Globally, companies have deployed an impressive range of business models for exploiting iPSC technology platforms. To date, iPSCs have found applications within academic research, drug discovery, toxicology testing, cell therapy, personalized medicine, disease modelling, industrial-scale manufacturing, biobanking, clean-meat production, and beyond.
The use of iPSCs within an academic research setting is self explanatory, and to date, an enormous amount of groundbreaking research has been completed within this setting. A larger segment of the iPSC market relates to drug discovery.
Use of iPSCs within Drug Discovery
Traditionally, drug discovery has involved high cost and uncertain outcomes. Only a few companies can take the risk of investing enormous amounts of money into research and testing only to see undesirable side effects emerge during the final human clinical trials. In many cases, companies spend millions of dollars to fail during clinical testing. Thus, some medicines are now being tested for safety on specialized cells developed from human iPSC lines.
Cells types which are frequently being using within drug discovery applications include iPSC-derived heart (cardiomyocytes) and liver cells (hepatocytes), which are the organs where 80% of drug failures occur.
Headquartered in Hamburg, Germany, Evotec is a major contender within this space. Evotec’s iPSC platform has been developed with the goal to industrialize iPSC-based drug screening as it relates to throughput, reproducibility, and robustness. Today, Evotec has one of the largest iPSC platforms globally. Evotec is also aligned with industry behemoths such as Bristol-Myers Squibb, an American pharmaceutical company headquartered in New York City that has a market cap of $140 billion. FUJIFILM CDI has also signed several collaborations within the pharmaceutical industry, including sequential agreements with Roche to test and validate their iPS-derived cardiomyocytes.
Other companies operate across multiple iPSC market segments. As an example, Stemgent (a ReproCELL brand) has developed close relationships with several the top academic researchers in the U.S. and China, enabling the company to gain access to their cutting-edge research. Stemgent has also signed collaborations with industry heavyweights, Pfizer and Fate Therapeutics, as well as a strategic partnership with Miltenyi Biotec for the co-development and marketing of stem cell research products.
Leveraging iPSCs for Toxicity Testing
Another critical market application is the use of iPSCs within toxicity testing applications. Several companies now provide iPSC-derived disease-specific neural cells, cardiomyocytes, and hepatocytes which can be used to test developmental, as well as cell-type specific, drug toxicities.
A renowned company involved in generating iPSC-derived cell types for this purpose is FUJIFILM CDI (FCDI). The company’s line of iCell products are fully differentiated human cells differentiated from iPSCs. The iCell GlutaNeurons offered by FCDI are a population of excitatory neurons that bring previously inaccessible human biology to the lab bench for both discovery and toxicity (seizurogenic) investigations. Similarly, iCell Hepatocytes offered by FCDI provide a relevant means for acute and sub-chronic toxicity testing in human tissue cells. The company also offers iCell Cardiomyocytes for testing cardiotoxicity.
Furthermore, FCDI signed a collaboration agreement with Axcelead, a Japanese Company, to develop new drug efficacy evaluation methods and toxicity testing to meet client-specific needs.
Within Europe, Ncardia has commercialized highly predictive human cellular assay systems for safety and efficacy testing. For example, its cardiac product portfolio encompasses a broad panel of hiPSC derived Cardiomyocytes (Pluricyte®, Cor.4U® and vCor.4U™) as well cardiac fibroblasts (FibroCor.4U™). In addition, the company offers its Cardioplate™ product line of quality controlled ready to use assay plates, and its neural cell portfolio contains the pan-neuronal product CNS.4U®, the peripheral neurons product Peri.4U®, and astrocyte product Astro.4U®.
Similarly, Takara Bio is regarded for its iPSC-derived hepatocytes designed for drug discovery and toxicology related studies.
Cell Therapy Applications of iPSCs
An emerging segment of the iPSC market relates to the cellular therapy applications of iPSCs. The major firms exploiting iPS technologies for therapeutic applications include Cynata Therapeutics, iPierian (now a Bristol-Myers Squibb company), Fate Therapeutics, Century Therapeutics, and BlueRock Therapeutics, among others.
In a world-first, Cynata Therapeutics received approval in 2016 to launch the world’s first formal clinical trial of an allogeneic iPSC-derived cell product (CYP-001) for the treatment of GvHD. Cynata’s proprietary technology utilizes iPSCs originating from an adult donor as the starting material for generating mesenchymoangioblasts (MCAs). It then differentiates these cells into mesenchymal stem cells (MSCs).
Today, Cynata Therapeutics has clinical trials underway for an impressive range of indications, including Graft vs. Host Disease (GvHD), knee osteoarthritis, acute respiratory distress syndrome (ARDS), diabetic foot ulcers, renal transplantation, and critical limb ischemia (CLI).
iPierian and Fate Therapeutics follow the same strategy of reprogramming somatic cells for developing cell-based models to screen small molecules for drug development. iPierian uses cellular reprogramming and differentiation technologies for advancing the understanding of human diseases for which there are poor in vivo and in vitro models and develop cell-based therapeutics for its own pipeline for the treatment of specific diseases. iPerian’s focus is on three neurological disorders, namely Parkinson’s disease, spinal muscular atrophy and amyotrophic lateral sclerosis.
Fate Therapeutics has developed an understanding of the pathways that can particularly activate and modulate adult stem cells and iPS-technology for screening stem cell modulators (SCMs), which are capable of modulating cell fate in vivo for repairing and regenerating tissues. Riding the momentum within the CAR-T field, Fate Therapeutics is also developing FT819, its off-the-shelf iPSC-derived CAR-T cell product candidate.
Currently, iPSC-derived cell therapeutics have yet to reach the market. Reasons for this include the prohibitively high cost of developing cell-based therapies and the challenging regulatory and scale-up issues associated within living therapeutics.
Industrial Scale iPSC Manufacturing
Within the world of industrial scale iPSC manufacturing, FUJIFILM CDI, Treefrog Therapeutics, and Rheincell Therapeutics are three companies who are leading the charge. While most people are familiar with FUJIFILM because it is a stalwart in the field, fewer people know about Treefrog Therapeutics.
Founded in 2018, Treefrog Therapeutics has developed C-StemTM, a high-throughput cell encapsulation technology allowing for the mass-production and differentiation of iPSCs in industrial bioreactors.
RheinCell Therapeutics is another relatively recent entrant into the iPSC marketplace. Founded in 2017, it focuses on the GMP-compliant generation of human iPSCs derived from HLA-homozygous allogeneic umbilical cord blood.
Cynata Therapeutics also has a unique Cymerus™ technology for nearly infinite expansion of iPSC-derived MSCs, but currently, it is using this technology exclusively for its own iPSC-derived cell therapy product development.
The cost for developing cell-based therapeutics from iPSCs is often prohibitively expensive. Yet, it has become possible to develop cell-based therapeutics, with the development of biobanks that have “ready-to-use” cells with close immunological matches to different populations.
Genetic testing and personalized medicine are the two important drivers of the global iPSC market. There is a growing demand for biobanking samples from clinical diagnostic labs for use in developing assays for genetic testing. Such samples are also utilized by biotech companies for developing new instruments and sequencing platforms for clinical and biomedical research.
Demand for iPSC lines is fueled by academic and commercial institutions where there is interest in developing “disease-in-a-dish” models for targeted drug discovery. Demand for iPSC lines is also driven by recent developments in gene editing technology.
Clean Meat Technology
Although not yet popular, lab-grown meat is fast becoming a real alternative to its farm-grown counterpart as billionaire entrepreneurs and industry heavyweights invest into start-ups from across the nascent field of “cellular agriculture”. Produced via induced pluripotent stem cells (iPSCs) derived from cows, pigs, fish, or sheep, the emerging clean meat industry has the potential to transform the global food market and create a new trillion dollar industry in the process.
By 2040, a projected 60% of the meat we eat will be created from muscle cells grown within laboratory bioreactors. These products will be sold in grocery stories under names such as cultured meat, clean meat, lab-grown meat, and meat produced via cellular agriculture.
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