Marseille, September 3, 2009 - Trophos SA, a clinical stage pharmaceutical company developing innovative therapeutics from discovery to clinical validation for indications with under-served needs in neurology and cardiology, announced today demonstration of proof of principle that its proprietary compound, TRO40303 significantly reduces myocardial infarct size and improves cardiac function. The company presented information on two posters at the European Society of Cardiology (ESC) Congress 2009 held in Barcelona, Spain from 29 August to 2nd September. Trophos expects the new presentations to help identify and obtain partners for this highly promising program for further development and commercialisation.
TRO40303 is a novel and promising cardioprotective agent that Trophos is developing to reduce cardiac ischemia-reperfusion injury following a myocardial infarction. This is a process that can be responsible for up to 50 percent of total infarct size, which is a key determinant of morbidity and mortality. TRO40303 is scheduled to enter the clinic in early 2010 followed rapidly by a phase 2 proof of concept clinical trial. The value of Trophos' approach and the need for such a product is supported by the scientific community and Trophos has received a significant grant to fund the program from the French Agence Nationale de la Recherche.
"These new data demonstrate that TRO40303 protects the myocardium against ischemia-reperfusion injury. This protection is at least in part mediated by prevention of opening of the mitochondrial permeability transition pore, recently validated in the clinic as a target for myocardial protection. Despite the use of treatments such as thromobolytics and stents, there is still a great need to reduce morbidity and mortality following myocardial infarction. TRO40303 could represent a new approach and we are actively seeking partners to help us exploit this promise," said Trophos CEO, Damian Marron.
The posters presented at the ESC were entitled:
TRO40303 reduces myocardial infarction size and promotes functional recovery after cardiac ischemia-reperfusion in mice (Augeul et al.), which demonstrated the activity of TRO40303 in a well characterised mouse model of cardiac ischemia-reperfusion injury. TRO40303 administered at a dose of 1mg/kg significantly reduced myocardial infarct size by 44 percent and 52 percent versus control and vehicle treated animals respectively (p<0.05). The TRO40303 treatment also resulted in improvements to important parameters of left ventricular cardiac function. Both infarct size and left ventricular function are known to be important determinants of morbidity and mortality post myocardial infarction.
and
The cardioprotective effect of TRO40303 is related to binding to the Mitochondrial Translocator Protein and inhibition of the Mitochondrial Permeability Transition Pore (Schaller et al.), which demonstrated that TRO40303 binds with high affinity and selectivity to the mitochondrial translocator protein (TSPO), which is closely associated to the mitochondrial permeability transition pore. Furthermore, TRO40303 was shown in rat cardiomyocytes to delay mPTP opening and increase survival of these cells following hypoxia reoxygenation stress. Finally, TRO40303 (0.3 - 3.0 mg/kg) was shown to significantly reduce infarct size in a dose-dependent manner in a rat model of myocardial infarction up to a maximum of over 50 percent versus control (p<0.01).
About Cardiac Ischemia Reperfusion Injury
Despite advances in treatment of myocardial infarction through removal of the occlusion, morbidity and mortality remain substantial, with about 5 to 6 percent of patients having a subsequent cardiovascular event by 30 days. The abrupt reperfusion of ischemic myocardium can itself inflict tissue damage, a phenomenon termed myocardial reperfusion injury. Experimental studies indicate that this form of myocardial injury accounts for up to 50 percent of the final size of the infarct, providing an important potential target for protection of the heart (Hausenloy et al., NEJM359:5. 2008) and a recently clinical trial employing cyclosporine A supports mitochondrial pore modulation as a therapeutic approach for cardiac ischemia reperfusion injury (Piot et al., NEJM 359:473-481, 2008).
About Trophos: www.trophos.com
Trophos is a clinical stage pharmaceutical company developing innovative therapeutics from discovery to clinical validation for indications with under-served needs in neurology and cardiology. The Company has a novel and proprietary cholesterol-oxime based chemistry platform generating a pipeline of drug candidates, with the lead product, olesoxime (TRO19622), in phase II clinical trials and a second product, TRO40303, planned to enter the clinic in 2009. Trophos' mitochondrial pore modulator compounds enhance the function and survival of stressed cells via modulation of dysfunctional mitochondria through interactions at the permeability transition pore (mPTP). Recently published clinical studies support the therapeutic rationale for mitochondria targeted drugs in neurology (Alzheimer's disease) and cardiology (ischemia-reperfusion injury), which Trophos is uniquely placed to exploit.
TRO40303 is a novel and promising cardioprotective agent that Trophos is developing to reduce cardiac ischemia-reperfusion injury following a myocardial infarction. This is a process that can be responsible for up to 50 percent of total infarct size, which is a key determinant of morbidity and mortality. TRO40303 is scheduled to enter the clinic in early 2010 followed rapidly by a phase 2 proof of concept clinical trial. The value of Trophos' approach and the need for such a product is supported by the scientific community and Trophos has received a significant grant to fund the program from the French Agence Nationale de la Recherche.
"These new data demonstrate that TRO40303 protects the myocardium against ischemia-reperfusion injury. This protection is at least in part mediated by prevention of opening of the mitochondrial permeability transition pore, recently validated in the clinic as a target for myocardial protection. Despite the use of treatments such as thromobolytics and stents, there is still a great need to reduce morbidity and mortality following myocardial infarction. TRO40303 could represent a new approach and we are actively seeking partners to help us exploit this promise," said Trophos CEO, Damian Marron.
The posters presented at the ESC were entitled:
TRO40303 reduces myocardial infarction size and promotes functional recovery after cardiac ischemia-reperfusion in mice (Augeul et al.), which demonstrated the activity of TRO40303 in a well characterised mouse model of cardiac ischemia-reperfusion injury. TRO40303 administered at a dose of 1mg/kg significantly reduced myocardial infarct size by 44 percent and 52 percent versus control and vehicle treated animals respectively (p<0.05). The TRO40303 treatment also resulted in improvements to important parameters of left ventricular cardiac function. Both infarct size and left ventricular function are known to be important determinants of morbidity and mortality post myocardial infarction.
and
The cardioprotective effect of TRO40303 is related to binding to the Mitochondrial Translocator Protein and inhibition of the Mitochondrial Permeability Transition Pore (Schaller et al.), which demonstrated that TRO40303 binds with high affinity and selectivity to the mitochondrial translocator protein (TSPO), which is closely associated to the mitochondrial permeability transition pore. Furthermore, TRO40303 was shown in rat cardiomyocytes to delay mPTP opening and increase survival of these cells following hypoxia reoxygenation stress. Finally, TRO40303 (0.3 - 3.0 mg/kg) was shown to significantly reduce infarct size in a dose-dependent manner in a rat model of myocardial infarction up to a maximum of over 50 percent versus control (p<0.01).
About Cardiac Ischemia Reperfusion Injury
Despite advances in treatment of myocardial infarction through removal of the occlusion, morbidity and mortality remain substantial, with about 5 to 6 percent of patients having a subsequent cardiovascular event by 30 days. The abrupt reperfusion of ischemic myocardium can itself inflict tissue damage, a phenomenon termed myocardial reperfusion injury. Experimental studies indicate that this form of myocardial injury accounts for up to 50 percent of the final size of the infarct, providing an important potential target for protection of the heart (Hausenloy et al., NEJM359:5. 2008) and a recently clinical trial employing cyclosporine A supports mitochondrial pore modulation as a therapeutic approach for cardiac ischemia reperfusion injury (Piot et al., NEJM 359:473-481, 2008).
About Trophos: www.trophos.com
Trophos is a clinical stage pharmaceutical company developing innovative therapeutics from discovery to clinical validation for indications with under-served needs in neurology and cardiology. The Company has a novel and proprietary cholesterol-oxime based chemistry platform generating a pipeline of drug candidates, with the lead product, olesoxime (TRO19622), in phase II clinical trials and a second product, TRO40303, planned to enter the clinic in 2009. Trophos' mitochondrial pore modulator compounds enhance the function and survival of stressed cells via modulation of dysfunctional mitochondria through interactions at the permeability transition pore (mPTP). Recently published clinical studies support the therapeutic rationale for mitochondria targeted drugs in neurology (Alzheimer's disease) and cardiology (ischemia-reperfusion injury), which Trophos is uniquely placed to exploit.
