Full Press Release Details
TONIX PHARMACEUTICALS HOLDING CORP. - 8-K
Tonix Pharmaceuticals Announces Data Presentations
on TNX-102 SL for Fibromyalgia at the 11th Global Conference on Pharmaceutics and Novel Drug Delivery Systems (PDDS 2024)
Presentations highlighted the proprietary formulation
technology and pharmacokinetic properties of TNX-102 SL (sublingual cyclobenzaprine HCl)
Composition and methods patents based on the eutectic
formulation of TNX-102 SL are expected to provide market exclusivity until at least 2034 in the U.S., E.U., Japan, China and other jurisdictions
U.S. FDA New Drug Application (NDA) submission on
track for October 2024; Fast Track designation granted by FDA; 2025 PDUFA date for FDA decision on approval expected
Results from the confirmatory Phase 3 RESILIENT study
of TNX-102 SL demonstrated statistically significant improvement in primary endpoint of fibromyalgia nociplastic pain and in all six key
secondary endpoints, including sleep quality
CHATHAM, N.J., September 23, 2024 (GLOBE NEWSWIRE)
- Tonix Pharmaceuticals Holding Corp. (Nasdaq: TNXP) (Tonix or the Company), a fully-integrated biopharmaceutical company with marketed
products and a pipeline of development candidates, announced data in two oral presentations and a poster presentation at the 11th Global
Conference on Pharmaceutics and Novel Drug Delivery Systems (PDDS 2024), held September 19-21, 2024, in Rome, Italy. Copies of the Company's
oral presentations and poster are available under the Scientific Presentations tab of the Tonix
website at www.tonixpharma.com following the conference.
Prof. Marino Nebuloni, Director, Qualified Person, Redox
Analytical Science Srl, in an oral presentation titled, "Mannitol as Eutectic Forming Agent for Improved Sublingual Delivery
of Cyclobenzaprine HCl," described the eutectic formation of cyclobenzaprine HCl and mannitol and how it provides a stable product
that dissolves rapidly and delivers cyclobenzaprine by the transmucosal route efficiently into the bloodstream. The eutectic protects
cyclobenzaprine HCl from interacting with the basifying agent that is also part of the formulation and required for efficient transmucosal
absorption. The work described included studies by Giorgio Reiner and his team at APR Applied Pharma Research S.A. and the team at Tonix.
"Patents based on TNX-102 SL's eutectic
composition and its properties have issued in the U.S., E.U., Japan, China and many other jurisdictions around the world," said
Seth Lederman, M.D., Chief Executive Officer of Tonix Pharmaceuticals. "The European Patent Office's Opposition Division maintained
Tonix's European Patent EP 2 968 992 in unamended form after an Opposition was filed against it by a Sandoz subsidiary, Hexal AG.
Hexal AG did not appeal that decision. Tonix had two pre-NDA meetings with the U.S. Food and Drug Administration (FDA) in the second quarter
of 2024. The FDA granted TNX-102 SL Fast Track designation in July 2024. The FDA New Drug Application (NDA) submission is on track for
October 2024, and a 2025 Prescription Drug User Fee Act (PDUFA) date for an FDA decision on approval is expected."
Bruce Daugherty, Ph.D., Executive Vice President, Research
at Tonix Pharmaceuticals, in the second oral presentation titled, "Pharmacokinetic Properties of TNX-102 SL, a Sublingual Formulation
of Cyclobenzaprine Hydrochloride," outlined the clinical pharmacology of TNX-102 SL via single dose and multiple dosage
administration. The formulation of TNX-102 SL was designed specifically for sublingual administration and transmucosal absorption for
bedtime dosing to target disturbed sleep, while reducing the risk of daytime somnolence. Clinical pharmacokinetic studies indicated that
the addition of a basifying agent was necessary for efficient transmucosal absorption. The addition of a basifying agent resulted in higher
levels of exposure during the first 2 hours after dosing and resulted in deceased levels of the long-lived active metabolite, norcyclobenzaprine
in both single dose and multiple dose studies, consistent with bypassing first pass hepatic metabolism. At steady state after 20 days
of dosing TNX-102 SL, the dynamic peak level of cyclobenzaprine is higher than the background level of norcyclobenzaprine. In contrast,
after 20 days of dosing oral cyclobenzaprine, the simulated peak level of cyclobenzaprine is lower than the simulated background level
of norcyclobenzaprine. Tonix believes that TNX-102 SL's dynamic levels of cyclobenzaprine exceeding norcyclobenzaprine levels after
steady state modeling of chronic dosing, contributes to the durability of its clinical benefits. Dr. Daugherty also presented evidence
showing that cyclobenzaprine interacts as an antagonist at four different receptors in the brain, which are believed to play roles in
sleep quality supporting the multi-functional mechanism of TNX-102 SL. The presentation also illustrated the prevalence of fibromyalgia
and the unmet need for new treatments in the U.S., despite the availability of three FDA-approved drugs. In the Phase 3 RESILIENT study
in fibromyalgia, TNX-102 SL met the pre-specified primary endpoint of significantly reducing daily pain as compared to placebo (p-value=0.00005).
TNX-102 SL also demonstrated broad syndromal benefits with statistically significant improvement in all six pre-specified key secondary
endpoints including those related to improving sleep quality, reducing fatigue, and improving patient global ratings and overall fibromyalgia
symptoms and function. TNX-102 SL was well tolerated with an adverse event profile comparable to prior studies and no new safety signals
Dr. Lederman continued, "There remains a significant
unmet need in fibromyalgia for an effective treatment given the frustrations with existing therapeutic options. TNX-102 SL has demonstrated
it has the potential to provide broad-spectrum symptom relief in fibromyalgia as a once-daily treatment at bedtime. With the support of
statistically significant results from two Phase 3 studies of TNX-102 SL in fibromyalgia, TNX-102 SL is potentially positioned to be the
first new treatment option for fibromyalgia patients in 15 years."
Siobhan Fogarty, Executive Vice President, Product Development
at Tonix Pharmaceuticals, in the poster presentation titled, "The Importance of In Vitro Discriminatory Tests in the Development
of a Sublingual Dosage Form of TNX-102 SL (Cyclobenzaprine HCl) Tablets," presented the development of in vitro techniques
used to assess characteristics of the TNX-102 SL tablet including dissolution, "disintegration time" and a proprietary "wetting
time" test. These in vitro tests assessed the impact of the particle size, excipient variation and compression force. The
data presented indicate that a dissolution test does not discriminate between tablets made with intentional modifications to particle
size, excipient content or compression strength. However, both "disintegration time" and "wetting time" are sensitive
tests to discriminate differences in particle size, concentration of the excipient Pearlitol Flash and compression strength.
Dr. Lederman concluded, "The in vitro "disintegration
time" and "wetting time" tests have supported an efficient clinical development process and provide a strategy to evaluate
manufacturing processes and product uniformity going forward. The in vitro discriminatory tests have been utilized by Tonix in
the scale-up, validation and launch preparation of TNX-102 SL at the contract drug manufacturing organization sites. Together, these data
suggest that TNX-102 SL has the potential to address a significant unmet need for fibromyalgia patients."
About Redox - Analytical Science Srl
Redox is an independent CRO company headquartered in
Monza, Italy with research and development activities and customer analytical support to pharmaceutical companies for more than 30 years.
For more than 25 years the analytical activities have been certified by national and international agencies (European Medicines Agency,
the Italian Medicines Agency (AIFA), FDA, etc. One of its main activities is the development of new drug products in order to improve
the pharmaceutical actions, in concert with improvement in the stability and reduction of the cost of the new drug substances. Several
unique and sophisticated analytical techniques and equipment are used in support of these research and development strategies, focused
on achieving optimal and effective pharmaceutical formulation in the shortest time frame. More than 30 professional people are dedicated
to Redox's efforts and many of its projects are ongoing in collaboration with the pharmaceutical industry as well as with Italian
and international universities.
Further information about Redox can be found at www.labredox.com.
About APR Applied Pharma Research S.A., a wholly-owned subsidiary of Relief
Therapeutics Holding AG
APR Applied Pharma Research S.A., a wholly-owned subsidiary
of Relief Therapeutics Holding AG, is a commercial-stage biopharmaceutical company committed to advancing treatment paradigms and delivering
improvements in efficacy, safety, and convenience to benefit the lives of patients living with select specialty and rare diseases. Relief
Therapeutics' portfolio offers a balanced mix of marketed, revenue-generating products, including the proprietary, globally patented Physiomimic
and TEHCLO platform technologies and a targeted clinical development pipeline consisting of risk-mitigated assets focused in three
core therapeutic areas: rare metabolic disorders, rare skin diseases and rare respiratory diseases. In addition, Relief Therapeutics is
commercializing several legacy products via licensing and distribution partners. Relief Therapeutics' mission is to provide therapeutic
relief to those suffering from rare diseases and is being advanced by an international team of well-established, experienced biopharma
industry leaders with extensive research, development and rare disease expertise. Relief Therapeutics is headquartered in Geneva, with
additional offices in Balerna, Switzerland, Offenbach am Main, Germany and Monza, Italy. Relief Therapeutics is listed on the SIX Swiss
Exchange under the symbol RLF.
Further information about APR can be found at www.relieftherapeutics.com
or by following Relief Therapeutics on LinkedIn and Twitter.
Tonix Pharmaceuticals Holding Corp.*
Tonix is a fully-integrated biopharmaceutical company
focused on developing, licensing and commercializing therapeutics to treat and prevent human disease and alleviate suffering. Tonix's
priority is to submit a New Drug Application (NDA) to the FDA in October of 2024 for TNX-102 SL, a product candidate for which two statistically
significant Phase 3 studies have been completed for the management of fibromyalgia. The FDA has granted Fast Track designation to TNX-102
SL for the management of fibromyalgia. TNX-102 SL is also being developed to treat acute stress reaction. Tonix recently announced the