Phase 1 Study With KIN-1901 in Healthy Subjects and Subjects With Ankylosing Spondylitis

Main Inclusion Criteria:

1. Capable of giving written informed consent, which includes compliance with studyrequirements and restrictions listed in the consent form.

2. Age requirements:

• Cohorts 1 through 4 (healthy): Male or female age ≥ 18 years and ≤ 50 years.

• Cohort 5 (AS): Male or female age ≥ 18 years and ≤ 75 years.

3. Females must agree to use a highly effective birth control method (<1% failure rateper year) throughout the study, reproductive status of non-childbearing based onmedical history, or is postmenopausal:

• Non-childbearing potential defined as pre-menopausal female with medical historyof bilateral tubal ligation, bilateral oophorectomy (removal of the ovaries) orhysterectomy; hysteroscopic sterilization,

• Postmenopausal defined as 12 months of spontaneous amenorrhea; with folliclestimulating hormone (FSH) confirmation.

• Woman of Childbearing potential (WCBP) who is already using an established methodof highly effective contraception or agrees to use one of the allowed BC methodsfor at least 28 days prior to the start of dosing (as determined by theInvestigator Brochure or Investigator or designee) to sufficiently minimize therisk of pregnancy throughout study participation (until completion their studyfollow-up visit).

4. Males who are sexually active must agree to use one of the allowed birth controlmethods. Male subjects must also agree to sufficiently minimize the risk of pregnancythroughout study participation (until completion their follow-up visit).

5. Body Mass Index (BMI):

• Cohorts 1-4 (healthy): BMI 18.5 to 31 kg/m2 at Screening

• Cohort 5 (AS): BMI 18 to 33 kg/m2 at Screening Additional Inclusion Criteria for Cohort 5 (AS) only:

6. AS diagnosis fulfilling the Modified New York criteria for AS.

7. Active AS, as defined by the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) ≥ 4 despite NSAID, corticosteroid or DMARD therapy.

8. BASDAI, item 2, spinal pain score ≥ 4 (out of 10).

9. AS diagnosis confirmed by Sacroiliac (SI) imaging within the last 2 years (confirmedby central reader during Screening).

10. Does not have a history of complete spinal ankylosis.

11. CRP > ULN at Screening.

12. Two prior failures to NSAID therapy (sub-optimal clinical response following fourweeks at maximum tolerated dose) or intolerance to NSAID therapy.

Main Exclusion Criteria: An individual will NOT be eligible for inclusion in this study if any of the followingcriteria apply.

1. Clinically significant illness which required medical treatment within 8 weeks or aclinically significant infection within 4 weeks prior to Screening.

2. Disease diagnosis that may influence the outcome of the study; such as psychiatricdisorders or disorders of the gastrointestinal tract, liver, kidney, respiratorysystem, endocrine system, hematological system, neurological system, cardiovascularsystem within 4 weeks prior to randomization, or individuals who have preexistingmetabolic congenital abnormality(ies).

3. Positive Quantiferon test.

4. Use of prescription and non-prescription drugs:

• Cohorts 1 through 4 (healthy): Use of prescription or non-prescription drugs,including vitamins, herbal and dietary supplements within 14 days or 5 half-lives (whichever is longer) prior to the first dose of study treatment, unless in theopinion of an Investigator and Medical Monitor the medication will not interferewith the study procedures or compromise subject safety or permitted under Section 5.10.1.

• Cohort 5 (AS):

• Current or prior treatment regimen that includes a biologic therapy (e.g.,anti-TNF-alpha, anti-IL-17A, anti-IL-6, or anti-IL-12/23)

• Use of parenteral and/or intra-articular steroids or immunosuppressants within 6weeks prior to the first dose of study treatment. Oral steroids are permitted if the dosage is ≤10 mg/day prednisone (or equivalent) andis stable for a minimum of 4 weeks before the first dose of study treatment andremains unchanged throughout the study. Also note: Oral NSAID treatment is permitted if the dosage is stable for a minimum of 2 weeksbefore the first dose of study treatment and remains unchanged throughout the study. Oral sulfasalazine treatment is permitted if the dosage is ≤ 3 g/d (max) and is stablefor a minimum of 4 weeks before the first dose of study treatment and remainsunchanged throughout the study. Oral methotrexate use is permitted if used for a minimum of 3 months, the dosage is ≤ 20 mg/week, and is the dose stable for a minimum of 4 weeks (including dosage ofconcomitant folate) before the first dose of study treatment and remains unchangedthroughout the study. Subcutaneous methotrexate use is permitted if the dosage is ≤ 20 mg/week and is stablefor a minimum of 4 weeks (including dosage of concomitant folate) before the firstdose of study treatment and remains unchanged throughout the study.

5. Individual who received an investigational product (including placebo) 30 days priorto the start of dosing (5 half-lives or twice the duration of the biological effect ofthe investigational product), whichever is longer.

6. Weight loss or gain of >10% between screening and up to the start of dosing.

7. Hemoglobin level ≤ 12 g/dL at Screening.

8. Positive result for HIV (HIV-1/HIV-2 Antibodies), HBsAg or HCVAb screening tests.

9. Known or suspected history of drug abuse (amphetamines, barbiturates, cannabinoids,cocaine, opiates and phencyclidine) or alcohol misuse* within 6 months prior toScreening, or a positive urine drug test and/or alcohol breathalyzer test at Screeningor baseline.