In the midst of the Covid-19 pandemic, while most scientists were busy plotting new ways to combat viruses, one startup quietly began a counterintuitive campaign: getting viruses to work for us, instead of against us.
Now, after three years in stealth, Prologue Medicines launched Tuesday morning and unveiled its plan to search through millions of viral proteins to find ones that could be repurposed as treatments for cancer, immune diseases, and metabolic conditions. The Cambridge, MA startup is backed with $50 million from Flagship Pioneering, the life science venture firm that’s built dozens of biotech companies, including Moderna.
“People have really focused on the prevention of viruses. And what we’re really doing is kind of flipping that on its head,” said Theonie Anastassiadis, founding president of Prologue and senior principal at Flagship.
When viruses infect us, their primary goal is to multiply and spread. To do that, they’ve developed many proteins that can help evade our immune systems or trick our cells into becoming viral factories. Prologue believes that many of those same proteins used by viruses for their own aims might be repurposed into being helpful.
It’s an idea Prologue’s leaders say is based on scattered observations dating back decades, but were never tested systematically. The basis of Prologue was the realization that “this is something that you can actually start looking for,” said Lovisa Afzelius, co-founder and CEO of Prologue and origination partner at Flagship.
She cited an old example of cytomegalovirus producing a protein related to the human cytokine IL-10. It’s shown promise in suppressing immune responses in preclinical models of collagen-induced arthritis — without some of the immune-activating properties that would impede the human protein’s use as a drug.
Afzelius wouldn’t name specific indications or viral proteins the company is working on, or when it plans to have a candidate ready for clinical trials.
Learning from evolution
When Flagship founded Prologue in 2021, it had already been thinking about new ways to tap human biology as a source of drugs with ProFound Therapeutics. That startup, which launched from stealth the following year, boldly claimed to have discovered tens of thousands of previously unknown human proteins which could form the basis of new drugs or targets.
The science of proteomics has experienced a surge of interest and investment as new tools make it cheaper and easier to study ever-larger numbers of proteins. And ProFound’s early work got Flagship leaders wondering what they would find if they looked beyond the human body and into the comparatively uncharted waters of the viral proteome.
ProFound and Prologue are also part of a broader trend for recent Flagship companies with sweeping remits to scour large chemical, genetic, or protein datasets from nature to find starting points for medicines. For instance, Empress Therapeutics is searching microbe DNA for leads on small molecule drugs; Metaphore Biotechnologies has said it’s mimicking nature to find drugs; and Montai Health aims to find drugs from molecules in foods, herbs and supplements.
Coupling huge amounts of biological data to machine learning techniques means the time is right for a company like Prologue, Anastassiadis said. “We can tackle things that historically we just haven’t been able to go after,” she added.
The startup is using AI to explore roughly 6.2 million virus proteins, the majority known only by their genetic sequences in public databases. “Everyone’s sequencing everything,” Anastassiadis said.
Afzelius said the company will use public and proprietary large language models to predict the function of viral proteins, how they may alter human biology, and where they may be useful in treating a disease.
The startup has about 20 employees now and will “grow quite substantially over the coming year,” Afzelius said.