The late Sir David Jack knew a thing or two about respiratory drugs.
Throughout the sixties and seventies, in their small lab on the outskirts of North London, Jack and his team developed a number of drugs that would go on to rake in billions of pounds for Glaxo.
Ventolin was the researchers’ first, and probably biggest, success – a bronchodilator that helps open up the airways in the lungs, particularly in asthma and chronic obstructive pulmonary disease (COPD) sufferers.
In fact, the drug remains one of the most prescribed medicines in the US to this day, racking up sales of almost US$1bn in 2018, half-a-century on from its initial discovery.
After a string of other successes, including salmeterol and fluticasone propionate, the two key ingredients used in GSK’s blockbuster Advair inhaler, Jack officially hung up his boots 1987.
RPL554, AKA ensifentrine
Verona is developing ensifentrine – previously known as RPL554 – in three different forms: a nebulized version which is inhaled through a mouth piece, a dry powder inhaler and a metered-dose inhaler.
In clinical studies so far, the drug has shown that it can ‘significantly improve’ lung function and symptoms, such as breathlessness, both on its own and as an add-on therapy for COPD.
“There is no question that this drug works,” says chief executive Jan-Anders Karlsson.
“It is effective as a standalone treatment , but more importantly for patients who have tried everything else, those who urgently need novel therapeutics, we believe ensifentrine can help them.”
Less competition for nebulised version
Mid-stage studies for the two inhalers are under way, but although this market is big – more than US$9bn a year according to recent industry data – Karlsson, a former Astra man, is most excited about the nebulized version.
Not only is there less competition in this space, but this formulation has been shown to help those patients with particularly bad COPD.
Those people, who tend to be older, prefer this form of the drug as they can sit in their homes, take their mouthpiece and gently breathe in the mist for a few minutes in the morning and again in the evening.
Even a slight hiccup in a small phase II study earlier in the year, which paired ensifentrine with another commonly used COPD treatment, Stiolto Respimat, hasn’t dented the boss’ enthusiasm for the drug.
“I think we were a little unfortunate,” he says, pointing to the fact that, although, the combo did not improve breathing by a ‘statistically significant’ amount on the morning of the third day – the trial’s main goal – patients did register ‘statistically significant improvements’ come the evening.
“We are now studying ensifentrine in 400 COPD patients for a month, to demonstrate that this really is a good medication.”
Phase III slated for next year
That longer phase IIb trial of nebulised ensifentrine kicked off in early May and will help researchers figure out the optimum dose, with results due towards the end of the year.
After that, bosses plan to sit down with US regulators early next year and discuss a pivotal phase III study, which is slated to begin at some point in 2020.
Phase III trials can be expensive, but unlike the majority of biotechs trying to take a drug through a late-stage study, Verona has plenty of cash in the bank: around US$70mln at the end of March.
Analysts suspect the company will have to find a little bit more than that in order to fund the study through to completion, but this isn’t something Karlsson is particularly worried about.
“We may need a little bit more, but we are looking at ways [to finance the trial],” he explains.
“One way is, as most biotechs do, we could raise more money. An alternative is to see if there’s any partner that would like to participate in taking a licence for part of the world – Europe, Japan or China for example.”
US and China the big target markets
Assuming the drug passes through the late-stage trial with flying colours, as Karlsson confidently predicts, the plan is to get it into the US market first, where there is huge demand for COPD treatments.
The US is the most profitable market in the world for drugmakers, given the sheer number of people over there and the fact that prices tend to be higher than in other countries.
But it’s not the only market Karlsson wants to tap into: China really excites him and his team.
“This [nebulised formulation] is incredibly interesting in China. China has around 100mln COPD patients, but only 10% or 15% of them are treated.
“Patients there go to hospitals for treatments, there are very few private clinics, so around 90% of all treatments are provided or sold in the hospital and, of course, this nebulizer is a typical hospital device.”
Lots of inflection points on the horizon
There’s a long way to go before that, though, and Karlsson, although excited about what the future may bring, is readying himself for a busy 12 months, with multiple inflection points on the horizon.
“This is a very important year for Verona Pharma,” he says, pointing to a chart of all the data readouts, trials and talks due to begin over the next year.
“On one hand, the lead formulation is going into phase III, which is extremely important, then we have these other small devices which are going through phase II.
“That’s a lot of datapoints in a relatively short amount of time.”