A Phase 2a, Randomized, Double-Blinded, Placebo-Controlled, Multicenter Study to Investigate the Antiviral Effect, Safety, Tolerability, and Pharmacokinetics of STP0404 in Adults With HIV-1 Infection

The purpose of this study is to evaluate the antiviral effect, safety, tolerability, and pharmacokinetics of STP0404 in adult participants living with Human Immunodeficiency Virus Type 1 (HIV-1) infection.

开始日期2023-05-23

申办/合作机构

ST Pharm Co., Ltd.

100 项与 Pirmitegravir 相关的临床结果

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100 项与 Pirmitegravir 相关的转化医学

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100 项与 Pirmitegravir 相关的专利（医药）

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项与 Pirmitegravir 相关的文献（医药）

bioRxiv : the preprint server for biology

The structural and mechanistic bases for the viral resistance to allosteric HIV-1 integrase inhibitor pirmitegravir

作者: Dinh, Tung ; Fuchs, James R ; Schinazi, Raymond F ; Perilla, Juan R ; Mengshetti, Seema ; Annamalai, Arun S ; Briganti, Lorenzo ; Amblard, Franck ; Kim, Baek ; Rey, Juan S ; Kvaratskhelia, Mamuka ; Tber, Zahira ; Kim, Kyungjin ; Cherepanov, Peter ; Haney, Reed

ABSTRACT:

Allosteric HIV-1 integrase (IN) inhibitors (ALLINIs) are investigational antiretroviral agents which potently impair virion maturation by inducing hyper-multimerization of IN and inhibiting its interaction with viral genomic RNA. The pyrrolopyridine-based ALLINI pirmitegravir (PIR) has recently advanced into Phase 2a clinical trials. Previous cell culture based viral breakthrough assays identified the HIV-1(Y99H/A128T IN)variant that confers substantial resistance to this inhibitor. Here, we have elucidated the unexpected mechanism of viral resistance to PIR. While both Tyr99 and Ala128 are positioned within the inhibitor binding V-shaped cavity at the IN catalytic core domain (CCD) dimer interface, the Y99H/A128T IN mutations did not substantially affect direct binding of PIR to the CCD dimer or functional oligomerization of full-length IN. Instead, the drug-resistant mutations introduced a steric hindrance at the inhibitor mediated interface between CCD and C-terminal domain (CTD) and compromised CTD binding to the CCDY99H/A128T+ PIR complex. Consequently, full-length INY99H/A128Twas substantially less susceptible to the PIR induced hyper-multimerization than the WT protein, and HIV-1(Y99H/A128T IN)conferred >150- fold resistance to the inhibitor compared to the WT virus. By rationally modifying PIR we have developed its analog EKC110, which readily induced hyper-multimerization of INY99H/A128Tin vitroand was ∼14-fold more potent against HIV-1(Y99H/A128T IN)than the parent inhibitor. These findings suggest a path for developing improved PIR chemotypes with a higher barrier to resistance for their potential clinical use.

IMPORTANCE:

Antiretroviral therapies save the lives of millions of people living with HIV (PLWH). However, evolution of multi-drug-resistant viral phenotypes is a major clinical problem, and there are limited or no treatment options for heavily treatment-experienced PLWH. Allosteric HIV-1 integrase inhibitors (ALLINIs) are a novel class of antiretroviral compounds which work by a unique mechanism of binding to the non-catalytic site on the viral protein and inducing aberrant integrase multimerization. Accordingly, ALLINIs potently inhibit both wild type HIV-1 and all drug-resistant viral phenotypes that have so far emerged against currently used therapies. Pirmitegravir, a highly potent and safe investigational ALLINI, is currently advancing through clinical trials. Here we have elucidated structural and mechanistic bases behind the emergence of HIV-1 integrase mutations in infected cell that confer resistance to pirmitegravir. In turn, our findings allowed us to rationally develop an improved ALLINI with substantially enhanced potency against the pirmitegravir resistant virus.

PLoS pathogens1区 · 医学

A highly potent and safe pyrrolopyridine-based allosteric HIV-1 integrase inhibitor targeting host LEDGF/p75-integrase interaction site

1区 · 医学

ArticleOA

作者: Mahboubi, Bijan ; Ahn, Seohyun ; Kim, Kyungjin ; Engelman, Alan N ; Koneru, Pratibha C ; Lindenberger, Jared ; Maehigashi, Tatsuya ; Kvaratskhelia, Mamuka ; Kim, Baek ; Oo, Adrian ; Kim, Uk-Il

Allosteric integrase inhibitors (ALLINIs) are a class of experimental anti-HIV agents that target the noncatalytic sites of the viral integrase (IN) and interfere with the IN-viral RNA interaction during viral maturation. Here, we report a highly potent and safe pyrrolopyridine-based ALLINI, STP0404, displaying picomolar IC50 in human PBMCs with a >24,000 therapeutic index against HIV-1. X-ray structural and biochemical analyses revealed that STP0404 binds to the host LEDGF/p75 protein binding pocket of the IN dimer, which induces aberrant IN oligomerization and blocks the IN-RNA interaction. Consequently, STP0404 inhibits proper localization of HIV-1 RNA genomes in viral particles during viral maturation. Y99H and A128T mutations at the LEDGF/p75 binding pocket render resistance to STP0404. Extensive in vivo pharmacological and toxicity investigations demonstrate that STP0404 harbors outstanding therapeutic and safety properties. Overall, STP0404 is a potent and first-in-class ALLINI that targets LEDGF/p75 binding site and has advanced to a human trial.

mBio

The structural and mechanistic bases for the viral resistance to allosteric HIV-1 integrase inhibitor pirmitegravir

Article

作者: Dinh, Tung ; Rey, Juan S. ; Perilla, Juan R. ; Mengshetti, Seema ; Annamalai, Arun S. ; Briganti, Lorenzo ; Amblard, Franck ; Kim, Baek ; Kvaratskhelia, Mamuka ; Tber, Zahira ; Kim, Kyungjin ; Cherepanov, Peter ; Haney, Reed ; Schinazi, Raymond F. ; Fuchs, James R.

ABSTRACT:

Allosteric HIV-1 integrase (IN) inhibitors (ALLINIs) are investigational antiretroviral agents that potently impair virion maturation by inducing hyper-multimerization of IN and inhibiting its interaction with viral genomic RNA. The pyrrolopyridine-based ALLINI pirmitegravir (PIR) has recently advanced into phase 2a clinical trials. Previous cell culture-based viral breakthrough assays identified the HIV-1 (Y99H/A128T IN) variant that confers substantial resistance to this inhibitor. Here, we have elucidated the unexpected mechanism of viral resistance to PIR. Although both Tyr99 and Ala128 are positioned within the inhibitor binding V-shaped cavity at the IN catalytic core domain (CCD) dimer interface, the Y99H/A128T IN mutations did not substantially affect the direct binding of PIR to the CCD dimer or functional oligomerization of full-length IN. Instead, the drug-resistant mutations introduced a steric hindrance at the inhibitor-mediated interface between CCD and C-terminal domain (CTD) and compromised CTD binding to the CCD Y99H/A128T + PIR complex. Consequently, full-length IN Y99H/A128T was substantially less susceptible to the PIR-induced hyper-multimerization than the WT protein, and HIV-1 (Y99H/A128T IN) conferred >150-fold resistance to the inhibitor compared with the WT virus. By rationally modifying PIR, we have developed its analog EKC110, which readily induced hyper-multimerization of IN Y99H/A128Tin vitro and was ~14-fold more potent against HIV-1 (Y99H/A128T IN) than the parent inhibitor. These findings suggest a path for developing improved PIR chemotypes with a higher barrier to resistance for their potential clinical use.

IMPORTANCE:

Antiretroviral therapies save the lives of millions of people living with HIV (PLWH). However, the evolution of multi-drug-resistant viral phenotypes is a major clinical problem, and there are limited or no treatment options for heavily treatment-experienced PLWH. Allosteric HIV-1 integrase inhibitors (ALLINIs) are a novel class of antiretroviral compounds that work by a unique mechanism of binding to the non-catalytic site on the viral protein and inducing aberrant integrase multimerization. Accordingly, ALLINIs potently inhibit both wild-type HIV-1 and all drug-resistant viral phenotypes that have so far emerged against currently used therapies. Pirmitegravir, a highly potent and safe investigational ALLINI, is currently advancing through clinical trials. Here, we have elucidated the structural and mechanistic bases behind the emergence of HIV-1 integrase mutations in infected cells that confer resistance to pirmitegravir. In turn, our findings allowed us to rationally develop an improved ALLINI with substantially enhanced potency against the pirmitegravir-resistant virus.

项与 Pirmitegravir 相关的新闻（医药）

2023-09-06

·Pharmaceutical Technology

FDA grants tentative approval for Viatris’ HIV therapy for children

The once-daily tablet is indicated for use in children weighing a minimum of 6kg to less than 25kg. Credit: Beenicebeelove/ Shutterstock.com. The US Food and Drug Administration (FDA) has granted tentative approval for Viatris’ new drug application of a single-tablet regimen to treat HIV-1 infection in the paediatric population. The once-a-day tablet for oral suspension comprises a fixed-dose combination of 60mg abacavir, 5mg dolutegravir and 30mg lamivudine. Recommended Reports Reports LOA and PTSR Model - Teropavimab in Human Immunodeficiency Virus (HIV) Infections (AIDS) GlobalData Reports LOA and PTSR Model - Pirmitegravir [Inn] in Human Immunodeficiency Virus (HIV) Infections (AIDS) GlobalData View all Viatris noted that the therapy is indicated for use in children weighing a minimum of 6kg to less than 25kg and has a strawberry flavour. The recommended dose of the treatment is weight proportionate and is not intended for usage in patients with a previous hypersensitivity reaction to abacavir as well as in individuals who are HLAB*5701-positive. This tentative approval will aid in making submissions to regulatory authorities, manufacturing and supply of the new paediatric formulation in 123 low and middle-income countries. Viatris has a licensing agreement in place with the Medicines Patent Pool for paediatric dolutegravir. To manufacture and supply HIV treatment, the company signed a development deal with ViiV Healthcare and the Clinton Health Access Initiative. The combination treatment is currently recommended by the World Health Organization as a first-line treatment for paediatric HIV patients. Viatris Emerging Asia and Access Markets India president Rakesh Bamzai said: “Over the years, we have continued to seek improvements to existing molecules to better meet patient needs – we have introduced novel heat-stable generic formulations, more convenient packaging options and paediatric therapies. “The approval of this single-tablet regimen – the fixed-dose combination of abacavir 60mg/dolutegravir 5mg/lamivudine 30mg – will reduce the pill burden for children living with HIV.”

引进/卖出上市批准临床研究免疫疗法

2022-08-10

·药明康德

过去一周，这16款创新疗法获得新临床进展

▎药明康德内容团队编辑近期，又有多种创新药物取得了早期进展，其中包括噬菌体疗法、溶瘤病毒疗法、六抗原靶向T细胞疗法等多种新颖的疗法类型，值得关注。在今天这篇文章里，药明康德内容团队将结合公开资料，与读者分享过去一周中部分创新疗法的早期临床进展。MT-601：通过IND申请开发机构：Marker Therapeutics疗法类型：六抗原靶向T细胞疗法适应症：复发/难治性非霍奇金淋巴瘤Marker Therapeutics是一家致力于开发用于治疗血液系统恶性肿瘤和实体肿瘤的下一代基于T细胞的免疫疗法的临床阶段的免疫肿瘤公司。MT-601是该公司开发的一种针对六种抗原的多肿瘤相关抗原（multiTAA）特异性T细胞产品，用于治疗复发/难治性非霍奇金患者。这些患者受抗CD19 CAR-T细胞治疗后疾病进展，或是不适合这种疗法。Marker Therapeutics的细胞治疗技术基于非工程化的肿瘤特异性T细胞的选择性扩增，这些T细胞能够识别肿瘤相关抗原，并杀死表达这些靶标的肿瘤细胞。这种T细胞组合在输注到患者体内后可以攻击多个肿瘤靶点，并激活患者的免疫系统以产生广谱抗肿瘤活性。Marker Therapeutics表示，由于这些T细胞没有进行基因工程改造，因此制造起来更容易、成本更低，毒性也更低。这项新的临床试验将建立在此前的五抗原靶向T细胞疗法的1/2期研究（TACTAL）中观察到的结果之上。在TACTAL研究中，multiTAA特异性T细胞产品具有出色的反应持久性，同时没有出现其他过继性细胞疗法中时常会发生的严重毒性（例如细胞因子释放综合征或神经毒性）。基于这些结果，FDA在IND中批准将WT-1作为第六种肿瘤相关抗原添加到MT-601中。ALRN-6924：修改1b期临床试验策略开发机构：Aileron Therapeutics疗法类型：MDM2/MDMX双重抑制剂适应症：p53突变乳腺癌Aileron Therapeutics致力于使化疗更安全，从而更有效地挽救更多患者的生命。ALRN-6924是Aileron Therapeutics开发的MDM2/MDMX双重抑制剂，旨在通过激活p53，进而上调p21（一种已知的细胞复制周期抑制剂）来治疗p53突变癌症患者。此次对方案的改进旨在加强ALRN-6924对p53突变乳腺癌患者免受化疗引起的严重中性粒细胞减少、脱发和潜在其他毒性的保护作用的证据。AGEN1571：完成首例患者给药开发机构：Agenus疗法类型：抗ILT2抗体适应症：晚期实体瘤Agenus是一家专注于发现和开发利用人体免疫系统对抗癌症和感染的疗法的临床阶段免疫肿瘤公司。AGEN1571是Agenus开发的一种旨在调节肿瘤相关巨噬细胞、T细胞、NK细胞和NKT细胞的新型抗ILT2抗体。ILT2是抗肿瘤免疫反应的主要抑制因子，也是导致患者对PD-1靶向疗法产生耐药性的原因之一。在临床前实验中，AGEN1571能够将巨噬细胞分化为促炎表型，并增强激活肿瘤微环境中的CD8阳性T细胞、NK和NKT细胞，以克服肿瘤对免疫检查点阻滞的耐药性。在这项1期临床试验中，受试者将接受AGEN1571作为单一药物或与botensilimab（Fc增强型抗CTLA-4抗体）和/或balstilimab（抗PD-1抗体）联合治疗。UCART20x22：通过IND申请开发机构：Cellectis疗法类型：同种异体双靶点CAR-T疗法适应症：B细胞恶性肿瘤Cellectis是一家利用基因编辑平台开发细胞和基因疗法的临床阶段的生物技术公司。UCART20x22是Cellectis开发的第一个同时靶向CD20和CD22的同种异体双靶点CAR-T疗法，用于复发或难治性非霍奇金淋巴瘤（r/r NHL）患者。CD20和CD22是经过验证的B细胞恶性肿瘤靶标，有潜力增强对肿瘤细胞的杀伤力并增加抗原靶向的广度。UCART20x22还使用TALEN基因编辑技术干扰TRAC基因（已被证明可降低移植物抗宿主病风险）和CD52基因（能够允许在患者的预处理方案中使用CD52定向单克隆抗体，并增强CAR-T细胞的植入、扩展和持久性）表达。该1/2a期临床试验（NatHaLi-01）将在今年下半年开始招募患者。AP-SA02：通过IND申请开发机构：Armata Pharmaceuticals疗法类型：噬菌体适应症：假体关节感染（PJI）Armata Pharmaceuticals是一家专注于开发抗生素病原体特异性噬菌体疗法来治疗耐药和难以治疗的细菌感染的生物技术公司。AP-SA02是该公司开发的一种靶向金黄色葡萄球菌的天然裂解噬菌体，具有强大的治疗特性，能对约95%的金黄色葡萄球菌临床分离株（包括耐甲氧西林和耐万古霉素的菌株）产生强大的抗菌活性，可与标准抗生素治疗产生协同作用，性质稳定。该1b/2a期试验将探索AP-SA02作为假体关节感染受试者标准抗生素治疗的辅助手段在静脉内和关节内剂量的安全性、耐受性和药代动力学。IMC-F106C：1期临床数据即将公布开发机构：Immunocore疗法类型：T细胞受体（TCR）双特异性免疫疗法适应症：实体肿瘤Immunocore是一家商业阶段的生物技术公司，其开发的新型TCR双特异性免疫疗法IMC-F106C将在今年ESMO大会上公布其在多个实体肿瘤中的1期临床数据。IMC-F106C是一种抗癌免疫动员单克隆TCR（ImmTAC）分子，被设计用于以超高亲和力识别细胞内的癌抗原，并通过与CD3受体结合，激活效应T细胞选择性地杀死这些癌细胞。根据Immunocore的新闻稿，ImmTAC的作用机制具有治疗血液肿瘤和实体肿瘤的潜力，包括免疫“冷”肿瘤及低突变率的肿瘤。BI-1607：完成首例患者给药开发机构：BioInvent International疗法类型：抗FcyRIIB抗体适应症：HER2阳性实体瘤BioInvent International是一家专注于发现和开发用于癌症免疫治疗的新型免疫调节抗体的生物技术公司。BI-1607是该公司开发的第二款抗FcγRIIB（一种抑制性Fc受体，是抗肿瘤免疫中的T细胞检查点）抗体，旨在提高现有癌症治疗（如曲妥珠单抗）的疗效并克服肿瘤的耐药性。近日，BI-1607联合曲妥珠单抗治疗HER2+实体瘤的1/2a期试验完成了首例患者给药。HER2是大约20%的乳腺癌（全球女性中最常见的癌症）以及胃和胃食管结合部腺癌中肿瘤形成和生长的驱动因素。临床前数据表明，使用BI-1607治疗可增强当前抗HER2方案（如曲妥珠单抗）的疗效。KB407：通过IND申请开发机构：Krystal Biotech疗法类型：基因治疗适应症：囊性纤维化（CF）Krystal Biotech是一家专注于开发可重复给药基因疗法的公司，其开发的KB407是一种吸入性、可重复给药的基因治疗产品，通过一种修饰的HSV-1载体携带囊性纤维化跨膜电导调节器（CFTR）基因的两种拷贝到肺呼吸细胞。通过诱导肺中全长正常CFTR蛋白的表达，KB407治疗有可能恢复肺细胞的离子和水的出入平衡，以纠正患者的肺部表现，且无论其潜在的基因突变如何。临床前研究显示，KB407能够在体外2D和3D类器官系统及啮齿类动物模型中成功应用。NVG-291：介绍1/2期研究设计开发机构：NervGen Pharma疗法类型：模拟肽适应症：阿尔茨海默病NervGen Pharma是一家致力于开发“first-in-class”神经修复药物以治疗神经系统损伤的临床阶段的生物技术公司。NVG-291是该公司开发的一种模拟受体蛋白酪氨酸磷酸酶σ（PTPσ）的细胞内结构域的治疗性多肽。PTPσ是一种可以与硫酸软骨素蛋白聚糖（CSPG）相互作用的细胞表面受体，这两者均已被证明可抑制神经系统损伤后的神经修复机制。NVG-291-R是NVG-291的啮齿动物形式，已被证明可通过增强可塑性、轴突再生和再髓鞘化在一系列动物模型中促进功能恢复和神经系统修复，包括脊髓损伤、周围神经损伤、多发性硬化和中风模型。NeuroNova：通过IND申请开发机构：Calidi Biotherapeutics疗法类型：溶瘤病毒适应症：复发性高级别胶质瘤Calidi Biotherapeutics是一家致力于开创基于同种异体细胞平台以彻底改变溶瘤病毒疗法的临床阶段的生物技术公司。NeuroNova（NSC-CRAd-S-pk7）是一种由装载了工程化溶瘤腺病毒的永生化神经干细胞（NSC）系组成的同种异体“现货型”疗法。在手术切除肿瘤后，将选择性递送溶瘤腺病毒的嗜肿瘤神经干细胞NeuroNova注射到切除腔的壁中可以导致病毒感染并摧毁剩余的肿瘤细胞。NeuroNova此前曾作为放射治疗和替莫唑胺治疗的辅助治疗开展过针对新诊断的神经胶质瘤患者的1 期剂量递增临床试验。结果显示，NeuroNova的耐受性良好，并显示出有希望的初步疗效。此次获批的临床试验旨在探索在复发性组织学证实的高级别胶质瘤（WHO III或IV级）成人患者中给予连续剂量NeuroNova的安全性和耐受性。CLBS201：完成1b期临试验最后一例患者给药开发机构：Caladrius Biosciences疗法类型：CD34+细胞疗法适应症：糖尿病肾病（DKD）Caladrius Biosciences是一家旨在开发治疗或逆转疾病疗法的临床阶段的生物医药公司。CLBS201是该公司开发的一种在研的用于肾内动脉给药的CD34+再生细胞治疗产品，用于治疗糖尿病肾病。Caladrius Biosciences于近日宣布完成了CLBS201的1b期临试验最后一例患者给药，预计将在2023年公布数据。人体中的所有组织都需要通过更换细胞来维持其功能，同时，还必须能够在受伤后生成新的血管。CD34+细胞是一种具有刺激新血管形成能力的干细胞，具有治疗由潜在缺血性损伤引起的包括糖尿病肾病在内的多种疾病的潜力。STP0404：1期临床数据公布开发机构：ST Pharm疗法类型：变构HIV-1整合酶抑制剂（ALLINI）适应症：艾滋病ST Pharm是一家致力于开发基于RNA的药物的创新公司。STP0404是该公司开发的新型强效HIV-1变构整合酶抑制剂，是一种通过阻断HIV再激活的新机制治疗艾滋病的候选疗法。ST Pharm在其新闻稿中表示，STP0404不仅对HIV野生型菌株具有抗病毒效果，对临床分离株和已产生耐药性的再激活病毒也表现出了优异的抗病毒活性。尽管利用ALLINI机制开发的针对HIV的疗法存在毒性问题，但在1期临床试验中，STP0404药物暴露随剂量增加的比例较小，并且尚未观察到严重的不良事件（AE）。基于此，ST Pharm将在今年启动STP0404的2a期研究。NX-13：1b期临床研究数据发布开发机构：Landos Biopharma疗法类型：NLRX1激动剂适应症：溃疡性结肠炎（UC）Landos Biopharma是一家专注于为自身免疫性疾病患者开发新型口服药物的临床阶段的生物制药公司。NX-13是该公司开发的一种新型口服小分子NLRX1激动剂，用于治疗溃疡性结肠炎（UC）。NLRX1是一种具有调节免疫反应能力的线粒体相关受体。NX-13可以通过激活NLRX1通路增加免疫细胞中的氧化磷酸化，减少效应CD4+ T细胞的分化，并减少胃肠道中炎性细胞因子的产生。NX-13的1b期临床试验结果显示，与安慰剂相比，NX-13用药四周后的耐受性良好。公司基于这些数据计划启动2期临床试验，以评估NX-13在UC患者中的安全性、有效性和最佳剂量。REGN5678：1/2期临床试验数据公布开发机构：Regeneron Pharmaceuticals疗法类型：PSMAxCD28共刺激性双特异性抗体适应症：转移性去势抵抗性前列腺癌（mCRPC）Regeneron Pharmaceuticals于近日宣布，其开发的PSMAxCD28共刺激性双特异性抗体REGN5678与PD-1抑制剂cemiplimab联用治疗前列腺癌的1/2期临床试验的初步数据令人鼓舞——当与标准剂量cemiplimab联合使用时，研究性REGN5678具有剂量依赖性的抗肿瘤活性，表明其具有克服mCRPC对PD-1抑制的耐药性的潜力。REGN5678是一种靶向CD28的共刺激双特异性抗体。基于对T细胞杀伤癌症能力的理解，Regeneron认为T细胞必须接受至少两种不同的刺激信号才能被完全激活以杀灭肿瘤细胞。该双抗一端与癌细胞表面的PSMA抗原结合，另一端与T细胞表面的CD28受体结合，通过选择性激活肿瘤部位T细胞的CD28通路，协同增强PD-1抑制剂和/或CD3双特异性分子的抗肿瘤活性。AVB-001：通过IND申请开发机构：Avenge Bio疗法类型：细胞疗法适应症：腹膜恶性肿瘤（卵巢癌）Avenge Bio是一家通过LOCOcyte免疫治疗平台开发用于治疗难治性实体瘤的转化细胞免疫治疗产品的生物技术公司。LOCOcyte平台可以利用递送到局部肿瘤环境的专有工程细胞，在肿瘤附近产生高浓度的免疫效应分子。这可以引起强大、局部和持久的全身性免疫反应，同时又避免了与全身性免疫疗法相关的毒性。基于该平台开发的AVB-001是一种把经工程设计可以分泌天然IL-2的细胞封装在可以激活免疫的藻蛋白酸盐胶囊中的疗法。该公司于近日宣布，FDA批准了AVB-001在腹膜恶性肿瘤中的IND申请。CRN04894：即将公布1期临床数据开发机构：Crinetics Pharmaceuticals疗法类型：促肾上腺皮质激素（ACTH）拮抗剂适应症：库欣病、先天性肾上腺皮质增生症（CAH）和其他ACTH过量的疾病Crinetics Pharmaceuticals是一家专注于发现、开发和商业化用于罕见内分泌疾病和内分泌相关肿瘤的新型疗法的临床阶段的医药公司。CRN04894是一种口服给药的非肽类小分子ACTH拮抗剂，用于治疗库欣病、先天性肾上腺皮质增生症（CAH）和其他ACTH过量的疾病。该公司宣布将于近期公布其1期临床试验结果，包括单剂量递增和多剂量爬坡研究的安全性、药代动力学和药效学。CAH是由基因突变引起的疾病，可导致皮质醇合成障碍。皮质醇的缺乏导致反馈机制的丧失，并引发持续高水平的ACTH，进而引起肾上腺皮质的过度刺激。由此引起的肾上腺增生和其他类固醇（尤其是雄激素）和类固醇前体的过度分泌，可导致性腺发育不良，严重者可因盐皮质激素失调危及生命。药明康德为全球生物医药行业提供一体化、端到端的新药研发和生产服务，服务范围涵盖化学药研发和生产、生物学研究、临床前测试和临床试验研发、细胞及基因疗法研发、测试和生产等领域。如您有相关业务需求，欢迎点击下方图片填写具体信息。▲如您有任何业务需求，请长按扫描上方二维码，或点击文末“阅读原文/Read more”，即可访问业务对接平台，填写业务需求信息参考资料：[1] Aileron Therapeutics Is Pleased to Outline Strategy to Strengthen Phase 1b Clinical Trial of ALRN-6924 in Patients with p53-Mutated Breast Cancer. Retrieved August 1, 2022, from https://investors.aileronrx.com/news-releases/news-release-details/aileron-therapeutics-pleased-outline-strategy-strengthen-phase[2] Study will evaluate safety and tolerability of AGEN1571 as a single agent and in combination with botensilimab and balstilimab. Retrieved August 1, 2022, from https://investor.agenusbio.com/news-releases/news-release-details/agenus-announces-first-patient-dosed-phase-1-study-agen1571-anti[3] Cellectis Receives IND clearance for UCART20x22, its First in-house Manufactured Product Candidate for the Treatment of B-cell Malignancies. Retrieved August 1, 2022, from https://cellectis.com/en/press/cellectis-receives-ind-clearance-for-ucart20x22-its-first-in-house-manufactured-product-candidate-for-the-treatment-of-b-cell-malignancies/[4] Armata Pharmaceuticals Announces Clearance of IND for Prosthetic Joint Infections. Retrieved August 1, 2022, from https://investor.armatapharma.com/2022-08-01-Armata-Pharmaceuticals-Announces-Clearance-of-IND-for-Prosthetic-Joint-Infections[5] Immunocore announces upcoming oral presentation of initial Phase 1 data of ImmTAC® candidate IMC-F106C targeting PRAME at European Society for Medical Oncology （ESMO） Congress 2022. Retrieved August 1, 2022, from https://ir.immunocore.com/news-releases/news-release-details/immunocore-announces-upcoming-oral-presentation-initial-phase-1[6] BioInvent enrolls first patient in Phase 1/2a trial of BI-1607 in HER2 positive solid tumors. Retrieved August 1, 2022, from https://bioinvent.com/media/press-releases/mfnsingle/?slug=bioinvent-enrolls-first-patient-in-phase-1-2a-trial-of-bi-1607-in-her2-positive-solid-tumors[7] Krystal Biotech Announces FDA Acceptance of KB407 IND Application for Cystic Fibrosis Clinical Trial. Retrieved August 1, 2022, from https://ir.krystalbio.com/news-releases/news-release-details/krystal-biotech-announces-fda-acceptance-kb407-ind-application[8] NervGen Presenting Study Design For Upcoming Phase 1b/2a In Alzheimer’s Disease At The 2022 Alzheimer’s Association International Conference. Retrieved August 2, 2022, from https://nervgen.com/nervgen-presenting-study-design-for-upcoming-phase-1b-2a-in-alzheimers-disease-at-the-2022-alzheimers-association-international-conference/[9] Calidi Biotherapeutics Announces FDA Authorization of IND for a Phase 1 Clinical Trial of NeuroNova in Patients with Recurrent High-Grade Glioma. Retrieved August 2, 2022, from https://calidibio.com/2022/08/02/calidi-biotherapeutics-announces-fda-authorization-of-ind-for-a-phase-1-clinical-trial-of-neuronova-in-patients-with-recurrent-high-grade-glioma/[10] Caladrius Biosciences Completes Enrollment in Phase 1b Study of CLBS201 for the Treatment of Diabetic Kidney Disease. Retrieved August 2, 2022, from https://ir.caladrius.com/news-releases/news-release-details/caladrius-biosciences-completes-enrollment-phase-1b-study[11] ST PHARM Present Phase 1 Clinical Trial Results of HIV Treatment Candidate at AIDS 2022. Retrieved August 4, 2022, from https://www.stpharm.co.kr/en/pr/all/st-pharm-present-phase-1-clinical-trial-results-of-hiv-treatment-candidate-at-aids-2022[12] LANDOS BIOPHARMA REPORTS POSITIVE TOP-LINE RESULTS FROM NX-13 PHASE 1B TRIAL. Retrieved August 3, 2022, from https://ir.landosbiopharma.com/news-releases/news-release-details/landos-biopharma-reports-positive-top-line-results-nx-13-phase[13] NOVEL COSTIMULATORY BISPECIFIC ANTIBODY SHOWS ENCOURAGING ANTI-TUMOR ACTIVITY WHEN COMBINED WITH PD-1 INHIBITOR LIBTAYO® （CEMIPLIMAB） IN ADVANCED METASTATIC CASTRATION-RESISTANT PROSTATE CANCER （MCRPC）. Retrieved August 3, 2022, from https://investor.regeneron.com/news-releases/news-release-details/novel-costimulatory-bispecific-antibody-shows-encouraging-anti[14] Avenge Bio Announces FDA Clearance of the AVB-001 IND for the Treatment of Ovarian Cancer, a Novel Cellular Therapy Leveraging the LOCOcyteTM Immunotherapy Platform. Retrieved August 3, 2022, from https://avengebio.com/wp-content/uploads/2022/08/AvengeBio_IND-Clearance-PR_v3AUG_Final-1.pdf[15] MARKER THERAPEUTICS ANNOUNCES FDA CLEARANCE OF IND FOR MT-601, THE SIX-ANTIGEN TARGETED T CELL THERAPY FOR THE TREATMENT OF RELAPSED/REFRACTORY NON-HODGKIN LYMPHOMA. Retrieved August 4, 2022, from https://ir.markertherapeutics.com/news-releases/news-release-details/marker-therapeutics-announces-fda-clearance-ind-mt-601-six[16] ADDITIONAL ANALYSES OF CRN04894 PRECLINICAL AND PHASE 1 RESULTS TO BE PRESENTED AT THE 10TH INTERNATIONAL CONGRESS OF NEUROENDOCRINOLOGY. Retrieved August 3, 2022, from https://crinetics.com/crinetics-pharmaceuticals-presenting-crn04894-preclinical-and-phase-1-at-icn2022/免责声明：药明康德内容团队专注介绍全球生物医药健康研究进展。本文仅作信息交流之目的，文中观点不代表药明康德立场，亦不代表药明康德支持或反对文中观点。本文也不是治疗方案推荐。如需获得治疗方案指导，请前往正规医院就诊。版权说明：本文来自药明康德内容团队，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。转载授权请在「药明康德」微信公众号回复“转载”，获取转载须知。分享，点赞，在看，聚焦全球生物医药健康创新

免疫疗法细胞疗法抗体基因疗法小分子药物

2022-08-03

·PRNewswire

ST Pharm Presents Phase 1 Clinical Trial Results of HIV Treatment Candidate at AIDS 2022

- STP0404 is the only clinical safety proven HIV treatment candidate with a novel mechanism that can block HIV re-activation. - STP0404 is expected to enter Phase 2a clinical trial in the US in 4Q 2022. SEOUL, South Korea, Aug. 3, 2022 /PRNewswire/ -- ST Pharm Co., Ltd. (237690:KOSDAQ) announced on 3rd August that the Phase 1 clinical trial results of STP0404, the HIV treatment candidate, was presented at the 24th International AIDS Conference took place in Montreal, Canada from 29th July to 2nd August. The International AIDS Conference is the biggest AIDS conference worldwide, held by the International AIDS Society (IAS) which has over 13,000 members from more than 170 countries. All submitted abstracts went through a blind peer-review process by international reviewers and only 300 abstracts were selected to be presented. Among those, the Phase 1 clinical trial results of STP0404 was selected with high score and was formally invited for poster presentation with a poster title, "The First-in-Human Clinical Trial of STP0404, a Novel Potent HIV-1 Allosteric Integrase Inhibitor". STP0404 is the world's first AIDS treatment with an ALLINI (Allosteric Integrase Inhibitor) mechanism in human clinical trials. All competing drugs developed with the same mechanism failed in preclinical stage due to toxicity issues. A total of 65 healthy male adult participants, aged from 18 to 45, were included in this Phase 1 clinical study. A total of 28 adverse events (AE) were reported. Headache and diarrhoea with mild to moderate intensity were most frequently reported as treatment emergent adverse events (TEAE). There were no severe AE, Serious AE reported and no clinically significant trend or abnormalities observed in laboratory tests, physical examination, vital signs and ECG evaluations. Since there were no clinically significant AEs reported at the highest dose levels (800 mg in single ascending dose part [SAD] and 400 mg in multiple ascending dose part [MAD]), the maximum tolerated dose was not confirmed. STP0404 also demonstrated consistent pharmacokinetics at various dose levels showing drug exposure increased less-proportionally with dose, and presented an elimination half-life can support once daily dosing regimen. ST Pharm stated, "From nonclinical studies, dosing with 0.01~10 μM of STP0404 in HIV reactivated T cells reduced the p24 level from over 270 pg/mL to 30 pg/mL. These results can be considered as potentially functional cure. STP0404 not only has optimal antiviral effects as mono-treatment against wild-type strains, but also presented excellent antiviral activities against clinical isolates and reactivated virus that have developed resistance. As the safety of STP0404 was confirmed in Phase 1 trial, a Phase 2a study is planned to be initiated this year." ST Pharm is further evaluating the clinical potential of co-administering STP0404 with marketed AIDS treatments, and is also developing long-acting injectables. Learn more at SOURCE ST Pharm Co., Ltd.

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