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.

• 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.

• 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

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

[1]Unless 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 (http://www.astrazeneca.com/) and follow the Company on Twitter @AstraZeneca (https://twitter.com/AstraZeneca).

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