Phase I Study of an Oncofetal Antigen Multi-Peptide Immunotherapy in Subjects With Hematologic Cancer

The current study is a Phase I, open-label, multi-center, dose escalation study designed to
evaluate safety, immunogencity, and potential anti-tumor activity of BB-MPI-03 at three
peptide plus adjuvant dose levels. Subjects with acute myelogenous leukemia (AML), multiple
myeloma (MM), smoldering multiple myeloma (sMM), or myelodysplastic syndrome (MDS) who are
off treatment and with stable disease or better or who are not eligible for or refuse
allogeneic hematopoietic stem cell transplantation (HSCT) are to be enrolled. The study will
be conducted at 2 to 4 study centers in the United States (US).

The study employs a sequential group, open-label, 3+3 dose- escalation design to determine
the safety and MTD of BB- MPI-03.

Inclusion Criteria

a. History of morphologically confirmed AML w/ classification other than WHO Acute
Promyelocytic Leukemia (FAB M3), based on bone marrow examination.

i. not a candidate for allogeneic HSCT or no intention to move to HSCT at time of
enrollment.

ii. Patient's AML could be in morphologic CR or no further cytotoxic chemotherapy is
currently being considered.

iii. Completed consolidation chemotherapy, if available and/or appropriate for patient.

iv. Can have history of allogeneic HSCT transplant, but must be off immunosuppression for
at least 2 wks. before enrollment and w/o GVHD and/or toxicities from HSCT.

b. Diagnosed in past 5 years w/ smoldering MM at high risk of progressing to symptomatic
MM.

i. Diagnosis defined as: Bone marrow infiltration with plasma cells (PCs) ≥10% and
presence of a monoclonal component, Ig G ≥3 g/dl or IgA ≥2 g/dl or Bence-Jones proteinuria
>1 g/dl and absence of lytic lesions on skeletal survey, absence of hypercalcemia
(corrected calcium <11 mg/dl), absence of renal failure (creatinine ≤1.5 x ULN), and
absence of anemia (hemoglobin >10 g/dl or not 2 g/dl below LLN).

ii. Must meet one of following:

- ≥10% PCs in bone marrow and IgG ≥3 g/dl or IgA ≥2 g/dl,

- ≥10% PCs in bone marrow and serum FLC ratio (involved : uninvolved) >100 in blood, or

- IgG ≥3 g/dl or IgA ≥2 g/dl and FLC ratio (involved: uninvolved) >100 in blood. c. MM
post-treatment disease that is clinically stable and does not require treatment at
least 4 weeks prior to enrollment.

i. At least one line of treatment and achieved at least PR by IMWG ii. Stable disease
or better per IMWG based on 2 subsequent assessments at least one month apart d.
history of morphologically confirmed MDS i. previously received at least one
treatment for MDS, including but not limited to chemotherapy or hypomethylating
agent(s). Subjects may be previously untreated if they refuse treatment with or are
not appropriate candidates for chemotherapy or hypomethylating agent(s) in the
investigator's opinion.

ii. intermediate, high, or very high risk MDS by IPSS-r iii. No curative intent option of
allogeneic HSCT or refused consideration for allogeneic HSCT iv. Could have history of
allogeneic HSCT transplant and relapsed, but must be off immunosuppression for at least 2
weeks before enrollment and without GVHD and/or toxicities from HSCT.

2. Low, moderate, to high levels of OFA expression by IHC analysis of tumor specimens.

3. HLA-A*02 haplotype.

4. ECOG performance status 0 to 2.

5. 18 years or older.

6. life expectancy ≥3 months.

7. Has following laboratory parameters w/in 28 days:

- ANC ≥500/mm3

- ALC >500/mm3

- PLT ≥25,000/mm3 and may be transfused

- Hgb >8 g/dL (may have been transfused)

- Serum creatinine ≤1.5 x ULN

- Total bilirubin ≤2.0 mg/dL, unless elevated bilirubin due to Gilbert's syndrome

- ALT and AST less than 5×ULN

8. If female of child-bearing potential, negative serum pregnancy test result w/in 28
of D1 and agree to abstain from heterosexual intercourse or use acceptable method of
birth control (hormonal or barrier method) from Screening through 30 days after last
dose

9. If male having sexual contact with a female of child-bearing potential, agrees to
use a latex condom dor agrees to ensure partner uses an acceptable method of birth
control (hormonal or barrier method)from Screening through 30 days after last dose

10. Able to provide written informed consent

Exclusion Criteria

1. Received chemotherapy, biological therapy, or radiation therapy less than one month
before D1

2. No prior history of active CNS involvement

3. Grade 2 or higher peripheral neuropathy w/in 28 days

4. Acute promyelocytic leukemia (FAB M3)

5. Other active systemic malignancy treated w/ cytotoxic chemotherapy in previous 12
mos.

6. Monoclonal gammopathy of undetermined significance

7. For smoldering MM, baseline bone lesions or plasmacytomas

8. For smoldering MM, lytic lesions on skeletal surveys and hypercalcemia (i.e., ≥11
mg/dL)

9. Known HIV or hepatitis virus infection

10. Active infection requiring antibiotics

11. History of prior or active autoimmune disease such as Lupus or rheumatoid arthritis

12. Significant kidney or liver disease, uncontrolled severe cardiovascular or pulmonary
disease, other uncontrolled medical condition that would compromise subject's ability
to tolerate study treatment

13. Received any investigational treatment w/in 30 days

14. Receiving systemic glucocorticosteroid >10 mg daily. Concurrent use after
registration on study should be restricted to equivalent of prednisone 10 mg per day.
Prior or concurrent topical or localized glucocorticosteroid therapy to treat
non-malignant comorbid disorders is permitted. Subject requiring routine use of
steroid inhalers are not eligible.

15. Major surgery w/in 4 wks.

16. G-CSF w/in 30 days