ICX-RHY is a skin repair and rejuvenation product. It has been designed to improve the structure, function and appearance of skin damaged by medical conditions such as EB, scarring and associated scar contractures or the aging process. It is being developed primarily for medical applications but has also demonstrated utility in aesthetic applications.

ICX-RHY is a suspension of human dermal fibroblasts (HDFs) in cell storage medium, for injection into the skin. When injected into the skin, the HDFs are believed to remodel and lay down collagen and other extracellular matrix within the dermis. An improvement should be apparent once the HDFs have begun to produce collagen.

Treatment Pipeline:

• Epidermolysis Bullosa
• Scar Contractures
• Acne Scarring
• Keloids

Epidermolysis Bullosa:

Epidermolysis bullosa (EB) refers to a clinically heterogeneous group of blistering skin disorders that occurs with similar incidence across all populations in Europe and throughout the world (Fine et al. J Am Acad Dermatol 2008; 58: 931-50). 

One of the most clinically severe subtypes of EB is RDEB. This autosomal recessive condition is caused by loss-of-function mutations in the COL7A1 gene, which encodes the skin protein type VII collagen (C7) (Dang and Murrell Exp Dermatol 2008; 17: 553-68).

Loss of C7, which is expressed in the basement membrane at the junction between the epidermis and the dermis, leads to structural defects in adhesion structures known as anchoring fibrils. These changes make the skin fragile and susceptible to blistering following trauma. Blistering often leads to chronic erosions and there is poor wound healing of traumatised skin. In addition, the impaired healing can be followed by scarring and contractures, as well as several major cutaneous and systemic complications (Fine and Mellerio J Am Acad Dermatol 2009; 61: 367-84 and 387-402).

These complications include an increased risk of skin malignancy, anaemia, oesophageal stricture, nutritional deficiencies, constipation, ocular scarring, dental decay, endocrine abnormalities, and osteoporosis. RDEB also has a major impact on quality of life, social and family interactions (Frew et al. Br J Dermatol 2009; 161: 1323-30) At present, there is no effective treatment for RDEB; current best practice involves application of protective dressings (which can take several hours each day and which is often painful) and monitoring/attempting to treat disease complications.

Nevertheless, several research groups around the world are trying to develop new therapies for RDEB. These attempts are based on developing gene, protein, cell and drug therapies.

Scar Contractures:

Injuries such as burns that involve damage to the dermis rarely heal without formation of a scar. Scar tissue is not identical to the tissue that it replaces and is usually more fibrous and of inferior functional quality. The scar shows an increase in the thickness of the new epithelial layer but the attachment of epidermis is poor making the surface vulnerable to further injury.  Sometimes the scarred skin extends beyond the three-dimensional boundary of the original tissue resulting in a raised or hypertrophic scar.  Hypertrophic scarring is seen in up to 50% of healed deep burns and this can lead to wound contracture if the scar affects a joint as the skin over the joint is firmer and less extensible and this in turn then limits movement of the joint. Both the contracture and hypertrophic scarring process peak between 3 and 6 months after injury and partially resolve at 12 to 18 months, frequently long after the patient has been discharged.

Restrictive contractures due to serious burn injuries can result in long term aesthetic and physical consequences. Skin contractures bridging or located proximal to a joint lead to joint deformities that severely restrict range of motion (ROM) of the effected joint.  Skin contractures are also often accompanied by debilitating levels of chronic pain requiring a high dependency on pain medication.  This pain medication can also lead to other undesirable side-effects and unwanted dependency on the drugs administered to control the pain.  These factors in isolation or combined can lead to significant disruption in both social and professional life, leading to a marked impact on wounded warrior’s quality of life

Burns account for approximately 10% of all combat casualties (Tina L. Palmieri MD ATAAC St. Pete Beach August 2008) and it has been shown in a study of almost 1000 patients that 38.7% of adult burn survivors admitted to a regional burn center developed at least one contracture and amongst these patients the mean number of contractures was three per patient (Schneider JC et al J. Burn Care Res 2006 pp 508-514).

Post-burn contractures are therefore a very significant problem for the injured war fighter and that any treatment that can alleviate this problem will be of tremendous benefit. Moreover, extensive traumatic skin loss and resulting contractures also occurs with other battlefield injuries that do not necessarily involve thermal burns and is particularly an issue with Improvise Explosive Devices (IEDs)

The current standard of care for a wound contracture involves surgical release or excision of the contracture itself and skin grafting which requires extensive and often repeated surgeries.

Previously, groups both in the UK and US have shown that simple injections of either cultured autologous (from the patient themselves) or cultured allogeneic (from an unrelated donor) human dermal fibroblasts can result in remodelling of the skin and significantly improve the quality the dermis and mobility of the affected joint(s) when injected into burn contractures. Wound contractures that have been present for many years can be improved and softened within weeks.  Allogeneic fibroblasts have been shown by many different laboratories not to illicit an immune reaction and they have the distinct advantage over autologous cells in that they can be cultured, banked and tested for things such as viral safety before use and can moreover be provided at point of need in almost unlimited amounts.

As the product is delivered in a series of superficial injections and can be carried out in a doctor’s office, this treatment could represent a new less invasive therapy of choice for patients with burn contractures, where current recourse would be to surgery. 

This advance could have significant positive benefits to the patient in terms of:

• No side-effects of surgery
• Treatment given in an out-patient environment without the need for expensive hospitalization
• Enhanced quality of life
• Lower costs

ICX-RHY has already been used to treat a small number of patients with restrictive contractures and the results led to a collaboration with the McGowan Institute for Regenerative Medicine that is funded by the U.S. Department of Defense to examine this treatment in a Phase I/IIa clinical study.

Acne Scarring:

Acne vulgaris or acne is a common human skin disease, characterized by areas of skin with seborrhea (scaly red skin), comedones (blackheads and whiteheads), papules (pinheads), pustules (pimples) and possibly scarring. Acne affects mostly skin with the densest population of sebaceous follicles; these areas include the face, the upper part of the chest, and the back.

Acne scars are the result of inflammation within the dermis brought on by acne. The scar is created by the wound trying to heal itself resulting in too much collagen in one spot.

Several different types of acne scar have been described:

Ice pick scars: Deep pits, that are the most common and a classic sign of acne scarring.

Box car scars: Angular scars that usually occur on the temple and cheeks, and can be either superficial or deep, these are similar to chickenpox scars.

Rolling scars: Scars that give the skin a wave-like appearance.

Hypertrophic scars: Thickened, or keloid scars.

A Phase II clinical study involved the use of ICX-RHY in acne scarring in a study conducted by Dr David Eccleston MB ChB, at the MediZen Clinic in Birmingham has been carried out.

Subjects were followed out to 6 months post-treatment with the following results:

The average satisfaction scores for the treatment at 6 months as assessed separately by both subjects and the investigator on a scale of 1 -10 (10 being the highest) were 6.8 and 6.3 respectively

No serious adverse events were observed and the product was well tolerated