J013 ANX005-HD-01b: clinical progression in patients in Enroll-HD prior to participation in the open-label phase 2a study HD-01 – post hoc analysis of the effect of ANX005

<h3>Background</h3> ANX005 is a humanized anti-complement C1q monoclonal antibody that blocks activation of the classical complement cascade. ANX005-HD-01 (HD-01; NCT04514367) was an open-label study of ANX005 in patients with manifest Huntington’s disease (HD). Enroll-HD is an ongoing, long-term observational registry study. HD-01b is a retrospective analysis of functional outcomes in patients from HD-01 who also participated in Enroll-HD before entering HD-01. <h3>Aims</h3> Determine the effect of ANX005 on clinical progression in patients with HD by comparing functional decline in Enroll-HD and while receiving ANX005 in HD-01. <h3>Methods</h3> Eighteen of 28 patients in HD-01 had Enroll-HD data (table 1). The trajectories prior to and while receiving ANX005 treatment of composite Unified Huntington’s Disease Rating Scale (cUHDRS) and its components were estimated using a piecewise linear regression mixed-effect model. <h3>Results</h3> In the 12 months prior to HD-01 participation, patients with higher HD-01 baseline complement activity showed greater reduction in cHDURS decline trajectory than those with lower baseline activity (0.0644 points/month vs -0.0425 points/month; p=0.046) (figure 1). Piecewise linear regression analysis suggests that ANX005 slowed the rates of decline in cUHDRS observed in Enroll-HD in patients with higher baseline complement activation (table 2). Rates of cognitive decline observed in Enroll-HD were reversed or attenuated by ANX005 treatment in patients with both higher and lower complement activity (table 2). <h3>Conclusions</h3> These results indicate that treatment with ANX005 may slow the rate of functional and cognitive decline in patients with HD. These results may help inform precision medicine approaches for future studies. <h3>Supported by</h3> Annexon Biosciences. <h3>DISCLOSURES</h3> DOC: research support from Annexon Biosciences. RK: consultancy/advisory fees and research support from Annexon Biosciences. PC, AW, BM, BDH, GEM: employees of Annexon Biosciences.