OriginCell's First GPC3-Targeted CAR-T Therapy for Liver Cancer Showcases Promising Clinical Data at ASCO

SHANGHAI, June 7, 2021 /PRNewswire/ -- On June 4, 2021 (ET), Oricell Therapeutics Holdings Limited ("Qrigincell Therapeutics"), together with Lishui Central Hospital Affiliated to Zhejiang University and Shanghai Changzheng Hospital, presented for the first time the latest clinical research data (Abstract ID: 4095) evaluating the GPC3-targeting CAR-T therapy (Ori-CAR-001) for the treatment of recurrent/refractory hepatocellular carcinoma (HCC) at the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting. Preliminary data from the study demonstrated that Ori-CAR-001 exhibited a favorable safety and efficacy profile in GPC3-positive recurrent/refractory patients.

Major Breakthrough in Cell Therapy for Solid Tumors

As of March 10, 2021, this study enrolled a total of 11 subjects with recurrent disease who received cell infusion, all of whom were patients with advanced hepatocellular carcinoma refractory to chemotherapy, TACE, and targeted drug therapy. Evaluated according to the Barcelona Clinic Liver Cancer (BCLC) staging criteria**, with the exception of 1 case at stage B (intermediate stage), the remaining 10 cases were all at stage C (advanced stage). All subjects presented with multiple metastatic lesions, among whom 6 (54%) had distant metastases, including pulmonary metastases. Excluding 2 subjects who withdrew from the study prior to evaluation, among the 9 evaluable patients, 4 achieved partial response (PR), 3 achieved stable disease (SD), and 2 experienced progressive disease (PD). The objective response rate (ORR) was 44.44%, and the disease control rate (DCR) was 77.78%.

Among them, Subject 007 maintained a partial response (PR) for over 6 months, with a tumor volume reduction exceeding 80%. As of the data cutoff date, this patient's duration of response has surpassed 8 months, and follow-up is ongoing. Another subject demonstrating significant clinical benefit, Subject 012, is a patient with highly advanced, diffusely infiltrative hepatocellular carcinoma who had previously undergone more than 12 TACE procedures. After radiotherapy and targeted therapy proved ineffective, the patient was enrolled in this study. MRI results at 28 days post-infusion showed that the maximum tumor diameter decreased from 133 mm to 9 mm, representing a reduction of over 90%. Currently, this subject is...Assessment at 3 months post-reinfusion, MRI scan results showed that the tumor had nearly disappeared. Correspondingly, 28 days post-reinfusion, AFP (alpha-fetoprotein, a tumor marker specific for the diagnosis of primary liver cancer) levels decreased from >80,000 to 1148.9 ng/mL,3 Months Post-Infusiondecreased to 746.7 ng/mL (normal range: 0–40 ng/mL), demonstrating the significant efficacy of Ori-CAR-001 in the treatment of advanced hepatocellular carcinoma.

Favorable safety profile

Among the 11 patients who received the infusion, Ori-CAR-001 demonstrated favorable safety and tolerability. Cytokine release syndrome (CRS) was observed in 9 patients, of whom 7 experienced Grade 1-2 CRS and 2 developed Grade 4 CRS following intravenous infusion. All patients recovered following treatment with corticosteroids and tocilizumab. No neurotoxicity was observed.

ForOri-CAR-001Treatment of Advanced Refractory/Results obtained in exploratory clinical studies for recurrent hepatocellular carcinoma, this clinical trial'sPIone of the Chief Scientists of the National Key Research and Development Program, Director of the Zhejiang Provincial Key Laboratory of Diagnostic Imaging and Minimally Invasive Interventional ResearchProfessor Ji Jiansong stated:“Recurrence/There are currently no effective treatments for refractory hepatocellular carcinoma, and cell therapy for solid tumors has struggled to achieve breakthroughs due to factors such as the tumor microenvironment. However, Qrigincell Therapeutics'Ori-CAR-001Relapse after cell therapy/The objective response rate in refractory hepatocellular carcinoma reached44%, the disease control rate reached77%, delivering a combination of a manageable safety profile and robust antitumor activity, an effect unattainable by currently marketed drugs. Based on the favorable efficacy and safety data from earlier phases,Ori-CAR-001Cellular therapeutics hold promise to become a novel treatment option for patients with advanced hepatocellular carcinoma, which instills us with great confidence in their future research prospects and fills us with pride in China's innovative drugs.”

Dr. He Xiaowen, Co-founder and Chief Scientific Officer of Qrigincell Therapeutics, stated: “Cellular immunotherapy for tumors has already demonstrated excellent therapeutic efficacy in hematological malignancies. In the future, to address the greater clinical demand in solid tumor treatment, Qrigincell Therapeutics will continue to explore, hoping to deliver more effective cellular immunotherapy solutions to numerous advanced-stage patients and clinicians.”。”

**Barcelona Clinic Liver Cancer (BCLC), a clinical staging system for hepatocellular carcinoma developed by the European Association for the Study of the Liver (EASL), is designed to assess patient condition, guide accurate treatment planning, and predict prognosis. It is primarily classified into stages 0, A, A1, A2, A3, A4, B, C, and D.

About Ori-CAR-001

“Ori-CAR-001Cells are the targetGPC3of the high-affinity chimeric antigen receptorTcells, intended for the treatment of refractory/Recurrent hepatocellular carcinoma (HCC）。Ori-CAR-001adopted GPC3 CARThe structure is composed of an anti-GPC3ofscFvhumanized antibody format,CD8 Hinge region, transmembrane region,4-1BB Co-stimulatory domain,CD3zintracellular activation domain, and throughT2Asimultaneously expressedOri2``composed of novel elements, transduced via lentivirus``TPost-cell suitability for memory phenotypeTexpanded and manufactured under a cell culture process. Compared with traditionalCAR-TCell comparison,Ori-CAR-001exhibits a significantly higher proportion of memory stem cells, resists the immunosuppressive microenvironment, and can significantly enhanceCAR-Texpansion and maintenance of cells, thereby enhancing their anti-tumor efficacy.”

It is worth noting that, in addition to the preliminary confirmation of the safety and efficacy of CAR-T therapy for HCC presented at the conference, Qrigincell Therapeutics and the researchers concurrently conducted translational medicine studies. By exploring administration routes, dosing regimens, PK/PD (pharmacokinetics/pharmacodynamics), and biomarkers, these investigations have advanced the application and development of cell therapy for solid tumors.

Currently, Qrigincell Therapeutics will further explore related clinical studies based on existing data, while the Investigational New Drug (IND) application to the National Medical Products Administration (NMPA) is proceeding concurrently.

About the American Society of Clinical Oncology

The American Society of Clinical Oncology (ASCO) is the world's leading professional academic organization in oncology, with over 40,000 members from more than 100 countries. Its mission is to prevent cancer, improve cancer care, and facilitate the translation of research findings into clinical practice. The annual ASCO Annual Meeting brings together leading experts in clinical oncology research worldwide and is widely recognized as the most important academic conference in oncology globally.

About QrigincellTherapeutics

Oricell Therapeutics Holdings Limited (formerly known as "Shanghai Yuanneng Cell Medical Technology Co., Ltd.", officially renamed on May 25, 2021) was established in 2015, securing nearly RMB 100 million in an exclusive Pre-A round investment from Qiming Venture Partners at the end of 2019, and completing an A-round financing exceeding RMB 200 million at the end of 2020. With the support of Qiming Venture Partners, Qrigincell Therapeutics was spun off as an independent entity from the innovative biologics R&D assets of the Yuanneng Cell Group, and will focus on the development of new products in the field of tumor immunotherapy in the future.。

Grounded in independent innovation, Qrigincell Therapeutics has invested heavily in establishing four synergistic, innovative product R&D technology platforms: the Ori™Ab Antibody Development and Optimization Technology Platform, the Ori™CAR High-Memory CAR-T Construct Technology Platform, the Ori™TIL High-Efficiency Cell Expansion and Culture Technology Platform, and the Ori™UCAR Universal CAR-T Technology Platform.

AboutOri™Ab—Antibody Discovery Technology PlatformPlatform

Has built 10¹¹Fully Human Antibody Phage Display Library and 10¹²The nanobody library and antibody engineering technology platform has yielded a series of independently developed, high-performance antibody drug candidates and CAR-T cell target antibodies.

AboutOri™CARTechnology PlatformPlatform

A unique signaling activation domain is integrated into a novel and proprietary CAR construct, exponentially enhancing the expansion efficiency of memory immune cells, effectively counteracting the immunosuppressive microenvironment of solid tumors, thereby augmenting the efficacy and persistence of CAR-T cells to efficiently suppress tumors and prevent recurrence.

AboutOri™TIL—High-Efficiency Cell Expansion and Culture Technology Platform 

Enables high-fold expansion of TIL cell yield, with quality attributes and process parameters breaking through industry bottlenecks to effectively ensure the clinical efficacy and safety of TIL therapy, while youthful TIL cells enhance tumor-killing activity.

AboutOri™UCARTechnology Platform 

Leveraging platform advantages such as highly efficient synergistic antibody technology, Ori technology, and gene editing and cell differentiation technologies to achieve the universality and convenience of future CAR-T products, while effectively reducing treatment costs.