*  Decision adds to existing collaboration agreement with Exelixis, permitting
    Ipsen to seek potential marketing authorizations for Cabometyx(®)
    (cabozantinib) in advanced pancreatic and extra pancreatic neuroendocrine
    tumors outside of the U.S. and Japan

* Agreement based on CABINET Phase III trial, led by the Alliance for Clinical

    Trials in Oncology, which demonstrated improvements in progression-free
    survival for Cabometyx versus placebo (1)

* Ipsen has engaged with regulatory authorities in the European Union and will submit a regulatory filing on the basis of these data
PARIS, FRANCE, 2 July 2024 - Ipsen (Euronext: IPN; ADR: IPSEY) announced today confirmation of an expanded collaboration and license agreement with Exelixis, Inc. for the development of Cabometyx(®) (cabozantinib) in advanced pancreatic neuroendocrine tumors (pNETs) and advanced extra-pancreatic neuroendocrine tumors (epNETs). The agreement is based on positive outcomes from the CABINET Phase III trial, led by the Alliance for Clinical Trials in Oncology and sponsored by the National Cancer Institute (NCI), which investigated Cabometyx versus placebo in people living with advanced pNETs or advanced epNETs whose disease had progressed after prior systemic therapy. An independent Data and Safety Monitoring Board recommended to stop accrual to the study, unblind patients and allow crossover from placebo to Cabometyx. This was due to early efficacy demonstrated at an interim analysis in both of the trial's cohorts, with clinically meaningful improvements in progression-free survival (PFS).(1)
"With many people diagnosed with neuroendocrine tumors at an advanced stage of disease and treatment options limited upon progression, the need for efficacious
new therapies is extensive," said Christelle Huguet, EVP and Head of Research and Development, Ipsen. "The positive results demonstrated for Cabometyx within the CABINET Phase III trial represent clinically meaningful improvements in progression-free survival at a challenging stage of disease where there are few or no available treatment options. We look forward to discussing these clinical findings with regulatory authorities."
Neuroendocrine tumors (NETs) are a group of uncommon tumors that develop in the cells of the neuroendocrine system throughout the body.(2)(,)(3) The symptoms of
NETs are often not distinct and difficult to identify, leading to delays in diagnosis, with 58% of people presenting with metastatic disease at diagnosis.(3) The number of people newly diagnosed with NETs is believed to be rising due to increasing awareness and better methods of diagnosis, with approximately 35 in every 100,000 people currently living with NETs globally.(3,)(4) The survival rate varies greatly depending on the primary site and stage of disease, however for people living with advanced pNETs which has spread to distant parts of the body, the prognosis is poor, with a five-year survival rate of 23%.(5)
CABINET Phase III trial
Data from the study, which demonstrated PFS benefits at interim analyses, were presented at the European Society for Medical Oncology Congress 2023 by Professor Jennifer Chan, MD, MPH, Dana-Farber Cancer Institute, Boston:(1)

  * In the pNET cohort, at a median follow-up of 16.7 months, median PFS based
    on local radiology review was 11.4 months for Cabometyx versus 3.0 months
    for placebo (hazard ratio (HR) 0.27 (95% confidence interval (CI)

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