The two senolytics companies profiled here employ quite different approaches to the selective destruction of senescent cells, and indeed also to the business side of the equation - which age-related conditions to tackle first, whether to build a therapy or a platform for therapies, and so forth. These are two representative companies of a much larger number of groups working in this part of the field. It isn't just biotech startups. While the longevity industry is still small enough for lists of companies to be reasonably complete, the evidence for senescent cell clearance to produce rejuvenation is now comprehensive enough and well-known enough for there to be any number of quietly invisible senolytics programs out there in the world, running inside Big Pharma entities and academic labs.
As a field of development, senolytics is in a fascinating state. The first senolytic treatment demonstrated to work, dasatinib and quercetin, is the combination of a cheap and readily accessible existing chemotherapeutic and supplement. Yet very few other approaches have yet produced published data involving greater efficacy. With few exceptions, the senolytic therapies for which we know the outcomes in animal studies result in clearance of 25% to 50% of senescent cells in the tissues in which they work the best. I don't envy those companies who must push a novel senolytic therapy through the regulatory pipeline at vast expense, only to launch it into a market in which the primary competition is dasatinib and quercetin, a ~$100 treatment that can be used off-label, and may well be just as good in most cases. The bar is unusually high for a comparatively young field of medicine.
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.
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. 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."
"We are not a senolytic company, per se. Our first and most advanced programme is our senolytic programme, but the Alembic platform that we have developed is agnostic." 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? 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."
Seattle-based Oisín Biotechnologies is creating therapies to combat a variety of age- related diseases. Their breakthrough gene therapy platform clears senescent cells in a highly precise way, with promising preclinical studies already showing significant median lifespan extension in mice. Oisín's therapy has been shown to efficiently eliminate senescent cells body-wide in multiple animal models and has demonstrated therapeutic benefit in both disease burden and lifespan. Treated mice lived 20% longer even when treatment was started in old age, and after a single treatment, senescent cell removal rates reached as high as 70%.
"The ultimate goal is to eliminate unnecessary suffering. I think that everyone who believes in the mission of longevity is striving towards this. By realizing these therapies, we can start to fundamentally change the way that humans think about aging and disease. Our approach is pretty much the exact opposite of the traditional pharmaceutical approach. With our approach, there is no drug, no poison at all - just a little program written in DNA. We've effectively taken targeting out of the realm of chemistry and brought it into the realm of information."
Oisín has seen that the effects of their therapy are comparable to transgenic mouse studies conducted by the Mayo Clinic and the Buck Institute. The company is now moving to functional studies and disease models in order to create a clinically approved therapy. They are currently working with European collaborators as well as others to develop their kidney disease clinical package and future pipeline indications.