Fibrocell translating personalized biologics into medical breakthroughs

Fibrocell Science (NASDAQ:FCSC) is developing a pipeline of cell and gene therapies for localized treatment of connective tissue and joint diseases using autologous fibroblasts to deliver a targeted gene.

“Our personalized biologics approach represents a dynamic new dimension to the field of cell therapy and regenerative medicine, aimed at treating the underlying cause of disease by extracting cells from skin to create localized therapies that are compatible with the unique biology of each patient,” David Pernock, chairman and CEO, says in an interview with

“We believe 2016 will be a breakthrough year for us in four major disease areas in connective tissue and joints,” he adds.

In the second quarter of this year, the company plans to release data from a Phase 2 trial for its lead azficel-T sBLA program for the treatment of chronic dysphonia, which is a significant voice impairment due to severe vocal cord scarring or atrophy. The treatment is intended to restore voice for those who have lost the ability to communicate verbally.

In addition, Fibrocell plans to initiate a Phase 1/2 trial, also in the second quarter, of its first gene-therapy product candidate, FCX-007, for the treatment of recessive dystrophic epidermolysis bullosa (RDEB).

RDEB is a congenital orphan skin disease characterized by devastating, progressive and painful blistering that often leads to death. RDEB, the most severe form of dystrophic epidermolysis bullosa, affects an estimated 1,100-to-2,500 patients in the U.S. FCX-007 has been granted orphan disease status as well as a rare pediatric disease designation by the FDA.

Fibrocell also plans to conduct a proof-of-concept study in the first half of this year, using its second gene-therapy product candidate, FCX-013, for the treatment of linear scleroderma.

Linear scleroderma is an autoimmune disease, which causes debilitating linear scars and skin thickening that can lead to pain, reduced joint mobility and deformity in patients between the ages of five and 15. The company hopes to file an IND for FCX-013 in the fourth quarter of 2016.

Fibrocell is developing cell and gene therapies for localized treatment of connective tissue and joint diseases using autologous fibroblasts to deliver a targeted gene.

Both FCX-007 and FCX-013 were developed in collaboration with Intrexon Corporation (NYSE:XON).

Further expanding on this relationship, Fibrocell and Intrexon recently announced a new collaborative development program focusing on chronic inflammatory and degenerative diseases of the joint, including arthritis.

According to the CDC, arthritis is the most common disease in the most common cause of disability in the U.S., affecting more than 52 million adults and 300,000 children. Current therapies are delivered systemically and focus on limiting symptoms and slowing disease progression.

The goal of the new collaborative program is to deliver a protein therapy locally at sites of joint inflammation to provide sustained efficacy while avoiding key side effects typically associated with existing systemic treatments. The program is being initiated in 2016.

Mr. Pernock explains that fibroblasts are the most common cell in skin and connective tissue. They repair tissue by producing extracellular matrix proteins, including collagen and growth factors.

“The key advantages of our autologous fibroblast/gene-therapy approach is that we focus on one-gene disorders, with a known mechanism of action; we genetically modify fibroblasts, with safety testing prior to administration; and we inject locally, rather than systemic delivery, another safety advantage,” he contends. In addition, using a patient’s own cells reduces rejection concerns.

“We are using our proprietary technology to create personalized biologics,” he adds.

In an earlier Phase 1 study, injections of azficel-T demonstrated sustained improvement from month three through month 12 in the speech of a majority of patients with chronic dysphonia. Mr. Pernock says there are about 125,000 patients in the U.S. with chronic dysphonia caused by benign vocal fold lesions.

According to Fibrocell, COL7 is the main component of anchoring fibrils that connect layers of skin, and without them, patients suffer from constant blistering.

The primary endpoints in the ongoing Phase 2 trial are mucosal wave grade assessment, voice handicap index and GRBAS scale, which measures grade, roughness, breathiness, asthenia and strain, after four months, he adds.

Fibrocell’s FCX-007 drug candidate is an autologous human dermal fibroblast transduced with a lentiviral vector containing the gene for COL7A1.

Mr. Pernock says pediatric RDEB patients do not produce functional Type VII collagen (COL7) due to mutation in the COL7A1 gene. COL7 is the main component of anchoring fibrils that connect layers of skin and without these fibrils, patients suffer from constant blistering, leading to infections and skin cancers. Children who inherit the condition are often called “butterfly children” because their skin is as fragile as a butterfly’s wings.

“We think we can correct the disease by taking a patient’s own fibroblasts, transducing them with the COL7 producing gene so that they function as normal cells. We then reintroduce the cells into the wound area so they can lay down COL7 in order to have layers of the skin attach to each other,” he suggests.

In earlier in vitro studies, Mr. Pernock says the company demonstrated the ability to successfully make the delivery vehicle for FCX-007, with full gene integration into the cell genome. In addition, FCX-007 produced functional COL7 in the correct size and structure, and the study results were reproducible. “So, we know we are making good COL7, which is important.”

Fibrocell’s proof-of-concept study in mice injected with FCX-007 detected COL7 in the dermal-epidermal junction where anchoring fibrils form, “so we know the COL7 went where it was supposed to go,” he adds.

A proposed Phase 1/2 study slated for the second quarter this year will evaluate safety and efficacy in three adult patients in the Phase 1 portion of the study, to be followed by six pediatric patients in the Phase 2 portion.

Mr. Pernock says preclinical studies are underway with the company’s FCX-013 drug candidate for the treatment of linear scleroderma. The genetically-modified autologous dermal fibroblasts are designed to deliver an enzyme to degrade the collagen found in excessive scar tissue associated with the disease.

Proof-of-concept animal study data are slated for release in the first half of 2016, with an IND submission in the fourth quarter.

There are some 200,000 patients with localized scleroderma in the U.S. and FCX-013 would target some 40,000 patients who have scleroderma over a major joint and exhibit severe joint pain.

Griffin Securities analyst, Keith Markey, writes that Fibrocell is advancing to important milestones in 2016. “A clinical trial of one therapy will end, another will enter a Phase 1/2 study and an IND will be submitted for a third therapy.”

He rates Fibrocell at “buy” with a price target of $16. The stock closed at $3.57 on Friday.

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