Safety and Efficacy of ONT01 in Lupus

Inclusion Criteria:

1. ≥ 18 years old and able to provide informed consent to participate.

2. Diagnosis of SLE and have fulfilled the ACR classification criteria for SLE duringthe course of their disease.

3. Active non-renal SLE, with one active non-renal clinical manifestation, who havefailed at least 1 disease modifying anti-rheumatic drug (DMARD) therapy (notincluding hydroxychloroquine and corticosteroids)

• Active non-renal SLE is defined as having a SLEDAI of 6 or greater (with atleast 1 non-renal clinical domain) OR Active nephritis defined as having a noor partial response after initial induction and maintenance therapy withmycophenolate mofetil (and other standard of care therapies) for 3 months ormore for class III, IV, IV, V (or combination) nephritis.

• Active LN is defined as follows: a. kidney biopsy showing Class III, IV, V,III+V, or IV+V, within 1 year from screening, AND b. 24-hour urineprotein/creatinine ratio >=1g/g at screening, AND c. absence of partial renalresponse (PRR)

• Partial renal response (PRR) is defined as a. 24-hour UPCR improved by >=25%after 3 months from the start of induction standard of care (SOC) therapy (baseline), or >= 50% after 6 months from the induction therapy (UPCR), AND b. 24-hour UPCR<2g/g if baseline was < 3g/g, OR < 3g/g if baseline at inductionwas >= 3g/g. AND d. EGFR>=60 ml/min/1.73 M2 or no less than 80% of BaselineeGFR (at induction) AND e. No intercurrent rescue therapy, death, or early SOCtreatment discontinuation or study withdrawal No response (NR) is defined as a.no achievement of at least a partial renal response, OR b. use of intercurrentrescue therapy, OR c. death

4. Female patients who are women of childbearing potential must agree to use a highlyeffective form of contraception during the study and for at least 120 days afterlast exposure to study drug. Male patients with female partners of childbearingpotential must use effective barrier contraception (i.e., condoms) during the studyand for at least 120 days after last exposure to study drug. Also, patients may notproceed with sperm or egg donation during the study and for at least 120 days afterthe last exposure to study drug

Exclusion Criteria:

1. Any condition, including any uncontrolled disease (eg, asthma, interstitial lungdisease, pulmonary arterial hypertension, morbid obesity), that in theSponsor-Investigator's opinion constitutes an inappropriate risk or acontraindication for participation in the study or that could interfere with thestudy objectives, conduct or evaluation.

2. Active central nervous system SLE associated with significant cognitive impairmentleading to inability to provide informed consent and/or comply with the protocol.

3. Comorbidities requiring systemic corticosteroid (CS) therapy, such as asthma orinflammatory bowel disease. Systemic is defined as oral, rectal or any injectableroute of administration (thus stable dosing by other routes is allowed, includinginhaled, topical, ophthalmic, otic, and intranasal).

4. Active clinically significant viral, bacterial or fungal infection, or any majorepisode of infection requiring hospitalization or treatment with parenteralanti-infectives within 4 weeks of or during the Screening Visit, or completion oforal anti-infectives within 2 weeks before or during the Screening Visit.

5. History of positive human immunodeficiency virus (HIV), hepatitis C antibody and/orpolymerase chain reaction, hepatitis B surface antigen (HBsAg) (+), and/or hepatitisB core IgG and/or IgM antibody (+) at the Screening Visit.

6. History, or current diagnosis, of active tuberculosis (TB), or untreated latent TBinfection (LTBI), determined by a positive QuantiFERON test at the Screening Visit

7. History of malignancy (hematologic or solid tumor) within 10 years prior toScreening Visit, except adequately treated basal cell or squamous cell carcinomas ofthe skin (no more than 3 lesions requiring treatment in lifetime) or adequatelytreated carcinoma in situ/cervical intraepithelial neoplasia of the uterine cervix.

8. Immunization with live or live-attenuated vaccines within 1 month before or duringthe Screening period.

9. Initiation of, or change in, dosing of an angiotensin-converting enzyme inhibitor orangiotensin receptor blocker within 2 weeks before the Screening Visit or during theScreening period.

10. Treatment with Voclosporin or Cyclophosphamide at time of screening.

11. Treatment with other investigational agents within the last 3 months or 5half-lives, or as per washout requirement from the previous protocol, whichever islongest, prior to the Screening Visit.

12. Clinically significant abnormalities in laboratory tests, unless attributable toactive SLE at the Screening Visit

• Aspartate aminotransferase, alanine aminotransferase or alkaline phosphataselevel > 2.5 × upper limit of normal (ULN), or

• Total bilirubin > 1.5 × ULN, or

• Hemoglobin < 5.0 mmol/L [9 g/dL], or

• White blood cells < 2.5 × 109/L, or

• Absolute neutrophil count < 1500 /mm3, or

• Platelets < 75 × 109/L

13. Clinically significant chest imaging (e.g. X-ray, computed tomography or magneticresonance imaging [MRI]) abnormalities per Sponsor-Investigator opinion (e.g.interstitial lung disease) or evidence of active TB on chest X-ray. Chest imagingstudy must have been performed in 3 months prior to the Screening Visit or duringthe Screening period.

14. Pregnant and/or breastfeeding. Women of childbearing potential must have a negativepregnancy test within 14 days of study entry.

15. Patients are unable or unwilling to adhere to the contraception requirementsoutlined in inclusion criteria 4.