A Study to Evaluate Long-term Safety in Participants Who Have Participated in Other Luspatercept (ACE-536) Clinical Trials

Inclusion Criteria:

Participants must meet all the following criteria to be enrolled in this study:

1. Participant is ≥ 18 years at the time of signing the informed consent form (ICF).

2. Participant is willing and able to adhere to the study visit schedule and otherprotocol requirements.

3. Participant has been participating in a luspatercept trial and continues to fulfillall the requirements of the parent protocol and the participant has been either:

4. Assigned to luspatercept treatment, continues to receive clinical benefit inthe opinion of the investigator and should continue to receive luspatercepttreatment, OR

5. Assigned to placebo arm in the parent protocol (at the time of unblinding or infollow-up) and should cross over to luspatercept treatment, OR

6. Assigned to the Follow-up Phase of the parent protocol, previously treated withluspatercept or placebo in the parent protocol who shall continue into LTPTFUphase in the rollover study until the follow-up commitments are met (unlessrequirements are met as per parent protocol to crossover to luspatercepttreatment).

7. Participant understands and voluntarily signs an informed consent document prior toany study-related assessments or procedures being conducted.

8. Participant demonstrates compliance, as assessed by the investigator, with theparent study protocol requirements.

9. Applies to on treatment Participants only- females of childbearing potential (FCBP)defined as a sexually mature woman who:

1. has achieved menarche at some point, 2) has not undergone a hysterectomy orbilateral oophorectomy, or 3) has not been naturally postmenopausal (amenorrheafollowing cancer therapy or amenorrhea due to other medical reasons does not ruleout childbearing potential) for at least 24 consecutive months (ie, has had mensesat any time in the preceding 24 consecutive months) must:

1. Have two negative pregnancy tests as verified by the investigator prior to startingstudy therapy. She must agree to ongoing pregnancy testing during the course of thestudy, and after end of study therapy. This applies even if the participantpractices true abstinence from heterosexual contact.

2. Agrees to use, and be able to comply with highly effective, contraception withoutinterruption, 35 days prior to starting investigational product (IP), during thestudy therapy (including dose interruptions), and for 84 days after discontinuationof study therapy.

3. Applies to on treatment participants only- Male participants must:

a. Agrees to use a condom during sexual contact with a pregnant female or a female of childbearing potential while participating in the study, during dose interruptions and for at least 84 days following investigational product discontinuation even if he has undergone a successful vasectomy.

Exclusion Criteria:

The presence of any of the following will exclude a participant from enrollment:

1. Applies to on treatment participants only- Concomitant use of anymedications/procedures that are prohibited in the parent luspatercept protocol.

2. Participant has met one or more criteria for study discontinuation as stipulated inthe parent luspatercept protocol.

3. Applies to on treatment participants only- More than 26 days between lastluspatercept dose in the parent protocol and first dose into ACE-536-LTFU-001protocol unless dose delay or dose discontinuation criteria met.

4. Applies to on treatment participants only- Pregnant or breastfeeding females.

5. Participant has any significant medical condition, laboratory abnormality,psychiatric illness, or is considered vulnerable by local regulations (eg,imprisoned or institutionalized) that would prevent the subject from participatingin the study.

6. Participant has any condition including the presence of laboratory abnormalities,which places the subject at unacceptable risk if he/she were to participate in thestudy.

7. Participant has any condition that confounds the ability to interpret data from thestudy.