Nathan Manley, Ph.D.
Nate joined Dark Horse Consulting in 2019, bringing his expertise in stem cell biology, neurobiology, and preclinical modeling to the team. Nate has had an extremely productive career in cell and gene therapy development, with fifteen publications and four pending patents. Throughout his fifteen years of development experience, he has contributed key preclinical and manufacturing advancements to experimental and clinical-stage therapies.
Nate’s first experience with developing cell and gene therapies was at Stanford University where he earned his Ph.D. and completed two postdocs. During his graduate research and first postdoc, Nathan led development of an immune cell based gene delivery system that selectively targeted sites of injury and inflammation. During this project, he designed virally engineered immune cells for gene delivery to the CNS. His second postdoc focused on developing neural stem cell transplantation therapies to treat stroke injury. There, he directed the preclinical pharmacology program, completed in vivo efficacy testing, and helped develop candidate release and potency assays for the neural stem cell therapy. He also designed novel viral vector-based tools to profile transplanted cells in vivo.
Nate left academia to join Asterias Biotherapeutics as a Scientist, and was soon promoted to Senior Scientist. In these roles, Nathan led all preclinical operations for AST-OPC1, a cell therapy to treat spinal cord injuries. He had a wide range of responsibilities and achievements, including the development of assays to characterize pluripotent cell banks, process intermediates, and the final AST-OPC1 product. Nate set up and managed the company’s in-house vivarium and completed animal studies and regulatory documents in support of the spinal cord injury clinical program. He also helped develop and optimize new methods for the therapy’s production to improve its reproducibility and manufacturability, and led efforts to demonstrate comparability of the new process to previous methods.
After four years as a scientist, Nate was promoted to Associate Director of the Neurobiology division at Asterias. In this role, he continued work on AST-OPC1, directing research efforts to understand the biology of the therapy, and helped to develop and refine two alternative differentiation methods to improve manufacturing reproducibility and scalability, which led to the filing of two additional patents. Nate also directed preclinical development efforts to expand AST-OPC1 into new indications, including stroke and multiple sclerosis. In addition, Nate led efforts to develop in-process characterization assays and improve the reproducibility and manufacturability of AST-VAC2, the company’s leading stem cell-based cancer immunotherapy.
- Onishi K, Manley NC, Halberstadt CR, Whiteley EM. Dorsally-derived oligodendrocyte progenitor cells from human pluripotent stem cells. United States Provisional Patent Application No. 62/796,077, filed January 23, 2019.
- Nair RR, Kayser S, Parikh AS, Shoukat-Mumtaz U, Whiteley EM, Manley NC, Halberstadt CR. Methods for differentiating pluripotent stem cells in dynamic suspension culture. United States Provisional Patent Application No. 62/733,621, filed September 19, 2018, pending status.
- Wirth ED, Priest CA, Lebkowski JS, Manley NC, Nishimoto KP, Okamura R. Pluripotent stem cell-derived oligodendrocyte progenitor cells for the treatment of spinal cord injury. United States Patent Application 15/156316, filed May 16, 2016, pending status.
- Manley NC, Spink KE (2019) Best Practices in Preclinical Development of Cell Therapy Products. www.cellandgene.com / www.bioprocessonline.com
- Manley NC, Priest CA, Denham J, Wirth ED 3rd, Lebkowski JS. (2017) Human Embryonic Stem Cell-Derived Oligodendrocyte Progenitor Cells: Preclinical Efficacy and Safety in Cervical Spinal Cord Injury. Stem Cells Transl Med. Oct;6(10):1917-29.
- Priest CA, Manley NC, Denham J, Wirth ED 3rd, Lebkowski JS. (2015) Preclinical safety of human embryonic stem cell-derived oligodendrocyte progenitors supporting clinical trials in spinal cord injury. Regen Med. 10(8): 939-58.
- Karlupia N, Manley NC, Prasad K, Schäfer R, Steinberg GK. (2014) Intraarterial transplantation of human umbilical cord blood mononuclear cells is more efficacious and safer compared with umbilical cord mesenchymal stromal cells in a rodent stroke model. Stem Cell Res Ther. 5(2): 45.
- Manley NC, Caso JR, Works MG, Cutler AB, Zemlyak I, Sun G, Munhoz CD, Chang S, Sorrells SF, Ermini FV, Decker JH, Bertrand AA, Dinkel KM, Steinberg GK, Sapolsky RM. (2013) Derivation of injury-responsive dendritic cells for acute brain targeting and therapeutic protein delivery in the stroke-injured rat. PLoS One 8(4): e61789.
Asterias Biotherapeutics, Inc.
Associate Director – Neurobiology
Senior Scientist – Preclinical Development
Scientist – Preclinical Development
Stanford University School of Medicine
Ph.D. in Biological Sciences
University of Washington
B.S. with College Honors in Biology