Paricam Therapeutics

Mode of action

Genes (DNA) are transcribed to mRNA in the nucleus. This single-stranded mRNA is transported to the cytoplasm where it is translated by ribosomes into proteins.

Short complementary DNA-oligonucleotides (asODN) can bind specifically to a targeted mRNA leading to their functional inactivation and enzymatical destruction.

Antisense-oligonucleotides (asODN) are not produced by the cell itself and have to be delivered externally.

Inside cells asODN have a half live that is defined by many factors including its chemical modifications.

Due to its tunable turn-over and applied doses, antisense action can be controlled.

Treatment

The main goal of current treatments of periodontitis is to control the bacterial infection. This involves mechanical scraping of the tartar from above and below the gum line and “root planning” to get rid of rough spots on the tooth that can act as foci for bacteria. More advanced cases require the surgical removal of diseased gum tissue, lifting back the gums to remove the dental calculus (tartar) and then suturing them back in place to fit the tissue back to the tooth. In addition to this flap surgery, bone or tissue grafts may be necessary to encourage new growth of bone or gum tissue destroyed by the disease.

Antibiotics are frequently used in conjunction with these mechanical treatments, with these being necessarily broad spectrum agents and there is little evidence of this being successful. Beside burden of the whole body with antibiotics, there remains always the risk of the manifestation of antibiotic resistance.

None of the current treatments with pharmaceutical drugs are really curative in a long term and the disease is progressive, requiring increasingly invasive and expensive interventions.

The antisense oligonucleotide drug P-3005 will be formulated in a specific and optimized composition of a pharmaceutically validated polaxomer-solution (Thermoplast II) which has been developed for an efficient uptake of the drug to the human mucosa (IP application in progress). All single ingredients are commercially available and proofed by FDA. The resulting Thermogel (Thermoplast II) is liquid under cooled conditions (and therefore easy to formulate and administer) and shows increased viscosity at higher temperatures. At 37° it is a semi-solid which cannot be removed simply by the clearing mechanism of the sulcus fluid in the oral cavity.

The underlying polaxomer products (compounds) are in everyday medicinal use in a broad range of products such as cleaning solutions for contact lenses, wound healing and dermal cleaning products and have also been used for the direct administration of tetracycline to dental pockets. Local administration of our anti-ICAM-1 API (Paricam-P-3005) will result in relatively high local concentrations in the target tissue with negligible whole body exposure. This offers the opportunity to specifically suppress inflammatory processes in the gingiva using low doses of the product and avoiding any potential side effects related to systemic exposure.

PARICAM P-3005
Novel solution

Periodontal diseases are caused by a mixed infection by several types of virulent bacteria, causing a chronic inflammation of the gingival mucosa. Although stimulation of the immune system to attack the offending bacteria is generally protective, immune hyper-responsiveness can be counter-productive as a result of the release of neutrophils, cytokines and prostaglandins contributing to bone resorption and the destruction of connective tissue.

ICAM-1 is a key mediator of inflammation, and its expression is markedly increased in inflamed gingival tissue, and this over-expression persists even after the acute disease is resolved, leading to a chronical phenotype. Prolonged high expression of ICAM-1 is known to play an important role in the manifestation of a variety of diseases, making its down-regulation an attractive target for novel therapeutics in indications ranging from Crohn’s Disease to Psoriasis.

Topical application is a common way of introducing medical drugs into the oral cavity. However, as a consequence of salivary and sulcus fluid flow (which is increased still further in gingivitis) there is an extremely high clearance rate unless some way can be found to promote retention of the therapeutic for it to exert the desired effect. To overcome this problem BC (company) has invented a novel formulation of an anti-ICAM-1 compound

(P-3005), encapsulated in a Thermogel that is semi-solid at 37°C and resists clearance. This provides a targeted, slow release delivery of P-3005 precisely where it’s needed.

In extensive pre-clinical studies BC (company) has confirmed the penetration of P-3005 deep into the mucosa in animal model systems and the down-regulation of induced ICAM-1 expression in human gingival mucosa tissue. Based on these results a clinical trial proposal has been worked out for a first-in man study on induced gingivitis in humans to investigate safety and tolerance of topical local applied Paricam in a clinical trial phase I/II. Concept and design of this study has been positively reviewed from the German regulatory agency (BfArM). Our commercial vision for the drug is that a single course of treatment could lead to a permanent reduction of inflammation to the point where normal immune responses and repair mechanisms can take over.

For the many millions of sufferings on periodontitis, Paricam P-3005 represents a global first opportunity to reverse the destructive impacts of acute periodontitis and restore oral health by treatment with a novel therapeutic antisense drug. In addition, based on this treatment a restorage of the whole periodontiom could be realized, resulting in a very high medical level.

Outcomes: the result is a stop of gums reduction process and a better aestetics of the smile.

Mode of action

Treatment

PARICAM P-3005 Novel solution

PARICAM P-3005
Novel solution