A Study to Evaluate the Efficacy and Safety of Itolizumab in Subjects Hospitalized With COVID-19

Inclusion Criteria:

1. Is willing and able to, or has a legally acceptable representative who is willing and
able to, provide informed consent to participate and to cooperate with all aspects of
the protocol.

2. Is male or female, age ≥18 years

3. Is hospitalized with COVID-19 pneumonia with a diagnosis of SARS-CoV-2 infection
confirmed by reverse transcriptase polymerase chain reaction (RT-PCR) or equivalent
local test within 14 days of randomization.

4. Has PaO2/FiO2 ratio of ≤200 (or equivalent SpO2/FiO2 ratio ~235 within 24 hours before
randomization. This ratio may be adjusted based on altitude.

Exclusion Criteria:

1. Has known severe allergic reactions to mAbs.

2. Has active TB or known history of inadequately treated latent or active TB.

3. Has any known active systemic or pulmonary bacterial, fungal, or viral (other than
SARS-CoV-2) infection at the time of randomization.

4. Has known active, uncontrolled hepatitis B or hepatitis C or severe liver function
impairment from any etiology, as defined by Child-Pugh Class C.

5. Has human immunodeficiency virus (HIV) with known CD4 counts <0.2 × 10^9/L.

6. Has a history of clinically significant cardiac abnormality within 6 months prior to
randomization, such as myocardial infarction or stroke, New York Heart Association
class III or IV, or clinically significant abnormalities of electrocardiogram (ECG) or
cardiac function.

7. Has been on mechanical ventilation for longer than 48 hours during their first
continuous episode since admission, is on their second or greater episode of
mechanical ventilation at the time of randomization during the concurrent
hospitalization, or has received extracorporeal membrane oxygenation (ECMO).

8. Has a declining clinical status with an expected survival <3 days in the opinion of
the Investigator.

9. Has received any systemic immunomodulatory or immunosuppressant agents for any
condition within 3 months prior to randomization. (Note: a stable, oral, low dose of
corticosteroids [prednisone or equivalent ≤10 mg/day] for a chronic condition or any
dose of systemic corticosteroids for current COVID-19 treatment are permitted.
Local/topical treatments are also permitted.)

10. Has received any biologic treatment for any acute (eg, COVID-19) or chronic conditions
(eg, TNFα inhibitors, anti-IL17A, tocilizumab, anti-cytokines, etc.) within 3 months
prior to randomization.

11. Is participating in another clinical study of an investigational product and/or
received an investigational product within 30 days or within 5 half-lives (whichever
is longer) prior to randomization.

12. Is pregnant or breastfeeding, or has a positive pregnancy serum or urine test during
Screening.

13. Does not agree to use contraception in the event of sexual activity for 130 days (+90
days for male subjects) after the last dose of study drug if a female of childbearing
potential or a male with a partner of childbearing potential. Note: this criterion
does not apply to subjects in same-sex relationships.

14. Has inadequate hematologic function during Screening defined as follows:

- Absolute neutrophil count (ANC) <1.0 × 109/L.

- ALC <0.5 × 109/L.

15. Requires renal dialysis, either acute or chronic, at the time of randomization.

16. Has a medical, psychiatric, or other condition or circumstance that, in the opinion of
the Investigator, could affect the subject's safety, the subject's participation in
the study, or the reliability of the study data.