Clinical Trials Infectious Diseases

Saif M Saifuddin, DVM, PhD

571-***-**** ************@*****.*** https://www.linkedin.com/in/mohammed-saifuddin-dvm-phd-71a9634/

Profile Summary

An accomplished molecular virologist trained at the Massachusetts Institute of Technology with 15+ years of discovery and preclinical research experience for prevention of emerging viral infections including Flavi (Dengue, Zika, Yellow Fever), Bunya (Rift Valley), HIV, Herpes, Parvo, Corona and Influenza virus. A subject matter expert in the areas of virology, immunology, neuroscience, biodefense and infectious diseases, is well-known for his leadership skills in laboratory technology, microbial characterization and safety/toxicology evaluation of antivirals and vaccines. He is particularly known for drug development strategy, team management and strong collaborations with various stakeholders including CROs, clinical operations and FDA regulatory affairs. At CONRAD, he played a leading role to obtain multi-million dollars funding, and to advance a number of antivirals (TMC120, UC781, MIV150) to clinical trials. He was a competent reviewer of NIH grant proposals, and was selected for the distinguished researcher award by Sigma Xi Society.

Professional Experience

Global Virus Biotek (GBV) & Monoamine Oxidase Deficiency Foundation (MAODF) 2022 – Present

Managing Director (GBV) & Chief Scientific Officer (MAODF) - Antivirals, Vaccines, ASO, Drug Repurposing

Develop treatment strategies for MAOD, a severe neurodevelopmental genetic rare disease

Provide API development services for antivirals and biotherapeutics

Support development of anti-sense oligonucleotide therapy for rare genetic disorders

Monitor complement activation by gene products and their impact on clinical development

Provide pharmacology/toxicology plans for all in vitro to in vivo nonclinical studies

Biomarker identification and development, assay feasibility, proof of concept and validation

Support immunogenicity evaluation during nonclinical and clinical studies

Clinical bioanalysis including immunogenicity, protocol design, results analysis and preparing reports

Strategic development of business objectives across product pipelines

Provide guidance in IND/NDA/BLA filing

Sarepta Therapeutics, Columbus, OH 2019 – 2022

AAV Gene Therapy Core Director

Built and managed a team of scientists responsible for production of AAV vectors and release of products

Developed molecular assays to evaluate novel capsids to enhance vector yield, infectivity & quality

Reviewed experimental protocols, methods, technical reports, batch records and SOPs

Led AAV vector process development and transfer to internal GMP manufacturing

Designed/evaluated strategy for preclinical in vivo safety & efficacy of AAV products

Assessed complement activation and immunogenicity and develop mitigation strategy

Selected lead candidates for clinical trials and acted as SME for IND/NDA filing

Krystal Biotech, Pittsburgh, PA 2018 –2019

Associate Director (Vector Production and Release)

Responsible for development/characterization of analytical product specifications

Played critical role in process development and release of HSV vectors

Facilitated development of new analytical methods and tech transfers into QC laboratory

National Center for Biodefense and Infectious Diseases, Manassas, VA 2017 – 2018

Principal Scientist (Development of Antivirals & Immune Modulators)

Designed strategy and experimental protocols to prevent emerging virus outbreaks

Met with key stakeholders (BARDA, WHO, manufacturers and consultants) to review best choice

Partnered with experts on key assays to validate methods at CROs (WuXi, CRL, PPD)

Developed animal models for testing countermeasures against Dengue, Yellow fever & HIV infections

WuXi AppTec Pharmaceuticals, Philadelphia, PA 2015 – 2017

Study Director (Antivirals, Vaccines and GT)

Played leading role in safety assay validation for Dengue vaccines to support clinical trials

Led analytical method development & tech transfer into QC lab

Developed infectivity assays for Dengue, Zika, Yellow Fever and Rift Valley fever virus

Established in vitro potency assay (functional infectivity) for AAV vectors using qPCR

CONRAD, Arlington, VA 2008 – 2015

Manager (Head of Virology), Discovery Research & Preclinical Development

Led preclinical development and clinical research studies to prevent HIV and other viral infections

Actively managed discovery, characterization & preclinical development of antivirals, & IND/NDA filing

Evaluated safety, toxicology & efficacy of antivirals in hu-mice and NHP to support clinical trials

Created partnerships with multi-disciplinary teams across academia and CROs (MPI, ABL, HLS, CRL)

Worked with federal agencies to develop prevention strategies against threats of emerging pathogens

Rush University Medical School, Chicago, IL 2006 – 2008

Assistant Professor, Department of Immunology/Microbiology

Overall management of a BSL-2 Retrovirology research laboratory

Supervised 11 graduate students (who are now in FDA, PPD, Pfizer, Wyeth or Academia)

Developed novel methods for human T-cell gene expression and virus lysis by immune serum

Investigated patterns of complement activation by viral agents and their impact on antivirals development

Established collaborations with outside investigators & initiated ideas for antimicrobial development

Education & Certificates

Post-doctorate in Molecular Immunology: Rush University Medical School, Chicago, IL

Research topic: Immunopathogenesis of virus infections (HIV, HTLV, MuLV, HSV, CMV, MHV)

Post-doctorate in Molecular Virology: Massachusetts Institute of Technology, Cambridge, MA

Research topic: Molecular pathogenesis of Aleutian Disease Parvovirus infection

Certificate on Applied Training: Harvard University, Cambridge, MA

Topic: Hands-on Training on Human Genetics & Molecular Biology

PhD in Virology: Department of Pathology & Public Health, Massey University, New Zealand

Thesis title: The Etiology and Pathogenesis of Inclusion Body Hepatitis

DVM (Doctor of Vet Medicine) and MS (Virology): Bangladesh Agricultural University, Mymensingh

Completed 5-Years-long both classroom and hands-on Veterinary Science trainings including

microbiology, virology, pharmacology, pathology, molecular genetics, biochemistry & MS Thesis

Certificate on preparation of FDA submissions and communicating with the FDA

Skills

Team building and management: CRO logistics manager, GLP/GMP validation, task force leader, vector process development & purification, regulatory audit responder, project team leader

In vitro bioassays: Drug activity, clone selection, serum-free media adaptation, 9 CFR virus testing, binding/neutralizing antibody, receptor blocking, cytokine-induced proliferation, enzyme inhibition, cytotoxicity, luminescence, method validation and transfer

Cell culture: B cells, PBMC, T cells, HEK293, HL60, mouse thymoma, C2C12, MDX, MDCK

Product safety: Assessment of complement activation and their impact on clinical development

FDA affairs: IND/NDA filing, ACH, CFR 21, 9 CFR, GMP, GLP, GCP, QA-QC, CAPA

Assays: ELISA, luciferase assays, flow cytometry, immunohistochemistry, HPLC, plaque formation, site-directed mutant growth kinetics, genotyping, phenotyping, density gradient ultracentrifugation

Purification: Ion exchange, affinity & size exclusion chromatography, tangential flow filtration

Molecular biology and cloning: Nucleic acid isolation & purification, plasmid preparation, RT-PCR, Western blot, SDS-PAGE, sequencing, RE digestion, ligation, transformation, transfection, ddPCR

C&G therapy: AAV, Lenti & Herpes vector construction/production/purification/release, bioreactors, CAR T-Cell, cell line development, gene editing, tech transfer, CMC manufacturing

Drug development: Discovery, R&D, preclinical development, in vivo safety/pharmacology/toxicology

Software: Excel, Powerpoint, Microsoft Project, Sharepoint, JMP, LIMS, Freezerworks, ELN, Bartender, Immunocapture, ImmunoSpot, Software validations (IQ/OQ/PQ)

Robotics: Ambr15 & Ambr250, Hamilton Star, Freedom EVO (Tecan), Biomek4000 (Beckman)

Selected Publications

(OUT OF 65)

Pinto DO, TA Scott, C DeMarino, ML Pleet, TT Vo, M Saifuddin et al. (2019): Effect of transcription inhibition and generation of suppressive viral non-coding RNAs. Retrovirology. 16: 13. Published online 2019 Apr 29.

Sampey GC, M Saifuddin, A Schwab et al. (2016): Exosomes from HIV-1 infected cells stimulate production of pro-inflammatory cytokines through transactivating response (TAR) RNA. J Biol Chem 291:1251-66.

Iordanskiy S, R Van Duyne, GC Sampey, CM Woodson, K Fry, M Saifuddin et al. (2015): Therapeutic doses of irradiation activate viral transcription and induce apoptosis in HIV-1 infected cells. Virology 485:1-15.

Guendel I, S Iordanskiy, GC Sampey, R Van Duyne, V Calvert, E Petricoin, M Saifuddin et al. (2015): Role of Bruton’s tyrosine kinase inhibitors in HIV-1-infected cells. J Neurovirol 21:257-75.

Jaworski E, A Narayanan, R Van Duyne, SS Meyering, S Iordanskiy, M Saifuddin et al. (2014): Human T-lymphotropic virus type 1 infected cells secrete exosomes that contain Tax protein. J Biol Chem 289:22284-305.

Saifuddin M, E Jaworski, G Sampey et al. (2014): The use of Nanotrap particles technology in capturing HIV-1 virions and viral proteins from infected cells. PLoS One 9:e96778.

Sampey GC, SS Meyering, MA Zadeh, M Saifuddin et al. (2014): Exosomes and their role in CNS viral infections. J Neurovirol (review) 20:199-208.

Guendel I, S Iordanskiy, R Van Duyne, K Kehn-Hall, M Saifuddin et al. (2014): Novel neuroprotective GSK-3β inhibitor restricts Tat-mediated HIV-1 replication. J Virol 88:1189-208.

Hadas E, W Chao, H He, M Saini, E Daley, M Saifuddin et al. (2013): Transmission of chimeric HIV by mating in conventional mice: prevention by pre-exposure antiretroviral therapy and reduced susceptibility during estrus. Dis Model Mech 6:1292-1298.

Zariffard MR, M Saifuddin, A Finnegan, GT Spear (2009): HSV-2 infection increases HIV DNA detection in vaginal tissue of mice expressing human CD4 and CCR5. AIDS Res Hum Retroviruses 25:1157-64.

Jiang Y, B Tian, MB Agy, M Saifuddin, CC Tsai (2009): Macaca fascicularis are highly susceptible to an RT-SHIV following intravaginal inoculation: A new model for microbicide evaluation. J Med Primatol 38 (Suppl 1):39-

Van Duyne R, J Cardenas, R. Easley, W Wu, K Kehn-Hall, Z Klase, S Mendez, C Zeng, H Chen, M Saifuddin, F Kashanchi (2008): Effect of transcription peptide inhibitors on HIV-1 replication in humanized mouse. Virology 376:308-322.

Tsai L, N Trunova, A Gettie, H Mohri, R Bohm, M Saifuddin et al. (2007): Efficient repeated low-dose intravaginal infection with X4 and R5 SHIVs in rhesus macaque: Implications for HIV-1 transmission in humans. Virology 362:207-216.

Takefman DM, GT Spear, M Saifuddin, CA Wilson: hCD59 incorporation onto porcine endogenous retrovirus particles: Implications for the use of transgenic pigs for xenotransplantation. J Virol 76:1999-2002.

Saifuddin M, KA Roebuck, CH Chang, JPY Ting, GT Spear: Activation of HIV-1 transcription by the MHC class II transactivator. J Immunol (Cut Edg) 164:3941-3945.

Saifuddin M, ML Hart, H Gewurz, YH Zhang, GT Spear: Interaction of Mannose binding lectin with primary isolates of HIV-1. J Gen Virol 81:949-955.

Jakubik JJ, M Saifuddin, DM Takefman, GT Spear: Immune complexes containing HIV-1 primary isolates bind to lymphoid tissue B-lymphocytes and are infectious for T lymphocytes. J Virol 74:552-555.

Rabbi MF, M Saifuddin, DS Gu, MF Kagnoff, KA Roebuck: U5 region of the HIV-1 long terminal repeat contains TRE-like cAMP-responsive elements that bind both AP-1 and CREB/ATF proteins. Virology 233:235-

Saifuddin M, C Crnich, T Long, MN Saarloos, Spear GT: Transfer of host T-cell membrane HLA-DR and CD25 to target cells by human retroviruses. J Acquir Immune Defic Syndr Hum Retrovirol 17:196-202.

Rabbi MF, L Al-Harthi, M Saifuddin, KA Roebuck: The cAMP-dependent protein kinase A and protein kinase C-beta pathways synergistically interact to activate HIV-1 transcription in latently infected cells of monocyte/macrophage lineage. Virology 245:257-269.

Saifuddin M, T Hedayati, JP Atkinson, MH Holguin, CJ Parker, GT Spear: Human immunodeficiency virus type 1 incorporates both glycosyl phosphatidylinositol-anchored CD55 and CD59 and integral membrane CD46 at levels that protect from complement-mediated destruction. J Gen Virol 78:1907-1911.

Sullivan BL, EJ Knopoff, M Saifuddin et al.: Susceptibility of HIV-1 plasma virus to complement-mediated lysis: Evidence for a role in clearance of virus in vivo. J Immunol 157:1791-1798.

Saifuddin M, JG Fox: Identification of a DNA segment in ferret Aleutian disease virus similar to a hypervariable capsid region of mink Aleutian disease parvovirus. Arch Virol 141:1329-1336.

Saifuddin M, CJ Parker, ME Peeples et al.: Role of virion-associated GPI-linked proteins CD55 and CD59 in complement resistance of cell line-derived and primary isolates of HIV-1. J Exp Med 182:501-509.

Saifuddin M, M Ghassemi, C Patki, CJ Parker, GT Spear: Host cell components affect the sensitivity of HIV-1 to complement-mediated virolysis. AIDS Res Hum Retroviruses 10:829-837.

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