CT327

CT327 is being developed as a novel topical treatment for psoriasis, atopic dermatitis and other conditions related to an overgrowth of keratinocytes. It is a new chemical entity (NCE) obtained through the application of Creabilis' proprietary MiniPEGylation approach. CT327 has displayed strong antiproliferative activity on keratinocytes by inhibiting the activity of the nerve growth factor (NGF) receptor TrkA.

CT327 has been shown to be safe and well tolerated in Phase I clinical trials and will enter Phase II studies in 2008.

C327 and MiniPEGylation
Creabilis' CT327 program has produced a new chemical entity which combines the features of a topical drug with the biological activity of K-252a - a kinase inhibitor known to be active in blocking the proliferation of keratinocytes in psoriasis. Creabilis used its proprietary MiniPEGylation approach to conjugate K-252a with low molecular weight PEG significantly improving the pharmacological characteristics of the resulting NCE.

Mechanism of action
CT327 interacts at a nanomolar level with TrkA, the receptor for NGF. NGF has been clearly identified as an agent which induces the proliferation of keratinocytes - a characteristic of a number of skin disorders. By blocking NGF activity, CT327 has been shown to inhibit keratinocyte proliferation.

Stage of Development
CT327 is one of Creabilis' most advanced projects and has been shown to be safe and well tolerated in Phase I clinical trials. Pre-clinical work has shown CT327 to be a powerful and selective inhibitor of TrkA and to block the proliferation of human keratinocytes in vitro. Further studies have shown dermal administration of CT327 leads to little or no systemic absorption - an important characteristic for the safety profile of the product candidate. In models of keratinocytes hyperproliferation, CT327 was shown to have a positive impact on a number of parameters relevant to psoriasis and atopic dermatitis.

SDS treated

SDS treated + CT327 0.5 mg

Creabilis is now advancing Phase II trial development for CT327 focusing on psoriasis and atopic dermatitis.

Psoriasis and dermatitis
Psoriasis is a chronic, recurring disease that causes raised red patches on the skin, scaling and irritation and often results in severe morbidity and disability. It is a common disorder, affecting 1-3% of the world's population. Current treatment depends on disease severity but is dominated by topical treatments, the market for which is more than $1.5 billion. There have been no significant new topical treatments developed for more than 15 years. Creabilis believes there is a substantial opportunity for CT327 as a new treatment which would improve the outcome for patients through excellent efficacy, lower toxicity and a clearly defined mechanism of action.

Table 1: Psoriasis prevalence, seven major markets, 2004

* UN population database 2004

Source: Datamonitor Stakeholder Insight: Psoriasis, 2004

Dermatitis (eczema) is a chronic, relapsing inflammatory skin disease that is characterized by intense itching (pruritus), dry skin (xerosis), redness (erythema) and exudation. The term dermatitis groups together several types of dermatitis. The most common form, atopic dermatitis, is becoming increasingly prevalent in northern, industrialized, temperate countries.

It has been estimated that there are around 40 million atopic dermatitis sufferers of all ages across the seven major markets (the US, Japan, France, Germany, Italy, Spain and UK) in 2007 (Table 2). The Atopic Dermatitis market was estimated to be worth $942m in 2005 (Datamonitor source).

Table 2: Atopic Dermatitis population, seven major markets, 2007

Source: Datamonitor Stakeholder Opinions: Atopic Dermatitis, 2007

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