Brian Wipke

Preclinical research, discovery and development of innovative and differentiated products across the Fannin Innovation portfolio companies

• Identified new therapeutic targets, developed project workplans with milestones and timelines, and defined target candidate profiles and success criteria. • Member of Senior Leadership team; worked with C-suite and Portfolio Strategy to expand early portfolio and identify new business development opportunities. Contributed target rationale and preclinical development strategies, and presented specific projects and workplans to potential partners. • Managed a group of up to 8 scientists (direct and indirect reports), with oversight of in vivo group. Contributed to troubleshooting of biological assay development for specific projects. Proposed translational biomarkers to enable demonstration of preclinical target engagement.

• Led and mentored team of 8-10 scientists and associates responsible for autoimmune therapeutics drug discovery and early candidate development from target validation through development candidate selection and generation of IND-enabling data packages. • Led multi-disciplinary project teams and coached junior project team leaders and team members on their projects. • As member of autoimmune senior leadership team, reviewed discovery portfolio and new project proposals, identified project priorities, and reviewed project timelines and milestones. • Actively managed two external translational academic collaborations with key academic researchers (Parkinson’s disease and Type 1 diabetes immunoregulatory pathways), resulting in one published manuscript. • Collaborated with BD and portfolio strategy groups to prioritize projects, revise development plans, and provide due diligence scientific assessments for specific targets, modalities and competitive landscape.

• Co-launched new autoimmune therapeutic area (2020) as spinout from New Ventures Laboratory. • Led three mRNA therapeutic development projects from lead ID and optimization through development candidate selection and IND-enabling Tox. Contributed to regulatory documentation for investigator brochure and IND submission; reached FIH milestone for most advanced biologic program (IL-2 mutein). • Created and led team of in vivo specialists responsible for selecting, establishing, and optimizing autoimmune and inflammatory animal models to drive target validation, biomarker discovery, and support early development candidates (e.g. pharmacokinetics profiling, pharmacodynamic endpoints, and proof of biology through preclinical efficacy models).

• As member of Acute Neurology Leadership Team, contributed to prioritization of projects and resources, setting timelines, and diligence and BD assessments for in-licensing opportunities. • Established translational in vivo preclinical capabilities in stroke and TBI indications for Acute Neurology Research Unit and managed a group of five scientists for discovery programs (PK/PD, pharmacology, efficacy and toxicity). Established external academic collaborations for specialized stroke and TBI models. • Project champion and biology lead for two small molecule programs in acute neurological indications (stroke, TBI, epilepsy).

• Preclinical expert for Tecfidera post-approval team (2016-2019). Provided scientific expertise and preclinical support, including data generation for drug mechanism of action, efficacy, and PK/PD studies. Delivered translational narrative and MOA scientific presentations on Tecfidera at 3 international Advisory Boards with external researchers and clinicians. • Preclinical consultant for several neuroinflammation and neuroimmunology in-licensing and diligence BD teams. Contributed to both early and later-stage diligence evaluations for potential partnering deals.

• Built new multiple sclerosis in vivo preclinical modeling group and established multiple demyelinating preclinical models for drug pipeline advancement and evaluation of novel and published targets. Identified and championed discovery neuroimmunology targets (multiple sclerosis, Alzheimer’s disease). • Co-led joint ASO therapeutic team with Ionis counterpart for Alzheimer's innate immune target (splicing correction based upon GWAS populational allelic risk data). Reached No Go decision based upon aged amyloid-beta transgenic mouse ASO study results.

• Directed and managed group of five researchers tasked with target validation, in vivo efficacy, PK/PD, and biomarker research in autoimmune disorders (multiple sclerosis, inflammatory bowel disease, and rheumatoid arthritis). • Preclinical pharmacology representative on Tysabri (natalizumab) subteam for characterizing drug mechanisms and PK/PD biomarkers in preclinical animal models. Explored impact of IgG4 arm switching for receptor occupancy in guinea pig model of MS (EAE). • Preclinical Pharmacology/Biology rep for novel pegylated small molecule program (from candidate discovery and optimization through IND and early Phase 1 dosing in multiple sclerosis patients). • Led matrixed project team of up to 25 researchers for internal receptor tyrosine kinase program through successful cell-based small molecule HTS campaigns for two different receptor kinase targets. • Led joint collaboration autoimmune project team for subcutaneous aptamer with industry partner (Archemix); team delivered data-based No Go decision via nonhuman primate pharmacology falling short of Target Product Profile.

• Identified early neutrophil dependency in initiation of joint inflammation in antibody-dependent murine model of rheumatoid arthritis, resulting in publication (Wipke and Allen, J Immunol 2001). • Collaboratively developed real-time tracking of arthritogenic antibodies in vivo using microPET scanner. Identified key cell types and immune pathways involved in accumulation of antibodies and initiation of joint inflammation using combination of genetically manipulated mouse lines and pharmacologic modulators (published in two papers: Wipke et al, Nat Immunol 2002 and Wipke et al, J Immunol 2004).

• Executed and documented final manufacturing lot release testing and lot stability testing of recombinant diagnostic antigens (HIV, Hepatitis B, Hepatitis C) and recombinant therapeutic proteins (e.g. SOD). • Bench scientist responsible for final physical and immunological characterization of proteins (pH, protein concentration, purity by SDS-PAGE, immunoreactivity by Western Blot and ELISA), and compliant documentation of results for regulatory records. • Contributed to troubleshooting of stability sample vial variability for HBV core antigen; pH variation was being introduced by freezing QC samples on dry ice, resulting in infiltration of carbon dioxide into vial contents.