2011- An Important Year for Clinical Data from ZFP Therapeutic® Programs
RICHMOND, Calif., Jan. 10, 2011 /PRNewswire/ -- Sangamo BioSciences, Inc. (Nasdaq: SGMO) announced today that the company completed enrollment of its Phase 2b double-blind, placebo-controlled clinical trial (SB-509-901) in subjects with diabetic neuropathy (DN). The company expects to have efficacy data from this study in the second half of 2011. The company also plans to present the first human clinical data from its Phase 1 trials of SB-728-T in HIV/AIDS in the first quarter of 2011.
"2011 will be a very important year for Sangamo's ZFP Therapeutic programs," said Edward Lanphier, Sangamo's president and CEO. "In our most advanced clinical program, a disease-modifying approach for DN, we have met our goal of fully accruing our Phase 2b study by the end of 2010, thus ensuring that the data from this trial will be available in the second half of 2011. In addition, we will present data from our Phase 1 trials of a ZFP Therapeutic approach to HIV/AIDS in the first quarter of this year. We also recently announced significant advances in our preclinical pipeline. In December 2010, data from studies of a ZFP Therapeutic for Parkinson's disease (PD) were published*and this drug candidate is currently being evaluated in primate models of PD. In addition, at the American Society of Hematology (ASH) meeting, we presented the first example of systemic delivery of a ZFP nuclease (ZFN) resulting in therapeutic correction of a hemophilia B in a mouse model, highlighting the broad therapeutic potential of our ZFP technology platform. These clinical and preclinical advances continue to demonstrate the value of our ZFP Therapeutic pipeline and our commitment to address major unmet medical needs for which functioning at the DNA level is uniquely appropriate to provide a therapeutic solution for patients."
Mr. Lanphier will provide an update on the company's ZFP Therapeutic pipeline and an overview of the company's business strategy and objectives for 2011 during his presentation at the 29th Annual J.P. Morgan Healthcare Conference at 12:30 pm PT, on Thursday, January 13, 2011. The presentation will be webcast and available at http://investor.sangamo.com/events.cfm.
Sangamo is developing SB-509, a transcriptional activator of the gene encoding vascular endothelial growth factor-A (VEGF-A) for DN and other neurological indications including ALS. The company has conducted several Phase 2 clinical trials which have provided direct histologic evidence of nerve and blood vessel regrowth with SB-509 treatment and mechanistic proof of concept for the drug's neuroregenerative effects. The Juvenile Diabetes Research Foundation (JDRF) provided $3.0 million funding for a previous Phase 2 study (SB-509-601) and committed to fund an additional $3.0 million of development costs for Sangamo's ongoing SB-509-901 Phase 2b trial.
"Peripheral neuropathy is a major complication of diabetes and represents a significant unmet medical need," stated Barbara Araneo, Ph.D., Director of Complications Therapies for JDRF. "While there are drugs that mask the painful symptoms of this condition, there are no therapeutic approaches that can halt or reverse the nerve loss. We are very pleased to support the development of SB-509 which is a novel disease-modifying approach designed to use the body's regenerative potential to protect and restore nerve function. We are also very pleased with the success that Sangamo has had in accruing subjects onto this Phase 2b trial and look forward to the data in the second half of 2011."
"The valuable clinical data that we have collected over several Phase 2 trials of SB-509 enabled us to design a very focused Phase 2b study," commented Dale Ando, Sangamo's chief medical officer and vice president of therapeutics. "We have accrued subjects with DN who we believe will be most responsive to SB-509 over the 180 day primary efficacy test period. The data generated to date suggests that SB-509 treatment results in statistically significant increases in nerve fiber density, nerve regeneration and an improvement in approvable end-points such as Neuropathy Impairment Score of the Lower Limb (NIS-LL) and sural nerve conduction velocity (sNCV). Information collected in our Phase 2b trial will allow us to confirm eligibility criteria and primary clinical endpoints for future Phase 3 trials."
Sangamo is developing SB-728-T, a ZFN approach to the treatment of HIV/AIDS and has an ongoing Phase 1/2 and two Phase 1 clinical trials to evaluate the safety and clinical efficacy of this approach in CD4+ T-cells. Sangamo's ZFNs are designed to permanently modify the DNA sequence encoding CCR5, a co-receptor that enables HIV to enter and infect cells of the immune system. Individuals carrying a naturally occurring mutation of their CCR5 gene, a variant known as CCR5-delta32, have been shown to be resistant to HIV infection. Building on this observation, a study published in Blood in December 2010 reported an effective cure when an AIDS patient with leukemia received a bone marrow transplant from a "matched" donor with this delta-32 CCR5 mutation. This approach transferred the HSCs residing in the bone marrow from the delta-32 donor, and provided a self-renewable and potentially lifelong source of HIV-resistant immune cells. After transplantation, the patient was able to discontinue all anti-HIV drug treatments, CD4 counts increased, and viral load dropped to an undetectable level, demonstrating effective transplantation of protection from HIV infection.
As part of a collaboration with scientists at City of Hope and the University of Southern California, under a $14.5 million CIRM Disease Team Research Award, Sangamo is also developing an approach to modify a patient's own hematopoietic stem cells (HSCs) to circumvent the need to find matched donors that carry the delta-32 CCR5 mutation and while providing a renewable and long-lasting source of HIV-resistant cells. Specifically, the grant funds the development of a ZFN approach to treat AIDS patients by first isolating their HSC, modifying them using CCR5-specific ZFNs, and then re-infusing them to reconstitute the immune system with CCR5-negative, HIV-resistant immune cells. Sangamo and its collaborators will provide an update of preliminary clinical data of SB-728-T as well as the preclinical stage program in HSCs in the first quarter of 2011.
"We begin 2011 with a solid foundation of commercial and technical successes and look forward to a year of significant clinical progress," commented Mr. Lanphier. "By the end of the year, we expect to have data from the Phase 2b clinical trial (SB-509-901) of our lead ZFP Therapeutic, SB-509 in DN, which will allow us to move forward with our partnering discussions. In addition, in the first quarter of 2011, we expect to have preliminary data from the two ongoing Phase 1 trials of our ZFN-based Therapeutic, SB-728-T for the treatment of HIV/AIDS. Finally, we look forward to advancing our extensive preclinical pipeline as well as participating in the continued commercial expansion of our ZFP technology through our partnerships in plant agriculture and in the growing area of research reagents, cell line engineering and transgenic animal model production."
About Diabetic Neuropathy
Diabetic neuropathy is a progressive degenerative disease that is one of the most frequent complications of diabetes, affecting between 14 and 16.5 million Americans in 2007. High blood glucose levels lead to nerve damage over time, primarily affecting peripheral nerves. Symptoms include numbness, tingling sensations and pain particularly in the toes or feet, which gradually evolve to loss of sensation and motor function as nerve damage progresses. Ulcers and sores may appear on numb areas of the foot as pressure wounds or injuries go unnoticed. Despite palliative treatment, these areas of trauma frequently become infected and this infection may spread to the bone, necessitating amputation of the leg or foot. More than 60 percent of non-traumatic lower-limb amputations in the United States occur among people with diabetes. In 2004, this translated to approximately 71,000 amputations. The Centers for Disease Control estimates that from 1980 through 2007, the number of Americans with diabetes increased from 5.6 million to 23.6 million and that of those about 60 percent to 70 percent have mild to severe forms of neuropathy.
HIV stands for Human Immunodeficiency Virus. HIV infection kills or impairs cells of the immune system progressively destroying the body's ability to fight infections and certain cancers resulting in AIDS (Acquired Immune Deficiency Syndrome). Individuals diagnosed with AIDS are susceptible to opportunistic infections, infections that usually are not severe in healthy individuals. According to UNAIDS/WHO, over 2.7 million people were infected with HIV in 2007. There are now over 33 million people living with HIV and AIDS worldwide.
* "An engineered zinc finger protein activator of the endogenous glial cell line-derived neurotrophic factor gene provides functional neuroprotection in a rat model of Parkinson's disease." J Neurosci. 2010 Dec 8;30(49):16469-74
Sangamo BioSciences, Inc. is focused on research and development of novel DNA-binding proteins for therapeutic gene regulation and modification. The most advanced ZFP Therapeutic® development program is currently in a Phase 2b clinical trial for evaluation of safety and clinical effect in patients with diabetic neuropathy and a Phase 2 trial in ALS. Sangamo also has a Phase 1 / 2 clinical trial and two ongoing Phase 1 clinical trials to evaluate safety and clinical effect of a treatment for HIV/AIDS as well as a Phase 1 trial of a treatment for recurrent glioblastoma multiforme. Other therapeutic programs are focused on Parkinson's disease, monogenic diseases, neuropathic pain and nerve regeneration. Sangamo's core competencies enable the engineering of a class of DNA-binding proteins known as zinc finger DNA-binding proteins (ZFPs). By engineering ZFPs that recognize a specific DNA sequence Sangamo has created ZFP transcription factors (ZFP TFs) that can control gene expression and, consequently, cell function. Sangamo is also developing sequence-specific ZFP Nucleases (ZFNs) for gene modification. Sangamo has established strategic partnerships with companies in non-therapeutic applications of its technology including Dow AgroSciences and Sigma-Aldrich Corporation. For more information about Sangamo, visit the company's website at http://www.sangamo.com/.
ZFP Therapeutic® is a registered trademark of Sangamo BioSciences, Inc.
This press release may contain forward-looking statements based on Sangamo's current expectations. These forward-looking statements include, without limitation, references to clinical trials of ZFP Therapeutics in diabetic neuropathy and HIV/AIDS, the timing and availability of clinical data, the research and development of novel ZFP TFs and ZFNs as ZFP Therapeutics, applications of Sangamo's ZFP technology platform to specific human disease as well as plant agriculture, high value research reagents, transgenic animals and cell-line engineering, establishing strategic partnerships for SB-509 and other therapeutic programs. Actual results may differ materially from these forward-looking statements due to a number of factors, including technological challenges, uncertainties relating to the initiation, completion and outcome of stages of ZFP Therapeutic clinical trials, Sangamo's ability to develop commercially viable products and technological developments by our competitors. See Sangamo's SEC filings, and in particular, the risk factors described in Sangamo's Annual Report on Form 10-K and most recent Quarterly Reports on Form 10-Q. Sangamo BioSciences, Inc. assumes no obligation to update the forward-looking information contained in this press release.
SOURCE Sangamo BioSciences, Inc.