Edgewise Therapeutics Announces Publication of Data Demonstrating the Elevation of Fast but Not Slow Skeletal Muscle Fiber Injury Biomarkers in the Circulation of Patients with Becker and Duchenne Muscular Dystrophy - Seite 2

Kevin Koch, Ph.D., President and Chief Executive Officer added, “These data are invaluable as we continue to advance EDG-5506 in clinical development. We are excited about the potential of EDG-5506 for patients affected by BMD and DMD, who are currently underserved with limited treatment options.”

About the Skeletal Muscle Study

One of the hallmarks of injured skeletal muscle is the appearance of elevated skeletal muscle proteins in circulation. Human skeletal muscle generally consists of a mosaic of slow (type I) and fast (type IIa, IIx/d) fibers, defined by their myosin isoform expression. Recently, measurement of circulating fiber‐type specific isoforms of troponin I has been used as a biomarker to suggest that muscle injury in healthy volunteers results in the appearance of muscle proteins from fast but not slow fibers. Data from this study demonstrates that this is also the case in severe myopathy patients with Becker and Duchenne muscular dystrophy (BMD, DMD).

An ELISA test that selectively measures fast and slow skeletal troponin I (TNNI2 and TNNI1) was used to measure a cross‐section of patient plasma samples from healthy volunteers (N=50), BMD (N=49) and DMD (N=132) patients. CK activity, which is a type of protein found in skeletal and heart muscles, was also measured from the same samples for comparison.

The fast skeletal troponin, TNNI2, was elevated in BMD and DMD and correlated with the injury biomarker, CK. In contrast, the slow skeletal troponin, TNNI1, levels were indistinguishable from levels in healthy volunteers. There was an inverse relationship between CK and TNNI2 levels and age but no relationship for TNNI1. Of note, a surprising discrepancy between TNNI1 and TNNI2 in patient plasma may have implications for the interpretation of elevated muscle protein levels in BMD, DMD and other dystrophinopathies.

This is the first cross-sectional, retrospective study to describe differences between fast and slow skeletal muscle fiber biomarkers in BMD and DMD patient plasma. Findings of differential troponin levels is consistent with previous studies of muscle injury after eccentric exercise in healthy volunteers. This appears to be distinct from muscle injury via sepsis or trauma where both fast and slow TNNI are elevated. Previous studies have demonstrated preferential fast fiber injury in DMD patients. Our data extend these findings to suggest that slow fibers do no not appear to leak muscle proteins in the context of BMD/DMD. The majority of healthy volunteers (83%) had TNNI2 levels below the lower level of detection of the ELISA (<0.1 ng/ml), while only 4% of BMD and 6% of DMD patients had non-measurable levels of TNNI2. This is in marked contrast to CK where large overlap exists, particularly between healthy volunteers and patients with BMD. As a result, TNNI2 may represent a more sensitive biomarker of muscle injury than CK, particularly in the setting of BMD or older DMD patients where plasma CK is commonly lower than in young DMD patients.