13 December 2023
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Singapore startup VVB Bio promises a dramatic reduction in ageing via a single jab. Now out of stealth mode, its founders reveal the science behind their breakthrough.

Forward: features are independent pieces written for Mewburn Ellis discussing and celebrating the best of innovation and exploration from the scientific and entrepreneurial worlds.

The villain of this story is a single cytokine called IL-11. In the mammalian body cytokines are used by the body to send signals. IL-11 seems to be a rogue operator.

‘We found it by fluke,’ says Stuart Cook, co-founder of VVB Bio. ‘We made a serendipitous observation six years ago while profiling a mouse as a control. It showed high levels of a protein called interleukin 11, or IL-11. We discovered it is basically a disease protein. It causes badness wherever it is.’

The cytokine appears to tell organs to age: ‘What we’ve found is that as we age, in both mice and humans, the amount of IL-11 goes up. It causes diseases in tissues. It causes fibrosis. It causes your kidneys to stop functioning properly. Stops your hearing working, your sight, your hair to go grey and you to lose your hair. All the things that happen when you age.’

The solution? Deleting the IL11 gene in mice using the CRISPR gene editing tool eliminates the associated cytokine. For those of us currently alive, an injectable treatment is possible: ‘We are creating an antibody treatment,’ says Sebastian Schäfer, VVB Bio co-founder. ‘You’ll be able to have a jab once every six months. The antibodies bind to IL-11 and switch it off. This removes all the bad effects of it in your body’

 

VBB Bio - Sebastian Schafer VBB Bio - Stuart Cook
Sebastian Schäfer, VVB Bio co-founder Stuart Cook, VVB Bio co-founder

 


This is a serious claim. A single cytokine is contributing significantly to ageing in multiple organs. And a straightforward antibody or gene therapy can inhibit IL-11-mediated signalling to reduce the speed at which the body ages and age-related diseases. The impact is dramatic. The attrition of telomeres – which cap the end of the DNA helix and which degrade over time – is curtailed. Mitochondrial function is preserved.

Quality not quantity

The idea raises questions asked since the ancient Greek historian Herodotus first wrote of a fabled Fountain of Youth supposedly hidden in the Horn of Africa: can ageing truly be slowed?

Both Cook and Schäfer wince at the analogy. ‘There are a lot of people peddling eternal youth!’ says Cook. ‘We are very careful not to do that. We are focused on health span, not life span. It’s about the quality of your health during your life, not the total number of years that matter.’

When pushed for a clarification of what treatment means for humans, Cook offers this metric: ‘Your age can be measured in two ways. There’s your age in weeks or years since you were born. That is your chronological age. And there’s your epigenetic clock. If you are, say, a 47-year-old who smokes, drinks, raves and barely sleeps, you might have an epigenetic age of 57. If you are a 47-year-old who eats carrots, sleeps well and goes for a run every day, you might have a biological or epigenetic age of 42. We can measure the epigenetic age of mice and humans.’

So they ran a test.

‘If we take two groups of mice, one given a placebo, the second with the IL11 gene deleted by genetic modification, we can compare them after two years of life. The modified mice are an estimated 55 weeks younger in epigenetic age. They are ageing less than half as fast as normal mice.’

He waits for this to sink in. ‘It’s a really massive reduction.’

There are other ways of measuring the impact of inhibiting IL-11. Schäfer says: ‘We did experiments to look at frailty in mice, examining at how well they grip. We took 75-week-old mice. If we administer the antibody and look again at 100 weeks, ageing has slowed.’

A variety of health indicators buttress the claims. Serum cholesterol and triglyceride levels are lowered. Pro-inflammatory fatty acid synthesis falls. Normally serum alanine aminotransferase and aspartate aminotransferase levels, markers of liver damage, are elevated in old mice, but not in those with inhibited IL-11.

‘We measured the weight of the thymus in mice,’ says Schäfer. ‘As you know, the immune system depends on the activity of the thymus. In human terms, if you gave the antibody to a human aged 50 and checked on them when they were 70, the thymus would be in the same condition. It is literally arresting the effects completely, at least in mice.’

The results are likely to be replicated in humans. ‘We see a one-to-one relationship between mice and humans for all things IL-11,’ says Cook. ‘We would expect to see, when IL-11 is inhibited, all the same effects. Less age-related obesity, better retention of muscle mass, joints are better, heart is better, sight is better, you are less grey, you lose less hair.’

These claims will be challenged, as all research must be. The longevity industry is replete with remarkable claims that fail to be replicated. Schäfer and Cook are ready. ‘We’ve put our findings in a paper and it’s out for review with one of the best scientific journals there is. People have seen our work and understood it. The claims are bold. But we are merely reporting the data. We understand the mechanisms at work.’

The credentials of the team at VVB Bio are beyond reproach. Cook is a professor at Imperial College London and Duke-NUS Medical School in Singapore. He has a distinguished career researching and publishing in the field of the genetics and genomics of human cardiovascular and metabolic disease. Schäfer is an assistant professor at Duke-NUS. The team includes Andrew Khoo. ‘We have a previous company that we started together,’ says Schäfer. ‘It’s called Enleofen Bio. We developed antibodies to treat fibrotic diseases.’ Like VVB Bio, Enleofen Bio is based in Singapore. In 2020 they partnered with biopharmaceutical giant Boehringer Ingelheim, which announced in May 2023 that the programme had entered into clinical development.

When pushed to quantify his excitement about this discovery, Cook says, with a huge smile: ‘Seb and I are first in the queue for the antibodies!’

The timeline

VVB Bio has been working on IL-11 and ageing projects for three years. Manufacturing the antibody will begin next year and clinical trials should commence in 2025. So roughly at the end of the decade, all being well, an anti-ageing antibody treatment for IL-11 could be commercially available.

‘We’ve got to make sure it’s safe,’ says Cook. ‘You don’t want to start taking a treatment and your ear to fall off. We’ll go through the clinical trials to ensure there are no significant downsides.’

Their intellectual property position is strong. VVB Bio works with Mewburn Ellis on IP strategy. ‘We’ve worked with Mewburn Ellis for a long time,’ says Schäfer. ‘It has been our go-to specialists for everything related to IP, including for our previous company, Enleofen Bio. We are super happy with the work Mewburn Ellis has done for us.’

The implications

If inhibiting IL-11 is reliably shown to slow ageing across multiple organs in humans, the effects could be profound. Pension funds, for example, could be underfunded as pensioners live beyond anything forecast on actuarial tables.

Schäfer and Cook talk down the ramifications. ‘It isn’t certain this necessarily changes lifespan,’ says Cook. ‘It is better to live a healthier life until a ripe old age and then crash at the last moment, than suffering and not being able to get out and about. Longer life is not what we are working on. What kills humans is cardiovascular disease, two-thirds; and cancer, one-third. You’d have to improve these to extend life.’

If anything, improved health spans could shorten the retirement period as workers stay in the workforce longer, opting to delay their pension age to swell the financial pot waiting for them.

The pair are sceptical about the attractiveness of other longevity approaches. ‘There’s rapamycin,’ notes Cook of a macrolide compound, also known as sirolimus, which has been consistently shown to improve life spans in mammals, in particular mice. ‘It might make you live a little longer, but it might just make you miserable as it doesn't improve your health span. That extra time comes at a cost.’

He’s also dubious of supplements. ‘Vitamin C, vitamin B, vitamin D have all failed in clinical trials. Other things hit only a single part of the ageing process rather than multiple aspects. We are trying to slow the ageing process itself, everywhere and all at once. I’m not aware of anything out there that comes near to what we have in IL-11.’

A philosophical question is why IL-11 exists. Why would the body possess a cytokine that degrades the performance organs? ‘It makes a lot of sense, from an evolutionary perspective,’ says Schäfer. ‘Our genetic code is not optimised for making us super long-living happy people. In the end, if you are not useful for reproduction, it doesn’t make sense for you to stay around.’

Cook likens the dynamic to that of octopus and salmon. ‘The salmon swims up the river, lays eggs and dies, so the nutrients enrich the water where the babies grow. The female octopus retreats to a little cave, has her offspring, then undergoes a programme of senescence, ageing within a matter of weeks before dying so the young have something to eat.’ It is possible IL-11 operates on the same logic. As Steve Jobs put it, shortly before succumbing to pancreatic cancer: ‘Death is very likely the single best invention of life. It’s life’s change agent. It clears out the old to make way for the new.’

And there’s more…

The world’s press adores stories of long life and miracle cures. VVB Bio is set to generate enthusiastic headlines.

Schäfer and Cook have a teaser to add to the drama: ‘We are working on two other programmes, which we haven’t talked about yet. We believe each is equally as exciting as this current one.’ No further clues are forthcoming.

On current evidence VVB Bio has more than enough to be working on with its current project. A treatment that slows ageing, and can even reverse damage in organs such as the thymus, is as appealing as it is profound.

Now VVB Bio has exited stealth mode and revealed its findings, competitors will enter the space. The race to market has begun. The clock is ticking on health span and longevity treatments.

 

VBB Bio - MiceUntreated and treated

These two mice are both 100 weeks old. The mouse on the left received a placebo, the mouse on the right had IL-11 deleted at the embryo stage using CRISPR. The treated mouse is visibly youthful. It is thinner, with a glossier coat, and has greater muscle mass.

The improvement is significant. In female mice body weight is 27% lower, fat mass 72% lower along with preserved lean mass, compared with mice given a placebo. Frailty scores improve including improvement in gait disorders and balance, and muscle strength. Fasting blood glucose concentrations are lower in treated mice, even in young adulthood. Inguinal subcutaneous white adipose tissue masses were reduced 61%.





Living better

Adam Gregory, Partner and Patent Attorney at Mewburn Ellis comments:

"VVB Bio’s technology is extremely exciting, and we’re very proud to be working with Stuart and Sebastian on this fascinating new venture.  The rapid growth in the field of longevity technology reflects changing attitudes to life and disease. People don’t want to live forever, but they do want to live better for a larger proportion of the time they have.”

 


 

Written by Charles Orton-Jones

Featured image source: http://www.scientificanimations.com/wiki-images/

Adam is a Partner and Patent Attorney at Mewburn Ellis. He works with biotech companies to build and manage their patent portfolios, drafting patent applications and co-ordinating prosecution worldwide. Adam has particular experience handling portfolios relating to therapeutics (particularly immunotherapies, including adoptive cellular therapies), antibody technology, diagnostics, and regenerative medicine.
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