Gene therapy for liver disease: The power of protecting new ideas (Guest blog)

When Jean-Philippe Combal co-founded Vivet Therapeutics in November 2016, the gene therapy start-up had just five employees. Within two years, they had a team of 14 in France and Spain. This year, they recruited their 21st employee.

The young company has made headlines by attracting investment from several leading supporters of medical innovation, including Novartis Venture Funds, Roche Venture Funds and HealthCap, amongst others. Then, in March 2019, more big news: a €45 million deal which could ultimately lead to Pfizer buying the company for €560m.

By some estimates, this €560m valuation is a few million euro less than the value of the Barcelona starting 11 (€520m) – and that team of superstars includes Lionel Messi!

So, how could a less than three-year-old start-up with a team so small that it would be unable to organise an 11-a-side football match be so highly valued?

The answer is a combination of new ideas, a path to market, potential expansion into other disease areas – and intellectual property protection. ‘We have intellectual property and knowhow,’ explains Combal. ‘On top of that have demonstrated some strong results in animal studies and have negotiated with regulatory authorities so that we are ready to demonstrate the value of this approach in humans.’

Vivet’s mission

At the heart of the Vivet story is the vision to match cutting-edge science with an unmet medical need. The team began with a mission: to develop liver gene therapies for orphan diseases – rare conditions for which there are currently no treatments.

Their most promising product aims to treat inherited liver disorders using a novel approach to delivering gene therapy and achieving a lasting effect. The first key target is Wilson’s disease, a rare but severe condition usually diagnosed in children. In patients with Wilson’s disease, a genetic mutation disables normal copper metabolism, leading to copper poisoning.

Advances in gene therapy have opened the door to fixing the problematic gene – but this still requires clearing several technical hurdles. To succeed, Vivet would have to solve a medical puzzle. ‘When a child’s liver grows, it can double in size,’ explains Combal. ‘This can lead to the loss of expression of a protein – some of the positive effect achieved through gene therapy would be lost.’

This was an enormous challenge that required heavy R&D investment. That’s where the backing of venture funds played a vital role in helping Vivet develop its science. Combal believes the team, notably led by Gloria Gonzalez, Vivet CSO, has cracked it through a combination of breakthroughs which are unique to the company. ‘Our approach could be used to treat other diseases so such modality has value beyond Wilson’s disease,’ says the Vivet co-founder.

Protecting assets

‘We have developed unique assets, as optimised construct for our Wilson VTX-801 product, that ensure the treatment is effective in the right cells with the highest possible gene expression,’ he says. ‘And, crucially, we are also progressing on making this effect durable.’
The durability challenge is an important part of the company’s value. Payers, if the treatment is approved by regulators, want to see an effect that lasts based on either up-front payment or new payer models with annual instalments related to outcome-based clinical measures. The attitude of regulators and payers is an important element of investors’ decision-making. Vivet’s solution helps to ensure that patients could be treated more than once, if required – something that is not typically the case in gene therapy.

Deterring copycats

As encouraging as these breakthroughs may be, investors committing millions of euro need to be sure that Vivet won’t simply be overtaken by copycats before they have a chance to turn science into sales. ‘To attract funding, we needed to be in control over our own destiny; to control our products,’ says Combal. ‘This means having full intellectual property protection and freedom to operate.’

While all start-ups can face competition if another company develops an alternative solution to the problem – a new and unique way to treat Wilson’s disease, for example – it is important to have patents in place for key technologies. This is something Vivet recognised early, not only for its gene therapy but for the vector that delivers the treatment to the targeted cells.

Combal’s company also secured orphan designation in the US and EU, granting it market exclusivity of seven and 10 years, respectively. Given the long road from bench to bedside, it offers investors additional confidence that they will have time to recoup the investments made, provided the treatment passes the scientific and regulatory barriers that lie ahead.

‘Orphan designation also saves on regulatory costs,’ he adds. ‘In the EU, orphan drug status saves up to €87,000 – this is a huge benefit to cash-strapped start-ups.’

Intellectual property protection explains why a modest start-up has such strong value. And, by enabling it to attract funds from investors, it solves another challenge facing start-ups: retaining key staff. The stability offered by funding and market exclusivity, mean the company can retain people – and their knowhow – for years.

‘Without investment and long-term incentives, it’s very difficult to retain key employees in a highly-competitive environment – top people in the industry regularly receive attractive offers to move to the US,’ he says. ‘It’s vital to have a long-term vision and long-term incentives, so that we can retain another important asset: people.’

The IP environment in Europe has helped companies like Vivet turn ideas into assets that create value, jobs and address unmet medical need. This in turn attracts investment which helps to protect the company’s ideas and retain the knowhow required to convert ideas into therapies. The result could be new gene therapies in the years ahead, propelling Vivet into the Champions League of European biopharma.

Jean-Philippe Combal

Jean-Philippe Combal, PharmD, Ph.D, is Co-founder and Chief Executive Officer of Vivet Therapeutics. He has 26...
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