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.
CELL AND GENE THERAPY
Biogen, Ginkgo Bioworks | May 22, 2021
Biogen and Ginkgo Bioworks announced a partnership in gene therapy today. The companies aim to redefine the industry standard for manufacturing recombinant adeno-associated virus (AAV)-based vectors by working together.
Recombinant AAV-based vectors are extensively used in the development of novel gene therapies with the ability to cure neurological and neuromuscular diseases, as well as other conditions in a variety of therapeutic areas. Manufacturing is now time-consuming and expensive, making it difficult to develop therapies for diseases with high dosage requirements and large patient populations.
Ginkgo intends to address these issues by using its mammalian cell programming platform to increase the performance of AAV-producing plasmid vectors and cell lines, potentially accelerating Biogen's development of novel gene therapies.
“We believe that Ginkgo's unique combination of cell programming expertise, proprietary tools, and biological system awareness makes them a perfect collaborative partner to explore a broad range of design ideas to optimize constructs,” said Alphonse Galdes, Ph.D., Biogen's Head of Pharmaceutical Operations and Technology.“They share our goal of ensuring that approved therapies are not delayed due to manufacturing constraints and are available to patients all over the world.”
“We are delighted to partner with Biogen as they seek to develop treatments that can potentially delay, stop, or cure neurological and neurodegenerative diseases, as well as to improve the industry standard for AAV manufacturing,” said Jason Kelly, CEO of Ginkgo Bioworks. “Synthetic biology is utilizing the power of living cells to develop the next generation of therapeutics, including CAR-T, CRISPR, and gene therapies, which we hope would have a significant effect on the lives of many people.”
Biogen will have access to Ginkgo's proprietary cell programming platform and capabilities under the terms of the agreement. Ginkgo will use its bioengineering facilities and resources to improve Biogen's gene therapy manufacturing processes' AAV output titers. Ginkgo will receive a $5 million initial payment and will be eligible for milestone payments of up to $115 million if the partnership programs achieve certain research, development, and commercial milestones.
Our mission at Biogen is clear: we are neuroscience pioneers. Biogen discovers, develops, and delivers innovative therapies for people suffering from severe neurological and neurodegenerative diseases, as well as related therapeutic adjacencies, around the world. Biogen was founded in 1978 by Charles Weissmann, Heinz Schaller, Kenneth Murray, and Nobel prize winners Walter Gilbert and Phillip Sharp as one of the world's first major biotechnology firms. Biogen currently has the leading portfolio of medicines for the treatment of multiple sclerosis, is the first approved treatment for spinal muscular atrophy, commercializes biosimilars of advanced biologics, and is focused on advancing research programs in multiple sclerosis and neuroimmunology, Alzheimer's disease, and dementia, neuromuscular disorders, movement disorders, ophthalmology, and neuropsychiatry.
About Ginkgo Bioworks
Ginkgo is building a platform for program cells in the same way as we program machines. The platform is enabling the growth of biotechnology across a wide range of markets, from food and agriculture to industrial chemicals and pharmaceuticals. Ginkgo is also closely involved in a variety of COVID-19 response efforts, such as community testing, epidemiological tracing, vaccine development, and therapeutics discovery.
CELL AND GENE THERAPY
2seventy bio, Inc | January 07, 2022
2seventy bio, Inc. announced that it has entered into an option and license agreement with Novo Nordisk for joint research and development of an in vivo gene editing treatment for hemophilia A. This agreement builds upon a successful existing multi-year research collaboration between the two companies. Under the terms of this agreement, Novo Nordisk will have the option to license 2seventy bio’s proprietary mRNA-based megaTAL™ technology for the development of a new treatment approach for hemophilia A patients with the goal of offering a sustained therapeutic effect.
“This collaboration aims to develop the first direct in vivo application of our megaTAL technology. We are excited to explore this technology with Novo Nordisk, with the goal of developing a new potential therapeutic approach for patients with hemophilia A. Moreover, we view this work as further validation and a natural extension of our technology platform. Based on what we continue to learn, this technology may play a potential role in expanding our gene editing platform toward future in vivo and ex vivo applications that can enhance our oncology pipeline. We are also excited to announce a partnership between 2seventy bio and Genevant Sciences for the use of Genevant’s lipid nanoparticle platform in our collaboration with Novo Nordisk.”
Philip Gregory, D. Phil., chief scientific officer, 2seventy bio
The collaboration agreement with Novo Nordisk builds upon the original research collaboration signed between bluebird bio and Novo Nordisk in 2019, focused on identifying a development gene therapy candidate for people with hemophilia A. The collaboration utilizes 2seventy bio’s megaTAL technology that has the potential to provide a highly specific and efficient way to silence, edit, or insert genetic components. Hemophilia A is a genetic bleeding disorder resulting from defective Factor VIII.
“We are excited to continue our partnership with 2seventy bio to jointly develop a next-generation in vivo genome editing treatment, with the ultimate ambition of offering people with hemophilia A lifetime free of factor replacement therapy,” said Karin Conde-Knape, senior vice president, Global Drug Discovery, Novo Nordisk. “This partnership reflects Novo Nordisk’s commitment to utilizing novel technology platforms to advance truly disease-modifying therapies for people with serious chronic diseases.”
Under the terms of the agreement, Novo Nordisk will obtain the option to exclusively license 2seventy bio’s in vivo mRNA platform and gene editing technology for use in the treatment of patients with hemophilia A. 2seventy bio will receive an upfront payment of $5 million and is eligible for near-term milestone and option exercise payments of up to $35 million, in addition to development, regulatory, and commercial milestones, as well as a royalty on net sales. Novo Nordisk will be responsible for funding all research and development activities.
Related to this collaboration, 2seventy bio has also entered into an agreement with Genevant Sciences for access to Genevant’s industry-leading LNP technology platform for use in 2seventy bio’s collaboration with Novo Nordisk for the treatment of patients with hemophilia A. 2seventy bio plans to use the Genevant LNP platform for efficient delivery of megaTAL mRNA to hepatocyte cells within the liver.
“We are very pleased that 2seventy bio has entrusted Genevant and our LNP platform with delivery for its important gene editing program in hemophilia A,” said Pete Lutwyche, Ph.D., president and chief executive officer, Genevant Sciences Corporation. “Our scientists have been at the forefront of the LNP field for more than 20 years, and we are excited for our innovative technology to be used for this important application with great unmet need.”
Under the terms of the agreement between 2seventy bio and Genevant, 2seventy bio obtained rights to license Genevant’s LNP technology for use with megaTAL mRNA products in the treatment of patients with hemophilia A. Genevant is eligible for upfront and near-term option exercise payments totaling $10 million, as well as development and commercialization milestones, and royalties in the mid-single digits on future product sales.
MegaTALs are single-chain enzymes that combine the natural DNA recognition and cleavage processes of Homing Endonucleases with the modular DNA binding properties of transcription activator-like effectors. This protein fusion architecture allows the generation of highly specific and active nucleases in a compact format compatible with all current viral and non-viral cell delivery methods.
About Novo Nordisk A/S
Novo Nordisk is a leading global healthcare company, founded in 1923 and headquartered in Denmark. Our purpose is to drive change to defeat diabetes and other serious chronic diseases such as obesity and rare blood and endocrine disorders. We do so by pioneering scientific breakthroughs, expanding access to our medicines, and working to prevent and ultimately cure disease. Novo Nordisk employs about 47,000 people in 80 countries and markets its products in around 170 countries.
About Genevant Sciences
Genevant Sciences is a leading nucleic acid delivery company with world-class platforms, the industry’s most robust and expansive lipid nanoparticle patent estate, and decades of experience and expertise in nucleic acid drug delivery and development. The Company’s scientists have pioneered LNP delivery of nucleic acids for over 20 years, and the Company’s LNP platform, which has been studied across more than a dozen discrete product candidates and is the delivery technology behind the first and only approved RNAi-LNP (patisiran), enables a wide array of RNA-based applications, including vaccines, therapeutic protein production, and gene editing.
About 2seventy bio
Our name, 2seventy bio, reflects why we do what we do - TIME. Cancer rips time away and our goal is to work at the maximum speed of translating human thought into action – 270 miles per hour — to give the people we serve more time. We are building the leading immuno-oncology cell therapy company, focused on discovering new therapies and leveraging platform technologies that truly disrupt the cancer treatment landscape.