DALLAS & PHILADELPHIA–(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, presented preclinical data on its lead investigational candidate, PT2385, at the American Association for Cancer Research Annual Meeting in Philadelphia, PA. PT2385 is the first clinical stage antagonist of hypoxia inducible factor-2α (HIF-2α), a transcription factor implicated in the development and progression of renal cancer.

“HIF-2α can act as a tumorigenic driver in cancer. As a transcription factor, HIF-2α has historically been seen by the scientific community as impossible to directly target,” said Eli Wallace, Ph.D., Vice President of Chemistry for Peloton. “Our preclinical evidence indicates that PT2385 is potent, selective, and readily absorbed. We believe this program has the potential to become a significant therapy for renal cancer.”

PT2385 is currently being investigated in a Phase 1 clinical trial for the treatment of advanced or metastatic clear cell renal cell carcinoma (ccRCC). Loss of the von Hippel-Lindau tumor suppressor (VHL) is the key oncogenic event in up to 95% 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 responsible for unrestrained cancer cell growth and proliferation, tumor angiogenesis, and suppression of anti-tumor immune responses characteristic of ccRCC.

“Loss of VHL, and resulting activation of HIF-2α, is the signature driving event in clear cell renal cell carcinoma but HIF-2α had been largely dismissed as ‘undruggable,’ which is one reason the potential of PT2385 is so exciting,” remarked William G. Kaelin, Jr., M.D., Professor in the Department of Medicine at the Dana-Farber Cancer Institute, Harvard Medical School, a scientific advisor to Peloton, and a noted expert on VHL and hypoxia inducible factors. “PT2385 is the first molecule to advance to the clinic that binds directly and specifically to HIF-2α and potently inhibits its transcriptional activity.”

About Renal Cell Cancer

The American Cancer Society estimates that more than 61,000 new cases of kidney cancer will be diagnosed and about 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

Peloton Therapeutics is a drug discovery and development company focused on advancing first-in-class small molecule therapies for cancer and other life-threatening diseases. Initial efforts are focused on hypoxia inducible factor-2α (HIF-2α), which has been implicated in the development and progression of several types of cancers. Peloton’s lead candidate, PT2385, is the first HIF-2α inhibitor to enter clinical development and is being evaluated in a Phase 1 clinical trial for the treatment of advanced or metastatic clear cell renal cell carcinoma (ccRCC). Peloton is headquartered in Dallas, TX and was founded in 2011 by Professor Steven McKnight and The Column Group. The company raised more than $30 million in a Series C financing in October 2014 to fund its development activities for PT2385 as well as advance its research pipeline. Peloton is backed by The Column Group, Remeditex Ventures, Tichenor Ventures, Topspin Fund, Nextech Invest, and other investors. For more information, please visit www.pelotontherapeutics.com.

Source: Business Wire Health