PARIS: Ipsen and Kartos Therapeutics announced Monday they have entered into a definitive merger agreement under which Ipsen will acquire Kartos Therapeutics for $450 million upfront, with additional milestone payments of up to $1.3 billion.
The acquisition adds navtemadlin, an investigational MDM2 inhibitor designed to restore the natural tumor-suppressing function of p53, to Ipsen’s late-stage oncology pipeline. The drug is being developed for patients with intermediate and high-risk TP53 wild-type myelofibrosis who have a suboptimal response to the current standard of care, ruxolitinib.
“This acquisition further strengthens our late-stage oncology pipeline and reflects our continued focus on bringing transformational treatments to people living with cancer,” said David Loew, CEO of Ipsen. “We are excited by the potential of navtemadlin to define a new treatment paradigm for patients with myelofibrosis who have a suboptimal response to current standard of care, addressing a critical care gap and offering the potential for a new therapeutic option as early as 2028.”
Navtemadlin is currently being evaluated in the global Phase III trial POIESIS, which is designed to enroll more than 600 patients across over 250 sites. The trial builds on earlier clinical evidence from a Phase Ib/II trial in which add-on navtemadlin demonstrated clinically meaningful and disease-modifying activity.
Data presented at the European Hematology Association Congress in 2023 showed that at Week 24, among patients with a suboptimal response to ruxolitinib (n=19), 42% achieved at least a 25% reduction in spleen volume, 32% achieved at least a 35% reduction, and 32% achieved a total symptom score improvement of at least 50%. The data also showed potential disease modification activity, with 71% of evaluable patients achieving a 20% reduction of driver variant allele frequency and 57% showing an improvement in bone marrow fibrosis of at least one grade by Week 24.
Current standard of care ruxolitinib improves splenomegaly and myelofibrosis-related symptoms. However, a significant proportion of patients experience a suboptimal response, resulting in treatment discontinuation. Patient outcomes after ruxolitinib discontinuation are poor, with a median overall survival of approximately one to two years.
“As a treating clinician who cared for more than a thousand patients with myelofibrosis, I have seen first-hand the significant care gap for patients with myelofibrosis who remain symptomatic or have persistent splenomegaly despite ruxolitinib treatment,” said Dr. Srdan Verstovsek, chief medical officer of Kartos Therapeutics. “Navtemadlin has the potential to enhance the existing standard of care through an add-on approach designed to move patients with a suboptimal response into a clinical responder group by optimizing their care. We believe this innovative treatment paradigm could meaningfully improve outcomes for patients while avoiding unnecessary over-treatment of those already responding well.”
Myelofibrosis is a myeloproliferative neoplasm frequently linked to alterations in the JAK/STAT pathway, in which patients develop bone marrow fibrosis due to the abnormal proliferation of hematopoietic stem cells. The condition affects approximately 1.5 per 100,000 people in the U.S. and Europe, with a median age at diagnosis of approximately 67 to 69 years. Approximately 75% to 89% of patients are intermediate- or high-risk at diagnosis, and more than 95% are TP53wt.
“Myelofibrosis remains a serious and rare blood cancer associated with a substantial symptom burden and progressive splenomegaly that significantly impact quality of life,” said Dr. John Mascarenhas, professor of medicine at the Icahn School of Medicine at Mount Sinai and director of the Center of Excellence for Blood Cancers and Myeloid Disorders. “The clinical rationale for combining navtemadlin with ruxolitinib is very compelling, and the emerging data suggest the synergistic potential to deepen responses and address the underlying biology of the disease.”
“The Phase III POIESIS trial has the potential to redefine how we treat patients with myelofibrosis,” said Dr. Pankit Vachhani, associate professor of medicine and director of Clinical Research Unit at the University of Alabama at Birmingham and global principal investigator of POIESIS. “It is the largest trial conducted in this disease and uniquely designed to reflect real-world clinical practice. The trial evaluates how adding navtemadlin can deliver more clinically meaningful and durable responses, thereby addressing a critical unmet need.”
Under the terms of the agreement, Ipsen, through a fully-owned subsidiary, will pay $450 million upfront at closing. Kartos Therapeutics shareholders are also eligible to receive additional milestone payments of up to $1.3 billion, including a significant regulatory approval milestone and sales-based milestones.
The transaction is expected to be accretive to Ipsen’s core operating income from 2029, with limited dilution to 2026 full-year guidance. The transaction is anticipated to close by the end of the third quarter of 2026, subject to fulfillment of customary closing conditions including the expiration of the waiting period under the Hart-Scott-Rodino Antitrust Improvements Act.
Orrick Herrington & Sutcliffe LLP is acting as legal counsel to Ipsen. Goldman Sachs & Co. LLC and PJT Partners are serving as financial advisors to Kartos Therapeutics. DLA Piper LLP is serving as legal counsel to Kartos Therapeutics.
Ipsen is a global biopharmaceutical company focused on oncology, rare disease and neuroscience. The company is listed in Paris (Euronext: IPN) and in the U.S. through a Sponsored Level I American Depositary Receipt program (ADR: IPSEY). Kartos Therapeutics is a clinical-stage biopharmaceutical company developing navtemadlin for patients with myeloproliferative neoplasms.
