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The Hallmarks of Ageing is a seminal 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 insight into why humans age and eventually die.

Not the most uplifting of topics you’d have thought – until you realise that the ‘hallmarks’ (there are nine in all) also potentially provide a roadmap to prolonging the natural human lifespan.

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

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

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

But as Eric Leire, chief executive of newly-listed Genflow Biosciences, points out, the current crop of longevity companies tend to focus on just a single point of ageing rather than taking a holistic approach.

‘You’ve only solved one-ninth of the problem with this approach,’ he observes.

Genflow’s solution sets out to target four out of the nine hallmarks directly, and two others indirectly (we’ve listed them at the foot of the article).

Unlike its American contemporaries, the drug developer has opted for the path less trodden, not by just by basing itself predominantly in Europe (it is headquartered in the UK and carries out R&D in Belgium though does have a presence in the US).

Genflow has listed on the London Stock Exchange, rather than taking the show to the Nasdaq exchange that has bred the generations of big biotechs.

This is a quite deliberate strategy, says Leire: ‘It was very important to me to capture the open field in Europe.

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

‘London’s history of investment in biotech is not matched by Euronext [the rival mainland Europe exchange]; neither is there the same [investor] expertise.’

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

The company’s R&D effort leans very heavily into the research carried out by Dr Vera Gorbunova at the University of Rochester in the US, who is also on the company’s scientific advisory board.

As Leire pointed out, tackling just one of the ageing hallmarks is unlikely to solve the puzzle.

The beauty of using SIRT6 is it focuses on four factors simultaneously. They are telomere attrition; genomic instability; epigenetic alterations; and loss of proteostasis (see the appendix at the end of this article).

‘There are perhaps two or more indirect effects,’ adds Leire. ‘The one we don’t have an effect on is mitochondrial dysfunction.’

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

Genflow will study a cluster population with Werner Syndrome in Sardinia, Italy (pictured)

Genflow will study a cluster population with Werner Syndrome in Sardinia, Italy (pictured)

Genflow’s work in the veterinary field with dogs is interesting with possibly lower costs associated with it than a fully human drug.

However, the two traditional human clinical programmes (GF-1002 and GF-3001) really catch the eye. 

Both are in early-stage (phase I/II) clinical studies for the treatment of Werner Syndrome, a hereditary condition associated with premature ageing and an increased risk of heart disease and cancer.

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

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

Not only are these prohibitively expensive and crowded fields, but proof of efficacy can also be difficult to ascertain.

The decision to focus on Werner Syndrome was a very deliberate one, Leire explains.

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

The disease, because of its rarity, also carries with it orphan drug designation which largely protects the company’s intellectual property but can also lead to an accelerated timeline to market.

If the treatment can show efficacy in Werner Syndrome ‘it will allow us to shift the mindset of the regulators’, says Leire.

He adds: ‘We will be in the best position to say, “okay, you see we have data on accelerated ageing”. We can also show we can improve ageing.’

The onward development of the business will be aided by the London IPO that brought in £3.7million of additional funding and sees the shares trading currently at 12.4p.

This seems a modest sum for such an ambitious undertaking. However, the group does receive very generous grants from the Belgian region of Wallonia, home of its research base.

‘If a pound is invested by us in R&D, then Wallonia will invest another three,’ Leire explains.

Its collaborations here in the UK with Oxford University may also open up opportunities for grants, the Genflow CEO adds.

One would imagine that longevity companies will, as they start to emerge with viable products, begin to provoke a moral and ethical debate.

The issue to date has been theoretical, or the subject of fiction.

Films such as Forever Young and Benjamin Button have grappled with and largely failed to properly tackle (not to say trivialised) the thorny issue of turning back the biological clock.

Wider society, meanwhile, seems obsessed with the strain that the ‘boomer’ generation, for example, is exerting on the health service – the economics in other words.

Genflow’s argument doesn’t seem to be one about limping towards immortality (and all the philosophical issues this unearths).

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

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

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

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

In other words, it is not just about improving lifespan, it is about ‘health-span’, or how we can live a healthy old age.

The nine hallmarks of ageing 

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

2. Genomic instability is the increased tendency for gene mutation, causing diseases such as cancer

3. Mitochondrial dysfunction, when our membrane-bound cell organelles don’t work as they are supposed

4. Cellular senescence is the cessation of cell division

5. Stem cell exhaustion, which is responsible for many of the physical problems associated with ageing, such as frailty and a weakened immune system

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

7. Deregulated nutrient sensing is an alteration to the way the body takes on the correct nutrients in the right amounts

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

9. And altered intercellular communication: The change in signals between cells that can lead to some of the diseases and disabilities of ageing

Some links in this article may be affiliate links. If you click on them we may earn a small commission. That helps us fund This Is Money, and keep it free to use. We do not write articles to promote products. We do not allow any commercial relationship to affect our editorial independence.

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It was a tough week for Advance Energy, which slumped 86 per cent to 0.625p after it warned of potential problems at its Buffalo-10 well, offshore Timor-Leste.

The Buffalo-10 well intersected its primary target, the Elang reservoir, with early data indicating hydrocarbons are present but the project operator cautioned that ‘information to date indicates that the seismic processing techniques employed on this project have not resolved the underlying seismic velocities or imaging resolution issues that are present in this field.’

Sector peer Reabold Resources saw its shares leap 51 per cent after the investment company, which specialises in upstream oil and gas projects, announced the initial results of independent analysis of the West Newton Extended Well Test (EWT) programme in Ghana.

Best of the Best saw its shares slump 34% this week after it warned on profits

Best of the Best saw its shares slump 34% this week after it warned on profits

The study indicated the potential for initial production rates of 35.6million cubic feet of gas per day from a horizontally drilled well situated in the gas zone, based on the data from the West Newton A-2 well.

It also indicated potential initial production rates of 1,000 barrels of oil per day from a horizontally drilled well situated in the oil zone.

88 Energy Ltd was wanted after it said it is on track for a February spud at the Merlin-2 well on Alaska’s North Slope.

The announcement allayed fears raised by reports than a protest group, the Center for Biological Diversity, had communications with the Bureau of Land Management in relation to the permit to drill.

The shares, some of the most volatile in the small caps space, rose 42 per cent on the week.

Helium One Global headed 48 per cent higher this week after a multispectral satellite spectroscopy study identified multiple additional surface helium anomalies at the explorer’s Rukwa, Eyasi and Balangida project areas.

A production update from Bluerock Diamonds sent the company’s shares 31 per cent northwards.

The AIM-listed diamond producer, which owns and operates the Kareevlei Diamond Mine in the Kimberley region of South Africa, produced 6,866 carats in the final quarter of 2021, up 44 per cent year-on-year, and sold 6,980 carats, up 3 per cent.

Thanks to the value per carat soaring by 64 per cent, fourth-quarter revenues rose 68 per cent to $3million from $1.8million the year before.

Away from the resources sector, Brave Bison Group charged ahead following a strong trading update.

The digital media and social video broadcaster said full-year results will be ahead of current market forecasts.

The shares shot up 31 per cent after the company said revenues and viewing numbers across the company’s advertising network have been robust, while Brave Bison’s agency won several new customers during the final quarter of the year.

Diversified UK entertainment business The Brighton Pier Group provided some post-festive cheer with its trading update covering the 26 weeks to Boxing Day.

Trading in the period was described as ‘extremely robust’ and while there was some impact in December due to the lockdown restrictions, over New Year the bars recovered their momentum, trading 9 per cent up on 2019.

The shares galloped 18 per cent higher as management said the group is in a strong position to deliver a good result for the year, comfortably in line with market expectations.

Digital media and social video broadcaster Brave Bison said full-year results will be ahead of current market forecasts

Digital media and social video broadcaster Brave Bison said full-year results will be ahead of current market forecasts

ReNeuron Group shares halved after it released ‘inconclusive’ results from its hRPC phase IIa trial in people with a degenerative eye disease called retinitis pigmentosa.

The company said it would now focus on the commercial potential of its exosome technology and out-license its human retinal progenitor cells (hRPC) programme.

In general, it has been a good time of late to be a recruiter but not so for Gattaca, the company formerly known as Matchtech.

Its shares lost just over a third of their value after the recruitment firm, which concentrates on the engineering and technology sections, issued a profit warning on Tuesday.

The group said the recovery of its contract business had been slower than anticipated. The contract side of the business typically generates three-quarters of the group’s net fee income.

2020, when Best of the Best was one of the year’s best performers, seems a long time ago as the weekly online competitions firm saw its shares slump 34 per cent after it warned that cost of acquiring new players had risen sharply in November and December.

Costs of acquiring new players in those months were roughly 37 per cent above the preceding six-month average, although early indications are that costs are trending back towards the mean.

Another company disappointing with its trading update was Eve Sleep, which describes itself as a ‘sleep wellness brand’.

The mattress seller – sorry, sleep wellness brand – said in the Christmas trading period high levels of Covid infection placed additional strain on the delivery network resulting in ‘customer service challenges’, which presumably meant ‘sleep wellness products’ (mattresses) not arriving at customers’ houses in time for Christmas.

‘We believe these challenges will be short lived and reflect the current peak of absence due to illness across the delivery network, and hence foresee customer experience returning to our usual high levels over the next few months,’ the company said.

Some links in this article may be affiliate links. If you click on them we may earn a small commission. That helps us fund This Is Money, and keep it free to use. We do not write articles to promote products. We do not allow any commercial relationship to affect our editorial independence.

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Angus Energy PLC jumped 46 per cent to 0.95p this week after it put itself up for sale.

The company said it has had a series of approaches from parties interested in buying some or all of the company’s 51 per cent interest in the Saltfleetby Gas Field asset. One approach led to a non-binding offer that is under consideration. Additionally, the board has received indications that certain parties may be interested in making an offer for the company.

The board has now determined to undertake a review of the company’s strategic options, which include a sale of the company.

The exotically named t42 IoT Tracking Solutions PLC – the IoT bit stands for ‘Internet of Things’ but what the t42 bit means is anyone’s guess – leapt 38 per cent to 22p after the company signed a five year US distribution contract to provide container tracking solutions for OpenBox Ventures Inc.

Market boost: Angus Energy is an onshore oil and gas operator whose share price jumped 46 per cent to 0.95p this week after it put itself up for sale

Market boost: Angus Energy is an onshore oil and gas operator whose share price jumped 46 per cent to 0.95p this week after it put itself up for sale

OpenBox distributes cutting edge technologies across the US security industry ensuring the integrity of goods transported in shipping containers.

‘The contract with OpenBox reflects our new strategic focus on the global shipping container market,’ said Avi Hartmann, the company’s chief executive officer.

Another nautical contract win was behind the 32 per cent rise in the share price of SRT Marine Systems PLC , the maritime domain and coastal surveillance and monitoring systems provider.

The company said its SRT-MDA System project has been adopted by a national coast guard; that’s an organisation, not just one person in a swimsuit.

The contract award is for the first of three phases of a project worth a gross total of £40million.

DigitalBox PLC, the digital media business that owns Entertainment Daily, The Daily Mash and The Tab, said all three brands traded better than anticipated in December.

The share price increased by around one-third as the company revealed that revenue and underlying earnings (EBITDA) for 2021 are expected to be significantly ahead of market guidance issued just a month ago.

Blue Star Capital PLC  was one of the week’s top performers, rising 34 per cent to 0.535p but no one seems to know why, not even the board of the investment company, which put a stock market announcement saying it knew of no reason for the recent rise in the share price.

Hornby, the company that makes the eponymous train sets as well as Airfix models and Scalextric racing kits, was given a leg-up by the news that Henry de Zoete, ‘an entrepreneur and alumnus of renowned Silicon Valley start-up accelerator Y Combinator’, is joining the board as a non-executive director.

New gear: Scalextric racing maker Hornby will see Henry de Zoete joining the board as a non-executive director. Pictured: A special edition Only Fools and Horses-themed Scalextric set

New gear: Scalextric racing maker Hornby will see Henry de Zoete joining the board as a non-executive director. Pictured: A special edition Only Fools and Horses-themed Scalextric set 

‘Hornby, Scalextric, Corgi, Humbrol and Airfix are all incredible, heritage brands that I grew up with. I am really excited to give strategic input as the brilliant team focuses on digital transformation and growth, to build the business for generations to come,’ De Zoete said.

The shares chugged 31 per cent higher to 54.5p.

M&C Saatchi PLC, the advertising group, confirmed it received a preliminary approach from an investment vehicle connected with its deputy chairman, Vin Murria. The statement came in response to press speculation.

AdvancedAdvT Limited confirmed on Friday it is interested in exploring a share exchange merger with M & C Saatchi, which would be a reverse takeover.

The likelihood that there will not be a cash offer took some of the gloss off the week’s gains for Saatchi but the shares still rose 16 per cent this week to 194p.

Faron Pharmaceuticals Ltd announced the appointment of Marie-Louise Fjällskog as its chief medical officer with immediate effect.

The news sent the shares 10 per cent higher to 161p.

Caspian Sunrise PLC lost around a quarter of its value this week as it confirmed it had decided to temporarily suspend its drilling and production activities in response to the ongoing political uncertainty in Kazakhstan.

Another stock hitting the skids was UniVision Engineering Ltd, the Hong Kong-based surveillance systems specialist, which is embroiled in what looks like a nasty dispute with one of its sub-contractors, T&P Solutions.

UniVision said T&P has submitted a winding-up petition to the High Court in Hong Kong, alleging outstanding debts owed by UniVision of HK$5,955,760, which is roughly £565,280, in relation to contractual agreements.

As is often the way of these things, not only is UniVision contesting the petition it is considering making a counter-claim against T&P for breach of contract.

The company lost a fifth of its value with the shares slumping to 0.6p.

Some links in this article may be affiliate links. If you click on them we may earn a small commission. That helps us fund This Is Money, and keep it free to use. We do not write articles to promote products. We do not allow any commercial relationship to affect our editorial independence.

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OptiBiotix is a pioneer of probiotics and prebiotics that work synergistically with the human microbiome, the ecosystem of bacteria found largely in the gut. Its discoveries have been or are being developed to tackle obesity, cardiovascular disease, inflammation and diabetes, stress and anxiety.   

Stephen O’Hara always had a clear vision for OptiBiotix Health, even if investors had a lot to learn about the commercial potential of the human microbiome and the challenges of taking new products, with new technologies, into new markets.

The plan was to get the company’s first innovative pro- and prebiotics out of the lab and onto the market in as quick and effective a manner as possible.

Having achieved his goal – and then some – the strategy going forward is to build on this momentum with a second generation of microbiome-focused fibres, modulators, and treatments.

Trailblazer: OptiBiotix is a pioneer of probiotics and prebiotics that work synergistically with the human microbiome, the ecosystem of bacteria found largely in the gut

Trailblazer: OptiBiotix is a pioneer of probiotics and prebiotics that work synergistically with the human microbiome, the ecosystem of bacteria found largely in the gut 

‘We believe the company is at an interesting stage, demonstrating strong early revenue momentum and divisional profitability and early commercial traction with its second-generation platforms,’ said the company’s broker Cenkos in a note initiating coverage of the group.

O’Hara concurs: ‘I think we are at a very exciting stage in our development as we now focus on delivering revenue and margin growth rather than developing a pipeline of products.’

Before looking at what lies in store for OptiBiotix, it’s worth assessing the considerable progress made to date.

The first-generation products and ingredients for weight management, nutrition and cholesterol reduction are available in 160 countries around the world via distributors, supplement makers and retailers.

Financially, the group is starting to make real headway. In 2020, revenues doubled, albeit to a comparatively modest £1.5million. In the six months after, sales were £1.1million (analysts expect the company to turn over £2.2million for the full-year).

‘For context, our products have only been on the markets for around two years,’ O’Hara says, pointing out that each of the company’s trading divisions is profitable.

With a strong recurring revenue base and some big contracts kicking in, including recent deals with Nahdi Medical Co and Apollo Hospitals, momentum is starting to build. The commercial push will be aided by new products, including the sports nutrition line called MyProtein.

OptiBiotix’s success to date has based around innovative technologies such as SlimBiome and LPLDL.

The latter is a Lactobacillus plantarum probiotic that has been scientifically and clinically validated to reduce cholesterol.

Indeed, studies show its performance stacks up favourably against statins in the way it reduces ‘bad cholesterol’ and its impact on atherosclerosis (furring of the arteries).

This know-how, which carries 28 patents and 15 trademarks, has been fashioned into CholBiome cardiovascular range. Indeed, the company’s science-led approach to developing its platforms and products has generated eight peer-reviewed articles and 17 poster abstracts presented at major international conferences. Meanwhile, SlimBiome, its functional weight management ingredient, has won multiple awards.

Looking forward, the group has pledged to increase marketing investment to support sales growth of SlimBiome and CholBiome, alongside moves into adjacent markets such as healthy ageing and sports nutrition with products WellBiome and LeanBiome, respectively.

Major customer: OptiBiotix is supplying Holland & Barrett here in the UK as well as international pharmacy chains Nahdi Medical and Apollo Hospitals

Major customer: OptiBiotix is supplying Holland & Barrett here in the UK as well as international pharmacy chains Nahdi Medical and Apollo Hospitals 

OptiBiotix’s strategy was to build brand recognition its LPLDL and SlimBiome ingredients through a business-to-business model.

However, it is now using its award-winning ingredient brands in finished products and in doing so is capturing more from the value chain.

It is supplying Holland & Barrett here in the UK as well as international pharmacy chains Nahdi Medical and Apollo Hospitals. It has also developed its own range of ‘GoFigure’ branded shakes and breakfast cereals.

Building on this first wave of products, what comes next should excite investors.

‘We have a second generation that I think is highly innovative,’ says the OptiBiotix CEO.

The first cab off the rank is a prebiotic sweetener with a clean flavour (no after-taste or off-notes), that is low-calorie and has a positive impact on the microbiome.

In September 2020, the company inked a manufacturing and commercialisation agreement with an unnamed US company for a number of the SweetBiotix products derived from this novel fibre.

It receives an annual six-figure licensing fee, milestone awards and royalties on future sales.

‘Annual licensing fees and milestone payments are highly unusual in the food and nutraceutical industry, so this gives an indication of the potential value of SweetBiotix to partners,’ O’Hara points out.

Beyond this, it is looking to team up with food and beverage firms and flavour houses, not just in the fizzy drinks space, but also in dairy and snacks.

In a separate foray, OptiBiotix is moving into drug development with an unnamed US partner and a separate tie-up with Seed Health. Seed has received US regulatory approval to embark on a clinical trial of DS-01, a probiotic containing LPLDL, which will be assessed as a potential treatment of irritable bowel syndrome.

Earlier in the pipeline are microbiome modulators that target specific gut and skin microbes and metabolites to support health and wellbeing.

Specifically, the company has developed techniques that allow it to create prebiotic ingredients that selectively enhance the growth of target microbial species.

‘Given the growing association between the microbiome and a wide range of diseases such as cancer, autism, diabetes and obesity, the ability to selectively manipulate the microbiome represents an attractive opportunity,’ said Cenkos in its note.

As the broker’s analysts point out, the second generation of innovative products bring with them a higher risk profile – but then this is more than matched with the potential rewards associated them.

What should be stressed is that OptiBiotix is not flying by the seat of its pants embarking on the next stage of its journey.

It has an established and growing revenue base from its initial commercial efforts – 85% of which is recurring, according to O’Hara.

At the same time, the group is financially resourced to meet its obligations.

It has previously raised money from the sale of shares in sister business Skinbiotherapeutics, in which it retains a 23.1 per cent stake. This holding effectively provides a source if non-dilutive funding if required.

It’s worth pointing out that OptiBiotix has received just over £8million to get to a market cap of around £41million, but, as noted above, is essentially self-funding.

Cenkos, using a sum-of-the-parts model, values the company at £160million.

Even if you think the company’s broker is being over-optimistic with its assumptions, it’s hard to explain OptiBiotix’s current discount market capitalisation given the operational and commercial progress made.

Perhaps the OptiBiotix’s potential will be recognised as the year unfolds.

‘With seven high profile large corporate, retail, and pharma partners in multiple territories, expanding product ranges and territories, a greater focus on direct-to-consumer, and greater investment in sales and marketing, 2022 should be a year of strong growth,’ O’Hara says.

Some links in this article may be affiliate links. If you click on them we may earn a small commission. That helps us fund This Is Money, and keep it free to use. We do not write articles to promote products. We do not allow any commercial relationship to affect our editorial independence.

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