Nasal Foralumab in Patients with Non-Active Secondary Progressive Multiple Sclerosis

Inclusion Criteria:

• Subjects must have enrolled in and successfully completed TILS-021 within thepreceding 90 days, including End of Treatment and End of Study assessments.

• Screening clinical laboratory studies are within the normal ranges or within theparameters specified below, and clinically acceptable in the opinion of theInvestigator. Exceptions must be approved by the Clinical Research Organization orSponsor's Medical Monitor.

• Adequate hematologic parameters without ongoing transfusion support:

1. Hemoglobin (Hb) ≥ 9 g/dL

2. Platelets ≥ 100 x 109 cells/L

• Creatinine ≤ 1.5 x the upper limit of normal (ULN), or calculated creatinineclearance ≥60 mL/minute x 1.73 m2 per the Cockcroft-Gault formula

• Total bilirubin ≤ 1.5 times the ULN unless due to Gilbert's disease.

• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.0 times ULN.

• Negative urine pregnancy test within 7 days prior to the first dose of study therapyfor women of childbearing potential, defined as a sexually mature woman who has notundergone a hysterectomy or who has not been naturally postmenopausal for at least 24 consecutive months (i.e., who has had menses any time in the preceding 24consecutive months).

• Sexually active women of childbearing potential and male patients must agree to usetwo effective methods to avoid pregnancy (oral, injectable, or implantable hormonalcontraceptives; tubal ligation; intra-uterine device; barrier contraceptive withspermicide; or vasectomized partner) throughout the study, and for 90 days after thecompletion of study treatment.

• Immunizations are current and up to date as adjusted for disease status andprior/current treatments and documented by the subject's treating neurologist.

• Ability and willingness to provide written informed consent.

Exclusion Criteria:

• Subjects that terminated TILS-021 early as defined as not undergoing an End ofTreatment visit.

• Subjects that terminated TILS-021 early as defined as not undergoing an End of Studyvisit.

• Subjects that terminated TILS-021 due to any adverse events.

• Corticosteroid use (oral or intravenous) within the last 60 days or anticipated needfor such treatment during the study period.

• Current use or use within 30 days prior to the Screening Visit of interferon,glatiramer acetate, fingolimod, siponimod, dimethyl fumarate, ponesimod, ozanimod,cyclosporin, methotrexate, azathioprine, mycophenolate mofetil, natalizumab or anyother chronic immunosuppressive medication. Concomitant immunomodulatory orimmunosuppressant treatments for MS are not permitted during study participation.

• Patient in whom the need to start or stop other pharmacologic treatment for MS isexpected during the time of the study or the need for initiation of B cell depletingtherapies (e.g.: ocrelizumab, ofatumumab, ublituximab, rituximab) during the study.

• Use of B cell depleting therapies (e.g.: ocrelizumab, ofatumumab, ublituximab,rituximab) at any time during study TILS-021 or after the patient has completedTILS-021 is not permitted.

• Subjects with any previous exposure to alemtuzumab, cyclophosphamide, cladribine,mitoxantrone, or daclizumab.

• Prior use of autologous hematopoietic stem cell transplantation or stem celltherapy.

• Nasal corticosteroids, nasal antihistamines, nasal flu dosing within the past 60days.

• Active COVID-19 disease; according to FDA guidelines.

• Female patient who is pregnant, lactating, breastfeeding, or planning on becomingpregnant during the study. Female patients of childbearing age will undergo a serumpregnancy test at Screening, but prior to receiving their first dose, and beexcluded from the study if positive. Urine pregnancy testing will be carried outprior to each dosing cycle, and the subject's study participation will be stopped ifthere is a positive result. Pregnancy testing will also be performed prior to eachMRI imaging session and participation in the imaging session and the study will beterminated if positive.

• Any history of malignancy or active malignancy. This includes any skin cancers atany time.

• Inflammatory bowel disease, rheumatoid arthritis, systemic lupus erythematosus,asthma, or type 1 diabetes.

• Patients with a history of gadolinium allergy/contraindications or any othercontraindications to MRI, such as metal implants, chronic renal disease and an eGRFof <30 mL/minute or claustrophobia. Or who are unable to lay flat in the PET or MRIscanner for the duration of the studies.

• Known positivity for human immunodeficiency virus, hepatitis B virus surface antigen (HBsAg), or hepatitis C virus or tuberculosis at Screening. If the subject has ahistory of positivity for any of these diseases, they are excluded even if currentScreening is negative.

• Any nasal pathology such as clinically significant deviated septum, nasal polyps,chronic rhinitis, or a history of sinusitis diagnosed or treated in the past 12months.

• Clinically significant cardiac condition or ECG abnormality at Screening or byhistory. An ECG will be done prior to each dosing cycle and patients will beexcluded or treatment discontinued for any significant ECG abnormality.

• Any other medical intervention or other condition which, in the opinion of thePrincipal Investigator, could compromise adherence to study requirements or confoundthe interpretation of study results.

• Other than nasal foralumab, receipt of an investigational drug/biological product inthe past 30 days of Screening, or concurrent receipt of an investigational drugduring this study, other than the product under study.