Over 20 Class 1 New Drugs Receive IND Approval in China from Companies Including Pfizer, MSD, and Haisco

▎WuXi AppTec Content Team Report

According to the official website of the Center for Drug Evaluation (CDE) under China's National Medical Products Administration (NMPA), in the past two weeks,More than 20First-in-class new drugObtained clinical trial implied permission (IND). After sorting out, these new drugs coverSmall molecule new drugs, molecular glues, antibody-drug conjugates (ADCs), monoclonal antibodies, tri-specific antibodies, etc., involving targets includingDGKα、LSD1、THR-β、DHX33、KRAS G12D、CD38Etc.This article will provide a brief introduction to some of these products.

Haisco: HSK42360 Tablets

Mechanism of Action:BRAF V600Inhibitor

Indications:BRAF V600Mutant Advanced Solid Tumors

According to the announcement by Haisco, HSK42360 is a product independently developed by the company.TargetedBRAF V600Mutant and Brain-Penetrant Small Molecule Inhibitors, Clinically intended for the treatment ofBRAF V600Mutant advanced solid tumors. Preclinical study results show that HSK42360 in multipleBRAF V600The mutant solid tumor efficacy model demonstrated promising anti-tumor effects, while also exhibiting good tolerability and a wide safety margin, making it a small-molecule anti-tumor drug with significant development potential.

CASI Pharmaceuticals: CID-103 Injection

Mechanism of Action:Anti-CD38 Monoclonal Antibody

Indications: Multiple Myeloma

CID-103 is a monoclonal antibody being developed by CASI that specifically targets the human CD38 epitope, which can activate effector T cells and NK cells to kill tumor cells. This product has been approved for clinical use in China and is indicated for patients with relapsed or refractory conditions who have previously received treatment.Adult patients with relapsed/refractory multiple myeloma (R/R MM)Treatment. Notably, in May 2022, Kexin Yuanda collaborated with Tianshi Tongda Pharmaceutical, granting the latter the rights to CID-103 for treatment.Autoimmune DiseasesThe global exclusive license.

Kaiyue Life: KY386 Injectable Concentrate Solution

Mechanism of Action: DHX33 Inhibitor

Indications: DHX33-positive malignant tumors

According to the press release from Kaiyue Life, KY386 Injection Concentrate is a highly efficient and selective product independently developed by the company.Novel DHX33 Inhibitor, The indication approved for clinical use this time isDHX33-positive recurrent/refractory advanced malignant tumors.DHX33 is a member of the intracellular RNA helicase family of proteins, which promotes cell proliferation and plays a significant role in the pathogenesis of cancer.Kaiyue Life has over a decade of foundational research experience in the field of RNA helicase drug development.

Pfizer: PF-07264660 Injection, PF-07275315 Injection

Mechanism of Action: Tri-Anti

Indications: Atopic Dermatitis

Pfizer's Two Class 1 New DrugsApproved for Clinical Use, both of which are intended to be developed for the treatment ofModerate to Severe Atopic Dermatitis in Adults. According to Pfizer's public information, both products are trispecific antibodies, among which PF-07264660 isAnti-IL-4/IL-13/IL-33 Tri-specific Antibody, PF-07275315 isAnti-IL-4/IL-13/TSLP Trispecific Antibody。These two trispecific antibodiesWhile more effectively blocking the IL-4/IL-13 signaling pathway, it can achieve broader effects by inhibiting TSLP or further suppress itching by blocking the IL-33 pathway., which is expected to have better efficacy in the treatment of atopic dermatitis.

Bristol-Myers Squibb: Golcadomide Capsule

Mechanism of Action: Molecular Glue

Indications:Large B-cell Lymphoma

Under Bristol-Myers SquibbCelgene's Class 1 New DruggOlcadomide CapsulesApproved for clinical use, intended to be developed forUntreated high-risk large B-cell lymphoma. This is aNovel E3 Ubiquitin Ligase Cereblon (CELMoD) Molecules, optimized for the characteristics of the disease, mainly distributed in lymphoid organs。In the phase 1/2 clinical study targeting B-cell lymphoma,The objective response rate (ORR) of this product reached 91.1%.As of now,Bristol-Myers SquibbThe company has had several molecular glue drugs approved or initiated Phase 3 clinical trials in China.

MSD: Bomedemstat Capsule

Mechanism of Action:LSD1 Inhibitor

Indications:Primary Thrombocythemia

Bomedemstat Capsules (MK-3543) is aOral Lysine-Specific Demethylase 1 (LSD1) InhibitorIn November 2022, MSD acquired Imago for approximately $1.35 billion in cash, thereby obtaining the latter's main candidate drug, which is currently in Phase 2 clinical trials. The product this time in ChinaApproved for Clinical Use, Intended to develop treatment forPrimary Thrombocythemia。LSD1 is an epigenetic regulatory protein that modulates the maturation of bone marrow stem cells and also plays a crucial role in many hematological malignancies, being considered as one of the emerging targets for treating various high-mortality blood cancers.

Bayer: BAY 2862789 Oral Solution, BAY 3018250

Mechanism of Action: DGKα Inhibitor、Protein drugs against a2AP

Indications: Advanced solid tumors, Stroke

Bayer(Bayer) Two Class 1 New Drugs in ChinaApproved for Clinical Use。BAY 2862789 Oral Solution is aSmall Molecule DGKα Inhibitor，Intended for the treatment ofAdvanced Solid Tumors,DGKα-specific inhibitors show promise in cancer treatment by exerting a dual anticancer effect of suppressing cancer cell proliferation while activating T-cell function.BAY 3018250 is aAnti-a2AP protein drugs,Intended for the treatment ofAcute Ischemic Stroke.α2-Antiplasmin (a2AP) is a plasmin inhibitor associated with an increased risk of ischemic stroke and tissue plasminogen activator (rt-PA) treatment failure.

Astellas: ASP3082 Injection

Mechanism of Action:KRAS G12D Protein Degrader

Indications:KRAS G12DMutant Solid Tumors

Astellas(Astellas) in developmentASP3082 Injection Approved for Clinical Trials in China, Intended for Development toCarryKRAS G12DPreviously Treated Locally Advanced (Unresectable) or Metastatic Malignant Solid Tumors with Mutations. This is a highly selectiveNew TypeKRAS G12D Protein Degrader, which binds to and selectively targets the KRAS G12D mutant protein for degradation by recruiting E3 ubiquitin ligase protein. This product is currently undergoing Phase 1 clinical trials internationally.

Gentle Force Pharma: GFH375 Tablets

Mechanism of Action:KRAS G12D Protein Degrader

Indications:KRAS G12DMutant Solid Tumors

Gyenno Medicine Under ResearchOral KRAS G12D (ON/OFF) InhibitorGFH375 Tablets Approved for Clinical Trials, Intended for Development as TreatmentKRAS G12DMutation-positive advanced solid tumorsPatient. The productBinding to KRAS G12D protein through non-covalent means, inhibiting its binding with downstream effector proteins, ultimately achieving highly efficient inhibition of tumor cell proliferation.In August 2023, GenFleet Therapeutics entered into a collaboration worth over $600 million with Verastem Oncology, granting the latter access to three drug candidates developed by GenFleet Therapeutics.Targeted RAS Pathway Innovative TherapiesGlobal development and commercialization rights outside of Greater China, including for this GFH375.

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Kaiski: CS060304 Tablets

Mechanism of Action:Novel THR-β Agonist

Indications:Non-alcoholic fattyHepatitis

Kasikedi's Class 1 new drug CS060304 tablets have received clinical trial tacit approval for the proposed development to treat non-alcoholic fatty liver disease/non-alcoholic steatohepatitis (NASH, also known as MASH). This is aSmall Molecule Agonists Targeting Thyroid Hormone Receptor β (THR-β), canHighly specific enrichment in liver tissue. The product has demonstrated positive and prominent preclinical data, particularly showing significant improvement in NAS scores and fibrosis in NASH mouse models, with characteristics of low effective dosage, remarkable efficacy, and good tolerability.

Zhengxiang Pharmaceutical: ZX-8177 Tablets

Mechanism of Action: ENPP1 Inhibitor

Indications: Advanced Solid Tumors

Zhengxiang Pharmaceutical's Research and DevelopmentSmall Molecule ENPP1 InhibitorZX-8177 TabletsApproved for Clinical Use, intended for the development of treatment for advanced solid tumors. ENPP1, the full name of which is Ectonucleotide Pyrophosphatase/Phosphodiesterase-1, can hydrolyze extracellular 2'3'-cGAMP, weakening the immune-stimulating tumor microenvironment, thereby promoting tumor progression. Therefore,Blocking ENPP1 in the tumor microenvironment is a potential strategy to combat tumors by enhancing innate immune responses.。

In addition to the aforementioned products, other Class 1 new drugs have received initial IND approval in China over the past two weeks, such asHengrui MedicineTwo Class 1 new drugs, HRS-7249 Injection and HRS-9813 Tablets, have been approved for clinical trials, intended for the treatment of hyperlipidemia and idiopathic pulmonary fibrosis, respectively;Baili TianhengADC product BL-M17D1,Kelun BotaiHaisco's ADC product, SKB518 for injection, has been approved for clinical trials, aiming to develop treatments for solid tumors, etc., limited by space, will not be introduced one by one here.It is hoped that the subsequent clinical research of these Class 1 new drugs will proceed smoothly, achieve breakthroughs as soon as possible, and benefit patients.

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