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With Key Data Nearing, Tonix Looks to Spotlight Robust Pipeline In Immunology And CNS Therapeutics

The following article is sponsored by the clinical communications unit of  Redington, Inc. The information contained in this article in no way represents investment advice or opinion on the part of Benzinga or its writers and is intended for informational purposes only.

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The following article is sponsored by the clinical communications unit of  Redington, Inc. The information contained in this article in no way represents investment advice or opinion on the part of Benzinga or its writers and is intended for informational purposes only.

Tonix Pharmaceuticals Holding Corp. (NASDAQ:TNXP) has been operating under the radar of major institutional investors, but that may soon change.

After a series of near misses in a handful of clinical trial programs, the company is closing in on data from two important programs. Positive readouts from either one promises to spotlight the company’s diverse portfolio built on unmet needs in billion-dollar medical categories.

Before yearend, Tonix expects to release data from advanced non-human primate studies of its lead Covid-19 T cell eliciting vaccine candidate utilizing live attenuated virus vectors. Vaccines made with attenuated viruses are known to confer long term immunity with a single dose (think vaccines for smallpox, measles, mumps and rubella) – and they are the only ones known to prevent forward transmission or contagion.

Tonix’s decision to develop T cell vs. antibody eliciting vaccines puts it in a race alongside Merck & Co. (NYSE:MRK), the only other US company developing Covid-19 vaccines with a similar approach.

Another expected fourth quarter highlight could position Tonix to tap into a nearly $9 billion fibromyalgia drug market, one that was created by Pfizer, Inc’s (NYSE:PFE) Lyrica and Eli Lilly and Company’s (NYSE:LLY) Cymbalta before both products went generic two years ago.

Tonix’s fibromyalgia candidate, TNX-102 SL, is more than half-way through a Phase 3 registration trial, with topline results due before yearend.

No new branded fibromyalgia drug has entered the market since Cymbalta and Lyrica went generic – a void Tonix hopes to fill with a better, more tolerable product following completion of its Phase 3 programs.

“We are nimble, focused and we work on big medical challenges,” said Tonix CEO Seth Lederman, MD in a recent interview with Benzinga. “Many other companies are focused on a particular proprietary technology, while we are opportunity-focused.”

Driven By Opportunity

In describing the driving philosophy underlying Tonix Pharmaceutical’s trials of its leading and exploratory drug candidates, Dr. Lederman emphasized the company’s focus on discovering impactful approaches to often overlooked clinical diagnoses.

This is particularly reflected in Tonix’s pursuit of a non-addictive treatment for fibromyalgia, a generalized pain disorder that is often misdiagnosed or mistreated due to the multifarious manifestations of the condition.

“We like the opportunity-focused model better because it fits more directly with our passion for tackling medical problems that others avoid because of past failures or other difficulties,” Dr. Lederman elaborated. “We believe we can win some victories for desperate patients that medicine has heretofore overlooked because the hill seemed too steep to climb. The solutions we seek have the potential to be tremendously meaningful and rewarding”

In this interview, Dr. Lederman spoke to the history and progress of both drug candidates as well as the unique markets they aim to serve. He also touches on his personal history in rheumatology, patient pain-management and immunology and what the future looks like for Tonix’s lead drug candidates and for the company.

The company’s strategy often involves looking at markets that have been created by blockbuster products, identifying their shortcomings, and then developing novel approaches to deliver a unique product profile.

“One of the big triumphs of rheumatology was the recognition some 15 years ago that fibromyalgia was a distinct disorder, not a stigmatized set of complaints offered up by folks who doctors thought were malingerers with fabricated symptoms,” Dr. Lederman explained.

That victory has led to other advances, for example, the understanding that fibromyalgia is a chronic pain disorder relating to central pain.

As the formal diagnoses of fibromyalgia were being advanced, Pfizer launched Lyrica and Lilly launched Cymbalta, which had combined peak sales of roughly $9 billion before they went off patent. Now there is only one remaining branded product on the market — Savella from AbbVie Inc. (NYSE:ABBV) — a Cymbalta-like drug selling at the rate of about $400 million a year.

“At peak sales, Cymbalta was a $5 billion product and Lyrica wasn’t far behind at $3.5 billion,” Dr. Ledrman elaborated. “Now that both are generic, the dollar value of the market is smaller, but the patients haven’t disappeared – in fact, if anything, they’ve grown in number – and there is still widespread dissatisfaction within their ranks. Our research indicates that doctors and patients are constantly on the search for other options. We think we can capitalize on that dissatisfaction with a substantially differentiated product.”

For Dr. Lederman, the pursuit is more than simply one of opportunity. He has a longstanding interest in the diagnosis of fibromyalgia dating back to his medical training with Columbia University’s Division of Rheumatology 35 years ago.

“It is all about knowing the cause and source of the pain,” he said.

Dr. Lederman explained that, as opposed to “nociceptive” and “neuropathic,” which denote pain caused by injury to the body or parts of the central nervous system, central pain originates in an individual’s brain. This distinction, as well as advances in patient care, helped to foster the recognition of fibromyalgia as a distinct medical condition affecting about seven million adults in the United States, with 95% of those being female over the age of 50 who generally begin experiencing symptoms with the onset of menopause.

With the introduction of FDA-approved Cymbalta and Lyrica – and later a drug called Savella – doctors moved many patients away from off-label treatments, but dissatisfaction still runs high with a lot of switching and on-off use, often due to side effects becoming intolerable.

As a result, there is still widespread use of addictive opiates. Although they are not approved for this indication, Dr. Lederman asserts that one-third of fibromyalgia patients end up on long-term opiates. “These patients often end up in a very bad place and become part of the rising death toll attributed to opiate overdose.

We believe TNX-102 SL will provide a meaningful alternative, a better option.”

Seeking Solutions To A Painful Syndrome

The current Phase 3 trial of TNX-102 SL in fibromyalgia was initiated last year following a prior, lower-dose trial that fell short of endpoint results.

TNX-102 SL aims to distinguish itself from existing fibromyalgia treatments by acting on a patient’s central nervous system to inhibit symptoms of pain by improving sleep quality, which Dr. Lederman sees as a key feature in addressing one of the most consistent aspects of the overall condition.

“Fibromyalgia is a syndrome that is defined by a collection of symptoms,”  he explained.  “By addressing this sleep disturbance symptom with TNX-102 SL, we've shown in two large studies that there was improvement in fibromyalgia that extends beyond sleep and into improvement across the spectrum of other fibromyalgia symptoms. Because TNX-102 SL provides improvement of many different symptoms, beyond the sleep quality improvement, we believe that TNX-102 SL acts at a syndrome-level and not just at the symptom-level.”

Dr. Lederman sees the opportunity in TNX-102 SL as an alternative for patients who might suffer deleterious side effects that impact the quality of the treatment or cause patients to stop taking them altogether.

“TNX-102 SL is a medicine taken every night at bedtime, and it has been well-tolerated in all the studies we've done, although some patients experience side effects like transient numbness in the mouth, sleepiness and dry mouth” explained Dr. Lederman. “Based on the two prior studies and our experience with the 5.6 mg dose in PTSD, we believe TNX-102 SL could have a tolerability edge.”

While the peaks sales numbers for Cymbalta and Lyrica may seem lofty, Dr. Lederman is encouraged by the numbers and the need they demonstrate for an array of fibromyalgia treatment options. Tonix is also exploring other potential indications for TNX-102 SL, including for symptoms associated with alcoholism and Alzheimer’s disease.

“This is an exciting time for our portfolio of 10 CNS indications, and especially for TNX-102 SL in fibromyalgia.  We look forward to an interim analysis in the Phase 3 study to be reported next month, and we expect top line data from that study in the fourth quarter of this year.”

Live Vaccines in An Ongoing Pandemic

In addition to progress on the TNX-102 SL trials, Dr. Lederman also touched on the other leading drug candidates that Tonix is currently putting resources toward investigating, several self-attenuated vaccines for the COVID-19 virus strain. The pursuit is especially dire in Dr. Lederman’s estimation, characterizing the ongoing pandemic as “the biggest global public health threat since the Spanish Flu in 1918.”

“We have several vaccine candidates in development, all based on our proprietary live attenuated-virus vector platform,” said Dr. Lederman. “Live attenuated viruses like horsepox or bovine parainfluenza virus can induce infected lung cells to present antigens to T cells directly. TNX-1800, our lead vaccine in development, is designed to express the spike protein from CoV-2, the virus that causes Covid-19.”

The interest in developing a novel and effective vaccine should be self-evident to most given the mounting infection rates. And while many of the potential early vaccine candidates from firms like Moderna, Inc. (NASDAQ:MRNA) or AstraZeneca PLC (NYSE:AZN) have progressed into trial stages, Dr. Lederman highlighted the need for a variety of vaccine platforms. This is in order to both find an ideal vaccine for the virus as well as a greater variety of effective vaccines that can be used in case others are ineffective in certain individuals.

“There are currently over 150 potential Covid-19 vaccines in various stages of development but relatively few utilize live attenuated viral platforms. Live attenuated viruses have the potential to confer long-term immunity and prevent forward transmission,” Dr. Lederman said. “These vaccines are live, attenuated vaccines, like the vaccines that successfully eradicated smallpox, and helped to contain rubella, mumps,  measles, and several other lethal viruses.”

In a practical sense, Dr. Lederman explained that the ability to prevent forward-transmission — the spread of the virus from one host to another — is what sets live-attenuated vaccines apart from vaccines derived from inactivated virus strains. The active stimulation of the immune system’s Tcells that result from effective live-attenuated vaccines is what evokes a strong, long-lasting and durable immunity to the virus strain.

The challenge of developing such a vaccine lies in working with similar viral strains as a platform and, even then, no one vaccine is 100% effective in all cases. This is another area of opportunistic research on the part of Tonix, which recently announced a sponsorship with Columbia University that Dr. Lederman explained is meant to “address these potential variables and to develop precision medicine tools that would allow tailoring of vaccines based on a person’s biomarkers.”

At the moment, Tonix is still exploring the potential of the horsepox and BPI virus platforms, with the former producing one of the company’s more viable vaccine candidates, TNX-1800, which is in pre-IND phase of development.

Should the animal studies prove positive, the company expects to start human trials of TNX-1800 next year.

Said Dr. Lederman, “We recently announced a partnership with Fujifilm Diosynth in College Station, Texas, who will be manufacturing the vaccine. We expect it will be manufactured at the level of quality and in a sufficient quantity to conduct clinical trials next year. We are also guiding that we will have the results of both small animal and non-human primate studies in the fourth quarter of this year. Those results will include studies of non-human primates that were challenged with the CoV-2 virus.”

Drawing the interview to a close, Dr. Lederman reflected that, between the phase 3 fibromyalgia treatment and the ongoing exploration of a COVID-19 vaccine, Tonix Pharmaceuticals is focused on exactly the specialized and targeted drug development that has guided its mission thus far.

“We are well-funded at the moment with $67 million pro forma cash on hand at June 30 and all in all, we think  this is a very exciting time for Tonix” he said”