A Study of JNJ-88549968 for the Treatment of Calreticulin (CALR)-Mutated Myeloproliferative Neoplasms

Inclusion Criteria:

• Be greater than or equal to (>=) 18 years of age (or the legal age of majority inthe jurisdiction in which the study is taking place, whichever the greater) at thetime of informed consent

• Positive for a calreticulin (CALR) driver mutation of essential thrombocythemia (ET)or myelofibrosis (MF)

• Participants with ET and MF with risk characteristics as described in the protocol

• Have an Eastern Cooperative Oncology Group (ECOG) performance status grade of lessthan or equal to (<=) 2

• For US sites: Eligible for ruxolitinib therapy as per drug label for participantsnaive to a janus kinase (JAK) inhibitor

Exclusion Criteria:

• Known allergies, hypersensitivity, or intolerance to the excipients of the studytreatment

• Concurrent or recently diagnosed or treated malignancies present at the time ofparticipant screening. Exceptions are squamous and basal cell carcinoma of the skin,carcinoma in situ of the cervix, and any malignancy that is considered cured or hasminimal risk of recurrence within 1 year of first dose of study treatment in theopinion of both the investigator and sponsor's medical monitor. Participants curedof another malignant disease with no sign of relapse greater than or equal to (>=) 3years after treatment ended are allowed to enter the study

• Prior solid organ transplantation

• Either of the following regarding hematopoietic stem cell transplantation:

1. Prior treatment with allogenic stem cell transplant less than or equal to (<=) 6 months before the first dose of JNJ-88549968 or

2. Evidence of graft versus host disease (GVHD) that requires immunosuppressanttherapy

• History of clinically significant cardiovascular disease within 6 months prior tothe first dose of study treatment