LONDON – AM-Pharma BV raised a further $52 million for the phase III trial of its recombinant alkaline phosphatase product, Recap, in treating sepsis-associated acute kidney injury (AKI), but now faces a delay in starting the study, as the COVID-19 crisis takes up more and more clinical resources.

The new funding consists of a $25.5 million extension to the $130.7 million series E round raised last July and a $26.5 million loan from the European Investment Bank (EIB).

The total of $176 million will fund what is billed as the largest-ever clinical trial in AKI, with 1,400 patients at 100 sites in 12 countries, and enable Utrecht, the Netherlands-based AM-Pharma to complete quality assurance of its commercial manufacturing and other steps needed to ready the file for approval.

“Raising more money was always part of the plan,” said Erik van den Berg, AM-Pharma’s CEO. “We knew we needed to increase funding because there is a lot we need to do, to set up and complete the infrastructure for market supply,” he told BioWorld.

It was intended to begin the study this summer, but COVID-19 and the strain it is putting on intensive care units has knocked that plan off course. “Current resources in hospitals have to be focused on addressing COVID-19,” van den Berg said. “We don’t know how long it will go on for; as a company we are preparing for multiple scenarios. We want to make sure we will be in the clinic to start as soon as circumstances allow.”

Erik van den Berg, CEO, AM-Pharma

Van den Berg said he hopes that will be before the end of the year. For now, in common with so many companies, AM-Pharma staff are working from home. That is causing some constraints. “You have to be creative,” van den Berg said. “I think we can manage the impact.”

AM-Pharma is better cushioned than most private biotechs to ride out the storm COVID-19 is now wreaking on the industry. Companies with limited cash runways face delays to completion of clinical studies that mean it will take longer to trigger milestone payments, or reach the next inflection point to raise more capital. It also will take longer to get paid R&D tax credits.

The $25.5 million equity investment in AM-Pharma came mainly from New York-based Cowen Healthcare Investments, which joined the existing syndicate of investors, including Life Science Partners, Andera Partners, Forbion, Kurma Partners and Gilde Healthcare, that put in $130.7 million last July.

The EIB money is from the Infectious Diseases Finance Facility, which is part of the EU’s Horizon 2020 R&D program.

“I think we can take this funding as a positive in these times when COVID-19 is using up so many resources,” van den Berg said. “There’s still unmet need in other areas.”

Indeed, COVID-19 infections are highlighting the extent of the medical need for a treatment for sepsis-related AKI, a severe immune reaction that results in a sudden drop in kidney function.

Initial reports of caring for critically ill COVID-19 patients indicate a number of them have experienced AKI. A summary of 72,314 case histories from the Chinese Center for Disease Control and Prevention, published in JAMA on March 23, showed 2,087 of the most severely affected had septic shock and multiple organ dysfunction or failure.

In another study, of 138 severely affected patients in Wuhan, China, also published in JAMA, five suffered AKI.

Outside the COVID-19 bubble, sepsis generally accounts for around half of all cases of AKI, which is associated with 700,000 deaths per annum in the U.S.

While not ruling out testing Recap if a suitable trial was set up, van den Berg noted that at present the focus in assessing potential COVID-19 treatments is squarely on antiretroviral drugs.

AM-Pharma’s research has shown that by removing phosphate from pro-inflammatory lipopolysaccharides and extracellular ATP, alkaline phosphatase acts as a detoxifying agent. As an additive effect, when ATP is dephosphorylated, the resulting adenosine further limits inflammation through activation of the immunosuppressive A2a receptor pathway.

In the phase II study published in March 2018, Recap showed a significant relative reduction in mortality of 40% in the treatment group, compared to placebo.

However, the product did not meet the primary endpoint of showing improvement in kidney function as a measured by creatinine clearance in the first seven days post-treatment.

As a result, then-partner Pfizer Inc. turned down its option to acquire AM-Pharma, leading the company to turn to private investors.

The trial design for phase III has been drawn up, and van den Berg said the protocol will be submitted soon. There will be a hard clinical endpoint of overall survival.