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Integrase Inks Antiviral Pact with UGARF; Hopes to Ride Coattails of Merck Approval

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In one of its largest technology licensing deals completed to date, the University of Georgia Research Foundation has granted a license to biopharma company Inhibitex for intellectual property covering a series of HIV integrase inhibitors, hepatitis C polymerase inhibitors, and other antiviral compounds, Integrase and UGARF said last week.
 
The deal, which also includes a three-year sponsored research agreement to further develop the compounds, could pay big dividends for Inhibitex and the University of Georgia if a first-in-class integrase inhibitor from Merck wins regulatory approval in the coming months, paving the way for alternative treatments that work on the same viral target.
 
Under the terms of the agreement, Inhibitex has entered into an exclusive, worldwide license with UGARF for US Patent No. 7,250,421, entitled, “Diketo acids with nucleobase scaffolds: anti-HIV replication inhibitors targeted at HIV integrase;” as well as several patent applications related to integrase inhibitors, a class of anti-retroviral compounds that block viruses from inserting viral DNA into the genome of a host cell.
 
In exchange for the IP, UGARF will receive an upfront license fee of an undisclosed amount, future milestone payments, and royalties on future net sales of any products resulting from the technology.
 
Sohail Malik, director of technology commercialization at the University of Georgia, declined to provide the amount of the upfront licensing fee, but told BTW that the agreement was one of the larger deals in the school’s history.
 
Malik also said that the milestone and royalty payment terms are fairly standard for a pharmaceutical licensing deal in that they will revolve around various stages of clinical trials. Inhibtex said in a statement that it plans to select a lead candidate from the UGA compounds and initiate studies in the first half of 2008 in preparation for an investigational new drug application in the area of HIV.
 
Joseph Patti, Inhibitex’s CSO, told BTW that the license with UGA is “somewhat broader than HIV and HCV, but I think out of the breadth of the antiviral possibilities, … the most progress has been made [in] HIV first, and HCV second, particularly HCV polymerase inhibitors.”
 
Inhibtex will pursue the HIV indication first because of the importance of the disease, but also because the integrase inhibitors represent an attractive target around which Inhibitex can refocus its business development strategy.
 
The company, which was founded in 1998 and went public in 2004, had traditionally focused on monoclonal antibodies and vaccines for microbial, hospital-based infections. However, one of its most promising lead candidates, a treatment for Staphylococcus infections in premature babies, went belly up last year after missing its primary endpoint in Phase III clinical trials.
 
“We went through a lot of strategic evaluations, and we decided that we were looking to retool the company with the human resources we had in anti-infectives, but to focus on antiviral compounds,” Patti said. As part of this strategy, Inhibitex will shortly wrap up the acquisition of FermaVir Pharmaceuticals, which has antiviral programs for shingles and cytomegalovirus. Inhibitex announced its plans in April to acquire FermaVir in a stock swap deal that, according to a Fermavir release, was expected to close in July.
 
“We’ve been on record that we wanted to add one or two more programs,” Patti said, noting that the UGA integrase inhibitors fit the bill because of their importance in HIV, HCV, and several other important retroviruses.
 
The compounds were all developed in the laboratory of Vasu Nair, professor and head of the department of pharmaceutical and biomedical sciences at the University of Georgia, and lead inventor on all the patents in the portfolio licensed to Inhibitex.
 
Nair said he has been developing the inhibitors for the better part of ten years, but it was only in the last few years that his lab made the breakthrough that made the technology an attractive licensing opportunity.
 
“We focused on this enzyme because it is probably the most devastating step in the invasion of the human body by HIV, the stage at which viral DNA is incorporated into human chromosomal DNA,” Nair said. “There is no human counterpart for this enzyme, and it is absolutely essential for HIV replication. It’s been a very tough enzyme to inhibit, but over the last few years there have been a number of companies that have found inhibitors.”
 
One of those companies is Merck, which two weeks ago announced that the Antiviral Drugs Advisory Committee of the US Food and Drug Administration voted unanimously to recommend accelerated FDA approval of its integrase inhibitor Isentress in combination with other antiretroviral therapy for treating HIV in treatment-experienced patients.
 
If approved, Isentress would be a first-in-class drug and, according to the major players in the UGA-Inhibitex deal, may pave the highway for additional drugs that work on the same mechanism.
 
“There was a lot of speculation early on, based on in vitro data and animal studies, about integrase inhibitors,” Malik said. “But there was no FDA-approved product on the market. So Merck’s first compound for treating HIV based on integrase inhibitors is a major news break.
 
“Here is a great opportunity in the area of integrase inhibitors, which were previously only really considered in the lab,” Malik added. “Merck’s product would be first to the market, and they would probably [gain approval] in October. The focus of this deal is in a similar area.”
 
According to a statement from Merck, the FDA granted the drug priority review status, a designation for investigational products that address unmet medical needs. Under this designation, the FDA is expected to review and act on the NDA for Isentress within six months of submission. Merck said that it anticipates FDA action by mid-October.
 

“It’s a different chemical compound, [a] slightly different mechanism of action, so the mutations that would occur in response to Merck’s integrase may be slightly different from the ones that occur to this, so you may be able to treat those types of mutant strains.”

“I think it says that if you have a safe and potent compound targeting the integrase enzyme, you can make some nice strides in treating HIV,” Inhibitex’s Patti said.
 
Since Inhibitex and UGA announced their deal on Sept. 11, Inhibitex’s stock has climbed almost 14 percent from $1.31 to $1.49.
 
“This is a good sign that people are looking toward new treatments for HIV and investors are going there,” Malik said. “Most of the major companies are trying to find breakthrough compounds in this area, so the timing is great.”
 
Nair added that the Merck news is “a big plus, because it does give validity to these integrase inhibitors, that they can be viable drugs for the treatment of HIV.”
 
Preclinical studies on the integrase inhibitors performed in Nair’s labs have to this point shown that the compounds are potent and orally bioavailable, exhibit multiple mechanisms of integrase inhibition, and have the potential to be active against HIV strains resistant to other integrase inhibitors currently in clinical development – namely the Merck compound, according to Patti.
 
“The attractive part of the Georgia technology suggests that this new compound … has the potential to be active against [HIV strains resistant to] other integrase inhibitors in development,” Patti said. “It’s a different chemical compound, [a] slightly different mechanism of action, so the mutations that would occur in response to Merck’s integrase may be slightly different from the ones that occur to this, so you may be able to treat those types of mutant strains.”
 
Nair and the University of Georgia will also retain their relationship with Inhibitex in the form of a three-year sponsored research agreement, worth an undisclosed amount, to better characterize the anti-HIV compounds and to further develop HCV compounds based on the integrase inhibitors. Specifically, Patti told BTW that Nair’s lab would continue to provide medicinal chemistry support and some antiviral work.
 
“We’re working in both the HIV and HCV area,” Nair said. “You need more than one compound in the pipeline for this particular area. I think we want to have a drug that has the best property in terms of activity, stability, and bioavailability. The current drugs are pretty good, but I think we may have something even better, and that’s why they’re supporting the research.”

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