On December 17, 2015 AstraZeneca reported 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 (Press release, AstraZeneca, DEC 17, 2015, View Source [SID:1234508592]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

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.

On December 17, 2015 Medigene AG (MDG1, Frankfurt, Prime Standard), a clinical stage immunotherapy company focussing on the development of T-cell therapy platforms for the treatment of cancer, and SynCore Biotechnology Co. Ltd., Taiwan, reported that they signed an asset purchase agreement for the complete transfer of EndoTAG to SynCore, replacing and terminating the license agreement from May 2013 (Press release, MediGene, DEC 17, 2015, View Source [SID:1234508589]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Within the framework of the agreement and in addition to licensing payments and proceeds from issued Medigene shares totalling EUR 6.3 m already received, Medigene will receive a payment of EUR 5m from SynCore to be paid in five annual instalments. Moreover, Medigene is eligible to milestone payments and royalties for EndoTAG-1.

The transfer of rights (closing) will take place early 2016, when the first instalment will be paid. Therefore, the agreement will have no impact on Medigene’s financial guidance for 2015.

Dr Frank Mathias, CEO of Medigene, comments: "The complete transfer of EndoTAG is a consequent step in our portfolio strategy and enables Medigene to further focus on its core business of immuno-oncology. We will use freed up resources for the clinical development of our innovative immunotherapy platforms."

Dr Muh-Hwan Su, General Manager of SynCore Biotechnology: "The new agreement provides a win-win situation for both partners and enables SynCore to act independently in the further development of the drug candidate and to fully exploit the value of EndoTAG."

About EndoTAG: EndoTAG is a novel composition of neutral and positive lipids. Loaded with the established cytostatic drug Paclitaxel, EndoTAG builds the drug candidate EndoTAG-1. Due to the positive charge, EndoTAG-1 interacts with newly formed, negatively charged endothelial cells, which are specifically required for the growth of tumour blood vessels. The EndoTAG-1 paclitaxel component attacks the activated endothelial cells as they divide, thus targeting the blood supply to tumours without affecting endothelial cells of healthy tissues. By doing this, EndoTAG-1 is expected to prevent the formation of new tumour blood vessels and to inhibit tumour growth.

On December 16, 2015 Aduro Biotech, Inc. (Nasdaq:ADRO) reported that it has received a milestone payment from Janssen Biotech, Inc. for the acceptance of an Investigational New Drug (IND) Application by the U.S. Food and Drug Administration for ADU-741, a LADD immunotherapy product candidate for the treatment of prostate cancer (Press release, Aduro BioTech, DEC 16, 2015, View Source [SID:1234508586]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Janssen, Aduro’s license partner for ADU-741, plans to initiate a multi-center Phase 1 trial to evaluate the safety and immunogenicity of intravenous administration of ADU-741 by the end of 2015.

"We are extremely pleased with the progress Janssen has made with the development of ADU-741," said Stephen T. Isaacs, chairman, president and chief executive officer of Aduro. "In addition to FDA acceptance of INDs for ADU-741 and ADU-214 in the past two months, we recently received clearance from the FDA for our IND in which we are collaborating with Incyte to begin a clinical trial evaluating the combination of CRS-207 and epacadostat in patients with platinum-resistant ovarian, fallopian and peritoneal cancer. We are thrilled to work with top-notch collaborators like Janssen, Novartis and Incyte, which share the same dedication to the development of novel therapies for patients who need it the most."

In May 2014, Aduro entered into an agreement granting Janssen an exclusive, worldwide license to certain product candidates specifically engineered for the treatment of prostate cancer based on its novel LADD immunotherapy platform. Under the agreement facilitated by Johnson & Johnson Innovation, Aduro received an upfront payment, milestone payments associated with both the submission and the acceptance of the IND, and is eligible to receive future development, regulatory and commercialization milestone payments up to a potential total of $345.5 million. In addition, Aduro is eligible to receive royalties on worldwide net sales upon successful launch and commercialization.

About LADD

LADD is Aduro’s proprietary platform of live-attenuated double-deleted Listeria monocytogenes strains that have been engineered to induce a potent innate immune response and to express tumor-associated antigens to induce tumor-specific T cell-mediated immunity. The LADD technology has been applied to several novel compounds in clinical and preclinical testing including CRS-207 (pancreatic cancer, mesothelioma and ovarian/fallopian/peritoneal cancer (collaboration with Incyte Corporation to be tested in combination with epacadostat)), ADU-623 (brain cancer), ADU-214 (lung cancer, licensed to Janssen Biotech, Inc.) and ADU-741 (prostate cancer, licensed to Janssen Biotech, Inc.).