Bayer and Curadev Enter €250 Million Collaboration to Co-Develop Small Molecule STING Antagonists for Inflammatory Diseases

Text | Shi Yuan

On March 23, Bayer and Indian pharmaceutical company Curadev announced a research collaboration and licensing agreement for a small-molecule stimulator of interferon genes (STING) antagonist program, jointly developing novel therapies for pulmonary diseases, cardiovascular diseases, and other inflammatory conditions. Bayer has obtained exclusive global rights to a series of novel small-molecule STING pathway inhibitors from Curadev. The two companies will optimize these candidates, as well as other candidates identified during the collaboration, and jointly advance them into human clinical trials.

Under the agreement, Curadev is eligible to receive an upfront payment from Bayer and funding for early-stage research. Curadev is also qualified to receive total milestone payments exceeding €250 million for preclinical research, clinical development, and commercial sales, as well as single-digit royalties based on net sales.

STING, also known as cGAS-STING, is a component of the human innate immune system and serves as the first line of defense against external pathogens such as bacteria and viruses. Existing studies have found that the pathogenesis of a series of chronic and rare diseases is associated with excessive STING signaling, including neurodegenerative diseases such as Parkinson's disease, pulmonary fibrosis, and non-alcoholic steatohepatitis (NASH). Meanwhile, STING agonists are being developed as a novel class of cancer immunotherapies because they can activate the body's adaptive immune response, producing sustained anti-tumor effects. However, due to the side effects of this therapy (particularly pancreatic inflammation) and the lack of efficacy in cancer trials, the development path has been fraught with difficulties.

STING is also one of the highly focused research and development areas. Currently, more than 10 biopharmaceutical companies, including Novartis and Merck & Co., are developing STING-related candidate drugs.

In March 2015, Novartis and Aduro reached a collaboration agreement targeting the STING agonist ADU-S100. Novartis paid Aduro a $200 million upfront payment, with approximately $500 million in subsequent milestone payments. Novartis also acquired a 2.7% equity stake in Aduro for $25 million, and was required to pay an additional $25 million in research and development fees to Aduro as part of the ongoing collaboration.

In early 2017, Merck & Co. initiated a clinical study of Keytruda in combination with the STING agonist MK-1454. In August 2017, Bristol-Myers Squibb (BMS) reached an acquisition agreement with IFM Therapeutics for STING agonists. Under the terms of the agreement, IFM Therapeutics was eligible to receive a $300 million upfront payment and up to $2 billion in milestone payments from BMS.

In September 2018, Novartis entered into an $840 million collaboration with IFM Therapeutics to jointly develop STING agonists for the treatment of rare diseases. The intended indications include Aicardi-Goutières syndrome (a rare pediatric autoimmune disease), STING-associated vasculopathy with onset in infancy (SAVI), and systemic lupus erythematosus (SLE).

In December 2018, Eli Lilly and Company entered into a $620 million collaboration with Aduro Biotech to jointly develop cGAS-STING pathway inhibitors for the treatment of autoimmune and inflammatory diseases.

In July 2019, AbbVie announced the acquisition of Mavupharma, thereby acquiring ENP1, an early-stage asset targeting the STING signaling pathway (an enzyme involved in regulating the STING signaling pathway), and officially entering the STING field.

At the 2019 ASCO Annual Meeting, Novartis announced Phase I clinical data for its STING agonist ADU-S100 in combination with the PD-1 antibody spartalizumab, showing a response rate of 9%. In December 2019, Novartis announced the termination of ADU-S100 development.