Press Release

Step Pharma (“the Company”), the global leader in CTPS1 inhibition for targeted cancer treatment, today announces that its Chief Scientific Officer, Philip Beer, will be presenting data on the identification of a CTPS1-dependent synthetic lethality in solid tumours at the 2025 EORTC-NCI-AACR International Conference on Molecular Targets and Cancer Therapeutics, being held from 22-26 October in Boston, MA.

The presentation will focus on the use of the AACR Project GENIE data, a publicly accessible cancer registry of real-world clinico-genomic data, to identify loss of CTPS2 as a novel biomarker to select solid tumours with a synthetic lethal dependency on CTPS1. Deletion of CTPS2 was subsequently identified as a frequent event in many cancer types, with the highest prevalence found in ovarian cancer. As tumours derived from epithelial tissues can utilise both CTPS1 and CTPS2 in the final step of the CTP synthesis cascade, loss of CTPS2 in solid tumours exposes a dependence which could be targeted with CTPS1 inhibition to prevent tumour cell proliferation.

As a result of these findings, dencatistat, an orally available and highly potent inhibitor of CTPS1, which is currently being evaluated in a phase 1a dose escalation study in patients with solid tumours, will be evaluated in safety expansion cohorts in patients with CTPS2 null cancers, with the first being ovarian cancer (NCT06297525). Selecting patients whose tumours have deleted CTPS2 represents a precision oncology approach that is expected to maximise the therapeutic potential of dencatistat.

Philip Beer, Chief Scientific Officer of Step Pharma, said:

“Our work analysing clinico-genomic data led us to identify patients with CTPS2 null solid tumours as a promising therapeutic application for dencatistat. About 15-20% of ovarian cancers harbour this deletion, and so through inhibition of CTPS1 with dencatistat, we can selectively target the de novo pyrimidine synthesis pathway in ovarian cancer and other solid tumours. I look forward to presenting at the EORTC-NCI-AACR international conference and to initiating the first expansion cohort in the near future.”

Session: AACR Project GENIE: Powering Drug Discovery Through an International Consortium’

Presentation title: Using GENIE data to drive oncology target identification and drug development.

Date: Thursday 23 October 2025

Time: 17:55 EDT

Contacts

Step Pharma
Andrew Parker, Chief Executive Officer
contact@step-ph.com

Media Relations
ICR Healthcare
Amber Fennell, Namrata Taak, Phillip Marriage
T. +44 (0) 20 3709 5700
steppharma@icrhealthcare.com

Step Pharma (“the Company”), the global leader in CTPS1 inhibition for targeted cancer treatment, today announces the completion of a €38 million Series C financing round.

The Series C round was led by new investor V-Bio Ventures, a Ghent-based life sciences venture capital fund, with participation from existing investors Pontifax, Bpifrance, Kurma Partners, Hadean Ventures, Sunstone Life Science Ventures and Inserm Transfert Initiative.

The financing will enable Step Pharma to continue advancing its ‘pipeline in a product’ strategy for dencatistat, a first-in-class, highly selective, orally bioavailable CTPS1 inhibitor currently in development for the treatment of cancers and blood disorders. All cancers appear to be highly reliant on CTPS1, a key component of the pyrimidine synthesis pathway, for DNA synthesis and cell proliferation.

Dencatistat is being evaluated in a phase 1/2 clinical trial for adult patients with relapsed/refractory T or B cell lymphoma, and received orphan drug designation for the treatment of T cell lymphoma in May 2025. The Company is also evaluating dencatistat in a phase 1 trial in solid tumour patients, with expansion cohorts in CTPS2-null ovarian, endometrial and lung cancer planned.

Clinical trials of dencatistat in lymphoma demonstrated that continual administration results in a dose dependent and reversible lowering of the platelet count. This led to the initiation of Step Pharma’s third clinical programme for dencatistat, in essential thrombocythaemia, a rare clonal blood disorder in which the bone marrow produces too many platelets.

Andrew Parker, Chief Executive Officer, Step Pharma, commented:

“This Series C financing will allow us to build upon the significant clinical progress we have made with dencatistat, with three clinical programmes underpinning our ‘pipeline in a product’ strategy. These funds will enable us to expand our clinical dataset, complete all ongoing phase 1 studies, and further derisk dencatistat as we enter phase 2 and explore its potential to improve patient outcomes through CTPS1 inhibition. I’d like to thank V-Bio Ventures for joining our investor syndicate and leading this round, and our existing investors for their continued participation and support.”

Ward Capoen, Partner, V-Bio Ventures, said:

“We are delighted to support Step Pharma in its next phase of growth through this Series C financing. The Company’s approach to inhibiting CTPS1 to selectively block the proliferation of cancer cells is highly promising, and the team has followed the data into essential thrombocythaemia after observing dencatistat’s effect on platelet levels. This multi-pronged clinical plan has further derisked dencatistat and positions Step Pharma to provide new therapeutic options for patients.”

Contacts

Step Pharma
Andrew Parker, Chief Executive Officer
contact@step-ph.com

Media Relations
ICR Healthcare
Amber Fennell, Namrata Taak, Phillip Marriage
T. +44 (0) 20 3709 5700
steppharma@icrhealthcare.com

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, commented: “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 tumours, 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 programme.”

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.

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

Contacts

Step Pharma
Andrew Parker, Chief Executive Officer
contact@step-ph.com

Media Relations
ICR Healthcare
Amber Fennell, Namrata Taak, Phillip Marriage
T. +44 (0) 20 3709 5700
steppharma@icrhealthcare.com

The designation highlights the significant unmet medical need in T cell lymphoma, a rare and aggressive group of blood cancers. It also recognises the potential of dencatistat as a novel, selective therapeutic option. Orphan drug designation provides incentives designed to support the development of drugs for rare diseases, including market exclusivity upon approval, tax credits for clinical trial costs, and waiver of certain FDA fees.

Andrew Parker, Chief Executive Officer of Step Pharma, commented:

“Receiving orphan drug designation from the FDA, which may confer seven years of market exclusivity for dencatistat, marks an important milestone in our mission to deliver highly selective cancer therapies for patients with difficult-to-treat cancers. T cell lymphoma remains a challenging disease with limited treatment options, and we believe CTPS1 inhibition represents a new therapeutic approach with the potential to meaningfully improve outcomes.”

Dencatistat is being evaluated in a phase 1/2 clinical trial for adult patients with relapsed/refractory T or B cell lymphoma. The Company is also evaluating dencatistat in a phase 1 trial in solid tumour patients, with expansion cohorts in CTPS2-null ovarian and lung cancer planned. Additionally, a phase 1b trial in essential thrombocythaemia is expected to commence in the first half of 2025, further supporting dencatistat’s potential as a targeted therapy across multiple cancer types.

Contacts

Step Pharma
Andrew Parker, Chief Executive Officer
contact@step-ph.com

Media Relations
Consilium Strategic Communications
Amber Fennell, Namrata Taak, Davide Salvi
T. +44 (0) 20 3709 5700
steppharma@icrhealthcare.com

Step Pharma (“the Company”), the global leader in CTPS1 inhibition for targeted cancer treatment, today announced that the first patient has been dosed at Next Oncology, San Antonio, TX USA, with its lead asset dencatistat (STP938) in a clinical trial for patients with solid tumours.

This open label trial is evaluating the safety, tolerability and pharmacokinetics of dencatistat, a first-in-class, highly selective, orally bioavailable CTPS1 inhibitor. The trial consists of two parts: a phase 1a dose escalation recruiting patients with solid tumours, followed by a phase 1b expansion cohort specifically for patients with CTPS2 null ovarian cancer, planned to start in Q1 2025.

Approximately 325,000 women worldwide are diagnosed with ovarian cancer each year. 15-20% of ovarian cancers harbour a deletion of the gene encoding CTPS2. Selecting patients whose tumours have deleted CTPS2 represents a precision oncology approach that is expected to maximise the therapeutic potential of dencatistat. The trial is recruiting patients with advanced cancer who have no other treatment options available.

Andrew Parker, Chief Executive Officer of Step Pharma, commented:

“The start of our first clinical trial of dencatistat for solid tumours marks a significant milestone in our ‘pipeline in a product’ strategy. Dencatistat, our first-in-class CTPS1 inhibitor, is now expanding from blood cancers to solid tumours, demonstrating its versatility. With a substantial number of ovarian cancer patients potentially harbouring CTPS2 deletions, and similar deletions observed in other cancer types, we are excited about the potential of dencatistat as a tumour-agnostic targeted treatment.”

Furthermore, the Company announces that the Clinical Trial Application for the phase 1 trial of dencatistat in patients with solid tumours has been approved by the UK Medicines and Healthcare products Regulatory Agency (MHRA). This approval, along with the previously cleared Investigational New Drug (IND) application to the US Food and Drug Administration (FDA), announced in June 2024, enables the Company to progress dencatistat into clinical trials in both the UK and the US.

The start of this solid tumour trial follows the ongoing phase 1/2 trial of dencatistat for adult patients with relapsed/refractory T or B cell lymphoma, which commenced in October 2022.

Step Pharma is pioneering a novel class of oral drugs that specifically inhibit nucleotide synthesis and the enzyme CTPS1 in particular, which was originally identified as an essential gene for lymphocyte proliferation. By targeting CTPS1, Step Pharma has unlocked the ability to selectively target the de novo pyrimidine synthesis pathway in cancer cells. This groundbreaking approach is predicted to enable the highly selective treatment of both blood cancers and solid tumours.

Further details of the planned Phase 1 trial can be found on clinicaltrials.gov under the identifier NCT06297525.

Contacts

Step Pharma
Andrew Parker, Chief Executive Officer
contact@step-ph.com

Media Relations
Consilium Strategic Communications
Amber Fennell, Namrata Taak, Davide Salvi
T. +44 (0) 20 3709 5700
steppharma@icrhealthcare.com

The therapeutic activity was observed for mantle cell lymphoma (MCL), including difficult-to-treat in vitro and in vivo models. Furthermore, Step Pharma’s CTPS1 inhibitors show significant synergy when combined with venetoclax, a selective BCL2 inhibitor that is commonly used to treat certain types of lymphoma and leukaemia.

CTPS1, an enzyme crucial in pyrimidine synthesis, plays a significant role in cancer cell proliferation. Step Pharma’s compounds selectively inhibit the de novo pyrimidine synthesis pathway by targeting CTPS1, providing a novel approach to cancer treatment. The Company’s lead asset, dencatistat (STP938), a first-in-class, highly selective, orally bioavailable CTPS1 inhibitor, is currently in phase 1 clinical development for T cell and B cell lymphoma (NCT05463263) with study sites open in France, the UK, and the USA.

MCL accounts for approximately 5% of B cell lymphoma. Despite recent advancements in the treatment of MCL, there is still an unmet clinical need for those who have not responded to Bruton’s Tyrosine Kinase (BTK) inhibitor therapy.

Andrew Parker, Chief Executive Officer of Step Pharma, commented

“The publication in Haematologica of these preclinical data provides additional evidence of the importance of inhibiting CTPS1 for the treatment of blood malignancies, including T and B cell lymphoma. The findings further support our approach as we continue to progress our phase 1 trial to develop targeted and efficient treatment options for individuals with blood cancer.”

David Chiron, CNRS researcher at CRCI²NA, Nantes University, added

“These data represent a significant advancement in our understanding of blood cancer biology, particularly regarding the role of CTPS1. Our research on inhibiting CTPS1 emphasises the potential of this approach to fill an important gap in current treatment methods. These findings support the targeted inhibition of CTPS1 as a promising therapeutic strategy and pave the way for further research to gain a deeper understanding of its role and broader applications in different types of blood cancers.”

Article citation: Selective pharmacological targeting of CTPS1 shows single-agent activity and synergizes with BCL2 inhibition in aggressive mantle cell lymphoma. Romane Durand, Celine Bellanger, Benoit Tessoulin, Charlotte Kervoelen, Christelle Dousset, Emmanuelle Menoret, Helene Asnagli, Andrew Parker, Philip Beer, Catherine Pellat-Deceunynck, and David Chiron. Haematologica, 2024; 109, 2574 – 2584.

Contacts

Step Pharma
Andrew Parker, Chief Executive Officer
contact@step-ph.com

Media Relations
Consilium Strategic Communications
Amber Fennell, Namrata Taak, Davide Salvi
T. +44 (0) 20 3709 5700
steppharma@consilium-comms.com

Contacts

Step Pharma
Andrew Parker, Chief Executive Officer
contact@step-ph.com

Media Relations
ICR Consilium
Amber Fennell, Namrata Taak, Davide Salvi
T. +44 (0) 20 3709 5700
steppharma@icrhealthcare.com

Contacts

Step Pharma
Andrew Parker, Chief Executive Officer
contact@step-ph.com

Media Relations
Consilium Strategic Communications
Amber Fennell, Namrata Taak, Davide Salvi
T. +44 (0) 20 3709 5700
steppharma@consilium-comms.com

Contacts

Step Pharma
Andrew Parker, Chief Executive Officer
contact@step-ph.com

Media Relations
Consilium Strategic Communications
Amber Fennell, Namrata Taak, Stella Lempidaki
T. +44 (0) 20 3709 5700
steppharma@consilium-comms.com