A Phase Ia/Ib, Open-label, Dose-escalation, and Dose-expansion Study to Evaluate the Safety, Pharmacokinetics and Pharmacodynamic of UBX-303061 in Subjects with Relapsed/Refractory B-Cell Malignancies

This is a first-in-human Phase 1a/1b multicenter, open-label study designed to evaluate the safety and anti-cancer activity of UBX-303061 in patients with relapsed/refractory B-cell malignancies.

开始日期2025-02-20

申办/合作机构

Ubix Therapeutics Co. Ltd.

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项与 Ubix Therapeutics Co. Ltd. 相关的文献（医药）

2025-04-21·Cancer Research

Abstract 1661: Discovery of an SHP2 degrader with potent anti-cancer activity as a monotherapy and exceptional combination effects in KRAS mutant cancers

作者: Han, Jeonghwa ; Kim, So Hyuk ; Kang, Ju Young ; Park, Ji Youn ; Lee, Song Hee ; Ryu, Je Ho ; Lee, Jihye ; Kim, Hyun-Hwi ; Lee, Soohyun ; Kim, Jiyoung ; Suh, Beomseon ; Kim, Han Wool ; Bae, Onnuri

AbstractBackground:SHP2 is a key regulator of the RTK/RAS/MAPK signaling pathway, which is often disrupted in various cancers. Numerous allosteric SHP2 inhibitors are being actively developed to treat cancers driven by this pathway. However, these inhibitors face certain challenges, including their inability to target the active form of SHP2 and a narrow therapeutic window that requires intermittent dosing to manage toxicity. To address these limitations, we have developed SHP2 protein degraders as next-generation therapeutic agents targeting SHP2. In this study, we present the compelling characteristics of our SHP2 degraders.Methods:For inhibitor combination assay, we did clonogenic assay in NCI-H358 KRAS G12C mutant NSCLC and 3D proliferation in various cell lines. For in vivo assessment of pharmacological profile, we utilized an NCI-H358 xenograft. SHP2 protein levels in cell lysates and tumors were analyzed to assess SHP2 degradation efficiency and DUSP6 mRNA levels were analyzed to evaluate downstream effects. For selectivity analysis, we analyzed phosphatase panel profiling and proteomics.Results:Our compounds showed superior degradation activity achieving sub-nanomolar DC50 levels and significant cell growth inhibition exhibiting single digit nanomolar IC50 levels in NCI-H358 NSCLC (non-small cell lung cancer). In clonogenic and 3D cell proliferation assay, compound 5 showed significant growth inhibition with various inhibitors such as EGFR, MEK, ALK, RAF and KRAS G12C inhibitors. Phosphatase panel profiling and proteomics demonstrated compound 5 degraded SHP2 selectively. In particular, the superior anti-cancer effects of combination treatments with other drugs were confirmed across various cancer cell lines. In vivo experiments using a KRAS mutant CDX model revealed compelling in vivo profiles. Once-weekly intravenous administration achieved strong tumor growth inhibition without inducing the hematological and liver toxicities that were issues in the clinical studies of SHP2 inhibitors.Conclusion:We have successfully identified new SHP2 degraders with exceptional activity. Our findings demonstrate that, by leveraging the characteristics of these degraders as a strategy to overcome toxicity, they have the potential to address the limitations of allosteric SHP2 inhibitors, offering a promising therapeutic approach for patients with RTK/RAS/MAPK-dependent cancers.Citation Format:Soohyun Lee, Jiyoung Kim, Ji Youn Park, Beomseon Suh, Han Wool Kim, So Hyuk Kim, Hyun-Hwi Kim, Onnuri Bae, Jeonghwa Han, Ju Young Kang, Jihye Lee, Je Ho Ryu, Song Hee Lee. Discovery of an SHP2 degrader with potent anti-cancer activity as a monotherapy and exceptional combination effects in KRAS mutant cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 1661.

2025-04-21·Cancer Research

Abstract 7009: Discovery of UBX-306 as a potent, selective, and orally bioavailable HPK1 degrader

作者: Ryu, Je Ho ; Lee, Song Hee ; Yoo, Sun-Mi ; Jang, Miyoung ; Choi, Ae-Ran ; Kim, Hyun-Hwi ; Jeong, Na-rae ; Im, Sun-Kyoung ; Lee, Hohyun ; Ahn, Jungmin ; Kim, So Hyuk ; Kim, Han Wool

AbstractBackground:Hematopoietic progenitor kinase 1 (HPK1), part of the MAP4K family, is a serine/threonine kinase critical for modulating immune cell signaling and function. HPK1 is predominantly expressed in hematopoietic cells, where it acts as a negative regulator of T-cell receptor (TCR) signaling and other immune pathways. Upon activation, HPK1 dampens immune responses by phosphorylating key adapter proteins, such as SLP-76, and promoting their degradation, ultimately inhibiting T-cell activation, proliferation, and cytokine production. Given the critical role of T-cells in anti-tumor immunity, HPK1 has emerged as an attractive target in immuno-oncology for enhancing immune responses.Results:UBX-306;NT2020 demonstrated robust HPK1 protein degradation, achieving single-digit nanomolar DC50 levels in the Jurkat cell line in a dose-dependent manner. The degradation effect of UBX-306-1 is strongly dependent on the ubiquitin-proteasome system (UPS). Both UBX-306-1 and UBX-306-3 significantly enhanced IL-2 secretion in Jurkat cells, demonstrating superior EC50 values compared to the warhead of UBX-306, AZ1, or reference HPK1 degrader. Treatment with UBX-306-1 increased IL-2 production in a concentration-dependent manner, even in the presence of immunosuppressive molecules such as PGE2 and NECA. UBX-306-2 effectively degrades HPK1 protein in Ramos, Raw264.7, THP-1, and KG-1 cell lines. In vivo pharmacodynamic (PD) data demonstrated that UBX-306-1 efficiently degraded the HPK1 protein in the mouse blood. UBX-306-1 induced peak degradation of HPK1 at 6 hours after oral administration, with the degradation activity sustained for up to 24 hours. The antitumor efficacy of UBX-306-1 was evaluated in the CT-26 (Colorectal cancer) syngeneic tumor mouse model. Daily oral administration of UBX-306-1 at doses of 10 mg/kg and 30 mg/kg resulted in robust tumor growth inhibition.Conclusion:We demonstrate that potent HPK1 degraders, effectively activate immune cells and inhibit tumor growth in mouse syngeneic tumor models as single agents. These degraders enhance IL-2 and IFNγ production while overcoming immunosuppressive factors. Further, in vivo studies will deepen our understanding of HPK1 degradation as a promising immunomodulatory strategy for enhancing anti-tumor immunity.Citation Format:Ae-Ran Choi, Na-rae Jeong, Sun-Mi Yoo, Han Wool Kim, So Hyuk Kim, Hyun-Hwi Kim, Sun-Kyoung Im, Miyoung Jang, Hohyun Lee, Jungmin Ahn, Je Ho Ryu, Song Hee Lee. Discovery of UBX-306 as a potent, selective, and orally bioavailable HPK1 degrader [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 7009.

2024-03-22·Cancer Research

Abstract 6069: Discovery and preclinical development of orally bioavailable potent BTK degrader, and its early clinical development for the treatment of relapsed and refractory B-cell malignancies

作者: Lee, Song Hee ; Lim, Ye Seul ; Yoo, Sun-Mi ; Lim, Jong Hwan ; Ryu, Je Ho ; Kim, Han Wool

AbstractBackground : Bruton tyrosine kinase (BTK) is an important signaling hub that activates the B-cell receptor (BCR) signaling cascade, which is critical for growth and survival of B-cell lymphoma or leukemia. BTK inhibitors have shown anti-tumor activity in patients with B-NHL. However, nearly half of the patients on current BTK inhibitors discontinue the treatment due to adverse effects and/or mutation-induced drug resistance. A degrader is a heterobifunctional chemical compound aimed at eliminating disease-causing proteins, rather than simply inhibiting proteins’ enzymatic function, through the ubiquitin-proteasome system (UPS)-mediated protein degradation. This approach offers a unique solution for addressing relapse or refractory disease by removing overexpressed and mutated proteins, unlike traditional inhibitors. We thus designed UBX-382, a degrader targeting BTK.Results : UBX-382 showed superior degradation activity for both wild-type (WT) and mutant BTK proteins in a single-digit nanomolar range of half-maximal degradation concentration when compared to the competing degrader programs in diffuse large B-cell lymphoma cell line. UBX-382 effectively addressed 7 out of 8 previously reported resistant BTK mutants in in vitro experiments and outperformed ibrutinib, ARQ-531, and MT-802 in inhibiting tumor growth in murine xenograft models harboring WT or C481S mutant BTK-expressing TMD-8 cells. Remarkably, oral dosing of UBX-382 for <2 weeks led to complete tumor regression in 3 and 10 mg/kg groups in murine xenograft models. Following this, further optimization was carried out for potency and PK profile. We nominated the candidate for IND filing and are planning a phase 1 clinical trial. For the first-in-human, open-label, multicenter, phase 1 study, patients in part 1 (dose escalation with BOIN design) had R/R B-cell malignancies and had received at least 2 prior therapies. The candidate will be administered orally at 5 mg once daily followed by 2 days, for a 7-day schedule over 28-day cycles. Part 2 (dose expansion) consisted of disease-specific cohorts, including CLL/SLL, DLBCL, MCL, FL, MZL, and WM. The primary endpoints were safety and tolerability, along with the definition of the maximum tolerated dose. Secondary endpoints included pharmacokinetics/pharmacodynamics and preliminary efficacy.Conclusions : We have discovered potent BTK degrader exhibiting excellent anti-tumor activity in vitro and in vivo. In pre-clinical safety studies, the candidate of UBX demonstrated an acceptable safety profile. The candidate of UBX is currently preparing phase 1 clinical trials for hematological malignancies.Citation Format: Song Hee Lee, Sun-Mi Yoo, Ye Seul Lim, Han Wool Kim, Je Ho Ryu, Jong Hwan Lim. Discovery and preclinical development of orally bioavailable potent BTK degrader, and its early clinical development for the treatment of relapsed and refractory B-cell malignancies [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6069.

项与 Ubix Therapeutics Co. Ltd. 相关的新闻（医药）

2024-12-30

·创鉴汇

8家创新药公司获融资！3家来自中国 | 一周融资

▎药明康德内容团队编辑据创鉴汇不完全统计，上周（12月23日至12月29日）全球大健康领域共披露融资事件12起，总额近18亿元。按照金额划分，亿元及以上融资9起。按照已披露的融资轮次划分，早期融资（B轮以前）3起，中后期融资（B轮及以后）7起。生物医药领域共8家公司获融资，涉及药物类型包括蛋白降解疗法、小核酸药物等。 #01 浩博医药完成7300万美元B轮融资关键词：小核酸药物最新融资：7300万美元B轮本轮投资机构：鼎晖创新与成长基金、汉康资本、启明创投、夏尔巴投资、元生创投等 12月27日，浩博医药宣布完成7300万美元B轮融资。本轮融资将主要用于推进核心小核酸创新药物AHB-137的中国和国际临床试验，以及早期商业化的准备工作。此外，资金还将支持公司新研发管线的拓展及团队的持续发展和建设。公开资料显示，浩博医药关注于HBV慢性乙肝功能性治愈和针对肝脏疾病的高效靶向治疗，并拓展了对肝脏以外新靶点的靶向小核酸治疗。该公司研发的具有乙肝“功能性治愈“潜力的非偶联型反义寡核苷酸（ASO）药物AHB-137注射液已经被中国NMPA纳入突破性治疗品种，目前该产品处于2期临床研究阶段。在临床前研究中，它可以激发所有乙肝病毒RNA的降解，并且显著降低乙型肝炎表面抗原（HBsAg）水平。 #02 华奥泰生物完成2亿元增资关键词：大分子药物最新融资：2亿元未知轮本轮投资机构：海璟创投 12月25日，华奥泰生物完成2亿元融资增资，由海璟创投独家投资。华奥泰生物成立于2013年，为华海药业旗下专注大分子药物的子公司，目前已经建立起覆盖单抗、双抗、融合蛋白及抗体偶联药物等多种药物形式的丰富研发管线。从回购条款可以看到华奥泰生物未来3-5年的经营目标，包括3年内完成一款产品获批上市，一款产品开展关键三期临床，一款产品进入2/3期临床，5年内完成两款产品获批上市，两款产品进入临床2/3期临床，以及约定时间实现首次公开募股（IPO）等。 #03 Ubix Therapeutics获257亿韩元Pre-IPO轮融资关键词：蛋白降解疗法最新融资：257亿韩元Pre-IPO轮本轮投资机构：Solidus Investment、TONY Investment、Union Investment Partners、韩国科技信贷担保基金、兴业银行等 12月25日，专注于开发靶向蛋白质降解（TPD）疗法的生物技术公司Ubix Therapeutics宣布，其已通过Pre-IPO轮吸引了价值257亿韩元的投资。本次Pre-IPO获得的资金将用于UBX-303-1在美国和韩国的临床开发、新药物管线的扩张，以及加快IPO的准备工作等。基于对人类免疫系统和靶蛋白的研究和理解，Ubix Therapeutics正在开发新的抗癌疗法。临床阶段候选药物UBX-303-1是一款BTK降解剂，通过降解过表达的BTK蛋白来发挥作用，并且具有与其他现有BTK抑制剂不同的独特作用机制，即分解和去除细胞中的BTK蛋白，这有望带来整体优势，特别是克服耐药性和增加选择性方面具有优势。UBX-303-1已经在非临床研究中表现出良好的PK/PD谱，在C481S突变型异种移植小鼠模型和野生型中均表现出较好的抗癌效果。Ubix Therapeutics期望UBX-303-1能够解决B细胞相关疾病（包括CLL和DLBCL）未满足的医疗需求，并扩大至免疫疾病适应症。 #04 Rznomics获203亿韩元Pre-IPO轮融资关键词：RNA编辑最新融资：203亿韩元Pre-IPO轮本轮投资机构：Aon、KB Investment、QUAD Investment Management、三星创投（Samsung Ventures）、Yuanta Investment 12月23日，开发基于RNA的基因疗法的生物技术公司Rznomics宣布，已通过Pre-IPO完成吸引203亿韩元的投资。至此，Rginumix迄今为止已获得总计812亿韩元的投资，并获得了约90亿韩元的政府资助研究资金。 Rgnomics的核心平台是基于RNA转拼核酶的RNA编辑技术，其概念是RNA替代酶靶向并切割特定的RNA，同时用治疗性RNA替换切割位点。该公司表示，与现有的DNA/RNA编辑技术不同，它不需要外部蛋白质或内部细胞工具，与编辑特定基因突变的碱基编辑技术相比，具有能够治疗更广泛种类突变的优势。主要疾病是癌症和罕见的无法治愈的遗传病。 #05 Pin Therapeutics宣布已完成约200亿韩元C轮融资关键词：蛋白降解疗法最新融资：约200亿韩元C轮本轮投资机构：CKD Venture Capital Corporation、DSC Investment、KB Investment、Korea Development Bank 、Korea Investment Partners 12月23日，靶向蛋白降解疗法（TPD）生物科技公司Pin Therapeutics宣布已完成约200亿韩元C轮融资。通过这项投资，Pin Therapeutics计划于2025年在美国和韩国推进主导项目CK1α选择性分子胶降解剂（MGD）PIN-5018进入1期临床试验。 Pin Therapeutics成立于2017年，是一家专注于靶向蛋白降解领域的生物技术公司，其正在开发新的平台和筛选系统，分别称为“PinE3”（用于新型E3连接酶）和“PinGLUE”（用于新型分子胶降解剂）平台，旨在解决当前TPD技术的局限性，并开发有临床应用前景的候选药物管线。目前，Pin Therapeutics正在开发两款候选药物，包括CK1α选择性分子胶降解剂（MGD），以及一款与大熊制药（Daewoong）联合开发的具有双重机制的PROTAC候选药物。读者们请星标⭐创鉴汇，第一时间收到推送免责声明：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：本文由药明康德内容团队根据公开资料整理编辑，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发/复制至其他平台。转发授权请在「创鉴汇」微信公众号留言联系我们。更多数据内容推荐点击“在看”，分享创鉴汇健康新动态

IPO临床2期临床3期

2024-12-27

·医药观澜

开发蛋白降解剂癌症新药，这家公司获257亿韩元Pre-IPO轮融资

▎药明康德内容团队报道近日，专注于开发靶向蛋白质降解（TPD）疗法的生物技术公司Ubix Therapeutics宣布，其已通过Pre-IPO轮吸引了价值257亿韩元的投资。本次Pre-IPO获得的资金将用于UBX-303-1在美国和韩国的临床开发、新药物管线的扩张，以及加快IPO的准备工作等。基于对人类免疫系统和靶蛋白的研究和理解，Ubix Therapeutics正在开发新的抗癌疗法。该公司的Degraducer®是一项基于泛素-蛋白酶体系统（UPS）的技术平台，基于该平台可以研发一种双功能分子，将与目标蛋白结合的“配体”和与E3泛素连接酶结合的“结合剂”通过连接子连接。通过将疾病相关的靶蛋白放置在E3连接酶附近，从而实现靶向蛋白质降解和随之而来的治疗效果。 Ubix Therapeutics公司的临床阶段候选药物UBX-303-1是一款BTK降解剂，通过降解过表达的BTK蛋白来发挥作用，并且具有与其他现有BTK抑制剂不同的独特作用机制，即分解和去除细胞中的BTK蛋白，这有望带来整体优势，特别是克服耐药性和增加选择性方面具有优势。UBX-303-1已经在非临床研究中表现出良好的PK/PD谱，在C481S突变型异种移植小鼠模型和野生型中均表现出较好的抗癌效果。Ubix Therapeutics期望UBX-303-1能够解决B细胞相关疾病（包括CLL和DLBCL）未满足的医疗需求，并扩大至免疫疾病适应症。 Ubix Therapeutics还正在对E3连接酶的新机制以及已知的E3连接酶的结合物如CRBN、VHL、IAP等进行研究，并将其应用于药物研发。此外，该公司正在从各个角度开发新技术，包括与Debiopharm公司共同开发的抗体分解药物偶联物（antibody-decomposing drug conjugates，ADeC）。参考资料： [1]유빅스, pre-IPO 257억.."BTK 분해약물 임상개발". Retrieved Dec 23，2024, From https://www.biospectator.com/news/view/23915 [2]Ubix官网.From http://ubixtrx.com/science 本文来由药明康德内容团队根据公开资料整理编辑，欢迎个人转发至朋友圈。转发授权及其他合作需求，请联系wuxi_media@wuxiapptec.com。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。

IPO抗体药物偶联物

2024-10-08

·PipelineReview

Ubix Therapeutics Accepted into Johnson & Johnson Innovation – JLABS

SEOUL, South Korea I October 08, 2024 I Ubix Therapeutics, Inc., a clinical-stage biotechnology company dedicated to the discovery and development of innovative oncology therapeutics using Targeted Protein Degradation (TPD) technology, announced today its acceptance as a member of the Johnson & Johnson Innovation – JLABS (JLABS) Korea community. JLABS is one of the largest global networks of health incubators pioneering the next wave of healthcare solutions with early-stage innovators. Powered by Johnson & Johnson, JLABS empowers its member companies working across the spectrum of healthcare with the experience, mentorship, partnerships and venture connections to accelerate their science. Ubix Therapeutics is currently conducting a phase 1 clinical trial for UBX-303-1, an oral small molecule degrader targeting B cell malignancies. In July, the company inked a license agreement granting Yuhan Corporation the rights to develop and commercialize AR degrader UBX-103, a prostate cancer drug candidate. “Our acceptance into JLABS is a tremendous opportunity for us to accelerate our R&D efforts.” said BK Seo, CEO of Ubix Therapeutics. “We plan to leverage the membership to further advance our pipeline, including UBX-106, a SHP2 degrader program set to enter IND-enabling studies, and to strengthen our efforts in building global partnerships.” About Ubix Therapeutics, INC. Ubix Therapeutics is a biotechnology company dedicated to discovery and development of TPD therapeutics. Ubix’ proprietary TPD platform technology, Degraducer®, leverages the body’s own natural protein degradation machinery to eliminate diseased proteins, thereby leading to near-complete inactivation of disease-causing pathways. Ubix’ wholly owned TPD pipeline includes its clinical program UBX-303-1, a BTK degrader for treatment of relapsed or refractory B cell malignancies, UBX-106, a SHP2 degrader set to enter IND-enabling studies for MAPK signaling dependent cancers, and multiple other preclinical and research stage degrader assets in targeted and immuno-oncology. For additional information, please visit http://en.ubixtrx.com SOURCE: Ubix Therapeutics

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药物(靶点)	适应症	全球最高研发状态

UBX-303-1 ( BTK )	B细胞恶性肿瘤更多	临床1期
UBX-144 ( SOS1 )	慢性粒细胞性白血病更多	临床前
UBX-306 ( HPK1 )	结直肠癌更多	临床前
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