This study is a multi-center, open-label study of intravenous (IV) ANX005 in subjects with, or at risk for, manifest Huntington's Disease (HD).

The objective of this study is to evaluate the effects of intravenous ANX005 administered for up to 22 weeks in subjects with, or at risk for, manifest Huntington's Disease.

Subjects will receive induction dosing of ANX005 administered by IV infusion on Days 1 and 5 or 6, followed by maintenance dosing every 2 weeks through Week 22, with follow up visits on Weeks 24, 28, and 36.

All subjects will be contacted (in clinic visit or phone call) 6 months after study completion.

Inclusion Criteria:

1. Diagnosis of or at risk for Huntington's disease: Genetically confirmed disease by direct DNA testing, total CAG-Age Product (CAP) score > 400 and UHDRS independence score ≥ 80.
2. Able to walk independently and self-sufficient in basic activities of daily living (e.g. eating, dressing, bathing).
3. All HD concomitant medications stable.
4. If female, must be postmenopausal (no menses for at least 2 years without an alternative medical cause), surgically sterilized (bilateral tubal ligation, bilateral oophorectomy, or hysterectomy), or agree to use highly effective methods of contraception.
5. Males with a woman of childbearing potential partner must agree to use highly effective methods of contraception.
6. Previously vaccinated against encapsulated bacterial pathogens (Neisseria meningitidis, Haemophilus influenzae, and Streptococcus pneumoniae) or willing to undergo vaccination.
7. Able to tolerate EEG and lumbar puncture (LP) procedures.

Exclusion Criteria:

1. Be at risk of suicide or self-harm within the preceding 12 months.
2. Chorea and/or cognitive deficits severe enough to interfere with study assessments.
3. Subjects with body weight > 150 kg.
4. Clinically significant findings on the screening laboratory testing or physical examination that are not specific to HD and may interfere with the conduct of the study or the interpretation of the data or increase subject risk.
5. Signs and symptoms of, or a diagnosis consistent with a chronic autoimmune disorder and/or an ANA titer ≥ 1:160.
6. History of previous infusion reactions, sensitivities, allergic, or anaphylactic reactions to previous medications, environmental stimuli or other substances.
7. Use of an experimental agent within 60 days or five half-lives prior to Screening or anytime over the duration of this study.
8. Prior treatment with any monoclonal antibody.
9. Presence of an implanted deep brain stimulation device.
10. Any history of gene therapy, RNA or DNA targeted HD specific investigational agents such as antisense oligonucleotides, cell transplantation or any experimental brain surgery.
11. Brain and spinal pathology that may interfere with cerebrospinal fluid homeostasis and circulation, increases intracranial pressure (implanted shunt or catheter), malformations or tumor.
12. Contraindication to undergoing an LP.
13. Hypersensitivity to any of the excipients in the ANX005 drug product.
14. Clinically significant intercurrent illness, medical condition, or medical history (including neurological or mental illness, HIV, any active infection, including Hepatitis B or C) that would jeopardize the safety of the subject, limit participation, or compromise the interpretation of the data derived from the subject.
15. Any known genetic deficiencies of the complement-cascade system.
16. History of chronic oral or intravenous steroid use or immunosuppressant medication use.
17. Hemoglobin, bilirubin, or lactate dehydrogenase (LDH) values that are outside normal limits and clinically significant or suggestive of hemolytic anemia.