Sharp et al; “Integrating fragment-based screening with targeted protein degradation and genetic rescue to explore eIF4E function”; Nat Commun., 2025
Churcher et al; “Return to Flatland“; Nat Rev Chem., 2025
Holvey et al; “Fragment-to-Lead Medicinal Chemistry Publications in 2023”; J. Med. Chem., 2025
Cambridge, UK, 21st October 2024 – Astex Pharmaceuticals, a pharmaceutical company based in Cambridge, UK, dedicated to the discovery and development of novel small molecule therapeutics for oncology and diseases of the central nervous system, announced today that it will make five key data presentations at the 36th EORTC-NCI-AACR Symposium on molecular targets and cancer therapeutics, 23rd-25th October 2024, Barcelona, Spain. The Astex presentations will focus on its novel small-molecule CBP/p300 HAT domain inhibitor, ASTX528 in preclinical development and its Phase II-ready MDM2 antagonist, ASTX295.
Astex data presentations at 36th EORTC-NCI-AACR Symposium, 23rd-25th October 2024, Barcelona
| Title | Presentation | Date/Time/Session Title/Presenter | Presentation number |
|---|---|---|---|
| A Novel Small-Molecule CBP/p300 HAT Domain Inhibitor Demonstrates Potent In Vivo Activity and a Favourable Safety Profile in Preclinical Species | Poster | Date: Wed, 23rd Oct 2024
Time: 12:00 – 19:00 Session Title: Molecular Targeted Agents Presenter: Gianni Chessari, Astex Pharmaceuticals, UK |
Catalog #42
Presentation #PB030 |
| Targeting the Catalytic HAT Domain of CBP/p300 for the Treatment of Hormone-Dependent Breast and Prostate Cancers | Poster | Date: Wed, 23rd Oct 2024
Time: 12:00 – 19:00 Session Title: Molecular Targeted Agents Presenter: John Lyons, Astex Pharmaceuticals, UK |
Catalog #73
Presentation #PB061 |
| From a Preclinical Therapeutic Concept to the Clinic. ASTX295: Discovery of a bone marrow sparing MDM2 antagonist | Oral | Date: Wed, 23rd Oct 2024
Time: 16:55 -17:15 Session Title: Optimising of preclinical models for drug development Presenter: Maria Ahn, Astex Pharmaceuticals, UK |
Workshop 2
Room 113+114 |
| Identification of Biomarkers Predictive of Response to ASTX295, a Next-Generation MDM2 Antagonist, in Solid Tumors Carrying Wild-type p53 | Poster | Date: Wed, 23rd Oct 2024
Time: 12:00 – 19:00 Session Title: Molecular Targeted Agents Presenter: Maria Ahn, Astex Pharmaceuticals, UK |
Catalog #28
Presentation #PB016 |
| Pulsatile Induction of the p53 Pathway by MDM2 Antagonist ASTX295 Shows an Enhanced Therapeutic Index in vivo | Poster | Date: Thu, 24th Oct 2024
Time: 9:00 – 17:30 Session Title: Translational Studies Presenter: Andrea Biondo, Astex Pharmaceuticals, UK |
Catalog #289
Presentation #PB277 |
ASTX528 – CBP/p300 HAT Domain Inhibitor – Preclinical
ASTX528 is a novel small molecule CBP/p300 HAT domain inhibitor with potent in vivo activity and a favourable safety profile in preclinical species that was discovered by Astex using its proprietary fragment-based drug discovery approach. CREB binding protein (CBP) and its paralog, EP300 (p300), are lysine acetyltransferases and transcriptional cofactors implicated in human cancers. Dose-limiting tolerability issues have been observed with dual CBP/p300 bromodomain (BRD) inhibitors, which may limit their clinical utility. We hypothesised that a dual inhibitor targeting the histone acetyltransferase (HAT) domain may improve the therapeutic window. Our presentations will describe the effects of CBP/p300 HAT domain inhibition in preclinical models of AR- and ER-driven cancers and the characterisation of ASTX528, a potent, fragment-derived CBP/p300 HAT domain inhibitor with a low predicted human dose and promising preliminary toxicity evaluation. Astex is interested in discussing the further development of ASTX528 with potential partners.
ASTX295 – Bone Marrow-Sparing MDM2 Antagonist, Phase II-ready
ASTX295 is an oral, potent inhibitor of the p53-MDM2 protein-protein interaction that was discovered by Astex using its proprietary structure-based drug design approach. The compound was specifically designed to overcome the on-target toxicity seen in the first generation MDM2 antagonist compounds which have shown dose-limiting haematological toxicities in the clinic. In contrast, ASTX295 is a potent MDM2 antagonist with a clean CYP/hERG profile and a shorter human half-life allowing for pulsatile pathway modulation while avoiding myelosuppression. ASTX295 therefore has bone-marrow sparing characteristics which permit a differentiated safety profile. ASTX295 was discovered by Astex in collaboration with the Cancer Research UK Drug Discovery Unit at Newcastle University. Astex has an exclusive license to research, develop and commercialise ASTX295 under its drug discovery alliance agreement with Newcastle University and Cancer Research Technology Limited.
-ENDS-
About Astex Pharmaceuticals
Astex is a leader in innovative drug discovery and development, committed to the fight against cancer and diseases of the central nervous system. Astex is developing a proprietary pipeline of novel therapies and has several partnered products being developed under collaborations with leading pharmaceutical companies. Astex is a wholly owned subsidiary of Otsuka Pharmaceutical Co. Ltd., based in Tokyo, Japan.
For more information about Astex Pharmaceuticals please visit: https://www.astx.com
For more information about Otsuka Pharmaceutical, please visit: https://www.otsuka.co.jp/en/
| Contact | |
| At the Company:
Jeremy Carmichael |
For Media Enquiries:
Sue Charles
|
Cambridge and Cardiff, UK, 13 February 2023, Astex Pharmaceuticals (UK) (“Astex”), a pharmaceutical company dedicated to the discovery and development of novel small molecule therapeutics for oncology and diseases of the central nervous system and The Medicines Discovery Institute, Cardiff University (“MDI”) announced today that they have entered into a multi-year, multimillion pound drug discovery research collaboration, aimed to identify new drugs to treat neurodegenerative diseases.
The collaboration brings together the world-leading research expertise of Dr Emyr Lloyd-Evans & Dr Helen Waller-Evans in lysosomal biology, the drug discovery capabilities of the MDI and the fragment-based drug discovery platform at Astex. The combined teams will focus on identifying compounds which modulate lysosomal activity as a way to develop potential new treatments for neurodegenerative diseases with high unmet medical need. Lysosomes are a subset of organelles that are crucial for cellular function and mutations in the genes encoding lysosomal and associated proteins are linked to a number of neurodegenerative and lysosomal storage diseases for which there are currently no effective treatments.
Under the terms of the agreement, scientists at the MDI and Astex will collaborate to carry out drug discovery research against a chosen lysosomal target with the aim to identify and optimise compounds that modulate its activity. Cardiff University will receive committed R&D funding and is eligible to receive development and regulatory payments if drug compounds progress and a royalty payment on the sales of any approved products. Further financial details are not disclosed.
Prof Simon Ward, Director, Medicines Discovery Institute commented “We are excited to be working with Astex in a way that allows each partner to play to its individual strengths and build a combined team which is greater than the sum of its parts. This is a validation of the scientific and translational capabilities we have been building at Cardiff University over the last few years and we look forward to delivering outputs that may ultimately benefit patients for whom current treatment options are so limited. This is an excellent demonstration of the power of academic and industrial teams working together to try to solve currently intractable medical problems.”
Dr David Rees, FMedSci, FRSC, Chief Scientific Officer of Astex commented, “We are very excited about this opportunity to work with Cardiff University, Medicines Discovery Institute. Astex has a long tradition of effective collaborations between academia and industry which we believe is critical for the successful translation of basic science. This partnership aims to support and advance ground-breaking research with the potential to transform the lives of patients with neurodegenerative diseases.”
About Astex Pharmaceuticals
Astex is a leader in innovative drug discovery and development, committed to the fight against cancer and diseases of the central nervous system. Astex is developing a proprietary pipeline of novel therapies and has a number of partnered products being developed under collaborations with leading pharmaceutical companies. Astex is a wholly owned subsidiary of Otsuka Pharmaceutical Co. Ltd., based in Tokyo, Japan.
For more information about Astex Pharmaceuticals please visit: https://www.astx.com
For more information about Otsuka Pharmaceutical, please visit: https://www.otsuka.co.jp/en/
About Cardiff University
Cardiff University is recognised in independent government assessments as one of Britain’s leading teaching and research universities and is a member of the Russell Group of the UK’s most research-intensive universities. The 2014 Research Excellence Framework ranked the University 5th in the UK for research excellence. Among its academic staff are two Nobel Laureates, including the winner of the 2007 Nobel Prize for Medicine, Professor Sir Martin Evans. Founded by Royal Charter in 1883, today the University combines impressive modern facilities and a dynamic approach to teaching and research. The University’s breadth of expertise encompasses: the College of Arts, Humanities and Social Sciences; the College of Biomedical and Life Sciences; and the College of Physical Sciences and Engineering, along with a longstanding commitment to lifelong learning. Cardiff’s flagship Research Institutes are offering radical new approaches to pressing global problems.
For more information about Cardiff University, please visit: www.cardiff.ac.uk
About MDI
The Medicines Discovery Institute is the leading, university-based, CNS drug discovery group in Europe, delivering modern drug discoveries to improve treatments for neurological illnesses. Grounded in the academic & clinical excellence of Cardiff University, the team combines profound insight with industry-standard drug discovery. A robust pipeline of novel drug projects stretches from early drug screening through to human clinical trials, run at Cardiff. The Institute is led by Professors Simon Ward & John Atack.
For more information about Medicines Discovery Institute, please visit: https://www.cardiff.ac.uk/medicines-discovery
CONTACTS
At Medicines Discovery Institute
Richard Angell
Commercialisation Lead
Medicines Discovery Institute
Cardiff University
Main Building
Park Place
Cardiff
CF10 3AT
Email: angellr@cardiff.ac.uk
Media Enquiries
Heath Jeffries
Head of Innovation Communication
Cardiff University
Tel: +44 29 2087 70917
Email: jeffrieshv1@cardiff.ac.uk
At Astex Pharmaceuticals (UK)
Jeremy Carmichael
SVP Corporate Development
Head of Business Development
Astex Pharmaceuticals
436 Cambridge Science Park
Milton Road, Cambridge
CB4 0QA, UK
Tel: +44 1223 226289
Email: jeremy.carmichael@astx.com
Media Enquiries
Sue Charles
Charles Consultants
Tel: +44 7968 726585
Email: sue@charles-consultants.com
Kidger et al., “Dual-mechanism ERK1/2 inhibitors exploit a distinct binding mode to block phosphorylation and nuclear accumulation of ERK1/2”; Mol Cancer Ther, 2020
Pleasanton, CA, September 3rd, 2019. Astex Pharmaceuticals, Inc., a wholly owned subsidiary of Otsuka Pharmaceutical Co. Ltd., based in Tokyo, Japan, announces that the US Food & Drug Administration (FDA) has granted orphan drug designation for the company’s orally administered fixed-dose combination of cedazuridine and decitabine (ASTX727 or C-DEC) for the treatment of myelodysplastic syndromes (MDS) including chronic myelomonocytic leukemia (CMML). The designation follows on from the recent announcement that the phase 3 ASCERTAIN study of ASTX727 in adults with intermediate and high-risk MDS or CMML met the primary endpoint of decitabine exposure equivalence of total 5-day dosing between oral ASTX727 and IV decitabine. The data from the study will be presented at an upcoming scientific meeting. The designation provides for seven years of marketing exclusivity in the US following product approval, as well as certain tax incentives and grants.
“We are delighted that the FDA has granted orphan drug designation for the fixed dose combination of cedazuridine with decitabine,” said Mohammad Azab, MD, Astex Pharmaceuticals’ president and chief medical officer. “Subject to regulatory review and approvals, ASTX727 could bring a new treatment option to patients with these deadly diseases. We are extremely grateful to all the patients, caregivers, partner research and manufacturing organizations, as well as the healthcare professionals who contributed to the clinical development program of ASTX727.”
ASTX727 is an investigational compound and is not currently approved in any country. Astex plans to file an NDA with the US FDA by the end of 2019.
Astex’s parent company, Otsuka Pharmaceutical Co., Ltd., and Taiho Pharmaceutical Co., Ltd. previously announced that, subject to regulatory approvals, commercialization of ASTX727 in the US and Canada will be conducted by Taiho Oncology, Inc. and Taiho Pharma Canada, Inc. respectively. Astex, Otsuka and Taiho are all members of the Otsuka group of companies.
About Cedazuridine and Decitabine Fixed-Dose Combination (ASTX727)
ASTX727 is a novel, orally administered fixed dose combination of cedazuridine, an inhibitor of cytidine deaminase,1 with the anti-cancer DNA hypomethylating agent, decitabine.2 By inhibiting cytidine deaminase in the gut and the liver, ASTX727 is designed to allow for oral delivery of the approved DNA hypomethylating agent, decitabine, at exposures which emulate exposures achieved with the approved intravenous form of decitabine administered over 5 days.3
ASTX727 has been evaluated in a phase 1/2 pharmacokinetics-guided dose escalation and dose confirmation study in patients with MDS and CMML (see https://www.clinicaltrials.gov NCT02103478) and a pivotal phase 3 study (ASCERTAIN) (see https://www.clinicaltrials.gov NCT03306264) conducted at investigator sites in the US and Canada and designed to confirm the results from the phase 1/2 study. The phase 3 study is being extended to include patients with acute myeloid leukemia (AML) unsuitable to receive intensive induction chemotherapy.
The concept of using cedazuridine to block the action of cytidine deaminase is also being evaluated in a low dose formulation of cedazuridine and decitabine for the treatment of lower risk MDS (see https://www.clinicaltrials.gov NCT03502668).
About Myelodysplastic Syndromes (MDS) and Chronic Myelomonocytic Leukemia (CMML)
Myelodysplastic syndromes are a heterogeneous group of hematopoietic stem cell disorders characterized by dysplastic changes in myeloid, erythroid, and megakaryocytic progenitor cells, and associated with cytopenias affecting one or more of the three lineages. US incidence of MDS is estimated to be 10,000 cases per year, although the condition is thought to be under-diagnosed.4,5 The prevalence has been estimated to be from 60,000 to 170,000 in the US.6 MDS may evolve into acute myeloid leukemia (AML) in one-third of patients.7 The prognosis for MDS patients is poor; patients die from complications associated with cytopenias (infections and bleeding) or from transformation to AML. CMML is a clonal hematopoietic malignancy characterized by accumulation of abnormal monocytes in the bone marrow and in blood. The incidence of CMML in the US is approximately 1,100 new cases per year,8 and CMML may transform into AML in 15% to 30% of patients.9 The hypomethylating agents decitabine and azacitidine are effective treatment modalities for hematologic cancers and are FDA-approved for the treatment of higher risk MDS and CMML. These agents are administered by IV infusion, or by large-volume subcutaneous injections.
About Astex Pharmaceuticals, Inc.
Astex Pharmaceuticals, Inc. is a leader in innovative drug discovery and development, committed to the fight against cancer. Astex is developing a proprietary pipeline of novel therapies and has multiple partnered products in development under collaborations with leading pharmaceutical companies. Astex is a wholly owned subsidiary of Otsuka Pharmaceutical Co. Ltd., based in Tokyo, Japan.
Otsuka Pharmaceutical Co., Ltd. is a global healthcare company with the corporate philosophy: “Otsuka–people creating new products for better health worldwide.” Otsuka researches, develops, manufactures and markets innovative and original products, with a focus on pharmaceutical products for the treatment of diseases and nutraceutical products for the maintenance of everyday health.
For more information about Astex Pharmaceuticals, Inc. please visit: https://stagin.astx.co.uk
For more information about Otsuka Pharmaceutical, please visit: http://www.otsuka.com/en/
Contact Details
Martin Buckland
Chief Corporate Officer
Astex Pharmaceuticals, Inc.
4420 Rosewood Drive, Suite 200
Pleasanton 94588, CA, USA
Tel: +1-925-560-2857
Email: info@astx.com
References
1. Ferraris D, Duvall B, Delahanty G, Mistry B, Alt, J, Rojas C, et al. Design, synthesis, and pharmacological evaluation of fluorinated tetrahydrouridine derivatives as inhibitors of cytidine deaminase. J Med Chem 2014; 57:2582-2588.
2. Oganesian A, Redkar S, Taverna P, Choy G, Joshi-Hangal R, Azab M. Preclinical data in cynomolgus (cyn) monkeys of ASTX727, a novel oral hypomethylating agent (HMA) composed of low-dose oral decitabine combined with a novel cytidine deaminase inhibitor (CDAi) E7727 [ASH Abstract]. Blood 2013;122(21): Abstract 2526.
3. Savona MR, Odenike O, Amrein PC, Steensma DP, DeZern AE, Michaelis LC, et al. An oral fixed-dose combination of decitabine and cedazuridine in myelodysplastic syndromes: a multicentre, open-label, dose-escalation, phase 1 study. Lancet Haematol [Internet]. 2019;6(4):e194-e203.
4. Garcia-Manero G. Myelodysplastic syndromes: 2015 update on diagnosis, risk-stratification and management. Am J Hematol 2015; 90(9) 831-841.
5. Ma X, Does M, Raza A, Mayne ST. Myelodysplastic syndromes: Incidence and survival in the United States. Cancer 2007;109(8):1536–1542.
6. Cogle C. Incidence and burden of the myelodysplastic syndromes. Curr Hematol Malig Rep 2015; 10(3): 272-281.
7. Shukron O, Vainstein V, Kündgen A, Germing U, Agur Z. Analyzing transformation of myelodysplastic syndrome to secondary acute myeloid leukemia using a large patient database. Am J Hematol 2012;87:853–860.
8. What are the key statistics about chronic myelomonocytic leukemia? American Cancer Society Web site. https://www.cancer.org/cancer/chronic-myelomonocytic-leukemia/about/key-statistics.html. Accessed 08 April 2019.
9. About chronic myelomonocytic leukemia (CMML). Cancer Research UK Web site. https://www.cancerresearchuk.org/about-cancer/other-conditions/chronic-myelomonocytic-leukaemia-cmml/about. Accessed 08 April 2019.
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