AC-100

AC-100 is Acologix’s most advanced program for hard tissue repair. Phase 2a or Phase 2b clinical studies are being planned, depending on the specific application. AC-100 has shown selective hard tissue repair activities in bone, cartilage, and dentin with high safety profile. While pursuing multiple hard tissue applications, the Company’s current corporate priority is cartilage repair for the latest promising data and large unmet needs in the area.

Compound and Activities
AC-100 is a novel hard tissue growth factor derived from a large molecule which is primarily produced by human bone and dental cells. AC-100 is a small peptide that can be manufactured by chemical synthesis. AC-100 has demonstrated new hard tissue formation activities in the defects in bone, cartilage, and dentin. A remarkable feature of this molecule is that its activities are selective to hard tissues and that it does not cause soft-tissue calcification, i.e., ectopic calcification or ossification.

Clinical Data
AC-100 was tested in a Phase 2 clinical study in the U.S. for its ability to promote new dentin formation. The study was designed to mimic a deep tooth cavity, similar to a condition where a root canal would have been considered as the primary treatment option. AC-100 treatment demonstrated a high safety profile as well as stimulation of new dentin formation in the deep dental cavities in this double-blind placebo-controlled study. Despite the small study size (N=17) the results showed a strong trend (p=0.06) toward new dentin formation with AC-100. The blinded histological analysis confirmed that the new dentin formed appeared normal and healthy as opposed to an irregular “reactive” dentin or osteodentin.

Cartilage and Bone Repair
AC-100 has been studied in multiple knee cartilage defect models in goats. These defects included non-severe defects affecting articular cartilage surface, both with or without a microfracture procedure. Another model involved severe deep defects affecting both cartilage and the underlying bone. Administration of 4 injections given on a weekly basis was accompanied by a rapid healing response. In a long term study, the blinded histological analysis confirmed the formation of hyaline cartilage (i.e., normal healthy cartilage) rather than a fibro-cartilage (i.e., a less resilient form of cartilage often formed following microfracture surgery). Further, in the deep defects where both cartilage and bones are affected, administration of AC-100 promoted the repair of both cartilage and the underlying subchondral bone. In addition, AC-100 has demonstrated bone repair activities following local injections in a closed fracture model as well as other bone defect models. As compared to bone morphogenetic proteins, or BMPs, AC-100 appears to form mature lamellar bone in a much shorter time after treatment.

Upcoming Clinical Development
Acologix believes that it has sufficient safety and efficacy data package to initiate Phase 2 clinical studies with AC-100 in any of the three areas—bone, cartilage, and dentin. In the cartilage area, the next step would be a double-blind, placebo-controlled Phase 2 study in osteoarthritis, joint trauma, and/or rheumatoid arthritis patients. In the bone area, a Phase 2 study with closed fracture patients is being contemplated. In the dental area, a Phase 2b study in a population with deep tooth defect, using a final commercial formulation would be the next step. Acologix seeks corporate partners in any of these three areas to advance the clinical development.

Market – Cartilage, Bone, and Dentin Areas
It is estimated that over 20 million suffer from osteoarthritis in the U.S. In particular, over a half of 65 years old or older population are believed to have osteoarthritis. The annual number of joint procedures including ligament injuries is approximately 23 million in the U.S. alone. Approximately 2.5 million have rheumatoid arthritis where cartilage is destroyed by immune reactions. Cartilage repair in these populations is a large unmet medical need. In more severe cases, repair of the underlying bone is also a large unmet need.

There are about 7 million new cases of bone fractures every year in the U.S. These fractures are typically caused by osteoporosis, injuries, and accidents. Approximately 700,000 critical bone fractures receive orthopedic intervention (e.g. surgery with placement of hardware or implants) to help repair these critical fractures. The target for AC-100 is a different population involving patients with less severe, closed fractures which do not necessarily require surgery. A simple AC-100 subcutaneous injection near the fracture site is expected to promote more rapid and predictable healing.

In the dental area, over 160 million common dental restoration procedures including pulp capping are performed every year in the U.S. In addition, 57 million crown placements and 19 million root canals are performed. AC-100 could be the first therapeutic drug which promotes dentin repair thereby reducing dental pain, irritation, and eventually, the necessity of a root canal. In a broader oral care field, AC-100 could be used with a scaffold in periodontal sockets to build the high quality bone required to support dental implants.