Annexon Stock (ANNX): Why The Price Substantially Dropped Today

By Amit Chowdhry ● Jan 5, 2022
  • The stock price of Annexon Inc (NASDAQ: ANNX) fell by over 35% during intraday trading today. This is why it happened.

The stock price of Annexon Inc (NASDAQ: ANNX) – a clinical-stage biopharmaceutical company developing medicines that stop destructive immune activity in complement-mediated autoimmune, neurodegenerative, and ophthalmic disorders – fell by over 35% during intraday trading today. Investors are responding negatively to Annexon announcing 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 known as 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.

The 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. And evaluable patients maintained clinical function, as measured by changes in mean Composite Unified Huntington’s Disease Rating Scale (cUHDRS), relative to baseline after 6 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. The NfL levels observed after 6 months of treatment remained generally consistent and were comparable to NfL levels described in published natural history data for HD patients. Overall, the 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.

ANX005 was generally well-tolerated in the study (n=28). And 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-Barré Syndrome (GBS). In the HD trial, 5 patients discontinued ANX005 treatment, 3 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.

The 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).


“People with HD face a devastating condition, with no cure or approved disease-modifying treatments available. 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.”

— Edward Wild, FRCP, Ph.D., consultant neurologist, NHNN Queen Square and associate director, UCL Huntington’s Disease Centre

“We are quite encouraged by the interim data generated with ANX005 in HD. We are particularly excited to see a heightened clinical response in patients with excess baseline complement activity, suggesting that the classical complement pathway plays a key role in the neurodegenerative disease process and that ANX005 has the potential to provide meaningful benefit to HD patients. These early data in HD patients, coupled with prior proof-of-concept data in GBS, provide a growing body of evidence for the potential role of anti-C1q in treating complement mediated neurodegenerative and autoimmune diseases, and we look forward to continuing to assess the full potential of our approach in several ongoing trials in diseases of high unmet need.”

— Douglas Love, Esq., president and chief executive officer of Annexon

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