Major Inclusion Criteria:
1. BMI ≥18.0 and ≤40.0 kg/m2 and weight ≥50 kg on Day -1.
2. Nonsmoker or willing to refrain from the use of nicotine or tobacco-containing products for at least 30 days prior to the first dose of study drug based on participant self-reporting and agrees to refrain from the use of these products throughout the study.
3. Known diagnosis of EPP.
4. History of consistent, non-painful prodrome prior to phototoxic attacks.
5. Experiences prodrome within 40 minutes of uncovered sunlight exposure.
6. Willing and able to follow protocol-specified contraception guidance.
7. Able to read and understand English and is willing and able to provide document informed consent to participate in the study at the time of the Remote Screening Visit and at the In-Clinic Screening Visit.
8. Able to understand the study procedures as described in the ICF and is willing and able to comply with the study requirements.
Major Exclusion Criteria:
1. Is mentally or legally incapacitated or has significant emotional problems identified or observed during the screening period or expected during the conduct of the study that could lead to difficulty complying with study procedures or interfere with the safe completion of the study.
2. History or presence of any illness or clinically significant medical or psychiatric condition or disease that, in the opinion of the PI or designee, might confound the results of the study or pose an additional risk to the participant by their participation in the study.
3. Current alcohol or drug use disorder, as defined by the DSM-V-TR.
4. History of gastrointestinal condition, including surgeries, which may affect absorption after oral administration.
5. History of cancer, with the exception of cutaneous non-melanoma skin cancer (basal or squamous cell carcinoma).
6. Received another investigational medicine within 5 half-lives, if the half-life is known, or within 28 days, if the half-life is unknown, prior to Day 1.
7. Surgical procedure planned within 28 days prior to Day 1.
8. Donation of blood or significant blood loss within 60 days prior to Day 1.
9. Plasma donation within 7 days prior to Day 1.
10. Unable to refrain from or anticipates the use of any of the following beginning 28 days (or 5 half-lives, whichever is longer) prior to the first dose of study drug and throughout the study:
1. Substrates of BCRP or MATE1/2-K
2. CYP3A4 substrates that cannot be separated by at least 2 hours from PORT-77 dosing
3. Moderate or strong P-gp inhibitors or inducers
4. Moderate or strong CYP3A4 inhibitors or inducers
5. Herbal supplements or food products containing grapefruit juice, star fruit, or Seville oranges
6. Illicit substances (eg, opiates, amphetamines, cocaine, cannabinoids \[including prescription medical cannabis\]).
11. With the following exceptions, is unable to refrain from or anticipates the use of any nonprescription medications and herbal/nutritional supplements beginning 14 days prior to the first dose of study drug and throughout the study:
1. A daily multivitamin
2. Single use of acetaminophen, aspirin, or ibuprofen at a dose equal to or lower than that recommended on the package
12. Estimated glomerular filtration rate \<60 mL/min/1.73 m2 using the CKD-EPI equation on Day -1.
13. In the absence of known mild hepatic impairment, alanine aminotransferase or aspartate aminotransferase ≥3 × ULN, or total bilirubin ≥2 × ULN (unless documented Gilbert syndrome) on Day -1.
14. Moderate (Class B) or severe (Class C) hepatic impairment as measured by the Child-Pugh score reported historically or calculated on Day -1.
15. Female participant with a positive pregnancy test on Day -1 or who is breastfeeding.
16. Positive urine drug or alcohol results on Day -1.
17. Positive results for HIV, HBsAg, or HCV antibody and HCV RNA on Day -1. Note, for participants successfully treated for HCV, positive antibody test with external laboratory evidence of negative RNA test is not exclusionary.
