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China CDE has approved the IND application for GLB-001

 China CDE has approved Glubio's GLB-001, a CK1α degrader, for the Investigational New Drug (IND) application in patients with myeloid neoplasm (AML/MDS). Glubio Therapeutics submitted the IND application on December 9th, 2023.  The FDA cleared the IND application for GLB-001 in April 2023, and the first-in-human trial ( NCT06146257 ) was initiated in January 2024, focusing on patients with relapsed or refractory acute myeloid leukemia (R/R AML) or higher-risk myelodysplastic syndromes (R/R HR-MDS). GLB-001 is a molecular glue targeting CK1α, different from their second degrader GLB-002, which is targeting Aiolos and Ikaros. Casein kinase 1 alpha ( CK1α ), encoded by gene CSNK1A1, is a ubiquitously expressed serine/threonine protein kinase in the CK1 kinase family. CK1α, as a key regulator of the Wnt/β-catenin pathway, directly phosphorylates β-catenin at Ser45 and thereby targets it for proteasomal degradation. CK1α was also known to regulate the protein stability of tumor suppr

China's CDE accepted the IND application for Phase 2 trial of TRS005

  Teruisi announced that the Investigational New Drug (IND) application for the phase 2 trial of TRS005 has been accepted by China's Center for Drug Evaluation (CDE). TRS005 is an antibody-drug conjugate (ADC) targeting CD20, utilizing anti-CD20 antibodies conjugated with MMAE (monomethyl auristatin E) for a more targeted therapeutic approach, with a drug-antibody ratio of 4:2. They have now progressed the candidate to a potential registrational study. TRS005  The single-arm Phase 2 study is aimed at rrDLBCL, with an estimated enrollment of 120-140 participants. The completion of the study may take two years, followed by an additional year for the Biologics License Application (BLA) review. Phase 1 Study Review Meeting The results of the Phase 1 trial in pts with rrNHL after receiving at least 2 standard treatment regimens, initiated in November 2018, were reported in 2022: " From Aug 24, 2020 to Apr 29, 2022, 40 pts received treatment, including 14 pts in dose-escalation pha

Beigene Initiates Phase 1 Trial of BG-C9074 Monotherapy and in Combo with Tislelizumab

 Beigene has registered a Phase 1 clinical trial ( NCT06233942 ) of BG-C9074, an anti-B7H4 antibody-drug conjugate (ADC), as monotherapy or in combination with tislelizumab: enrolling approximately 150 patients with pretreated solid tumors. The study (still no IND application submission in China yet) is estimated to start in May 2024, which is in line with the target for 2024 H1. According to the Beigene slide deck, BG-C9074, a novel B7-H4-targeted ADC with a drug-to-antibody ratio (DAR) of 6 , is designed to balance efficacy and toxicity, utilizing DualityBio ADC technology.  BG-C9074 The efficacy of BG-C9074 was evaluated in a B7-H4 low/heterogeneous PDX model, as measured by tumor volume reduction. The 10 mpk dose resulted in a greater degree of tumor shrinkage compared to the 3 mpk dose. B7-H4 low/heterogeneous PDX model In addition to BG-C9074, Beigene plans to initiate another ADC targeting B7-H3 with stable DAR8 and a strong bystander effect. -----------------------------------

Chia Tai-Tianqing has initiated a clinical study of TQB3454 in AML/MDS

 Chia Tai-Tianqing (CTTQ) has initiated a clinical study ( NCT06218771 ) of TQB3454, an IDH1 inhibitor, in patients with AML/MDS. This trial started in July 2023, while the study of IDH2 inhibitor TQB3455 was terminated in 2021 due to slow enrollment . IDH mutations for cancer The first Investigational New Drug (IND) application for TQB3454 was filed for the treatment of solid tumors and blood cancers in China in 2020. The first-in-human clinical trial was initiated in August of that year enrolling patients with advanced solid tumors or hematologic malignancies. While no results from this initial trial have been publicly reported, several other clinical trials for TQB3454 are currently ongoing and recruiting participants. In 2023, CTTQ initiated a phase 1 clinical study ( NCT05987358 ) of TQB3454 in patients with  advanced biliary carcinoma , with an estimated enrollment of 165 participants. IDH1 mutations occur in approximately 13% of patients with intrahepatic cholangiocarcinoma. A

Jing Medicine has submitted the IND application for HJ-002-03

  Jing Medicine (和径医药) has submitted the IND application for HJ-002-03, an EGFR-PROTAC, intended for patients with non-small cell lung cancer in China. HJ-002 is the first PROTAC in the IND stage developed by Jing Medicine. https://doi.org/10.1016/j.ejmech.2022.114533 In 2022, Jing Medicine received IND approval for HJM-353 , an EED inhibitor, in both China and the United States, however, no clinical study has been initiated as of yet. In 2021, Jing Medicine filed a patent (WO2022268229) claiming the PROTACs targeting EGFR, ALK, and ROS1.  These CRBN-based PROTACs, designed with Brigatinib analogs that target ALK and EGFR kinases, may offer a potential new approach for treating lung cancer by inducing targeted protein degradation.  Brigatinib and Embodiments in the Patent E95 and E123 demonstrated potent degradation activity, with DC50 values around single-digit nM and achieving over 90% degradation (Dmax) for EGFR-DTC (Del19/T790M/C797S), EGFR-LTC (EGFR L858R/T790M/C797S), and EGFR-

China CDE cleared the IND application for LF0376 in patients with DLBCL

  China CDE has cleared the Investigational New Drug (IND) application for LF0376, a CCR2/5 antagonist developed by Lingfang Biotech, for use in patients with DLBCL. Lingfang Biotech initiated a phase 1a trial of LF0376 in 2022, targeting patients with solid tumors (colorectal cancer, pancreatic cancer, liver cancer) and lymphomas. The administered doses are 50 mg or 100 mg once daily (QD), and as of now, no clinical data has been reported. In 2019, Lingfang Biotech filed a patent claiming CCR2/5 antagonists with compounds named WX*** (following Wuxi Apptech naming rules). Anti-tumor activity of WX001 in combination with anti-PD-1 antibody was investigated in vivo using a colon cancer MC38 tumor model in mice as above. "the WX001+PD-1 combination group had a significant enhanced efficacy compared to the PD-1 single-use group." The curves of the PD-1 group and CVC+PD-1 group appear to closely overlap, with the CVC+PD-1 group exhibiting numerically higher values. Additionally,

Clinical Trials Terminated or Suspended by Chia Tai-Tianqing

 Due to the pharmaceutical industry's cold spell, an increasing number of enterprises are facing insufficient cash flow to support a multitude of clinical trials. Consequently, there is a rising trend of termination of clinical trials. It is well-known that the collaboration between CTTQ and Wuxi Apptec is very close.  Here we summarize the clinical trials terminated or suspended by Chia Tai-Tianqing: 1.  TQB3015 for cancer: ATR inhibitor CTR20233919: phase 1 trial suspended without explanation Initiated in 2023.12.05, suspended in 2023.12.19 2. TQC3564 for asthma: CRTH2 antagonist CTR20220230: phase 1b study terminated as strategy adjustment Initiated in 2022.1.29, terminated in 2023.5.9 3.  TQC3564  for allergic rhinitis :  CRTH2  antagonist CTR20220964: phase 1b study terminated as strategy adjustment Initiated in 2022.8.17, terminated in 2023.5.9 4.  TQB3823 for cancer: PARP  inhibitor CTR20211789: phase 1 trial terminated as strategy adjustment Initiated in 2021.9.14, termin

Accutar Biotech Has Terminated the Trial of AC0682 in ER-Positive Breast Cancer

  Accutar Biotech  has terminated the phase 1 clinical study (NCT05489679/ CTR20221967 , due to strategy adjustment) of AC682 (AC0682), an orally administrated ERα-PROTAC, in ER-positive breast cancer, with 6 patients enrolled. The trial, which commenced in November 2021 in the United States, is currently active but not recruiting. Alongside AC0682, Accutar has initiated the clinical trial for another ER degrader, AC699, which is currently ongoing. AC682 is positioned as a potential best-in-class, while AC699 is positioned as having the potential to be the best-in-class with broad mutant coverage. The trial of AC699 was initiated exclusively in the United States in December 2022. Accutar Pipeline In April 2022, the IND application of AC682 was cleared by China CDE. Accutar promptly initiated the trial, and the first patient was enrolled in October.  "In the preclinical studies, AC0682 demonstrated potent and selective ERα protein degradation with favorable pharmacological properti

Dizal Pharma Initiated the phase 2 study of DZD8586 in patients with CLL/SLL

Dizal Pharma has initiated a phase 2 study ( CTR20240120 ) of DZD8586, a fully blood-brain barrier (BBB) penetrable LYN/BTK dual inhibitor, for the treatment of CLL/SLL in China. The sponsor aims to enroll an estimated 155 patients with rr-CLL/SLL. The patients in the three groups will receive DZD8586 at doses of 25 mg, 75 mg, and 100 mg. https://doi.org/10.1038/nchembio.502 Recently, Dizal highlighted various results from preclinical and clinical studies of DZD8586. As DZD8586 inhibits both LYN and BTK simultaneously, it demonstrated anti-proliferative effects in cell lines expressing C481X and pirtobrutinib resistance mutations . Additionally, DZD8586 exhibited potent cell growth inhibition and induced cell death in a variety of DLBCL cell lines. Moreover, it demonstrated profound tumor growth inhibition in both CNS tumor models, attributed to its specific blood-brain barrier (BBB) penetration. DZD8586 demonstrated consistent results in the early human study . The dose escalation a

Alphamab has filed the IND application for anti-HER3xTROP2 ADC in China

 Alphamab Oncology has submitted the IND application for JSKN016, an anti-HER3xTROP2 ADC designed for the treatment of solid tumors in China. JSKN016 represents a potential first-in-class bispecific ADC, developed using the glycan-specific conjugation platform to target both HER3 and TROP2. No further details have been reported, and we will provide updates as they become available. Anti-TROP2 ADC, sacituzumab govitecan, has received approval for the treatment of breast cancer and urothelial cancer. Lung cancer may be the next targeting indication. Concurrently, anti-HER3 ADCs are widely investigated for their therapeutic potential in both lung cancer and breast cancer.

CSPC and Megalith Biopharma have advanced the anti-HER3 ADC SYS6023 into the IND stage

  CSPC and its subsidiary, Megalith Biopharma, have submitted the Investigational New Drug (IND) application for SYS6023, an anti-HER3 ADC, in China. In 2021, Megalith Biopharma filed a patent (WO2023088382) covering anti-HER2, anti-HER3, and anti-EGFR ADC, as well as the use thereof. Megalith made a notable change to the payload, opting for JSSW-001, which differs from Daiichi Sankyo's Patritumab deruxtecan (HER3-DXd). In experiments involving the Difi and SW620 colorectal cancer models, the Tumor Growth Inhibition (TGI) of Patritumab-JSSW-001 (DAR=7.36) exceeded that of the HER3 DXd. Hengrui's anti-HER3 ADC, SHR-A2009, is currently in phase 1/2 trials, both as a monotherapy and in combination with Adebrelimab (anti-PD-L1 mAb) or Almonertinib (EGFRi) for non-small cell lung cancer (NSCLC). The first IND application for SHR-A2009 was submitted in August 2021. In October 2023, Hengrui reported the results of phase 1 trial: In evaluable NSCLC pts, ORR was 25.0% (9/36; 95% CI 12.1

Betta Pharma has submitted the IND application for BPI-221351 in China

 China CDE has accepted the IND application for BPI-221351, an IDH1/2 inhibitor developed by Betta Pharma . BPI-221351 is potentially developed specifically for patients with glioma. As reported , BPI-221351 demonstrates excellent blood-brain-barrier penetration, resulting in a higher drug concentration in the brain compared to the plasma. In an IDH-mutant xenograft model, BPI-221351 reduced 2-HG to baseline level up to 24 h after a single oral dose administration. In 2022, Betta Pharma applied for a patent (WO/2023/174235) claiming an IDH1/2 inhibitor for use in glioma. The reference compound is Vorasidenib (AG-881), an orally administered brain-penetration inhibitor. In August 2023, Servier reported the results of the phase 3 trial of Vorasidenib in patients with residual or recurrent grade 2 IDH-mutant glioma. " Progression-free survival was significantly improved in the vorasidenib group as compared with the placebo group (median progression-free survival, 27.7 months vs. 11.

Leado Pharmatech filed an IND application for LD09163 (TRPA1 inhibitor)

 On December 26, 2023, Leado Pharmatech filed an IND application for LD09163 a TRPA1 inhibitor, in China.  According to their pipeline information on the website, LD09163 is specifically designed for patients with ulcerative colitis and Crohn's disease. Companies such as Lilly have explored the use of their TRPA1 inhibitor for pain relief before. As reported by Yiding Chen , " In animal studies, mice with experimental colitis exhibited an increased TRPA1-mediated colonic neuropeptide release, while the experimental colitis appeared to be less severe after the inhibition of TRPA1 by the antagonist or genetic depletion." https://doi.org/10.3389/fimmu.2020.00180 LD09163 is a novel ion channel drug developed by Leado Pharmatech for the treatment of Inflammatory Bowel Disease (IBD). After oral administration, it can selectively accumulate in the gastrointestinal tract, increasing drug concentration in target tissues and reducing systemic toxicity. Its performance in various ef

Henlius has filed the IND application for HLX6018 (GARP/TGF-β1) in China

 On December 26th, 2023, Henlius filed the Investigational New Drug (IND) for HLX6018 (monoclonal antibody targeting the GARP/TGFβ1 complex) for the treatment of chronic inflammatory diseases in China. As  reported by Niklas Zimmer ,  "Regulatory T cells (Treg) play a critical role in immune homeostasis by suppressing several aspects of the immune response. Herein, Glycoprotein A repetitions predominant  (GARP) , the docking receptor for  latent transforming growth factor (LTGF-β) , which promotes its activation, plays a crucial role in maintaining  Treg mediated immune tolerance . After activation, Treg uniquely express GARP on their surfaces. Due to its location and function, GARP may represent an important target for immunotherapeutic approaches, including the inhibition of Treg suppression in cancer or the enhancement of suppression in autoimmunity. In 2022, Henlius submitted a patent (WO/2022/116877) for an anti-GARP/TGFβ antibody and its method of use. The binding ability wa

China Pharma/Biotech License-out Deals (Upfront $100M+)

An increasing number of drug candidates made in China have been out-licensed. Here are the ones aimed for approval in foreign countries. ★ BL-B01D1, anti-EGFRxHER3 ADC,  SystImmune 2023.12  Announced in Ph3, BMS " $800 million in an upfront payment and up to $500 million in contingent near-term payments. SystImmune is eligible to receive additional payments of up to $7.1 billion contingent upon the achievement of certain development, regulatory and sales performance milestones for a total potential consideration of up to $8.4 billion. The companies will share certain global development expenses and profits and losses in the United States. Through its affiliates, SystImmune will retain exclusive development and commercialization rights in Mainland China, where Bristol Myers Squibb will receive a royalty on net sales. Outside the United States and Mainland China, SystImmune will receive a tiered royalty on net sales. The agreement is subject to customary clearance by antitrust regu

Janssen has submitted the IND for JNJ-80948543, a T-cell redirecting CD79b x CD20 x CD3 trispecific antibody, in China

  JNJ-80948543 is a fully human immunoglobulin G1 trispecific antibody composed of an anti- CD3ɛ single-chain variable fragment (scFv), an anti- CD20 scFv, and an anti- CD79b fragment antigen-binding (Fab) domain and an effector-silent Fc.  Now it is still under investigation among patients with NHL and CLL in the Phase 1 study ( NCT05424822  monotherapy, 2022.08, NCT06139406  in combination with JNJ-87801493) conducted in the U.S., Europe, and Australia. https://doi.org/10.1182/blood-2022-168739 Polatuzumab vedotin-piiq, an anti-CD79b ADC, has been extended to patients with untreated DLBCL. Additionally, the anti-CD20xCD3 BsAbs (Glofitamab, Mosunetuzumab, Epcoritamab) have been approved for NHL." As reported in ASH2022 , JNJ-80948543 prevented the growth of CARNAVAL (GCB-DLBCL) xenografts and induced dose-dependent regression of OCI-Ly10 (ABC-DLBCL) xenograft tumors.

Sotio Biotech Suspended a Phase 1/2 Study of SOT102 (ADC Targeting Claudin 18.2)

 On November 29th, 2023, Sotio Biotech  suspended the only phase 1/2 trial (CLAUDIO-01, NCT05525286) of  SOT102 (ADC Targeting Claudin 18.2) for patients with advanced inoperable or metastatic gastric/GEJ adenocarcinoma or inoperable or metastatic pancreatic adenocarcinoma. Sotio recently presented an  overview of the CLAUDIO-01 phase 1/2 study at the ESMO Congress in 2023. According to the records on clinicaltrials.gov , the suspension was initiated by the sponsor's decision without a more in-depth explanation. The study was initiated (FPI) on March 31st, 2022, with an anticipated enrollment of 269 patients. And according to the poster at the ESMO Congress, 24 patients were treated in 4 escalating dose levels in Part  A and 2 patients in first escalating dose level in Part B. In 2021, the company unveiled the findings from the preclinical study : " Complete responses (2 mg/kg) were observed in all 10 patient-derived mouse xenograft models, including those for gastric, panc

Zai Lab has submitted the IND for anti-CCR8 antibody ZL-1218 in China

 Zai Lab ($ZLAB) submitted the Investigational New Drug (IND) application for ZL-1218, a novel anti-CCR8 antibody , in China on November 28th, 2023. ZL-1218 demonstrates binding affinity to human CCR8, facilitating potent Antibody-Dependent Cell-Mediated Cytotoxicity (ADCC) activity. This capability enables NK cell-mediated elimination of CCR8-expressing Tregs. The Phase 1 study ( NCT05859464 ) of ZL-1218 as monotherapy or in combination with an-PD-1 antibody (Pembrolizumab) for patients with solid tumors commenced in May 2023, with clinical sites in the U.S. and Spain. The preclinical results  of ZL-1218 were reported at the AACR conference in 2022: " We have recently explored the potential for ZL-1218 in combination immunotherapy, examining the enhanced antitumor activity when ZL-1218 is combined with anti-PD-1. Using human dissociated tumor samples, we further observed that different tumor types may induce different CCR8 expression levels on intratumoral Tregs leading to multi

Avanc/Fochon/Fosun Pharma has submitted the NDA for the CDK4/6 inhibitor FCN-437c

 Avanc Pharma, a subsidiary of Fosun Pharma, has submitted the NDA for the CDK4/6 inhibitor FCN-437c in China. The phase 3 study for first-line (1L) and second-line (2L) breast cancer was initiated in 2021. As of October 2023, Fosun has invested 514 million RMB in the development of FCN-437c. Fosun, Avanc, and Fochon Pharma have submitted the NDA for the CDK4/6 inhibitor FCN-437c in China. https://t.co/M8YRhItQo7 pic.twitter.com/BHIF5lClxl — Pharmews (@Pharmews) November 21, 2023 FCN-437c is a second-generation CDK4/6 inhibitor. Clinical results have indicated improved antitumor activity in patients (pts) with HR+, HER2– advanced breast cancer (ABC) who were treated with FCN-437c + fulvestrant or letrozole in the phase 1/2 study. The results announced in 2023 for the Phase 2 trial in + fulvestrant in post-menopausal pts (Cohort 1, treatment-naïve or 2L), FCN-437c + letrozole + goserelin in pre-menopausal pts (Cohort 2, treatment-naïve): " FCN-437c in combination with fulvestra