Final Report Summary - PRIMOMED (Use of PRIMate MOdels to support translational MEDicine and advance disease modifying therapies for unmet medical needs) Executive Summary:The focus of Primomed was the translational medicinal approach of the SMEs, i.e. developing disease modifying therapeutics for high unmet medical needs in chronic inflammatory and degenerative disorders. The Primomed project utilized well characterized non-human primate models so that the SMEs can capitalize on subsequent clinical successes of their therapeutic lead compounds.The power of the Primomed project was the creation of a consortium bringing together four small and early-stage biotech companies owning innovative and proprietary drugs and two of the most renowned European primate research centres which performed research activities with the new disease modifying molecules of the SME’s.The disease areas of interest in Primomed are asthma, multiple sclerosis and Parkinson disease. Project Context and Objectives:The main objectives of the project are:(1) to demonstrate proof of concept that drug compounds of the SME’s are efficacious in primate models relevant for the diseases of interest, and(2) to determine the immune responses in biological samples generated by the research activities in the different animal models.Project Results:The Parkinson Disease (PD) study yielded interesting results. The drug compound NRG-101 might be a potentially new clinical candidate for reduction of parkinsonism and disease progression.Potential Impact:PD is a disease where therapies to reduce the impact of the diseases exist, but they are far from ideal with unwanted side effects and a lack of therapeutic efficacy. Moreover, these therapies have significant limitations in addressing the needs of patients. The most common drugs used in the treatment of Parkinson disease (PD) are comprised of dopamine agonists, catechol O–methyl transferase inhibitors (COMT inhibitors), monoamine oxidase inhibitors (MAOIs) and dopaminergics. The key unmet medical need is for curative treatments or treatments that modify the disease progression. PD shows a rich product pipeline. However, the therapy area has suffered the worst attrition rate (27%) in the sectorwith 34 candidates lost to failures or other reasons in preclinical-clinical studies in 2009. The PD pipeline currently lacks innovation but the introduction of cell therapies and biologics is expected to expand the market significantly. Currently, the PD pipeline consists of two categories of therapies, symptomatic and neuroprotective.Symptomatic drugs treat both the motor and non-motor effects of PD. There are already several treatments for Parkinson’s symptoms, however, these medications have side effects and do not address certain symptoms; for example, none of them help with the common problems of fatigue, constipation or balance. So, one goal is to find better symptomatic drugs. The other option is to study drugs that have already been approved by the FDA, eitherfor use in Parkinson’s or for another condition, to see if they might work for additional Parkinson’s symptoms.In the last years there was excitement about the possibility of developing neuroprotective treatments, those that would slow or prevent the progression of PD. So far, no therapies have been proven to be really neuroprotective and most of the candidates are in the early stages of the development process, years away from approval. For instance, one of the most advanced candidates for neuroprotective therapy is creatine. Preclinical studies have suggested that it can improve the function of mitochondria, which produce energy inside cells. It also may act as an antioxidant that prevents damage from compounds that are harmful to cells in the brain. In a mouse model of PD, creatine is able to prevent loss of the cells that are typically affected. This molecule was investigated in a double-blind, placebo-controlled, phase III study on 1700 patients and was finally halted because patients taking creatine showed no differences in disease progression compared to those taking the placebo.In earlier development stage there is ProSavin® (Oxford Biomedica), which is a gene therapy that is administered surgically into the brain. It consists of a genetically engineered virus that delivers the genes for three enzymes that are required for the synthesis of dopamine. ProSavin® was evaluated in a Phase I/II study testing three ascending dose levels in patients with mid-stage Parkinson's disease. ProSavin® has demonstrated a longterm safety profile, up to 48 months post-treatment. All patients treated have shown an improvement in motor function at the six-month efficacy endpoint relative to baseline. A second example of a gene therapy approach uses CERE-120 (Ceregene), a viral vector engineered to deliver the nervous system growth factor neurturin (NRTN). Another interesting neuroprotective candidate being studied is isradipine (DynaCirc® CR). Isradipine is a calcium channel blocker that is already used to treat high blood pressure, and is investigated in a randomized, double blind, placebo controlled phase II study to find out if it can be used safely, is tolerated by patients with PD and if it slows the progress of the disease.In earlier preclinical discovery phase, much of the excitement surrounds neuroprotective strategies, and much effort is put on the study of the use of growth factors and neuroregenerative approaches as an attempt to not only stop the progress of Parkinson's disease, but also to reverse it. For instance, gene therapy based on neurotrophic factor delivery (GDNF) is currently developed by Uniqure; naturally-occurring brain proteins called activity-dependent neuroprotective protein (ADNP) and activity-dependent neurotrophic factor (ADNF) have also proven pre-clinical efficacy. An oligopeptide, PN277, has beenfound to have significant immune-mediated neurorestorative activities in several preclinical models for acute and chronic neurodegenerative conditions, including PD.MindNRG plans to pursue the development of its product candidates based on the deep knowledge of its scientific team concerning the pathophysiology of neuropsychiatric diseases, the pharmacology of the compound and the limitations of current therapies. NRG-101 and its analog represent a differentiated treatment option that could overcome the limitations of current therapies and address the unmet needs of patients and their families.The strategy is to develop and commercialize products with transformative potential addressing critical unmet medical needs in the neuropsychiatric therapeutic area. Pursuing this strategy will be based on the following principles: unwavering commitment to neuropsychiatric patients and community; scientific rigor applied to drug development and the clinical trial process; leveraging patient and caregiver insights to drive scientific advancements; and integrity.For NRG-101 it will be possible to access European and the United States and Latin America markets through a focused, specialized task force where the population dynamics would prove efficient. Alternatively, executing distribution and other marketing arrangements with third parties for the drug candidate is an option. Subject to receiving marketing approvals, it is expected to commence commercialisation activities by building a focused sales and marketing organization in the United States, EU and Latin America to sell the product candidate. Such an organization will be able to target the community of physicians who are the key specialists in treating the patient populations for which our product candidate is being developed. In parallel with building thisorganisation, developing educational initiatives with respect to approved products and relationships with thought leaders in relevant fields of medicine is important. As part of this commitment to supporting optimal patient care and sustainable healthcare systems globally, the importance of fully understanding the needs of the patient communities which is served is importante. One of the best ways to accomplish this is by working with patient organizations, which are closely connected to patients’ most important concerns and interests. List of Websites:www.primomed.fp7sme.euprimomed@fp7sme.eu
