RA Capital Management has several bets on emerging therapies that use the cell’s own system to remove disease-causing proteins. These investments are biotechnology for problematic proteins in cells. But extracellular proteins can also cause diseases, and the company set out to study whether they can also be treated with drugs.
It turns out that the answer is yes. However, instead of injecting funds into existing biotechnology to advance the science, RA Capital chose to establish a new company. The startup, Avilar Therapeutics in Waltham, Massachusetts, emerged from its invisibility on Thursday with the support of a $60 million seed financing.
“In the field of seed financing, this is a considerable amount of financing,” said CEO Dan Grau. “The scale of financing is related to opportunity.”
The process of breaking down old or damaged proteins in cells is called protein degradation. Old or damaged proteins are identified and processed by molecular tags attached to them. These labeled proteins enter the cell processing system called the proteasome. The use of this cell system to treat diseases is called targeted protein degradation. The drug is a small molecule designed to recruit molecular tags to target proteins.
Arvinas, based in New Haven, Connecticut, was the first biotechnology company to introduce protein degradants into human testing, and this progress paid off this summer $1 billion Pfizer partnershipThe pharmaceutical giant believes that biotech drugs are expected to become a new method for the treatment of breast cancer. Arvinas happens to be one of RA Capital’s target protein degradation investments.Other RA Capital portfolio companies in this area include C4 Therapeutics and Audiovisual.
Grau said that about 18 months ago, RA Capital formed a team to study whether protein degradation can solve the problem of extracellular proteins. The team is led by Milind Deshpande, the company’s venture partner and former CEO of Achillion Pharmaceuticals. The research team discovered that extracellular proteins can be degraded through a natural process using asialoglycoprotein receptor (ASGPR). Grau said that ASGPR is expressed in liver cells, and they are an important way for nature to degrade various proteins in the body.
Although targeted protein degradation agents opened the door to Avilar’s approach, Grau said that the pursuit of extracellular degradation requires Avilar to develop new technologies. The startup’s drug is called ASGPR Targeted Chimera, or ATAC. Similar to barbells, they are bifunctional molecules composed of two linked ligands, one binding to ASGPR and the other binding to the target protein. Binding to the target allows the Avilar molecule to direct the protein to the endolysosome of the liver cell, which is a different cell processing system. Grau said ATAC can process proteins circulating in the body and proteins on cell membranes.
The human proteome, the complete set of expressed proteins, is estimated to have a total of approximately 20,000 proteins. Grau says that about 40% of these proteins are extracellular or membrane proteins. He added that the company believes that approximately 2,000 of these proteins are non-membrane targets, and in this group, hundreds of proteins have been well validated as disease targets.
“The first wave of ATAC products will [be for] Grau said: “These goals have been fully verified, but the existing methods have not been fully resolved, or in some cases not resolved at all.” “This is the space where our pipeline will appear.”
Grau joined Avilar in May. In the past six months, he said the company’s progress includes testing ATAC in non-human primates. The results showed rapid and profound degradation of extracellular proteins. As was the case with most early-stage biotech companies, Avilar did not disclose specific disease targets. But Grau said that potential extracellular targets cover rare and common diseases. The company will focus on developing treatments for rare diseases, and the more common disease target may be an opportunity to collaborate with large companies. He added that oncology is another potential application.
Avilar’s science is new, but the company is not the first to find protein targets outside the cell. Lycia Therapeutics is developing a drug called Lysosome Targeted Chimera or LYTAC, which can direct extracellular proteins to the lysosome. In August, Eli Lilly and Company paid US$35 million to a San Francisco-based biotechnology company to launch a research alliance for up to five LYTAC drugs.
Grau said that the $60 million seed funding is now not new cash, but financing from the past 18 months. The company did not disclose a timetable for how long the cash will last, but Grau said the plan is to continue developing the technology and transform the platform into a drug pipeline.
