Several biotechnology companies have licensed Benitec Biopharma’s ddRNAi technology for their own human therapeutics programs.
City of Hope
Until late 2010, Benitec Biopharma supported the development of an RNA-based HIV/AIDS therapeutic, of which one component was a ddRNAi construct directed at a key HIV replicative gene. This program was undertaken from 2007-2010 in collaboration with the City of Hope in Duarte, California.
The product candidate was taken into a Phase I/II pilot human clinical trial funded by Benitec that produced promising interim results for safety and proof of feasibility. The data was published in Science Translational Medicine in June 2010.
This study is now being progressed by the research and clinical team at the City of Hope.
In March 2012, Benitec Biopharma announced the execution of a non-exclusive licensing agreement with US-based biotech company Calimmune for the use of ddRNAi in the area of HIV/AIDS world-wide. The agreement covers the application of ddRNAi to target up to three key viral and cellular genes identified as significant therapeutic targets to inhibit HIV/AIDS infection.
Calimmune’s approach to the application of ddRNAi to HIV/AIDS is highly innovative and has been developed with core technology from the lab of Dr David Baltimore, a Nobel Laureate in the area of HIV/AIDS. Benitec Biopharma is proud to be involved in this program through the provision of the license to Calimmune.
Calimmune’s approach involves extraction of T cells from HIV patients, ex vivo silencing of the gene that codes for the CCR5 protein and is associated with low HIV loads, and re-injecting the modified cells, thereby conferring resistance to HIV. In its Phase l/ll clinical trial of the treatment, Calimmune is about to complete enrolment of the first cohort. Read Calimmune’s latest presentation.
In 2004, Benitec licensed its shRNA technology to Revivicor Inc, Blacksburg VA, USA: “to generate and propagate transgenic pigs to provide human compatible organs, tissues or cells isolated there from for use in transplantation.” Revivicor is attempting to develop pigs which will be suitable as organ donors for humans (xenotransplantation). The critical shortage of human organs for all types of transplantation underscores the importance of developing a xenogenic source as an alternative. Pigs offer the best potential alternative and significant progress have been made towards this goal. A major obstacle is the potential risk of cross-species transmission of porcine endogenous retroviruses (PERV). PERVs are gammaretroviruses that are ubiquitous and integral to the porcine genome, and there a specific need is to inhibit PERVs present in the pigs. ddRNAi is a unique potential solution to this problem.
Revivicor Inc. is a small privately held company with core competencies in xenografts and tolerance technologies. It was spun out from PPL Therapeutics plc (USA division). Revivicor's focus is the commercialization of treatments for diabetes and whole organ transplantation, as a result of their significant advances in their core fields of competence. Revivicor is still in the pre-clinical phase of xenograft development, and Benitec Biopharma understands that they are making significant progress toward advancing towards providing a range of xenografts for human therapeutics.
Rhodopsin-linked autosomal dominant retinitis pigmentosa (RHO-adRP) is an orphan disease which affects around 1 in 30,000 people. There are around 19,000 patients in the EU and there is no current treatment.
Sufferers experience severe visual dysfunction due to the death of rod and cone photoreceptor cells. The disease is caused by any of one of over one hundred inherited defects in the rhodopsin (RHO) gene, which has made a single treatment very difficult until now.
In July 2012, Genable Technologies executed an exclusive worldwide licensing agreement with Benitec Biopharma to use ddRNAi technology to develop a single treatment for patients with RHO-adRP, regardless of which of the RHO mutations causes the disease. The treatment involves suppression of the mutant and normal genes, and replacement with a normal RHO gene that has been modified to be resistant to ddRNAi gene silencing. The program has established proof of concept studies in an in vivo model of the disease. Results of the program were reported at the World Gene Therapy Congress in May 2012 in London.
Genable Technologies Limited is a privately held, venture-backed bio- pharmaceutical company based in Dublin, Ireland. It is developing new gene medicines to treat “dominant” genetic diseases based on the pioneering work of Professor Jane Farrar, Dr Paul Kenna & Professor Peter Humphries.
Genable utilizes well-established, clinically safe and effective AAV vectors to cause expression of RNA interference (RNAi) molecules that suppress expression of both faulty and normal gene copies, and replaces them with a gene that becomes refractory to suppression but still encodes a normal wild type protein. The combination of suppression and replacement (S&R) overcomes the significant hurdle of mutation variability, by eliminating the need to target specific mutations. Genable’s technology is protected by a broad suite of granted patents and patent applications in the USA, EU and worldwide.