Matt Chu

Leading a team of >20 talented scientists across Japan and US for early-stage antibody engineering research with a focus on oncology drug development for patients.

• Built the Protein Engineering function enabling Design-Discovery-Production-Analysis capabilities to lead/support Cancer Cell Therapy & Tumor Microenvironment programs • Fostered collaboration with a number of Astellas groups including the Tsukuba Biologics Engineering, Pharmaceutical Science & Technology Labs, Astellas Gene Therapy, Advanced Informatics & Analytics, as well as the Functional Chapters in AI Drug-Discovery and Biologics Research • As a member of the Xyphos leadership team, helping shape both the science and culture on site in South San Francisco More update soon: https://xyphosinc.com/company/management-team/

Group leader of the Protein Sciences Team to oversee protein/antibody-related activities • Managing 3 direct reports and CROs to support antigen/antibody production and analytics/characterization • Leading new target identification and validation; champion of an exploratory immunomodulator project • Supporting CMC activities for development and manufacture of two clinical drugs (TTX-030 and -080), and IND filing • Other responsibility: Member of senior management team to support the leadership team

Head of Protein Sciences

Co-Research Project Lead for a newly initiated program to target cancer immunosuppression • Worked closely with biology lead to define project strategy, surveyed competitive landscape / IP profiles, drafted work plan and timeline, and presented to leadership team • Managed a direct report to design various bispecific and multivalent cell-type specific targeting antibodies for programs • Other responsibilities: First- and co-authored two submitted publications for the studies of cytokine therapeutics and bispecific T-cell engager in different formats, respectively

Protein Engineering Lead to advance the top-priority targeted-cytokine program from lead selection to pre-IND • Designed and engineered novel, targeted antibody-cytokine fusion variants through structure-based and saturation mutagenesis approaches; Delivered >100 constructs for lead selection under a tight timeline • Developed scalable purification process to generate challenging antigens and antibody-cytokine proteins in high quality and high yield for pre-clinical studies • Analyzed and presented biophysical, biosensor, in vitro / in vivo and structural data with project teams to facilitate the iterative process for lead optimization and engineering • Managed collaboration and represented the site to provide project updates to the process development team to facilitate manufacture of the lead molecule • Other responsibilities: Started a cytokine-receptor project as a postdoc-mentorship research proposal; Managed five Äkta Avant systems and provided training for the site; Co-authored of an anti-OX40 antibody paper

GPCR crystallographer and Principal Investigator for a Phase I / Phase II SBIR grant awarded project • GPCR engineering and crystallography lead: Managed and oversaw all crystallography-related activities • Developed purification strategies using different detergents and lipids to prepare stable GPCR–G-protein/nanobody complexes for crystallography and cryo-EM studies, and contributed to two publications in Nature • Leading author of a Small Business Innovation Research (SBIR) proposal, awarded a $1.3M 3-year Phase I/II grant • Solved two crystal structures of Family A GPCRs to trigger milestone payments in the collaboration with UCB (Press Release in February 2016; publication submitted in 2020), and published one of the structures in PNAS

Advisor: Prof. William I. Weis Designed, executed and published research on the molecular basis of Wnt–receptor interaction and signaling • Optimized the expression and purification for various challenging Wnt signaling components (Extracellular ligands: Wnt, Dkk1, Norrin; Receptors: Frizzled, LRP6; Intracellular signaling molecules: Dvl, Axin, GSK-3, CK1) • Devised biophysical and structural approaches to demonstrate the ligand-induced conformation change of LRP6, and uncover the spatial relationship of its large ectodomain to Wnts, Dkk1 and Frizzled for signaling • Developed a quantitative Native PAGE mobility shift assay for the analysis of LRP6–Wnt, LRP6–DKK1 and LRP6–Fab protein complex formation using fluorescent-dye conjugated antibodies • Crystallized and solved the first apo structure of a Wnt ligand, subsequently identified a LRP6-binding site • Determined five crystal structures of Axin-bound GSK-3 kinase in complex with peptides derived from the LRP6 inhibitory motifs, and revealed a substrate binding pocket for the design of more selective inhibitors against GSK-3 • Mentored 1 junior postdoctoral fellow on a new project extended from my previous findings

Advisors: Prof. Kenneth T. Douglas and Dr. Patrick A. Eyers PhD thesis: “Biochemical & Structural Analysis of the Human Mitotic Kinase Mps1” • Dissected the phosphoregulation of Mps1 by mutagenesis study and kinase activity assays • Solved the first crystal structure of Mps1 and subsequently 6 more structures in complex with different small molecule ligands, laying the groundwork for the future development of specific Mps1 inhibitors for cancer therapy • Invited to author a book chapter in the “Encyclopedia of Signaling Molecules” and a review in the “UCSD-Nature Molecule Pages” on Mps1 • Co-authored two more publications for the study of drug-resistance mitotic kinase mutants in cancer

Advisor: Prof. Mary Miu-Yee Waye and Prof. Sai-Ming Ngai M.Phil. thesis: “Characterization of spike glycoprotein fusion core and 3C-like protease substrate specificity of the SARS-CoV: Perspective for anti-SARS drug development” • Took the opportunity to expose to biomedical research during the SARS epidemic in Hong Kong • Characterized the biophysical properties of the conserved S2 subunit of the spike glycoprotein, one of the most important therapeutic targets of SARS-CoV • Synthesized and identified S2 subunit-derived peptides as potential SARS-CoV entry inhibitors • Set up collaboration and screened for small-molecule lead compounds that target the SARS-CoV spike glycoprotein • Co-developed a high-throughput screening method to study the substrate specificity of SARS 3C-like protease by peptide synthesis and MALDI-TOF MS with another Master student