Since kicking off operations in 2005, Profectus BioSciences Inc. has licensed five early stage HIV programs from the University of Maryland.

Profectus' strong relationship with the university stems from the fact that the Baltimore-based company and the university's Institute for Human Virology (IHV) share the same founding team: HIV co-discoverer Robert Gallo and university professors William Blattner and Robert Redfield. The three scientists saw Profectus as a partner to develop and commercialize their research.

So far, the lead program in Profectus' pipeline is an immune modulating drug that targets the signaling molecule nuclear factor kappa B (NFkB).

The molecule's role in the inflammatory pathway has made it a popular target - so popular, in fact, that Ariad Pharmaceuticals Inc. filed a series of lawsuits claiming that drugs like Amgen Inc.'s Enbrel (etanercept), Wyeth's Rapamune (sirolimus), Eli Lilly & Co.'s Evista (raloxifene) and many others infringe on its NFkB patents. (See BioWorld Today, May 5, 2006.)

Shawn Patrick O'Brien, president and CEO of Profectus, said his company has intellectual property covering NFkB in HIV, where the molecule plays a role in viral entry, integration and replication. Profectus is working on lead optimization for the program and has identified three "quite spectacular" candidates, O'Brien said. Preclinical proof-of-concept studies will begin soon to evaluate the chosen lead candidate as an early monotherapy for HIV that potentially could delay the need for highly active antiretroviral therapy (HAART). Additionally, the NFkB drug could be used in combination with antivirals to overcome resistance problems or to give patients a drug holiday from HAART.

Which leads to Profectus' second HIV program: a proprietary viral entry inhibitor to be used in combination with its NFkB immune modulator. The company also plans to collaborate with manufacturers of existing antivirals as part of its combination therapy program.

Third up in the pipeline is a vaccine for HIV. Earlier this month at the annual meeting of the American Association for the Advancement of Science, HIV expert David Baltimore bemoaned the fact that after 20 years, an HIV vaccine is no closer than when the virus was discovered. He pointed to last year's disappointing failure of front runner V520, Merck and Co Inc.'s T-cell vaccine, which actually seemed to increase infection in some subjects. (See BioWorld Today, Feb. 15, 2008.)

Timothy Fouts, director of research and development at Profectus, said the Merck failure reinforces his company's strategy, which is "contrarian" in that it focuses on an antibody rather than T-cell response. Additionally, the antibodies triggered by Profectus' vaccine target specific, conserved epitopes associated with the HIV-1 envelope glycoprotein (gp120), decreasing the likelihood of mutations and resistance.

In a paper published last year in the Proceedings of the National Academy of Sciences, monkeys vaccinated with the immunogen from Profectus' vaccine and then challenged with SHIV cleared the virus from their blood faster than the control group and did not have long-term tissue viremia.

Fouts said Profectus is conducting lead optimization studies with its vaccine and hopes to begin preclinical studies in the next year or two. Wyeth optioned the rights in HIV and is evaluating whether to license the program, while Merial Ltd. has an option for rights in an undisclosed indication.

O'Brien noted that the vaccine technology "could be used with any envelope-based virus" and that Profectus is "willing to collaborate" with other partners for other indications.

Also on the table for potential partnering are Profectus' fourth and fifth programs: a vaccine adjuvant and thermal stabilizer.

The adjuvant stimulates dendritic cells to kick off the release of multiple cytokines rather than focusing on a single cytokine. The thermal stabilizers are based on thermophilic bacteria and other extremophiles that potentially could be used to stabilize vaccines and allow for room-temperature storage and transport.

For having so many programs in development, Profectus hasn't raised much money yet.

The company secured $5.3 million in a Series A financing and $3 million through a note and warrant deal, as well as some additional income from its option deals and government grants.

But O'Brien said the company plans to close a sizable Series B round later this year that would support advancement of the NFkB and vaccine programs.