Philip Beer, Chief Scientific Officer at Step Pharma, reflects on the myleproliferative neoplasms field, and specifically the treatment of essential thrombocythaemia, 16 years after completing his PhD in the subject:
Plus ça change, plus c’est la même chose. These famous words (meaning ‘the more things change, the more they stay the same’) from the French critic Jean-Baptiste Alphonse Karr posed a relevant question as I returned to the field of myeloproliferative neoplasms after over a decade away. Step Pharma’s phase 1b study in essential thrombocythaemia (ET), a rare clonal blood disorder where platelet numbers are increased, opened to recruitment at the end of 2025, years after I completed my PhD with Tony Green in Cambridge studying ET and related myeloproliferative neoplasms (MPN).
My time in Tony’s lab saw a seismic shift in our understanding of MPN biology, with the discovery of activating mutations in the JAK2 gene followed closely by similar mutations in the thrombopoietic receptor (MPL) acting as key drivers for these diseases. The identification of signalling via JAK2 as the key nodal point driving MPN biology led to the rapid development of therapeutic JAK inhibitors, setting a new benchmark for bench to bedside translation. JAK inhibitors have gone on to improve outcomes, including symptom control and survival, for individuals living with myelofibrosis.
But what of ET? Advances in biology have delivered much change, including streamlined diagnosis and better prognostic tools; however, much has also stayed the same, including the treatment of ET which is essentially unchanged over the last 16 years. Unmet need remains for the significant number of individuals failing hydroxycarbamide (hydroxyurea). Whilst new therapies have entered clinical development for ET, none have yet demonstrated convincing proof of concept as a well-tolerated, easy to administer, efficacious therapy. In this regard, Step’s ET study is timely, bringing a novel mechanism of action that has already been extensively derisked in ongoing clinical trials in cancer indications. The ET study, which is recruiting individuals who are resistant to or intolerant of existing therapies, originated from Step’s study of lead asset dencatistat in lymphoma. This trial revealed a dose-dependent reduction in platelet count with continual dosing which we now understand to be mechanism-based (and which can be mitigated by intermittent dosing for individuals with lymphoma or solid tumours). This effect on platelets, along with the strong safety profile demonstrated from our studies in cancer indications, provided a clear rationale to expand into ET.
Along with updating myself on science and clinical development in the MPN space, a particular highlight of our work in ET has been re-engaging with the people who are striving to make a difference in our understanding and treatment of this condition. Many field-leading clinicians and scientists from my PhD days are still active, along with a new cohort of experts, including several contemporaries, who have made their mark on the field.
The next year will be an exciting time for Step Pharma on several fronts, including the possibility of fomenting real change in the treatment of ET.
