of 2024 CAMBRIDGE, Mass., April 1, 2024 /PRNewswire/ -- NeuroBo Pharmaceuticals, Inc. (Nasdaq: NRBO), a clinical-stage biotechnology company focused on transforming cardiometabolic diseases, today announced the completion of enrollment of Part 1 of its two-part, Phase 2a clinical trial evaluating the efficacy and safety, of DA-1241, a novel G-Protein-Coupled Receptor 119 (GPR119) agonist for the treatment of metabolic dysfunction-associated steatohepatitis (MASH). Approximately 49 patients with presumed MASH have been randomized into Part 1 with a 1:2:1 ratio into 3 treatment groups: DA-1241 50 mg, DA-1241 100 mg, or placebo. "Enrollment of the final patient in Part 1 our Phase 2a clinical trial of DA-1241, in patients with presumed MASH, is another important event in the clinical development of our cardiometabolic assets," stated Hyung Heon Kim, President and Chief Executive Officer of NeuroBo. "Part 2 of this Phase 2a trial, exploring the efficacy of DA-1241 in combination with sitagliptin, a DPP-4 inhibitor, continues to enroll patients, which we believe will show synergistic effects compared to DA-1241 alone. As previously reported, DA-1241 was well tolerated in healthy volunteers and in patients with type 2 diabetes mellitus (T2DM). Based on the pre-clinical and clinical evidence to date, we believe that the unique mechanism of action of this promising cardiometabolic asset, targeting the inflammation associated with MASH, will translate into a safe and effective treatment for this disease. We look forward to reporting the full trial data expected in the second half of this year." Each of the two-parts of the Phase 2a trial of DA-1241 are designed to be 16-week, multicenter, randomized, double-blind, placebo-controlled, parallel clinical studies to evaluate the efficacy and safety of DA-1241 in subjects with presumed MASH. Part 2, which will explore the efficacy of DA-1241 in combination with sitagliptin versus placebo, is expected to enroll approximately 37 subjects who will be randomized in a 2:1 ratio into 2 treatment groups: DA-1241 100 mg/sitagliptin 100 mg or placebo. For both Part 1 and Part 2, the primary endpoint is the change from baseline in alanine transaminase (ALT) levels at Week 16. Secondary efficacy endpoints include the proportion of subjects with normalization of ALT, absolute change in total cholesterol, low and high-density lipoprotein cholesterol, triglycerides, and free fatty acids from baseline, among others. Safety will be evaluated by monitoring adverse events (AEs) and serious adverse events (SAEs) leading to discontinuation and laboratory abnormalities. For more information on this clinical trial, please visit: NCT06054815. About DA-1241 DA-1241 is a novel G-Protein-Coupled Receptor 119 (GPR119) agonist with development optionality as a standalone and/or combination therapy for both MASH and type 2 diabetes (T2D). Agonism of GPR119 in the gut promotes the release of key gut peptides GLP-1, GIP, and PYY. These peptides play a further role in glucose metabolism, lipid metabolism and weight loss. DA-1241 has beneficial effects on glucose, lipid profile and liver inflammation, supported by potential efficacy demonstrated during in vivo preclinical studies. The therapeutic potential of DA-1241 has been demonstrated in multiple pre-clinical animal models of MASH and T2D where DA-1241 reduced hepatic steatosis, inflammation, fibrosis, and improved glucose control. Furthermore, in Phase 1a and 1b trials, DA-1241 was well tolerated in both healthy volunteers and those with T2DM. About NeuroBo Pharmaceuticals NeuroBo Pharmaceuticals, Inc. is a clinical-stage biotechnology company focused on transforming cardiometabolic diseases. The company is currently developing DA-1241 for the treatment of Metabolic Dysfunction-Associated Steatohepatitis (MASH) and Type 2 Diabetes Mellitus (T2DM), and is developing DA-1726 for the treatment of obesity. DA-1241 is a novel G-protein-coupled receptor 119 (GPR119) agonist that promotes the release of key gut peptides GLP-1, GIP, and PYY. In preclinical studies, DA-1241 demonstrated a positive effect on liver inflammation, lipid metabolism, weight loss, and glucose metabolism, reducing hepatic steatosis, hepatic inflammation, and liver fibrosis, while also improving glucose control. DA-1726 is a novel oxyntomodulin (OXM) analogue that functions as a glucagon-like peptide-1 receptor (GLP1R) and glucagon receptor (GCGR) dual agonist. OXM is a naturally-occurring gut hormone that activates GLP1R and GCGR, thereby decreasing food intake while increasing energy expenditure, thus potentially resulting in superior body weight loss compared to selective GLP1R agonists. For more information, please visit . Forward Looking Statements Certain statements in this release may be considered forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Words such as "believes", "expects", "anticipates", "may", "will", "should", "seeks", "approximately", "intends", "projects," "plans", "estimates" or the negative of these words or other comparable terminology (as well as other words or expressions referencing future events, conditions or circumstances) are intended to identify forward-looking statements. Forward-looking statements are predictions, projections and other statements about future events that are based on current expectations and assumptions and, as a result, are subject to risks and uncertainties. Many factors could cause actual future events to differ materially from the forward-looking statements in this release, including, without limitation, those risks associated with NeuroBo's ability to execute on its commercial strategy; the timeline for regulatory submissions; ability to obtain regulatory approval through the development steps of NeuroBo's current and future product candidates, the ability to realize the benefits of the license agreement with Dong-A ST Co. Ltd., including the impact on future financial and operating results of NeuroBo; the cooperation of our contract manufacturers, clinical study partners and others involved in the development of NeuroBo's current and future product candidates; potential negative interactions between our product candidates and any other products with which they are combined for treatment; NeuroBo's ability to initiate and complete clinical trials on a timely basis; our ability to recruit subjects for its clinical trials; whether NeuroBo receives results from NeuroBo's clinical trials that are consistent with the results of pre-clinical and previous clinical trials; impact of costs related to the license agreement, known and unknown, including costs of any litigation or regulatory actions relating to the license agreement; effects of changes in applicable laws or regulations; effects of changes to NeuroBo's stock price on the terms of the license agreement and any future fundraising; and other risks and uncertainties described in our filings with the SEC. Forward-looking statements speak only as of the date when made. NeuroBo does not assume any obligation to publicly update or revise any forward-looking statements, whether as a result of new information, future events or otherwise, except as required by law. Contacts: NeuroBo Pharmaceuticals Marshall H. Woodworth Chief Financial Officer +1-857-299-1033 [email protected] Rx Communications Group Michael Miller +1-917-633-6086 [email protected] SOURCE NeuroBo Pharmaceuticals, Inc.

关注并星标CPHI制药在线放射性药品是指用于临床诊断或者治疗的放射性核素制剂或者其标记化合物。正电子发射断层扫描 （Positron emission tomography, PET） 和单光子发射计算机断层扫描 （single-photon emission computed tomography , SPECT）放射性药物可用于诊断和监测神经系统疾病、癌症、心血管疾病和感染等疾病的进展。比较常见的放射性药物有用于磁共振MRI的含钆对比剂(GBCA)。另一方面，由于放射性元素引起的辐射危害，治疗性放射性药物会引起一定的药理作用。在为治疗应用设计放射性药物时，选择适当的放射性核素是主要决定因素。放射性核素如18F、11C是放射性药物中用于治疗应用的核素。125碘、131碘、132碘等10多种核素是我国国家药品标准收载药物常用的元素。近日，诺华公司的 Salvatore Bongarzone等人在ACS Pharmacology & Translational Science发表文章[1]，简单讲述了一系列的放射性药物及其原理。文章链接https://doi.org/10.1021/acsptsci.3c00347。     放射性药物在近期是非常热门的研究方向。2023年12月26日，百时美施贵宝以每股62.50美元的现金收购RayzeBio，价值约为41亿美元的巨额并购引起了热烈的讨论和人们对放射性药物的重新认识。值得注意的是，百时美施贵宝不是首个对放射性药物感兴趣的跨国药企。2023年9月20日，罗氏旗下的基因泰克与PeptiDream达成一项高达10亿美元的合作和许可协议，该协议目的在于开发新型大环肽-放射性同位素（肽-RI）偶联药物；10月3日，礼来宣布将以14亿美元收购Point Biopharma Global，正式向癌症靶向放射治疗（核素偶连药物）领域发起进攻的号角。众多重量级的并购把放射性药物这个不算热门的研究领域放在了聚光灯下。  在国内，“医药一哥”恒瑞，在2024年的新年伊始，手握4款核药进入临床，引起了一个小轰动，并且登上了著名的央视《新闻联播》。虽然放射性药物近期很热门，但并不能掩盖人们对放射性药物认识的贫乏，大众熟悉各类心血管、肠胃、感冒用药等药品，唯独对放射性药物知之甚少。Salvatore Bongarzone等人的文章无疑是一篇扫盲读物，并且提到，现今的放射性药物主要分成以下不同的类型。1  用于脑成像的放射性药物富含亮氨酸的激酶LRRK2是与帕金森病（PD）进展和表现相关的靶标。在非人灵长类动物 （NHP） 中发现了[18F]1的高脑渗透性，并且使用异源阻断对死后 NHP 脑组织进行放射自显影验证了其与 LRRK2 的特异性结合。[11C]2 用于对多系统萎缩 （MSA） 和 PD 中存在的错误折叠聚集形式的 α-突触核蛋白进行成像。[11C]2显示了MSA中α-突触核蛋白成像的几个有前景的特性。在体内，[11C]2迅速代谢为极性代谢产物。值得注意的是，这些代谢物未显示出与α-突触核蛋白原纤维的结合。[18F]4具有已知靶向CB2R的支架、碳硼烷部分和氘代丁基链，以提高代谢稳定性。啮齿动物的动态 PET 扫描显示脾脏和肝脏摄取快，肝脏清除快，脾脏结合不可移位。在保持高亲和力和选择性的同时，代谢稳定性的整体提高是未来优化CB2R PET配体的重要起点。[18F]6靶向亨廷顿病中的突变亨廷顿蛋白（mHTT）聚集体。体外研究表明，[18F]6比领先的临床配体 CHDI-180 具有更高的 mHTT 特异性和人体代谢稳定性。在非人灵长类中，[18F]6 显示出快速的大脑摄取和快速清除特征。图 1 部分用于脑成像的放射性示踪剂结构式[1](图片来源于ACS Pharmacology & Translational Science )2  用于癌症成像和治疗的放射性药物[18F]15用于雌激素受体β（ERβ）成像。啮齿动物的PET成像证实了该化合物对ERβ的特异性。[18F]16和荷瘤小鼠的离体生物分布研究显示出突出的肿瘤摄取和高对比度。[18F]17用于体内BTK表达水平和靶标占有率的PET成像。图2  部分用于癌症成像和治疗的放射性示踪剂结构式[1](图片来源于ACS Pharmacology & Translational Science )3  其他用于成像的放射性药物选择性基质金属蛋白酶-13（MMP-13）PET 放射性示踪剂的合成和临床前评估，用于早期检测作为急性缺血危险因素的不稳定斑块。离体主动脉放射自显影和研究显示，[18F]20特异性结合动脉粥样硬化斑块内的MMP-13，并定位于富含脂质的区域。GPR119是一种G蛋白偶联受体，在胰腺中高度表达，调节胰岛素和肠促胰岛素的分泌，是治疗糖尿病药物开发的靶点。在体内测量GPR119水平可以显着推进基于 GPR119 的药物开发策略，包括靶点参与、占有率和分布。 [18F]21能被胰腺组织选择性吸收。图3用于动脉粥样硬化斑块和胰腺组织成像的放射性示踪剂[1](图片来源于ACS Pharmacology & Translational Science )4  总结无论是出于诊断，还是治疗，放射性药物都是一个活跃的研究领域。从上述的结构式可以看出，大部分化合物是添加18F作为核素，这些设计策略为我们设计药物提供了参考。在众多的报道中，大部分是讲述放射性药物的前景，甚少提及到这类药物的设计和特点，因此，了解相关化合物的结构，有助于提高药物的设计成功率。参考文献[1]Lindsley C W, Müller C E, Bongarzone S. Diagnostic and Therapeutic Radiopharmaceuticals: A “Hot” Topic[J]. ACS Pharmacology & Translational Science, 2023, 7(1): 1-7.https://doi.org/10.1021/acsptsci.3c00347.【智药研习社近期直播预告】来源：CPHI制药在线声明：本文仅代表作者观点，并不代表制药在线立场。本网站内容仅出于传递更多信息之目的。如需转载，请务必注明文章来源和作者。投稿邮箱：Kelly.Xiao@imsinoexpo.com▼更多制药资讯，请关注CPHI制药在线▼点击阅读原文，进入智药研习社~