A Highly Disruptive Regenerative Medicine Company - RepliCel
BEND, OR / ACCESSWIRE / March 16, 2017 / RepliCel (REPCF) (TSX-V:RP.V) is a regenerative medicine company focused on developing innovative products for sports medicine and aesthetics markets - degenerated and chronically painful tendons, aging and sun-damaged skin, and hair loss due to androgenetic alopecia.
RepliCel's products are autologous cell therapies involving a local injection of cells into areas where the need (aging skin, degenerated tendon, hair loss) is related to the resident cells no longer capable of meeting demand. The newly injected cells are being developed and designed to do what's needed (rejuvenate skin, regenerate tendon, and grow new hair in areas of hair loss).
The conditions RepliCel is actively addressing chronic tendinosis, skin aging, and androgenetic alopecia (pattern baldness). Each disease state is consistent with a deficit of a specific cell type which RepliCel believes is critical to normal function. All treatments under development are based on RepliCel's innovative technology which utilizes cells isolated from a patient's own healthy hair follicles. These products are built on RepliCel's proprietary manufacturing platforms and are covered by issued and filed patents as well as trade secrets. RepliCel is also developing a programmable cell injector device designed for dermal injections of cells, currently approved dermal filler products, and a variety of other products injected through the skin.
The Potential of Autologous Cell Therapy
RepliCel's treatments use autologous cell therapy ("ACT"), which is one of the most rapidly developing areas of regenerative medicine in the development of novel treatments for numerous human disorders. ACT involves isolating an individual's own cells from harvested tissues and growing more of those cells, or 'expanding' those cells, in controlled conditions in a regulatory compliant manufacturing facility. These purified, expanded cells are then reintroduced to the donor to treat a specific condition. The benefits of autologous (derived from the same person) therapy (as compared to heterologous or derived from a different person) includes minimized risks of systemic immunological (anaphylactic) reactions, bio-incompatibility, and disease transmission. Furthermore, the effects of ACT may be longer lasting than pharmacological or surgical interventions.
Source: Company February Investor Presentation
RCT-01: Treatment for Chronic Tendinosis
Background
Tendinosis refers to a chronic disease of the tendon. It is a function of an imbalance of tendon breakdown and tendon repair initiated first by an injury which does not heal properly. This leads to cycles of compromised repair and subsequent re-injury until such time as there is no healing and a degenerative process has set in. Typically, this chronic condition is linked to aging, overuse, and to general health. We believe that the current standard of care is failing to provide a satisfactory solution to this chronic condition.
Treatment
Chronic tendon injuries resulting from sports-related or occupational overuse are a significant unmet medical need. These are people with frequent or consistent pain in their ankle or Achilles tendon, patellar tendon (jumper's knee), both tendons of the elbow (Tennis Elbow or Golfer's Elbow), shoulder (rotator cuff) etc.
Tendons consist of specialized connective tissues that attach muscles to bones. When mechanical loads exceed the strength of a tendon or tensile range is lost due to aging, micro-tears of the collagen fibers within tendon occur. Once a tendon is injured, healing can but does not always occur intrinsically via tenocyte activation within the injured site or extrinsically via recruitment of collagen-producing cells from the surrounding area. Naturally healed tendon does not return to the same physiological state as 'intact' tendon, but does allow for normal function. Inadequate rest and improper healing often result in re-injury and rupture. The goal of RepliCel's injection of cells highly expressive of collagen is to make this healing more efficient and complete.
Current treatments manage pain and facilitate healing processes; however, they do not mediate complete recovery and leave patients demobilized for several months during treatment. RepliCel believes that improved therapeutic strategies are therefore in considerable demand. RepliCel's fibroblast technology for tendinosis, which RepliCel refers to as RCT-01, has been developed over five years of research, experimentation and trials.
RCT-01 is a tissue-engineered product made from a procedure using collagen-producing fibroblasts isolated from non-bulbar dermal sheath (NBDS) cells within the hair follicle that are replicated in culture. These fibroblasts are efficient producers of type I collagen and because they are of anagen hair follicle mesenchymal origin, they have the potential to replicate efficiently in culture. The use of these fibroblasts is, therefore, ideal for treating chronic tendon disorders that arise due to either a degeneration of collagen producing cells or a deficit of active collagen producing cells.
Because RCT-01 directly provides a source of collagen expressing cells to the site of injury, addressing the underlying cause of tendinosis, we believe it has advantages over current treatments such as the use of non-steroidal anti-inflammatory medication or corticosteroids which are limited in efficacy. Another advantage of RCT-01 is the autologous nature of the cellular product, thereby reducing the likelihood of adverse immune reactions upon administration.
Phase 1 Clinical Trial
Phase 1 human pilot clinical trials were conducted by RepliCel's collaborative partner, Dr. David Connell, which focused on tendinosis of the Achilles, patellar and lateral elbow (commonly referred to as tennis elbow) using skin tissue derived fibroblasts. In these trials, where 90 patients were injected with cultured, autologous fibroblasts, no adverse events were reported. RepliCel has expanded on Dr. Connell's approach by isolating NBDS fibroblasts from the hair follicle that express upwards of five times the amount of type I collagen than fibroblasts derived from skin tissue as pursued by Dr. Connell.
Phase 1/2 Clinical Trial
On December 1, 2014, RepliCel announced Health Canada's clearance to initiate a Phase 1/2 clinical trial in subjects who have failed traditional tendon treatments and who are otherwise in good health. Trial design was randomized, double-blinded, placebo-controlled with a treatment-to-placebo ration of 3:1. The mechanics of RepliCel's treatment involve the extraction of hair follicles from the back of a patient's scalp via a single punch biopsy. NBDS cells are isolated from the hair follicle sheath, replicated in a current Good Manufacturing Practices (cGMP) facility and are then reintroduced under ultrasound guidance directly into the area of damaged tendon. The collagen rich fibroblast cells are expected to initiate and complete the healing of the chronically injured tendon. After injections are performed, subjects will return to the clinic for assessments of safety, function and pain, as well as changes in tendon thickness, echotexture, interstitial tears and neovascularity.
The primary end point is safety while a secondary end point of efficacy is being measured at six months. RepliCel will report data from this trial in the next few days and if the data is positive, RepliCel may have a transformational and highly disruptive therapeutic option, in these indications where no true option exists. The value of this program, assuming safety and efficacy are shown, could be in the billions. RepliCel will pursue further indications of other tendon populations including patellar tendinosis (jumper's knee) and lateral and medial epicondylitis (tennis and golfer's elbow).
RCH-01
RCH-01 is an autologous cell therapy utilizing dermal sheath cup (DSC) cells isolated from the hair follicle to treat androgenetic alopecia. Dermal sheath cup cells are isolated from a small punch biopsy taken from the back of the subject's scalp. These cells are replicated and then reintroduced into balding areas on the subject's scalp. After injections are performed, subjects return to the clinic for assessment of total, terminal and vellus hair density and cumulative hair thickness, as well safety.
On March 15, 2017, RepliCel released data from the Phase I study for RCH-01. The study focused on safety and efficacy, and consisted of 19 patients all of whom suffer androgenetic alopecia. The initial data indicated that the primary endpoint of the trial, safety, was fully achieved, and the secondary endpoint proved highly promising despite the study not being powered for efficacy.
Specifically, to the secondary endpoint, remember, the trial was not powered for (intended to prove) efficacy, regardless the top 10 participants reported at least a 5% or greater increase in hair density at six months' post-injection with an average increase of 11.8%. This group demonstrated a sustained response at 24 months which averaged a 4.2% increase over baseline hair density. While there was a high degree of variability in hair density between individual participants at 24 months' post-injection compared to baseline, an overall stabilization of hair loss was observed among all the patients treated per protocol.
Management indicated that RepliCel already has a much more mature product than the one used in this trial, and they anticipate even stronger efficacy results during the Phase II efficacy study, when powered for efficacy. Recent animal studies conducted by the Company have showed increased efficacy by combining smaller doses of RCH-01, with multiple injection sites. Additionally, the Company believes that using the RepliCel injector will increase the consistency of the results.
The Phase I study was conducted at Tokyo Medical University Hospital and Toho University Ohasi Medical Center, by Drs. Tsuboi and Niiyama, and is being financed by the Shiseido Company. Each product being injected will be manufactured by Shiseido at their SPEC (Cell-Processing and Expansion Center) facility in Kobe, Japan. RepliCel helped Shiseido design, validate, and prepare the SPEC facility for certification by Japan's PMDA (Pharmaceuticals and Medical Device Agency). Shiseido's SPEC team was also trained by RepliCel and Innovacell in the GMP (Good Manufacturing Practice) compliant production protocols for RCH-01. Data from this trial is expected in the latter half of 2018 and may be sufficient to commercially launch the product in Japan. If this study proves efficacy, this product also may be worth billions of dollars given there are no viable treatment options for mild to moderate androgenetic alopecia (hair loss). Below is an illustration of the hair follicle cycle.
Source: Company February Investor Presentation
Hair Restoration Treatment Options
Medical hair restoration consists of a variety of surgical hair restoration treatments designed to reduce baldness. Follicular unit hair transplant ("FUT") surgery is by far the dominant hair restoration treatment and involves the surgical removal of large portions of hair-bearing scalp from the back of the head.
These sections of scalp skin are then dissected by hand into smaller hair follicle clusters (follicular units) and transplanted to the balding areas of a patient's scalp. Scalp flap surgery, scalp reduction surgery and scalp expansion surgery are other forms of surgical hair restoration. Combined, these treatments represent a far smaller patient base than hair transplant surgery.
Follicular unit extraction or ("FUE") is another type of hair transplant technique in which a small round punch is used to extract follicular units from a patient's baldness-resistant donor area. These 1, 2, 3 and 4-hair follicular unit grafts are then transplanted into a patient's balding areas. This is a time consuming and tedious procedure and a physician is often limited to transplanting only 500 to 600 follicular unit grafts in one day which means a patient often has to come in a number of times to achieve the desired result. While the FUE procedure has grown in popularity, largely due to the minimally invasive way in which follicular unit grafts are removed, the standard strip excision method is still the leading hair transplant procedure.
However, FUT and FUE hair transplant surgery will always be limited by the availability and quality of donor hair follicles. Hair replacement surgery is a complicated procedure that may require several hair transplant sessions over a period of one-to-two years before the desired result is achieved. Ultimately, the act of hair transplantation does not 'create' new hair. The process simply relocates viable hair from the back of the scalp to the front. Most women will not undergo this extremely invasive surgery. In terms of cosmetic results, both FUT and FUE surgery are quite dependent upon the skill of the surgeon.
Non-Surgical Restoration
Only two hair restoration treatments approved by the United States Food and Drug Administration ("FDA") are available today: minoxidil and finasteride. Minoxidil is marketed as Rogaine®. Finasteride is marketed as Propecia®. These two products can be effective in hair loss prevention and may grow new hair. However, once a patient begins using Rogaine® or Propecia®, he or she must continue to use the products indefinitely. If an individual stops using the drug, any new hair grown as a result of the drug will likely fall out. As with any drug, adverse reactions can sometimes occur.
Rogaine® (Minoxidil)
Rogaine® (minoxidil) was introduced in 1988 as the first drug approved for treatment of baldness by the FDA. It is now available over-the-counter in several countries including the USA. Minoxidil remains the only product available without a prescription that has been approved by the FDA as a proven treatment against hair loss. Minoxidil is no longer under patent so it is also marketed as a number of topical treatments made by several different companies. Minoxidil stimulates hair growth in individuals with male and female pattern baldness; however, the mechanism of action is unknown. It comes in 2% and 5% topical formulations and known side effects include itching and skin irritation of the treated scalp, as well as unwanted hair in areas adjacent to treatment sites which can be distressing to women when the face is involved. Once treatment is stopped, all results will be lost within 3 to 6 months.
Propecia® (Finasteride)
Finasteride is marketed by Merck under the trademark names Proscar® and Propecia®, among other generic names. It is a synthetic antiandrogen that inhibits type II 5-alpha reductase, the enzyme that converts testosterone to DHT. Only available by prescription, it was developed to treat mild to moderate male pattern hair loss on the vertex (top of head) and anterior mid-scalp area (middle front of head) in men only. There is insufficient evidence that Propecia® works for receding hairlines at the temples. Listed side effects include erectile dysfunction and depression. Once treatment is stopped, all results will be lost within 6 to 12 months.
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