BioWorld Today Contributing Writer

Extending a partnership that dates back to 1999, Genfit, of Lille, France, has inked an agreement with Sanofi-Aventis SA, of Paris, to pursue therapies for the treatment of metabolic disorders.

The deal gives Sanofi exclusive worldwide rights to develop and commercialize molecules resulting from the collaboration. In exchange, Genfit will receive annual payments to fund selected research projects. As part of a risk-sharing arrangement, the company also could receive milestone payments of up to $54.5 million, based on the progress of preclinical and clinical development and the subsequent registration and commercialization of successful products. Genfit also will receive royalties from future sales of products developed under the agreement.

The partners will seek to identify molecules that aim to correct the mitochondrial dysfunction associated with certain pathologies, including metabolic diseases. Based on clinical observations, the cellular mechanisms that regulate energy production under normal conditions – and their capacity to adapt to stress – may have therapeutic potential in such disorders, according to Genfit.

Company officials were meeting in France and did not reply to requests for an interview, but in a statement, Jean-François Mouney, Genfit's founder and chairman, said the new Sanofi deal demonstrates "the strong commitment of both parties" to continue their collaborative research.

Genfit faces a crowded field in metabolic disorders – diabetes, in particular. If any of its molecules shows efficacy in obesity, however, together with a satisfactory safety profile, Genfit could have a tiger in its tank. Just this week, Amylin Pharmaceuticals Inc. and Takeda Pharmaceutical Co. Ltd. suspended an ongoing study of pramlintide/metreleptin for obesity, becoming the latest in a string of obesity candidates stopped in their tracks by safety problems. (See BioWorld Today, March 17, 2011.)

Previously, Orexigen Therapeutics Inc., of San Diego, received a complete response letter for Contrave. (See BioWorld Today, Feb. 2, 2011.)

The FDA also has blocked new drug applications for Vivus' Qnexa and Arena Pharmaceuticals Inc.'s lorcaserin due to safety concerns. (See BioWorld Today, Jan. 24, 2011, and Dec. 23, 2010.)

And in October 2010, Abbott voluntarily removed its weight loss drug Meridia from the market due to its cardiovascular risk profile. (See BioWorld Today, Oct. 11, 2010.)

Powered largely by strategic partnerships, Genfit has grown steadily since its launch in September 1999 with capital of $1.8 million) invested by research partners University of Lille and the Lille branch of Paris-based Institut Pasteur along with commercial entities Rhone-Poulenc Rorer, Sanofi-Synthilabo, Lipha Merck and UCB Pharma, plus several venture capitalists.

Sanofi was the company's first partner, signing a collaboration the same year Genfit was founded to develop therapeutic targets for Type II diabetes and vascular inflammatory diseases. AVE0897, a peroxisome proliferator-activated receptor agonist (PPaR) in Phase I trials for diabetes, is a result of the collaboration, which has been renewed four times.

Genfit has a research partnership with Solvay, of Brussels, Belgium, designed to identify and develop selective modulators for a nuclear receptor that plays a key role in regulating lipoprotein metabolism. That collaboration has several molecules in preclinical development, with one compound, SLV341, in Phase I trials for diabetes.

The company also has a partnership with French pharmaceutical company Servier that was initiated in 2004 for programs targeting insulin resistance and Type II diabetes.

GFT505, Genfit's lead proprietary compound for the treatment of prediabetes and diabetes, has progressed to Phase II trials. A mixed PPARa/d agonist, the "next-generation" GFT505 originates from Genfit's selective nuclear receptor modulator platform, which was developed to identify drug candidates that are more effective and/or safer than existing therapies. GFT505 simultaneously targets several micro- and macrovascular risk factors, including hyperglycemia and insulin resistance, dyslipidemia, inflammation and hepatic steatosis.

In January 2010, the company reported positive results from a 28-day, pilot Phase II trial showing that GFT505 has the potential to reduce global cardiovascular risk in prediabetic patients who suffer from impaired fasting plasma glucose, impaired glucose tolerance and abdominal obesity. Data showed that treatment with GFT505 led to a significant reduction in fasting plasma glucose levels compared to the placebo group (-5 percent vs. placebo), while also demonstrating significant reductions in fasting plasma insulin (-25 percent vs. placebo) and C-peptide (-11 percent vs. placebo).

Mouney has indicated the company's intention to partner with a pharmaceutical company for Phase III trials of the compound. (See BioWorld Today, Sept. 26, 2007.)

Genfit has at least one other unpartnered compound, G15750, which is in preclinical development for neurodegenerative diseases, including Alzheimer's.

The company's stock (ALGFT) is listed on the Alternext market of the Euronext stock exchange in Paris. In September 2010, the company reported revenues of €4.08 million (US$5.7 million) for the first half of the year, including €2.06 million from its industrial alliances. The company also reported €18.01 million in cash and equivalents as of June 30, 2010.