Epigenetic Heterogeneity in Friedreich Ataxia Underlies Variable FXN Reactivation

Rodden LN, Gilliam KM, Lam C, Lynch DR and Bidichandani SI (2021); Front. Neurosci. 15:752921. doi: 10.3389/fnins.2021.752921 

Treatment of the same PBMCs from this cohort with HDACi-109 significantly increased FXN transcript to levels seen in asymptomatic heterozygous carriers, albeit with the expected inter-individual variability. Response to HDACi-109 correlated significantly with the prevalence of unmethylated and partially methylated FXN molecules, supporting the model that FXN reactivation involves a proportion of genes that are amenable to correction in non-dividing somatic cells, and that heavily methylated FXN molecules are relatively resistant to reactivation. FXN reactivation is a promising therapeutic strategy in FRDA, and inter-individual variability is explained, at least in part, by somatic epigenetic heterogeneity.

Indefinite suspension of further development of the Company’s XCUR-FXN program for the treatment of Friedreich’s ataxia

CHICAGO & CAMBRIDGE, Mass., December 10, 2021--(BUSINESS WIRE)--Exicure, Inc.® (NASDAQ: XCUR) announced the results of its previously disclosed independent internal investigation and a number of strategic actions aimed to reduce cash spend and prioritize the Company’s therapeutic pipeline

The results of the investigation are summarized below.

• Beginning in the autumn of 2020, Dr. Corbett misreported raw data from certain research and development experiments related to XCUR-FXN;

• Dr. Corbett misreported the results of at least three different experiments that were conducted through at least February 2021;

• The misreported data related solely to efficacy rather than safety of XCUR-FXN;

• The misreported data was included in various public presentations and SEC filings from as early as January 7, 2021 through as late as August 12, 2021;

Directors has implemented the following approved plan:

• Indefinite suspension of further development of the Company’s XCUR-FXN program for the treatment of Friedreich’s ataxia

• Douglas Feltner, M.D., the Company’s Chief Medical Officer, has agreed to assist in the wind down of the cavrotolimod and XCUR-FXN programs and will depart the Company on January 31, 2022.