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San Francisco August 27, 2019 – Synchronicity Pharma (“Synchronicity”), a clinical-stage company focused on therapeutic translation of circadian clock biology, today announced the publication of new preclinical research demonstrating that the modulation of circadian clock components may provide a novel therapeutic approach for treating glioblastoma, the most common form of brain cancer. The paper, which highlighted research led by scientific co-founder, Steve Kay, Ph.D. and collaborator, Jeremy Rich, M.D., was published in the latest edition of Cancer Discovery, a leading peer-reviewed oncology journal.
The results demonstrate that glioblastoma stem cells (GSCs) have a specific dependence on core clock proteins for their growth and survival. A similar reliance on these core clock proteins was not seen in non-malignant cells nor mature glioblastoma cells. Researchers showed that the clock transcription factors, BMAL1 and CLOCK, were guided by epigenetic mechanisms to bind to specific regions of the GSC genome. This resulted in the upregulation of metabolic pathways necessary for GSC self-renewal and viability. When BMAL1 and CLOCK activity was inhibited through a number of different methods, including the use of a small molecule cryptochrome stabilizer provided by Synchronicity, GSC proliferation was reduced in vitro and survival was improved in xenograft models.
“It is gratifying that our circadian clock research has led to potentially useful insights into the vulnerabilities of glioblastoma stem cells given their apparent central role in making the disease so resistant to achieving a durable remission,” said Dr. Kay, provost professor of neurology, biomedical engineering and biological sciences at the Keck School of Medicine of the University of Southern California. “We are hopeful these new insights may lead to exploiting a key vulnerability in the armor of glioblastoma’s historically intractable nature.”
Synchronicity’s platform focuses on modulation of the circadian clock. The company’s most advanced molecule, SHP-1705, is a cryptochrome stabilizer, which has been shown to be well tolerated and demonstrated active core clock control in clinical testing. Synchronicity’s SHP-1705 represents the first ever clinical-stage molecule capable of modulating the circadian core clock in a targeted manner.
“This research provides further validation of our conviction that the burgeoning field of circadian biology has the potential to lead to transformative therapies,” said Jamie Cope, Ph.D., senior vice president of research and translational medicine at Synchronicity. “We feel privileged to be positioned to explore the potential of our clinical-stage asset in translating these exciting findings into important therapies for patients with glioblastoma, as well as other cancers with similar underlying resistance mechanisms.”