Kristin DeSouza, PhD

Provided IND/CTA and NDA/MAA enabling expert guidance on safety assessment, regulatory strategy and risk throughout the drug development process for diverse Biotech and Pharma clients. ~ Authored Modules 2.4, 2.6.6, and 2.6.7 for IND/CTA and NDA/MAA as well as PMRs/PAMs for FDA and EMA. ~ Enabled full IND approval for Phase 1 clinical trial by navigating an equivocal genotoxicity outcome. ~ Developed Carcinogenicity Weight of Evidence (WOE) Waivers based on ICH/FDA collaborative S1B(R1) guidance. ~ Expertise in design, execution, and interpretation of in vitro and in vivo General Toxicology studies as well as, Safety Pharmacology, Juvenile/Reprotox, Genotoxicity, and Carcinogenicity studies. ~ Proficient conducting in silico (Q)SAR modeling and expert rule-based analysis in alignment with ICH M7 guidelines. Utilized Instem Leadscope Model Applier to provide expert review and a full report. ~ Utilized a diverse CRO network to provide oversight on nonclinical safety programs for clients including CRO selection, budget, timelines and monitoring. ~ Experience preparing the DSUR annual report and providing OEL/PDL assessment review.

Developed the toxicology program for novel small molecules targeting protein ‘hotspots’ for allosteric regulation of proteins to treat cancers and autoimmune diseases. Leveraged nonclinical expertise and technical experience to develop and manage the nonclinical program. ~ Designed and led pivotal nonclinical studies utilizing expertise and problem-solving skills to accelerate study completion facilitating an IND-enabling package, meeting company goals. ~ Collaboratively developed and ran pharmacokinetic studies in small and large animal models establishing appropriate starting doses and aid non-clinical GLP study designs. ~ Lead nonclinical toxicology expert for a cross-functionl drug development team. ~ Successfully managed and interacted with CROs for nonclinical programs to ensure timely delivery of regulatory compliant study reports for IND filings. ~ Clearly conveyed nonclinical scientific findings to diverse audiences, including senior management. ~ Developed visual graphics to express detailed data in easily consumable formats for multiple audiences.

Designed and implemented nonclinical IND/CTA-enabling programs and regulatory submissions for ASO (Elsunersen) and small molecule (Relutrigine) to treat rare disease pediatric epilepsies by regulating target protein levels. ~ Lead toxicologist on a multi-disciplinary, matrixed, rare disease product development team from discovery through marketing, networking with Discovery, DMPK, CMC, Regulatory, and Clinical teams. ~ Designed and managed a streamlined nonclinical strategy enabling accelerated timelines for early IND submission. ~ Authored nonclinical sections 2.4, 2.6.6, and 2.6.7 of three separate indications, including an ASO, for regulatory submissions to support IND (FDA – neurology division) and CTA (BfArM, AEMPS, and Anvisa) approval. ~ Designed and executed the pivotal nonclinical study for the ASO Elsunersen, delivering robust safety and efficacy data supporting IND approval and the successful Phase 1/2 clinical trial – EMBRAVE. Elsunersen is now in Phase 3. ~ Developed nonclinical FDA complete response letters (CRL) response package, enabling successful clinical trials. ~ Created target safety assessment profiles for discovery-level ASO target compound, PRAX-080. ~ Devised a Carcinogenicity Weight of Evidence (WOE) Waiver to expedite marketing approval. ~ Architected IND-enabling studies for Relutrigine, facilitating the EMBOLD and EMERALD clinical trials. Utilized Agile Program Management tools and team design to drive efficient and effective pipeline development. ~Encourage cross-functional, team collaboration to ensure creativity and open communication for peak agility and alignment, leading to efficient program progress. ~Skilled liaison between functional and/or program teams and other stakeholders. ~Maintained clear and detailed toxicology objectives and key results for each business cycle.

Directed studies for GLP and non-GLP preclinical safety assessment of ADCs, mAbs, RNAi, small molecules, vaccines and gene/cell therapies in mice, rats, dogs, rabbits (vaccines) and primates. ~Completed risk assessment per: FDA, MHRA and MHLW regulations; ICH and OECD guidelines; SEND and INHAND standards for global clients (US, UK, EU, Japan, South Korea, Israel and Australia). ~Delivered study design consulting services for small biopharmaceutical companies ensuring appropriate risk assessment and developing innovative solutions for challenging drug candidates. ~Toxicology Lead Scientific Liaison for large US/UK and EU based pharmaceutical companies. ~Designed 85+ toxicology study protocols and developed schedules by coordinating with multidisciplinary teams including Covance drug development. ~Subject Matter Expert for transgenic mouse or rat carcinogenicity and radioactive general toxicology studies. ~Ensured timely progress and completion of studies, overseeing multidisciplinary teams at all stages of in-life and post-life data collection and data analysis. ~Leveraged extensive experience in diverse scientific contributions including Bioanalysis, TK/PK, Immunogenetics/Immunotoxicity, Cytokine Analysis, Anti-Drug Antibody response, Safety Pharmacology, Neurological Exams (FOB) and Gene Expression to complete studies. ~Authored Quality Assurance-audited reports for regulatory submission, finalizing 15-20 reports/year. ~Routinely utilized written and verbal communication skills with clients and internal/external contributing scientists establishing good working relationships and collaborations. Project team leader for study deviation process improvement. ~Led team to innovatively streamline workflows for Toxicology Departments across Covance sites internationally utilizing data analysis, study impact assessment and SOP/Policy revisions. ~Presented conclusions to the VP team of Covance Early Development.

Directed nonclinical safety assessment of acute – chronic toxicology, micronucleus assay and carcinogenicity studies. ~Conducted non-GLP range-findings studies and GLP compliant studies according to: FDA, MHRA and MHLW regulations; IHC and OECD guidelines. ~Developed study protocols, study schedules and reviewed cost estimates with clients. ~Oversaw study preparation, in-life activities and post-life analysis procedures of 50+ studies. ~Analyzed and interpreted study data and authored toxicology reports. ~Generated Quality Assurance-audited reports for regulatory submission in support of INDs and NDAs. ~Conducted primary communication with sponsor and contributing scientists/principle investigators. Lean Six Sigma Process Improvement Initiative - Green Belt Project. ~Led a multi-department project establishing timely Quality Assurance review of study protocols.

Designed and managed research projects to understand the molecular pathways controlling bladder development, function and pathogenesis. ~Trained, directed, and managed junior staff ~Performed a joint research project as part of a collaborative research team ~Optimized and conducted RNA In Situ Hybridization studies to characterize mRNA sub-tissue localization ~Developed a database to organize and store complex data gathered from characterization studies ~Designed and optimized biochemical protein-DNA interaction studies utilizing Electromobility Shift Assays. ~Developed an organ explant based cell culture system for the laboratory ~Designed Tissue-specific Microdissection Laser Capture and RNA microarray study. ~Optimized a beta-galactosidase assay for lacZ transgenic mice ~Extracted and manipulated genomic DNA for a DNA methylation microarray study

Designed and performed research projects to understand organ development and regulatory pathways. ~Performed RNAi studies on transgenic organisms to identify novel targets of a key regulatory gene ~Applied molecular genetic techniques to generate tissue specific GFP reporter assays and to alter transgene promotor regulatory sequences ~Data mined the literature to identifiy a list of genes with specific expression patterns of interest ~Generated transgenic organisms by genetic engineering ~Conducted bioinformatics analysis of Gene Ontology (GO) terms of transport genes. ~Established scientific collaborations with a fellow research group (international)

~Led Honors Biology Laboratory classes ~Member of the committee to redesign the Hnors BiologyLaboratory lab manual. ~Teaching Assistant for DAN Finger Printing Workshop (mentored undergraudate & high school students) ~Taught Advanced Genetics discussion-style classes and led review sessions ~Teaching assistant for Advanced Cell Biology ~Taught Introductory Biology discussion-style classes

Performed research studying the effects of arbuscular mychorrizal fungi on plant adaptation ~Demonstrated plants can adapt to changes in soil composition and nutrient levels by shifting their dependence on symbiotic fungi

Thesis: "Multiple mechanisms contribute to regulation of gene expression in C. elegans excretory system"