The 11th Alzheimer's Disease Drug Discovery International Conference, held in Jersey City, NJ, USA, included topics covering new therapeutic developments in the field of Alzheimer's disease. This conference report highlights selected presentations on targeting pathological tau for the prevention or treatment of Alzheimer's disease. Investigational approaches discussed include aminothienopyridazine inhibitors of tau aggregation, the alternative splicing of tau pre-mRNA, protein phosphatase 2A as a potential therapeutic target, and immunotherapy and macroautophagy approaches for clearing aberrant tau protein from the brain.
The HDAC Inhibitors meeting, held in Boston, included topics covering new therapeutic developments in the field of HDAC inhibitors. This conference report highlights selected presentations on HDAC inhibitors for the treatment of cancer, inflammation, and neurodegenerative and other CNS diseases. Investigational drugs discussed include several compounds under evaluation by Karus Therapeutics Ltd, OCID-4681 (Orchid Research Laboratories Ltd) and EVP-0334 (EnVivo Pharmaceuticals Inc).
The Natural Peptides to Drugs congress, held in Zermatt, Switzerland, included topics covering new therapeutic developments in the field of peptide-and protein-based drugs derived from natural products. This conference report highlights selected presentations on drug discovery from natural peptides, natural peptide-based drugs in preclinical and clinical development, and peptide candidates. Investigational drugs discussed include novel small peptides from KAI Pharmaceuticals Inc, XEP-018 (Atheris Laboratories), MKC-253 (MannKind Corp), AEZS-108 (AEterna Zentaris Inc) and XG-102 (Auris Medical AG/Xigen SA).
The JPMorgan Healthcare Conference, held in San Francisco, included presentations by various pharmaceutical companies summarizing their achievements in 2009 and expectations for 2010. This conference report highlights presentations from Exelixis Inc and Nektar Therapeutics. Investigational drugs from Exelixis, including XL-184 (in collaboration with Bristol-Myers Squibb Co), XL-147 and XL-765 (both in collaboration with sanofi-aventis), and from Nektar, including NKTR-118 and NKTR-119 (both now licensed to AstraZeneca plc), NKTR-171, NKTR-181, NKTR-194, NKTR-102, and NKTR-105, are discussed.
SMi's fifth annual ADMET Conference, held in London, included topics covering new developments in the field of ADMET. This conference report highlights selected presentations on ADME optimization in drug discovery; targeting drugs to the brain; predicting bonds that might be attacked during metabolism; treating Caco-2 membranes with vinblastine to enhance P-glycoprotein interactions; predictive ADMET in hit-to-lead optimization; structure-based studies of ADMET targets; an accelerated process for integrated drug development; building hypotheses in lead selection and optimization; supersaturation effects; the prediction of drug-drug interactions; developing a mechanism-based pharmacokinetic/pharmacodynamic model; drug transporter assays in drug discovery; time-dependent inhibition screens in early drug discovery; the system-dependent inhibition of CYP enzymes; the integrating predictive toxicology framework OpenTox; high-content analysis for predictive cytotoxicity testing; and emerging in vitro toxicity assays.
The 2010 Summer Meeting of the American Academy of Dermatology, held in Chicago, included topics covering new therapeutic developments in the field of dermatological diseases, including psoriasis. This conference report highlights selected presentations on the use of etanercept, adalimumab and briakinumab in the treatment of psoriasis.
The role of Natural Products in Drug Discovery and development in the New Millennium meeting, held in London, included topics covering new developments in the field of natural products in drug discovery. This conference report highlights selected presentations on the value of natural products, natural-product screening opportunities and technological improvements to enhance the use of natural compounds in drug discovery and development.
The Fifth Annual Immunotherapeutics and Vaccine Summit (ImVacS), held in Boston, included topics covering new developments in the field of adjuvants and delivery systems for vaccines. This conference report highlights selected presentations on vaccines for infectious diseases, the use of adenovirus 5 (Ad5) for oral vaccination, modes of delivery for vaccines, and the strategy of DNA vaccination.
The 50th annual Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC), held in Boston, included topics covering new therapeutic developments in the field of infectious disease. This conference report highlights selected presentations on research with novel antimicrobial agents. Investigational drugs discussed include the chitin synthase inhibitor nikkomycin Z (Valley Fever Solutions/University of Arizona), the glycosylphosphatidylinositol biosynthesis inhibitor E-1210 (Eisai), the β-1,3-d-glucan synthesis inhibitor MK-3118 (Merck & Co/SCYNEXIS), the metalloenzyme inhibitors VT-1129 and VT-1161 (both Viamet Pharmaceuticals), and the anti-inflammatory nanoemulsion NB-003 (NanoBio).
Informa Life Sciences' Fifth Annual Conference on Cell-Based Assays, held in Cologne, Germany, included topics covering new technical developments in the field of cell-based assays. This conference report highlights selected presentations on cell-based assays for compound screening and 3D cell-based assays.
The 23rd International Conference on Antiviral Research (ICAR), organized by the International Society for Antiviral Research (ISAR) and held in San Francisco, included topics covering new therapeutic developments in the field of antivirals. This conference report highlights selected presentations on CD4-BFFI (Roche Holding AG), a CD4 mAb-based bifunctional HIV entry inhibitor; a CLDC-HBsAg vaccine (Juvaris BioTherapeutics Inc/China National Biotec Group) against HBV; ODE-(S)-MPMPA (University of California San Diego), a potent anti-HCV compound; the anti-human CMV activity exhibited by tricin; the protective activity of Ingavirin against influenza A; and Prosetta Bioconformatics's approach to identifying small-molecule antivirals.
The Antibody Engineering & Design 2010 conference, held in Frankfurt, included topics covering new developments in the field of therapeutic antibodies. This conference report highlights selected presentations on 'fit for purpose' biologics, improving the pharmaceutical properties of antibodies, the selection of antibody fragments for therapeutic use, challenges in biopharmaceutical manufacturing, developing dual-targeting antibodies, epitope mapping, and the development of two novel mAbs. Investigational drugs discussed include 1D4.1-ABT325 (Abbott Laboratories), Sym-004 (Symphogen A/S) and CNTO-607 (Johnson & Johnson).
Medichem--BIT Life Sciences' First Annual International Conference, held in Beijing, included topics covering new developments in the field of medicinal chemistry for drug discovery. This conference report highlights selected presentations on research into the basic biology of signaling, ion channels and natural products; tools and techniques in medicinal chemistry; and medicinal chemistry for developing drugs for neurological, neoplastic and inflammatory diseases. Investigational drugs discussed include TTA-A8 (Merck & Co Inc).
Ruxolitinib (INCB-018424) is a potent, orally available, selective inhibitor of both JAK1 and JAK2 of the JAK-STAT signaling pathway, being developed by Incyte Corp and Novartis AG. Ruxolitinib was initially developed to target the constitutive activation of the JAK-STAT pathway in patients with myeloproliferative neoplasms (MPNs). Meaningful reductions in spleen size and constitutional symptoms have been noted in patients with myelofibrosis (both primary and post-essential thrombocythemia/polycythemia vera). Data from a phase I/II clinical trial led to ongoing registration trials in the US and Europe. Toxicity (primarily decreased erythropoiesis and thrombocytopoiesis) has been managed by close control of dosing. The inhibition of inflammatory cytokine signaling through JAK1 inhibition has led to intriguing results in patients with rheumatoid arthritis and psoriasis (using a topical cream formulation). Ruxolitinib is a well tolerated, first-in-class JAK2 inhibitor with various potential clinical indications.
New lipid-lowering agents include microsomal triglyceride transfer protein (MTP) inhibitors, which may have a role in the treatment of hypercholesterolemia. Clinical applications of MTP inhibitors have been focused primarily on high-dose monotherapy to produce substantial reductions in LDL-cholesterol levels (particularly for patients with homozygous familial hypercholesterolemia). However, this strategy has been associated with a high rate and severity of gastrointestinal and hepatic adverse events that has prohibited the use of these agents. Data suggest the LDL-cholesterol-lowering efficacy of low-dose lomitapide (AEGR-733, formerly BMS-201038), under development by Aegerion Pharmaceuticals Inc, in patients with familial hypercholesterolemia, both as a single agent and in combination with commonly prescribed lipid-lowering therapies. MTP inhibition with lomitapide may offer a treatment option for patients who cannot tolerate statin therapy or who experience insufficient LDL-cholesterol reduction with available therapies. However, the safety concerns for MTP inhibitors for the treatment of hyperlipidemia must be fully addressed, and the assessment of the risk-to-benefit ratio for MTP inhibitors in patients at different levels of cardiovascular-disease risk is required before clinical use of this class of drugs may be recommended.
Ifosfamide is a chemotherapeutic prodrug used in the treatment of several tumor entities, including bone and soft-tissue sarcoma. However, the application of high-dose ifosfamide is not feasible because of severe side effects caused by metabolites. The active metabolite isophosphoramide mustard is not suitable for administration because of chemical instability. ZIOPHARM Oncology Inc, under license from Dekk-Tec Inc, is developing palifosfamide, a formulation of isophosphoramide mustard with tris(hydroxymethyl)aminomethane salt-stabilization (palifosfamide-tris) and previously with lysine-stabilization (palifosfamide-lys). Preclinical studies and phase I and I/II clinical trials demonstrated that palifosfamide-tris had an antitumor efficiency comparable or superior to that of ifosfamide. Patients treated with palifosfamide-tris did not display any of the neurotoxic or nephrotoxic side effects associated with ifosfamide. At the time of publication, data from phase II trials were being evaluated and phase III trials were being planned. palifosfamide-tris is expected to be a safer and less toxic alternative to ifosfamide; however, considering other new approaches under investigation for tumors such as sarcoma, such as molecular-based treatment strategies, it is unclear what position palifosfamide-tris might occupy on the market.
Adopting an appropriate IP strategy is an important but complex area, particularly in the pharmaceutical and biotechnology sectors, in which aspects such as regulatory submissions, high competitive activity, and public health and safety information requirements limit the amount of information that can be protected effectively through secrecy. As a result, and considering the existing time limits for patent protection, decisions on how to approach IP in these sectors must be made with knowledge of the options and consequences of IP positioning. Because of the specialized nature of IP, it is necessary to impart knowledge regarding the options and impact of IP to decision-makers, whether at the level of inventors, marketers or strategic business managers. This feature review provides some insight on IP strategy, with a focus on the use of a new 'gaming' approach for transferring the skills and understanding needed to make informed IP-related decisions; the game Patentopolis is discussed as an example of such an approach. Patentopolis involves interactive activities with IP-related business decisions, including the exploitation and enforcement of IP rights, and can be used to gain knowledge on the impact of adopting different IP strategies.
Current in vivo approaches for the delivery of siRNAs have been hindered by inefficient targeting to cells and by the triggering of immune responses. The cellular delivery of siRNA by immunoprivileged cells avoids the immune response, because the siRNA is delivered from one cell interior to another via gap junctions, thereby avoiding the extracellular compartment. Human mesenchymal stem cells (hMSCs) can be delivered focally or systemically, and have also exhibited the ability to migrate to targeted tissue in vivo. These features suggest the potential use of hMSCs as a cellular delivery system for siRNA. This feature review discusses the role of gap junctions to facilitate the transfer of siRNA directly to target cells, thus avoiding the disadvantages involved with approaches that are dependent on the extracellular space for siRNA delivery.
The 101st Annual Meeting of the American Association of Cancer Research, held in Washington, DC, included topics covering new therapeutic developments in the field of cancer research. This conference report highlights selected presentations on preclinical data on the novel pan-PI3K pyrimidine-derived inhibitor BKM-120 (Novartis AG), the dual inhibition of mTOR/PI3K in NSCLC by PF-4691502 (Pfizer Inc), the small-molecule PDK-1 inhibitors PF-05177624 and PF-05197281 (both Pfizer) and the ability of RO-5323441 (F Hoffmann-La Roche Ltd/ThromboGenics NV/BioInvent International AB) to block tumor growth in vivo. Phase I clinical trial results for VB-111 (VBL Therapeutics) are also presented.
