Date: 2015-03-30
Type of information: Research agreement
Compound: ADU-S100 and novel immuno-oncology products derived from Aduro’s cyclic dinucleotide (CDN) approach to target the STING (Stimulator of Interferon Genes) receptor
Company: Aduro Biotech (USA - CA) Novartis (Switzerland)
Therapeutic area: Cancer - Oncology
Type agreement: R&D - development - commercialisation
Action mechanism:
- immunomodulating agent/dinucleotide. Cyclic dinucleotides (CDNs) are small molecules – naturally expressed by bacteria and immune cells – that are known to activate the STING (Stimulator of Interferon Genes) signaling pathway in immune cells. STING is known to be a central mediator of innate immune response and, when stimulated, induces the expression of various interferons, cytokines and T cell recruitment factors that amplify and strengthen immune activity. Aduro’s proprietary CDN product candidates are synthetic small molecule immune modulators that are designed to target and activate the STING receptor. Once activated, the STING receptor initiates an innate immune response through multiple pathways, inducing the expression of a broad profile of cytokines, including interferons and chemokines. This subsequently leads to the development of an effective tumor antigen-specific T cell adaptive immune response.
- ADU-S100 is a novel synthetic CDN-based molecule that was developed based on its ability to stimulate human immune cells from a large pool of human donors that comprised all of the known STING receptors. In preclinical mouse tumor models, the data showed that direct intratumoral injection of ADU-S100 into melanoma, colon and breast tumors profoundly inhibited tumor growth both locally and systemically, with a durable response that provided protection against tumor regrowth and significantly inhibited growth of distal tumors. In addition, Aduro believes the immune-mediated destruction of distal tumors could be significantly enhanced by a combination of ADU-S100 and radiotherapy, a combination that may eventually be tested in human clinical trials.
Disease:
Details:
- • On March 30, 2015, Aduro Biotech announced the establishment of a major collaboration with Novartis for the worldwide research, development and commercialization of novel immuno-oncology products derived from Aduro’s cyclic dinucleotide (CDN) approach to target the STING (Stimulator of Interferon Genes) receptor, that, when activated, is known to initiate broad innate and adaptive tumor-specific immune responses.The agreement covers the joint research, development and commercialization of CDN-based therapies in the field of oncology. Aduro maintains rights to its CDN technology in all other therapeutic areas, including infectious disease and autoimmunity, among others.
Last year, Dr. Dubensky presented preclinical data at the American Association for Cancer Research Tumor Immunology and Immunotherapy Conference demonstrating potent anti-tumor activity in preclinical models treated with ADU-S100, the company’s compound based on its CDN technology. The preclinical studies included evaluation of ADU-S100 to stimulate and activate the STING pathway as an approach to generate an immune response that can specifically attack tumor cells. Novartis also announced that it has launched a new immuno-oncology research group led by renowned cancer vaccine expert Glenn Dranoff, MD.
- The addition of STING agonists adds firepower to Novartis' diverse portfolio of immunotherapies that includes chimeric antigen receptor T-cell (CART) technology and novel checkpoint inhibitors. Currently the CART program, CTL019, is in phase 2 clinical trials and checkpoint inhibitors targeting PD1, LAG3, and TIM3 are expected to enter the clinic in mid-2015.
Financial terms:
- Under the terms of the agreement, Novartis will make an upfront payment of $200 million to Aduro and, if all development milestones are met, Aduro is eligible to receive up to an additional aggregate amount of $500 million. In addition, Novartis has made an initial 2.7 percent equity investment in Aduro for $25 million, with a commitment for another $25 million investment at a future date.Aduro will lead commercialization activities and will book sales in the United States for any products developed and commercialized pursuant to this collaboration, with Novartis leading commercialization activities in all other regions. The companies will share in profits, if any, in the United States, Japan and major European countries. Novartis will pay Aduro a mid-teens royalty for sales in the rest of the world.
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