Marlborough, Massachusetts based RXi Pharmaceuticals Corporation and privately-held, Cambridge, MA-headquartered MirImmune LLC, have jointly announced their entering into an exclusive license agreement to develop RXi’s novel and proprietary sd-rxRNA technology for use in developing innovative cell-based cancer immunotherapies. The companies say this collaboration has potential to yield novel, more effective and patient-friendly cancer treatments that could be a significant advance toward personalized medicine.
RNAi technology enhances anti-tumor activity of ex-vivo propagated immune cells by simultaneously protecting them from multiple immunosuppression mechanisms. Mirimmune have achieved protection from immunosuppression by eliminating the expression of immunosuppressive receptors or proteins during immune cell cultivation by the treatment of the cells with self-deliverable RNAi molecules (sdRNA), which is based on use of heavily modified, stabilized iRNA-like molecules with enhanced hydrophobic properties. The company notes that a combination of stabilizing and hydrophobic modifications results in spontaneous cellular uptake and gene silencing by RNAi mechanism, and potent sdRNAs can be selected against virtually any gene target.
sdRNAs penetrate cells without any additional formulation or transfection procedure, as it is simply used as an additional media component. sdRNAi treatment is compatible with established cell growth and expansion protocols, and because sdRNAi delivery is not cell type specific, any cell type can be transfected.
Cellular uptake of sdRNAi results in specific, potent and long-lasting gene knockdown, and multiple genes can be silenced simultaneously. As a result, Mirimmune researchers have been able to obtain immune cells protected from multiple suppression mechanisms and, consequently, able to exert more potent and long-lasting anti-tumor activity. This approach is applicable in combination with any anti-cancer cell-based therapy involving ex-vivo cultivation and propagations of immune cells, such as adoptive T-cell or NK-cell transfer, CAR- and TCR-cell therapy and dendritic cell vaccines.
Under the terms of the agreement with RXi Pharmaceuticals, MirImmune will be responsible for all research, development, manufacturing, regulatory and commercialization activities for the licensed products. The company will develop cell-based therapeutics utilizing RXi’s sd-rxRNA technology to target immune inhibitory pathways (checkpoints) that currently limit the efficacy of cancer immunotherapies. According to the agreement’s terms, MirImmune will gain access to RXi’s sd-rxRNA and rxRNAori patent families for ex vivo modification of cells for the cancer treatment, including the composition of the sd-rxRNA and rxRNAori RNAi structures, as well as potential targets for cell-based therapeutics.
The license terms also provide that RXi is to receive an annual licensing fee, clinical milestone payments, sublicensing income and single digit royalties. Pending MirImmune’s passage of specified gating milestones, RXi will also have the right to acquire a double-digit equity stake in MirImmune.
“We are pleased to provide MirImmune access to our novel self-delivering RNAi compounds for ex vivo cell therapy for the treatment of cancer,” says Dr. Geert Cauwenbergh, President and CEO of RXi Pharmaceuticals in a release. “This license agreement marks the latest milestone for the Company to partner and collaborate with industry to provide new and innovative therapeutics, while also providing the potential for a long-term financial return for our shareholders.”
Dr. Cauwenbergh, who was appointed President and Chief Executive Officer of RXi Pharmaceuticals Corporation in April, 2012, previously served as Chairman and Chief Executive Officer of Barrier Therapeutics, Inc., a publicly-traded biopharmaceutical company he founded in 2001 that focused on dermatology drug development. He is a member of the board of directors of Ablynx NV and Euroscreen S.A., both European biotechnology companies. In 2005, Dr. Cauwenbergh was inducted into the New Jersey High-Tech Hall of Fame, and, from 2009 to 2010, he served as Chairman of the Board of Trustees of BioNJ. He has authored more than 100 publications and has been a guest editor for a number of books in mycology and infectious diseases.
Dr. Craig Mello, Chairman of RXi Pharmaceuticals Scientific Advisory Board, observes that, “Not only is this collaboration a visionary step forward by RXi because it has the potential to develop cutting edge cell-based therapeutics for cancer immunotherapy and possibly other unmet medical needs, it also further validates the Company’s proprietary self-delivering RNAi technology platform.”
“We are delighted to work with RXi Pharmaceuticals and their cutting-edge, self-delivering RNAi compounds as we progress research and development efforts with our cell-based therapy approach,” says MirImmune LLC CEO Alexey Eliseev. “Following careful evaluation of the various siRNA delivery platforms, we believe RXi’s self-delivering technology is best suited for cell-based therapeutics for the following reasons:
• sd-rxRNA easily transfect any cell type;
• sd-rxRNAs do not require formulation in a complex delivery system for efficient cellular uptake. This allows for a streamlined manufacturing process;
• The sd-rxRNA platform was demonstrated to be safe and well-tolerated in GLP toxicology studies (dermal and systemic) and in dermal clinical trials; and
• sd-rxRNA allows for the ability to target multiple genes of interest simultaneously.
• Access to RXi’s technology transforms our ability to move forward with our efforts to develop targeted cancer cell therapeutics.
Cancer cells are formed in the body on an ongoing basis but we are normally not affected by them as they are destroyed by the body’s immune system — a complex network of cells and organs working in synergy to attack foreign and non-self invaders. However, if the immune system weakens, cancer cells can evolve into the dreaded disease.
Cancer immunotherapy therefore attempts to treat the disease by stimulating the immune system to reject and destroy tumors. The three main classes of this type of immunotherapy are cell-based therapies, antibody therapies and cytokine therapies.
Cell-based cancer immunotherapy, also known as Autologous Immune Enhancement Therapy (AIET), is a treatment methodology that employs a patient’s own cells. With this form of therapy, immune cells (peripheral blood-derived NK cells, Cytotoxic T Lymphocytes and others) are removed from the body, cultured and processed to become active (in this case with sd-rxRNA compounds) and reinfused to attack cancer cells. Researchers have determined that this type of cell therapy primarily targets cancer cells and not healthy cells, as opposed to chemotherapy and radiotherapy during which healthy cells are also destroyed.
RXi Pharmaceuticals Corporation
RXi Pharmaceuticals Corporation