Wang Y.,Process Research and Development |
Milkiewicz K.L.,Process Research and Development |
Kaufman M.L.,Process Research and Development |
He L.,Process Research and Development |
And 7 more authors.
Organic Process Research and Development | Year: 2017
Cinchona alkaloid-based thiourea catalysts (1a and 1b) belong to an important class of bifunctional organocatalysts, which has been widely used for a variety of asymmetric reactions. The commercial availability of these catalysts is sporadic, and limited to sub-gram quantities. Herein is described a general, scalable, and practicable process for the preparation of these catalysts that was used to synthesize more than 14 kg of catalyst per batch. © 2017 American Chemical Society.
Deshpande P.P.,Chemical Development |
Singh J.,Process Research and Development |
Pullockaran A.,Process Research and Development |
Kissick T.,Process Research and Development |
And 25 more authors.
Organic Process Research and Development | Year: 2012
A practical synthesis of the SGLT-2 inhibitor β-C-aryl-d-glucoside (1) has been developed. The route employed 2,3,4,6-tetra-O-trimethlysilyl-d- glucano-1,5-lactone as the key chiral building block, prepared efficiently from the commercially available, inexpensive raw materials, d-gluconolactone and trimethylsilyl chloride. The salient step in the synthesis is the Lewis acid-mediated stereoselective reduction of a methyl C-aryl peracetylated glycoside using a silyl hydride to set the stereochemistry of the crucial anomeric chiral center. Several novel cocrystalline complexes of 1 with l-phenylalanine and l-proline were discovered. Single-crystal structures of these complexes and several synthetic intermediates have been determined. The l-phenylalanine complex was developed and used to purify and isolate the API. All steps were implemented at multikilogram scale. © 2012 American Chemical Society.
Lisberger M.,Nurnberg University of Applied Sciences |
Hagn S.,Process Research and Development |
Scheuringer H.,Scheuch GmbH
ZKG International | Year: 2012
Gebr. PfeitTer SE has developed a forward-looking concept for a new mill and a new drive. The new MVR vertical roller mill for grinding cement raw material, cement and granulated blast furnace slag has a modular design, which enables operation to be continued even if one roller module fails. The new MultiDrive® drive system, which consists of up to six identically sized drive units, incorporates the same actively redundant design principle as the mill's roller modules. This significantly reduces unplanned stoppage times, even in the case of main component failure. The main components of the MVR vertical roller mill are the four or six grinding rollers with a cylindrical wear part geometry, the flat grinding table, the gas-guiding housing with nozzle ring and classifier and the drive, which can optionally consist of the MultiDrive® or of a conventional drive system with planetary gear unit. The load distribution to the individual electric motors is performed by a primary control system through frequency converters associated with each drive module.
Kim S.-H.,Bristol Myers Squibb |
De Mas N.,Process Research and Development |
De Mas N.,Lonza Biologics Inc. |
Parlanti L.,Process Research and Development |
And 20 more authors.
Organic Process Research and Development | Year: 2011
We describe the synthesis, chromatographic purification, and isolation of the epothilone-folic acid conjugate BMS-753493, an investigational new drug candidate for the treatment of cancer. The main challenges for process development were the instability of BMS-753493 in aqueous solution, the design and optimization of the preparative chromatography, and the removal of phosphate salts and water from the purified material. The operating conditions of the batch chromatographic purification were optimized using a column adsorption model. The free-salt active pharmaceutical ingredient was isolated via the precipitation of its zwitterion following a careful determination of the isolation parameters that controlled thermal and pH-related decomposition. This process enabled the manufacturing of several batches (10-30 g) of cGMP quality BMS-753493. © 2011 American Chemical Society.
News Article | November 3, 2016
LEXINGTON, Mass., Nov. 03, 2016 (GLOBE NEWSWIRE) -- Curis, Inc. (NASDAQ:CRIS), a biotechnology company focused on the development and commercialization of innovative and effective drug candidates for the treatment of human cancers, today reported its financial results for the third quarter ended September 30, 2016. "We are pleased with our progress this quarter, and remain focused on patient enrollment within our two clinical programs. CA-170’s Phase 1 trial is progressing rapidly through the dose escalation stage with no limiting adverse safety effects,” said Ali Fattaey, Ph.D., Curis's CEO. “Additionally, we continue to enroll at multiple centers in the Phase 2 trial of CUDC-907 in patients with relapsed/refractory DLBCL. Our goal is to assess CUDC-907’s efficacy in patients with MYC-altered DLBCL and we expect to use this information for discussion with the FDA in 2017.” Dr. Fattaey continued, “Our collaboration with Aurigene continues to progress well. In September, we completed a $24.5M financing with Aurigene. In October, we licensed a second immuno-oncology program, designating CA-327 as an oral small molecule development candidate targeting PDL1 and TIM3. We expect to file an IND for CA-327 in 2017." Curis reported a net loss of $28.3 million, or $(0.21) per share on both a basic and diluted basis for the third quarter of 2016, as compared to a net loss of $5.5 million, or $(0.04) per share on both a basic and diluted basis for the same period in 2015. Curis reported a net loss of $49.1 million or $(0.38) per share on both basic and diluted basis for the nine months ended September 30, 2016, as compared to a net loss of $45.5 million, or $(0.37) per share on both basic and diluted basis for the same period in 2015. The net loss for the three and nine months ended September 30, 2016 includes a non-cash in-process research and development charge of $18.0 million related to the amendment of Curis's license agreement with Aurigene. The net loss for the nine months ended September 30, 2015 includes a non-cash in-process research and development charge of $24.3 million related to Curis's license agreement with Aurigene. Revenues for the third quarter of 2016 were $1.8 million, as compared to $2.0 million for the same period in 2015. Revenues for both periods comprise primarily royalty revenues recorded on Genentech and Roche's net sales of Erivedge®. Revenues for the nine months ended September 30, 2016 were $5.2 million, as compared to $5.8 million for the same period in 2015. Operating expenses were $29.5 million for the third quarter of 2016, as compared to $6.9 million for the same period in 2015. Operating expenses for the nine months ended September 30, 2016 were $52.4 million, as compared to $49.0 million for the same period in 2015, and comprised the following: Costs of Royalty Revenues. Costs of royalty revenues, primarily amounts due to third-party university patent licensors in connection with Genentech and Roche's Erivedge net sales, were $0.1 million for both the third quarter of 2016 and 2015. Cost of royalty revenues for the nine months ended September 30, 2016 and 2015 were $0.3 million for both periods. In-Process Research and Development Expense. In-process research and development expense was $18.0 million for the third quarter of 2016, as compared to $24.3 million for the same period in 2015. These charges are associated with the stock issuances of 10,208,333 and 17,120,131 shares of Curis common stock to Aurigene, respectively. These shares were issued as consideration for the rights granted under the terms of the September 2016 amendment to the collaboration agreement and partial consideration for the rights granted under the terms of the January 2015 collaboration agreement, respectively. Research and Development Expenses. Research and development expenses were $6.8 million for the third quarter of 2016, as compared to $4.0 million for the same period in 2015. The increase was primarily due to increased direct spending related to clinical activities of CUDC-907 and programs under the Aurigene collaboration over the prior year period. Employee-related expenses increased over the prior year period primarily due to additional headcount to support the multiple programs. Research and development expenses were $22.4 million for the nine months ended September 30, 2016 as compared to $14.7 million for the same period in 2015. General and Administrative Expenses. General and administrative expenses were $4.7 million for the third quarter of 2016 as compared to $2.8 million for the same period in 2015. The increase in general and administrative expenses was driven primarily by higher personnel costs and stock-based compensation expense due to increased headcount and an increase in legal service costs. General and administrative expenses were $11.7 million for the nine months ended September 30, 2016, as compared to $9.7 million for the same period in prior 2015. Other expense, net was $0.6 million for the third quarter of 2016, as compared to $0.7 million for the same period in 2015. Other expense, net primarily consisted of interest expense related to the loan made by BioPharma-II (an investment fund managed by Pharmakon Advisors) to Curis Royalty (a wholly owned subsidiary of Curis). Other expense, net was $1.8 million and $2.3 million for the nine months ended September 30, 2016 and 2015, respectively. As of September 30, 2016, Curis's cash, cash equivalents, marketable securities and investments totaled $53.4 million and there were approximately 140.0 million shares of common stock outstanding. Curis expects that it will make presentations at the following conferences through December 2016: Curis management will host a conference call today, November 3, 2016, at 8:30 a.m. EDT, to discuss these financial results, as well as provide a corporate update. To access the live conference call, please dial (877) 868-1829 from the United States or (253) 237-1135 from other locations, shortly before 8:30 a.m. EDT. The conference ID number is 6507701. The conference call can also be accessed on the Curis website at www.curis.com in the Investors section. Curis is a biotechnology company focused on the development and commercialization of innovative and effective drug candidates for the treatment of human cancers. The Company's clinical drug candidates include CUDC-907, which is being investigated in a Phase 2 trial in patients with Diffuse Large B Cell Lymphoma, or DLBCL, and in a separate Phase 1 trial in patients with solid tumors. As part of a broad collaboration with Aurigene, Curis has an exclusive license to CA-170, an oral small molecule PDL1/VISTA antagonist that is currently being investigated in a Phase 1 trial in patients with solid tumors or lymphoma. Curis also has an exclusive license to oral small molecule antagonists of the PD1 and TIM3 pathways, including PDL1/TIM3 antagonist CA-327, as well as to molecules designed to inhibit the IRAK4 kinase, including CA-4948. Curis is also party to a collaboration with Genentech, a member of the Roche Group, under which Genentech and Roche are commercializing Erivedge® for the treatment of advanced basal cell carcinoma, and are further developing Erivedge in other diseases including idiopathic pulmonary fibrosis and myelofibrosis. For more information, visit Curis' website at www.curis.com. This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, including without limitation statements regarding the potential advantages and benefits of small molecule checkpoint inhibitors and the Company's plans and expectations for the collaboration with Aurigene, including its plans to discover and develop multiple first-in-class oral, small molecule checkpoint inhibitors for the treatment of patients with cancer. Forward-looking statements may contain the words "believes," "expects," "anticipates," "plans," "seeks," "estimates," "assumes," "will," "may," "could" or similar expressions. These forward-looking statements are not guarantees of future performance and involve risks, uncertainties, assumptions and other important factors that may cause actual results to be materially different from those indicated by such forward-looking statements. For example, Curis may experience adverse results, delays and/or failures in its drug development programs and may not be able to successfully advance the development of its drug candidates in the time frames it projects, if at all. Curis's drug candidates may cause unexpected toxicities, fail to demonstrate sufficient safety and efficacy in clinical studies and/or may never achieve the requisite regulatory approvals needed for commercialization. Favorable results seen in preclinical studies and early clinical trials of Curis's drug candidates may not be replicated in later trials. There can be no guarantee that the collaboration agreement with Aurigene will continue for its full term, that Curis or Aurigene will each maintain the financial and other resources necessary to continue financing its portion of the research, development and commercialization costs, or that the parties will successfully discover, develop or commercialize drug candidates under the collaboration. Regulatory authorities may determine to delay or restrict Genentech's and/or Roche's ability to continue to develop or commercialize Erivedge in BCC. Erivedge may not demonstrate sufficient or any activity to merit its further development in disease indications other than BCC. Competing drugs may be developed that are superior to Erivedge. Curis faces risks relating to its wholly-owned subsidiary's royalty-collateralized loan transaction, including the risk that it may not receive sufficient levels of royalty revenue from sales of Erivedge to satisfy the debt obligation or may otherwise lose its rights to royalties and royalty-related payments as a result of a foreclosure of the loan. Curis will require substantial additional capital to fund its business and such capital may not be available on reasonable terms, or at all. Curis faces substantial competition. Curis also faces risks relating to potential adverse decisions made by the FDA and other regulatory authorities, investigational review boards, and publication review bodies. Curis may not obtain or maintain necessary patent protection and could become involved in expensive and time consuming patent litigation and interference proceedings. Unstable market and economic conditions and unplanned expenses may adversely affect Curis's financial conditions and its ability to access the substantial additional capital needed to fund the growth of its business. Important factors that may cause or contribute to such differences include the factors set forth under the caption “Risk Factors” in our in our most recent Form 10-K and Form 10-Q and the factors that are discussed in other filings that we periodically make with the Securities and Exchange Commission (“SEC”). In addition, any forward-looking statements represent the views of Curis only as of today and should not be relied upon as representing Curis's views as of any subsequent date. Curis disclaims any intention or obligation to update any of the forward-looking statements after the date of this press release whether as a result of new information, future events or otherwise, except as may be required by law.
Siva Prasad A.,Process Research and Development |
Siva Prasad A.,Jawaharlal Nehru University |
Mohonty S.,Process Research and Development |
Satyanarayana B.,Process Research and Development
Der Pharma Chemica | Year: 2012
An improved process for the preparation of pure Zolmitriptan described via an in situ preparation of hydrazine followed by indole cyclisation of Oxazolidine derivative. In this article which we have provided improved reaction conditions, which ex-cluded the usage of column chromatography, and an overall yield of 60% with 99.9% HPLC purity has been achieved.
Thomson N.M.,Pfizer |
Seibert K.D.,Eli Lilly and Company |
Tummala S.,Bristol Myers Squibb |
Bordawekar S.,Process Research and Development |
And 4 more authors.
Organic Process Research and Development | Year: 2015
A number of strategies have been employed within the pharmaceutical industry in order to mitigate the risk of applying design space boundaries developed on the laboratory scale to commercial drug substance manufacturing. The following communication presents a number of case histories from members of the International Consortium for Innovation and Quality in Pharmaceutical Development (IQ), with the aim of exemplifying strategies used to confirm applicability of design spaces developed on the laboratory scale. The strategies presented have a common aim of ensuring that appropriate quality standards are developed, maintained, and enhanced during the product lifecycle whilst delivering rapid and cost-effective mechanisms for drug substance commercialization. © 2014 American Chemical Society.
Cullen S.C.,Process Research and Development |
Shekhar S.,Process Research and Development |
Nere N.K.,Process Research and Development
Journal of Organic Chemistry | Year: 2013
A convenient method for the preparation of aryl trifluoromethylsulfones from the reactions of diaryliodonium salts with sodium trifluoromethanesulfinate in the presence of copper catalysts is described. Cuprous oxide in DMF was found to be the optimal catalyst for the reaction. The reaction conditions are tolerant of various functional groups as well as of various counteranions of the iodonium salt. The synthetic utility of the process is demonstrated by performing the reaction on a preparative scale (88 g). © 2013 American Chemical Society.
Voight E.A.,Abbott Laboratories |
Daanen J.F.,Abbott Laboratories |
Hannick S.M.,Abbott Laboratories |
Shelat B.H.,Abbott Laboratories |
And 3 more authors.
Tetrahedron Letters | Year: 2010
Starting from a variety of substituted chroman-4-ones, a highly enantioselective CBS reduction using in situ-generated B-H catalyst gave (S)-chroman-4-ols. Azide inversion and reduction gave crude (R)-chroman-4- amines, which could be purified without chromatography by isolation as the (R)-mandelic or d-tartaric acid salts with good yields and excellent ee. © 2010 Elsevier Ltd. All rights reserved.
Bordawekar S.,Process Research and Development |
Kuvadia Z.,University of California at Santa Barbara |
Dandekar P.,University of California at Santa Barbara |
Mukherjee S.,Process Research and Development |
Doherty M.,University of California at Santa Barbara
Crystal Growth and Design | Year: 2014
Crystal habit of drug molecules can have significant influence on the processing and performance of pharmaceutical products. During the development of Trilipix, a pharmaceutical product used for the treatment of mixed dyslipidemia, several crystal habits were observed for the active ingredient choline fenofibrate. The dissolution and performance of the drug product were not impacted by changes in crystal habit of the active ingredient due to high solubility of the drug. However, the formulation process was impacted by variations in crystal habit of the active ingredient, requiring robust control of the crystal habit. The crystal habit was greatly influenced by supersaturation during crystallization from a mixed solvent system comprising methanol and isopropanol. In addition to supersaturation, trace levels of a polymeric impurity in the starting material fenofibrate had a detrimental effect on the crystal habit. This article discusses the effects of these factors on the crystal habit of choline fenofibrate and the design of a crystallization process to deliver the target crystal habit, most suited to the formulation process. The article also provides preliminary mechanistic insights into the crystal habit of this organic salt using an extension of the spiral growth model for morphology prediction of organic molecular crystals. An attempt is made to explain the effect of supersaturation and impurity on the crystal habit of choline fenofibrate using the concepts of stability of surfaces, building units, periodic bond chain theory, and the spiral growth model. © 2014 American Chemical Society.