Home Address: 4058 Gunsmith Court Current Work Address: Istanbul Medipol University

MUSTAFA GUZEL, Ph.D.

(Associate Professor of Medical Pharmacology)

Home Address: 4058 Gunsmith Court Current Work Address: Istanbul Medipol University

Jamestown, NC 27282 Kavacik Mah. Beykoz, Ist. TR

Tel: (336) 471-0222 Tel:+90-(507) 735 9431

Career Objectives and Interests

·  14 years of teaching experience, 7 years at college level chemistry/organic chemistry/medicinal chemistry courses and related laboratory courses (Clemson University, Northeastern University, and currently Istanbul Medipol University), and 6 years of chemistry teaching experience at various high schools complemented with 14 years of industrial research experience in medicinal chemistry with increased responsibilities and various positions at pharmaceutical companies. (ArQule and TransTech Pharma Inc.currently vTv Therapeutics)

·  Research and development in medicinal chemistry specifically Oncology and Kinase Inhibitors, GPCRs for the treatment of diabetic disorders (NIDDM), obesity, CNS disorders, inflammation disorders (RA, COPD), viral and bacterial infectious diseases.

·  Instrumental in discovery and development of several NCEs as preclinical and clinical candidates for the treatment of diabetes, obesity, inflammation, oxidative stress and CNS disorders. Key accomplishments on oncology programs to identify and progress in selection of pre-clinical candidates. Contributed on several projects from hit identification to clinical candidate selection.

·  Research and development with an emphasis in design and synthesis of both symmetric and asymmetric organic compounds leading to new drug substances and natural products. Discovery of drugs to treat unmet medical needs in US and in the world at large.

·  Interests include but not limited to; chemical development of libraries and the ligand design for drug discovery, elucidation of the catalytic asymmetric induction reactions and their mechanisms, development of new enantioselective catalysts and their applications in the synthesis of biologically active agents.

·  Accomplished scientist and manager with 16 + years of Pharmaceutical R&D experience leading interdisciplinary teams during discovery, preclinical and clinical development phases of NCE programs. Proven ability to deliver development–ready small molecule drug candidates, manage their preclinical evaluation, contract manufacturing for IND-enabling toxicology and pharmacology studies. Excellent leadership, presentation and communication skills. Structure-based drug design (SBDD) for the discovery and optimization of novel therapeutic targets. .

CAREER HIGHLIGHTS AND Professional Experience

2017-Current Associate Professor, Istanbul Medipol University., International School of Medicine, Dept. of Medical Pharmacology (Chair), Istanbul, Turkey

Lead Investigator- Istanbul Medipol University., Regenerative and Restorative Medicine Research Center (REMER), Molecular Discovery and Development Laboratory (http://remer.medipol.edu.tr/team/assist-prof-mustafa-guzel/), Istanbul, Turkey

·  Leading 5 domestic molecular discovery projects as PI (2 anti-cancer drug discovery, 1 anti-Leishmaniasis drug discovery, 1 anti-diabetic drug discovery and development (Novel Metabolic Targets for T2DM), 1 anti-Parkinson drug discovery and 3 International projects with NIH, European Union COST Projects with joint proposals. (Please visit “grg.medipol.edu.tr” web-link for our research group as well as details of the research projects).

·  Collaborating three joint projects with US researchers; a) Augusta University Georgia Cancer Center to discover novel drug candidates in cancer as co-PI. (Prof. Hasan Korkaya, Calprotectin Inhibitors), b) Wake Forest University, School of Medicine Cancer Biology (Prof. William Gmeiner, Development of DTX Conjugated Aptamer Complexes for CRPC An), c) Georgetown University, School of Medicine Cancer Biology (Prof. Aykut Uren, Development of Novel Biomarkers in Rare Cancer Types)

·  Submitted a joint proposal action as “the Main Proposer” with 12 other professors from 9 different European countries to European Cooperation in Science and Technology (COST) for the development of novel drugs in neurodegenerative disorders specifically focus on Alzheimer’s Disease (AD).

·  Currently Teaching Pharmacology, Medical Pharmacology Clinical Research, Special Topics in Biotechnology, Special Topics in Medicinal Chemistry, Professional English, Medicinal Chemistry, Organic Chemistry, Advanced Medicinal Chemistry, Advanced Organic Chemistry, and their laboratory courses for undergraduate and graduate level.

·  Supervising 2 Post-doctoral researchers, 5 PhD students, 4 Master Students, and several undergraduate students in the drug discovery and development laboratory at Istanbul Medipol University

·  Serving as a member in steering committee for R&D programs of the university.

2014-2016 Assistant Professor, Istanbul Medipol University., School of Pharmacy, Dept. of Pharmaceutical Sciences (Chair), Istanbul, Turkey

·  Spearheaded Molecular Discovery Projects for entire department (4 projects as PI and 3 projects as co-PI)

·  Collaborating two projects with Harvard Medical School to discover novel drug candidates in Parkinson's disease as co-PI. (A2A-Adenosine Receptor Antagonists).

·  Teaching Pharmacology, Clinical Research, Special Topics in Biotechnology, Special Topics in Medicinal Chemistry, Professional English, Medicinal Chemistry, Organic Chemistry, Advanced Medicinal Chemistry, Advanced Organic Chemistry, and their laboratory courses for undergraduate and graduate level.

·  Serving as a member in steering committee for R&D programs of the university.

2010-2013 Senior Research Investigator, TransTech Pharma Inc., Med. Chem. Labs, High Point, NC

Contributed on design, synthesis, discovery and development of the following drug candidates which are currently on clinical trials or pre-clinical studies:

·  TTP488 (RAGE Inhibitor) currently on Phase III studies for Alzheimer's Disease (granted and designated as fast track drug by FDA)

·  TTP854 (BACE Inhibitor) currently on Phase I studies for Alzheimer's Disease

·  TTP607 (AK Inhibitor) currently on Phase I studies for cancer

·  TTP737 (PDE-4D Inhibitor) currently on Phase I studies for inflammation

·  TTP399 (GK Activator) currently on Phase II studies for diabetes

·  TTP547 (GK Activator) currently on Phase II studies for diabetes

·  TTP054 (GLP-1R Activator) currently on Phase I studies for diabetes

·  TTP593 (GLP-1R Activator) currently on Phase I studies for diabetes

·  TTP404 (AGRP Inhibitor) currently on Phase I studies for obesity

·  TTP971 (HMOX-1 Activator) currently on Phase I studies for oxidative stress and inflammation

·  TTP253 (HK-2 Inhibitor) currently on pre-clinical studies for cancer

·  TTP886 (HK-2 Inhibitor) currently on pre-clinical studies for cancer

·  Spearheaded HK-2 (hexokinase-2) Inhibitors Project to discover novel drugs for treatment of cancer and explore cancer metabolism.

·  Initiated the discovery of novel anti-cancer agents that pioneered the conception of 4 different patents.

·  Designed and discovered potent/efficacious drug candidates which are being evaluated in later stages of pre-clinical studies on PK/PD models.

·  Assigned as the first medicinal chemist on newly established anti-cancer project (Hexokinase-2 inhibitors) to develop new chemical entities for cancer metabolism.

·  Spearheaded the Oxidative Stress (HMOX-1 Activators) project to discover and develop drug candidates, which are currently in pre-clinical stages for treatment of inflammatory disorders and cancer chemoprevention.

2008-2010 Research Investigator, TransTech Pharma Inc., Medicinal Chemistry Labs, High Point, NC

·  Successfully completed Oxidative Stress (HMOX-1 Activators) project by discovering and developing drug candidates for treatment of inflammatory disorders and cancer chemoprevention. (4 super-qualifiers selected for pre-clinical studies).

·  Achieved two patent applications with two different novel pharmaceutical compositions for Heme Oxygenase (HMOX-1) project to treat Oxidative Stress.

·  Worked on BACE project for treatment of Alzheimer’s disease and designed and synthesized series of active BACE-1 inhibitors at sub-micro-molar level.

·  Achieved a patent publication by discovering series of lead compounds for inflammation project (PDE-4D Inhibitors) for treatment of COPD.

·  Completed process development and efficient synthetic route (kilo-batch) of a drug candidate for pre-clinical studies.

·  Promoted to research investigator based on the recent success on anti-inflammation project.

·  Leading a group of scientists (3 Ph.D.’s and 2 M.Sc.’s) and supervised projects.

·  Selected to the President’s Award (employee of the year) for 2007.

·  Discovered new series of compounds whose PK and ADME properties showed excellent results and selected to be as super-qualifiers for Inflammation Regulation Project.

·  Designed and synthesized the most potent compounds (pico-molar level) for TNF-a inhibition.

·  Achieved double digit pico-molar potency in PBMC assay (IC50=80 pM).

·  Achieved nano-molar potency in whole blood assay.

·  Completed two patent applications for anti-inflammation project by discovering new scaffolds.

2005-2007 Principal Research Scientist, TransTech Pharma Inc., Medicinal Chem. Labs, High Point, NC

·  Supervised a group of medicinal chemists who are in junior levels (2 M.Sc. and 3 Ph.D. levels).

·  Discovered and developed series of lead compounds with different templates, which are 10-15 times more potent than current prescribed drugs (i.e. spironolactone).

·  Invented and patented novel scaffolds for treatment of inflammation and pain. Currently working on improving potency and efficacy in animal models.

·  Designed and synthesized novel therapeutic drugs for anti-inflammation and anti-arthritic (rheumatoid arthritis).

·  Invented and patented a novel method for asymmetric resolution of chiral intermediates which is essential for a drug substance to prepare for Phase I clinical studies to treat Type II diabetic and obese patients.

·  Developed a method to synthesize two drugs for GLP-1R activation to treat Type II diabetics in multi kilo-gram scale.

·  Worked on GLP-1R (Glucagon Like Peptide-1 Receptor) activators project for the treatment of Type-II diabetes, obesity, as well as food intake control.

·  Selected to be one of the leading Medicinal Chemists for GLP-1R project. Quickly established synthesizing new scaffolds and identified new lead compounds for GLP-1R.

·  Applied medicinal chemistry knowledge with increasing strength in the projects and closely coordinated with group members to establish better motivation and problem solving. Supervised scientists, research associates, and research interns.

·  Demonstrated good motivation and performance on each projects. Participated to finish certain tasks and goals with solid coordination, helped team members to accomplish and complete sub-projects and goals within a limited timeline. Impacted the direction of projects by way of synthesizing various new classes of compounds.

·  Became a mature and highly skilled medicinal chemist and influenced the streamline of the projects by discovering numerous different scaffolds and lead compounds in the projects involved such as PTP-1B, Factor-IXa, GK, RAGE, I7L, DegP, GLP-1 and Anti-inflammatory regulators.

2003-2004  Senior Research Scientist, TransTech Pharma Inc., Medi.&Combi.Chem. Labs, High Point, NC

·  Discovered several hits, which initiated the establishment of the project (BACE). Resulted second and third patent application for GK project by participating in design, synthesis, execution and analysis of new urea series. (Approximately 1600 single compounds have been synthesized. Among those 50% of the compounds found to be highly potent as GK activators).

·  Discovered a drug candidate, which is currently in Phase I for the treatment of Type-II diabetic complications and food intake control.

·  Designed and synthesized highly potent compounds for GlucoKinase activity. Among these compounds, 47 of them have showed activity at the nano-molar range and 10 of these compounds have been selected as front-runner candidates. Furthermore, one of these out of 10 (ten) compounds has been selected as one of the super qualifier candidates to move forward for Pre-Clinical Trials (Toxicology, PK, and PD studies) in GlucoKinase activation.

·  Actively involved by designing and synthesizing small molecules for RAGE project (Receptor of Advanced Glycation End Products) for the treatment of Alzheimer’s disease. Synthesized numerous nano-molar level active compounds some of which showed good PK profile for RAGE project.

·  Designed and synthesized compounds for DegP project (serine protease inhibitors) for the treatment of anthrax and SARS (antibacterial activity)

·  Actively worked in I7L project (cysteine protease inhibitors, a collaboration project with SIGA) for the treatment of smallpox (antiviral activity).

·  Resulted the I7L patent by discovering lead compounds and synthesizing several “Oxadiazole based compounds” which showed good PK profile for I7L project (antiviral activity) which are currently being evaluated in PK and Toxicology studies to be the lead candidates.

2000-2002 Research Scientist, TransTech Pharma Inc., Medicinal&Combi. Chem. Labs, High Point, NC

·  Designed and synthesized numerous active compounds against Glucokinase resulting three patent applications.

·  Assigned on a team to first collaborative project with Novo/Nordisk of Denmark. Participated in the chemistry group addressing a novel series of drug candidates as Glucokinase activators for the treatment of type II diabetes.

·  Invented many potent and active compounds as GlucoKinase activators (Synthesized numerous compounds that are being tested in vivo animal studies, from 12/2000 to 12/2002)

·  Worked in the areas of solution and solid-phase organic chemistry technology as applied to lead discovery for Factor IX inhibition, and PTP-1B inhibition.

·  Actively involved in drug discovery programs of the company, developed synthetic methodology for the libraries, using solid phase techniques, synthesized numerous compounds that has shown biological activity and selectivity, supervised B.S. and M.S. level research associates in the robotics and laboratory setting for combinatorial chemistry.

12/2000 Sr. Synthetic Organic Chemist, ArQule Inc., Synthetic Prep. Chemistry Labs, Woburn, MA

·  Developed chemical processes for a multi-step synthesis, testing a variety of conditions including time, temperature, solvent, catalyst, base, etc. Investigated chemical procedures for technology transfer to the production facility.

08/2000 Organic Lab Coordinator, Northeastern University, Chemistry Department, Boston, MA

·  Managed and coordinated organic chemistry teaching labs for all sections from 03/2000 to 07/2000.

1999-2000 Visiting Research Assistant, Northeastern U., Bioorganic & Medi. Chem. Labs, Boston, MA

·  Prepared a series of mixed ligand arene chromium carbonyl based catalysts for asymmetric cycloaddition reactions starting from enantiopure 1,2-naphthalene diol. Directed graduate level research projects.

·  Synthesized novel isomannide based chiral auxiliaries for asymmetric Diels-Alder reaction.

·  Designed and stereoselectively synthesized arene chromium carbonyl complexes whose skeleton mimics the mitomycin family of antitumor agents. Trained graduate students in advanced synthetic methods.

1998-1999 Visiting Teaching Assistant, Organic & General Chem Labs, Northeastern Univ., Boston, MA

·  Taught both freshmen and sophomore level organic and general chemistry laboratories.

1997–1998 Teaching Assistant, Organic and General Chemistry Laboratories, Clemson Univ. Clemson, SC

·  Taught both freshmen and sophomore level organic, general, and computer-assisted chemistry laboratories.

1993-1997 Research Assistant, for Izmir Institute of Tech., Izmir, Turkey, at Clemson Univ., Clemson, SC

·  Developed and published enantioselective alkylation catalysts using mixed ligand arene chromium carbonyls. One of the synthesized catalysts afforded among the highest stereoselectivity ever reported for aliphatic aldehyde methylation.