Dr. Seth Lederman founded Tonix Pharmaceuticals with a deep desire to change the treatment landscape for patients. The company’s rich pipeline features therapeutic options for fibromyalgia, post-traumatic stress disorder (PTSD), long COVID, chronic migraine, gastric and colorectal cancer, and—more recently—Prader-Willi syndrome (PWS). Through developing and providing these offerings, Tonix aims to contribute to the enhancement of patient lives and outcomes.

Prader-Willi syndrome is the company’s first area of focus within the rare disease sphere. To date, there are no effective or FDA-approved treatment options to address hyperphagia (excessive hunger) in people living with PWS. However, Tonix is working to overcome that through the development of TNX-2900, a proprietary oxytocin formulation.

In his recent discussion with Patient Worthy, Dr. Lederman provided insights into Tonix and its mission, what PWS is, and his goals for TNX-2900 and how it could significantly address current barriers in PWS treatment.

About Dr. Seth Lederman, MD

Dr. Seth Lederman, MD earned his AB in Chemistry from Princeton University and his MD from Columbia University’s College of Physicians and Surgeons. He is trained in Internal Medicine and served as attending physician in the Edward Daniels Arthritis and Autoimmunity Clinic at Columbia Presbyterian Hospital for several years.

Prior to becoming a biopharmaceutical and biotech entrepreneur, Dr. Lederman was a professor at Columbia Medical School, where he directed basic science research into autoimmune disease therapeutic development, molecular immunology, and infectious diseases. His lab discovered the CD40-ligand, a protein that is primarily expressed on activated T-cells, and which plays a central role in the regulation of our immune response. He also founded Tangent Pharmaceuticals, which focused on the development of late-stage oncology drugs.

Dr. Lederman later went on to found Tonix Pharmaceuticals, a clinical-stage biopharmaceutical company that is focused on the development of novel therapeutics for a variety of indications, from immunology to infectious disease. As CEO, Dr. Lederman leads this company in the development of a rich pipeline of products. He shares:

“I believe that there is a bottleneck in taking drugs from the bench to the bedside. We specialize in getting our treatments through to Phase 2 and beyond. Tonix Pharmaceuticals has built a great team of experts in drug development and clinical testing, regulatory affairs, and more to advance drugs from the idea stage to the testing stage.”

An Overview of Prader-Willi Syndrome (PWS)

Dr. Lederman explains Prader-Willi syndrome as:

“a rare genetic disorder that is mostly found in people with novel, or spontaneous, gene mutations in the area of chromosome 15. It is not typically inherited. One of the key manifestations is failure to thrive in infants, where there is a noticeable lack of sucking behavior, and this is later replaced by hyperphagia, or never feeling full, marked by obesity and a compulsion to eat.”

Typically, symptoms of Prader-Willi syndrome—including hyperphagia—begin around two years old. Symptoms vary between individuals and may change over time. Potential symptoms outside of hyperphagia can (but do not always) include:

• Hypotonia (low/poor muscle tone)
• Poor sucking reflex
• Underdeveloped genitalia
• Intellectual impairments
• Poor growth and physical development
• Weight gain
• Behavioral and speech problems
• A narrow forehead, almond-shaped eyes, and a triangular mouth
• Short stature
• Small hands and feet

Treatment options vary and may include weight management, behavioral and physical therapy, human growth hormone (HGH) or sex hormone treatment, and nutritional changes. Shares Dr. Lederman:

“There is an approved biologic for Prader-Willi syndrome. While useful and beneficial, PWS can still be devastating in some cases. Improved therapeutics would be a huge addition to this sphere. There are also no current drugs approved for the treatment of PWS-related hyperphagia. Having an FDA-approved drug would be a great lift for the field and offer a mechanistic understanding of brain circuitry that leads to compulsion to eat.”

Developing TNX-2900

Tonix’s journey to developing a therapeutic for PWS-related hyperphagia began with another focus: chronic migraines. The company began developing TNX-1900, an intranasal formulation of oxytocin potentiated with magnesium, and in the midst of this development, Dr. Lederman and his team learned about research which suggested that oxytocin had a profound treatment effect on Prader-Willi syndrome. He says:

“I was fascinated by the exciting work in animal models of Prader-Willi syndrome performed by Professor Francoise Muscatelli in Marseille, France. Dr. Muscatelli identified NECDIN and MAGEL2 genes as potentially related to PWS and analyzed their phenotype in mice models that she created. She found that treating the mice with oxytocin could essentially reverse or even prevent Prader-Willi syndrome development. We actually licensed this technology used to make TNX-2900 from her.”

As the team at Tonix learned more about Professor Muscatelli’s research, and additional research from Dr. Maithé Tauber focused on human newborns, they found compelling evidence that oxytocin could improve hyperphagia symptoms.

Eventually, this led the team to begin developing TNX-2900. On the Tonix website, the company explains that:

“Tonix’s patented potentiated oxytocin formulation is believed to increase specificity for oxytocin receptors relative to vasopressin receptors as well as to enhance the potency of oxytocin.”

Tonix Pharmaceuticals was granted Orphan Drug status for TNX-2900. Orphan Drug designation is granted to drugs or biologics intended to treat, prevent, or diagnose rare conditions (those affecting fewer than 200,000 people within the United States).

Currently, TNX-2900 is still in its pre-IND stage and has not yet been evaluated in the clinical setting. But Dr. Lederman is proud of how far the company has come in developing the product formulation and actuator device. The actuator contains the medication and administers it intranasally. In the future, Tonix hopes to file the IND and, upon clearance, begin the first in-human trials.

Planning a Trial

There remains a lot of interest, medically speaking, in Prader-Willi syndrome and drug development. Yet planning a trial can prove challenging, especially in the rare disease space. Rare conditions by default have less available volunteers. Dr. Lederman already suspects that the recruitment phase, as well as lining up doctors who are knowledgeable about PWS, may be challenging. But he believes that Tonix’s patient-centric focus will help with this. He shares:

“Patients are really welcomed into our entire process. Right now, we’re mostly engaging with the Foundation for Prader-Willi Research. But we’re already gearing up to reach out to patients when the IND is approved. We want to hear from patients about what is most important to them, about protocols, and about what they want to see out of this. If we can make a difference for patients, that will be immensely rewarding.”