A Safety, Pharmacokinetic and Dose-Escalation Study of KD019 (Tesevatinib) in Subjects With ADPKD

Phase 1:

- Primary purpose is to determine the safety of KD019.

- Dosing is for 28 days daily. After the 28-day treatment period, subjects will, at the
discretion of the investigator, continue to receive study treatment for 24 months from
their first dose or until the development of unacceptable toxicity, noncompliance, or
withdrawal of consent by the subject, or investigator decision. Subjects may continue
beyond 24 months at the discretion of the investigator after consultation with the
medical monitor.

- All participants receive active KD019 study drug.

- KD019 is an oral once daily tablet. Tablets are 50 mg, 100 mg and 150 mg in strength.
Participants will enroll into three sequential dosing cohort levels (50 mg, 100 mg and
150 mg.). Participants in Phase 1b will have their dose increased or decreased to the
MTD.

- Study participants will have MRI of the abdomen (kidneys) at Screening and 6 months
thereafter to explore effects of KD019.

- Echocardiogram will be performed at Screening, Day 28, months 3 and 6 and every 6 months
thereafter.

Phase 2:

- Primary purpose is to compare the annualized change in glomerular filtration rate (GFR)
in subjects with ADPKD when treated with KD019.

- Two alternate dosing schedules will be explored to determine if they are more tolerable
than daily dosing when used chronically in subjects with ADPKD.

- Subjects will receive study treatment for 24 months from their first dose or until the
development of unacceptable toxicity, noncompliance, or withdrawal of consent by the
subject, or investigator decision. Subjects may continue beyond 24 months at the
discretion of the investigator after consultation with the sponsor.

- All participants receive active KD019 study drug.

- Tablets are 50 mg, 100 mg, and 150 mg in strength.

- Study participants will have MRI of the abdomen (kidneys) at Screening and Month 6 visit
and every 6 months after to explore effects of KD019.

- Echocardiogram will be performed at Screening, Day 28, and Months 3 and 6 and 6 months
thereafter.

Inclusion Criteria:

- The subject has a confirmed diagnosis of ADPKD.

- The subject has a GFR ≥ 35 mL/min/1.73 m2.

- Cysts must be at least 1 cm in size.

- Adequate bone marrow, kidney, and liver function.

- Must agree to use two forms of birth control for those of child bearing potential

- Normal amylase and lipase levels

- The subject has a htTKV ≥ 1000 mL

Exclusion Criteria:

- The subject has had a previous partial or total nephrectomy.

- The subject has tuberous sclerosis, Hippel-Lindau disease, or acquired cystic disease.

- The subject has congenital absence of one kidney and/or need for dialysis.

- Presence of renal or hepatic calculi (stones) causing symptoms.

- The subject has received any investigational therapy within 30 days prior to study
entry.

- Active treatment (within 4 weeks of study entry) for urinary tract infection.

- Subject is known to be immunocompromised

- Subject is pregnant or nursing

- History of pericardial effusion or presence of pericardial effusion on screening
echocardiogram

- Uncontrolled hypertension

- History of pancreatitis or has known risk factors for pancreatitis

- Subject has received EGFR inhibitor at any time

- The subject is aphakic due to previous cataract surgery or congenital anomaly