Getting comfortable with senotherapeutics

UNITY Biotech’s CEO on data that builds conviction and pioneering novel treatment paradigms.

UNITY Biotech is a company working on therapeutics to slow, halt or reverse diseases of aging. With an initial focus on age-related eye diseases and neurological conditions, UNITY is in the happy position of having recently announced positive results from the long-term follow-up of its Phase 2 BEHOLD study of UBX1325 in patients with diabetic macular edema (DME).

Longevity.Technology: We sat down with Anirvan Ghosh, the CEO of UNITY Biotechnology to find out more about UNITY’s recent trial and its results, what’s next for the company and what excites him about the senotherapeutic space.

Anirvan Ghosh on…

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The fundamental concept behind senolytics applies to diseases across the body; there’s a accumulation of senescent cells in many tissues and organs. That was what got me interested in UNITY – that broad promise that we could develop senolytic therapies that would have impact across diseases.

We also felt it was important to show proof of concept – that targeting senescent cells can provide therapeutic benefit. We needed to find a disease and an organ system where we could demonstrate that, and eye diseases turned out to be really good place to work – we had seen evidence that there is accumulation of senescent cells in eye diseases like AMD and DME and we had a wealth of preclinical evidence that suggested that elimination of senescent cells could restore tissue health in the eye.

After a single injection of UBX1325, our lead senolytic molecule, remarkably – and this is just two week old news – 48 weeks out, patients had gained about six-and-a-half letters compared with where they started and over half the patients did not need any other injection during that entire period. Importantly, there were patients who were moving from non-driving vision into driving vision, which in terms of their function, has a huge impact.

Modifying disease

The impact of durability is more than just patient convenience. The mechanism works by removing senescent cells and restoring the health of the vasculature of the eye, bringing it to a better state. We believe that this could represent potential for disease modification – so over time, the fact that you need fewer injections reflects the fact that you have modified the course of disease, and are maybe getting better.

This is part of the core mission of UNITY – to provide therapies like this. And this is in contrast with an anti-VEGF, which not only has a heavy treatment burden, but the underlying disease continues to progress.

Pioneering treatment paradigms

It’s a tough market out there! It’s hard to raise money as a small cap public company… I’m learning that there is this added element of “what it takes to get public investors comfortable with a new concept. We’re really talking about pioneering never-before-seen treatment paradigms, and for most people – even in the industry or in the investor community – what a senolytic agent is or what it might do is quite foreign. There aren’t a bunch of senescent companies out there! UNITY was really far ahead in deciding to target senescence as a way of affecting age-related diseases.

We need to continue to develop strong, compelling clinical data and I believe the data we just released is going to create a lot of confidence, both with the markets and potential partners; as we develop these agents and go into late stage, I think partnerships with other larger pharma companies or biotech companies is going to be critical. We need to deliver the kind of data sets we have to build conviction, and then people will look back and appreciate that we saw that this drug was doing something way back when.

Potential for success for senotherapeutics

It’s still early days, but it’s a very exciting phase in the growth of senescence-directed therapies.

In the next few years, I think we’ll see new ways of targeting senescent cells; among the approaches that I find particularly interesting is looking to see if one can reprogram senescent cells . Senescent cells secrete damaging factors, causing havoc in the tissue, so those approaches that reprogram it so the senescent-related factors are not produced are very excited.

Also, approaches that arm the the immune system or engineered cells to go hunt senescent cells are very interesting. Can we identify, target and eliminate them specifically? That would be a very exciting development!

Photograph: Freepik