A Phase I/II Study of OPN-305 in Second-line Lower Risk Myelodysplastic Syndrome

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