Ligand Conjugated Antisense Oligonucleotide for the Treatment of Transthyretin Amyloidosis: Preclinical and Phase 1 Data

Nicholas J. Viney; Shuling Guo; Bruce L. Tai; Brenda F. Baker; Mariam Aghajan; Shiangtung W. Jung; Rosie Z. Yu; Sheri Booten; Heather Murray; Todd Machemer; Sebastien A. Burel; Sue Murray; Gustavo Büchele; Sotirios Tsimikas; Eugene Schneider; Richard S. Geary; Merrill D. Benson; Brett P. Monia

doi:10.1002/ehf2.13154

Key Points

To evaluate the preclinical profile and phase 1 clinical utility of ION-682884, a ligand-conjugated antisense oligonucleotide designed to target transthyretin production in hepatocytes.
Assessed preclinical characteristics and phase 1 clinical application of the ligand-conjugated antisense oligonucleotide ION-682884.
Targeted receptor-mediated uptake mechanisms in hepatocytes to diminish circulating transthyretin levels.
Ligand conjugation improved delivery of the antisense pharmacophore specifically to hepatocytes, the primary source of circulating transthyretin.
Enhanced tissue delivery supports higher drug potency, enabling lower and less frequent dosing regimens for ATTR polyneuropathy and cardiomyopathy.

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Implication

Phase 1 trial reveals targeted hepatocyte delivery of an antisense drug, indicating potential for lower dosing in transthyretin amyloidosis.

Abstract

AIMS: (ION-682884) is a ligand-conjugated antisense drug designed for receptor-mediated uptake by hepatocytes, the primary source of circulating transthyretin (TTR). Enhanced delivery of the antisense pharmacophore is expected to increase drug potency and support lower, less frequent dosing in treatment. METHODS AND CONCLUSIONS: for the treatment of ATTR polyneuropathy and cardiomyopathy.

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Viney et al. (2020) studied this question.

synapsesocial.com/papers/6a026e677adabae4d9372911 https://doi.org/10.1002/ehf2.13154

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Ligand Conjugated Antisense Oligonucleotide for the Treatment of Transthyretin Amyloidosis: Preclinical and Phase 1 Data

Key Points

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Implication

Abstract

Discussion

Cite This Study

Ligand Conjugated Antisense Oligonucleotide for the Treatment of Transthyretin Amyloidosis: Preclinical and Phase 1 Data

Key Points

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

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