AstraZeneca accelerates early oncology pipeline across key strategic scientific platforms at AACR

| 9 april, 2021 | 0 kommentarer

Leadership in DNA damage response demonstrated in multiple presentations for AZD5305, a next-generation PARP1 selective inhibitor

AstraZeneca will share updates from the Company’s innovative early oncology pipeline across multiple strategic platforms during the virtual American Association of Cancer Research (AACR) Annual Meeting, 10 to 15 April 2021.

Five presentations will unveil the next-generation PARP1 selective inhibitor AZD5305, underscoring AstraZeneca’s commitment to advancing therapies that selectively kill cancer cells by targeting the system that cells rely on to repair damage to DNA. Additionally, research across multiple presentations will highlight novel technologies that enable early detection of disease recurrence to inform earlier interventions for patients who are more likely to benefit from treatment.

In total, data from more than 40 presentations will showcase progress with the next wave of anticancer medicines, novel insights in targeting resistance to therapy, and approaches that are advancing the personalised treatment of cancer.

Susan Galbraith, Senior Vice President and Head of Research and Early Development, Oncology R&D, said: “Our data at AACR reflect a robust early-stage pipeline, poised to deliver life-changing medicines to patients living with cancer. Data for AZD5305 will demonstrate how the next wave of DNA damage response medicines can build on the success of PARP inhibitors, potentially allowing patients to stay on treatment longer. This innovative molecule is designed to optimise the therapeutic window of PARP inhibition, providing new opportunities for combination treatment with chemotherapy and targeted medicines.”

The Company will share a Spotlight Theater Presentation: The Orchestrated Immune Response: Dynamic Forces Guiding Cancer Immunity, introducing a novel framework for understanding the role of the immune system in cancer, with the potential to reshape the way scientists develop medicines to counteract tumour growth.

AstraZeneca leaders will also participate in two educational symposia:

  • DNA Damage Response (DDR) Treatment: Evolving Diagnostic Approaches, Understanding of Replication Stress, and Resistance Mechanisms to DDR Targeting Therapies (Session #ADT04), with a discussion on targeting the replication stress response, which occurs when the genome is exposed to stresses that impede DNA replication.
  • Advances in Drug Delivery (Session #ADT08), with a discussion on the advances and innovations fueling the development of the next generation of antibody drug conjugates.

Key presentations will include:

  • Structural disclosure and key preclinical data for AZD5305, a next-generation PARP1 selective inhibitor
  • The introduction of AZD8853, a novel antibody targeting GDF15 for tumours refractory to immunotherapy treatment
  • Research from the HUDSON Phase II trial using deep learning algorithms on pathological images to identify features associated with progression on immunotherapy for patients with non-small cell lung cancer
  • A pooled analysis of interstitial lung disease data in patients treated with Enhertu across eight cancer trials
  • Two presentations from genome-wide CRISPR screenings that identify signalling in the Hippo pathway as an important driver of resistance in EGFR-mutated lung cancer and BRAF-mutated colon cancer
  • Data identifying a novel immunosuppressive myeloid gene signature for clinical biomarker development
  • Results from the ATRiUM Phase I trial, externally sponsored scientific research evaluating ceralasertib, an ATR inhibitor, and gemcitabine as combination therapy in biliary tract cancer

Key AstraZeneca presentations during AACR 2021

Presenter Abstract title Presentation details1
DNA damage response
Johannes, J Discovery and first structural disclosure of AZD5305, a next generation, highly selective PARP1 inhibitor and trapper Abstract #ND05Oral Presentation: New Drugs on the Horizon: Part 210 April 202116:03 – 16:23 ET
Hande, S Structure-based and property-based drug design of AZD5305, a highly selective PARP1 inhibitor and trapper Abstract #296Poster: Lead Identification and Optimization
Staniszewska, AD The novel PARP1-selective inhibitor, AZD5305, is efficacious as monotherapy and in combination with standard of care chemotherapy in the in vivo preclinical models Abstract #1270Poster: Novel Antitumor Agents
Illuzzi, G In vitro cellular profiling of AZD5305 revealed that PARP1 selectivity and optimal trapping lead to best in class targeted therapy properties Abstract #1272Poster: Novel Antitumor Agents
Gill, SJ The novel PARP1-selective inhibitor AZD5305 has reduced hematological toxicity when compared to PARP1/2 inhibitors in pre-clinical models Abstract #1374Poster: Pharmacology, Pharmacogenetics, and Pharmacogenomics
Nam, A-R Co-Targeting PARP and ATR in biliary tract cancer Abstract #2073Poster: DNA Damage and Repair
De Paula, BH ATRiUM: A first-in-human dose escalation phase I trial of ceralasertib (AZD6738) and gemcitabine as combination therapy Abstract #CT214Phase I Clinical Trials in Progress
Immuno-Oncology
Dillon, L Deep learning identifies pathobiological features within H&E images associated with genomic alterations and progression on anti-PD(L)1 in HUDSON, an AstraZeneca-sponsored Phase II clinical trial Abstract #LB016Poster: Artificial Intelligence and Machine Learning
Srinivasan, SS Identification of a novel immunosuppressive myeloid gene expression signature for clinical biomarker development Abstract #390Poster: Biomarkers Predictive of Therapeutic Benefit
Sodergren, MH Up-regulation of C/EBPα inhibits suppressive activity of myeloid cells and potentiates antitumor response in mice and cancer patients Abstract #1730Poster: Immunomodulatory Agents and Interventions
Hurt, E AZD8853: A novel antibody targeting GDF15 for immunotherapy refractory tumors Abstract #1828Poster: Therapeutic Antibodies, Including Engineered Antibodies
Tumour drivers and resistance
Thorpe, H Genome-wide CRISPR screens reveal Hippo pathway activation as a resistance mechanism in BRAF mutant colon cancer Abstract #1081Poster: Drug Resistance in Molecular Targeted Therapies
Pfeifer, M Gain and loss of function genome-wide CRISPR screens identify Hippo signaling as an important driver of resistance in EGFR mutant lung cancer Abstract #1100Poster: Drug Resistance in Molecular Targeted Therapies
Antibody drug conjugates
Powell, CA Pooled analysis of drug-related interstitial lung disease (ILD) in 8 single-arm trastuzumab deruxtecan (T-DXd) studies Abstract #CT167Poster: Phase II Clinical Trials
Precision medicine
Christie, AL A novel circulating tumor DNA (ctDNA) assay enables monitoring of disease progression and treatment response in disseminated preclinical hematologic cancer models Abstract #2957Poster: Mouse Models of Human Cancer

1Unless otherwise specified, all posters/presentations will be available starting 08:30 EDT on 10 April 2021.

AstraZeneca in oncology

AstraZeneca is leading a revolution in oncology with the ambition to provide cures for cancer in every form, following the science to understand cancer and all its complexities to discover, develop and deliver life-changing medicines to patients.

The Company’s focus is on some of the most challenging cancers. It is through persistent innovation that AstraZeneca has built one of the most diverse portfolios and pipelines in the industry, with the potential to catalyse changes in the practice of medicine and transform the patient experience.

AstraZeneca has the vision to redefine cancer care and, one day, eliminate cancer as a cause of death.

AstraZeneca 

AstraZeneca (LSE/STO/Nasdaq: AZN) is a global, science-led biopharmaceutical company that focuses on the discovery, development and commercialisation of prescription medicines, primarily for the treatment of diseases in three therapy areas – Oncology, Cardiovascular, Renal & Metabolism, and Respiratory & Immunology. Based in Cambridge, UK, AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. Please visit astrazeneca.com and follow the Company on Twitter @AstraZeneca.

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