WATERTOWN, Mass.—Enanta Pharmaceuticals Inc., a research anddrug development company, has entered into an exclusive collaboration andlicense agreement with Switzerland-based Novartis for the development ofEDP-239, Enanta's lead candidate from its NS5A hepatitis C virus (HCV)inhibitor program. The venture could be worth up to $440 million.
Under the terms of the agreement, Novartis has agreed to payEnanta $36 million up front, and as much as $404 million more if Enanta hitscertain clinical, regulatory and commercial milestones. Enanta is also eligibleto receive tiered double-digit royalties on worldwide sales of products, andretains co-development rights in the United States.
Research efforts have shown that targeting NS5A gives riseto profound antiviral activity, and as a result, this protein has emerged as animportant target for antiviral drug development, Enanta states.
HCV is a liver disease affecting more than 170 millionpeople worldwide, according to the World Health Organization (WHO). The virusis spread through direct contact with the blood of an infected person. HCVincreases a person's risk of developing chronic liver disease, cirrhosis, livercancer and death. Liver disease associated with HCV infection is growingrapidly, and there is an acute need for new therapies that are safer and moreeffective.
Enanta has already received Investigational New Drug (IND)approval for EDP-239 from the U.S. Food & Drug Administration. Under thenew deal, Novartis will pick up all costs associated with the development,manufacture and commercialization of EDP-239. Also, Novartis will fund someother compounds that Enanta is working on that target NS5A.
"Novartis is a recognized leader in the field of HCV, andaccess to its global expertise combined with our shared vision forcommercializing HCV therapies will support the successful development andcommercialization of products targeting NS5A," Jay R. Luly, president and CEOof Enanta Pharmaceuticals, stated in a Feb. 21 news release. "We believeEDP-239 has great potential as a potent ingredient in combination drug therapy,and our preclinical studies have demonstrated high potency against multiplegenotypes of the virus."
Luly tells ddn,"Enanta did not need to partner with Novartis for EDP-239, but there arecircumstances for both companies that supported doing the deal now. NS5A is a'hot target,' and for good reason. Research efforts have shown that targetingNS5A gives rise to profound antiviral activity, and as a result, candidatesaimed at this target are being tested in the much-anticipated all-oral,interferon-free drug regimens."
In HCV, pharmaceutical companies are looking at theperformance of drug combinations at very early stages in development, he says.
"People are still trying to figure out what the bestcombinations are," Luly says. "And they are looking to identify the minimumcombination of agents that can be put together to effectively treat the virusand stave off the possibility of resistance."
Enanta has now done two early-stage deals "that allow ourHCV compounds to participate in multiple potential combination regimens—our HCVprotease inhibitor program, ABT-450 is partnered with Abbott, and now our NS5Ainhibitor, EDP-239, is partnered with Novartis," he says.
Novartis has a late-stage cyclophilin inhibitor, alisporivir,which it licensed from Debiopharm SA, Luly says. Many believe that the rapidantiviral activity of an NS5A inhibitor and the durable treatment effect fromcyclophilin inhibition is a compelling clinical combination.
"There are still several years of clinical development aheadfor EDP-239 given that it hasn't started in human clinical trials yet," Lulysays. "But there is a broader sense of urgency in the development of new HCVcompounds due to the constant threat of drug resistance and the need fortherapeutic regimens that are better tolerated and effective—even in thedifficult-to-treat genotype 1 cases of HCV."
Luly is aware of the competition among companies to come upwith an effective treatment for HCV.
"There are a number of companies developing drug candidatesfor HCV, some bigger, some smaller," Luly says. " I believe Enanta is unique inthat we have applied our novel chemistry approach and drug discoverycapabilities to develop one of the broadest pipelines of candidates targetedagainst HCV. And we are more broadly focused on infectious diseases. We aredeveloping a new class of antibiotics, called cicyclolides, which overcomebacterial resistance."
Novartis spokesman Jeffrey Lockwood is also optimistic aboutthe possibilities of discovering an effective treatment for HCV.
"We believe that oral combination therapy is the likelyfuture of HCV treatment," Lockwood tells ddn. "An NS5A inhibitor is an attractive potential partner for Novartis'cyclophilin inhibitor, Alisporivir (also known as DEB025 in Phase III trials).The combination of a highly potent NS5A inhibitor plus a cyclophilin inhibitorwith high barrier to resistance may provide an effective combination for HCVtreatment, especially considering that both also have broad genotypiccoverage."
In October, Enanta won a five-year, $42.7 million contractfrom the National Institute of Allergy and Infectious Diseases, a NationalInstitutes of Health division, to support the company's efforts in developingtreatments of infections stemming from methicillin-resistant Staphylococcusaureus (MRSA), vancomycin resistant enterococci (VRE) and resistantstreptococci.