Efficacy and Safety of Pozelimab and Cemdisiran Combination Therapy in Patients With Sporadic Inclusion Body Myositis

Inclusion Criteria:

• 1. Age ≥45 years to 75 years of age 2. Diagnosed with sIBM based on the ENMC IBMResearch Diagnostic Criteria 3. Willing and able to comply with clinic visits andstudy-related procedures. 4. Provide informed consent signed by the study patient orlegally acceptable representative.

5. Able to understand and complete study-related questionnaires. 6. Able to ambulateat least 20 ft/6 meters with or without assistive device Once arising from thechair, the participant may use any walking device, i.e. walker/frame, cane,crutches, or braces. They cannot be supported by another person and cannot usefurniture or walls for support.

6. If female, the subject must be: (a) surgically sterilized via hysterectomy,bilateral oophorectomy, or bilateral tubal ligation. or (b) of childbearingpotential and using a birth control method, such as:

•Combined (estrogen and progestogen-containing) hormonal. contraception associatedwith inhibition of ovulation: o Oral

• Intravaginal

• Transdermal

• Progestogen-only hormonal contraception associated with inhibition ofovulation:

• Oral

• Injectable

• Implantable • Intrauterine device • Intrauterine hormone-releasing system • Bilateral tubal occlusion

• Vasectomized partner

• Sexual abstinence or of non-childbearing potential (i.e., no menses for ≥12 consecutive months without any other underlying medical cause) Thesubject must agree to continue using her selected method of birth controlwith her sexual partner during the study and for 120 days after studycompletion.

8. If male, the subject must have had a vasectomy or must use a reliablemethod of birth control with their partner or maintain total abstinencefrom sexual intercourse. The subject must agree to continue using hisselected method of birth control with his sexual partner during the studyand for 120 days after the study completion.

Exclusion Criteria:

• 1. Other neurological conditions (e.g., hemiplegia post-stroke, Parkinson's Disease)or musculoskeletal conditions (e.g., severe osteoarthritis) causing mobilityimpairment.

2. Any known active malignancy 3. Significant illness or history of significantillness that, in the investigator's opinion, may adversely affect the patient'sparticipation in this study.

3. Any previous treatment with a complement inhibitor 5. History of meningococcaldisease 6. No documented meningococcal and pneumococcal vaccination within 5 yearsprior to screening visit unless vaccination will be administered during thescreening period and prior to initiation of study treatment.

4. Known contraindication to meningococcal (group ACWY conjugate and group Bvaccines) and pneumococcal vaccines.

5. Subject unwilling to receive meningococcal and pneumococcal vaccinations. 9.Patients with screening serum ALT levels >3×ULN and/or total bilirubin >2×ULN (unless bilirubin elevation is due to suspected Gilbert's syndrome).

6. Active or recent systemic infection within 2 weeks prior to Baseline. 11.Pregnant, planning to become pregnant, or lactating female subjects. 12. Treatmentwith an experimental drug within 30 days or 5 half-lives of the experimental drug.

7. Participation in another concurrent interventional clinical trial. 14. Subjectswith functional and anatomic asplenia 15. Subjects with positive tests for hepatitisB, hepatitis C, or HIV at screening 16. Presence of active or latent tuberculosis

8. Presence of any other form of myositis or myopathy or myositis overlap withother autoimmune diseases 18. Presence of other autoimmune or autoinflammatorydiseases