21 First-in-Class Innovative Drugs Receive IND Approval in China: AbbVie, Johnson & Johnson, Hengrui Among Sponsors

▎WuXi AppTec Content Team Report

According to the official website of the Center for Drug Evaluation (CDE) under China's National Medical Products Administration and publicly available information, in the past two weeks (September 30 ~ October 12),There is21 Class 1 innovative drugs received clinical trial implied permission (IND) in China for the first time, including drug types such asBispecific Antibody,Antibody-drug conjugates (ADC), bispecific antibodies, ADCs, radiopharmaceuticals, protein degradation therapies, gene editing therapies, TCR-T cell therapies, mesenchymal stem cell drugs, CAR-T cell drugs for solid tumors, bicyclic peptide conjugates, and small molecule drugsEtc.。This article will introduce these products based on publicly available information.

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Radioligand Medicine:Lu[¹⁷⁷Lu]PSMA-0057 Injection,Gallium[⁶⁸Ga]PSMA-0057 Injection

Mechanism of Action: PSMA-Targeted Radiopharmaceuticals

Indications: Prostate Cancer

Raycore Pharma Class 1 New Drug Lutetium[¹⁷⁷Lu]PSMA-0057 Injection Approved for Clinical Use in China,Intended for the treatment of prostate-specific membrane antigen (PSMA) positive prostate cancer. At the same time, the company's gallium[⁶⁸Ga]PSMA-0057 Injection Approved for Clinical Use, Intended forScreening for Suitable Candidates to Receive Lutetium[¹⁷⁷LuPSMA-0057 Injection Treatment for PSMA-Positive Prostate Cancer PatientsPublic data shows that PSMA is overexpressed on the surface of more than 90% of prostate cancer cells, and radiopharmaceuticals targeting it have been clinically validated for the treatment of prostate cancer.

Guangdong Innovative Drug Translational Medicine Research Institute Co., Ltd.; OrigForce Life Sciences: INV-9956 Capsule

Mechanism of Action: CYP11A1 Inhibitor

Indications: Prostate Cancer

The INV-9956 capsule, jointly submitted by Guangdong Innovative Drug Translational Medicine Research Institute Co., Ltd. and Original Force Life Sciences, has been approved for clinical trials and is expected to be developed for use.Advanced Metastatic Castration-Resistant Prostate Cancer. According to the press release from Original Force Life Sciences, this is its independently developedA potent and highly selective oral CYP11A1 inhibitor`, which has previously been approved for IND in the United States.`Steroid hormones are one of the key factors driving prostate cancer.Cytochrome P450 11A1 (CYP11A1)Is an important rate-limiting enzyme in the process of steroid synthesis,Targeting CYP11A1 provides an effective means of inhibiting steroid hormone production.。

AbbVie: ABBV-706 Lyophilized Powder for Injection

Mechanism of Action: ADC Targeting SEZ6

Indications: Small Cell Lung Cancer

ABBV-706 Lyophilized Powder for Injection, a Class 1 new drug developed by AbbVieApproved for Clinical Use`, Intended`Monotherapy for Relapsed/Refractory Small Cell Lung Cancer. Public information shows that ABBV-706 is aAn antibody-drug conjugate (ADC) targeting SEZ6, with a TOP1i payload, is currently in Phase 1 clinical trials internationally.. This product is expected to be used for the treatment of small cell lung cancer, central nervous system tumors, and neuroendocrine cancer.

Ruiyue Bio: CG009301 for Injection

Mechanism of Action: GSPT1-Targeted Protein Degrader

Indications: Hematologic Malignancies

Ruiyue Bio's Class 1 New Drug CG009301 for Injection Approved for Clinical Trials, Intended for Development in TreatmentRelapsed/Refractory Hematologic Malignancies (including but not limited to AML, ALL, high-risk MDS, etc.)According to the press release from Ruiyue Biotech, CG009301 isHighly Selective GSPT1-Targeted Protein Degrader. Public data show that GSPT1 is a protein highly expressed in many cancers, including hematologic and solid tumors.

Sanctuary Bio: SYN818 Tablets

Mechanism of Action: Small Molecule Inhibitors Targeting DNA Polymerase θ (Polθ)

Indications: Advanced Solid Tumors

Shengyu Bio's Class 1 innovative drug SYN818 tablets have been approved for clinical trials and are intended for the treatment of advanced solid tumors. According to Shengyu Bio's press release, SYN818 is aA novel potent and highly selective inhibitor drug that effectively inhibits DNA damage repair in tumor cells by precisely targeting DNA polymerase θ (Polθ), thereby selectively killing tumor cells.. Research shows that SYN818 is not only effective forHomologous Recombination Deficiency (HRD)Tumor cells have the potential to be developed into standalone drugs and also possess the potential to be combined with PARP inhibitors, radiotherapy and chemotherapy, antibody-drug conjugates, and other treatments for various types of cancer.

Pylon Biotech: GTA182 Tablets

Mechanism of Action: Brain-Permeable PRMT5 Inhibitor

Indications: MTAPnull/lost advanced solid tumors

Pylon Biotech's Class 1 New Drug GTA182 Tablets Approved for Clinical Trials, Intended for Development in TreatmentMTAPnull/lost Advanced Solid TumorsAccording to the public information from湃隆生物, GTA182 is aA protein arginine methyltransferase 5 (PRMT5) inhibitor that can penetrate the blood-brain barrier, with methythioadenosine (MTA) synergy, exhibits high selectivity for MTAP-deficient cancer cells., without affecting non-cancerous cells with normal MTAP expression. This selectivity is expected to offer a more effective and safer treatment option for patients with MTAP-deficient cancers.

Bintie Biologics: IX001 TCR-T Injection

Mechanism of Action: TargetingKRAS  G12VMutant TCR-T Cell Therapy

Indications: Pancreatic Cancer

Bintie Bio's Class 1 New Drug IX001 TCR-T Injection Approved for Clinical Trials, Intended Indication Under DevelopmentGenotype isHLA-A*11:01Advanced pancreatic cancer with positive expression of tumor antigen KRAS G12V。According to the public information from Bintie Biotech, this is the company's first product under development to have applied for registration in clinical trials. It is aTCR-T Cell Therapy Targeting KRAS G12V Mutation。This product uses gene modification technology to specifically identifyKRAS G12VMutated TCR gene sequences are transferred into T cells, enabling them to precisely recognize and effectively kill pancreatic cancer cells.。

Zhenzhi Medicine: IPM001 Injection

Mechanism of Action: Multi-Antigen Targeted Autologous Immune Cell Injection

Indications: Primary Hepatocellular Carcinoma

IPM001 Injection, submitted by Zhenzhi Medicine, has been approved for clinical trials and is proposed for development toTreatment of advanced primary hepatocellular carcinoma that has failed or is intolerant to second-line systemic anti-tumor therapyAccording to the introduction in Zhenzhi Medicine's press release, IPM001 is independently developed by them.Multi-Antigen Targeted Autologous Immune Cell Injection, an engineered T-cell injection that targets dozens of liver cancer-related antigens and neoantigens specific to the Chinese population.In the early investigator-initiated clinical trial (IIT), the product demonstrated good drug safety and showed promising clinical efficacy in patients with advanced primary hepatocellular carcinoma who had failed multiple lines of systemic anti-tumor therapy.

Yuantian Biotech: YT001 Injection

Mechanism of Action:Mesenchymal Stem Cell Therapy Products

Indications: Knee Osteoarthritis (KOA)

Yuantian Biotech's Class 1 biological product new drug YT001 injection has been approved for clinical trials, intended for the development of treating knee osteoarthritis (KOA). According to Yuantian Biotech's press release, this is a product they have developed.Mesenchymal Stem Cell Therapy ProductsMesenchymal stem cells have immunomodulatory effects, can alleviate inflammatory responses, and promote damage repair.Its immunomodulatory and damage repair functions can help regulate the disordered microenvironment within the joint cavity, alleviating cartilage degradation.。

Hengrui Medicine, TopBiomics: SHR-6934 Injection

Mechanism of Action: New Biologics Drug

Indications: Heart Failure

SHR-6934 Injection, jointly submitted by Hengrui Medicine and TopBoundary Biologics for clinical trial approval, is proposed for development to treatHeart Failure. The mechanism of action of this product has not been found through public channels yet. From the acceptance number, it is known to be a therapeutic biological product. Heart failure has an extremely high incidence and mortality rate, with poor prognosis—about half of heart failure patients die within five years of diagnosis. As the life expectancy of patients with heart disease, diabetes, and other conditions extends, and the degree of aging deepens, the global number of heart failure patients will continue to grow.

Sidaopharm: Injectable DM001

Mechanism of Action: EGFR/TROP2 Bispecific Antibody ADC

Indications: Solid Tumors

Sida Pharmaceutical's Class 1 new drug DM001 for injection has been approved for clinical trials and is proposed for development toAdvanced or metastatic HR+, HER2- breast cancer, metastatic triple-negative breast cancer, advanced or metastaticEGFRmut orEGFRWT Non-Small Cell Lung Cancer and Other Solid Tumors. According to the Sidao Pharmaceuticals press release, DM001 is aInjectable EGFR/TROP2 Bispecific Antibody ADC. This product has previously received FDA IND approval in the United States and is currently in Phase 1 clinical trials in the U.S. and Australia.

Ruifeng Bio: RM-101 Injection

Mechanism of Action:AAV-Based Gene Editing Drugs

Indications:Usher Syndrome Type 2-Related RP

RF Bio's RM-101 Injection Approved for Clinical Trials, Intended for TreatmentUSH2ARP (retinitis pigmentosa) associated with Usher syndrome type 2 or non-syndromic RP caused by mutations in exon 13 of the gene. According to the public information from Ruifeng Bio, RM-101 isAAV-Based Gene Editing Drugs, can specifically targetUSH2ARNA, regulating alternative splicing biological processes, restoring the expression of functionally normal proteins. This product is administered through subretinal injection, with the potential to achieve long-term efficacy with a single dose. Usher syndrome is the most common syndrome associated with retinitis pigmentosa.USH2AGene mutations lead to retinitis pigmentosa, patients usually gradually develop night blindness and peripheral vision loss during adolescence, which may eventually lead to total blindness.

Ruihongdi Pharmaceuticals: RGL-193 Injection

Mechanism of Action: AAV Dual-Gene Drug

Indications: Parkinson's Disease

RGL-193 Injection, a Class 1 new drug submitted by Ruihongdi Medicine, a subsidiary of Hengrui MedicineApproved for Clinical Use, aiming to develop a treatment for Parkinson's disease. Public information shows that this is an independently developed product by Ruihongdi Pharmaceutical targeting Parkinson's disease.A Dual-Gene AAV Drug, using stereotactic technology to inject into the patient's brain.It can improve the conversion efficiency of levodopa, while also playing a role in protecting and repairing damaged dopaminergic neurons, with potential effects of slowing disease progression and reducing the dosage of oral anti-Parkinson's medications.

Yimiao Medical: IM96 Chimeric Antigen Receptor T-Cell Injection (IM96 CAR-T Cell Injection)

Mechanism of Action: CAR-T Therapy Targeting GUCY2C

Indications: Colorectal Cancer

IM96 CAR-T Cell Injection, submitted by Yimiao Healthcare, has been approved for clinical trials and is intended to be developed for the treatment of colorectal cancer. According to the press release from Yimiao Healthcare, this is a brand-new generation of anti-tumor drug developed in collaboration with Peking University Cancer Hospital, aimed at treating metastatic colorectal cancer.CAR-T Therapy Targeting Guanylate Cyclase 2C (GUCY2C)The preclinical study data of this product was selected for the American Society of Clinical Oncology (ASCO) Annual Meeting in June this year. The study showed that IM96 achieved a best objective response rate (ORR) of 50% in colorectal cancer, with only 5.0% of patients experiencing neurotoxicity and cytokine release syndrome (CRS) of grade ≥3.

BicycleTx：BT8009

Mechanism of Action: Bicyclic Peptide Conjugate Targeting Nectin-4

Indications: Urothelial Carcinoma

Bicycle's BT8009 Approved for Clinical Trials, Aiming to Develop TreatmentUrothelial Carcinoma. Publicly available information shows,BT8009Developed by Bicycle TherapeuticsSecond-generation bicyclic peptide conjugate toxin under research, targeting Nectin-4。Bicycle Company is committed to developing transformative drugs by leveraging the research achievements of Nobel Prize in Chemistry laureate Sir Gregory Winter and bicyclic peptide technology.Bicyclic PeptidesIt is a polypeptide composed of 9-20 amino acids, which can bind to targets with high affinity and selectivity.Characterized by high tumor permeability, and the nature of peptides provides a "tunable" pharmacokinetic half-life and renal clearance pathway.Globally, the phase 2/3 registrational trial of BT8009 has been initiated for metastatic urothelial cancer.

Kangkang Bio: KGX101

Mechanism of Action: IL-12 Cytokine Prodrug Product

Indications: Advanced or metastatic solid tumors

Kangkang Bio's New Drug under Research: KGX101 (Injectable Tumor-Specific Recombinant IL-12 Fc Fusion Protein)Approved for Clinical Use, intended for development in late-stage or metastatic solid tumors. According to publicly available information from Kangkang Bio, KGX101 is aNext-Generation Cytokine IL-12 Prodrug ProductIt masks proteins by fusing them with a linker that is cleaved by tumor-specific proteases.This not only increases the accumulation of active drugs in the tumor area but also reduces the systemic toxicity of cytokines.Once the Linker is cleaved by specific metalloproteinases in the tumor microenvironment, KGX101 can effectively stimulate immune cells in the tumor, reshape the tumor microenvironment, and achieve the therapeutic purpose, similar to IL-12.

Hengrui Medicine: HRS-9563 Injection

Mechanism of Action: New Chemical Drug

Indications: Hypertension

Hengrui Medicine's HRS-9563 Injection Approved for Clinical Trials, Intended for Hypertension Treatment. The product’s specific indications have not been disclosed publicly yet, but from the application number, it is identified as a new chemical drug.

Wuhan Humanwell Innovative Drug R&D Center: HW211026 Ointment

Mechanism of Action: Chemical Drug

Indications:Actinic Keratosis

HW211026 Ointment, a Class 1 new drug developed by Wuhan Humanwell Innovative Drug Research and Development Center, has been approved for clinical trials and is intended for use in...Actinic KeratosisTreatment. From the application number, it can be seen that this is a new chemical drug. Actinic keratosis (solar keratosis) is a precancerous growth caused by long-term sun exposure, leading to rough and scaly skin in various colors, which can progress to squamous cell carcinoma.

Johnson & Johnson: JNJ-78278343 Injection

Mechanism of Action: KLK2-CD3 Bispecific Antibody

Indications: Prostate Cancer

Johnson & Johnson（Johnson & Johnson）Class 1 New Drug JNJ-78278343 InjectionApproved for Clinical Use, intended for development to treatAdult male patients with advanced prostate cancer. According to publicly available information from Johnson & Johnson, this is aKLK2-CD3 Bispecific Antibody: A New Drug in Research, currently in Phase 1 clinical research internationally. KLK2 is a highly prostate-specific antigen. JNJ-78278343 is designed to target KLK2 and induce T-cell activation by binding to CD3 on T cells. After administration, the product binds to CD3 on T cells and KLK2 on KLK2-expressing tumor cells, redirecting T cells to the tumor cells, resulting in T cell-mediated lysis of KLK2-expressing tumor cells.

Bozhi Bio: Injectable PTX-912

Mechanism of Action: IL-2 Prodrug Fusion Protein

Indications: Locally Advanced/Metastatic Solid Tumors

Bozhi Bio's PTX-912 Injection Granted Clinical Approval, Intended for TreatmentLocally Advanced/Metastatic Solid Tumors. According to public data from Bozhi Biotech, PTX-912 is independently developed by the company.A Novel Prodrug Fusion Protein Targeting IL-2 in Immune Cells, leveraging proprietary prodrug technology to specifically activate the IL-2 prodrug in the tumor microenvironment, thereby addressing the peripheral toxicity issues of IL-2. Meanwhile, PTX-912 can target and localize the activated IL-2 to tumor-specific effector T-cell subsets, fully harnessing IL-2’s immune activation and anti-tumor effects. Currently, this product has entered Phase 1 clinical trials in the United States.

Yayao Biotech: YY2201 Tablets

Mechanism of Action:ATR Kinase Inhibitor

Indications:Advanced Solid Tumors

YY2201 Tablets Developed by Yayaao Biotech Approved for Clinical Trials, Intended for TreatmentAdvanced Solid Tumors. Public information shows that this is developed by Yayao Biotechnology.ATR Kinase Inhibitor Small Molecule DrugATR is a key kinase in DNA repair and a "synthetic lethality" anti-tumor target. In the completed series of non-clinical studies, YY2201 tablets demonstrated good in vivo and in vitro activity, pharmacokinetic characteristics, and safety.

References:

[1] Official website of the Center for Drug Evaluation (CDE) of the National Medical Products Administration (NMPA) of China.Retrieved Oct 13，2024, From https://www.cde.org.cn/main/xxgk/listpage/4b5255eb0a84820cef4ca3e8b6bbe20c