Volastra Therapeutics is a clinical-stage biotechnology company headquartered in New York City, committed to transforming cancer care. The company’s groundbreaking research focuses on chromosomal instability (CIN), a fundamental vulnerability in cancer biology that fuels tumor heterogeneity and resistance to treatments. By targeting CIN, Volastra is opening new therapeutic avenues to address some of the most challenging cancers. Chromosomal instability is characterized by a heightened frequency of errors during mitosis, the process of cell division. Unlike healthy cells, which rely on tightly regulated checkpoints to ensure genetic integrity, cancer cells exploit CIN to drive genomic chaos. This genomic instability fosters diversity within cancer cells, allowing tumors to evolve, evade immune defenses, and resist current medical therapies.

Volastra’s CINtech Strategy: Innovation in Action

At the heart of Volastra’s research lies its proprietary CINtech platform. This innovative approach integrates cutting-edge technology, advanced screening methods, and computational modeling to characterize chromosomal instability in unprecedented ways. CINtech enables the identification of CIN-specific therapeutic targets, coupled with biomarkers that help determine which patients are most likely to benefit from these interventions. By leveraging decades of oncology data and applying their CINtech lens, Volastra is uncovering novel insights into cancer cell vulnerabilities. This data-driven approach allows the company to make informed decisions in drug discovery and development, accelerating the journey from lab to clinic.

Therapeutic Approaches: Synthetic Lethality and Immune Activation

Volastra employs two complementary strategies to target chromosomally unstable cancers: synthetic lethality and immune activation.

• Synthetic Lethality: This approach aims to selectively kill cancer cells by targeting pathways that are essential for the survival of chromosomally unstable cells but dispensable for normal cells.

• Immune Activation: Cancer cells often evade immune detection by suppressing the body’s ability to sense chromosomal instability. Volastra’s immune activation strategy seeks to reverse this suppression, reawakening the immune system to recognize and eliminate cancer cells.

Targeting KIF18A: A Key Driver of CIN: One of Volastra’s most promising areas of research focuses on KIF18A, a protein critical for the survival of chromosomally unstable cancer cells. During mitosis, KIF18A plays a pivotal role in aligning chromosomes at the midline of dividing cells. While normal cells can perform mitosis without KIF18A, chromosomally unstable cancer cells rely heavily on this protein to manage their chaotic division process. By inhibiting KIF18A, Volastra aims to disrupt the mitotic process in cancer cells, leading to cell death. Importantly, this selective approach spares normal cells, minimizing potential side effects and enhancing the safety profile of KIF18A-targeted therapies.

Lead Programs: Advancing KIF18A Inhibitors

Volastra is currently advancing two differentiated KIF18A inhibitors—Sovilnesib and VLS-1488—through clinical trials:

• Sovilnesib: A potent oral KIF18A inhibitor in development for advanced solid tumors, including platinum-resistant high-grade serous ovarian cancer. Sovilnesib recently completed a Phase 1 clinical trial, and a Phase 1b trial is underway to evaluate its safety, tolerability, and efficacy. It has received fast-track designation from the FDA, highlighting its potential to address unmet medical needs.

• VLS-1488: Another oral KIF18A inhibitor being evaluated in a Phase 1 trial for advanced cancers with high levels of chromosomal instability.

Both programs exemplify Volastra’s commitment to precision medicine, with the goal of delivering therapies tailored to the unique biology of each patient’s cancer.

Beyond KIF18A: Expanding the Pipeline

In addition to its KIF18A inhibitors, Volastra is pursuing other CIN-specific targets through its partnerships and internal research. The company’s collaboration with Bristol Myers Squibb focuses on synthetic lethal targets, while its in-licensed sovilnesib program from Amgen has strengthened its pipeline of innovative therapies. Volastra is also exploring immune activation approaches, aiming to develop therapies that can restore the immune system’s ability to detect and eliminate cancer cells with chromosomal instability. This dual focus on synthetic lethality and immune activation underscores the company’s holistic approach to targeting CIN.

Strategic Partnerships: Driving Innovation Forward

Collaboration is a cornerstone of Volastra’s strategy. The company has forged strategic partnerships with industry leaders to enhance its capabilities and accelerate progress.

• Microsoft Partnership: In April 2021, Volastra teamed up with Microsoft to develop AI-based models that measure CIN in tumor tissues. This partnership is enhancing target discovery and biomarker development, supporting Volastra’s mission to deliver precision oncology solutions.

• Bristol Myers Squibb Collaboration: Launched in March 2022, this multi-target drug discovery partnership focuses on CIN-specific synthetic lethal targets. Together, the two companies are pushing the boundaries of cancer research to uncover new therapeutic opportunities.

• Amgen Agreement: In February 2023, Volastra acquired Amgen’s KIF18A inhibitor program, sovilnesib. This acquisition has strengthened Volastra’s position as a leader in targeting chromosomal instability.

Clinical Trials: A Path to Impact

Volastra is conducting clinical trials to evaluate the safety and efficacy of its CIN-directed therapies. Key studies include:

• Sovilnesib in Ovarian Cancer: A Phase 1b trial is assessing sovilnesib in patients with high-grade serous ovarian cancer, a challenging-to-treat cancer with limited options.

• VLS-1488 in Advanced Cancers: A first-in-human Phase 1/2 study is underway to examine the safety and preliminary efficacy of VLS-1488 in patients with advanced cancers.

These trials represent a critical step in Volastra’s mission to bring transformative therapies to patients.

Looking Ahead: A Vision for the Future

With its focus on chromosomal instability, Volastra Therapeutics is poised to redefine cancer treatment. By leveraging groundbreaking science, strategic partnerships, and a patient-centered approach, the company is advancing therapies that address the root causes of cancer’s resilience and adaptability. Through its innovative CINtech platform, Volastra is not only developing new drugs but also contributing to a deeper understanding of cancer biology. As it continues to build on its successes, the company remains steadfast in its mission: to harness the power of science to deliver hope and healing to patients around the world.

Charles Hugh-Jones, M.D., FRCP, Chief Executive Officer

"At Volastra Therapeutics, our mission is to revolutionize cancer treatment by targeting chromosomal instability and unlocking new therapeutic possibilities for patients battling the toughest cancers."