Data and ML are creating a golden age of drug discovery
The biotech sector is poised to reap the benefits of the AI revolution, with lifesaving effects
Leveraging data to develop highly tailored therapies
Since its founding in 2018, Neuron23 has been working to develop personalized therapies that precisely target neurodegenerative diseases like Parkinson’s. “Finding the right drug for the right patient at the right time is sort of the holy grail of drug discovery and development,” says CEO Nancy Stagliano.
The availability of massive data sets and computational techniques like machine learning have been critical to breakthroughs in the area of precision medicine, Stagliano says. “Using data to answer questions in medicine is something we've been doing for a long time. What you learn from the use of tools like computational biology and machine learning models is that you can take some of the bias out of those analyses, you can ask questions that you might not have thought to ask, and you see results that you might not necessarily have expected to see.” (For a more detailed look at Neuron23, read our Q&A with Nancy Stagliano.)
While the techniques are revolutionizing the drug discovery process today, Stagliano sees them impacting the life sciences field more broadly. “Regardless of which area you're pursuing, and which discipline you are focused on, this approach gives us the ability to open our minds to possibilities,” she says. “I’m very excited about the areas of prevention and wellness and trying to get ahead of certain diseases. The idea that we can understand better what we're predisposed to as humans with genetic testing, routine exams with deeper attention to our biology and our history.” Stagliano says immunology, which is thought to be central to neurodegenerative diseases, cancer, cardiovascular diseases, and other conditions, is also thriving. “Understanding how the immune system can work for or against us is a foundational paradigm and something that's doing incredible things for patients,” she adds. “And I think that will continue to grow.”
Stagliano describes the recent correction in valuations in biotech as a healthy reset that will not impact the overall advances being made by agile and focused teams in the sector. “I think the valuable companies, the valuable technologies and assets are being recognized, and that this settling of the sector in the marketplace is probably the right thing,” she says. “Good companies will succeed and good companies will continue to create value. It's a very exciting time to be in our business, and I think 2024 is going to be a very good year.”
Tapping viruses to deliver new gene therapies
For nearly a decade, South San Francisco-based Encoded Therapeutics has been developing gene therapies for brain disorders, including Dravet syndrome—a type of epilepsy that affects 1 in 15,000 live births and can cause children to suffer up to hundreds of seizures a day.
Encoded has developed an approach that allows it to use non-pathogenic viruses to deliver payloads that have therapeutic benefits. “What we incorporate into viruses are genes that direct the expression of proteins that have a corrective function in cells,” says Kartik Ramamoorthi, co-founder and CEO. “These proteins can replace a missing or dysfunctional protein or alternatively modulate a dysregulated pathway. This approach offers the potential for a single treatment to deliver long-term benefit to patients with serious disorders.”
The Encoded platform optimizes key features of therapeutic payloads. Massive amounts of data, combined with machine learning algorithms, enables the company to determine the effect that various DNA sequences have on their intended targets. “We leverage computational tools and machine learning to understand the features of genetic sequences that drive therapeutic outcomes in the disorders that we're interested in, whether that is cell-selective expression, high potency, or some other characteristic,” Ramamoorthi says. “Encoded has developed a unique capability using an iterative process that leverages our understanding of biology with computational methods that is at the heart of what the company does.”
Dravet syndrome was an ideal first disease target for Encoded, not only because success would mean addressing a significant medical need for tens of thousands of patients but also because the disease biology is well understood, Ramamoorthi says. “We believe that our approach to gene therapy can unlock treatments for other brain disorders, including common brain disorders,” he adds. The company plans to begin clinical tests of its Dravet Syndrome therapy next year and has a portfolio of other therapies in earlier stages of development.
Ramamoorthi says that recent advances at the intersection of biology and computing, from gene editing to artificial intelligence, make this an exciting and hopeful time in the world of biotechnology. “We are truly in an era of fundamentally changing how we think about disease,” he says. “There are now so many ways to approach treatment of a wide variety of diseases such as cancer, genetic disorders, and brain disorders. The technologies that are being developed by biotech companies today are enabling development of new therapeutics. This isn't something that's going to happen 100 years from now. In our lifespan, we may all benefit from this.”
Using ML to understand how to target cancers with T cells
For the past five years, ArsenalBio has been building a platform to discover and develop innovative cell therapies for the treatment of various solid tumors. By simultaneously digitizing the genetic makeup and behavior of human T cells through high throughput screens, ArsenalBio applies CRISPR gene editing tools to insert a single, large DNA sequence in those T cells to direct a more precise and potent attack on tumors in patients. Using this and other novel techniques, the company has developed an ovarian cancer therapy that is undergoing human clinical trials. Health care therapies targeting kidney cancer, prostate cancer, and other solid tumors are in pre-clinical development phases.
CEO Ken Drazan says the ability to sequence the entire human genome of cancer cells and the patient’s immune cells, then feed the resulting data into machine learning algorithms has been especially critical to discovering how T cells could be modified to be more effective at attacking tumors. “Every cell in the body has 3 billion letters of DNA programming in it,” Drazan says. “That is an awesome database to manipulate and model. Imagine if you wanted to make changes to different sequences of letters and in multiple locations in the genome, you would need to support larger and multiple databases and significant scale of computing to understand it. ArsenalBio creates novel databases as a training data set for using machine learning, which is enabling us to identify new ways to target difficult-to-treat solid tumor cancers.”
Drazan, who prior to ArsenalBio held leadership roles at two other successful startups in the biotech industry, believes that a multidisciplinary approach that puts data at the center of innovation will be increasingly critical to success not only in life sciences but also in other sectors. “In order to conquer a new product strategy, you have to think about data at a large scale,” he says.
Despite an investor pullback over the past two years in the life sciences sector, Drazan remains extremely bullish, not only about ArsenalBio, but about the overall life sciences sector. “The pullback compels companies to be very analytical about each dollar invested versus dollar saved,” he says. “And it also requires you to have a best-in-class strategy versus a follow-on strategy. The rewards tend to go to the most innovative and those that arrived there first.” ArsenalBio, he says, is using capital from strategic partners, in addition to that from bluechip institutional life science investors, to blend its cost of capital and accelerate product development.
“The United States is not only an enormous market for healthcare but also among the most innovative,” Drazan says. “I have a lot of confidence, after three decades of working in this area, that we'll continue to see investment and amazing contributions to human health. It's an incredibly exciting time for a person like myself, who's been working at pushing the snowball up the hill in the field of human health. So I'm incredibly optimistic about it.”