inclusion criteria: subjects are required to meet all of the following criteria for enrollment into the part 1 of the study: 1. male or female adults who are between 18 and 60 years old inclusive; 2. weigh at least 45kg, with a bmi of 19 to 30 kg/m2 inclusive; 3. no serious underlying disease which would adversely affect the study conduct and data interpretation per the investigator; 4. female subjects should have negative results in serum pregnancy test at screening and negative urine pregnancy test at admission: 1. subjects of reproductive age and their partners agree to take 2 forms of effective contraceptive measures. note: using a medically acceptable form of birth control for at least 1 month prior to screening (3 months on oral contraceptives) \[e.g., hormonal contraceptives (oral, patch, injectable or vaginal ring), implantable device (implantable rod or intrauterine device), or a double barrier (e.g., diaphragm, cervical cap, oral, patch or vaginal hormonal contraceptive, condom, spermicide, or sponge)\] 2. surgically sterile, with documentation, for at least 3 months prior to screening by one of the following means: bilateral tubal ligation, bilateral salpingectomy (with or without oophorectomy), surgical hysterectomy, bilateral oophorectomy (with or without hysterectomy), postmenopausal, defined as the following: last menstrual period greater than 12 months prior to screening 3. postmenopausal status confirmed by serum follicle stimulating hormone (fsh) and estradiol levels at screening 5. agree to refrain from alcohol during the study; 6. subjects should have normal (or abnormal but not clinically significant) laboratory results per the pi's judgement including the complete blood count, biochemistry, coagulation indices and urinalysis; 7. subjects should have a normal (or abnormal but not clinically significant) ecg and chest x-ray at screening; 8. subjects should be willing to cooperate and able to participate in this study, comply with all protocol requirements, and sign an informed consent; 9. male subjects with female partners of childbearing potential must agree to use condoms for the duration of the study and until 12 weeks after completion of dosing with the study drug and must refrain from donating sperm for this same period; 10. current non-smokers and those who have not smoked within the last 6 months. this includes the use of cigarettes, e-cigarettes, and nicotine replacement products.

inclusion criteria: subjects are required to meet all of the following criteria for enrollment into the part 1 of the study: 1. male or female adults who are between 18 and 60 years old inclusive; 2. weigh at least 45kg, with a bmi of 19 to 30 kg/m2 inclusive; 3. no serious underlying disease which would adversely affect the study conduct and data interpretation per the investigator; 4. female subjects should have negative results in serum pregnancy test at screening and negative urine pregnancy test at admission: 1. subjects of reproductive age and their partners agree to take 2 forms of effective contraceptive measures. note: using a medically acceptable form of birth control for at least 1 month prior to screening (3 months on oral contraceptives) \[e.g., hormonal contraceptives (oral, patch, injectable or vaginal ring), implantable device (implantable rod or intrauterine device), or a double barrier (e.g., diaphragm, cervical cap, oral, patch or vaginal hormonal contraceptive, condom, spermicide, or sponge)\] 2. surgically sterile, with documentation, for at least 3 months prior to screening by one of the following means: bilateral tubal ligation, bilateral salpingectomy (with or without oophorectomy), surgical hysterectomy, bilateral oophorectomy (with or without hysterectomy), postmenopausal, defined as the following: last menstrual period greater than 12 months prior to screening 3. postmenopausal status confirmed by serum follicle stimulating hormone (fsh) and estradiol levels at screening 5. agree to refrain from alcohol during the study; 6. subjects should have normal (or abnormal but not clinically significant) laboratory results per the pi's judgement including the complete blood count, biochemistry, coagulation indices and urinalysis; 7. subjects should have a normal (or abnormal but not clinically significant) ecg and chest x-ray at screening; 8. subjects should be willing to cooperate and able to participate in this study, comply with all protocol requirements, and sign an informed consent; 9. male subjects with female partners of childbearing potential must agree to use condoms for the duration of the study and until 12 weeks after completion of dosing with the study drug and must refrain from donating sperm for this same period; 10. current non-smokers and those who have not smoked within the last 6 months. this includes the use of cigarettes, e-cigarettes, and nicotine replacement products.

inclusion criteria: subjects are required to meet all of the following criteria for enrollment into the part 1 of the study: male or female adults who are between 18 and 60 years old inclusive; weigh at least 45kg, with a bmi of 19 to 30 kg/m2 inclusive; no serious underlying disease which would adversely affect the study conduct and data interpretation per the investigator; female subjects should have negative results in serum pregnancy test at screening and negative urine pregnancy test at admission: subjects of reproductive age and their partners agree to take 2 forms of effective contraceptive measures. note: using a medically acceptable form of birth control for at least 1 month prior to screening (3 months on oral contraceptives) [e.g., hormonal contraceptives (oral, patch, injectable or vaginal ring), implantable device (implantable rod or intrauterine device), or a double barrier (e.g., diaphragm, cervical cap, oral, patch or vaginal hormonal contraceptive, condom, spermicide, or sponge)] surgically sterile, with documentation, for at least 3 months prior to screening by one of the following means: bilateral tubal ligation, bilateral salpingectomy (with or without oophorectomy), surgical hysterectomy, bilateral oophorectomy (with or without hysterectomy), postmenopausal, defined as the following: last menstrual period greater than 12 months prior to screening postmenopausal status confirmed by serum follicle stimulating hormone (fsh) and estradiol levels at screening agree to refrain from alcohol during the study; subjects should have normal (or abnormal but not clinically significant) laboratory results per the pi's judgement including the complete blood count, biochemistry, coagulation indices and urinalysis; subjects should have a normal (or abnormal but not clinically significant) ecg and chest x-ray at screening; subjects should be willing to cooperate and able to participate in this study, comply with all protocol requirements, and sign an informed consent; male subjects with female partners of childbearing potential must agree to use condoms for the duration of the study and until 12 weeks after completion of dosing with the study drug and must refrain from donating sperm for this same period; current non-smokers and those who have not smoked within the last 6 months. this includes the use of cigarettes, e-cigarettes, and nicotine replacement products.

inclusion criteria: subjects are required to meet all of the following criteria for enrollment into the part 1 of the study: male or female adults who are between 18 and 60 years old inclusive; weigh at least 45kg, with a bmi of 19 to 30 kg/m2 inclusive; no serious underlying disease which would adversely affect the study conduct and data interpretation per the investigator; female subjects should have negative results in serum pregnancy test at screening and negative urine pregnancy test at admission: subjects of reproductive age and their partners agree to take 2 forms of effective contraceptive measures. note: using a medically acceptable form of birth control for at least 1 month prior to screening (3 months on oral contraceptives) [e.g., hormonal contraceptives (oral, patch, injectable or vaginal ring), implantable device (implantable rod or intrauterine device), or a double barrier (e.g., diaphragm, cervical cap, oral, patch or vaginal hormonal contraceptive, condom, spermicide, or sponge)] surgically sterile, with documentation, for at least 3 months prior to screening by one of the following means: bilateral tubal ligation, bilateral salpingectomy (with or without oophorectomy), surgical hysterectomy, bilateral oophorectomy (with or without hysterectomy), postmenopausal, defined as the following: last menstrual period greater than 12 months prior to screening postmenopausal status confirmed by serum follicle stimulating hormone (fsh) and estradiol levels at screening agree to refrain from alcohol during the study; subjects should have normal (or abnormal but not clinically significant) laboratory results per the pi's judgement including the complete blood count, biochemistry, coagulation indices and urinalysis; subjects should have a normal (or abnormal but not clinically significant) ecg and chest x-ray at screening; subjects should be willing to cooperate and able to participate in this study, comply with all protocol requirements, and sign an informed consent; male subjects with female partners of childbearing potential must agree to use condoms for the duration of the study and until 12 weeks after completion of dosing with the study drug and must refrain from donating sperm for this same period; current non-smokers and those who have not smoked within the last 6 months. this includes the use of cigarettes, e-cigarettes, and nicotine replacement products.

inclusion criteria: subjects are required to meet all of the following criteria for enrollment into the part 1 of the study: 1. male or female adults who are between 18 and 60 years old inclusive; 2. weigh at least 45kg, with a bmi of 19 to 30 kg/m2 inclusive; 3. no serious underlying disease which would adversely affect the study conduct and data interpretation per the investigator; 4. female subjects should have negative results in serum pregnancy test at screening and negative urine pregnancy test at admission: 1. subjects of reproductive age and their partners agree to take 2 forms of effective contraceptive measures. note: using a medically acceptable form of birth control for at least 1 month prior to screening (3 months on oral contraceptives) [e.g., hormonal contraceptives (oral, patch, injectable or vaginal ring), implantable device (implantable rod or intrauterine device), or a double barrier (e.g., diaphragm, cervical cap, oral, patch or vaginal hormonal contraceptive, condom, spermicide, or sponge)] 2. surgically sterile, with documentation, for at least 3 months prior to screening by one of the following means: bilateral tubal ligation, bilateral salpingectomy (with or without oophorectomy), surgical hysterectomy, bilateral oophorectomy (with or without hysterectomy), postmenopausal, defined as the following: last menstrual period greater than 12 months prior to screening 3. postmenopausal status confirmed by serum follicle stimulating hormone (fsh) and estradiol levels at screening 5. agree to refrain from alcohol during the study; 6. subjects should have normal (or abnormal but not clinically significant) laboratory results per the pi's judgement including the complete blood count, biochemistry, coagulation indices and urinalysis; 7. subjects should have a normal (or abnormal but not clinically significant) ecg and chest x-ray at screening; 8. subjects should be willing to cooperate and able to participate in this study, comply with all protocol requirements, and sign an informed consent; 9. male subjects with female partners of childbearing potential must agree to use condoms for the duration of the study and until 12 weeks after completion of dosing with the study drug and must refrain from donating sperm for this same period; 10. current non-smokers and those who have not smoked within the last 6 months. this includes the use of cigarettes, e-cigarettes, and nicotine replacement products.

inclusion criteria: subjects are required to meet all of the following criteria for enrollment into the part 1 of the study: 1. male or female adults who are between 18 and 60 years old inclusive; 2. weigh at least 45kg, with a bmi of 19 to 30 kg/m2 inclusive; 3. no serious underlying disease which would adversely affect the study conduct and data interpretation per the investigator; 4. female subjects should have negative results in serum pregnancy test at screening and negative urine pregnancy test at admission: 1. subjects of reproductive age and their partners agree to take 2 forms of effective contraceptive measures. note: using a medically acceptable form of birth control for at least 1 month prior to screening (3 months on oral contraceptives) [e.g., hormonal contraceptives (oral, patch, injectable or vaginal ring), implantable device (implantable rod or intrauterine device), or a double barrier (e.g., diaphragm, cervical cap, oral, patch or vaginal hormonal contraceptive, condom, spermicide, or sponge)] 2. surgically sterile, with documentation, for at least 3 months prior to screening by one of the following means: bilateral tubal ligation, bilateral salpingectomy (with or without oophorectomy), surgical hysterectomy, bilateral oophorectomy (with or without hysterectomy), postmenopausal, defined as the following: last menstrual period greater than 12 months prior to screening 3. postmenopausal status confirmed by serum follicle stimulating hormone (fsh) and estradiol levels at screening 5. agree to refrain from alcohol during the study; 6. subjects should have normal (or abnormal but not clinically significant) laboratory results per the pi's judgement including the complete blood count, biochemistry, coagulation indices and urinalysis; 7. subjects should have a normal (or abnormal but not clinically significant) ecg and chest x-ray at screening; 8. subjects should be willing to cooperate and able to participate in this study, comply with all protocol requirements, and sign an informed consent; 9. male subjects with female partners of childbearing potential must agree to use condoms for the duration of the study and until 12 weeks after completion of dosing with the study drug and must refrain from donating sperm for this same period; 10. current non-smokers and those who have not smoked within the last 6 months. this includes the use of cigarettes, e-cigarettes, and nicotine replacement products.

inclusion criteria: - 1) male or female adults who are between 18 and 60 years old inclusive - 2) weigh at least 45kg, with a bmi of 19 to 30 kg/m2 inclusive - 3) no serious underlying disease which would adversely affect the study conduct and data interpretation per the investigator - 4) female subjects of reproductive age should have negative results in serum pregnancy test at screening and negative urine pregnancy test at admission. 1. subjects of reproductive age and their partners agree to take effective contraceptive measures. . note: using a medically acceptable form of birth control for at least 1 month prior to screening (3 months on oral contraceptives) [e.g., hormonal contraceptives (oral, patch, injectable or vaginal ring), implantable device (implantable rod or intrauterine device), or a double barrier (e.g., diaphragm, cervical cap, oral, patch or vaginal hormonal contraceptive, condom, spermicide, or sponge)] 2. surgically sterile, with documentation, for at least 3 months prior to screening by one of the following means: - bilateral tubal ligation - bilateral salpingectomy (with or without oophorectomy) - surgical hysterectomy - bilateral oophorectomy (with or without hysterectomy) - postmenopausal, defined as the following: - last menstrual period greater than 12 months prior to screening 3. postmenopausal status confirmed by serum follicle stimulating hormone (fsh) and estradiol levels at screening - 5) agree to refrain from alcohol during the study - 6) subjects should have normal (or abnormal but not clinically significant) laboratory results per the pi's judgement, including complete blood count, biochemistry, coagulation indices and urinalysis - 7) subjects should have a normal (or abnormal but not clinically significant) ecg and chest x-ray at screening - 8) subjects should be willing to cooperate and able to participate in this study, comply with all protocol requirements, and sign an informed consent. - 9) male subjects with female partners of childbearing potential must agree to use condoms for the duration of the study and until 12 weeks after completion of dosing with the study drug and must refrain from donating sperm for this same period - 10) current smokers and those who have not smoked within the last 6 months. this includes the use of cigarettes, e-cigarettes, and nicotine replacement products.

inclusion criteria: - 1) male or female adults who are between 18 and 60 years old inclusive - 2) weigh at least 45kg, with a bmi of 19 to 30 kg/m2 inclusive - 3) no serious underlying disease which would adversely affect the study conduct and data interpretation per the investigator - 4) female subjects of reproductive age should have negative results in serum pregnancy test at screening and negative urine pregnancy test at admission. 1. subjects of reproductive age and their partners agree to take effective contraceptive measures. . note: using a medically acceptable form of birth control for at least 1 month prior to screening (3 months on oral contraceptives) [e.g., hormonal contraceptives (oral, patch, injectable or vaginal ring), implantable device (implantable rod or intrauterine device), or a double barrier (e.g., diaphragm, cervical cap, oral, patch or vaginal hormonal contraceptive, condom, spermicide, or sponge)] 2. surgically sterile, with documentation, for at least 3 months prior to screening by one of the following means: - bilateral tubal ligation - bilateral salpingectomy (with or without oophorectomy) - surgical hysterectomy - bilateral oophorectomy (with or without hysterectomy) - postmenopausal, defined as the following: - last menstrual period greater than 12 months prior to screening 3. postmenopausal status confirmed by serum follicle stimulating hormone (fsh) and estradiol levels at screening - 5) agree to refrain from alcohol during the study - 6) subjects should have normal (or abnormal but not clinically significant) laboratory results per the pi's judgement, including complete blood count, biochemistry, coagulation indices and urinalysis - 7) subjects should have a normal (or abnormal but not clinically significant) ecg and chest x-ray at screening - 8) subjects should be willing to cooperate and able to participate in this study, comply with all protocol requirements, and sign an informed consent. - 9) male subjects with female partners of childbearing potential must agree to use condoms for the duration of the study and until 12 weeks after completion of dosing with the study drug and must refrain from donating sperm for this same period - 10) current smokers and those who have not smoked within the last 6 months. this includes the use of cigarettes, e-cigarettes, and nicotine replacement products.