Transaction includes late-stage, potential best-in-class irreversible small molecule BTK inhibitor, acalabrutinib
Opportunity for first regulatory submissions in haematological malignancies in 2016
Investment establishes in-house expertise in blood cancers and complements strategic use of immunotherapy in haematological malignancies and solid tumours
AstraZeneca announced that it has entered into an agreement to invest in a majority equity stake in Acerta Pharma, a privately-owned biopharmaceutical company based in the Netherlands and US. The transaction provides AstraZeneca with a potential best-in-class irreversible oral Bruton's tyrosine kinase (BTK) inhibitor, acalabrutinib (ACP-196), currently in Phase III development for B-cell blood cancers and in Phase I/II clinical trials in multiple solid tumours.
Pascal Soriot, Chief Executive Officer of AstraZeneca, said: “The investment is consistent with our focus on long-term growth and reflects the role targeted business development plays in our business model. We are boosting a key area in our comprehensive oncology portfolio with a late-stage, potential best-in-class medicine that could transform treatment for patients across a range of blood cancers.”
“Acalabrutinib provides us with a small molecule presence in blood cancers to complement our existing immunotherapy approach, in collaboration with Celgene in haematological malignancies. Furthermore, we look forward to working closely with the Acerta team and benefiting from the considerable clinical expertise they bring in this complex area of medicine.”
Under the terms of the agreement, AstraZeneca will acquire 55% of the entire issued share capital of Acerta for an upfront payment of $2.5 billion. A further unconditional payment of $1.5 billion will be paid either on receipt of the first regulatory approval for acalabrutinib for any indication in the US, or the end of 2018, depending on which is first. 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. The options can be exercised at various points in time, conditional on the first approval of acalabrutinib in both the US and Europe and when the extent of the commercial opportunity has been fully established, at a price of approximately $3 billion net of certain costs and payments incurred by AstraZeneca and net of agreed future adjusting items, using a pre-agreed pricing mechanism.
An extensive development programme is underway for acalabrutinib with the opportunity for initial regulatory submissions in the second half of 2016 for the treatment of patients with specific types of haematological malignancies. Expanding further into B-cell cancers, acalabrutinib is estimated to reach potential peak-year sales in excess of $5 billion globally. AstraZeneca will also benefit from the substantial expertise in haematological cancers offered by Acerta’s approximately 150 employees.
The BTK inhibitor class is transforming the treatment of B-cell blood cancers, allowing a potentially more effective treatment option with limited side effects, replacing current chemotherapy and antibody-containing regimens. Acalabrutinib is a highly selective, irreversible, next-generation small molecule oral BTK inhibitor supported by strong clinical evidence, with approximately 1,000 patients treated to date, of whom more than 600 were on the potential medicine as monotherapy. Data indicate that acalabrutinib offers enhanced BTK inhibition. Phase I/II data presented at the recent American Society of Haematology Annual Meeting 2015 showed a 95% response rate in patients with relapsed chronic lymphocytic leukaemia, the most prevalent form of adult leukaemia, and a 100% overall response rate in the difficult-to-treat 17p deletion patients1.
In addition, acalabrutinib has the potential to address an unmet medical need for patients who are intolerant to or unsuitable for first generation BTK inhibitor treatment. Currently 20-30% of patients discontinue first-generation therapy due to tolerability issues2.
John C. Byrd MD, Professor and Director, Division of Haematology, Department of Medicine, at The Ohio State University School of Medicine, said: “The BTK inhibitor class has been transformational in the management of B-cell cancers but a portion of patients treated with ibrutinib (the first generation BTK inhibitor), can’t tolerate the side effects and sadly discontinue their treatment. The acalabrutinib data are highly encouraging as they show that high selectivity, a short half-life and an optimised dosing schedule result in very high efficacy and a significantly better tolerability profile with very low discontinuation rates. Acalabrutinib may potentially offer improved long-term benefit over other options available for these patients.”
In addition to blood cancers, acalabrutinib is currently being explored in Phase I/II studies in combination with immunotherapy or chemotherapies in a range of solid tumours. Pre-clinical data show that acalabrutinib has an immune-modulatory effect that, as monotherapy and alongside PD-1/PD-L1 antibodies, has the potential to enhance anti-tumour activity.
Acerta will initially be a majority owned subsidiary of AstraZeneca; if AstraZeneca acquires the remaining shares of the company in the future, Acerta would become a wholly-owned subsidiary. The transaction will be accounted for as a business combination and is expected to complete by the end of the first quarter of 2016, subject to customary closing conditions. The initial acquisition payment of $2.5 billion will be funded from cash and debt. The agreement is expected to be moderately dilutive to AstraZeneca’s core earnings in the near term.
For the purposes of the UK Listing Authority’s Listing Rule LR 10.4.1 R (Notification of class 2 transactions), the fair value of gross assets acquired with the transaction is estimated to be $5.7 billion and, in view of the development phase of the medicine, a pre-tax loss of $80 million was attributable to Acerta during the year to 31 December 2014.
Full Year 2016 guidance is expected to be provided at Full Year 2015 results on 4 February 2016.