Margarida Maia PhD, Author at Friedreich's Ataxia News

Exicure is drawing to a close its XCUR-FXN program for the treatment of Friedreich’s ataxia for an unknown period of time, the company announced. The decision comes after an internal investigation concluded that data from the program's preclinical phase would not support steps into a clinical trial, planned for this year. “Although this unfortunate event will have residual effects, I strongly believe there is great value to be unlocked at Exicure with our proprietary spherical nucleic acid (SNA) technology, and I look forward to advancing our promising programs in pain and other neuroscience diseases and continuing to closely work with our partners to develop innovative therapies for the treatment of genetic disorders,” Brian Bock, who has been appointed president and CEO of Exicure, said in a press release. An SNA comprises short lab-made oligonucleotides (small sequences nucleotides, the building blocks of DNA) densely packed around a tiny spherical fat particle, which allows the molecules to be better taken up by cells. In the case of XCUR-FXN, the oligonucleotides are designed to bind a particular region frataxin's messenger RNA (mRNA) — the molecule derived from DNA and used as a template for protein production — and increase production of frataxin, the protein that is lacking in FA patients. XCUR-FXN comprises two oligonucleotides with two distinct targets and mechanisms. One works to prevent the mRNA from being degraded in the cell’s nucleus, and the other stabilizes the mRNA outside the nucleus, allowing more protein copies to be generated per mRNA molecule. Initial studies showed that XCUR-FXN was able to increase the amount of frataxin made by lab-grown nerve cells derived from two patients with Friedreich’s ataxia. Early last year, the company announced it planned to file an application to the U.S. Food and Drug Administration (FDA) by the end of 2021 to begin testing XCUR-FXN in clinical trials. In November, however, Grant Corbett, PhD, the company’s former group lead of neuroscience, resigned from his position, claiming to have committed “improprieties” related to XCUR-FXN program. An internal investigation was set forward by the company’s audit committee of the board of directors, along with an outside counsel, that determined that Corbett had misreported research data related to the efficacy — but not safety — of XCUR-FXN beginning in the autumn of 2020, and he failed to inform the company of his actions until his resignation. This resulted in misreported data in public presentations and regulatory documentation of at least three different experiments. Corbett was determined to have acted alone, and no other therapeutic program was directly affected by his actions. Besides suspending the XCUR-FXN program, the company decided to take additional strategic measures such as reducing its workforce by about half, restructuring the company's executive team, and stopping further enrollment into a Phase 1b/2 clinical trial of cavrotolimod (AST-008) in patients with solid tumors. The company now plans to continue the development of its preclinical program targeting SCN9A for neuropathic pain and to advance its partnerships to develop SNA-based treatments for Huntington’s disease, Angelman syndrome, and hair loss disorders.

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After ‘Improprieties,’ Exicure to Wind Down XCUR-FXN Program

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