RTX001 Autologous Engineered Macrophages for Liver Cirrhosis

Individuals eligible to participate in this study must meet the following criteria:

Inclusion Criteria:

1. Male or female age ≥18-75 years.

2. Patient confirms willingness/ability to comply with all study procedures.

3. Diagnosis of liver cirrhosis based on at least one of:

4. Clinical and radiological features that correlate with a diagnosis ofcirrhosis.

5. Transient elastography (Fibroscan) >15 kPa.

6. Previous liver biopsy confirming histological features of cirrhosis.

7. Aetiology of liver disease of steatotic liver disease including MASLD or Met-ALD orALD a. Participants with alcohol-related liver disease (ALD or Met-ALD) only if they areconfirmed to not be drinking alcohol above Met-ALD limits defined in this protocol. (N.B. No more than 34% of the total treated participants in this protocol will beALD [excludes Met-ALD]).

8. Hospitalised as an inpatient for a recent major hepatic decompensation eventincluding ascites, hepatic encephalopathy, variceal bleed, HRS-AKI or SBP, thisbeing the only hospitalisation for an hepatic decompensation event hospitalisationwithin the last 6 months, and where recent is defined as within 6 weeks of hospitaldischarge.

9. Outpatient: Medically refractory ascites (ONLY), that recurs (i.e., secondtherapeutic LVP) within a 6-month period. Medically refractory ascites is defined bythe repeated (≥2) need for LVP (i.e., therapeutic, not diagnostic) at least once per 8 weeks despite best medical attempts to control the ascites by sodium restrictionand diuretic treatment, as confirmed by the Investigator. Onset is defined as thedate of the second therapeutic LVP.

10. Confirmatory PEth alcohol test <200 ng/ml

11. MELD score of 12-20 taken within two weeks of 'qualifying' decompensation event.

12. No known contradictions to filgrastim or leukapheresis procedure.

13. Contraceptive use by men and women should be consistent with local regulationsregarding the methods of contraception for those participating in clinical studies.

14. Willing and able to give signed informed consent, and if applicable assent.

Participants are excluded from the study if any of the following criteria apply:

Exclusion Criteria:

1. Liver cirrhosis due to:

2. any viral hepatitidies, or

3. autoimmune and cholestatic aetiologies including, but not limited to, primarybiliary cholangitis and primary sclerosing cholangitis.

4. Acute liver disease in the absence of underlying liver cirrhosis, including, but notlimited to, drug induced liver injury.

5. Any current organ failure requiring more than outpatient supportive care, and notassociated with the participant's qualifying hepatic decompensation event.

6. Known splenomegaly ≥16 cm.

7. Thrombocytopenia <50×109/L.

8. Presence or suspicion of any of the following co-morbidities:

9. History of liver transplantation or other organ transplant.

10. ACLF.

11. Sepsis (with positive microbial cultures) or as defined by the PrincipalInvestigator, unless stable and is at least 4 weeks after having completed afull course of IV antibiotics.

12. Known human immunodeficiency virus.

13. Known syphilis.

14. Known human T-lymphotropic virus 1.

15. Pulmonary embolism.

16. Hepatocellular carcinoma, or any active malignant disease within the last fiveyears, (excluding non-melanoma skin cancer, cervical carcinoma in situ,superficial bladder cancer, benign polyps etc.).

17. Co-hepatic morbidities e.g., portal vein thrombosis.

18. Participants with hepatic hydrothorax are excluded unless it is a smallhydrothorax, not clinically apparent, that is detected incidentally byradiologic evaluation that does not require clinical intervention.

19. Chronic renal impairment (on dialysis) or unresolved AKI.

20. Acute or chronic heart failure (New York Heart Association Grade III/IV).

21. Porto-pulmonary hypertension.

22. Severe chronic lung disease e.g., chronic obstructive pulmonary disease orinterstitial lung disease where the forced expiratory volume in the firstsecond (FEV1) is less than 50% and/or FEV1/forced vital capacity is less than 60%.

23. Hepatopulmonary syndrome.

24. Previous or current treatment with multiple infusions of albumin fortherapeutic intent. [Use of albumin infusion at the time of large volumeparacentesis for circulatory support is allowed.]

25. Significant untreated/unstable psychiatric disease.

26. Transjugular intrahepatic portosystemic shunt (TIPSS).

27. As judged by the Investigator, any evidence of intercurrent illness that is eitherlife threatening or of clinical significance such that it might limit compliancewith study procedures.

28. Current or planned use of immunomodulators or immunosuppressive medication; note:low doses of corticosteroids up to 10 mg/kg/day prednisone or equivalent arepermitted, or inhaled steroids to manage asthma.

29. Received a gene or cell therapy at any time.

30. Current or planned use of a live attenuated vaccines four weeks or fewer prior toenrolment (and for 3 months after the last administered dose of RTX001).

31. Received any investigational product within the past 6 months, or five half-lives (whichever is longer) or participated in another investigational interventionalstudy within 30 days prior to the screening visit.

32. Participants with a known hypersensitivity to dimethyl sulfoxide (DMSO).

33. Judgment by the Investigator that the participant should not participate in thestudy if the participant is unlikely to comply with study procedures, restrictionsand requirements.

34. For female participants only - pregnant or breast-feeding or plans to becomepregnant over the next year, or of childbearing potential and unwilling to complywith contraceptive requirements.

35. Alcohol misuse in the period between identification of the participant aspotentially suitable for this study to Screening (Visit 1), defined as alcoholintake greater than three units/day for females and four units/day for males, orbinge drinking (>14 units/day) as determined by the Investigator. N.B. One unit isequivalent to 14 g of alcohol: a half-pint (~240 mL) of beer, one glass (125 mL) ofwine or one (25 mL) measure of spirits.

36. Intake of non-medically supervised drugs of abuse that are judged (by theInvestigator) to be a high risk to the participants acute health or which makes theparticipant likely to be non-compliant with follow-up.