AstraZeneca PLC American Society for Bone and Mineral Research (ASBMR) 2026 Annual Meeting

Thank you, operator. Good morning, good afternoon, and good evening, everyone. I am Marc Dunoyer, Chief Executive Officer at Alexion and Chief Strategy Officer at AstraZeneca. I would like to welcome you and thank you for joining us to hear about the efzimfotase alfa phase III program in patients with hypophosphatasia, or HPP, including the HICKORY data presented yesterday at the 2026 American Society for Bone and Mineral Research in Boston. As always, the materials presented today will be published on the AstraZeneca investors relation website following this presentation. Next slide, please. Here are our usual forward-looking statement, which I encourage you to read. Next slide, please. This is the agenda for today's call. We are delighted to be joined by Dr. Raja Padidela, Consultant Paediatric Endocrinologist in metabolic bone diseases at Royal Manchester Children's Hospital, who will walk us through the phase III HICKORY data presented at ASBMR.

Next slide, please. Before we discuss the data, I want to remind everyone of AstraZeneca's broader ambition and the role our rare disease portfolio plays in delivering our ambition. I will also cover our strategy contributes not only to 2030, but well beyond. With this, next slide. This slide captures how we think about growth today, preparing for tomorrow, and investing for the day after. Over the past two years, we have continued to deliver strong commercial performance and substantial pipeline progress, further strengthening our confidence in sustained growth through 2030 and beyond. Rare disease remains an important contributor to our outlook. We will drive growth through new launches, such as Ultomiris in IgAN and Klygefa in gMG, while advancing a pipeline of pioneering medicines, including efzimfotase alfa, which we will discuss in more detail today.

In addition to the efzimfotase alfa data, we expect several high-value catalysts across our biopharmaceuticals and oncology therapy areas over the next 12 to 18 months, reinforcing the breadth of our pipeline and confidence in the durability of our long-term growth outlook. Next slide. We view rare disease as one of the healthcare's greatest areas of unmet need, defined by delayed diagnosis, limited scientific understanding, and the absence of approved therapies for most conditions. We believe these gaps require a pioneering approach to innovation, combining novel science, new modalities, advanced diagnosis, and close partnership with patients to develop transformative medicine where few or no treatment options exist. Next slide. Against this backdrop of significant unmet need, we focus our expertise across five disease areas where we believe we can make the greatest difference.

Across each, we are pursuing medicines with the potential to be first or best in class or meaningfully change outcome for patients. Today, we are focusing on efzimfotase alfa, one of the leading assets within our bone and endocrine disorders portfolio. To provide some context, Gianluca will first introduce HPP, discuss the significant burden this disease places on patients, and provide an overview of the global phase III program. Dr. Raja Padidela will then walk us through the HICKORY phase III data presented at ASBMR and share his perspective on the potential implications for patients living with HPP. Next slide. With this, over to you, Gianluca.

Thank you, Marc. I'm Gianluca Pirozzi, the Head of Development, Rare Disease, and Safety at Alexion. HPP is a rare inherited lifelong disease caused by deficient alkaline phosphatase activity, affecting patients at all ages. The disease is heterogeneous and multisystemic, with a range of skeletal and functional manifestations significantly impacting quality of life. In its perinatal and infantile forms, HPP can be life-threatening and is often fatal before age 2 without treatment. In children, rickets, impaired growth, deformities, and fractures can affect development throughout life. Adult patients with HPP, their disease is generally milder, but it's far from benign. They may experience slow-healing fractures, tooth loss, chronic pain, muscle weakness, fatigue, and progressive disability, all of which can affect work, independence, and daily activities. Next slide, please. Efzimfotase alfa is a great example of patient-centered innovation, a second-generation enzyme replacement therapy developed from more than a decade of experience with Strensiq.

Both medicines replace the deficient alkaline phosphatase enzyme, but efzimfotase alfa has four key differences to reduce treatment burden, improve tolerability, and support broader patient access. It has enhanced enzyme activity, allowing for a similar effect as Strensiq, but a lower simple weight-banded dosing regimen with a smaller injection volume. Its optimized Fc design reduces off-target interactions, while enhanced glycosylation extends the mean half-life to around 6 days, supporting dosing once every 2 weeks rather than 3 to 6 times per week as per Strensiq. Finally, an optimized manufacturing process improves production efficiency and reduces wastage, supporting broader global access. Next slide, please. The efzimfotase alfa development program was intentionally designed to capture all patients living with HPP.

Recognizing that pain and fatigue are among the most prevalent symptoms experienced by patients, the program expanded beyond traditional skeletal endpoints to evaluate outcomes that directly affect daily functioning and quality of life. The phase III program enrolled 196 patients across 22 countries, representing the largest clinical program in HPP to date. Importantly, it was the first to include patients with adult-onset disease and those without skeletal manifestation, using tailored endpoints to generate data that reflects all patients living with HPP. The program includes treatment-naive children in MULBERRY, children transitioning from Strensiq in CHESTNUT, and treatment-naive adolescents and adults in HICKORY. Next slide, please. These slides provide a recap of results from MULBERRY and CHESTNUT pediatric studies, which were presented at ICCBH in June.

While today's discussion is focused on HICKORY data presented at ASBMR, it is important to consider these results within the context of the broader phase III program. In MULBERRY, efzimfotase alfa demonstrated statistically significant and clinically meaningful improvement in bone. At week 25, the median Radiographic Global Impression of Change score was +1.67 versus zero with placebo, with a P value of 0.0003. The Rickets Severity Score confirms significant improvement, showing substantial rickets healing within six months, while placebo-treated children showed no change. Importantly, MULBERRY also evaluated outcome beyond bone health alone, demonstrating improvements in physical function, motor proficiency, and quality of life, providing evidence of the broad and clinically meaningful treatment effect. CHESTNUT investigated the safety switching between two enzyme replacement therapies. Adverse events were comparable between children who switched to efzimfotase alfa and those who remained on Strensiq.

Clinical benefits were maintained across bone health, physical functions, and quality of life. Taken together, these studies provide important evidence supporting the potential of efzimfotase alfa across all pediatric patients with HPP. With that context, I'll now hand it over to Dr. Raja Padidela, who will walk through the HICKORY data presented yesterday.