Ambrilia Biopharma Inc.

Ambrilia Biopharma Inc.

August 17, 2006 08:00 ET

Ambrilia Reports Further Data Suggesting PPL-100 HIV Protease Inhibitor is a Once-Daily, Un-Boosted, First-Line Therapy to treat a Large Spectrum of HIV/AIDS Patients

Final Phase Ia data and pharmacokinetic modeling and target attainment analysis results presented at the XVI International AIDS Conference

MONTREAL, QUEBEC--(CCNMatthews - Aug. 17, 2006) - Ambrilia Biopharma Inc.(TSX:AMB), a biopharmaceutical company developing innovative therapeutics in the fields of cancer and infectious diseases, announced today the latest findings on its lead HIV protease inhibitor (PI), PPL-100. Final results of the first-in-man, single dose escalation studies confirmed PPL-100 to be safe and well tolerated with a favorable pharmacokinetic (PK) profile. Using these final clinical data, the scientists, led by Drs. George Drusano and Paul G. Ambrose, at the Institute of Clinical Pharmacodynamics (ICPD), Ordway Research Institute, Albany, NY, conducted population PK modeling and Pharmacokinetic-Pharmacodynamic (PK-PD) target attainment analyses. Modeling and simulation results predict a favorable steady-state PK profile for PPL-100, suggesting that it could be a first-line, once-daily PI without the need of ritonavir (a boosting agent) co-administration for the treatment of both PI-naive and experienced HIV/AIDS patients infected with highly resistant strains of the virus. These analyses also indicate that PPL-100 offers excellent "forgiveness" in the event of a missed dose, an important characteristic to address the non-adherence issues in HIV therapy. PPL-100 could be an asset to both physicians and patients in the fight against HIV/AIDS by potentially addressing the need for safer, more convenient and effective PIs.


The first part of the presentation details the results, as reported by Ambrilia on June 14th, 2006, of in vitro resistance selection studies confirming PPL-100's high genetic barrier, a key characteristic of first-line PIs in fighting the emergence of resistant HIV viruses, and its favorable cross-resistance profile when compared to marketed PIs.

The second part of the presentation discusses the final data of the first-in-man, single-dose escalation studies evaluating the safety and pharmacokinetics (PK) of PPL-100 in healthy male subjects (n equals 64). Safety assessment confirmed PPL-100 to be safe and well tolerated up to 2400 mg oral dose with only mild (grade 1 and 2) adverse events reported for all cohorts (8 subjects per cohort). The PK profile indicates drug exposure; Area Under the Curve (AUC) increased linearly with doses. Maximum plasma concentrations (Cmax) of the drug increased linearly until 1200 mg and less thereafter. The clinical data indicate that the most striking characteristic of PPL-100 is its long elimination half-life (30-37 hours) that supports once-daily dosing. Finally, the data indicate that there is no significant difference in drug exposure in the absence or presence of a light meal, suggesting that PPL-100 can be administered without regard to food, giving patients added convenience.

Population PK modeling predicts that drug accumulation at steady-state is significant. For example, the drug accumulation ratio of the steady-state to the single dose is 3.7 for 600 mg dosing, resulting in the steady-state trough drug concentration of 376 ng/ml and Inhibitory Quotient (IQ), a parameter used to model the activity of PIs against HIV strains in vivo, of 18.9. The PK-PD target attainment analyses of different regimens based on 5,000 simulated subjects predict that PPL-100 would be effective as a once-daily PI without the need of ritonavir boosting for both PI-naive and experienced patients when dosed with 600 mg or higher. When compared with the cross-resistance profile generated by Monogram Biosciences Inc., as reported by the Company on February 3, 2005, these analyses suggest that PPL-100 would be effective as an un-boosted, once-daily PI against highly resistant HIV strains which fail a number of boosted PI regimens. Furthermore, the model predicts that the plasma drug concentrations are sustained through 48 hours post-dosing at steady-state due to its long elimination half-life, giving excellent "forgiveness" for PI-naive and some PI-experienced patients in the event of missing a dose. Population PK modeling has previously been shown to accurately predict responsiveness of HIV infected patients to other PIs.


Protease Inhibitors (PIs) such as PPL-100, are a key component to the current HIV standard of care, the Highly Active Anti-Retroviral Treatment (HAART) consisting of a cocktail of reverse transcriptase inhibitors and PIs. Unfortunately, most PIs are associated with side effects, a high pill burden, and as it is the case with all anti-HIV drugs, the development of viral resistance. In addition, the majority of PIs are administered in combination with a small dose of ritonavir (a PI) which is used to increase ("boost") the amount of available drug in the system but which at the same time increases the adverse events. More than ever, there is a pressing need for safer, more convenient and effective PIs.


The ICPD serves as a center for translational science collaboration to the world. We help pharmaceutical and biotechnology companies develop more effective and safer drugs for patients through advanced methods of pharmacokinetic and pharmacodynamic system analysis. For more information, please visit the ICPD's web site:


Ambrilia Biopharma Inc. (TSX:AMB) is a biopharmaceutical company developing innovative and proprietary early- to mid-stage therapeutics in the fields of oncology and infectious diseases. Ambrilia's product portfolio includes an anti-cancer therapeutic peptide (PCK3145), a novel anti-cancer therapy (TVT-Dox), two oncology specialty generics (Octreotide, Goserelin), the first of which is late-stage and value-added, and promising anti-HIV treatments (PPL-100, SPC3). Ambrilia's head office, research and development and manufacturing facilities are located in Montreal with a regional office in France. For more information, please visit the Company's web site:

Forward-looking statements

This press release contains forward-looking statements that reflect the Company's current expectation regarding future events. The forward-looking statements involve risks and uncertainties. Actual events could differ materially from those projected herein and depend on a number of factors including, but not limited to, changing market conditions, successful and timely completion of clinical studies, uncertainties related to the regulatory approval process, establishment of corporate alliances and other risks detailed from time to time in the Company's filings. Such statements are also based on various assumptions, including the successful and timely completion of clinical studies on Ambrilia's products demonstrating efficacy and safety for human use, their successful commercialization within the forecasted timelines and the attainment of the forecasted milestone payments and other revenues. While Ambrilia anticipates that subsequent events and developments may cause Ambrilia's views to change, Ambrilia specifically disclaims any obligation to update these forward-looking statements.

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