Study to Assess Safety, Tolerability and Efficacy of MB-106 in Patients With Relapsed or Refractory B-Cell NHL or CLL

Inclusion Criteria:

1. For Phase 1: Patient must have relapsed or refractory B-cell NHL (with the exceptionof Burkitt lymphoma and lymphoblastic lymphoma) or CLL that has progressed afterstandard therapies, including chemotherapy and anti-CD20 antibody combinations andmolecularly targeted therapies. Patients may also have undergone prior stem celltransplant and/or prior CD19-directed CAR-T cell therapy.

2. For Phase 2: Patient must have the following:

• Arm 1E: Relapsed or refractory DLBCL, including high-grade B-cell lymphoma withMYC and BCL2 and/or BCL6 rearrangements, primary mediastinal large B-celllymphoma and transformed FL. All patients must have progressed after at least 2lines of therapy, including induction therapy with an anthracycline-basedregimen with anti-CD20 antibody, as well as a second systemic therapy. Patientsmay have also received prior stem cell transplant and/or CD19-directed CAR-Ttherapy.

• Arm 2E: Relapsed or refractory FL. All patients must have progressed after atleast 2 lines of therapy. Patients may have also received prior stem celltransplant and/or CD19-directed CAR-T therapy.

• Arm 2E-Basket: Relapsed or refractory B-cell NHL subtypes that have progressedafter available therapies. This "basket" arm will include but is not limited toMCL, MZL, WMG, Burkitt and Burkitt-like lymphoma, and HCL. Patients may havealso received prior stem cell transplant and/or CD19-directed CAR-T therapy.

• Arm 3E: Relapsed or refractory CLL/SLL All patients must have progressed afterprior Bruton's tyrosine kinase (BTK) and/or BCL-2 directed therapy. Patientsmay have also progressed or have been intolerant to prior BTK and anti-CD20antibody therapy. Patients may have also received prior stem cell transplantand/or CD19 CAR-T therapy.

3. For patients treated with prior CD19-directed CAR-T therapy (all arms): relapsedfrom PR or CR of ≥ 3 months' duration with CD19-positive or -negative disease, orrelapsed from PR or CR at any time with CD19-negative disease.

4. For patients treated with prior CD19-directed CAR-T therapy, the peripheral bloodabsolute CD19+ B-cell count, as measured by flow cytometry, has recovered to atleast 20 cells/μl.

5. For patients with NHL, at least 1 measurable lesion according to the revisedInternational Working Group Response Criteria for Malignant Lymphoma. Patients withWaldenstrom macroglobulinemia may qualify for enrollment based on a measurablelesion or an elevated IgM level >0.5 g/dL.

6. For patients with CLL, diagnosis of CLL that meets published diagnostic criteria.Measurable disease is not required.

7. Evidence of CD20 expression on the tumor specimen obtained from the originaldiagnostic biopsy or another tissue biopsy performed prior to enrollment into thisstudy.

8. At least 2 weeks or 5 half-lives, whichever is shorter, have elapsed since any priornon-investigational systemic therapy before the patient's planned leukapheresis,with the exception of prior BTK inhibitor therapy, which can continue until day -6 (1 day prior to lymphodepletion). At least 6 months have elapsed since the lastadministration of bendamustine before patient's planned leukapheresis.

9. Males and females ≥18 years of age at the time of consent.

10. Capable of understanding, willing to comply with, and voluntarily sign and date aninformed consent form prior to the conduct of any study relatedassessments/procedures.

11. Able to adhere to the study visit schedule and other protocol requirements.

12. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

13. Life expectancy of ≥ 16 weeks, as assessed by the Principal Investigator.

14. All patients must meet all of the following laboratory criteria unless, in theopinion of the Investigator, the cytopenias are considered to be the result of bonemarrow infiltration by lymphoma/CLL:

• Absolute neutrophil count (ANC) ≥ 0.75×10e9/L.

• Platelet count ≥ 75×10e9/L.

• Hemoglobin ≥ 8.5 g/dL.

• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < 2.5× theupper limit of normal (ULN).

• Calculated creatinine clearance ≥ 45.0 mL/minute as estimated byCockcroft-Gault formula.

• Total bilirubin ≤ 1.5×upper limit of normal (ULN), unless due to suspectedGilbert's syndrome.

15. Adequate pulmonary function, defined as ≤ Grade 1 dyspnea and oxygen saturation (SaO2) ≥ 92% on room air. If pulmonary function tests (PFTs) are performed based onthe clinical judgment of the treating physician, patients with forced expiratoryvolume in 1 second (FEV1) ≥ 50% of predicted and diffusing capacity for carbonmonoxide (DLCO) (corrected) of ≥ 40% of predicted will be eligible.

16. Left ventricular ejection fraction ≥ 50%, as determined by echocardiography (ECHO)or multi-gated acquisition scan (MUGA).

17. Females of childbearing potential must have a negative serum or urine pregnancy testat screening and a negative serum or urine pregnancy test prior to initiation of thelymphodepletion regimen.

18. If procreative potential exists, patient must agree to use a highly effective methodof contraception from the start of the study until 1 year after the completion oflymphodepletion for females and 4 months after completion of lymphodepletion formales.

Exclusion Criteria:

• Patients who meet ANY of the following criteria will be excluded from the study. Noexemptions will be granted.:

1. Previous treatment with anti-CD20 or anti-CD19 therapy (including antibodies,antibody-drug conjugates [ADCs], bispecific antibodies, etc.) or anyinvestigational agent within 4 weeks before leukapheresis.

2. Concurrent known additional malignancy that is progressing and/or requiresactive treatment. Exceptions include squamous or basal cell carcinoma of theskin, superficial bladder cancer, and prostate cancer not requiring treatment.

3. Presence of active acute or chronic Graft versus Host Disease (GVHD).

4. Active central nervous system (CNS) lymphoma, including primary CNS lymphoma.

5. Corticosteroid dependence on doses greater than physiological replacement,i.e., requirement for prednisone > 7.5 mg/day or hydrocortisone ≥ 12 mg/m2/day.

6. Ongoing prior therapy-related toxicities ≥ Grade 2, according to the CommonToxicity Criteria for Adverse Events (CTCAE), version 5.0, with the exceptionof alopecia or vitiligo or Grade 2 peripheral neuropathy.

7. Active systemic infections, active, uncontrolled coagulation or bleedingdisorders, or other active, uncontrolled major medical illnesses of therespiratory or immune system.

• Simple upper respiratory tract infection, uncomplicated bacterialpharyngitis and/or urinary tract infection are permitted if responding toactive treatment and after consultation with the study Medical Monitor.

8. Cardiac involvement with lymphoma, including pericardial involvement andmalignant pericardial effusion.

9. Significant cardiovascular diseases within the past 6 months includinguncontrolled congestive heart failure (>New York Heart Association class II),myocardial infarction, unstable angina, or uncontrolled arrhythmia. However,patients with ischemic heart disease who have had acute coronary syndrome,myocardial infarction and/or revascularization > 6 months before Screening, whoare without cardiac symptoms, may enroll.

10. Requirement for urgent therapy due to tumor mass effects such as bowelobstruction or blood vessel compression.

11. Documented human immunodeficiency virus (HIV) infection or any form of primaryimmunodeficiency, such as severe combined immunodeficiency disease.

12. Known active infection with hepatitis B, hepatitis C, severe acute respiratorysyndrome coronavirus 2 (SARS-CoV-2), or other viral infections requiringsystemic therapy.

13. History of autoimmune disease (e.g., Crohn's disease, rheumatoid arthritis,systemic lupus) resulting in end organ injury or requiring systemicimmunosuppression/systemic disease modifying agents within the previous 2years.

14. If female, pregnant, planning to become pregnant, or breastfeeding.

15. Any other clinically significant medical disease or condition that, in thePrincipal Investigator's opinion, may interfere with protocol adherence or thepatient's ability to provide informed consent.