Benzinga | Jan 4, 2022 04:09PM EST

Annexon Biosciences Reports Interim Phase 2 Data Showing ANX005 'Has Been Generally Well-Tolerated and Has Shown Full Target Engagement of C1q in the CSF'

ANX005 Has Been Generally Well-Tolerated and Has Shown Full Target Engagement of C1q in the CSF

Improvements in Clinical Outcome Measures Observed in Greater than 50% of All Evaluable Patients and 75% of Evaluable Patients with Excess Baseline Complement Activity

NfL Levels Remained Consistent and Were Comparable to Published Natural History Data for HD Patients

Phase 2 Trial Ongoing with Full Data Expected in the Second Quarter of 2022

Company to Host Conference Call Today at 4:30 p.m. ET

BRISBANE, Calif., Jan. 04, 2022 (GLOBE NEWSWIRE) -- Annexon, Inc. (NASDAQ:ANNX), a clinical-stage biopharmaceutical company developing medicines that stop destructive immune activity in complement-mediated autoimmune, neurodegenerative and ophthalmic disorders, today announced interim data from its ongoing, open-label Phase 2 clinical trial of ANX005 in patients with Huntington's disease (HD) who completed the 24-week treatment period. Annexon is developing ANX005, its lead monoclonal antibody candidate, for the treatment of a range of complement-mediated disorders, including HD.

HD is a fatal, progressive movement disorder involving the activation of the classical complement pathway. C1q, the initiator of the classical pathway, is recognized as a major driver of a destructive immune response that leads to synapse loss and neurodegeneration. ANX005 is designed to disrupt the disease course, stopping the start of damaging complement activation by blocking C1q and the entire classical complement pathway.

Interim data from the ongoing Phase 2 trial show that treatment with ANX005 has been generally well-tolerated, with full target engagement of C1q in both serum and cerebrospinal fluid (CSF) observed in evaluable patients through the dosing period. Evaluable patients maintained clinical function, as measured by changes in mean Composite Unified Huntington's Disease Rating Scale (cUHDRS), relative to baseline after six months of treatment, and improvement in cUHDRS was observed in more than half of all evaluable patients and in 75% of evaluable patients who showed excess complement activity at baseline. NfL levels observed after six months of treatment remained generally consistent and were comparable to NfL levels described in published natural history data for HD patients. Overall, these interim findings appear to build on the scientific hypothesis of Annexon scientific founder, the late Ben Barres, who believed that blocking C1q protects synaptic loss and can lead to rapid functional impact on clinical outcomes in neurodegenerative diseases.

"People with HD face a devastating condition, with no cure or approved disease-modifying treatments available," said Edward Wild, FRCP, Ph.D., consultant neurologist, NHNN Queen Square and associate director, UCL Huntington's Disease Centre. "I believe the interim data from this open-label trial of ANX005 are encouraging, showing complete CSF target engagement and that ANX005 has been generally well-tolerated, with no concern regarding the NfL levels seen in this early readout. The apparent stabilization of cUHDRS observed relative to normal disease progression, together with the potential improvement seen in patients with elevated baseline C4a, supports the hypothesis that protecting synapses via C1q inhibition could produce meaningful functional benefit in HD, and justifies the continued development of ANX005 for this indication."

ANX005 Interim Safety and Target Engagement Data

ANX005 has been generally well-tolerated in the study (n=28). As of the data cutoff date of October 17, 2021, the most common adverse events (AEs) reported were first dose-associated infusion-related reactions, including transient skin rash, consistent with the experience observed in the company's Phase 1b trial of ANX005 in patients with Guillain-Barr? Syndrome (GBS). In the HD trial, five patients discontinued ANX005 treatment, three of whom discontinued due to a drug-related AE. Two patients experienced a drug-related serious adverse event, including one event of systemic lupus erythematosus (mucocutaneous), whose symptoms resolved post-study drug discontinuation, and one event of idiopathic pneumonitis, which stabilized post-study drug discontinuation. Of note, no cases of serious infection were identified, and no deaths were reported.

Interim data show that treatment with ANX005 has led to full target engagement of C1q in both serum and CSF through the dosing period in patients who were evaluable as of the cutoff date of October 17, 2021 (n=13).