Forget about personalized medicine. Pharnext, a Paris-based biotech company headed by a world reknowned pioneer in genome science, is teaming with Ipsen, a speciality pharmaceutical group, on a different approach that could revolutionize drug discovery.
Paris-based Pharnext is developing drugs for diseases that currently have no treatment by repositioning drugs already on the market. It mixes drugs in new ways, combining them in so-called “pleocompounds”, and administers them in mini-doses to restore normal cell functions while reducing side effects. Its an approach known as network pharmacology, which a November 8 article in Nature referred to as “the next paradigm in drug discovery.”
Pharnext’s chief executive, Daniel Cohen, considered to be one of the founders of modern genetics, genomics and pharmacognenomics, says he believes this approach, which Pharnext calls pleotherapy “will generate many novel therapies in the central nervous system disease area and indeed, in other fields of medicine. “
On June 15 Pharnext announced an agreeement with Ipsen covering R &D and marketing of the first “pleocompound” treatment, which is targeted toward Charcot Marie-Tooth disease, a neuromuscular disorder that primarily impacts peripheral nerves. There is currently no treatment for the disease, which impacts three million people worldwide. Under the agreement, Ipsen acquires an exclusive option on Pharnext’s program on Charcot-Marie-Tooth disease and subscribes to the issuing of convertible bonds. If the option is exercised at the end of a phase II clinical trial, Ipsen will pay Pharnext milestones, up to a cumulative €91 million, as well as double-digit royalties on net product sales and will have the ability to convert its convertible bonds into Pharnext shares. If Ipsen develops the drug candidate for treatment of another disease Pharnext could earn additional revenues from development milestones.
Pharnext says it believes that pleocompound therapy can be applied to Alzheimer’s disease, amyotrophic lateral sclerosis, multiple sclerosis, schizophrenia and geneticially inherited childhood disorders such as Down’s syndrome, cystic fibrosis and Duchenne muscular dystrophy.
Pharnext’s repurposing of existing drugs comes as the pharmaceutical industry is undergoing what some refer to as an innovation crisis. The number of new drugs has been steadily decreasing over the last few years while the cost of developing new drugs continues to climb. Although tough regulatory constraints can partly explain the problem it is also the case that often the new molecules in the pipelines of drug companies are only marginally effective and a significant number turn out to be toxic. That is why reusing approved drugs for new indications, an approach called drug repositioning, accounts for an ever-growing share — an estimated 4 billion euros in 2008 — of the pharmaceutical industry’s R &D expeniture.
Like Pharnext, Boston-based CombinatoRX is focusing on repurposing existing drugs. But the U.S. company is taking a different tact. CombinatorRX, which focuses primarily on cancer and inflammatory disease, uses high througjput screening restricted to all of the possible combinations of two non-patent drugs using general assays. Good indications are identified after a further step. Pharnext selects the indication before screening the human genomics data in order to identify a set of 50 patent protectable Pleocompound candidates. Pharnext says it results demonstrate the efficiency of the initial in silico filtering. By reducing the initial number of molecules by a factor of 20 t0 40, the company says its filtering enables more detailed experimental screening, allowing it to produce “intelligent” combinations of more than two molecules that are validated in animals.
Cohen, the founder of the CEOH, the GENETHON center for human genome research and Millenium in Boston; a former chief science officer for Genset and the former worldwide head of genetics at Serono, has assembled a team of recognized pioneers in genome science to work at Pharnext. The company, which was founded in 2007, has so far raised €3.5 million from Paris-based Truffle Capital, received €2 million in tax credits and a €3.4 million success-conditioned repayable advance from Oseo, a French government agency that supports small innovative companies.