With three new mechanisms for treating viral infections in its pipeline, Presidio Pharmaceuticals Inc. closed a $26 million Series B financing round.

David Jobes, co-founder and vice president of business development at Presidio, said the funding will be used to drive two lead HIV programs into the clinic and should last between 18 and 24 months, depending on how quickly the San Francisco-based company moves.

If precedent serves, Presidio will be moving pretty fast. Since its founding in 2006, the company recruited a management team, raised a $1.4 million Series A and the current Series B and built a pipeline by licensing three anti-infective programs.

Lead candidate PPI-802 is a prodrug of the small-molecule PPI-801 (MIV-410), licensed from Medivir AB.

The HIV drug is a nucleoside reverse transcriptase inhibitor (NRTI), but rather than immediately terminating the growth of the nucleoside chain like traditional NRTIs, PPI-802 allows one more nucleoside to be added at an odd angle. The benefit of that unique mechanism, Jobes explained, is that the kinked nucleoside chain makes it more difficult for the virus to establish resistance by cutting the drug out of the chain and resuming its growth.

"It's a known class of molecules with a twist," said Srinivas Akkaraju, managing director with Series B lead investor Panorama Capital.

In preclinical studies, PPI-802 has shown an "excellent profile . . . of inhibiting multidrug-resistant isolates," Presidio's co-founder, President and CEO Omar Haffar noted. It also has exhibited a good safety profile in standard in vitro toxicity assays and in vivo animal studies. Investigational new drug-enabling studies are under way, and Akkaraju predicted the Series B funding will carry the program through Phase I/IIa trials, where viral load reduction can be evaluated.

If PPI-802 is successful, it may offer a once-daily, low-dose treatment option for patients who have become resistant to other NRTIs. World-renowned HIV expert Marcus Conant, who came out of semi-retirement to serve as Presidio's chief medical officer, told BioWorld Today that many patients have developed resistance to older NRTIs like AZT (zidovudine, GlaxoSmithKline plc), and in the San Francisco area, 20 percent of newly diagnosed HIV patients carry drug-resistant strains of the virus.

Another company seeking to address resistance to NRTIs is New Haven, Conn.-based Achillion Pharmaceuticals Inc., which is in Phase II with its new NRTI, elvucitabine. Melbourne, Australia-based Avexa Ltd. recently completed Phase II with a new NRTI, apricitabine, also aimed at drug-resistant HIV strains. And San Diego-based Adventrx Pharmaceuticals Inc. has shown in preclinical studies that ANX-201 may be able to resensitize NRTI-resistant virus strains.

Presidio's second program also involves a new mechanism for treating HIV. The PPI-367 series of small molecules, which were derived from Nuclear Exclusion Technology (NEXT) licensed from Cytokine PharmaSciences, are designed to block HIV's movement from the cytoplasm into the nucleus. If the approach is successful, it could theoretically be applied to a wide variety of viral diseases.

The PPI-367 compounds are undergoing lead optimization, and Akkaraju said the Series B financing likely would carry the selected lead into early clinical trials.

Behind its HIV programs, Presidio is working on an early stage HCV program licensed from Stanford University that involves identifying molecules that mimic an inhibitory peptide shown to interrupt the ability of the NS5A protein to anchor the viral nucleoprotein complex to cellular membranes.

Additional proceeds from the Series B financing will be used to expand Presidio's management team through the addition of a chief scientific officer. Funding also may be used to in-license additional programs.

Panorama Capital, an independent spinout of JPMorgan Partners, led the Series B round. Akkaraju told BioWorld Today that Presidio initially was looking to raise $20 million to $22 million, but the company had $30 million to $35 million worth of investment interest before deciding to close the round at $26 million.

New investors in the round included Baker Brothers Investments, Bay City Capital, Ventures West Capital and Nexus Medical Partners. All three existing investors - Sagamore Bioventures, George Rathmann Fund and Peninsula Overview Partners - also participated.

Concurrent with the financing, Akkaraju joined Presidio's board of directors, as did Felix Baker of Baker Bros. Advisors LLC, Daniel Perez of Bay City Capital, Kenneth Galbraith of Ventures West Capital and John (Jack) Obijeski, previous special advisor to the company.