Press Release

St. Genis-Pouilly, France, 24 July 2024

Step Pharma, the world leader in CTPS1 inhibition for the targeted treatment of cancer, today announces the publication in the August edition of Haematologica of preclinical data from the University of Nantes (CRCI²NA) further supporting the therapeutic activity of Step’s highly selective CTPS1 inhibitors in the treatment of blood cancers.

St. Genis-Pouilly, France, 25 June 2024

Step Pharma, the global leader in CTPS1 inhibition for targeted cancer treatment, today announced that its lead asset dencatistat (STP938), a first-in-class selective CTPS1 inhibitor, has cleared an investigational new drug (IND) application by the US Food and Drug Administration (FDA), enabling Step Pharma to progress dencatistat into a Phase 1 clinical trial for patients with solid tumours, anticipated to start in Q3 2024.

The open label trial will evaluate the safety, tolerability and pharmacokinetics of dencatistat in adults living with advanced solid tumours, with a safety expansion in advanced CTPS2 null ovarian cancer. Selecting patients whose tumours have deleted CTPS2 represents a precision oncology approach that is expected to maximise the therapeutic potential of dencatistat. The trial will recruit patients with advanced cancer who have no other treatment options available.

Step Pharma is pioneering a novel class of oral drugs that specifically inhibit nucleotide synthesis and the enzyme cytidine triphosphate synthase 1 (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.

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

“The approval by the US FDA to initiate clinical evaluation of dencatistat in solid tumours is a significant milestone for Step Pharma as we continue to advance our lead candidate beyond blood cancers and into solid tumours, bringing us a step closer to a potentially paradigm-shifting treatment for patients. We look forward to starting the study in Q3 2024 and continuing our progress in driving a step change in the way we treat cancer, making a real difference to patients’ lives.”

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

St. Genis-Pouilly, France, 30 May 2024

Step Pharma, the global leader in CTPS1 inhibition for targeted cancer treatment, today announced it has received an issue notification from the United States Patent and Trademark Office (USPTO), indicating the grant of a new US patent, and that the International Nonproprietary Names (INN) expert committee has approved the name “dencatistat” for the Company’s lead compound STP938.

The patent, US Patent No 11,987,573, covers one of the key compounds within the Company’s extensive portfolio of CTPS1 inhibitor assets. This patent issue strengthens Step Pharma’s intellectual property, which is safeguarded by a range of published and unpublished patent families.  Previously, the Company announced that the European Patent Office (EPO) granted patent EP3870574, which covers the same key compounds.

In addition, Step Pharma announces that the United States Adopted Names (USAN) Council, and the World Health Organization (WHO) INN expert committee has approved “dencatistat” as the nonproprietary (generic) name for the Company’s lead compound STP938. Dencatistat (STP938) is a first-in-class oral cancer therapeutic specifically inhibiting CTPS1. This compound is currently in a Phase 1/2 clinical trial to evaluate its safety, tolerability, pharmacokinetics, and preliminary efficacy in adult patients with relapsed or refractory T cell and B cell lymphomas.

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

“The issue notification of our new US patent, combined with the recent European patent grant, significantly strengthens our intellectual property portfolio and reinforces our leadership in developing CTPS1 inhibitors. These milestones are crucial as we continue to advance our lead compound STP938, which has now been assigned the name dencatistat, through multiple clinical trials. We are committed to bringing this innovative treatment to patients with high unmet medical needs, aiming to improve outcomes for those affected by blood cancers and solid tumours.”

St. Genis-Pouilly, France, 10 May 2023

Step Pharma, the world leader in CTPS1 inhibition for the targeted treatment of cancer, today announces that members of its management team will be participating at a number of conferences in May and June 2023.

By targeting CTPS1, an enzyme that catalyses a rate-limiting step in pyrimidine synthesis, Step Pharma has unlocked the ability to selectively inhibit the de novo pyrimidine synthesis pathway, enabling a highly selective treatment of cancer.

23^rd Bio€quity Europe, Dublin, Ireland, 15-16 May & 22-23 May Digital Partnering

• In person corporate presentation by Andrew Parker, CEO at 1.28pm on 5 May

2023 ASCO Annual Meeting, Chicago, IL, US, 2-6 June

• Poster presentation: A phase 1/2 study of STP938, a first-in-class inhibitor of CTP synthase 1, in patients with relapsed/refractory B or T cell lymphoma.

Authors: Manish Patel, Matthew Ahearne, Kim Linton, Christopher Fox, David Lewis, Maureen Higgins, Brian Schwartz, Philip Beer, Michael Tees

Session Title: Hematologic Malignancies – Lymphoma and Chronic Lymphocytic Leukemia

Session Date and Time: 6/5/2023, 8:00 AM-11:00 AM CST

Track: Hematological Malignancies

Subtrack: Non-Hodgkin Lymphoma

Clinical Trial Registration Number: NCT05463263

Abstract #TPS7591

Poster Bd #135b

BIO International Convention Congress, Boston, MA, US, 5-8 June

International Conference of Malignant Lymphoma, Lugano, Switzerland, 13-17 June

St. Genis-Pouilly, France, 04 April 2023

• Preclinical data published in HemaSphere demonstrate potential of inhibiting CTPS1 as a novel treatment approach for cancer
• Data further support rationale for developing STP938, currently in clinical trials for the treatment of T cell and B cell lymphoma

Step Pharma, the world leader in CTPS1 inhibition for the targeted treatment of cancer, today announces the publication of compelling preclinical data detailing the therapeutic potential of inhibiting CTPS1 in haematological malignancies.

The data, published in HemaSphere (the official journal of the European Hematology Association), describe the identification and characterisation of CTP synthase 1 (CTPS1), an enzyme that catalyses a rate-limiting step in pyrimidine synthesis, as a novel therapeutic target in T cell and B cell malignancies.

Step Pharma’s selective CTPS1 inhibitors induced cell death of neoplastic lymphoid cells in vitro and demonstrated anti-tumour activity in vivo in models of both T cell and B cell malignancies.

STP938, a first-in-class, highly selective, orally bioavailable inhibitor of CTPS1 recently entered a Phase 1/2 trial for T cell and B cell lymphomas (NCT05463263) and study sites are open in the UK and the USA.

Lymphoma is the most common haematological malignancy. Despite improvements in patient survival with modern immunochemotherapy treatments, there remains a significant need for novel targeted agents to treat both T cell and B cell malignancies.

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

“Our deep understanding of the pyrimidine synthesis pathway and CTPS1 biology has yielded a new targeted approach to treating blood and solid tumours. This publication summarises the important work undertaken by Step Pharma, providing compelling evidence for CTPS1 being a key therapeutic target in T and B cell malignancies. We are pleased to have developed a host of CTPS1 small molecule modulators and to be conducting Phase 1/2 clinical trials with the most advanced CTPS1 inhibitor in the world, STP938. Our ultimate goal is to drive a step change in the way we treat cancer and make a real difference in patients’ lives.”

Article citation: Asnagli et al. CTP Synthase 1 Is a Novel Therapeutic Target in Lymphoma. HemaSphere 7(4):p e864, April 2023. | DOI: 10.1097/HS9.0000000000000864

St. Genis-Pouilly, France, 09 March 2023

Step Pharma, the world leader in CTPS1 inhibition for the targeted treatment of cancer, today announces that the European Patent Office (”EPO”) has granted patent EP3870574, which covers key compounds in the Company’s broad portfolio of CTPS1 inhibitor assets. The granting of this patent strengthens the Company’s patent portfolio covering its CTPS1 inhibitor assets, which is currently protected by a range of published and unpublished patent families.

By targeting CTPS1, an enzyme that catalyses a rate-limiting step in pyrimidine synthesis, Step Pharma has unlocked the ability to selectively inhibit the de novo pyrimidine synthesis pathway, enabling a highly selective treatment of cancer.

EP3870574 has a filing date of October 2019 and could protect this technical space until October 2039, with a potential for further extensions depending on the timing of future regulatory approvals. The patent will be validated in a number of strategically important countries across Europe.

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

“The European patent granted to Step Pharma for key CTPS1 inhibitor compounds provides further protection for our pioneering research into CTPS1 biology. Our broad portfolio of CTPS1 inhibitors with its proprietary chemistry has the potential to bring a step change in cancer treatment with one asset, STP938, already in Phase 1/2 trials for T cell and B cell lymphoma.”

St. Genis-Pouilly, France, 04 January 2023

Philip is a board-certified haematologist with over 16 years of frontline healthcare experience as well as biopharmaceutical industry experience, particularly in translational medicine, drug development, and biomarker discovery.

He joined Step Pharma in June 2021 as Vice President, Head of Research & Translation Medicine and has led the Company’s research strategy and execution on the run up to Step Pharma’s lead asset, the targeted CTP synthase 1 (CTPS1) inhibitor STP938, entering the clinic in both the UK and US with compelling preclinical data in support.
Philip is being promoted to Chief Scientific Officer from Vice President, Head of Research & Translational Medicine at Step Pharma. In his new role, he will lead the Company’s research activities with a focus on further development of STP938, a first-in-class, highly selective, orally bioavailable inhibitor of CTPS1 currently being evaluated for safety and efficacy in T cell and B cell lymphomas.

Prior to joining Step Pharma, Philip held senior leadership roles in biotech and biopharma companies, overseeing oncology drug development and biomarker discovery programmes. He is a cofounder of Gabriel Precision Oncology, a clinical software company also focussed on improving outcomes for those living with cancer.

Andrew Parker, Chief Executive Officer of Step Pharma said:

“It has been a privilege working with Philip and advancing STP938 to the clinic with a strong pre-clinical data package built under his stewardship. As Chief Scientific Officer and with his extensive experience in leading oncology drug discovery and development programmes, he will continue his invaluable work to progress our pipeline of a novel class of oral drugs that specifically inhibit CTPS1, with the potential to yield highly selective, safe and effective treatments for both blood cancers and solid tumours..”

Dr Philip Beer, Chief Scientific Officer of Step Pharma, commented:

“I am honoured to be working with such a driven leadership team and thrilled to be promoted to the role of Chief Scientific Officer. Step Pharma is a highly innovative, research driven company with high quality science which has the potential to transform how we treat cancer.  I remain committed to bringing Step Pharma’s targeted therapies to the clinic and to continue to develop life-saving treatments for patients.”

Philip is a Member of the Royal College of Physicians, UK, and a Fellow of the Royal College of Pathologists, UK. He holds a PhD in molecular cancer biology from the University of Cambridge, UK. Following this he conducted post-doctoral research studies at the BC Cancer Agency, Vancouver, Canada, and has more than 100 peer-reviewed publications. Philip is an Honorary Professor of Translational Medical at the Hull York Medical School, UK.

St. Genis-Pouilly, France, 12 December 2022

St. Genis-Pouilly, France and London, UK, 12 December 2022 – Step Pharma, the world leader in CTPS1 inhibition for the targeted treatment of cancer, today announces that encouraging pre-clinical data on its first-in-class, highly selective, orally bioavailable CTPS1 inhibitor, STP938, were presented at the 64th American Society of Hematology (ASH) Annual Meeting held from the 10-13 December, 2022 in New Orleans, Louisiana and virtually.

The data presented by Step Pharma collaborators demonstrates the potential of STP938, a highly selective CTPS1 inhibitor, as a therapeutic for the treatment of mantle cell lymphoma and multiple myeloma both as a single agent and in combination with other targeted inhibitors.

In pre-clinical models of mantle cell lymphoma, STP938 showed strong anti-tumour effects, which were further enhanced by combined administration with venetoclax, a selective BCL-2 inhibitor currently in clinical development for treatment of this lymphoma type.

Single agent STP938 also showed activity in preclinical models of multiple myeloma and demonstrated strong synergy when combined with an inhibitor of the DNA damage response pathway (ATR, CHEK1 or WEE1).

“We are encouraged by the promising pre-clinical data produced by our collaborators showing the anti-tumour effects of STP938 in mantle cell lymphoma and multiple myeloma models”,

said Andrew Parker, Chief Executive Officer of Step Pharma.

“These data reinforce our conviction that by inhibiting CTPS1, a key component of the pyrimidine synthesis pathway to which all cancers are addicted, STP938 has broad therapeutic potential. We have commenced clinical trials to test the safety and efficacy of STP938 in T cell and B cell lymphomas to bring this potentially lifesaving therapy to patients in our efforts to drive a step change in the way we treat cancer.”

Full details of the poster presentations, which were both presented on Sunday, December 11, 2022 at 6:00 PM-8:00 PM EST in Hall D (Ernest N. Morial Convention Center), are:

• Title: STP938, a Selective CTPS1 Inhibitor, Shows Single Agent Activity and Synergy with BCL2 Inhibition in Preclinical Models of Mantle Cell Lymphoma

Authors: David Chiron, PhD, Emmanuelle Menoret, PhD, Charlotte Kervoelen, PhD, Sophie Maïga, Celine Bellanger, Benoit Tessoulin, MD, Cyrille Touzeau, Hélène Asnagli, PhD, Andy Parker, PhD, Philip Beer, MD, PhD and Catherine Pellat-Deceunynck, PhD

• Title: CTPS1 is a Novel Therapeutic Target in Multiple Myeloma that Synergizes with Inhibition of ATR, CHEK1 or WEE1

Authors: Christina Pfeiffer, MSc, Alexander Michael Grandits, PhD, Hélène Asnagli, PhD, Anja Schneller, MSc, Julia Huber, MSc, Niklas Zojer, MD, Martin Schreder, MD, Andrew Parker, PhD, Arnold Bolomsky, PhD, Philip Beer, MD, PhD, Heinz Ludwig, MD

Step Pharma also recently entered clinical development with STP938 in a Phase I/II trial for T cell and B cell lymphomas. An abstract outlining the study design was published by ASH in the journal Blood. Full details are:

• Title: A Phase 1/2 Study of STP938, a First in Class Inhibitor of CTP Synthase 1, in Patients with Relapsed/Refractory B or T Cell Lymphoma

Authors: Philip Beer, Maureen Higgins, Hélène Asnagli, Eef Hoeben, Michael Hubank, Andrew Parker, Brian Schwartz

St. Genis-Pouilly, France, 3 November 2022

St. Genis-Pouilly, France and London, UK, 07 December 2022 – Step Pharma, the world leader in CTPS1 inhibition for the targeted treatment of cancer, and Concr, a techbio company with a statistical learning-powered biomarker prediction engine, today announced a partnership to identify biomarkers to improve therapeutic response to inhibitors of cytidine triphosphate synthase 1 (CTPS1), an enzyme to which all cancers appear to be addicted.

Concr’s proprietary data modelling will be used to identify biomarkers for Step Pharma’s cancer drug assets, which includes its first-in-class, highly selective, orally bioavailable CTPS1 inhibitor, STP938, by effectively integrating diverse experimental data with patient and tumour-centric datasets. Concr adopts cosmology methods to effectively combine diverse data types into a single holistic tumour model with superior predictive power. The biological insights generated will be utilised by Step Pharma in its pre-clinical and clinical development programmes, with the overall aim of improving patient response and outcomes.

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

“We are committed to bringing our targeted treatments, including STP938, to patients as fast as possible. To this end, we are excited to partner with Concr and employ its integrated analysis of complex datasets to explore the potential to accelerate the development of our targeted cancer therapy assets and maximise their utility. Our collaboration with Concr is aimed at deepening our understanding of CTPS1 biology and identifying patients most likely to respond to CTPS1 inhibition.”

Matt Foster, Chief Executive Officer of Concr, added:

“There is a significant need for novel targeted therapies across a range of cancer types. However, only with successful application of biomarkers can such cutting edge therapeutic developments be optimally applied in a clinical setting. Concr is excited to be enabling this to happen with Step Pharma – utilising our approach to ensure inhibitors of CTPS1 have the greatest chance of translational success by being applied to patients who will truly benefit.”

Step Pharma recently entered clinical development with its first in class CTPS1 inhibitor STP938 in a Phase I/II trial for T cell and B cell lymphomas and is the latest company to utilise the potential of data and predictive modelling for translational research. By inhibiting the enzyme CTPS1, Step Pharma can selectively target the de novo pyrimidine synthesis pathway in cancer cells, enabling highly selective treatment of both blood cancers and solid tumours. Concr’s existing partnerships are investigating biomarkers of response in multiple cancer types, including breast cancer and cancer of unknown primary.