Metastatic cancer is responsible for most cancer deaths, but people whose disease has spread to other parts of the body don’t have enough effective treatment options. Volastra Therapeutics wants to change that by developing drugs that target chromosomal instability, a hallmark of solid tumors that’s linked to metastasis.
The company bumped its seed round from the $12 million it raised in February to $44 million, adding Vida Ventures and Catalio Capital Management to a list of backers that includes Polaris Partners, Droia Ventures, Arch Venture Partners and Quark Venture. The proceeds will bankroll Volastra’s work in three approaches to predict and target metastasis as well as build out the technology that underpins them, CEO Charles Hugh-Jones, M.D. said.
That technology comes from the labs of Lewis Cantley, Ph.D., and Olivier Elemento, Ph.D., at Weill Cornell Medicine and the lab of Samuel Bakhoum, M.D., Ph.D., at Memorial Sloan Kettering Cancer Center.
“Most, if not all, of the therapies we have at the moment are unable to effectively prevent or, ultimately, treat metastases,” Hugh-Jones said. “At the core of metastatic cancer behavior is this concept of chromosomal instability. It’s been known about for a long time, but one of the difficulties has been accurately targeting it.”
Chromosomal instability has been difficult to target because it has been difficult to identify,” Hugh-Jones added.
Volastra is teaming up with Microsoft to solve this issue, the company said in a separate announcement. The duo will develop algorithms to detect and predict the potential of metastasis in human tissue samples. The goal is to use automated machine learning tools to speed up what would take a human much longer to do.
“A pathologist or physician may take up to an hour of looking down a microscope to identify chromosomal instability in a single patient. We are looking at doing this at scale using artificial intelligence,” Hugh-Jones said. The hope is to create a database linking chromosomal instability data with genetic and clinical data that will allow Volastra to pinpoint genes and phenotypes associated with the cancers it’s going after.
While healthy cells divide in an orderly manner, cancer cells divide in a way that is error-prone, Hugh-Jones said. The process leads to cells with chromosomes that haven’t separated properly and to fragments of DNA "getting pinched off" and forming micronuclei in the cytosol, the liquid found within cells. These fragile organelles can then burst, exposing these pieces of damaged DNA to metabolic pathways that drive metastasis.
Volastra is working on three approaches to tackle chromosomally unstable cancers: activating the immune system so that immune cells target those cancer cells, bringing about synthetic lethality and targeting downstream pathways to see whether it can beat back metastatic cancer.
It has inked an R&D deal with Dewpoint Therapeutics to discover drugs that target biomolecular condensates to prevent cancer progression and metastasis. The goal is to identify compounds that block the formation of condensates—membraneless organelles whose main job is to surround and contain reactants for chemical reactions—in cancer cells where chronic, pro-inflammatory signaling happens. The deal focuses on early discovery, but it has the option to add development and commercialization.
Dewpoint and Volastra have landed on a synthetic lethal target that they’re not disclosing yet, Hugh-Jones said. Volastra is also working on a target in immune activation on its own.
The financing will allow Volastra to hire more scientists to help it understand the biology and immunology involved in chromosomal instability, and then to identify new targets. As it adds more targets to its list, the company wants to develop its programs in-house, but it's interested in partnering as well, Hugh-Jones said.