FORM 6-K

SECURITIES AND EXCHANGE COMMISSION

Washington, D.C. 20549

Report of Foreign Issuer

Pursuant to Rule 13a-16 or 15d-16 of

the Securities Exchange Act of 1934

For the month of November 2023

Commission File Number: 001-11960

AstraZeneca PLC

1 Francis Crick Avenue

Cambridge Biomedical Campus

Cambridge CB2 0AA

United Kingdom

Indicate by check mark whether the registrant files or will file annual reports under cover of Form 20-F or Form 40-F.

Form 20-F X Form 40-F __

Indicate by check mark if the registrant is submitting the Form 6-K in paper as permitted by Regulation S-T Rule 101(b)(1):

Indicate by check mark if the registrant is submitting the Form 6-K in paper as permitted by Regulation S-T Rule 101(b)(7): ______

Indicate by check mark whether the registrant by furnishing the information contained in this Form is also thereby furnishing the information to the Commission pursuant to Rule 12g3-2(b) under the Securities Exchange Act of 1934.

Yes __ No X

If “Yes” is marked, indicate below the file number assigned to the Registrant in connection with Rule 12g3-2(b): 82-_____________

AstraZeneca PLC

INDEX TO EXHIBITS

1. 9M and Q3 2023 results

AstraZeneca

9 November 2023

9M and Q3 2023 results

Strong momentum in the year to date leads to increased guidance for Total Revenue ex COVID-19 medicines and Core EPS

Revenue and EPS summary

		9M 2023			Q3 2023
		% Change			% Change
	$m	Actual	CER[1]	$m	Actual	CER
- Product Sales	32,466	1	4	11,018	4	5
- Alliance Revenue[2]	1,004	99	99	377	76	75
- Collaboration Revenue	317	(28)	(28)	97	(46)	(47)
Total Revenue	33,787	2	5	11,492	5	6
Total Revenue ex COVID-19	33,453	12	15	11,492	12	13
Reported[3] EPS[4]	$3.22	>2x	>2x	$0.89	(16)	(6)
Core[5] EPS	$5.80	10	17	$1.73	4	9

Financial performance (9M 2023 figures unless otherwise stated, growthnumbers at CER)

‒    Total Revenue $33,787m, up 5% despite a decline of $2,896m from COVID-19 medicines[6]

‒    Excluding COVID-19 medicines, both Total Revenue and Product Sales increased 15%

‒    Total Revenue from Oncology medicines increased 20%, CVRM[7] 19%, R&I[8] 9%, and Rare Disease 12%

‒    Core Product Sales Gross Margin[9] of 82%, up two percentage points, reflecting the decline in sales of lower margin COVID-19 medicines

‒    Core Operating Margin of 35% increased by three percentage points including the previously-announced gain from an update to the contractual relationships for Beyfortus, totalling $712m and recorded in Core Other operating income

‒    Core EPS increased 17% to $5.80

‒    FY 2023 Total Revenue excluding COVID-19 medicines now expected to increase by a low-teens percentage at CER

‒    FY 2023 Core EPS now expected to increase by a low double-digit to low-teens percentage at CER

Pascal Soriot, Chief Executive Officer, AstraZeneca, said:

"Our company continued its strong growth trajectory in the third quarter with Total Revenue from our non-COVID-19 medicines up 13% compared to last year.

We initiated several Phase III trials of high-potential molecules this quarter, including for volrustomig, our PD-1/CTLA-4[10] bispecific antibody. Our portfolio of bispecifics has the potential to replace the first-generation checkpoint inhibitors across a range of cancers. We also initiated a fixed dose combination study of zibotentan with Farxiga which has the potential to significantly improve outcomes for patients with kidney disease not well controlled on current standard of care.

I am excited about the acceleration of our cardiometabolic and obesity pipeline with today's licensing agreement for ECC5004, a potential best-in-class, oral GLP-1RA[11]. This molecule could offer an important advance, as both a monotherapy and in combinations, for the estimated one billion people living with cardiometabolic diseases such as type-2 diabetes and obesity.

Given the momentum in the year to date we have increased our full-year guidance for Total Revenue excluding COVID medicines as well as for Core EPS." 

Key milestones achieved since the prior results announcement

‒    Key positive read-outs: datopotamab deruxtecan in metastatic HR[12]-positive breast cancer (TROPION-Breast01); Imfinzi in liver cancer (EMERALD-1); Fasenra in EGPA[13] (MANDARA)   

‒    Key regulatory approvals: EU approval for Enhertu in HER2[14]-mutant lung cancer (DESTINY-Lung02); China approvals for Forxiga in heart failure regardless of ejection fraction (DELIVER); Calquence in r/rCLL[15] (ASCEND); Soliris in NMOSD[16]. Japan approvals for Lynparza in prostate cancer (PROpel); Enhertu in HER2-mutant lung cancer (DESTINY-Lung02)

‒    Other milestones: Tagrisso granted US Breakthrough Therapy Designation and US Priority Review in combination with chemotherapy for treatment of patients with locally advanced or metastatic EGFRm[17] NSCLC[18] (FLAURA2); Enhertu granted US Breakthrough Therapy Designations in HER2-positive colorectal

cancer (DESTINY-CRC01, DESTINY-CRC02) and multiple types of HER2-expressing tumours (DESTINY-PanTumor02)

Guidance

The Company updates its Total Revenue and Core EPS guidance for FY 2023 at CER, based on the average foreign exchange rates through 2022.

Total Revenue is expected to increase by a mid single-digit percentage

(previously low-to-mid single-digit).

Excluding COVID-19 medicines, Total Revenue is expected to increase by a low-teens percentage

(previously low double-digit).

Core EPS is expected to increase by a low double-digit to low-teens percentage

(previously high single-digit to low double-digit).

Other elements of the Income Statement are expected to be broadly in line with the indications issued in the Company's H1 2023 results announcement.

The Company is unable to provide guidance on a Reported basis because it cannot reliably forecast material elements of the Reported results, including any fair value adjustments arising on acquisition-related liabilities, intangible asset impairment charges and legal settlement provisions. Please refer to the cautionary statements section regarding forward-looking statements at the end of this announcement.

Currency impact

If foreign exchange rates for October to December 2023 were to remain at the average rates seen in September 2023, it is anticipated that FY 2023 Total Revenue would incur a low single-digit adverse impact versus the performance at CER, and Core EPS would incur a mid single-digit adverse impact (previously a low-to-mid single-digit adverse impact).

The Company's foreign exchange rate sensitivity analysis is provided in Table 19.

Table1: Key elements of Total Revenue performance in Q3 2023

% Change 

Revenue type	$m	Actual	CER
Product Sales	11,018	4	5	∗   Double-digit growth at CER in Oncology, CVRM and Rare Disease
Alliance Revenue	377	76	75	∗   $266m for Enhertu (Q3 2022: $160m) ∗   $74m for Tezspire (Q3 2022: $26m)
Collaboration Revenue	97	(46)	(47)	∗   $71m for Beyfortus regulatory milestone
Total Revenue	11,492	5	6	∗   Excluding COVID-19 medicines, Q3 2023 Total Revenue increased by 12% (13% at CER)
Therapy areas	$m	Actual %	CER %
Oncology	4,664	15	17	∗   Strong performance across key medicines and regions ∗   No milestones from Lynparza in the quarter (Q3 2022: $75m)
CVRM	2,687	14	16	∗   Farxiga up 41%,Lokelma up 30% (31% at CER), roxadustat up 31% (39% CER), Brilinta declined 2% (1% at CER)
R&I	1,549	3	5	∗   Fasenra up 10%, Breztri up 66% (69% CER). Saphnelo and Tezspire also continue to grow rapidly during their launch phase, partially offset by a 12% decline (10% at CER) in Symbicort following entry of a generic competitor in the US during the quarter
V&I[19]	312	(64)	(65)	∗   $nil revenue from COVID-19 mAbs and Vaxzevria in the quarter (Q3 2022: $536m and $180m respectively) ∗   Beyfortus $138m, including $50m of Product Sales from product supplied to Sanofi, $71m of Collaboration Revenue for a regulatory milestone and $17m of Alliance Revenue for AstraZeneca's share of gross profit outside US
Rare Disease	1,974	13	14	∗   Ultomiris up 50% (49% at CER), partially offset by decline in Soliris of 13% (12% at CER) ∗   Strensiq up 20% (21% at CER) and Koselugo up 81% reflecting strong patient demand
Other Medicines	306	(36)	(32)	∗   Nexium generic competition in Japan
Total Revenue	11,492	5	6
Regions inc. COVID-19	$m	Actual %	CER %
US	4,859	5	4
Emerging Markets	2,964	4	12
- China	1,452	(6)	1
- Ex-China Emerging Markets	1,513	15	25
Europe	2,392	16	9
Established RoW	1,276	(10)	(6)
Total Revenue inc. COVID-19	11,492	5	6	●     Growth rates impacted by lower sales of COVID-19 medicines (see table below)
Regions ex. COVID-19	$m	Actual %	CER %
US	4,859	12	12
Emerging Markets	2,964	8	16
- China	1,452	(6)	1
- Ex-China Emerging Markets	1,513	25	36
Europe	2,392	23	16
Established RoW	1,276	5	10
Total Revenue ex. COVID-19	11,492	12	13

Table 2: Key elements of financial performance in Q3 2023

Metric	Reported	Reported change	Core	Corechange	Comments[20]
Total Revenue	$11,492m	5% Actual      6% CER	$11,492m	5% Actual      6% CER	∗       Excluding COVID-19 medicines, Q3 2023 Total Revenue increased by 12% (13% at CER) ∗       See Table 1 and the Total Revenue section of this document for further details
Product Sales Gross Margin	81%	+9pp Actual      +10pp CER	81%	+1pp Actual      +1pp CER	+  Favourable mix of sales from Oncology and Rare Disease medicines +  No sales of COVID-19 medicines ‒   Increasing mix of products with profit-sharing arrangements, where AstraZeneca books Product Sales and records an expense in COGS[21] for the profit share due to its partner ∗       Variations in Product Sales Gross Margin can be expected between periods due to product seasonality, foreign exchange fluctuations and other effects
R&D expense	$2,584m	5% Actual      4% CER	$2,485m	5% Actual      5% CER	+  Increased investment in the pipeline ∗       Core R&D-to-Total Revenue ratio of 22%(Q3 2022: 21%) ∗       Year-on-year comparisons can be impacted by differences in cost phasing driven by study starts and execution
SG&A expense	$4,800m	12% Actual      12% CER	$3,355m	6% Actual      7% CER	+  Market development for recent launches and pre-launch activities +  Reported SG&A impacted by increased charges for legal provisions, including a $425m charge to provisions relating to a legal settlement in Q3 2023 (see Note 6) ∗       Core SG&A-to-Total Revenue ratio of 29%(Q3 2022: 29%) ∗       Year-on-year comparisons can be impacted by differences in cost phasing
Other operating income (and expense)[22]	$70m	-34% Actual      -33% CER	$70m	-35% Actual      -34% CER	‒   Discontinuation of brazikumab development
Operating Margin	17%	+6pp Actual      +7pp CER	31%	Stable at Actual     +1pp CER	∗   See Product Sales Gross Margin, expenses and Other operating income and expense commentary above
Net finance expense	$291m	-9% Actual      -6% CER	$223m	-12% Actual      -7% CER	+  Higher interest received on cash and short-term investments, broadly offset by higher rates on floating debt and bond issuances
Tax rate	17%	n/m Actual      n/m CER	19%	+1pp Actual      +1pp CER	∗   Variations in the tax rate can be expected between periods
EPS	$0.89	-16% Actual      -6% CER	$1.73	4% Actual      9% CER	∗   Further details of differences between Reported and Core are shown in Table 14

Table3: Pipeline highlights since prior results announcement

Event	Medicine	Indication / Trial	Event
Regulatory approvals and other regulatory actions	Lynparza	mCRPC[23] (1st-line) (PROpel)	Regulatory approval (JP)
	Enhertu	HER2m[24] NSCLC (2nd-line+) (DESTINY-Lung02)	Positive CHMP Opinion (EU), Regulatory approval (EU, JP)
	Calquence	CLL[25] (ASCEND)	Regulatory approval (CN)
	Forxiga	HFpEF[26] (DELIVER)	Regulatory approval (CN)
	Soliris	NMOSD	Regulatory approval (CN)
Regulatory submissionsor acceptances*	Tagrisso	EGFRm NSCLC (1st-line) (FLAURA2)	Regulatory submission (US, EU, CN), Priority Review (US)
	Imfinzi	NSCLC (neoadjuvant) (AEGEAN)	Regulatory submission (US)
	capivasertib	HR+/HER2-negative breast cancer (2nd-line) (CAPItello-291)	Regulatory submission (CN)
	roxadustat	Chemotherapy-induced anaemia	Regulatory submission (CN)
	FluMist	Self-administered influenza vaccine	Regulatory submission (US)
Major Phase III data readouts and other developments	Imfinzi	Liver cancer (locoregional) (EMERALD-1)	Primary endpoint met
	datopotamab deruxtecan	HR+/HER2-breast cancer (inoperable and/or metastatic) (TROPION-Breast01)	Primary endpoint met
	Fasenra	EGPA (MANDARA)	Primary endpoint met

*US, EU and China regulatory submission denotes filing acceptance

Upcoming pipeline catalysts

For a table of anticipated timings of key trial readouts, please refer to page 2 of the Clinical Trials Appendix, available on www.astrazeneca.com/investor-relations.html.

Other pipeline updates

Ultomiris discontinued plans to deliver subcutaneous administration for adults with aHUS[27] or PNH[28]. This decision follows persistent efforts to reliably secure the availability of the on-body delivery system.

Table 4: Phase III trials started since 1 January 2023

Medicine	Trial name	Indication
datopotamab deruxtecan	AVANZAR	NSCLC (1st-line)
	TROPION-Lung07	Non-squamous NSCLC (1st-line)
camizestrant	CAMBRIA-1	HR-positive/HER2-negative adjuvant breast cancer
	CAMBRIA-2	HR-positive/HER2-negative adjuvant breast cancer
capivasertib	CAPItello-292	HR-positive/HER2-negative advanced breast cancer
volrustomig	eVOLVE-Cervical	High-risk locally advanced cervical cancer
	eVOLVE-Lung02	mNSCLC (1st-line) with PD-L1[29] <50%
zibo/dapa	ZENITH High Proteinuria	CKD[30] and high proteinuria
Saphnelo	DAISY	Systemic sclerosis
Tezspire	CROSSING	Eosinophilic oesophagitis
Breztri	LITHOS	Mild to moderate asthma
Breztri	ATHLOS	COPD[31]
pMDI[32] portfolio	HFO1234ze	Mucociliary clearance in healthy volunteers
pMDI portfolio	HFO1234ze	Well-controlled or partially-controlled asthma
tozorakimab	MIRANDA	Symptomatic COPD
AZD3152	SUPERNOVA	COVID-19 prophylaxis
Ultomiris	ARTEMIS	Cardiac surgery-associated acute kidney injury

Corporate and business development

In September, AstraZeneca and Verge Genomics (Verge) announced a multi-target collaboration to identify novel drug targets for rare neurodegenerative and neuromuscular diseases. Verge is a clinical-stage drug discovery company using artificial intelligence and patient tissue data. Under the terms of the four-year agreement, Verge will receive up to $42 million, consisting of upfront fee, equity, and near-term payments, with potential downstream royalties. AstraZeneca will take an equity position in Verge.

In September, AstraZeneca completed the definitive purchase and licence agreement for a portfolio of preclinical rare disease gene therapy programmes and enabling technologies from Pfizer Inc. The agreement has a total consideration of up to $1bn, plus tiered royalties on sales.

Cellectis

In November, AstraZeneca announced a collaboration and investment agreement with Cellectis, a clinical-stage biotechnology company, to accelerate the development of next generation therapeutics in areas of high unmet need, including oncology, immunology and rare diseases. Under the terms of the collaboration agreement, AstraZeneca will leverage the Cellectis proprietary gene editing technologies and manufacturing capabilities, to design novel cell and gene therapy products, strengthening AstraZeneca's growing offering in this space. As part of the agreement, 25 genetic targets have been exclusively reserved for AstraZeneca, from which up to 10 candidate products could be explored for development.

In Q4 2023, Cellectis will receive an initial payment of $105m from AstraZeneca, which comprises a $25m upfront cash payment under the terms of a research collaboration agreement and an $80m equity investment. A further $140m equity investment is expected to close in early 2024 subject to the signing of a final binding agreement. Post-closing of this second investment, AstraZeneca will hold a total equity stake of approximately 44% in Cellectis. Under the terms of the research collaboration, Cellectis is also eligible to receive an investigational new drug option fee and development, regulatory and sales-related milestone payments, ranging from $70m up to $220m, per each of the 10 candidate products, plus tiered royalties.

Eccogene licence

In November, AstraZeneca and Eccogene entered into an exclusive licence agreement for ECC5004, an investigational oral once-daily glucagon-like peptide 1 receptor agonist (GLP-1RA) for the treatment of obesity, type-2 diabetes and other cardiometabolic conditions. Preliminary results from the Phase I trial have shown a differentiating clinical profile for ECC5004, with good tolerability and encouraging glucose and body weight reduction across the dose levels tested compared to placebo.

Under the terms of the agreement, Eccogene will receive an initial upfront payment of $185m and up to an additional $1.825bn in future clinical, regulatory, and commercial milestones and tiered royalties. AstraZeneca is granted exclusive global rights for the development and commercialisation of ECC5004 for any indication in all territories except China, where Eccogene has the right to co-develop and co-commercialise alongside AstraZeneca.

Sustainability summary

This quarter AstraZeneca entered into long-term renewable energy partnerships in the UK and Sweden. The UK agreement will support the transition away from fossil fuels at Company sites in Macclesfield, Cambridge, Luton and Speke. The Sweden agreement corresponds to approximately 80 percent of total electricity needs at both the Company's Gothenburg site and at Södertälje, one of the world's largest drug manufacturing centres. See the Sustainability section for further details.

Conference call

A conference call and webcast for investors and analysts will begin today, 9 November 2023, at 14:00 UK time. Details can be accessed via astrazeneca.com.

Reporting calendar

The Company intends to publish its full year and fourth quarter results on Thursday 8 February 2024.

Operating and financial review

All narrative on growth and results in this section is based on actual foreign exchange rates, and financial figures are in US$ millions ($m), unless stated otherwise. The performance shown in this announcement covers the nine-month period to 30 September 2023 ('the period' or '9M 2023') compared to the nine-month period to 30 September 2022 ('9M 2022'), or the three-month period to 30 September 2023 ('the quarter' or 'Q3 2023') compared to the three-month period to 30 September 2022 ('Q3 2022'), unless stated otherwise.

Core financial measures, EBITDA, Net debt, Product Sales Gross Margin (formerly termed as Gross Margin), Operating Margin and CER are non-GAAP financial measures because they cannot be derived directly from the Group's Interim financial statements. Management believes that these non-GAAP financial measures, when provided in combination with Reported results, provide investors and analysts with helpful supplementary information to understand better the financial performance and position of the Group on a comparable basis from period to period. These non-GAAP financial measures are not a substitute for, or superior to, financial measures prepared in accordance with GAAP.

Core financial measures are adjusted to exclude certain significant items, such as:

‒    Amortisation and impairment of intangible assets, including impairment reversals but excluding any charges relating to IT assets

‒    Charges and provisions related to restructuring programmes, which includes charges that relate to the impact of restructuring programmes on capitalised IT assets

‒    Alexion acquisition-related items, primarily fair value adjustments on acquired inventories and fair value impact of replacement employee share awards

‒    Other specified items, principally the imputed finance charges and fair value movements relating to contingent consideration on business combinations or asset acquisitions, imputed finance charges and remeasurement adjustments on certain Other payables arising from intangible asset acquisitions, legal settlements and remeasurement adjustments relating to Other payables assumed from the Alexion acquisition

‒    The tax effects of the adjustments above are excluded from the Core Tax charge

Details on the nature of Core financial measures are provided on page 63 of the Annual Report and Form 20-F Information 2022.

Reference should be made to the Reconciliation of Reported to Core financial measures table included in the financial performance section in this announcement.

Product Sales Gross Margin (formerly termed Gross Margin) is the percentage by which Product Sales exceeds the Cost of Sales, calculated by dividing the difference between the two by the sales figure. The calculation of Reported and Core Product Sales Gross Margin excludes the impact of Alliance Revenue and Collaboration Revenue and any associated costs, thereby reflecting the underlying performance of Product Sales.

EBITDA is defined as Reported Profit before tax after adding back Net finance expense, results from Joint ventures and associates and charges for Depreciation, amortisation and impairment. Reference should be made to the Reconciliation of Reported Profit before tax to EBITDA included in the financial performance section in this announcement.

Operating Margin is defined as Operating profit as a percentage of Total Revenue.

Net debt is defined as Interest-bearing loans and borrowings and Lease liabilities, net of Cash and cash equivalents, Other investments, and Net derivative financial instruments. Reference should be made to Note 3 'Net debt' included in the Notes to the Interim financial statements in this announcement.

The Company strongly encourages investors and analysts not to rely on any single financial measure, but to review AstraZeneca's financial statements, including the Notes thereto, and other available Company reports, carefully and in their entirety.

Due to rounding, the sum of a number of dollar values and percentages in this announcement may not agree to totals.

Total Revenue

Table5: Therapy area and medicine performance - Product Sales and Total Revenue

	9M 2023				Q3 2023
			% Change				% Change
Product Sales	$m	% Total	Actual	CER	$m	% Total	Actual	CER
Oncology	12,692	38	17	20	4,389	38	16	17
- Tagrisso	4,380	13	7	10	1,465	13	5	6
- Imfinzi[33]	3,102	9	53	56	1,126	10	53	54
- Lynparza	2,070	6	6	9	702	6	7	8
- Calquence	1,839	5	25	26	654	6	16	15
- Enhertu	178	1	>3x	>3x	73	1	>3x	>3x
- Orpathys	33	-	(3)	4	12	-	6	13
- Zoladex	699	2	(3)	5	239	2	-	5
- Faslodex	217	1	(16)	(10)	64	1	(21)	(16)
- Others	174	1	(36)	(32)	54	-	(33)	(30)
BioPharmaceuticals: CVRM	7,887	23	14	18	2,683	23	14	16
- Farxiga	4,358	13	36	40	1,554	14	41	41
- Brilinta	996	3	(2)	-	331	3	(2)	(1)
- Lokelma	300	1	44	49	102	1	30	31
- roxadustat	208	1	41	51	74	1	31	39
- Andexxa	129	-	16	19	40	-	(3)	(5)
- Crestor	860	3	4	11	275	2	(1)	6
- Seloken/Toprol-XL	496	1	(30)	(23)	153	1	(36)	(29)
- Onglyza	180	1	(12)	(8)	53	-	(20)	(17)
- Bydureon	123	-	(40)	(40)	35	-	(48)	(49)
- Others	237	1	(16)	(13)	66	1	(23)	(21)
BioPharmaceuticals: R&I	4,517	13	5	8	1,451	13	2	3
- Symbicort	1,842	5	(4)	(1)	555	5	(12)	(10)
- Fasenra	1,134	3	12	13	389	3	10	10
- Breztri	478	1	69	73	171	1	66	69
- Saphnelo	191	1	>2x	>2x	76	1	>2x	>2x
- Tezspire	51	-	>10x	>10x	21	-	>10x	>10x
- Pulmicort	493	1	3	10	148	1	2	7
- Bevespi	42	-	(2)	(2)	13	-	(5)	(4)
- Daliresp/Daxas	41	-	(74)	(74)	11	-	(79)	(79)
- Others	245	1	(30)	(27)	67	1	(31)	(28)
BioPharmaceuticals: V&I	667	2	(82)	(81)	224	2	(74)	(74)
- COVID-19 mAbs[34]	126	-	(91)	(90)	-	-	n/m	n/m
- Vaxzevria	28	-	(98)	(98)	-	-	n/m	n/m
- Beyfortus	52	-	n/m	n/m	50	-	n/m	n/m
- Synagis	383	1	-	6	99	1	(5)	(1)
- FluMist	78	-	32	28	75	1	28	23
Rare Disease	5,793	17	11	12	1,974	17	13	14
- Soliris	2,429	7	(17)	(15)	781	7	(13)	(12)
- Ultomiris	2,141	6	56	58	777	7	50	49
- Strensiq	847	3	23	24	285	2	20	21
- Koselugo	246	1	65	65	87	1	81	81
- Kanuma	130	-	17	18	44	-	21	19
Other Medicines	910	3	(27)	(22)	297	3	(27)	(22)
- Nexium	735	2	(25)	(20)	244	2	(22)	(17)
- Others	175	1	(33)	(31)	53	-	(43)	(41)
Product Sales	32,466	96	1	4	11,018	96	4	5
Alliance Revenue	1,004	3	99	99	377	3	76	75
Collaboration Revenue	317	1	(28)	(28)	97	1	(46)	(47)
Total Revenue	33,787	100	2	5	11,492	100	5	6

Table 6: Alliance Revenue

	9M 2023				Q3 2023
			% Change				% Change
	$m	% Total	Actual	CER	$m	% Total	Actual	CER
Enhertu	741	74	>2x	>2x	266	70	66	65
Tezspire	179	18	>4x	>4x	74	20	>2x	>2x
Vaxzevria: royalties	-	-	n/m	n/m	-	-	n/m	n/m
Other royalty income	59	6	16	15	18	5	10	9
Other Alliance Revenue	25	2	>2x	>2x	19	5	>3x	>3x
Total	1,004	100	99	99	377	100	76	75

Table 7: Collaboration Revenue

	9M 2023				Q3 2023
			% Change				% Change
	$m	% Total	Actual	CER	$m	% Total	Actual	CER
COVID-19 mAbs: licence fees	180	57	n/m	n/m	-	-	n/m	n/m
Farxiga: sales milestones	28	9	n/m	n/m	3	3	n/m	n/m
tralokinumab: sales milestones	20	6	(82)	(82)	20	21	(50)	(50)
Lynparza: regulatory milestones	-	-	n/m	n/m	-	-	n/m	n/m
Beyfortus: regulatory milestones	71	22	n/m	n/m	71	73	n/m	n/m
Other Collaboration Revenue	18	6	(76)	(76)	3	3	(95)	(95)
Total	317	100	(28)	(28)	97	100	(46)	(47)

Table 8: Total Revenue by therapy area

	9M 2023				Q3 2023
			% Change				% Change
	$m	% Total	Actual	CER	$m	% Total	Actual	CER
Oncology	13,458	40	17	20	4,664	41	15	17
BioPharmaceuticals	13,599	40	(10)	(7)	4,548	40	(4)	(2)
- CVRM	7,926	23	14	19	2,687	23	14	16
- R&I	4,729	14	6	9	1,549	13	3	5
- V&I	944	3	(74)	(73)	312	3	(64)	(65)
Rare Disease	5,793	17	11	12	1,974	17	13	14
Other Medicines	937	3	(30)	(26)	306	3	(36)	(32)
Total	33,787	100	2	5	11,492	100	5	6

Table9: Total Revenue by region

	9M 2023				Q3 2023
			% Change				% Change
	$m	% Total	Actual	CER	$m	% Total	Actual	CER
US	13,940	41	6	6	4,859	42	5	4
Emerging Markets	9,242	27	3	10	2,964	26	4	12
- China	4,495	13	(2)	5	1,452	13	(6)	1
- Ex-China	4,747	14	8	15	1,513	13	15	25
Europe	6,765	20	5	5	2,392	21	16	9
Established RoW	3,840	11	(16)	(9)	1,276	11	(10)	(6)
Total	33,787	100	2	5	11,492	100	5	6

Table10: Total Revenue by region - excluding COVID-19 medicines

	9M 2023				Q3 2023
			% Change				% Change
	$m	% Total	Actual	CER	$m	% Total	Actual	CER
US	13,940	42	14	14	4,859	42	12	12
Emerging Markets	9,038	27	12	20	2,964	26	8	16
- China	4,495	13	(1)	6	1,452	13	(6)	1
- Ex-China	4,544	14	28	37	1,513	13	25	36
Europe	6,748	20	14	14	2,392	21	23	16
Established RoW	3,726	11	-	8	1,276	11	5	10
Total	33,453	100	12	15	11,492	100	12	13

Oncology

Oncology Total Revenue of $13,458m in 9M 2023 increased by 17% (20% at CER), representing 40% of overall Total Revenue (9M 2022: 35%). There was no Lynparza Collaboration Revenue in 9M 2023 (9M 2022: $250m), and Enhertu Alliance Revenue was $741m (9M 2022: $335m). Product Sales increased by 17% (20% at CER) in 9M 2023 to $12,692m, reflecting new launches and expanded reimbursement across key brands; partially offset by declines in legacy medicines.

Tagrisso

Total Revenue	Worldwide	US	Emerging Markets	Europe	Established RoW
9M 2023  $m	4,380	1,679	1,261	821	619
Actual change	7%	14%	4%	6%	(4%)
CER change	10%	14%	11%	6%	5%

Region	Drivers and commentary
Worldwide	∗   Increased global demand for Tagrisso in adjuvant and 1st-line settings combined with expanded reimbursement in the adjuvant setting
US	∗   Continued growth in demand in 1st-line and adjuvant settings
Emerging Markets	∗  Growing demand in adjuvant and 1st-line settings offset by impact of NRDL[35] renewal price in China effective March 2023, some additional impact in China in the third quarter resulting from reduced promotional activities following the government campaign announced at the end of July 2023
Europe	∗   Increased demand growth in 1st-line and growing adjuvant demand
Established RoW	∗   Increased demand in 1st-line and adjuvant settings offset by mandatory price reduction in Japan effective June 2023

Imfinzi and Imjudo

Total Revenue	Worldwide	US	Emerging Markets	Europe	Established RoW
9M 2023  $m	3,102	1,708	270	547	577
Actual change	53%	55%	20%	36%	90%
CER change	56%	55%	31%	35%	>2x

Region	Drivers and commentary
Worldwide	∗   Includes $161m of Total Revenue from Imjudo, which launched in Q4 2022 following approvals in the US for patients with unresectable liver cancer (HIMALAYA) and Stage IV NSCLC (POSEIDON) ∗  Growth across all regions, driven by recent launches (BTC[36], HCC[37], Stage IV NSCLC) and established indications (Stage III NSCLC, SCLC[38])
US	∗   Continued demand growth for BTC and HCC indications, increased uptake in SCLC
Emerging Markets	∗   Growth across markets driven by BTC launches and recovery of diagnosis and treatment rates following the COVID-19 pandemic, slightly offset by decreased promotional activities in China due to the government campaign announced at the end of July 2023
Europe	∗   Competitive share gain in SCLC, and expanded reimbursement for new launch indications (BTC, HCC and Stage IV NSCLC)
Established RoW	∗   Growth driven by launch of HCC and BTC and increased share across indications in Japan

Lynparza

Total Revenue	Worldwide	US	Emerging Markets	Europe	Established RoW
9M 2023  $m	2,070	902	409	543	216
Actual change	(6%)	1%	14%	(27%)	7%
CER change	(3%)	1%	24%	(27%)	16%

Product Sales	Worldwide	US	Emerging Markets	Europe	Established RoW
9M 2023  $m	2,070	902	409	543	216
Actual change	6%	1%	14%	10%	7%
CER change	9%	1%	24%	10%	16%

Region	Drivers and commentary
Worldwide	∗   Lynparza remains the leading medicine in the PARP[39] inhibitor class globally across four tumour types (ovarian, breast, prostate, pancreatic), as measured by total prescription volume ∗   No regulatory milestones received in the period
US	∗   Continued share growth within the PARP inhibitor class, offset by declining class use and the label restriction in 2nd-line ovarian cancer effective September 2023
Emerging Markets	∗  Increased demand, offset by price reduction in China associated with NRDL renewal that took effect March 2023 for ovarian cancer indications (PSR[40] and BRCAm[41] 1st-line maintenance) and new NRDL enlistment in prostate cancer (PROfound) as well as some impact in the third quarter resulting from reduced promotional activities following the government campaign announced end of July 2023
Europe	∗   Demand growth from increased uptake in 1st-line HRD-positive ovarian cancer, gBRCAm[42] HER2-negative early breast cancer and mCRPC, offset by reduced use in 2nd-line ovarian cancer and pricing ∗   Total Revenue in the prior year period included $250m of milestones
Established RoW	∗   Growth driven by increased uptake in testing and use in 1st-line HRD-positive ovarian cancer

Enhertu

Total Revenue	Worldwide	US	Emerging Markets	Europe	Established RoW
9M 2023  $m	919	518	179	204	17
Actual change	>2x	>2x	>3x	>2x	>3x
CER change	>2x	>2x	>3x	>2x	>3x

Region	Drivers and commentary
Worldwide	∗   Combined sales of Enhertu, recorded by Daiichi Sankyo Company Limited (Daiichi Sankyo) and AstraZeneca, amounted to $1,844m in 9M 2023 (9M 2022: $750m) ∗   AstraZeneca's Total Revenue of $919m in the period includes $741m of Alliance Revenue from its share of gross profit and royalties in territories where Daiichi Sankyo records product sales
US	∗   US in-market sales, recorded by Daiichi Sankyo, amounted to $1,087m in 9M 2023 (9M 2022: $532m) ∗   Increased demand across launched indications. Q3 2023 impacted by HER2-low bolus depletion
Emerging Markets	∗   Continued uptake driven by recent approvals and launches including strong demand growth in China following HER2-positive and HER2-low breast cancer launches
Europe	∗   Continued growth driven by increasing adoption in HER2-positive and HER2-low metastatic breast cancer
Established RoW	∗   In Japan, AstraZeneca receives a mid-single-digit percentage royalty on sales made by Daiichi Sankyo

Calquence

Total Revenue	Worldwide	US	Emerging Markets	Europe	Established RoW
9M 2023  $m	1,839	1,337	69	353	80
Actual change	25%	12%	>2x	76%	64%
CER change	26%	12%	>2x	77%	74%

Region	Drivers and commentary
Worldwide	∗  Increased penetration globally; leading BTKi[43] in key markets
US	∗   Leadership maintained in growing BTKi class, sustained leading share in the front-line setting, offset by some competitive impact in relapsed refractory setting and increased utilisation of free goods program in Q3
EU	∗   Solid growth continued amidst growing competitive pressure ∗   Increased new patients starts following expanded access in key markets

Orpathys

Orpathys Total Revenue of $34m declined 1% (6% increase at CER), (9M 2022: $35m), following its inclusion in the updated NRDL in China from March 2023, for the treatment of patients with NSCLC with MET exon 14 skipping alterations.

Other Oncology medicines

9M 2023 Change

Total Revenue	$m	Actual	CER
Zoladex	723	(2%)	5%	∗   Underlying growth due to continued demand growth in Emerging Markets, partially offset by price reduction in China following NRDL renewal
Faslodex	217	(16%)	(10%)	∗   Generic competition
Other Oncology	174	(36%)	(32%)	∗   Generic competition

BioPharmaceuticals

BioPharmaceuticals Total Revenue decreased by 10% (7% at CER) in 9M 2023 to $13,599m, representing 40% of overall Total Revenue (9M 2022: 45%). The decline was driven by COVID-19 medicines, partially offset by strong growth from Farxiga and newer R&I medicines.

BioPharmaceuticals - CVRM

CVRM Total Revenue increased by 14% (19% at CER) to $7,926m in 9M 2023, driven by the strong Farxiga performance, and represented 23% of overall Total Revenue (9M 2022: 21%).

Farxiga

Total Revenue	Worldwide	US	Emerging Markets	Europe	Established RoW
9M 2023  $m	4,389	1,000	1,655	1,356	378
Actual change	37%	34%	35%	42%	35%
CER change	41%	34%	43%	41%	45%

Region	Drivers and commentary
Worldwide	∗   Farxiga volume is growing faster than the overall SGLT2[44] market in most major regions, fuelled by launches in heart failure and CKD ∗   Additional benefit from continued growth in the overall SGLT2 inhibitor class
US	∗  Growth driven by heart failure and CKD for patients with and without T2D[45] resulting in an increasing market share
Emerging Markets	∗   Solid growth despite generic competition in some markets
Europe	∗   Benefited from the addition of cardiovascular outcomes trial data to the label and growth in HFrEF[46], CKD and the HFpEF approval in February 2023. ESC[47] guidelines updated in August 2023 to also include treatment of patients with HFpEF ∗   Continued strong volume growth in the quarter and expanded class leadership in several key markets
Established RoW	∗   In Japan, AstraZeneca sells to collaborator Ono Pharmaceutical Co., Ltd, which records in-market sales. Continued volume growth driven by HF and CKD launches. Generics launched in Canada in the third quarter

Brilinta

Total Revenue	Worldwide	US	Emerging Markets	Europe	Established RoW
9M 2023  $m	996	551	224	203	18
Actual change	(2%)	2%	1%	(5%)	(54%)
CER change	-	2%	10%	(5%)	(51%)

Region	Drivers and commentary
US	∗   Sales in the third quarter benefitted from channel inventory movements
Emerging Markets	∗   Sales declined by 16% (4% at CER) in the third quarter driven by tender phasing
Europe	∗   Sales partly impacted by clawbacks
Established RoW	∗   Sales decline driven by generic entry in Canada

Lokelma

Lokelma Total Revenue increased 44% (49% at CER) to $300m with strong demand growth in all regions.

Roxadustat

Total Revenue increased 40% (50% at CER) to $212m, benefitting from increased demand in both the dialysis- and non-dialysis-dependent populations

Andexxa

AndexxaTotal Revenue increased 7% (9% at CER) to $129m.

Other CVRM medicines

9M 2023 Change

Total Revenue	$m	Actual	CER
Crestor	862	4%	11%	∗   Continued sales growth in Emerging Markets, partly offset by declines in the US and Established RoW
Seloken	496	(30%)	(23%)	∗   Ongoing impact of China VBP implementation
Onglyza	180	(12%)	(8%)	∗   Continued decline for DPP-IV class
Bydureon	123	(40%)	(40%)	∗   Continued competitive pressures
Other CVRM	237	(16%)	(13%)

BioPharmaceuticals - R&I

Total Revenue of $4,729m from R&I medicines in 9M 2023 increased 6% (9% at CER) and represented 14% of overall Total Revenue (9M 2022: 14%). This reflected growth in Fasenra, Tezspire, Breztri and Saphnelo, offsetting a decline in Symbicort and other mature brands.

Fasenra

Total Revenue	Worldwide	US	Emerging Markets	Europe	Established RoW
9M 2023  $m	1,134	718	48	262	106
Actual change	12%	11%	62%	14%	(1%)
CER change	13%	11%	69%	14%	6%

Region	Drivers and commentary
Worldwide	∗   Retained market share leadership in severe eosinophilic asthma across major markets
US	∗   Expanded leadership in eosinophilic asthma and maintained total share in a growing market, leading to double-digit volume growth, partially offset by managed market price difference
Emerging Markets	∗   Continued strong volume growth driven by launch acceleration across key markets
Europe	∗   Expanded leadership in severe eosinophilic asthma, with strong volume growth partially offset by price in some markets
Established RoW	∗   Maintained class leadership in Japan while market growth remained stable

Breztri

Total Revenue	Worldwide	US	Emerging Markets	Europe	Established RoW
9M 2023  $m	478	263	123	55	37
Actual change	69%	60%	73%	>2x	48%
CER change	73%	60%	86%	>2x	58%

Region	Drivers and commentary
Worldwide	∗  Continued to gain market share within the growing FDC[48] triple class across major markets
US	∗  Consistent share growth within the FDC triple class in new-to-brand[49]and the total market
Emerging Markets	∗   Maintained market share leadership in China with strong triple FDC class penetration
Europe	∗   Sustained growth across markets as new launches continue to progress
Established RoW	∗   Increased market share gains within COPD in Japan and strong launch performance in Canada

Tezspire

Total Revenue	Worldwide	US	Emerging Markets	Europe	Established RoW
9M 2023  $m	230	179	-	28	23
Actual change	>5x	>4x	-	n/m	n/m
CER change	>5x	>4x	-	n/m	n/m

Region	Drivers and commentary
Worldwide	∗   Tezspire is approved in the US, EU and Japan (as well as other countries) for the treatment of severe asthma without biomarker or phenotypic limitation ∗   Amgen records sales in the US, and AstraZeneca records its share of US gross profits as Alliance Revenue. AstraZeneca books Product Sales in markets outside the US ∗   Combined sales of Tezspire by AstraZeneca and Amgen were $438m in 9M 2023
US	∗   Increased new-to-brand market share with majority of patients new to biologics ∗   Pre-filled pen approved in February 2023
Europe	∗   Achieved and maintained new-to-brand leadership in key markets ∗   Pre-filled pen approved in January 2023
Established RoW	∗   Japan maintained new-to-brand leadership

Saphnelo

Total Revenue	Worldwide	US	Emerging Markets	Europe	Established RoW
9M 2023  $m	191	178	1	5	7
Actual change	>2x	>2x	n/m	>4x	>3x
CER change	>2x	>2x	n/m	>4x	>3x

Region	Drivers and commentary
Worldwide	∗   Demand acceleration in the US, and additional growth driven by ongoing launches in Europe and Japan

Symbicort

Total Revenue	Worldwide	US	Emerging Markets	Europe	Established RoW
9M 2023  $m	1,842	589	600	408	245
Actual change	(4%)	(18%)	26%	(8%)	(12%)
CER change	(1%)	(18%)	36%	(8%)	(7%)

Region	Drivers and commentary
Worldwide	∗  Symbicort remained the global market leader within a stable ICS[50]/LABA[51] class
US	∗   Generic competition entered the US market in the third quarter, leading to price and volume share declines
Emerging Markets	∗   Strong underlying demand. Growth in China benefitted from the post-COVID-19 recovery at the start of the year
Europe	∗   Continued price and volume erosion from generics and a slowing overall market
Established RoW	∗   Generic erosion in Japan

Other R&I medicines

9M 2023    Change

Total Revenue	$m	Actual	CER
Pulmicort	493	3%	10%	∗   80% of revenues from Emerging Markets ∗   China market share has stabilised, with VBP having been in effect for over 12 months
Bevespi	42	(2%)	(2%)
Daliresp	41	(74%)	(74%)	∗   Impacted by uptake of multiple generics following loss of exclusivity in the US
Other R&I	278	(41%)	(38%)	∗   Collaboration Revenue of $20m (9M 2022: $110m) ∗   Product Sales of $245m decreased 30% (27% at CER) due to generic competition

BioPharmaceuticals - V&I

Total Revenue from V&I medicines declined by 74% (73% at CER) to $944m (9M 2022: $3,673m) and represented 3% of overall Total Revenue (9M 2022: 11%). In Q3 2023, no revenue was generated from COVID-19 medicines.

COVID-19 mAbs

Total Revenue	Worldwide	US	Emerging Markets	Europe	Established RoW
9M 2023  $m	306	-	185	7	114
Actual change	(79%)	n/m	11%	(97%)	(51%)
CER change	(78%)	n/m	11%	(96%)	(45%)

Region	Drivers and commentary
Worldwide	∗   All Product Sales in 9M 2023 were derived from sales of Evusheld in the first quarter
Emerging Markets	∗   $180m license fee from Serum Institute of India in Q2 2023 recorded as Collaboration Revenue

Vaxzevria

Total Revenue	Worldwide	US	Emerging Markets	Europe	Established RoW
9M 2023  $m	28	-	18	10	-
Actual change	(98%)	n/m	(98%)	(97%)	n/m
CER change	(98%)	n/m	(98%)	(97%)	n/m

Region	Drivers and commentary
Worldwide	∗   Revenue in the period decreased by 98% due to the conclusion of Vaxzevria contracts

Other V&I medicines

9M 2023 Change

Total Revenue	$m	Actual	CER
Beyfortus	139	n/m	n/m	∗   In Q3 2023 AstraZeneca reported $50m of Product Sales, $17m of Alliance Revenue, and also $71m of Collaboration Revenue relating to a regulatory milestone ∗   The Product Sales relates to sales to Sanofi of Beyfortus product manufactured by AstraZeneca. In Q3 Product Sales benefitted from stock building for the 2023-2024 RSV[52] season ∗   The Alliance Revenue consists of AstraZeneca's 50% share of gross profits on sales of Beyfortus in major markets outside the US. AstraZeneca will also book 25% of revenues in rest of world markets. AstraZeneca has no participation in US profits or losses
Synagis	383	-	6%	∗   Performance broadly in-line with prior year
FluMist	88	49%	45%	∗   $10m milestone received from Daiichi Sankyo in the second quarter following FluMist approval in Japan

Rare Disease

Total Revenue from Rare Disease medicines increased by 11% (12% at CER) in 9M 2023 to $5,793m, representing 17% of overall Total Revenue (9M 2022: 16%).

Performance was driven by the continued growth and durability of the C5[53] franchise, and also the strength of Strensiq and Koselugo patient demand.

Ultomiris

Total Revenue	Worldwide	US	Emerging Markets	Europe	Established RoW
9M 2023  $m	2,141	1,260	47	495	339
Actual change	56%	63%	38%	43%	54%
CER change	58%	63%	39%	42%	68%

Region	Drivers and commentary
Worldwide	∗   Growth in neurology indications, expansion into new markets and continued conversion from Soliris ∗   Quarter-on-quarter variability in revenue growth can be expected due to Ultomiris every eight-week dosing schedule and lower average annual treatment cost per patient compared to Soliris
US	∗  Growth in naïve patients in gMG[54] and NMOSD as well as successful conversion from Soliris across shared indications
Emerging Markets	∗   Continued progress following launches in new markets
Europe	∗   Strong demand generation following launches in new markets, particularly in neurology indications, as well as accelerated conversion from Soliris in key markets
Established RoW	∗   Continued conversion from Soliris and strong demand following new launches, particularly NMOSD in Japan

Soliris

Total Revenue	Worldwide	US	Emerging Markets	Europe	Established RoW
9M 2023  $m	2,429	1,313	338	530	248
Actual change	(17%)	(22%)	55%	(15%)	(36%)
CER change	(15%)	(22%)	74%	(15%)	(31%)

Region	Drivers and commentary
US	∗   Decline driven by successful conversion of Soliris patients to Ultomiris in PNH, aHUS and gMG, partially offset by Soliris growth in NMOSD
Emerging Markets	∗   Continued progress, launching in new markets
Europe,Established RoW	∗   Decline driven by successful conversion from Soliris to Ultomiris, partially offset by growth in NMOSD

Strensiq

Total Revenue	Worldwide	US	Emerging Markets	Europe	Established RoW
9M 2023  $m	847	690	29	64	64
Actual change	23%	26%	14%	9%	12%
CER change	24%	26%	16%	8%	22%

Region	Drivers and commentary
Worldwide	∗   Strong patient demand particularly in the US and Japan

Other Rare Disease medicines

9M 2023 Change

Total Revenue	$m	Actual	CER	Commentary
Koselugo	246	65%	65%	∗   Driven by patient demand and expansion in new markets
Kanuma	130	17%	18%	∗   Continued demand growth in ex-US markets

Other medicines (outside the main therapy areas)

9M 2023 Change

Total Revenue	$m	Actual	CER	Commentary
Nexium	748	(30%)	(25%)	∗   Generic launches in Japan in the latter part of 2022
Others	189	(31%)	(29%)	∗   Continued impact of generic competition

Financial performance

Table11: Reported Profit and Loss

9M 2023 9M 2022 % Change  Q3 2023 Q3 2022 % Change

	$m	$m	Actual	CER	$m	$m	Actual	CER
Total Revenue	33,787	33,144	2	5	11,492	10,982	5	6
- Product Sales	32,466	32,200	1	4	11,018	10,590	4	5
- Alliance Revenue	1,004	504	99	99	377	214	76	75
- Collaboration Revenue	317	440	(28)	(28)	97	178	(46)	(47)
Cost of sales	(5,960)	(9,491)	(37)	(38)	(2,095)	(2,982)	(30)	(31)
Gross profit	27,827	23,653	18	22	9,397	8,000	17	20
Product Sales Gross Margin	81.6%	70.5%	+11pp	+12pp	81.0%	71.8%	+9pp	+10pp
Distribution expense	(394)	(380)	4	6	(129)	(126)	2	2
% Total Revenue	1.2%	1.1%	-	-	1.1%	1.1%	-	-
R&D expense	(7,862)	(7,137)	10	12	(2,584)	(2,458)	5	4
% Total Revenue	23.3%	21.5%	-2pp	-2pp	22.5%	22.4%	-	-
SG&A expense	(13,845)	(13,798)	-	2	(4,800)	(4,277)	12	12
% Total Revenue	41.0%	41.6%	+1pp	+1pp	41.8%	38.9%	-3pp	-2pp
OOI[55] & expense	1,233	325	>3x	>3x	70	106	(34)	(33)
% Total Revenue	3.6%	1.0%	+3pp	+3pp	0.6%	1.0%	-	-
Operating profit	6,959	2,663	>2x	>2x	1,954	1,245	57	69
Operating Margin	20.6%	8.0%	+13pp	+14pp	17.0%	11.3%	+6pp	+7pp
Net finance expense	(945)	(936)	1	1	(291)	(324)	(9)	(6)
Joint ventures and associates	(12)	(4)	>2x	>2x	(11)	1	n/m	n/m
Profit before tax	6,002	1,723	>3x	>3x	1,652	922	79	91
Taxation	(1,000)	668	n/m	n/m	(274)	720	n/m	n/m
Tax rate	17%	-39%			17%	-78%
Profit after tax	5,002	2,391	>2x	>2x	1,378	1,642	(16)	(6)
Earnings per share	$3.22	$1.54	>2x	>2x	$0.89	$1.06	(16)	(6)

Table12: Reconciliation of Reported Profit before tax to EBITDA

9M 2023 9M 2022 % Change Q3 2023 Q3 2022 % Change

	$m	$m	Actual	CER	$m	$m	Actual	CER
Reported Profit before tax	6,002	1,723	>3x	>3x	1,652	922	79	91
Net finance expense	945	936	1	1	291	324	(9)	(6)
Joint ventures and associates	12	4	>2x	>2x	11	(1)	n/m	n/m
Depreciation, amortisation and impairment	4,060	4,000	2	3	1,282	1,334	(4)	(4)
EBITDA	11,019	6,663	65	77	3,236	2,579	25	32

EBITDA for the comparative 9M 2022 was negatively impacted by $3,175m unwind of inventory fair value uplift recognised on the acquisition of Alexion. EBITDA for the comparative Q3 2022 was negatively impacted by $857m unwind of inventory fair value uplift recognised on the acquisition of Alexion. This unwind had a $78m negative impact on 9M 2023 and a $23m negative impact on Q3 2023. It will continue to be minimal and will unwind fully over the next quarter.

Table13: Reconciliation of Reported to Core financial measures: 9M 2023

9M 2023 Reported Restructuring Intangible Asset Amortisation & Impairments Acquisitionof Alexion Other[56] Core Core % Change

	$m	$m	$m	$m	$m	$m	Actual	CER
Gross profit	27,827	133	24	82	(4)	28,062	4	8
Product Sales Gross Margin	81.6%					82.4%	+1pp	+2pp
Distribution expense	(394)	-	-	-	-	(394)	4	6
R&D expense	(7,862)	117	386	5	1	(7,353)	5	7
SG&A expense	(13,845)	163	2,863	7	1,107	(9,705)	5	8
Total operating expense	(22,101)	280	3,249	12	1,108	(17,452)	5	7
Other operating income & expense	1,233	(61)	-	-	-	1,172	>3x	>3x
Operating profit	6,959	352	3,273	94	1,104	11,782	10	16
Operating Margin	20.6%					34.9%	+2pp	+3pp
Net finance expense	(945)	-	-	-	220	(725)	(1)	(2)
Taxation	(1,000)	(81)	(617)	(22)	(329)	(2,049)	12	19
EPS	$3.22	$0.17	$1.72	$0.05	$0.64	$5.80	10	17

Table14: Reconciliation of Reported to Core financial measures: Q3 2023

Q3 2023 Reported Restructuring Intangible Asset Amortisation & Impairments Acquisitionof Alexion Other[57] Core Core % Change

	$m	$m	$m	$m	$m	$m	Actual	CER
Gross profit	9,397	15	8	25	(1)	9,444	6	7
Product Sales Gross Margin	81.0%					81.4%	+1pp	+1pp
Distribution expense	(129)	-	-	-	-	(129)	3	2
R&D expense	(2,584)	48	49	2	-	(2,485)	5	5
SG&A expense	(4,800)	61	957	3	424	(3,355)	6	7
Total operating expense	(7,513)	109	1,006	5	424	(5,969)	6	6
Other operating income & expense	70	-	-	-	-	70	(35)	(34)
Operating profit	1,954	124	1,014	30	423	3,545	4	9
Operating Margin	17.0%					30.8%	-	+1pp
Net finance expense	(291)	-	-	-	68	(223)	(12)	(7)
Taxation	(274)	(29)	(189)	(7)	(125)	(624)	8	13
EPS	$0.89	$0.06	$0.53	$0.01	$0.24	$1.73	4	9

Profit and Loss drivers

Gross profit

‒    The calculation of Reported and Core Product Sales Gross Margin excludes the impact of Alliance Revenue and Collaboration Revenue. The change in Product Sales Gross Margin (Reported and Core) in the nine months was impacted by:

‒    Positive effects from product mix. The increased contribution from Rare Disease and Oncology medicines had a positive impact on the Product Sales Gross Margin. Vaxzevria sales, which are dilutive to Product Sales Gross Margin, declined substantially

‒    Dilutive effects from product mix. The rising contribution of Product Sales with profit sharing arrangements (Lynparza, Enhertu and Tezspire) has a negative impact on Product Sales Gross Margin because AstraZeneca records product revenues in certain markets but pays away a share of the gross profit to its collaboration partners

‒    Dilutive effects from geographic mix. Emerging Markets, where Product Sales Gross Margin tends to be below the Company average, grew as a proportion of Total Revenue excluding COVID-19 medicines

‒    Variations in Product Sales Gross Margin performance between periods can continue to be expected due to product seasonality, foreign exchange fluctuations and other effects.

R&D expense

‒    The change in R&D expense (Reported and Core) in the period was impacted by:

‒    Recent positive data read-outs for several high priority medicines that have ungated late-stage trials

‒    Investment in platforms, new technology and capabilities to enhance R&D productivity

‒    Reported R&D expense was also impacted by intangible asset impairments

SG&A expense

‒    The change in SG&A expense (Reported and Core) in the period was driven primarily by market development activities for launches

‒    Reported SG&A expense was also impacted by amortisation of intangible assets related to the Alexion acquisition and other acquisitions and collaborations

‒    Reported SG&A expense was also impacted by a $510m charge to provisions relating to a legal settlement in Q2 2023 with Bristol-Myers Squibb and Ono Pharmaceutical, and a $425m charge to provisions in Q3 2023 for product liability litigations related to Nexium and Prilosec. The prior nine month period was impacted by a $775m legal settlement with Chugai Pharmaceutical Co. Ltd

Other operating income and expense

‒    Reported and Core Other operating income and expense in the period included a $712m gain resulting from an update to the contractual relationships for Beyfortus (nirsevimab), a $241m gain on the disposal of the US rights to PulmicortFlexhaler, and other disposal proceeds on the sale of tangible assets, and royalties on certain medicines

‒    In the third quarter Reported and Core Other operating income decreased by $36m and $37m respectively, principally due to the discontinuation of brazikumab development. Prior to this, AstraZeneca received quarterly development contributions for brazikumab development from AbbVie, which were recognised as Other operating income

Net finance expense

‒    Reported Net finance expense was impacted by the discount unwind on acquisition-related liabilities. Core Net finance expense reduced by 1% (2% at CER) with higher interest received on cash and short-term investments, broadly offset by higher rates on floating debt and bond issuances

Taxation

‒    The effective Reported Tax rate for the nine months to 30 September 2023 was 17% (9M 2022: (39%)) and the effective Core Tax rate was 19% (9M 2022: 18%). The Q3 2022 effective Reported Tax rate was lower as it included a one-time favourable adjustment of $883m relating to deferred taxes arising from an internal reorganisation to integrate the Alexion business

‒    The cash tax paid for the nine months to 30 September 2023 was $1,710m (9M 2022: $1,335m), representing 28% of Reported Profit before tax (9M 2022: 77%)

‒    On 20 June 2023, Finance (No.2) Act 2023 was substantively enacted in the UK, introducing a global minimum effective tax rate of 15%. The legislation implements a domestic top-up tax and a multinational top-up tax, effective for accounting periods starting on or after 31 December 2023. The Company is currently assessing the impact of these rules upon its financial statements.  The Company has applied the exception under the IAS 12 'Income Taxes' amendment for recognising and disclosing information about deferred tax assets and liabilities related to top-up income taxes

Table15: Cash Flow summary

	9M 2023	9M 2022	Change
	$m	$m	$m
Reported Operating profit	6,959	2,663	4,296
Depreciation, amortisation and impairment	4,060	4,000	60
Decrease in working capital and short-term provisions	150	3,458	(3,308)
Gains on disposal of intangible assets	(247)	(88)	(159)
Fair value movements on contingent consideration arising from business combinations	202	293	(91)
Non-cash and other movements	(623)	(973)	350
Interest paid	(826)	(608)	(218)
Taxation paid	(1,710)	(1,335)	(375)
Net cash inflow from operating activities	7,965	7,410	555
Net cash inflow before financing activities	4,978	4,699	279
Net cash outflow from financing activities	(6,276)	(6,465)	189

In 9M 2022, the Reported Operating profit of $2,663m included a negative impact of $3,175m relating to the unwind of the inventory fair value uplift recognised on the acquisition of Alexion. This was offset by a corresponding item (positive impact of $3,175m) in Decrease in working capital and short-term provisions. Overall, the unwind of the fair value uplift had no impact on Net cash inflow from operating activities. This unwind had $78m negative impact on 9M 2023 Reported Operating profit and offsetting positive impact on Working capital movements, and will continue to be minimal in the next quarter. As a result of the update to the contractual relationships between AstraZeneca, Sobi and Sanofi relating to the future sales of Beyfortus (nirsevimab) in the US, a gain of $712m has been recorded in non-cash and other movements, with no overall net impact on the Net cash inflow from operating activities.

Included within Net cash inflow before financing activities is a movement in the profit-participation liability of $190m, including a cash receipt from Sobi in Q1 2023 after achievement of a regulatory milestone. The associated cash flow is presented within investing activities.

The decrease in Net cash outflow from financing activities of $189m is primarily driven by the Issue of loans and borrowings of $3,816m, offset by the increase in Repayment of loans and borrowings of $3,394m.

Capital expenditure

Capital expenditure amounted to $836m in the nine months to 30 September 2023 (9M 2022: $719m).

Table16: Net debt summary

	At 30   Sep 2023	At 31  Dec 2022	At 30  Sep 2022
	$m	$m	$m
Cash and cash equivalents	4,871	6,166	4,458
Other investments	244	239	440
Cash and investments	5,115	6,405	4,898
Overdrafts and short-term borrowings	(515)	(350)	(743)
Lease liabilities	(979)	(953)	(878)
Current instalments of loans	(4,857)	(4,964)	(4,665)
Non-current instalments of loans	(22,225)	(22,965)	(23,013)
Interest-bearing loans and borrowings (Gross debt)	(28,576)	(29,232)	(29,299)
Net derivatives	90	(96)	(141)
Net debt	(23,371)	(22,923)	(24,542)

Net debt increased by $448m in the nine months to 30 September 2023 to $23,371m. Details of the committed undrawn bank facilities are disclosed within the going concern section of Note 1. Details of the Company's solicited credit ratings and further details on Net Debt are disclosed in Note 3.

Capital allocation

The Board's aim is to continue to strike a balance between the interests of the business, financial creditors and the Company's shareholders. The Company's capital allocation priorities include: investing in the business and pipeline; maintaining a strong, investment-grade credit rating; potential value-enhancing business development opportunities; and supporting the progressive dividend policy.

In approving the declaration of dividends, the Board considers both the liquidity of the company and the level of reserves legally available for distribution. Dividends are paid to shareholders from AstraZeneca PLC, a Group holding company with no direct operations. The ability of AstraZeneca PLC to make shareholder distributions is dependent on the creation of profits for distribution and the receipt of funds from subsidiary companies. The consolidated Group reserves set out in the Condensed consolidated statement of financial position do not reflect the profit available for distribution to the shareholders of AstraZeneca PLC.

Summarised financial information for guarantee of securities of subsidiaries

AstraZeneca Finance LLC ("AstraZeneca Finance") is the issuer of 0.700% Notes due 2024, 1.200% Notes due 2026, 4.875% Notes due 2028, 1.750% Notes due 2028, 4.900% Notes due 2030, 2.250% Notes due 2031 and 4.875% Notes due 2033 (the "AstraZeneca Finance Notes"). Each series of AstraZeneca Finance Notes has been fully and unconditionally guaranteed by AstraZeneca PLC. AstraZeneca Finance is 100% owned by AstraZeneca PLC and each of the guarantees by AstraZeneca PLC is full and unconditional and joint and several.

The AstraZeneca Finance Notes are senior unsecured obligations of AstraZeneca Finance and rank equally with all of AstraZeneca Finance's existing and future senior unsecured and unsubordinated indebtedness. The guarantee by AstraZeneca PLC of the AstraZeneca Finance Notes is the senior unsecured obligation of AstraZeneca PLC and ranks equally with all of AstraZeneca PLC's existing and future senior unsecured and unsubordinated indebtedness. Each guarantee by AstraZeneca PLC is effectively subordinated to any secured indebtedness of AstraZeneca PLC to the extent of the value of the assets securing such indebtedness. The AstraZeneca Finance Notes are structurally subordinated to indebtedness and other liabilities of the subsidiaries of AstraZeneca PLC, none of which guarantee the AstraZeneca Finance Notes.

AstraZeneca PLC manages substantially all of its operations through divisions, branches and/or investments in subsidiaries and affiliates. Accordingly, the ability of AstraZeneca PLC to service its debt and guarantee obligations is also dependent upon the earnings of its subsidiaries, affiliates, branches and divisions, whether by dividends, distributions, loans or otherwise.

Please refer to the consolidated financial statements of AstraZeneca PLC in our Annual Report on Form 20-F and reports on Form 6-K with our quarterly financial results as filed or furnished with the SEC[58] for further financial information regarding AstraZeneca PLC and its consolidated subsidiaries. For further details, terms and conditions of the AstraZeneca Finance Notes please refer to AstraZeneca PLC's reports on Form 6-K furnished to the SEC on 3 March 2023 and 28 May 2021.

Pursuant to Rule 13-01 and Rule 3-10 of Regulation S-X under the Securities Act of 1933, as amended (the "Securities Act"), we present below the summary financial information for AstraZeneca PLC, as Guarantor, excluding its consolidated subsidiaries, and AstraZeneca Finance, as the issuer, excluding its consolidated subsidiaries. The following summary financial information of AstraZeneca PLC and AstraZeneca Finance is presented on a combined basis and transactions between the combining entities have been eliminated. Financial information for non-guarantor entities has been excluded. Intercompany balances and transactions between the obligor group and the non-obligor subsidiaries are presented on separate lines.

Table17: Obligor group summarised Statement of comprehensive income

	9M 2023	9M 2022
	$m	$m
Total Revenue	-	-
Gross profit	-	-
Operating loss	(2)	(3)
Loss for the period	(695)	(404)
Transactions with subsidiaries that are not issuers or guarantors	9,758	502

Table18: Obligor group summarised Statement of financial position

	At 30 Sep 2023	At 30 Sep 2022
	$m	$m
Current assets	6	5
Non-current assets	-	-
Current liabilities	(4,760)	(3,067)
Non-current liabilities	(22,077)	(22,556)
Amounts due from subsidiaries that are not issuers or guarantors	12,921	7,349
Amounts due to subsidiaries that are not issuers or guarantors	(295)	(301)

Foreign exchange

The Company's transactional currency exposures on working-capital balances, which typically extend for up to three months, are hedged where practicable using forward foreign exchange contracts against the individual companies' reporting currency. Foreign exchange gains and losses on forward contracts for transactional hedging are taken to profit or loss. In addition, the Company's external dividend payments, paid principally in pounds sterling and Swedish krona, are fully hedged from announcement to payment date.

Table19: Currency sensitivities

The Company provides the following currency-sensitivity information:

Average rates vs. USD Annual impact ($m) of 5% strengthening (FY2023 average rate vs. FY 2022 average)[59]

Currency	Primary Relevance	FY    2022[60]	YTD   2023[61]	Change  (%)	Sep 2023[62]	Change[63]  (%)	Total Revenue	Core Operating Profit
EUR	Total Revenue	0.95	0.92	3	0.94	1	323	159
CNY	Total Revenue	6.74	7.04	(4)	7.30	(8)	309	174
JPY	Total Revenue	131.59	138.18	(5)	147.71	(11)	181	122
Other[64]							385	202
GBP	Operating expense	0.81	0.80	1	0.81	0	46	(92)
SEK	Operating expense	10.12	10.59	(4)	11.08	(9)	7	(55)

Sustainability

Since the last quarterly report, AstraZeneca:

Access to healthcare

‒    Hosted the first dedicated side-event on Chronic Kidney Disease (CKD) "How improving kidney health can transform health systems for all" during the 78th United Nations General Assembly (UNGA) meeting in New York, with public, private and patient voices represented. During UNGA, the Company also engaged with the cancer community on access, services within universal health coverage (UHC) and the need for investment in cancer and non-communicable diseases (NCDs)

‒    Continued to make a high-level contribution to the work of the Partnership for Health System Sustainability and Resilience (PHSSR), which provides a valuable platform for dialogue with policymakers, the Company and other stakeholders. In Canada, a workshop with participation from the Minister of Health of Quebec fed into the discussions on transformation of Quebec's health system. In Japan, AstraZeneca's Chair Michel Demaré participated in a PHSSR roundtable co-hosted by the British Embassy, which focused on health equity and digital healthcare. PHSSR also engaged at leading global and regional healthcare events, including the European Health Forum Gastein, the Global Congress on Population, Health and Development, ICHOM 2023 and the World Health Summit in Berlin

‒    Ruud Dobber, EVP BioPharmaceuticals Business Unit, delivered the opening keynote address at the POLITICO EU Healthcare Summit in Brussels where he called for bold action and collaboration across the healthcare ecosystem to support early diagnosis and treatment. He highlighted the need for regulatory frameworks that accelerate access to medical innovation, as well as the urgency to combat the effects of the climate crisis on health

‒    Marked World Heart Day and the ninth anniversary of Healthy Heart Africa (HHA)'s launch, by convening African health stakeholders to take stock of the programme's achievements and share insights on the critical role of public-private partnerships in supporting primary healthcare. Speakers included representatives of Ministries of Health from nine countries and HHA implementing partners, with more than 70 attendees. HHA has trained more than 11,000 healthcare workers and conducted over 43 million blood pressure screenings, identifying 8.6 million with elevated blood pressure since launch, moving closer to the programme ambition of 10 million by 2025, and achieving one million screenings per month since February 2023 (data as at end of September 2023)

‒    Young Health Programme is now active in 40 countries, with new programmes launched in Costa Rica and Taiwan. Through the Young Health Programme Impact Fellowship, the Company supported a delegation of 17 young health leaders from 13 countries to attend One Young World 2023 in Belfast. Three of these changemakers joined AstraZeneca leadership in on-stage appearances, discussing their impact on NCD prevention for young people in their communities. AstraZeneca and Plan International UK were awarded 'Highly Commended' at the Corporate Engagement Awards for Best Educational Programme

Environmental protection

‒    Entered into an agreement in Sweden with Statkraft, Europe's largest renewable energy producer, on wind power deliveries that will increase the supply of renewable electricity in Sweden. The agreement is based on the commissioning of new wind farms. Under the agreement, AstraZeneca commits to purchasing 200 gigawatt-hours per year for 10 years, equivalent to two terawatt-hours. This corresponds to approximately 80 percent of total electricity needs at both the Company's Gothenburg site and at Södertälje, the largest manufacturing centre and one of the world's largest drug manufacturing centres

‒    Agreed a 15-year partnership with Future Biogas to establish the first unsubsidised industrial-scale supply of biomethane in the UK. This biomethane will support the transition away from fossil fuels at Company sites in Macclesfield, Cambridge, Luton and Speke. A new biomethane plant will add renewable energy capacity to existing UK infrastructure and supply more than 100 gigawatt hours of biomethane, equivalent to the heat needs of more than 8,000 homes. Using crops grown locally as part of diverse crop rotations, the plant will also contribute to the development of a circular economy, supporting UK farms with sustainable land management practices

‒    In China, CEO Pascal Soriot and EVP and China President Leon Wang witnessed the launch of the Sustainable Markets Initiative (SMI) China Council Health Working Group. Inspired by the SMI Health Systems Task Force, members of this new partnership will collaborate to accelerate the delivery of a net zero health system, for domestic and global impact. AstraZeneca China will co-chair this Working Group, which comprises China-based organisations and Chinese affiliates of global pharmaceutical companies

‒    In the U.S., advocated for climate action and sustainable healthcare reform during Climate Week NYC by convening high-level representatives from the US government, WHO, civil society and philanthropy at a plenary event with Climate Group on "Addressing the climate-health-equity nexus: The path to a sustainable future". The Company also discussed accelerating health sector decarbonisation at the Forbes Sustainability Leaders Summit in a session on "How the healthcare industry is responding to climate change" alongside US National Academy of Medicine President Dr. Victor J. Dzau. Furthermore, the Company participated in an event on water stewardship

‒    Contributed to a joint report on Advancing water stewardship through supplier collaboration in partnership with the World Wide Fund for Nature

‒    Ranked in first position for climate action in a new STAT Report "Climate rankings: How top drug companies measure up in combating climate change", which noted that "Companies like AstraZeneca are the exception in an industry that, as a whole, could be doing much more to measure and report its climate impacts, according to organizations that pool data on this topic"

‒    Received the EcoVadis Gold Medal for 2023, improving on the 2022 Silver rating. AstraZeneca was scored in four areas: Environment, Ethics, Labor and Human Rights, and Sustainable Procurement, and received an Advanced rating in the Environment and Human Rights categories

‒    Recognised with two awards from My Green Lab and the International Institute for Sustainable Laboratories' in the 2023 Freezer Challenge: the Top Organization Award and the Small Size Lab Award for our site in Gothenburg, Sweden

Ethics and transparency

‒    Received three supplier diversity awards from the Diversity for Science Alliance including 2023 Company of the year

‒    Launched Global Ethics training ahead of Global Ethics Day in October, an annual reminder to employees of the Company's commitment to high ethical standards in all areas of AstraZeneca's business, marking the day with local and virtual events and an #EmpoweringEthics employee social campaign

‒    Held an internal Power of Diversity panel discussion with members of the Company's Global Inclusion & Diversity (I&D) Council on the topic of putting an I&D lens over our AZ Values. This focused on building a sense of belonging through allyship, mutual support and the sharing of diverse perspectives. Supporting materials were made available through employee communication channels

Research and development

This section covers R&D events and milestones that have occurred since the prior results announcement on 28 July 2023, up to and including events on 8 November 2023.

A comprehensive view of AstraZeneca's pipeline of medicines in human trials can be found in the latest Clinical Trials Appendix, available on www.astrazeneca.com/investor-relations. The Clinical Trials Appendix includes tables with details of the ongoing clinical trials for AstraZeneca medicines and new molecular entities in the pipeline.

Oncology

AstraZeneca presented new data across its diverse portfolio of cancer medicines at two major medical congresses during the quarter: the 2023 World Conference on Lung Cancer (WCLC) in September and the 2023 European Society of Medical Oncology (ESMO) in October. At WCLC, AstraZeneca presented more than 40 abstracts featuring eight approved and potential new medicines, including nine oral presentations and a late-breaking plenary Presidential Symposium presentation of results from the FLAURA2 Phase III trial of Tagrisso plus chemotherapy in 1st-line EGFRm NSCLC. At ESMO, AstraZeneca presented nearly 100 abstracts featuring 19 approved and potential new medicines including 26 oral presentations and two late-breaking Presidential Symposia of the TROPION-Lung01 and TROPION-Breast 01 Phase III trials of monotherapy Dato-DXd versus conventional chemotherapy in lung and breast cancers.

Tagrisso

Event		Commentary
Breakthrough Designation	US	Tagrisso in combination with chemotherapy for the treatment of adult patients with locally advanced or metastatic EGFRm lung cancer. (FLAURA2, August 2023)
Presentation: WCLC	FLAURA2	Interim analysis of the Phase III FLAURA2 trial, presented at WCLC, demonstrated Tagrisso plus chemotherapy extended median PFS[65] by nearly nine months and reduced the risk of disease progression by 38% in EGFRm advanced lung cancer vs. Tagrisso monotherapy. (September 2023)
Priority Review	US	Tagrisso in combination with chemotherapy for the treatment of adult patients with locally advanced or metastatic EGFRm lung cancer. (FLAURA2, October 2023)
Presentation: ESMO	FLAURA2   CNS analysis	Prespecified exploratory analysis of the Phase III FLAURA2 trial, presented at ESMO, showed  Tagrisso plus chemotherapy demonstrated a 42% improvement in CNS[66] PFS vs. Tagrisso monotherapy in patients with EGFRm advanced lung cancer and brain metastases at baseline, representing 40% of patients in the trial, as assessed by blinded independent central review. (October 2023)

Imfinzi and Imjudo

Event		Commentary
Positive Opinion	EU	The Committee for Medicinal Products for Human Use (CHMP) issued a positive opinion for Type II Extension of Indication Variation for Imfinzi as monotherapy for the first line treatment of adults with advanced or unresectable HCC. (HIIMALAYA, July 2023)
Presentation: ESMO	MATTERHORN	Interim analysis of the Phase III MATTERHORN III trial, presented at ESMO, showed that Imfinzi in combination with standard-of-care FLOT[67] neoadjuvant chemotherapy demonstrated a statistically significant and clinically meaningful 12% improvement in the key secondary endpoint of pCR[68] vs. neoadjuvant chemotherapy alone for patients with resectable, early-stage and locally gastric and GEJ[69] cancers. (October 2023)
Phase III data readout	EMERALD-1	Positive high-level results from the EMERALD-1 Phase III trial showed Imfinzi in combination with TACE[70] and bevacizumab demonstrated a statistically significant and clinically meaningful improvement in the primary endpoint of PFS versus TACE alone in patients with HCC eligible for embolisation. The trial continues to follow the secondary endpoint of OS[71]. (November 2023)

Lynparza

Event		Commentary
Approval	Japan	Lynparza in combination with abiraterone and prednisolone for the treatment of adult patients with BRCAm mCRPC. (August 2023)
Label restriction	US	Restriction of the Lynparza indication for the maintenance treatment of adult patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in a complete or partial response to platinum-based chemotherapy to the BRCAm (germline or somatic) patient population only. (September 2023)
Presentation: ESMO	DUO-E (Lynparza and Imfinzi)	Primary analysis of the Phase III DUO-E Phase III trial, presented at ESMO, showed that treatment with Imfinzi plus chemotherapy followed by either Imfinzi monotherapy or Imfinzi plus Lynparza demonstrated a reduction in the risk of disease progression or death, by 45% and 29%, respectively, vs. chemotherapy alone in patients with advanced or recurrent endometrial cancer. (October 2023)

Enhertu

Event		Commentary
Approval	Japan	For the treatment of adult patients with unresectable advanced or recurrent NSCLC with HER2 (ERBB2) mutations that has progressed after chemotherapy. (DESTINY-Lung02, August 2023)
Breakthrough Designation	US	For the treatment of adult patients with unresectable or metastatic HER2-positive (IHC[72] 3+) solid tumours that have progressed following prior treatment and who have no alternative treatment options. (DESTINY-PanTumor02, August 2023)
		For the treatment of patients with HER2-positive (IHC 3+) metastatic colorectal cancer who have received two or more prior regimens. (DESTINY-CRC01, DESTINY-CRC02, August 2023)
Presentation: WCLC	DESTINY-Lung02	Results from the primary analysis of the DESTINY-Lung02 Phase II trial, presented at WCLC, showed Enhertu provided a median PFS of 9.9 months at a dose of 5.4mg/kg, and 15.4 months at a dose of 6.4mg/kg, with a favourable safety profile that confirm 5.4mg/kg is the optimal dose in this tumour type. (September 2023)

Approval EU As monotherapy for the treatment of adult patients with advanced NSCLC whose tumours have an activating HER2 (ERBB2[73]) mutation and who require systemic therapy following platinum-based chemotherapy with or without immunotherapy. (DESTINY-Lung02, October 2023)

Presentation: ESMO DESTINY-PanTumor02 Primary analysis of the Phase II DESTINY-PanTumor02 trial, presented at ESMO, showed that treatment with Enhertu resulted in confirmed ORR[74] of 37.1%, a median PFS of 6.9 months and median OS of 13.4 months in previously treated patients across multiple HER2-expressing advanced solid tumours. (October 2023)

Calquence

Event		Commentary
Approval	China	For the treatment of adult patients with CLL or SLL[75] who have received at least one prior therapy. (ASCEND, September 2023)

datopotamab deruxtecan (Dato-Dxd)

Event		Commentary
Presentation: WCLC	TROPION-Lung04	Results from a planned interim analysis of the Phase Ib TROPION-Lung04 trial, presented at WCLC, showed that Dato-DXd in combination with Imfinzi, with or without carboplatin demonstrated objective response rates of 77% and 50% and disease control rates of 92% and 93% respectively, with no new safety signals in patients with previously untreated advanced or metastatic NSCLC without actionable genomic alterations. (September 2023)
Presentation: ESMO	BEGONIA	Updated results from the Phase Ib/II BEGONIA trial, presented at ESMO, showed Dato-DXd plus Imfinzi demonstrated a confirmed objective response rate of 79% and a median PFS of 13.8 months in patients with previously untreated advanced or metastatic triple-negative breast cancer. (October 2023)
Presentation: ESMO	TROPION-Lung01	Primary analysis for the Phase III TROPION-Lung01 trial, presented at ESMO, showed that Dato-DXd reduced the risk of disease progression or death by 25% in the overall population and by 37% in non-squamous tumours vs. docetaxel in patients with previously treated NSCLC. (October 2023)
Presentation: ESMO	TROPION-Breast01	Primary analysis for the Phase III TROPION-Breast01 trial, presented at ESMO, showed that Dato-DXd reduced the risk of disease progression or death by 37%, providing a two-month median PFS benefit, and was well tolerated in the post-endocrine therapy setting vs. investigator's choice of chemotherapy in patients with inoperable or metastatic HR-positive, HER2-low or HER2-negative breast cancer previously treated with endocrine-based therapy and at least one systemic therapy. (October 2023)

Other oncology pipeline

Event		Commentary
Trial update	MONETTE	Phase II trial of ceralasertib + Imfinzi in unresectable or advanced melanoma and resistance to PD-(L)1 inhibition stopped enrolment following a pre-specified futility (efficacy) assessment. There were no concerning safety signals identified at this interim analysis or during the two prior data review meetings.
Presentation: ASCO Virtual Plenary	NCT04805307	Interim analysis for the Phase I trial (NCT04805307) of CMG901 (Claudin 18.2 ADC[76]) demonstrated promising clinical efficacy in patients with heavily pre-treated CLDN18.2-positive gastric/GEJ cancer, with a manageable safety profile. (November 2023)