A Phase 2 Study of RO7490677 In Participants With Myelofibrosis

Inclusion Criteria:

1. Participants must be ≥18 years of age at the time of signing the Informed Consent Form (ICF);
2. Participants must voluntarily sign an ICF;
3. Participants must have a pathologically confirmed diagnosis of PMF as per the WHO diagnostic criteria or post ET/PV MF;
4. At least Grade 2 marrow fibrosis according to the WHO Grading of Bone Marrow Fibrosis;
5. Intermediate-1, intermediate -2, or high risk disease according to the IWG -MRT Dynamic International Prognostic Scoring System
6. A bone marrow biopsy must be performed within four weeks prior to Cycle 1 Day 1 treatment to establish the baseline fibrosis score;
7. Participants must not be candidates for ruxolitinib based on EITHER:

   1. Platelet count \< 50 x 10e9/L, OR
   2. Hgb \< 100 g/L, have received ≥ 2 units PRBC in the 12 weeks prior to study entry, and be intolerant of or had inadequate response to ruxolitinib;
8. Participants must have an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2. (Appendix F);
9. Life expectancy of at least twelve months;
10. At least four weeks must have elapsed between the last dose of any MF- directed drug treatments for myelofibrosis (including investigational therapies) and study enrollment;
11. Recovery to ≤ Grade 1 or baseline of any toxicities due to prior systemic treatments, excluding alopecia;
12. Women of child bearing potential (WCBP), defined as a sexually mature woman not surgically sterilized or not post-menopausal for at least 24 consecutive months if ≤55 years or 12 months if \>55 years, must have a negative serum pregnancy test within four weeks prior to the first dose of study drug and must agree to use adequate methods of birth control throughout the study. Adequate methods of contraception are outlined in the protocol.
13. Ability to adhere to the study visit schedule and all protocol requirements;
14. Must have adequate organ function as demonstrated by the following:

    * ALT (SGPT) and/or AST (SGOT) ≤ 3x upper limit of normal (ULN), or ≤ 4 x ULN (if upon judgment of the treating physician, it is believed to be due to extramedullary hematopoiesis \[EMH\] related to MF);
    * Direct bilirubin ≤ 1.5 x ULN; or ≤ 2x ULN (if upon judgment of the treating physician, it is believed to be due to EMH related to MF);
    * Serum creatinine ≤ 2.5 mg/dL x ULN.

Exclusion Criteria:

1. White blood cell count \> 25 x 10e9/L or \> 10% peripheral blood blasts;
2. Other invasive malignancies within the last 3 years, except non- melanoma skin cancer and localized cured prostate and cervical cancer;
3. History of stroke, unstable angina, myocardial infarction, or ventricular arrhythmia requiring medication or mechanical control within the last 6 months;
4. Presence of active serious infection;
5. Any serious, unstable medical or psychiatric condition that would prevent, (as judged by the Investigator) the participant from signing the informed consent form or any condition, including the presence of laboratory abnormalities, which places the participant at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study;
6. Known history of human immunodeficiency virus (HIV), or known active hepatitis A, B, or C infection;
7. Organ transplant recipients other than bone marrow transplant;
8. Women who are pregnant or lactating.