New Frontiers in Targeting Chromosomal Instability

It’s hard to believe that exactly five years have passed since our first full-time staff members joined Volastra.

At the time, we were a new biotech company with a bold vision and singular mission: to deeply understand how to target the complex biology of chromosomal instability (CIN), a devastating driver of cancer progression.

While we have grown significantly since that first day, our mission has remained the same. We are using this groundbreaking knowledge to develop innovative therapies that address unmet patient needs. Some of these therapies are now advanced in clinical trials, offering new hope to cancer patients worldwide.

This anniversary provides our team with a unique opportunity to reflect on the remarkable insights and progress we’ve made over these past 5 years.

In a series of articles that will run through 2025, we will shine light on the key achievements that have defined our journey and share our vision for the future.

CIN, characterized by ongoing errors in chromosome segregation during cell division, was first observed over a century ago by German zoologist Theodor Boveri. He hypothesized this phenomenon, now known as CIN, could be a driver of human cancers - and he was correct.

We now know that CIN is present in 60-80% of all human cancers, with some tumors being almost universally unstable and other tumor types only partially so. For example, certain ovarian and breast cancers are examples of near universal instability. Through the resultant genetic diversity, CIN may provide cancer cells with survival advantages.

But despite its prevalence, CIN remained an untapped therapeutic opportunity—until Volastra was founded.

At Volastra, we recognized at our inception that targeting CIN could unlock a new frontier in cancer treatment. This vision, championed by our pioneering founders - Dr. Lewis Cantley, Dr. Samuel Bakhoum, and Dr. Olivier Elemento - has rapidly evolved into a company that is redefining what’s possible in oncology. And indeed, we have only just this past week welcomed Dr. Bakhoum as our full-time Chief Scientific Officer.?

We are now able to target CIN from all sides - through synthetic lethality, where CIN acts as a critical component, and the downstream immunological effects of CIN. This progress is happening in both our broad discovery research and our ongoing clinical trials.

With our ultramodern laboratory in West Harlem, New York City, we have built an incredible team with exceptional capabilities spanning bench to bedside. Collaboration has been a key driver of our success, among both our internal teams and our external partnerships with oncology leaders. We’ve also harnessed the power of artificial intelligence to propel our patient-focused science forward.

Some of our exciting work has been on KIF18A, a “molecular motor” critical to cell division. KIF18A fine-tunes spindle tension and aligns chromosomes at metaphase. While cancer cells with high levels of CIN rely heavily on KIF18A for division, normal cells can divide without it. This makes KIF18A an ideal target for synthetic lethality - cancer cells are trapped mid-division, then collapse and die, while normal cells survive.

This has laid the foundation for what may become the first CIN-based approach to selectively destroy cancer cells while sparing healthy ones. Our therapies have the potential to fulfill our vision of creating more effective and more tolerable therapies for cancer patients.

As we stand on the threshold of our next chapter, we’re excited to see our oral KIF18A inhibitor programs progressing through Phase I clinical testing. These trials build on the promise of our preclinical studies as we prepare for late-stage development. We see immense potential for KIF18A inhibitors to treat a range of tumors, not least ovarian, lung, and breast cancers.

Equally as exciting, our proprietary biomarker work - developed in collaboration with Tailor Bio and Microsoft Research - offers the potential to precisely identify and treat cancers with heterogenous levels of CIN. By leveraging sophisticated genomic and visual signatures, we aim to bring hope to thousands more patients across other tumor types, helping them live longer, healthier lives.

But Volastra is so much more than our lead program. We’ve built a deep and expanding pipeline of future medicines targeting different aspects of CIN across numerous cancer types and cellular mechanisms. ?Through all these programs we stay committed to that original mission – to understand the complex biology of CIN to deliver life-changing treatments to those who need them most.

The remarkable discoveries from our team at Volastra define an exciting future—a future we are moving toward swiftly and with unwavering focus.

The heart of Volastra’s success over the past five years has been our team—a passionate group of scientists, clinicians, innovators, experts, and partners. Over the next few months, you will be hearing more from this team about their work and how it will redefine the oncology landscape.

We look forward to our next five years, to important new medicines and to the limitless possibilities ahead.