Scripta Therapeutics emerges from stealth to target Alzheimer’s, Parkinson’s and ALS by modifying transcription factors.
British biotech Scripta Therapeutics has emerged from stealth with $12 million in seed funding to develop disease-modifying therapeutics that work by altering the activity of transcription factors. The company’s initial focus is on neurodegeneration, including Alzheimer’s disease, Parkinson’s disease and ALS, where transcription factor disruption is known to play a prominent role.
Binding to specific DNA sequences to turn genes on or off, transcription factors are proteins that play a crucial role in controlling how cells behave. Oxford-based Scripta aims to treat these master regulators of gene expression as the fundamental maps of age-related disease biology. Founder and CEO Peter Hamley told us that transcription factors have “long been linked” to longevity.
“Genetic studies often point to specific transcription factors that occur more often in longer-lived individuals,” he said. “They’re also central to cell reprogramming, where the right combinations can, in effect, turn back the biological clock. What’s particularly interesting is that the same transcription factors tied to longevity often show up in neurodegenerative diseases, which means these two areas are more connected than we used to think.”
The new financing, led by Oxford Science Enterprises and Apollo Health Ventures, will support further development of the Scripta’s platform, which is built on the premise that conventional drug discovery starts in the wrong place. The company claims that most drug discovery focuses on downstream effects of disease or on targets that have gained attention through prior publication and investment. According to Scripta, this creates a funnel that only includes a narrow subset of biological mechanisms, so the company is adopting a different model based on identifying and modulating upstream drivers of disease.
Building on the work of scientific co-founder, University of Oxford professor Noel Buckley, Scripta is leveraging genome-wide mapping to build a detailed picture of how transcription factors behave in neurodegenerative disease states. The company argues that by reconstructing and perturbing transcriptional networks, it is possible to find therapeutic opportunities that lie outside of well-trodden areas of drug development.
“We’re flipping the script on conventional target-based drug discovery to find therapies that genuinely move the needle for patients,” said Hamley, formerly of another Apollo Health-backed startup, Samsara Therapeutics. “By focusing on understanding and manipulating the master controllers of biology, we’re searching for drugs with the potential not just to delay disease progression but to stop it in its tracks.”
Using transcriptomic data to infer the activity of individual transcription factors through patterns of gene expression, Scripta aims to reveal which networks have shifted away from healthy function. The company then uses computational models to identify molecules capable of modulating those networks, including indirect mechanisms that influence transcription factor activity. According to Scripta, its analyses of Alzheimer’s patient data have already identified both known and previously uncharacterized transcription factors associated with the disease.
Scripta describes its approach as “biology-first”, employing high-content imaging, patient-derived cellular models and AI-driven screening to test whether predicted modulators restore healthy transcriptional patterns. And, with transcription factor dysregulation a shared feature across cancer, fibrosis, inflammation and many other conditions, the company suggests its platform has potential longevity applications well beyond neurodegeneration.
In addition to OSE and Apollo, the seed funding round was joined by AlbionVC, YZR Capital and Parkwalk Advisors.
“Manipulating transcription factors in disease has long been seen as an intractable challenge, yet it holds tremendous promise for treating neurodegeneration and other life-limiting conditions,” said Apollo Health partner Marianne Mertens. “Scripta’s innovative approach could deliver transformational therapies and exemplifies one of Apollo’s key investment strategies: reprogramming diseased cells into healthy ones to tackle the root causes of age-related diseases and enable disease-modifying treatments.”
