Advanced Therapies in the CNS – Time to Get Smart


  • Joel S. Sandler, PhD, Associate Principal, Defined Health, a Cello Health business


  • Steven Gray, PhD, Associate Professor, Department of Pediatrics, University of Texas Southwestern Medical Center
  • Michael C. Rice, MS, MBA, Principal, Defined Health, a Cello Health busines

Neurology-focused advanced therapy deals are becoming increasingly prominent: Pfizer/Sangamo, AbbVie/Voyager, Takeda/Wave Life, Novartis/Avexis, Axovant/Oxford BioMedica, PTC/Agilis. And that’s just in 2018. So far.

Each of these has served to underscore the excitement surrounding early-stage but potentially disease-modifying therapeutic approaches positioned across a range of challenging disorders. Indeed, such success stories have emerged on the shoulders of myriad prior failures, and patients are only beginning to benefit from the confluence of events that have been building over time and now seem to be converging at once: sequencing of the human genome as a pretext for subsequent elucidation of genotype/phenotype relationships underlying different disease states; improved delivery and payload technologies sufficient to achieve organ- or even tissue-specific expression of aberrant or compensatory gene products; compressed discovery, lead optimization, and regulatory timelines needed to defray development costs and decrease clinical risk; de-risked commercial models predicated on the ability to achieve premium pricing for effective therapies that address exceedingly small patient populations.

Despite such enthusiasm, however, a host of fundamental scientific, clinical, and commercial questions remain unanswered: What is the optimal therapeutic modality for a given disorder? Where is the risk in being supplanted, and how does one create formidable barriers to entry? What are the clinical benchmarks that an intrathecal or multidose regimen must achieve for commercial success? How can companies create a sustainable business model around curative treatments for ultrarare monogenic disorders? And what obstacles and opportunities exist for approaches that go beyond correction of single-gene disorders to address more heterogenous and prevalent conditions like Alzheimer’s or Parkinson’s?

With timelines from translation to commercialization compressed to an unprecedented extent, we thought it fitting to engage in a discussion between what have until now been a disparate set of stakeholders. Join us as we attempt to tackle some of the most pressing topics of the day.