An Open-Label, Phase 1 Study to Evaluate Safety, Tolerability and Pharmacokinetics of the CTPS1 Inhibitor STP938 in Adult Subjects With Advanced Solid Tumors, With a Safety Expansion in Advanced CTPS2 Null Ovarian Cancer

The Phase 1a part of the study is a dose escalation of STP938 as a monotherapy.
The Phase 1b part of the study is a safety expansion cohort of STP938 as a monotherapy.

开始日期2024-08-02

申办/合作机构

Step Pharma SAS初创企业

NCT05463263 / Recruiting临床1/2期

An Open-Label, First in Human, Phase 1/2 to Evaluate Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of the CTPS1 Inhibitor STP938 In Adult Subjects With Relapsed/Refractory B-Cell and T-Cell Lymphomas

The Phase 1 part of the study is a dose escalation of STP938 as monotherapy.
The Phase 2 part of the study is cohort expansion of STP938 as a monotherapy in 5 different B and T cell lymphomas.

开始日期2022-08-03

申办/合作机构

Step Pharma SAS初创企业

100 项与 Step Pharma SAS 相关的临床结果

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0 项与 Step Pharma SAS 相关的专利（医药）

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项与 Step Pharma SAS 相关的文献（医药）

2024-01-01·Leukemia

CTPS1 is a novel therapeutic target in multiple myeloma which synergizes with inhibition of CHEK1, ATR or WEE1

Article

作者: Schreder, Martin ; Ludwig, Heinz ; Beer, Philip A ; Pfeiffer, Christina ; Schneller, Anja ; Bolomsky, Arnold ; Grandits, Alexander M ; Parker, Andrew E ; Zojer, Niklas ; Asnagli, Hélène ; Huber, Julia

Targeting nucleotide biosynthesis is a proven strategy for the treatment of cancer but is limited by toxicity, reflecting the fundamental nucleotide requirement of dividing cells. The rate limiting step in de novo pyrimidine synthesis is of interest, being catalyzed by two homologous enzymes, CTP synthase 1 (CTPS1) and CTPS2, that could be differentially targeted. Herein, analyses of publicly available datasets identified an essential role for CTPS1 in multiple myeloma (MM), linking high expression of CTPS1 (but not CTPS2) with advanced disease and poor outcomes. In cellular experiments, CTPS1 knockout induced apoptosis of MM cell lines. Exposure of MM cells to STP-B, a novel and highly selective pharmacological inhibitor of CTPS1, inhibited proliferation, induced S phase arrest and led to cell death by apoptosis. Mechanistically, CTPS1 inhibition by STP-B activated DNA damage response (DDR) pathways and induced double-strand DNA breaks which accumulated in early S phase. Combination of STP-B with pharmacological inhibitors of key components of the DDR pathway (ATR, CHEK1 or WEE1) resulted in synergistic growth inhibition and early apoptosis. Taken together, these findings identify CTPS1 as a promising new target in MM, either alone or in combination with DDR pathway inhibition.

2020-03-12·JCI insight1区 · 医学

Impaired lymphocyte function and differentiation in CTPS1-deficient patients result from a hypomorphic homozygous mutation

1区 · 医学

ArticleOA

作者: Lenoir, Christelle ; Sobrino, Steicy ; Boschat, Anne-Claire ; de Villartay, Jean Pierre ; Leite-de-Moraes, Maria ; Minet, Norbert ; Sanquer, Sylvia ; Bourne, Tim ; Hughes, Stephen M ; Briggs, Tracy A ; Soudais, Claire ; Arkwright, Peter D ; Wynn, Robert F ; Latour, Sylvain ; Lawrence, Monica G ; Fischer, Alain ; Hambleton, Sophie ; Patel, Smita ; Picard, Capucine ; Martin, Emmanuel

Cytidine triphosphate (CTP) synthetase 1 (CTPS1) deficiency is caused by a unique homozygous frameshift splice mutation (c.1692-1G>C, p.T566Dfs26X). CTPS1-deficient patients display severe bacterial and viral infections. CTPS1 is responsible for CTP nucleotide de novo production involved in DNA/RNA synthesis. Herein, we characterized in depth lymphocyte defects associated with CTPS1 deficiency. Immune phenotyping performed in 7 patients showed absence or low numbers of mucosal-associated T cells, invariant NKT cells, memory B cells, and NK cells, whereas other subsets were normal. Proliferation and IL-2 secretion by T cells in response to TCR activation were markedly decreased in all patients, while other T cell effector functions were preserved. The CTPS1T566Dfs26X mutant protein was found to be hypomorphic, resulting in 80%-90% reduction of protein expression and CTPS activity in cells of patients. Inactivation of CTPS1 in a T cell leukemia fully abolished cell proliferation. Expression of CTPS1T566Dfs26X failed to restore proliferation of CTPS1-deficient leukemia cells to normal, except when forcing its expression to a level comparable to that of WT CTPS1. This indicates that CTPS1T566Dfs26X retained normal CTPS activity, and thus the loss of function of CTPS1T566Dfs26X is completely attributable to protein instability. This study supports that CTPS1 represents an attractive therapeutic target to selectively inhibit pathological T cell proliferation, including lymphoma.

HemaSphere

CTP Synthase 1 Is a Novel Therapeutic Target in Lymphoma

Article

作者: Lane, Rebecca ; Minet, Norbert ; Hoeben, Eef ; Parker, Andrew E ; Asnagli, Hélène ; Laughton, David ; Beer, Philip A ; Latour, Sylvain ; Novak, Andrew ; Ludwig, Heinz ; Pfeiffer, Christina ; Birch, Louise ; Jones, Geraint ; Fischer, Alain

Lymphoma is the most common hematological malignancy and is among the 10 most prevalent cancers worldwide. Although survival has been improved by modern immunochemotherapeutic regimens, there remains a significant need for novel targeted agents to treat both B-cell and T-cell malignancies. Cytidine triphosphate synthase 1 (CTPS1), which catalyzes the rate-limiting step in pyrimidine synthesis, plays an essential and nonredundant role in B-cell and T-cell proliferation but is complemented by the homologous CTPS2 isoform outside the hemopoietic system. This report describes the identification and characterization of CTPS1 as a novel target in B- and T-cell cancers. A series of small molecules have been developed which show potent and highly selective inhibition of CTPS1. Site-directed mutagenesis studies identified the adenosine triphosphate pocket of CTPS1 as the binding site for this small molecule series. In preclinical studies, a potent and highly selective small molecule inhibitor of CTPS1 blocked the in vitro proliferation of human neoplastic cells, showing the highest potency against lymphoid neoplasms. Importantly, pharmacological CTPS1 inhibition induced cell death by apoptosis in the majority of lymphoid cell lines tested, thus demonstrating a cytotoxic mechanism of action. Selective CTPS1 inhibition also inhibited the growth of neoplastic human B- and T- cells in vivo. These findings identify CTPS1 as a novel therapeutic target in lymphoid malignancy. A compound from this series is in phase 1/2 clinical studies for the treatment of relapsed/refractory B- and T-cell lymphoma (NCT05463263).

项与 Step Pharma SAS 相关的新闻（医药）

2024-07-10

·BioSpace

Concr launches trial using digital twins for outcome prediction in breast cancer

London, United Kingdom, 10 July 2024 – Concr announces that first patients have been recruited to the VISION trial, an observational clinical study evaluating Concr’s therapeutic response predictive algorithm defining biomarkers of chemotherapy and immunotherapy response in early Triple Negative Breast Cancer (TNBC). VISION (NCT06409221) is an observational retrospective study focusing on women who were previously diagnosed with early TNBC and received chemotherapy followed by curative breast surgery. The 24-month-long study will collect historical clinical data and pro cancer biopsy samples from up to 200 women in order to identify and validate biomarkers of chemotherapy response, with and without immunotherapy. “Triple Negative breast cancer is an aggressive subtype of breast cancer. Hence, Concr has prioritised this clinical indication as a key research area by sponsoring the VISION study. The VISION study will test the value created through the combination of clinical data, genomic data and machine learning approaches for enabling treatment stratification at an individual level. We believe this approach will represent the next generation of diagnostic platforms in cancer care” shared Dr Uzma Asghar, Concr’s Chief Scientific Officer and VISION Project Lead. The multi-centre study featuring UK and Australian sites backed by a prestigious Innovate UK Precision Medicine project grant (AI-VISION) was announced earlier this year, with key partners The Institute of Cancer Research, London, and The Institute for Computational Cosmology at Durham University. Patients will be recruited from The Royal Marsden NHS Foundation Trust, a globally-leading specialist cancer hospital, going live as the primary clinical site last month. Dr Navita Somaiah, Principal Investigator and Clinician Scientist at The Institute of Cancer Research, London, and Clinical Oncologist at The Royal Marsden, said: “We’re very pleased to take the next step in this innovative project, which is using AI to try to uncover new methods to predict which women with triple negative breast cancer may respond better or less well to current therapies. We hope this collaboration will ultimately help to guide treatment for some women with this form of breast cancer”. Concr’s FarrSight®-Twin technology will utilise genomic data from diagnostic and surgical breast cancer samples together with whole-slide imaging and clinical data from trial participants to create a “digital twin” of every individual patient, which will be used to predict treatment response to chemotherapy (anthracycline, taxanes, platinum, anti-metabolites) and immunotherapy (pembrolizumab). Subsequently, FarrSight® will be used to explore biological mechanisms behind sensitivity to chemotherapy +/- immunotherapy. This approach could pave a way to better stratify and treat TNBC, which disproportionately affects black women, while simultaneously testing a novel approach that could be readily deployed in clinic. “While much of the dialogue surrounding AI in healthcare focuses on its potential, we must not overlook the fact that AI tools can - and do - deliver tangible benefits to patients today. VISION is testing a novel individualised care approach designed by clinicians, leveraging latest technology alongside existing diagnostic tests, to facilitate rapid adoption.” commented Concr’s CEO Dr Irina Babina. For more information on VISION: ClinicalTrials.gov To request a demo of FarrSight®: concr.co/FarrSight To learn more about Concr’s technology: concr.co/technology For media inquiries, interviews, or further information about Concr, please contact: Emre Misirlioglu Concr info@concr.co [END] About Concr Concr is a techbio company providing predictive modelling solutions to enhance confidence and foresight about therapeutic efficacy of existing and emerging cancer drugs. By accurately predicting response for individual patients and cohorts, we enable more efficacious and informative trials, thereby improving probability of success of novel cancer therapeutics. Our technology, built on decades of astrophysics research, models diverse data interactions to simulate human disease biology, enabling accurate predictions with minimal data. This is especially valuable in early-stage trials and rare cancers. Validated through collaborations with Roche, Step Pharma, The Institute of Cancer Research, The Christie NHS Foundation Trust, Durham University, and The University of Queensland, our solutions are trusted by researchers in industry, academia and healthcare. Concr’s investors include the University of Cambridge Enterprise, R42 Group, Oncology Ventures, Debiopharm, Cambridge Angels, Parkwalk Advisors, Deep Science Ventures and SyndicateRoom. The company has also received a grant from Innovate UK to trial Concr’s technology for improving treatment decision-making in clinic. The company’s HQ is in London, England, with a wholly owned subsidiary in Brisbane, Australia. See our website and follow us on LinkedIn. About The Royal Marsden NHS Foundation Trust The Royal Marsden opened its doors in 1851 as the world’s first hospital dedicated to cancer diagnosis, treatment, research and education. Today it operates as a specialist cancer hospital and National Institute for Health and Care Research (NIHR) Biomedical Research Centre for Cancer, working closely with its principal academic partner, the Institute of Cancer Research (ICR). Together, The Royal Marsden and the ICR are ranked in the top five cancer centres in the world for the impact of their research, treating over 59,000 NHS and private patients every year. It is a centre of excellence with an international reputation for groundbreaking research and pioneering the very latest in cancer treatments and technologies, as well as specializing in cancer diagnosis and education. About The Institute of Cancer Research The Institute of Cancer Research, London, is one of the world’s most influential cancer research organizations. Scientists and clinicians at The Institute of Cancer Research (ICR) are working every day to make a real impact on cancer patients’ lives. Through its unique partnership with The Royal Marsden NHS Foundation Trust and ‘bench-to-bedside’; approach, the ICR is able to create and deliver results in a way that other institutions cannot. Together the two organizations are rated in the top four centers for cancer research and treatment globally. The ICR has an outstanding record of achievement dating back more than 100 years. It provided the first convincing evidence that DNA damage is the basic cause of cancer, laying the foundation for the now universally accepted idea that cancer is a genetic disease. Today it is a world leader at identifying cancer-related genes and discovering new targeted drugs for personalised cancer treatment. The ICR is a charity and relies on support from partner organizations, funders, and the general public. A member institution of the University of London, it is one of the UK’s leading higher education institutions, placing first for biological sciences and second overall in the definitive REF 2021 rankings of UK university research quality, impact and environment, and provides postgraduate higher education of international distinction. The ICR’s mission is to make the discoveries that defeat cancer. For more information visit ICR.ac.uk. About The Institute for Computational Cosmology Durham University’s Institute for Computational Cosmology is a leading international center for research into the origin and evolution of the Universe. Cosmologists use statistical techniques, advanced simulations and huge data sets to address some of the most fundamental questions in physics. Many of these topics concern the creation of the first objects after the Big Bang, the nature of the dark matter and dark energy, and the eventual fate of our Universe. However, the same statistical techniques can be applied to other fields, from pollution and space debris monitoring, pandemic control, and healthcare. For more information about Durham University visit: .

临床研究免疫疗法

2023-11-16

·BioSpace

Memo Therapeutics AG Appoints Erik van den Berg as Chief Executive Officer

Mr. van den Berg is an industry veteran with proven track record in building high-performance teams and delivering on strategic and financial transactions ZURICH--(BUSINESS WIRE)-- Memo Therapeutics AG (“MTx”), a late-stage biotech company developing best-in-class therapeutic antibodies, announced today the appointment of Erik van den Berg as Chief Executive Officer (CEO). This press release features multimedia. View the full release here: Erik van den Berg, CEO of Memo Therapeutics AG (Photo: Business Wire) Mr. van den Berg joins MTx with over 25 years’ industry experience and proven track record in leading and growing companies. During his career, Mr. van den Berg has successfully completed over 20 transactions and partnerships, including a $600 million alliance with Pfizer, $290 million partnership with Kyowa Kirin and $500M in equity and debt financings for biotechnology companies from seed through IPO. He succeeds Dr. Karsten Fischer, who stepped down to pursue other opportunities. “As Memo continues to make progress to address unmet medical needs of patients, Erik is the perfect person to lead the company through late-stage clinical development and towards potential commercialization of our lead program, AntiBKV. On behalf of the Board and entire team, I’d like to welcome Erik to MTx and look forward to our future endeavors,” said Elias Papatheodorou, Chairman of MTx’s Board of Directors. “I’d also like to thank Dr. Karsten Fischer who served as our CEO for the past 5 years for his dedication and leadership in taking our technological approach into the clinic with multiple antibody candidates.” Mr. van den Berg was CEO of AM-Pharma for over 12 years and remains on its Board. He is also Chairman of Step Pharma, TargED Therapeutics, co-founder and previous (executive) Chairman of Lava Therapeutics and co-founder and previous (executive) Chairman of Heatmatrix Group (sold to BosNieuwkerk). Previously, Mr. van den Berg also held business development roles at Organon and IsoTis (sold to Integra Lifesciences). Mr. van den Berg holds a master’s degree in chemistry from the University of Utrecht and an MBA from Manchester Business School. “Memo has already made great strides in its development of novel antibody candidates. As CEO, I look forward to continuing this momentum and build on the great progress made recently with AntiBKV in the clinic and its Fast Track designation from the FDA, as well as the recent successful Series C fundraising,” said Mr. van den Berg. About Memo Therapeutics AG Memo Therapeutics AG (“MTx”) is a late-stage biotech company developing best-in-class therapeutic antibodies to transform the lives of patients with virus infections and cancer. MTx’s lead program, AntiBKV, is a highly effective and safe neutralizing antibody to treat BK virus infection in kidney transplant recipients. This infection can lead to loss of kidney function, as well as organ failure and rejection. MTx’s pipeline consists of additional candidate therapeutic antibodies focusing on infectious diseases, such as cytomegalovirus (“CMV”), immuno-oncology targets as well as a partnership with Ono Pharmaceutical. MTx is a private company located in Schlieren / Zurich, Switzerland. View source version on businesswire.com: Contacts Memo Therapeutics AG info@memo-therapeutics.com Halsin Partners Mike Sinclair +44 (0) 7968 022075 msinclair@halsin.com Source: Memo Therapeutics AG Smart Multimedia Gallery Photo Erik van den Berg, CEO of Memo Therapeutics AG (Photo: Business Wire) Logo View this news release and multimedia online at:

高管变更快速通道

2022-11-03

·GlobeNewswire-Health Care

Step Pharma to Present Promising Data on the Therapeutic Potential of Selective Small Molecule Inhibition of CTPS1 at the 64th American Society of Hematology Annual Meeting

Step Pharma to Present Promising Data on the Therapeutic Potential of Selective Small Molecule Inhibition of CTPS1 at the 64th American Society of Hematology Annual Meeting St. Genis-Pouilly, France, 3 November - Step Pharma, the world leader in CTPS1 inhibition for the targeted treatment of cancer, today announces that it will be presenting pre-clinical data on its lead candidate STP938 at the 64th American Society of Hematology Annual Meeting being held from the 10-13 December, 2022 in New Orleans, Louisiana and virtually. Step Pharma and collaborators will present two posters on STP938, its potent and highly selective small molecule inhibitor of CTPS1, reporting its potential as a targeted therapeutic for the treatment of Mantle Cell Lymphoma and Multiple Myeloma. Full details of the posters are: Poster presentation: CTPS1 is a Novel Therapeutic Target in Multiple Myeloma that Synergizes with Inhibition of ATR, CHEK1 or WEE1 Authors: Christina Pfeiffer, Alexander Grandits, Hélène Asnagli, Anja Schneller, Julia Huber, Niklas Zojer, Martin Schreder, Andrew Parker, Arnold Bolomsky*, Philip Beer*, Heinz Ludwig* * co-senior authors Date and Time: Available online from November 3, 09:00 EDT on the Congress platform Poster Presentation: 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 Date and Time: Available online from November 3, 09:00 EDT on the Congress platform -Ends- About Step PharmaStep 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. 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. For more information please contact: Step PharmaAndrew Parker, Chief Executive Officercontact@step-ph.com Consilium Strategic CommunicationsAmber Fennell, Namrata Taak, Stella LempidakiTel: +44 (0) 20 3709 5700steppharma@consilium-comms.com

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