On June 6, 2018 Peloton Therapeutics, Inc., reported dosing of the first patient in a Phase 2 trial evaluating the efficacy and safety of lead investigational oncology agent , PT2977, to treat von Hippel-Lindau (VHL) disease-associated kidney cancer (Press release, Peloton Therapeutics, JUN 6, 2018, View Source [SID1234527212]). PT2977 is a once-daily, oral inhibitor of HIF-2α, a transcription factor that has been implicated in the development and progression of renal cell carcinoma (RCC).

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"The initiation of this Phase 2 trial is an important milestone for Peloton and a critical step towards helping patients with this rare condition which can have serious lifelong health consequences," said Mohammad Hirmand, M.D., Peloton’s Chief Medical Officer. "The safety, pharmacokinetics, and clinical activity that we have observed in a Phase 1 trial of PT2977 provides insights into its potential to improve outcomes for patients with kidney cancer. We look forward to continuing clinical evaluation of this novel oral HIF-2α inhibitor."

The primary objective of the Phase 2 trial is to evaluate the efficacy of PT2977 for the treatment of VHL disease-associated renal tumors as measured by overall response rate. Secondary objectives include duration of response, time to response, progression free survival, and time to surgery for VHL disease-associated renal tumors. The trial will also evaluate the efficacy of PT2977 in other VHL disease-associated tumor types as well as the safety and pharmacokinetics of PT2977. Patients will be evaluated radiologically approximately every 12 weeks while continuing in the study.

"Unfortunately, there are no approved systemic therapies available for VHL disease. Currently, the only option is surgery, sometimes required multiple times which can be devastating for patients and does not cure the disease," said Eric Jonasch, M.D., Professor, Department of Genitourinary Medical Oncology, Division of Cancer Medicine; Director, VHL Clinical Center, The University of Texas MD Anderson Cancer Center. "We are excited about the opportunity to study PT2977 which may offer a new option as an orally available agent that could reduce the need and frequency of surgical intervention for patients with VHL-associated kidney disease."

Peloton’s drug discovery and development efforts focus on identifying novel compounds capable of modulating complex protein-protein interactions that drive disease which have eluded conventional small molecule approaches. Peloton has the only clinical stage small-molecule inhibitors of HIF-2α, and PT2977 has demonstrated a favorable profile in a Phase 1 study in patients with advanced solid tumors including RCC.

The study will enroll 50 patients at clinical trial centers across the United States and Europe. More information about the trial is available at www.clinicaltrials.gov, identifier NCT NCT03401788.

About VHL Disease

Von Hippel-Lindau (VHL) disease is a rare, hereditary cancer syndrome in which affected individuals have a mutation and/or deletion of the tumor suppressor VHL gene, and are at risk for the development of multiple tumors including renal cell cancer. The global incidence of VHL is estimated to be one in 36,000 people.

About PT2977

Peloton has succeeded in creating a series of orally-available small molecules that bind to HIF-2α and inhibit its transcription of disease-promoting genes. PT2977 is a once-daily, orally-active agent that blocks hypoxia-inducible factor-2α (HIF-2α). It is a structurally-related compound designed to be more potent with less pharmacokinetics variability compared to PT2385. PT2977 has demonstrated anti-tumor activity with a favorable safety profile in an early-stage clinical study in patients with solid tumors. Given its superior profile, PT2977 is the lead agent being developed in oncology by Peloton. In addition to the international Phase 2 trial of PT2977 in VHL disease-associated RCC, Peloton is evaluating the agent in a Phase 1 clinical trial for the treatment of advanced RCC.