Study of Dutogliptin in Combination With Filgrastim in Post-Myocardial Infarction

Dutogliptin 60 mg administered by twice daily subcutaneous (SC) injection for 14 days in
combination with a fixed standard dose of filgrastim (10 µg/kg) administered SC daily for 5
days. This study will be conducted in adults with ST-elevation myocardial infarction (STEMI)
with successful revascularization following percutaneous coronary intervention (PCI) and
stent implantation.

Primary Objective

• To evaluate the safety and tolerability of dutogliptin in combination with filgrastim in
subjects with STEMI compared with placebo

Secondary Objectives

- To assess preliminary efficacy of dutogliptin in combination with filgrastim in subjects
with STEMI compared with placebo as determined by cardiac magnetic resonance imaging
(cMRI)

- To determine the pharmacokinetics (PK) of dutogliptin in a subset of the study
population

- To establish the pharmacodynamics (PD) of dutogliptin (plasma DPP4 activity) in a subset
of the study population

Exploratory Objectives

- To examine the effects of dutogliptin in combination with filgrastim on:

- Change from baseline in plasma stromal cell-derived factor (SDF)-1a levels

- Change from baseline in plasma biomarkers, including N-terminal pro-b-type natriuretic
peptide (NT-proBNP) and high sensitivity troponin

Inclusion Criteria:

1. 1. Male or female born between 1933 and 2000.

2. Body weight <96 kg (212 lb).

3. Able to provide written informed consent, including signing and dating the informed
consent form (ICF).

4. Diagnosis of STEMI (defined as new ST-segment elevation at the J point of at least 2
continuous leads of >2 mm [0.2 mV] in men or >1.5 mm [0.1 mV] in women in leads V2 and
V3 OR >1 mm in any other contiguous precordial leads or the limb leads [for both men
and women]) with PCI (bare metal or drug-eluting stent) and Thrombolysis in Myocardial
Infarction flow grade 2 or 3 occurring >2 hours and <24 hours after symptom onset.

5. LVEF ≤45% obtained by cECHO performed within 36 hours post-stent placement.

6. Receiving standard medical therapy for post-MI treatment, according to local
procedures and Principal Investigator discretion

7. Female subjects of childbearing potential must have a negative serum pregnancy test at
Screening and an additional negative urine pregnancy test prior to the first dose of
IMP unless regulated differently by national legislation.

8. Sexually active female subjects of childbearing potential (i.e., women who are not
postmenopausal or who have not had a bilateral oophorectomy, hysterectomy, or tubal
ligation) and all male subjects (who have not been surgically sterilized by vasectomy)
must agree to use effective contraception during the study.

Exclusion criteria

1. Previous MI prior to Screening.

2. Complex peri/post-MI clinical course, including arrhythmias, cardiogenic shock,
pulmonary edema requiring mechanical ventilation, or requirement for vasopressor
medications.

3. Significant pre-existing cardiomyopathy with known LVEF ≤45% or moderate to severe
mitral or aortic valvular disease.

4. Amyloidosis, hypertrophic obstructive cardiomyopathy, restrictive cardiomyopathy, or
constrictive pericarditis.

5. Existing heart transplant.

6. Ventricular tachycardia or fibrillation not associated with an acute ischemic episode.

7. Uncontrolled hypertension (systolic >180 mmHg or diastolic >120 mmHg).

8. Treatment with any DPP4 inhibitors (e.g., alogliptin, linagliptin, vildagliptin,
saxagliptin, sitagliptin) or G-CSF medication (e.g., filgrastim, lenograstim,
pegfilgrastim, lipegfilgrastim) within 4 months prior to Randomization.

9. Contraindication to treatment with filgrastim, including known allergy to filgrastim
or other G-CSF medication.

10. Anemia defined as hemoglobin <9 g/dL prior to Randomization.

11. Thrombocytosis (platelets >500 k/µL).

12. Known positive serology for hepatitis B, hepatitis C, or human immunodeficiency virus
(HIV).

13. Alanine aminotransferase (ALT) concentrations >3 times the upper limit of normal (ULN)
or bilirubin >2 x ULN prior to Randomization, according to local laboratory
assessments.

14. History of cirrhosis and Child-Pugh score B or C.

15. Current fever greater than 101.4 °F (38.6 °C) or recent systemic infection within 2
weeks prior to Randomization.

16. Contraindication to cMRI procedure, including prior implantable cardioverter
defibrillator placement, known reaction to gadolinium, claustrophobia,
non-MRI-compatible, cochlear implant, morbid obesity, or presence of ferromagnetic
material including shunts, shrapnel, penile prostheses, or blood vessel coil.

17. Pregnant, planning to become pregnant, or nursing female subjects.

18. Autoimmune disease requiring immunosuppressive therapy or chronic steroid treatment >5
mg/day prednisolone or equivalent.

19. Significant renal impairment defined as estimated glomerular filtration rate <45
mL/min/1.73 m2, using the Chronic Kidney Disease Epidemiology Collaboration equation.

20. Active neoplasm requiring surgery, chemotherapy, or radiation within the prior 12
months (subjects with a history of malignancy who have undergone curative resection or
otherwise not requiring treatment for at least 12 months prior to Screening with no
detectable recurrence are allowed).

21. Malignant hematological disease, i.e., chronic myeloid leukemia or myelodysplastic
syndrome.

22. History of cerebrovascular accident or transient ischemic attack in the past 6 months.

23. History of pneumonia in the last 4 weeks.

24. History of any significant medical or psychiatric disorder that in the opinion of the
investigator would make the subject unsuitable for participation in the study.

25. Treatment with an investigational drug within 30 days or 5 half-lives (whichever is
longer) or treatment with an investigational biologic drug within 6 weeks prior to
randomization.

26. Participation in another concurrent clinical trial involving a therapeutic
intervention (participation in observational studies and/or registry studies is
permitted).

27. Unable or unwilling to comply with the requirements of the study.

28. Subject and/or an immediate family member is an employee of the investigational site
directly affiliated with this study, the sponsor or the contract research
organization.

29. Considered by the investigator to be unsuitable to participate in the study for any
other reason.

30. Persons who are in an institution as a result of an administrative or judicial order,
or soldiers.

31. History of alcohol or drug abuse.