Marseille, May 29th, 2008 - Trophos SA, a biopharmaceutical company specializing in the discovery and development of drugs for neurological disorders, announced today that a paper entitled “Specific antinociceptive activity of cholest-4-en-3-one, oxime (TRO19622) in experimental models of painful diabetic and chemotherapy-induced neuropathy” has been accepted for publication in the Journal of Pharmacology and Experimental Therapeutics [available online in Fast Forward section at http://jpet.aspetjournals.org].
The studies reported in the paper by Bordet et al., (see below) demonstrate that daily oral administration of TRO19622 improves motor nerve conduction and reverses neuropathic pain behavior in a preclinical model of induced diabetic neuropathy. While TRO19622 also reversed neuropathic pain behavior in a preclinical model of chemotherapy-induced neuropathic pain it did not suppress pain behavior in response to noxious stimulation or nerve trauma. These results suggest TRO19622 affects underlying mechanisms involved in painful diabetic or chemotherapy-induced neuropathic pain that are distinct from normal acute or inflammatory pain states. The absence of general anesthetic or sedation effects with TRO19622 suggests the Trophos drug candidate will avoid side effects associated with currently prescribed drugs. Moreover, the additional benefits on nerve conduction suggest TRO19622 could reverse the peripheral neuropathy induced by diabetes or chemotherapy, as well as treat the neuropathic pain.
TRO19622 is representative of novel cholesterol-like compounds that target the mitochondria identified employing the proprietary neuronal cell screening platform developed at Trophos (see Bordet et al., JPET 322:709-720, 2007). TRO19622 has successfully completed Phase I/Ib studies in both healthy volunteers and ALS patients demonstrating the product is well tolerated, has an excellent safety profile and that once-a-day dosing achieves the predicted exposure level required for efficacy, based on preclinical models. The company is currently performing three clinical studies with TRO19622: a Phase Ib study in Spinal Muscular Atrophy (SMA) and two Phase IIa trials in painful diabetic neuropathy and nonalcoholic steatohepatitis (NASH). A Phase IIa proof of concept trial in post-chemotherapy induced neuropathic pain is expected to begin enrolling patients in 2H 2008.
“Trophos and its collaborators are proud to have this body of work accepted for publication in a well recognized journal such as JPET,” said Rebecca Pruss, CSO at Trophos. “Since the underlying cause of neuropathic pain is still unknown, current treatment strategies are limited and do not provide satisfactory relief. Given the unmet medical needs in neuropathic pain, we believe TRO19622 and other compounds in this class that target the mitochondria represent a significant scientific breakthrough, one that has substantial commercial potential in this neurological disorder. In addition, they are likely to be effective in other indications where mitochondrial dysfunction leads to cell death such as neurodegenerative conditions, ischemia-reperfusion injury and hepatitis.”
Author List: Thierry Bordet, Bruno Buisson, Magali Michaud, Jean-Louis Abitbol, Rebecca Pruss (Trophos), Fabian Marchand, John Grist, Marzia Malcangio (Neurorestoration Group Wolfson CARD, Kings’ College, London), Emile Andriambeloson (Neurofit, France)
About Neuropathic Pain: Diabetes affects almost 250 million people worldwide and ~30% will develop symptomatic peripheral neuropathy (International Diabetes Federation; www.idf.org). Chemotherapy is used to treat many types of cancer and painful neuropathy is a common and serious treatment limiting side effect. While the mechanisms underlying neuropathic pain remain poorly understood the market for current therapies is estimated at USD 4Bn, and growing. As current therapies have recognized limitations in terms of efficacy and associated dose-limiting side effects, a significant unmet need and commercial opportunity exists for novel therapeutic products; in particular, for an agent that addresses the underlying neuropathy in addition to providing symptomatic pain relief. About Trophos: www.trophos.com Trophos is a biopharmaceutical company committed to the discovery and development of novel therapeutic compounds to treat neurological disorders and other diseases with high unmet medical needs. The Trophos discovery strategy has enabled it to develop a portfolio of proprietary products, such as its lead product TRO19622 and drug candidate TRO40303, that confer a survival benefit to stressed neuronal and non-neuronal cells. This is achieved through a mitochondria-based mechanism of action with a robust scientific rationale predicted to exhibit therapeutic benefits in neurodegenerative diseases and indications such as ischemia-reperfusion injury and hepatitis. The company is focusing its efforts on the orphan indicates ALS and SMA while seeking to establish clinical proof of concept and partnerships in other indications, such as neuropathic pain, ischemia-reperfusion injury and hepatotoxicity. The company is currently performing three clinical studies with TRO19622: a Phase Ib study in SMA and two Phase IIa trials to assess i) the analgesic effect in patients with painful diabetic neuropathy and ii) the effect on circulating liver enzymes, markers of oxidative stress and apoptosis in patients with NASH, respectively. Trophos was founded in 1999, is based in Marseille, France and currently has 32 employees.
