AstraZeneca will present new data underscoring the breadth of the Company's early oncology portfolio at the American Association for Cancer Research (AACR) Annual Meeting in New Orleans, 8 to 13 April 2022.

Data from 60 presentations, including 5 oral and 3 mini-oral presentations, will feature the Company's next wave of potential cancer medicines spanning its immuno-oncology (IO), DNA Damage Response (DDR) and Antibody Drug Conjugate (ADC) scientific platforms. This includes key data shared from three potential new medicines that illustrate the Company's innovative approach to designing molecules that address key challenges in treating cancer, including the ability to target different, complementary mechanisms.

Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca, said: "We are serious about leading a revolution in oncology, which is why we continue to pioneer new ways to target cancer earlier and with greater precision, for the benefit of patients. Our data at AACR from next-wave Immuno-Oncology medicines, PARP inhibitors and antibody drug conjugates demonstrate the potential of our diverse portfolio and reflect our vision to target cancer from every angle."

Introducing the next wave of IO therapies

The first clinical results will be shared for MEDI5752, a novel bispecific antibody, that simultaneously targets the immune checkpoint proteins PD-1 and CTLA-4, in solid tumours. Bispecific antibodies are a promising IO approach that combines the potential benefits of two medicines in one. MEDI5752 was engineered to achieve combined blockade of CTLA-4 and PD-1, to improve the therapeutic index when compared to targeting these proteins using two separate medicines.

A presentation from the NeoCOAST randomised Phase II trial in resectable, early-stage non-small cell lung cancer will highlight improved disease responses with novel Imfinzi (durvalumab) combinations including with oleclumab, an anti-CD73 monoclonal antibody, and with monalizumab, an anti-NKG2A checkpoint inhibitor, when compared to Imfinzi alone.

Additionally, four presentations will describe novel molecules targeting interleukin-12 (IL-12) and leukaemia inhibitor factor (LIF) and illustrate the potential of targeting non-redundant mechanisms to modulate the immune tumour microenvironment.

Building the next generation of PARP inhibitors

The first data will be presented from the PETRA Phase I clinical trial investigating AZD5305, a next-generation PARP1-selective inhibitor, in patients with tumours harbouring specific homologous recombination repair gene mutations. AZD5305 is designed to selectively target PARP1, killing cancer cells by targeting tumour cell DNA damage repair mechanisms. This approach could allow PARP inhibitors to expand into new settings and offer new opportunities for combinations with DNA damage pathway activating agents such as ADCs. Preclinical data will be presented that support this hypothesis showing the activity of Enhertu (trastuzumab deruxtecan) in combination with DDR agents including PARP1-selective inhibitors.

Additionally, four presentations will describe the discovery of AZD9574, a novel PARP1 selective inhibitor designed to cross the blood brain barrier to enable the targeting of primary and secondary brain malignancies.

Innovative approaches to deliver a next-wave ADC

The first preclinical data will be shared on AZD8205, a novel ADC targeting B7-H4, a protein overexpressed in a range of solid tumours. This molecule is the first ADC to incorporate AstraZeneca's proprietary linker technology, demonstrating the Company's progress in establishing in-house ADC expertise and building leadership in this field.

Key AstraZeneca presentations during AACR 2022

[]
Presenting Abstract title Presentation details
author
IO
Tran, B MEDI5752, a Abstract #CT016OralSession CTPL04 - Combination
novel PD-1/CTLA Immunotherapy Clinical Trials12 April 202211:46
-4 bispecific - 12:01 CDT
checkpoint
inhibitor for
advanced solid
tumors: First-in
-human study
Cascone, T NeoCOAST-2: a Abstract #CT124 / 6Poster - Trial in progress
randomized, open (TiP)Session PO.CT02.03 - Phase II Trials in
-label, phase 2 Progress11 April 202209:00 - 12:30 CDT
study of
neoadjuvant
durvalumab plus
novel
immunotherapies
and chemotherapy
(CT) followed by
adjuvant
durvalumab plus
novel agents, in
patients with
resectable non
-small-cell lung
cancer (NSCLC)
Cascone, T NeoCOAST: open Abstract #CT011OralSession CTPL03 - Neoadjuvant
-label, and Perioperative Immunotherapy Clinical
randomized, Trials11 April 202211:16 - 11:31 CDT
phase 2,
multidrug
platform study
of neoadjuvant
durvalumab alone
or combined with
novel agents in
patients (pts)
with resectable,
early-stage non
-small-cell lung
cancer (NSCLC)
Shrestha, Durvalumab (D) + Abstract #CT024Mini-oralSession CTMS01 -
P platinum Biomarker Advances in Clinical Trials10 April
-etoposide (EP) 202215:50 - 160:00 CDT
in 1L extensive
-stage small
-cell lung
cancer (ES
-SCLC):
Exploratory
analysis of SCLC
molecular
subtypes in
CASPIAN
Reinmuth, Durvalumab (D) Abstract #CT533Poster - Clinical TrialSession
N plus OPO.CT02.01 - Phase II Clinical Trials8 April
tremelimumab (T) 202212:00 - 13:00 CDT
in platinum
-refractory/resis
tant extensive
-stage small
cell lung cancer
(ES-SCLC):
Efficacy, safety
and ctDNA
dynamics from
Arm A of the
phase 2 BALTIC
study
Fayette, J INTERLINK-1: A Abstract #CT236 / 7Poster - TiPSession
phase 3, PO.CT03.02 - Phase III Trials in Progress12
randomized, April 202213:30 - 17:00 CDT
double-blind,
placebo
-controlled,
multicenter,
global study of
monalizumab in
combination with
cetuximab in
patients with
recurrent or
metastatic head
and neck
squamous cell
carcinoma
previously
treated with an
immune
checkpoint
inhibitor
Carneiro, First-in-human Abstract #CT183 / 8Poster - Clinical
BA study of TrialSession PO.CT01.02 - Phase I Clinical
MEDI1191 (mRNA Trials 212 April 202209:00 - 12:30 CDT
encoding IL-12)
plus durvalumab
in patients
(pts) with
advanced solid
tumors
O'Kane, G A phase 2 trial Abstract #CT126 / 9Poster - TiPSession
of first-line PO.CT02.03 - Phase II Trials in Progress11 April
AZD0171 + 202209:00 - 12:30 CDT
durvalumab and
chemotherapy
(CT) in patients
with metastatic
pancreatic
ductal
adenocarcinoma
(PDAC) and CD8+
T cell
infiltration
Purroy, N First-in-human Abstract #CT218 / 18Poster - TiPSession
trial of PO.CT01.03 - Phase I Trials in Progress 112
intravenous April 202209:00 - 12:30 CDT
MEDI9253, an
oncolytic virus,
in combination
with durvalumab
in patients with
advanced solid
tumors
Candido, J AZD0171 (anti Abstract #1293 / 3PosterSession PO.IM02.08 -
-LIF) combines Immune Mechanisms Invoked by Other Therapies11
productively April 202209:00 - 12:30 CDT
with
chemotherapy and
anti-PD-L1 in
mouse models of
cancer
DDR
Yap, TA PETRA: First in Abstract #CT007OralSession CTPL02 - Clinical
class, first in Trials Targeting the DNA Damage Response and
human trial of KRAS10 April 202216:01 - 16:16 CDT
the next
generation PARP1
-selective
inhibitor
AZD5305 in
patients (pts)
with BRCA1/2,
PALB2 or
RAD51C/D
mutations
Pike, A Evaluation of Abstract #5076PosterSession OPO.CH01.01 - Drug
the CNS Discovery, Design, and Delivery8 April 202212:00
penetration of a - 13:00 CDT
next generation
PARP inhibitor,
AZD9574, in
cynomolgus
monkey using
positron
emission
tomography
Davies, BR AZD9574 is a Abstract #2609 / 22PosterSession PO.ET04.02 -
novel, brain DNA Damage Response and Repair12 April 202209:00
penetrant PARP-1 - 12:30 CDT
selective
inhibitor with
activity in an
orthotopic,
intracranial
xenograft model
with aberrant
DNA repair
Ghosh, A Structure-based Abstract #6302PosterSession OPO.CH01.01 - Drug
and property Discovery, Design, and Delivery8 April 202212:00
-based drug - 13:00 CDT
design of
AZD9574, a CNS
penetrant PARP1
selective
inhibitor and
trapper
Schou, M Discovery and Abstract #5977PosterSession OPO.TB07.01 - In
preclinical Vivo Imaging8 April 202212:00 - 13:00 CDT
validation of
[[11]C]AZ3391: A
first in class
blood-brain
barrier
permeable,
subtype
selective PARP-1
PET radioligand
Shapiro, Ceralasertib and Abstract #CT201 / 1Poster - TiPSession
GI olaparib in the PO.CT01.03 - Phase I Trials in Progress 112
treatment of April 202209:00 - 12:30 CDT
homologous
recombination
repair (HRR)
-deficient
platinum
-sensitive
ovarian cancer
after
progression on
PARP inhibitors
ADCs
Kinneer, K Discovery and Abstract #1765 / 17PosterSession PO.ET01.04 -
first disclosure Antibody-Drug Conjugates11 April 202213:30 -
of AZD8205, a B7 17:00 CDT
-H4-targeted
antibody-drug
conjugate
utilizing a
novel
topoisomerase I
linker-warhead
Wortmann, Development and Abstract #452 / 3PosterSession PO.BCS02.02 -
P implementation Artificial Intelligence and Digital Pathology10
of image April 202213:30 - 17:00 CDT
analysis-based
Quantitative
Continuous Score
(QCS) for B7-H4
IHC to
understand
AZD8205
pharmacodynamics

Wallez, Y Activity and Abstract #5298PosterSession OPO.ET07.01 -
tolerability of Biological Therapeutic Agents8 April 202212:00 -
combinations of 13:00 CDT
trastuzumab
deruxtecan (T
-DXd) with
inhibitors of
the DNA damage
response in
preclinical
models
Mettetal, Activity and Abstract #1142 / 6PosterSession PO.ET05.02 -
J tolerability of Preclinical and Clinical Pharmacology11 April
combination of 202209:00 - 12:30 CDT
trastuzumab
deruxtecan with
the next
generation PARP1
-selective
inhibitor
AZD5305 in
preclinical
models

AstraZeneca obtained full oncology rights to monalizumab from Innate Pharma in October 2018 through a co-development and commercialisation agreement initiated in 2015

Notes

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 in Oncology, Rare Diseases, and BioPharmaceuticals, including 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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