MARIUSZ W. STEMPNIAK, PH.D. mariusz.stempniak@gmail.com 8635 Milbury Road San Diego, CA 92129 858.538.3525 HIGHLIGHTS 18 years of Pharma R&D experience Recipient of numerous awards for drug discovery At Pfizer developed the assays that led to the identification of XALKORI ® (Crizotinib), “one of top five most important advances in cancer treatment in 2011” (according to American Society for Clinical Oncology), with expected sales of $800 million/year Expertise in cell biology, molecular biology, immunology and drug development 2010 - current, Principal Scientist, Multimeric Biotherapeutics, Inc. 1994 - 2010, Principal Scientist, Pfizer Global Research & Development Self-starter, well organized and creative scientist PERSONAL U.S. citizen, born in Poland Spouse: Mariola Stempniak (deceased 2010) Children: Marek, Magdalena, Michal, Mateusz EDUCATION Ph.D. Department of Biology University of Adam Mickiewicz, Poznan, Poland Advisor: Prof. Eugeniusz Biesiadka PROFESSIONAL EXPERIENCE Multimeric Biotherapeutics, Inc. – La Jolla, CA 2010-present Principal Scientist Product development of B cells as antigen-presenting cells for cancer immunotherapy Generation of anti-tumor CD8+ cytotoxic T cells (CTLs) for the adoptive immunotherapy for cancer Work on vaccine for nicotine to help smoking cessation MARIUSZ STEMPNIAK 2858.538.3525 Pfizer Global Research & Development – La Jolla Labs, San Diego, CA Principal Scientist - Exploratory Technologies Department PAGE 2 1994 - 2010 Provided target validation for urokinase-type plasminogen activator (uPA) and its receptor (uPAR) for cancer therapy - Produced antagonist mAbs to block uPA-uPAR axis - Design, production & purification of immunogens - Hybridoma fusion and cloning - Established assays, screened and selected functional mAbs - Characterized mAbs with functional cell based assays - Established stem cells co-culture models useful for in vivo characterization Established target validation for placenta growth factor (PlGF) as a novel anti-cancer therapeutic target - Assay development and successful in vitro proof of concept Provided proof of principle for inhibitory activity of Transferrin-fusion peptides on angiogenic targets (Endostatin, Flt-1, TRAIL, etc.) - Generation of transferrin constructs, fusion protein expression & purification, functional cell based assay development, development of rat aorta angiogenesis assays and characterization of leads. Successful validation of Neuromedin-U (NmU) as a novel anti-cancer mAb target - Generation and testing of anti-NmU mAbs - Cloning of multiple NmU, NmUR1 & NmUR2 constructs, expression and purification, assay development, proof of concept Screening and selection of novel anti-N-Cadherin therapeutic mAbs - Biochemical and functional cell based assay development and screening - Biochemical and in vivo functional epitope mapping - shRNA N-Cad silencing, protein expression, generation of stably expressing cell lines - Functional characterization of leads by inhibition of cell-cell adhesion, cell invasion, Akt pathway, and cytotoxicity Assay development and support of Wnt-1 neutralizing mAb program - Luciferase reporter assay development and screening, cytotoxicity, soft agar assay development, gene silencing Hepatitis C viral protease small molecule inhibitor project - Design, construction and expression of HCV polyprotein clones - Set up and validation of HCV NS2 & NS3 protease assay using rabbit reticulocyte lysate and inhibitor screening - Structural and functional analysis of HCV NS3 protease, identification of Zn2+dependence for activity, successful generation of forms suitable for purification, crystallization and functional activity, development of assay system for testing NS3 inhibitors in mammalian cells Cloning and characterization of tankyrase and development of assays to monitor activity Cloning, expression, and purification of human RNaseH for support of HIV antiviral efforts ELISA assays development for multiple mAb and small molecule projects (uPAR, HGFR, N-Cadherin, PTPa, NmU, FAK, Wnt-1 and other) MARIUSZ STEMPNIAK 858.538.3525 PAGE 3 VA Medical Center, Sepulveda, CA 1991 - 1994 Staff Research Associate Functional and structural study of human rheumatoid factor and lupus anti-DNA antibodies Gene cloning for antigens involved in multiple sclerosis and lupus nephritis. Novel application of PCR in genetic engineering – modification of splice-overlap PCR that simplifies production of fusion proteins from long transcripts. Chimeric antibody therapy of cancer – engineering host defense mechanisms to produce tumoricidal activity – evaluating the efficacy of human chimeric IgA and IgG anti-CEA antibodies in neutrophil ADCC of human colon cancer. In vitro study (using mammalian cell lines) of anti-DNA mAb 3E10 that binds extracellular matrix protein and is transported into the cell nucleus – implications for autoimmunity. Transcytosis of genetically engineered antibodies by epithelial-like MDCK cells expressing polymeric IgA receptor – possible implications for therapy of mucosal tumors and viral infections. MAJOR ACCOMPLISHMENTS AND AWARDS XALKORI® (Crizotinib) c-Met/ALK inhibitor project: Established biochemical and cell based assays to identify and characterize novel c-Met/ALK kinase inhibitors. Identified and selected XALKORI® (Crizotinib) based on cellular activity and kinase selectivity profile. The lead drug candidate XALKORI® is now an FDA approved drug with sales of $800 million/year P-Cadherin mAb project: Performed cell based functional assays including permeability, matrigel invasion, branching morphogenesis, in vivo binding profile of selected mAbs and growth inhibition/cytotoxicity which led to selection and characterization of PF03732010, a fully human anti-P-Cadherin mAb with advanced ADCC activity, which is currently in clinical trials for patients with advanced solid tumors 2010 Pfizer, Inc. Individual Performance Award: For exceptional performance and leader behaviors 2006 Pfizer, Inc. Certificate of Excellence in Recognition of Outstanding Research 2005 Pfizer, Inc. Project Recognition Award: “For single-handedly generating cellbased assays and providing the team with c-Met mutant cell lines leading to CAN selection of PF-02341066” MANAGEMENT EXPERIENCE - Recruiting, hiring, supervision and training of junior staff. - General lab management (maintaining supplies, inventory, and equipment). - Project development and coordination. - Preparation and management of staff research programs. - Preparation and presentation of written, oral and graphic reports. MARIUSZ STEMPNIAK 858.538.3525 PAGE 4 TECHNICAL SKILLS Cell Biology: Cell based functional assays (invasion, migration, adhesion, cell-cell adhesion, proliferation, branching tubulogenesis, cytotoxicity, scattering, permeability, Luciferase reporter, immunocytochemistry, etc.), isolation of peripherial blood mononuclear cells, isolation of lymphocyte subpopulations from PBMCs, growing CD40-B cells for immunotherapy, generation of anti-tumor CD8+ cytotoxic T lymphocytes for adoptive cancer therapy, generation of regulatory T cells for inducing immunological tolerance, target modulation in cell lines, generation of stable cell lines, transfection, mutagenesis, microinjection, gene expression and silencing, small and large molecule screening, target identification and validation, cell line generation, cell culture. Molecular Biology: DNA/RNA purification, PCR, qRT-PCR, cDNA cloning, Southern and Northern blotting, recombinant protein expression & purification, cell-free translation, genetic engineering. Biochemistry: ELISA assay development, Western Blot, immunostaining, immunoprecipitation, kinase and other target activity/inhibition enzyme assays, high and medium throughput screening. Antibody Technologies: Antigen generation, hybridoma fusion, screening & selection, production and purification of functional mAbs. Animal Techniques: Immunization, blood collection, sacrifice and dissection, dosing, surgery, tumor implantation. SELECTED PUBLICATIONS AND ABSTRACTS R. S. Kornbluth, M. Stempniak: Facile Generation of CD40-B cell APCs Using Soluble Multimeric CD40L as a B Cell Proliferation Stimulus. Roche – Nature Medicine Symposium, 2011. H. Zou, Q. Lee, M. Arango, M. Stempniak, S. Yamazaki, T.Koudriakova, G. Alton, P. Kung, M. Nambu, J. Cui, G. Los, J. Christensen, D. Romero, J. Skaptason, M. Tran-Dube, L. Jia, M. Parish, J. Meng, H. Shen: Identification and characterization of an orally bioavailable small molecule inhibitor of c-Met kinase with cytoreductive antitumor properties in vivo (Late Breaking Poster). AACR 2006 Weisbart, R. H., Stempniak M., Harris, S., Zack, D. J., Ferreri, K.: An Antibody is Modified for Use as a Delivery System to Target the Cell Nucleus: Therapeutic Implications. Journal of Autoimmunity, 1998, 11, 539-546 Stempniak, M., Hostomska, Z., Nodes, B. R., Hostomsky, Z.: The NS3 Proteinase Domain of Hepatitis C Virus Is a Zinc-Containing Enzyme. Journal of Virology, 1997, 71: 2881-2886. R. H. Weisbart, M. Stempniak, S. Harris, D. J. Zack, K. Ferreri: An Autoantibody is used as a Delivery System to Target the Cell Nucleus: Implications for Therapy. AACR 1997 MARIUSZ STEMPNIAK 858.538.3525 PAGE 5 Zack, D. J., Stempniak, M., Wong,A. L., Taylor, C., and Weisbart, R. H.: Mechanisms of Cellular Penetration and Nuclear Localization of an Anti-Double Strand DNA Autoantibody. The Journal of Immunology, 1996, 157: 2082-2088. Zack, D. J., Wong, A. L., Stempniak, M., and Weisbart, R. H.: Two Kappa Immunoglobulin Light Chains are Secreted by an Anti-DNA Hybridoma: Implications for Isotypic Exclusion. Mollecular Immunology, 1995, 32; 17,18: 1345-1353. Zack, D.J., Stempniak M., Wong, A. L., and Weisbart, R. H.: Localization of an Fc-Binding Reactivity to the Constant Region of Human IgG4. Implications for the Pathogenesis of Rheumatoid Arthritis. The Journal of Immunology, 1995, 155: 5057-5063. Zack, D. J., Yamamoto, K., Wong, A. L., Stempniak, M., and Weisbart, R. H.: DNA Mimics a Self Protein Which May Be a Target For Some Anti-DNA Antibodies in SLE. The Journal of Immunology, 1995, 154: 1987-1994. D. J. Zack, M. Stempniak, R. H. Weisbart, A. L. Wong: Expression of Two Functional Ig Kappa Light Chains by Anti-DNA Hybridoma: Contribution of the Light Chains to DNA Binding. AACR 1994 D. J. Zack, K. Yamamoto, A. L. Wong, M. Stempniak and R. H. Weisbart: A Self Protein Mimics DNA in Binding a Lupus Autoantibody. 1994. FASEB Journal, 8 (4): A499, Abstract 2888. FASEB 1994 M. Stempniak, A. L. Wong, D. J. Zack, R. H. Weisbart: A Simplified Method for Producing Chimeric Antibodies by Splice Overlap Extension PCR. 1993, A & R 36 (9): S239 Abstract D45. AACR 1993