Executive Summary

OrthodontiCell’s mission is to create the smiles that can light up a room in less than half the time with significantly less pain than currently available orthodontic treatments. This is all made possible through OrthodontiCell’s Tooth Movement Accelerator™, a bioelectric stimulation mouthpiece that only needs to be used 3 times a week for 20 minutes.
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Vision

Create great smiles in less than half the time of current orthodontic treatments by accelerating tooth movement by up to 80% while reducing the patient’s pain by over 70%. Once tooth alignment is completed, permanently “freeze” the teeth in place to minimize the need for a long-term retainer or other follow-up treatments.

Product

Orthodonticell uses a bioelectric stimulation mouthpiece to generate the signals for tooth movement through molecules including Receptor Activator of Nuclear Factor Kappa B Ligand (RANKL), Vascular Endothelial Growth Factor (VEGF), and Osteoprotegerin (OPG) for accelerated tooth movement and long-term stabilization.

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Problem

Roughly 12 million people worldwide seek orthodontic treatment with braces or aligners every year. Although the time necessary to complete orthodontic treatment with braces or aligners varies considerably, the average patient requires up to 2 years for treatment. Lengthy wearing of such equipment can result in unwanted side effects and a loss of motivation to complete the treatment. While the market for children and teenagers is huge, the adult market is growing rapidly due to many being unhappy with their smile despite the embarrassment of having braces as an adult. Cost can also be a significant challenge for families and adults as the cost of braces typically ranges from $3,000 to over $8,000. As a result, alternatives such as invisible aligners are gaining significant market share due to the high cost and cosmetic effects of standard braces. One provider of invisible aligners treated nearly one million patients in 2017, generating sales of $1.5 billion.

RANKL

A powerful biological signal driving osteoclastic formation, function, and survival that supports the bone remodeling process that occurs in dental alignment. Often considered the most important “upstream” regulator of tooth movement, RANKL has been shown to promote osteoclastic activity and accelerated tooth movement followed by subsequent alveolar bone formation. The figure to the right shows the tooth movement results from a mouse model with an orthodontic appliance and daily injections of RANKL (compared to control injections of PBS). After 7 days, significantly accelerated tooth movement was seen in the mice receiving RANKL injections. Bioelectric stimulation is likely to upregulate the production of RANKL.

Osteoclasts play a key role in bone remodeling with increased activity contributing to accelerated tooth movement. In addition to increased tooth movement, mice receiving RANKL injections were also found to have a higher osteoclast count during the first 21 days of injections compared to PBS Figure to the left. This initial increase in osteoclast count may be a contributing factor to the accelerated tooth movement seen in the study.

OPG – OPG promotes the genesis of osteoblasts which assist in bone hardening and subsequent tooth stabilization. As bioelectric stimulation can enhance OPG production, teeth are more likely to anchor in place post-treatment. OPG also decreases bone breakdown by acting as a decoy receptor for RANKL, inhibiting osteoclastogenesis and the bone resorption process. OPG injection studies have demonstrated the ability to stabilize teeth in their final position after alignment with minimal required use of a retainer.

OrthodontiCell
Bio-Electric Tooth Movement Accelerator™
Bio-Electric Teeth Position Stabilizer™

OrthodontiCell’s Tooth Movement Accelerator™ is a bioelectric stimulation mouthpiece that produces the same amount of RANKL and OPG in the periodontal tissues that have been used in successful needle injection studies. The Tooth Movement Accelerator emits small electric pulses that control expression of signaling molecules such as RANKL and OPG while attracting cells such as osteoclasts to enhance tooth movement. The result for the patient is accelerated tooth movement with increased RANKL and OPG levels without the painful injections or the side effects associated with systemic administration of these signaling molecules.

Patients using OrthodontiCell’s patented technology may enjoy the following benefits over standard dental alignment techniques (e.g. braces):
• Up to 80% tooth movement acceleration
• Over 70% reduction in pain associated with tooth alignment
• Long term tooth alignment stabilization through controlled OPG expression
• Improved overall results due to enhanced treatment compliance

Orthodonitcell is working with Leonhardt Launchpads Utah to conduct further research into the OPG protein to enhance long-term tooth alignment stabilization for the next generation of Orthodonticell’s products.

A video with additional information on the Bio-Electric Tooth Movement Accelerator™ and Bio-Electric Teeth Position Stabilizer™ can be found at: https://vimeo.com/267150484

Market:

• Orthodontics market – $11 billion (annual)
• Worldwide 12 million patients begin orthodontic treatment each year including 4 million in the U.S.
• A leading clear dental aligner has already treated over five million patients. In 2018 alone, 1.3 million patients received clear aligner treatment.
• A market leader in invisible aligners had a market capitalization of over $21 billion in November 2019.
• Since 2018, over $450M of private investment has been made in dental alignment companies
• One company in this field recently completed an IPO that raised $1.35 billion on a valuation of $9 billion.

Competition:

OrthodontiCell’s proprietary technology can accelerate tooth movement by up to 80% while significantly reducing the patient’s pain compared to currently available options. Standard braces or aligners rely on mechanical force for dental alignment, requiring an average of 2 years to complete treatment while causing the patient a significant amount of pain. Standard braces are also expensive and can have a significant negative cosmetic appearance for the patient, especially over long time periods. Orthodonticell’s technology is also the only therapy that improves alignment stabilization through controlled OPG expression. Other treatment options often require continued retainer use to stabilize dental alignment as up to one-third of treated patients will experience tooth movement and become misaligned after completing treatment.

 

 OrthodonticellAcceleDentMicro-osteoperforationStandard Braces
MechanismBioelectric signaling to control expression of RANKL, VEGF, and OPG. Small vibrations to enhance tooth movementTiny punctures in the bone stimulates inflammatory responseMechanical force
Accelerated tooth movement (compared to standard treatment)Up to 80% (average - 70%)Up to 50%50%
Frequency20 minutes,
3 days per week
20 minutes everyday dayWeekly to monthly by orthodontistPermanent during treatment
Pain Reduction20 minutes,
3 days per week
20 minutes everyday dayWeekly to monthly by orthodontistPermanent during treatment
MiscThe OPG protein will enhance long-term alignmentUsed with other alignment optionsUsed with other alignment optionsNegative cosmetic appearance during treatment

Patents:

Over 13 patent claims have been issued, pending, licensed or optioned for controlling RANKL, VEGF, and OPG protein expression. Additional patents using RANKL and VEGF for accelerating tooth movement and OPG for stabilization have been filed. This patent portfolio includes US 20170274206A1 – Orthodontic Treatment.

Pre-clinical

Rat animal model testing has shown that RANKL and electrical stimulation can accelerate orthodontic tooth movement including increasing pro-movement factors such as the number of fibroblasts, blood vessels, and osteoclasts. When compared to other acceleration techniques such as laser therapy in rats, electrical stimulation has also been shown to be more effective at tooth movement. Canine model testing has also confirmed that electrical stimulation is effective for increasing the rate and amount of orthodontic tooth movement.

Clinical

• In a 4 week human study comparing the combined effect of direct electrical current and orthodontic force, the application of electrical current resulted in a 30% greater movement compared to orthodontic force alone. Tooth movement was greater during the first two weeks of treatment. These results suggest that the exogenous electric current can accelerate orthodontic tooth movement by as much as one-third and have the potential to reduce the duration of orthodontic treatment.

• In a recent 40 patient trial, the space gain in the canine-to-canine interval (lower arch) was compared between patients treated with only a nickel/titanium (NiTi) wire and a test group that received 5 minutes of electrical stimulation immediately after wire installation (NiTi), 48 hours after wire installation, and once a week for 4 weeks. The test group receiving electrical stimulation showed a significant increase in the space gain compared to the wire only group (figure 3, *p=0.04).

• The percentage of space gain between the two groups was also compared over the two month treatment period. The test group receiving electrical stimulation experienced a significantly great amount of space gain compared to the patients treated with only a NiTi wire (p=0.04).

• The pain level in these 40 patients was also compared after changing the NiTi wire using the Visual Analog Scale (VAS). Patients in the test group that received electrical stimulation had significantly lower pain levels at 24 and 48 hours after the wire change compared to patients in the control group (*p<0.05). Not only was the pain level in the electrical stimulation group lower than the wire only group, but it remained low at under 15 on the VAS in the 72 hours following the wire change.

• The pain level in these 40 patients was also compared after changing the NiTi wire using the Visual Analog Scale (VAS). Patients in the test group that received electrical stimulation had significantly lower pain levels at 24 and 48 hours after the wire change compared to patients in the control group (*p<0.05). Not only was the pain level in the electrical stimulation group lower than the wire only group, but it remained low at under 15 on the VAS in the 72 hours following the wire change.

• Representative cases for the control group treated with only a NiTi wire and the test group that also received electrical stimulation are shown below. The test group reached alignment before the control group with less pain.

Team

Howard Leonhardt, Executive Chairman and CEO, is an inventor and serial entrepreneur with over 21 issued U.S. patents and dozens more pending. He developed the leading endovascular stent graft system and the first percutaneous heart valve, both now a part of Medtronic. He has founded over 30 startups and has numerous successful exits.

Dr. John Marchetto, Co-Founder, Chief Medical Officer and President, received his Doctorate of Dental medicine and his orthodontics certificate at Tufts University School of Dental Medicine. Dr. Marchetto is a member of the American Association of Orthodontists and the American Dental Association, among many others. Dr. Marchetto is on staff at Memorial Hospital for Joe DiMaggio Children’s Hospital Craniofacial Team where they care for children with facial anomalies such as cleft lips and palates.

Dr. Jorge Genovese, Collaborative Researcher, Co-Inventor, is an expert in the research and development of electrical stimulation regeneration technologies. He has led research departments and teams at multiple companies and has been a Research Professor at universities around the world. Dr. Genovese received his doctorate degree from Buenos Aires University.

Dr. Leslie Miller
Vice President Clinical Affairs
Alex Richardson
Vice President Engineering & Product Development
Michael Angerbauer
Chief Bioengineer
Dr. Alonzo Moreno
Senior Advisor, Lab Researcher
Brian Hardy
Director of Marketing

Research Facilities:

BioInnovations Gateway
2500 S State St. #224, Salt Lake City, Utah

Center for Medical Innovation Research Park
417 S Wakara Way Suite 3321, Salt Lake City, Utah

References

Kim, D., Park, Y., Kang, S. The effects of electrical current from a micro-electrical device on tooth movement. The Korean Journal of Orthodontics. 2008 Oct 30: 38(5); 337-346.

Li, C., Chung, C.J., Hwang, C., et al. Local injection of RANKL facilitates tooth movement and alveolar bone remodelling. Oral Diseases. 2019; 25:550-560.

Showkatbakhsh, A., Younessian, F., Dianat, O., et al. Effect of Intra-Canal Direct Current Electric Stimulation on Orthodontic Tooth Movement: An Experimental Study in Canines. Journal of Dental School 2016; 34(3): 157-67.

Spadari, G.S., Zaniboni, E., Vedovello, S.A.S. et al. Electrical stimulation enhances tissue reorganization during orthodontic tooth movement in rats. Clin Oral Invest (2017) 21: 111.

Zaniboni, E., Bagne, L., Camargo, T. et al. Do electrical current and laser therapies improve bone remodeling during an orthodontic treatment with corticotomy? Clin Oral Invest (2019).

 

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