Patients with acute myeloid leukemia — a rare cancer of the bone marrow and blood — have long faced limited treatment options. 

That is until now, thanks to a drug developed through innovative research by Jolanta Grembecka and Tomasz Cierpicki, professors of pathology in the Medical School, providing a promising new option. 

KOMZIFTI™ (ziftomenib), the first and only once-daily oral therapy for patients with relapsed or refractory NPM1-mutant acute myeloid leukemia, recently received approval by the U.S. Food and Drug Administration. 

The drug was discovered by Grembecka and Cierpicki in the Department of Pathology in collaboration with Kura Oncology and is being developed and commercialized by Kura Oncology and Kyowa Kirin.  

“Acute myeloid leukemia is a very aggressive blood cancer with poor clinical outcomes,” said Grembecka, also the Richard and Susan Rogel Professor of Cancer Therapeutics. “Seeing our pioneering work on menin inhibitors evolve into an FDA-approved treatment for leukemia patients is extremely rewarding. It is remarkable to witness the direct impact of our research, which resulted in a drug that benefits leukemia patients. This is an achievement we could only dream of, and now it’s a reality.”

Research led by Grembecka and Cierpicki, in collaboration with College of Pharmacy researchers including Duxin Sun, the Charles R. Walgreen Jr Professor of Pharmacy, professor of pharmaceutical sciences and director of the Pharmacokinetic and Mass Spectrometry Core in the College of Pharmacy, resulted in foundational discoveries that were licensed to Kura Oncology in 2014 with the help of Innovation Partnerships. 

The research team identified first-in-class small molecule inhibitors blocking the protein, menin. These inhibitors were designed to disrupt the protein-protein interactions that drive leukemia cell growth and survival, allowing the cells to mature into white blood cells instead of cancerous ones. This is a transformative approach for AML patients with NPM1 mutations, who often do not respond to standard therapies.

“To develop menin inhibitors, we had to pioneer an entirely new area of research — producing the human protein, creating robust biochemical assays, conducting high-throughput screening and solving the crystal structure of menin,” said Cierpicki, also professor of biophysics in LSA. “We accomplished this at a time when the pharmaceutical industry remained skeptical that targeting protein-protein interactions was even feasible.”

A collaboration between Grembecka and Cierpicki with Kura Oncology led to the discovery of ziftomenib. Clinical trials for patients with AML using ziftomenib were launched by Kura in 2019. In late 2024, Kura partnered with the Japanese pharmaceutical and biotechnology company Kyowa Kirin to expand development and commercialization globally.

Cierpicki and Grembecka’s research began at the University of Virginia School of Medicine before they moved to U-M in 2009. In addition to Kura Oncology, their research has been funded by Blood Cancer United (formerly known as the Leukemia & Lymphoma Society), the National Institutes of Health and the American Cancer Society.

“The achievement of Drs. Cierpicki and Grembecka illustrates how sustained federal support for science, combined with the vital contributions of research foundations, fuels discoveries that positively impact patient lives,” said Kelly Sexton, associate vice president for research – innovation partnerships and economic impact. “This FDA approval highlights U-M’s commitment to translating research discoveries into medical breakthroughs that serve patients and advance the public good.”

Ongoing clinical trials are exploring the use of KOMZIFTI (ziftomenib) in combination with other therapies for leukemia and solid tumors.

Cierpicki, Grembecka and U-M have a financial interest in Kura Oncology. The technology was licensed to Kura Oncology by Innovation Partnerships.

Tags:

• cancer
• College of Pharmacy
• Department of Pathology
• Innovation Partnerships
• Medical School