Preclinical, Clinical and Translational Sciences

Hot Topic: PK/PD and Translational Considerations for LNP Delivered Gene Editing Products

Hot Topic Speaker(s)

• 

  Bahru Habtemariam, Pharm.D.

  Vice President, Clinical Pharmacology
  Beam Therapeutics
  Cambridge , Massachusetts

Hot Topic Moderator(s)

• SI

  Salvatore Iovino

Decades of progress in cell biology, genetic medicines, and delivery mechanisms have propelled the development of LNP delivered gene editing products. These products are currently in early phase of nonclinical and clinical development and are expected to transform the treatment and management of many rare and prevalent diseases in the coming decades. While there has been considerable progress in the basic science and pre-clinical development of LNP delivered gene editing products, several gaps exist in the seamless translation of the nonclinical data towards clinical development. As LNP delivered gene editing products are developed for single dose or single course treatment regimen and the formulations contain ionizable lipids with potential toxicity, traditional PKPD concepts maybe not be applicable. In addition, due to the single dose or single course nature of the therapeutic modality, the established allometric scaling approach for human dose projections may not be optimal. As such, enhanced understanding dose-exposure/response relationships and drivers for safety and efficacy of LNP delivered gene editing products is critical in the development of such therapeutics.

Within the AAPS GCTP Community, we have formed an ADME working group which consists of subject matter experts from different companies working in the area of cell and gene therapies. The AAPS GCTP ADME Working Group members are currently discussing the translational and clinical pharmacology aspects and challenges related to LNPs for gene editing products in detail and the learnings from those discussions will be shared through this symposium presentation. This symposium presentation will discuss key PK and PD analysis approaches and translational considerations including human exposure projection for key components of the LNP product. The presentation will include considerations for FIH trial dose selections.