LONDON – A new company has been founded with €18million (US$25 million) in series A funding to have another go at scaling the sheer cliffs of sepsis.

Inotrem SA will focus on the TREM-1 (triggering receptor expressed on myeloid cells) pathway, which functions as an amplifier of the immune response and is markedly up-regulated in patients suffering from sepsis.

The series A will fund development of the lead small-molecule program through late-stage preclinical and onto phase II proof of concept, and in addition enable the Nancy, France-based company to assess the compound’s potential in other inflammatory diseases.

Picking up the reins as CEO of Inotrem is Jean-Jaques Garaud, a former head of research and early development at Roche AG. Having read the file on the history of drug program failures in sepsis he initially was doubtful about having another go, but said, “What’s interesting and different is the quality of the biology and understanding of the molecular mechanisms behind the TREM-1 pathway.”

The pathway is responsible for maintaining excessive inflammation when an infection goes out of control. “It seems to play a very critical role in driving [inflammation]. It’s not just a trigger, like TNF [tumor necrosis factor], it’s the amplification loop,” Garaud told BioWorld Today.

TREM-1 has been shown to boost the initial immune system response to infection, promoting the production of chemokines and cytokines. In animal models of sepsis, blocking TREM-1 reduces inflammation.

It’s not only the understanding of the basic biology, but the quality of the preclinical work, which the academic researchers, Sebastien Gibot, professor of critical care medicine at the University of Lorraine Medical School and Marc Derive, co-founder and CSO of Inotrem have carried out, that helped convince Garaud.

“Biology is just cells and molecular biology, and that’s not good enough. You need proof of concept in animal models. The group in Nancy has done the most complete suite of experiments, which show in a consistent fashion that [the lead molecule] prevents organ failure and improves survival,” Giraud said. “Compared to other programs I’ve ever looked at, it’s the most complete preclinical package, and that’s what brought me into the field.”

There’s another reason to hope that Inotrem will succeed in this area of huge medical need – where more than two dozen other drug programs have failed: The researchers have identified biomarkers which indicate if the TREM-1 pathway is activated.

“Stratification has been tried in the past, but not from the start [of development]. This is an opportunity to do everything in parallel, and coming from Roche, I’m very familiar with this,” Garaud said. The quality of the biology helps in driving the personalized medicine approach, which increases the chances of success, he added.

Inotrem is trumpeting the €18 million round as the biggest series A in Europe this year, but since 2014 is only 11 weeks old, this hardly seems a claim to fame. However, it is a large series A by European standards, especially given that sepsis is such a risky and difficult indication.

The most recent failure of a sepsis program was of Cytofab (AZD9773), a polyclonal ovine antibody designed to neutralize TNF Alfa, which missed the endpoint in a 300-patient phase IIb trial funded by AstraZeneca plc that reported in August 2012.

Six months earlier, Agennix AG’s talactoferrin, a recombinant version of the human milk protein lactoferrin failed in a phase II/III trial. In January 2011, the Toll-like receptor 4 antagonist eritoran (E5564), which was developed by Eisai Co. Ltd., of Tokyo, missed the endpoint in phase III. Also in 2011, Xigris (drotrecogin alfa) the only drug to have FDA approval in treating severe sepsis, was withdrawn by its owner Indianapolis-based Eli Lilly and Co., after a new study showed it was no better than placebo.

The investors hoping that Inotrem can finally tame sepsis are co-leaders of the round Edmond de Rothschild Investment Partners and Sofinnova Partners, both of Paris; Basel, Switzerland-based Biomed Invest; and the French seed investment firm Inserm Transfert Initiative. Gilles Nobécourt, of Edmond de Rothschild Investment Partners, and Graziano Seghezzi, of Sofinnova Partners, have joined the board of Inotrem.

“I’m more than pleased with the round; I think it’s a blessing,” Garaud noted. “I learned one thing is the quality of the science; the other is the quality of the people. The third pillar is the quality of the VC syndicate.”

It is still open what happens next in terms of funding if Inotrem delivers positive results in a phase II proof-of-concept study. “Let’s get to the next stepping stone. If we are successful, opportunities will pop up,” Garaud said.