On May 16, 2018 Peloton Therapeutics, Inc., reported that it will present first-in-human Phase 1 clinical data for its lead investigational oncology agent and hypoxia-inducible factor-2α (HIF-2α) inhibitor, PT2977, at the annual meeting of the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) taking place June 1-5, 2018 in Chicago (Press release, Peloton Therapeutics, MAY 16, 2018, View Source [SID1234526831]). PT2977 is a selective, orally available HIF-2α antagonist with improved potency and a superior pharmacokinetics profile relative to Peloton’s first-generation agent PT2385, which had demonstrated clinical activity in patients with clear cell renal cell carcinoma (ccRCC) as reported in a study published in the Journal of Clinical Oncology (JCO).

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The ASCO (Free ASCO Whitepaper) abstract (#2508) titled "A First-in-Human Phase 1 Dose-Escalation Trial of the Oral HIF-2α Inhibitor PT2977 in Patients with Advanced Solid Tumors," was accepted for an oral presentation to be delivered on Friday, June 1, 2018 at 5:09 p.m., Eastern time. In this Phase 1 dose-escalation trial, patients with locally advanced or metastatic solid tumors, who had received at least one prior systemic therapy, were treated with PT2977 once daily. The primary objective of the study was to determine the recommended Phase 2 dose and evaluate the safety, pharmacokinetics (PK) and pharmacodynamics (PD) of PT2977. PT2977 had a favorable safety profile and demonstrated early evidence of clinical activity.

"HIF-2α is a transcription factor that has been implicated in cancer initiation, progression, and metastasis especially in renal cell carcinoma. We are excited about the availability of a once-daily oral, potent, and selective inhibitor of HIF-2α," said Kyriakos P. Papadopoulos Co-Director of Clinical Research, START Center for Cancer Care (San Antonio, TX) and presenter of the Phase 1 data at ASCO (Free ASCO Whitepaper). "PT2977 had a favorable safety, pharmacokinetics, and pharmacodynamics profile."

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Patients were treated with PT2977 in doses ranging from 20 to 160 milligrams (mg). Exposure increased with dose along with dose-dependent reductions in erythropoietin levels (a PD marker). No treatment-related, dose-limiting toxicities were observed. Anemia (13 percent) was the most common Grade 3 adverse event. Early evidence of clinical antitumor activity including radiographic response and durable disease control were observed.

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"We are encouraged by the results from this Phase 1 dose-escalation study of our superior HIF-2α antagonist PT2977, which support further clinical development and evaluation of this novel agent," said John A. Josey, Ph.D., Peloton’s Chief Executive Officer. "Based on the favorable PK and PD findings from this study, a dose of 120 mg has been selected for further clinical development and we have recently recruited 50 patients into an expansion arm to evaluate PT2977 in patients with advanced renal cell carcinoma, a malignancy with poor prognosis where effective tolerable therapies continue to be in desperate need."

Further information on the clinical trial of PT2977 can be found on clinicaltrials.gov (Study identifier: NCT02974738).

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 pharmacokinetics profile, PT2977 is the lead agent being developed in oncology by Peloton. Peloton is currently evaluating PT2977 in an international Phase 2 trial in von Hippel-Lindau (VHL) disease-associated RCC and a Phase 1 clinical trial for the treatment of RCC.