A Phase 1 Safety and PK Study of IV TP-271

Up to 5 cohorts of 8 subjects each (up to a total of 40 subjects) will be enrolled. The 8
subjects within each cohort will be randomized 6:2 to receive multiple IV doses of TP-271 or
placebo. Study drug will be administered IV once daily on the morning of Days 1 through 7
following an overnight fast (minimum 8 hours). The planned doses for study drug for Cohorts A
- E are 0.5 mg/kg TP-271 or placebo, 1.0 mg/kg TP-271 or placebo, 2.0 mg/kg TP-271 or
placebo, 2.5 mg/kg TP-271 or placebo and 3.0 mg/kg TP-271 or placebo respectively.

During the Screening period (Days -28 to -2 prior to the subject receiving TP-271 or
placebo), each subject will be assessed for eligibility. Each subject must sign and date the
ICF prior to undergoing any study-related procedures.

All cohorts will follow the same study design. On Day -1, subjects will be admitted to the
study unit and eligibility confirmed. On Day 1, eligible subjects will be enrolled and
randomized to receive either TP-271 or placebo and will receive the assigned drug from Days 1
through 7. Subjects will be required to stay at the study unit from Days -1 through 11 to
assess safety and obtain the required PK samples. On Day 11, subjects will be discharged from
the study unit. A final safety assessment will be performed once between Days 14 and 20, 7 to
13 days following administration of the subject's final dose of study drug.

After all 8 subjects in a cohort have completed study procedures through Day 11, the
Principal Investigator and the Sponsor's Medical Monitor will evaluate all blinded safety and
plasma PK data to determine whether any criteria that would require a meeting of the Safety
Monitoring Committee (SMC) are met. If no such criteria are met, the study may proceed to the
subsequent cohort at the next higher dose of TP-271 without consulting the SMC.

Inclusion Criteria:

1. Be within the age range of 18 to 50 years, inclusive, at the time of Screening

2. Voluntarily sign an Institutional Review Board (IRB)/Independent Ethics Committee
(IEC) approved ICF to participate in the study after all relevant aspects of the study
have been explained and discussed with the subject and before undergoing any
study-related procedures

3. Have a body mass index (BMI) ≥18.0 and ≤33.0 kg/m2

4. Have a negative history of and negative screening results for human immunodeficiency
virus 1 and 2 and hepatitis B and C antibodies

5. Have the ability to communicate with the study unit staff in a manner sufficient to
carry out all protocol procedures as described

6. For female subjects, be of non-childbearing potential, either 1 year postmenopausal or
surgically sterile (bilateral oophorectomy, bilateral tubal ligation, or complete
hysterectomy)

7. For male subjects, be willing and able to use a barrier method of contraception or
practice abstinence (including males who had a vasectomy) from dosing through 90 days
after administration of the final dose of study drug

Exclusion Criteria:

1. History and/or presence of any clinically significant disease or disorder such as
cardiovascular, pulmonary, renal, hepatic, neurological, gastrointestinal, endocrine,
psychiatric, or mental disease or disorder, or mental or legal incapacitation, which,
in the opinion of the PI or Sub-Investigator(s), may either put the subject at risk
because of participation in the study, influence the results of the study, or
influence the subject's ability to participate in the study

2. Clinical laboratory values that fall outside the eligibility range specified in
Appendix D; for laboratory values that are not included in Appendix D, values outside
the reference range are exclusionary, with the following exceptions (Table 4.
Acceptable Out-of-Range Clinical Laboratory Values

3. Known allergy to tetracycline antibiotics or to any of the excipients in TP-271

4. Clinically significant abnormality on a 12-lead ECG, including the following:

- Rhythm other than sinus

- Corrected QT interval using Fridericia's formula (QTcF) >450 msec

- Evidence of second- or third-degree atrioventricular block

- Pathological Q-waves (defined as Q-wave >40 msec or depth >0.4 to 0.5 mV)

- Evidence of ventricular pre-excitation

- Evidence of complete left bundle branch block (BBB), right BBB, or incomplete
left BBB

- Intraventricular conduction delay with QRS duration >120 msec

- ST segment abnormalities, unless judged by the PI or Sub-Investigator(s) to be
non pathologic

5. History of seizures

6. History within 3 years of a positive result on a urine screen for drugs of abuse or a
positive result at Screening for any of the following drugs of abuse:
tetrahydrocannabinols, cocaine, opioids, phencyclidines, amphetamine, benzodiazepine,
and barbiturates

7. Use of tobacco, nicotine, or nicotine-replacement products within 3 months prior to
administration of the study drug through the last visit

8. Typical weekly alcohol consumption of 7 or more alcoholic drinks, where 1 alcoholic
drink is defined as 1 glass of beer (approximately 10 to 12 oz), 1 can (12 oz) of
beer, 1 glass of wine (approximately 4 to 5 oz), or distilled spirits (approximately 1
oz or 30 mL of liquor)

9. Alcohol consumption within 48 hours prior to dosing

10. Participation in a clinical study within 10 half-lives of the prior study drug
administration or within the previous 3 months if the half-life or dose of the
investigational agent is unknown or planned participation in another clinical study
concurrent with the current clinical study

11. History of difficulty donating blood or poor venous access

12. Blood donation (1 unit or approximately 350 mL) within 1 month prior to receiving
study drug or plans to donate prior to receiving study drug or during the clinical
study

13. Use of any prescription or nonprescription medication, including vitamins or herbal
medications, vaccination, or immunization within 7 days or 5 half-lives (if known),
whichever is longer, prior to dosing of study drug, with the following exceptions:
medications used to treat an AE, and the use of acetaminophen, naproxen, and ibuprofen
(except for within 24 hours prior to dosing)

14. Male subject donates or plans to donate sperm during the study and for at least 90
days after study drug administration.

15. Unwillingness or inability to follow the procedures outlined in the clinical study
protocol