A slew of therapies are currently in development for inherited diseases, but these genetic medicines only address part of a broader genetic picture. Disease-causing mutations aren’t limited to the ones identified at birth. Scientific research is uncovering insights into the mutations that happen as we age and the roles that these changes play in disease. Startup TenSixteen Bio is developing new medicines based on this emerging biology and it’s now launching backed by $40 million.
The San Francisco-based company name is a reference to 10 to the 16th power, which is the estimated number of times that cells divide over the course of a person’s lifetime. Mark Chao, the company’s CEO and co-founder, said that each of those divisions represents an opportunity for changes that lead to disease. Chao saw those changes firsthand when he was practicing medicine as a hematologist.
Many of Chao’s patients had aggressive blood cancers that were unresponsive to multiple lines of treatment. In such cases, he was unable to offer another therapy because the cancer’s numerous mutations made it resistant to treatment. He recalled thinking that it would be better to treat the cancer when it had only one or two mutations rather than 20 to 30. TenSixteen’s therapies may offer a way to provide that earlier intervention.
The accumulation of mutations is called somatic mosaicism. TenSixteen is focusing on a particular form of somatic mosaicism found in the blood called clonal hematopoiesis of indeterminate potential, or CHIP. It stems from mutations in a set of genes associated with cancer. CHIP science has emerged in the last decade. Chao said that despite the cancer association, CHIP can also lead to other conditions, such as atherosclerosis, heart failure, autoimmune diseases, cirrhosis, and even infection. He added that research has shown that people who have CHIP have a greater risk of developing disease, or for their disease to progress.
“There are no therapeutics that are targeting CHIP yet,” CHAO said. “We really want to be the first to target this biology. We see a changing paradigm shift.”
In order to intervene in disease earlier, the mutations will have to identified. There is no CHIP specific assay yet, but TenSixteen is developing one. The company’s drugs will come from its technology platform, which analyzes various data sources, such as biobanks and electronic health records, in order to find insights into CHIP. The company applies artificial intelligence and machine learning techniques in its analysis, which aims to identify novel drug targets and the patients that are at the highest risk of a CHIP-driven disease. The technology will also help identify likely responders to TenSixteen’s treatments.
Though CHIP represents accumulated genetic mutations, TenSixteen’s drugs will not be genetic medicines, such as gene editors or gene therapies. Chao said the company is developing small molecules and monoclonal antibodies that target the mutations and their associated downstream effects. The company already has drug candidates in its pipeline, though Chao declined to offer specific details. He would only say that TenSixteen is focusing first on oncology and cardiovascular disease before expanding to other therapeutic areas.
Chao is a physician/scientist who practiced medicine at Stanford Health Care before co-founding Forty Seven, a cancer immunotherapy developer that went on to be acquired by Gilead Sciences. Chao said he began working with Foresite Capital about nine months ago, attracted to firm’s interest in disruptive companies at the intersection of technology and healthcare. TenSixteen’s science has roots in the research of it academic co-founders at Vanderbilt University, Harvard University, and Stanford University. TenSixteen’s cash infusion comes from Foresite Capital and GV. The startup has been incubating within Foresite Labs, the life sciences incubator of Foresite Capital.
TenSixteen currently employs 10 full time. With the new capital, Chao said he’s looking to build his team, which he projects could top 30 employees by the end of this year. The cash will also be used to further develop the technology platform and continue work on the drug pipeline. Eventually, Chao envisions TenSixteen looking beyond CHIP to develop therapies that address somatic mosaicism in other tissues.
Public domain image from the National Cancer Institute
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