Study of LQT-1213 on QTc-induced Prolongation in Healthy Adult Subjects (Part1) and on Congenital Long QT in Patients Diagnosed With Type 1, 2 or 3 Long QT Syndrome (Part 2).

Inclusion Criteria:

Part1:

1. Male and female subjects between 19 and 60 years of age (inclusive) at Screening

2. Not previously enrolled in a clinical study with LQT-1213

3. Normal general health

4. Body mass index within 18 to 32 kg/m 2 , inclusively at Screening

5. Female subjects of non-childbearing potential must be either surgically sterile (hysterectomy, bilateral tubal ligation, salpingectomy, and/or bilateraloophorectomy at least 26 weeks before Screening) or postmenopausal, defined asspontaneous amenorrhea for at least 2 years, with follicle-stimulating hormone inthe postmenopausal range at Screening, based on the central laboratory's ranges.

6. Female subjects of childbearing potential (ie, ovulating, premenopausal, andnotsurgically sterile) must use a highly effective contraceptive regimen duringtheir participation in the study and for 30 days after the last administration ofstudy drug. Highly effective contraceptive methods are defined as those with <1%failure rate per year. Acceptable methods of contraception for female subjectsenrolled in the study include the following:

• Combined (estrogen- and progestogen-containing) hormonal contraceptionassociated with inhibition of ovulation: oral, intravaginal, transdermal

• Progestogen-only hormonal contraception associated with inhibition ofovulation:oral, injectable, implantable

• Intrauterine device

• Intrauterine hormone-releasing system

• Bilateral tubal occlusion

• Vasectomized partner

• Heterosexual abstinence

7. Male subjects and their partners must use highly effective methods of contraception (ie, condom and spermicide) for the entire duration of the study. Male subjects mustcontinue to use contraception and refrain from fathering a child and sperm donationfor 90 days after the last administration of study drug. Acceptable methods ofcontraception for male subjects enrolled in the study include the following:

• Condoms and spermicide

• Surgical sterilization (vasectomy) of the subject at least 26 weeks beforeScreening

• Heterosexual abstinence (subject must agree to use condom and spermicide ifthey become sexually active)

8. Understand the requirements of the study and voluntarily consent to participate inthe study.

Part 2:

1. Male and female participants between 18 years of age or older at Screening.

2. Body weight of at least 45 kg at Screening.

3. Female participants of nonchildbearing potential must be either surgically sterile (hysterectomy, bilateral tubal ligation, salpingectomy, and/or bilateraloophorectomy at least 26 weeks before Screening) or postmenopausal, defined asspontaneous amenorrhea for at least 2 years, with follicle-stimulating hormone inthe postmenopausal range (>40 mlU/mL) at Screening, based on the centrallaboratory's ranges.

4. Female participants of childbearing potential (ie, ovulating, premenopausal, and notsurgically sterile) must use a highly effective contraceptive regimen during theirparticipation in the study and for 30 days after the last administration of studydrug. Highly effective contraceptive methods are defined as those with <1% failurerate per year. Acceptable methods of contraception for female participants enrolledin the study include the following:

• Combined (estrogen- and progestogen-containing) hormonal contraceptionassociated with inhibition of ovulation: oral, intravaginal, transdermal

• Progestogen-only hormonal contraception associated with inhibition ofovulation: oral, injectable, implantable

• Intrauterine device

• Intrauterine hormone-releasing system

• Bilateral tubal occlusion

• Vasectomized partner

• Heterosexual abstinence

5. Male participants and their partners must use highly effective methods ofcontraception (ie, condom and spermicide) for the entire duration of the study. Maleparticipants must continue to use contraception and refrain from fathering a childand sperm donation for 90 days after the last administration of study drug. Acceptable methods of contraception for male participants enrolled in the studyinclude the following:

• Condoms and spermicide

• Surgical sterilization (vasectomy) of the participant at least 26 weeks beforeScreening

• Heterosexual abstinence (participant must agree to use condom and spermicide ifthey become sexually active)

6. LQT1, LQT2 or LQT3 mutation:

• LQTS 1/2: Participants with potassium voltage-gated channel subfamily (KCNQ1/KCNH2) mutations that are dominant negative and considered to bepathologic or likely pathologic by the screening laboratory (or historicaldocumentation, if available) can be included after approval from the sponsor.Participants with haploinsufficiency will not be eligible for this study.

• LQTS 3: Participants with a sodium voltage-gated channel alpha subunit 5 (SCN5A) gene chromosome 3 mutations that are mutations and considered to bepathologic or likely pathologic by the screening laboratory (or historicaldocumentation, if available) can be included after approval from the sponsor.Participants with mutations not associated with Brugada syndrome or overlapsyndromes or where mutations affect the window current or the persistent 'late'Na current to exert a primary or major role in the phenotype, will be eligiblefor this study.

7. QTcF interval ≥480 and ≤560 ms determined at Screening and on Day -1 triplicate ECGSas assessed by a physician trained in complex ECG interpretation.

8. The first 2 participants with LQT2 require having an implantable cardioverterdefibrillator (ICD) before further participants with LQT2 are enrolled and the first 2 participants with LQT3 require having an implantable cardioverter defibrillator (ICD) before further participants with LQT3 are enrolled. This stipulation may bealtered based on agreement between the principal investigator and Sponsor based onemerging data. The ICD implantation must have been at least 2 months beforeScreening. Note: Subsequent participants may or may not have had an ICD. The resultsof the ICD interrogation within the last 6 months should be available for reviewunless waived by the investigator and sponsor.

9. Understand the requirements of the study and voluntarily consent to participate inthe study.

Exclusion Criteria:

Part 1:

1. On Day 1 of the first cycle of dofetilide at 3 hours post dose, the QTcF on thetriplicate ECGs will be measured semiautomatically and manually confirmed bycardiologist experienced in ECG interval measurements. The ECG measurements atbaseline and at the 3-hour time points will be performed by the same technician andcardiologist. If the mean QTcF increase from baseline is <25 ms on the triplicatesafety ECGs compared to the mean from baseline (all ECG QTcF measurements averaged),the subject will be disqualified from further study participation.

2. Clinically significant gastrointestinal, renal, hepatic, neurologic, hematologic,endocrine, oncologic, pulmonary, immunologic, psychiatric, or cardiovascular diseaseor any other condition, which, in the opinion of the investigator, would jeopardizethe safety of the subject or impact the validity of the study results. No history ofmyocardial infarction or angina or ischemic heart disease, non-sustained orsustained ventricular tachycardia, atrial fibrillation, stroke, transient ischemicattack, syncope, congestive heart failure, family history of LQTS, Torsades dePointes, or sudden cardiac death.

3. Female subjects must not be pregnant, lactating, or breastfeeding, and must not beplanning to become pregnant.

4. Female subjects of childbearing potential must have a negative result for the serumpregnancy test at Screening and Check-in.

5. Clinically significant abnormal findings on the physical examination or medicalhistory during Screening as deemed by the investigator.

6. Participated in a previous clinical study in the previous 3 months before dosing.

7. Donation of blood volume greater than 300 mL within 30 days before Screening andagree to avoid donation from Screening and throughout the study.

8. From Screening through pre-dose on Day 1, any 12-lead ECG demonstrating any of thefollowing: PR >220 ms; QRS >110 ms, or QTcF <390 ms and >440 ms; second- orthird-degree atrioventricular block; branch bundle block, significant ST-Twaveabnormalities or flat T waves that could interfere with QT analysis. Heart rate<50or >85 bpm.

9. Known sensitivity to kinase inhibitors.

10. Abnormal renal function with an estimated glomerular filtration rate (eGFR) of<70mL/min/1.73 m 2 *eGFR calculated by the Chronic Kidney DiseaseEpidemiologyCollaboration [CKD-EPI] formula at Screening. One retest of the exclusionary eGFRvalue is allowed at the discretion of the investigator.

11. Subject has abnormal liver function tests (transaminases or total bilirubin) greaterthan 2.5 × the upper limit of normal at Screening or baseline. One retest ofexclusionary abnormal liver function tests is allowed at the discretion of theinvestigator.

12. Subject has a positive serology test for HIV antibodies, hepatitis B surfaceantigen, or hepatitis C virus antibody at Screening.

13. Subject has a hemoglobin <11.0 g/dL, potassium <3.8 mg/dL, magnesium<1.9 mg/dL, orcalcium <8.5 mg/dL at Screening or baseline. One retest of exclusionary hemoglobin,potassium, magnesium, and calcium is allowed at the discretion of the investigator.

14. Subject has a history of hypersensitivity to drugs with a clinically significantreactionor any clinically significant hypersensitivities.

15. Subject has an allergy to band aids, adhesive dressing, or medical tape.

16. Subject has a history within the past 2 months of strenuous exercise (e.g., marathonrunning) and is unwilling to refrain from strenuous exercise from 7 daysbeforeCheck-in and until the end of the study. Subject has abnormal creatinephosphokinase test greater than 3 × the upper limit of normal at Screening andbaseline. One retest of exclusionary abnormal creatine phosphokinase tests isallowed at the discretion of the investigator.

17. Subject is unable to refrain from or anticipates the use of any drug, includingprescription and nonprescription medications (with the exception of hormonalcontraception), herbal remedies, or vitamin supplements beginning 14 days before thefirst dose and until the end of the study. After dosing, acetaminophen (up to 2 gper 24 hours) may be administered at the discretion of the investigator or designee.

18. Hepatic or renal clearance altering agents within 30 days before the first doseand until the end of the study.

19. Avoid vaccinations from Screening until the end of the study.

20. Has consumed cruciferous vegetables (eg, kale, broccoli, watercress, collardgreens, kohlrabi, Brussels sprouts, and mustard greens) or charbroiled meatswithin 7 days before Day -2 through the Follow-up Visit.

21. Use of any drugs known to be significant strong inducers of cytochromeP450(CYP) 3A enzymes, including St. John's Wort, for 28 days before Day -1or 5half-lives (whichever is longer) and through the Follow-up Visit.

22. Has consumed Seville oranges, grapefruit and/or grapefruit juice within 14 daysbefore Check-in and is unwilling to abstain from consuming these items untilthe end of the study.

23. Subject is considering or scheduled to undergo any surgical procedure during thestudy.

24. Subject has experienced an acute illness that has resolved in less than 14 daysbefore the first study drug dose or has had a major illness or hospitalizationwithin 1 month before the first study drug dose.

25. Subject is unwilling to abstain from ingestion of caffeine- or xanthine-containingproducts (eg, tea, coffee, chocolate, cola, etc.) beginning 96 hours before Check-inuntil the final PK sample of each study period has been collected.

26. Subject is unwilling to abstain from alcohol beginning 48 hours before Check-in anduntil the final PK sample of each study period has been collected.

27. Subject has a history of high alcohol consumption within 9 months before Screening,defined as an average weekly intake of >14 units for males or >10 units for females.One unit is equivalent to 8 g of alcohol: a half-pint (~240 mL) of beer, 1 glass(125mL) of wine, or 1 measure (25 mL) of spirits.

28. Subject has a history of drug abuse in the 3 years before Screening or positivescreen for drugs of abuse or alcohol at Screening or baseline. Subjects may undergoa repeat urine drug screen at the discretion of the investigator.

29. Subject uses or has used tobacco-or nicotine-containing products (eg, cigarettes,cigars, chewing tobacco, snuff, etc.) within 6 months before Screening and isunwilling to abstain from tobacco-containing products until the end of the study,based on subject self-reporting.

30. Subject, who, for any reason, is deemed by the investigator to be inappropriate forthis study or has any condition which would confound or interfere with theevaluation of the safety, tolerability, or PK of the investigational drug or preventcompliance with the study protocol.

Part 2:

1. Clinically significant gastrointestinal, renal, hepatic, neurologic, hematologic,endocrine, oncologic, pulmonary, immunologic, psychiatric, or significant structuralcardiovascular disease or any other condition beyond LQT2 or LQT3, which, in theopinion of the investigator or sponsor, would jeopardize the safety of theparticipant or impact the validity of the study results. History of myocardialinfarction or ongoing angina or active ischemic heart disease, atrial fibrillation,stroke, or transient ischemic attack within the past 12 months, greater than NewYork Heart Association Class II congestive heart failure, bundle branch block,hemodynamically significant ventricular tachycardia not due to Torsades de Pointes,or Brugada syndrome.

2. Participant has a history of an aborted cardiac arrest, ICD implantation, syncopalepisode due to a ventricular arrhythmia or where confidence in the etiology cannotbe established, or appropriate ICD therapy for ventricular tachycardia/ventricularfibrillation within 2 months before Screening. Participants with LQT1, LQT2 or LQT3can be enrolled after the 2-month time period has lapsed.

3. Female participants must not be pregnant, lactating, or breastfeeding, and must notbe planning to become pregnant.

4. Female participants of childbearing potential must have a negative result for theserum pregnancy test at Screening and Check-in.

5. Clinically significant abnormal findings on the physical examination at Check-in ormedical history during Screening as deemed by the investigator.

6. Currently participating in another interventional clinical study.

7. Donation of blood volume greater than 300 mL within 30 days before Screening andunwilling to avoid donation from Screening and throughout the study.

8. Screening diastolic blood pressure <45 or >95 mm Hg, systolic blood pressure <90 or >150 mm Hg, or with sponsor and investigator approval.

9. At Screening and on Day -1, if the 12-lead ECG demonstrates any of the following: PR >250 ms; QRS >110 ms, or QTcF >560 ms and <480 ms; bundle branch block orsignificant ST-T wave abnormalities or flat T waves that could interfere with QTanalysis. Heart rate <45 bpm, unless receiving a beta-blocker in which case <40 bpm,or HR >95 bpm. If any of these exclusionary criteria are met, then 2 more ECGs maybe acquired, and the mean values may be used.For participants on beta blockade, thePR interval may be higher than 250 ms with sponsor and investigator approval.

10. Atrial pacing rate set to ≥80 bpm in those with atrial pacing.

11. Participant has a pacemaker or ICD that is actively used for ventricular pacing.

12. Known sensitivity to kinase inhibitors or clinically significant drug allergies toany of the components of LQT-1213..

13. Abnormal renal function with an eGFR of <60 mL/min/1.73 m2 , with eGFR calculated bythe CKD-EPI formula at Screening. One retest of the exclusionary eGFR value isallowed at Screening and Check-in at the discretion of the investigator.

14. Participant has abnormal liver function tests (transaminases greater than 2 × theupper limit of normal (ULN)) or total bilirubin > 1.5 × ULN.If the participant hasdocumented Gilbert's Syndrome, participation is at the combined principalinvestigator and Sponsor's discretion after review of historical liver and bilirubintests.

15. Participant has a positive serology test for HIV antibodies, hepatitis B surfaceantigen, or hepatitis C virus antibody at Screening.

16. Participant has a hemoglobin <11.0 g/dL, potassium <3.8 mg/dL, magnesium <1.8 mg/dL,or calcium <8.5 mg/dL at Screening or baseline. One retest of exclusionaryhemoglobin, potassium, magnesium, and calcium is allowed at the discretion of theinvestigator.

17. Participant has a history of hypersensitivity to drugs with a clinically significantreaction or any clinically significant hypersensitivities.

18. Participant has a clinically significant allergy to band aids, adhesive dressing,ECG electrodes, or medical tape.

19. Participant has abnormal creatine phosphokinase test greater than 3 × the upperlimit of normal at Screening or baseline. One retest of exclusionary abnormalcreatine phosphokinase tests is allowed at the discretion of the investigator.

20. Participant is currently taking, within the last 7 days before Spaulding admissionor 5 half-lives (whichever is longer), or anticipates the use of any antiarrhythmicmedications (including mexilitene except beta-blockers which are allowed,) or drugsknown to affect the QT interval (including ranolazine; refer to drug lists for "Drugs with known, possible, or conditional risk of TdP" that are known to prolongthe QT interval at https://crediblemeds.org), unless approved by the sponsor andprincipal investigator..

21. Participant is not permitted to use/consume the following:

22. Any drugs known to be significant strong inducers of CYP 3A enzymes, includingSt. John's Wort, for 28 days before Day -1 or 5 half-lives (whichever islonger) and through the Follow-up Visit.

23. Seville oranges, grapefruit and/or grapefruit juice within 7 days beforeCheck-in and is unwilling to abstain from consuming these items until the endof the study.

24. Participant is considering or scheduled to undergo any surgical procedure during thestudy.

25. Participant has experienced an acute illness that has resolved in less than 14 daysbefore the first study drug dose or has had a major illness or hospitalizationwithin 1 month before the first study drug dose.

26. Participant is unwilling to abstain from ingestion of caffeine- or xanthine-containing products (eg, tea, coffee, chocolate, cola, etc.) beginning 96 hoursbefore Check-in until the final PK sample of the study has been collected.

27. Participant is unwilling to abstain from alcohol beginning 48 hours before Check-inand until the final PK sample of the study has been collected.

28. Participant has a history of high alcohol consumption or substance abuse that wouldpose a risk for the participant's safety and compliance with the study protocol.Participant must not have positive screen for drugs of abuse at Screening orbaseline and alcohol at baseline, except with sponsor permission. Participants mayundergo a repeat urine drug screen at the discretion of the investigator.

29. Participant, who, for any reason, is deemed by the investigator to be inappropriatefor this study or has any condition which would confound or interfere with theevaluation of the safety, tolerability, or PK of the investigational drug or preventcompliance with the study protocol.