Vibha Jawa PhD FAAPS

Responsible for scientific strategy and expanding the application of computational biology and bioinformatics for predicting risk of immunogenicity from discovery to development and commercialization.

Provide input to the work packages related to preclinical and clinical questions related to development of AAV based gene therapies in rare disease patients

Head of Biotherapeutics Bioanalysis in Clinical Pharmacology, Pharmacometrics and Bioanalysis (CPP-B) organization. Responsible for supporting PK bioanalysis and immunogenicity assessments for entire biotherapeutic portfolio from discovery to development, which includes a wide range of modalities in BMS portfolio such as monoclonal antibodies, fusion proteins, ADC, gene and cellular therapies. Provide scientific oversight and responsible for supporting BMS developmental portfolio. Work collaboratively with all stakeholder functions (ClinPharm/PK, PCO, Nonclinical Safety, clinical study teams) to ensure appropriate methods are established in a timely manner. Provide oversight and mentorship for Biotherapeutic Bioanalytical Project Leaders who participate in matrix project and study teams and provide functional expertise to advance project goal. Provide responsibility for the oversight of authoring high quality dossier contributions, interactions with global health authorities and to ensure progress of development programs to successful marketing authorizations. Provide leadership and strategic direction to the function and be responsible for solving emerging assay issues.

Lead a group that supports immunogenicity risk assessment and mitigation approaches from discovery to clinical trial support as part of pharmacodynamics and modeling group. Develop systems based models incorporating risk assessment outputs and mined preclinical and clinical data to predict clinical immunogenicity Support sequence optimization and re-engineering to reduce or increase immunogenic potential of biologics or vaccines respectively Support viral gene therapy related strategy for viral and transgene specific immune response Support personalized cancer vaccine related projects by improving antigenicity of tumor neoantigens

Support the drug product teams from early research ( preclinical) to commercial phase of development Maintain drug product in commercial phase and address post marketing commitments Develop and maintain collaborations with key opinion leaders in translational groups like therapeutic discovery, toxicology, pharmacokinetics, manufacturing and process development Concept development and supervision of experimental designs for in-house and external collaborations

Supprt Drug Development from preclinical to commercial phase of drug development Develop innovative cell mediated immune biomarker assays

• Supervised and Gene therapy for plaque reduction in atherosclerosis by reverse cholesterol transport using ApoA1-Milano as transgene. • Established immune based assays to look for T and B cell mediated immune responses following AAV delivery by various routes (intramuscular, intravenous and intra hepatic modes) • Develop strategies to induce tolerance to transgene ApoA1 Milano • Authored a review article on the immune responses to gene therapy vectors

•Responsible for establishing a state of the art immunology research program to define and address the immunogenicity to viral vector based human therapeutic products. •Contributed to ongoing clinical investigations as well as established relevant preclinical models to investigate the immunology of viral vector mediated gene delivery in humans. • Initiated studies on toxicology of viral vectors in animal models of hemophilia • Introduced new technology to aid in understanding the toxicology of gene therapy vectors in metabolic diseases like Gaucher’s disease and phenylketonuria and gene defect based disorders like hemophilia and Parkinson’s disease •Utilized the animal handling expertise to lead projects involving animal surgeries and evaluated the tissues for toxic effects of agents delivered

Conducted research to demonstrated the usefulness of recombinant adeno-associated virus (rAAV) and recombinant lentiviruses (r LV) as a potential vector to target functional genes to correct retinal degenerative diseases Envisioned and investigated ways to evaluate toxicology of viral vectors used for targeting functional genes to the eye for gene therapy Identified the variability in immune responses in the retina generated by administering adenovirus (AdV), lentiviruses and AAV Involved in chimeroplasty studies used for generation of single point mutations in the genome by targeting oligonucleotides useful for generation of knockout animal models Characterized an adenoviral vector coding for the choroideremia gene by invitro gene transfer to lymphoblasts and fibroblasts from the patients and successful in demonstrating the _expression and functional properties of the transduced gene product Proposed the existence of an immune deviant nature of the subretinal space, which confers a tolerizing response to the intra-ocularly administered antigen Initiated collaborations with other groups within UPENN on projects related to immune privileged status of the eye Trained and guided summer interns, helped in streamlining and conceptualizing their research projects and monitored their progress Participated in the AAV mediated gene therapy studies for treating blindness in canine models and evaluated immune mediated toxicities due to viral and/or transgene product Mentored 6+ Ph.D. and M.D./ Ph.D. candidates by teaching and providing both scientific knowledge and technical guidance in several projects related to viral vector and transgene induced T cell mediated immune responses—specifically examined the role of suppressive cytokines and immune deviant nature of sub-retinal space and breach of immune privilege tyrosine on systemic immunity

Studies the role of complement receptors on monocytes and macrophages in autoimmune disease pathogenesis