Companies To Watch: Volastra Therapeutics
By Ben Comer, Chief Editor, Life Science Leader
Developing biomarkers and therapies targeting chromosomal instability, a hallmark of cancer cell replication.
Snapshot
New York City-based Volastra Therapeutics – whose founders and scientific advisors are leading chromosomal instability researchers and experts – have in four years’ time advanced two drug candidates into Phase 1 clinical trials. Both of Volastra’s clinical candidates (one discovered internally, one in-licensed from Amgen) inhibit KIF18A, a kinesin protein that helps stabilize chromosomes as they line up in the middle of a cell, just before the cell divides. Tumors including certain types of ovarian cancer, triple negative breast cancer, and squamous non-small cell lung cancer (NSCLC) exhibit a high prevalence of chromosomal instability and require the KIF18A protein to grow. Normal or healthy cells, however, don’t need KIF18A to undergo cell division (mitosis), making the inhibition of KIF18A in tumors with high levels of chromosomal instability a new and novel approach to cancer treatment. Partnerships with Microsoft, Function Oncology, and Tailor Bio aim to help identify biomarkers that can, in turn, identify patients that could benefit from KIF18A inhibition across a range of other tumor types. In addition to investors including Polaris Partners, ARCH Venture Partners, Eli Lilly, and others, Volastra entered into a drug discovery collaboration with BMS in 2022.
What’s At Stake
The link between cancer and chromosomal instability was first proposed over a century ago, but drug developers have only in recent years begun to develop therapies that leverage chromosomal instability as a mechanism and target for cancer treatments. Volastra’s founders and research scientists characterized KIF18A in 2020, and founded the company soon after, says Charles Hugh-Jones, CEO at Volastra. “We were then excited that three academic groups published [on KIF18A] in 2021, in Nature and Nature Communications,” he says. “It was interesting to see that not only had we identified [KIF18A] in our computational screens, but that academic groups also identified it as a promising target.”
While certain ovarian cancers, breast cancers, and NSCLC have near universal (~100%) chromosomally unstable tumors, 60% to 80% of all cancers have some level of chromosomal instability, says Hugh-Jones. KIF18A is a “really interesting molecule, it’s like a little molecular motor that helps stabilize chromosomes in the cell” before division, he says. “If you can remove this protein, it stops the cancer cells from dividing, but normal cells can keep on dividing as they regularly do.”
Because the aforementioned cancer types have a near 100% prevalence of chromosomal instability, those tumors can be addressed without a biomarker, explains Hugh-Jones. Then, Volastra can test its proprietary biomarkers on those tumor types, to assess predictive power. From there, the biomarkers can be used to identify new patient groups with different cancer types that are likely to benefit from KIF18A inhibition. “A core understanding of the biology of chromosomal instability is absolutely at the core of what Volastra is about,” says Hugh-Jones.
Volastra is likely to choose only one of its two Phase 1 KIF18A inhibitor candidates (sovilnesib, in-licensed from Amgen, and VLS-1488, developed internally) for later stage clinical development. The company’s development strategy, per Hugh-Jones, is to “take two of what we think are really promising KIF18A inhibitors, develop them in parallel in Phase 1, and then see which one is best.” Amgen’s early research data on sovilnesib is being “triangulated across both development programs, to really give each one the best chance of success,” says Hugh-Jones.
A presentation given by Samuel Bakhoum, cofounder and scientific advisor at Volastra, at the American Association for Cancer Research (AACR) Annual Meeting in 2021, drew a lot of attention. Less than a year later, BMS had signed on for a multi-year discovery collaboration which included $30 million up-front, and up to $1.1 billion in development, regulatory, and commercial milestone payments and royalties. Amgen took an equity position in Volastra as part of the sovilnesib in-licensing deal, says Hugh-Jones, and sits on the company’s capitalization table. “We’ve gone from one or two people with a telephone and an empty office to 35 people and two drug candidates in Phase 1 clinical trials, which is remarkable progress in what is essentially a four-year time frame.”
Volastra’s location in New York City – West Harlem to be more specific – is beneficial, says Hugh-Jones. “We have access to great scientists, great developers, and great lab space. There is also good access to capital and innovation … we see it as a real competitive advantage, being based in New York City.”
Vital Statistics
Employees: 35
Headquarters: New York City (West Harlem)
Funding: $75 million in Series A funding, eligible for up to $1.1 billion in milestones and royalties from BMS.
Latest Updates:
April 2024: Dosed first patient in Phase 1b clinical trial evaluating sovilnesib in patients with platinum-resistant or refractory high-grade serious ovarian cancer.
March 2024: Added Function Oncology and Tailor Bio as partners for genomic assessment of chromosomal instability across patients and cancer types, and to develop new biomarkers.