Step Pharma announced on September 2, 2025, that the first participant has been dosed with dencatistat in a phase 1b clinical trial for essential thrombocythaemia (ET), expanding the company's clinical program into a third indication for this first-in-class CTPS1 inhibitor.
Novel Approach to Rare Blood Disorder
Essential thrombocythaemia 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 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.
The rationale for investigating dencatistat in ET stems from observations in lymphoma trials, where continual administration of the drug resulted in dose-dependent and reversible lowering of platelet counts. This finding, which has been mitigated by intermittent dosing for patients with lymphoma or solid tumours, combined with the drug's excellent tolerability profile, provides strong scientific justification for the ET indication.
Trial Design and Patient Population
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 study is being conducted at 12 sites across France and the UK, with trial details available on clinicaltrials.gov under identifier NCT06786234.
Andrew Parker, Chief Executive Officer of Step Pharma, stated: "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."
CTPS1 Inhibition Mechanism
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, with all cancers appearing to be addicted to CTPS1 for DNA synthesis.
The drug entered clinical development in October 2022 for the treatment of T cell and B cell lymphoma and in September 2024 for solid tumours. According to Step Pharma, 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.
Strategic Expansion
This milestone marks the third indication for dencatistat, demonstrating its versatility as what Step Pharma calls a "pipeline in a product." The expansion into essential thrombocythaemia, alongside ongoing trials in lymphoma and solid tumours, further illustrates the potential versatility of dencatistat as a targeted therapy.
Step Pharma, founded in 2014 and based in Saint-Genis-Pouilly, France, positions itself as the world leader in CTPS1 inhibition. The company was established based on scientific discoveries by Prof. Alain Fischer and Dr Sylvain Latour, with backing from a syndicate of investors led by Kurma Partners and including Bpifrance, Pontifax, Hadean Ventures, Sunstone Life Science Ventures, and others.
