Tobira's Next-Generation Once-Daily CCR5/CCR2 Antagonist Demonstrates Potent CCR2 Inhibition, Antiviral Activity, Safety and Tol

TBR-652 Phase IIa Data Presented at XVIII International AIDS Conference Showcase Potentially Important Anti-Inflammatory Benefits

VIENNA, July 19 /PRNewswire/ -- Phase II data for TBR-652, a novel compound being developed by Tobira Therapeutics for the treatment of HIV infection, demonstrate that the dual CCR5/CCR2 antagonist provides potent antiviral activity and inhibition of the CCR2 receptor and is generally safe and well-tolerated in treatment-experienced patients with HIV. The data were presented here today in an oral presentation at the XVIII International AIDS Conference.

In a Phase IIa trial involving 54 patients, a 10-day course of once-daily TBR-652 monotherapy produced a median nadir decline from baseline in HIV viral load of up to 1.8 log10 copies/mL. There were no serious adverse events, deaths or study drug-related discontinuations in the proof-of-concept study. Investigators also observed dose-dependent changes in concentrations of monocyte chemoattractant protein-1 (MCP-1), the primary ligand for the CCR2 chemokine receptor and a potent chemoattractant for monocytes and macrophages. This latter finding provides further evidence of TBR-652's dual action on CCR5 and CCR2, suggesting a potential anti-inflammatory benefit of the compound. Importantly, to date, no significant safety signals have been identified with CCR2 antagonists.  

"This study of TBR-652 showed a statistically significant, dose-dependent effect on MCP-1 levels -- an important biomarker for CCR2 activity," observed David E. Martin, Pharm.D., Senior Vice President, Drug Development/Regulatory Affairs, Tobira Therapeutics, Inc. "The potential anti-inflammatory benefits of this dual CCR5/CCR2 antagonist will be further investigated in a series of Phase IIb sub-studies to evaluate the effects of TBR-652 on immunologic and inflammatory parameters, including cardiovascular and metabolic endpoints."

Dr. Martin presented data from Study 652-2-201, a double-blind, placebo-controlled, dose-escalation trial in which patients were randomized four-to-one to receive doses of TBR-652 of 25mg, 50mg, 75mg, 100mg, 150mg and placebo.  

All patients were HIV treatment-experienced, though none had previously been treated with a CCR5 antagonist. Most adverse events in the study were mild in severity (Grade 1). There were no clinically significant trends in adverse events, laboratory tests, vital signs, or electrocardiogram measurements. Additionally, there were no liver function test elevations greater than Grade 1.

The following dose-escalation chart outlines the antiviral activity (as evidenced by reductions in HIV viral load) and inflammation-marker change (as evidenced by increases in MCP-1 levels) of TBR-652:

Dosing cohort

HIV-1 RNA: median nadir
change from baseline
(log10 copies/mL)

MCP-1: mean change
from baseline after 10
days (pg/mL)

25 mg



50 mg



75 mg



100 mg



150 mg






*P=0.002 vs. placebo; **P<0.001 vs. placebo; P less than or equal to 0.02 vs. placebo

Dr. Martin described the dose-dependent increase in MCP-1 concentrations as a promising development, as was the favorable and predictable pharmacokinetic profile observed with TBR-652. "Our unique, dual CCR5/CCR2 investigational drug may provide a new strategy that would complement the well-established benefits of currently available virus-suppressing treatments for HIV," Dr. Martin said.

"Chronic inflammation increases the risks of cardiovascular disease, neurocognitive deficits, age-related disorders and non-AIDS-defining malignancies. These events account for nearly half of deaths in HIV-infected patients," said Kathleen Squires, M.D., Professor of Medicine, Director, Division of Infectious Diseases at Jefferson Medical College. "The development of a novel,  combination antiretroviral agent that is safe, tolerable,  potent and can modulate the chronic inflammation associated with HIV could have a powerful impact on improving and extending lives of people with HIV," she added.

About Tobira Therapeutics, Inc.

Tobira Therapeutics is a private biopharmaceutical company which is focused on developing and commercializing innovative antiviral compounds to treat HIV disease. The company was founded in 2006 by Eckard Weber, M.D., a partner at Domain Associates, to develop novel treatments for HIV disease. Tobira has assembled a highly experienced management team with decades of clinical and commercial development experience specifically in HIV/AIDS drug development.

SOURCE Tobira Therapeutics, Inc.