Alexander W. Fischer

Lead key pipeline siRNA therapeutic projects in cardiovascular, heart failure and MASH space. Manage projects directly and in matrixed setting. Design and oversee entire project life cycle from target identification and in vitro screening through in vivo PK/PD in rodents and non-human primates (NHP), efficacy and disease proof-of-concept (PoC) and lead nomination to IND-enabling studies. - Design preclinical strategy, source disease models, develop biomarker strategy, and identify and conduct due diligence on contract research organizations (CROs) and external collaborators. Manage interaction with CROs to drive project within timelines and budgets, ensuring compliance in steering meetings. - Review, interpret and compile data and regularly communicate strategy and findings to key stakeholders, supporting key Go/No-Go decisions. - Responsible for all aspects of projects, including research of disease mechanisms and unmet need, design of target product profile (TPP), project management and identification of KOLs and collaborators. - Support asset development through cross-functional collaboration: identify partnering opportunities and support generation of pitch decks with Business Development (BD) unit; support IP strategy with legal team and survey market and competitive landscape with competitive intelligence (CI) team.

Established and led Animal Models and Pharmacology team of 5 Research Associates and 1 scientist. Directed the planning, execution, and analysis of all in vivo and downstream ex vivo activities within Moderna Genomics, supporting 4 research units by managing 100+ studies/year. Studies included candidate screening, PK/PD, disease modeling and biomarker discovery for novel gene editing medicines and mRNA drugs. - Designed an efficient in vivo pharmacology strategy to generate high quality data under ambitious timelines in a fast-paced environment and pivoted quickly to meet company goals. - Collaborated with Gene Editing Innovation, Protein Design, Rare Disease and Formulations Discovery Units, enabling discovery of novel gene editors and lipid nanoparticle (LNP)delivery modalities. - Interviewed and hired team of 6 direct reports, directed team in weekly team meetings and 1:1 meetings and supported career development . - Wrote IACUC protocols, worked with veterinarians and facility management to ensure compliance with animal regulations. Established SOPs and data storage and reporting system to ensure compliance and data accountability. - Developed and managed budget and space allocation for all in vivo activities within Moderna Genomics. Oversaw expansion of animal facility, working with architects, contractors, safety, and facility management ensuring completion within budget and timelines. - Sourced in vivo models and managed model generation at CROs to support research efforts in Moderna Genomics and other functions within Moderna. - Established novel surgical models and trained team members in surgical techniques. - Subject matter expert (SME) for metabolic disease/obesity/MASH, supporting target validation for Moderna Genomics and Rare Disease programs and enabling publication (Molecular Metabolism, 2024) - Led scientific efforts to mitigate immunogenic effects of nucleic acid drugs, in collaboration with Immunology and in vitro pharmacology groups.

- Led project team to elucidate regulation and physiological importance of transcription factor sequestration on lipid droplets. Understanding the feedback regulation of lipid storage has therapeutic implications for NAFLD/NASH and obesity. - Spearheaded in vivo pharmacology research projects to elucidate feedback loops regulating de novo lipogenesis and investigated anti-obesity effects of genetic and pharmacological DGAT inhibition (ELife and Cell Reports). - Collaborated on neurodegeneration discovery project identifying novel clinical biomarkers (Nature Communications) and with Hotamisligil lab at HSPH to assess protein quality control mechanisms in adipose tissues (Nature Medicine). - Provided matrix mentorship to graduate students in Germany and Denmark, resulting in lead author publication in Molecular Metabolism and successful grant applications. - Successfully wrote grant proposals (~$330k), generated and adhered to timelines, budgets and milestones while mitigating risks in weekly team meetings. - Strong organizational skills: Managed laboratory inventory, negotiated supply deals, identified alternative supply sources, and ensured preventative maintenance of technical equipment to support essential experimental activities for 15+ peers

- Led project team to elucidate importance of lysosomal lipid processing in endothelial cells for adipogenic differentiation, enabling publication in Cell Metabolism and successful junior investigator grant application

- Identified PID1 as a potential novel target to treat dyslipidemia and diabetes (Molecular Metabolism, BBA-Molecular Basis of Disease) - Established collaboration with Joslin Diabetes Center Boston and BERG Health, Framingham, to investigate role of de novo lipogenesis in mitochondrial turnover. Resulted in finding that genetic or pharmacological inhibition of lipogenesis can improve brown adipose tissue thermogenic activity (Cell Reports) - Collaborated with Center for Applied Nanotechnology Hamburg, Germany to develop nanoparticles to target liver endothelial cells for delivery of antigens with applications for autoimmune diseases. Resulted in successful patent application

- Established and managed intravital microscopy imaging and analysis platform using Nikon A1 confocal microscope and Adobe AfterEffects/PremierPro software packages, enabling in-house and collaborative publications and grant proposals - Performed pharmacological studies in preclinical models of NAFLD and metabolic disease using biologics (FGF21, Insulin) as well as small molecules (CL316,243, BAY 41-8543), resulting in publications and successful grant application

Assistance in the LUPS observational study (Lufthansa Präventionsstudie). - Preparation of sampling tubes and questionaires - Processing of blood samples - Data management

Studies on lipid droplet formation. - Expression and purification of recombinant proteins - Colocalization studies using expression of fluorescently tagged proteins in cell lines - Confocal microscopy, live cell imaging and superresolution microscopy - CRISPR-based gene knockout in cell lines Mentors: Prof. Dr. Bob Farese, Prof. Dr. Tobias Walther

- Led projects to decipher relationship between environmental temperature and metabolic rates to improve translatability of preclinical research. Resulted in several publications and was widely featured by news agencies - Persevered with project, eventually leading to paradigm-shifting finding that leptin does not affect brown adipose tissue thermogenesis but rather affects central neuronal regulation of body temperature, published in Cell Reports and reviewed in Endocrine Reviews - Collaborated with other members of the group resulting in first- and coauthor publications in Nature Communications, American Journal of Physiology and Cellular and Molecular Life Sciences, enabling successful grant applications from the Swedish Research Council and Novo Nordisk Foundation (~$500k)

Identification of interaction partners of the cytoskeleton protein FHOD3 in cardiomyocytes. - Yeast two hybrid screens - Expression and purification of recombinant proteins - Pulldown experiments using recombinant proteins Mentor: Dr. Elisabeth Ehler