Study of PER977 Administered to Subjects With Steady State Edoxaban Dosing and Re-anticoagulation With Edoxaban

This is a randomized, single-blind, sequential group, ascending PER977 reversal dose study in
healthy volunteers. Subjects will be randomized in a 4:1 ratio to receive either PER977 or
placebo. All subjects will receive a single dose of edoxaban 60 mg on Days 1-4. On Days 3 and
4, study drug will be administered 3 hours following edoxaban. Beginning with Cohort 2, study
drug will be administered only to those subjects with a minimum increase in whole blood
clotting time >25% above baseline.

Pharmacokinetic assessment of PER977 and tis metabolite, and edoxaban and its metabolite will
be performed. Pharmacodynamic assessment of WBCT and Point of Care prothrombin time will be
performed. Safety will be assessed throughout the study.

Inclusion Criteria:

1. Adults age 18 to 65 years, inclusive

2. Laboratory values are not clinically significant

3. No clinically significant findings on 12-lead electrocardiogram

4. Body mass index (BMI) 18 to ≤ 32 kg/m2, inclusive

5. Male subjects agree to use appropriate contraception .

6. Female subjects may be post-menopausal or, if of child-bearing potential, must have a
negative serum pregnancy test prior to enrollment, and must agree to use two forms of
acceptable contraception for the duration of the study and for a minimum of one
complete menstrual cycle or 28 days following discharge from the study.

7. Subjects must sign informed consent

Exclusion Criteria:

1. History or current evidence of clinically significant disease, liver function tests
greater than the upper limit of normal (presence of Gilbert's syndrome is acceptable),
QTcF > normal (440±10 msec for males or 460±10 msec for females).

2. History of unexplained syncope

3. History of major bleeding, trauma, surgical procedure of any type, or vaginal delivery
within six months prior to screening

4. History of peptic ulcer, gastrointestinal bleeding, including the mouth, within six
months prior to screening

5. History of minor bleeding episodes such as epistaxis, rectal or hemorrhoidal bleeding
or gingival bleeding within 1 month prior to screening

6. Personal or family history of clotting disorder or abnormality, excessive bleeding,
thrombovascular disease or any hematologic disorder involving platelets or clotting
abnormalities or any condition requiring treatment with transfusions, or history of
heparin-induced thrombocytopenia

7. Females with a history of dysfunctional uterine bleeding, menorrhagia , metrorrhagia
or polymenorrhea

8. Pregnant or breast-feeding

9. Males with a history of hormone therapy within 3 months prior to screening

10. Administration of any blood product or anticoagulant within 3 months prior to study
entry or any non steroidal anti-inflammatory drug or cyclooxygenase inhibitor within 2
weeks prior to screening

11. Taking any type of chronic medication within the 4 weeks prior to study entry (use of
hormonal contraceptives is acceptable)

12. Positive serologic test for HIV, HCV-Ab, or HBsAG

13. Donation of blood or blood products within 56 days prior to screening

14. Smokers or use of tobacco and/or nicotine containing products within 3 months prior to
dosing as determined by the subject's verbal history

15. Participation in any study with an investigational compound or device within 30 days
prior to signing informed consent

16. History of participation in any prior study of PER977 or edoxaban

17. Active drug or alcohol dependence within the prior 12 months or any condition that, in
the opinion of the Investigator, would interfere with adherence to study protocol