The human element: A biotech upstart hopes to carve a path around faulty animal models
It’s been a rough few years for lab mice in the literature. Report after report scapegoated science’s furry subjects for the piling number of drugs that fail the clinic. A Science study proposed building a new “wildling” lab mouse. A well-covered Nature paper indicated the differences between mice and human brains were responsible for billions of dead-ended Alzheimer research dollars. One Translational Medicine review cited the success rate of translating cancer drugs at 8% and another concluded that “even if the next several decades were spent improving the internal and external validity of animal models, the clinical relevance of those models would, in the end, only improve to some extent.” [italics theirs]
The failure of our mice experiments to consistently model drugs has fueled interest in more human-centric designs. That includes an emerging technology aimed at directly programming human cells. And one of the fields most closely watched startups — the newly renamed bit bio — has now announced an expanded team, bringing in former executives from Tessa Therapeutics and Horizon Discovery Group for the C-suite and experts in immunotherapy, stem cells, and cell programming for the scientific advisory board.
Paul Morrill will be chief business officer and Florian Schuster COO and CFO, joining founder and CEO Mark Kotter.
The scientific advisory board points to the big potential Kotter has already billed for his company. Joining are Ramy Ibrahim, the CMO for the Parker Institute of Cancer Immunotherapy and a former immuno-oncology developer at Bristol-Myers Squibb, and Marius Wernig, who all but introduced the concept of human cell programming in a 2010 Nature paper. Roger Pederson, a pioneer in the pluripotent stem cells you know and love, will serve as chief scientific advisor.
The group will be building a technology that promises to shortcut the sometimes months-long process of generating stem cells — which itself was a Nobel prize-winning achievement twelve years ago — and convert one cell type directly into any another. Originally known as Elpis Biomed, after an ancient Greek word for the spirit of hope, they changed their name to bit bio to underscore how their cell reprogramming works similar to giving a computer new code.
“It’s basically rebooting a cell with a new program,” Kotter told Endpoints News.
Since last year’s launch, Kotter has hinted at the broad capacity he believes his “Opti-OX” platform has. He’s spoken of expediting cell therapy, building off-the-shelf CAR-T, improving regenerative medicine, and even — at the behest of a company in the Netherlands — cultured meat.
At the top of their list now, though, are the cells involved in immunotherapy, including macrophages and dendritic cells that can be leveraged for attacking solid tumors.
Kotter, though, is a neurosurgeon by training and he runs a Cambridge University lab that is tasked with translational research for spinal injuries and diseases. As he tells it, the technology is originally a response to problems in translational research; repeatedly he was stymied by animal cells that didn’t properly model the human ones.
“We realized that the animal cells we used for research were very different from human cells,” Kotter said. “I looked around and realized that this not my problem alone. It’s the main reason that drugs fail.”
Currently, the company lists only two cells in its product offerings: human-induced skeletal myocytes and human-induced glutamatergic cortical neurons. But they’re building more, testing thousands of transcription factors — the code or “bit” — and comparing the artificially converted cells with the real things. They then offer these cells out for uses including genetic or drug screening.
Could these engineered human cells one day replace mice? Kotter is hesitant. A cell isn’t an organism, he noted. You won’t be able to see the whole-body effects of a drug. He does wonder, though, about a future where programmed “organs-on-a-chip” built with this tech are connected and used to simulate a full organism.
“What I do know is that a lot of analog experiments that we do at this point tell us little about what we do in humans,” he said. “These animal models are not predictive. I think the only solution is to bring the human element back into the process.”
Kotter told Endpoints a funding announcement was coming soon. Last year, he said he hoped to initially raise £5 million, then worth roughly $6.5 million, and had the support of a UK “Tier one VC.”
Another biotech aimed at direct cell reprogramming, Mogrify, announced $16 million in Series A funding last week. Mogrify was a finalist for the 2018 Cambridge Startup of the Year. bit bio won.