RICHMOND, Calif.—Sangamo BioSciences Inc. recentlyannounced the initiation of two new clinical trials related to its ZFPTherapeutics program, one of them a Phase 2b study in diabetic neuropathy and the other a Phase 1 trial inglioblastoma—as well as announcing the renewal of $3 million in funding for thePhase 2b trial by the Juvenile Diabetes Research Foundation International(JDRF).
"We are developing our lead therapeutic, SB-509,for neurological indications including diabetic neuropathy and ALS. The datagenerated to date in diabetic neuropathy, our most advanced program, providedirect histologic evidence of nerve regrowth with SB-509 treatment and amechanistic proof of concept for its neuroregenerative effects," says EdwardLanphier, Sangamo's president and CEO. "Our enthusiasm for the potential andimportance of this drug is shared by JDRF who, after extensive review of theclinical data, has committed to fund a further $3 million of development costsfor this new Phase 2b trial. While we continue active discussions withpotential corporate partners, timely initiation of this trial enables us tomaximize the future value of this program."
The glioblastoma trial itself is notable for beingSangamo's third ZFP Therapeutic and the second zinc finger nuclease (ZFN)-basedprogram to enter the clinic, Lanphier notes.
This follows news late last year that theCalifornia Institute for Regenerative Medicine had granted a $14.5 millionDisease Team Research Award to develop an AIDS-related lymphoma therapy basedon the application of Sangamo's ZFN gene-editing technology in stem cells. Thefour-year grant supports an innovative research project conducted by amultidisciplinary team of investigators led by Dr. John Zaia, the Aaron D. andEdith Miller Chair in Gene Therapy and chair of virology at City of Hope.
"Sangamo scientists have developed a ZFN-mediatedgene-editing technology that has been demonstrated to make hematopoietic stemcells and mature immune system cells resistant to HIV infection," Dr. Zaiasays. "This will be the first test of whether hematopoietic stem cells made HIVresistant using Sangamo's technology can correct the disease. If successful,our work could open the door to ZFN-based cell therapies for other importantdiseases."
The support of the HIV-related ZFN-based therapysupports earlier research that also moved to the clinic just under a year ago,thanks to work by Dr. Carl June and colleagues at the University ofPennsylvania, with whom Sangamo opened a Phase 1 clinical trial to evaluateSB-728-T for the treatment of HIV/AIDS.
The idea for the HIV-based applications for ZFNtechnologies was inspired in part from a case in which a man with leukemiareceived a bone marrow transplant from a donor who was naturally immune to HIV,and seems to have subsequently been cured of AIDS. With that case in mind, theplan was to mimic that natural mutation in human blood cells to endow patientswith immunity to HIV.
The challenge has been the inability to makeprecise alterations to human DNA, though, June and his team have noted, whichseems to be overcome by the ZFN technology which, in principle, should work onalmost any site on any chromosome.
"Our ZFP technology functions at the DNA leveland, as this application demonstrates, enables us to address highly validatedtherapeutic targets that have proven difficult to drug at the protein and RNAlevels," said Lanphier when the SB-728-T trial was announced. "ZFPs can beengineered to regulate or modify any gene, in any cell type, which providesnumerous opportunities for its therapeutic applications. This trial is anotherimportant step in establishing our ZFP technology as a major new therapeutic productdevelopment platform."