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 February 2016

Commission File Number:  001-11960

AstraZeneca PLC

2 Kingdom Street, London W2 6BD

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-_____________
 
 
 
4 February 2016
Full-Year and Q4 2015 Results

Financial Summary
 
FY 2015
 
Q4 2015
 
$m
% change
 
$m
% change
   
CER1
Actual
   
CER1
Actual
Total Revenue2
24,708
1
(7)
 
6,399
2
(5)
               
Core3 Op. Profit
6,902
6
(1)
 
1,556
28
31
Core EPS
$4.26
7
-
 
$0.94
22
26
               
Reported Op. Profit
4,114
100
93
 
1,088
n/m4
n/m4
Reported EPS
$2.23
137
128
 
$0.63
n/m4
n/m4

·
 Core EPS in the year up by 7% and by 22% in Q4 2015
·
 Total Revenue growth of 1% in the year, with the gross margin on Product Sales up by 1% point
·
Top-line and gross-margin growth underpinned continued investment in R&D. Core R&D costs up by 21% in the year, reflecting the investment in the pipeline
·
 Core SG&A costs down by 2% in the year (Q4 2015: down by 11%), in line with commitments
·
 Reported EPS in the year up by 137%, at $0.63 in Q4 2015 (Q4 2014: loss per share of $0.25)
·
A second interim dividend of $1.90 per share, bringing the dividend for the full year to $2.80; the Board reaffirms its commitment to the progressive dividend policy
·
FY 2016 CER guidance - a low to mid single-digit percentage decline in Total Revenue and a low to mid single-digit percentage decline in Core EPS; includes dilutive effects from recent transactions

FY 2015 Commercial Highlights
The Growth Platforms grew by 11% in the year, representing 57% of Total Revenue. ‘New Oncology’ is included for the first time, reflecting its long-term importance for the Company’s future growth:
1.  
Respiratory: +7%, before completion of the acquisition of Takeda’s Respiratory business
 2.
Brilinta/Brilique: +44%, underpinned by a recently-extended US label and positive CHMP opinion
3.  
Diabetes: +26%, including +76% in Emerging Markets. Global Farxiga/Forxiga growth of 137%
4.  
Emerging Markets: +12%, including China and Latin America each growing by 15%
5.  
Japan: +4%, including +8% in Q4 2015
6.  
New Oncology: Contributed $119m, comprising Lynparza, Iressa (US) and Tagrisso

Achieving Scientific Leadership: Progress since the last results announcement
Regulatory Approvals
 
 Zurampic (lesinurad) - gout (US)
 Tagrisso (osimertinib, formerly AZD9291) - lung cancer (US, EU)
 
Regulatory Submission Acceptances
 
 brodalumab - psoriasis (US, EU)
 ZS-9 - hyperkalaemia (EU)
 
Other Key Developments
 
 CHMP positive opinions (EU):
 Zurampic, Brilique - prior MI (PEGASUS trial), Tagrisso
 

Pascal Soriot, Chief Executive Officer, commenting on the results said:
We delivered a strong pipeline and financial performance in 2015 as we begin the next phase in our strategic journey. The Growth Platforms delivered an 11% rise in Product Sales that, along with the 7% increase in Core EPS, demonstrated the underlying strength of our business. Our culture of innovation continued to drive R&D productivity, with six regulatory approvals in the year. This momentum will continue in 2016 as we anticipate six regulatory submissions and around ten major data readouts. We strengthened the strategic importance of Oncology, bringing to patients next-generation therapies such as Tagrisso in lung cancer and Lynparza in ovarian cancer, as well as a promising immuno-oncology pipeline. Alongside this organic progress, we also continued to invest in our main therapy areas through key agreements with Acerta Pharma, ZS Pharma, and Takeda.

As we face the transitional period of patent expiry for Crestor in the US, we’re confident that our strong execution on strategy, combined with the benefits of focused investments and new launches, keeps us on track to return to sustainable growth in line with our targets.

FY 2016 Guidance
All guidance is shown at CER1.

 
 Total Revenue
 
A low to mid single-digit percentage decline
 
 Core Earnings Per Share
 
A low to mid single-digit percentage decline

The above guidance incorporates the dilutive effects arising from the Acerta Pharma and ZS Pharma transactions announced in 2015.

The guidance also assumes the loss of exclusivity for Crestor in the US from May 2016. Externalisation Revenue is expected to be ahead of that in FY 2015, including an increasing element of recurring income arising from prior agreements. This is in line with the Company’s long-term business model.

Core R&D costs are expected to be at a similar level to FY 2015. The Company is also committed to materially reducing Core SG&A costs in FY 2016. These measures are based on constant exchange rates.

Currency Impact
The weakness of key trading currencies against the US dollar has continued. Based on average exchange rates in January 2016 and the Company’s published currency sensitivities, an adverse impact of around 3% from currency movements on Total Revenue and Core EPS in FY 2016 would be anticipated. Further details on currency sensitivities are contained within the Operating and Financial Review.

Pipeline: Forthcoming Major Newsflow
Innovation is critical to addressing unmet medical need and is at the heart of the Company’s growth strategy. The focus on research and development at AstraZeneca is anticipated to yield a productive year for the pipeline, particularly in Oncology:
 
 
H1 2016
 
  Zurampic: Regulatory decision (EU)
  PT003 - COPD: Regulatory decision (US)
  benralizumab - severe asthma: Data readout
 
  Brilinta/Brilique - stroke: Data readout, regulatory submission
  saxagliptin/dapagliflozin - type-2 diabetes: Regulatory submission (US)
  ZS-9: Regulatory decision (US)
 
  Tagrisso: Regulatory decision (JP)
  tremelimumab - mesothelioma: Data readout
  Lynparza - gastric cancer: Data readout
 
H2 2016
 
  benralizumab - severe asthma: Regulatory submission (US, EU)
 
  Brilinta/Brilique - peripheral arterial disease: Data readout
  saxagliptin/dapagliflozin: Regulatory decision (EU)
  roxadustat - anaemia: Rolling regulatory submission (CN)
 
  Lynparza - ovarian cancer: Data readout
  Lynparza - breast cancer: Data readout
  tremelimumab - mesothelioma: Regulatory submission
  cediranib - ovarian cancer: Regulatory decision (EU)
  durvalumab - head & neck cancer: Data readout
  acalabrutinib - blood cancer: Data readout, regulatory submission (US)
  selumetinib - lung cancer: Data readout
 
  CAZ AVI - serious infections: Regulatory decision (EU)

 
Notes
 
1.  
All growth rates and guidance are shown at constant exchange rates (CER) unless specified otherwise.
2.  
Total Revenue defined as Product Sales and Externalisation Revenue.
3.  
See the Operating and Financial Review for a definition of Core financial measures and a reconciliation of Core to Reported financial measures.
4.  
Q4 2014 results reflected a Reported Operating Loss of $349m and a Reported Loss Per Share of $0.25; a percentage comparison to the Reported results in Q4 2015 is not meaningful.

The performance shown in this announcement covers the twelve and three month periods to 31 December 2015 (the year and the quarter respectively) compared to the twelve and three month periods to 31 December 2014 (the prior year and the prior quarter respectively).

Results Presentation
A presentation and accompanying live webcast for investors and analysts, hosted by management, will begin at midday GMT today. Details can be accessed via www.astrazeneca.com/investors.
 
Reporting Calendar
The Company intends to publish its first-quarter financial results on 29 April 2016.
 
About AstraZeneca
AstraZeneca is a global, innovation-driven biopharmaceutical business that focuses on the discovery, development and commercialisation of prescription medicines, primarily for the treatment of diseases in three main therapy areas - Respiratory, Inflammation and Autoimmunity (RIA), Cardiovascular and Metabolic Disease (CVMD) and Oncology – as well as in Infection and Neuroscience. AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. For more information, please visit: www.astrazeneca.com.
 

 
Contacts at AstraZeneca
 
 
Media Enquiries
 
     
     Esra Erkal-Paler
 
UK/Global
+44 20 7604 8030
     Neil Burrows
UK/Global
 
+44 20 7604 8032
     Vanessa Rhodes
 
UK/Global
+44 20 7604 8037
     Karen Birmingham
UK/Global
 
+44 20 7604 8120
     Jacob Lund
 
Sweden
+46 8 553 260 20
     Michele Meixell
US
+1 302 885 2677

 
    Investor Enquiries
 
   
        UK
 
  
T     Thomas Kudsk Larsen
 
+44 7818 524185          
E      Eugenia Litz
RIA
+44 7884 735627
Ni    Nick Stone
CVMD
+44 7717 618834
C     Craig Marks
Finance
+44 7881 615764
C     Christer Gruvris
Consensus Forecasts
+44 7827 836825
    US
   
Li     Lindsey Trickett
Oncology, ING
+1 240 543 7970
M    Mitchell Chan
Oncology
+1 240 477 3771
T     Toll-Free
 
+1 866 381 7277
 
 
Key: RIA - Respiratory, Inflammation & Autoimmunity, CVMD - Cardiovascular & Metabolic Disease,
ING - Infection, Neuroscience & Gastrointestinal

Operating and Financial Review
_____________________________________________________________________________

All narrative on growth and results in this section relates to Core performance, based on constant exchange rates (CER) unless stated otherwise. Financial figures are in $ millions ($m). The performance shown in this announcement covers the twelve and three-month periods to 31 December 2015 (the year and the fourth quarter respectively) compared to the twelve and three months to 31 December 2014. Core measures, which are presented in addition to Reported financial information, are non-GAAP measures provided to enhance understanding of the Company’s underlying financial performance. Core financial measures are adjusted to exclude certain significant items, such as:

− amortisation and impairment of intangibles, including impairment reversals but excluding any charges relating to IT assets
− charges and provisions related to our global restructuring programmes (this will include such charges that relate to the impact of our global restructuring programmes on our capitalised IT assets)
− other specified items, principally comprising legal settlements and acquisition-related costs, which include fair value adjustments and the imputed finance charge relating to contingent consideration on business combinations

More detail on the nature of these measures is given on page 72 of the 2014 Annual Report and Form 20-F Information.

Total Revenue
Total Revenue increased by 1% to $24,708m in the year, comprising Product Sales of $23,641m (down by 1%) and Externalisation Revenue of $1,067m (up by 140%). Based on actual exchange rates, Total Revenue declined by 7% in the year, reflecting the particular weakness of key trading currencies against the US dollar.

Product Sales
The decline in Product Sales was primarily driven by the US market entry of Nexium generic products from February 2015, as well as full-year adverse impacts from Synagis guideline changes in 2014 and the change in accounting for the US Branded Pharmaceutical Fee, following issuance of final regulations in 2014.

Within Product Sales, the Growth Platforms grew by 11% in the year, representing 57% of Total Revenue. ‘New Oncology’ is included for the first time, given its long-term importance for the Company’s future growth:

 
FY 2015
Q4 2015
Growth Platform
Product Sales ($m)
% CER change
Product Sales ($m)
% CER change
Respiratory
4,987
7
1,289
4
Brilinta/Brilique
619
44
174
43
Diabetes
2,224
26
585
24
Emerging Markets
5,822
12
1,428
10
Japan
2,020
4
541
8
New Oncology
119
n/m
57
n/m
         
TOTAL1
14,003
11
3,588
11
1 Total Product Sales for Growth Platforms adjusted to remove duplication on a product and regional basis.


Externalisation Revenue
Externalisation Revenue of $1,067m for the year (Q4 2015: $192m) primarily reflected income generated from a strategic collaboration in haematology with Celgene Corporation (upfront receipt of $450m) and a co-development and co-commercialisation arrangement with Daiichi Sankyo Co., Ltd. (Daiichi Sankyo) for Movantik in the US (upfront receipt of $200m). Other Externalisation Revenue reflected a number of collaboration agreements, including the acceleration of the development of brodalumab with Valeant Pharmaceuticals International, Inc. (upfront receipt of $100m) and the co-commercialisation of Nexium in Japan (milestone income of $123m) with Daiichi Sankyo.

Product Sales
________________________________________________________________________________

The performance of a selection of key medicines is shown below. A geographical split of the performance is shown in Notes 8 and 9.

 
FY 2015
 
Q4 2015
   
% Change
   
% Change
 
$m
CER
Actual
 
$m
CER
Actual
               
Respiratory, Inflammation & Autoimmunity
             
Symbicort
3,394
(3)
(11)
 
859
(6)
(12)
Pulmicort
1,014
15
7
 
274
9
2
Tudorza/Eklira
190
n/m
n/m
 
47
n/m
n/m
Daliresp
104
n/m
n/m
 
32
n/m
n/m
Duaklir
27
n/m
n/m
 
12
n/m
n/m
               
Others
258
(5)
(15)
 
65
(4)
(14)
TOTAL
4,987
7
(2)
 
1,289
4
(4)
               
Cardiovascular & Metabolic Disease
             
Brilinta/Brilique
619
44
30
 
174
43
31
Onglyza
786
2
(4)
 
192
3
(4)
Bydureon
580
35
32
 
155
28
26
Farxiga/Forxiga
492
137
119
 
152
76
63
Byetta
316
2
(3)
 
72
10
4
               
Legacy:
             
Crestor
5,017
(3)
(9)
 
1,322
-
(5)
Seloken/Toprol-XL
710
4
(6)
 
160
5
(8)
Atacand
358
(15)
(29)
 
86
(15)
(26)
               
Others
611
(10)
(18)
 
147
(9)
(17)
TOTAL
9,489
4
(3)
 
2,460
6
(1)
               
Oncology
             
Iressa
543
(2)
(13)
 
129
(5)
(14)
Lynparza
94
n/m
n/m
 
36
n/m
n/m
Tagrisso
19
n/m
n/m
 
18
n/m
n/m
               
Legacy:
             
Zoladex
816
7
(12)
 
198
4
(13)
Faslodex
704
9
(2)
 
185
12
2
Casodex
267
(6)
(17)
 
63
(7)
(15)
Arimidex
250
(5)
(16)
 
60
(1)
(12)
               
Others
132
6
(7)
 
27
(26)
(33)
TOTAL
2,825
7
(7)
 
716
9
(3)
Infection, Neuroscience & Gastrointestinal
             
Nexium
2,496
(26)
(32)
 
564
(26)
(32)
Seroquel XR
1,025
(12)
(16)
 
241
(18)
(22)
Synagis
662
(26)
(26)
 
275
(32)
(32)
Losec/Prilosec
340
(10)
(19)
 
77
(23)
(30)
FluMist/Fluenz
288
-
(2)
 
191
46
43
Movantik/Moventig
29
n/m
n/m
 
15
n/m
n/m
               
Others
1,500
-
(12)
 
379
25
11
TOTAL
6,340
(16)
(23)
 
1,742
(13)
(18)
               
TOTAL PRODUCT SALES
23,641
(1)
(9)
 
6,207
-
(7)

 
FY 2015 Product Sales Summary


During 2014, final regulations relating to the US Branded Pharmaceutical Fee were issued, affecting how the fee is recognised. AstraZeneca accrues for the obligation as each sale occurs, and, as under the final guidelines the fee is based on actual Product Sales in the current year, the fee is recognised as a deduction from Product Sales rather than a charge to SG&A, impacting individual medicine sales in the US by an average of 2%.

Respiratory, Inflammation & Autoimmunity

Symbicort
FY 2015 sales declined by 3% to $3,394m.

In the US, sales of $1,520m represented growth of 1%, with lower net prices reflecting additional access and co-pay assistance. Strong volume growth was driven by higher market share within a growing market.

In Europe, sales declined by 14% to $1,076m with a modest volume decline and a significant price decline reflecting increased competition from recently-launched analogue medicines. In contrast, Emerging Markets sales grew by 22% to $394m with China sales growing by 38% to $124m, primarily reflecting volume growth.

Pulmicort
Pulmicort sales in the year were $1,014m, an increase of 15%. Growth was driven primarily by the performance of Pulmicort Respules in Emerging Markets, where Pulmicort sales grew by 35% to $609m. China sales increased by 43% to $485m, reflecting sustained investment in supporting asthma and chronic obstructive pulmonary disease (COPD) patients, both in hospitals and at home.

Tudorza/Eklira
Sales in the year were $190m; over half of the medicine’s sales were in the US, where the brand name is Tudorza. In March 2015, the Company completed the acquisition of the Actavis plc (Actavis) rights to the product.

Daliresp
Rights were acquired in March 2015 from Actavis for Daliresp in the US and Canada. Sales were $104m in the year.

Duaklir
Duaklir was successfully launched in the year, principally in Europe. Sales of $27m reflected good progress of this leading LAMA/LABA medicine, with an encouraging formulary uptake in the UK and a strong market-share performance in Germany.

The encouraging performances of Tudorza/Eklira, Daliresp and Duaklir under the Company’s ownership were in line with expectations.

Cardiovascular & Metabolic Disease

Brilinta/Brilique
Sales in the year were $619m, an increase of 44%. AstraZeneca announced in H2 2015 that the US Food and Drug Administration (FDA) had approved Brilinta tablets at a new 60mg dose to be used in patients with a history of heart attack beyond the first year of treatment.

FY 2015 sales in the US increased by 64% to $240m. The expanded indication launched in the second half of the year, underpinned ongoing new-to-brand prescription share growth, with share standing at 12% at the end of the year; this represented a four percentage point increase in the twelve-month period.

In Europe, Brilique continued to perform strongly, with an increase in full-year sales of 18% to $230m, reflecting indication leadership across a number of markets. Emerging Markets sales grew by 91% to $112m, with China representing the largest single market for the medicine, where sales were up by 160% to $38m.

Onglyza
Sales were up 2% in the year to $786m, with sales in Q4 2015 increasing by 3%.

US sales in the year declined by 13% to $420m as a consequence of a greater emphasis on the promotion of Farxiga. Competitive pressures in the DPP-4 class drove lower volumes and a decline in the net price.

Sales in Europe grew by 8% to $141m, while Emerging Markets sales increased by 41% to $159m.

Farxiga/Forxiga
Sales of Farxiga/Forxiga were up 137% in the year to $492m.

In the US, sales of $261m represented growth of 114%. Promotional activity underpinned increasing total-prescription market-share growth in the year; this was accompanied by overall growth in the market.

Sales in Europe reached $126m in the year, up by 126%. Launches of Forxiga in the year in a number of international markets, such as Australia, have been successful.

Bydureon/Byetta
Combined sales were $896m in the year, representing growth of 21%; Bydureon represented approximately 65% of total Bydureon/Byetta sales.

In the US, sales were $691m, up by 21%, with higher volumes driven by market growth and higher net prices. The majority of the remaining sales of Bydureon/Byetta were in Europe, totalling $143m; Bydureon sales in Europe grew by 65% to $81m, reflecting the Company’s ongoing effort to expand its Diabetes presence.

Legacy: Crestor
Sales of Crestor declined in the year by 3% to $5,017m; pricing was stable. The volume performance primarily reflected ongoing competition from generic statins.

In the US, Crestor sales declined by 3% to $2,844m, driven by lower market share and destocking, partially offset by favourable price movements.

In Europe, sales declined by 9% to $916m, reflecting prevailing competitive trends. Crestor consolidated its position as the leading statin in Japan, with sales growth in the year of 8% to $468m. Sales in China grew by 13% to $258m.

Oncology

Iressa
Sales of Iressa in the year declined by 2% to $543m, driven by the competitive environment in Europe where sales were down by 8% to $128m; Japan sales declined by 13% to $121m. Following the US launch in July 2015, Iressa saw an encouraging number of new-patient starts.

Emerging Markets sales grew by 4% to $272m, with China sales increasing by 5% to $146m and Latin America sales increasing by 17% to $11m.

Lynparza
Sales of Lynparza reached $94m in 2015. US sales of $70m followed the launch of the medicine in December 2014. Growth was driven by addressing the accumulated needs of eligible patients awaiting treatment, as well as patients newly tested for BRCA mutation. By the end of 2015, the medicine had been launched in 15 countries, including France and Germany.

Tagrisso
Sales of Tagrisso were $19m in 2015; the medicine was launched in November 2015 in the US with a strong performance in the number of new-patient starts.

Legacy: Zoladex
Sales increased by 7% to $816m, with a notable performance in China where sales reached $121m, reflecting growth of 29%.

Legacy: Faslodex
Sales were up 9% to $704m in 2015. US sales grew by 5% to $356m, accompanied by Europe sales of $207m, up by 2% in the year. The notable performance was in the Emerging Markets, where sales of $87m represented growth of 49%. Supported by the launch of 500mg Faslodex, China sales accelerated in the year to $11m (Q4 2015: growth of 100%, Q3 2015: growth of 50%). AstraZeneca Russia also achieved federal reimbursement for the medicine in the year.

Infection, Neuroscience & Gastrointestinal

Nexium
Sales of Nexium declined by 26% in the year to $2,496m.

US sales declined by 52% to $902m following the loss of exclusivity at the start of the year, directly impacting both pricing and volumes. Sales in Europe declined by 7% to $284m.

Nexium sales in Emerging Markets were up by 3% to $761m, with growth in Latin America of 18% to $127m. Japan sales increased by 30% in the year to $405m.

Seroquel XR
Sales declined by 12% in the year to $1,025m.

In the US, sales were down 3% at $716m. Sales in Europe declined by 30% to $202m, a function of generic-product competition.

Synagis
FY 2015 sales of Synagis declined by 26% to $662m.

A 43% decline in US sales in the year to $285m reflected the reduction in demand as a result of the American Academy of Pediatrics Committee on Infectious Disease guidelines issued in 2014. These guidelines were more restrictive than the approved label, which further reduced patients eligible for preventative therapy with Synagis.

FluMist/Fluenz
Sales in the year were stable at $288m. US sales declined by 6% to $206m, reflecting supply issues. In contrast, Europe sales increased by 16% to $76m.

Movantik/Moventig
Sales in the year totalled $29m (Q4 2015: $15m); the medicine was launched in March 2015. The majority of sales were in the US, where the Company announced a co-commercialisation agreement in 2015 with Daiichi Sankyo for Movantik.

Regional Product Sales

 
   
FY 2015
 
Q4 2015
 
     
% Change
   
% Change
 
   
$m
CER
Actual
 
$m
CER
Actual
 
 
US
9,474
(6)
(6)
 
2,572
(3)
(3)
 
                   
 
Europe
5,323
(6)
(19)
 
1,421
(7)
(17)
 
                   
 
Established ROW1
3,022
-
(14)
 
786
4
(8)
 
   
Japan
2,020
4
(9)
 
541
8
-
 
   
Canada
533
4
(10)
 
134
2
(14)
 
   
Other Established ROW
469
(19)
(32)
 
111
(10)
(26)
 
                   
 
Emerging Markets2
5,822
12
(1)
 
1,428
10
(4)
 
   
China
2,530
15
13
 
599
10
6
 
   
Ex. China
3,292
10
(9)
 
829
9
(10)
 
                   
 
Total
23,641
(1)
(9)
 
6,207
-
(7)
 
 
1 Established ROW comprises Japan, Canada, Australia and New Zealand.
2 Emerging Markets comprises all remaining Rest of World markets, including Brazil, China, India, Mexico, Russia and Turkey.

US
US sales declined in the year by 6% to $9,474m. The US Branded Pharmaceutical Fee was recognised as a deduction from Product Sales in the year rather than as a charge to SG&A, impacting individual medicine sales by an average of around 2%.

The decline in sales in the US also reflected the entry of Nexium generic products from February 2015; Nexium sales in the US declined by 52% to $902m in the year. Adverse Synagis guideline changes were reflected in a 43% decline in US Synagis sales to $285m in the year.

Favourable performances were delivered by Brilinta, Farxiga, Bydureon and Lynparza as well as the acquired Respiratory medicines Tudorza and Daliresp. Tagrisso, launched earlier than originally anticipated in the fourth quarter, delivered an encouraging number of new-patient starts.

Continued growth in demand for Farxiga was supported by a strong promotional programme. Bydureon benefitted from the launch of the Bydureon Pen as well as growth in demand in the overall GLP-1 class.

Europe
Sales in Europe declined by 6% to $5,323m in the year. Strong growth from the Diabetes portfolio was more than offset by continued generic competition facing Crestor and Seroquel XR. A 14% decline in Symbicort sales to $1,076m reflected adverse pricing movements driven by competition from analogues in key markets. Duaklir more than doubled its first-half sales in the final quarter, bringing the full-year total to $26m. Lynparza was launched in Europe in 2015, contributing sales of $23m in the year.

Established ROW
Sales in the Established Rest Of World (ROW) were stable in the year at $3,022m.

Japan sales in the year increased by 4% to $2,020m. Sales of Crestor continued to grow strongly in the full year, up 8% to $468m. This reflected a continued increase in the usage of the 5mg dosage. Nexium sales rose by 30% to $405m, flattered by the impact of a product recall in FY 2014. Symbicort sales in the year fell by 2% to $176m in Japan, with a Q4 2015 sales decline of 16%. The strong performance in Q4 2014 reflected restocking. Underlying Symbicort sales growth in the year was estimated at around 5%. The Established ROW market share of Symbicort was broadly stable in the fourth quarter and over the full year.

Canada sales grew by 4% to $533m in the year, driven by the performances of Onglyza with sales up 27% to $53m and Symbicort sales increasing by 8% to $149m.

Emerging Markets
The Company continues to focus on delivering innovative medicines by accelerating investment in its Emerging Markets capabilities, with a focus on China and other leading markets, such as Russia and Brazil.

Emerging Markets sales in the year increased by 12% to $5,822m, with contributions to growth generated from across the region. Around 60% of Emerging Markets sales were derived outside of China in the year. Emerging Markets sales in the final quarter increased by 10% to $1,428m, ahead of the Company’s long-term forecast of mid to high single-digit percentage growth in the region’s Product Sales.

China sales in the year increased by 15% to $2,530m, while Brazil sales grew by 16% to $381m and Russia sales grew by 21% to $231m.

 
Financial Performance


FY 2015
Reported
Restructuring
Intangible
Amortisation & Impairments
Diabetes Alliance
Other1
Core
% Change
FY
2015
FY 20142
CER
Actual
Product Sales
23,641
-
-
-
-
23,641
26,095
(1)
(9)
Externalisation Revenue
1,067
-
-
-
-
1,067
452
140
136
Total Revenue
24,708
-
-
-
-
24,708
26,547
1
(7)
                   
Cost of Sales
(4,646)
158
369
-
-
(4,119)
(4,888)
(6)
(16)
                   
Gross Profit
20,062
158
369
-
-
20,589
21,659
2
(5)
Gross Margin3
80.3%
       
82.6%
81.3%
+0.8
+1.3
                   
Distribution
(339)
-
-
-
-
(339)
(324)
17
5
% Total Revenue
1.4%
       
1.4%
1.2%
-0.2
-0.2
                   
R&D
(5,997)
258
136
-
-
(5,603)
(4,941)
21
13
% Total Revenue
24.3%
       
22.7%
18.6%
-3.8
-4.1
                   
SG&A
(11,112)
618
921
54
254
(9,265)
(10,216)
(2)
(9)
% Total Revenue
45.0%
       
37.5%
38.5%
+1.1
+1.0
                   
Other Operating Income
1,500
-
178
-
(158)
1,520
759
104
100
% Total Revenue
6.1%
       
6.2%
2.9%
+2.9
+3.3
                   
Operating Profit
4,114
1,034
1,604
54
96
6,902
6,937
6
(1)
% Total Revenue
16.7%
       
27.9%
26.1%
+1.3
+1.8
                   
Net Finance
Expense
(1,029)
-
-
409
115
(505)
(493)
   
Joint Ventures
(16)
-
-
-
-
(16)
(6)
   
                   
Profit Before Tax
3,069
1,034
1,604
463
211
6,381
6,438
7
(1)
Taxation
(243)
(217)
(344)
(152)
(34)
(990)
(1,040)
   
Tax Rate
8%
       
16%
16%
   
Profit After Tax
2,826
817
1,260
311
177
5,391
5,398
7
-
                   
Non-controlling Interests
(1)
-
-
-
-
(1)
(2)
   
Net Profit
2,825
817
1,260
311
177
5,390
5,396
7
-
                   
Weighted Average Shares
1,264
1,264
1,264
1,264
1,264
1,264
1,262
   
                   
Earnings Per Share
2.23
0.65
1.00
0.24
0.14
4.26
4.28
7
 
-
 
1 Other adjustments include provision charges and settlement income related to certain legal matters (see Note 7) and fair value adjustments to contingent consideration liabilities arising on business combinations (see Note 6).
2 2014 comparatives have been restated to reflect the reclassification of Externalisation Revenue from Other Operating Income.
3 Gross Margin reflects Gross Profit derived from Product Sales, divided by Product Sales.
4 All financial figures, except Earnings Per Share, are in $ millions ($m). Weighted Average Shares are in millions.

Q4 2015
Reported
Restructuring
Intangible
Amortisation & Impairments
Diabetes Alliance
Other1
Core
% Change
Q4 2015
Q4 20142
CER
Actual
Product Sales
6,207
-
-
-
-
6,207
6,683
-
(7)
Externalisation Revenue
192
-
-
-
-
192
33
490
482
Total Revenue
6,399
-
-
-
-
6,399
6,716
2
(5)
                   
Cost of Sales
(1,269)
34
26
-
-
(1,209)
(1,359)
3
(11)
                   
Gross Profit
5,130
34
26
-
-
5,190
5,357
2
(3)
Gross Margin3
79.6%
       
80.5%
79.7%
-0.7
+0.8
                   
Distribution
(99)
-
-
-
-
(99)
(88)
23
13
% Total Revenue
1.5%
       
1.5%
1.3%
-0.3
-0.2
                   
R&D
(1,746)
78
101
-
-
(1,567)
(1,360)
21
15
% Total Revenue
27.3%
       
24.5%
20.3%
-3.7
-4.2
                   
SG&A
(2,668)
260
237
(270)
(20)
(2,461)
(2,953)
(11)
(17)
% Total Revenue
41.7%
       
38.5%
44.0%
+5.7
+5.5
                   
Other Operating Income
471
-
22
-
-
493
228
100
116
% Total Revenue
7.4%
       
7.7%
3.4%
+3.2
+4.3
                   
Operating Profit
1,088
372
386
(270)
(20)
1,556
1,184
28
31
% Total Revenue
17.0%
       
24.3%
17.6%
+4.8
+6.7
                   
Net Finance
Expense
(279)
-
-
104
25
(150)
(112)
   
Joint Ventures
(7)
-
-
-
-
(7)
(4)
   
                   
Profit Before Tax
802
372
386
(166)
5
1,399
1,068
29
31
Taxation
6
(78)
(97)
(11)
(20)
(200)
(119)
   
Tax Rate
(1)%
       
14%
11%
   
Profit After Tax
808
294
289
(177)
(15)
1,199
949
22
26
                   
Non-controlling Interests
-
-
-
-
-
-
-
   
Net Profit
808
294
289
(177)
(15)
1,199
949
22
26
                   
Weighted Average Shares
1,264
1,264
1,264
1,264
1,264
1,264
1,263
   
                   
Earnings Per Share
 
0.63
0.24
0.23
(0.15)
(0.01)
0.94
0.76
22
26
 
1 Other adjustments include provision charges and settlement income related to certain legal matters (see Note 7) and fair value adjustments to contingent consideration liabilities arising on business combinations (see Note 6).
2 2014 comparatives have been restated to reflect the reclassification of Externalisation Revenue from Other Operating Income.
3 Gross Margin reflects Gross Profit derived from Product Sales, divided by Product Sales.
4 All financial figures, except Earnings Per Share, are in $ millions ($m). Weighted Average Shares are in millions.

 
Profit and Loss
 
Gross Profit
Core Gross Profit increased by 2% in the year to $20,589m. Excluding the impact of externalisation, the Core Gross-Profit margin increased by one percentage point. Drivers of the margin increase included the mix of Product Sales and manufacturing efficiencies.

Operating Expenses
Core R&D costs were up 21% in the year to $5,603m as the Company continued to focus on its pipeline. Oncology attracted over 40% of total Core R&D investment in the year, reflecting a number of active trials.

In line with commitments made in early 2015 to reduce Core SG&A costs for the full year, Core SG&A costs declined by 2% to $9,265m. Core SG&A costs also declined in the year by one percentage point as a proportion of Total Revenue. A number of ongoing programmes designed to address Core SG&A costs are progressing. These initiatives are focused on:

-  
Sales, marketing and medical-cost effectiveness
-  
Centralisation of selected functions and process improvements
-  
Reduced third-party spend
-  
Additional efficiencies gained across support functions and IT
-  
Continued footprint optimisation, including presence in the UK and US

Resources will continue to be deployed selectively to meet changing customer needs and the evolving portfolio, while driving top-line growth.

Other Operating Income
Core Other Operating Income of $1,520m in the year increased by 104% and included:

·  
$380m of income related to the disposal of the US rights to Entocort
·  
$322m of royalty income arising from a number of agreements
·  
$215m of income related to the disposal of the rest-of-world rights to Entocort
·  
$193m of income related to the disposal of Myalept
·  
$165m of income related to the disposal of Caprelsa

Operating Profit
Core Operating Profit increased by 6% to $6,902m in the year. The Core Operating Margin increased by one percentage point to 28% of Total Revenue. The increase reflected the decline in Core SG&A costs and the increase in Externalisation Revenue and Core Other Operating Income, while the Company continued to invest in the pipeline and the Growth Platforms.

Reported Operating Profit of $4,114m was $1,977m higher than FY 2014 principally due to the difference in Core adjustments between FY 2015 and FY 2014. Most significantly, fair value adjustments to contingent consideration relating to the Bristol-Myers Squibb Company (BMS) share of the global Diabetes alliance increased Reported Operating Profit by $378m in FY 2015, whereas fair value adjustments to contingent consideration reduced Reported Operating Profit by $529m in FY 2014. These fair value movements reflect estimates for future liabilities that can change materially over time. In addition, restructuring costs of $1,034m in FY 2015 were significantly lower than restructuring costs of $1,558m in FY 2014.

Finance Expense
The Core Net Finance Expense was $505m in the year, compared with $493m in FY 2014. The Reported Net Finance Expense of $1,029m included a charge of $524m relating to the discount unwind on contingent consideration liabilities recognised on business combinations, principally relating to the acquisition of the BMS share of the global Diabetes alliance.

Taxation
Excluding the previously disclosed one-off tax benefit of $186m following agreement of US federal tax liabilities of open years up to 2008, other net reductions in provisions for tax contingencies and non-Core revaluations of contingent consideration arising on business combinations, partially offset by the impact of internal transfers of intellectual property, the Core and Reported tax rates for the year ended 31 December 2015 were 21% and 22% respectively. Including the impact of these items, the Core and Reported tax rates for the year were 16% and 8% respectively. The cash tax paid for the year was $1,354m, which was 44% of Reported Profit Before Tax and 21% of Core Profit Before Tax.

Both the underlying Reported and underlying Core tax rates for the year ended 31 December 2014 were around 18%. Taking into account the one-off benefits totalling $309m in respect of a transfer pricing matter, non-Core revaluations of contingent consideration arising on business combinations, and the benefit of the UK Patent Box, the Reported and Core tax rates fell to 1% and 16% respectively.
 
 
Earnings Per Share (EPS)
Core EPS in the year increased by 7% to $4.26.

Reported EPS was up by 137% at $2.23. Core profit adjustments were lower in the year and represented 40% of Core Operating Profit compared to 69% in 2014, mainly as a result of the fair value movements described above.

Dividends
The Board has declared a second interim dividend of $1.90 per share (131.0 pence, 16.26 SEK) bringing the dividend per share for the full year to $2.80 (188.5 pence, 23.97 SEK). The Board reaffirms its commitment to the Company’s progressive dividend policy.

For holders of the Company’s American Depositary Shares (ADSs), the $1.90 per Ordinary Share equates to $0.95 per ADS. Following the ratio change to the Company’s NYSE-listed sponsored Level 2 American Depositary Receipt programme on 27 July 2015, two ADSs equal one Ordinary Share.

Productivity
Restructuring charges of $372m were recognised in the fourth quarter, bringing the full-year total to $1,034m, as the Company continued to make good progress in implementing its restructuring plans.

These charges included $683m related to the Phase 4 programme, initially announced in March 2013 and subsequently expanded. A $233m charge was associated with previously-announced site exits (including Avlon in the UK) and the integration of the Diabetes and Respiratory businesses acquired from BMS and Almirall respectively. A charge of $102m was associated with targeted restructuring of the Company’s commercial business, implemented in late 2015, principally in Venezuela, in response to challenging economic conditions, and Europe.

Furthermore, as part of the ongoing commitment to improve productivity, the Company is initiating multi-year transformation programmes within back-office functions (principally finance and human resources) with anticipated costs by the end of 2018 of $270m. Once complete, these should deliver annualised benefits of approximately $100m by the end of 2018.

Final estimates for programme costs, benefits and headcount impacts in all functions will be subject to completion of the requisite consultation in the various areas. The Company’s priority in undertaking these restructuring initiatives is to work with affected employees on the proposed changes, acting in accordance with relevant local consultation requirements and employment law.

Cash Flow and Balance Sheet

Cash Flow
The Company generated a cash inflow from operating activities of $3,324m in the year compared with $7,058m in the comparative period. Cash generated from operating activities reflects a modest increase in investment in working capital of $49m compared to a decline of $2,508m in 2014. Working capital improvements made in 2014 have been sustained, minimising the impact of increased acquired diabetes and launch product inventory balances.

Net cash outflows from investing activities were $4,239m compared with $7,032m in the prior year. This reflects cash payments relating to business acquisitions in FY 2014 of $4,461m, which primarily related to the BMS Diabetes alliance and Almirall acquisitions, being higher than those in FY 2015 of $3,025m, which primarily related to the ZS Pharma acquisition. In addition, there was a cash inflow from the disposal of intangible assets of $1,130m in FY 2015, principally related to the disposals of Entocort, Myalept and Caprelsa.

Debt and Capital Structure
At 31 December 2015, outstanding gross debt (interest-bearing loans and borrowings) was $15,053m (31 December 2014: $10,843m). In November 2015, the Company issued a total of $6bn of notes, with the proceeds of the issue to be used to fund corporate and business development activity, repay certain outstanding commercial paper obligations and for general corporate purposes. Of the gross debt outstanding at 31 December 2015, $916m was due within one year (31 December 2014: $2,446m). The Company’s net debt position at 31 December 2015 was $7,762m (31 December 2014: $3,223m).

Shares in Issue
During the year, one million shares were issued in respect of share option exercises for a consideration of $43m. The total number of shares in issue as at 31 December 2015 was 1,264 million.

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. After providing for investment in the business, supporting the progressive dividend policy and maintaining a strong, investment-grade credit rating, the Board will keep under review investment in earnings-accretive opportunities.

Sensitivity: Foreign-Exchange Rates

The Company provides the following currency sensitivity information:

       
Average Exchange Rates Versus USD
     
Impact Of 5% Weakening In Exchange Rate Versus USD ($m)2
Currency
 
Primary Relevance
 
FY
2015
 
YTD 20161
 
Change %
 
Total Revenue
 
Core Operating Profit
EUR
 
Product Sales
 
0.90
 
0.92
 
(2)
 
(178)
 
(103)
JPY
 
Product Sales
 
121.04
 
118.27
 
2
 
(102)
 
(66)
CNY
 
Product Sales
 
6.28
 
6.57
 
(4)
 
(133)
 
(62)
SEK
 
Costs
 
8.43
 
8.54
 
(1)
 
(8)
 
71
GBP
 
Costs
 
0.65
 
0.69
 
(6)
 
(34)
 
96
Other3
                 
(201)
 
(122)
                         
 
1Based on average daily spot rates between 1 January 2016 and 29 January 2016
2Based on 2015 actual results at 2015 actual exchange rates
3Other important currencies include AUD, BRL, CAD, KRW and RUB

Currency Hedging

AstraZeneca monitors the impact of adverse currency movements on a portfolio basis, recognising correlation effects. The Company may hedge to protect against adverse impacts on cash flow over the short to medium term. As at 31 December 2015, AstraZeneca had hedged around 85% of forecast short-term currency exposure that arises between the booking and settlement dates on non-local currency purchases and Product Sales.

Corporate and Business Development Update


The highlights of the Company’s corporate and business development activities since the prior results announcement on 5 November 2015 are shown below.

a) Investment in Acerta Pharma
On 17 December 2015, AstraZeneca announced that it had entered into an agreement to invest in a majority equity stake in Acerta Pharma B.V. (Acerta), a privately-owned biopharmaceutical company based in the Netherlands and the US. The transaction will provide AstraZeneca with a potentially best-in-class irreversible oral Bruton's tyrosine kinase (BTK) inhibitor, acalabrutinib (ACP-196), currently in Phase II/III development for B-cell blood cancers and in Phase I/II clinical trials in multiple solid tumours.

On 2 February 2016, on completion of the agreement, AstraZeneca acquired 55% of the entire issued share capital of Acerta for an upfront payment of $2.5bn. A further payment of $1.5bn will be paid either on receipt of the first regulatory approval for acalabrutinib in the US, or the end of 2018, whichever is sooner. The agreement also includes options, which if exercised, provide the opportunity for Acerta shareholders to sell, and AstraZeneca to buy, the remaining 45% of shares in Acerta (see Note 5).

b) Acquisition of ZS Pharma
On 6 November 2015, AstraZeneca announced that it had entered into an agreement to acquire ZS Pharma Inc. (ZS Pharma), a biopharmaceutical company based in San Mateo, California. The transaction, completed in Q4 2015, gives AstraZeneca access to the potassium-binding compound ZS-9. This is a potential best-in-class treatment for hyperkalaemia, a condition associated with increased mortality in chronic kidney disease (CKD) and chronic heart failure (CHF). Under the terms of the agreement, AstraZeneca acquired ZS Pharma for $90 per share (see Note 4).

c) Respiratory portfolio acquisition
On 16 December 2015, AstraZeneca announced that it had entered into a definitive agreement to acquire the core Respiratory business of Takeda Pharmaceutical Company Limited (Takeda). The transaction, once completed, will include the expansion of rights to roflumilast (marketed as Daliresp in the US and Daxas in other countries), the only approved oral PDE4 inhibitor for the treatment of COPD.

Under the terms of the agreement, AstraZeneca will make a payment of $575m. Upon completion approximately 200 staff will transfer to AstraZeneca.

d) Allergan - ATM-AVI
On 29 January 2016, it was announced that AstraZeneca had entered into a global agreement with Allergan plc (Allergan) to develop and commercialise ATM-AVI, an investigational, fixed-dose antibiotic, combining aztreonam and avibactam. Together, the two companies will evaluate the combination to treat serious infections caused by metallo βlactamase MBL-producing Gram-negative pathogens, a difficult-to-treat sub-type of carbapenem-resistant Enterobacteriaceae, for which there are currently very limited treatments. ATM-AVI may present a new treatment option for patients with MBL-producing pathogens.

Under the terms of the agreement, Allergan will maintain commercialisation rights in the US and Canada and AstraZeneca will retain commercialisation rights in all other countries. AstraZeneca initiated a Phase I trial for ATM-AVI in 2012.

e) Agreement on rights to Entocort in the US
On 15 December 2015, AstraZeneca completed an agreement with Perrigo Company plc (Perrigo) for the divestment of US rights to Entocort (budesonide), a gastroenterology medicine for patients with mild to moderate Crohn’s disease. Under the terms of the agreement, Perrigo paid AstraZeneca $380m to acquire the rights to sell Entocort capsules and the authorised generic Entocort capsules marketed by Par Pharmaceuticals Companies, Inc.

The transaction did not include the transfer of any AstraZeneca employees or facilities. As a divestment, the income was recorded within Other Operating Income.

f) Strategic investments in China
On 16 December 2015, AstraZeneca announced a range of strategic initiatives to accelerate the delivery of innovative biologics and targeted medicines to patients in China. The initiatives and investments include a strategic alliance with WuXi AppTec, a leading Chinese biologics manufacturer and contract research organisation, to produce innovative biologics locally in China. Under the agreement, AstraZeneca has the option to acquire WuXi AppTec’s biologics manufacturing capacity in Wuxi City in the next few years through an overall investment approximating $100m. Prior to that, WuXi AppTec remains the Company’s exclusive partner for R&D manufacturing for innovative biologics in China.
 

 
Research and Development Update
 


A comprehensive table with AstraZeneca’s pipeline of medicines in human trials can be found later in this document.

Since the prior results announcement on 5 November 2015:

Regulatory Approvals
3
- Zurampic (US)
- Tagrisso (US, EU)
 
Regulatory Submission Acceptances
3
- brodalumab (US, EU)
    - ZS-9 (EU)
 
Other Key Developments
3
 
- CHMP positive recommendations (EU):
   Zurampic, Brilique, Tagrisso
 
New Molecular Entities (NMEs) in Pivotal Trials or under Regulatory Review*
15
RIA
- PT003* - COPD
- brodalumab*
- benralizumab
- tralokinumab - severe asthma
- PT010 - COPD
- anifrolumab - lupus (SLE)
 
CVMD
- roxadustat
- ZS-9*
 
Oncology
- cediranib*
- tremelimumab
- durvalumab - multiple cancers
- acalabrutinib
- moxetumomab pasudotox - leukaemia
- selumetinib
 
ING
- CAZ AVI*
 
Projects in clinical pipeline
125
 

Key: RIA - Respiratory, Inflammation & Autoimmunity, CVMD - Cardiovascular & Metabolic Disease, ING - Infection, Neuroscience & Gastrointestinal

1.  
Respiratory, Inflammation & Autoimmunity (RIA)

Steady progress continues to be made in the RIA pipeline, which now includes six programmes in pivotal trials or under registration. AstraZeneca’s Respiratory portfolio includes a range of differentiated potential medicines such as novel combinations, biologics and devices for the treatment of asthma and COPD. The pipeline also includes a number of assets in inflammatory and autoimmune diseases within areas such as psoriasis, systemic lupus and rheumatoid arthritis.

a) Symbicort (asthma)
Symbicort comprises budesonide (a corticosteroid, ICS) and formoterol (a long-acting beta agonist, LABA). The FDA required all manufacturers of medicines indicated for the treatment of asthma, containing LABA-based medicines, to conduct identical trials evaluating the safety when used in combination with an inhaled corticosteroid compared to the ICS alone.

The Symbicort LABA safety trial met its primary endpoint in the period, based on top-line results, demonstrating that the risk of serious asthma-related events for Symbicort is no different to that of budesonide alone. The trial was a randomised, double-blind, 26-week, active-controlled trial in 11,700 patients, aged at least 12 years of age and suffering from asthma.

b) Zurampic (gout)
On 22 December 2015, AstraZeneca announced that the FDA had approved Zurampic (lesinurad) 200mg tablets in combination with a xanthine oxidase inhibitor (XOI) for the treatment of hyperuricemia associated with gout in patients who have not achieved target serum uric-acid levels with an XOI alone. The approval was based on data from three pivotal Phase III trials, CLEAR1, CLEAR2 and CRYSTAL. These represent the largest clinical trial data set of gout patients (n=1,537) treated with combination urate-lowering therapy.

On 18 December 2015, AstraZeneca announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion recommending the marketing authorisation of Zurampic 200mg tablets. Zurampic is recommended for the adjunctive treatment of hyperuricaemia in adult gout. Zurampic will now be reviewed by the European Commission (EC). AstraZeneca anticipates a final decision in the first half of 2016.

c) Brodalumab (psoriasis)
During the period, regulatory submissions for brodalumab for the treatment of moderate-to-severe psoriasis were accepted in the US and EU. The submissions were supported by data from the three AMAGINE Phase III pivotal trials. The results indicated that brodalumab has an effective mechanism of action that delivers clinical benefit and could help a significant number of moderate-to-severe plaque psoriasis patients achieve total clearance of skin disease.

Under a collaboration agreement, Valeant Pharmaceuticals International Inc. (Valeant) has an exclusive license to develop and commercialise brodalumab globally, except in Japan and certain other Asian countries. Valeant assumes decisions on future development and development costs associated with the regulatory approval of brodalumab, as well as decisions on future development.

d) Tralokinumab (IPF)
A Phase II trial for tralokinumab in idiopathic pulmonary fibrosis (IPF), a potential exploratory indication for the medicine, was terminated in the period due to lack of efficacy on endpoints of IPF progression. No safety issues were detected. The Phase III programme for severe asthma, the lead indication for tralokinumab, is ongoing, with top-line results expected in 2017. Tralokinumab is anticipated to become AstraZeneca’s second biologic medicine in Respiratory diseases after benralizumab.

e) Anifrolumab (lupus)
Positive new data on anifrolumab in systemic lupus erythematosus (SLE) were presented at the American College of Rheumatology’s annual scientific meeting in San Francisco. The trial met primary and secondary endpoints in Phase II, with anifrolumab significantly reducing lupus disease activity compared with placebo across multiple endpoints.

In line with the Company’s dedication to personalised medicines, anifrolumab is being developed with an interferon-gene signature test designed to identify patients who may be more likely to benefit from treatment. The anifrolumab Phase III programme in SLE was initiated in July 2015 and is expected to read out with top-line results in 2018. Additional ongoing trials include a Phase II lupus nephritis trial and a Phase I trial with a subcutaneous route of administration.

2.  
Cardiovascular & Metabolic Disease (CVMD)

AstraZeneca's strategy in CVMD focuses on ways to reduce morbidity, mortality and organ damage by addressing multiple risk factors across CV disease, Diabetes and CKD indications. The patient-centric approach is reinforced by science-led life-cycle management programmes and technologies, including early research into regenerative methods.

a) Brilinta/Brilique (CV disease)
On 18 December 2015, AstraZeneca announced that the CHMP adopted a positive opinion, recommending approval of the 60mg dose of Brilique for the treatment of patients with a history of heart attack and at high risk of having a further coronary event. The opinion stated that treatment may be started as continuation therapy after an initial one-year treatment with dual anti-platelet therapy. The 90mg dose of Brilique is currently indicated in the EU to reduce the rate of cardiovascular death, myocardial infarction (MI, also known as heart attack) and stroke in patients with acute coronary syndrome.

b) Saxagliptin/dapagliflozin (type-2 diabetes)
AstraZeneca has continued to work closely with the FDA following the receipt of a Complete Response Letter in October 2015. The Company plans to submit additional clinical data for saxagliptin/dapagliflozin from a trial that is now completed and anticipates a new regulatory submission in the first half of 2016.

c) ZS-9 (hyperkalaemia)
The acquisition of ZS Pharma was completed on 17 December 2015 and ZS-9 (sodium zirconium cyclosilicate), a potential best-in-class treatment for hyperkaelemia, was accepted in the period by CHMP for regulatory review, in line with the Company’s expectations.

3.  
Oncology

 
AstraZeneca has a deep-rooted heritage in Oncology with a rejuvenating portfolio of medicines that has the potential to transform patients’ lives and the Company’s future. With at least six new medicines molecular entities to be launched between 2014 and 2020 and a broad pipeline of small molecules and biologics in development, the Company is committed to advance Oncology as one of AstraZeneca’s six Growth Platforms, focusing on lung, ovarian, breast and blood cancers. By exploiting the power of four scientific platforms -- immuno-oncology (IO), the genetic drivers of cancer and resistance, DNA damage repair and antibody drug conjugates -- and by championing the development of personalised medicines combinations, AstraZeneca has the vision to redefine cancer treatment and, one day, eliminate cancer as a cause of death.
 

a) Faslodex (breast cancer)
On 29 January 2016, the Company received notification that the FDA had accepted for regulatory submission a supplemental new drug application (sNDA) for Faslodex. The aim of the sNDA is to supplement the currently-approved indication for Faslodex to encompass the positive results of the Phase III PALOMA-3 trial. This trial tested adding Ibrance (palbociclib) to Faslodex versus Faslodex alone in women with HR-positive, HER2-negative metastatic breast cancer. The trial was conducted by Pfizer Inc., in collaboration with AstraZeneca.

b) Lynparza (ovarian and other cancers)
In January 2016 Breakthrough Therapy designation was granted by the FDA for Lynparza for prostate cancer patients with BRCA1/2 or ATM gene-mutated metastatic castrate-resistant prostate cancer (mCRPC) who have received previous taxane-based chemotherapy and one newer hormonal agent (abiraterone or enzalutamide). Accompanying this designation, Lynparza received a positive Phase III investment decision in the period from the Company for development in mCRPC.

These developments highlighted Lynparza’s significant future potential, in addition to the approved use in treating patients with a particular form of ovarian cancer.

c) Tagrisso (lung cancer)
On 13 November 2015, Tagrisso was approved by the FDA for patients with epidermal growth factor receptor (EGFR) T790M mutation-positive metastatic non-small cell lung cancer (NSCLC) who have progressed on an EGFR tyrosine kinase inhibitor (TKI). This followed one of the fastest medicine-development programmes in history, from the start of clinical trials to approval in two years and eight months. Tagrisso provides an important new option for patients, with an objective response rate of 59% and a median duration of response of over one year.

On 3 February 2016, Tagrisso received conditional approval in the EU for the treatment of adult patients with locally-advanced or metastatic EGFR T790M mutation-positive NSCLC. Tagrisso is the first T790M-directed inhibitor to receive marketing authorisation by the EU. Tagrisso’s indication includes patients with T790M NSCLC regardless of previous treatment with an EGFR TKI, underlining the unmet medical need in the small number of EGFR-mutated NSCLC patients who are initially (de novo) diagnosed with the T790M mutation. The approval follows the positive opinion received on 18 December 2015.

Interactions with regulatory authorities in the rest of the world, including the accelerated review process in Japan, are ongoing.

The ADAURA Phase III trial in adjuvant EGFRm NSCLC began enrollment in the quarter and will measure disease-free survival.

d) Durvalumab (multiple cancers)
Monotherapy
As announced on 18 December 2015, the preliminary findings of the ATLANTIC trial supported the clinical activity of durvalumab. In the trial of 3rd-line or later-stage NSCLC patients, durvalumab demonstrated expected clinical activity and durable response in heavily pre-treated patients. The treatment and regulatory landscape in lung cancer is evolving however, and the Company does not anticipate any regulatory submission as a monotherapy for 3rd-line PD-L1-positive NSCLC patients. Durvalumab is a cornerstone of the IO portfolio, with a fast-advancing development programme focused primarily on novel combinations.

Combination therapy
New data from the Phase Ib durvalumab + tremelimumab (durva + treme) combination trial in NSCLC were presented at the Society for Immunotherapy of Cancer meeting in November 2015. The trial investigators presented updated safety and efficacy results for 102 patients. In 84 of the patients evaluable for efficacy, results showed an overall response rate of 25% (21/84, 95% CI of 16-36%), consistent with data presented at the American Society of Clinical Oncology’s meeting in 2015. Response rates did not appear dependent on PD-L1 status: 35% (PD-L1-positive), 22% (PD-L1-negative, <25% tumour-cell staining) and 33% (PD-L1-negative, 0% tumour-cell staining). Higher response rates were observed in those patients who had only received one prior treatment: 47% (15/32, 95% CI of 29-65%).

The CAURAL trial, combining Tagrisso and durvalumab, remains on clinical hold, based on an increase in the incidence of interstitial lung disease, compared to what has been previously reported with each medicine used on its own. Investigation of the safety signal is ongoing.

During the period, first patients were dosed in a number of durva + treme combination trials, including NEPTUNE, EAGLE, KESTREL, DANUBE and ALPS as well as in the safety lead-in of the triple combination trial in NSCLC with chemotherapy. AstraZeneca is planning a Phase III trial with durvalumab in small cell lung cancer that will include the first IO-IO-chemotherapy triple-combination arm. A second, earlier-stage trial will also pair durvalumab with other portfolio medicines such as Lynparza and AZD1775 (WEE-1).

The MYSTIC trial saw its primary endpoint updated to a co-primary endpoint of progression-free survival (PFS) and overall survival. The trial is recruiting ahead of expectations and is expected to be the first IO-IO combination 1st-line NSCLC trial to provide PFS data, in the first half of 2017.

An update on ongoing trials with durvalumab is provided over the page:


LUNG CANCER
Name
 
Phase
Line of treatment
Population
Design
Timelines
Status
Early disease
 
Monotherapy
ADJUVANT1
 III
N/A
Stage Ib-IIIa NSCLC
durvalumab vs placebo
FPD Q1 2015
Data expected 2020
Recruiting
PACIFIC
 III
N/A
Stage III unresectable NSCLC
durvalumab vs placebo
FPD Q2 2014
Data expected 2017
Recruiting; >50% of patients now randomised
Advanced/metastatic disease
 
Combination therapy
ARCTIC
 III
3rd line
PD-L1 neg. NSCLC
durvalumab vs tremelimumab vs durva + treme vs SoC
FPD Q2 2015
Data expected H1 2017
Recruiting
MYSTIC
 III
1st line
NSCLC
durvalumab vs durva + treme vs SoC
FPD Q3 2015
Data expected H1 2017
Recruiting
NEPTUNE
 III
1st line
NSCLC
durva + treme vs SoC
FPD Q4 2015
Data expected 2018
First patient now dosed
 -
 III
1st line
NSCLC
durvalumab + chemotherapy +/- tremelimumab
-
First patient now dosed in safety lead-in
 -
 III
1st line
SCLC
durva + treme + chemotherapy vs SoC
-
Awaiting first patient dosed
1Conducted by the National Cancer Institute of Canada
METASTATIC OR RECURRENT HEAD AND NECK CANCER
Name
Phase
Line of treatment
Population
Design
Timelines
Status
Monotherapy
HAWK
 II
2nd line
PD-L1 pos. SCCHN
durvalumab (single arm)
FPD Q1 2015
 
Data expected
H2 2016
Recruiting
 
Indication granted FDA Fast Track designation
Combination therapy
CONDOR
 II
2nd line
PD-L1 neg. SCCHN
durvalumab vs tremelimumab vs durva + treme
FPD Q2 2015
 
Data expected 2017
Recruiting
EAGLE
 III
2nd line
SCCHN
durvalumab vs durva + treme vs SoC
FPD Q4 2015
 
Data expected 2018
First patient now dosed
KESTREL
 
 III
1st line
SCCHN
durvalumab vs durva + treme vs SoC
FPD Q4 2015
 
Data expected 2018
First patient now dosed
 
OTHER METASTATIC CANCERS
Name
Phase
Line of treatment
Population
Design
Timelines
Status
DANUBE
 III
1st line
Cisplatin chemo-
therapy- eligible/
ineligible bladder cancer
durvalumab vs durva + treme vs SoC
FPD Q4 2015
 
 
Data expected 2018
First patient now dosed
ALPS
 II
2nd line
Metastatic pancreatic cancer
durva + treme (single arm)
FPD Q4 2015
 
Data expected 2017
First patient now dosed
  -
 II
2nd/3rd line
Metastatic gastric cancer
durvalumab vs tremelimumab vs durva + treme
-
In preparation
  -
 II
2nd line
Unresectable liver cancer
durvalumab vs tremelimumab vs durva + treme
-
In preparation
 
FPD=First Patient Dosed, LPD=Last Patient Dosed, SoC=Standard of Care, SCCHN = Squamous Cell Carcinoma of the Head and Neck

e) Early-stage Oncology
New Oncology programmes that progressed into human trials during the period included MEDI9197, a TLR 7/8 agonist, in solid tumours and a GITR fusion protein, MEDI1873. Furthermore, two small-molecule programmes developed in collaboration with BIND Therapeutics moved into clinical trials: AZD0156, a first-in-class ATM kinase inhibitor which further strengthens the Company’s leading position in DNA damage response and AZD2811, a nanoparticle formulation of a novel, selective inhibitor of Aurora B kinase that has been shown to be active in both solid and haematological tumours.

Additionally the Company now has a HER2-targeted, bi-specific antibody drug conjugate, MEDI4276, in a Phase I trial in solid tumours. HER2 (receptor tyrosine-protein kinase) is over-expressed in several cancers, including breast and gastric cancers. AZD3759, an EGFR inhibitor designed to cross the blood brain barrier, progressed into Phase II expansion cohorts in leptomeningeal disease, a form of brain cancer, and in patients with brain metastases.

ASTRAZENECA DEVELOPMENT PIPELINE 31 DECEMBER 2015
Includes AstraZeneca-sponsored or directed studies only
Phase III / Pivotal Phase II / Registration
 
NMEs and significant additional indications
 
Regulatory submission dates shown for assets in Phase III and beyond. As disclosure of compound information is balanced by the business need to maintain confidentiality, information in relation to some compounds listed here has not been disclosed at this time.
 
†     US and EU dates correspond to anticipated acceptance of the regulatory submission.
#     Partnered and/or in collaboration.

Compound
Mechanism
Area Under Investigation
Date Commenced Phase
Estimated Regulatory Submission / Submission Acceptance†
US
EU
 
Japan
China
Respiratory, Inflammation and Autoimmunity
 
anifrolumab# TULIP
IFN-alphaR mAb
systemic lupus erythematosus
Q3 2015
2019
(Fast Track)
2019
2019
 
benralizumab#
CALIMA SIROCCO ZONDA BISE BORA
GREGALE
IL-5R mAb
severe asthma
Q4 2013
H2 2016
H2 2016
N/A
N/A
benralizumab#
TERRANOVA GALATHEA
IL-5R mAb
COPD
Q3 2014
2018
2018
N/A
N/A
brodalumab#
AMAGINE-1,2,3
IL-17R mAb
psoriasis
Q3 2012
Accepted1
Accepted
N/A
N/A
Zurampic (lesinurad)
CLEAR 1,2
CRYSTAL
selective uric acid reabsorption inhibitor (URAT-1)
chronic treatment of hyperuricemia in patients with gout
Q4 2011
Approved
Accepted2
   
PT003 GFF PINNACLE
LABA/LAMA
COPD
Q2 2013
Accepted
H2 2016
2017
2017
PT010
LABA/LAMA/ ICS
COPD
Q3 2015
2018
2018
2017
2019
tralokinumab
STRATOS 1,2
TROPOS
MESOS
IL-13 mAb
severe asthma
Q3 2014
2018
2018
2018
 
Cardiovascular and Metabolic Diseases
Brilinta/Brilique3
P2Y12 receptor antagonist
arterial thrombosis
 
Launched
Launched
Accepted
Launched
Epanova#
omega-3 carboxylic acids
severe hypertrigly-ceridemia
 
Approved
 
2018
2019
Farxiga/Forxiga4
SGLT2 inhibitor
type-2 diabetes
 
Launched
Launched
Launched
Accepted
roxadustat# OLYMPUS ROCKIES
hypoxia-inducible factor prolyl hydroxylase inhibitor
anaemia in CKD/ESRD
Q3 2014
2018
N/A
N/A
H2 20165
ZS-9 (sodium zirconium cyclosilicate)
 
potassium binder
hyperkalaemia
 
Accepted
Accepted
 
 
Oncology
acalabrutinib#6
Bruton's tyrosine kinase (BTK) inhibitor
B-cell blood cancers
 
H2 2016
     
cediranib
ICON 6
VEGFR tyrosine kinase inhibitor
PSR ovarian cancer
Q2 2007
 
Accepted (Orphan Drug)
   
durvalumab# + tremelimumab
ALPS
PD-L1 mAb + CTLA-4 mAb
metastatic pancreatic ductal carcinoma
Q4 2015
2017
2017
2017
 
durvalumab#
PACIFIC
PD-L1 mAb
stage III NSCLC
Q2 2014
2017
2020
2020
 
durvalumab#
HAWK
PD-L1 mAb
2nd-line SCCHN (PD-L1 positive)
Q1 2015
 
2017
(Fast Track)
2019
2019
 
durvalumab# +
tremelimumab
ARCTIC
PD-L1 mAb + CTLA-4 mAb
3rd-line NSCLC
Q2 2015
2017
2017
2017
 
durvalumab# + tremelimumab
CONDOR
PD-L1 mAb + CTLA-4 mAb
2nd-line SCCHN (PD-L1 negative)
Q2 2015
2017
2019
2019
 
durvalumab# + tremelimumab
DANUBE
PD-L1 mAb + CTLA-4 mAb
1st-line bladder
Q4 2015
2018
 
2018
2018
 
durvalumab# + tremelimumab
EAGLE
PD-L1 mAb + CTLA-4 mAb
2nd-line SCCHN
Q4 2015
2019
2019
2019
 
durvalumab# + tremelimumab
KESTREL
PD-L1 mAb + CTLA-4 mAb
1st-line SCCHN
Q4 2015
2018
2018
2018
 
durvalumab# + tremelimumab
MYSTIC
PD-L1 mAb + CTLA-4 mAb
1st-line NSCLC
Q3 2015
2017
2017
2017
 
durvalumab# + tremelimumab
NEPTUNE
PD-L1 mAb + CTLA-4 mAb
1st-line NSCLC
Q4 2015
2019
2019
2019
 
moxetumomab pasudotox#
PLAIT
anti-CD22 recombinant
immunotoxin
hairy cell leukaemia
Q2 2013
2017
(Orphan Drug)
2018
   
selumetinib#
ASTRA
MEK inhibitor
differentiated thyroid cancer
Q3 2013
2018
2018
   
selumetinib#
SELECT-1
MEK inhibitor
2nd-line KRASm NSCLC
Q4 2013
2017
2017
   
Tagrisso (AZD9291)
AURA, AURA 2
EGFR tyrosine kinase inhibitor
≥2nd-line advanced EGFRm T790M NSCLC
 
Q2 2014
Launched
(Breakthrough designation, Priority Review, Orphan Drug)
Approved7 (Accelerated assessment)
Accepted (Priority Review)
2017
Tagrisso (AZD9291)
AURA 3
EGFR tyrosine kinase inhibitor
≥2nd-line advanced EGFRm T790M NSCLC
 
Q3 2014
2017
2017
2017
 
tremelimumab DETERMINE
 
CTLA-4 mAb
mesothelioma
Q2 2014
H2 2016
(Orphan Drug, Fast Track)
H2 2016
H2 2016
 
Infection, Neuroscience and Gastrointestinal
 
CAZ AVI#
 
cephalosporin/
beta lactamase inhibitor
serious infections, complicated intra-abdominal infection, complicated urinary tract infection
Q1 2012
N/A
Accepted
 
2017
CAZ AVI#
cephalosporin/ beta lactamase inhibitor
hospital-acquired pneumonia/ ventilator-associated pneumonia
Q2 2013
N/A
Accepted
 
2017
MEDI-550
pandemic influenza virus vaccine
pandemic influenza prophylaxis
 
N/A
H1 20168
N/A
N/A
Zinforo#
extended spectrum cephalosporin with affinity to penicillin-binding proteins
pneumonia/skin infections
 
N/A
Launched
N/A
Submitted
¶     Registrational Phase II/III trial.
1     US regulatory submission accepted Q1 2016.
2     CHMP Positive Opinion received December 2015.
3     Brilinta in the US; Brilique in rest of world.
4     Farxiga in the US; Forxiga in rest of world.
5     Rolling NDA submission to be initiated in H2 2016.
6     Completion of the agreement with Acerta Pharma Q1 2016
7     CHMP Positive Opinion received December 2015. Approval received Q1 2016.
8     MAA submitted December 2015. Regulatory acceptance anticipated H1 2016.

Phases I and II
 
NMEs and significant additional indications
 
Compound
Mechanism
Area Under Investigation
Phase
Date Commenced Phase
 
Respiratory, Inflammation and Autoimmunity
abediterol (AZD0548)
LABA
asthma/COPD
II
Q4 2007
anifrolumab#
IFN-alphaR mAb
lupus nephritis
II
Q4 2015
AZD7594
inhaled SGRM
asthma/COPD
II
Q3 2015
AZD7624
inhaled P38 inhibitor
COPD
II
Q4 2014
AZD9412#
inhaled interferon beta
asthma/COPD
II
Q3 2015
mavrilimumab#
GM-CSFR mAb
rheumatoid arthritis
II
Q1 2010
MEDI-551#
CD19 mAb
neuromyelitis optica1
II
Q1 2015
MEDI2070#
IL-23 mAb
Crohn’s disease
II
Q1 2013
abrilumab#
alpha(4)beta(7) mAb
Crohn’s disease / ulcerative colitis
II
Q4 2012
MEDI9929#
TSLP mAb
asthma / atopic dermatitis
II
Q2 2014
PT010
LABA/LAMA/ICS
asthma
II
Q2 2014
RDEA3170
selective uric acid reabsorption inhibitor (URAT-1)
chronic treatment of hyperuricemia in patients with gout
II
Q3 2013
tralokinumab
IL-13 mAb
atopic dermatitis
II
Q1 2015
anifrolumab#
IFN-alphaR mAb
systemic lupus erythematosus (subcutaneous)
I
Q4 2015
lesinurad+allopurinol
selective uric acid reabsorption inhibitor (URAT-1)+xanthine oxidase inhibitor
chronic treatment of hyperuricemia in patients with gout
I
Q4 2015
AZD1419#
TLR9 agonist
Asthma
I
Q3 2013
AZD7986
DPP1
COPD
I
Q4 2014
AZD8871
MABA
COPD
I
Q4 2015
AZD8999
MABA
COPD
I
Q4 2013
AZD9567
oral SGRM
rheumatoid arthritis
I
Q4 2015
MEDI4920
anti-CD40L-Tn3 fusion protein
primary Sjögren’s syndrome
I
Q2 2014
MEDI5872#
B7RP1 mAb
systemic lupus erythematosus
I
Q4 2008
MEDI7836
IL-13 mAb-YTE
Asthma
I
Q1 2015
Cardiovascular and Metabolic Diseases
AZD4076
anti-miR103/107 oligonucleotide
non-alcoholic fatty liver disease/non-alcoholic steatohepatitis (NASH)
I
Q4 2015
MEDI6012
LCAT
ACS
II
Q4 2015
MEDI0382
GLP-1/
glucagon dual agonist
diabetes / obesity
I
Q1 2015
MEDI4166
PCSK9/GLP-1 mAb + peptide fusion
diabetes / cardiovascular
I
Q4 2015
MEDI8111
Rh-factor II
trauma / bleeding
I
Q1 2014
Oncology
AZD1775#
WEE-1 inhibitor
ovarian cancer
II
Q4 2012
AZD2014
mTOR serine/ threonine kinase inhibitor
solid tumours
II
Q1 2013
AZD3759 BLOOM
EGFR tyrosine kinase inhibitor
brain metastases in advanced EGFRm NSCLC
II
Q4 2015
Tagrisso (AZD9291)
BLOOM
EGFR tyrosine kinase inhibitor
AZD4547
FGFR tyrosine kinase inhibitor
solid tumours
II
Q4 2011
AZD5069+durvalumab#
CXCR2 + PD-L1 mAb
SCCHN
II
Q3 2015
AZD9150#+durvalumab#
STAT3 inhibitor + PD-L1 mAb
AZD5363#
AKT kinase inhibitor
breast cancer
II
Q1 2014
durvalumab#
PD-L1 mAb
solid tumours
II
Q3 2014
durvalumab# + tremelimumab
PD-L1 mAb + CTLA-4 mAb
gastric cancer
II
Q2 2015
MEDI-551#
CD19 mAb
diffuse B-cell lymphoma
II
Q1 2012
MEDI-573#
IGF mAb
metastatic breast cancer
II
Q2 2012
savolitinib/
volitinib#
MET tyrosine kinase inhibitor
papillary renal cell carcinoma
II
Q2 2014
selumetinib#
MEK inhibitor
2nd-line KRAS wt NSCLC
II
Q1 2013
AZD0156
ATM serine/threonine kinase inhibitor
solid tumours
I
Q4 2015
AZD2811
Aurora B kinase inhibitor
solid tumours
I
Q4 2015
AZD5312#
androgen receptor inhibitor
solid tumours
I
Q2 2014
AZD6738
ATR serine/threonine kinase inhibitor
solid tumours
I
Q4 2013
AZD8186
PI3 kinase beta inhibitor
solid tumours
I
Q2 2013
AZD8835
PI3 kinase alpha inhibitor
solid tumours
I
Q4 2014
AZD9150#
STAT3 inhibitor
haematological malignancies
I
Q1 2012
Tagrisso (AZD9291) + (durvalumab# or selumetinib# or savolitinib#)
TATTON
EGFR tyrosine kinase inhibitor + (PD-L1 mAb or MEK inhibitor or MET tyrosine kinase inhibitor)
advanced EGFRm NSCLC
I
Q3 2014
AZD9496
selective oestrogen receptor downregulator (SERD)
ER+ breast cancer
I
Q4 2014
durvalumab#
PD-L1 mAb
solid tumours
I
Q3 2014
durvalumab# + MEDI0680
PD-L1 mAb + PD-1 mAb
solid tumours
I
Q2 2014
durvalumab# + MEDI6383#
OX40 agonist + PD-L1 mAb
solid tumours
I
Q2 2015
durvalumab# + dabrafenib + trametinib2
PD-L1 mAb+ BRAF inhibitor + MEK inhibitor
melanoma
I
Q1 2014
durvalumab# + tremelimumab
PD-L1 mAb + CTLA-4 mAb
solid tumours
I
Q4 2013
Iressa + durvalumab#
PD-L1 mAb+ EGFR tyrosine kinase inhibitor
NSCLC
I
Q2 2014
MEDI0562#
humanised OX40 agonist
solid tumours
I
Q1 2015
MEDI-551# + rituximab
CD19 mAb + CD20 mAb
haematological malignancies
I
Q2 2014
MEDI-565#
CEA BiTE mAb
solid tumours
I
Q1 2011
MEDI0639#
DLL-4 mAb
solid tumours
I
Q2 2012
MEDI0680
PD-1 mAb
solid tumours
I
Q4 2013
MEDI1873
GITR agonist fusion protein
solid tumours
I
Q4 2015
MEDI3617#
ANG-2 mAb
solid tumours
I
Q4 2010
MEDI4276
HER2 bispecific ADC mAb
solid tumours
I
Q4 2015
MEDI6383#
OX40 agonist
solid tumours
I
Q3 2014
MEDI9197#
TLR 7/8 agonist
solid tumours
I
Q4 2015
MEDI9447
CD73 mAb
solid tumours
I
Q3 2015
Infection, Neuroscience and Gastrointestinal
AZD3241
myeloperoxidase inhibitor
multiple system atrophy
II
Q2 2015
(Orphan Drug)
AZD3293#
beta-secretase inhibitor
Alzheimer’s disease
II
Q4 2014
CXL#
beta lactamase inhibitor / cephalosporin
methicillin-resistant S. aureus
II
Q4 2010
MEDI7510
RSV sF+GLA-SE
prevention of RSV disease in older adults
II
Q3 2015
MEDI8852
influenza A mAb
influenza A treatment
II
Q4 2015
MEDI8897#
RSV mAb-YTE
passive RSV prophylaxis
II
Q1 2015
(FDA Fast Track)
MEDI4893
mAb binding to S. aureus toxin
hospital-acquired pneumonia / serious S. aureus infection
II
Q4 2014
(FDA Fast Track)
ATM AVI#
monobactam/ beta lactamase inhibitor
targeted serious bacterial infections
I
Q4 2012
AZD8108
NMDA antagonist
suicidal ideation
I
Q4 2014
MEDI1814
amyloid beta mAb
Alzheimer’s disease
I
Q2 2014
MEDI3902
anti-Psl/PcrV
prevention of nosocomial pseudomonas pneumonia
I
Q3 2014
(FDA Fast Track)

1     Neuromyelitis optica: Now lead indication. Multiple sclerosis trial completed in 2015.
2     MedImmune-sponsored trial in collaboration with Novartis AG.

Significant Life-Cycle Management
 
Compound
Mechanism
Area Under Investigation
Date Commenced Phase
Estimated Regulatory Submission Acceptance
US
EU
Japan
China
Respiratory, Inflammation and Autoimmunity
Duaklir Genuair#
LAMA/LABA
COPD
 
2018
Launched
2018
2018
Symbicort
SYGMA
ICS/LABA
as-needed use in mild asthma
Q4 2014
N/A
2018
 
2019
Symbicort
ICS/LABA
breath actuated Inhaler asthma/COPD
 
2018
     
Cardiovascular and Metabolic Diseases
Brilinta/Brilique1 EUCLID
P2Y12 receptor antagonist
outcomes trial in patients with peripheral artery disease
Q4 2012
2017
2017
2017
2018
Brilinta/Brilique1 HESTIA
P2Y12 receptor antagonist
prevention of vaso-occlusive crises in paediatric patients with sickle cell disease
Q4 2014
2020
2020
   
Brilinta/Brilique1
PEGASUS-
TIMI 54
P2Y12 receptor antagonist
outcomes trial in patients with prior myocardial infarction
Q4 2010
Launched
(Priority Review)
Accepted2
Accepted
H2 2016
Brilinta/Brilique1 SOCRATES
P2Y12 receptor antagonist
outcomes trial in patients with stroke or TIA
Q1 2014
H1 2016
H1 2016
H2 2016
2017
Brilinta/Brilique1 THEMIS
P2Y12 receptor antagonist
outcomes trial in patients with type-2 diabetes and CAD, but without a previous history of MI or stroke
Q1 2014
2018
2018
2018
2019
Bydureon EXSCEL
GLP-1 receptor agonist
type-2 diabetes outcomes trial
Q2 2010
2018
2018
2018
 
Bydureon weekly
suspension
GLP-1 receptor agonist
type-2 diabetes
Q1 2013
2017
2017
   
Epanova
STRENGTH
omega-3 carboxylic acids
outcomes trial in statin-treated patients at high CV risk, with persistent hypertriglyceridemia plus low HDL-cholesterol
Q4 2014
2020
2020
2020
2020
Epanova/
Farxiga/Forxiga3
 
omega-3 carboxylic acids/ SGLT2 inhibitor
non-alcoholic fatty liver disease/non-alcoholic steatohepatitis (NASH)
Q1 2015
       
Farxiga/Forxiga3
DECLARE-
TIMI 58
SGLT2 inhibitor
type-2 diabetes outcomes trial
Q2 2013
2020
2020
   
Farxiga/Forxiga3
SGLT2 inhibitor
type-1 diabetes
Q4 2014
2018
2017
2018
 
Kombiglyze XR/Komboglyze4
DPP-4 inhibitor/ metformin FDC
type-2 diabetes
 
Launched
Launched
 
Submitted
Onglyza SAVOR-TIMI 53
DPP-4 inhibitor
type-2 diabetes outcomes trial
Q2 2010
Accepted
Launched
 
H2 20165
saxagliptin/
dapagliflozin FDC
DPP-4 inhibitor/ SGLT2 inhibitor FDC
type-2 diabetes
Q2 2012
Accepted6
Accepted
   
Xigduo XR/
Xigduo7
SGLT2 inhibitor/ metformin FDC
type-2 diabetes
 
Launched
Launched
   
Oncology
Faslodex
FALCON
oestrogen receptor antagonist
1st-line hormone receptor +ve advanced breast cancer
Q4 2012
H2 2016
H2 2016
H2 2016
2020
Lynparza (olaparib) SOLO-1
PARP inhibitor
1st-line BRCAm ovarian cancer
Q3 2013
2017
2017
2017
 
Lynparza (olaparib) SOLO-2
PARP inhibitor
2nd-line or greater BRCAm PSR ovarian cancer, maintenance monotherapy
Q3 2013
H2 2016
2017
2017
 
Lynparza (olaparib) SOLO-3
PARP inhibitor
gBRCA PSR ovarian cancer
Q1 2015
2018
     
Lynparza (olaparib) GOLD
PARP inhibitor
2nd-line gastric cancer
Q3 2013
   
2017
 
Lynparza (olaparib)
OlympiA
PARP inhibitor
gBRCA adjuvant breast cancer
Q2 2014
2020
2020
2020
 
Lynparza (olaparib) OlympiAD
PARP inhibitor
gBRCA metastatic breast cancer
Q2 2014
H2 2016
2017
2017
 
Lynparza (olaparib) POLO
PARP inhibitor
pancreatic cancer
Q1 2015
2018
2018
2018
 
Lynparza (olaparib)
PARP inhibitor
prostate cancer
Q3 2014
 
(Breakthrough Therapy Designation)8
     
Tagrisso (AZD9291)
ADAURA
EGFR tyrosine kinase inhibitor
adjuvant EGFRm NSCLC
Q4 2015
2022
2022
 
 
Tagrisso (AZD9291)
FLAURA
EGFR tyrosine kinase inhibitor
1st-line advanced EGFRm NSCLC
Q1 2015
2017
2017
2017
2020
Tagrisso (AZD9291) +dur-valumab#
CAURAL9
EGFR tyrosine kinase inhibitor + PD-L1 mAb
≥2nd-line advanced EGFRm T790M NSCLC
Q3 2015
       
Infection, Neuroscience and Gastrointestinal
Diprivan#
sedative and anaesthetic
conscious sedation
 
N/A
Launched
Accepted
Launched
linaclotide#
GC-C receptor peptide agonist
irritable bowel syndrome with constipation
(IBS-C)
 
N/A
N/A
N/A
Accepted10
Nexium
proton pump inhibitor
stress ulcer prophylaxis
       
H2 2016
Nexium
proton pump inhibitor
paediatrics
 
Launched
Launched
H2 2016
Accepted

1     Brilinta in the US; Brilique in rest of world.
2     CHMP Positive Opinion received December 2015.
3     Farxiga in the US; Forxiga in rest of world.
4     Kombiglyze XR in the US; Komboglyze in the EU.
5     Timing of China submission dependent on US regulatory approval.
6     Complete Response Letter received October 2015.
7     Xigduo XR in the US; Xigduo in the EU.
 
8
Breakthrough Therapy designation granted for prostate cancer patients with BRCA1/2 or ATM gene mutated mCRPC who have received previous taxane-based chemotherapy and one newer hormonal agent (abiraterone or enzalutamide).
 
9
Temporarily closed to enrolment.
10  Submission accepted January 2016.

Terminations (discontinued projects between 1 October and 31 December 2015)

NME / Line Extension
Compound
Reason for Discontinuation
 
Area Under Investigation
NME
AZD5847
Safety / efficacy
tuberculosis
NME
AZD9977
Safety / efficacy
diabetic kidney disease
NME
durvalumab#
ATLANTIC
Strategic
3rd-line NSCLC (PD-L1 positive)
LCM
durvalumab# after Tagrisso (AZD9291) or Iressa or selumetinib# +docetaxel or tremelimumab
Strategic
NSCLC
LCM
tralokinumab
Safety / efficacy
idiopathic pulmonary fibrosis

Completed Projects / Divestitures

Compound
Mechanism
Area Under Investigation
Completed/
Divested
Estimated Regulatory Submission Acceptance
US
EU
Japan
China
AZD49011
NK3 receptor antagonist
polycystic ovarian syndrome
Divested in Phase II
 
       

1     Divested to Millendo Therapeutics, Inc. Agreement announced January 2016.

 
Condensed Consolidated Statement of Comprehensive Income
 
For the year ended 31 December
 
2015 
$m 
 
Restated
2014*
$m 
Product sales
 
23,641 
 
26,095 
Externalisation revenue
 
1,067 
 
452 
Total revenue
 
24,708 
 
26,547 
Cost of sales
 
(4,646)
 
(5,842)
Gross profit
 
20,062 
 
20,705 
Distribution costs
 
(339)
 
(324)
Research and development expense
 
(5,997)
 
(5,579)
Selling, general and administrative costs
 
(11,112)
 
(13,000)
Other operating income and expense
 
1,500 
 
335 
Operating profit
 
4,114 
 
2,137 
Finance income
 
46 
 
78 
Finance expense
 
(1,075)
 
(963)
Share of after tax losses in joint ventures
 
(16)
 
(6)
Profit before tax
 
3,069 
 
1,246 
Taxation
 
(243)
 
(11)
Profit for the period
 
2,826 
 
1,235 
         
Other comprehensive income
       
Items that will not be reclassified to profit or loss
       
Remeasurement of the defined benefit pension liability
 
652 
 
(766)
Tax on items that will not be reclassified to profit or loss
 
(199)
 
216 
   
453 
 
(550)
Items that may be reclassified subsequently to profit or loss
       
Foreign exchange arising on consolidation
 
(528)
 
(823)
Foreign exchange arising on designating borrowings in net investment hedges
 
(333)
 
(529)
Fair value movements on derivatives designated in net investment hedges
 
14 
 
100 
Amortisation of loss on cash flow hedge
 
 
Net available for sale (losses)/gains taken to equity
 
(32)
 
245 
Tax on items that may be reclassified subsequently to profit or loss
 
87 
 
50 
   
(791)
 
(956)
Other comprehensive income for the period, net of tax
 
(338)
 
(1,506)
Total comprehensive income for the period
 
2,488 
 
(271)
         
Profit attributable to:
       
Owners of the Parent
 
2,825 
 
1,233 
Non-controlling interests
 
 
   
2,826 
 
1,235 
         
Total comprehensive income attributable to:
       
Owners of the Parent
 
2,488 
 
(266)
Non-controlling interests
 
 
(5)
   
2,488 
 
(271)
         
Basic earnings per $0.25 Ordinary Share
 
$2.23 
 
$0.98 
Diluted earnings per $0.25 Ordinary Share
 
$2.23 
 
$0.98 
Weighted average number of Ordinary Shares in issue (millions)
 
1,264 
 
1,262 
Diluted weighted average number of Ordinary Shares in issue (millions)
 
1,265 
 
1,264 
* 2014 comparatives restated for reclassification of Externalisation revenue (see Note 1)

Condensed Consolidated Statement of Comprehensive Income
 
 
For the quarter ended 31 December
 
2015 
$m 
 
Restated 
2014*
$m 
Product sales
 
6,207 
 
6,683 
Externalisation revenue
 
192 
 
33 
Total revenue
 
6,399 
 
6,716 
Cost of sales
 
(1,269)
 
(1,667)
Gross profit
 
5,130 
 
5,049 
Distribution costs
 
(99)
 
(88)
Research and development expense
 
(1,746)
 
(1,499)
Selling, general and administrative costs
 
(2,668)
 
(4,084)
Other operating income and expense
 
471 
 
273 
Operating profit
 
1,088 
 
(349)
Finance income
 
13 
 
33 
Finance expense
 
(292)
 
(260)
Share of after tax losses of joint ventures
 
(7)
 
(4)
Profit before tax
 
802 
 
(580)
Taxation
 
 
259 
Profit for the period
 
808 
 
(321)
         
Other comprehensive income
       
Items that will not be reclassified to profit or loss
       
Remeasurement of the defined benefit pension liability
 
618 
 
(268)
Tax on items that will not be reclassified to profit or loss
 
(187)
 
89 
   
431 
 
(179)
Items that may be reclassified subsequently to profit or loss
       
Foreign exchange arising on consolidation
 
(169)
 
(411)
Foreign exchange arising on designating borrowings in net investment hedges
 
(11)
 
(237)
Fair value movements on derivatives designated in net investment hedges
 
(10)
 
64 
Net available for sale gains taken to equity
 
31 
 
172 
Tax on items that may be reclassified subsequently to profit or loss
 
 
20 
   
(156)
 
(392)
Other comprehensive income for the period, net of tax
 
275 
 
(571)
Total comprehensive income for the period
 
1,083 
 
(892)
         
Profit attributable to:
       
Owners of the Parent
 
808 
 
(321)
Non-controlling interests
 
 
   
808 
 
(321)
         
Total comprehensive income attributable to:
       
Owners of the Parent
 
1,083 
 
(892)
Non-controlling interests
 
 
   
1,083 
 
(892)
         
Basic earnings/(loss) per $0.25 Ordinary Share
 
$0.63 
 
($0.25)
Diluted earnings/(loss) per $0.25 Ordinary Share
 
$0.63 
 
($0.25)
Weighted average number of Ordinary Shares in issue (millions)
 
1,264 
 
1,263 
Diluted weighted average number of Ordinary Shares in issue (millions)
 
1,265 
 
1,265 
* 2014 comparatives restated for reclassification of Externalisation revenue (see Note 1)

Condensed Consolidated Statement of Financial Position
 
   
At 31 Dec
2015
$m
 
At 31 Dec 2014
$m
ASSETS
Non-current assets
       
Property, plant and equipment
 
6,413 
 
6,010 
Goodwill
 
11,868 
 
11,550 
Intangible assets
 
22,646 
 
20,981 
Derivative financial instruments
 
446 
 
465 
Investments in joint ventures
 
85 
 
59 
Other investments
 
458 
 
502 
Other receivables
 
907 
 
1,112 
Deferred tax assets
 
1,294 
 
1,219 
   
44,117 
 
41,898 
Current assets
       
Inventories
 
2,143