Tazemetostat Hydrobromide

iStock, Cristina Gaidau The star of Ipsen’s acquisition is an MDM2 blocker being proposed as an add-on therapy to ruxolitinib for myelofibrosis. The drug could be available to patients “as early as 2028,” according to Ipsen CEO David Loew. Ipsen will absorb California-based Kartos Therapeutics in a back-heavy agreement that will give the French biotech a late-stage drug candidate for a rare blood cancer. The deal involves a $450 million upfront payment from Ipsen, according to a news release on Monday morning . The company could also be on the hook for up to $1.3 billion in future payments, including a “significant regulatory approval milestone,” plus sales-based commitments. Ipsen and Kartos expect to close the deal in the third quarter. The centerpiece of the acquisition is navtemadlin, an orally available blocker of MDM2, a protein that inhibits the expression of a key tumor suppressor called p53. Navtemadlin is designed to restore this expression. Kartos is testing navtemadlin as an add-on therapy to the JAK inhibitor ruxolitinib for high-risk myelofibrosis. The current standard of care for myelofibrosis is Ruxolitinib, which ameliorates enlarged spleen and related symptoms. A “significant proportion” of patients respond suboptimally to the drug, however, often prompting them to drop the treatment, according to Ipsen’s release. Prognosis after discontinuation is poor, with median overall survival ranging from around 1 to 2 years. Phase 1b/2 data released in 2023 demonstrated that 44% of patients saw at least a 25% decrease in spleen volume at the 24-week follow-up after navtemadlin treatment. Meanwhile, 31% saw at least a 35% reduction in spleen volume. The drug also lowered the frequency of disease-causing genetic variants and improved bone marrow fibrosis, which Ipsen said on Monday is a signal of “potential disease modification activity.” Navtemadlin is being studied in the Phase 3 POIESIS trial, which is set to enroll more than 600 patients across over 250 sites. The trial will focus on high-risk patients who have responded suboptimally to prior ruxolitinib treatment and who harbor no pathologic mutations in the gene encoding the p53 protein. Navtemadlin has the potential “to define a new treatment paradigm for patients with myelofibrosis,” Ipsen CEO David Loew said in a prepared statement on Monday, adding that the drug could be available to patients “as early as 2028.” The Kartos acquisition comes after Ipsen in March withdrew its lymphoma and sarcoma therapy Tazverik from the market after detecting a heightened risk of secondary cancers in treated patients. Data from the Phase 1b/3 SYMPHONY-1 trial , conducted in patients with relapsed or refractory follicular lymphoma, showed that those on Tazverik plus lenalidomide and Roche’s Rituxan had a higher risk of secondary blood cancers than those on lenalidomide plus Rituxan. An independent data board found that Tazverik’s risks outweigh its benefits. Tazverik was first approved in January 2020 for epithelioid sarcoma and picked up the follicular lymphoma indication in June of that year .