Inclusion Criteria:

          -  Written informed consent

          -  Age ≥ 18 years

          -  Diagnosis of MDS (de novo or secondary) by bone marrow aspirate based on the World
             Health Organization (WHO) classification - Low and Intermediate-1 risk categories MDS
             using the IPSS (International Prognostic Scoring System)

          -  AZA/decitabine (this applies to standard of care and investigational drugs) failure
             (Dose confirming and Dose expansion parts):

          -  defined as discontinuation due to any of the following:

               -  Lack of response after at least 4 cycles

               -  Loss of response (patient must have received therapy for at least 4 cycles)

               -  Progressive disease

               -  Adverse events

        Note: Patients are eligible if additionally they have failed an ESA

          -  HMA Naïve group:

               -  Never received a hypomethylating agent for MDS

               -  Failed or ceased to respond to ESA(s)

               -  ESA ineligible; defined as endogenous serum erythropoietin level > 200 U/L for
                  subjects not previously treated with ESAs

          -  Red blood cell transfusion dependent defined as ≥ 2 Red blood cells (RBC) units
             required in the 8 weeks prior to starting in the study. In addition, there should be
             no 8 consecutive weeks without red blood cell transfusions in the 16 weeks prior to
             enrolment.

          -  Life expectancy ≥ 3 months

          -  Eastern Cooperative Oncology Group (ECOG) performance status Grade 0-2

          -  Serum bilirubin levels ≤2 x upper limits of normal (ULN)

          -  Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels ≤2.5
             x ULN

          -  Del 5q patients who have failed or are not eligible for Revlimid

          -  Creatinine clearance >30 ml/min calculated by the Cockcroft-Gault formula

          -  Willingness to comply with the protocol procedures for the duration of the study,
             including scheduled follow-up visits and examinations

          -  Negative urine β-human chorionic gonadotropin (β-HCG) pregnancy test for fertile women
             at screening and confirmed by serum pregnancy test in the 48 hours prior to OPN-305
             administration

          -  If sexually active female, patient must be/have one of the following:

          -  Post-menopausal defined as the absence of menses for at least one year (serum
             Follicle-stimulating hormone (FSH) ≥20IU/L can also be measured according to local
             practice),OR

          -  Surgically sterile defined as a bilateral tubal ligation at least 6 months prior to
             administration of study drug, bilateral oophorectomy, or complete hysterectomy, OR

          -  Using an effective means of contraception that is planned to continue for the duration
             of treatment and for a further 3 months.

          -  If sexually active male, patient must: Agree to use an effective means of
             contraception (per site-specific guidelines) that is planned to continue until 6
             months after the last dose of OPN-305.Agree not to donate sperm until 6 months after
             the last dose of OPN-305

        Exclusion Criteria:

          -  Diagnosis of MDS by bone marrow aspirate of Intermediate-2 and High risk category MDS
             based on the World Health Organization (WHO) classification using the IPSS
             (International Prognostic Scoring System)

          -  Patients with 5q deletion (del) MDS eligible for Revlimid (lenalidomide)

          -  Hypomethylating agent (HMA) Naïve group:

               -  Have received a hypomethylating agent for MDS

               -  Have not failed or ceased to respond to an ESA

               -  Are not ESA ineligible as defined in inclusion criteria

          -  Prior history of acute leukemia or AML

          -  Unable/unwilling to undergo bone marrow sampling

          -  Prior history of bone marrow transplantation

          -  Prior malignancy (other than non-invasive malignancy including in situ cervical
             cancer, Bowen's disease, basal cell cancer of the skin and non-invasive or excised
             skin squamous cell carcinoma) unless treated with curative intent and without evidence
             of disease for 3 years before randomization

          -  Active viral or bacterial infections: this includes any infections that are being
             actively treated even if the signs and symptoms appear to have resolved. Courses of
             antibiotics or anti-viral treatment should be completed before the patients is
             enrolled

          -  Unstable angina, congestive heart failure [NYHA (New York Heart Association) >class
             II], uncontrolled hypertension [diastolic > 100 mmHg], uncontrolled cardiac
             arrhythmia, or recent (within 1 year) myocardial infarction, uncontrolled diabetes
             mellitus

          -  Clinical Evidence of Central Nervous System (CNS) disease

          -  Less than 4 weeks since any therapy for MDS

          -  Prior history of anaphylaxis to similar products

          -  History or presence of a medical condition or disease or substance abuse that in the
             investigator's assessment would place the patient at an unacceptable risk for study
             participation

          -  Lactating or pregnant woman