This Phase 1b study of DISC-0974 will assess the safety, tolerability, pharmacokinetics (PK) and Pharmacodynamics (PD) of DISC-0974 in adult participants with Non-Dialysis Dependent Chronic Kidney Disease and Anemia.

Inclusion criteria:

1. Aged ≥18 years of age at the time of signing informed consent.

2. Non-dialysis-dependent chronic kidney disease, Stages 2-5, defined as eGFR <90 mL/min/1.73 m2 using the 2021 Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula

3. Hgb <11.0 g/dL

4. Serum ferritin ≥50 μg/L at screening

5. Transferrin saturation ≤35%

6. AST and ALT <2× upper limit of normal (ULN) at screening

7. Total and direct bilirubin <ULN at screening

8. If female, then EITHER postmenopausal, defined as at least 12 months of natural, spontaneous amenorrhea and serum follicle-stimulating hormone >40 mIU/mL at screening, or at least 6 weeks following surgical menopause (bilateral oophorectomy or hysterectomy); OR agreeable to use of highly effective contraception (listed below) on Day 1 (or earlier) for at least 8 weeks after the last dose of study drug:

   • Stable hormonal contraceptive (≥3 months) in conjunction with a barrier method (eg, condom [male or female] or diaphragm)
   • Intrauterine device in place for at least 3 months
   • Tubal ligation or single male partner with vasectomy in conjunction with a barrier method (eg, condom [male or female] or diaphragm)

9. If male with female sexual partner(s) of childbearing potential, agrees to use one of the following acceptable methods of contraception during the study and for at least 8 weeks after the last study drug dose:

   1. Stable hormonal contraceptive (≥3 months; female partner) in conjunction with a barrier method (eg, condom or diaphragm [female partner])
   2. Intrauterine device in place for at least 3 months (female partner)
   3. Surgically sterile hysterectomy, bilateral oophorectomy, or bilateral tubal ligation (female partner) in conjunction with a barrier method (eg, condom [male or female] or diaphragm)
   4. Confirmed successful vasectomy in conjunction with a barrier method (eg, condom [male or female] or diaphragm)

10. Able to understand and provide written informed consent

11. Able to comply with all study procedures

Exclusion Criteria:

1. Treatment within 2 days prior to screening with oral iron or iron-containing supplements. Participants may be considered for the study if they undergo a 2-day washout period prior to signing the informed consent form (ICF) and screening for oral iron or iron-containing supplements. Between screening and 2 days prior to baseline visit, participants may continue oral iron or iron-containing supplements at the discretion of the Investigator, but any study-related lab draws will require a 48-hour washout from oral iron
2. Treatment within 30 days prior to screening with one of the following anemia treatments: blood transfusion, ESAs, or IV iron. Participants may be considered for the study if they undergo a 30-day washout period prior to signing the ICF and screening for erythropoietin-stimulating agents or IV iron
3. Acute dialysis or acute kidney injury within 12 weeks prior to screening or expected need to start dialysis within 24 weeks of screening
4. Hospitalization for a CV, renal, or cardiorenal condition within 30 days prior to screening
5. Positive direct antiglobulin test with reactive eluate at screening or active hemolytic anemia. This test can be performed prior to other screening procedures after the participant is consented for the prescreening testing
6. History of hereditary hemochromatosis
7. History of hemoglobinopathy or intrinsic red blood cell defect associated with anemia
8. History of total splenectomy
9. Hematopoietic stem cell or solid organ transplant within the past 10 years
10. Medical history of anemia from B12 or folate deficiency, infection, or bleeding in the 3 months prior to screening
11. Stroke, myocardial infarction, deep venous thrombosis, pulmonary or arterial embolism within 6 months prior to screening
12. If female, pregnant or breastfeeding
13. Any major surgery within 8 weeks before screening or incomplete recovery from any previous surgery
14. History of malignancy within the last 3 years. The following history/concurrent conditions are allowed: basal or squamous cell carcinoma skin cancer, carcinoma in situ of the cervix, carcinoma in situ of the breast, histologic finding of prostate cancer (T1a or T1b using the tumor, nodes, metastasis [TNM] clinical staging system). A history of completed treatment (medical or surgical) of Stage 1-2 cancers may be permitted with prior Sponsor agreement
15. Participation in any other clinical protocol or investigational study that involves administration of experimental therapy and/or therapeutic devices within 30 days of screening
16. A history or known allergic reaction to any investigational product excipients or history of anaphylaxis to any food or drug
17. History of anti-drug antibody formation
18. History of inadequately controlled heart disease (New York Heart Association Classification 3 or 4) and/or have a known left ventricular ejection fraction <35%
19. Uncontrolled fungal, bacterial, or viral infection (defined as ongoing signs/symptoms related to the infection without improvement, despite appropriate treatment)
20. Human immunodeficiency virus positive, active hepatitis B, or active hepatitis C
21. Uncontrolled diabetes mellitus (defined as diabetes mellitus requiring initiation of insulin therapy within 3 months of screening)
22. Significant medical condition, laboratory abnormality, or psychiatric condition that would prevent the patient from participating in the study
23. Any condition or concomitant medication that would confound the ability to interpret data from the study

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)