1/ #018: A Tour of All Senolytics Companies.

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

Inspired by @ElieDolgin ’s Nature article on senolytics, I compiled a profile of all the senolytics companies in the industry.

Here’s what I learned THREAD…

2/ Senescent cells should really just be thought of as damaged cells that lose the ability to divide. Aging is only one way that cells can enter this state.

Unfortunately there is no universal biomarker for cell senescence. Biomarkers we do have can also be seen in normal cells.

3/ Senescent cells are the evil twin of cancer cells. Cancer cells divide uncontrollably. Senescent cells can’t divide. Both caused by some sort of damage.

Developing drugs for either have the same problem: How do you kill damaged cells without killing healthy cells?

4/ Unity Biotechnology is miles ahead of all other senolytics companies in terms of clinical development. They are on their 2nd clinical trial. But first is not always best. Their approach of using cancer drugs to target Bcl-xL and MDM2-p53 pathways is crude compared to next gen

5/ It seems like the majority of senolytics companies have all moved on to targeted approaches (prodrugs, nanoparticles, gene therapy) or other pathways (FOXO4-p53) — 2nd gen senolytics. But who knows, maybe Unity’s 1st gen drugs are sufficient for use.

6/ Oisin Biotechnologies’ gene therapy is the most interesting of the bunch. Scalable, flexible, repeatable targeting of p16 with a systemic gene therapy (iCasp suicide gene + lipid protein NP). High risk, high reward. They have done preclinical on mice, dogs, and NH primates…

7/ …So Oisin should really apply their therapy for dog life extension. Changing the target should be easy (it’s a gene) and they’ve already done the tox studies on dogs……Someone should be licensing this for development in pets!

8/ Many more senolytics trials are coming in 2021 - 2022. Rubedo, Senolytic Therapeutics, FoxBio, Numeric Biotech have indicated their intentions to initiate trials soon.

9/ More senolytics companies will go public as clinical development progresses. These companies will need more funding for trials. FoxBio’s parent company, Juvenescence, plans to IPO within 6 months.

10/ Majority of companies are pursuing senolytics (kill SnCs) vs senomorphics (modulate SnCs to stop SASP). I’m excited to see which approaches will work. Senolytics Therapeutics is furthest in clinical development of senomorphics.

11/ Indications: Most companies are targeting fibrotic diseases of the lungs and kidneys first. Also applications for cancer (in combination with chemotherapy). Indications do not necessarily need to be age-related. Damage —> senescent cells.

12/ I couldn’t seem to find any studies that showed extension of maximal life span through senolytics. Even the Baker 2016 paper only showed median life span increases. Many senolytics do seem to improve health span and youthful function in mice, though.

13/ Increasing median lifespan is nothing to sneeze at. There’s a pretty wide gulf between median (~80y) and maximum (~120y) lifespan in humans.

14/ Would another Unity $UBX trial failure impact the senolytics industry? Yes and no. Perhaps capital from unsophisticated investors will dry up. But there are so many other more targeted approaches being developed.

It only takes one success for the floodgates to open.

15/ Companies to watch:

Unity Biotechnology
Senolytic Therapeutics
Rubedo Life Sciences
Oisin Biotechnologies
Cleara Biotech
FoxBio
Numeric Biotech
Siwa Therapeutics
Atropos Therapeutics
Deciduous Therapeutics
Dorian Therapeutics
Rejuversen
Oncosence
Senisca