Company leverages mechanobiology and advanced imaging to find small molecules capable of modulating cellular reprogramming.
It’s official – cellular reprogramming is hot. Companies like Altos Labs, Retro Bioscience and NewLimit have already attracted massive funding as they attempt to harness the power of reprogramming to rejuvenate cells, treat disease and potentially reverse the aging process itself. But the science is still far from being fully understood, and it’s doubtful that any company is yet close to finding the solution to translating this powerful technology into human applications.
As a result, new players continue to enter the cellular reprogramming race, including Focal Biosciences, a spin-out from the renowned ETH Zurich. The company is supported by biotech VC fund and company builder Apollo Health Ventures and the Paul Scherrer Institute (PSI) in Switzerland.
Longevity.Technology: Focal Biosciences is building on the work of scientific founder G V Shivashankar, a professor at both PSI and ETH Zurich, and a recognized leader in mechanogenomics and cellular reprogramming. Rather than focusing on transcription factors, the company says its approach to reprogramming leverages aspects of mechanobiology, imaging and machine learning to identify potential small molecule modulators of reprogramming. To learn more, we caught up with Focal Biosciences CSO Dr Xian Zhang, and Apollo Health Ventures partner Jan Adams.
In a nutshell, Focal has created a small molecule, epigenetic reprogramming platform to identify pharmaceuticals capable of modulating cell reprogramming in an anti-aging context. But there is much more to the company’s approach.
“There is exciting data from Shivashankar’s group, which shows that if you exert mechanical force on a cell and restrict its space, then you can rejuvenate a cell and dial it back in time to a much younger state,” says Adams. “It sounds crazy, but this is what excited us in the first place to reach out to Shiva and build this company. We worked with him for about a year, conceptualizing the milestones and how to leverage the knowledge and science that was in his lab to come up with a very sophisticated screening platform.”
Drug-modulated cellular reprogramming
According to Zhang, Focal is uniquely positioned based on its use of cutting-edge technology.
“We’re looking for small molecule compounds to modulate the whole cellular programming process,” he says. “Our novel approach uses a combination of mechanobiology and imaging – chromatin and nuclear fingerprint readout based on DNA staining.”
“We also use novel and physiologically relevant 3D assays and advanced machine learning and AI to decipher the imaging data coming out from the assays,” he adds, pointing out that most high-throughput assays are typically 2D, while Focal uses 3D assays with mechanical stiffness that mimic the situation in vivo.
All this technology comes together to form Focal’s drug discovery platform, which allows the company to screen large numbers of compounds for pharmaceuticals with the potential to modulate cell reprogramming and revert cells from aged, disease states to healthy, young states.
“We have initial data that demonstrates we’re looking at a level of biology that nobody else has been able to look at,” says Adams. “Our approach provides a granularity that helps us to see the difference between things that superficially look the same. This gives us a completely new view on biology that can help us to be successful in finding modulators where other people have not been.”
Initial focus on fibrosis
Another key aspect of Focal’s approach is that it is looking at cellular reprogramming in a disease-specific context. The first area of interest for the company is likely to be fibrotic disease.
“Fibrosis is a process where fibroblasts reprogram into myofibroblasts, which causes stiffening of the extracellular matrix,” says Zhang. “Our therapeutic angle for fibrosis is to find out if we can reprogram myofibroblasts back into fibroblasts, in the tissue context.”
Another reason Focal is looking at fibrosis is because a lot of work has already been conducted into the mechanobiology of the condition.
“The setup we have is uniquely advantageous towards fibrosis,” says Zhang. “And fibrosis is also a huge unmet medical need, because it’s not just one disease – you can have fibrosis across different organs in your body, and many of them are severe, if not fatal.”
Of course, Focal believes there are many other diseases and conditions that could benefit from its approach, including cancer and a host of immunology related diseases.
“Mechanobiology is a relatively new field” says Zhang. “And people are beginning to realize that the mechanical forces are key, if not critical, in terms of determining cell fate, reprogramming from different stages, and the aging of the cell. This has the potential to bring new insights and new angles into a whole range of different diseases.”
The company is now gearing up for its first high-throughput screening in collaboration with ETH Zurich and expects to have its first “hits” by the end of the year.
