Collaboration revenue is expected to increase substantially, driven by success based milestones and certain anticipated transactions. Other operating income, on the other hand is anticipated to decrease substantially. Recall that in 2023, it included a one-off gain of around $700 million related to the renegotiated Beyfortus agreement and another $240 million related to the sale of [indiscernible 0:17:45] in the U.S. If FX rates for February to December were to remain at average rates seen in 2024 January, we anticipate a low single digit adverse FX impact on both revenue and core EPS in 2024. Cash flow from operating activities increased by $537 million in 2023. We continue to focus on improving our cash conversion and have already made significant progress in this area.
Deal payments amounted to approximately $4 billion of which nearly half related to past business development payments including milestone payments to Daiichi Sankyo. For this year, we again anticipate about $2 billion in deal payments relating to historical transactions. CapEx in 2023 was around $1.4 billion, in 2024 we anticipate a significant step up in CapEx, potentially in the 50% range driven by investments in new manufacturing capabilities such as API, inhaled product and cell therapy. Our net debt at the end of 2023 was $22.5 billion, and given very recent BD transactions, totaling about $2 billion, we anticipate this to remain at about the same level in 2024. With this in mind, our finance expense is expected to increase given the current interest rate environment.
Our net debt to adjusted EBITDA ratio is 1.6 times on the last 12-month basis. Our capital allocation priorities remain unchanged with our number 1 priority to reinvest in the business, both in the pipeline and behind new launches. We remain committed to keeping a strong investment-grade rating and we’ll continue to pursue value-enhancing business development transactions. Towards the end of last year, we announced a license agreement with EcoGen and the proposed acquisitions of icosavax and Gracell. Finally, we maintain our progressive dividend policy defined as either a stable or increasing dividend. With that, I will hand over to Dave.
David Fredrickson: Thanks, Aradhana. Really appreciate that. So oncology total revenues of $18.4 billion in the full year period grew 21% versus the prior year, and that was driven by strong global demand of our key medicines. Tagrisso global revenues grew 6% in the fourth quarter, reflecting strong double-digit growth for the U.S. and Europe. Performance in the quarter was partially offset by continued impact from the June 2023 mandatory price reduction in Japan, as well as expected impact from hospital ordering dynamics in China and a rebate reclassification in Australia. In the fourth quarter, Lynparza delivered 8% product sales growth and remains the leading PARP inhibitor globally despite ongoing class challenges. In the period, we recognized $245 million in regulatory milestones from Merck, following the U.S. PROPEL approval and BRCA-mutated prostate cancer.
Imfinzi, inclusive of IMJUDO grew 52% in the fourth quarter, fueled by further global demand growth in gastrointestinal tumors. In 2024, we expect continued progress with TOPAZ-1 and HIMALAYA, although TOPAZ-1 demand in the U.S. will moderate as the regimen is now established as the clear standard of care. In Japan, a 25% price reduction based on sales took effect in February of this year. An additional mandatory price reduction is anticipated later this year based on recent fixed dosing approvals. Calquence total revenues increased 14% in the fourth quarter, driven by continued new patient share gains across both frontline and relapsed/refractory CLL. In HER2 total revenues of $364 million in the fourth quarter increased 68% year-on-year. In the U.S. and Germany, we’re very encouraged by new patient share gains in the HER2-positive setting firmly establishing in HER2 is the undisputed standard of care across HER2-positive and HER2 low metastatic breast cancer.
In November of last year, we received approval for Truqap, our novel AKT inhibitor in the U.S. and for Imfinzi Topaz-1 in China. Importantly, we received a priority review designation for HER2 and HER2-expressing tumors an adjuvant use of Tagrisso was added for the first time to the NRDL in China at no discount. With the exciting approval of Truqap, we have the opportunity to further extend our leadership in breast cancer, including in the hormone receptor positive landscape. And HER2 is the established standard of care in late-line HER2 low, and we look forward to the results of the Destiny Breast 06 trial in the first half of this year and the opportunity to bring in HER2 1 line earlier and expand into HER2 ultra-low tumors. Data from the Tropion-BREST-01 trial of DATADx in hormone receptor positive HER2 low breast cancer was presented at ESMO last year during the presidential symposium.
Discussions with health authorities and prelaunch planning activities are already well underway. Finally, align with our ambition to establish a new endocrine therapy backbone, we now have several pivotal trials ongoing in the frontline for our next-generation oral SERD camizestrant, including in combination with CDK4/6 inhibitors and Truqap. Truqap is being very well received by the clinical community in the United States, and we are already seeing rapid adoption with the majority of new starts in patients with biomarker altered tumors, who have previously received a CDK4/6 inhibitor, which is consistent with our views of the addressable population. We see potential for Truqap to become the new standard of care in second line for endocrine treated patients with PIK3CA, AKT1 or P10 altered tumors.
And with that, we’ll advance to the next slide, and I’ll hand over to Susan to cover R&D highlights in the quarter.
Susan Galbraith: Thank you, Dave. In December, we entered into a definitive agreement to acquire Gracell technologies, which furthers our cell therapy ambition across oncology and autoimmune diseases. Gracell has a proprietary cell therapy manufacturing platform called FasTCAR. The FasTCAR platform has several key benefits. First, it significantly reduces the manufacturing time from between 1 and 3 weeks to 22 to 36 hours, with the opportunity to improve medium turnaround time and also enable increased manufacturing capacity as well as predictability of CAR-T delivery. Second, a lower dose of cells need to be manufactured for each patient, which reduces the risk of cytokine release syndrome, and that can improve the safety profile.
And third, the shorter manufacturing time delivers fitter T-cells, and this potentially improves the efficacy of this CAR-T. This proposed acquisition also enriches our growing pipeline of cell therapies with GC012F, a novel clinical stage dual BCMA and CD19 targeting autologous CAR-T. Phase 1 data were presented at the ASH meeting in December. In 22 patients with newly diagnosed high-risk multiple myeloma, the objective response rate was 100%, and we saw a minimal residual disease negativity rate between 95% and 100%, 6 to 12 months after infusion. This demonstrates the promise of this potential therapy when you move it into an earlier line setting. Safety was also favorable with only 27% of patients experiencing either grade 1 or 2 cytokine release syndrome and no grade 3 or above events.
Additionally, we did not see any neurological toxicity, which can be associated with this type of therapy. With a median follow-up time of 18.8 months median PFS and median duration of response had not been reached also highlighting the durability of the response. We believe that GC012F has potential applications across hematologic malignancies, including multiple myeloma and will further bolster our hematology pipeline, adding to Calquence AZD-0486, our CD19 CD3 next-generation bispecific T cell engager and AZD0305, our GPRC5D targeting antibody drug conjugate. We also have 2 further homegrown hematology molecules, which have just entered the clinic. A CD123 antibody drug conjugate, ASD-9829 and a PRMT5 inhibitor AZD3470. We look forward to updating you on our exciting hematology pipeline over the course of this year.
And with that, can you please advance to the next slide, and I’ll pass over to Ruud to cover biopharmaceuticals performance.
Ruud Dobber: Thank you so much, Susan. Biopharmaceuticals delivered total revenue of $18.4 billion in 2023 and driven by growth of 18% in CRM and 10% in RNI. Key highlights for the year included Farxiga nearing $6 billion in total revenue and R&I returning to double-digit growth. Turning now to the fourth quarter, where within R&I, nearly half of the total revenue came from Fasenra, Despres, Sanalla and Breztri. These medicines grew by a combined 40% and more than offsetting the impact of Symbicort generic entry. And in V&I, Beyfortus continued to see strong demand in its first RSV season, generating $95 million of product sales and alliance revenue for AstraZeneca in the quarter. Lastly, we received our first sales related milestone payments from Sanofi totaling $27 million.
We have recently launched 3 innovative new medicines within biopharmaceuticals. Launches in new areas of science and medicine require us to raise awareness among patients and practitioners and often to build additional sales forces, maximizing early momentum for these launch brands is critical to delivering on their full potential. Eplontersen is an amyloidosis treatment that we are developing in partnership with Ionis. In January, it launched with the brand-new Wainua for patients with ATTR polyneuropathy, a debilitating ultra-rare disease, which is generally fatal within a decade if left untreated. AirSupra is the first rescue medicine to reduce exacerbation and treat the underlying inflammation. And we have shown with the Mandela trial, a 28% reduction in the risk of severe asthma exacerbation in adult patients compared to albuterol.
