In the search for new drugs, much of the low-hanging fruit has been picked. But there’s still bounty to be found and Atavistik Bio aims to uncover it by looking in uncharted places. Though still in its infancy, the promise of its technology has drawn investor interest leading to a $60 million Series A round of funding.
The traditional way small molecule drugs work is by binding to an active site on a protein, a pocket that is the typical place for the two to connect. However, some proteins associated with disease lack these binding sites. Cambridge, Massachusetts-based Atavistik aims to discover and develop allosteric drugs, drug that bind to other, less obvious places on a protein. The trick is finding those places.
Atavstik’s research focuses on metabolites, substances formed from metabolic reactions in cells. The scientists at Atavistik see metabolites as more than byproducts. Enzymes evolved over millions of years to be regulated by metabolites within pathways that are now well-defined, said John Josey, a venture partner at The Column Group and the Atavistik’s acting CEO. The name Atavistik refers to atavism, which in biology is the reappearance of a previous genetic trait. Josey said that the company sees its approach as leveraging past knowledge and learning from evolution.
The Atavistik technology allows for comprehensive screening of a large number of proteins against a large number of metabolites in order to discover their interactions, said Marion Dorsch, the company’s president and chief scientific officer. Artificial intelligence and machine learning techniques are used to explore the data and analyze them. With new knowledge of allosteric interactions, Atavstik will then use traditional chemistry to design and develop small molecules that will render the desired pharmacological effect. The startup’s initial targets are metabolic diseases and cancer, but Dorsch, a biotech industry veteran who was most recently the top scientist at Blueprint Medicines, said that there are many potential applications.
“It is a platform-based approach that we’re hoping to be sustainable over time that we hope will enable new targets, new drugs over time,” she said. “We’re not a single asset company.”
Because Atavistik’s technology is a platform, Josey is leaving the door open to partnerships with larger companies that could pursue areas are outside of the startup’s disease focus. The Atavistik technology comes from the lab of scientific co-founder Jared Rutter, a professor of biochemistry at the University of Utah whose research includes novel protein-metabolite interactions. The other scientific co-founder, Ralph DeBerardinis, is a professor and the chief of the division of pediatric genetics and metabolism at the University of Texas Southwestern Medical Center. Josey said DeBerardinis is an expert in metabolism and cancer. Their research, as it applies to specifically to Atavistic, has not yet been published, though Josey said he expects some papers will be coming out in coming months.
Atavistik’s peers in the pursuit of allosteric drug targets are further along in development. Gain Therapeutics raised $40 million in March to support plans for clinical testing of its two lead allosteric drug candidates, which are in development for treating rare enzyme deficiencies. When Roivant Sciences unveiled its $450 million acquisition of Silicon Therapeutics in February, it said the startup’s artificial intelligence capabilities would help it in its drug research efforts, which includes allosteric inhibitors. Black Diamond Therapeutics has reached clinical trials with its lead cancer drug, discovered by the company’s allosteric drug platform. Last year, HotSpot Therapeutics raised $65 million with plans to bring its autoimmune disease programs into the clinic by the end of 2021.
Atavistik just emerged from Rutter’s lab last month, Josey said. The company’s first order of business is establishing its Cambridge operations. Josey estimates that the $60 million in funding will support the company for four years. The first 18 months will be to establish the technology, analyze many proteins, and do some initial screening for sites that could be binding locations for new drugs. From there, the research will proceed to lab tests, then preclinical research.
“I would hope within the next three years we would be in the situation where we have a molecule, or molecules, heading to the clinic,” Josey said.
The Series A financing was led by The Column Group. The other investors in the round are LUX Capital and Nextech Invest.
Photo by Atavistik Bio