CELL AND GENE THERAPY
Innovent Biologics | February 21, 2022
Innovent Biologics, Inc. a world-class biopharmaceutical company that develops, manufactures and commercializes high-quality medicines for the treatment of oncology, metabolic, autoimmune and other major diseases, today announced the first patient dosing for its first-in-class IgG-based universal "modular" Claudin 18.2-targeting chimeric antigen receptor T (CAR-T) cell product (development code: IBI345) for the treatment of advanced Claudin18.2-positive solid tumors in an investigator-initiated-trial (IIT). Since Innovent announced its strategic cooperation with Roche on June 9, 2020, this is the first disclosure of the development milestone for the cell therapy products based on Roche's proprietary innovative technology platform.
CAR-T cell therapy has established a meaningful role in the treatment of hematological tumors with 5 products approved by the FDA, and 2 by the NMPA in China, respectively; however, antitumor efficacy for solid tumors remains a challenge calling for technological breakthroughs. As the world's first universal "modular" CAR-T cell product, IBI345 has potentially differentiated advantages over conventional CAR-T cell therapy products, including: 1) leveraging antibody function to target tumor antigens and consequently amplifying the tumor antigen signal to guide CAR-T cells to enter the tumor, thus aiding in the initiation of tumor recognition and killing; 2) controlling the functional activity of the CAR-T cells via concomitantly administered antibodies which act as a bridge between the target cell and CAR-T cell, potentially providing a better safety profile; 3) allows for the sequential or simultaneous administration of more than one antibody targeting different antigen targets without changing CAR-T cells, to treat tumors with highly heterogeneous antigen expression or relapsed tumors due to antigen-loss, thereby improving the accessibility and increasing the flexibility of CAR-T cell therapy for patients.
The principal investigator of the study, Professor Weichang Chen, the Secretary of the Party Committee and Chief Physician of the Department of Gastroenterology of the First Hospital Affiliated to Soochow University, pointed out: "As gastric and pancreatic cancer are highly aggressive tumors with high incidence rates in the world, patients are in urgent need of novel treatment options to improve clinical outcomes. IBI345, with its unique design to control CAR-T functional activity through the antibody bridging, will likely provide improved safety and efficacy. We look forward to the positive results of the safety, tolerability and efficacy data of IBI345 in patients with solid tumors, which will potentially provide a new option for the treatment of patients with advanced gastric or pancreatic cancer."
"IBI345 is a highly differentiated CAR-T cell product with a new mechanism of action developed by Innovent based on Roche's proprietary technology. As a universal "modular" CAR-T cell therapy product, equipped with a precisely targeted antibody switch, it regulates the expansion of CAR-T cells to control side effects, potentially providing an opportunity to switch to another antibody that targets different antigens to prevent recurrence and treat different tumors. Our preclinical studies have validated this "modular" CAR-T technology, which provides us with the sufficient scientific data to initiate clinical studies. In the following clinical studies, we will explore the safety, tolerability, pharmacokinetics and preliminary efficacy of IBI345, and optimize the clinical dosage and regimen to support the subsequent IND application. We firmly believe that Innovent will be able to introduce more innovative cell therapies through platform technology innovation, product transformation and in-depth collaboration with the clinical academic community that will ultimately benefit more patients and families."
Dr. Xu Wei, VP of Innovent, R&D Head of Cell Therapy
About Claudin 18.2
Claudin protein is a critical component of tight junction complex molecules which play an important role in the life activities of the human body. On the one hand, tight junctions can function as a "barrier" to select the size and charge of substances, thereby regulating the transport of substances in the para-cellular pathway. For example, brain vascular endothelial cells can pass through this barrier, preventing blood from mixing with the extracellular fluid in the brain. On the other hand, tight junctions can also function as "fences", maintaining cell polarity by regulating the free diffusion of lipids and proteins between the apical and the basolateral membrane.
About Gastric and Pancreatic adenocarcinoma
Gastric and pancreatic cancer are both malignant tumors of the digestive system that seriously endanger human life and health. The latest global cancer statistics show that there will be about 1.089 million new cases of gastric cancer worldwide in 2020, accounting for 5.6% of the global cancer incidence, and about 768,000 deaths, accounting for 7.7% of the global cancer deaths. There are about 495,000 new cases of pancreatic cancer, accounting for 2.6% of the global cancer incidence, and about 466,000 deaths, accounting for 4.7% of the global cancer deaths. According to the national cancer statistics released by the National Cancer Center of China in 2019, the incidence of gastric cancer in China in 2015 was about 403,000, accounting for 10.26% of the total cancer incidence, second only to lung cancer at 20.03%, with an incidence rate of 29.31/100,000 people, and about 291,000 deaths, accounting for 12.45% of the total cancer deaths, behind lung and liver cancer, with a mortality rate of 21.16/100,000 people. In 2015, the number of cases and deaths of pancreatic cancer nationwide were 95,000 and 85,000 respectively, ranking the 10th and 6th in the incidence and mortality of malignant tumors. The mortality ratio of pancreatic cancer was 0.89, making it a true "King of Cancer". Despite the treatment progress in recent years, drug resistance, recurrence and metastasis are still inevitable. The 5-year survival rate of patients with advanced gastric cancer is about 5-20%, and the median survival rate is about 10 months. Pancreatic cancer has a worse prognosis, with a 5-year survival rate of only 6 to 8%.
IBI345 is the first universal "modular" CAR-T cell product developed by Innovent based on Roche's proprietary technology. It is an internationally pioneered highly differentiated CAR-T cell product with a new mechanism of action. Different from conventional CAR-T cells that directly recognize and kill tumor cells, IBI345 comprises of two components, anti-Claudin18.2 antibodies and "modular" CAR-T cells where anti-Claudin18.2 antibody recognizes tumor antigen, thus calibrating and amplifying the antigen signal, and guides "modular" CAR-T cells to enter the tumor to initiate the cytotoxic and antitumor activity of CAR-T cells. Compared with conventional CAR-T cells, IBI345 has a variety of potential advantages, including dual effects of antibodies and CAR-T cells to increase antitumor efficacy, and flexible control of side effects by regulating CAR-T cell activity through antibodies; in addition, as having a universal CAR molecule, "modular" CAR-T cells can be easily switched to different antibodies without changing CAR-T cells, by sequentially or simultaneously administering more than one antibody targeting different antigen targets, to treat tumors with highly heterogeneous antigen expression or antigen-loss relapsed tumors, which holds a great potential to reduce the cost of CAR-T cell therapy and improve the accessibility of CAR-T cell therapy for patients.
Innovent announced that first patient dosing has been completed in February 2022 in the investigator-initiated clinical trial of IBI345 for the treatment of advanced Claudin18.2-positive solid tumors, and enrollment is currently ongoing. The safety, tolerability, pharmacokinetics and preliminary efficacy of IBI345 will be explored, and the clinical dosage and regimen will be explored to provide clinical data support for the subsequent IND application.
Inspired by the spirit of "Start with Integrity, Succeed through Action," Innovent's mission is to develop, manufacture and commercialize high-quality biopharmaceutical products that are affordable to ordinary people. Established in 2011, Innovent is committed to developing, manufacturing and commercializing high-quality innovative medicines for the treatment of cancer, autoimmune, metabolic and other major diseases. On October 31, 2018, Innovent was listed on the Main Board of the Stock Exchange of Hong Kong Limited with the stock code: 01801.HK.
ZS, Seven Bridges | May 07, 2021
ZS and Seven Bridges disclosed a collaboration today that will merge ZS's experience in biomedical testing facilities and data science with Seven Bridges' technology platform, which enables multi-omics analytics through the translational and clinical continuum. The hybrid offers biopharmaceutical and biotechnology firms a one-stop-shop for multi-omics analysis innovation and scalability. ZS and Seven Bridges work together to help clients produce breakthrough science, promote drug development, and improve the probability of approval for potential drug candidates.
"Working side by side with our clients to help streamline R&D data and maximize pace and market to enhance patients' lives is at the heart of what we do at ZS," said Aaron Mitchell, principal, and leader of ZS's research and development excellence program. "Our collaboration with Seven Bridges allows our clients, and eventually patients, to gain access to new therapies and diagnostics more quickly."
"Drug discovery, translational medicine, and preclinical drug research all require study at the molecular and genomic levels of implementation, and our collaboration with Seven Bridges provides our clients with a new option for innovation and scalable capacity," said John Piccone, principal, and leader of ZS's biomedical research service line.
"We are building a talent pool of molecular natives with a strong knowledge of chemistry, data science, and technology to collaborate with our clients in the discovery of potential drug targets, the selection of drug candidates, and the solution of key translational medicine challenges. The integration of the Seven Bridges Platform and experts with the ZS consulting teams results in a modular approach for clients with growing multi-omics data and analytics requirements."
"We are delighted to be combining the Seven Bridges platform with ZS's innovative apps for drug discovery and translational medicine. Integrating our multi-omics analysis platform and ARIATM, a centralized solution for molecular and patient-level phenotypic analysis at scale, with their research data lake is a critical requirement for ZS's pharmaceutical clients "said Bruce Press, Seven Bridges' Chief Revenue Officer.
About Seven Bridges
Seven Bridges allows researchers to derive meaningful insights from genomic and phenotypic data, thereby advancing precision medicine. A compliant analytic platform, intelligently curated content, innovative algorithms, unmatched access to federated data sets, and specialist on-demand technical resources comprise the Seven Bridges Ecosystem. Researchers at the world's leading academic, biotechnology, clinical diagnostic, government, medical centers, and pharmaceutical institutions are using this systematic approach to bioinformatics to maximize R&D effectiveness, improve hypothesis resolution, isolate vital biomarkers, and even transform a failing clinical trial around while also minimizing computational workflow times and data storage costs.
ProteoNic | October 20, 2020
ProteoNic BV, a leading provider of technology and services in the field of production of biologics, today announced it has licensed its premium 2G UNic™ technology for boosting therapeutic protein production to Immunomedics, Inc. (NASDAQ: IMMU), a biopharmaceutical company developing immuno-therapeutics for the treatment of cancer and other diseases. Under the agreement, Immunomedics gains commercial rights for application of ProteoNic's technology platform to the development of specified proprietary products from mammalian cells. Financial details of the agreement were not disclosed. ProteoNic's protein expression technology improves production levels across a range of host cells, selection systems and protein targets. It increases transcription and translation rates via a combination of novel genetic elements, which together exert a powerful positive effect on recombinant protein production levels without impacting product quality or cell line stability attributes. 2G UNic™ can be readily combined with other protein expression-enhancing technologies to improve their performance.