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Etern Therapeutics Ready for YAP/TEAD Inhibitor ETS-006

Etern Therapeutics announced that the U.S. FDA has granted orphan drug designation to the YAP/TEAD inhibitor ETS-006 for treating patients with malignant mesothelioma. Etern has not yet submitted the IND application in either China or the U.S. Hippo pathway dysregulation can lead to diseases like cancer. Drug development focuses on targeting Hippo kinases, YAP/TAZ levels, and YAP-TEAD interactions, aiming to disrupt YAP-TEAD activity and inhibit disease progression. The core Hippo pathway ETS-006 ETS-006, an orally available YAP/TEADs PPI inhibitor, is discovered by Etern Therapeutics. YAP, with TEAD transcription factors, drives Hippo pathway signaling and regulates cancer progression. Its overactivation promotes metastasis, immune evasion, and drug resistance. Inhibiting YAP/TEAD interactions effectively suppresses YAP’s transcriptional activity. In 2022, Etern filed a patent (WO2023155927) for the YAP/TEAD inhibitors. The structure of example 124 is shown below. Structures in the pa

Simcere has submitted the IND application for SIM0505 (CDH6-ADC) in China

Simcere/Zenshine/Xianxiang has submitted the IND application for the CDH6 antibody-drug conjugate (ADC) SIM0505 in China. According to the company statement, this ADC is being developed as a potential treatment for malignant tumors, such as ovarian and renal cancer. CDH6 is a type II classical cadherin, also known as K-cadherin, consisting of 790 amino acids, located in the lateral basement membrane of epithelial cells, where it mediates calcium-dependent cell-cell adhesion. CDH6 is expressed in various cancer types, including kidney, ovarian, and thyroid cancers. CDH6‐activated αIIbβ3 crosstalks with α2β1 to trigger cellular adhesion SIM0505 SIM0505 is a CDH6-targeting antibody-drug conjugate (ADC) by linking a CDH6-specific monoclonal antibody, which binds selectively to tumor cells, with camptothecin toxoid molecules. The company described the product is designed by combining the tumor targeting of antibodies with the high-efficiency killing effect of toxin molecules, while avoiding

Beigene has filed the IND application for BG-T187, an anti-EGFR×c-MET×c-MET trispecific antibody

Beigene has submitted the IND application for its anti-EGFR×c-MET×c-MET tri-specific antibody BG-T187 in China. This marks the company's first in-house tri-specific antibody entering the clinical stage. In NSCLC, BeiGene has strategically targeted numerous molecular pathways, including PD-1, TIGIT, TIM3, LAG3, OX40, PanKRASi, HPK1, PRMT5i, B7H3 ADC, CEA ADC, and EGFR degrader. BG-T187 EGFR is a critical biomarker for the diagnosis and treatment of non-small cell lung cancer (NSCLC). Beigene had not previously targeted this pathway, but they have now discovered therapeutic approaches beyond single inhibitors, such as TsAb and degraders. Prevalence of EGFRm in NSCLC BG-T187 is an anti-EGFR×c-MET×c-MET tri-specific antibody that is registered as a monotherapy or in combo with the other therapeutic agents (not disclosed) in the phase 1 trial ( NCT06598800 ).  In 2023, Beigene submitted a patent (WO2024153168) covering anti-cMET antibodies, including multispecific antibodies such as the

BeBetter Med has submitted the IND application for BEBT-507, a siRNA targeting TMPRSS6.

BeBetter Med has submitted the IND application for BEBT-507, a siRNA that targets TMPRSS6, in patients with iron metabolism disorders ( Polycythemia Vera, Disease of Iron Overload, etc.) . This marks BeBetter's first potential RNAi therapy to reach the clinical stage. The second siRNA therapy targets  NAFLD/MAFLD. BEBT-507 TMPRSS6 is a serine protease expressed in the liver that negatively regulates the iron-regulatory hormone hepcidin. Using siRNA to silence TMPRSS6 can increase hepcidin levels, offering a therapeutic approach for iron overload and related conditions. TMPRSS6 BEBT-507 is a GalNac-conjugated siRNA targeting TMPRSS6 as a treatment for patients with  Polycythemia Vera and  β-thalassemia. The patent (WO2024109722 ) filed by BeBetter in 2022 showed the in vivo efficacy of several examples such as BBD-2051.210-GalNac in comparison with  Divesiran  . Patent TMPRSS6 Therapies in the Clinical Stage Different technology modalities, such as ASO, siRNA, and antibody, are bein

Beigene has submitted the IND application for PRMT5 inhibitor BGB-58067

Beigene has submitted the IND application for the PRMT5 (Protein arginine methyltransferase 5) inhibitor BGB-58067 in China. This aligns with the plan to enter the clinic in Q4 2024. BGB-58067 BGB-58067 is a second-generation MTA-cooperative PRMT5 inhibitor with brain-penetrating and good intracranial efficacy. MTAP-deletion lung cancer and GI cancers are the target diseases for the PRMT5 inhibitor. 2nd generation PRMT5 inhibitor BG PRMT5i In 2019 and 2023, Beigene filed patents for PRMT5 inhibitors, providing several examples. Patents [Update]  In September 2024, Beigene registered a phase 1 trial ( NCT06589596 ) of BGB-58067 monotherapy in solid tumors patients. The potential of combining PRMT5 inhibitor with IO therapy (anti-PD-1, etc.) may be explored. PRMT5 Inhibitors in China Currently, no PRMT5 inhibitors are under investigation in the clinical stage. SIM0272 , discovered by Simcere, was terminated from the phase 1 trial as an R&D strategy adjustment.  GTA182 GTA182 is

DualityBio has initiated a trial of DB-1419, an anti-B7H3xPD-L1 BsAb ADC

Duality Biologics has initiated a trial ( NCT06554795 ) of an anti-B7H3xPD-L1 BsAb ADC, DB-1419, in the United States, Australia, and China. However, Duality Bio has not yet submitted the IND application in China. In 2023, BioNTech and DualityBio entered into a partnership to globally develop, manufacture, and commercialize two assets, including an ADC (DB-1311/BNT324) targeting B7H3. Duality and BioNTech DB-1419 DB-1419 is a bispecific antibody-drug conjugate targeting B7H3 and PD-L1. It was discovered by Duality Biologics and is still in the preclinical stage according to the pipeline on the official website.  In 2022 and 2023, Duality Biologics filed patents (WO2024140846 ) covering anti-B7H3xPD-L1 BsAb ADCs. The patent includes examples of bispecific antibody-drug conjugates comprising the following components: an anti-B7H3 and PD-L1 bispecific antibody or an antigen-binding fragment thereof, a linker unit L, and TOP1 inhibitor, with a drug-to-antibody ratio (DAR) of 4, 6, or 8. D

Huadong moves HDP-101 to the IND application stage

 Huadong Medicine submitted the IND application for HDP-101, an anti-BCMA Antibody-Drug Conjugate, in China. In 2022, Huadong Medicine acquired Asia (excluding Japan) rights for HDP-101 and HDP-103, which is an anti-PSMA ADC, from  Heidelberg . The agreement also included an exclusive opt-in right for two additional candidates, amounting to a total of 930 million USD. HDP-101 HDP-101 is a novel ADC targeting BCMA linked to amanitin as a payload with a DAR of 2. The product is under-investigated in the phase 1/2 clinical study in patients with multiple myeloma. HDP-101 During the 2024 AACR Annual Meeting, Heidelberg presented the stage 1 results of a clinical trial. There were no dose-limiting toxicities (DLT) among the first 4 cohorts, but 3 DLTs related to thrombocytopenia occurred in cohort 5. The dose optimization for cohort 5 is still ongoing. Regarding the efficacy, 1 patient in cohort 3 archived stable disease. In cohort 5, 2 patients archived PR, and 2 have SD.  The first approv

Rezubio Pharma has submitted the IND application for GPR40 agonist RZ-629 in China

Rezubio Pharmaceuticals (宁康瑞珠) has filed the IND application for novel small-molecule gut-restricted GPR40 agonist RZ-629 in China. Rezubio Pharmaceuticals Co., Ltd is a biotech company founded by Yusheng Xiong and Hong-Ping Guan in Zhuhai, China. Rezubio RZ-629 According to the ACS Meeting Spring 2024 , RZ-629 is a novel gut-restricted membrane-anchored drug GPR40 agonist discovered by Rezubio. RZ-629 showed outstanding efficacy in both glucose and body weight reductions, with shallow blood exposure. The gut-restricted compound design effectively avoided liver and potential pancreas toxicities as nearly 100% of the parent drug was excreted in feces, with bile and urine accounting for less than 0.01% of the dose. In 2020 and 2022, Rezubio filed patents (WO2023134712/WO2022028317) covering GPR40 agonists, which can be used for treating various disorders, conditions, or diseases such as Type 2 diabetes. In some examples, compounds covalently linked to the hydrophilic group  T A  have a s

Junshi has filed the IND application for the HDAC inhibitor JS125/WJ47156 in China

 China CDE has accepted the IND application for JS125/WJ47156 submitted by Junshi Bioscience.  JS125/WJ47156, a novel HDAC1/2/3 inhibitor, is co-developed by Junshi and Wigen Biomedicine. In 2020, they announced the first collaboration agreement  including  4 cancer drug candidates (XPO1 inhibitor, Aurora-A inhibitor, EGFR-exon20 inhibitor, and 4th generation EGFR inhibitor). In the 2022 interim financial results, Junshi disclosed that they had expanded their collaboration with Wigen to include four additional cancer drug candidates (IDH1 inhibitor, SHP2 inhibitor, FGFR2 inhibitor, and ATR inhibitor).  JS125/WJ47156  may be part of the third collaboration (not disclosed so far) patch between Junshi and Wigen Biomedicine. JS125/WJ47156 JS125/WJ47156, a novel HDAC inhibitor, is co-developed by Junshi and Wigen Biomedicine as a cancer treatment. According to the press release ,  JS125/WJ47156 selectively inhibits HDAC1, HDAC2, and HDAC3, leading to cell cycle arrest, cell differentiation

Yayao Biotech has submitted the IND for its ATR inhibitor YY2201 in China

Jiangsu Yayao Biotech submitted the Investigational New Drug (IND) application for YY2201, an ATR Inhibitor, in China on June 28, 2024. This marks the first time a novel Category 1 drug from the company has reached the IND stage. According to the company's public information, the IND application for YY2201 is also underway in the USA. Yayao Biotech Logo YY2201 Yayo Biotech was founded by scientists who returned to China and local experts in the Pharmaceutical Valley of the Jiangbei New District in Nanjing. They prioritize the development of generic drugs, followed by novel drugs. Currently, their first p53-MDM2 inhibitor is in the process of being patented, although they already filed the first patent covering MDM2 inhibitors in 2021. In 2022, Yayao Biotech filed a patent (CN117247386) covering novel pyrazolopyrimidine compounds as ATR inhibitors with inventors XIAO Fei ( 肖飞 ), WENG Yali ( 翁亚丽 ), and WU Meng ( 吴萌 )  in China. The positive control drug is ceralasertib developed

ApicHope Pharma filed the IND application for oral GLP-1R agonist APH01727

 ApicHope Pharma has submitted the IND application for an oral small molecule GLP-1R agonist APH01727 for patients with type 2 diabetes and obesity in China. ApicHope Pharmaceutical founded by Li Hanxiong engages in the research and development, production, and sales of traditional Chinese medicine products,  chemical medicine,   and biological vaccines. Li Hanxiong APH01727  In the press release issued by ApicHope, it was stated that APH01727 is intended to be a daily dose small molecule GLP-1 receptor agonist. In 2022, ApicHope filed a patent (WO2024046342) covering the benzo bicyclic compounds aimed at treating GLP-1 receptor agonist-mediated diseases and/or disorders. The patent indicates that compound 4 has an EC 50 value of approximately 0.08 nM, demonstrating significantly higher potency compared to danuglipron, which has an EC50 of around 13 nM. Compounds in the patent Oral GLP-1R Agonists in China Although Pfizer and vTv (Huadong) terminated their oral small molecule GLP-1R a

Hutchmed expanded its presence in blood cancers by developing a Menin inhibitor

 HUTCHMED (formerly Hutchison MediPharma) has introduced its Menin-MLL inhibitor HMPL-506 into a phase 1 trial, aiming to broaden its footprint in hematological malignancies. The company filed the IND application for HMPL-506 in January 2024 in China.  Menin binds to KMT2A, activating leukemogenic genes like HOX and MEIS1. However, when a Menin inhibitor binds to the pocket of menin and displaces KMT2A, it deactivates HOX and MEIS genes, halting the growth of leukemic cells. Targeting Menin Currently, HUTCHMED possesses several drug candidates targeting SYK, PI3Kδ, IDH1/2, BTK, CD47, and Menin, in addition to the in-licensed EZH2 inhibitor tazemetostat, all of which are part of the pipeline for blood cancers. HUTCHMED Pipeline in 2024Q1 HMPL-506 MLL gene rearrangements (MLL-r, also known as KMT2A) are found in 5%-10% of acute leukemias and are linked to a poorer prognosis. On the other hand, nucleophosmin 1 mutations (NPM1m) are the most frequent genetic changes seen in acute myeloid l