Ipsen to Acquire Kartos Therapeutics in Up to $1.75B Deal, Adds Myelofibrosis Drug Navtemadlin

Ipsen has agreed to acquire Kartos Therapeutics in a transaction valued at up to $1.75 billion, strengthening its hematologic oncology portfolio with navtemadlin, an investigational oral MDM2 inhibitor currently in Phase III development for myelofibrosis. The deal includes $450 million upfront, with up to $1.3 billion in additional regulatory and commercial milestone payments. The acquisition is expected to close by the end of the third quarter of 2026, subject to customary closing conditions.

Navtemadlin is being developed as an add-on treatment for patients with intermediate- and high-risk TP53 wild-type myelofibrosis who continue to experience splenomegaly or symptoms despite treatment with ruxolitinib, the current first-line standard of care. Ipsen expects the program could support a potential regulatory filing as early as 2028 if the ongoing Phase III study is successful.

Navtemadlin targets p53 pathway to improve outcomes

Navtemadlin inhibits MDM2, a protein that suppresses the tumor suppressor p53. By restoring p53 activity, the therapy promotes apoptosis of malignant cells while preserving normal hematopoietic function. This mechanism offers a complementary approach to JAK inhibition and may improve both disease control and underlying disease biology.

Myelofibrosis is a rare myeloproliferative neoplasm characterized by progressive bone marrow fibrosis, splenomegaly, severe constitutional symptoms, and an increased risk of transformation to acute myeloid leukemia. Although ruxolitinib improves symptoms and spleen enlargement, many patients eventually develop an inadequate response or discontinue treatment, leaving limited therapeutic options and a median survival of only one to two years after discontinuation.

Phase III POIESIS trial evaluates add-on therapy

Navtemadlin is currently being evaluated in the global Phase III POIESIS registrational trial (NCT06479135), which plans to enroll more than 600 patients across over 250 clinical sites. The study is investigating whether adding navtemadlin to standard-dose ruxolitinib improves outcomes in patients with intermediate- or high-risk TP53 wild-type myelofibrosis who have a suboptimal response to ruxolitinib. Top-line results are expected in 2027.

The Phase III program builds on findings from the Phase Ib/II KRT-232-109 study (NCT04485260). Among 19 patients with a suboptimal response to ruxolitinib, 42% achieved at least a 25% reduction in spleen volume, 32% achieved at least a 35% spleen volume reduction, and 32% experienced at least a 50% improvement in total symptom score after 24 weeks of treatment.

The study also reported signals of disease modification. Among evaluable patients, 71% achieved at least a 20% reduction in driver mutation variant allele frequency, while 57% showed at least a one-grade improvement in bone marrow fibrosis by central pathology review at Week 24.

Acquisition strengthens Ipsen’s late-stage oncology pipeline

Ipsen Chief Executive Officer David Loew said the acquisition expands the company’s late-stage oncology pipeline and supports its strategy of developing transformational cancer therapies. He noted that navtemadlin could establish a new treatment approach for patients whose disease remains inadequately controlled with ruxolitinib.

Clinical investigators also emphasized the potential benefit of combining navtemadlin with JAK inhibition. They noted that the POIESIS trial reflects routine clinical practice and may determine whether the combination can deliver deeper, more durable responses while addressing disease biology beyond symptom control.

If approved, navtemadlin could become one of the first targeted combination therapies to improve outcomes for patients with myelofibrosis who do not achieve adequate benefit from current standard treatment.

Reference

Ipsen to acquire Kartos Therapeutics, expanding hemato-oncology late-stage pipeline