Safety, Tolerability and Pharmacokinetic First in Human (FIH) Study for Intravenous (IV) TKM-100802

Approximately 20 male and female healthy adult subjects, 18 to 50 years of age at the time
of dosing, will participate in this study. The SAD phase of the study is planned to have up
to 4 cohorts with 4 subjects (3 receiving TKM-100802 and 1 receiving saline) in each cohort.
Additional cohorts may be enrolled in the SAD phase if a MTD is not established after the
initial 4 cohorts. In the multiple-dose phase, one cohort is planned with 4 subjects (3
receiving TKM-100802 and 1 receiving saline) at a maximum dose of 0.24 mg/kg TKM-100802.

Inclusion Criteria:

1. Informed of the nature of the study and are able to read, review, agree to, and sign
the informed consent document at Screening.

2. Able to comply with all protocol-specified visit schedules and requirements.

3. Healthy male and female subjects 18 to 50 years of age, inclusive, at the time of
dosing.

4. Body mass index (BMI) between 22 kg/m2 to 35 kg/m2, inclusive, and weigh at least 110
lbs (50 kg).

4a. Systolic blood pressure ≥110 mmHg (subject in the seated position and legs dangling)
also, 5 minutes after moving from the supine to seated position any drop in systolic
pressure must be <15 mmHg and any increase in pulse <10 bpm.

5. Judged by the PI to be in good health as documented by the medical history, physical
examination (including but may not be limited to an evaluation of the cardiovascular,
gastrointestinal, respiratory and central nervous systems), vital sign assessments,
12-lead ECG, clinical laboratory assessments, and by general observations. Any
abnormalities or deviations outside the normal ranges for any of clinical testing
(laboratory tests, ECG, vital signs) can be repeated at the discretion of the PI and if
judged not to be clinically significant, the subject may be considered for study
participation.

6. Adequate hepatic, renal, hematologic and clotting function as defined by total
bilirubin, AST, ALT, serum creatinine, D-dimer and International normalized ratio (INR)
within normal range as determined by the PI and Sponsor Medical Monitor.

7. Female subjects must be one of the following:

- naturally postmenopausal (no menses) for >2 years and has a documented FSH level >40
mIU/mL; or

- have a documented history of ovarian failure; or

- surgically postmenopausal (bilateral oophorectomy or hysterectomy). Female subjects
that are surgically postmenopausal must provide documentation of the bilateral
oophorectomy or hysterectomy prior to Day 1 dosing to be eligible for participation
in the study; or

- Women of childbearing potential (FSH ≤40 mIU/mL) must have negative serum hCG at
Screening, a negative urine pregnancy test prior to the first study treatment, and
must agree to utilize highly effective contraception methods (2 separate forms of
contraception, 1 of which must be an effective barrier method, or be
non-heterosexually active, or have a vasectomized partner) from Screening throughout
the duration of study treatment and for 1 month after the last administration of
study treatment. 8. Male subjects who are sexually active must be willing to use
effective barrier contraception (e.g., condom with spermicide) during heterosexual
intercourse from Screening throughout the duration of study treatment and for 1 month
after the last dose of study treatment.

Exclusion Criteria:

1. Evidence or history of clinically significant hematologic, renal, endocrine,
pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic or
allergic disease at Screening or medication for comorbidity which according to the PI
and Sponsor Medical Monitor preclude subject participation in the clinical study.

2. Reports an uncontrolled psychiatric disorder or neurologic disease or seizure
disorder not controlled by medication.

3. Subject has a history of, or existing clinically significant cardiovascular disease
(for example, uncontrolled hypertension, unstable angina, congestive heart failure or
serious cardiac arrhythmias). In addition New York Heart Association Functional
Classification Class II or greater will be excluded.

4. Reports history of coronary heart disease (CHD), CHD-equivalent disease or CHD risk
>20% as designated by the National Cholesterol Education Program Adult Treatment
Panel III.

5. Current diagnosis or known history of liver disease (e.g., acute or chronic hepatitis
or liver cirrhosis).

6. History of allergy to cosyntropin (MAD cohort only).

7. Presence of any clinically significant results from laboratory tests, vital signs
assessments and ECGs as judged by the PI.

8. Reports receiving investigational drugs, biologics, or devices, or any antiviral
drugs within 28 days prior to study treatment or planned use during the course of the
study.

9. Reports receiving naturopathic medications, herbal supplements, or lipid lowering
therapies within 28 days prior to study treatment or planned use during the course of
the study.

10. A medical condition requiring a prescription treatment which it would be unsafe to
discontinue.

11. Recent treatment with alternative therapies which, in the view of the PI or the
Sponsor Medical Monitor, could potentially confound clinical and laboratory
assessments.

12. Demonstrates a marked baseline prolongation of QT/QTc interval (e.g., repeated
demonstration of a QTc interval >450 ms).

13. Reports concomitant use of any medication that prolongs the QT/QTc interval.

14. Reports a history of additional risk factors for torsades de pointes (e.g., heart
failure, hypokalemia, family history of Long QT Syndrome).

15. When confirmed upon additional testing, demonstrates a reactive screen for hepatitis
B surface antigen, hepatitis C antibody, or HIV antibody.

16. Reports infections requiring antibiotic therapy within 28 days of Screening (as
determined by the PI).

17. Reports a history of Ebola virus exposure.

18. Reports an occupational health risk of exposure to Ebola virus known to be higher
than that of the general population.

19. Reports a known or suspected hypersensitivity or previous severe reactions to any of
the constituents of the TKM-100802 including oligonucleotide- or lipid-based
products, liposomal drug products, and phospholipid-based products (parenteral
nutrition, Intralipid).

20. Reports a history of clinically significant allergies including food or drug
allergies.

21. Demonstrates a positive drug or alcohol screen.

22. Reports a history of drug or alcohol addiction or abuse within the past 1 year.

23. Subject is unwilling to refrain from alcohol consumption when it is completely
restricted or when it is not completely restricted, is unwilling to limit alcohol
consumption to 2 drinks/day, <12 drinks/week for males and 1 drink/day, <6
drinks/week for females (1 drink is equal to 12 ounces of beer, 5 ounces of wine, or
1 ounce of liquor).

24. Reports donating blood within 28 days prior to study treatment. All subjects will be
advised not to donate blood for 4 weeks after completing the study.

25. Reports donating plasma (e.g., plasmapheresis) within 28 days prior to study
treatment. All subjects will be advised not to donate plasma for 4 weeks after
completing the study.

26. Demonstrates, in the opinion of study staff, veins unsuitable for repeated
venipuncture or IV infusion (e.g., veins difficult to locate, access, or puncture;
veins with a tendency to rupture during or after puncture).

27. Pregnant, lactating, breastfeeding, or intends to become pregnant over the course of
the study.

28. Demonstrates a positive pregnancy screen.