Manager Development

Kirk P. Van Ness, PhD DABT

FIELDS OF EXPERTISE:

Toxicology: Nonclinical safety evaluation of pharmaceuticals; regulatory and mechanistic toxicology of small and large molecules in drug development, renal and hepatic toxicology.

EDUCATION:

Ph.D., University of Washington, Toxicology-Department of Environmental Health: Dissertation Title: Analyses of Aflatoxin B1 8, 9-Epoxide Conjugation Activities in Glutathione-S-Transferase-Yc Isoenzymes

M.S., University of Washington, School of Fisheries: Thesis title: Characterization of Toxicity and Relative Abundance of Some PCB Isomers In Muscle Tissues of Puget Sound, WA English sole, Pacific cod, Sablefish and Squid.

B.A., Indiana University, Biology

SUMMARY OF RELEVANT EXPERIENCE:

Technical expert in the utilization of renal microphysiological systems to research kidney disease and toxicity using relevant biomarkers, RNA transcript analyses and image analyses. Routinely execute research studies to evaluate chemical and drug exposures to proximal tubule epithelial cells to develop mechanistic hypothesis for pathophysiology in the context of organ-on-a chip system used to recapitulate a functional human kidney proximal tubule.

Extensive preclinical drug development experience with small molecules (antisense RNA) and biologics (recombinant cytokines, mAbs, Fc-fusion proteins) supporting all phases of drug development, including GLP toxicology safety assessment studies, clinical trials and regulatory submissions.

Comprehensive knowledge of the preclinical regulatory guidance required to advance successful drug candidates through the pipeline. Experienced with nonclinical study designs that support all phases of clinical development and that require adherence to ICH guidelines.

Former leader of the mechanistic toxicology group at ZymoGenetics. Implemented investigational in vivo and in vitro studies focused on primary and off-target organ toxicities (primarily hepatic, renal, cardiac and immune systems) for clinical and nonclinical safety evaluation of biopharmaceuticals.

Broad regulatory writing experience that includes: authoring influential white papers submitted to the EMA, GLP toxicology study reports and program summaries, Investigator Brochures, INDs, and questions to be submitted to the FDA.

Capable of serving as Study Monitor for numerous GLP and non-GLP toxicity studies placed at CROs with responsibilities including: CRO selection, budget and timeline management, issue mitigation.

Board certified toxicologist (Diplomate of the American Board of Toxicology). Certified through 2019.

PROFESSIONAL EXPERIENCE

University of Washington, Seattle WA 2015-current

Department of Pharmaceutics-School of Pharmacy

Research Scientist/Lab Manager

Utilize and develop microfluidic devices (organs-on-a-chip) with renal epithelial cells and human hepatocytes to evaluate the toxicity and pharmacology of exposure to drugs and environmental toxicants.

Manage a core facility to develop and analyze the integration of multiple organ-on-chip systems to assess fundamental toxicology and pharmacology investigations.

University of Washington, Seattle WA 2014-2015

Depart of Environmental and Occupational Health Sciences

Research Manager

Led the development and implementation of a large interdisciplinary research team at the Institute of Risk Analysis and Risk Communication within the Department of Environmental and Occupational Health.

Coordinated molecular and genomic analysis across service cores and research centers.

Integrated ongoing mechanistic-based research studies in toxicology and risk assessment with a special emphasis on mechanistic research on children’s health and reproductive and developmental toxicology.

Developed 3D in vitro microphysiological systems (organs-on-a-chip) for the testis and neuronal cell systems. These systems will be used for rapid toxicity screens and to integrate with other organ-on-a-chip systems (kidney and liver).

KPVN Consulting LLC, Bainbridge Island, WA 2008-ongoing

Principal Toxicologist

Consultation for preclinical toxicology study design, management and report finalization.

Active Expert Witness in toxicology supporting King County public defenders with cases involving drug-related charges that includes DUIs and drug-drug interaction scenarios.

Toxicology study data interpretations and program recommendations.

Work collaboratively with development project teams to ensure on time quality deliverables with consideration of budget.

Conduct comprehensive literature searches, biomarker evaluations, regulatory writing support, troubleshooting, and issue mitigation.

Intertox Inc., Seattle, WA 2011-2013

Senior Toxicologist

Provided clients with strategic project support in a wide range of toxicological and pharmacological services including: pharmaceutical development, nonclinical safety studies, regulatory services, and environmental health and safety projects. Provided litigation support services on exposure and risk assessments and interpretations of animal toxicology study results from inhalation and oral exposures to industrial chemicals.

Examples of nonclinical toxicology support includes: interpretation of DART study data for potential maternal toxicity influences, cardiotoxicity evaluation, nonclinical study designs for a peptide/adjuvant oncology vaccine and for a Class III medical device.

Sarepta Therapeutics (formerly AVI BioPharma), Bothell, WA 2010-2011

Senior Manager, Preclinical Development

Designed toxicology programs to support regulatory filings for five antisense RNA programs (antiviral programs: Ebola and Marburg; Duchenne’s muscular dystrophy).

Authored nonclinical sections of regulatory documents, including INDs, Annual Reports, Investigator Brochures, and questions to the FDA.

Designed and served as Study Monitor for numerous GLP and non-GLP preclinical studies including chronic NHP and rodent toxicity studies, genotoxicity assays, and a complex juvenile rat toxicity (DART) study.

Successfully implemented a renal biomarker initiative that led to the company’s adoption of suggested renal biomarkers in clinical and preclinical studies.

ZymoGenetics, Inc., Seattle, WA 2005-2008

Scientist, PreClinical Development-Safety Assessment (Toxicology)

Responsibilities included support of preclinical safety studies through study design, study monitoring, and report finalization. (IL-21, interferon lambda IL-29, atacicept) for oncology, antiviral and autoimmune therapies.

Strong immunotoxicology background specialized in immunosuppression and immunostimulation

Leader of the mechanistic toxicology group. Supervised two PhDs: a toxicologist and a pathologist

Designed and led in vivo and in vitro mechanistic toxicology investigations.

Wrote regulatory white papers concerning mechanistic toxicology issues.

Served as Study Director and Monitor for toxicology assessment studies.

Led proteomics initiative to characterize potential biomarkers.

Led preclinical effort to justify species selection process.

Amgen/ Immunex Corporation, Seattle, WA 1998-2005

Senior Staff Scientist/Postdoctoral Fellow, Cell Sciences Department

Optimized and characterized commercial upstream CHO development processes using small-scale bioreactors and shake flasks for mABs and Fc-fusion proteins.

Experienced with all phases of CHO cell line development from clone selection to bioreactor optimization studies.

Designed and ran complex, multi-factorial experiments that investigated the influences of vitamins and amino acids on productivity and viability.

Pacific Northwest Cancer Foundation/ Northwest Biotherapeutics, Seattle, WA 1996-1998

Postdoctoral Fellow/Staff Scientist

Analyzed the structure/function of human fucosyltransferases by site-directed mutagenesis and photoaffinity probes.

Immunex Corporation, Seattle, WA 1987-1990

Research Associate, Protein Chemistry Department

As part of running the protein sequencing facility (Edman degradation chemistry), obtained sequences for novel proteins and confirmed sequences for all vialed lots of recombinant proteins.

Helped company obtain FDA approval of Leukine by maintaining excellent QA/QC protein sequencing records and having a demonstrated expertise in protein sequencing and protein chemistry.

Children’s Hospital Medical Center: Harvard Medical School, Boston, MA 1980-1983

Research Associate, Department of Orthopaedic Research

Served as a laboratory technician in a prominent collagen biochemistry research laboratory under the direction of Harvard University’s Dr. David Eyre. (currently at the University of Washington).

Isolated and characterized collagen cross-links and developed an HPLC method to quantify hydroxypyridinium crosslinks.

PUBLICATIONS:

Koob, T.J., Eyre, D.R, and Van Ness, K.P., Detection and photolysis of hydroxypyridinium crosslinks in cartilage collagen, In situ., Trans. Orthop. Res. Soc. 8:28, 1984.

Eyre DR, Koob TJ, Van Ness KP. Quantitation of hydroxypyridinium crosslinks in collagen by high-performance liquid chromatography.

Anal. Biochem. 1984 Mar;137(2):380-8.

Landolt, M.L., Hafer, F.R., Nevissi, A., van Belle, G., Van Ness, K., and Rockwell, C., Potential Toxicant Exposure Among Consumers of Recreationally Caught Fish From Urban Embayments of Puget Sound. NOAA Technical Memorandum, NOS OMA 23, Rockville, Maryland, 104 pp. 1985

Landolt, M.L., Kalman, D., Nevissi, A., van Belle, G., Van Ness, K., and Hafer,F., Potential Toxicant Exposure Among Consumers of Recreationally Caught Fish From Urban Embayments of Puget Sound. NOAA Technical Memorandum, NOS OMA 33, Rockville, Maryland, 111 pp.

Mearns, A.J., Van Ness, K.P., Order from Chaos? History Of Chlorinated Pesticide Contamination of the U.S. Coastal Fauna, Proc. OCEANS 87.

Long, E., Mac Donald, D., Matta, M., Van Ness, K., Buchman, M., and Harris, H., Status and Trends of Concentrations of Toxicants and Measures of Biological Stress in San Francisco Bay, NOAA/OMA/OAD. 1987.

Dickson, I., Eyre, D.R., and Van Ness, K.P., Collagen cross-linking in human bone and articular cartilage: Age-related changes in the content of mature hydroxypyridinium residues. Biochem. J. 252: 495-500.

Van Ness KP, Koob TJ, Eyre DR. Collagen cross-linking: distribution of hydroxypyridinium cross-links among invertebrate phyla and tissues. Comp. Biochem, Physiol. B. 1988;91(3):531-4.

Black, R. A., Kronheim, S. R., Sleath, P. R., Greenstreet, T. A., Van Ness, K. P., Glackin, P. J., Griffin, A., Hendrickson, Ronald, C.,Merriam, J. A., and March, C. J. Identification of a protease that processes interleukin-1 b . In: Molecular and Cellular Biology of Cytokines. Wiley-Liss, Inc., New York, p. 69-74, 1990.

Williams, D. E., Eisenman, J., Baird, A., Rauch, C., Van Ness, K., March, C. J., Park, L. S., Martin, U., Mochizuki, D. Y., Boswell, H. S.,Burgess, G. S., Cosman, D. and Lyman, S. D. Identification of a ligand for the c-kit proto-oncogene. Cell 63:167, 1990.

Burns Jr., J.M., Scott, J.M., Carvalho, E.M., Russo, D.M., March, C.J., Van Ness, K.P., and Reed, S.G. Characterization of a membrane antigen of Leishmania amazonensis that stimulates human immune responses. J. Immunol. 146:742, 1991.

Cerretti, D.P., Kozlosky, C.J., Mosley, B., Nelson, N., Van Ness, K., Greenstreet, T., March, C.J., Kronheim, S.R., Druck, T.,Cannizzaro, L.A., Huebner, K., Pickup, D.J., Ray, C.A. and Black, R.A. Molecular cloning of the IL-1β processing enzyme. In: Pathophysiology and Pharmacology of Cytokines, Biomedical Press, p. 3, 1992.

Kronheim, S.R., Mumma, A., Greenstreet, T., Glackin, P.J., Van Ness, K., March, C.J., and Black, R.A. Purification of interleukin-1 converting enzyme, the protease that cleaves the interleukin-1β precursor. Arch. Biochem. Biophys. 296:698, 1992.

Cerretti, D.P., Kozlosky, C.J., Mosley, B., Nelson, N., Van Ness, K., Greenstreet, T.A., March, C.J., Kronheim, S.R., Druck, T.,Cannizzaro, L.A., Huebner, K., and Black, R.A. Molecular cloning of the interleukin-1β converting enzyme. Science 256:97, 1992.

Van Ness KP, Buetler TM, Eaton DL. Enzymatic characteristics of chimeric mYc/rYc1 glutathione S-transferases. Cancer Res. 1994 Sep 1;54(17):4573-5

Van Ness KP, McHugh TE, Bammler TK, Eaton DL. Related Articles, Identification of amino acid residues essential for high aflatoxin B1-8,9-epoxide conjugation activity in alpha class glutathione S-transferases through site-directed mutagenesis. Toxicol. Appl. Pharmacol. 1998 Sep;152(1):166-74.

Sazani P, Van Ness KP, Weller DL, Poage DW, Palyada K, and Shrewsbury SB, Repeat-Dose Toxicology Evaluation in Cynomolgus Monkeys of AVI-4658, a Phosphorodiamidate Morpholino Oligomer (PMO) Drug for the Treatment of Duchenne Muscular Dystrophy. Int. J. Toxicol. 2011 May; 30: 313-321.

Sazani P, Van Ness KP, Weller DL, Poage DW, Nelson K, and Shrewsbury SB. Chemical and Mechanistic Toxicology Evaluation of Exon Skipping Phosphorodiamidate Morpholino Oligomers in mdx mice. Int. J. Toxicol. 2011 May; 30: 322-333.

Chang, S-Y, Weber, EJ, Van Ness KP, Eaton DL, and Kelly EJ. Liver and Kidney on Chips: Micro-Physiological Models to Understand Transporter Function (Review). Clin. Pharmacol. Ther. 2016 100 (5): 464-478.

Harris S, Pacheco Shubin S, Wegner S, Van Ness K, Green F, Hong S, Faustman, Presence of Macrophages and Inflammatory Responses in an In Vitro Testicular Co-Culture Model of Male Reproductive Development Enhance Relevance to In Vivo Conditions. Tox. In Vitro 2016 36: 210-215.

Kim1 HY, Wegner1 SH, Van Ness1 KP, Pacheco1 SE, Park1 JJ, Workman T, Hong S, Griffith W and Faustman EM 1equal contribution. Differential Epigenetic Effects of Chlorpyrifos and Arsenic in Proliferating and Differentiating Human Neural Progenitor Cells. Reproductive Tox. 2016 65:212-223.

Van Ness KP, Chang S-Y, Weber EJ, Zumpano D, Eaton DL, and Kelly EJ. Microphysiological Systems to Assess Nonclinical Toxicology. Current Protocols in Toxicology. 2017 77,

14.18.1–14.18.28.

Chang S-Y, Voellinger, JL, Van Ness KP, Chapron B, Shaffer RM, Neumann T, White CC, Kavanagh, TJ, Kelly EJ & Eaton DL. Characterization of Rat or Human Hepatocytes Cultured in Microphysiological Systems (MPS) To Identify Hepatotoxicity. In vitro Toxicology (2017- Apr; 40:170-183).

Van Ness KP and Kelly EJ, Book Chapter: “Excretory Processes in Toxicology-Drug Transporters in Drug Development” in Comprehensive Toxicology, (3rd Edition). (2017-In press).

PATENTS:

Van Ness, K., Trentalange, M., Dell, B., and McGrew, J. US Patent 6,872,549: Methods for Increasing Polypeptide Production. March 29, 2005.

Lyman, S.D., Van Ness, K.P., Paxton, R.J. US Patent 7,288,633 B2, Modified Human Thymic Stromal Lymphopoietin, Oct 30, 2007.

Ponce, R., Wallis, W., Holdren, M., Zuckerman, L., Littau, A., and Van Ness, K. P., Combination of BLyS Inhibition and Immunosuppressants for Treatment of Autoimmune Disease . US 8,852,591 B2 Oct. 7, 2014.

AWARDS AND SCHOLARSHIPS:

1985- Stroum Scholarship Award

1992-1995 Pathobiology Training Grant

1993- Society of Toxicology Graduate Student Travel Award

1993- Award for Meritorious Graduate Research by the Carcinogenesis Specialty Section at the Society of Toxicology Annual Meeting, New Orleans, LA

PRESENTATIONS:

Sierra Biomedical Inc.: Biotechnology Symposium, San Diego, CA, 2005

“An Informed Clinical Strategy For rIL-21 Phase I Using PD Models And Mechanistic Hypotheses”

Charles River Laboratories PreClinical Services Symposium on Biotechnology Derived Therapeutics: Pharmacology and Toxicology Perspectives in Nonclinical Development of Pharmaceuticals and Immunomodulation-Coranado, CA, 2006 “Immunosuppression and Cancer”

Pharmaceutical Education Associates: Immunotoxicology V Conference: Alexandria, VA, 2007.

"Immunosuppression and Cancer of Biotherapeutics"

POSTERS:

Society of Toxicology, 32nd Annual Meeting, New Orleans, Louisiana. 1993.

“Identification of amino acid residues essential for high aflatoxin B1-8,9-epoxide conjugation activity in alpha class glutathione S-transferases through site-directed mutagenesis”

ISSX. GST Workshop, Noordwijkerhout, The Netherlands. 1995.

“Enzymatic characteristics of chimeric mYc/rYc1 glutathione S-transferases”

Society of Toxicology, 47th Annual Meeting, Seattle Washington. 2008.

"Preclinical Evaluation of Immunomodulatory Activity and Safety of Recombinant Human Interleukin-21" Van Ness, K., Hughes, S., Ponce, R., Laursen, S., and Miller, D.

Society of Toxicology, 54th Annual Meeting, San Diego, California. 2015. “Urinary microRNA Profiles as Potential Biomarkers of Pesticide Exposure” Weldon, B., Pacheco, S. Van Ness, K., Workman, T. Thompson, B., and Faustman, E.

Society of Toxicology, 55th Annual Meeting, New Orleans, California. 2016. “Nephrotoxicity Of Engineered-Nanoparticles: Exposure Effects Of Silver Nanoparticles In A Kidney Microphysiological System” Kirk P. Van Ness, Elijah J. Weber, Thomas Neumann, Edward J. Kelly. Pharmaceutics, University of Washington, Seattle, WA, Nortis, Inc, Seattle, WA

Society of Toxicology, 56th Annual Meeting, Baltimore, Maryland. 2017. “Microphysiological System Assessment of Nephrotoxicity of Quantum Dot with a Cadmium/Selenium Core” Kirk P. Van Ness, Terrance J. Kavanagh and Edward J. Kelly, University of Washington, Seattle, WA.

PROFESSIONAL ORGANIZATIONS:

Society of Toxicology 1990-

Pacific Northwest Association of Toxicologists (PANWAT) 1990-

Diplomate of the American Board of Toxicology (DABT) 2009-

Organization of Regulatory and Clinical Associates (ORCA)

Board of Directors: Washington Agricultural Families Assistance (WAFA)

CONTINUING EDUCATION:

Charles River Biotech Symposium Workshop: Metabolic Syndrome: Models, Methods & Challenges, 2012.

SOT-Current Nonclinical Strategies and Methods for Evaluating Drug-Induced Cardiovascular Tox, 2011.

World Pharmaceuticals Congress: Short course-Translating Safety Biomarkers from the Lab to the Clinic, 2010.

ACT-Considerations Regarding NHP Use in Nonclinical Safety Assessment, 2010.

SOT-CE Course: Segment Specific Renal Pathology for the Non-Pathologist, 2010.

Primer in Pathology: Interpreting and Integrating Nonclinical Study Results

PANWAT, Seattle, WA, Sept., 2009.

Mid-America Toxicology Course, Kansas City, MO- April 2009.

Study Director Training-American College of Toxicology, Indian Wells, CA, Nov. 2007.

AAI Advanced Course in Immunology, Minneapolis, MN, Aug. 2007.

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