At Ceregene, we are developing a pipeline of products to treat serious diseases of the brain and eyes. All of products use neurotrophic growth factors, coupled with our gene delivery technology, not only to substantially reduce the serious symptoms of each neurodegenerative or ocular disease, but also to reverse or halt disease progression. We believe that successful development and commercialization of our products could revolutionize the treatment of these debilitating, and often fatal, diseases.
Ceregene’s disease targets
We are focused on developing therapies for serious neurological disorders for which only symptomatic (or palliative) therapies currently exist. All of these conditions rob their victims of productive and satisfying lives, as well as their human dignity. They include Parkinson's disease, Alzheimer's disease, amyotrophic lateral sclerosis (ALS), and Huntington's disease.
We are also targeting degenerative ocular diseases that result in serious vision impairment and blindness, such as retinitis pigmentosa (RP), age-related macular degeneration (AMD) and glaucoma.
Ceregene's approach
For each of our products, the gene for a therapeutic neurotrophic factor is delivered to the precise anatomical location where the major cell degeneration occurs in that particular disease. We employ our proprietary method of preparing adeno-associated virus (AAV) vectors for delivering the neurotrophic gene (see Gene Delivery Technology).
Once the therapeutic gene is inserted into the cell, the AAV vector quickly disintegrates and the cell's own biological machinery should then produce the therapeutic neurotrophic protein indefinitely.
Ceregene's pipeline currently includes four products at varying stages of development: CERE-110, CERE-120, CERE-135, and CERE-140.
CERE-110 (AAV-NGF)
CERE-110 is composed of an AAV vector carrying the gene for nerve growth factor (NGF). NGF is a naturally occurring neurotrophic factor that has profound protective and restoring effects on cholinergic neurons in the brain. These neurons are particularly vulnerable in Alzheimer’s disease (AD) and are strongly implicated as playing a key role in the memory loss and other cognitive disorders characteristic of the early phases of AD. CERE-110 is selectively delivered to these neurons by a neurosurgical procedure. Interim data from a Phase 1 clinical trial of CERE-110 for AD revealed that after nearly three years of follow-up, the administration of CERE-110 was well tolerated. Ceregene has initiated a multi-center, controlled Phase 2 clinical trial in collaboration with the Alzheimer’s Disease Cooperative Study (ADCS).
For information on participation, see www.clinicaltrials.gov. or www.adcs.org
CERE-120 (AAV-NTN)
CERE-120 is composed of an AAV vector carrying the gene for neurturin (NTN), a naturally occurring protein known to repair damaged and dying dopamine-secreting neurons, keeping them alive and functioning normally. NTN is a member of the same protein family as glial cell-derived neurotrophic factor (GDNF). The two naturally-occurring molecules have similar biological properties, and both have been shown to benefit the midbrain dopamine neurons that degenerate in Parkinson’s disease and are responsible for the major motor impairments. CERE-120 is delivered by neurosurgical procedure in a highly targeted fashion directly to the affected area of the brain, which results in stable, long-lasting, local expression of NTN. Thus, a single neurosurgical procedure is anticipated to provide therapeutic benefit for the remainder of the patient’s life.
Data from a double-blind, controlled, multicenter Phase 2 clinical trial in 58 patients with advanced Parkinson’s disease were released in November 2008. The clinical trial failed to demonstrate an appreciable difference between patients treated with CERE-120 versus those in the control group. Both groups showed an approximate 7 point improvement in the protocol-defined primary endpoint (Unified Parkinson’s Disease Rating Scale- motor off), relative to a mean baseline of approximately 39 points. Both groups had a substantial number of patients who demonstrated a meaningful clinical improvement from baseline. CERE-120 appeared to be safe and well tolerated. Ceregene believes it understands why the Phase 2 clinical trial did not reach its primary endpoint and new clinical studies are ongoing.
For information on participation in clinical studies, see www.clinicaltrials.gov or www.pdtrials.org. See Newsroom section for related press releases.
[Note: Both CERE-120 clinical studies in the United States were partially funded by the Michael J. Fox Foundation]
CERE-135 (AAV-IGF-1)
CERE-135 carries the gene for insulin-like growth factor (IGF-1), delivered to the muscles and nerves of ALS patients via our proprietary gene delivery technology. IGF-1 is known to enhance the function and provide protective support of motor neurons that originate in the spinal cord and control all of our muscles. Degeneration of these motor neurons is a hallmark of amyotrophic lateral sclerosis (ALS) and is directly or indirectly responsible for the death of all ALS patients. Still in nonclinical research, we are working with our collaborators to enhance the biological characteristics and targeted delivery of CERE-135 to assure maximum safety and efficacy prior to advancing to human clinical trials.
CERE-140 (AAV-NT4)
CERE-140 carries the gene for neurotrophic factor 4 (NT4) within one of our proprietary gene delivery vectors. NT4 is a neurotrophic factor that benefits many cells in the retina and thus may prove useful for treating ocular diseases. It is closely related to another neurotrophic factor, brain-derived neurotrophic factor (BDNF), which has shown promise in several animal models of retinal degeneration of the eye. CERE-140 is delivered to the retina via an injection of our proprietary gene delivery technology. In nonclinical studies, we have shown CERE-140 to protect against retinal degeneration and lost function in several animal models of retinitis pigmentosa. We are extending these studies while also evaluating the safety of CERE-140 in anticipation of initiating testing of CERE-140 in human patients with retinal degeneration. A single injection into each eye is expected to provide therapeutic benefit for the lifetime of the patient. While our initial clinical effort will be directed toward retinitis pigmentosa, it is likely that CERE-140 might also provide novel and important benefits to patients with wet and dry age-related macular degeneration (AMD) as well as glaucoma.