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 twenty publications and four pending patents. Throughout his years of development experience, he has contributed key preclinical and manufacturing advancements to experimental and clinical-stage therapies.
At Dark Horse, Dr. Manley helps clients build an operational plan for FIH from a CMC and nonclinical perspective, complete with building out program timelines and budget analyses. For a brand new academic spinout that may involve building a plan de novo, whereas for other clients it may be a case of evaluating existing development plans to identify operational gaps and recommended remediation strategies. Along all stages of these paths, he assists clients with regulatory strategy and execution: determining the right type of meeting (and optimal timing of that meeting) and helping clients identify must-have vs. nice-to-have data sets to enable successful regulatory engagement. He can also lead authorship of the regulatory submission, from meeting requests and briefing books. For clinical stage programs that are undergoing process changes or optimization, he helps clients identify how to execute those process changes and how to build out an appropriate comparability plan, taking into account both a technical scientific point of view and a regulatory strategy to ensure regulatory alignment on that comparability plan. Nate supports a wide range of product types within the CGT field but predominantly focuses on cell and gene-modified cell therapies. Nate works often with pluripotent-based and gene-edited products, and has also worked across the entire spectrum of immunotherapy-based products. His core expertise in product development is in nonclinical development strategy. Nate routinely helps clients build out nonclinical development plans from a high level but he also drills down to specific study design or protocols, analyses data, and helps draft study reports for future regulatory submission.
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.