People, R&D, Venture

Award-winning sepsis project gets $13M and a shot at reopening an R&D avenue as FDA pitches out old gold standard

As chair of the British Heart Foundation’s translational awards committee, David Grainger was powerfully attracted to some research that Glasgow University professor James Leiper was doing on a common symptom of septic shock, a major killer that is responsible for more than a quarter million deaths in the US each year.

That was good for an award.

David Grainger

But now Grainger, a partner at Medicxi, has followed through with an $13 million venture round to create a virtual company called Critical Pressure that could take this asset through early-stage studies and into the hands of commercial buyer.

And this time, it’s personal.

Sepsis is a severe, often life threatening bacterial infection that is fought off with antibiotics. During that fight the human body can experience toxic shock after generating nitric oxide, which drives down blood pressure to a critical point. For years now, doctors have fought back with noradrenaline to constrict blood vessel tissue and drive the pressure back up, which can also be harmful.

So in research primarily at University College London, Leiper developed CPL001, a chemical compound that inhibits an enzyme called DDAH1.

James Leiper

“Inhibiting DDAH1 prevents the dramatic loss of blood pressure that often accompanies sepsis,” said the professor. “The body naturally produces a chemical, nitric oxide, that kills bacteria but also lowers blood pressure. Blocking DDAH1 prevents the drop in blood pressure, without losing the ability to fight the infection.”

“It is trying to stabilize the patient so that the attempts to deal with the underlying infection have the time to be effective,” Grainger tells me. It’s something he’s seen first hand, when his mother died from sepsis several years ago.

Even so, Grainger says that sepsis as a focus in R&D has been as quiet as a graveyard in biotech, almost entirely because of the high bar set by the FDA in gaining new approvals for the condition. Regulators have demanded a 28-day all cause mortality benefit as the gold standard for the last 25 years.

“The FDA has set the bar so high that no one has been able to achieve it,” he says. “It’s only in the last 6 to 9 months that the FDA changed their position.”

In pre-IND talks with the FDA, regulators — in writing — backed off that standard, instead turning to a much more pliant noradrenaline-sparing standard for the pivotal endpoint.

The next step is straightforward. Starting with healthy volunteers but quickly looping in some sepsis patients, Grainger has established a completely virtual company which will take the drug through an early-stage program. In about two years, he says, the money in the startup round will deliver proof-of-principle data that a commercial biopharma can use to see if this is something that could be quickly shepherded into the market, perhaps after a small pivotal study to confirm the earlier finding.

Grainger isn’t known as a high roller in the development world. He and Medicxi are known for ruthlessly cutting costs to a bone, and there will be no full timers on board to spend money. He’s executive chairman, the single-asset company will be based under an umbrella group in Babraham in Cambridge, UK, and a part-time COO will manage the day-to-day.

It’s not complicated, he adds. This is something that should be quickly apparent if it’s working and safe to use.


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