February 15, 2014 (Vol. 34, No. 4)

Speedy Drug Delivery Platforms Broaden Indications and Add New Therapeutic Options

Tonix Pharmaceuticals is staking out its territory in drug reformulations. Drug reformulation enables pharma companies to maximize the value of existing drugs, and also provides an alternative to an orphan drug development strategy for companies seeking an early revenue stream.

“Reformulation is essential for getting the most value from active drugs. The way to create value is to make a significant improvement for patients that’s cost effective for insurers,” stresses Seth Lederman, M.D., CEO, Tonix Pharmaceuticals. “It’s one thing to have a small molecule and a target. For optimal effect, the molecule must be delivered to the right place in the body at the right time.”

Fibromyalgia is a big problem for insurers. Most patients are dissatisfied and physicians are frustrated by the lack of available treatments. “To make an impact in fibromyalgia would be a game-changer for patients and for the healthcare system,” Dr. Lederman says.

Tonix is optimizing cyclobenzaprine, an FDA-approved muscle relaxant to treat fibromyalgia and post-traumatic stress disorder (PTSD), by moving absorption up one hour and developing a sublingual (under the tongue) delivery mechanism. The one hour difference in absorption makes an important improvement in adherence because in a fibromyalgia treatment regimen, the drug must be administered before bedtime.

Cyclobenzaprine originally was developed by Merck and approved by the FDA in 1977. In each of the past few years, more than one billion tablets have been prescribed, mostly for its approved indication of muscle spasm. “We have strong data,” Dr. Lederman declares.

Cyclobenzaprine has not been optimized for fibromyalgia. For that indication, designing the formulation for immediate release has been the greatest concern. “Merck’s pharmacokinetic studies showed no significant levels of cyclobenzaprine in the blood for more than one hour after administration,” Dr. Lederman remarks. “With our new formulations, we get measurable levels after 10 minutes and significant blood levels within 30 minutes. With this faster absorption time, it can be taken at bedtime.”

Trials have reported statistically significant reductions in musculoskeletal pain, pain sensitivity, fatigue, and altered mood. A pivotal Phase IIb trial for TNX-102 SL for fibromyalgia began enrolling September 2013.

Additional Programs

The company has announced it is working on at least four reformulation programs, “any one of which would be an important advance for medicine,” Dr. Lederman asserts. For PTSD, “We’re hoping to file an IND in the first quarter and launch Phase IIa trials in the second quarter.” Dr. Lederman adds.

The company met with the FDA and refined its protocol during the autumn. It also is advancing its alcohol program, TXN-301 and TNX-201 for tension headaches. “This is a significant problem, and patient offerings are limited,” Dr Lederman observes. “The only approved prescription drugs contain butalbital, a barbiturate.”

According to Dr. Lederman, the commonality in these conditions is that many of the available therapeutics either do not benefit or actually harm the patients: “Fibromyalgia and PTSD patients are treated with opiates, which lack sustained benefits and which many believe transform episodic events into chronic disease. Patients go to opiates in desperation.”

The key to fast absorption is the rapid disintegration formulation Tonix has developed. Rather than going through the digestive and circulatory systems, Tonix designed a delivery system that dissolves rapidly in the saliva under the tongue and crosses the mucus membrane.

“We’ve added an excipient that increases the pH of the saliva, making it more basic, thereby shifting equilibrium between the charged and uncharged form of cyclobenzaprine,” explains Dr. Lederman. “The uncharged form becomes slightly greater proportionally, and can go rapidly across the mucous membranes under the tongue.”

“We’re not looking for formulation challenges, but for big medical problems,” Dr. Lederman says. The company isn’t built around orphan drugs or orphan indications, and “that surprises people.” Instead, this microcap company repurposes existing therapeutics to meet unmet medical needs.

Fibromyalgia, for example affects five million people in the United States, and only about half are treated. PTSD affects 3–4% of Americans, and alcoholism is a very significant problem. All of Tonix’ programs are reformulations with 505b2 status. “By leveraging the existing safety information, we can be more bold and creative in targeting larger problems,” Dr. Lederman remarks.

TNX-102 SL is designed to provide absorption times shorter than those provided by oral formulations—just 30 minutes following sublingual administration, cyclobenzaprine reaches significant levels in the blood. Fast onset facilitates ease of use and compliance, particularly since the drug can be delivered before bedtime, aligning exposure with the sleeping period. In addition, since TNX-102 SL avoids first-pass metabolism by the liver, norcyclobenzaprine, a psychoactive metabolite of cyclobenzaprine, is not generated.

Business Issues

Tonix is in the enviable position of owning all of its technology outright. “That’s a strength,” Dr. Lederman stresses, “but the market is waiting for us to partner as a validation of our work.”

Tonix is interested in partnering with a company with the infrastructure to take the drug to commercialization. Dr. Lederman says Tonix would consider either a global licensing deal or multiple regional deals. The European market, he confides, is particularly appropriate: “So far, the three drugs approved in the United States for fibromyalgia are not approved in the European Union.

“Our plan is to form a partnership deal after we have data from the first pivotal study and work with that partner to conduct a second Phase III study and file an NDA.

Tonix was founded in 2007 and did a reverse merger in 2011 to acquire a public company. In August 2013, Tonix was listed on the NASDAQ stock exchange. Until that point, it was funded largely by insiders. In 2012, it did two PIPE (private investment in public equity) deals that attracted small institutional and individual investors as well as the venture capital group Technology Partners. Total funding to date has been nearly $27 million.

Tonix Pharmaceuticals

Location: 509 Madison Avenue, Suite 306, New York, NY 10022

Phone: (212) 980-9155

Website: www.tonixpharma.com

Principal: Seth Lederman, M.D., CEO

Number of Employees: 5

Focus: Tonix identifies potential therapeutics for unmet medical needs from among known pharmaceutical agents, with the objective of expanding indications and improving therapeutic options. Its lead product is designed to improve sleep hygiene and pain management.

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