Developing therapeutics is difficult—developing neurotherapeutics is even harder. The blood-brain barrier protecting the brain from unwanted substances makes it extremely difficult for neurotherapeutics to reach their target. 

Herophilus, a San Francisco neurotherapeutics startup, is taking a new approach to drug discovery with human brain organoid models. But designing drugs for neurological diseases is so complex, innovative technology can benefit strongly from experienced leadership.

Today, Herophilus announced it has appointed Sharath Hegde as the new Chief Scientific Officer to accelerate drug discovery for brain diseases. With 30 years of industry expertise, Hedge’s goal at Herophilus is to unlock and accelerate paths to new therapeutics to cure complex and frequently devastating illnesses including Rett syndrome, Parkinson’s disease, and Alzheimer’s disease. The company ultimately hopes to bring transformative medicines to millions. 

“Working in neuroscience is very close to my heart. Like many others, I have witnessed the devastating effects that neurological diseases can have on patients and their caregivers,” says Hedge. 

Three Drugs to Market and Counting

Previously, Hedge was the Chief Scientific Officer at Recursion Pharmaceuticals and accelerated critical work with new chemical products while building the company’s reputation of harnessing technological advances to industrialize drug discovery. Recursion Pharmaceuticals is now worth $4 billion. 

“I'm a very passionate drug hunter. I was fortunate to have participated in the discovery of three marketed medicines and many others in late-stage development,” says Hedge. 

Bringing three drugs to market may not sound like a lot but drug discovery is a very high-risk endeavor that can take a decade or more to achieve. Designing a safe, efficacious drug that reaches the right target at the right time is extremely difficult. Hedge says discovering a therapeutic molecule takes over $2 billion. In this context, bringing three drugs to market is a notable achievement. Hedge was involved in the discovery of 16 clinical-stage molecules, including Vibativ® (telavancin), Yupelri® (revefenacin), and other medicines. 

For Saul Kato, co-founder and CEO of Herophilus, bringing Hedge to the Herophilus team is a turning point for both the company and the potential of the technology. “I think this is a signal moment. We’re bringing on a Chief Science Officer with 30 years of experience in pharma who has a huge track record with three drugs. Sharath has a real awareness of what has worked and what hasn't worked. He saw the opportunity in [Herophilus’] new approach to drug discovery of getting back to very deep, hard biological investigations, but in a scalable format,” says Kato.

Human Brain Models Could Finally Lead to Effective Treatments

Hedge’s appointment appeared shortly after the release of two new research papers from Herophilus: “Hierarchical confounder discovery in the experiment–machine learning cycle” and “Demuxalot: scaled up genetic demultiplexing for single-cell sequencing.” They are the first in a series of papers about the company's groundbreaking advancements in machine learning and biotechnology.

Herophilus’ platform centers on brain organoid science. Organoids are not full human organs but rather models that are grown in the lab from human stem cells taken from blood cultures. “We don't grow full brains, but we grow what you might think of as a biopsy or a piece of brain tissue. These organoids exhibit far richer, more realistic biology,” says Kato. 

This is a critical piece of Herophilus’ approach. Older research models like animal models don’t have the same characteristics as human disease. And some diseases don’t occur naturally in animals. For example, mice don’t get Alzheimer's. The Herophilus team expects that the growing field of organoid science will advance neurotherapeutics where old approaches have failed. 

Organoids aren’t enough to develop therapeutics for difficult-to-treat neurological conditions. The team also focuses on the phenotypic properties of brain diseases. These are the observable characteristics of an organism or illness, in this case, at the biochemical variations in brain diseases. 

The name of the company stems from the earliest days of phenotyping. Sato credits the ancient Greek physician, Herophilus, as the first to study the disease characteristics in patients. “Now we take a modern approach to bio-phenotyping in controlled, in vitro conditions using robotics, automation, and machine learning. But fundamentally, it's the same idea: if you want to understand and cure disease, you've got to go in and study it at a microscopic level,” says Kato.

Helophilus Sets Its Sights on Rett Syndrome

Now with Hedge on the Herophilus team, the company is pushing forward on its first therapeutic target, Rett syndrome. Rett is a rare, genetic condition that affects about 20,000 girls and women in the United States. Rett syndrome is an X chromosome-linked disease meaning that it is typically fatal to male children. For female children who survive, the disease leads to severe cognitive impairment and affects motor function and speech.

Both Hedge and Kato look forward to finding solutions to complex diseases like Rett. “I'm excited about Herophilus because I am convinced that Herophilus is going to be a pioneer in the application of technological innovations to the discovery of neurotherapeutics,” says Hedge. 

Patients suffering from complex brain disease have been medically underserved for a very long time. Caregivers and families are also in need of better therapeutics. Caring for a person with a brain disease can often be exhausting and emotionally painful. Many will be watching closely to see how Herophilus’ new approach progresses.

Thank you to Lana Bandoim for additional research and reporting in this article. I’m the founder of SynBioBeta, and some of the companies that I write about are sponsors of the SynBioBeta conference and weekly digest. Register now for SynBioBeta 2021