A Study to Investigate Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of AZD5492 in Adult Participants With Systemic Lupus Erythematosus or Idiopathic Inflammatory Myopathies.

Inclusion Criteria:

1. Participant must be 18 to 65 years of age inclusive, at the time of signing theinformed consent.

2. Diagnosis of SLE:

3. Diagnosis of SLE according to the 2019 EULAR/ACR classification criteria forSLE

4. Positive for one or more of: anti-nuclear antibodies (titre ≥ 1:80), anti-dsDNAor anti-Sm performed by the central laboratory at screening. If anti-dsDNA oranti- Sm tests are negative, documented history of test results may be used.

5. Active, moderate-severe disease at screening, defined as clinical SLEDAI-2K ≥

7. Intolerance or inadequate response to ≥ 3 available treatments, used for atleast 3 months each, such as the following: corticosteroids, anti-malarialdrugs, calcineurin inhibitor, methotrexate, azathioprine, leflunomide,mycophenolic acid or its derivatives, cyclophosphamide, belimumab, anifrolumab,or B-cell depleting monoclonal antibodies.

8. Diagnosis of IIM:

9. Must have "probable" or "definite" diagnosis of PM or DM (excluding IBM andcancer associated myositis) according to the 2017 EULAR/ACR classificationcriteria for adult myositis.

10. Positive for ≥ 1 disease-specific autoantibody performed by the centrallaboratory at screening.

11. MMT-8 score of ≤ 142/150.

12. Fulfill at least one of the following criteria of active disease at screening:

(i) One or more muscle enzyme elevation (CK, AST, ALT, aldolase, LDH) ≥ 1.3 × ULN (ii) If criterion 3(d)(i) is not met, then at least one of the following criteriamust be met: a. Report from MRI performed within 3 months prior to screening with evidence ofmuscle inflammation b. Report from muscle biopsy performed within 3 months prior toscreening that demonstrates active inflammation c. Report from electromyographyperformed within 3 months prior to screening that exhibits irritable myopathicpattern.

(e) Intolerance or inadequate response to corticosteroids and ≥2 of the followingtreatments, used for at least 3 months each: calcineurin inhibitor, methotrexate,azathioprine, leflunomide, mycophenolic acid or its derivatives, cyclophosphamide,intravenous immunoglobulin (IVIG), or B-cell depleting monoclonal antibodies.

4. Must be receiving one of the following therapy regimens at screening:

5. Oral prednisolone (or equivalent) without additional immunosuppressivemedication: Daily dose between 7.5 mg and 20 mg (inclusive) a day for ≥ 2months prior to signing the ICF. Dose must be stable for ≥ 2 weeks prior tosigning the ICF.

6. Immunosuppressive treatment with one of the following medications, at a stabledose for ≥ 3 months prior to signing the ICF:

(i) Methotrexate ≤ 25 mg/week, without change of route of administration for 8 weeksprior to signing the ICF. (ii) Mycophenolate mofetil ≤ 2g/day (iii) Azathioprine ≤ 200 mg/day (iv) Leflunomide ≤ 15 mg/ day (v) Tacrolimus ≤ 0.1 mg/kg/day with maximumdose of 5 mg/day (vi) Cyclosporin ≤ 3 mg/kg/day with maximum dose of 200 mg/day

5. Blood B-cells above 50 cells/μL at screening.

6. IgG levels > 6g/L at screening.

Exclusion Criteria:

1. Any complications of the disease under study which are judged by the investigator tobe life or organ threatening or to require treatments which are not permitted in theprotocol, including but not limited to:

2. Active severe SLE-driven renal disease.

3. History of, or current diagnosis of, catastrophic or severe APS (for examplediagnosis of an arterial or central/pulmonary venous clot) within 1 year priorto signing the ICF. Participants with clinically evident APS which isadequately controlled by anticoagulants or aspirin for at least 12 weeks can berecruited into the study.

4. Rapidly progressive and/or severe ILD or ILD that requires oxygensupplementation/therapy (of any type).

5. Inclusion Body Myositis or cancer associated myositis.

6. Active severe, unstable or history of neuropsychiatric SLE including, but notlimited to: aseptic meningitis; cerebral vasculitis; myelopathy; demyelinationsyndromes (ascending, transverse, acute inflammatory demyelinatingpolyradiculopathy); acute confusional state; impaired level of consciousness;psychosis; acute stroke or stroke syndrome; cranial neuropathy; status epilepticus;cerebral ataxia' and mononeuritis multiplex.

7. IIM: Pulmonary function tests at screening (or within one month of screening,provided participant confirms no change in respiratory symptoms in the interim)which meet any of the following criteria:

8. FVC ≤60% of predicted

9. DLCO ≤70% of predicted

10. Deterioration in either FVC or DLCO at screening compared to pulmonary functiontests performed ≥3 months previously. 4 Infections

11. Any clinical suspicion or diagnosis of active infection at screening.

12. Opportunistic infection that meets criteria to be an SAE within 3 years.

13. Clinically significant chronic infection (eg, osteomyelitis, bronchiectasis)with treatment completed less than 2 months prior to signing the ICF (exceptfor chronic nail infections, which are allowed).

14. Any history of infection requiring:

(i) Hospitalisation within the previous two months (ii) Treatment with IVanti-infectives with treatment completed less than 4 weeks prior to signing the ICF (iii) Oral anti-infectives within 2 weeks prior to signing the ICF. (e) History ofrecurrent infection requiring hospitalisation or IV antibiotics eg 3 or more of thesame type of infection, including systemic fungal infections, over the previous 52weeks.

5 Participants with HIV infection (confirmed by central laboratory at screening) 6 Participants with active EBV or CMV. 7 Participants with evidence of chronic or active hepatitis B defined as HBsAg positive or HBcAB positive 8 Participants with evidence of chronic or active hepatitis C defined as:

(a) HCV IgM Ab positive (b) Detectable HCV RNA (c) Positive result for HCV IgG Ab is acceptable in the following circumstances: (i) HCV RNA is undetectable >12 weeks after completion of curative antiviral treatment for HCV. (ii) HCV RNA is undetectable on two occasions at least 12 weeks apart following resolution of HCV infection if not treated. 9 Participants with positive COVID-19 PCR. For participants with a positive COVID-19 reverse transcription PCR at screening, rescreening will be conducted not earlier than 6 weeks after the positive result. Only one rescreening is allowed. 10 Known history of a primary immunodeficiency, splenectomy, or any underlying condition that predisposes the participant to infection.

11 CNS pathology including but limited to the following: CNS vasculitis, severe brain injury, dementia, Parkinson's disease, neurodegenerative diseases, cerebellar disease, stroke, seizure disorder/epilepsy, PML, severe uncontrolled mental illness, psychosis, CNS involvement of autoimmune diseases.

12 Receipt of B-cell-depleting therapy including CD19 or CD20 directed monoclonal antibodies (including but not limited to, ocrelizumab, ofatumumab, obinutuzumab, or rituximab) <3 months prior to signing the ICF. If therapy was administered ≥3 months ago, exclude if absolute B-cell less than the lower limit of normal.

13 Prednisolone (or equivalent) > 20 mg within 2 months of signing the ICF.