bit.bio is industrialising human cell manufacturing, unleashing the potential of synthetic biology for reproducible research and affordable regenerative medicines

• Data presented at International Society for Stem Cell Research conference shows unparalleled level of consistency across manufacturing of multiple human cell products
• World leading stem cell biologists call the technology “a watershed moment for biology” and “a true disruptive innovation in stem cell biology, much as CRISPR has been for genetics”
• bit.bio’s ioCells are already being used and enable large-scale experiments that underpin preclinical research and drug development
• The consistency of the cells is enabling scientific breakthroughs and applications ranging from biohybrid devices, novel targets for neurodegeneration, and cultured meat.

15 June 2023 -- Boston, US and Cambridge, UK -- bit.bio, a synthetic biology company focused on human cells, has achieved a milestone in the manufacture of human cells. Based on their opti-oxTM 1- based transcription factor reprogramming technology, bit.bio has reached a new level of precision and consistency of their induced pluripotent stem cells (iPSC)-derived cell products.

The data that will be presented at the International Society for Stem Cell Research (ISSCR) conference show an unparalleled level of consistency with regards to multiple human cell products for research use. Samples of cells were selected from different manufacturing lots and time periods and different users carried out the opti-ox reprogramming step to manufacture the mature cell types. Analysis of the samples show fewer than 1% differentially expressed genes in bulk-mRNA sequencing experiments between manufacturing lots. This achievement sets a new standard for the manufacture of human cells.

Commenting on the data, Dr Marius Wernig, professor in the Departments of Pathology and Chemical and Systems Biology and co-director of the Institute for Stem Cell Biology and Regenerative Medicine at Stanford University and bit.bio SAB member said: "Out of 20,000 genes, not a single one is differentially expressed across three independently produced batches of bit.bio’s glutamatergic neurons. This seems like a watershed moment for biology. The team at bit.bio has achieved a level of consistency that is outside of the realm of what was thought possible. It is another proof point that transcription-factor based programming of cells can solve the challenges that have restricted the use of stem cell-derived cells in drug development and cell therapy."

Human stem cell pioneer Roger Pedersen, senior research scientist at Stanford University School of Medicine and chair of bit.bio’s SAB said: "These new results are both compelling and biologically fascinating. bit.bio's opti-ox approach seems to remove interfering sources of stochasticity, thereby enabling deterministic reprogramming of iPSCs into somatic cells of any lineage. The homogeneity achieved by opti-ox is amazing, and I would never have thought such a high level of control over differentiation was possible. This is a true disruptive innovation in stem cell biology, much as CRISPR has been for genetics."

Bertie Göttgens, professor and director at University of Cambridge Stem Cell Institute commented: "bit.bio is an integral partner within the Cambridge Stem Cell community, where they have pushed the boundaries of what the field thought was possible with regards to consistent differentiation of human stem cells. From what I have seen, the data are astonishing. If this can be generalised to other cell types, these data will be seen as a landslide moment for the human stem cell field, which demonstrate that it is possible to industrialise the manufacture of human cells."

The consistency and scale of manufacturing achieved, with billions of cells now being produced on a daily basis, has opened doors to the creation of human cell standards. This has the potential to address the lack of reproducibility that has plagued the life sciences industry. By using reliable and standardised human cells, researchers worldwide can accelerate their studies and enhance the reliability of their findings.

Thore Graepel, SVP of Computational biology at Altos Laboratories and bit.bio SAB member said: "I have never seen such consistency in biological data before. The data has made me rethink what level of consistency is possible in cell biology. Like in other application areas of machine learning, the quality of training data is of crucial importance and bit.bio’s cell products have the potential to super-charge AI models of biological systems."

Sir David Klenerman, professor of Biochemistry University of Cambridge, 2020 Breakthrough Prize in Life Sciences recipient 2022 who is best known for his work on next-generation sequencing of DNA as the technological basis for Illumina, said:
"This is a significant technological step forward, removing the cell-to-cell variation that has been a problem in the field."

Cells produced using the opti-ox technology have already been used in a range of research applications, including the identification of novel targets for neurodegenerative diseases such as Alzheimer’s. They have been used for the generation of biohybrid implant devices aiming to restore paralysed limb function, and 3D printing of brain models.

The ability to produce cells at an industrial scale allows large-scale experimentation, such as high-throughput screening – for example, underpinning bit.bio’s partnership with leading contract research organisation Charles River Laboratories. This means scientists can now conduct experiments on a significantly larger scale in human models, leading to faster discoveries and a deeper understanding of cellular mechanisms.

In addition, bit.bio is developing their technology for use in the field of cell therapy. Large scale manufacturing of human cells based on the ability to precisely reprogramme iPSC into specific somatic cell types will enable off the shelf regenerative medicines that are available to millions of patients as mainstay treatments.

Rahul Singhvi, CEO National Resilience stated: "This is an important breakthrough for the manufacture of human cells. The data are impressive and have set a new bar of what is possible. We are excited to support bit.bio in the development of their cell therapy pipeline."

Loïc Vincent, CSO Affini-T Therapeutics said: "A scalable source of consistent human cells will have a transformational impact on research, drug discovery and cell therapy. It can tackle major challenges such as the reproducibility of scientific research all the way to scale up challenges for cell therapies and regenerative medicine. bit.bio's preclinical data show extraordinary consistency. The fact that this has been achieved across multiple cell types is also astonishing. bit.bio’s genomic safe harbour technology, opti-ox, is really pushing the boundaries."

Outside of medicine, the extraordinary scale enabled by opti-ox has enabled the manufacture of trillions of fat and muscle cells in a porcine background for cultured meat applications. Meatable held their first tasting in Singapore this year7 and is due to launch its first products by the end of the year.

Meatable co-founder and CEO Krijn de Nood said: "Meatable is creating a world in which we can enjoy meat that is innocent. At the heart of our approach and enabling this dream is opti-ox. It allows us to manufacture at scale, and in the future reach price parity with meat derived from farmed animals. Whilst it is surprising to see these levels of consistency in the data, it is also what we experience on a daily basis. We found that opti-ox enables the manufacture of cells at all levels of scale, from the smallest experiment to the largest industrial bioreactor."

"The beauty of the data and how consistently bit.bio can produce human cells using our forward programming technology is mind-boggling” said Mark Kotter, CEO of bit.bio. “The team has developed solid processes and we haven’t had a single failed manufacturing run in the past two years. This is paving the way for ground-breaking research and future cell-based therapies. We are excited to collaborate with researchers and industry partners to unlock the full potential of human cells."

Hermann Hauser KBE, serial entrepreneur and venture capitalist, eg, behind Acorn Computers, ARM, Solexa/Illumina and chair of the bit.bio Board said: "When I joined bit.bio I sensed that bit.bio’s opti-ox technology has the potential to create a category leader in the human cell space. The consistency that we detected in bit.bio’s products is astonishing. This is the bottom line if one gets everything right in a manufacturing process. I am proud of this fantastic achievement by the team."

bit.bio's human cell manufacturing technology is set to reshape the future of scientific research and biomedicine. By ensuring reliability, scalability, and reproducibility, bit.bio is driving forward the frontiers of cellular biology and transforming the possibilities of what can be achieved.

Data for multiple cell types - glutamatergic neurons, sensory neurons and GABAergic neurons - will be presented at ISSCR, showing the approach may be generalisable to any human cell type.

About bit.bio
bit.bio is a synthetic biology company providing human cells for research, drug discovery and cell therapy, enabling a new generation of medicines. This is possible with our precision cellular reprogramming technology, opti-ox – a breakthrough gene engineering approach that enables unlimited batches of any human cell to be manufactured consistently at scale through direct reprogramming of stem cells. The company was founded in 2016 by Dr Mark Kotter from his labs at the University of Cambridge after his discovery of the opti-ox technology. It has raised over $150m in funding so far, has over 180 employees and is headquartered in Cambridge, UK and San Francisco, US. Visit:
www.bit.bio.