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Inside the nucleus of every cell, two meters of DNA are folded and packed into structures called chromatin. Those folds and packing structure decide which genes speak and which stay silent. And “misfoldings” can lead to serious problems.
If DNA is the architect's plans for a building, chromatin is the way those plans are organized and stored in the architect's office.
Sometimes the plans are neatly rolled up and put away in a tube (condensed chromatin), making them hard to read, but easy to store and move around. Other times, the plans are spread out on a big table (open chromatin), where the architect and builders can easily read them and use the information to build parts of the building.
The project manager (special proteins) decides which plans get rolled up and which ones stay open, depending on what needs to be built that day. But sometimes, things go wrong with this system. If the manager accidentally leaves the wrong plans open or keeps important plans rolled up when they should be available, the builders will likely make mistakes. This can cause problems for the whole building, just like poorly packaged, dysfunctional chromatin can lead to cells not working properly.
Chomatin is a key part of epigenetics - the study of how identical DNA code can be interpreted by your cells in different ways. In humans, epigenetic issues resulting in dysfunctional chromatin can drive everything from pediatric brain tumors to Alzheimer’s disease to triple negative breast cancer.
TippingPoint aims to develop novel treatments for these diseases by developing drugs that fix dysfunctional chromatin.
Other companies have tried (and mostly failed) to fix dysfunctional chromatin by targeting single “binding pockets” on specific proteins. This is akin to trying to fold a t-shirt by poking it.
TippingPoint on the other hand, is developing drugs that target the entire misfolded chromatin network (more like folding a t-shirt by picking it up with two hands). This is a complex, multivariate problem that is only made solvable by TippingPoint’s novel screening platform.
TippingPoint’s platform recreates disease-specific, dysfunctional chromatin states in the lab, then identifies small molecules (drugs) that restore the whole network to its proper state without disturbing healthy chromatin. The platform is built on three pillars:
Laura and Geeta’s work has defined much of the underlying biological characterization of protein-protein interfaces that represent the crux of TippingPoint’s ability to drug whole chromatin networks.
TippingPoint's first disease target is DIPG, a rare and fatal pediatric brain cancer with no FDA approved disease modifying treatments.
DIPG's rare disease designation gives TippingPoint an accelerated path to the clinic, but we believe that long term, the platform has the potential to develop treatments for all sorts of diseases from cancer to neurodegeneration, and maybe someday even address “human performance” domains like aging and cognitive enhancement.
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How? It is well known that chromatin structure drifts with age. As we age, our body’s ability to respond to environmental factors that influence epigenetic change may be weakened, and restoring our ability to respond to these perturbations (and fix aberrant ones) could be a game changer. Epigenetics impacts everything from stress resiliency to metabolic efficiency.
Here's how we view TippingPoint against our Human 3 criteria:
TippingPoint is backed by IndieBio, BrightEdge (American Cancer Society), Mission BioCapital, and three foundations.
We’re excited about TippingPoint’s potential to solve complex diseases and make systems level connections that will help shape our understanding of how these diseases begin in the first place.
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