Next month Genkyotex should find out if its attempt at reinvention holds any water. The company is set to report results from a mid-stage primary biliary cirrhosis study of GKT831, a NOX 1 & 4 inhibitor that flunked in diabetic nephropathy in 2015.
The company’s chief executive, Elias Papatheodorou, put the previous failure down to the trial being too short and the dose being too low. He told Vantage that GKT831 could still have a future in diabetic kidney disease, as well as other fibrotic disorders including the current flavour of the month, Nash.
Investors remain unconvinced, with Genkyotex’s market cap sitting at just under €110m ($125m), well below GKT831’s net present value of $566m, based on EvaluatePharma sellside consensus. In the next couple of weeks it should become apparent whether the buyside or the sellside has a better handle on the company’s future prospects.
As easy as PBC?
Genkyotex’s future looks precarious. With just €9.3m in the bank, everything hinges on the group getting a smash hit in primary biliary cirrhosis (PBC) as a gateway to raising more funds.
All should be revealed in early November, when interim results are due from the phase II trial; final data are expected in spring 2019.
Unlike the earlier diabetic nephropathy trial, which evaluated three months’ treatment, the trial in PBC – an autoimmune disease of the liver – will test six months of GKT831 therapy. The primary endpoint of the latter is change in serum gamma-glutamyl transferase (GGT), a biomarker that is elevated in patients with liver diseases.
The interim analysis will involve six-week data from around 90 of the total 111 enrolled patients. As well as looking at the primary endpoint, results will also be available on various secondary endpoints, including change in serum alkaline phosphatase and bilirubin.
The early look should give an indication of whether the study will ultimately succeed; overall, Genkyotex hopes for a 25-30% reduction in GGT, Mr Papatheodorou said, adding that it would be “too early to file” on these data, so the company would also have to fund phase III.
Failure would be “a huge surprise”, the chief exec believes, “because in the diabetic nephropathy trial we saw an effect on GGT”. He continued: “If the [diabetic nephropathy study] had been called a liver trial it would have been successful. But the primary endpoint was in the kidney, which wasn’t met.”
The group did not have the cash to run a study longer than three months, he said. It is worth noting that Mr Papatheodorou became Genkyotex’s chief exec after the diabetic nephropathy trial had failed, though he had been at the company as chief business officer.
Despite its failure, he said the signs in that study were promising enough for the Juvenile Diabetes Research Foundation (JDRF) to fund a new trial of GKT831 in diabetic kidney disease. “That’s treating for one year, and we’re going to go for the higher dose from the previous trial.”
Mr Papatheodorou reckons that GKT831, which is designed to hit pathways involved in oxidative stress-mediated tissue damage, could be useful in any disease in which fibrosis plays a role. “We’re interested in three organs: liver, kidney and lung.”
As well as the aforementioned studies, the US NIH is funding a phase II trial in the lung disorder idiopathic pulmonary fibrosis, slated to start next year.
Further into the future, Nash might be another target. In this respect Genkyotex is taking a similar approach to Intercept, which initially got approval for Ocaliva in PBC but is now looking at the larger Nash indication.
This is where the similarities end, however, according to the chief exec. Ocaliva is a farnesoid X receptor agonist, which works by “flushing out” bile from the liver. But this does not treat the underlying cause of the diseases, he claimed. “The reason the bile has accumulated is because you have a slow destruction of the bile ducts from inflammation and fibrosis – that’s where we come in.”
GKT831 is more analogous to Gilead’s rival Nash therapy, the Ask1 inhibitor selonsertib, which also targets fibrosis. Results from phase III Nash trials of both selonsertib and Ocaliva will be reported early next year (Liver disease is set for its pivotal year, August 10, 2018).
A positive readout with selonsertib could help validate Genkyotex’s approach, Mr Papatheodorou believes, adding that the company might be able to run phase III trials in Nash on its own.
But at current funding levels this will be a hard task.
A Product Manager with expertise in pharma marketing and sales operations