Cure Therapeutics Inc.

Cure Therapeutics hopes to help the millions of athletes and workers who suffer from tendonitis. The company is developing transdermally delivered nitric oxide drugs designed to lessen the pain and speed recovery from chronic musculoskeletal conditions like swimmer's shoulder, tennis elbow, jumper's knee, and Achilles tendonitis.

Patching tendonitis

140 West 57th Street

Suite 3B

New York, NY 10019

Phone: [phone]

Fax: [phone]

Web Site: www.curetherapeutics.com

Contact: Robert Ang, MD, COO

Industry Segment: Pharmaceuticals

Business: Nitric oxide–based drugs for musculoskeletal conditions

Founded: January 2005

Founder: Robert Ang

Employees: 2

Financing to Date: Undisclosed

Investors: Carrot Capital Healthcare Ventures (CCHV)

Board of Directors: David M. Geliebter (CCHV); Sven M. Jacobson (CCHV); Robert Ang; Ronald Burch, MD, PhD (CEO)

Scientific Advisory Board: Jose R. Berrezueta, MD, PhD (Universitary Hospital Marqués de Valdecilla, Santander, Spain); Bruce M. Gans, MD (Kessler Institute for Rehabilitation, West Orange, NJ); Frank Kochinke, PhD (EntrePreneurial Solutions); William Maichle (ProEthic Pharmaceuticals); George A. C. Murrell, MD, PhD (University of New South Wales, Sydney, Australia); Barry P. Simmons, MD (Brigham & Women’s Hospital); Lee S. Simon, MD (Harvard Medical School, Beth Israel Deaconess Medical Center); Susan L. Michlovitz, PhD, Special Advisor (Columbia University)

Although Cure Therapeutics Inc. only boasts two employees, the company hopes to help the millions of athletes and workers who suffer from tendonitis. The company is developing nitric oxide–based drugs designed to lessen the pain and speed recovery from musculoskeletal conditions such as swimmer’s shoulder, tennis elbow, jumper’s knee, and Achilles tendonitis.

About 30 million Americans develop tendonitis each year. According to Cure, roughly two-thirds of these patients have simple acute tendonitis and can be helped by nonsteroidal antiinflammatory drugs (NSAIDs) and rest. However, around 10 million progress to chronic tendonitis, which does not respond to NSAID treatment. For these patients, treatments range from physical therapy to splinting to surgical intervention. "If you look at the landscape, what’s currently offered in terms of both drug therapy and physical interventions is very limited and has very poor efficacy," Robert Ang, Cure’s COO, says.

That’s where Cure’s OrthoDerm patches and their nitroglycerin payloads come in. The idea for Cure’s technology was spawned by George A. C. Murrell while he was an orthopedic fellow at the Hospital for Special Surgery in New York. Although nitric oxide was known to play a role in healing skin tissue, Murrell wondered whether it could also promote musculoskeletal healing, particularly in tendons. He found that when nitric oxide production was turned off with a nitric oxide synthase inhibitor, healing of rat tendons was impaired. But if nitric oxide levels were augmented using supplementation or nitric oxide synthase induction, the healing rate was accelerated in the rat model. Murrell’s in vitro and in vivo experiments indicate that nitric oxide promotes tissue healing through its effects on fibroblasts. It induces fibroblasts to proliferate, differentiate, and increase collagen production, which in turn accelerates tendon repair.

With animal results in hand, Murrell’s next step was to determine if augmentation of nitric oxide improves the course of chronic tendonitis in humans. The path to clinical testing was made easier because nitroglycerin, which releases nitric oxide, has already been approved and marketed for the treatment of angina. In fact, nitroglycerin was first used to treat angina back in 1879, and received FDA approval in 1938. Nitroglycerin acts as a vasodilator, causing blood vessels to dilate, so it improves blood flow to the heart and relieves and prevents angina attacks. A number of companies, including Novartis AG , Schwarz Pharma AG , 3M Co.’s 3M Pharmaceuticals Inc., Mylan Laboratories Inc.’s Mylan Technologies Inc., and Schering-Plough Corp., sell nitroglycerin patches. Hercon Laboratories Corp., a division of Health-Chem Corp., released the first generic nitroglycerin transdermal patch in the United States in 1986.

Murrell used fragments of nitroglycerin patches to determine if nitric oxide could facilitate healing of chronic tennis elbow, chronic supraspinatus (rotator cuff) tendonitis, and chronic Achilles tendonitis in humans. More than 200 patients participated in three double-blind, randomized clinical trials at the University of New South Wales in Sydney, Australia, in 2002 and 2003. Because the treatment of tendonitis requires lower doses than the treatment of angina, one-fourth of a Schering-Plough 5 mg/24 hour Nitro-Dur patch was used in the trials.

All three studies produced encouraging results: patients receiving nitroglycerin experienced reduced pain and increased function as early as two weeks after initiation of therapy compared with patients receiving placebo. At six months, tennis elbow patients receiving nitroglycerin had a 64% decrease in elbow tenderness, whereas placebo receivers had only a 31% decrease. Shoulder patients receiving nitroglycerin had a 40% increase in supraspinatus power after six months, compared with only a 7% increase in patients receiving placebo. For the Achilles patients, nitroglycerin receivers had a 42% increase in peak force versus a 24% increase for the control group after six months. After analyzing the trials’ results, Murrell believed the product could be commercialized.

But it was Robert Ang who supplied the necessary spark to move the project from academia to industry. Ang graduated from the University of Western Australia in 1997, and he completed a medical internship at Sir Charles Gairdner Hospital. After starting a surgical residency, he decided to switched gears and become a management consultant with Boston Consulting Group’s Sydney office. He then completed an MBA at Columbia University. In 2004, Ang was working as a licensing associate for HSS Ventures, the tech transfer and VC arm of the Hospital for Special Surgery. He ran across Murrell’s research and thought it looked interesting, but no potential licensees had come forward. Despite Ang’s urging, HSS declined to provide seed funding.

Later that year, Ang joined Carrot Capital Healthcare Ventures (CCHV) as a senior associate, where he pitched Murrell’s research to David M. Geliebter, managing partner at CCHV. This time he was successful. Cure Therapeutics was officially formed in January 2005, coincident with completion of the license agreement with HSS, which gives the company worldwide exclusive rights to several patents covering technologies related to nitric oxide and musculoskeletal disease. As part of the license agreement, CCHV was bound to fund the company in a seed fashion, explains Ang. Since then, CCHV has supplied enough funding to take the company through Phase II trials.

Ronald Burch, now Cure’s CEO, first joined the company in mid-2005 as a member of its Scientific Advisory Board. At that time, he was CEO of AlgoRx Pharmaceuticals, a company focused on the development of pain medications that he had co-founded in 2001. After AlgoRx completed a reverse merger with Corgentech in December 2005, Burch left the merged company (Anesiva) and decided to head up Cure’s efforts. Burch has previously held management positions in R&D with Purdue Pharma, Zeneca Pharmaceuticals, and Rhone Poulenc Rorer Pharmaceuticals.

Burch says he was attracted to Cure because of positive experiences he had developing repurposed therapeutics at Purdue Pharma and AlgoRx. Since nitroglycerin patches are already approved for the treatment of angina, Cure is essentially repurposing the same chemical for other indications, he explains. Although unable to protect the molecule itself, the company’s intellectual property strategy relies upon methods of use and formulation claims. For example, Cure will still deliver nitroglycerin through a transdermal patch, but the dose and formulation will be different, so they can be protected, Burch says. In addition to the patents filed by HSS, Cure has filed seven additional patent applications, all still pending.

The trade-off for lack of IP protection of the molecule may be that repurposed therapeutics often lend themselves to a straightforward development plan. Importantly, the FDA has agreed that Cure can use the preclinical and human safety database that has been established for nitroglycerin in its use for angina.

Burch and Ang wrote the IND for OrthoDerm and filed it with the FDA in late December 2006. They have just begun a Phase II dose-ranging study that aims to enroll about 160 patients at six clinical sites. The parallel group study will be placebo-controlled and double-blinded. The patch will be applied daily for eight weeks, and responders will be followed for three months following treatment cessation. Efficacy data are expected in early fall.

Burch and Ang hope the trial will confirm effectiveness and clarify optimal dosing. The goal is to use the lowest possible dose to achieve efficacy, so they will test doses roughly equal to, slightly above, and slightly below those used in Murrell’s trials. Patients using nitroglycerin patches for the treatment of angina can experience headaches, flushing, dizziness, and skin irritations at the patch site. But because dosing is lower than in the patches used to treat angina, Burch says Cure is expecting side effects to be of relatively low incidence.

Cure plans to move directly into a Phase III plan after completion of the Phase II dose-ranging study. According to Burch, the Phase III plan should be relatively quick, so they expect to be in a position to submit an NDA in 2009.

"I think this compound has huge potential—the patient population is so very large," Burch says, adding that they will be seeking a pharmaceutical partner or partners after completion of Phase II. The company estimates that gross revenues will start at $50 million in 2010, assuming a $300 price for each two-month treatment regime. Their projections ramp up to worldwide revenue of $627 million by 2018.

Ang says there aren’t many drugs in development for tendonitis, even though current therapies are limited. Applied Pharma Research SA of Balerna, Switzerland, and German company Labtec GMBH developed a nonsteroidal ketoprofen transdermal patch. ProEthic Pharmaceuticals Inc. licensed the US and Canadian rights to the drug from them, but it subsequently sublicensed the rights to Endo Pharmaceuticals Holdings Inc. ’s Endo Pharmaceuticals Inc. , which is currently conducting Phase III trials. [See Deal] "This is a product that would be much more applicable to acute tendonitis, not chronic tendonitis, and we know of no other drugs that are targeting this particular indication," says Ang.

Another area of ongoing research is in the use of physical therapy, such as eccentric loading, to treat tendonitis. But Ang views eccentric loading as complementary, rather than competitive, to Cure’s approach. He also notes that historically, physical therapy regimes have had difficulty demonstrating statistical differences in treatment outcomes for tendonitis.

Cure Therapeutics’ IP estate also includes protection for a number of other indications, and the company plans to perform more preclinical studies to evaluate and prioritize opportunities. One area of interest is the possible use of the OrthoDerm patches to treat muscle and ligament sprains.

Another direction is to use nitric oxide–releasing drugs to facilitate bone healing. According to Burch, the market for synthetic bone growth hormones, marketed by Medtronic Inc. and Stryker Corp. , topped $1 billion in 2005. Because protein drugs have a much higher cost of goods than nitric oxide drugs, nitric oxide drugs should be price competitive if results are comparable, but further formulation and preclinical work is needed before clinical trials could be considered. Hercon Laboratories, a manufacturer of generic transdermal nitroglycerin patches, has assisted Cure with its drug manufacturing efforts to date.

What is Cure’s exit strategy? "Because what we have here is really a platform, we could continue to develop new products. Having said that, given the potential, I think it’s likely that if we partner for Phase III, the most likely exit would be a sale of the company [to the partner]," says Burch.

In the meantime, Burch and Ang will execute the next phase of the company’s business plan on their own. For tendonitis sufferers everywhere, it’s a doubles team worth rooting for—Carolyn Riley Chapman