Meet The Company Democratizing Access To Human Cells

In the latter decades of the 20th century, stem cells—cells that can self-renew and differentiate into other cell types—took the research world by storm. They began to be applied to a wide range of degenerative disease research programs, promising cures for spinal cord injuries, cancer, osteoarthritis, Alzheimer’s disease, and more.

Although stem cell therapies are still under development, and some are used clinically (mainly for cancer), the hype around them eventually died down, and for 20 years, they haven’t been mentioned much outside of niche communities. They’re hard to work with and difficult to scale, limiting their application. But thanks to the Cambridge-based biotechnology company bit.bio, stem cell research is about to make a big comeback.

Providing pure, functional human iPSC PSC -derived cells

Bit.bio was founded in 2016 by Mark Kotter and Florian Schuster to solve the biggest challenges facing stem cells by leveraging synthetic biology.

Stem cells are either derived from embryos (embryonic stem cells) or by engineering somatic cells to return them to a pluripotent state (induced pluripotent stem cells; iPSCs)—a state of unlimited potential to turn into any type of cell you want. iPSCs—used more often than embryonic stem cells because of ethical concerns—are notoriously inconsistent, with batches of differentiated cells often containing a mixed population of the cells you want plus many cell types you don’t want. This severely limits the pace of discovery, innovation, and, ultimately, the ability to use these cells at scale in the clinic.

Seven years ago, bit.bio introduced their opti-ox (optimized inducible overexpression) technology to the world (which I wrote about in Forbes in 2020), achieving highly functional, consistently pure, and defined human iPSC-derived cells. Their portfolio of ioCells™ includes wild-type GABAergic and glutamatergic neurons, sensory neurons, microglia, and skeletal myocytes, which have been used by a range of research labs all over the world.

But Kotter and the rest of the bit.bio team wasn’t satisfied. “It’s not only about health states,” says Kotter, “it’s much more about disease states where differences between animal models and human biology seem to be heightened.” So they’ve developed an extensive portfolio of disease model cells as well, with an expansion of those offerings to include custom disease model cells announced at SynBioBeta 2023 last week.

“Now our customers can study their disease mutation of interest in a robust, highly reproducible context,” Kotter explained. “Providing everyone access to their own mutation of interest allows us to help more people in terms of drug discovery.”

Driving personalized medicine

I sat down with Kotter and bit.bio Associated Director of Sales Timothy Smith after bit.bio’s announcement to talk more about what this means for the biopharma industry and the company's future, which has already built incredible momentum. The custom disease model offering is the 10th launch in only the last year. Kotter quickly turned the discussion to personalized medicine, an area with incredible potential but few real-world examples.

“One of the most exciting areas is personalized, n equals one medicines, where you have rare diseases that can, for example, be treated via gene correction, and we need to build a regulatory environment that allows you to, within constraints, generate those solutions. You likely require a model to demonstrate that your drug has the desired effect. We think our new offering can open up exactly that—where n equals one medicines can be tested and demonstrated in an extremely robust system,” Kotter explained. One of the biggest application areas for this type of research is in rare diseases, something that Smith is especially passionate about.

“There is a lot of opportunity to create personalized medicines for these rare diseases where there are only a handful of patients worldwide. This is hugely ambitious and with pediatric patients, the time is often limited. For instance, in the context of certain neurodevelopmental conditions affecting the brain, you may only have 12-24 months because once the damage has been done, it will be difficult to reverse. The whole drug discovery and development workflow has to be challenged,” he explained.

One company that is tackling rare diseases in children and using bit.bio’s cells to do it is Everlum.bio. They recently made a big breakthrough studying potential therapies to correct a mutation in the HNRNPH2 (H2) gene that has impacted the founder’s daughter, Rose, slowing her development and then slowly robbing her of the functional abilities she did develop. The company uses antisense oligos—short oligonucleotide strands designed to bind to complementary DNA or RNA sequences—to correct mutations that cause rare diseases. In the case of the H2 mutation, fibroblasts, which are the most commonly used cells, wasn’t a good model. Everlum needed neurons. bit.bio had just what they needed.

“At Everlum, we created a new model to make and deliver rare disease therapeutics to patients faster than ever before. Partnering with other companies that want to help these children with innovation is critical to our success. bit.bio fits the bill. They have been a crucial partner by providing human neurons to us for testing our drugs. Using these bit.bio GABAergic neurons, we have identified the first therapeutic ever for Rose’s disease, and we hope soon for so many more!” said Casey McPherson, Everlum’s founder and CINO.

Keeping the momentum going

Custom disease model cells are certain to push the rare disease research field further than it's ever been before — but that wouldn’t be possible without the basic, inherent purity and consistency characteristics of bit.bio’s cells. Something the company has always been proud of, they’ve now hit the optimization ceiling, Kotter told me. The company has optimized its platform to the extent that they see no batch-to-batch differences—a first for the iPSC world.

“The data blows me away,” Kotter told me. “Essentially, we’ve generated a manufacturing paradigm that is as good as manufacturing an iPhone - you cannot tell the difference between one that’s produced in January versus one that’s produced in March. If you think about biology being a fuzzy sort of science, we’ve proven that there is a reality in biology that is not fuzzy, that is, deterministic. That’s a watershed moment.”

It truly is remarkable what the company has achieved in less than ten years — an achievement that Kotter says is possible only because of synthetic biology. And he sees this as just the starting point for an incredibly fruitful (and too long in coming) marriage between synbio and biopharma. But although Kotter allows himself to dream big, he remains pragmatic.

“We have a responsibility, a stewardship to bring this technology to its potential. Lots of ideas can die; we must allow this to flourish,” he says.

When I asked him what “flourishing” looked like years down the road, Kotter painted an incredibly inspiring picture.

“The ultimate achievement would be to allow cell therapy to become the mainstage treatment for various degenerative diseases and other conditions. It should be as simple and as cost-effective as biologics. And, if we can democratize access to human cells and enable others to generate drugs, there is the potential to impact a billion patients. I think it’s possible.”

I think it’s possible, too. And based on what I’ve seen in just the past five years from bit.bio, I’d say the likelihood is high that they’re going to allow what they have to flourish.

Thank you to Embriette Hyde for additional research and reporting on this article. I’m the founder of SynBioBeta, and some of the companies I write about, including bit.bio, are sponsors of the SynBioBeta conference. For more content, you can subscribe to my weekly newsletter and follow me on Twitter and LinkedIn.