HIV Program

The Human Immunodeficiency Virus type 1 (HIV-1) is the viral agent that causes the deadly immune system disease, Acquired Immune Deficiency Syndrome (AIDS). AIDS is characterized by the progressive loss of the CD4+ helper T lymphocytes (known as T cells), leading to severe immune suppression, opportunistic infections, and eventually death.

As of 2007, there are approximately 33 million people worldwide infected with HIV, which translates to approximately 1 in every 100 adults aged 15 to 49, of which, an estimated 1.2 million reside in North America. Since the AIDS epidemic began, an estimated 25 million people have died as a result of AIDS-related complications (UNAIDS, 2008).

The market for anti-HIV drugs has supported much of the growth of the total antiviral market, driven by a large number of new infections (6,800/day globally), broader access to medication, and an aging population of HIV/AIDS patients who have failed older therapies and switched to new, more expensive therapeutic regimens. Current sales of anti-HIV drugs are estimated to be $9 billion worldwide, with the U.S. market accounting for approximately 60% of global sales.

Despite the mature nature of the HIV market, new drugs are still needed to combat the issues related to chronic use, most notably drug resistance and long-term toxicity. With Presidio’s emphasis on developing drugs against novel targets and/or mechanisms of action, we aim to help address these ongoing concerns by identifying new small molecules that can be combined with current therapy to enhance the quality of life for patients.

PPI-802

PPI-801/802 (formerly called MIV-410) is a nucleoside reverse transcriptase inhibitor (NRTI) with a novel mechanism of action. Unlike other NRTIs that act as obligate chain terminators (AZT, 3TC, ddI, d4T, abacavir, etc.), PPI-801 is incorporated into the nascent cDNA chain and terminates at a penultimate position following addition of at least one additional nucleoside.

This mechanism of action could prevent the excision of PPI-801 via the standard escape mechanism associated with Thymidine Analog Mutations (TAM) and Nucleoside Analog Mutations (NAM), which lead to resistance to other NRTIs.

PPI-801 is effective at inhibiting a wide variety of NRTI resistant mutants and exhibits a good safety and activity profile in standard in vitro toxicity assays and in vivo animal studies including rodents and non-human primates (Bottiger & Oberg, 2000).

Because of the broad-spectrum activity of PPI-801 in vitro, it is a promising alternative for individuals failing existing NRTIs, as well as a potential first-line therapy for newly infected individuals. Presidio is advancing PPI-802, a structurally modified form of PPI-801 (a prodrug) exhibiting improved drug properties, through preclinical and IND-enabling studies over the coming year.

HIV References:
Bottiger Disa and Bo Oberg. 2000. Predictive value of treatment effects in SIV/SHIV infections in monkeys. Current Opinion in Anti-infective Investigational Drugs 2(3): 255-264.

UNAIDS Report on the global AIDS epidemic. July 2008.

<< HCV Program

Intellectual Property >>