A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of AK002

Inclusion Criteria

• •1. Provided written informed consent
• •2. Male or female aged ≥18 and ≤65 years at the time of signing the informed consent form
• •3. Confirmed diagnosis of ISM based on World Health Organization (WHO) criteria (Appendix 1)
• •4. Presence of at least 1 of the following SM related symptoms:
• •1. Flushing (at least 1 episode per week)
• •2. Pruritus (minimum MAS2 score of 4) (Appendix 2)
• •3. Diarrhea (minimum MAS2 score of 4) (Appendix 2)
• •4. Anaphylaxis (at least 1 episode \[grade 2 or higher\] within the last 12 months)
• •5. Serum total tryptase exceeded 15 ng/mL\* at 2 or more measurements obtained 1 or more months apart within the last 2 years (\*Note: this varies from the minor criterion of "persistently exceeds 20 ng/mL" in the WHO criteria for diagnosis of ISM)
• •6. Willing and able to comply with the study procedures and visit schedule, including follow-up visits
• •7. Able to communicate effectively with the study site personnel
• •8. Negative Screening urine drug tests (alcohol, amphetamines/methamphetamines, barbiturates, benzodiazepines, cannabinoids, cocaine, cotinine, methadone, methaqualone, opiates, phencyclidine)
• •9. Negative Screening ova and parasite test
• •10. Determined by the Investigator to be in good health as documented by the medical history, physical examination (PE), vital sign assessments, 12- lead ECG, clinical laboratory assessments, and by general observations
• •11. Women of child bearing potential, must be using highly effective methods of birth control (failure rate \<1% per year when used consistently and correctly) at least 4 weeks prior to Screening until Day 85. Women should be informed of the potential risks associated with becoming pregnant while enrolled. Accepted forms of contraception are implants, injectables, combined oral contraceptives, and some intrauterine devices (IUDs). In addition, a barrier method must always be used concomitantly to the highly effective method. Double-barrier is not considered a highly effective method. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) is not an acceptable means of contraception. Female patients are considered to not be of child-bearing potential when they are post-menopausal for at least 2 years with follicle-stimulating hormone (FSH) levels \>40 mIU/mL, are surgically sterilized, or have undergone hysterectomy.
• •12. Male patients with female partners of childbearing potential must agree to use a condom without spermicide during sexual activity with female partners of childbearing potential. Female sexual partners of male patients must be willing to avoid pregnancy according to the above described methods.