Full Press Release Details
Tonix Pharmaceuticals Holding Corp. 8-K
Pharmaceuticals Completes Clinical Phase of PREVAIL Proof-of-Concept Study of TNX-102 SL for the Treatment of Fibromyalgia-Type
Results Expected Third Quarter 2023
COVID Afflicts Approximately 19% of Patients Following COVID-191, and is Expected to be a Global Health Burden
Long COVID with Multi-Site Pain Affects Approximately 40% of Long COVID Patients
N.J., August 7, 2023 - Tonix Pharmaceuticals Holding Corp. (Nasdaq: TNXP) (Tonix or the Company), a biopharmaceutical company,
today announced the completion of the clinical phase of the Phase 2 proof-of-concept PREVAIL study of TNX-102 SL as a potential
treatment for fibromyalgia-type Long COVID. Topline results for the PREVAIL study are expected in the third quarter of 2023.
40% of U.S. Long COVID patients have fibromyalgia-like multi-site pain symptoms based on our observational studies of Long COVID
patients from the TriNetX claims database,"2,3 said Seth Lederman, M.D., Chief Executive Officer of Tonix Pharmaceuticals.
"In addition to multi-site pain, these individuals often suffer from one or more other symptoms typically associated with
fibromyalgia such as fatigue, sleep disturbance, and brain fog. We have termed this subgroup, Fibromyalgia-type Long COVID.'
Given our encouraging results with TNX-102 SL as a potential treatment for fibromyalgia4, we are testing TNX-102 SL
as a bedtime medicine for the management of Fibromyalgia-type Long COVID. In completing this clinical milestone, marked by the
last enrolled patient finishing their final visit, we can now begin to look forward to topline results from the 63-patient PREVAIL
study later this quarter."
Lederman continued, "TNX-102 SL improves sleep quality in fibromyalgia, and we believe this is the mechanism by which TNX-102
SL improves other symptoms, like multi-site pain.5 Recently, the U.S. National Institutes of Health (NIH) has identified
improving sleep quality as a target for potential therapeutics for Long COVID6,7,8, consistent with the proposed mechanism
symptoms of Long COVID, including multi-site pain, fatigue, unrefreshing sleep, and cognitive dysfunction, or brain fog,'
are also hallmarks of conditions like fibromyalgia and chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME),"9
said Herbert Harris, M.D., Ph.D., Executive Vice President and Head of Translational Medicine of Tonix Pharmaceuticals.
"Defining subgroups of Long COVID patients that overlap with fibromyalgia and CFS/ME is expected to facilitate the development
of new treatments.4 It can be challenging to distinguish fibromyalgia and CFS/ME clinically, given the high level of
symptom overlap between them. Each of these conditions is defined by a constellation of symptoms, and there is no widely
recognized diagnostic laboratory test that distinguishes them."
Harris continued, "The recent identification of Long COVID subgroups in the National Institutes of Allergy and Infectious
Diseases (NIAID)-sponsored RECOVER study10 was an important step. In their recent publication, cluster analysis of
the symptom frequencies in the RECOVER study identified four subgroups of Long COVID patients. Cluster #4 represented approximately
one-quarter of the population (28%) and reported the highest frequencies of pain (back pain (58%), joint pain (64%) or muscle
pain (60%)), high frequencies of fatigue (94%) and 'Brain Fog,' (94%) and a high level of impairment of Quality of
Life. We believe Cluster #4 is a subgroup of Long COVID that shares many clinical features with fibromyalgia and
disease mechanisms. We also believe that Cluster #3, representing another approximately 29% of the RECOVER cohort, includes many
patients with fibromyalgia-type Long COVID because 100% of that group suffer from Brain Fog', 94% experience fatigue
and approximately one-third experience pain (back pain (32%), joint pain (36%) or muscle pain (34%))."
Harris concluded, "With no FDA approved treatment for Long COVID, we understand the need to better understand long COVID
and to develop treatments for subgroups of this unserved population of patients. Fibromyalgia has been recognized by the U.S.
Food and Drug Administration (FDA) with three approved medicines. Consequently, measuring daily pain is a validated endpoint for
FDA registrational studies in fibromyalgia. We believe that daily pain has the potential to be an endpoint for registrational
studies in fibromyalgia-like long COVID."
the Phase 2 PREVAIL Study
Phase 2 PREVAIL study is a 14-week double-blind, randomized, multicenter, placebo-controlled study to evaluate the efficacy and
safety of TNX-102 SL taken daily at bedtime in patients with multi-site pain associated with post-acute sequelae of SARS-CoV-2
infection (PASC). The trial is being conducted at approximately 30 sites in the U.S. The primary efficacy endpoint will be the
change from baseline in the weekly average of daily self-reported worst pain intensity scores at the Week 14 endpoint. Key secondary
efficacy endpoints include change from baseline in self-reported scores for sleep disturbance, fatigue, and cognitive function.
Topline results are expected in the third quarter of 2023.
more information, see ClinicalTrials.gov Identifier: NCT05472090.
Long COVID or Post-Acute Sequelae of COVID-19 (PASC)
sequelae of COVID-19, or PASC is the formal name for a condition now widely known as Long COVID. Although most people recover
from COVID-19 within weeks of the acute illness, a substantial portion develops a chronic syndrome called Long COVID.11
These individuals experience a constellation of disabling symptoms long past the time of recovery from acute COVID-19. Most Long
COVID patients who have been studied appear to have cleared the SARS-CoV-2 infection from their systems. The symptoms of Long
COVID can include fatigue, sleep disorders, multi-site pain, fevers, shortness of breath, cognitive impairment described as "brain
fog" or memory disturbance, gastrointestinal symptoms, anxiety, and depression. According to the Centers for Disease Control
and Prevention (CDC), 1 in 13 adults in the U.S. (7.5%) have Long COVID symptoms.1 Long COVID is typically associated
with moderate or severe COVID-19, but can occur after mild COVID-19 or even after asymptomatic SARS-CoV-2 infection. More than
40% of adults in the United States reported having COVID-19 in the past, and nearly one in five of those (19%) are currently still
having symptoms of Long COVID.1 Long COVID is a chronic disabling condition that is expected to result in a significant
global health and economic burden.12-15 In response to the urgent need for therapies that address Long COVID, Congress
awarded $1.15 billion to the National Institutes of Health to study Long COVID in December 202016 The U.S. Department
of Health and Human Services National Research Action Plan on Long COVID17, released in August 2022, addresses
the overlap of Long COVID with CFS/ME, which, like fibromyalgia, is one of the overlapping chronic pain syndromes with central
and peripheral sensitization.18 A published survey19 found comparable pain, fatigue, and functional
impairment between Long COVID, fibromyalgia, and CFS/ME. This symptom overlap between these conditions has suggested that altered
neurologic function is one of the leading hypotheses to explain
them.20 While the vaccines available in the U.S.,
through either FDA approval or under Emergency Use Authorization, have been shown to prevent acute COVID, their ability to prevent
Long COVID is unknown. There is currently no approved drug for the treatment of Long COVID. Fibromyalgia-type Long COVID, like
fibromyalgia and CFS/ME, appears to be one of several chronic overlapping pain conditions that have in common the neurological
process called central and peripheral sensitization, which is increasingly known by the term nociplastic pain.
SL is a patented sublingual tablet formulation of cyclobenzaprine hydrochloride which provides rapid transmucosal absorption and
reduced production of a long half-life active metabolite, norcyclobenzaprine, due to bypass of first-pass hepatic metabolism.
As a multifunctional agent with potent binding and antagonist activities at the 5-HT2A-serotonergic, 1-adrenergic, H1-histaminergic,
and M1-muscarinic receptors, TNX-102 SL is in development as a daily bedtime treatment for fibromyalgia, Long COVID (formally
known as post-acute sequelae of COVID-19 [PASC]), alcohol use disorder and agitation in Alzheimer's disease. The United
States Patent and Trademark Office (USPTO) issued United States Patent No. 9636408 in May 2017, Patent No. 9956188 in May 2018,
Patent No. 10117936 in November 2018, Patent No. 10,357,465 in July 2019, and Patent No. 10736859 in August 2020. The Protectic
protective eutectic and Angstro-Technology formulation claimed in the patent are important elements of Tonix's proprietary
TNX-102 SL composition. These patents are expected to provide TNX-102 SL, upon NDA approval, with U.S. market exclusivity until
SL is an investigational new drug and is not approved for any indication
Pharmaceuticals Holding Corp.*
is a biopharmaceutical company focused on commercializing, developing, discovering and licensing therapeutics to treat and prevent
human disease and alleviate suffering. Tonix Medicines, our commercial subsidiary markets Zembrace SymTouch (sumatriptan
injection) 3 mg and Tosymra (sumatriptan nasal spray) 10 mg under a transition services agreement with Upsher-Smith
Laboratories from whom the products were acquired on June 30, 2023. Zembrace SymTouch and Tosymra are each indicated for the treatment
of acute migraine with or without aura in adults. Tonix's development portfolio is composed of central nervous system (CNS),
rare disease, immunology and infectious disease product candidates. Tonix's CNS development portfolio includes both small
molecules and biologics to treat pain, neurologic, psychiatric and addiction conditions. Tonix's lead development CNS candidate,
TNX-102 SL (cyclobenzaprine HCl sublingual tablet), is in mid-Phase 3 development for the management of fibromyalgia, having completed
enrollment of a potentially confirmatory Phase 3 study in the third quarter of 2023, with topline data expected in the fourth
quarter of 2023. TNX-102 SL is also being developed to treat fibromyalgia-type Long COVID, a chronic post-acute COVID-19 condition.
Enrollment in a Phase 2 proof-of-concept study has been completed, and topline results are expected in the third quarter of 2023.
TNX-601 ER (tianeptine hemioxalate extended-release tablets) is a once-daily oral formulation being developed as a treatment for
major depressive disorder (MDD), that completed enrollment in a Phase 2 proof-of-concept study in the third quarter of 2023, with
topline results expected in the fourth quarter of 2023. TNX-4300 (estianeptine) is a single isomer version of TNX-601, small molecule
oral therapeutic in preclinical development to treat MDD, Alzheimer's disease and Parkinson's disease. Relative to
tianeptine, estianeptine lacks activity on the -opioid receptor while maintaining activity in the rat Novel Object Recognition
test in vivo and the ability to activate PPAR- / and neuroplasticity in tissue culture. TNX-1900 (intranasal
potentiated oxytocin), is in development for preventing headaches in chronic migraine, and has completed enrollment in a Phase