Rgenta Therapeutics, Inc.

GSK and Duality Biologics have entered into an exclusive option agreement worth over $1bn for DualityBio’s preclinical antibody-drug conjugate (ADC). The deal gives GSK an exclusive option to obtain a licence to develop and commercialise DB-1324 globally, except in mainland China, Hong Kong and Macau. The candidate leverages DualityBio’s Duality Immune Toxin Antibody Conjugate (DITAC) platform against a gastrointestinal cancer target. Gastrointestinal cancers account for one in four cancer cases and one in three cancer-related deaths globally. ADCs are a relatively new class of cancer drugs that combine the selectivity of antibodies with the cell-killing properties of chemotherapy or other anti-cancer agents. Unlike chemotherapy, which works by attacking lots of different cells as well as the cancer, ADCs are designed to target and kill tumour cells while sparing healthy cells. DB-1324 has the potential to “unlock multiple combination therapy opportunities to strategically complement” GSK’s oncology portfolio, according to DualityBio. DualityBio will initially receive $30m upfront and additional pre-option milestone payments and, if GSK exercises its option, the biotech will be in line for an option exercise fee as well as potential development, regulatory and commercial milestone payments totalling up to $975m, plus tiered royalties on net sales in GSK’s territories. Hesham Abdullah, senior vice president, global head oncology, research and development, GSK, said: “Given the unique ability of ADCs to address certain targets on tumour cells while sparing healthy ones, we are confident in our strategic focus on this modality as it could advance new therapeutic treatments for the most challenging tumour types.” Also commenting on the agreement, John Zhu, chief executive officer of DualityBio, said: “We are very glad to have entered into this agreement with GSK. Through this collaboration, we will work together to advance our innovative ADC programme in gastrointestinal cancer to address unmet medical needs.” The deal is not GSK’s first of the month, with the company also recently partnering with Rgenta Therapeutics to develop RNA-targeting small molecule splice modulators for disease areas including oncology in an agreement worth nearly $500m per target. GSK also entered into a strategic partnership worth $650m with Vesalius Therapeutics in November to discover and develop new treatments for Parkinson’s disease and one additional neurodegeneration indication.

Data provide support for planned expanded clinical development of best-in-class RGT-61159 in MYB-dependent hematologic cancers, including AML Potent anti-tumor activity observed, providing further evidence for the promising mechanism of RGT-61159 as the company advances the drug candidate in its ongoing Phase 1a/b clinical trial in patients with relapsed or refractory ACC or CRC WOBURN, Mass., Dec. 9, 2024 /PRNewswire/ -- Rgenta Therapeutics, a clinical-stage biotechnology company pioneering the development of a new class of oral small molecules targeting RNA for oncology and neurological disorders, announced today the presentation of preclinical data demonstrating anti-tumor activity of RGT-61159, a potent, selective oral small molecule inhibitor of MYB, a master oncogene in human malignancies. The data, which are being presented at the 66th American Society of Hematology Annual Meeting and Exposition being held December 7-10, 2024, in San Diego, CA, support the development of RGT-61159 as a potential treatment for acute myeloid leukemia (AML). "As demonstrated by the data being presented at ASH, RGT-61159 leads to the elimination of MYB RNA and protein in cancer cells and results in significant anti-tumor activity," said Simon Xi, Ph.D., co-founder and chief executive officer of Rgenta. "Importantly, RGT-61159 is active in a range of AML models harboring the most prevalent genetic alterations found in patients that often lead to resistance to current treatments. These data support our plans to extend our clinical development of RGT-61159 beyond our existing programs in solid tumors, adenoid cystic carcinoma (ACC) and colorectal cancer (CRC), and into hematologic malignancies such as AML." RGT-61159 is a potent, selective oral small molecule inhibitor of the MYB oncogene that functions by inducing the inclusion of a cryptic exon into MYB RNA transcripts, resulting in the activation of the nonsense mediated decay pathway and promoting MYB mRNA depletion and thus, MYB protein degradation. The data presented at ASH demonstrate that RGT-61159 potently eliminates MYB RNA and protein in a dose-dependent manner in AML cancer cell lines. As a single agent, RGT-61159 showed significant anti-tumor activity in several AML cell line-derived xenograft (CDX) models that harbor the most prevalent genetic alterations found in patients. In addition, RGT-61159 driven MYB inhibition led to a robust, dose-dependent increase in the differentiation markers CD11b and CD14 on the surface of THP-1 AML cells and the reduction of master oncogenes such as MYC and BCL2 across a broad panel of AML cell lines, providing a strong rationale for its development as a treatment for patients with AML. "Genomic analyses of different AML cell lines treated with RGT-61159 shed further light on key oncogenes including BCL2 and MYC that are significantly regulated by MYB inhibition and further demonstrate RGT-61159's anti-tumor activity of leukemic cells is driven by inhibition of MYB signaling," said Travis Wager, Ph.D., co-founder, president and chief scientific officer. "These data also confirm the role of MYB as a convergent dependency across AML tumors and highlight the potential of RGT-61159, a best-in-class MYB inhibitor, as a novel therapeutic approach to address this malignancy." About RGT-61159 RGT-61159 is an orally available small molecule designed to specifically modulate splicing of the transcription factor MYB resulting in the inhibition of the oncogenic MYB protein production, which has the potential to induce cell death of the cancer cells overexpressing MYB protein. MYB acts as a master regulator of cell proliferation, self-renewal, and differentiation processes and its aberrant expression has been demonstrated in multiple forms of human cancer including adenoid cystic carcinoma (ACC), acute myeloid leukemias (AML), T-cell acute lymphoblastic leukemias (T-ALL), colorectal cancer (CRC), small cell lung cancer (SCLC) and breast cancer. Rgenta is evaluating RGT-61159 in an ongoing multi-center, open-label Phase 1a/b clinical trial in patients with advanced relapsed or refractory ACC or CRC. The Phase 1a/b study is designed to evaluate safety, tolerability, pharmacokinetics and target engagement and clinical efficacy of RGT-61159 in patients with ACC or CRC. Additional information about the Phase 1a/b clinical trial can be accessed at ClinicalTrials.gov (NCT06462183). About Acute Myeloid Leukemia (AML) AML is a blood cancer that starts in the bone marrow, begins to make large numbers of abnormal cells, is characteristically fast growing, and moves quickly into the blood. AML is the most common type of acute leukemia in adults, and it accounts for about 10% of all new blood cancers each year. In the United States, there are about 20,000 new cases of AML per year. The average age of people diagnosed with AML is 68 years old, and while it is uncommon in people under 45, it can occur in adolescents and children. While complete remission can be achieved in up to 70% of patients with newly diagnosed AML, prognosis remains poor with only approximately 32% of patients that remain alive 5 years after diagnosis. Allogeneic hematopoietic cell transplantation (HCT) remains the only potentially curative strategy for most patients. Up to 40% of patients relapse after allogeneic HCT, and 5-year overall survival (OS) rates for these patients are low, approximately 30–40%. About Rgenta Therapeutics Rgenta Therapeutics is a clinical stage biotechnology company developing a pipeline of oral RNA-targeting small molecule medicines with an initial focus on oncology and neurological disorders. Our proprietary platform mines the massive genomics data to identify targetable RNA processing events and design small-molecule glues to modulate the interactions among the spliceosome, regulatory proteins, and RNAs. Our lead programs and unique approach are unlocking the therapeutic potential of historically undruggable targets in human diseases. Learn more at: . Contacts Investors: Sylvia Wheeler Wheelhouse Life Science Advisors [email protected] Elizabeth Wolffe, Ph.D. Wheelhouse Life Science Advisors [email protected] Media Aljanae Reynolds Wheelhouse Life Science Advisors [email protected] SOURCE Rgenta Therapeutics WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

关注并星标CPHI制药在线 12月第一周，跨国大药企（MNC）葛兰素史克（GSK）接连达成三笔交易，充分践行了不"将鸡蛋放在一个篮子里"的布局思路。那么透过这三笔密集交易，我们一起看看GSK正在下一盘什么样的大棋。 牵手映恩生物，欲重建抗肿瘤雄风 12月4日，第一笔交易公布，映恩生物宣布与GSK就一项ADC药物(DB-1324)，达成独家授权协议。根据协议，GSK 将获得该药全球（不包括中国大陆、中国香港和中国澳门地区）的独家授权，以推进该ADC药物的研发与商业化进程。 DB-1324是一种创新型ADC分子，基于映恩生物独有的DITAC平台开发而成。目前还处于临床前开发阶段，适应症可能针对胃肠道（GI）癌症。值得一提的是，该ADC药物有潜力与GSK多个抗肿瘤产品联合用药，从而战略性地补充GSK的肿瘤产品组合。 在抗肿瘤领域，GSK的核心单品为Jemperli，这是一种能够与PD-1受体结合，并阻断其与配体PD-L1和PD-L2交互作用的抗体。自2021年首次获FDA加速批准以来，Jemperli目前已获FDA批准多项适应症，包括dMMR晚期或复发性子宫内膜癌、dMMR或MSI-H原发性晚期或复发性子宫内膜癌、dMMR复发或晚期实体瘤。此外，GSK还正在多个3期临床研究中继续探索该药的治疗潜力。 除PD-1产品外，GSK在抗肿瘤领域还大力布局ADC。2023年10月、12月，GSK与翰森制药就翰森旗下两款临床阶段ADC达成合作，首付款合计高达1.7亿美元。这两款ADC分别是靶向B7-H3 的HS20093和靶向B7-H4的HS-20089。HS20093由全人源抗B7-H3单抗与拓扑异构酶抑制剂(TOPOi)有效载荷共价连接而成，目前正在中国开展用于小细胞肺癌的Ⅲ期临床研究，以及肉瘤、头颈癌、食管癌及其他实体瘤的多项Ⅰ期及Ⅱ期临床研究。HS-20089目前正在中国进行用于治疗晚期实体瘤的Ⅱ期临床研究（主要针对妇科癌症）。 另外，GSK在2022年还与Mersana Therapeutics合作，获得一款Sting激动剂型的ADC--XMT2056，但是由于临床试验中出现安全性问题，进展并不顺利。 从目前来看，GSK在抗肿瘤领域的管线稍显单薄，这次与映恩生物合作，或是寄希望于在ADC上寻找能与Jemperli联用的疗法，试图重振抗肿瘤业务。 携手Rgenta Therapeutics，再次押注RNA药物 12月5日，GSK宣布了第二笔交易，与Rgenta Therapeutics建立多年期多靶点的战略研究联盟。旨在推进用于包括肿瘤学在内的多个疾病领域的口服RNA小分子药物的发现和开发。该联盟的核心管线为RGT-61159，它是一种口服小分子候选药物，旨在特异性调节转录因子MYB的剪接，目前处在Ia/b期研究，拟用于治疗腺样囊性癌、结直肠癌及其他实体瘤。 之前，GSK在RNA药物的布局主要针对乙肝治疗。该业务管线进展较快的药物为bepirovirsen，这是一款反义寡核苷酸（ASO）药物，具有抑制乙肝病毒（HBV）复制，同时促进人体自身免疫清除HBV的双重功能。目前已进入Ⅲ期临床研究阶段，已公布的临床研究结果显示，bepirovirsen可持续清除HBsAg和HBV-DNA。该药物将为乙肝患者带来新的治疗方案。 首付超2亿元，GSK助力开发神经退行性疾病领域 12月6日，GSK宣布第三笔交易，与生物技术公司Muna Therapeutics宣布建立研究联盟，以确定和验证治疗阿尔茨海默病的新药物靶点。双方将探索Muna的MiND MAP平台，该平台将空间转录组学应用于阿尔茨海默病患者、认知弹性个体、健康对照组以及有和没有认知障碍的百岁老人的大脑样本。根据协议条款，Muna将从GSK获得3350万欧元（约3530万美元）的预付款，还将有资格获得每个靶点高达1.4亿欧元（约1.475亿美元）的里程碑付款，以及产品净销售额的分层特许权使用费。 由近期的三笔交易，可以观察到GSK正在将BD交易分散化，覆盖抗肿瘤、慢病、以及神经退行性疾病，瞄准的都是临床存在巨大需求的领域。除ADC外，下一个BD重点会是双抗吗？ 主要参考资料： 1.https://www.businesswire.com/news/home/20240602370374/en. 2.https://www.prnewswire.com/news-releases/muna-therapeutics-announces-strategic-alliance-with-gsk-to-accelerate-development-of-novel-treatments-for-alzheimers-disease-302322958.html. END 【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~