更新于：2024-05-01

17β-HSD5

醛酮还原酶家族1成员C3

更新于：2024-05-01

基本信息

别名

醛酮还原酶家族成员1C3、17-beta-HSD 5、17-beta-hydroxysteroid dehydrogenase type 5

+ [24]

简介

Cytosolic aldo-keto reductase that catalyzes the NADH and NADPH-dependent reduction of ketosteroids to hydroxysteroids. Acts as a NAD(P)(H)-dependent 3-, 17- and 20-ketosteroid reductase on the steroid nucleus and side chain and regulates the metabolism of androgens, estrogens and progesterone (PubMed:10622721, PubMed:11165022, PubMed:7650035, PubMed:9415401, PubMed:9927279). Displays the ability to catalyze both oxidation and reduction in vitro, but most probably acts as a reductase in vivo since the oxidase activity measured in vitro is inhibited by physiological concentration of NADPH (PubMed:14672942, PubMed:11165022). Acts preferentially as a 17-ketosteroid reductase and has the highest catalytic efficiency of the AKR1C enzyme for the reduction of delta4-androstenedione to form testosterone (PubMed:20036328). Reduces prostaglandin (PG) D2 to 11beta-prostaglandin F2, progesterone to 20alpha-hydroxyprogesterone and estrone to 17beta-estradiol (PubMed:15047184, PubMed:20036328, PubMed:10622721, PubMed:11165022, PubMed:10998348, PubMed:19010934). Catalyzes the transformation of the potent androgen dihydrotestosterone (DHT) into the less active form, 5-alpha-androstan-3-alpha,17-beta-diol (3-alpha-diol) (PubMed:10998348, PubMed:14672942, PubMed:11165022, PubMed:7650035, PubMed:9415401, PubMed:10557352). Also displays retinaldehyde reductase activity toward 9-cis-retinal (PubMed:21851338).

关联

项与 17β-HSD5 相关的药物

AST-001

靶点

17β-HSD5

作用机制

17β-HSD5刺激剂

在研机构

深圳艾欣达伟医药科技有限公司初创企业

原研机构

深圳艾欣达伟医药科技有限公司初创企业

在研适应症

肿瘤 [+13]

非在研适应症-

最高研发阶段临床2期

首次获批国家/地区-

首次获批日期1800-01-20

AST-3424

靶点

17β-HSD5

作用机制

17β-HSD5抑制剂

在研机构

深圳艾欣达伟医药科技有限公司初创企业 [+1]

原研机构

Obi

在研适应症

急性髓性白血病 [+19]

非在研适应症

去势抵抗性前列腺癌 [+1]

最高研发阶段临床2期

首次获批国家/地区-

首次获批日期1800-01-20

FOR-7191

靶点

17β-HSD5

作用机制

17β-HSD5抑制剂

在研机构

Forendo Pharma Oy

原研机构

Forendo Pharma Oy

在研适应症

多囊卵巢综合征

非在研适应症-

最高研发阶段临床前

首次获批国家/地区-

首次获批日期1800-01-20

项与 17β-HSD5 相关的临床试验

KCT0008915 / Recruiting临床3期

A Multicenter, Randomized, Double-blind, Placebo-controlled, Phase III Clinical Trial to Evaluate the Efficacy and Safey of AST-001 Followed by an Open-Label Extension Treatment Period in Children with Autism Spectrum Disorder

开始日期2023-08-29

申办/合作机构

Astrogen Co., Ltd.初创企业

NCT06245330 / Recruiting临床1/2期

A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Efficacy and Correlation With AKR1C3 Enzyme Expression of AST-001 in Subjects With Advanced Solid Tumors

A first-in-human open-label, Phase I/II study to evaluate the safety, tolerability, MTD/RP2D, PK, and preliminary efficacy of AST-001 administered as a single agent.

开始日期2022-07-07

申办/合作机构

深圳艾欣达伟医药科技有限公司初创企业

CTR20220934 / Recruiting临床1期

评价AST-001治疗恶性肿瘤患者的安全性、耐受性、药代动力学、初步疗效以及疗效与AKR1C3表达相关性的临床研究

主要目的： - 评估实体瘤受试者接受AST-001静脉输注给药的安全性和耐受性 - 评估实体瘤受试者中AST-001及其主要代谢产物AST 2660的药代动力学特征 - 确定实体瘤受试者接受AST-001单药治疗的最大耐受剂量（MTD），并确定II期临床推荐剂量（RP2D）次要目的： - 根据受试者的客观缓解率（ORR）、疾病控制率（DCR）、缓解持续时间（DOR）和无进展生存期（PFS）初步评估AST-001单药治疗恶性肿瘤的疗效 - 探索肿瘤组织经免疫组织化学（IHC）确定的AKR1C3表达与疗效之间的关系 - 评估AST-001在人体内的代谢产物谱探索性目的: - 探索DNA损伤修复相关基因的突变情况

开始日期2022-07-01

申办/合作机构

深圳艾欣达伟医药科技有限公司初创企业

100 项与 17β-HSD5 相关的临床结果

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100 项与 17β-HSD5 相关的转化医学

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0 项与 17β-HSD5 相关的专利（医药）

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1,074

项与 17β-HSD5 相关的文献（医药）

2024-02-16·Human nature (Hawthorne, N.Y.)

Discriminative Grandparental Investment in China : Evidence from an Undergraduate Questionnaire Study.

Article

作者: Liqun Luo ; Yinan Zuo ; Xinzhu Xiong

Many studies in Western societies show a pattern of discriminative grandparental investment as follows: maternal grandmothers (MGMs) > maternal grandfathers (MGFs) > paternal grandmothers (PGMs) > paternal grandfathers (PGFs). This pattern is in line with the expectation from evolutionary reasoning. Yet whether or not this pattern applies in China is in question. The present study was based on a questionnaire survey at a university in Central China (N = 1,195). Results show that (1) when grandparent-grandchild residential distance during grandchildren's childhood is controlled, in the case of grandsons and granddaughters as a whole and granddaughters only, both grandparental caregiving and grandchildren's emotional closeness to grandparents display a rank order of MGM > MGF > PGM > PGF, but in the case of grandsons only, this order is not statistically significant. (2) There are stable relationships between grandparental caregiving/grandchildren's emotional closeness and residential distance/similarity in appearance. (3) The effects of residential distance on either PGFs' or PGMs' caregiving exceed those on either MGFs' or MGMs'. (4) The PGF and PGM prefer grandsons to granddaughters in their caregiving, whereas the MGF and MGM do not have a sex preference, and (5) the fact that the PGF and PGM invest more in grandsons than in granddaughters does not depend on grandsons' duration of living in a rural area. Our results suggest that (1) in general, the Chinese display a pattern of differential grandparental investment predicted by an evolutionary perspective, (2) the evolutionary perspective that combines the two factors of paternal uncertainty and sex-specific reproductive strategies is applicable to grandparental investment in China, and (3) the traditional son-preference culture also plays some role in affecting grandparental investment in China, though the roles of culture and urban-rural cultural difference should not be exaggerated.

2024-02-07·European journal of medicinal chemistry

Structure-guided optimization of 3-hydroxybenzoisoxazole derivatives as inhibitors of Aldo-keto reductase 1C3 (AKR1C3) to target prostate cancer.

Article

作者: Agnese Chiara Pippione ; Sandra Kovachka ; Chiara Vigato ; Laura Bertarini ; Iole Mannella ; Stefano Sainas ; Barbara Rolando ; Enrica Denasio ; Helen Piercy-Mycock ; Linda Romalho ; Edoardo Salladini ; Salvatore Adinolfi ; Daniele Zonari ; Caterina Peraldo-Neia ; Giovanna Chiorino ; Alice Passoni ; Osman Asghar Mirza ; Karla Frydenvang ; Klaus Pors ; Marco Lucio Lolli ; Francesca Spyrakis ; Simonetta Oliaro-Bosso ; Donatella Boschi

AKR1C3 is an enzyme that is overexpressed in several types of radiotherapy- and chemotherapy-resistant cancers. Despite AKR1C3 is a validated target for drug development, no inhibitor has been approved for clinical use. In this manuscript, we describe our study of a new series of potent AKR1C3-targeting 3-hydroxybenzoisoxazole based inhibitors that display high selectivity over the AKR1C2 isoform and low micromolar activity in inhibiting 22Rv1 prostate cancer cell proliferation. In silico studies suggested proper substituents to increase compound potency and provided with a mechanistic explanation that could clarify their different activity, later confirmed by X-ray crystallography. Both the in-silico studies and the crystallographic data highlight the importance of 90° rotation around the single bond of the biphenyl group, in ensuring that the inhibitor can adopt the optimal binding mode within the active pocket. The p-biphenyls that bear the meta-methoxy, and the ortho- and meta-trifluoromethyl substituents (in compounds 6a, 6e and 6f respectively) proved to be the best contributors to cellular potency as they provided the best IC₅₀ values in series (2.3, 2.0 and 2.4 μM respectively) and showed no toxicity towards human MRC-5 cells. Co-treatment with scalar dilutions of either compound 6 or 6e and the clinically used drug abiraterone led to a significant reduction in cell proliferation, and thus confirmed that treatment with both CYP171A1-and AKR1C3-targeting compounds possess the potential to intervene in key steps in the steroidogenic pathway. Taken together, the novel compounds display desirable biochemical potency and cellular target inhibition as well as good in-vitro ADME properties, which highlight their potential for further preclinical studies.

2024-02-04·medRxiv : the preprint server for health sciences

Distinguishing different psychiatric disorders using DDx-PRS.

作者: Wouter J Peyrot ; Georgia Panagiotaropoulou ; Loes M Olde Loohuis ; Mark J Adams ; Swapnil Awasthi ; Tian Ge ; Andrew M McIntosh ; Brittany L Mitchell ; Niamh Mullins ; Kevin S O'Connell ; Brenda W J H Penninx ; Danielle Posthuma ; Stephan Ripke ; Douglas M Ruderfer ; Emil Uffelmann ; Bjarni J Vilhjalmsson ; Zhihong Zhu ; Schizophrenia Working Group of the Psychiatric Genomics Consortium ; Bipolar Disorder Working Group of the Psychiatric Genomics Consortium ; Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium ; Jordan W Smoller ; Alkes L Price

Despite great progress on methods for case-control polygenic prediction (e.g. schizophrenia vs. control), there remains an unmet need for a method that genetically distinguishes clinically related disorders (e.g. schizophrenia (SCZ) vs. bipolar disorder (BIP) vs. depression (MDD) vs. control); such a method could have important clinical value, especially at disorder onset when differential diagnosis can be challenging. Here, we introduce a method, Differential Diagnosis-Polygenic Risk Score (DDx-PRS), that jointly estimates posterior probabilities of each possible diagnostic category (e.g. SCZ=50%, BIP=25%, MDD=15%, control=10%) by modeling variance/covariance structure across disorders, leveraging case-control polygenic risk scores (PRS) for each disorder (computed using existing methods) and prior clinical probabilities for each diagnostic category. DDx-PRS uses only summary-level training data and does not use tuning data, facilitating implementation in clinical settings. In simulations, DDx-PRS was well-calibrated (whereas a simpler approach that analyzes each disorder marginally was poorly calibrated), and effective in distinguishing each diagnostic category vs. the rest. We then applied DDx-PRS to Psychiatric Genomics Consortium SCZ/BIP/MDD/control data, including summary-level training data from 3 case-control GWAS ( N =41,917-173,140 cases; total N =1,048,683) and held-out test data from different cohorts with equal numbers of each diagnostic category (total N =11,460). DDx-PRS was well-calibrated and well-powered relative to these training sample sizes, attaining AUCs of 0.66 for SCZ vs. rest, 0.64 for BIP vs. rest, 0.59 for MDD vs. rest, and 0.68 for control vs. rest. DDx-PRS produced comparable results to methods that leverage tuning data, confirming that DDx-PRS is an effective method. True diagnosis probabilities in top deciles of predicted diagnosis probabilities were considerably larger than prior baseline probabilities, particularly in projections to larger training sample sizes, implying considerable potential for clinical utility under certain circumstances. In conclusion, DDx-PRS is an effective method for distinguishing clinically related disorders.

项与 17β-HSD5 相关的新闻（医药）

2024-03-18

·GlobeNewswire-Health Care

OBI Pharma Announces Poster Presentations at the AACR 2024 Annual Meeting for OBI-992 and GlycOBI™ ADC platform

Poster Presentations to highlight the latest research on OBI-992 (anti-TROP2 ADC) and OBI’s novel GlycOBI ADC platformTAIPEI, Taiwan, March 18, 2024 (GLOBE NEWSWIRE) -- OBI Pharma, Inc. (TPEx: 4174) today announced preclinical data for OBI-992, a potential best-in-class anti-TROP2 Antibody-Drug Conjugate (ADC). When evaluated against comparative TROP2 ADCs, OBI-992 demonstrated greater antitumor efficacy, superior PK/PD properties, and a favorable safety profile across various preclinical animal models. Additionally, preclinical data will be presented on the novel site-specific proprietary GlycOBI™ ADC platform, demonstrating improved in vivo efficacy and stability in animal model studies. These data will be presented at the American Association of Cancer Research (AACR) Annual Meeting from April 5 to 10, 2024 in San Diego, California (USA). “Our data suggest OBI-992 has the potential to become a best-in-class TROP2 ADC. OBI-992 binds to a TROP2 epitope that is distinct from that of datopotamab and sacituzumab. OBI-992 shows lower non-specific binding, which should lead to decreased off-target cytotoxicity compared to benchmark ADCs. OBI-992 demonstrated remarkable anti-tumor efficacy in several CDX and PDX models. In addition, OBI-992 showed excellent bystander effect and synergistic efficacy in combination with PARP inhibitors or anti-PD1 in animal models. OBI-992 was stable in circulation and well tolerated in cynomolgus monkeys, suggesting a good safety profile” said OBI’s Chief Scientific Officer, Ming-Tain Lai, Ph.D. “In addition, OBI developed a proprietary site-specific conjugation GlycOBI ADC platform to produce homogeneous ADCs. Preclinical studies demonstrated that the ADCs derived from GlycOBI platform showed better anti-tumor efficacy and PK profile. We are excited about the potential of applying this platform to generate novel ADCs to address unmet medical needs and provide cancer patients with better treatment options. These encouraging results warrant further clinical development.” Title: OBI-992, a novel TROP2 targeting antibody-drug conjugate, displayed excellent antitumor efficacy in various animal models 1 Authors*: Wan-Fen Li, Ming-Feng Chiang, Hao-Cheng Weng, Jhih-Jie Yang, Hsin-Shan Wu, Chun-Jung Lin, Ping-Tzu Chiu, and Ming-Tain LaiSession Title: Antibody-Drug Conjugates and Bispecific AntibodiesLocation: Poster Section 23Poster Board Number: 4Abstract Presentation Number: 1893Session Date and Time: Monday April 8, 2024. 9:00 AM - 12:30 PM Title: In vitro characterization of a novel TROP2-targeting antibody-drug conjugate OBI-992 2 Authors*: Tzer-Min Kuo, Ting-Yu Chang, Jye-Yu Huang, Wei-Chien Tang, Chun-Jung Lin, Yi-Chen Wu, Chi-Huan Lu, Hao-Cheng Weng, Yu-Jung Chen, Yu-Hsuan Tsao, Cheng-Yen Wei, Lifen Shen, Wan-Fen Li, and Ming-Tain LaiSession Title: Antibody-Drug ConjugatesLocation: Poster Section 21Poster Board Number: 11Abstract Presentation Number: 3130Session Date and Time: Monday April 8, 2024. 1:30 PM - 5:00 PM Title: Development of a novel site-specific ADC glycan platform with potential for improved in vivo efficacy and stability of the ADC in animal studies 3 Authors*: Teng-Yi Huang, Yin-Cheng Hsieh, Ka-Shu Fung, Yu-Chao Huang, Chi-Sheng Shia, Ming-Feng Chiang, Nan-Hsuan Wang, Wan-Fen Li, and Ming-Tain LaiSession Title: Antibody-Drug ConjugatesLocation: Poster Section 21Poster Board Number: 30Abstract Presentation Number: 3149Session Date and Time: Monday, April 8, 2024. 1:30 PM - 5:00 PM Title: OBI-992, a novel TROP2 targeting antibody drug conjugate demonstrates superior in vivo PK/PD properties and a favorable safety profile 4 Authors*: Chi-Sheng Shia, Shih-Ni Wen, Ren-Yu Hsu, Jyy-Shiuan Tu, Hui-Wen Chang, Wan-Fen Li, and Ming-Tain LaiSession Title: Pharmacology and PharmacogeneticsLocation: Poster Section 24Poster Board Number: 20Abstract Presentation Number: 7179Session Date and Time: Wednesday April 10, 2024. 9:00 AM - 12:30 PM * OBI Pharma, Inc., Taipei, Taiwan. 1, 2, 3, 4 : AACR Annual Meeting 2024 Abstracts online The e-posters will be available for browsing at the AACR Annual Meeting beginning at 12:00 PM ET on April 5, as well as on the OBI Pharma website (http://www.obipharma.com) beginning on April 11. About OBI-992 OBI-992 is a TROP2-targeted antibody-drug conjugate (ADC) that carries a potent topoisomerase I inhibitor payload to kill tumor cells. TROP2 is highly expressed in a variety of solid tumors such as lung, breast, ovarian, and gastric cancer, rendering it an ideal target for cancer therapy. OBI-992 uses a unique hydrophilic, enzyme-cleavable linker that is stable in circulation but releases the cytotoxic payload inside tumor cells. OBI-992 demonstrates remarkable antitumor efficacy, improved pharmacokinetic characteristics, and a favorable safety profile in animal models. OBI-992 received US IND clearance in January 2024, Phase 1/2 efficacy and safety human studies are planned to commence early Q2, 2024. The TROP2 targeting antibody was in-licensed from Biosion, Inc. www.Biosion.com, in December 2021. OBI Pharma owns ex-China commercial rights for OBI-992. About GlycOBI™ OBI has developed a unique glycan ADC platform (GlycOBI™), which are in a ‘Plug and Play’ format and compatible with any antibodies, linkers, and payloads in various Drug Antibody Ratio (DAR). Utilizing OBI’s proprietary enzymatic technology (EndoSymeOBI™), GlycOBI generates site-specific homogenous ADCs with an efficient and scalable process. The conjugation process of GlycOBI avoids disrupting the antibody structure and ensures the ADC has similar biophysical characteristics to the native antibody. Furthermore, OBI’s linker technology has improved conjugation efficiency of the payload and reduced aggregation propensity, and also expanded the half-life of the ADC products. GlycOBI has overcome the limitations of traditional ADCs and achieved better efficacy and stability in various in vivo tests. GlycOBI™ and EndoSymeOBI™ are trademarks of OBI Pharma. Inc. About OBI Pharma OBI Pharma, Inc., is a clinical stage oncology company that is headquartered in Taiwan and established in 2002. Its mission is to develop novel cancer therapeutic agents for patients with high unmet medical needs. The company’s novel first-in-class immuno-oncology portfolio targeting Globo H includes: two Globo H active immunotherapy vaccines, Adagloxad Simolenin (formerly OBI-822) and OBI-833. Using the company’s unique ADC platforms, including GlycOBI™, OBI created its novel ADC pipelines, OBI-992, OBI-902 and OBI-904, targeting TROP2 and Nectin-4, respectively. OBI’s pipeline also includes the first-in-class AKR1C3-targeted small-molecule prodrug OBI-3424, which selectively releases a potent DNA-alkylating antitumor agent in the presence of the aldo-keto reductase 1C3 (AKR1C3) enzyme. Additional information can be found at www.obipharma.com. Forward-Looking Statements Statements included in this press release that are not a description of historical facts are forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Such forward-looking statements include, but are not limited to, statements about future clinical trials, results and the timing of such trials and results. Such risk factors are identified and discussed from time to time in OBI Pharma’s reports and presentations, including OBI Pharma’s filings with the Taiwan Securities and Futures Bureau. COMPANY CONTACT:Kevin Poulos, CBOOBI Pharma, Inc.1.619.537.7698 Ext. 102kpoulos@obipharmausa.com

免疫疗法抗体药物偶联物AACR会议临床申请

2024-03-18

·BioSpace

OBI Pharma Announces Poster Presentations at the AACR 2024 Annual Meeting for OBI-992 and GlycOBI™ ADC platformPoster Presentations to highlight the latest research on OBI-992 (anti-TROP2 ADC) and OBI’s novel GlycOBI ADC platform

TAIPEI, Taiwan, March 18, 2024 (GLOBE NEWSWIRE) -- OBI Pharma, Inc. (TPEx: 4174) today announced preclinical data for OBI-992, a potential best-in-class anti-TROP2 Antibody-Drug Conjugate (ADC). When evaluated against comparative TROP2 ADCs, OBI-992 demonstrated greater antitumor efficacy, superior PK/PD properties, and a favorable safety pro various preclinical animal models. Additionally, preclinical data will be presented on the novel site-specific proprietary GlycOBI™ ADC platform, demonstrating improved in vivo efficacy and stability in animal model studies. These data will be presented at the American Association of Cancer Research (AACR) Annual Meeting from April 5 to 10, 2024 in San Diego, California (USA). “Our data suggest OBI-992 has the potential to become a best-in-class TROP2 ADC. OBI-992 binds to a TROP2 epitope that is distinct from that of datopotamab and sacituzumab. OBI-992 shows lower non-specific binding, which should lead to decreased off-target cytotoxicity compared to benchmark ADCs. OBI-992 demonstrated remarkable anti-tumor efficacy in several CDX and PDX models. In addition, OBI-992 showed excellent bystander effect and synergistic efficacy in combination with PARP inhibitors or anti-PD1 in animal models. OBI-992 was stable in circulation and well tolerated in cynomolgus monkeys, suggesting a good safety profile” said OBI’s Chief Scientific Officer, Ming-Tain Lai, Ph.D. “In addition, OBI developed a proprietary site-specific conjugation GlycOBI ADC platform to produce homogeneous ADCs. Preclinical studies demonstrated that the ADCs derived from GlycOBI platform showed better anti-tumor efficacy and PK profile. We are excited about the potential of applying this platform to generate novel ADCs to address unmet medical needs and provide cancer patients with better treatment options. These encouraging results warrant further clinical development.” Title: OBI-992, a novel TROP2 targeting antibody-drug conjugate, displayed excellent antitumor efficacy in various animal models1 Authors*: Wan-Fen Li, Ming-Feng Chiang, Hao-Cheng Weng, Jhih-Jie Yang, Hsin-Shan Wu, Chun-Jung Lin, Ping-Tzu Chiu, and Ming-Tain Lai Session Title: Antibody-Drug Conjugates and Bispecific Antibodies Location: Poster Section 23 Poster Board Number: 4 Abstract Presentation Number: 1893 Session Date and Time: Monday April 8, 2024. 9:00 AM - 12:30 PM Title: In vitro characterization of a novel TROP2-targeting antibody-drug conjugate OBI-992 2 Authors*: Tzer-Min Kuo, Ting-Yu Chang, Jye-Yu Huang, Wei-Chien Tang, Chun-Jung Lin, Yi-Chen Wu, Chi-Huan Lu, Hao-Cheng Weng, Yu-Jung Chen, Yu-Hsuan Tsao, Cheng-Yen Wei, Lifen Shen, Wan-Fen Li, and Ming-Tain Lai Session Title: Antibody-Drug Conjugates Location: Poster Section 21 Poster Board Number: 11 Abstract Presentation Number: 3130 Session Date and Time: Monday April 8, 2024. 1:30 PM - 5:00 PM Title: Development of a novel site-specific ADC glycan platform with potential for improved in vivo efficacy and stability of the ADC in animal studies3 Authors*: Teng-Yi Huang, Yin-Cheng Hsieh, Ka-Shu Fung, Yu-Chao Huang, Chi-Sheng Shia, Ming-Feng Chiang, Nan-Hsuan Wang, Wan-Fen Li, and Ming-Tain Lai Session Title: Antibody-Drug Conjugates Location: Poster Section 21 Poster Board Number: 30 Abstract Presentation Number: 3149 Session Date and Time: Monday, April 8, 2024. 1:30 PM - 5:00 PM Title: OBI-992, a novel TROP2 targeting antibody drug conjugate demonstrates superior in vivo PK/PD properties and a favorable safety pro >4 Authors*: Chi-Sheng Shia, Shih-Ni Wen, Ren-Yu Hsu, Jyy-Shiuan Tu, Hui-Wen Chang, Wan-Fen Li, and Ming-Tain Lai Session Title: Pharmacology and Pharmacogenetics Location: Poster Section 24 Poster Board Number: 20 Abstract Presentation Number: 7179 Session Date and Time: Wednesday April 10, 2024. 9:00 AM - 12:30 PM * OBI Pharma, Inc., Taipei, Taiwan. 1, 2, 3, 4 : AACR Annual Meeting 2024 Abstracts online The e-posters will be available for browsing at the AACR Annual Meeting beginning at 12:00 PM ET on April 5, as well as on the OBI Pharma website ( ) beginning on April 11. About OBI-992 OBI-992 is a TROP2-targeted antibody-drug conjugate (ADC) that carries a potent topoisomerase I inhibitor payload to kill tumor cells. TROP2 is highly expressed in a variety of solid tumors such as lung, breast, ovarian, and gastric cancer, rendering it an ideal target for cancer therapy. OBI-992 uses a unique hydrophilic, enzyme-cleavable linker that is stable in circulation but releases the cytotoxic payload inside tumor cells. OBI-992 demonstrates remarkable antitumor efficacy, improved pharmacokinetic characteristics, and a favorable safety pro animal models. OBI-992 received US IND clearance in January 2024, Phase 1/2 efficacy and safety human studies are planned to commence early Q2, 2024. The TROP2 targeting antibody was in-licensed from Biosion, Inc. , in December 2021. OBI Pharma owns ex-China commercial rights for OBI-992. About GlycOBI™ OBI has developed a unique glycan ADC platform (GlycOBI™), which are in a ‘Plug and Play’ format and compatible with any antibodies, linkers, and payloads in various Drug Antibody Ratio (DAR). Utilizing OBI’s proprietary enzymatic technology (EndoSymeOBI™), GlycOBI generates site-specific homogenous ADCs with an efficient and scalable process. The conjugation process of GlycOBI avoids disrupting the antibody structure and ensures the ADC has similar biophysical characteristics to the native antibody. Furthermore, OBI’s linker technology has improved conjugation efficiency of the payload and reduced aggregation propensity, and also expanded the half-life of the ADC products. GlycOBI has overcome the limitations of traditional ADCs and achieved better efficacy and stability in various in vivo tests. GlycOBI™ and EndoSymeOBI™ are trademarks of OBI Pharma. Inc. About OBI Pharma OBI Pharma, Inc., is a clinical stage oncology company that is headquartered in Taiwan and established in 2002. Its mission is to develop novel cancer therapeutic agents for patients with high unmet medical needs. The company’s novel first-in-class immuno-oncology portfolio targeting Globo H includes: two Globo H active immunotherapy vaccines, Adagloxad Simolenin (formerly OBI-822) and OBI-833. Using the company’s unique ADC platforms, including GlycOBI™, OBI created its novel ADC pipelines, OBI-992, OBI-902 and OBI-904, targeting TROP2 and Nectin-4, respectively. OBI’s pipeline also includes the first-in-class AKR1C3-targeted small-molecule prodrug OBI-3424, which selectively releases a potent DNA-alkylating antitumor agent in the presence of the aldo-keto reductase 1C3 (AKR1C3) enzyme. Additional information can be found at Forward-Looking Statements Statements included in this press release that are not a description of historical facts are forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Such forward-looking statements include, but are not limited to, statements about future clinical trials, results and the timing of such trials and results. Such risk factors are identified and discussed from time to time in OBI Pharma’s reports and presentations, including OBI Pharma’s filings with the Taiwan Securities and Futures Bureau. COMPANY CONTACT: Kevin Poulos, CBO OBI Pharma, Inc. 1.619.537.7698 Ext. 102 kpoulos@obipharmausa.com

免疫疗法AACR会议抗体药物偶联物

2024-01-09

·美通社

博奥信合作伙伴OBI Pharma宣布TROP2 ADC在美国获批临床

- 该TROP2 ADC将开展安全性和有效性试验，预计今年初将完成首例患者给药 2024年1月8日，博奥信合作伙伴OBI Pharma（4174.TWO）宣布其新一代TROP2 抗体偶联药物（ADC）OBI-992（博奥信项目号：BSI-992）的临床I/II期试验已获美国食品药品监督管理局（FDA）批准。用于该ADC开发的抗体分子由博奥信专有的 SynTracer®高通量抗体内吞筛选平台发现和开发，并于2021年12月授权给OBI Pharma。OBI Pharma拥有OBI-992（BSI-992）在中国大陆、澳门、香港以外的产品开发及商业化权利，博奥信保留中国大陆、澳门、香港的权利。 "我们很高兴合作伙伴OBI Pharma在美国获得OBI-992（BSI-992）的临床试验批准，"首席商务和开发官，博奥信美国分公司总裁Hugh Davis博士表示。"临床前研究数据显示，对比其他TROP2 ADC，OBI-992具有差异化优势。这也表明博奥信SynTracer®高通量抗体内吞筛选平台在发现适用于新型ADC疗法的抗体方面具备独特优势。我们期待该药物在未来能为全球患者带来新的治疗方案。" OBI-992临床试验计划以晚期实体瘤患者为收治对象，包括非小细胞肺癌（NSCLC）、小细胞肺癌（SCLC）、胃癌（GC），及其他数种癌症病患亦列为潜在目标。OBI Pharma首席医学官Wayne Saville博士指出，这项试验旨在评估OBI-992安全性、药代动力学和初步疗效，他相信OBI-992具有相当潜力发展为同类最佳（best-in-class）的TROP2 ADC，预计I/II期试验将于2024年初展开，并为首位患者给药。 OBI Pharma首席执行官王慧君博士也表示，"OBI-992是由浩鼎自行设计、制造的新型TROP2 ADC，与其他TROP2 ADC相比，它在许多临床前试验中都显现出色的疗效、良好的安全性和高稳定性；我们对OBI-992首度进入人体临床试验感到兴奋，OBI Pharma将以『急病人之所急』原则，快速将有潜力的癌症疗法推进临床。" OBI-992（BSI-992）是以TROP2为靶点所设计的抗体偶联药物（Antibody Drug Conjugate; ADC）。TROP2在多种实体肿瘤都有高度表达，包括肺癌、乳癌、卵巢癌、胃癌等不同癌症，因此被认为是优秀的癌症治疗靶点。 OBI-992（BSI-992）以连接子（linker）将抗体和强效的TOP1（topoisomerase I）抑制剂相结合，这个独特的连接子具有高度亲水性，必须由癌细胞内的酶裂解，从而释放药物。OBI-992（BSI-992）在血液中维持稳定，一旦与癌细胞表面的TROP2结合内吞，就会在癌细胞内释放小分子药物，毒杀癌细胞。多种动物模型已经充分显示，OBI-992（BSI-992）具有高效的抗肿瘤活性，优异的药代动力学表现，和良好的安全性。 TROP2抗体为博奥信发现并开发，2021年12月授权给OBI Pharma。OBI Pharma负责ADC构建、研发，并拥有中国大陆、香港、澳门以外的商业化权利。台湾浩鼎生技（OBI Pharma, Inc.）成立于 2002年，是一已发展到临床阶段的癌症医药公司，以满足还未有效医疗的需求为使命，致力于开发癌症治疗的新药与多元化治疗组合。台湾浩鼎针对Globo H所开发的首创型（first-in-class）免疫疗法新药产品组合，包括两种以Globo H为标的之主动免疫疗法疫苗Adagloxad Simolenin（又称OBI-822）和OBI-833。另外，该公司利用独特的ADC平台，包括GlycOBI™，开创了多样性ADC新药产品线，如以TROP2为标靶的OBI-992、OBI-902、以Nectin4为标靶的OBI-904和以HER2为标靶开发的OBI-905。此外，浩鼎产品线还包括首创小分子前驱药OBI-3424。它系以醛酮还原酶AKR1C3为标靶的小分子前驱药，AKR1C3可将原本活性极低的前驱药，活化为具有疗效的DNA烷化剂（DNA alkylating agent）抗肿瘤药物。欲进一步了解台湾浩鼎相关信息，请上官网www.obipharma.com。博奥信是一家处于临床阶段的全球化创新生物技术公司，致力于应用其专有的抗体技术平台开发创新疗法，使患者在免疫及肿瘤疾病的治疗中获益。成立于2017年，博奥信通过内部专有的H³（高通量，高含量，高效率）抗体发现平台、SynTracer® 高通量抗体内吞筛选平台、Flexibody® 双功能抗体技术平台及全球合作建立了一系列创新药物管线。自研产品Bosakitug（BSI-045B/TQC2731，抗TSLP单抗）正在中美开展针对严重哮喘、慢性鼻窦炎伴鼻息肉和特应性皮炎的临床II期试验，另有5项自研合作产品在中美开展临床I期或II期试验。更多公司及管线信息，请访问www.biosion.com。内容来源于网络，如有侵权，请联系删除。

抗体药物偶联物引进/卖出申请上市