Technology

Our main asset in dermatology, TEM1657, is a brand-new small molecule that shows major efficacy at pre-clinical stage to remit psoriasis symptoms both when administered orally or topically. Thanks to its very strong efficacy and favorable safety profile, TEM1657 will be an alternative to both current oral and topical solutions.

1

Rapid efficacy

Symptoms are significantly reduced after the first application of TEM1657.

2

Complete remission of psoriasis symptoms

No erythema – Regulated desquamation – Normal skin thickness.

3

No side effect

No skin thinning (unlike corticosteroids), no observed side effect on animals in toxicity tests.

Oral

At pre-clinical stage, TEM1657 administered systematically allowed to very efficiently alleviate psoriasis symptoms. After the second administration, all clinical components of psoriasis decreased drastically, namely erythema, skin induration, and desquamation. In 7 days, the skin is healthy and the healing process is more efficient than Otezla at the same dose.

Topical

Still at pre-clinical stage, TEM1657 applied topically was also very efficacious. Improvements appeared after the first application. In 4 days, the healing process is as efficient as with Dermoval (containing 0.05% Clobetasol, a strong acting corticosteroid). The advantage of TEM1657 over corticosteroids is that, additionally to its efficacy, it does not trigger skin atrophy, but rather preserves skin structure integrity.

The pathology

Psoriasis is a relapsing and remitting inflammatory disease that affects skin and sometimes nails and joints. It has an overall prevalence of about 2% of the world’s population, with important geographical variation that may be attributed to differences in climate, genetic background and antigen exposure.

 

Psoriasis can take many different forms, the most prevalent of them being plaque psoriasis characterized by skin patches with intense desquamation and loosely adherent silvery-white scales, which preferentially affect the elbows, knees, lower back, buttocks, and scalp. Lesser common forms comprise guttate psoriasis, pustular forms, erythrodermic psoriasis, and lichenified hands.

 

Psoriatic lesions are very impacting on patients everyday life by causing stigmatization and embarrassment leading to loneliness and the self-imposition of limitations. Established psoriasis can have serious consequences. Population studies have shown that about a third of patients develop psoriatic arthritis, and that severe forms of psoriasis are linked with impacting comorbidities such as cardiovascular disease, Crohn’s disease, type II diabetes mellitus, obesity, dyslipidemia, the metabolic syndrome, and lymphoma.

 

Skin lesions are due to the dysregulation of immune mediators, leading hyperproliferation and aberrant differentiation of epidermal cells, increased dermal vascularity, and massive infiltration of immune cells. Involved immune mediators include IL-17, IL-23, IL-20, IL-22, IL-1β, IL-6, and TNF-α, which interact as a network in the pathogenesis of psoriasis. The inflammation associated with psoriasis is generally limited to the skin, but can also progress to the joints causing psoriatic arthritis.

How it works

The Th17/23 axis is a natural warning signal delivered by certain immune cells that triggers immunity in case of pathogen infection with bacteria and fungi in the body. When abnormally activated or for too long after pathogen removal, the Th17/23 axis leads to chronic inflammation and generates autoimmune pathologies such as psoriasis.

 

This mechanism is common to other chronic inflammatory diseases such as rheumatoid arthritis, ankylosing spondylitis, Crohn’s disease, multiple sclerosis, vasculitis and atherosclerosis, lung disorders, asthma, and chronic obstructive pulmonary disease.

 

TEM1657 is able to modulate the activity of the Th17/23 axis, explaining its efficacy at reducing psoriasis symptoms. Preliminary results indicate its efficacy at reducing Crohn’s symptoms.

 

TEM1657 is currently being developed as a cream for application on local lesions as well as an oral treatment for generalized forms of psoriasis.

 

Once-a-day treatments of TEM1657 using either the cream or a systemic administration allowed to greatly improve skin symptoms in 4 days only at pre-clinical stage.

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