KENILWORTH, N.J. & DALLAS—Merck and Peloton Therapeutics, Inc. announced today that the companies have entered into a definitive agreement wherein Merck, through a subsidiary, will acquire privately-held Peloton. Peloton is a clinical stage biopharmaceutical company focused on the development of novel small molecule therapeutic candidates targeting hypoxia-inducible factor-2α (HIF-2α) for the treatment of patients with cancer and other non-oncology diseases.
Peloton’s lead candidate PT2977 is a novel investigational oral HIF-2α inhibitor being evaluated in multiple clinical studies. PT2977 has a Phase 2 clinical trial in von Hippel-Lindau (VHL) disease-associated renal cell carcinoma (RCC); a Phase 2 clinical trial in combination with cabozantinib, a VEGFR-targeting agent, in metastatic RCC; a Phase 1/2 dose-escalation and dose-expansion clinical trial in patients with metastatic RCC; and an expansion arm of its Phase 1/2 clinical trial in glioblastoma multiforme (GBM).
In cancer, HIF-2α is aberrantly activated in these diseases as a result of the inactivity of the VHL tumor suppressor. This inactivation of the VHL tumor suppressor is observed in over 90% of clear cell RCC, the most common form of kidney cancer. Results from a Phase 1/2 study of PT2977 demonstrated favorable safety and early signs of anti-tumor activity as a monotherapy for patients with advanced or metastatic RCC.
“This acquisition exemplifies Merck’s strategy to pursue novel therapeutic candidates based on exceptionally promising and innovative research,” said Dr. Roger M. Perlmutter, president, Merck Research Laboratories. “Peloton scientists have applied their unique expertise in HIF-2α biology to develop PT2977, which has already shown intriguing activity in the treatment of renal cell carcinoma. We look forward to advancing this late-stage asset as part of our broad oncology R&D program.”
Under the terms of the agreement, Merck will acquire all outstanding shares of Peloton in exchange for an upfront payment of $1.05 billion in cash. Peloton shareholders will be eligible to receive a further $1.15 billion, contingent upon successful achievement of future regulatory and sales milestones for certain candidates. The closing is subject to conditions, including the expiry of the waiting period under the Hart-Scott-Rodino Antitrust Improvements Act and other customary conditions. The companies anticipate that the acquisition will close in the third quarter of 2019.
“Merck is recognized as a leader in cancer research and shares our commitment to accelerating the development of candidates targeting HIF-2α to help patients with advanced cancers and other diseases,” added John A. Josey, Ph.D., Peloton Therapeutics’ chief executive officer. “We are proud to have advanced PT2977 to this stage of development and believe that Merck is well suited to build upon the progress our company has made.”
Peloton also recently presented updated clinical data from the company’s Phase 1/2 clinical trial of PT2977 at the European International Kidney Cancer Symposium in Dubrovnik, Croatia. In the Phase 2 portion of the trial, highlighted in an oral presentation and a poster session, PT2977 showed encouraging anti-tumor activity with a favorable safety profile in patients with previously-treated RCC.
The presentation, entitled “A First-in-Human Phase 1/2 Trial of the Oral HIF-2α Inhibitor PT2977 in Patients with Advanced RCC,” was delivered by lead author Toni K. Choueiri, M.D., director of the Lank Center for Genitourinary Oncology at Dana-Farber Cancer Institute and the Jerome and Nancy Kohlberg Chair and Professor of Medicine at Harvard Medical School.
The Phase 1/2 study evaluated the safety and efficacy of PT2977. The Phase 1 portion included a once daily administration schedule dose escalation cohort of 37 patients with advanced solid tumors. Based on the results of this cohort, 120 mg once daily was selected as the recommended Phase 2 dose (RP2D). In the Phase 2 portion, 52 patients with advanced clear-cell RCC who had received at least one prior therapy received PT2977 at the RP2D.
The data presented included all 52 patients from the Phase 2 portion and three RCC patients from the Phase 1 portion treated at the RP2D, for a total of 55 patients. Among the 55, 12 patients (22%) had a confirmed partial response. Median progression free survival (PFS) was not yet reached in the study with a median follow-up of 9 months, and 36% of patients remained on study at the time of the data cut-off (January 1, 2019).
“The data from this trial indicate that HIF-2α inhibition has the potential to become a promising new treatment option for patients with renal cancer,” noted Choueiri. “The data show that PT2977 can provide clinically meaningful responses in heavily pre-treated patients with a favorable safety and tolerability profile.”
PT2977 was well tolerated. The most common adverse event was anemia, which was anticipated given regulation of erythropoietin (EPO) by HIF-2α. Two patients discontinued treatment for drug-related adverse events and three other patients required dose reductions for drug-related adverse events.
“We are delighted with these results,” Josey concluded. “The data … pave the way for a planned monotherapy Phase 3 trial that will further explore this exciting new mechanism of action in patients with advanced kidney cancer.”