Anadys Pharmaceuticals, Inc. (ANDS) is a relatively new public company focusing on developing anti-infective medicines. The company combines its expertise in biology and medicinal chemistry to develop drugs for hepatitis C, hepatitis B, and bacterial infections. To strengthen its drug development capabilities it has formed significant alliances with Roche, Daiichi, Gilead, LG Life Sciences, Aphoenix, and Amgen. These alliances have so far helped to generate revenue for the company through milestones and collaborative research and development (R&D) payments. In June 2005, ANDS signed a major deal with Novartis to develop and commercialize anti-infective drugs. The company also receives research grants and awards from the National Institute of Health (NIH). The company discontinued development of both its clinical compounds, ANA380 for hepatitis B virus (HBV) infection and ANA975 for both HBV and hepatitis C virus (HCV) infections. The company is now focusing all its resources on two products in pre-clinical development, ANA598 for chronic HCV infection and ANA773 for the treatment of certain cancers. The IND application of ANA773 was accepted during the third quarter of 2007 and phase I trials of the candidate are expected to commence shortly. The company undertook an extensive restructuring program in August 2007 and will look to reduce headcount by 1/3rd, resulting in annual savings of $4 million - $5 million. Anadys Pharmaceuticals, Inc. is based in San Diego, CA and employs about 86 people.
Drugs under Development
ANA598: In June 2007, Anadys nominated ANA598 for clinical development as an orally-administered direct antiviral for the treatment of chronic HCV infection. The decision to nominate ANA598 was based on pre-clinical studies that showed that the compound demonstrated favorable antiviral, metabolic, pharmacokinetic, and preliminary toxicologic properties. The company presented data from preclinical studies of ANA598 at the 14th International Symposium on Hepatitis C Virus and Related Viruses in September 2007. ANA598 was well tolerated in 14-day dose range finding (DRF) animal toxicology studies at all doses tested (1 to 1000mg/kg). Results from in-vivo preclinical studies designed to be predictive of potential human doses showed that trough plasma concentrations of ANA598 24 hours post dosing exceeded the EC95 for HCV genotype 1a and 1b replicon inhibition at doses corresponding to estimated human doses. The EC95 is the concentration required to suppress hepatitis C viral RNA levels by 95% in the replicon assay. Additional pre-clinical studies are being conducted and submission of an Investigational New Drug application (IND) is expected in the second quarter of 2008.
ANA598 was selected from the company's internal NS5b discovery effort, based on an optimized balance of preclinical properties, which include potency, oral bioavailability, pharmacokinetics, and tolerability. The compound has excellent potency against genotype I replicon. ANA598 also has excellent oral bioavailability of 50%-70% in various animal species. Furthermore, the pharmacokinetic properties are such that drug levels are maintained for 24 hours following a single, oral dose, corresponding to a reasonable human dose. The company evaluated the preliminary safety and toxicity of ANA598 in animals in 14-day dose-range finding studies that included histopathology analysis. A very clean profile was observed over 14 days, even at exposures well above what might be needed for efficacy. Anadys is currently conducting scale-up chemistry activities required to have the drug manufactured for IND enabling studies. In addition, the company continues to characterize the antiviral activity of ANA598, including the potential for combinations with interferon and/or direct antivirals such as protease inhibitors.
ANA773: ANA773 is a TLR7 agonist prodrug which will be studied for the treatment of certain cancers. Despite the discontinuation of the development of ANA975, Anadys is optimistic about the future of this compound. Results from pre-clinical studies suggest that the compound is more potent, with a favorable metabolic profile, than ANA975. Data from an in-vitro study of ANA773 presented at the Annual Meeting of the American Association of Cancer Research (AACR) showed that the active metabolite of ANA773 (an oral Toll-like receptor 7 (TLR7) agonist prodrug) induced the secretion of interferon-alpha (IFN-alpha) and various other cytokines from human peripheral blood mononuclear cells (PBMC) cultured in-vitro. Human PBMC stimulated with the active metabolite of ANA773 increased NK cell cytotoxicity and cytokine secretion against both K562 erythroleukemic cells and transformed B cell lines. These in vitro effects were reduced by the neutralization of IFN-alpha, confirming the role of cytokines induced by the TLR7 agonist in the killing of tumor cells. In addition to enhancing direct NK cell killing tumor cells, ANA773's active metabolite also enhanced ADCC. This study showed that transformed B cells, targeted by addition of the anti-CD20 antibody rituximab, were killed more efficiently when PBMC containing the killer cells were treated with the active metabolite of ANA773.
On the second quarter conference call, the company announced that it has manufactured adequate drug supplies for phase I clinical studies. The FDA accepted the IND for ANA773 during the third quarter of 2007 and a phase I trial of the candidate is expected to commence soon. Preclinical data presented at the 2007 AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics showed that a change in the dosing schedule of ANA773 in-vivo modulated the immunostimulatory responses in cancer patients. The company plans to evaluate the dosing schedule of dependency of various components of immune stimulation in cancer patients.