OVERVIEW
Kineta has multiple development efforts that focus on anti-infectives and inflammation caused by autoimmune diseases. In both areas we focus on the host side of the pathogen-host interaction. These are areas in which our team has proven scientific leadership and cutting-edge commercial development success. Our goal is to develop broad-spectrum products with novel mechanisms of action. We believe such therapies will not only be extremely effective, but also produce fewer side effects and will be far less likely to result in drug resistance.

PRECLINICAL
ShK Analogs: Novel Compounds with Tremendous Potential for Multiple Sclerosis and Other Autoimmune Diseases

On July 7, 2009, Kineta announced the acquisition of a portfolio of novel compounds from Airmid Incorporated. These unique, first in class compounds will be applied to an array of autoimmune diseases. Initial development of these compounds will be focused on multiple sclerosis, but they also have strong potential for other autoimmune diseases including: type I diabetes mellitus, rheumatoid arthritis and orphan diseases such as Wegener's granulomatosis and muscular inflammatory diseases (myopathies).

The ShK analogs were developed after more than twenty years of research by K. George Chandy, MD, Ph.D. and other colleagues at the University of California, Irvine. As with many potent pharmaceuticals, ShK-analogs are products of the natural world; they are derived from the Caribbean sea anemone. Airmid scientists have since made modifications to further improve their drug function.

The novel class of compounds includes potent and highly specific Kv1.3 potassium channel blockers. They are designed to suppress activation of effector memory T cells (a subset of white blood cells) that trigger inflammation and tissue damage in autoimmune diseases. These compounds have been shown to significantly reverse disease in animal models of multiple sclerosis and rheumatoid arthritis. They also have potential against a number of other autoimmune diseases controlled by effector memory T cells including type 1 diabetes and Crohn's disease. Animal models have demonstrated that efficacy is achieved without the generalized immunosuppression that is a common, problematic side effect of competing therapies.

Kineta scientists have designed a development plan to bring a lead drug to clinical trials by mid-2010. This program is owned and managed by Kineta One, LLC - a subsidiary of Kineta, Inc.

Key Program Features:

• 12-15 months to first FDA filing and clinical trials
• New class of drug
• Designed to restore normal immune function
• Improved tolerability and efficacy

• Kv1.3 potassium channels as a therapeutic target in multiple sclerosis.
  Rangaraju S, Chi V, Pennington MW, Chandy KG.
  Expert Opin Ther Targets. 2009 Aug;13(8):909-24.
  
  
• Engineering a stable and selective peptide blocker of the Kv1.3 channel in T lymphocytes.
  Pennington MW, Beeton C, Galea CA, Smith BJ, Chi V, Monaghan KP, Garcia A, Rangaraju S, Giuffrida A, Plank D, Crossley G, Nugent D, Khaytin I, Lefievre Y, Peshenko I, Dixon C, Chauhan S, Orzel A, Inoue T, Hu X, Moore RV, Norton RS, Chandy KG.
  Mol Pharmacol. 2009 Apr;75(4):762-73.
  
  
• Imaging of effector memory T cells during a delayed-type hypersensitivity reaction and suppression by Kv1.3 channel block.
  Matheu MP, Beeton C, Garcia A, Chi V, Rangaraju S, Safrina O, Monaghan K, Uemura MI, Li D, Pal S, de la Maza LM, Monuki E, Flügel A, Pennington MW, Parker I, Chandy KG, Cahalan MD.
  Immunity. 2008 Oct 17;29(4):602-14.
  
  
• Kv1.3 channels are a therapeutic target for T cell-mediated autoimmune diseases.
  Beeton C, Wulff H, Standifer NE, Azam P, Mullen KM, Pennington MW, Kolski-Andreaco A, Wei E, Grino A, Counts DR, Wang PH, LeeHealey CJ, S Andrews B, Sankaranarayanan A, Homerick D, Roeck WW, Tehranzadeh J, Stanhope KL, Zimin P, Havel PJ, Griffey S, Knaus HG, Nepom GT, Gutman GA, Calabresi PA, Chandy KG.
  Proc Natl Acad Sci U S A. 2006 Nov 14;103(46):17414-9.
  
  
• Potassium channels, memory T cells, and multiple sclerosis.
  Beeton C, Chandy KG.
  Neuroscientist. 2005 Dec;11(6):550-62.
  
  
• The voltage-gated potassium channel Kv1.3 is highly expressed on inflammatory infiltrates in multiple sclerosis brain.
  Rus H, Pardo CA, Hu L, Darrah E, Cudrici C, Niculescu T, Niculescu F, Mullen KM, Allie R, Guo L, Wulff H, Beeton C, Judge SI, Kerr DA, Knaus HG, Chandy KG, Calabresi PA.
  Proc Natl Acad Sci U S A. 2005 Aug 2;102(31):11094-9.
  
  
• Targeting effector memory T cells with a selective peptide inhibitor of Kv1.3 channels for therapy of autoimmune diseases.
  Beeton C, Pennington MW, Wulff H, Singh S, Nugent D, Crossley G, Khaytin I, Calabresi PA, Chen CY, Gutman GA, Chandy KG.
  Mol Pharmacol. 2005 Apr;67(4):1369-81.
  
  
• The voltage-gated Kv1.3 K(+) channel in effector memory T cells as new target for MS.
  Wulff H, Calabresi PA, Allie R, Yun S, Pennington M, Beeton C, Chandy KG.
  J Clin Invest. 2003 Jun;111(11):1703-13.
  
  
• Selective blockade of T lymphocyte K(+) channels ameliorates experimental autoimmune encephalomyelitis, a model for multiple sclerosis.
  Beeton C, Wulff H, Barbaria J, Clot-Faybesse O, Pennington M, Bernard D, Cahalan MD, Chandy KG, Beraud E.
  Proc Natl Acad Sci U S A. 2001 Nov 20;98(24):13942-7.
  
  

DISCOVERY SCIENCE
RIG-I Pathway: Leading us to new therapies for fighting deadly viruses

Kineta has developed a proprietary screening platform to identify drugs that activate the retinoic acid inducible gene I protein (RIG-I) switch, even after a viral infection is established.

RIG-I, is a molecular "on/off" switch that triggers the human body's immune defenses against virus infection. When activated, RIG-I mediates the expression of numerous antiviral genes thereby establishing an environment in cells that is inhospitable to virus replication and the advancement of disease. Kineta's RIG-I program holds great promise toward the development of a unique broad spectrum antiviral drug that is more effective, less toxic and less likely to cause virus mutation and resistance.

Our expertise in understanding immune system function and finding novel drug targets also gives Kineta a substantial lead in the development of additional new compounds capable of regulating the immune system.