Roche, with HER2 franchise under pressure, pays $70M for breast cancer brain metastases prospect

Roche is stepping up the defense of its critical HER2 franchise, committing $70 million in upfront and near-term payments to secure global rights to Zion Pharma’s early-phase treatment of brain metastases.

Up to 50% of patients with advanced HER2-positive breast cancer develop brain metastases. Secondary tumors in the central nervous system pose a challenge to physicians because molecules need to cross the blood-brain barrier to act on the metastatic cancer cells. The treatment toolkit is expanding, though, with AstraZeneca and Daiichi Sankyo’s Enhertu among the drugs to trigger responses in recent trials

Roche’s Kadcyla is facing a tough battle from Enhertu in metastatic breast cancer, leading the Swiss drugmaker to forecast that sales will be “stable” in the coming years. Faced with rising competition, Roche has picked out Zion’s ZN-A-1041 as a drug candidate that could boost its HER2 franchise. 

The candidate is an orally administered selective tyrosine kinase inhibitor that targets HER2. Designed to cross the blood-brain barrier, ZN-A-1041 could reach metastatic cancer cells and bind to HER2. Stopping signaling mediated by HER2 may lead to the death of cells that express the receptor and the regression of metastatic brain cancer. Roche has committed up to $610 million in milestones to land the asset. 

Suzhou Zanrong Pharma, another name for Zion, began exploring whether that idea holds up in humans in 2020 in a clinical trial that is testing ZN-A-1041 as a monotherapy and in combination with other drugs in patients with HER2-positive advanced solid tumors. The combination cohorts are testing ZN-A-1041 with the chemotherapy capecitabine and anti-HER2 antibody trastuzumab, also known as Herceptin.

Zion will remain in charge of development during the transition period, beyond which Roche will take the reins and handle all subsequent activities. ClinicalTrials.gov lists the estimated completion date for the phase 1 study as June 30, 2024.