AstraZeneca, Bristol Myers Squibb, Huaxia Yingtai and Others Receive Chinese IND Approvals for Novel Class 1 Drugs

Bristol-Myers Squibb: Alnuctamab Injection

Mechanism of Action: BCMA and CD3 Targeting Bispecific T Cell Engager

Indications: Multiple Myeloma

Alnuctamab is Bristol-Myers Squibb（Bristol Myers Squibb）One in the pipelineBispecific T-cell engager targeting BCMA and CD3（TCE). This interaction aims to drive myeloma cell death by inducing T-cell activation and the release of pro-inflammatory cytokines as well as cytolytic enzymes. Alnuctamab was initially developed by Celgene, and in 2019,Bristol-Myers SquibbAcquired Celgene for $74 billion, thereby gaining this product. The product has been approved for clinical trials this time and is intended to be developed for the treatment of relapsed or refractory multiple myeloma (R/R MM).

Huaxia Yingtai: YTS104 Cell Injection

Mechanism of Action: STAR-T Cell Therapy

Indications: Myeloid Leukemia

YTS104 is a LILRB4-specific synthetic developed independently by Huaxia Yingtai(Beijing)Biotechnology Co., Ltd.T Cell Receptor Antigen Receptor（STAR）T-cell Therapy ProductsLILRB4 is an immunosuppressive receptor in acute myeloid leukemia (AML) of monocytes.Highly expressed on blast cells (FAB M4 and M5 AML subtypes), making it an ideal therapeutic target for monocytic AML. Additionally, in the current field of cellular therapy,Commonly used CAR-T technology comparison，STAR-T is more characteristic of natural T cells, featuring natural dual targets, low toxicity, slow exhaustion, and strong infiltration., making it more likely to achieve a breakthrough in the treatment of solid tumors. The indication for which this product has been approved for clinical trials is relapsed/refractory myeloid leukemia.

Huiyong Pharmaceutical: Injectable LN005

Mechanism of Action: GRP78-Targeted PDC

Indications: Malignant Tumors

LN005 is a product developed by Huiyong Pharmaceutical.Peptide Conjugate Drugs（PDC), composed of a pH-sensitive linker conjugating the homing peptide VAP with doxorubicin (DOX), targetingGlucose-regulated protein 78（GRP78). Studies show that GRP78 is highly expressed in many tumors and is closely related to the proliferation and metastasis of tumor cells as well as drug resistance.LN005 This TimeApproved for Clinical UseTargetingThe indications areMalignant tumor.

Baiji Bio: BST02 Injection

Mechanism of Action: TIL Cell Therapy Product

Indications: Advanced Hepatocellular Carcinoma

BST02 is a product developed by Baiji Biotech based on the patient's ownTumor-Infiltrating Lymphocytes（TIL) Expanded T-cell therapy product. This drug utilizes adoptive immune cell therapy technology and has the potential to treat all types of liver cancer. Compared with traditional TIL drugs, BST02 has more advantages, such as being a cryopreserved product that breaks the distance limitation and does not require high-dose interleukin-2 adjuvant therapy. The product has been approved for clinical trials this time.TargetingThe indications areAdvanced Hepatocellular Carcinoma (including Hepatocellular Carcinoma and Intrahepatic Cholangiocarcinoma)。

AstraZeneca: AZD3470 Film-Coated Tablets

Mechanism of Action: Next-Generation PRMT5 Inhibitor

Indications: Solid Tumors

ARC01 isAn mRNA therapeutic tumor vaccine developed by ORO Biopharma, a subsidiary of Grand Pharmaceutical, throughLiposome Nanoparticles（LNP) delivery technology, transfecting autologous cells with mRNA encoding the E6 and E7 antigens from human papillomavirus type 16 (HPV-16) and translating the corresponding antigens, which, under the co-action of the TriMix immunoadjuvant, stimulate the body to produce specific humoral and cellular immune responses, ultimately achieving an anti-tumor effect. The product has been approved for clinical development this time.For Recurrent and Metastatic HPV-16 Positive Solid Tumors。

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Novartis: HRO761

Mechanism of Action: WRN Inhibitor

Indications: Solid tumors with high microsatellite instability or mismatch repair deficiency

HRO761It's Novartis（Novartis）A targeted one under researchWerner Syndrome RecQ Helicase（WRN) Oral medication.WRN is a newly discovered "synthetic lethality" target in recent years.，Has a "synthetic lethal" effect on microsatellite instability-high (MSI-H) tumorsMSI-H is caused by mutations in genes responsible for repairing DNA mismatches, leading to abnormal repetitive nucleotide sequences in the DNA. WRN is a multifunctional enzyme with helicase and exonuclease activities, playing a crucial role in various cellular processes that maintain genome stability. The product has been approved for clinical development, intended for use inAdvanced unresectable or metastatic MSI-H or mismatch repair-deficient solid tumors。

China-Japan Intelligent Medicine: GMCN-508B Autologous Hematopoietic Stem and Progenitor Cell Injection

Mechanism of Action: LVV Gene Therapy

Indications: Transfusion-dependent β-thalassemia

GMCN-508B is a product developed by Zhongji Zhiyao.Lentiviral Vector（LVV) Gene therapy. For patients with transfusion-dependent β-thalassemia, the currently effective treatments are allogeneic hematopoietic stem cell transplantation and gene therapy. GMCN-508B mainly uses the LVV transduction system to genetically modify the patient's hematopoietic stem cells. The modified hematopoietic stem cells are then reinfused into the patient’s body, where they rebuild the modified cell population through self-renewal and differentiation, thereby achieving the goal of treating transfusion-dependent β-thalassemia. The product has been approved for clinical trials this time and is proposed for development.For Transfusion-Dependent β-Thalassemia。

ACRIS: Injectable ACR246

Mechanism of Action: 5T4-Targeted ADC

Indications: Advanced Solid Tumors

ADC2154 is an antibody-drug conjugate (ADC) developed by Aikang Ruisi targeting tumor-initiating cells (TIC).Targeting 5T4 Highly Expressed in Multiple Solid TumorsADC2154 features a novel topoisomerase inhibitor as its payload and a linker with a unique release mechanism, offering stability in the circulatory system, targeted delivery to tumor tissues, and intracellular release. This product has been approved for clinical trials in China.Intended for development in advanced solid tumors, including but not limited to esophageal cancer, colorectal cancer, non-small cell lung cancer, prostate cancer, ovarian cancer, cervical cancer, pancreatic cancer, renal cancer, breast cancer.

In addition to the aforementioned products, other Class 1 new drugs have been approved for clinical trials.Due to space limitations, this article will not go into details one by one. Hopefully, the ongoing therapies mentioned will progress smoothly and benefit patients as soon as possible.

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References:

[1] Official website of the Center for Drug Evaluation (CDE) of the National Medical Products Administration (NMPA) of China. Retrieved Jan 27, 2024, from https://www.cde.org.cn/main/xxgk/listpage/4b5255eb0a84820cef4ca3e8b6bbe20c

[2] Official websites of various companies and publicly available information