Volastra Therapeutics is a cutting-edge biotechnology company headquartered in New York, dedicated to transforming cancer treatment through innovative approaches. Founded by a team of esteemed scientists including Lewis Cantley, Ph.D., Olivier Elemento, Ph.D., and Samuel Bakhoum, M.D., Ph.D., Volastra is at the forefront of leveraging chromosomal instability (CIN) as a pivotal target in cancer therapy.

Their groundbreaking research focuses on exploiting the unique vulnerabilities of cancer cells, particularly those driven by CIN, to develop targeted therapies. Through their proprietary CINtech research strategy, which combines advanced technology, screening techniques, and computational modeling, Volastra identifies CIN-specific targets and biomarkers, enabling the precise selection of patients who may benefit most from their treatments.

With a commitment to advancing scientific understanding and revolutionizing cancer care, Volastra is pioneering two complementary approaches: synthetic lethality and immune activation. Their synthetic lethality approach aims to directly eliminate cancer cells by targeting vulnerabilities specific to chromosomally unstable cells. Meanwhile, their immune activation approach seeks to enhance the body's immune response against cancer by reawakening immune sensing mechanisms disrupted by chromosomal instability.

Through relentless innovation and a dedication to patient-centric research, Volastra Therapeutics is poised to make significant strides in cancer therapy, offering hope to patients facing some of the most challenging forms of the disease.

 Understanding Mitosis: A Fundamental Cellular Process

Mitosis, the process by which cells divide into two genetically identical cells, plays a critical role in the growth and maintenance of organisms. This intricate multistep process involves the duplication of chromosomes followed by the precise division of each chromosome pair into two daughter cells. In normal cells, mitosis is tightly regulated, with checkpoints ensuring the accurate execution of each step and the detection and correction of errors.

Chromosomal Instability in Cancer Cells: A Disruption of Normal Mitosis

Cancer cells, however, exhibit aberrant behavior during mitosis. They have evolved mechanisms to bypass the checkpoints that regulate normal cell division, allowing them to proliferate despite mitotic errors. As a result, cancer cells often produce daughter cells with abnormalities in chromosome structure and number, contributing to the genetic diversity that enables them to evade the body's natural defenses and conventional cancer therapies. This phenomenon, known as chromosomal instability, is a hallmark of cancer.

The Role of KIF18A: A Potential Target for Cancer Therapy

One protein that has emerged as a potential target for cancer treatment is KIF18A, which plays a crucial role in aligning chromosomes at the midline of dividing cells during metaphase. While normal cells can undergo mitosis without KIF18A, chromosomally unstable cancer cells rely on this protein to complete their chaotic division process successfully. By binding to and influencing the stability of microtubules, KIF18A helps fine-tune the tension required for proper chromosome alignment.

Targeting KIF18A for Cancer Therapy: Volastra's Approach

Volastra Therapeutics is at the forefront of developing novel inhibitors targeting KIF18A for cancer therapy. These inhibitors work by preventing KIF18A from performing its function during mitosis, thereby stalling cell division and leading to cancer cell death. Importantly, since normal cells do not rely on KIF18A to the same extent as cancer cells, selectively targeting this protein allows for the elimination of cancer cells while sparing healthy cells.

Lead Programs: Advancing KIF18A Inhibitors in Clinical Trials

Volastra is currently advancing two distinct KIF18A inhibitors in Phase I clinical trials for challenging-to-treat cancers. By designing each inhibitor with different molecular scaffolds, the company aims to explore diverse drug profiles while targeting the same essential protein. These lead therapeutic programs hold promise in selectively and potently targeting KIF18A, offering a tailored approach to combating cancer with minimal impact on healthy cell mitosis.

Volastra's Pipeline: Targeting Chromosomally Unstable Cancer Cells

Volastra Therapeutics boasts a diverse pipeline comprising multiple programs aimed at harnessing the unique biology of chromosomally unstable cancer cells. These programs are complemented by innovative biomarker strategies meticulously designed to match each therapy with the patients poised to derive the greatest benefit.

Therapeutic Programs

1. Synthetic Lethal Approach

Sovilnesib (KIF18A Inhibitor) Sovilnesib, previously known as AMG650, represents a groundbreaking oral small molecule KIF18A inhibitor tailored for advanced solid tumors. Having completed a Phase 1 clinical trial, Sovilnesib is set to embark on a Phase 1b trial in early 2024. Notably, it has garnered fast track designation for its efficacy in platinum-resistant high-grade serous ovarian cancer.

VLS-1488 (KIF18A Inhibitor) VLS-1488 is another novel oral small molecule KIF18A inhibitor currently under investigation in a Phase 1 clinical trial (NCT05902988) targeting advanced solid tumors characterized by heightened chromosomal instability.

2. Immune Activation

New Target Discovery Volastra's Immuno-Oncology initiative takes a novel approach by focusing on tumor cell-intrinsic Immunoevasion. The company is spearheading an early pipeline of targets designed to reinvigorate anti-tumor immunity by leveraging chromosomal instability as a catalyst for immune activation.

Partnerships In collaboration with Bristol Myers Squibb, Volastra is advancing chromosomal instability-specific synthetic lethal endeavors against two undisclosed targets. These partnerships underscore the company's commitment to fostering innovation and maximizing therapeutic efficacy in the fight against cancer.

Each program within Volastra's pipeline represents a strategic endeavor to exploit the vulnerabilities inherent in chromosomally unstable cancer cells, offering promising avenues for the development of targeted and effective cancer therapies.

The Visionary Leader

Charles Hugh-Jones, M.D., FRCP is the Chief Executive Officer of Volastra Therapeutics. Charles is an experienced biotech leader and a board-certified physician. Prior to joining Volastra, Charles served as the global chief medical officer at Allergan PLC, where he led complex interdisciplinary teams and supported the launch of novel medicines in multiple therapeutic areas. Before Allergan, Charles worked for Pfizer Oncology as their chief medical officer and had medical oversight of all late-stage drug development and commercialization activities. He began his career at Schering AG, Enzon Pharmaceuticals and Sanofi, where he held various positions of increasing responsibility. Charles received his bachelor’s in neuroanatomy and M.D. from the University of London. He went on to complete higher specialist training in diagnostic radiology.

“Volastra Therapeutics is committed to transforming cancer treatment by leveraging cutting-edge science and innovative approaches to target chromosomal instability and unlock new therapeutic opportunities for patients.”