Bayer and Suzhou Puhe BioPharma Co. Ltd., a clinical-stage biotechnology company, on Wednesday announced that they have entered into a global license agreement for Puhe BioPharma's oral, small molecule PRMT5 inhibitor that selectively targets MTAP-deleted tumors. Under the agreement, Bayer obtains an exclusive worldwide license to develop, manufacture and commercialize the MTA-cooperative PRMT5 inhibitor. Bayer has enrolled the first participant in a Phase I first-in-human dose escalation study investigating MTA-cooperative PRMT5 inhibitor under the development name BAY 3713372 for the treatment of MTAP-deleted solid tumors.

"We are looking forward to exploring the potential of the PRMT5 inhibitor, which could improve outcomes for patients with MTAP-deleted tumors who often have a poor prognosis," said Juergen Eckhardt, M.D., Head of Business Development and Licensing at Bayer's Pharmaceuticals Division. "The highly selective targeting of cancer cells while sparing healthy cells, based on the innovative mechanism of action is very promising. This will support our mission to build one of the most transformative and differentiated precision oncology pipelines in the industry."

"We see great potential in MTA-cooperative PRMT5 inhibitors in treating MTAP-deleted tumors. Our MTA-cooperative PRMT5 inhibitor, PH020, now named BAY 3713372, has demonstrated competitive selectivity for PRMT5 bound to MTA and activity in preclinical studies, as well as brain penetration capabilities," said Guo Yongqi, CEO of Puhe BioPharma. "We are excited to partner with Bayer, a global leader in the field of life sciences, to advance our PRMT5 inhibitor into the clinic. Together with Bayer, we look forward to bringing this therapeutic option to patients worldwide."

PRMT5 (protein arginine methyltransferase 5) and a specific gene called MTAP (metabolic enzyme 5'-deoxy-5'-methylthioadenosine phosphorylase) play important roles in cell metabolism and are critical for cell survival. MTAP deletions, which occur in approximately 10 to 30 percent of all cancers, lead to elevated levels of MTA in tumor cells and BAY 3713372 is designed to bind the PRMT5-MTA complex thus specifically exploiting tumor vulnerability. 

"Loss of the MTAP gene occurs in a variety of tumor types, including those with few treatment options and poor prognosis, such as pancreatic cancer and glioblastoma," said Dominik Ruettinger, M.D., Ph.D., Global Head of Research and Early Development for Oncology at Bayer's Pharmaceuticals Division. "We look forward to advancing this program as we are driven by our ambition to develop innovative medicine that will improve and extend the lives of cancer patients we serve, focusing on areas of highly unmet medical need."

Protein arginine N-methyltransferase 5 (PRMT5) plays a crucial role in modifying proteins that control the cell cycle. The metabolic enzyme 5'-deoxy-5'-methylthioadenosine phosphorylase (MTAP) is involved in the methionine salvage pathway which recycles methionine from methylthioadenosine (MTA). This targeted approach takes advantage of the unique relationship between MTA and PRMT5, creating a specific vulnerability that can be exploited to effectively treat MTAP deficient cancer cells.