Koronis: Developing a new treatment for HIV

I recently had the opportunity to conduct a brief interview with Jeff Parkins, Vice President of Clinical Development and Regulatory at Koronis on his company and the future of the biotechnology industry:

Can you tell me a little bit about Koronis and its mission?

Koronis Pharmaceuticals develops anti-viral therapeutics based on Viral Decay Acceleration TM (VDA), a novel drug mechanism that accelerates the accumulation of genetic mutations in a viral genome and causes a degradation of viral fitness.  Degrading fitness diminishes the viability of a viral population in a host and results in a decrease in viral replication.  In vitro experiments have demonstrated that this process leads to collapse of the viral population.

Koronis’ lead program is in phase 2a trials against human immunodeficiency virus (HIV); a second program against hepatitis C virus (HCV) is in preclinical development.

How long has Koronis been around?

Koronis was founded in 1999 to commercialize the research published by Drs. Larry Loeb and James Mullins at University of Washington, and Dr. John Essigmann at Massachusetts Institute of Technology in the Proceedings of the National Academy of Science in 1999.

Their research paralleled the earlier thinking of Nobel Laureate Manfred Eigen who coined the term “quasispecies” to describe an immensely large number of variant viral strains that result from a high replication rate in an error-prone virus.  Both HIV and HCV are excellent examples of such viruses.  Eigen hypothesized an “error threshold” that defines the population tipping point and leads to “error catastrophe” and a collapse of that viral population.

Serious commercial development began in 2000 when an investment syndicate was formed by Pacific Horizon Ventures. Pacific Horizon provides interim general management today.  The three founding scientists—Loeb, Mullins and Essigmann–continue their involvement as development collaborators and members of the Koronis’ Scientific Advisory Board.

Can you talk about your HIV lead, KP-1461?

KP-1461 is in phase 2 clinical development and since 2005 the drug has been administered to 61 HIV-infected patients—37 in a placebo-controlled, dose-escalating, 14-day dosing, phase 1b trial (KP-1461-102), and 24 in an open-label, 124-day dosing, phase 2a trial (KP-1461-201).  In each study the drug was found to be generally safe and well tolerated.

Human studies have shown evidence of anti-viral drug activity.  Today, further tests are being designed to confirm efficacy and define an optimal drug dose and formulation to support a pivotal trial design leading to product registration.

How is KP-1461 different from other treatments on the market?

If approved, KP-1461 would be the first HIV drug to utilize a non-inhibitory mechanism to control viral replication.  By avoiding direct suppression of viral replication, a VDA agent such as KP-1461 is expected to be better tolerated and more durable therapeutic against HIV.

All existing approved drugs suppress viral replication by inhibiting a critical enzymatic process or blocking viral entry to uninfected T-lymphocytes.  Each of these approved drugs exerts selective pressure on the virus as a consequence of suppressing replication.  It is selective pressure that leads to drug resistance and it is suppression of a particular enzymatic process that provokes the adverse side effects that characterize antiretroviral therapy today.

What is the biggest challenge facing Koronis right now?

Koronis’ biggest challenge is attracting the financial resources necessary to develop a novel drug mechanism for a disease that people mistakenly believe to be a well served chronic condition based on existing and derivative products utilizing current inhibitory mechanisms.

Koronis believes—as does the Center for Disease Control—that the HIV epidemic is far from over.  However, funding for HIV drug development has ebbed as the financial community has come to believe that the existing group of approved products is sufficient to address this epidemic.

What do you think is the biggest challenge facing the biotech industry as a whole?

Koronis’ challenges are shared broadly by other companies in the biotech industry as economic conditions, regulatory considerations and attitudes toward risk combine to influence the allocation of financial resources to later-stage and derivative products.  If there are to be next-generation products for tomorrow’s healthcare needs, it is necessary for the industry to address the shortage of development stage financing.

What’s up next for Koronis?

As Koronis concludes the proof-of-concept for VDA in HIV, the next step is a development partnership to fund additional late-stage clinical development.  In addition, Koronis is seeking a development partner for the preclinical HCV program.

About Koronis:

Koronis Pharmaceuticals, a Redmond, Washington-based company, was one of the winners of the Biotechnology Industry Organization 2009 International Convention’s Be the Buzz of BIO contest.