SHIRISH T. DHUME, Ph.D.

Framingham, MA and Cheshire, CT (203) 687-9154, shirish_dhume@yahoo.com

Support drug development objectives utilizing experience in Biotechnology analytics, knowledge of CMC, regulatory, compliance guidelines and project management tools to accomplish department goals, in line with the mission of the company. PROFILE: Project leader for campaigns between in-house and external, including international clients and vendors, meeting milestones, budget within time and resources. Contributed to BLA of Solaris - marketed for paroxysmal nocturnal hemoglobinuria (PNH) and Bexxar - marketed for non-Hodgkins lymphoma (NHL), 14 INDs and several IND amendments. Function as a project and people managerial, technical resource; sound understanding of business processes and close collaboration with QA, QC, IP, Formulation, Finance, Business Development, Upstream and Downstream Process Development and Manufacturing. Experience in drug and vaccine development strategies targeted towards oncology, pulmonary, cardiology, dermatology, infectious disease and immunology, including orphan diseases. Hands-on assay development, validation, transfer, comparability, stability, release, characterization, process and formulation support. Technical expertise includes antibodies, enzymes, peptides, proteins, vaccines, glycosylation, biosimilars, pegylation, protein modification, small molecule fermentation/cell culture feed and residual analysis.

SELECTED ACCOMPLISHMENTS:

At Alexion, devoid of an Analytical development department at the time, established and maintained post approval inspection-ready cGMP compliant Analytical Laboratory with an annual $650k cost savings through in-sourcing of assays. As project manager in Xcellerex for LFB Biotechnologies, France, successfully directed cross-functional teams to execute changing client needs for increased IgG product yields within time, budget and resources using diverse project and scientific approaches. Developed a group of relatively inexperienced team in GlaxoSmithKline in-charge of protein, carbohydrate and small molecule assays through pre-clinical to clinical development and IND to BLA filings. Co-pioneered high resolution and high sensitivity HPLC assay for recombinant protein carbohydrates to substitute a popular but high maintenance, low resolution and low sensitivity carbohydrate assay. Rapid analytical support to Department of Defense Bioterrorism projects, DTRA and DARPA. Supported aggressive timelines for upstream and downstream manufacturing through development and execution of inprocess and final product analytical methods for unknown antigens.

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PROFESSIONAL EXPERIENCE:

Through STRATACUITY and TUNNELL Sep 2010-Present Analytical Development/QC Consultant Oversee gene therapy assays, viral vector analysis, vector stability, variability reduction, assay validation, comparability and reference standard characterization Led LC, LC-MS group of 5 to implement Shires pipeline analytical plans for recombinant enzyme and IgG orphan drug therapeutics. Manage and co-ordinate CROs for transduction and potency assays Part-time remote consulting for Accutest, India, starting Biotechnology Analytical and Clinical services XCELLEREX INC., Marlborough, MA Jan 2008-Sep 2010 Group Leader, Analytical Development and Quality Control Project Manager for monoclonal antibody projects from LFB Biotechnologies, France Oversee analytical support for defense department projects, DTRA and DARPA, USA Supervise analytical support for Yellow fever vaccine program Oversee viral quantitation (plaque, ELISA and PCR) and Vero host cell assays development to lot release and process support. Assure validation of large and small equipment, utilities (WFI), instruments, computer and other systems for manufacturing. Analytical Lead for recombinant hGH from Prolor Biotech, Israel Analytical support for rFSH biosimilars, Itero Biopharmaceuticals, USA Final product comparison with Innovator molecules using oligosaccharide mapping, monosaccharide and sialic acid analysis. In-process reverse-phase HPLC support for protein purification. CURAGEN CORPORATION, Branford, CT Sep 2006-May 2007 Group Leader, Biopharmaceutical Sciences Led a group in-charge of analytical support for oncology portfolio containing toxin-conjugated mAbs from CHO and Velafermin (basic FGF) from E. coli. Methods utilized: peptide mapping, glycosylation analysis, HIC, SEC, Heparin affinity, ion-exchange, Isoquant kit, LC-MS, turbidimetry, reverse phase of mAbs and hard-to-formulate Velafermin. Member of CMC management team to strategize, oversee execution, presentation and review of development, qualification, validation, stability, comparability and other analytical campaigns. ALEXION PHARMACEUTICALS, INC. Cheshire, CT May 2003-Sep 2006 Senior Manager and Head, Process Analytics Established and led Analytical Laboratory giving CMC support for 5 IgG and 1 scFv projects, contributing to the successful BLA filing of Solaris. Invited author for 4 chapters in Methods in Molecular Biology on fluorescence and mass spectrometry methods for protein glycosylation. Methods utilized chromatographic (LC, GC), spectroscopic (MS, UV-VIS, fluorescence, CD), electrophoretic (SDS-PAGE, IEF), immunological (Western Blots), microbiological (Endotoxin), bioassays and cell-based assays.

SHIRISH T. DHUME, Ph.D. -3-

GLAXOSMITHKLINE PHARMACEUTICALS, May 1996-May 2003 King of Prussia, PA Senior Investigator, Bioanalytical Development Led, trained group of 3, responsible for (1) protein pegylation project (2) carbohydrate characterization and (3) small molecule residual analysis. Due diligence, filing of 9 INDs, several IND amendments and BLA of Bexxar for non-Hodgkins lymphoma. Analytical project manager for cytokine project: plan, co-ordinate and assist in release-testing, stability and comparability campaigns. Primary contact for Boehringer Ingelheim, contract manufacturer in Austria. Developed 22 methods, protocols for 9 projects: characterization, qualification, validation, release, transfer, in-process, process development support and stability-indicating methods for proteins, peptides, carbohydrates, small molecules and protein degradents of toxin-conjugated protein. Co-pioneered and authored publication on utilization of fluorescent tag for high resolution and high sensitivity HPLC of oligosaccharides. NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH 1995-1996 SCIENCES, RTP, NC Scientist Researched and published mechanism of action of swainsonine's anticancer, anti-tumorigenic and anti-metastatic properties. STATE UNIVERSITY OF NEW YORK, Stony Brook, NY 1992-1994 Research Associate Characterized egg and bone glycoproteins. Published (1) two-step model of sperm-egg interaction and (2) determinants of primitive bone formation. LOUISIANA STATE UNIVERSITY, Baton Rouge, LA 1985-1991 Research Assistant Elucidation of the structure of polylactosamine on human red cells by NMR and its role in malaria invasion. Published its role in dyserythropoeitic anemia; Invited lecturer in biochemistry. UNIVERSITY OF KENTUCKY, Lexington, KY 1982-1985 Teaching Assistant Synthesized and analyzed plant hormone, cyclopropyl amino acid. Reported decarboxylation mechanism; Instructed organic chemistry lab. EDUCATION: Louisiana State University, Baton Rouge, LA Ph.D., Department of Biochemistry University of Kentucky, Lexington, KY M.S., Chemistry Department University of Mumbai, Mumbai 400028, India B.Sc. (Tech), Dyes and Intermediates, Minor: Chemical Engineering 1991

1985

1982

SHIRISH T. DHUME, Ph.D. -4-

PROFESSIONAL MEMBERSHIPS/ AWARDS:

GlaxoSmithKline Impact Awards for seamless technology transfer, client support, timely submission of regulatory deliverables. Massachusetts Biotechnology Council Project Management Certification. 4.00/4.00 GPA in Temple University QA/RA Certificate program. Listed in Marquis's Who's Who in America. 4.00/4.00 GPA in Ph.D Major: Biochemistry. Phi Lambda Upsilon, Honorary Chemistry Society (Treasurer, 1989). Member of American Biomolecular Resource Facility Advisor for Distressed Children and Infants International (DCI), foundermember of India Chapter Cell line Switch from NS0 to CHO Causes Several Changes in Glycosylation of Recombinant IgGs, Bruce R. Kilgore, Adam Lucka, Rekha Patel, Bruce Andrien, and Shirish T. Dhume, American Chemical Society, New England Regional Meeting (NERM), Fairfield, CT, 14-17 Jul 2005 (Oral presentation). Rapid Oligosaccharide Mapping Using Fluorescent Anthranilic Acid Detection, Shirish T. Dhume and Sandra Batz, Association of Biomolecular Resource Facilities (ABRF) 2001, San Diego, CA, 24-27 Feb 2001. Rapid Methods for High Resolution and High Sensitivity Oligosaccharide Mapping and Characterization by HPLC with Fluorescent Anthranilic Acid, Shirish T. Dhume, Sandra A. Batz and Kalyan R. Anumula. 33rd Middle Atlantic Regional Meeting (MARM), Newark, DE, 15-17 May 2000 (Oral presentation). Evaluated Various Fluorescent Tags for Oligosaccharide Mapping and Characterization. Shirish T. Dhume and Kalyan R. Anumula. 3rd Symposium on the Analysis of Well Characterized Biotechnology Pharmaceuticals (WCBP), 5-8 Jan 1999, Washington D.C. High resolution and high sensitivity methods for oligosaccharide mapping and characterization by normal phase high performance liquid chromatography following derivatization with highly fluorescent anthranilic acid. Shirish T. Dhume and Kalyan R. Anumula. 1998 Society for Glycobiology Annual Conference, Baltimore, MD, 11-14 Nov 1998, Glycobiology, 8, Abstract no. 34. Novel Fluorescent Method for Oligosaccharide Mapping and Characterization Following Derivatization with Anthranilic Acid (AA). Shirish T. Dhume and Kalyan R. Anumula. Annual Analytical Sciences Colloquium, 1-2 Jul 1998, Cambridge, UK. 1. B. R. Kilgore, A. W. Lucka,, R. Patel, B. A. Andrien, Jr. and S. T. Dhume (2008) Comparability Issues with N-linked Oligosaccharides of Recombinant Monoclonal Antibodies Obtained from two Different Cell Lines, Methods in Molecular Biology, Posttranslational Modifications of Proteins 2nd edition (C. Kannicht, ed), Humana Press, New Jersey. 2. A.W. Lucka, B. R. Kilgore, R. Patel, B. A. Andrein, Jr. and S. T. Dhume (2008) Mass Spectrometry and HPLC with Fluorescent Detection Based Orthogonal Approaches to Characterize N-linked Oligosaccharides of Recombinant Monoclonal Antibodies, Methods in Molecular Biology,

SELECTED PRESENTATIONS:

PUBLICATIONS:

SHIRISH T. DHUME, Ph.D. -5-

Posttranslational Modifications of Proteins 2nd edition (C. Kannicht, ed), Humana Press, New Jersey. 3. S. T. Dhume, G. N. Saddic and K. R. Anumula. (2008) Monitoring Glycosylation of Therapeutic Glycoproteins for Consistency Using Highly Fluorescent Anthranilic Acid, Methods in Molecular Biology, Posttranslational Modifications of Proteins 2nd edition (C. Kannicht, ed), Humana Press, New Jersey. 4. G. N. Saddic, S. T. Dhume and K. R. Anumula. (2008) Carbohydrate Composition Analysis of Glycoproteins Using Highly Sensitive Fluorescence Detection Methods, Methods in Molecular Biology, Posttranslational Modifications of Proteins 2nd edition (C. Kannicht, ed), Humana Press, New Jersey. 5. I. Majsterek, E. McAdamas, E. Adachi, S., T. Dhume, and A. Fertala. (2003) Prospects and Limitations of the Rational Engineering of Fibrillar Collagens. Protein Sci., 12:2063-2072. 6. S. T. Dhume, M. B. Ebert, G. N. Saddic and K. R. Anumula. (2002) Monitoring Glycosylation of Therapeutic Glycoproteins for Consistency Using Highly Fluorescent Anthranilic Acid, Methods in Molecular Biology, Vol. 194, Posttranslational Modifications of Proteins (C. Kannicht, ed), Humana Press, New Jersey, pp 127-142. 7. G. N. Saddic, M. B. Ebert, S. T. Dhume and K. R. Anumula. (2002) Carbohydrate Composition Analysis of Glycoproteins Using Highly Sensitive Fluorescence Detection Methods, Methods in Molecular Biology, Vol. 194, Posttranslational Modifications of Proteins (C. Kannicht, ed), Humana Press, New Jersey, pp 23-36. 8. Roberts, J.D., Klein, J.L., Palmantier, R., Dhume, S.T., George, M.D. and Olden, K. (1998) The role of protein glycosylation inhibitors in the prevention of metastasis and therapy of cancer. Cancer Detection and Prevention. 22 (5) 455-462. 9. Anumula, K.R. and Dhume, S.T. (1998) High resolution and high sensitivity methods for oligosaccharide mapping and characterization by normal phase high performance liquid chromatography following derivatization with highly fluorescent anthranilic acid. Glycobiology. 8 (7) 685-694. 10. Dhume, S.T., Stears, R.L. and Lennarz, W.J. (1996) Sea urchin egg receptor for sperm: the oligosaccharide chains stabilize sperm binding. Glycobiology. 6 (1) 59-64. 11. Dhume, S.T. and Lennarz, WJ. (1995) The involvement of O-linked oligosaccharide chains of the sea urchin egg receptor for sperm in fertilization. Glycobiology. 5 (1) 11-17. 12. Dhume, S.T., Adams-Burton, C.R., Shumak, K.H. and Laine, R.A. (1994) Polylactosamines are not obligate receptors for invasion of Plasmodium falciparum malaria as shown in HEMPAS variant II-gal-erythrocytes. Glycobiology. 4 (6) 903-908. 13. Ohlendieck, K., Dhume, S.T., Partin, J.S. and Lennarz, W.J. (1993) The sea urchin egg receptor for sperm: isolation and characterization of the intact, biologically active receptor. Journal of Cell Biology. 122 (4) 887895.