Announcing TenSixteen Bio, a Pioneering Company to Pursue the Biology of Somatic Mosaicism, Starting with CHIP
We are all mosaics
While our genetic code is handed down to us before birth, our personal genome is dynamic and changes as we age. As our genes change over time, this creates distinct cell populations in our body — a process called somatic mosaicism. These cell mosaics bring different disease risks and define a new avenue of genetic susceptibility to human disease. I am happy to announce today the launch of TenSixteen Bio, a precision medicine therapeutics company incubated by Foresite Labs and backed by GV (formerly Google Ventures), to therapeutically target the fundamental biology of somatic mosaicism in age-related diseases.
Treating patients earlier through somatic mosaicism: a personal experience
As a hematologist, I am fascinated with our blood system and how certain blood cells develop cancer through mutations in their genetic code. On the other hand, I have often seen how these mutations drive the deadly nature of cancer. In my early years as a physician, I took care of a 30-year-old woman who was married with two twin girls and full of optimism. She developed acute myeloid leukemia, an aggressive blood cancer with only a 50% chance of cure. She did well initially and achieved remission following a bone marrow transplant from her sister. When we sequenced her genes upon initial diagnosis, we saw that the genetic makeup of her leukemia was simple: there were only a few gene mutations. Encouragingly, these mutations were at low levels during her remission. Unfortunately, a year later, she relapsed. When we sequenced her genes this time, the leukemia’s genetic code was very complex. She had a dramatic increase in the number of mutations, with distinct cell populations having mutations in different genes. In part because of this increase in her somatic mosaicism, her leukemia was resistant to subsequent therapies we gave her. I remember standing outside her hospital room at Stanford University with the latest test results, wondering how I was going to deliver the news. She passed away a few months later, still fighting to the end to preserve every precious moment with her family. As a doctor, those moments triggered a feeling of utter helplessness. More importantly, however, they also brought an unrelenting passion to do better, because people like her are dying every day.
What if we could have treated her disease earlier, before the leukemia mutated and became resistant? Better yet, what if we could have eliminated the precancerous cells and prevented her leukemia in the first place? In her DNA, we had found evidence of a mutation that was likely present before her leukemia, a type of somatic mosaicism in the blood that researchers now call CHIP. If we could have targeted CHIP, we would have had the possibility of diagnosing and eliminating disease earlier, and she might still be alive today. This is somatic mosaicism at work, a novel approach that can fundamentally change the paradigm of patient care: a core vision of TenSixteen.
TenSixteen: A number that highlights the magnitude of somatic mosaicism
We named TenSixteen after the number 10¹⁶, which is the estimated number of times cells divide in a person’s lifetime. Each cell division is an opportunity for these genetic changes to take place, leading to a new risk of developing diseases. 10¹⁶ highlights this massive opportunity to understand the biology around somatic mosaicism and our dynamic personal genome.
CHIP: Witnessing a new revolution in biology
Perhaps the most impactful occurrence of somatic mosaicism is in the blood, through a phenomenon called CHIP (clonal hematopoiesis of indeterminate potential). The first evidence of clonal hematopoiesis was demonstrated in the 1990s, when non-random X chromosome inactivation was observed in people without cancer. In the last decade, researchers have discovered that as we age, we accumulate mutations in a specific set of genes in our blood cells (CHIP mutations) that lead to multiple diseases including cancer and heart disease among others. In some instances, having CHIP mutations can lead to a greater than tenfold increased risk of developing cancer or serious heart disease. In another CHIP setting, patients have a near 100% chance of developing blood cancer. Despite these life-threatening risks, there are no available drugs for patients with CHIP. Why is this important? Because CHIP can impact everyone. As we age, many of us will develop CHIP or be at risk to do so in our lifespan. In fact, 10% of the entire world over the age of 70 is estimated to have CHIP. The prevalence is significantly higher when we use more sensitive methods to detect the presence of CHIP. Thus, being able to identify patients with CHIP and treat those who are most in need will be key to the way we treat age-related diseases. CHIP represents another biologic revolution that will see exponential interest in the coming years.
TenSixteen’s approach: assembling an extensive data platform on CHIP for drug discovery and precision medicine
Because of the broad-reaching biology of CHIP, the ability to analyze large amounts of data is critical to discovering important clinical insights and developing tailored therapies. TenSixteen is building a comprehensive multi-omics and clinical data platform on CHIP through mining public data and through collaborations with academic and healthcare institutions. Coupled with a proprietary diagnostic assay on CHIP, this platform will enable TenSixteen to 1) discover therapeutic targets of CHIP; 2) identify which patients are at highest risk; and 3) bring tailored therapies to these patients in a biomarker-enriched fashion.
Join us on our journey
While the journey is just beginning, we are fortunate to stand on the shoulders of our co-founders and other luminaries who have ushered in this field and with our investors who believe in this transformative area and our team. We are bringing together the world’s experts in CHIP, large scale data, genomics and drug development and welcome others to join our incredible team. They include professors and division chiefs at Harvard, Columbia, Stanford and Vanderbilt as well as industry pioneers in diverse areas of science from Genentech, GRAIL, Regeneron, Foundation Medicine, Calico and others. I look forward to the exciting journey ahead as we translate this big area of biology into paradigm-shifting patient impact. If you are interested in joining us please reach out at tensixteen.bio website.
Mark Chao MD, PhD
Co-founder and CEO of Tensixteen Bio