Testing the Efficacy and Safety of BIO101 for the Prevention of Respiratory Deterioration in COVID-19 Patients

Inclusion Criteria:

1. Age: 45 and older (in France: 55 and older)

2. A confirmed diagnosis of COVID-19 infection, within the last 28 days, prior to
randomization, as determined by PCR or other approved commercial or public health
assay, in a specimen as specified by the test used.

3. Hospitalized, in observation or planned to be hospitalized due to COVID-19 infection
symptoms with anticipated hospitalization duration >=3 days

a. Patients can be included even if treated with: oxygen supplementation, High-flow
oxygen (HFO2), BiPAP and CPAP

4. With evidence of pneumonia based on all of the following:

1. Clinical findings on a physical examination

2. Respiratory symptoms developed within the past 14 days

5. With evidence of respiratory decompensation that started not more than 7 days before
start of study medication and present at screening, meeting one of the following
criteria, as assessed by healthcare staff:

1. Tachypnea: ≥25 breaths per minute

2. Arterial oxygen saturation ≤92%

3. A special note should be made if there is suspicion of COVID-19- related
myocarditis or pericarditis, as the presence of these is a stratification
criterion

6. Without a significant deterioration in liver function tests:

1. ALT and AST ≤ 5x upper limit of normal (ULN)

2. Gamma-glutamyl transferase (GGT) ≤ 5x ULN

3. Total bilirubin ≤ 5×ULN

7. Willing to participate and able to sign an informed consent form (ICF)

8. Female subjects should be:

at least 5 years post-menopausal (i.e., persistent amenorrhea 5 years in the absence
of an alternative medical cause) or surgically sterile; OR

1. Have a negative urine pregnancy test at screening

2. Be willing to use a contraceptive method as outlined in inclusion criterion 9
from screening to 30 days after last dose.

9. Male subjects who are sexually active with a female partner must agree to the use of
an effective method of birth control throughout the study and until 3 months after the
last administration of investigational product; Note: medically acceptable methods of
contraception that may be used by the subject and/or partner include combined oral
contraceptive, contraceptive vaginal ring, contraceptive injection, intrauterine
device, etonogestrel implant, each supplemented with a condom, as well as
sterilization and vasectomy.

10. Male subjects must agree not to donate sperm for the purpose of reproduction
throughout the study and until 3 months after the last administration of
investigational product;

11. For France only: Being affiliated with a European Social Security.

Exclusion Criteria:

1. Not needing or not willing to remain in a healthcare facility during the entire study
medication (i.e. while receiving study medication)

2. Moribund condition (death likely in days) or not expected to survive for >7 days - due
to other and non-COVID-19 related conditions

3. Patient on invasive mechanical ventilation via an endotracheal tube, or extracorporeal
membrane oxygenation (ECMO)

4. Patient within 7 days of participating in other therapeutic clinical trial with
angiotensin-converting-enzyme inhibitors (ACEi), angiotensin receptor blockers (ARB)
or recombinant ACE-2

5. Patient not able to take medications by mouth (as capsules or as a powder, mixed in
water).

6. Disallowed concomitant medication:

a. Consumption of any herbal products containing 20-hydroxyecdysone and derived from
Leuzea carthamoides; Cyanotis vaga or Cyanotis arachnoidea is not allowed (e.g.
performance enhancing agents)

7. Any known hypersensitivity to any of the ingredients, or excipients of the study
medication, BIO101

8. In France:

- Non-affiliation to compulsory French social security scheme (beneficiary or
right-holder)

- Being under tutelage or legal guardianship