Asfotase alpha

CAMBRIDGE, United Kingdom--( BUSINESS WIRE )--AstraZeneca: Revenue and EPS summary H1 2024 % Change Q2 2024 % Change $m Actual CER $m Actual CER - Product Sales 24,629 15 18 12,452 14 18 - Alliance Revenue 939 50 50 482 42 42 - Collaboration Revenue 49 (78) (78) 4 (98) (98) Total Revenue 25,617 15 18 12,938 13 17 Reported EPS $2.65 13 23 $1.24 6 15 Core 2 EPS $4.03 (1) 5 $1.98 (8) (3) Financial performance for H1 2024 (Growth numbers at constant exchange rates) Total Revenue up 18% to $25,617m, driven by an 18% increase in Product Sales and continued growth in Alliance Revenue from partnered medicines Total Revenue growth from Oncology was 22%, CVRM 22%, R&I 22%, and Rare Disease 15% Core Product Sales Gross Margin 3 of 82% Core Operating Margin of 33% Core Tax Rate of 20% Core EPS increased 5% to $4.03. The increase in Core EPS was lower than Total Revenue growth principally due to gains recognised in the prior year, specifically a $241m gain on the disposal of Pulmicort Flexhaler US rights (Q1 2023), and a $712m gain relating to updates to contractual arrangements for Beyfortus (Q2 2023) Interim dividend increased 7c to $1.00 (77.6 pence, 10.79 SEK) has been declared Guidance for FY 2024 increased, with Total Revenue and Core EPS anticipated to grow by a mid teens percentage at CER (previously a low double-digit to low teens percentage). An increase in Collaboration Revenue is not assumed in the upgraded guidance Pascal Soriot, Chief Executive Officer, AstraZeneca, said: “ Building on our strong growth in the first half of the year and continued underlying demand for our medicines we are upgrading our FY 2024 guidance for both Total Revenue and Core EPS. At our Investor Day in May we set out a new revenue ambition to deliver $80 billion of Total Revenue by 2030. This is a clear reflection of the substantial growth potential we see from both our approved medicines and those in our late-stage pipeline. Already this year we have announced five positive, potentially practice-changing Phase III studies that are anticipated to meaningfully contribute to our growth. In the year to date we have continued to make encouraging progress with several disruptive technologies, including antibody drug conjugates, bispecifics, cell and gene therapies, radioconjugates, and weight management medicines, all of which have the potential to drive our growth beyond 2030.” Key milestones achieved since the prior results announcement Positive read-outs for Imfinzi in combination with chemotherapy in muscle-invasive bladder cancer (NIAGARA), Calquence in untreated mantle cell lymphoma (ECHO), Enhertu in HR-positive, HER2-low metastatic breast cancer (DESTINY-Breast06) US approvals for Imfinzi in combination with chemotherapy followed by Imfinzi monotherapy for primary advanced or recurrent endometrial cancer that is mismatch repair deficient (DUO-E). EU approvals for Truqap in combination with Faslodex for biomarker-positive estrogen receptor-positive, HER2‑negative advanced breast cancer (CAPItello-291), Tagrisso with the addition of chemotherapy for 1st‑line EGFR m NSCLC (FLAURA2). Japan and China approvals for Tagrisso with the addition of chemotherapy for the 1st­­‑line EGFR m NSCLC (FLAURA2) Guidance Due to strong underlying growth in Product Sales and Alliance Revenue, the Company raises its Total Revenue and Core EPS guidance for FY 2024 at CER, based on the average foreign exchange rates through 2023. Total Revenue is expected to increase by a mid teens percentage (previously a low double-digit to low teens percentage) Core EPS is expected to increase by a mid teens percentage (previously a low double-digit to low teens percentage) An increase in Collaboration Revenue is not assumed in the upgraded guidance (previously assumed a substantial increase) Other operating income is expected to decrease substantially (FY 2023 included a $241m gain on the disposal of Pulmicort Flexhaler US rights, and a $712m one-time gain relating to updates to contractual arrangements for Beyfortus ) The Core Tax rate is expected to be between 18-22% The Company is unable to provide guidance on a Reported basis because it cannot reliably forecast material elements of the Reported results, including any fair value adjustments arising on acquisition-related liabilities, intangible asset impairment charges and legal settlement provisions. Please refer to the cautionary statements section regarding forward-looking statements at the end of this announcement. Currency impact If foreign exchange rates for July 2024 to December 2024 were to remain at the average rates seen in June 2024, it is anticipated that FY 2024 Total Revenue would incur a low single-digit percentage adverse impact compared to the performance at CER, and Core EPS would incur a mid single-digit percentage adverse impact. The Company’s foreign exchange rate sensitivity analysis is provided in Table 17. Table 1: Key elements of Total Revenue performance in Q2 2024 % Change Revenue type $m Actual % CER % Product Sales 12,452 14 18 Alliance Revenue 482 42 42 • $344m Enhertu (Q2 2023: $255m) • $104m Tezspire (Q2 2023: $62m) Collaboration Revenue 4 (98) (98) • Q2 2023 included $180m for COVID-19 mAbs Total Revenue 12,938 13 17 Therapy areas $m Actual % CER % Oncology 5,331 15 19 • Tagrisso up 8% (12% at CER) due to strong global demand, Calquence up 21% (22% at CER) with sustained leadership in 1L CLL. Enhertu Total Revenue up 46% (49% at CER) CVRM 3,160 18 22 • Farxiga up 29% (32% at CER) , Lokelma up 36% (41% at CER) R&I 1,905 23 26 • Breztri up 44% (47% at CER). Saphnelo up 65%, Tezspire up 97% (>2x at CER), Symbicort up 20% (25% CER) V&I 119 (57) (53) • The drop in V&I revenue was primarily driven by lower Collaboration Revenue from COVID-19 mAbs • Beyfortus revenue was $35m (Q2 2023: $2m), which more than offset a $6m decline in Synagis Rare Disease 2,147 10 14 • Ultomiris up 33% (36% at CER), partially offset by decline in Soliris of 14% (8% at CER) • Strensiq up 13% (14% at CER) and Koselugo up 43% (45% at CER) Other Medicines 276 (11) (5) Total Revenue 12,938 13 17 Regions $m Actual % CER % US 5,571 17 17 Emerging Markets 3,386 9 18 - China 1,630 13 18 - Ex-China Emerging Markets 1,756 5 18 Europe 2,732 24 24 Established RoW 1,249 (5) 6 Total Revenue 12,938 13 17 Key partnered medicines Combined sales of Enhertu , recorded by Daiichi Sankyo Company Limited (Daiichi Sankyo) and AstraZeneca, amounted $1,772m in H1 2024 (H1 2023: $1,169m). Combined sales of Tezspire , recorded by Amgen and AstraZeneca, amounted to $507m in H1 2024 (H1 2023: $257m). Table 2: Key elements of financial performance in Q2 2024 Metric Reported Reported change Core Core change Comments 4 Total Revenue $12,938m 13% Actual 17% CER $12,938m 13% Actual 17% CER • See Table 1 and the Total Revenue section of this document for further details Product Sales Gross Margin 82% Stable Actual Stable CER 83% Stable Actual Stable CER • Variations in Product Sales Gross Margin can be expected between periods due to product seasonality (e.g. FluMist and Beyfortus in H2), foreign exchange fluctuations and other effects R&D expense $3,008m 13% Actual 13% CER $2,872m 12% Actual 13% CER + Increased investment in the pipeline • Core R&D-to-Total Revenue ratio of 22% (Q2 2023: 22%) SG&A expense $4,929m -1% Actual 1% CER $3,735m 13% Actual 16% CER + Market development for recent launches and pre-launch activities • Core SG&A-to-Total Revenue ratio of 29% (Q2 2023: 29%) Other operating income and expense 5 $60m -92% Actual -92% CER $60m -92% Actual -92% CER ‒The prior year quarter included a $712m gain relating to updates to contractual arrangements for Beyfortus Operating Margin 21% Stable Actual +1pp CER 32% -6pp Actual -5pp CER • See commentary above on Gross Margin, R&D, SG&A and Other operating income and expense Net finance expense $343m -7% Actual -7% CER $285m 10% Actual 10% CER + Higher level of Net debt Tax rate 20% +7pp Actual +7pp CER 19% +2pp Actual +2pp CER • Variations in the tax rate can be expected between periods EPS $1.24 6% Actual 15% CER $1.98 -8% Actual -3% CER • Further details of differences between Reported and Core are shown in Table 12 Table 3: Pipeline highlights since prior results announcement Event Medicine Indication / Trial Event Regulatory approvals and other regulatory actions Imfinzi Primary advanced or recurrent endometrial cancer with mismatch repair deficiency (DUO-E) Regulatory approval (US), CHMP positive opinion (EU) Imfinzi + Lynparza Primary advanced or recurrent endometrial cancer with mismatch repair proficiency (DUO-E) CHMP positive opinion (EU) Tagrisso EGFR m NSCLC (1st-line) (FLAURA2) Regulatory approval (EU, JP, CN) Truqap Biomarker-positive ER-positive HER2-negative locally advanced or metastatic breast cancer (CAPItello-291) Regulatory approval (EU) Regulatory submissions or acceptances* Tagrisso EGFR m NSCLC (Stage III unresectable) (LAURA) sNDA acceptance and Priority Review (US) Dato-DXd Non-squamous NSCLC (2nd- and 3rd-line) (TROPION-Lung01) Regulatory submission (EU) sipavibart Prevention of COVID-19 (SUPERNOVA) Regulatory submission (EU) Major Phase III data readouts and other developments Calquence Mantle cell lymphoma (1st‑line) (ECHO) Primary endpoint met Dato-DXd Locally advanced or metastatic NSCLC (TROPION-Lung01) Dual primary endpoint OS not met in the intention to treat population Enhertu HER2-low breast cancer (2nd-line) (DESTINY-Breast-06) Primary endpoint met Imfinzi Muscle-invasive bladder cancer (NIAGARA) Primary endpoint met Imfinzi Adjuvant use in early-stage PD-L1 ≥25% NSCLC (Adjuvant BR.31) Primary endpoint not met Truqap Locally advanced or metastatic TNBC (CAPItello-290) Primary endpoint not met sipavibart Prevention of COVID-19 (SUPERNOVA) Primary endpoint met *US, EU and China regulatory submission denotes filing acceptance Upcoming pipeline catalysts For recent trial starts and anticipated timings of key trial readouts, please refer to the Clinical Trials Appendix, available on www.astrazeneca.com/investor-relations.html . Corporate and business development In May 2024, AstraZeneca announced its intention to build a $1.5 billion manufacturing facility in Singapore for antibody drug conjugates (ADCs), enhancing global supply of its ADC portfolio. ADCs are next-generation treatments that deliver highly potent cancer-killing agents directly to cancer cells through a targeted antibody. The planned greenfield facility, supported by the Singapore Economic Development Board, will be AstraZeneca’s first end-to-end ADC production site, fully incorporating all steps of the manufacturing process at a commercial scale. Manufacturing of ADCs is a multi-step process that comprises antibody production, synthesis of chemotherapy drug and linker, conjugation of drug-linker to the antibody, and filling of the completed ADC substance. In May 2024, AstraZeneca completed an additional $140m equity investment in Cellectis, a clinical-stage biotechnology company. The equity investment and a research collaboration agreement, announced in November 2023, will leverage the Cellectis proprietary gene editing technologies and manufacturing capabilities, to design up to 10 novel cell and gene therapy products for areas of high unmet need, including oncology, immunology and rare diseases. In Q4 2023, Cellectis received an initial payment of $105m from AstraZeneca, which comprised a $25m upfront cash payment under the terms of a research collaboration agreement and an $80m equity investment. Now that the additional $140m equity investment has closed, AstraZeneca holds a total equity stake of c.44% in Cellectis and AstraZeneca continues to treat its investment in Cellectis as an associate. In June 2024, AstraZeneca completed the acquisition of Fusion Pharmaceuticals Inc., a clinical-stage biopharmaceutical company developing next-generation radioconjugates. The acquisition marks a major step forward in AstraZeneca delivering on its ambition to transform cancer treatment and outcomes for patients by replacing traditional regimens like chemotherapy and radiotherapy with more targeted treatments. The acquisition complements AstraZeneca’s leading oncology portfolio with the addition of the Fusion pipeline of radioconjugates, including FPI-2265, a potential new treatment for patients with mCRPC, and brings new expertise and pioneering R&D, manufacturing and supply chain capabilities in actinium-based radioconjugates to AstraZeneca. See Note 5 for further information. In July 2024, AstraZeneca completed the acquisition of Amolyt Pharma, a clinical-stage biotechnology company focused on developing novel treatments for rare endocrine diseases. The acquisition bolsters the Alexion, AstraZeneca Rare Disease late-stage pipeline and expands on its bone metabolism franchise with the notable addition of eneboparatide (AZP-3601), a Phase III investigational therapeutic peptide with a novel mechanism of action designed to meet key therapeutic goals for hypoparathyroidism. In patients with hypoparathyroidism, a deficiency in parathyroid hormone production results in significant dysregulation of calcium and phosphate, which can lead to life-altering symptoms and complications, including chronic kidney disease. See Note 7 for further information. Sustainability highlights At the 77th World Health Assembly in Geneva, Switzerland in May, AstraZeneca convened Ministers of Health, industry, civil society and patient groups. Areas of focus for engagement, led by Ruud Dobber, EVP BioPharmaceuticals, included the need to increase early action to prevent, diagnose and treat disease and to accelerate collaboration to build resilient, equitable and net zero health systems. Conference call A conference call and webcast for investors and analysts will begin today, 25 July 2024, at 11:45 UK time. Details can be accessed via astrazeneca.com . Reporting calendar The Company intends to publish its 9M and Q3 2024 results on 12 November 2024. To read AstraZeneca's H1 and Q2 2024 Financial Results press release in full including the glossary, please click here . 1 Constant exchange rates. The differences between Actual Change and CER Change are due to foreign exchange movements between periods in 2024 vs. 2023. CER financial measures are not accounted for according to generally accepted accounting principles (GAAP) because they remove the effects of currency movements from Reported results. 2 Core financial measures are adjusted to exclude certain items. The differences between Reported and Core measures are primarily due to costs relating to the amortisation of intangibles, impairments, legal settlements and restructuring charges. A full reconciliation between Reported EPS and Core EPS is provided in Table 11 and Table 12 in the Financial performance section of this document. 3 The calculations for Reported and Core Product Sales Gross Margin exclude the impact of Alliance Revenue and Collaboration Revenue. 4 In Table 2, the plus and minus symbols denote the directional impact of the item being discussed, e.g. a ‘+’ symbol next to a comment related to the R&D expense indicates that the item resulted in an increase in the R&D spend relative to the prior year. 5 Income from disposals of assets and businesses, where the Group does not retain a significant ongoing economic interest, continue to be recorded in Other operating income and expense in the Company’s financial statements.

Preclinical research demonstrates that CRISPR/Cas9-based precision B cell gene engineering coupled with artificial intelligence-guided protein design produces active tissue-nonspecific alkaline phosphatase (“ALP”) Data presented at American Society of Gene & Cell Therapy 27th Annual Meeting CAMBRIDGE, Mass.--(BUSINESS WIRE)-- Be Biopharma, Inc. (“Be Bio”), a company pioneering the discovery and development of Engineered B Cell Medicines (BCMs), today presented results from new preclinical research demonstrating production of active ALP by a BCM, which highlights BCMs as a potential treatment for Hypophosphatasia (HPP). Researchers used CRISPR/Cas9 precision gene engineering and artificial intelligence-guided protein design to modify primary human B cells to produce ALP, an enzyme deficient in people living with HPP. The findings were presented during a poster presentation at the American Society of Gene & Cell Therapy (ASGCT) 27th Annual Meeting on Friday, May 10, at 12:00pm ET. HPP is a rare genetic disease caused by loss of function mutations in the ALPL gene which leads to deficient ALP activity. People living with HPP can experience wide ranging systemic complications, with impaired bone mineralization, such as rickets/osteomalacia, being a major clinical hallmark of severe disease. The only approved therapy for HPP is an enzyme replacement therapy, asfotase alfa, which requires multiple injections every week and is approved only for use in patients with pediatric-onset forms of HPP. “This study demonstrates how BCMs coupled with artificial intelligence-guided protein design broaden the potential of our medicines to express highly effective conjugated therapeutic proteins such as ALP-Fc fusion proteins,” said Rick Morgan, Chief Scientific Officer. “BCMs are designed to provide constant and durable protein levels without preconditioning, are redosable, and can be applied to a wide range of diseases, including a potential first-in-class medicine for people living with HPP.” In this study, primary human B cells were expanded and precision engineered by CRISPR/Cas9 genome editing with AAV-mediated homology directed repair (HDR) to insert an ALP gene expression cassette into various loci, including CCR5 (a safe harbor locus). Guided by an artificial intelligence-based ALP protein structure design engine, protein constructs were optimized for activity and stability of ALP-Fc fusion proteins. Engineered BCMs secreted active ALP proteins up to 200 ng/1e6 cells/24hr. Robust in vitro phenotypic correction using ALP secreting BCMs (ALP-BCMs) was demonstrated in the MC3T3 osteoblast precursor mineralization model. About Engineered B Cell Medicines – A New Class of Cellular Medicines The B cell is a powerful cell that produces thousands of proteins per cell per second at constant levels, and over decades. Precision genome editing can now be used to engineer B Cells that produce therapeutic proteins of interest, driving a new class of cellular medicines – Engineered B Cell Medicines (BCMs) – with the potential to be durable, allogeneic, redosable, and administered without pre-conditioning. The promise of BCMs could transform therapeutic biologics with broad application — across protein classes, patient populations and therapeutic areas. About Be Biopharma Be Biopharma (“Be Bio”) is pioneering Engineered B Cell Medicines (BCMs) to dramatically improve the lives of patients who are living with Hemophilia B and other genetic diseases, cancer, and other serious conditions. With eyes locked on the patient, our team of purpose-driven scientists, technologists, manufacturing experts and business builders collaborate to create a bold new class of cell therapies. Be Bio was founded in October 2020 by B cell engineering pioneers David Rawlings, M.D., and Richard James, Ph.D., from Seattle Children’s Research Institute. Be Bio is backed by ARCH Venture Partners, Atlas Venture, RA Capital Management, Alta Partners, Longwood Fund, Bristol Myers Squibb, Takeda Ventures, Seattle Children’s Research Institute and others. Since our founding, Be Bio’s investors have committed over $180 million to enable the Company to re-imagine medicine based on the power of B cell therapy. For more information, please visit us at Be.Bio and our LinkedIn page. View source version on businesswire.com: Contacts Investors: ir@be.bio Media: media@be.bio Source: Be Biopharma, Inc. View this news release online at: