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IDEAS FOR SMALL CAP SHARE: Genflow Biosciences

The Hallmarks of Aging is a groundbreaking work. The 2013 paper was published in the highly regarded journal Cell.

In it, Carlos López-Otín and his collaborators, Maria Blasco, Linda Partridge, Manuel Serrano, and Guido Kroemer, provided a coherent understanding of why people age and eventually die.

Not the most uplifting of topics you would have thought – until you realize that the ‘features’ (there are nine in all) may also provide a roadmap to extending natural human lifespan.

Genflow's focus is on the Sirtuin 6 gene, which is seen as the 'main regulator of healthy ageing'

Genflow’s focus is on the Sirtuin 6 gene, which is seen as the ‘main regulator of healthy ageing’

In a sense, Lopez-Otin et al. have also constructed the intellectual framework and foundations for a fledgling longevity industry, spawning R&D-based companies such as Unity Biotechnology, Samumed, Bioage, and Frequency Therapeutics.

But as Eric Leire, chief executive of newly listed Genflow Life Sciencespoints out that the current generation of longevity companies tends to focus on just a single point of obsolescence rather than taking a holistic approach.

‘With this approach you only solved a ninth of the problem’, he notes.

Genflow’s solution addresses four of the nine attributes directly and two others indirectly (we’ve listed them at the bottom of the article).

Unlike its American contemporaries, the drug developer has chosen the less trodden path, not just settling mainly in Europe (headquartered in the UK and conducting R&D in Belgium, but with a presence in the US).

Genflow is listed on the London Stock Exchange, rather than taking the show to the Nasdaq exchange that has spawned generations of major biotech companies.

This is a very conscious strategy, says Leire: ‘It was very important for me to conquer the open field in Europe.

“We get a very generous grant, non-dilutive grants, so that’s always very attractive and better than the US. We chose the London Stock Exchange’s standard list because it is a senior market.

London’s history of investing in biotech is unmatched by Euronext [the rival mainland Europe exchange]; neither is the same [investor] expertise.’

The focus of Genflow is on the Sirtuin 6 gene, or SIRT6 for short, which is seen as the ‘master regulator of healthy aging’.

The company’s R&D efforts rely heavily on research conducted by Dr. Vera Gorbunova at the University of Rochester in the US, who also serves on the company’s scientific advisory board.

As Leire noted, solving the puzzle is unlikely to solve the puzzle by addressing just one of the hallmarks of aging.

The beauty of using SIRT6 is that it targets four factors at once. They are telomere gradient; genomic instability; epigenetic changes; and loss of proteostasis (see the appendix at the end of this article).

‘There may be two or more indirect effects’, adds Leire. “The one we have no effect on is mitochondrial dysfunction.”

Overexpression of SIRT6 has been shown to extend the healthy lifespan of mice. In humans, the goal is to find an ethical, safe and efficient delivery system for the SIRT6 gene variant found in centenarians.

Genflow will study a cluster population with Werner syndrome in Sardinia, Italy (photo)

Genflow will study a cluster population with Werner syndrome in Sardinia, Italy (photo)

Genflow will study a cluster population with Werner syndrome in Sardinia, Italy (photo)

Genflow’s work in the veterinary field with dogs is interesting at a potentially lower cost than an all-human drug.

However, the two traditional human clinical programs (GF-1002 and GF-3001) really stand out.

Both are in early stage (Phase I/II) clinical trials for the treatment of Werner’s syndrome, an inherited condition associated with premature aging and an increased risk of heart disease and cancer.

The difference between the two programs is the delivery mechanism for SIRT6: one will be intravenous, the other via dermal fibroblast (cells in the dermal layer of the skin).

Leire believes that some of the companies in the aging world have ‘set the bar too high’ for complex diseases such as Parkinson’s or osteoarthritis.

Not only are these prohibitively expensive and crowded fields, but evidence of efficacy can be difficult to establish.

The decision to focus on Werner syndrome was a very conscious one, explains Leire.

It has two very well-defined but small cluster populations – one in Japan, the other in Sardinia. So this makes the process of clinical trials simpler and easier. Genflow will collaborate with the Italian cohort.

The disease, due to its rarity, also carries with it orphan drug status that largely protects the company’s intellectual property, but could also lead to an accelerated timeline to get to market.

If the treatment can work in Werner’s syndrome, “it will allow us to change the mindset of the regulators,” Leire says.

He adds, “We’re in the best position to say, ‘Okay, you see we have data on accelerated aging’. We can also show that we can improve aging.’

The company’s further development will be supported by the London IPO, which raised £3.7m in additional funding and shares are currently listed at 12.4p.

That seems like a modest amount for such an ambitious undertaking. The group does receive very generous grants from the Belgian region of Wallonia, home of its research base.

‘If we invest one pound in R&D, Wallonia will invest another three’, explains Leire.

The partnerships here in the UK with Oxford University could also provide opportunities for grants, adds Genflow’s CEO.

You might imagine that when longevity companies start with viable products, they start to provoke a moral and ethical debate.

The issue thus far has been theoretical, or the subject of fiction.

Movies like Forever Young and Benjamin Button have grappled with the thorny issue of turning back the biological clock and have largely failed to properly tackle (not to say downplayed) the thorny problem of reversing the biological clock.

Meanwhile, wider society seems obsessed with the pressure that the boomer generation, for example, is putting on healthcare, in other words the economy.

Genflow’s argument doesn’t seem to be one about staggering towards immortality (and all the philosophical issues it brings to light).

It is about a longer and better life in old age; one that is devoid of the diseases that can make the last years of life grueling and painful.

There is also an economic benefit if the general elderly population is more vibrant in its golden years.

‘You look at the demographics; for the first time in human history there are more people over the age of 65 than people under the age of five’, says Leire.

‘Yes, the economic pressure will be unsustainable, but the quality of life is also a major problem if you are living through your last years with Alzheimer’s or undergoing chemotherapy.’

In other words, it’s not just about improving longevity, it’s about ‘health span’, ie how we can grow old healthily.

The Nine Signs of Aging

1. Telomere attrition, the gradual loss of the protective caps on our chromosomes

2. Genomic instability is the increased propensity for gene mutation, which causes diseases such as cancer

3. Mitochondrial dysfunction, when our membrane-bound cell organelles don’t work the way they’re supposed to

4. Cellular aging is the cessation of cell division

5. Stem cell depletion, which is responsible for many of the physical problems associated with aging, such as fragility and a weakened immune system

6. Loss of proteostasis, or in other words a malfunction of the cell’s protein-building machinery

7. Deregulated Nutrient Detection is an alteration in the way the body absorbs the right nutrients in the right amounts

8. Epigenetic changes are changes in the chemical structure of DNA

9. And Altered Intercellular Communication: The Change in Signals Between Cells That May Lead to Some of the Diseases and Disabilities of Aging

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