NEW YORK – Spanish molecular diagnostics company DeepUll is betting that PCR's recent pandemic-driven resurgence will provide a steppingstone for the firm's forthcoming molecular test to guide therapy selection for patients with sepsis.
The Barcelona-based company last week announced that it raised €13 million in Series B financing to fund its efforts to offer a multiplex PCR-based alternative to blood culture, still the go-to technology for diagnosing and treating sepsis patients.
"Fifteen or 20 years ago, blood culture was still seen as the true gold standard," DeepUll CEO Jordi Carrera said this week. "In 2022, blood culture is considered to be a good technology, but everyone understands it has its downsides."
Carrera cofounded DeepUll in 2020 with Rafel Bru. The two were also cofounders of Stat-Dx, a Barcelona-based molecular diagnostics firm that developed and launched a multiplex PCR-based infectious disease testing platform, including respiratory and gastrointestinal pathogen panels. After Qiagen bought Stat-Dx in 2018 for $191 million, the duo decided to focus on sepsis testing as an application area where they felt molecular testing could make a difference. Given the amount that Western healthcare systems spend on treating sepsis, they also saw the market as a business opportunity.
"There is the mortality part, which is that worldwide, sepsis kills about 11 million people annually, which is devastating," noted Carrera. He noted that the US spends about $60 billion per year to treat the condition, and that when combined with Europe's healthcare spend, it could be that the US and Europe spend around $100 billion annually on treating sepsis.
By saving healthcare systems money, and detecting sepsis earlier in patients, thus saving more lives, Carrera believes that DeepUll's platform could become a viable alternative to blood culture, which lacks the sensitivity and turnaround time of a molecular platform.
"We wanted to attempt to make something that was needed," said Carrera. "That, if it worked, would both help patients and make our company a substantial business opportunity."
Two-year-old DeepUll is still in startup mode and does not have its own website. Carrera said it is based in the Barcelona Science Park and employs about 20 people at the moment though the firm aims to scale headcount substantially. The company developed all of its technology in-house and owns all the intellectual property related to its technique.
In a statement announcing its recent financing, DeepUll claimed its technology could not only identify a sepsis-causing agent within "a few hours" but also provide phenotypic antimicrobial susceptibility results within eight hours, after detecting more than 250 different pathogens and 15 resistance genes from 10 mL of whole blood. DeepUll also said its system relies on artificial intelligence to assist decision making across all phases of patient management. The firm aims to offer such testing in an automated, desktop format that can be used in intensive care units.
Carrera declined to go into great detail about the company's technology, but stressed that it performs fully automated testing of whole blood. He also noted that the workflow includes a concentration step, and that the system relies on multiplex PCR. Carrera also declined to provide a timeline for when the system would reach the market, but affirmed that the US and Europe are the two main target markets for DeepUll now.
"Once you get regulatory approval in Europe, to get approval in many other geographies, you just have to change your file a bit," said Carrera. "Of course, China and Japan and other markets are of interest, but if you look at it globally, the US and Europe together are probably 75 percent of the market," he said. "So it's a no-brainer to go in this direction."
On cost, Carrera was similarly tight-lipped, but said that DeepUll is targeting a price point that will make it feasible for adoption in ICUs, and for the routine testing of patients with suspected sepsis. DeepUll is therefore developing a system that consists of "different bricks of technology" that can be run in an automated, continuous way and that is easy to use.
"Our vision is to one day be a first-line test," said Carrera, "and that means the system needs to be at a price point that all geographies and hospitals can afford." A higher-cost system, he noted, would result in a niche product for only critically ill patients, who would be less likely to benefit from more guided therapy selection.
"Those patients sometimes already have one foot in the grave, and it's too difficult to change their outcomes, so then your business case falls apart," commented Carrera. "But with lower pricing, there are more opportunities to change the outcome, and it becomes a win-win situation."
DeepUll is already liaising with clinical partners in the UK, the Netherlands, Denmark, and Germany, Carrera said, but he declined to name them. He also said the company has been in discussion with some US sites.
Many other companies are pursuing early sepsis diagnostics. In terms of molecular approaches, some newer entrants include Molzym, which is developing an automated, PCR-based multiplex sepsis test; Great North Research & Innovation, a UK company that is developing a rapid sepsis diagnostic; and Gradientech, which this year obtained a CE-IVD mark for its antimicrobial susceptibility testing platform.
However, according to some industry observers, this flurry of activity, while promising, does not portend that molecular tests will replace blood culture immediately. Vanya Gant, a senior lecturer in microbiology and infection at University College London Hospital, said that while the technology exists to support a move to molecular testing for sepsis, questions remain about its application.
Molecular techniques, he noted, can pick up bacteria in blood that might not be relevant. And PCR, in his opinion, "does not find unknown unknowns" and is "specific to specific bugs." Moreover, Gant said the idea that speed is of the essence in treating sepsis is not always true. Instead, he said that patients typically become critically ill quickly, making therapeutic intervention paramount, while others remain feverish and can wait for the results of culture-based antimicrobial resistance testing.
"I think the price of molecular is going to come down massively, but it's not ready yet to replace blood culture, because it can't look at all resistance," said Gant. "I am a complete believer in molecular technology," he added, "but the blank statement that molecular is better is not that simple." Gant said that such technologies need to be delivered at scale, as frontline tests in hospital settings, and studies must be run to demonstrate that they can help to save people's lives.
"We still don't know the answer to that question," Gant said.
Still, Carrera contended that laboratories have grown more familiar with PCR-based testing because of the COVID-19 pandemic, and that DeepUll believes this could help the company gain traction where others have struggled in the past. He also cited Roche's Septifast PCR System as one example of a "pioneer" product that has generated a lot of data supporting the use of PCR instead of blood culture for diagnosing pathogens in blood.
As to why molecular testing has not yet replaced blood culture for sepsis testing, Carrera said that a "constellation of elements" had hindered adoption in the past, but that perhaps previous offerings would have fared better in today's market, where PCR is considered a powerful technology and used routinely in almost all other areas of infectious disease testing but sepsis.
Enabling the move from culture to PCR in sepsis testing is "just a matter of sensitivity and automation and nothing else," Carrera said. "The use of blood culture for sepsis testing has been around for more than 40 years," he said. "This is the next frontier in infectious disease testing."