DUBLIN – Astrazeneca could garner as much as $400 million from a deal with Takeda Pharmaceutical Co. Ltd. to co-develop its preclinical alpha-synuclein-targeting antibody, MEDI-1341, which is slated to enter clinical development in Parkinson's disease before year-end. The headline value of the alliance covers an up-front payment as well as development and sales milestones.
London-based Astrazeneca will conduct the upcoming phase I study, but Osaka, Japan-based Takeda will lead clinical development thereafter. The two companies will share development and commercialization costs and will also split product sales, should they materialize.
Although it has a long track record in neuroscience, Astrazeneca has de-emphasized its focus on the area in recent years. It shuttered a major neuroscience R&D facility in Södertälje, Sweden, more than five years ago and has since identified five key growth areas: respiratory disease, cardiovascular and metabolic disease, Japan, emerging markets, and oncology. "Clearly, neuroscience falls outside our three main therapeutic areas," a company spokesman told BioWorld.
The present deal derisks a nonstrategic program therefore – it ensures that it will have the resources to progress without adding too much red ink to the company's balance sheet.
Astrazeneca and Takeda face plenty of competition. Alpha-synuclein has emerged as a popular target in Parkinson's disease, following the identification 20 years ago of mutations in the gene encoding the protein, which were associated with familial, autosomal dominant and early onset forms of the condition in a family of Italian descent, as well as in three unrelated Greek families. Subsequent work suggests that alpha-synuclein monomers fold into toxic oligomers or protofibrils, which disrupt neuronal function and lead to cell death.
Dublin-based Prothena Corp. and Basel, Switzerland-based Roche Holding AG are currently recruiting about 300 patients in a phase II trial of PRX-002 (RO-7046015). Cambridge, Mass.-based Biogen Inc. is conducting a phase I trial of BIIB-054, an alpha-synuclein-targeting antibody it acquired from Neurimmune Holding AG, of Schlieren, Switzerland. Bioarctic AB, of Stockholm, licensed a portfolio of antibodies against alpha-synuclein to North Chicago-based Abbvie Inc. last year. Lundbeck A/S and Genmab A/S are also collaborating on an antibody directed against alpha-synuclein, Lu-AF82422.
Astrazeneca said it believes MEDI-1341 has characteristics that could distinguish it from the field. "We have demonstrated target engagement in the CNS of the antibody in preclinical species – and shown that our antibody is able to prevent spreading of alpha-synuclein from neuron to neuron," the spokesman said. "We believe this is a key differentiating feature provided by the higher affinity of our antibody, which of course requires demonstration in clinical studies."
Several non-antibody-based approaches are also in train. Vienna-based Affiris AG is targeting alpha-synuclein with a vaccine, Affitope PD-03A, which recently completed a phase I trial. Brussels-based UCB SA entered an alliance with San Diego-based Neuropore Therapies Inc. to develop a small molecule, NPT-200-11, which stabilizes alpha-synuclein and prevents it from folding into toxic oligomers. It, too, has completed a phase I trial. Prana Biotechnology Ltd., of Parkville, Australia, is also working on a small-molecule approach. It recently published data on PBT-434, a quinazolinone in preclinical development, which blocks alpha-synuclein accumulation and also prevents neurodegeneration.
Commenting on the company's second-quarter results late last month, Astrazeneca's management characterized 2017 as a "defining year" for the company. In truth, it's been more of a mixed bag so far. Its mammoth deal with Kenilworth, N.J.-based Merck & Co. Inc., on its poly ADP ribose polymerase (PARP) inhibitor Lynparza (olaparib), which is worth $1.6 billion up front and up to $8.5 billion in total, coincided with the failure of a combination of its PD-L1 inhibitor Imfinzi (durvalumab) and its CTLA-4 inhibitor tremelimumab to demonstrate better efficacy than platinum-based standard-of-care chemotherapy in a phase III trial in metastatic non-small-cell lung cancer (NSCLC). While the setback did not spell the end of the road for Imfinzi, it did take the shine off the drug, one analyst noted. (See BioWorld Today, July 31, 2017.)
The prospect of Astrazeneca hitting its long-term strategic growth target of $45 million in annual revenue by 2023 is now looking increasingly remote – unless it were to move the goalposts by buying the additional growth through a large-scale M&A transaction. The company will miss a key interim growth milestone – restoring its 2013 revenues by 2017 – by a wide margin. It posted $10.5 billion for the first half of this year, having delivered $25.8 billion for the full year in 2013. Its sales, in fact, have continued on a downward trajectory, as new products have yet to compensate for the loss of exclusivity on old reliables such as the statin Crestor (rosuvastatin) and the atypical antipsychotic Seroquel XR (quetiapine fumarate). The total reached by the end of June was 11 percent down on the total reported for the same period last year.