Tobira Therapeutics Presents Positive Phase 2b Clinical Results For Cenicriviroc in Treatment-Naïve HIV Infection in Late

  Tobira Therapeutics Presents Positive Phase 2b Clinical Results For
  Cenicriviroc in Treatment-Naïve HIV Infection in Late Breaker Session at
  CROI

CROI 2013

Business Wire

SOUTH SAN FRANCISCO, Calif. -- March 5, 2013

Tobira Therapeutics presented positive results from the Phase 2b clinical
trial (Study 202) of cenicriviroc (CVC) today at the 20th Conference on
Retroviruses and Opportunistic Infections (CROI 2013). CVC is a novel, oral,
once-daily, dual CCR5/CCR2 inhibitor in clinical development for the treatment
of HIV infection.

Study 202 is a randomized, double-blind, double-dummy, dose-finding,
controlled study that enrolled 143 HIV-1 infected patients with CCR5-tropic
HIV infection. At week 24, 100mg or 200mg of once-daily CVC plus Truvada®
(emtricitabine/tenofovir disoproxil fumarate) demonstrated similar virologic
success rates (76% and 73%) compared to once-daily Sustiva® (efavirenz or EFV)
plus Truvada (71%). A favorable safety and tolerability profile was observed
in CVC-treated patients. In addition, a significant decrease in monocyte
activation, measured by reduction in sCD14 levels, was seen in CVC-treated
patients. The complete week 24 results from Study 202 were presented as a Late
Breaker Abstract Presentation by Joseph C. Gathe, MD during the session titled
“New Agents and New Insights” in a talk titled “Week 24 Primary Analysis of
Cenicriviroc vs Efavirenz, in Combination with FTC/TDF, in Treatment-naïve
HIV-1 Infected Adults with CCR5-tropic Virus,” (Abstract 106LB).

“In this study CVC showed compelling antiviral activity and favorable safety
when compared to the current standard of care,” said Dr. Gathe. “Based on
these positive data, CVC has the potential to become an important addition to
novel HIV treatment strategies.”

“The promising data generated by Study 202 reinforce our resolve to make CVC a
key component in the future treatment of HIV,” said Andrew Hindman, Tobira’s
President and Chief Executive Officer. “Based on these data, we are actively
planning for the initiation of Phase 3 registrational studies of CVC,
including fixed-dose combinations and complete single-tablet regimens
containing CVC.”

Study 202 Result Highlights: At the primary endpoint of 24 weeks, the
percentage of patients in the 100mg and 200mg CVC study arms achieving
virologic success, defined as HIV viral load< 50 copies/mL, was 76% and 73%,
respectively compared to 71% in the EFV arm. Cenicriviroc was well tolerated
and lower rates of adverse events were observed in the CVC arms when compared
to the EFV arm. LDL cholesterol levels decreased among patients receiving CVC,
while both LDL and HDL cholesterol levels increased among patients receiving
EFV. Anti-inflammatory markers correlating to the CCR2 ligand (MCP-1)
increased in a dose-dependent manner among patients who received CVC. Finally,
levels of sCD14, a marker of monocyte activation and an independent predictor
of mortality in HIV infection, decreased over the course of the study for
CVC-treated subjects, but increased for EFV-treated subjects.

Study 202 Design: Study 202 is a double-blind, double-dummy, randomized,
controlled Phase 2b trial, evaluating once-daily doses of CVC 100mg or 200mg
compared to once-daily Sustiva^® (efavirenz), each in combination with
open-label Truvada^® (emtricitabine/tenofovir disoproxil fumarate). The study
enrolled a total of 143 treatment-naïve, HIV-1 infected adults with
CCR5-tropic virus. Patients with CCR5-tropic virus represent approximately 80%
of the treatment-naïve HIV-infected population. The primary objective of this
trial is to determine the efficacy and safety of CVC when compared to
efavirenz, both as part of combination HIV therapy. Additionally, the trial
assesses changes in biomarkers associated with inflammation, metabolic
parameters, and immune function. The study will continue for a total duration
of 48 weeks for further evaluation of efficacy and safety.

Phase 3 Development Strategy: Based on the results of Study 202, Tobira is
preparing for CVC’s Phase 3 registrational program. Tobira plans to conduct
two, randomized, controlled, double-blinded, double-dummy, Phase 3 trials,
each in approximately 750 HIV-1 infected adults with CCR5-tropic HIV virus.
These trials will evaluate efficacy and safety of CVC-containing combination
regimens compared to treatment guideline-preferred first-line treatment
options. The trials will be designed with a 48-week primary analysis to
support global regulatory filings, and will continue for 96-weeks in the final
analysis. The trials will also assess the effect of CVC on inflammatory and
metabolic comorbidities often associated with chronic HIV-1 infection.
Patients with HIV infection, even those well-controlled on antiretroviral
therapy, experience these diseases earlier and at higher rates than uninfected
individuals.^1

About Cenicriviroc

Cenicriviroc (CVC) is a novel, oral, once-daily, fixed-dose combinable, dual
inhibitor of chemokine receptors CCR5 and CCR2 being developed for the
treatment of HIV-1 infection. CVC was designed to bind and block two cellular
chemokine receptors: CCR5 and CCR2. The CCR5 receptor is a key avenue for
entry of HIV into human T-cells. CCR2 is involved in monocyte-related immune
activation, which is implicated in several inflammation-mediated diseases.
Tobira’s HIV development program evaluates CVC as a single-agent tablet and in
fixed-dose combination tablets with other HIV antiretrovirals, for use in
complete regimens for treatment of HIV infection. Annually, the U.S. CDC and
UNAIDS estimate 47,500 and 2.5 million new HIV infections occur in the U.S.
and globally, respectively.

About Tobira Therapeutics

Tobira Therapeutics is a privately held biopharmaceutical company developing
innovative therapies for treatment of HIV infection. The company’s lead
development candidate is cenicriviroc (CVC), a novel, oral, once-daily,
fixed-dose combinable, dual inhibitor of chemokine receptors CCR5 and CCR2.
Tobira has financial support from a syndicate of leading life science
investors including Domain Associates, Frazier Healthcare Ventures, Montreux
Equity Partners, Novo Ventures and Canaan Partners. Learn more at
www.TobiraTherapeutics.com.

^1 Volberding and Deeks, Antiretroviral therapy and management of HIV
infection. Lancet Vol. 376 (July 3, 2010), and The Journal of Infectious
Diseases 2012:205

Contact:

Tobira Therapeutics
Caroline Loewy, 650-741-6625
EVP & CFO
cloewy@tobiratherapeutics.com
or
BCC Partners for Tobira Therapeutics
Karen L. Bergman, 650-575-1509
kbergman@bccpartners.com
Michelle Corral, 415-794-8662
mcorral@bccpartners.com