A Clinical Study of Allogeneic Human Dermal Fibroblasts for Remodeling Scar Contractures

Restrictive scar contracture (a condition where tissue thickens and tightens, pulling the
surrounding healthy skin toward the damaged area) due to a serious burn injury can result in
long term aesthetic and physical consequences.

Skin contractures adjacent to a joint lead to joint deformities that severely restrict range
of motion (ROM) of the affected joint. Skin contractures are also often accompanied by
crippling levels of chronic pain resulting in a high level of dependency on pain
medications. These isolated or combined factors can lead to a significant disruption in both
social and professional life, leading to a marked impact on an individual's quality of life.

The current standard of care for restrictive scar contracture involves the surgical excision
of the contracture itself and/ or skin grafting. These standard therapies require extensive
and often repeated surgeries. Physicians are continually seeking less invasive therapies to
treat patients with burn contractures.

ICX‐RHY‐013 is an investigational medicinal product comprised of viable allogeneic human
dermal fibroblast (HDFs) cells suspended in HypoThermosol®-FRS. HDFs are isolated from
neonatal foreskin, cryopreserved, thawed and expanded in culture under good manufacturing
practice at Intercytex Ltd., United Kingdom. The drug formulation will be 20 million cells
per 1 milliliter of HypoThermosol® and will be administered to subjects via intradermal
injections at a maximum dose of 0.25 ml (or 5 million cells) per cm² of tissue.

If determined to be safe and effective, it is believed this therapy could, in the future, be
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 outpatient environment without the need for expensive
hospitalization

- enhanced quality of life

- lower costs

Cohort 1 will consist of 4 participants who are scheduled to have elective body contouring
surgery which will consist of the removal of an abdominal incision scar. The investigational
drug will be injected into the existing surgical incision (scar) with the investigational
drug, ICX-RHY-013. The purpose of this cohort is to evaluate the initial safety of the
investigational drug (ICX-RHY-013) in a series of doses on your surgical scar that will then
be surgically removed.

Cohorts 2 through 5 will consist of 4 participants each who have burn scars with restrictive
scar contractures. The purpose of these cohorts is to evaluate the ongoing safety of the
investigational drug (ICX-RHY-013) in post burn scars with restrictive scar contractures.
The investigational drug will be injected directly into these scar contractures. Each cohort
is unique in that the dose and frequency of the investigational drug received will be
different. We will evaluate the safety of the drug between each cohort by assessing all side
effects that the participants may experience.

Inclusion Criteria:

1. Subjects who are male or female, military or civilian, age 18 to 65 years of age and
able to provide informed consent

2. Subjects who have suffered an injury which has occurred no less than 6 weeks prior to
their screening date which has resulted in a stable restrictive scar contracture

1. Stable restrictive scar contracture that has resulted from abdominal surgical
incision and does not transverse a joint (Cohort 1 only).

2. Stable restrictive scar contracture has resulted from a burn injury and may
transverse a joint (Cohorts 2-5 only)

3. Subjects will have a minimum scar length of 7 cm and a maximum scar area size of
80cm² (Cohort 1 only)

4. Subjects will have a minimum scar area size of 1cm² and a maximum scar area size of
80cm² (Cohort 2-5 only).

5. Subjects who are, in the opinion of the Investigator, able to understand the study,
comply with the study design and are willing to return to the clinic for all the
research required follow-up visits

Exclusion Criteria:

1. Subjects with previous use of cellular therapy (e.g. Isolagen) in the treatment area

2. Subjects with a known history of keloids

3. Subjects with a known history of bleeding disorders

4. Subjects who have facial restrictive scar deficits, not to exclude the neck area.

5. Subjects who have had contracture-release procedures in the treatment area within the
previous six months

6. Subjects with a known allergy to any of the constituents of HypoThermosol-FRS

7. Subjects taking immunosuppressive therapy including systemic steroids will be
excluded if they have received any dose >7.5 mg of prednisone equivalent/day for more
than one week within 90 days of the first treatment or planning immunosuppressive
therapy at any time during the study (Intranasal/inhaled steroids are acceptable)

8. Diagnosis of cancer within last 12 months and /or actively receiving chemotherapy or
radiation treatment

9. Subjects with a life expectancy of <9 months, terminal conditions or factors making
follow-up difficult (e.g. no fixed address, telephone etc)

10. Subjects with a history of hypersensitivity to additional study-associated
drugs/therapies (e.g. isopropyl alcohol, EMLA cream, adrenaline, lidocaine, etc)

11. Subjects with planned major surgical intervention during the course of the study.

12. Subjects with known idiopathic or drug-associated coagulopathy

13. Subjects taking medicinal products known to reduce hemostasis (e.g. heparin,
Coumadin, etc.) in the 2 weeks prior to commencing treatment or planning to take
medicinal products known to reduce hemostasis during the 12 week study period

14. Subjects who have taken any other investigational product within 30 days prior to
screening or planned use of any other investigational product during the study
period.

15. Subjects who are pregnant, lactating, planning pregnancy and women of child-bearing
potential who are not abstinent or practicing an acceptable means of contraception,
as determined by the Investigator, for the duration of the treatment phase

16. Subjects with abnormal blood biochemistry or any other abnormal laboratory finding
considered clinically significant in that it would deem the subject inappropriate for
surgical procedures, as determined by the investigator (i.e. CBC with Differential,
platelets, comprehensive metabolic panel to include electrolytes, bun/creatinine,
liver function test and coagulation tests).

17. Subjects who have, as determined by the investigator a history or clinical
manifestations of significant renal, hepatic, cardiovascular, metabolic, neurologic,
psychiatric, or other condition that would preclude participation in the study (i.e.
Type 1 and Type 2 diabetic patients) or any condition within the last 14 days
requiring hospitalization or surgical intervention.

18. Subjects with evidence of any past or present clinically significant medical
condition that would impair wound healing

19. Subjects with a known hypersensitivity to gentamycin, amphotericin B, Bovine serum or
porcine products.

20. Subjects with known alcohol or narcotic drug dependency

21. Subjects with diagnosed autoimmune disorders known to affect wound healing, such as
Systemic Lupus Erythematosis (SLE), psoriasis, infection and inflammation (seborrheic
dermatitis).

22. Subjects receiving an immunosuppressive medication regime including transplant
anti-rejection agents.

23. Subjects with an Axis II to diagnosis DSM-IV (e.g., Schizophrenia, Bipolar Disorder).
Subjects who are found to be stable on medication and receive psychiatric clearance
could be eligible for study participation per the Physician's discretion