Ariad Pharmaceuticals entered three separate agreements for the out-license of various aspects of its Argent™ cell-signaling regulation technology. The licenses provide the company with a combination of equity ownership in partners, up-front payments, ongoing fees for supply of certain research reagents, potential milestones, and royalties. Ariad will use the resources for its core focus of cancer drug development.
Bellicum Pharmaceuticals and ReGenX Biosciences inked license agreements to use Argent in the development of biotherapeutics, and Clontech has taken over rights to supply the platform worldwide. Argent combines chemistry and genetics to allow specific cell-signaling and gene-expression events to be chemically activated in whole animals and cultured cells, Ariad explains. The platform includes a portfolio of distinct small molecule dimerizer compounds optimized for specific applications.
Bellicum Pharmaceuticals expanded its license arrangement with Ariad such that it now includes additional cancer immunotherapies and products to treat complications of cell transplantation, such as graft-vs-host disease (GvHD). The decision to broaden the license was prompted by promising clinical data from previously licensed Argent-regulated cancer vaccine and cell therapy candidates.
Bellicum’s first product candidate, BPX-101 DeCIDe™ immunotherapy, is an autologous dendritic-cell cancer vaccine that includes an Argent-inducible regulatory construct. DeCIDe vaccines are designed to kill targeted cells by inducing a potent, durable, fully activated antigen-specific T-cell immune response. In the Phase I/II trial of patients with metastatic castrate-resistant prostate cancer, patients received the Bellicum immunotherapy followed by AP1903, Ariad’s small molecule dimerizer, one day later.
Bellicum’s second product candidate, CaspaCIDe™ DLI, is a donor lymphocyte infusion that contains the Argent-inducible safety switch. CaspaCIDe is a cell therapy safety switch, permitting the rapid elimination of cells in the event of toxicity. CaspaCIDe DLI is administered following a T-cell-depleted hematopoietic stem cell transplant (HSCT). In the ongoing Phase I/II study, pediatric patients with acute lymphoblastic leukemia or acute myeloid leukemia undergoing HSCT received the CaspaCIDe cell therapy followed by administration of AP1903 upon diagnosis of GvHD.
Ariad has an equity stake in Bellicum and is eligible to receive milestones on clinical and regulatory progress as well as royalties on future product sales. Bellicum is responsible for all manufacturing, clinical, and regulatory activities and will hold the IND applications for these programs.
Separately, ReGenX Biosciences has taken over exclusive rights to the Argent technology in the development and commercialization of human therapeutics and vaccines based on in vivo gene delivery. Under terms of the deal, Ariad has taken an equity stake in ReGenX and will receive clinical and regulatory milestones plus royalties and a portion of sublicensing revenues.
ReGenX initially plans to develop the Argent products for specific ocular diseases, metabolic disorders, and infectious diseases. Initial applications will involve the use of Ariad’s small molecule dimerizer drug AP22594.
Ariad and ReGenX report that their previous collaborative efforts have established proof of concept in nonhuman primates, showing sustained regulated production of a therapeutic protein in response to Ariad’s small molecule dimerizer drugs for over six years. ReGenX is combining the Argent platform with its NAV™ gene delivery technology.
Ariad exclusively licensed the Argent technology for use in the research market to Clontech Laboratories. Clontech will assume full responsibility for supplying the technology worldwide for research applications. Ariad will continue to manufacture and will supply to Clontech small molecule dimerizers designed for use with research kits.
Clontech will combine Argent with its other research technologies including LivingColors® fluorescent proteins and Lenti-X™ viral expression systems. Ariad will receive an up-front payment as well as money for sale of dimerizer reagents to Clontech. Ariad will also receive milestones based on Clontech achieving predefined annual sales levels, royalties on net sales of all products incorporating the Argent technology, as well as a portion of sublicensing revenues.
“Through the creative licensing of the Argent technology in multiple transactions, we are able to leverage our early investment in this innovative science and benefit from other companies’ expertise in three distinct areas, while maintaining our focus on our core oncology therapeutic programs,” states Timothy P. Clackson, Ph.D., president of R&D and CSO of Ariad. “Each of these transactions provides the opportunity for building short-term and long-term value for Ariad, at no further cost to us.”
Ariad’s lead candidate is ridaforolimus, an mTOR inhibitor. In May 2010, Merck & Co. revised the terms of its deal with Ariad, paying $50 million to take over full development and commercialization rights to ridaforolimus. Ariad is eligible to receive up to $514 million in regulatory and sales milestones if the drug is approved for multiple cancer indications as well as global royalties in lieu of a profit split.
Potential milestone payments of over $65 million are associated with the sarcoma indication, which is the most advanced program. In January the firms reported that ridaforolimus met its primary endpoints in the sarcoma trial.
Ariad’s next candidate is ponatinib, a pan-BCR-ABL inhibitor. It is in a Phase II trial in patients with chronic myeloid leukemia and Ph+ acute lymphoblastic leukemia. In March the company signed on MolecularMD to develop and commercialize a companion diagnostic test for the drug that would identify the T315I mutation of the BCR-ABL gene.