Pediatric Patients Aged 4 to 11 Years With APDS

Diagnosis and main criteria for inclusion and exclusion:

Patients must satisfy all of the following criteria at the screening visit unless otherwise
stated:

   1. Patient is male or female and between the age of 4 to 11 years old at the time of the
   first study procedure.

   2. Patient weighs ≥13 kg and <45 kg at baseline.

   3. Patient has a confirmed PI3Kδ genetic mutation of either the PIK3CD (APDS1) or PIK3R1
   (APDS2) gene.

   4. Patient has at least 1 measurable nodal lesion on magnetic resonance imaging/low-dose
   computed tomography within 6 months of screening.

   5. Patient has nodal or extranodal lymphoproliferation and clinical findings consistent
   with APDS (eg, a history of repeated oto-sino-pulmonary infections and/or organ
   dysfunction consistent with APDS).

   6. Patient has the ability to ingest unaltered study-related medications without
   difficulty in the investigator's opinion.

   7. At screening, vital signs (systolic blood pressure [BP], diastolic BP, and pulse rate)
   will be assessed in the sitting position after the patient has been at rest for at
   least 3 minutes. Patient's sitting vital signs should be within the following ranges:

      - Systolic BP: Less than the 95th percentile adjusted for sex, age, and height
      percentile.

      - Diastolic BP: Less than the 95th percentile adjusted for sex, age, and height
      percentile.

      - Heart rate (HR):

      i) Age 4 to <10 years: 60 to 140 bpm ii) Age ≥10 years: 50 to 100 bpm

   8. Institutional review board-/independent ethics committee-approved written informed
   consent/assent and privacy language as per national and local regulations must be
   obtained from the patient and parent/legal guardian prior to any study-related
   procedures.

   9. Patient parent/legal guardian is willing and able to complete the informed
   consent/assent process and comply with study procedures and visit schedule.

10. Patient parent/legal guardian agrees patient will not participate in any other
   interventional study while enrolled in this study.

11. Female patients should be of non-childbearing potential at screening (should not have
   reached menarche). Male patients with partners of childbearing potential should be
   willing to use a highly effective method of contraception for at least 30 days after
   the last study procedure if at risk of pregnancy.

12. Female patient and parent/legal guardian must agree to the following if menses
   develops after screening, up to 30 days after the last study procedure:

      - True sexual abstinence defined as refraining from heterosexual activity during
      the entire period of the study through 6 months post-study or

      - Using a highly effective method of contraception for at least 30 days after the
      last study procedure if at risk of pregnancy.

Patients will be excluded from the study if they satisfy any of the following criteria at
the screening visit unless otherwise stated:

   1. Patient has previous or concurrent use of immunosuppressive medication such as:

   a. An mTOR inhibitor (eg, sirolimus, rapamycin, everolimus) or a PI3Kδ inhibitor
   (selective or non-selective PI3K inhibitors) within 6 weeks prior to first dose.

   i. Short-term use for up to a total of 5 days is allowed but only up to 1 month prior
   to enrollment in the study.

   b. B cell depleters (eg, rituximab) within 6 months prior to first dose of study
   medication.

   i. If patient has received prior treatment with a B cell depleter, absolute B
   lymphocyte counts in the blood must have regained normal values.

   c. Belimumab or cyclophosphamide within 6 months prior to first dose of study
   medication.

   d. Cyclosporine A, mycophenolate, 6-mercaptopurine, azathioprine, or methotrexate
   within 3 months prior to first dose of study medication.

   e. Systemic glucocorticoids above a dose equivalent to either ≥2 mg/kg of body weight
   or ≥20 mg/day of prednisone/prednisolone or equivalent.

   f. Other immunosuppressive medication where effects are expected to persist at start
   of dosing of study medication.

   2. Patient has a history or current diagnosis of electrocardiogram (ECG) abnormalities
   indicating significant risk of safety for patients participating in the study such as:

      1. History of familial long QT syndrome or known family history of Torsades de
      Pointes.

      2. Concomitant clinically significant cardiac arrhythmias (eg, sustained ventricular
      tachycardia, and clinically significant second or third degree atrioventricular
      block without a pacemaker).

      3. Resting QTc (Fridericia preferred, but Bazett acceptable) >460 msec if the
      measurement is confirmed with an additional ECG repeated as soon as possible.

      4. Concomitant use of agents known to prolong the QT interval unless it can be
      permanently discontinued for the duration of the study.

   3. Patient is currently using a medication known to be a strong inhibitor or moderate or
   strong inducer of isoenzyme cytochrome P450 (CYP)3A, if treatment cannot be
   discontinued or switched to a different medication prior to starting study treatment.

   4. Patient is currently using medications that are metabolized by isoenzyme CYP1A2 and
   have a narrow therapeutic index (drugs whose exposure-response indicates that
   increases in their exposure levels by the concomitant use of potent inhibitors may
   lead to serious safety concerns [eg, Torsades de Pointes]).

   5. Patient had been administered live vaccines (this includes any attenuated live
   vaccines) starting from 6 weeks before the anticipated first study drug
   administration, during the study, and up to 7 days after the last dose of leniolisib.

   6. Patient has clinically significant abnormalities in hematology or clinical chemistry
   (blood chemistry or urinalysis) parameters as determined by the investigator or
   medical monitor.

   7. Patient has liver disease or liver injury as indicated by clinically significant
   abnormal liver function tests (alanine aminotransferase and aspartate aminotransferase
   >2.5 times upper limit of normal), history of renal injury/renal disease (eg, renal
   trauma, glomerulonephritis, or one kidney only), or presence of impaired renal
   function as indicated by a serum creatinine level >1.5 mg/dL (133 μmol/L).

   8. Patient has moderate or severe hepatic impairment (Child-Pugh Class B or C).

   9. Patient is receiving concurrent treatment with another investigational therapy or use
   of another investigational therapy less than 4 weeks from the first study procedure.

10. Patient has active hepatitis B (eg, hepatitis B surface antigen reactive) or active
   hepatitis C (eg, hepatitis C virus RNA [qualitative] is detected) at screening.

11. Patient has human immunodeficiency virus (HIV) infection (HIV 1 or 2) at screening.

12. Patient has a positive coronavirus disease 19 result (polymerase chain reaction or
   antigen) within 1 week prior to first dose. The patient can be rescreened after a
   subsequent negative result.

13. Patient has a history of malignancy (except lymphoma) within 3 years before the first
   study procedure or has evidence of residual disease from a previously diagnosed
   malignancy.

14. Patient has a previous diagnosis of lymphoma that has been treated with chemotherapy,
   radiotherapy, or transplant within 1 year of the first study procedure or is
   anticipated to require lymphoma treatment within 6 months of the first study
   procedure.

15. Patient has a history of uncontrolled diabetes mellitus within 3 months of the first
   study procedure.

16. Patient has had major surgery requiring hospitalization or radiotherapy within 4 weeks
   prior to the first study procedure.

17. Patient has uncontrolled chronic or recurrent infectious disease (with the exception
   of those that are considered to be characteristic of APDS) or evidence of tuberculosis
   infection as defined by a positive Mantoux tuberculin skin test at screening. If
   presence of latent tuberculosis is established, then treatment according to local
   country guidelines must have been completed before patients can be considered for
   enrollment.

18. Patient has a known allergy or history of hypersensitivity to study defined
   medications or any ingredients of the medications, including the following common
   excipients:

      - Lactose monohydrate

      - Microcrystalline cellulose

      - Sodium starch glycolate (Type A)

      - Hypromellose

      - Magnesium stearate

      - Colloidal silicon dioxide

      - Opadry yellow

19. Patient has a planned or expected major surgical procedure.

20. Patient or parent/legal guardian is unable or unwilling to comply with study
   procedures or is unable to travel for repeat visits.

21. Patient or parent/legal guardian is unwilling to keep study results/observations
   confidential or to refrain from posting confidential study results/observations on
   social media sites.

22. Patient or parent/legal guardian refuses to sign consent/assent form.

23. Patient has other underlying medical condition that, in the opinion of the
   investigator, would impair the ability of the patient to receive or tolerate the
   planned procedures or follow-up.