When proteins in the body age or become damaged, cells have a way to deal with them. Molecular tags attached to these proteins mark them for removal by the cell’s built-in processing system. The problem is that sometimes important proteins get tagged and then send them to this dumpster. The resulting low levels of key proteins can lead to disease.
Removing molecular tags seems like a straightforward way to avoid important proteins being discarded, but it’s easier said than done. A research collaboration between Novartis and UC Berkeley has found a way to launch a new company, Vicinitas Therapeutics.The startup, which launched last week, got $65 million in Series A funding funds.
The collaboration between Novartis and Berkeley began in 2017 to find ways to reach targets for diseases considered “resistant to drugs.” Vicinitas founder and Berkeley professor of chemical biology Daniel Nomura’s lab focuses on chemical proteomics, the analysis of protein and small molecule interactions. The lab is developing molecules capable of drugging about 90 percent of human proteins thought to be undruggable.
some Novartis-Berkeley Research Bifunctional molecules that can bind to disease-causing proteins and deliver them to cellular processing systems are explored. This approach is called targeted protein degradation. This is a nascent field of drug research that is also getting crowded. A growing number of biotech fields have raised hundreds of millions of dollars to develop such drugs. Some of them are now working with big pharma. Nomura Says Novartis-Berkeley Research across multiple modes What the partners decided to pursue for Vicinitas was essentially the opposite of targeting protein degradation.
“We want to stabilize and restore these proteins,” he said.
Degradation of proteins depends on proximity. A targeted protein-degrading drug is a small molecule that binds a target protein at one end and ubiquitin at the other end, a molecular tag that labels the protein for processing. Combining these elements allows the target protein to enter the cellular trash.
Tags can be inappropriately placed on important proteins for a number of reasons, Nomura said, such as genetic mutations or upregulation of enzymes that catalyze the transfer of tags to proteins. In Vicinitas small molecules, the moiety that targets the desired protein is linked to a deubiquitinase, a different enzyme that removes the ubiquitin tag. The challenge, Nomura says, is to develop small molecules that don’t inhibit deubiquitinases. The Novartis-Berkeley consortium has developed a technology to identify protein-binding agents, enabling the enzyme to de-tagging. The technique is called deubiquitinase-targeted chimeras, or DUBTAC.
Nomura’s team shows how DUBTAC stabilizes key proteins in cystic fibrosis and cancer. In cystic fibrosis, genetic mutations result in the degradation of the CTFR protein required to maintain salt and water balance on the lung surface. Berkeley scientists have developed a DUBTAC molecule that stabilizes CFTR protein levels and improves the function of human cystic fibrosis bronchial cells. Inappropriate labeling and degradation of tumor suppressor proteins can also lead to cancer. The Berkeley scientists also showed that DUBTACS stabilizes a tumor suppressor protein in liver cancer cells.
publication The Novartis-Berkeley study, published in the journal Nature Chemical Biotechnology in February, sparked investor interest. Vicinitas’ Series A financing was co-led by Andreessen Horowitz and Deerfield Management. Other participants include Droia Ventures, GV, the Mark Foundation for Cancer Research and the Berkeley Catalyst Fund. Nomura said the startup will use the cash to build its drug pipeline, allowing the new company to work on multiple projects simultaneously. The company is still identifying disease targets, but preliminary research will look at cancer and genetic diseases, he said.
Vicinitas isn’t the only startup pursuing targeted protein stabilization as a treatment for disease. Stablix Therapeutics is also developing such drugs using technology from Columbia University. Last summer, the New York City-based startup announced a $63 million Series A round.
Nomura had previous experience turning his research into a new company.he co-founded Frontier Drugs, a startup developing drugs that address undruggable or hard-to-treat targets.in a Partner with AbbViethe South San Francisco-based biotech company is developing drugs that target protein degradation for potential applications in cancer and immunology.
With the launch of Vicinitas, Novartis and Berkeley expand their partnership The goal is to find other ways to track undruggable targets. Nomura will be involved in this work. While he will serve on Vincinitas’ scientific advisory board, Nomura said he will continue his position at Berkeley and continue his research there. Vicinitas is now looking for a CEO to lead the company.
Here are some other recent biotech financings:
— Seattle-based Ozette closed a facility about 15 months after using artificial intelligence to perform single-cell analysis of cancer patients’ cells $26 million in Series A funding financed. The startup plans to use the new cash to further expand the company. Ozette co-founder and CEO Ali Ansari was interviewed by MedCity News last yearexplaining how the startup’s AI technology has potential applications in cancer treatment.
— Replay, a genome-writing company whose technology can overcome the capacity limitations of engineered viruses for delivering genetic medicines, Launched with $55 million in seed fundingThe San Diego-based company’s business model includes forming subsidiaries around specific areas of disease research. The company has formed such “product companies” to pursue disease targets including Duchenne muscular dystrophy and Parkinson’s.
—NEOsphere Biotechnologies, a targeted protein degradation startup, Closed Series A financing financed. Munich, Germany-based NEOsphere did not disclose the total amount raised or the investors in the round, but said the funding will be used to expand its technology platform, which screens small molecule libraries for those with potential applications as protein degraders. .
— In other chemical proteomics news, BridGene Biosciences, in partnership with Takeda Pharmaceuticals, shuts down $38.5 million Series B financingThe San Jose, California-based company said it will use the new funding to continue developing its IMTAC technology, which screens small molecules against the entire complement of human proteins for drug candidates that can address undruggable targets.
– Carmot Therapeutics closed a $160 million Series D financingThe Berkeley-based startup said it will use the cash to support clinical development of metabolic disease drugs in Phase 1 and Phase 2 testing, as well as the development of preclinical programs.
Photos by Flickr users Henry Silvering through Creative Commons license
