AZ taps Orca for oral T cell inhibitors

AstraZeneca (AZ) has forged an R&D alliance with Orca Pharmaceuticals focusing on the development of a new class of compound with potential in autoimmune disease therapy.

UK-based Orca was formed in 2013 to concentrate on the development of inhibitors of retinoic acid-related orphan nuclear receptor (ROR) gamma, a target that plays a role in the activation of pro-inflammatory T cells.

In particular, the receptor is thought to be involved in the creation of a subset of T helper cells that are involved in the production of interleukin-17 (IL-17), a cytokine that is being targeted by a new generation of biologic anti-inflammatory drugs including Novartis’ Cosentyx (secukinumab), which was approved in Europe last month.

Orca’s ROR gamma inhibitors are small molecules and so could form the basis of an orally-active therapy acting via the IL-17 pathway and inhibiting the T cells subset, known as TH17. The pathway has been implicated in a number of autoimmune conditions, including inflammatory bowel disease, psoriasis, arthritis and multiple sclerosis.

AZ’s head of respiratory, inflammation and autoimmune disease R&D, Dr Maarten Kraan, said the collaboration could lead to the development of “potentially best-in-class candidate drugs for patients who currently do not have any oral medicines available to treat their chronic conditions”.

Under the terms of the agreement, AZ will get access to ROR gammainhibitors developed by Orca and will integrate them into its in-house programme, while scientists from the two firms will work together on the candidates.

AZ has the option to acquire the Orca compounds outright at the end of the collaboration, which will last for three years in the first instance.

While still in the early stages of development, a number of other companies are working on ROR gamma as a drug target and there have been several licensing deals in the last few years.

These include Merck & Co’s $300 million collaboration with Lycera signed in 2011 – which was doubled to $600 million in 2013 – as well as alliances involving Exelixis/Bristol-Myers Squibb, Orphagen/Japan Tobacco, Pfizer/Karo Bio and Johnson & Johnson/Phenex Pharma.

Last week, Sanofi threw its hat into the ROR gamma ring after signing a licensing agreement with Dutch biotech Lead Pharma for candidates that are expected to enter the clinic within the next three-to-four years.

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