Short Course

Monday, March 13, 2023  8:00 - 10:00 am

SC1: Safety and Toxicity of Nucleic Acids

Detailed Agenda
Nucleic acid drugs continue to deliver on their promise to become a third therapeutic modality, in addition to small molecules and biologics. Several antisense oligonucleotide drugs have been on the market for some time, while the first RNAi approval was granted in 2018. In addition, numerous mRNA and CRISPR therapeutic programs have entered clinical stages. Despite the common “nucleic acid” component, the mechanisms of action and of non-specific effects differ for each of these drug types.
Sarah Lamore, PhD, Director, Toxicology, Pre-Clinical Development Sciences, Wave Life Sciences
Xiao Shelley Hu, PhD, Vice President, Head of DMPK and Clinical Pharmacology, Wave Life Sciences

ROOM LOCATION: Salada

8:00 am

Opening Remarks from Instructors

8:10 am

Nonclinical Considerations for the Development of Oligonucleotide Therapeutics

Sarah Lamore, PhD, Director, Toxicology, Pre-Clinical Development Sciences, Wave Life Sciences

This presentation will review some of the common toxicities associated with oligonucleotide administration, discuss the regulatory expectations for the nonclinical safety evaluation of oligonucleotide therapeutics in the context of the applicable guidance documents, and present case studies based on recently approved products.

8:50 am

ADME and PK/PD Considerations for Preclinical Development of Antisense Oligonucleotides (ASOs)

Xiao Shelley Hu, PhD, Vice President, Head of DMPK and Clinical Pharmacology, Wave Life Sciences

ASOs are an emerging class of medicines for unmet medical needs. The ADME and PK/PD entail specific considerations to support effective preclinical development. This talk will focus on factors relevant to preclinical development of ASOs.

9:30 am

Interactive Discussion with Instructors and Attendees

INSTRUCTOR BIOGRAPHIES:

Sarah Lamore, PhD, Director, Toxicology, Pre-Clinical Development Sciences, Wave Life Sciences

Sarah is currently Director of Toxicology and head of Investigative Toxicology at Wave Life Sciences. Prior to joining Wave, Sarah was a Toxicologist at Biogen where she worked on several modalities including small molecules and antisense oligonucleotides. She did her postdoctoral training at AstraZeneca and then joined the company as a Discovery Safety Scientist. She holds a PhD in Pharmacology and Toxicology from University of Arizona and is a Diplomate of the American Board of Toxicology.

Xiao Shelley Hu, PhD, Vice President, Head of DMPK and Clinical Pharmacology, Wave Life Sciences

Dr. Xiao Shelley Hu, PhD, is a Vice President at Wave Life Sciences in Boston, currently the head of the DMPK and Clinical Pharmacology department. Her group is responsible for ADME, PK/PD, and Pharmacometric studies in preclinical and clinical stages in neuromuscular, CNS, and hepatic diseases. Prior to joining Wave Life Sciences, she was a Director at Akebia Therapeutics in Boston, leading the Clinical Pharmacology, Pharmacometrics and Bioanalytical function. Shelley joined Akebia from Biogen, where her responsibility evolved from pre-clinical DMPK to Clinical Pharmacology, and later to Pharmacometrics for both small molecules and large molecules from discovery to post-market in Neurology, Rheumatology, Oncology, and Immunology. Shelley received her PhD in Pharmaceutical Sciences from the Ohio State University, MS in Pharmaceutical Sciences from Ohio State University, MS in Environmental Chemistry from Chinese Academy of Sciences, and BS in Pharmaceutical Sciences from Peking University Health Science Center. She has fourteen publications in peer-reviewed journals and one book chapter and serves as reviewers for various journals.





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