Peloton Therapeutics, Inc. Announces Publication of Data from Its First-in-Class HIF-2a Antagonist in Kidney Cancer in the Journal Cancer Research
- A Small-Molecule Antagonist of HIF2α Is Efficacious in Preclinical Models of Renal Cell Carcinoma
(Wallace et al., Cancer Research, September 2016)
September 12, 2016, 8:00 AM Central Daylight Time
DALLAS, TX – (BUSINESS WIRE) – Peloton Therapeutics, Inc., a drug discovery and development company focused on advancing first-in-class, small molecule cancer therapies targeting unexploited molecular vulnerabilities, announced today a publication in the journal Cancer Research that describes PT2385, Peloton’s first-in-class small molecule inhibitor of HIF-2α, including its potential as a treatment for patients with kidney cancer.
The paper titled “A Small-Molecule Antagonist of HIF2α Is Efficacious in Preclinical Models of Renal Cell Carcinoma” (Wallace et al., Cancer Research, September 2016) characterizes the efficacy of PT2385 in cell line and patient-derived xenograft models of kidney cancer. PT2385’s selectivity for HIF-2α over HIF-1α, its nanomolar potency, and its inhibition of HIF-2α transcriptional activity is also described. Importantly, the research demonstrates that PT2385 had no effect on cardiovascular parameters, unlike sunitinib, a drug commonly given as standard of care for kidney cancer. The researchers also propose the molecular mechanism of PT2385-mediated dimer disruption, thereby providing insight into this novel allosteric protein:protein inhibition.
“We are pleased to have this work published so soon after our two publications in Nature earlier this week,” said John A. Josey, Ph.D., Peloton’s Chief Executive Officer. “We are making significant progress in characterizing our HIF-2a antagonists and their effects in vitro and in vivo.”
PT2385 is a first-in-class small molecule antagonist of hypoxia-inducible factor-2α (HIF-2α), a transcription factor implicated in the development and progression of kidney cancer. It is currently being investigated in a Phase 1 clinical trial for the treatment of advanced or metastatic clear cell renal cell carcinoma (ccRCC) as monotherapy and in combination with the immuno-oncology agent nivolumab. Loss of the von Hippel-Lindau tumor suppressor (VHL) is the key oncogenic event in up to 95 percent of patients with ccRCC. With the loss of the VHL protein (pVHL), the transcription factor HIF-2α accumulates and drives the unbalanced expression of numerous gene products. Preclinical data indicate that orally bioavailable PT2385 disrupts HIF-2α activity in ccRCC and thereby blocks the expression of multiple tumorigenic factors. Clinical data in patients with advanced ccRCC has shown PT2385 to have encouraging efficacy, including a number of responses and a favorable tolerability profile, with no dose-limiting toxicities nor evidence of cardiovascular adverse events.
About Kidney Cancer
The American Cancer Society estimates that more than 62,000 new cases of kidney cancer will be diagnosed and more than 14,000 people will die from this disease this year. The National Cancer Institute reports that the prognosis for any treated renal cell cancer patient with progressing, recurring, or relapsing disease is poor, regardless of cell type or stage.
About Peloton Therapeutics
Peloton Therapeutics, Inc. is a clinical-stage biotechnology company that discovers and develops first-in-class, small molecule cancer therapies targeting unexploited molecular vulnerabilities. Peloton Therapeutics’ lead candidate, PT2385, is a first-in-class small molecule targeting hypoxia-inducible factor-2α (HIF-2α), a transcription factor implicated in the development and progression of kidney and other cancers. To learn more about Peloton Therapeutics, visit www.pelotontherapeutics.com.
Michael F. Haller, Ph.D.
Chief Business Officer
Phone: +1 (972) 629-4100
Sam Brown Inc.
Phone: +1 (312) 961-2502