Step Pharma Announces First Participant Dosed in a Phase 1b Trial of Dencatistat for Essential Thrombocythaemia

Step Pharma recently announced the first participant has been dosed with its lead asset dencatistat in a phase 1b clinical trial for essential thrombocythaemia (ET).

ET is a rare clonal blood disorder in which the bone marrow produces too many platelets, increasing the risk of blood clots that can lead to serious thrombotic complications such as stroke or heart attack. Current treatments aim to lower platelet counts in order to reduce the risk of complications, but they can be associated with side effects or may not be suitable for all individuals, highlighting the need for more targeted therapies with improved safety profiles.

Clinical trials of dencatistat in lymphoma have demonstrated that continual administration of dencatistat results in a dose dependent and reversible lowering of the platelet count. This finding (which has been mitigated by intermittent dosing for patients with lymphoma or solid tumours), along with the excellent tolerability profile of the drug, provides a strong rationale for investigating dencatistat as a treatment for ET.

Andrew Parker, Chief Executive Officer of Step Pharma, said “Initiating the clinical evaluation of dencatistat in essential thrombocythaemia represents a significant milestone in our ‘pipeline in a product’ strategy. We believe we can harness selective CTPS1 inhibition to provide a safer, targeted approach to the treatment of ET. This expansion into a new indication, alongside our ongoing trials in lymphoma and solid tumors, further demonstrates the    potential versatility of dencatistat as a targeted therapy. We look forward to collaborating with clinical investigators and those living with ET to advance this important program.”

The Phase 1b open-label trial will evaluate the safety, tolerability, and preliminary activity of dencatistat in approximately 20 adult participants with high-risk ET who are resistant to, or intolerant of, hydroxycarbamide (hydroxyurea) therapy. The trial is being conducted at 12 sites across France and the UK.

Andrew Parker, Chief Executive Officer of Step Pharma, said “Initiating the clinical evaluation of dencatistat in essential thrombocythaemia represents a significant milestone in our ‘pipeline in a product’ strategy. We believe we can harness selective CTPS1 inhibition to provide a safer, targeted approach to the treatment of ET. This expansion into a new indication, alongside our ongoing trials in lymphoma and solid tumors, further demonstrates the    potential versatility of dencatistat as a targeted therapy. We look forward to collaborating with clinical investigators and those living with ET to advance this important program.”

Further details of the phase 1b trial for ET can be found on clinicaltrials.gov under the identifier NCT06786234.

Dencatistat (STP938) is a first-in-class, highly selective, orally bioavailable inhibitor of CTP synthase 1 (CTPS1), a key component of the pyrimidine synthesis pathway. CTPS1 inhibition blocks the proliferation of cancer cells and results in cell death. All cancers appear to be addicted to CTPS1 for DNA synthesis. Dencatistat entered clinical development in October 2022 for the treatment of T cell and B cell lymphoma and in September 2024 for the treatment of solid tumors. Dencatistat has the potential to become the backbone of treatment regimens for a broad range of haematological and solid tumours, as well as being a potent monotherapy for hard-to-treat blood cancers.

Step Pharma’s goal is to bring about a step change in how cancer is treated with targeted therapies that kill cancer cells and leave healthy cells unharmed. The Company is the world leader in CTPS1 inhibition, a new approach with the potential to yield highly selective, safe and effective treatments for both blood cancers and solid tumors.

Step Pharma was founded in 2014 by Kurma Partners, the Imagine Institute and Sygnature Discovery, based on the scientific discoveries of Prof. Alain Fischer and Dr Sylvain Latour. Step Pharma is based in Saint-Genis-Pouilly, France, and is supported by a strong syndicate of investors led by Kurma Partners and including Bpifrance (Fonds Biothérapies Innovantes et Maladies Rares and InnoBio2 Fund), Pontifax, Hadean Ventures, Sunstone Life Science Ventures, Inserm Transfert Initiative, Idinvest, Sygnature Discovery and the Imagine Institute. For more information, visit www.step-ph.com.