Ten Novel Class 1 Drugs Receive IND Approval in China

▎WuXi AppTec Content Team Report

According to the official website of the Center for Drug Evaluation (CDE) of the National Medical Products Administration (NMPA) and publicly available information, this week (August 19th to August 25th), there were10First-in-Class Innovative Drug First Approved in ChinaReceived clinical trial implied permission (IND). After sorting out, these products includeTwo "synthetic lethality" target innovative drugs, namely PARG inhibitors and Polθ inhibitors, as well as small molecule covalent inhibitors, small molecule allosteric inhibitors, ADCs, trispecific antibodies, and various other drug types.. This article will introduce relevant information about these products based on publicly available data.

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Qiaoji Bio: BGC515 Capsule

Mechanism of Action: Covalent TEAD Inhibitor

Indications: Advanced Solid Tumors

BridGene Biosciences' ApplicationBGC515 CapsuleApproved for Clinical Use, intended for the development of treatments for advanced solid tumors.Public information shows that this is internally developed by Qiaoji Bio.AOral Covalent TEAD Inhibitor。TEAD proteins are key components of the Hippo signaling pathway, which plays a crucial role in various types of tumors. Studies show that genetic alterations in the Hippo pathway occur in approximately 10% of patients across all cancer types.

Zhiren Medicine: ZG-002 Tablets

Mechanism of Action: TYK2 Allosteric Inhibitor

Indications: Moderate to Severe Plaque Psoriasis

Huana Da Pharmaceutical's holding subsidiary, Shanghai Zhigen Pharmaceutical, has received clinical approval for its ZG-002 tablet, which is being developed to treat moderate to severe plaque psoriasis. According to Huana Da Pharmaceutical's press release, ZG-002 isPotent, Highly Selective TYK2 Allosteric Inhibitor, demonstrating superior TYK2 inhibitory activity and high selectivity in in vitro pharmacological studies.

Danqing Pharmaceutical: DAT-2645 Tablets

Mechanism of Action: PARG Inhibitor

Indications: Advanced Solid Tumors

DAT-2645 is a novel, highly selective compound developed by Danqing Pharmaceuticals.Oral Small Molecule PARG Inhibitor, which specifically kills tumor cells carrying specific DNA damage repair defects through the synthetic lethality mechanism. ThisApproved for Clinical UseThe indications are: carrying breast cancer susceptibility gene 1/2 (BRCA1/2) Patients with advanced or metastatic solid tumors with loss-of-function mutations and/or other defects in the DNA damage repair (DDR) pathway. According to the news release from Danqing Pharmaceuticals,This product is expected to expand the indications for which PARP inhibitors are ineffective and address the pain point of PARP inhibitor resistance, showing potential clinical application prospects for "broad-spectrum therapeutics."

Simcere Pharmaceutical: SIM0508 Tablet

Mechanism of Action: Polθ Small Molecule Inhibitor

Indications: Solid Tumors

According to the public information from Simcere Pharmaceutical, SIM0508 is aSmall Molecule Inhibitors of DNA Polymerase θ (Polθ), which is considered by Simcere Pharmaceutical as "a highly potential" innovative R&D product. Polθ is a potential new target for "synthetic lethality" therapy, a DNA polymerase whose mediated MMEJ repair pathway is one of the critical routes for DNA double-strand break repair and also a potential DNA damage repair target for treating HR-deficient (HRD) tumors. SIM0508 this timeApproved for Clinical Use, intended for the treatment of adult patients with locally advanced or metastatic solid tumors.

Pliant Therapeutics: Bexotegrast Tablets

Mechanism of Action: Small Molecule αvβ6 and αvβ1 Integrin Dual Inhibitor

Indications: Idiopathic Pulmonary Fibrosis

Pliant's bexotegrast tablets have been approved for clinical trials, intended for the development of treatment for idiopathic pulmonary fibrosis. Public information indicates that this is aAn orally administered small-molecule dual inhibitor of αvβ6 and αvβ1 integrins, which reduces the expression of multiple pro-fibrotic genes by inhibiting the TGF-β signaling pathway.In May this year, Pliant announced positive results from a Phase 2 clinical trial of bexotegrast for idiopathic pulmonary fibrosis. Positron emission tomography (PET) imaging of patients treated with bexotegrast showed a reduction in total lung collagen levels, while total lung collagen levels increased in the placebo group, suggesting that bexotegrastIt is possible to reverse fibrosis.

Hongye Pharmaceutical, Hezheng Pharmaceutical: HZ-L105 Tablet

Mechanism of Action: Novel Bcl-2 Inhibitor

Indications: Mature B-cell Malignancies

HZ-L105 was jointly developed by Hezheng Pharmaceuticals and Hongye Pharmaceuticals.The All-New Generation Bcl-2 InhibitorAccording to preclinical research results presented at the 2023 American Association for Cancer Research (AACR) Annual Meeting, the product exhibits high activity, high selectivity, and the ability to overcome resistance that arises from long-term use of Venetoclax.Bcl-2Characteristics of mutation resistance. In addition, HZ-L105 has excellent oral pharmacokinetic properties, anti-tumor activity, and good safety.Providing Potential Treatment Strategies for Clinically Bcl-2-Dependent Hematological Tumor Therapy. This product has been approved for clinical use this time and is proposed to be developed for the treatment of mature B-cell malignancies.

Baochuan Biotech: BC011 Antibody Injection

Mechanism of Action: TNFR2 Non-Blocking Fully Human Antibody Drug

Indications: Advanced Solid Tumors

According to publicly available data from BioShip Biotech, BC011 is a novel non-blocking therapeutic antibody targeting TNFR2. It can promote the proliferation of CD8+ T cells and increase the proportion of effector T cells in the tumor microenvironment. Studies have shown that BC011, both as a monotherapy and in combination with anti-PD-1/L1 antibodies, demonstrated strong anti-tumor activity in mouse tumor models. The drug has been approved for clinical trials for the indication of advanced solid tumors.

SHOUYAO HOLDINGS: SY-7166 Tablet

Mechanism of Action: Chemical Drug

Indications: Multiple Myeloma

SHOUYAO HOLDINGS' SY-7166 Tablets Approved for Clinical Trials, Intended for the Treatment of Multiple Myeloma. From the application number (CXHL2400586), it is known that this is a new chemical drug. According to the introduction on SHOUYAO HOLDINGS’ official website, this project was independently researched and developed by the company, which also independently conducts clinical trials and commercialization.

Puzhong Discovery: Injectable AMT-676

Mechanism of Action: ADC Targeting CDH17

Indications: Advanced Solid Tumors

Puzhong Discovery Pharmaceutical Technology(Shanghai) Co., Ltd. announced the submission of AMT-676 for injectionApproved for Clinical Use, intended for the treatment of advanced solid tumors. According to publicly available information from Puzhong Discovery, this is aAnti-CDH17 Antibody-Drug Conjugate (ADC), and it is also a drug under research for pan-gastrointestinal tumors. Cadherin 17 (CDH17, also known as CA17) is an emerging target in the field of gastrointestinal tumor treatment in recent years. Studies have shown that it plays an important role in the invasion and metastasis of various tumors, especially in digestive system tumors. Puzhong Discovery Pharmaceutical Technology(Shanghai) Co., Ltd. has already initiated a first-in-human Phase 1 clinical study of AMT-676 in Australia.

SCTB41 Injection

Mechanism of Action: Tri-specific Antibody Products

Indications: Advanced Malignant Solid Tumors

According to the announcement by ShenZhou Cell, SCTB41 is a product independently developed by the company with the goal of achieving differentiated advantages.Tri-specific Antibody Injection for Immunotherapy of Multiple Solid Tumors. This clinical approval is intended for monotherapy treatment of advanced malignant solid tumors.

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