PT2385 for the Treatment of Von Hippel-Lindau Disease-Associated Clear Cell Renal Cell Carcinoma

This open-label Phase 2 study will evaluate the efficacy, safety, PK, and PD of PT2385 in
patients with VHL disease who have at least 1 measurable VHL disease-associated ccRCC tumor
(as defined by RECIST 1.1). PT2385 will be administered orally and treatment will be
continuous. Changes in VHL disease-associated non-ccRCC tumors will also be evaluated.

Inclusion Criteria:

- Has at least 1 measurable ccRCC tumor and no solid ccRCC tumor greater than 3.0 cm,
based on radiologic diagnosis (histologic diagnosis not required); may have VHL
disease-associated lesions in other organ systems

- Has a diagnosis of von Hippel Lindau disease, based on a germline VHL alteration

Exclusion Criteria:

- Has had prior radiotherapy or systemic anti cancer therapy for ccRCC (includes
anti-VEGF therapy or any systemic investigational anti cancer agent)

- Has a prior or concomitant non-VHL disease-associated invasive malignancy with the
exception of adequately treated basal or squamous cell carcinoma of the skin, cervical
carcinoma in situ or any other malignancy from which the patient has remained disease
free for more than 2 years

- Has any history of metastatic disease

- Has had radiotherapy to any non-ccRCC site within 4 weeks prior to entering the study
or has not recovered from adverse events (AE)

- Has had any surgical procedure for VHL disease or any major surgical procedure
completed within 4 weeks prior to entering the study or has any surgical lesions from
recent major surgical procedures that are not well healed