Eli Lilly will partner with Aduro Biotech to develop novel immunotherapies for autoimmune and other inflammatory diseases using Aduro’s cGAS-STING Pathway Inhibitor program, through a license agreement that could generate up to approximately $620 million per treatment developed.
Lilly and Aduro did not disclose the number of treatments to be developed in either their announcement or a regulatory filing.
The companies did say, however, that Lilly will gain access to novel molecules from Aduro that are designed to inhibit the cyclic GMP-AMP synthase (cGAS) stimulator of interferon genes (STING) pathway, which has been shown to modulate the immune response associated with various autoimmune diseases.
Aduro’s STING Pathway Activator platform is based on the activation of the cytoplasmic STING receptor to lead to a tumor-specific immune response. When stimulated, according to Aduro, STING induces the expression of type I interferon, cytokines, and T-cell recruitment factors that result in the activation of macrophages and dendritic cells, innate effector cells such as natural killer (NK) cells, and priming of tumor-specific T cells.
Aduro has developed synthetic STING Pathway Activators it says have shown significantly higher activity than the natural STING ligands produced by bacteria and mammalian cells. The synthetic STING Pathway Activators are being developed for direct injection into tumors, with the goal of fighting cancer by stimulating an immune response against antigens present in the tumor.
Using a Tumor as a “Vaccine”
The process is designed to use the tumor as a “vaccine,” enabling the induction of a tumor-specific immune response that is unique to the treated individual—what the company calls an off-the-shelf small molecule approach to personalized immunotherapy.
STING Pathway Activators can be developed as monotherapies and in combination with other cancer therapies, including chemotherapy, radiation, and monoclonal antibodies, according to Aduro.
The companies agreed to advance the cGAS-STING molecules, as well as others from Lilly, into clinical development.
“As we continue to strengthen our leadership in the STING pathway at Aduro, we are thrilled to collaborate with Lilly to identify and develop novel cGAS-STING pathway inhibitors,” Aduro chairman, president, and CEO Stephen T. Isaacs said in a statement. “This partnership represents an exceptional opportunity to leverage Lilly’s expertise in immunology while expanding the potential for our technology into therapeutic approaches for autoimmune and other inflammatory diseases.”
Lilly agreed to pay Aduro $12 million upfront and up to $620 million per product, plus royalty payments in the single- to low-double digits tied to successful commercialization of a therapy.
The agreement also entitles Aduro to research funding from Lilly, and gives Aduro the option to co-fund clinical development of each product in exchange for an increase in royalty payments. Lilly agreed to fund all costs of global commercialization.
“At Lilly, we continue to explore new areas of science and are committed to developing novel immunology treatments,” added Ajay Nirula, M.D., Ph.D., Lilly’s vp of immunology research. “We are pleased to collaborate with Aduro, and hope to utilize their expertise with the cGAS-STING pathway to identify promising pathway inhibitors that could one day become breakthrough medicines.”
Immunology is one of Lilly’s five therapeutic areas of focus; the other four are oncology, pain, neurodegeneration, and diabetes.
Lilly announced its collaboration with Aduro yesterday—a day before telling investors it projects 2019 revenues of between $25.3 billion and $25.8 billion, and is on pace to deliver on the company’s goal to launch 20 new medicines in 10 years.
Positive Preliminary STING Results
Lilly is one of three pharma giants with which Aduro is collaborating on the development of new therapies. Aduro launched an up-to-$750 million partnership with Novartis in 2015 to research, develop, and commercialize new immuno-oncology products. Aduro’s alliance with Novartis has generated Aduro’s lead STING pathway inhibitor candidate, ADU-S100, a novel synthetic molecule designed to activate human STING.
At the Society for Immunotherapy of Cancer’s (SITC) 33rd Annual Meeting, held November 7–11 in Washington, DC, Aduro trumpeted positive preliminary results from two ongoing Phase I trials of ADU-S100, formerly called MIW815.
In one Phase I trial (NCT02675439), assessing ADU-S100 alone and in combination with Bristol-Myers Squibb’s approved CTLA-4 inhibitor Yervoy® (ipilimumab), two of the 40 patients treated had a partial response, while 11 achieved stable disease, including five patients who had received prior checkpoint inhibitor therapy. Increases in key systemic cytokines, including IL-6, MCP-1, and IFN-β, were observed after administration, indicating target engagement of ADU-S100 and activation of the STING pathway, Aduro said.
In the other Phase I trial, (NCT03172936 ) assessing the combination of ADU-S100 and Novartis’ Phase III anti-PD-1 monoclonal antibody spartalizumab, clinical responses were seen in several tumor types, including two patients who had previously shown responses to checkpoint inhibitor therapy alone. Investigators also found reduced tumor volume in injected and non-injected lesions in some patients.
Aduro is also partnering with Merck & Co. to develop combination cancer therapies that combine Aduro’s live, attenuated double-deleted (LADD) Listeria-based immunotherapy CRS-207 with Merck’s anti-PD-1 drug Keytruda® (pembrolizumab), a collaboration that expanded in May 2017.
Aduro also maintains partnerships with two research universities, Johns Hopkins and the University of California, Berkeley.