Long-term Safety and Efficacy of Leniolisib in PIDs With Immune Dysregulation

Inclusion Criteria:

1. Subject must have participated in LE 7201.

2. Subject is deemed by the Investigator to benefit from continued leniolisib therapy.

3. Subject or their legal representatives (for a patient under the age of 18 years)must be able to communicate with the Investigator and understand and comply with therequirements of the study, including an ability to provide written informed consentbefore any assessment is performed.

Exclusion Criteria:

1. Subject has had a successful allogeneic hematopoietic stem cell transplant.

2. Previous or concurrent use of immunosuppressive medication, such as:

3. Use of an mTOR inhibitor or a PI3K delta inhibitor, besides leniolisib, within 3 weeks prior to first dosing of study medication.

4. Rituximab or other B-cell depleting antibodies, belimumab, cyclophosphamide, oralemtuzumab within 6 months prior to first dosing of study medication.

5. Cyclosporine A, mycophenolate mofetil, 6-mercaptopurine, azathioprine,methotrexate, tacrolimus, ruxolitinib or other Janus kinase (JAK) inhibitorswithin 3 weeks prior to first dosing of study medication.

6. Corticosteroids above 25 mg prednisone or equivalent per day within 2 weeksprior to first dosing of study medication.

7. Other immunosuppressive agents expected to have a significant impact on immunecell number or function.

8. Subject is receiving concurrent treatment with another investigational therapy oruse of another investigational therapy less than 4 weeks or 5 half lives (whicheveris longer) prior to first dosing of study medication.

9. History of hypersensitivity to the study drug or to drugs of similar chemicalclasses.

10. Current use of medication known to be a strong inhibitor or moderate or stronginducer, of isoenzyme cytochrome P450 (CYP)3A.

11. Current use of medications that to a larger extent are breast cancer resistantprotein (BCRP), organic anion transporting polypeptide (OATP)1B1, and/or OATP1B3substrates.

12. History of acquired immunodeficiency diseases, including a positive humanimmunodeficiency virus (HIV) test result at screening.

13. Uncontrolled chronic or recurrent infectious disease (except those considered to becharacteristic of PID), or evidence of tuberculosis (TB) infection as defined by apositive QuantiFERON TB-Gold test at Screening.

14. Any surgical or medical condition which may jeopardize the subject in case ofparticipation in the study, or might significantly alter the absorption,distribution, metabolism, or excretion of drugs (conditions due to underlyingclinical PID phenotype may be permitted):

15. Uncontrolled hypertension

16. Congestive heart failure (New York Heart Association status of class III or IV)

17. Diagnosis of electrocardiogram (ECG) abnormalities indicating a significantrisk of safety

18. Chronic obstructive pulmonary disease (Global Initiative for ChronicObstructive Lung Disease [GOLD] stage 3-4)

19. Chronic need for supplemental oxygen or invasive or non-invasive respiratorysupport

20. Major GI tract surgery that may affect drug absorption (such as gastric bypasssurgery, gastroenterostomy)

21. Acute pancreatitis

22. Liver failure or clinically significant liver disease or dysfunction asindicated by ALT or AST greater than 2.5 times the upper limit of normal,bilirubin greater than 2 times the upper limit of normal, INR greater than 1.5in the absence of anticoagulation, or presence of diuretic refractory ascites

23. History of significant renal injury/renal disease severely affecting renalfunction or presence of impaired renal function as indicated by estimatedglomerular filtration rate (eGFR) of less than 30 mL/min/1.73 m2.

24. A positive hepatitis B surface antigen (HBsAg), positive hepatitis B polymerasechain reaction (PCR), positive hepatitis C PCR, or positive hepatitis C antibodyresult at screening.

25. Administration of live vaccines (this includes any attenuated live vaccines)starting from 6 weeks prior to first dosing of study medication, during the study,and up to 7 days after the last dose of leniolisib.

26. Subject has a previous diagnosis of lymphoma that has been treated withchemotherapy, radiotherapy, or transplant within 1 year prior to first dosing ofstudy medication or is anticipated to require lymphoma treatment within 6 months ofthe first dose of study medication.

27. Subject has a history of malignancy (except lymphoma) within 3 years prior to firstdosing of study medication or has evidence of residual disease from a previouslydiagnosed malignancy, except for adequately treated cancers of the skin (basal orsquamous cell) or carcinoma in situ of the uterine cervix.

28. Subject has uncontrolled post-transplant lymphoproliferative disease-likeEpstein-Barr-virus-related lymphoproliferative disease.

29. Subject has had major surgery requiring hospitalization or radiotherapy within 4weeks prior to first dosing of study medication or has a planned or expected majorsurgical procedure during the study period.

30. Pregnant or nursing (lactating) women.

31. An individual of child-bearing potential who is physiologically capable of becomingpregnant, unless using highly effective methods of contraception.