Inotrem and Roche Diagnostics sign a R&D collaboration agreement in the field of septic shock to develop a companion diagnostic test

Paris, November 10, 2017. Inotrem S.A., a biotechnology company specialized in the control of acute inflammatory syndromes, such as septic shock, today announced a R&D collaboration agreement with Roche Diagnostics to develop a companion diagnostic test using a soluble plasma circulating protein (sTREM-1) developed by Inotrem and the Roche proprietary Elecsys® platform. It is Roche Diagnostics’ first collaboration agreement with a start up biotech company.
Under the terms of the agreement, Roche and Intorem will work together to develop an in vitro robust prototype assay for quantitative measurement of soluble TREM-1 (sTREM-1) in plasma samples of septic shock patients. sTREM-1 is a marker of the activation of the TREM-1 immune amplification pathway and high sTREM-1 plasma concentrations have been shown to be associated to a negative outcome in septic shock patients. Measurement of sTREM-1 in blood could provide a valuable indicator for the diagnosis and outcome prediction of septic shock patients1,2,3.
Inotrem is currently conducting a clinical Phase 2 trial in patients with septic shock to demonstrate the benefit of its lead compound, Motrem™ (LR12) in the treatment of septic shock4. The collaboration with Roche Diagnostics may lead to a companion diagnostic supporting the development of Motrem™.
One of the main issues with septic shock is the heterogeneity of this patient population. This collaboration proposes to develop a test to allow a certain stratification of sepsis patients to ideally identify patients who are more likely to respond to Motrem treatment,” said Jean-Jacques Garaud, CEO and co-founder of Inotrem. “It shows our shared willingness to accelerate the development of targeted therapeutic solutions for these patients.”
The physiopathology of septic shock is characterized by an intense and excessive systemic inflammatory reaction in response to a serious infection5. Its consequences include the dysfunction of vital organs and major hemodynamic disorders that may prove fatal for patients. Activation of the TREM-1 pathway is recognized as a key factor contributing to septic shock6.
“As a leader in in vitro diagnostics solutions7, it is a great opportunity to participate to the opening of a new front in critical care medicine, particularly in an area known for its difficult and highly heterogeneous population in septic shock”, shared Jean-Claude Gottraux, Head of Roche Diagnostics, Centralized and Point of Care Solutions. “We are particularly pleased as this is the first time Roche Diagnostics is collaborating with a start-up biotech company.”

Media contact for Inotrem
Anne REIN | S&I | | +33 6 03 35 92 05

About Inotrem
Inotrem S.A., is a biotechnology company specialized in the control of acute inflammatory syndromes, such as septic
shock. The company has developed a new concept of immunomodulation to control unbalanced inflammatory
responses. Focusing on targeted immunotherapy for acute inflammatory syndromes in the critical care setting, the
company has been founded in 2013 by Dr. Jean-Jacques Garaud, a former head of research and early development
at the Roche Group, Prof. Sébastien Gibot and Dr. Marc Derive. Inotrem’s lead product candidate (LR12) opens new
personalized treatment options in a number of therapeutic indications such as septic shock or myocardial infarction.
Inotrem is supported by leading European investors — Sofinnova Partners, Edmond de Rothschild Investment
Partners, Biomed Invest and Inserm Transfert Initiative.

About TREM-1 and LR12
Inotrem focuses on targeted immunotherapy for acute inflammatory syndromes in the critical care setting and has a
significant expertise in the biology of TREM-1 receptor.
TREM-1 is an immunoreceptor expressed by innate immune cells. Upon activation, TREM-1 can directly amplify an
inflammatory response. TREM-1 was initially characterized for its pathophysiological role during septic shock, and
since, in other acute diseases such as ischaemia/reperfusion injury after myocardial infarction, haemorrhagic shock,
ischaemia-reperfusion, pancreatitis and acute kidney injury. TREM-1 is one of the most upregulated pathways during
the genomic storm observed in septic shock patients. Engagement of TREM-1 leads to a hyperactivated and exuberant
inflammatory response which is responsible for the onset and progression from sepsis to septic shock. Currently, there
is no specific causal treatment for septic shock, and previous attempts to develop treatments have failed.
LR12 is a synthetic peptide aiming at controlling the amplification loop of the inflammatory response by inhibiting the
TREM-1 receptor. The therapeutic efficacy of LR12 is documented in several preclinical septic shock models in different
species which have shown an appropriate inflammatory response, an improvement in hemodynamic parameters and
survival rates.

1 Gibot S, et al: Combination biomarkers to diagnose sepsis in the critically ill patient. Am J Respir Crit
Care Med. 2012 Jul 1;186(1):65-71.
2 Charles PE, et al: Significance of soluble triggering receptor expressed on myeloid cells-1 elevation in
patients admitted to the intensive care unit with sepsis. BMC Infect Dis. 2016 Oct 12;16(1):559.
3 Su L, et al: Role of sTREM-1 in predicting mortality of infection: a systematic review and metaanalysis.
BMJ Open. 2016 May 13;6(5):e010314.
4 Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of 3 Doses of MOTREM in Patients
With Septic Shock. A Randomised, Double-blind, Two-Stage, Placebo Controlled Study. (2017).
(registered at NCT03158948 ; Drug Product name: MOTREM, EudraCT
Number: 2016-005032-14).
5 Nduka OO, Parrillo JE. The pathophysiology of septic shock. Crit Care Clin. 2009 Oct;25(4):677-702
6 Bouchon A, Facchetti F, Weigand MA, Colonna M. TREM-1 amplifies inflammation and is a crucial
mediator of septic shock. Nature. 2001 Apr 26;410(6832):1103-7.
7 Source: Roche Annual Report 2014. January 2015. * Status 2016.
8 Derive M, et al: Soluble TREM-like transcript-1 regulates leukocyte activation and controls microbial
sepsis. J Immunol. 2012 Jun 1;188(11):5585-92.
9 Derive M, et al: Effects of a TREM-like transcript 1-derived peptide during hypodynamic septic shock
in pigs. Shock. 2013 Feb;39(2):176-82.