Rogocekib

KANAGAWA, Japan, June 7, 2022 /PRNewswire/ -- Chordia Therapeutics Inc. ("Chordia"), a biotech company engaged in the research and development of novel therapies for cancers, today announced that it has presented the interim results from the Phase 1 clinical trial of CTX-712, a selective pan-CDC-like kinase ("CLK") inhibitor discovered by Chordia, at the 2022 Annual Meeting of the American Society of Clinical Oncology (ASCO), which was held from June 3 to June 7. A Phase 1 clinical trial of CTX-712 in solid tumors and hematological malignancies demonstrated a clinically acceptable safety profile. As for antitumor efficacy, it was observed in multiple subjects, establishing an initial Proof of Concept (POC). Dose limiting toxicities (DLTs) observed included dehydration, decreased platelet count, and hypokalemia, and the maximum tolerated dose (MTD) for twice-weekly dosing was determined to be 140 mg. Additionally, two partial responses (PRs) and two complete responses (CRs) were observed in patients with ovarian cancer and acute myeloid leukemia, respectively. A dose-dependent increase in systemic exposure was observed in pharmacokinetics (PK) analysis, and a dose-dependent increase in exon skipping of RNAs set as pharmacodynamics (PD) markers confirmed mRNA splicing modification by CTX-712. Further studies are currently underway to determine the recommended Phase 2 dosing. "It is a great honor to be involved in the first-in-human clinical trial of a new anticancer drug candidate with a novel mechanism of action," said Dr. Noboru Yamamoto, Director of the Department of Experimental Therapeutics at the National Cancer Center Hospital and Principal Investigator of the study. "Although it is still in the early stages of clinical trials, we hope that CTX-712 will become an effective treatment for patients with advanced, relapsed, or refractory malignancies in the future." ASCO abstract number: 3080 Title: A First-in-Human Phase 1 Study of CTX-712 in Patients with Advanced, Relapsed or Refractory Malignant Tumors About CTX-712 CTX-712 is a first-in-class, orally available and selective small molecule inhibitor of CDC-like kinase (CLK), a key regulator of the RNA splicing process that plays an important role in cell growth. CTX-712 inhibits the growth of various human tumor cell lines in vitro, and in addition, exhibits antitumor activity in multiple xenograft mouse models in vivo. Details of Phase 1 Clinical Trial The Phase 1 clinical trial in Japan is investigating the tolerability, safety, and pharmacokinetics (PK) of CTX-712 in patients with advanced, relapsed, or refractory malignancies. For details of the study, please refer to JapicCTI-184188. About RNA Splicing The RNA immediately after transcription is called precursor messenger RNA which contains noncoding sequences (introns) as well as coding sequences (exons) that are needed to make proteins. RNA splicing is a process to remove the introns and connect the exons to form mature mRNA, which is then translated into protein. About CDC-like Kinases (CLKs) Kinase is a general term for enzymes that catalyze the transfer of phosphate groups in biological substances, such as ATP, over to target substances that are called substrates. Over 500 protein kinases are known in humans, of which the CLK family consists of four members – CLK1, CLK2, CLK3, and CLK4, and phosphorylates serine/arginine-rich (SR) proteins as substrates. About Serine/Arginine-rich Proteins (SR Proteins) SR protein is a general term for a group of proteins with serine (S) and arginine (R)-rich SR domains, of which about 10 types have been reported in humans. The serine in the SR domain is phosphorylated by CLK kinase. The phosphorylated SR proteins bind to the exon region of the precursor mRNA and facilitate the incorporation of the bound exon into the mature mRNA during splicing. About Exon Skipping When CTX-712 inhibits CLK kinases and the SR protein dephosphorylates, a splicing change called exon skipping occurs, in which the exons fail to be incorporated into the mature mRNA. Important Notice In this press release, the definition of "press release" covers any oral presentation, question and answer session, and written and/or oral materials discussed or distributed by Chordia Therapeutics in connection with this press release. This press release (including the oral description and related questions and answers) is not intended to constitute, represent, or form part of any offer, invitation, or solicitation to purchase and/or acquire anything, including securities. Disclaimer Any announcements by Chordia Therapeutics, including this press release, may contain information on products derived from pharmaceutical developments, but are intended to inform the latest information related to Chordia's business, and not intended as promotions, solicitations, advertisements, or to provide medical advice. Forward-Looking Statements This press release and materials distributed in connection with this press release may contain forward-looking statements, information, beliefs, and opinions concerning our future operations, future positioning, and performance, including estimates, projections, goals, and plans. Forward-looking statements may include, but are not limited to, expressions such as "goals," "plans," "beliefs," "hopes," "continues," "expects," "intends," "assures," "will," "may," "should," "would," "could," "estimates," "projects," and/or other similar expressions, or the negative thereof. These forward-looking statements are based on assumptions concerning a number of important factors, including the following, which could cause actual results to differ materially from those expressed or implied by the forward-looking statements; highly influential factors that include economic conditions surrounding our global business, which include general economic conditions in Japan and the United States, competitive pressures and developments including changes in applicable laws and regulations, which include global healthcare reform, uncertainty as to our clinical success, and challenges inherent in new product development (which include regulatory decisions and their timing,) uncertainty as to the commercial success of new and existing products manufacturing difficulties, delays fluctuations in interest rates and exchange rates claims or concerns regarding the safety or efficacy of commercial products or product candidates the impact of a health crisis, such as the COVID-19 pandemic, on Chordia and its customers and suppliers (including foreign governments in countries in which the Company conducts business) or other aspects of its business. We undertake no obligation to update any forward-looking statements contained in this press release or any other forward-looking statements we may make, except as required by law or stock exchange rules. Past performance is not indicative of future operating results, and any of our operating results or statements in this press release are not estimates, forecasts, warranties, or projections of our future operating results. About Chordia Therapeutics Chordia was established in November 2017 at Shonan Health Innovation Park ("Shonan iPark") in Fujisawa, Kanagawa Prefecture, as a biotech company engaged in the research and development of novel therapies for cancers, with the goal of researching and developing first-in-class anti-cancer drugs and creating innovative new drugs. In addition to its leading program for CTX-712, Chordia is engaged in the research of several developments in our pipeline, including CTX-439, a CDK12 inhibitor, which is expected to be effective in cancers with specific abnormalities, as well as GCN2 inhibitors. This press release is an English translation of a Japanese-language press release. The official language of this press release is Japanese, and the Japanese version takes precedence over the English version in terms of content and interpretation. View original content: SOURCE Chordia Therapeutics Inc.

2022年美国临床肿瘤学会年会(2022 ASCO)于6月3-7日举行，小编将报告中提到了部分first-in-class新药临床进展做了简单汇总，供读者参考。1. 名称：CT-0508    公司：Carisma TherapeuticsCT-0508是一款first-in-class靶向人表皮生长因子受体2（HER2）的嵌合抗原受体巨噬细胞（CAR-M）疗法。本次大会上， Carisma公司将公布首个I期多中心临床试验（NCT04660929）初步结果。该研究共招募18例复发或转移HER2阳性实体瘤患者，他们的癌症目前尚无有效的治疗方法。试验分两组，第一组患者将按计量递增的方式分3次输入这种疗法（5亿、15亿、30亿细胞）。第二组患者在1天内输入50亿细胞。试验主要终点是评估CT-0508的安全性（包括但不限于CRS的频率和严重程度）和耐受性，次要终点是评估其疗效（ORR、PFS）。7例患者（中位年龄64岁）接受了治疗（乳腺癌(2)、食管癌(2)、胆管癌、卵巢癌和腮腺癌）。既往治疗中位线数是3(2-10)，大部分患者(85.7%)既往接受过抗HER2治疗。研究结果表明成功生产了具有高活力、纯度和CAR表达的CT-0508，且耐受性良好，无剂量限制性毒性或导致停药或剂量调整的AE。同一例患者报告了2例相关SAE（1级CRS，住院监测；2级输液反应，1h内消退）。另外3例患者发生1-2级CRS；在4天内消退，无需使用托珠单抗。未出现主要器官毒性和脱靶肿瘤毒性。在大多数患者中，输注后细胞因子一过性升高，且具有自限性。在达到第8周的4例患者中，最佳总体缓解为疾病稳定(n=3)，1例患者疾病进展，中位随访时间为8周。在前2例患者的所有肿瘤活检组织中均检测到CT-0508 CAR mRNA。CT-0508可激活TME，增加骨髓细胞活化，T细胞浸润、活化和增殖。TCR测序显示外周扩增的T细胞富含肿瘤浸润淋巴细胞克隆，提示出现肿瘤反应性T细胞扩增。2. 名称：CTX-712    公司：Chordia TherapeuticsCTX-712是一款靶向CDC2样激酶(CLK)的firsit-in-class、口服、高效选择性小分子抑制剂。此次公布的首个人体I期研究（JapicCTI-184188）旨在评价CTX-712在实体瘤(ST)和血液恶性肿瘤(HM)患者中的最大耐受剂量(MTD)和剂量限制性毒性(DLT)、安全性、药代动力学(PK)和药效学(PD)特征以及通过初步疗效来确定推荐剂量(RD)。截至2021年12月31日，入组了30名患者，其中，16名患者入组ST剂量递增队列，10名患者入组ST扩展队列，4名患者入组HM剂量递增队列。在ST剂量递增队列中，2例患者观察到DLT（140mg（血小板计数降低、低钾血症），175mg（脱水）），MTD确定为140mg。基于该安全性信息，ST剂量扩展队列和HM剂量递增队列的起始剂量为105mg，每周两次。在所有入组患者中，最常见的≥3级AE为低钾血症(10%)、淀粉酶升高和血小板计数降低(7%)。在PK分析中，观察到CTX-712的全身暴露量呈剂量依赖性增加。使用从外周血细胞中提取的RNA评估PD反应。检测到两个标记RNA的外显子跳跃呈剂量依赖性增加。在ST和HM中分别观察到2例部分缓解和2例完全缓解。3. 名称：Zotatifin (eFT226)    公司：eFFECTOR TherapeuticsZotatifin是一款first-in-class的RNA解旋酶eIF4A1的有效、序列选择性抑制剂。此次公布的I/II期研究（NCT04092673）旨在评估Zotatifin在实体瘤患者中的疗效。该项研究纳入了携带ERBB2、FGFR1、FGFR2、EGFR或KRAS突变/扩增的特定实体瘤或胰腺癌患者，接受剂量递增（Part 1），并以RP2D接受剂量扩展（Part 2）研究。截至2022年1月13日，Part 1纳入了37例患者，在3例患者中观察到DLT：2级血小板减少症（0.035 mg/kg每周）、3级贫血(0.1 mg/kg)和3级胃肠出血导致贫血(0.1 mg/kg)。剂量递增阶段最常见TEAE包括：疲乏、贫血、腹泻和呼吸困难。MTD/RP2D为0.07 mg/kg IV，给药2周停药1周。RP2D水平最常见的AE（n= 16例患者；Part 1和 2）包括：贫血（25%，均为1级或2级）、疲乏（25%，均为1级或2级）和呼吸困难（19%；13%，均为1级或2级）。药代动力学通常呈线性且与剂量成比例，MTD/RP2D下的暴露量与临床前模型中的目标药理学水平一致。扩展队列患者治疗前和治疗中活检数据显示靶蛋白表达降低。剂量递增部分无患者出现客观肿瘤缓解。4. 名称：SEL24/MEN1703    公司：Menarini Ricerche SpA  SEL24是一款first-in-class口服PIM/FLT3双重抑制剂，本次大会公布的I/II期DIAMOND-01研究旨在评估SEL24在IDH1/2突变的急性髓系白血病（AML）患者中的安全性和初步疗效。截至2022年1月10日，14例患者入组IDHm队列。7例患者携带IDH2、1例携带IDH1/2、4例携带IDH1突变。在2例患者中检测到FLT3/ITD的伴随突变。中位治疗线为2（范围1-8）。安全性数据(N=12)显示，治疗中出现的严重AE(TEAE；≥5%)为肺炎(33%)、皮肤感染和梭状芽胞杆菌性胃肠炎（各8%）。这些事件均与研究药物无关。药物相关TEAE为肝损伤、药物过量和低钠血症（各8%）。1例患者发生药物相关肝损伤，他同时也接受了其他已知具有肝毒性的药物。≥3级TEAE(≥10%)为感染性肺炎(33%)和乏力(17%)，均与研究药物不相关。未见分化综合征。在完成≥1个治疗周期且有≥1次基线后评估或明确疾病进展的7例患者中，ORR为28.6%；1例患者在周期(C)3时达到CRi并接受造血干细胞移植，1例患者在C4时达到PR（在C7时确证，仍在接受治疗），4例患者疾病进展，1例因非药物相关AE而停药。其余7例患者中，3例在完成C1前停药，无进展或缓解，而4例患者正在进行中，尚未进行任何基线后评估。5. 名称：NVG-11   公司：NovalGenNVG-11是一款first-in-class、人源化、scFv ROR1/CD3双抗，本次大会将公布NVG-111治疗复发性/难治性(R/R)CLL和MCL患者的首个人体I/II期研究的I期初步临床结果。这些患者既往接受过≥2种全身治疗，并且在最后一线治疗后达到稳定或部分缓解。截至2022年1月，6例患者（均为男性，中位年龄60岁）入组研究；5例患有CLL，1例患有MCL，所有受试者在接受NVG-111治疗期间均继续接受伊布替尼治疗。最常见的不良事件为1级嗜睡、头痛、恶心、呕吐和血小板减少。暴露于固定剂量30 mg/天NVG-111的所有3例患者在第1个周期的第1周均发生1级CRS。1例患者发生一过性、3级免疫效应细胞相关神经毒性综合征样症状(ICANS)。在该剂量水平下的后续治疗周期中未观察到CRS或ICANS。在NVG-111治疗3个周期后完成疗效评估的所有5例可评价疗效患者中均观察到缓解。其中，2例患者血液中检测不到MRD，1例患者骨髓中MRD阴性。剂量递增研究正在进行中。6. 名称：SRF388    公司：Surface OncologySRF388是一款靶向IL-27的全人源IgG1抗体，本次大会将公布SRF388单药或联合帕博利珠单抗在晚期实体肿瘤患者中首个人体I/II期研究（ NCT04374877）临床结果。单药治疗剂量递增部分入组了29例患者，剂量范围为0.003-20mg/kg。约80%的患者既往接受过PD-(L)1阻断治疗，48%的患者既往接受过≥4种治疗。21%的患者发生治疗相关不良事件(TRAE)，且均为低级别。疲乏是唯一≥10%的TRAE(n = 3)。未观察到DLT或≥3级TRAE。中位治疗时间为9周（范围0-59）。1例高度难治性NSCLC患者在第8周出现经证实的部分缓解(PR)，持续20周。9例患者(31%)在第8周时疾病稳定，6个月时，9例患者中的6例显示疾病持续控制。7例ccRCC患者中，3例(43%)实现了≥20周的持久疾病控制（范围：20-32）。PK特征和安全性特征支持每3周或每4周给药一次。基于安全性、耐受性、PK、外周pSTAT1抑制和初步疗效，选择10mg/kg作为RP2D。SRF388给药后观察到几种血清细胞因子和趋化因子的变化，包括循环IL-27水平的预期内增加。7. 名称：Modakafusp alfa(TAK-573)    公司：TakedaTAK-573是一款first-in-class的免疫靶向减毒细胞因子，旨在将减毒干扰素α-2b(IFNα2b)片段递送至表达CD38肿瘤细胞。本次大会将公布TAK-573治疗转移性实体瘤的Ib/II期研究(NCT04157517)中的剂量递增阶段的安全性、药代动力学、免疫原性、药效学(PD)和初步疗效数据。21例患者在剂量递增阶段接受0.1(n=3)、0.2(n=3)、0.4(n=3)、0.75(n=3)、1.0(n = 3)和1.5mg/kg(n = 6)Q3W给药；中位年龄63岁；男性57.1%；GI恶性肿瘤71.4%；中位既往治疗线数3（范围2-7）。2例患者在cycle 1的1.5mg/kg剂量水平发生了DLT；1例基线骨浸润患者发生了4级血小板减少，1例患者发生了3级意识模糊。截至2021年11月，所有剂量组的患者接受中位2个治疗周期（范围1-11）。81%的患者报告的TRAE包括输注相关反应(52.4%)、寒战(47.6%)和恶心(33.3%)。42.9%的患者报告的≥3级TRAE包括中性粒细胞减少症(14.3%)和高血压(9.5%)。在14例可评价疗效的患者中，7例的最佳缓解为疾病稳定，包括1例靶病灶缩小21%的皮肤黑色素瘤患者。8. 名称：BCA10    公司：Bicara TherapeuticsBCA10是一款first-in-class双功能融合蛋白，由抗EGFR单抗和TGFβ受体2胞外域(TGFβRII-ECD)组成。此次会议上将报告BCA101单药和与帕博利珠单抗联合治疗标准治疗难治的晚期实体瘤患者的安全性、PK、PD和初步疗效数据。截至2022年2月8日，45例患者接受BCA101单药治疗，15例接受BCA101联合帕博利珠单抗治疗。归因于BCA101常见AE包括皮疹(70%)、疲乏(23%)、瘙痒和鼻衄（各17%）；所有等级(G)均≤2。在1250mg剂量下观察到1例DLT（G3贫血、血尿）。未观察到药物相关G4 AE或死亡。数据截止时，单药组39例可评价患者中的15例(39%)最佳缓解为疾病稳定(SD)。联合用药时，在3/11例(27%)可评价患者（SCAC 2例，HNSCC 1例）中观察到PR，DCR为9/11例(82%)。9. 名称：nadunolimab(CAN04)    公司：Cantargia ABNadunolimab是一种全人源化ADCC增强IgG1抗体，靶向IL1RAP并阻断IL-1α和IL-1β。此次大会上将报告nadunolimab联合帕博利珠单抗在既往抗PD-(L)1治疗后进展的实体瘤患者(pts)中开展的Ib期临床试验CIRIFOUR的初始数据。15例患者接受了至少1剂5mg/kg nadunolimab联合pembrolizumab治疗：中位年龄63岁，27%为女性，100%为IV期，93%和7%既往接受过帕博利珠单抗或纳武利尤单抗治疗，7%ECOG为0，93%ECOG为1。这些患者既往接受过平均2.3线治疗（范围1-6线）。47%的患者报告了SAE，其中1例被认为与治疗相关（发热性中性粒细胞减少症）。报告了2例治疗相关3级AE：1例发热性中性粒细胞减少症(DLT)和1例非感染性肺炎。没有患者因为治疗相关AE终止治疗。最佳缓解为1例患者(7%)达到未确证PR，8例患者(53%)达到SD，6例(40%)显示iUPD。10. 名称：CBP-1008     公司：同宜医药CBP-1008是一款靶向TRPV6和FRα的first-in-class双配体偶联药物。此次大会上，将报告CBP-1008在晚期实体瘤患者中安全性，耐受性，药代动力学特征和初步疗效数据。CBP-1008通过静脉输注给药。Ia期研究包括加速滴定期和剂量扩展期。Ib期临床扩展研究包括3个队列，铂类耐药卵巢癌(OC)、转移性三阴性乳腺癌(TNBC)和其他实体瘤。主要目的是评估安全性和初步疗效。截至2022年1月13日，共106例患者接受了至少一次CBP-1008治疗（Ia期：n = 30；Ib期：n=76），既往接受的治疗方案中位数为3。在Ia期研究中，3例患者（0.12、0.15、0.18 mg/kg，各n=1）观察到DLT，包括4级低磷血症、中性粒细胞减少、发热性中性粒细胞减少和3级高血糖、丙氨酸氨基转移酶(ALT)。尚未达到MTD。大多数不良事件为轻度至中度。最常见的3/4级治疗期间出现的不良事件(TEAE)为中性粒细胞减少症(37.7%)、AST升高(6.6%)、ALT升高(5.7%)、高血糖症(2.8%)、低血红蛋白血症(2.8%)和恶心(1.9%)。未观察到药物相关死亡。共有69例接受0.15 mg/kg或以上剂量的患者可用于疗效评估。11例达到PR(OC n=8，ER+/Her2+BC n=2，TNBC n=1)，30例达到SD。在32例FRα和（或）TRPV6阳性的晚期铂类药物耐药OC患者中，观察到6例PR和16例SD。此外，在FRα/TRPV6受体高表达OC患者中观察到33.3%(6/18)PR和44.4%(8/18) SD。由于篇幅有限，本文不再一一列举，给公众号回复“ASCO”获取本届会议摘要集731页PDF，之后在PDF中进行关键词检索“first-in-class”和“first in class”，可获得所有first-in-class药物相关进展。资源专区大礼包：来了！2022跨年医药数据资源大礼包来了推荐阅读：2021年市场表现最好的20款新药最新！全球药企排名TOP102022年全球CRO排名Top102022 AACR总结：最值得关注的小分子药物研发方向TOP102022 AACR总结：7大赛道10款产品，国内创新药“靓仔”来袭