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Rick Mullin - One of the best experts on this subject based on the ideXlab platform.

  • PARTNERSHIPS DEBUT AT INFORMEX: FINE CHEMICALS: Trade show finds suppliers vying for position on high-tech outsourcing
    Chemical & Engineering News, 2010
    Co-Authors: Rick Mullin
    Abstract:

    EXHIBITORS at the annual Informex trade show in San Francisco last week put a positive spin on business in the fine chemicals sector, pointing to a continuing trend toward pharmaceutical outsourcing and signs of an upturn in the general economy. Several companies announced partnerships they claim will position them to take advantage of new opportunities to supply active pharmaceutical ingredients (APIs) and intermediates. Dishman Group and Ampac Fine Chemicals announced collaborations with Codexis under which both companies will have access to Codexis’ enzymebased biocatalysis technology. Nick Green, president of Dishman Contract Research & Manufacturing Services, says the firm will manufacture products for Codexis and will also use the technology in its own contract production of APIs and intermediates. Aslam Malik, president of Ampac, says the agreement will allow his firm to add enzyme biocatalysis to its tools for chiral chemistry, which include simulated moving bed separations. Meanwhile, Albemarle’s...

  • Codexis Wins $10 Million Investment From Pfizer
    Chemical & Engineering News, 2004
    Co-Authors: Rick Mullin
    Abstract:

    Biocatalysis and fermentation process development firm Codexis received a major boost last week with a $10 million equity investment from Pfizer. The investment accompanies a new research agreement...

  • Codexis wins 10 million investment from pfizer
    Chemical & Engineering News, 2004
    Co-Authors: Rick Mullin
    Abstract:

    Biocatalysis and fermentation process development firm Codexis received a major boost last week with a $10 million equity investment from Pfizer. The investment accompanies a new research agreement...

Sheela Muley - One of the best experts on this subject based on the ideXlab platform.

Vildová Iveta - One of the best experts on this subject based on the ideXlab platform.

  • Effect of changes in selected tax atcs on economic status of the state
    Vysoká škola ekonomická v Praze, 2014
    Co-Authors: Vildová Iveta
    Abstract:

    Bakalářská práce ověřuje pozitivní vliv změn zákonů o dani z příjmu na ekonomiku, vzhledem k postupnému snižování sazeb daní za několik posledních let a negativní vliv změn zvyšující se sazby daně z přidané hodnoty. Teoretická část nabízí pohled základních studií, které se vyjadřují ke vztahu změn daňového zatížení a ekonomické situaci země. V praktické části je provedena regresní analýza na základě dat do roku 2012 získaných z portálu Českého statistického úřadu, právních systémů ASPI a Codexis. Jako signifikantní vysvětlující proměnné zůstaly v modelu základní statutární sazby daně z příjmu právnických osob i daně z přidané hodnoty, obě s negativním dopadem na HDP. V závěru práce výsledky studie potvrzují shodu s odbornými články vzhledem k vlivu jednotlivých sazeb daně na HDP.This thesis verifies the positive impact of income law changes on economy due to relative reduction of statutory income tax rate during last years and negative impact growing statutory value added tax rate. The theoretical part presents studies that comment on the tax burden and economic state of the country. In practical part is performed the regression analysis on the data by 2012 obtained mainly from Czech Statistical Office and legal systems ASPI and Codexis. Basic statutory rates of corporate and value-added taxes are significant with negative effect on GDP. Finally, the work confirms the results of other studies regarding the influence of these taxes on economic state of the country

  • Effect of changes in selected tax atcs on economic status of the state
    Vysoká škola ekonomická v Praze, 2013
    Co-Authors: Vildová Iveta
    Abstract:

    This thesis verifies the positive impact of income law changes on economy due to relative reduction of statutory income tax rate during last years and negative impact growing statutory value added tax rate. The theoretical part presents studies that comment on the tax burden and economic state of the country. In practical part is performed the regression analysis on the data by 2012 obtained mainly from Czech Statistical Office and legal systems ASPI and Codexis. Basic statutory rates of corporate and value-added taxes are significant with negative effect on GDP. Finally, the work confirms the results of other studies regarding the influence of these taxes on economic state of the country

Martin Koller - One of the best experts on this subject based on the ideXlab platform.

  • The VITAL Amyloidosis Study: A Randomized, Double-Blind, Placebo-Controlled, Global, Phase 3 Study of NEOD001 in Patients with AL Amyloidosis and Cardiac Dysfunction
    Blood, 2016
    Co-Authors: Michaela Liedtke, Giampaolo Merlini, Heather Landau, Raymond L. Comenzo, Vaishali Sanchorawala, Brendan M. Weiss, Jeffrey A. Zonder, Jackie Walling, Gene G. Kinney, Martin Koller
    Abstract:

    Background: Amyloid light chain (AL) amyloidosis is caused by the deposition of misfolded light chain (LC) proteins, which may cause organ failure and death. Current treatments, which target the plasma cells that produce LC, induce organ responses in only 30% to 40% of patients. There is a substantial need for a safe and effective amyloid-directed therapy to improve recovery of organ function. NEOD001, a monoclonal antibody that targets misfolded LC, is hypothesized to neutralize circulating LC aggregates and to clear insoluble organ deposits. In an ongoing phase 1/2 study (NCT02613182; Gertz M et al. J Clin Oncol. 2016;34(10):1097-1103) in 27 patients with AL amyloidosis and persistent organ dysfunction, monthly NEOD001 infusions were well tolerated and produced no infusion-related hypersensitivity reactions. In a best response analysis of subjects who fulfilled eligibility criteria at baseline, 57% met cardiac and 60% met renal response criteria. Supported by these positive results, the current study (VITAL; NCT02312206) is a randomized, double-blind, placebo-controlled, phase 3 trial of NEOD001 in patients with cardiac AL amyloidosis. Here we present the study design for this trial in progress. Patients and Methods: Eligible patients (estimated enrollment, 236) with a diagnosis of AL amyloidosis (newly diagnosed, treatment naive) and cardiac dysfunction (N-terminal probrain natriuretic peptide [NT-proBNP] ≥650 and 12 mm, or cardiac biopsy-detected amyloidosis) and with estimated glomerular filtration rate ≥30 mL/min/1.73 m2 will be randomly assigned (1:1) to receive NEOD001 (24 mg/kg q28d) plus standard of care (SOC) chemotherapy or placebo plus SOC therapy. Subjects will be stratified according to Mayo Clinic stage, renal stage, and 6-minute walk test (6MWT) distance. The primary end point is a composite, evidence-based measure consisting of all-cause mortality or cardiac hospitalization. Key secondary end points include cardiac response measured by NT-proBNP (as defined by Comenzo RL et al. Leukemia. 2012;26(11):2317-2325) and change in 6MWT distance, Short Form-36 Health Survey response, Neuropathy Impairment Score-Lower Limb and renal response (as defined by Palladini G et al. Blood. 2014;124(15):2325-2332). Disclosures Liedtke:Gilead: Research Funding; Pfizer: Consultancy, Research Funding; Novartis: Research Funding; Amgen: Consultancy, Research Funding; Prothena: Consultancy, Research Funding; Takeda: Consultancy, Research Funding; Celgene: Research Funding. Merlini:Takeda and Janssen-Cilag: Honoraria. Landau:Janssen: Consultancy; Spectrum Pharmaceuticals: Honoraria, Membership on an entity9s Board of Directors or advisory committees; Onyx/Amgen: Research Funding; Takeda: Membership on an entity9s Board of Directors or advisory committees, Research Funding; Prothena: Honoraria, Membership on an entity9s Board of Directors or advisory committees. Comenzo:Takeda: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; Prothena: Consultancy, Research Funding; Karyopharm: Research Funding. Sanchorawala:Prothena: Research Funding; Takeda: Research Funding; Celgene: Research Funding. Weiss:Janssen: Consultancy, Other: Travel, accommodations, Research Funding; Millennium: Consultancy, Other: Travel, accommodations; GlaxoSmithKline: Consultancy; Prothena: Other: Travel, accommodations, Research Funding; Novartis: Consultancy. Zonder:Array Biopharma: Consultancy; Prothena: Consultancy; Celgene: Consultancy, Research Funding; BMS: Consultancy; Takeda: Consultancy; Janssen: Consultancy; Seattle Genetics: Consultancy. Walling:Stealth: Consultancy; KaloBios: Consultancy; Exelixis: Consultancy; Newgen: Consultancy; Mateon (was Oxigene): Consultancy; Apex: Consultancy; Corcept: Consultancy; Aduro: Consultancy; Prothena: Consultancy; BioMarin: Equity Ownership; Amgen: Equity Ownership, Patents & Royalties; NuMedii: Consultancy; Pharm-Olam: Consultancy; Crown Bioscience: Consultancy; Codexis: Consultancy; Upsher Smith: Consultancy, Patents & Royalties. Kinney:Prothena: Employment, Equity Ownership, Other: Leadership. Koller:Prothena: Employment, Equity Ownership, Other: Travel, accommodations. Gertz:Ionis: Research Funding; Prothena Therapeutics: Research Funding; Novartis: Research Funding; Alnylam Pharmaceuticals: Research Funding; Annexon Biosciences: Research Funding; Research to Practice: Honoraria, Speakers Bureau; Med Learning Group: Honoraria, Speakers Bureau; Celgene: Honoraria; NCI Frederick: Honoraria; Sandoz Inc: Honoraria; GSK: Honoraria.

  • NEOD001 Demonstrates Organ Biomarker Responses in Patients with Light Chain Amyloidosis and Persistent Organ Dysfunction: Results from the Expansion Cohort of a Phase 1/2 Study
    Blood, 2016
    Co-Authors: Morie A. Gertz, Heather Landau, Raymond L. Comenzo, Vaishali Sanchorawala, Brendan M. Weiss, Jeffrey A. Zonder, Jackie Walling, Gene G. Kinney, Martin Koller, Dale Schenk
    Abstract:

    Introduction: Systemic amyloidoses are a group of rare disorders characterized by the accumulation of misfolded proteins in tissue, resulting in the dysfunction of vital organs (eg, heart and kidneys). In amyloid light chain (AL) amyloidosis, the most common form of systemic amyloidosis, the amyloidogenic protein is a misfolded light chain (LC) or a fragment of an LC produced by clonal plasma cells. Current therapies used to treat AL amyloidosis limit LC production but do not directly target deposits underlying multiorgan failure. NEOD001, a monoclonal antibody, targets misfolded LC and is thought to neutralize circulating LC aggregates and to clear insoluble deposits. In an interim analysis of a phase 1/2 dose-escalation study in 27 patients with AL amyloidosis and persistent organ dysfunction ([NCT01707264][1]; EudraCT2012-002683-27), monthly infusions of NEOD001 were safe, well tolerated, and associated with renal and cardiac responses.1 Here we report updated results from the escalation phase and new results from the expansion phase of this study. Patients and Methods: Inclusion criteria for this trial were that patients complete ≥1 PCD treatment before enrollment, attain partial hematologic response (HR) or better to any previous therapy, and have persistent organ dysfunction. NEOD001 was administered intravenously every 28 days. During the dose-escalation phase, 27 patients received NEOD001 at 0.5, 1, 2, 4, 8, 16, or 24 mg/kg in a 3+3 study design. An additional 42 patients with renal, cardiac, or peripheral nerve involvement were enrolled and treated (24 mg/kg) in the expansion phase. We assessed safety/tolerability, pharmacokinetics, immunogenicity, cardiac and renal responses based on consensus criteria, and neuropathy responses using the Neuropathy Impairment Score-Lower Limb (NIS-LL). Results: The 42 additional patients enrolled in the expansion study included cohorts with renal (16 patients), cardiac (15 patients), and peripheral nerve (11 patients) involvement. In the overall population (n = 69), the median age was 60 years, and 61% of patients were men. Median (range) time since diagnosis was 2.8 (0.4-12.8) years, and 45% of patients underwent ≥3 previous plasma cell-directed regimens. The total number of infusions administered was 913 over a mean of 13.2 (range, 3-35) months. NEOD001 treatment was not associated with dose-limiting toxicities or discontinuations; patients did not develop antidrug antibodies or treatment-related serious adverse events. The most frequent treatment-emergent adverse events, regardless of relationship to study drug, were fatigue, upper respiratory tract infection, nausea, and diarrhea. In a best response analysis, 53% of cardiac-evaluable patients (N = 36) and 63% of renal-evaluable patients (N = 35) met respective criteria for organ response; no patients experienced disease progression. The median time to initial response was 2 months (cardiac) and 4 months (renal). After 9 months of treatment, 82% of patients with measurable peripheral neuropathy at baseline (N = 11) achieved a peripheral neuropathy response based on the NIS-LL score. Conclusions: Our interim results demonstrated that monthly NEOD001 infusions were safe and well tolerated and that organ response rates compared favorably with traditional chemotherapy. These updated results from the escalation phase and these new results from the expansion phase, including results from patients with peripheral nerve involvement, support the design of ongoing late-stage clinical studies. Antibody therapy may allow for effective treatment of patients with AL amyloidosis. Reference: 1. Gertz MA, Landau H, Comenzo RL, et al. First-in-human phase 1/2 study of NEOD001 in patients with light chain amyloidosis and persistent organ dysfunction. J Clin Oncol . 2016;34(10):1097-1103. Disclosures Gertz: Prothena Therapeutics: Research Funding; Novartis: Research Funding; Alnylam Pharmaceuticals: Research Funding; Research to Practice: Honoraria, Speakers Bureau; Med Learning Group: Honoraria, Speakers Bureau; Celgene: Honoraria; NCI Frederick: Honoraria; Sandoz Inc: Honoraria; GSK: Honoraria; Ionis: Research Funding; Annexon Biosciences: Research Funding. Comenzo: Karyopharm: Research Funding; Janssen: Consultancy, Research Funding; Takeda: Consultancy, Research Funding; Prothena: Consultancy, Research Funding. Landau: Janssen: Consultancy; Spectrum Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees, Research Funding; Prothena: Honoraria, Membership on an entity's Board of Directors or advisory committees; Onyx/Amgen: Research Funding. Sanchorawala: Celgene: Research Funding; Takeda: Research Funding; Prothena: Research Funding. Weiss: Prothena: Other: Travel, accommodations, Research Funding; GlaxoSmithKline: Consultancy; Millennium: Consultancy, Other: Travel, accommodations; Janssen: Consultancy, Other: Travel, accommodations, Research Funding; Novartis: Consultancy. Zonder: BMS: Consultancy; Celgene: Consultancy, Research Funding; Prothena: Consultancy; Array Biopharma: Consultancy; Takeda: Consultancy; Janssen: Consultancy; Seattle Genetics: Consultancy. Walling: Stealth: Consultancy; BioMarin: Equity Ownership; Apex: Consultancy; Pharm-Olam: Consultancy; NuMedii: Consultancy; Amgen: Equity Ownership, Patents & Royalties; Crown Bioscience: Consultancy; KaloBios: Consultancy; Exelixis: Consultancy; Newgen: Consultancy; Mateon (was Oxigene): Consultancy; Corcept: Consultancy; Prothena: Consultancy; Aduro: Consultancy; Codexis: Consultancy; Upsher Smith: Consultancy, Patents & Royalties. Kinney: Prothena: Employment, Equity Ownership, Other: Leadership. Koller: Prothena: Employment, Equity Ownership, Other: Travel, accommodations. Schenk: Prothena: Employment, Equity Ownership, Other: Leadership. Guthrie: Prothena: Employment, Equity Ownership, Other: Leadership. Liu: Prothena: Employment, Equity Ownership; Weston Brain Institute: Honoraria. Liedtke: Prothena: Consultancy, Research Funding; Takeda: Consultancy, Research Funding; Amgen: Consultancy, Research Funding; Celgene: Research Funding; Gilead: Research Funding; Pfizer: Consultancy, Research Funding; Novartis: Research Funding. [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT01707264&atom=%2Fbloodjournal%2F128%2F22%2F644.atom

  • Organ Biomarker Responses in Patients with Light Chain Amyloidosis Treated with NEOD001 Are Independent of Previous Hematologic Response
    Blood, 2016
    Co-Authors: Michaela Liedtke, Heather Landau, Raymond L. Comenzo, Vaishali Sanchorawala, Brendan M. Weiss, Jeffrey A. Zonder, Jackie Walling, Gene G. Kinney, Martin Koller, Dale Schenk
    Abstract:

    Introduction: In amyloid light chain (AL) amyloidosis, the most common form of systemic amyloidosis, misfolded light chain (LC) or a fragment of an LC produced by clonal plasma cells accumulates in tissue, resulting in the dysfunction of vital organs and systems (eg, heart, kidneys, nervous system). Current therapies used to treat AL amyloidosis limit LC production but do not directly target deposits underlying multiorgan failure. Approximately 75% of patients do not achieve organ responses and have persistent organ dysfunction. Amyloid-directed therapies may stabilize and potentially reverse organ damage by specifically targeting existing LC aggregates. NEOD001, a monoclonal antibody, targets misfolded LC and is thought to neutralize circulating LC aggregates and to clear insoluble deposits. We have previously reported that monthly infusions of NEOD001 were safe and well tolerated. In addition, NEOD001 was associated with renal and cardiac responses. Here we analyzed the association between organ response and depth and time since last plasma cell-directed (PCD) treatment in the entire cohort of 69 patients enrolled in both the dose-escalation and the expansion phases of the phase 1/2 study. Methods: Inclusion criteria for this trial were that patients complete ≥1 PCD treatment before enrollment, attain partial hematologic response (HR) or better to any previous therapy, and have persistent organ dysfunction. NEOD001 was administered intravenously every 28 days. During the dose-escalation phase, 27 patients received NEOD001 at 0.5, 1, 2, 4, 8, 16, or 24 mg/kg in a 3+3 study design. An additional 42 patients with renal, cardiac, or nerve involvement were enrolled and treated (24 mg/kg) in the expansion phase. We assessed cardiac and renal responses based on consensus criteria and neuropathy responses using the Neuropathy Impairment Score-Lower Limb (NIS-LL). For this analysis, we focused on the relationship between organ response after treatment with NEOD001 to the time since last or best HR and the depth of best and last HR. Results: A total of 69 patients were enrolled, 27 in the dose-escalation and 42 in the expansion cohorts. The entire population included 36 cardiac-evaluable patients, 35 renal-evaluable patients, and 11 patients evaluated for peripheral neuropathy; 39% were women, and the median age was 60 years. Time since diagnosis was 2.8 (0.4-12.8; median, range) years, and 45% of patients had undergone ≥3 previous PCD regimens. Of the patients evaluable for organ response, best response rates indicating organ response were observed in 53% of cardiac-evaluable patients (n = 19/36) and 63% of renal-evaluable patients (n = 22/35). NIS-LL scores indicated that 82% (n = 9/11) of patients met criteria for a peripheral neuropathy response to NEOD001. Cardiac and renal response rates for NEOD001-treated patients could not be attributed to previous PCD treatment regimens. For example, 37% of the NEOD001 cardiac responders and 35% of nonresponders received cyclophosphamide-bortezomib-dexamethasone. Similarly, for NEOD001 renal responders vs nonresponders, 27% vs 25% were treated with autologous stem cell transplantation and 27% vs 31% were treated with bortezomib-dexamethasone. There was no relationship between NEOD001 cardiac, renal, or peripheral nerve organ response and time since last chemotherapy, time since last or best HR, or depth of last or best HR. Finally, an equivalent percentage of evaluable patients experienced renal or cardiac response regardless of whether they had received their most recent PCD treatment ≤6 months or >6 months before NEOD001 initiation. The median time since last PCD treatment to the start of NEOD001 intervention for all patients was 6.5 (range, 0.6-85.8) months and the median time to first cardiac response after NEOD001 treatment for all cardiac responders was 2 months. NEOD001 treatment was safe and well tolerated. Conclusions: Patients treated with monthly NEOD001 infusions had high organ response rates that were independent of time since previous chemotherapy, depth of hematologic response, or predominant type of PCD treatment. Ongoing studies of NEOD001 include VITAL (phase 3 in patients with newly diagnosed AL amyloidosis) and PRONTO (phase 2b in previously treated AL amyloidosis patients with persistent cardiac dysfunction). Disclosures Liedtke: Gilead: Research Funding; Prothena: Consultancy, Research Funding; Amgen: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Novartis: Research Funding; Takeda: Consultancy, Research Funding; Celgene: Research Funding. Comenzo: Takeda: Consultancy, Research Funding; Karyopharm: Research Funding; Janssen: Consultancy, Research Funding; Prothena: Consultancy, Research Funding. Landau: Takeda: Membership on an entity9s Board of Directors or advisory committees, Research Funding; Prothena: Honoraria, Membership on an entity9s Board of Directors or advisory committees; Onyx/Amgen: Research Funding; Spectrum Pharmaceuticals: Honoraria, Membership on an entity9s Board of Directors or advisory committees; Janssen: Consultancy. Sanchorawala: Prothena: Research Funding; Takeda: Research Funding; Celgene: Research Funding. Weiss: Prothena: Other: Travel, accommodations, Research Funding; GlaxoSmithKline: Consultancy; Millennium: Consultancy, Other: Travel, accommodations; Janssen: Consultancy, Other: Travel, accommodations, Research Funding; Novartis: Consultancy. Zonder: Prothena: Consultancy; Celgene: Consultancy, Research Funding; BMS: Consultancy; Takeda: Consultancy; Janssen: Consultancy; Seattle Genetics: Consultancy; Array Biopharma: Consultancy. Walling: Corcept: Consultancy; Stealth: Consultancy; Codexis: Consultancy; Exelixis: Consultancy; Newgen: Consultancy; Mateon (was Oxigene): Consultancy; Apex: Consultancy; Aduro: Consultancy; Prothena: Consultancy; Upsher Smith: Consultancy, Patents & Royalties; KaloBios: Consultancy; NuMedii: Consultancy; Pharm-Olam: Consultancy; Crown Bioscience: Consultancy; BioMarin: Equity Ownership; Amgen: Equity Ownership, Patents & Royalties. Kinney: Prothena: Employment, Equity Ownership, Other: Leadership. Koller: Prothena: Employment, Equity Ownership, Other: Travel, accommodations. Schenk: Prothena: Employment, Equity Ownership, Other: Leadership. Guthrie: Prothena: Employment, Equity Ownership, Other: Leadership. Liu: Prothena: Employment, Equity Ownership; Weston Brain Institute: Honoraria. Gertz: Annexon Biosciences: Research Funding; Ionis: Research Funding; Prothena Therapeutics: Research Funding; Novartis: Research Funding; Alnylam Pharmaceuticals: Research Funding; Research to Practice: Honoraria, Speakers Bureau; Med Learning Group: Honoraria, Speakers Bureau; Celgene: Honoraria; NCI Frederick: Honoraria; Sandoz Inc: Honoraria; GSK: Honoraria.

Tao Li - One of the best experts on this subject based on the ideXlab platform.

  • efficient chemoenzymatic process for manufacture of the boceprevir bicyclic 3 1 0 proline intermediate based on amine oxidase catalyzed desymmetrization
    Journal of the American Chemical Society, 2012
    Co-Authors: Tao Li, Jack Liang, Alexandre Ambrogelly, Tim Brennan, Guy Gloor, Gjalt W Huisman, James Lalonde, Azzeddine Lekhal, Ben Mijts, Sheela Muley
    Abstract:

    The key structural feature in Boceprevir, Merck’s new drug treatment for hepatitis C, is the bicyclic [3.1.0]proline moiety “P2”. During the discovery and development stages, the P2 fragment was produced by a classical resolution approach. As the drug candidate advanced through clinical trials and approached regulatory approval and commercialization, Codexis and Schering–Plough (now Merck) jointly developed a chemoenzymatic asymmetric synthesis of P2 where the net reaction was an oxidative Strecker reaction. The key part of this reaction sequence is an enzymatic oxidative desymmetrization of the prochiral amine substrate.