A Phase 1, Randomized, Double-Blind, Placebo-Controlled, Single Ascending Dose Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Intravenous ANX105 in Normal Healthy Volunteers

Participants are eligible to be included in the study only if all the following
criteria apply:

Age
1. Participants must be 18 (or the legal age of consent in the jurisdiction in
which the study is taking place) to 55 years of age inclusive, at the time of
signing the informed consent.

Type of Participant and Disease Characteristics
2. Participants who are overtly healthy as determined by medical evaluation
including medical history, physical examination, and laboratory tests.

Weight
3. Body weight within the range 45 kg to 110 kg and body mass index (BMI)
within the range >=18.0 kg/m2 to <=33.5 kg/m2 (inclusive) at the Day -1 visit.

Sex and Contraceptive/Barrier Requirements
4. Participants who are male or female
Contraceptive use by men and women should be consistent with local regulations
regarding the methods of contraception for those participating in clinical
studies.
a. Male participants:
Male participants are eligible to participate if they agree to the following
during the intervention period and for at least 90 days after the dose:
• Refrain from donating fresh unwashed semen
Plus, either:
o Be abstinent from heterosexual intercourse as their preferred and usual
lifestyle (abstinent on a long-term and persistent basis) and agree to remain
abstinent
OR
o Must agree to use a male condom and should also be advised of the benefit for
a female partner to use a highly effective method of contraception as a condom
may break or leak when having sexual intercourse with a woman of childbearing
potential who is not currently pregnant
b. Female participants:
• A female participant is eligible to participate if she is not pregnant or
breastfeeding, and one of the following conditions applies:
o Is a woman of nonchildbearing potential (WONCBP) as defined in protocol
Appendix 4: Contraceptive and Barrier Guidance.
OR
o Is a WOCBP and using a contraceptive method that is highly effective, with a
failure rate of <1%, as described in protocol Appendix 4: Contraceptive and
Barrier Guidance during the study intervention period and for at least 90 days
after the dose. The Investigator should evaluate the potential for
contraceptive method failure (eg, noncompliance, recently initiated) in
relationship to the first dose of the study intervention.
• A WOCBP must have a negative highly sensitive pregnancy test (urine or serum
as required by local regulations) within 24 hours before the first dose of
study intervention, see Protocol Section 8.2.7: Pregnancy Testing.
o If a urine test cannot be confirmed as negative (eg, an ambiguous result), a
serum pregnancy test is required. In such cases, the participant must be
excluded from participation if the serum pregnancy result is positive.
• Additional requirements for pregnancy testing during and after study
intervention are outlined in protocol Section 8.2.7: Pregnancy Testing
• The Investigator is responsible for the review of medical history, menstrual
history, and recent sexual activity to decrease the risk for inclusion of a
woman with early undetected pregnancy.

Informed Consent
5. Capable of giving signed informed consent as described in protocol Section
10.1.3 which includes compliance with the requirements and restrictions listed
in the informed consent form (ICF) and this protocol.

Participants are excluded from the study if any of the following criteria apply:

Medical Conditions
1. History or presence of clinically relevant cardiovascular, respiratory,
hepatic, renal, gastrointestinal, endocrinological, hematological, or
neurological disorders.
2. History or presence of conditions capable of significantly altering the
disposition of drugs that constitute a risk when taking the study intervention
or interfere with the interpretation of data.
3. History of any autoimmune disease (eg, rheumatoid arthritis, systemic lupus
erythematosus, multiple sclerosis, autoimmune vasculitis, Guillain-Barré
syndrome, autoimmune hepatitis, or psoriasis).
4. History of meningitis or septicemia.
5. Clinically significant infection (eg, viral, bacterial, fungal, or
mycobacterial), with the exception of onychomycosis, within 30 days prior to
Day 1 that required medical intervention (not including antibiotic prophylaxis).
6. Known genetic deficiencies of the complement cascade system or
immunodeficiency.
7. Abnormal blood pressure as determined by the Investigator.
8. Significant allergies to humanized monoclonal antibodies.
9. Clinically significant drug allergies, intolerance to topical
corticosteroids, or severe post-treatment hypersensitivity reactions
(including, but not limited to, erythema multiforme major, linear
immunoglobulin A [IgA] dermatosis, toxic epidermal necrolysis, and exfoliative
dermatitis).
10. History or presence of any malignancy (excluding basal cell carcinoma).
11. Liver disease or liver function tests such as alanine transaminase (ALT) or
aspartate transaminase (AST) >1.5xULN (upper limit of normal), serum total
bilirubin (isolated bilirubin >1.5xULN is acceptable if total bilirubin is
fractionated and direct bilirubin <35%), or alkaline phosphatase above the
1.5xULN
12. Known hepatic or biliary abnormalities (except for Gilbert's syndrome or
asymptomatic gallstones).
13. The following ECG abnormalities at Screening:
• QRS >120 msec; heart rate <40 beats per minute.
• Presence of second- or third-degree heart block.
• QTcF >450 msec for male participants and >470 msec for female participants.
The ECG may be repeated twice with a manually measured QTcF and the average of
3 manually measure QTcF values will be obtained to determine the participant*s
eligibility.
• PR interval >200 msec and any other clinically relevant abnormality.
14. Abnormalities in the lumbar spine were previously known .
15. History of clinically significant back pain, back pathology, and/or back
injury (for example, degenerative disease, spinal deformity, or spinal surgery)
that may predispose the participant to complications or technical difficulty
with a lumbar puncture.
16. Evidence or history of significant active bleeding or coagulation disorder
that affects coagulation or platelet function within 14 days prior to lumbar
catheter insertion.
17. Allergy to lidocaine (Xylocaine®) or its derivatives.
18. Medical or surgical conditions for which lumbar puncture is contraindicated.
19. History or presence of anemia or neutropenia.

Prior/Concomitant Therapy
20. Past or intended use of over-the-counter medication including herbal
medications within 7 days prior to Day 1 .
21. Past or intended use of prescription medication within 14 days prior to Day
1.
22. Treatment with biologic agents (such as monoclonal antibodies including
marketed drugs) within 3 months or 5 half-lives (whichever is longer) prior to
Day 1.
23. Use of immunosuppressants including high dose systemic corticosteroids (ie,
>10 mg/day prednisone or equivalent) within 30 days prior to Day 1.

Prior/Concurrent Clinical Study Experience
24. Current enrollment or past participation in any other clinical study
involving an investigational study intervention (ie, biologics) or any other
type of medical research within the last 90 days or 5 half-lives (whichever is
longer) prior to Day 1.

Diagnostic Assessments
25. A positive test result for human immunodeficiency virus type 1 (HIV 1)
antibody, hepatitis B surface antigen (HBsAg), or a hepatitis C antibody test
or C RNA test result at Screening.
26. Alcohol or substance abuse as assessed by the Investigator.
27. Smoker, use of nicotine or nicotine-containing products (nicotine patches
are allowed) within 90 days prior to Day 1.
28. ANA titer >=1:160 at Screening.

Other Exclusions
29. Alcohol-related conditions as defined by clinical interpretation and liver
function test at screening.
30. Regular use of known drugs of abuse.
31. Have poor venous access limiting phlebotomy.
32. Sensitivity to heparin or heparin-induced thrombocytopenia.
33. Sensitivity to any of the study interventions, or components thereof, or
drug or other allergies that, in the opinion of the Investigator or Medical
Monitor, contraindicates participation in the study.
34. Any other medical or psychiatric conditions or any other issue that may, in
the opinion of the Investigator, affect the interpretation of study results,
preclude adherence to the study visit schedule, or safe participation in the
study.
35. Donation or loss of > 500 mL whole blood within 30 days prior to Day 1 or
donation of plasma within 14 days prior to Day 1.
36. Hospitalization during the 4 weeks prior to Screening. Participants who
were hospitalized within 4 weeks of Screening may be rescreened after this
window has elapsed.
37. Employees of the Sponsor or research site personnel directly affiliated
with this study or their immediate family members, defined as a spouse, parent,
child, or sibling, whether biological or legally adopted.