Ceregene is developing a pipeline of products, all of which use neurotrophic factors and its gene delivery technology to offer novel treatments to patients that might not only substantially reduce the serious symptoms of terrible neurodegenerative diseases, but also halt or reverse disease progression.

Neurological disorders

Ceregene concentrates on devastating neurological disorders for which no effective treatment currently exists. These conditions include Parkinson’s disease, Alzheimer’s disease, amyotrophic lateral sclerosis (ALS or Lou Gehrig’s disease), and Huntington’s disease. Ceregene also is targeting degenerative diseases of the eye that result in serious vision impairment and blindness, such as retinitis pigmentosa (RP), age-related macular degeneration (AMD) and glaucoma.

Ceregene’s products

For each of Ceregene’s products, the gene for a therapeutic neurotrophic factor is delivered to the precise location where the major cell degeneration is occurring in that particular disease. Ceregene employs its own proprietary method of preparing adeno-associated virus (AAV) vectors for delivering the neurotrophic gene.

Once the therapeutic gene is inserted into the cell, the AAV vector harmlessly disintegrates and the cell’s own machinery then produces the therapeutic neurotrophic protein indefinitely.

Ceregene’s pipeline currently includes four major products at varying stages of development: CERE-110, CERE-120, CERE-130, and CERE-140.

CERE-120 (AAV-NTN)

CERE-120 is Ceregene’s lead program. CERE-120 contains the gene for NTN which is delivered to the area of the brain degenerating in Parkinson’s disease, using Ceregene’s proprietary gene delivery technology. Neurturin (NTN), a naturally occurring neurotrophic factor, promotes survival and improves function of dopamine motor neurons. These are the neurons that degenerate in Parkinson’s disease (PD) and are most closely associated with loss of motor function. . An extensive preclinical safety and efficacy program established that CERE-120 can deliver NTN selectively to the targeted region of the brain in a controlled and predictable fashion. Clear evidence of efficacy was observed in several different models of PD and very large doses were without any apparent toxicity or side effects. These studies supported an initial Phase 1 trial in PD subjects, the results of which were recently reported (see 10-10-06 press release). Ceregene is initiating a larger, multi-center, double-blind controlled Phase 2 clinical trial before the end of 2006.

CERE-120 also has potential therapeutic benefit for Huntington’s disease (HD), ocular diseases (such as retinitis pigmentosa, macular degeneration and glaucoma) and amyotrophic lateral sclerosis (ALS or Lou Gehrig’s disease). These are being investigated in preclinical studies.

CERE-110 (AAV-NGF)

Nerve growth factor (NGF), a naturally occurring protein, has profound protective and function restoring effects on ‘cholinergic neurons’ in the brain. These neurons are strongly implicated as playing a key role in the memory loss and other cognitive disorders characteristic of the early phases of Alzheimer’s disease. CERE-110 carries the gene for NGF, which is delivered to the major region in the AD brain where degenerating cholinergic neurons exist. Following completion of an extensive nonclinical safety and efficacy program, Ceregene initiated and is completing.a Phase I clinical trial. A larger, multi-center, controlled Phase 2 clinical trial is in planning stages.

CERE-130 (AAV-IGF-1)

Insulin-like growth factor (IGF-1) is known to enhance the function and provide protective support of motor neurons that originate in the spinal cord and control all our muscles. Degeneration of these motor neurons is a hallmark of amytrophic lateral sclerosis (ALS) and is responsible for the death of all ALS patients. CERE-130 carries the gene for IGF-1, delivered via Ceregene’s proprietary gene delivery technology. Still in preclinical research, Ceregene and collaborators are working to enhance the biological characteristics of CERE-130 to help assure maximum safety and efficacy when the product advances to human trials.

CERE-140 (AAV-NT4/5)

Neurotrophic factor 4/5 (NT4/5) is a neurotrophic factor that may prove useful for treating ocular diseases. It is closely related to another neurotrophic factor, BDNF, that has shown promise in several animal models of retinal (eye) degeneration. CERE-140 carries the gene for NT4/5, licensed from Genentech, which is delivered to the retina via Ceregene’s proprietary gene delivery technology. In preclinical studies, Ceregene is optimizing the biological effects of CERE-140 prior to initiating a full scale preclinical safety/tox program for retinal degeneration.