Development Director

Mark C. Grier Bedford, MA ***** • **********@*****.*** http://www.linkedin.com/pub/mark-grier/3a/150/8b9 • 857-***-****

PROFILE Medicinal chemistry leader of 12+ years in the pharmaceutical industry with expertise in all aspects of drug discovery and early clinical development. Demonstrated drug discovery accomplishments supported by 20+ accounts of pharmaceutical related patents, publications and presentations. Proven proficiency in all phases of research including target elucidation, hit compound identification, hit to lead optimization and preclinical development that delivered IND clinical candidates. Success in a broad range of synthetic challenges resulting in patented process synthetic methodology to support a clinical candidate. Proven accomplishments in the art of new chemical entity synthesis to generate libraries of broad chemical diversity. Skillful in the discovery of novel synthetic methodology and the application of new technology to advance chemical diversity and novel scaffolds of interest. Extensive experience in the use and application of modern instrumentation towards medicinal chemistry. Competent at directing teams and managing CRO's for consistent improvement in performance and productivity. A team leader in the proposal, design and planning of innovative projects to fulfill company goals and objectives.

AREAS OF EXPERTISE medicinal chemistry structure based drug design parallel synthesis hit-to-lead generation target validation lead optimization

PROFESSIONAL EXPERIENCE

Technical Services Specialist - EMD Millipore, Billerica, MA 2012 – 2013

Principal Scientist - Frontier Scientific/Kalyra Pharmaceuticals, Logan, UT 2012 – 2012 Contractual Medicinal Chemistry leader.

• Developed synthetic routes for pharmaceutical intermediates

• Synthesized complex compounds for biological evaluation

• Directed exploratory discovery of novel antibacterials

CSO/Founder - Synthegenix Pharmaceuticals, Medford, MA 2012 – 2012 Medicinal chemistry leader and CRO managing director.

• Managed the proposal, design and execution of research and development projects

• Originated and composed research grant proposals to various government agencies

Principal Scientist - Paratek Pharmaceuticals, Boston, MA 2002 – 2011 Medicinal chemistry leader of various projects on the following.

synthetic organic chemistry pharmaceutical intermediates natural product derivatization solid & solution phase chemistry drug discovery & development pharmaceutical target biochemistry

diversity oriented synthesis computational chemistry peptide synthesis modern instrumentation project & CRO management ADME/DMPK

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Discovery and Development of Broad spectrum Antibacterials: Investigation of novel patentable tetracyclines as next generation antibiotics towards soft tissue and community associated infections.

• Delivered multiple IND clinical candidates PTK-0796 and P005672 for infectious disease

• Contributed of novel methodology regarding tetracycline modification resulting in three patents

• Discovered antibacterial libraries that overcome bacterial antibiotic resistance

• Developed a patented process methodology and synthetic route towards clinical candidates

Development of Clostridium difficile Associated Diarrhea (CDAD) Antibacterials: The investigation of the CDAD antibiotic action of tetracycline derived compounds.

• Afforded expansive medicinal chemistry support of sancycline and minocycline derivatization

• Developed an SAR on the narrow spectrum antibiotic action of tetracycline compounds

• Provided scientific guidance and insight on the medicinal chemistry strategy plan

Structure Activity Relationship Analysis of Broad Spectrum Antibacterials: The investigation of the antibiotic activity and pharmacokinetic profile of tetracycline modified compounds.

• Innovative discovery of methodology to expand the diversity oriented synthesis of tetracyclines

• Developed an SAR on the spectrum of antibiotic activity towards tetracycline derivatives

• Evolved a pro-drug strategy to improve the oral bioavailability of phase III candidate PTK-0796

Discovery and Development of Bacterial Virulence Transcriptional Factor Inhibitors: A single agent or antibiotic combination therapy targeting virulence inhibition for the treatment of gram negative infections.

• Managed and planned the medicinal chemistry strategy direction and research methods

• Planned and executed the synthesis of compounds to establish a structure activity relationship

• Advanced new methodology to expand throughput and chemical diversity of compound libraries

Discovery and Development of Peptide Based Gram-Negative Active Antibacterials: The synthesis and biological evaluation of polymyxin related compounds.

• Improved solid-phase peptide synthesis methodology and techniques to generate libraries

• Supplied expansive medicinal chemistry support to produce patentable novel peptides

• Delivered extensive support towards the synthesis of unique non-natural amino acids

EDUCATION

Doctorate of Philosophy, Ph. D., 06/1998

Bachelor of Science, B. S., 05/1992 Major: Organic Chemistry

Major: Chemistry University of Utah, Salt Lake City, Utah

Iowa State University, Ames, Iowa Research Director: Gary E. Keck

Research Advisor: Walter S. Trahanovsky Dissertation: New Synthetic Studies in Asymmetric

Research Topic: Thermolysis of Aryl Substituted Amino Intermolecular Reactions

Compounds

PATENTS AND PUBLICATIONS

“N-Hydroxybenzimidazole inhibitors of ExsA MAR transcription factor in Pseudomonas aeruginosa: In vitro anti- virulence activity and metabolic stability” Grier, Mark C.; Garrity-Ryan, Lynne K.; Bartlett, Victoria J.; Klausner, Kevin A.; Donovan, Peter J.; Dudley, Caroline; Alekshun, Michael N.; Tanaka, Ken S.; Draper, Michael P.; Levy, Stuart B. Bioorganic & Medicinal Chemistry Letters (2010), 20(11), 3380.

“N-hydroxybenzimidazoles as Novel Inhibitors of a Transcription Factor LcrF in Yersinia: Potent Anti-Virulence Agents” Kim, Oak K.; Garrity-Ryan, Lynne K.; Grier, Mark C.; Verma, Atul K.; Medjanis, Gabriel; Bartlett, Victoria J.;

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Alekshun, Michael N.; Donatelli, Janice E.; Macone, Ann B.; Levy, Stuart B. J. Med. Chemistry (2009), 52(18), 5626.

“Polyfunctional antibiotics affecting bacterial membrane dynamics” Nelson, Mark L.; Grier, Mark C.; Barbaro, Susan E.; Ismail, Mohamed Y. Anti-Infective Agents in Medicinal Chemistry (2009), 8(1), 3.

“Methods for synthesizing substituted tetracycline compounds” Seyedi, Farzaneh; Warchol, Tadeusz; Grier, Mark PCT Int. Appl. (2009), WO 200-***-**** A1 20090115.

“Preparation of substituted benzoimidazole compounds as transcription factor modulators” Garrity-Ryan, Lynne; Grier, Mark; Kim, Oak K.; Levy, Stuart B. PCT Int. Appl. (2009), WO 200-***-**** A2 20090108.

“Substituted tetracycline compounds for treatment of bacterial infections and neoplasms” Abato, Paul; Assefa, Haregewein; Berniac, Joel; Bhatia, Beena; Bowser, Todd; Grier, Mark; Honeyman, Laura; Ismail, Mohamed; Kim, Oak K.; Nelson, Mark; Pan, Jingwen; Verma, Atul. (Paratek Pharmaceuticals, Inc., USA). PCT Int. Appl. (2008), 224pp. WO 200-***-**** A2 20080703.

“Novel anti-infection agents: Small-molecule inhibitors of bacterial transcription factors” Bowser, Todd E.; Bartlett, Victoria J.; Grier, Mark C.; Verma, Atul K.; Warchol, Taduesz; Levy, Stuart B.; Alekshun, Michael N. Paratek Pharmaceuticals, Inc., Boston, MA, USA. Bioorganic & Medicinal Chemistry Letters (2007), 17(20), 5652-5655.

“Preparation of 10-substituted tetracycline compounds as antibiotics” Abato, Paul; Assefa, Haregewein; Berniac, Joel; Bowser, Todd; Chen, Jackson; Grier, Mark; Honeyman, Laura. (Paratek Pharmaceuticals, Inc., USA). PCT Int. Appl. (2007), 96pp. WO 200-***-**** A2 20070201.

“Prodrugs of 9-aminomethyltetracycline compounds“ Amoo, Victor; Assefa, Haregewein; Bhatia, Beena; Berniac, Joel; Bowser, Todd; Chen, Jackson; Grier, Mark; Honeyman, Laura; Kim, Oak K.; Mechiche, Rachid; Ohemeng, Kwasi; Pan, Jingwen. (Paratek Pharmaceuticals, Inc., USA). U.S. Pat. Appl. Publ. (2006), 34pp., Cont.-in-part of U.S. Ser. No. 877,454. US 200-***-**** A1 20061221.

“Preparation of substituted tetracycline compounds for the treatment of bacterial infections and neoplasms” Abato, Paul; Assefa, Haregewein; Berniac, Joel; Bhatia, Beena; Bowser, Todd; Chen, Jackson; Grier, Mark; Honeyman, Laura; Ismail, Mohamed Y.; Nelson, Mark; Kwasi, Ohemeng; Pan, Jingwen. (Paratek Pharmaceuticals, Inc., USA). PCT Int. Appl. (2006), 126 pp. WO 200-***-**** A2 20060504.

“Use of 4-aminotetracyclines in treatment of bacterial infections and neoplasm” Berniac, Joel; Bhatia, Beena; Grier, Mark; Nelson, Mark L.; Pan, Jingwen. (Paratek Pharmaceuticals, Inc., USA). PCT Int. Appl. (2006), 49 pp. WO 200-***-**** A2 20060504.

“Substituted benzoimidazole compounds as transcription factor-modulating compounds useful as anti-infectives” Levy, Stuart B.; Alekshun, Michael N.; Podlogar, Brent L.; Ohemeng, Kwasi; Verma, Atul K.; Warchol, Tadeusz; Bhatia, Beena; Bowser, Todd; Grier, Mark. (Paratek Pharmaceuticals, Inc., USA). U.S. Pat. Appl. Publ. (2005), 463 pp., Cont.-in- part of U.S. Ser. No. 139,591. US 200-***-**** A1 20050609.

“Preparation of prodrugs of 9-aminomethyltetracycline” Ohemeng, Kwasi; Amoo, Victor; Kim, Oak; Bowser, Todd; Assefa, Haregewein; Bhatia, Beena; Berniac, Joel; Chen, Jackson; Grier, Mark; Honeyman, Laura; Pan, Jingwen; Mechiche, Rachid. (Paratek Pharmaceuticals, Inc., USA). PCT Int. Appl. (2005), 45 pp. WO 200-***-**** A1 20050203.

“Preparation of substituted tetracycline analogs for use in antibiotic pharmaceutical compositions” Nelson, Mark L.; Ohemeng, Kwasi; Amoo, Victor; Kim, Oak; Abato, Paul; Assefa, Haregewein; Berniac, Joel; Bhatia, Beena; Bowser, Todd; Chen, Jackson; Grier, Mark; Hohos, Aaron; Honeyman, Laura; Ismail, Mohamed Y.; Mechiche, Rachid; Nihlawi, Mohammed; Sizensky, Emmanuelle. (Paratek Pharmaceuticals, Inc., USA). PCT Int. Appl. (2005), 81 pp. WO 200-***-**** A2 20050203.

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“Substituted benzimidazole compounds as transcription factor-modulating compounds useful as anti-infectives” Levy, Stuart B.; Alekshun, Michael N.; Podlogar, Brent L.; Ohemeng, Kwasi; Verma, Atul K.; Warchol, Tadeusz; Bhatia, Beena; Bowser, Todd; Grier, Mark. (Paratek Pharmaceuticals, Inc., USA). PCT Int. Appl. (2004), 237 pp. WO 200-***-**** A2 20040521.

“SR-141716A-Induced Stimulation of Locomotor Activity. A Structure-Activity Relationship Study” C. E. Bass, G. Griffin, M. C. Grier, A. Mahadevan, R. K. Razdan, B. R. Martin Pharmacol. Biochem. Behav. 2002, 74, 31.

“A Structure Activity Relationship Study on Arvanil, an Endocannabinoid and Vanilloid Hybrid” V. D. Marzo, G. Griffin, L. E. Petrocellis, I. Brandi, T. Bisogno, W. Williams, M. C. Grier, S. Sanjitha, A. Mahadevan, R. K. Razdan and B. R. Martin J. Pharmacol. Exp. Ther. (2002), 300(3), 984.

“Novel Pyrazole Cannabinoids: Insights into CB1 Receptor Recognition and Activation” J. L. Wiley, Jefferson R. G., M. C. Grier, A. Mahadevan, R. K. Razdan and B. R. Martin J. Pharmacol. Exp. Ther. (2001), 296(3), 1013.

“Generation and Reactivity of Oxazolidinone Derived N-Acyl Radicals” G. E. Keck and M. C. Grier, Synlett (1999), 10, 1657.

“Catalytic Asymmetric Allylation (CAA) Reactions. Extension to Methallylstannane, Comparison of Procedures, and, Observation of a Non-Linear Effect” G. E. Keck, D. Krishnamurthy and M. C. Grier J. Org. Chem. (1993), 58(24), 6543.

SELECTED PRESENTATIONS

“A Novel Anti-virulence Approach for Treatment of Caused by Pseudomonas aeruginosa Pneumonia” Michael P. Draper; Lynne K. Garrity-Ryan; Peter Donovan; Oak K. Kim; Mark Grier; Victor Amoo; Raina Gay; Beth Hanley; Victoria J. Bartlett; Ann Macone; Janice Donatelli; Michael N. Alekshun; S. Ken Tanaka; Stuart B. Levy, 47th ICAAC Meeting 2007, Interscience Conference on Antimicrobial Agents and Chemotherapy, Poster F2 - 968a, Chicago, IL, September 17 - 20, 2007.

“Synthesis and Biological Activity of PTK-0796: A Novel Semisynthetic Tetracycline in Phase I Clinical Trials” Nelson, Mark L.; Ismail, Mohamed; Bowser, Todd; Honeyman, Laura; Macone, Ann; Bhatia, Beena; Verma, Atul; Grier, Mark; Berniac, Joel; Mechiche, Rachid; Ohemeng, Kwasi; Cannon, Pat; Donatelli, Janice; McKenney, David; Levy, Stuart B. Abstracts of Papers, 231st ACS National Meeting, Med. Chem. Div. Paper # 198 Atlanta, GA March 26-30, 2006.

“Non-Antibacterial Tetracyclines Demonstrate Disease Protection in Preclinical Studies” D. McKenney; C. L. Jackson; J. Berniac; T. Bowser; M. C. Grier; K. Ohemeng; E. P. Cannon; P. Abato; T. K. Stanton; M. P. Draper, Neuroscience 2004, the Society for Neuroscience’s 34th Annual Meeting in San Diego Paratek Pharmaceuticals, Boston, MA, USA.

“Novel Anti-Infection Agents: Small Molecule Transcription Factor Modulators” M. N. Alekshun, V. J. Bartlett, T. Bowser, A. Verma, M. Grier, T. Warchol, K. Ohemeng, S. B. Levy, and S. K. Tanaka, 44th ICAAC Meeting 2004, Interscience Conference on Antimicrobial Agents and Chemotherapy, Abstract F-1523, Poster 279, Washington, D. C. October 30 - November 2, 2004.

REFERENCES

Mark L. Nelson, Ph.D.

Stuart B. Levy, M.D. Director of Business Dev.

CSO Paratek Pharmaceuticals Echelon Biosciences Inc.

Professor of Microbiology 675 Arapeen Dr. Ste. 302

Tufts School of Medicine Salt Lake City, UT 84108

Boston, MA 02111 Phone: 801-***-**** ext. 308

Phone: 617-***-**** email: *******@*******-***.***

email: ******.****@*****.*** http://www.tufts.edu/med/microbiology/faculty/levy/ Oak Kim, Ph. D. Director of Antiinfective Research Paratek Pharmaceuticals 75 Kneeland Street Boston, MA 02111 Phone: 617-***-**** email: ****@************.***

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