Ruby Fernandez-Boyanapalli, Ph.D

Lexington, MA **420 419-***-**** ad003s@r.postjobfree.com

Associate Director of Research

Dynamic and visionary scientific leader with a proven track record in leading and managing several drug discovery programs. Strong expertise in gene therapies, strategic leadership, and preclinical research in rare diseases. Adept at identifying therapeutic targets and providing early development leadership to drive successful project outcomes. Experienced in nurturing scientific talent and fostering an environment conducive to innovation. Areas of Expertise

Project Management and Leadership Non-clinical Drug Discovery in Rare Disorders Small Molecules, Viral and Non-viral Gene Therapy, Enzyme Replacement Therapy, Antibody Drug Conjugates, Engineered Protein-based Modalities Therapeutic Target Identification Lead Optimization and Validation IND Enabling Studies Ex Vivo and In Vivo Assay Development Excellent Written and verbal communication Problem-solving and Attention to detail Adaptable in Dynamic Work Environments Budget & Resource Management Career Highlights

● Led 12 drug discovery projects moving the drug discovery pipeline ranging from ideation to IND filing, achieving impactful results. Established and executed the scientific strategy for gene editing technology, driving innovation and accelerating pipeline expansion.

● Identified therapeutic targets within the rare disease area, generating proof of concept results to support pipeline growth into genomic medicines.

● Provided early development leadership and strategic guidance to project teams, collaborating across pharmacology, CMC, and clinical development functions.

● Identified, negotiated, and delivered partnerships with academic institutions and industry to assess new technologies and enhance the organization's capabilities.

● Established and managed project goals, timelines, and deliverables for efficient program delivery.

● Extensive knowledge of small and large molecule drug discovery, preclinical PK/PD, efficacy, toxicology, safety and translational planning/execution (animal models and clinical biomarkers).

● Successfully led, mentored and coached over 10 direct reports (Ph.D. level project leads, scientist and associate scientists) in the design, optimization, validation, and execution of studies within aggressive timelines.

● Oversaw the design and execution of in vivo and in vitro functional target validation experiments, providing critical biology and pharmacology support for early-stage drug discovery and development.

● Selected for a prestigious one-year leadership program at Takeda, and obtained Women in Leadership certification.

● Collaborated with academic and industry partners to identify and develop new technologies.

● Managed external research through collaboration with CROs and academic institutions, aligning with program goals and milestones.

● Effectively communicated results and progress to executive management, global research leadership and cross-functional teams.

Professional Experience

Takeda Pharmaceuticals

Associate Director, Rare Disease Drug Discovery Unit (2022 – 2023)

● Led impactful small molecule, biologics, and gene therapy programs targeting rare metabolic diseases.

● Identified novel engineered proteins for ERTs and gene therapies through collaboration with partners.

● Led several discovery programs from ideation to various milestones, achieving significant preclinical program progress in short time frames.

● Led the Pompe (metabolic disorder with cardiovascular impact) gene therapy from ideation to candidate selection (2.5 years): A novel AAV-based vector that enhances muscle expression of an engineered GAA variant with lower immunogenicity and higher potency that halts and reverses the impact on cardiovascular and skeletal muscle in Pompe disease. IND enabling preclinical PK/PD, safety, tolerability and toxicology in mouse and monkey completed and ready for IND filing.

● Led the Sanfilippo (metabolic disorder with neurological impact) gene therapy program from ideation to candidate nomination (11 months): A novel AAV based gene therapy for Sanfilippo A using a liver directed gene therapy with a BBB penetrable protein fusion for neurological efficacy. Ex vivo and In vivo preclinical IND enabling studies for PoM/PoC and lead candidate identification were completed.

● Co-inventor on three patents and corresponding author on four manuscripts. Principal Scientist, Rare Disease Drug Discovery Unit (2021 – 2022)

● Independently led scientific research projects, driving strategy and model development for diverse indications.

● Led the Pompe engineered ERT program from ideation to candidate selection (2 years): Novel engineered protein with improved enzymatic activity, increased uptake into muscle, stability and ability to cross the BBB identified and efficacy studies resulting in improved muscle function and pathology compared to un-engineered protein demonstrated in small and large animal preclinical models

● Led the small molecule program for Pompe to identify targeting proteins upstream of the disease pathway to prevent accumulation of glycogen in the muscles (GYS1 inhibitor). Ex vivo and In vivo PoC studies were run.

● Led the small molecule program for Stargardt’s disease targeting mTOR to clear accumulated debris in the retinal epithelial cells to prevent loss of vision. Generated a rabbit model of Stargardt's disease, screened several compound libraries to identify lead candidates, Ex vivo and In Vivo PoC studies completed

● Managed CROs, guided bench scientists, and collaborated across departments.

● Contributed to regulatory document preparation and editing for submissions. Senior Scientist, Rare Disease Drug Discovery Unit (2018 – 2021)

● Led a team of scientists to generate vivo and in vivo data, advancing projects from validation to pre-clinical proof of concept across diverse indications including Stargardts, Pompe disease, C3 glomerulopathy, Paroxysmal Nocturnal (PNH), Hemoglobinuria, Hereditary angioedema (HAE), Systemic Lupus Erythematosus (SLE)

● Managed CROs, guided bench scientists, and collaborated across departments.

● Contributed to regulatory document preparation and editing for submissions. Shire Pharmaceuticals (2015 – 2018)

Scientist, Discovery Biology

● Designed experiments and managed projects in hematological and oncology domains, focusing on critical indications such as Hereditary angioedema and Acute Myeloid Leukemia.

● Developed assays, managed vendors, and presented comprehensive data to support project goals. National Jewish Medical and Research Center (2006 – 2015) Senior Scientist, Pediatrics

● Pioneered research on oxidants in innate immunity and endogenous signals for inflammation resolution, leveraging mouse models and patient samples. Identified a small molecule activator of PPAR gamma that ameliorates disease in an autoimmune disorder, Chronic Granulomatous disease.

● Key contributor to a clinical trial at NIH, overseeing immunological assays and effectively communicating findings in scientific forums.

Medical University of Ohio (2004 – 2006)

Postdoctoral Research Fellow

● Identification and functional characterization of new genes that play important roles in adipogenesis a key driver in obesity, diabetes and cardiovascular diseases.

● Investigated DNA binding proteins and protein interactions in prostate cancer malignancy and obesity

● Developed novel cell line systems and contributed insights into drug mechanisms. Effectively communicated research through presentations at scientific meetings. Education

Ph.D. in Molecular Biology - University of North Texas at Denton, 2004 Master of Science (M. S.), Environmental Microbiology - Jawaharlal Nehru Technological University, India, 2000 Bachelor of Science (B.S.), Microbiology - Osmania University, India, 1997 Select Publications and Abstracts

• Andrew Melber, Simon Moore, Vivian Choi, Madhusudan Natarajan and Ruby Boyanapalli. Towards a safer and more effective treatment of Pompe Disease: An AAV-based vector that enhances muscle expression of a GAA variant with lower immunogenicity and higher potency improves correction in a mouse model of Pompe Disease. Manuscript in preparation. 2023

• Rod Moreland, Andrew Melber, Simon Moore, Bob Crooker, Kathleen Palmieri and Ruby Boyanapalli. Combined transcriptome and proteome analysis of extracellular vesicles in urine and blood from the Pompe mouse model. Manuscript in preparation. 2023

• Andrew Melber, Mugdha Deshpande, Anitha Saravanakumar, Brian Miller, Kathleen Palmieri, Meera Modi and Ruby Boyanapalli. Sanfilippo A GT using a liver directed gene therapy with a BBB penetrable protein fusion for neurological efficacy. Manuscript in preparation. 2023.

• Sophia J. Lang, Arthur Dopler, Katharina Welsch, Brijesh Garg, Marco Mannes, Amira Akilah, Britta Höchsmann, Hubert Schrezenmeier, Markus Anliker, Ruby Boyanapalli, Markus Huber-Lang, Christoph Q. Schmidt. A potent, targeted, enzyme-like inhibitor of all three complement activation pathways. Manuscript submitted. 2023.

• Ruby F. Fernandez-Boyanapalli, S. Courtney Frasch, Stacey M. Thomas, Kenneth C. Malcolm, Michael Nicks, Ronald J. Harbeck, Claudia V. Jakubzick, Raphael Nemenoff, Peter M. Henson, MD, Steven M. Holland, MD, and Donna L. Bratton. Pioglitazone restores phagocyte mitochondrial oxidants and bactericidal capacity in patients with chronic granulomatous disease. J Allergy Clin Immunol. 2015.

• Donna Bratton, S. Courtney Frasch, Kenneth Malcolm, Ruby Fernandez-Boyanapalli. Treatment Of Murine Chronic Granulomatous Disease (CGD) With The PPARγ Agonist Pioglitazone Enhances Phagocyte Mitochondrial Reactive Oxygen Species (ROS) Production and Antimicrobial Responses. Abstracts of the American Academy for Asthma, Allergy and Immunology, 2014.

• Donna Bratton, Ruby Fernandez-Boyanapalli, Karin Zemski-Berry, Robert Murphy, S. Courtney Frasch. The Oxidant-Modified Lipid Lysophosphatidylserine (lysoPS) Made by Exudate Neutrophils Limits Neutrophil Accumulation in Vivo. Abstracts of the American Academy for Asthma, Allergy and Immunology, 2013. Frasch SC, Fernandez-Boyanapalli RF, Berry KA, Murphy RC, Leslie CC, Nick JA, Henson PM, Bratton DL. Neutrophils regulate tissue Neutrophilia in inflammation via the oxidant-modified lipid lysophosphatidylserine. J Biol Chem. 15; 288(7), 2013.

• Fernandez-Boyanapalli R, Goleva E, Kolakowski C, Min E, Day B, Leung DY, Riches DW, Bratton DL, Sutherland ER. Obesity impairs apoptotic cell clearance in asthma. J Allergy Clin Immunol. 131(4):1041-7, 2013.

• Ruby Fernandez-Boyanapalli, Courtney Frasch, Peter M. Henson and Donna L. Bratton. Pioglitazone (Pio), a peroxisome proliferator-activated receptor (PPAR)y agonist, restores efferocytosis of neutrophils in Chronic Granulomatous Disease (CGD) by enhancing oxidant production and “eat me” signaling. Abstracts of the American Academy for Asthma, Allergy and Immunology, 2012.

• Frasch SC, Fernandez-Boyanapalli RF, Berry KZ, Leslie CC, Bonventre JV, Murphy RC, Henson PM, Bratton DL. Signaling via macrophage G2A enhances efferocytosis of dying neutrophils by augmentation of Rac activity. J Biol Chem. 86(14): 12108-22, 2011.

• Korns D, Frasch SC, Fernandez-Boyanapalli R, Henson PM, Bratton DL. Modulation of macrophage efferocytosis in inflammation. Front Immunol. 2:57, 2011.

• Fernandez-Boyanapalli R, Frasch SC, Riches DWH, Vandivier RW, Henson PM, Bratton DL. (PPAR)y activation normalizes resolution of acute sterile inflammation in murine Chronic Granulomatous Disease. Blood. 2010 Nov 25; 116(22): 4512-22.

• Fernandez-Boyanapalli R, McPhillips KA, Frasch C, Janssen WJ, Dinauer MC, Riches DWH, Henson PM, Byrne A, Bratton DL. Impaired phagocytosis of apoptotic cells by macrophages in Chronic Granulomatous Disease Is Reversed by IFN y in a nitric oxide-dependent manner. J Immunol. 185:4030-4041, 2010.

• Fernandez-Boyanapalli R, Frasch SC, McPhillips K, Vandivier RW, Harry BL, Riches DWH, Henson PM, Bratton DL. Impaired apoptotic cell clearance in CGD due to altered MØ programming is reversed by phosphatidylserine dependent production of IL- 4. Blood. 113(9): 2047-55, 2009.

• Frasch S, Fernandez-Boyanapalli R, Zemski Berry K, Leslie C, Bonventre J, Murphy R, Henson P, Bratton DL. Lyso-phosphatidylserine made by dying neutrophils enhances efferocytosis by G2A-dependent augmentation of RAC activity. J Biol Chem. 2011 Apr 8; 286(14):12108-22.

• Frasch SC, Berry KZ, Fernandez-Boyanapalli R, Jin HS, Leslie C, Henson PM, Murphy RC, Bratton DL. NADPH oxidase-dependent generation of lysophosphatidylserine enhances clearance of activated and dying neutrophils via G2A. J Biol Chem. 2008 Nov 28; 283(48):33736-49.

• Liu K, Zhou S, Kim JY, Tillison K, Majors D, Rearick D, Lee JH, Fernandez-Boyanapalli RF, Barricklow K, Houston MS, Smas CM. Functional analysis of FSP27 protein regions for lipid droplet localization, caspase-dependent apoptosis, and dimerization with CIDEA. Am. J Physiol Endocrinol Metab. 2009 Dec; 297(6).

• Ruby F. Fernandez and D. A. Kunz. 2005. Bacterial cyanide oxygenase is a suite of enzymes catalyzing the scavenging and adventitious utilization of cyanide as a nitrogenous growth substrate. J. Bacteriol. 187: 6396-6402.

• Ruby F. Fernandez, E. Dolghih, and D. A. Kunz. 2004. Enzymatic assimilation of cyanide via pterin- dependent oxygenolytic cleavage to ammonia and formate in Pseudomonas fluorescence NCIMB 11764. Appl. Env.Microbiol.70:121-128.

• Kunz, D.A.; R. Fernandez and P. Parab. 2001. Evidence that cyanide oxygenase is a pterin- dependent hydroxylase. Biochem. Biophy. Res.Comm. 287:514 - 518. Professional Affiliations: Member, American Society for Cell and Gene Therapy (ASGCT) Member, American Society for Hematology (ASH) Cure Sanfilippo Member, Society of Leukocyte Biology Member, American Society for Microbiology

(ASM) European Federation of Biotechnology (EFB)

Awards and Grants: CGD-research trust grant in collaboration with Dr. Donna Bratton, UK, 2009 - 2013; Crawford foundation grant, 2009 and 2010; AAAAI STAR Program award recipient, 2009; National Jewish pilot grant, 2008; AAAAI STAR Program award recipient, 2008; Finalist Student Award Competition Society for Leukocyte Biology Meeting, 2008; American society of Microbiology Travel award, 2004; Outstanding Teaching Assistant award, 2004; J.B. Mc Bryde award, Outstanding graduate student, 2001; Brij Kishore Gold Medal in Environmental Science, 2000

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