Multiple First-in-Class Innovations: Solid Tumor CAR-T, hESC-Derived MSC, Allogeneic Fibroblasts, and FIC PD-L1 ADC Highlight CDE Weekly Updates

According to the Center for Drug Evaluation of the National Medical Products Administration of China（CDE）According to incomplete statistics from the official website and publicly available information, last week(June 23 - June 29)，Approximately 16 Innovative DrugsNDA Application Accepted/IND Approved for Clinical Tacit Consent/IND Application Accepted.(Note: This article only counts new molecular modal innovative drugs such as bispecific antibodies, ADCs, CAR-T, small nucleic acids, and oncolytic viruses.)

These 16 innovative drugs mainly cover tracks such as ADC, CAR-T, stem cell therapy, and small nucleic acids. With technological innovation and rapid clinical progress, several of these drugs have achieved international/domestic "firsts." Due to limited public information,Limit,Hengrui Medicine's SHR-4506 Injection, Qilu Pharmaceutical's QLC5508 for injection, and Zai Lab's ZL-1109 Injection, among other Class 1 innovative drugs, are not included in the following table.

The following will introduce some innovative drugs with more publicly available information.

CARsgen Therapeutics Autologous CLDN18.2 CAR-T Suruji Orlen Injection（CT041）New Drug Marketing Application（NDA）Officially Submitted to the National Medical Products Administration of China（NMPA）Center for Drug Evaluation（CDE）, intended for the treatment of CLDN18.2-positive patients who have failed at least two prior lines of therapyAdvanced Gastric/Esophagogastric Junction Adenocarcinoma（G/GEJA）Patient.

The official press release stated that Surge Kiorin Injection isThe World's First and OnlyA CAR-T therapy for solid tumors submitted for NDAT cells. If successfully launched, it will become the world'sThe Earliest CommercializationSolid tumor CAR-T products.(Recommended Reading:World's First! CARsgen Therapeutics Submits Marketing Application for Solid Tumor CAR-T Therapy)

According to the official disclosure by Beijing Yimiaoshenzhou Medical Technology Co., Ltd., IM96 CAR-T Cell Injection is the company's original CAR-T for solid tumors, targeting GUCY2C. GUCY2C is highly expressed in intestinal malignant tumors, with a high positive rate in colorectal cancer.80%, The positive rate of gastric cancer exceeds60%. Currently, IM96 has received clinical trial approval by default from the CDE and is intended to treat colorectal cancer.The First in ChinaCAR-T for this indication. In addition, IM96 has been approved by the FDA for clinical trials and is planned to be developed for the treatment of gastric cancer and colorectal cancer.

Public information shows that IMS001 Injection is an allogeneic mesenchymal stem cell product derived from a human embryonic stem cell line, developed by ImStem Biotechnology.（hESC-MSC）, relying on the company's unique embryonic stem cell-derived mesenchymal stem cell differentiation and application technology platform（T-MSC）R&D. T-MSC can ensure no quality difference between batches and an unlimited number of cells, making large-scale production of T-MSC as a cell drug possible.

Preclinical trials confirmed that IMS001 has immunomodulatory repair capabilities and the ability to cross the blood-brain barrier. (BBB) The ability to demonstrate its advantages in the treatment of neurological diseases, etc. In March 2022, IMS001 completed the first dosing in a multiple sclerosis patient in the United States.World's FirstThe clinical trial of systemic administration of hESC-MSC in humans.

According to official materials from VertiCell Medicine, allogeneic human fibroblast injection（FibroCell）A cell therapy candidate drug for the treatment of early to mid-stage intervertebral disc degeneration submitted by the company, and alsoThe First InternationalA cellular candidate drug for managing intervertebral disc degeneration by inducing the transformation of degenerative nucleus pulposus cells into fibroblasts, administered through minimally invasive injection. In the IIT clinical trial of the first dosing group, all subjects were discharged smoothly within two days after injection, with significant improvement in lower back pain symptoms.Reading Recommendation:First in China, Zhiyuan Medicine Fibroblast Therapy Submits Clinical Application for Treating Lumbar Disc Degeneration）

According to public information, Pfizer's PF-08046054(Freeze-dried Powder Injection)It is a potential "first-in-class" PD-L1 targeted ADC, composed of an anti-PD-L1 antibody, a linker, and the microtubule-disrupting agent MMAE, which exerts antitumor activity through direct cytotoxicity, bystander killing, and immunogenic cell death.

It not only inherits the broad-spectrum nature of the PD-L1 target but also combines the efficacy of ADC and IO. Compared with anti-PD-L1 monoclonal antibodies, this ADC can achieve faster internalization and proteolytic cleavage. Currently, PF-08046054 has entered phase 1 clinical trials.

YJH-012 Injection is a small interfering RNA submitted by Livzon Pharmaceutical.（siRNA）, aims to develop a treatment for gout. It utilizes the liver-targeted delivery system GalNAc to deliver chemically modified double-stranded molecules to the primary site of uric acid synthesis, thereby reducing the production of key pathogenic proteins at the source. Due to factors such as the strong stability of chemically modified siRNA, the creation of an intracellular sustained-release reservoir through liver-targeted delivery, and the long half-life of the RISC complex, a single dose of YJH-012 can achieve3-6 monthsThe sustained effect of lowering uric acid.

Preclinical validation: Single-dose administration in cynomolgus monkey models（10 mg/Kg）The effect of lowering uric acid lasts up to180 DaysAccording to the company's official press release, a dosing regimen of subcutaneous abdominal injection once every 3 months or 6 months is planned for Phase 1 clinical trials.

JWK002 Injection is a new AAV gene therapy drug independently developed by Jinweike Biotechnology, intended for the treatment of X-linked retinoschisis.（XLRS）JWK002, through systematic design of targeted serotypes and gene expression elements, can efficiently restore retinoschisin 1 in retinal cells.（RS1）The expression of gene mutations, thereby improving the patient's retinal structure and function. In addition, it utilizes the "two-plasmid packaging process system" independently developed by Jinweike, with stable suspension HEK293 cell packaging technology that is easy to scale up.Significantly reduced production costs, with high patient accessibility.

Jiachen Xihai's Replicating RNA Herpes Zoster Vaccine(JCXH-105 Injection)Approved for clinical implied consent, intended for the prevention of shingles in adults aged 40 and above. JCXH-105, as a new generation RNA vaccine, showed good tolerability in head-to-head clinical trials compared with Shingrix. It achieved immunogenicity results equivalent to Shingrix at a dose of 50 μg per shot while inducing lower reactogenicity, especially after the second dose.

HDM2020 for injection is a targeted fibroblast growth factor receptor 2b application filed by Sinopharm Holding Zhongmei Huadong Pharmaceutical Co., Ltd.（FGFR2b）The ADC, intended for development to treat advanced solid tumors. According to publicly available data, HDM2020 can specifically bind to tumor cells expressing human FGFR2b and exert a tumor-killing effect by releasing toxin payload into the cells, with a DAR value of8。

Preclinical studies have demonstrated that HDM2020 is effective in gastric cancer and squamous non-small cell lung cancer with positive targets.（sq-NSCLC）Demonstrated robust anti-tumor activity in pharmacodynamic models, with favorable drug-like properties and safety.

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