Paris and Biocitech (Romainville), France, September 16, 2008. The French Muscular Dystrophy Association (Association française contre les myopathies, AFM) and Cellectis S.A. (the rational genome engineering company) have announced the launch of a joint research program on meganuclease-based genome surgery with a view to treating several genetic diseases.
Cellectis has been developing meganuclease-based genome surgery since 2000 and the technology has now become an industrial reality for many different applications. Meganucleases are enzymes that cut DNA like "molecular scissors". They are able to cut out a gene portion with surgical precision and thus remove a mutation. A healthy gene portion can then be inserted in order to physically repair the gene in patient's cells. Cellectis has set up an industrial platform for generating custom meganucleases targeted to any pre-defined gene. The company is already applying these molecules in several industrial fields. Cellectis Genome Surgery, the group's therapy-focused subsidiary, was recently set up with a view to making genomic surgery available for use in the clinic and notably for treating genetic diseases, viral infections, certain forms of cancer and other therapeutic indications.
Meganuclease-based genome surgery brings tangible hope for treating monogenic diseases because it corrects the direct cause of the problem: the gene mutation itself. The joint program launched today by AFM and Cellectis includes, over a 5 year period, the production of meganucleases specific for 7 different target genes, including those coding for beta-globin (mutated in sickle cell anaemia and beta thalassaemia) and dystrophin (involved in Duchenne and Becker muscular dystrophies). These molecules will then be validated in cell-based and animal systems - a prerequisite for subsequent extension to clinical applications.
The 8.3-million program will be funded by the AFM, thanks to the donations from France's annual Telethon event. Under the terms of the agreement, the AFM will receive a share of any revenues earned by Cellectis through exploitation of tools developed during the collaboration.
"We are particularly delighted to start this program with the AFM because delivering a therapeutic solution to patients suffering from genetic diseases was one of the key drivers to launch our therapy-focused subsidiary", commented Frederic Pâques, Director of Cellectis Genome Surgery. "There are still many steps ahead but our approach brings very significant hope for the therapy of severe genetic diseases", he added. According to Laurence Tiennot-Herment, President of AFM: "Meganucleases represent a very promising and innovative therapeutic approach.They offer fresh hope of a cure for our patients. By interfacing with the network of scientific and clinical skills coordinated by AFM, this ambitious partnership with Cellectis, a key player in the biotech sector, should help optimize the chances of successfully developing this new generation of therapeutics". About meganucleases.
A meganuclease is a protein that cuts DNA at a highly precise site on a chromosome. Once DNA has been cut, it has to be repaired by the cell’s natural endogenous maintenance systems. By providing a specifically engineered DNA molecule (called a repair matrix) which will be used as a template to repair the break, one can channel the repair pathway into an insertion, deletion or correction process. Hence, meganucleases can be used to trigger precise modification of specific genes in a variety of cells and organisms. By combining a meganuclease’s capacity to cut DNA with the cell's ability to repair DNA, Cellectis is creating new generations of products for a wide spectrum of applications, including human health - notably for certain viral infections and for diseases which result from a single mutation in a specific gene. By eliminating the mutation, gene correction targets the cause of the disease, rather than its consequences.
About AFM The French Muscular Dystrophy Association ("Association française contre les myopathies", AFM) was founded in 1958 by a group of highly motivated patients and their parents, who refused to accept that their diseases were necessarily incurable and thus decided to take charge of their destiny. The AFM notably organizes France's annual Telethon fundraising TV event and is highly committed to both research and patient support. It acts independently and always in the patients' sole interest. The association's objective is to cure neuromuscular diseases and reduce the handicap that these generate. To this end, the AFM is pursuing a balanced, multifaceted strategy which benefits to all genetic diseases, rare diseases and a number of frequent diseases. Since its creation, AFM has always adopted the same approach: initiate innovative projects alone or in collaboration, achieve proof of concept and then transfer the skills and knowledge to the public- or the private-sectors. The AFM intervenes when it can make an effective difference, accelerate research work, enable decisive breakthroughs or improve quality of life. This strategy has paid off, with a huge rise in the number of investigational treatments: 34 AFM-funded clinical trials (in 29 different diseases) are underway or in the planning stages. www.afm-telethon.fr
About Cellectis S.A. Cellectis SA (www.cellectis.com) is a world-leading company in genome engineering and genome surgery. The company is focused on developing and producing custom meganucleases for in vivo genome surgery. Cellectis' products induce unique, site-directed, double-strand DNA breaks in living cells and can be used in a wide range of biotechnological and therapeutic applications. A strong intellectual property portfolio. Cellectis holds a portfolio of 148 patents and patent applications, providing the company with a strong position in the field of homologous recombination (3 granted US patents) and both naturallyoccurring and engineered-specificity meganucleases and the uses thereof (18 granted US patents). A significant part of this portfolio has been exclusively licensed to Cellectis by the Pasteur Institute (Paris, France), which spun out the company in 2000. The Pasteur Institute hosts pioneering research groups in the field of homologous recombination - a major scientific breakthrough which prompted the award of a Nobel Prize in 2007. Furthermore, the group of researchers which discovered meganucleases and performed the cornerstone work on the benchmark I-SceI homing endonucleases came out of the Pasteur Institute. The pioneering nature of this research was accompanied by some very early patent filings (from the 1980s onwards) and has given Cellectis a strong position as the exclusive licensee. A solid scientific basis. The Pasteur Institute and Cellectis research groups involved in the discovery of meganucleases have published tens of cornerstone publications in prestigious, peer-reviewed journals such as Cell, Nature, Science, PNAS, JBC and JMB. In 2007 alone, Cellectis published 5 major scientific publications in peerreviewed journals, with a further 3 papers since the beginning of 2008.
Proven technology. Cellectis is currently developing an incremental pipeline of 20 or so custom meganucleases (derived from the I-CreI meganuclease), with applications in the follows sectors: healthcare and the therapeutic field, where the major indications are severe inborn genetic diseases, DNA virus infections, transplantation and cancer; biotools, where the major application is research kit development for pharmacogenomic studies in general and drug screening in particular; agricultural biotechnology, where the major targets are crop improvement, biofuels and biofibers; biomanufacturing, where the major indications are cell line and recombinant protein improvement. A very active partnering strategy The company has signed over 50 industrial partnerships with pharmaceutical companies (Astra-Zeneca, GSK, Shire), agricultural biotechnology groups (Limagrain, Bayer, BASF, DuPont-Pioneer HiBred) and healthcare-focused biotech firms (Genentech, TransGenic, Lexicon). Cellectis is also involved in over 20 academic collaborations, including those with the Gustave Roussy cancer centre (Paris, France), Necker Children's Hospital (Paris, France), Children's Hospital Boston and the Harvard Gene Therapy Initiative (USA). Financing. The company raised over 24 million in a successful February 2007 IPO on NYSE-Euronext Alternext, in order to increase its annual meganuclease production capacity. To date, the company has raised over 40 million in both private and public rounds of financing. Cellectis is listed on the NYSE-Euronext Alternext market (ticker code: ALCLS).
For further information, please contact: Cellectis: AFM: David J.D. Sourdive Mathilde Maufras Vice President, Corporate Development Service de presse AFM +33 1 41 83 99 00 +33 1 69 47 25 96 press@cellectis.com presse@afm.genethon.fr
ALIZE RP Caroline Carmagnol Tel.: +33 6 64 18 99 59 E-mail: caroline@alizerp.com
