Fight Aging!

Here I'll point out a very high level review of the present senolytics biotech companies. These companies are all quite young, focused on various means of selectively destroying the senescent cells that accumulate with age. Animal data from mice shows that these cells are an important contributing cause of aging and age-related disease, as clearing them reverses the progression many aspects of aging and age-related diseases, while also extending life span. Senescent cells exhibit the senescence-associated secretory phenotype (SASP), producing a mix of molecules that provoke chronic inflammation and tissue dysfunction. The biochemistry of senescence is, so far as the research community has determined to date, very similar in all its important aspects in mice and humans. It is thus hoped that senolytic therapies will be the first rejuvenation treatments worthy of title.

Unity Biotechnology is way ahead of the pack: No other company is in the clinic (though Mayo Clinic has a Dasatinib + Quercetin Phase 2 trial). Unity has already completed a Phase 2 (UBX0101, failed) and they are currently conducting a new Phase 1 (UBX1325). But first is not always best - Unity's approach is somewhat crude compared to the targeted approaches of newer senolytics companies. But perhaps it will be enough. More senolytic trials are coming: Unity won't be alone in the clinical stage for long. I believe that FoxBio, Senolytic Therapeutics, Numeric Biotech, and Rubedo Life Science will be in the clinic within 12 - 24 months.

1st Gen vs 2nd Gen: Dasatinib, Navitoclax, UBX0101 were 1st generation senolytics developed by hypothesis: That existing drugs that targeted anti-apoptotic pathways might also clear senescent cells. Unfortunately, many of these 1st gen drugs have off-target effects that kill non-senescent cells, too. Now it appears the majority of the industry is focusing on 2nd generation therapies through high-throughput screens to improve selectivity. Novel targeted modalities (peptides, monoclonal antibodies, gene therapy, immunotherapy, RNA) and delivery (nanoparticles and conjugate prodrugs) are being developed as well.

Unity Biotechnology is the only senolytics company to go public so far. However, Juvenescence is planning to go public within ~6 months, at which point you will be able to own a slice of FoxBio. The current market is amenable to IPOs so I wouldn't be surprised if another senolytics company went public just before their Phase 1 trials - perhaps in the next two to three years, should markets hold up.

The majority of companies are focussing on killing senescent cells with senolytics. However, four companies have senomorphic pipelines (Senolytic Therapeutics, Senisca, Atropos Therapeutics, Dorian Therapeutics). I'm excited to see which approach will prove most effective, though I am less sanguine on the clinical prospects of approaches that merely slow senescence.

Would a second Unity Biotechnology failure have an impact on the future of senolytics? Yes and no. Unity is just one of many companies developing senolytics and their current clinical trials are only testing the earliest senolytic strategy (1st gen). There are many more senolytics companies aiming for clinical trials in the next two years and some will be testing 2nd generation targeted therapies. If UBX1325 were to fail in Phase 2 the immediate effect would be a decrease in unsophisticated capital in the senolytics space - from those who don't understand the other promising targets and modalities in development. This might be a notable amount of money in the short term but long term I am optimistic about senolytics. All it takes is one success for the floodgates to open.

Link: https://longevitymarketcap.substack.com/p/018-a-tour-of-all-senolytics-companies