Profiles of Two Senolytics Companies with Quite Different Approaches

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.

Rubedo Life Sciences: Senolytic start-up gears up for clinical trials

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."

Oisín Biotechnologies: Promising restorative therapy potentially 5 years away

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.

Comments

Disclaimer: I have never been a principle in a publicly traded company, and am not familiar with the downsides of going public. That said, I think there is a lot of money in the equity markets for biotech startups, and that most rejuvenation companies would be better off going the UBX route and going public asap rather than going through multiple rounds of private equity seed funding.

Posted by: JohnD at January 29th, 2021 7:05 PM

Dasatinib and quercetin gets mentioned a lot here. My relative in the early stages of dementia got a prescription for Dasatinib off label from an anti aging doctor. He used D&Q within on/off cycles at the recommended dosages for about 3 months. Results - his mind continued to degrade. A year later, fortunately, he was able to get ahead of the disease by using an exercise bike using HITT.

Posted by: Brian at January 30th, 2021 5:00 PM

Great to hear that your relative is benefitting from HIIT exercise. I am a 74 year old man who has always hated long endurance training. I have found HIIT on a recumbent bike raises my heart rate and can monitor how effectively it returns to a reasonable rate (preferable 40 beats below peak within 2 minutes). Less time needed and much less expensive and possibly dangerous pharmeaeuticals.

Posted by: Lawrence Rosen at January 31st, 2021 10:34 AM

Many readers of this blog understand from the data available so far that the best course of action seems to be to first remove the senescent cells enabling better response to NAD increasing therapies. You need the NAD. HITT training is an excellent way to increase NAD, more so with less senescent cell burden.
https://www.lifespan.io/news/exercise-reverses-age%E2%80%90related-decline-in-nad-salvage-capacity/
article on clearing senescent cells before nad therapy:
https://www.liebertpub.com/doi/full/10.1089/rej.2019.2218

Posted by: august33 at February 1st, 2021 8:21 PM

Dasatinib is prescription drug only and in my jurisdiction you be can get 8 years term in jail if your physician prescribe it to you for other use than registered illness. The same if customs snail it at the border. So if IV phase clinical trial will be completed in around 20 years or more, from the point of view of 50 years old... it will be NEVER. So instead lets talk about cheaper and safer and even broader range anticancer substances/senolytics and their enhancers that are available NOW. Like fisetin (now 15$ a dose, but comparing its cost of making to quercetin it should be 0,10$ a dose), wogonin (no one refines it so no cost :<, but it sould be no more than 2$ a dose), luteolin (6$ a dose, but I recently purchased it locally for 2$ a dose), AHCC (12$ a dose), tyrosinase from Agaricaceae (quercetin activates it) (1$ a dose), etc. and you get 'good enough' senolytic at 20$-30$ a dose at most. Indeed, very little money to make a fortune in startup space... unless you sell it to sizeable part of the population of the world, you probably won't recover your costs.

Posted by: SilverSeeker at February 2nd, 2021 8:58 AM

@SilverSeeker
If Dasatinib worked that well the (il) legality wouldn't be stopping anybody. The senecent cell burden is higher after 65, so faced with some potential charges vs suffering in a decrepit state there will little consideration , provided the medicine works.

As for the pricing, Dasatinib has a bunch of patents that expire in a few months and a a bunch of others that expire in a few years. There were estimates that the production costs curious be a couple of dollars per dose. Still quite high compared to medication such costs a dollar the while bottle. In fact of it is not medical grade certified it can be found for as low as 200nusd per kg. Of course, caveat emptor.
Fisetin seems to be expensive but can be found in bulk powder much cheeper than the pills. Ironically, it might end being more expensive than generic Dasatinib.

Having said that I want to start that you don't want Dasatinib in its current form. It is a very blunt tool. Line capet and napalm bombing. As a cancer drug it is an ok trade-off. But for general use we need quite compelling evifrnve. A pro-drug modified form similar to what was studied with Naviticlacs could release near the senecent cells , at least the ones having the most notorious and studied marker , beta-galactosidase( almost impossible to type on a phone). That would be probably orders of magnitude better targeted and could be much more efficient and safer at the same time.

I would call these the second generation senolytics.

So you want the second or event the third generation of senolytics.

I have high hopes on OISIN but they have been silent for quite a long time

Posted by: Cuberat at February 4th, 2021 9:04 PM

fisetin is so costly 'cause it's market is very tiny (I must import it from US across 'the pond' ;/) and refined form rhus family (which is poisonous so refining it to >98% costs a lot). Refined from cotinus coggygria (which is not poisonous) to 80-90% purity, cost should be magnitude or two lower than quercetin is now (uncomparable abundance of raw material, wood and leaves versus flowers only). And dasatanib expiring patents is what drives the research push to find the new uses - every will be covered by a new patent. It's just marketing noise. By checking herbs that I was trying with psoriasis one time or the other I was able to find half a dosen potential combination candidates that might work even better... then there must be hundreds and hundreds of them waiting nearby. Just no tools available at the moment to check which works at all and works better than the other, outside of checking which combination is causing psoriasis flare (like heavier flu every time due to increased apoptosis), and how much TGFBeta get lowered with naringin and kaempferol by checking if I can withstand the previous dose or do I must lower it :<<).
And the safety concern with dasatanib is the most important - you need a doctor to monitor your health while taking it.

Posted by: SilverSeeker at February 9th, 2021 7:56 AM

They are trying to develop products that slow down aging when we already have the means. Exercise creates longer telemeres and supports NAD levels. And fasting creates autophagy. The only problem is that people are too lazy to do either one. There are also a myriad of other things to slow down aging such as cold water therapy etc. But, people want a pill.....it's sickening!

Posted by: Bert Convo at April 12th, 2021 1:41 PM

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