Step Pharma, Author at Step Pharma

Step Pharma announces first patient dosed in a phase 1 trial of dencatistat for patients with solid tumours

Press Release

St. Genis-Pouilly, France, 3 September 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.

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

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About dencatistat

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 tumours.

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.

About Step Pharma

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 tumours.

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. More information on the company can be found at www.step-ph.com.

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Step Pharma In Press Release

Step Pharma announces publication in Haematologica of key data supporting CTPS1 inhibition as a therapeutic target in blood cancer

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.

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

+ DOWNLOAD PDF

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 cancer treatments for both blood cancers and solid tumours.

The Company’s lead product STP938 has received both IND and CTA clearance to proceed into first in human trials in the US and UK for the treatment of T cell and B cell lymphomas. Clinical trials in lymphoma commenced in September 2022. STP938 has the potential to be the backbone of a multitude of cancer therapies as well as a potent monotherapy for hard-to-treat blood cancers.

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Step Pharma In Press Release

Step Pharma announces US FDA clearance for a Phase I clinical trial in solid tumours with dencatistat (STP938)

Press Release

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.

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

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About dencatistat

Dencatistat (previously 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 September 2022 for the treatment of T cell and B cell lymphoma.

About Step Pharma

The Company’s lead asset, dencatistat, previously received investigational new drug (IND) and clinical trial application (CTA) clearance to proceed into first in human trials in the US, UK and EU for the treatment of T cell and B cell lymphomas, and has now received clearance in the US to commence clinical development for the treatment of solid tumours. Clinical trials in lymphoma commenced in September 2022; the solid tumour clinical trial is expected to commence recruitment Q3 2024.

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Step Pharma In Press Release

Step Pharma announces US patent to be granted for CTPS1 inhibitor and assignment of drug name dencatistat for lead compound STP938

Press Release

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.”

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

+ DOWNLOAD PDF

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 cancer treatments for both blood cancers and solid tumours.

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Step Pharma In Blog

Trailblazing a new concept for treating cancer

Over the years, there have been a number of significant advances in the treatment and management of cancer.

However, cancer has been, and continues to be, one of the most challenging diseases to solve. Despite decades of research dedicated to the search for cures, cancer is currently the world’s biggest killer, responsible for the deaths of around 10 million people globally, young and old, every year. For this reason, there is a need to explore new ideas and new concepts.

With 18 million new cases of cancer worldwide reported in 2020, and 10 million deaths, there is a need to explore new ideas and new concepts.

Cancer is caused by faults, called mutations, in the DNA of cancer cells that causes them to grow uncontrollably. These cancer cells have a frustrating capability to outsmart attack by our immune system, the first line of defence. In addition, response to chemotherapy and targeted therapy is frequently not long-lasting due to the development of resistance. To add further fuel to the fire, because of the large variety of different mutations, a treatment that works for one individual might not have the same result in another. Because of this complexity, scientists across the globe are searching for different approaches to target cancer in new ways.

One of the new approaches being applied by scientists is to precisely target a vulnerability of cancer cells. This includes important concepts such as synthetical and collateral lethality, whereby DNA mutations found in cancer cells render them highly sensitive to precision cancer treatments. A potential advantage of this approach is maximising the effects of the drug against cancer cells whilst sparing normal tissues. Challenges include identifying the right cancers, which often requires the development of new assays based on genomics or protein expression.

Having overseen the development of many new cancer drugs across a career in pharma and biotech spanning close to 30 years, Brian Schwartz was in search of a company pursuing science that no-one has applied. In 2022, he joined Step Pharma as its CMO. Brian and the team at Step Pharma are homing in their efforts on targeting an enzyme called cytidine triphosphate synthase (CTPS) 1.

But why is CTPS1 so important?

Dividing cancer cells require a continual supply of nucleotides to replicate their DNA. Pyrimidines, one of the essential classes of nucleotide, are supplied by the de novo pyrimidine synthesis pathway. Every step in this pathway is catalysed by a single enzyme, except the final step where two enzymes, CTPS1 and CTPS2, can catalyse the conversion of UTP to CTP. Recent studies have shown that cancer cells are addicted to CTPS1 in order to keep dividing, whereas CTPS2 is sufficient for the proliferation of healthy cells. This is why the Step Pharma team believes that selectively targeting CTPS1 is so important.

“What gets me up in the morning is working for a company that is trailblazing a new journey to improve outcomes for those living with cancer. Our concept selectively targets an Achilles’ heel of cancer cells which we hope will stop cancer in its tracks.”

Brian Schwartz, CMO, Step Pharma

Targeting the key pathways on which cancer cells depend has the potential to improve outcomes for those living with cancer. In addition, the development of highly selective drugs has the potential to decrease unwanted effects on normal cells. The net result is treatments that are more effective at killing cancer cells but with fewer unwanted side effects.

“Whilst the ultimate wish of those living with cancer is to be cured of their disease, freedom from treatment associated side effects is also very important. Through the development of highly selective drugs targeting key cancer pathways, we are aiming to improve both survival and quality of life.”

Brian Schwartz, CMO, Step Pharma

Step Pharma In Blog

Bringing precision into cancer treatment with genomic testing

Philip Beer, Chief Scientific Officer at Step Pharma, who is also the Chair of the Genomics Working Group of the British In Vitro Diagnostics Association (BIVDA), provides his perspectives on the recently published report titled “Leveraging partnerships to realise the UK’s potential in genomics” which focuses on the UK genomics landscape and patient access to genomic testing. Philip details the reasons he got involved in BIVDA’s Genomics Working Group and the difference genomic testing can make in cancer treatment.

Genetic testing to identify DNA changes in cancer samples has the potential to match the right patient with the right drug at the right time, thus improving outcomes and making a significant difference to the lives of those living with cancer. The findings of this report highlight ways forward to improve access to genomic medicines for the benefits of patients.

Why are you involved with the British In Vitro Diagnostics Association and what is your role there?

I have a longstanding interest in the use of biomarkers, genomics in particular, as a means to power oncology drug development. Biomarker profiling is the process of analysing biological samples, including cancer DNA, to better understand how patients are likely to respond to different treatments. An optimal approach is to embed comprehensive biomarker profiling into routine clinical care pathways. The NHS has articulated an ambitious vision to do this, but we still have some work to do to make this a reality.

I got involved with BIVDA to find out how the organisation engaged emerging and existing technologies for genomic testing, as many of the barriers to implementation relate to technological pathways and processes. This led to my taking up the Chair of the newly convened Genomics Working Group. The report that was just published, in collaboration with Charles River Associates, is the first fruits of the labour of this working group.

How can biomarkers be utilised in the process of developing novel cancer treatments at Step Pharma and the industry as a whole?

New cancer drugs that enter clinical development with a selection biomarker are far more likely to succeed. This reflects a better understanding of both the mechanism of action of the drug and the selection of the right cancer types to target. The majority of cancer types are not single entities. What we call colorectal cancer, for example, is a complex mixture of different disease types. By breaking down a complex disease into smaller, molecularly defined entities, we can increase success rates for the therapeutic targeting of specific pathways. At Step Pharma we have plans for biomarker selected studies in solid tumour patients that we believe will have increased sensitivity to inhibition of CTPS1.

What is your hope for the future regarding the role of biomarkers in cancer treatment?

Embedding comprehensive biomarker profiling into routine clinical practice has the potential to accelerate oncology drug development. In an ideal world, all patients would have access to biomarker profiling at the time of diagnosis with advanced cancer. Genomic and clinical outcome data from all patients could then be collated and made available to industry and academic researchers. Large, high quality clinico-genomic datasets have the potential to power all stages of drug development, from target discovery to patient selection.

Step Pharma In Press Release

Step Pharma to participate at upcoming scientific and business conferences

Press Release

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

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

+ DOWNLOAD PDF

About Step Pharma

The Company’s lead asset, STP938, has received both IND and CTA clearance to proceed into first in human trials in the US and UK for the treatment of T cell and B cell lymphomas. Clinical trials in lymphoma commenced in September 2022. STP938 has the potential to be the backbone of a multitude of cancer therapies as well as a potent monotherapy for hard-to-treat blood cancers.

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Step Pharma In Blog

Driving a step change in the treatment of cancer

Blog

April 2023

There are over a hundred different types of blood cancer with the forms of leukemia, lymphoma and myeloma being the most common. Every 3 minutes someone in the US is diagnosed with a blood cancer.

For solid tumours, the most common cancers include breast, lung, colon and prostate.

Andrew Parker, CEO of Step Pharma, discusses his motivation to lead the Company to focus on a novel target, CTPS1, which is considered to be an Achilles Heel of cancer, in the search for highly selective, safe and effective treatments for both blood cancers and solid tumours.

What was your motivation to join Step Pharma?

I have always been intrigued by how a single mutation in our DNA can be irreversibly disruptive, leading to the transition of a normal cell into a cancerous cell. The human genetic story of how a mutation resulting in the loss of CTPS1, a key enzyme that is required for the synthesis of DNA and RNA, leads to the understanding that this could be a novel approach to treat lymphoma exemplifies this concept.

Humans with CTPS1 deficiency demonstrated an impaired capacity to proliferate lymphocytes but importantly have no other negative consequences. This highlighted that inhibiting CTPS1 could be a targeted approach to treat lymphoproliferative disorders such as leukemia and lymphoma without the side effects often seen with cancer drugs. This level of genetic validation is very compelling and quite unusual in drug discovery. The Company’s deep understanding of CTPS1 biology and chemistry has ultimately led to the discovery of STP938, a selective CTPS1 inhibitor with excellent pharmaceutical properties.

Consequently, I was convinced by the scientific concept, coupled with the belief and passion of the founding scientists and the enthusiasm of the investors.

In joining Step Pharma in 2019, I had the opportunity to lead and build a team of like-minded drug developers who are focussed on bringing about highly selective cancers treatments without the significant side effects associated with current and emerging cancer therapies.

You’ve previously worked in senior roles in pharma across other disease areas. How are you applying this experience as CEO of a cancer biotechnology company?

I have had many different roles across big pharma, biotech and VC, each of which has always taught me something new. Drug development requires deep knowledge of the disease area so it is essential to have the right minds engaged. The team at Step Pharma is a perfect balance of deep understanding of oncology, in particular blood cancers, as well as the organisational and drug development skills required to successfully advance a small molecule program.

The biotech CEO role is focused on the bigger picture, building the right team, setting the strategic direction, ensuring we have enough money to succeed, but the most important thing I have learned is to never allow this to disconnect you from the science and the detail of the preclinical and clinical data.

What is the issue you are trying to solve with current treatments for T cell and B cell malignancies?

The successful treatment of lymphoma, which develops from white blood cells called lymphocytes, is quite different when comparing T cell with B cell lymphoma. In all cases the frontline therapy is chemotherapy which brings a successful outcome for many patients but is associated with significant side effects. However, a significant number of patients treated with chemotherapy will relapse.

For B cell lymphomas there are a range of second-line and third-line drugs which offer limited benefit for these patients and a significant number will still relapse. In T cell lymphomas there are very few second line agents and none of them are particularly effective.

We aim to bring forward treatments that will add to the armoury of options for B cell lymphoma patients and transform the way T cell lymphoma is treated.

Why is CTPS1 inhibition going to address this need?

Targeting the pathways that make nucleotides, which are required for the synthesis of DNA and RNA, is a well explored and validated concept in oncology. However, until now this has been achieved through non-selective drugs, which cause unacceptable side effects.

Human genetics and the identification of a handful of individuals that lack CTPS1 demonstrated the crucial role that CTPS1 plays in allowing lymphocytes, T and B cells, to proliferate. Importantly, the lack of CTPS1 in these individuals had no other effects. This means that selective inhibition of CTPS1 should block proliferation of cancerous T and B cells and not bring unexpected side effects. The reason this can be achieved is due to the related enzyme CTPS2 which is able to maintain nucleotide synthesis in healthy cells, something unique to this step in the pathway and a key differentiation for our approach.

Targeted therapies for cancer is a crowded and challenging space, what makes Step Pharma stand out from others in the field and why do you believe you will succeed?

We believe that our investigational therapy, STP938, has the potential to transform the way lymphomas are treated. T cell lymphoma patients have no good options following relapse and there are few alternative drugs in development. The high unmet need for novel therapies brings the potential for the accelerated approval of STP938 following successful Phase II clinical studies.

B cell lymphoma treatment is complex and, despite the recent success seen with CAR-T therapies, many patients are not fit enough to withstand the trauma of a CAR-T therapy. As more data accumulates, it is becoming clear that the majority of CAR-T patients will also relapse. The future of cancer treatment lies in moving away from chemotherapy and towards the use of appropriate combinations of targeted therapies to maximise the benefit to patients. These combinations should be driven by science, and we have spent considerable time developing an understanding of the most appropriate drugs that could ultimately combine with STP938.

We also believe that inhibition of CTPS1 will be successful in the treatment of some solid tumours. We are developing a biomarker that will enable selection of patients sensitive to CTPS1 inhibition, with an initial focus on ovarian and lung cancer, aiming to start clinical studies next year. In addition, the combination of STP938 with drugs that inhibit the DNA Damage Response pathway has shown incredible synergy in pre-clinical experiments across a range of solid tumours.

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Step Pharma In Press Release

Step Pharma publishes data identifying the key role of CTP Synthase 1 in haematological malignancies

Press Release

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

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

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About STP938

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 neoplastic lymphoid cells and results in cell death. All cancers appear to be addicted to CTPS1 for DNA synthesis. STP938 entered clinical development in September 2022 for the treatment of T cell and B cell lymphoma.

About Step Pharma

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Step Pharma In Press Release

Step Pharma granted European patent on key CTPS1 inhibitor compounds further strengthening its existing portfolio of patents

Press Release

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.

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.”

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

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About Step Pharma

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cookielawinfo-checkbox-functional	11 months	The cookie is set by GDPR cookie consent to record the user consent for the cookies in the category "Functional".
cookielawinfo-checkbox-necessary	11 months	This cookie is set by GDPR Cookie Consent plugin. The cookies is used to store the user consent for the cookies in the category "Necessary".
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