415 Clyde Ave. Unit 107 Mountain View, CA 94043 [email protected]
February 2021
Rejuvenation Technologies is Extending Telomeres to Extend Life Rejuvenation Technologies (“Rejuvenation”) is a venture-backed biotech company founded out of Stanford University to develop anti-aging therapeutics. Rejuvenation’s lead compound, TERT mRNA, safely extends telomeres to substantially reverse cell aging and disease impact. After researching this mechanism for a decade and testing it on human cells in-vitro, the founding team proved its effectiveness on mice in-vivo in 2018 using a new vehicle to deliver TERT mRNA by intravenous injection — leveraging breakthroughs in mRNA delivery. Subsequently, they launched the company and licensed patents they had filed while at Stanford. In 2020, the founders proved TERT mRNA’s effectiveness in mitigating liver fibrosis, reducing fibrotic tissue by 27% and extending survival duration by 42% in a mouse model of liver disease. Their liver formulation is targeting human clinical trials in 2022. While currently focused on treating fatal diseases, the long-term objective is to apply this technology to broader use cases such as meaningfully extending longevity and healthspan.
Short Telomeres are a Major Cause of Aging Telomeres are protective caps at the ends of chromosomes. In childhood, telomeres are long and form loops over each end. However, as cells divide over time, telomeres shorten. When telomeres become too short, their protective loops are unable to form, exposing the chromosome’s tips. These uncovered tips are interpreted as broken DNA, causing the cell to senesce, die, or mutate. If the cell becomes senescent, it secretes inflammatory molecules that contribute to aging and disease. If the cell dies, it reduces the number of cells available to perform normal functions and regenerate tissues. For decades, the scientific community has known that telomerase reverse transcriptase (“TERT”) extends telomeres and can rejuvenate cells in culture. Yet the challenge has been to find a safe and effective way to increase TERT levels in cells through limited dosing, in order to avoid runaway cell growth.
Rejuvenation’s Breakthrough Drug While at Stanford, Rejuvenation’s founders spent 10 years developing a process to increase TERT levels in cells through limited dosing. Their process became viable in 2018, due to advancements in mRNA technology. By encoding TERT in synthetic mRNA modified to reduce immunogenicity, they were able to deliver it to cells. Within only a few hours, the added TERT extended telomeres enough to reverse years of shortening. This increase in TERT levels was temporary and safe because the mRNA degraded after several hours. When the treatment ended, telomeres resumed shortening at their normal rate. The combination of TERT mRNA’s speed and transience is the catalyst that makes Rejuvenation’s approach so effective. A single dose of TERT mRNA once every few years may be enough to keep telomeres and cells young.
TERT mRNA Visibly Extends Humans Telomeres From their test on human cells, the images below show the impact of TERT mRNA on two cells (blue) from the same person. The intensity of the yellow telomere signal is proportional to telomere length. The cell on the right was treated with TERT mRNA, causing its telomeres to be extended by approximately 1kb. This extension is evidenced by the yellow telomere signal’s increased brightness. A 1kb telomere extension, which took place within days, is sufficient to reverse over a decade of telomere shortening during normal aging. This result has since been repeated in other cell types, including in cells from a patient with a loss-of-function mutation in TERT.
From Acute Diseases to Longevity Rejuvenation’s ultimate goal is to meaningfully extend the human healthspan and to mitigate disease. Doing so will require a clinical trial with endpoints such as improved function and delayed all-cause mortality. To start, the company is focusing on fatal diseases of accelerated aging, which are known to be caused or exacerbated by short telomeres. In the mouse liver, the team has shown that TERT mRNA decreases senescent cell count and reduces liver fibrosis in mouse models of chronic liver disease. In the mouse lung, they invented a lipid nanoparticle formulation that could target the lung alveolar epithelial cells with mRNA at high efficiency via intravenous injection. With regard to the immune system, the team was able to increase telomerase activity in human hematopoietic stem cells.
Team Rejuvenation’s management team consists of John Ramunas, Glenn Markov, and Will Olsen. John and Glenn did their PhDs together in the lab of Stanford University Professor Helen Blau, who is also a co-founder. Will joined Rejuvenation in 2019 after selling Luminist, a liver diagnostics company that he founded. Rejuvenation has a world-class advisory board, including: liver model expert Hide Tsukamoto, DVM, PhD, Director of the Liver Disease center at USC; IND/regulatory expert Larry Couture, PhD founder of translational research at City of Hope and serial entrepreneur; drug development expert Bill Bradford, MD, PhD who led efforts for the approval of one of the two approved pulmonary fibrosis drugs; and clinicians Veeral Ajmera, MD and Sammy Saab, MD, who are medical directors and liver transplant experts at UCSD and UCLA respectively, and would be enroll patients into the first clinical trials. In total, Rejuvenation has six full-time and five part-time employees at their Mountain View, CA lab.
Founding, IP, and Funding Rejuvenation participated in Stanford’s SPARK program and Y Combinator’s Anti-Aging Program in 2018, which provided the funding to license the fundamental patents they filed while at Stanford. Rejuvenation’s 2019 seed round was led by Khosla Ventures and Shanda. Rejuvenation is currently planning a financing round to gain IND approval in 2022 to enter human trials.