Rubedo’s first target is respiratory disease, with COVID-19 expected to drive an increase in lung disease over the next 10 years.
Late last year, Silicon Valley start-up Rubedo Life Sciences secured a sizeable seed funding round of $12 million to develop senolytic therapies that selectively target and clear senescent cells from aged or pathological tissues. The company is now conducting preparatory work for IND-enabling studies, ahead of moving to Phase 1 clinical trials, potentially as early as 2022.
Senescent cells are cells that “forget” to die at the end of their lifespan, but remain metabolically active even though they have stopped replicating and growing. They play a key role in the progression of chronic disorders, so targeting and eliminating these cells is thought to have potential for Longevity benefits in humans.
Longevity.Technology: Senolytics is a hot area for Longevity investment right now, and Rubedo is clearly a very interesting player in this field. We recently spoke with the company’s CEO and co-founder Dr Marco Quarta to learn more about Rubedo’s origins and where the company is headed.
Italian-born Quarta has been interested in aging since he was a child.
“I was six, seven years old when I naively decided that I wanted to cure ageing, but that’s what I decided to do,” he says. “And I went on a mission and I never stopped.”
Quarta was fascinated by the concept of life and the fact that different organisms age in different ways. It became clear to him that the way humans age was not set in stone, and that it should be possible to change or improve that process. This fascination drove him through his studies in biotechnology and bioengineering, and eventually led to his work in regenerative medicine under Prof. Thomas Rando at Stanford University.
But Quarta has always had an entrepreneurial spirit, and has been the co-founder of several start-ups over the years, including Stanford Longevity spin-out Turn.bio, where he is still a director, before Rubedo was founded in 2018.
“Aging is not a clinical indication yet, but the chronic diseases that result from it are, and they are mostly all unmet needs.”
Appropriately, in alchemy, the word “rubedo” refers to the final phase of the creation of the mythological elixir of life, which delivers rejuvenation and immortality. And Rubedo has borrowed another term from alchemy to name its discovery platform, Alembic, which refers to the apparatus used by alchemists to prepare their medicine.
“I’m so happy to see that in the past 10 years, and even more in the past five, the scientific and biotech communities have reached that level of initial maturity, the critical mass to accept the idea that aging is the main driving process of age-related diseases,” says Quarta. “There is a change in biology, and we accept this idea that it can be probably targeted. Aging is not a clinical indication yet, but the chronic diseases that result from it are, and they are mostly all unmet needs.”
Rubedo’s founders wanted to address this challenge by making new medicines that are customised for older people (well-tolerated), and target the biological events or cellular targets that are behind the hallmarks of aging and drive age-related disease.
“We are not a senolytic company, per se,” says Quarta. “Our first and most advanced programme is our senolytic programme, but the Alembic platform that we have developed is agnostic.”
“Alembic allows us to identify novel targets, to identify the specific signatures, and use this information to design and engineer more molecules that are special, targeted therapeutics.”
Alembic is used is to profile and identify the biological changes that emerge with age and disease. It can be used, for example, to identify metabolic signatures as specific characteristic of certain cells.
“What is emerging with age, what’s happening at that inflection point?” asks Quarta. “What are the cells that are emerging, or the changes in any cell types, in different tissues, across ages, across species, across diseases? Alembic allows us to identify novel targets, to identify the specific signatures, and use this information to design and engineer more molecules that are special, targeted therapeutics.”
Quarta speaks of a “symbiotic relationship” between Alembic and the people who work at Rubedo, with experimental data being entered into the platform every day, which in turn provides new information and predictions to the scientists that use it. Unlike some other companies, Rubedo is not using Alembic to screen existing drugs – its focus is on designing novel drugs that are only activated in certain target cells – cancer cells, stem cells or senescent cells, for example.
“Senescent cells are one of those cells that emerge with age, and are clearly involved in driving chronic inflammation, fibrosis, promoting cancer, and so on,” says Quarta. “Having strong expertise in that field, we decided to go after senescence as a master regulator of many diseases. We’re developing compounds that can target selectively certain types of senescent cells in a disease model and disease tissue, while protecting the other cells.”
The company’s early animal model work is the subject of a preprint paper, currently undergoing peer review, which showed that its targeted senolytic was well-tolerated and improved frailty, muscle regeneration and cognitive functions in geriatric mice.
“Interestingly, even before the pandemic hit, we decided that lung disease was definitely the space that we wanted to move on first.”
Rubedo has developed a proprietary chemistry to design and make these compounds, quickly run efficacy studies in vitro and in vivo, identify the lead compounds, optimize them, and ultimately nominate clinical candidates to go into IND-enabling studies and into the clinic. The company spent around a year narrowing down its options based on a wide range of factors, and eventually arrived at respiratory disease as a key target.
“Interestingly, even before the pandemic hit, we decided that lung disease was definitely the space that we wanted to move on first,” says Quarta. “When we started to use Alembic to analyse and look into clinical data from patients and identify the role of senescence, we found that there is clear evidence in relation to the severity of the disease itself. There is a strong hypotheses that they are a driver of the pathology and very important, so we decided to focus on that.”
Then the pandemic hit, and, with COVID-19 expected to accelerate the aging process of survivors’ lung tissue, Quarta hopes Rubedo’s work can benefit people who may be at increased risk of lung disease as a result.
“Unfortunately, as those people age, we will probably see a surge of pulmonary fibrosis and other respiratory conditions,” says Quarta. “So that’s another reason why we definitely want to bring a therapeutic to the clinic that can really help those people that will struggle. Hopefully as soon as possible.”
“Best case scenario, we might be ready for a Phase 1 clinical trial in a couple of years.”
Rubedo is currently in the lead optimization stage for its lead compound, and is conducting preparatory work for IND-enabling studies. The new funding is expected to take the company through those studies, at which point a Series A will be raised to take the company through to Phase 1 clinical trials.
“The hope is that in 2021, we will be ready to initiate the conversation with the FDA to start IND-enabling studies,” says Quarta. “Best case scenario, we might be ready for a Phase 1 clinical trial in a couple of years. But, of course, things can go faster or slower than that.”
Speaking about the broader potential for seeing age-targeting drugs on the market, the Rubedo co-founder believes that the world is now ready to target aging as an intervention to treat age-related diseases.
“I think we will start seeing the first results in the next five years, including some approved drugs,” he says. “And I’m a strong believer that senolytics will play a major role in this, across multiple interventions and multiple indications.”
“In the future, those multiple interventions will open the opportunity to change the trajectory of how we age. It will take time though, there is more to learn, and we need to go one step at a time.”
Images courtesy of Rubedo Life Sciences