Tonix Pharmaceuticals Announces IND Clearance for TNX-102 SL as a Potential Treatment for Long COVID Syndrome, Also Known as Post-Acute Sequelae of COVID-19 (PASC) Phase 2 Clinical Trial of TNX-102 SL for the Treatment o

Tonix Pharmaceuticals Holding Corp. 8-K

Tonix Pharmaceuticals Announces IND Clearance for

TNX-102 SL as a Potential Treatment for Long COVID Syndrome, Also Known as Post-Acute Sequelae of COVID-19 (PASC)

Phase 2 Clinical Trial of TNX-102 SL for the

Treatment of Long COVID Expected to Start Second Quarter 2022

Long COVID Afflicts More Than 30% of Patients

Following Infection with SARS-CoV-2, the Virus that Causes COVID-19, and is Expected to be a Global Health Burden

CHATHAM, N.J., April 6, 2022 (GLOBE NEWSWIRE)

-- Tonix Pharmaceuticals Holding Corp. (Nasdaq: TNXP) (Tonix or the Company), a clinical-stage biopharmaceutical company, today announced

the U.S. Food and Drug Administration (FDA) has cleared the Investigational New Drug (IND) application to support a Phase 2 clinical trial

with TNX-102 SL1 as a potential treatment for a subset of patients with Long COVID Syndrome (Long COVID) whose symptoms overlap

with fibromyalgia. Long COVID is now known officially as Post-Acute Sequelae of COVID-19 (PASC2).

"We are excited to have received the

FDA's IND clearance to begin clinical trials of TNX-102 SL for the treatment of Long COVID," said Seth Lederman, M.D., Chief

Executive Officer of Tonix Pharmaceuticals. "Over 30% of people who recover from COVID-19 continue to experience a constellation

of symptoms long past the time that they have recovered from acute COVID-19 illness3-4. The symptoms of Long COVID, which can

include fatigue, multi-site pain, sleep disturbances, fevers, shortness of breath, cognitive impairment, gastrointestinal symptoms, anxiety,

and depression, can persist for many months and can range from mild to incapacitating5. Our study will focus on testing TNX-102

SL in the treatment of patients with multi-site pain associated with Long COVID. This group of patients

have symptoms that overlap with other chronic pain conditions, which as a group have been termed, chronic overlapping pain conditions.'6,7

This type of pain syndrome is increasingly recognized as nociplastic pain,8 and the underlying mechanism as central

sensitization.'9 Fibromyalgia is considered one of the chronic overlapping pain conditions and our experience

with TNX-102 SL in fibromyalgia is the motivation for undertaking the development of TNX-102 SL in patients with Long COVID whose symptoms

overlap with fibromyalgia."

About the Phase 2 Study

Phase 2 study will be a double-blind randomized, placebo-controlled 14-week trial to evaluate

the safety and efficacy of sublingual TNX-102 SL 5.6 mg daily at bedtime in the treatment of patients with multi-site pain associated

with Long COVID. The trial will be conducted at approximately 30 sites to enroll

approximately 470 patients (235 per arm) who will be randomized in a 1:1 ratio to treatment with

TNX-102 SL or placebo tablets. The primary efficacy endpoint will be Change from Baseline in the weekly average of daily self-reported

worst pain intensity scores at the Week 14 endpoint. An interim analysis is expected to

be completed after the first 50% of enrolled patients have completed the study for the purpose of possible sample size re-estimation.

About Long COVID or Post-Acute Sequelae

of SARS-CoV-2 (PASC)

Although most people recover from COVID-19

within weeks of the acute illness, a substantial portion develop a chronic syndrome called Long COVID. 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. Long COVID can persist for many months and can range in severity from mild to incapacitating. Several cohort

studies have reported that persistence of symptoms following SARS-CoV-2 infection occurs in more than 30% of patients.3-5 While

typically associated with moderate or severe COVID-19, Long COVID can occur after mild COVID-19 or even after asymptomatic SARS-CoV-2

infection. Patients with Long COVID are sometimes referred to as "long-haulers". Long COVID is a chronic disabling condition

that is expected to result in a significant global health and economic burden.10-13 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 2020.14

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.

SL is an investigational new drug and has not been approved for any indication.

24, 2021 - White House COVID-19 Response Team press briefing; Feb 25, 2021 - policy brief from the World Health Organization on long COVID.

JK, et al. (2021) "Sequelae in Adults at 6 Months After COVID-19 Infection". JAMA Netw Open. ;4(2):e210830. doi:10.1001/jamanetworkopen.2021.0830

A et al.. (2020) "Persistent symptoms in patients after acute COVID-19." JAMA 324.6: 603-605.

Ani, et al. (2021) "Post-acute COVID-19 syndrome." Nature Medicine27(4): 601-615.

W, et al.. (2016) "Overlapping Chronic Pain Conditions: Implications for Diagnosis and Classification". J Pain. 17(9

C, et al. (2015): Impact of chronic overlapping pain conditions on public health and the urgent need for safe and effective treatment:

2015 analysis and policy recommendations. Chronic Pain Research Alliance. http://www.chronicpainresearch. org/public/CPRA_WhitePaper_2015-FINAL-Digital.pdf.

Accessed July 26, 2021.

AP, Perrot S. (2019) "New concepts of pain". Best Pract Res Clin Rheumatol. 33(3):101415.

J, George SZ, Clauw DJ, et al. (2021) "Central sensitisation in chronic pain conditions: latest discoveries and their potential

for precision medicine". The Lancet Rheumatology. 3(5):e383-e392. doi:10.1016/s2665-9913(21)00032-1

A, and Vassall, A. (2021) "Count the cost of disability caused by COVID-19." Nature 593(7860): 502-505.

V, et al. (2022) "Long COVID Through a Public Health Lens: An Umbrella Review." Public Health Rev. 43:1604501. Published

2022 Mar 15. doi:10.3389/phrs.2022.1604501

HE., et al. (2021) "Characterizing long COVID in an international cohort: 7 months of symptoms and their impact." EClinicalMedicine 38:

C, et al. (2021) "A model framework for projecting the prevalence and impact of Long-COVID in the UK." PLoS One. 16(12):e0260843.

Published 2021 Dec 2. doi:10.1371/journal.pone.0260843

NIH provision of Title III Health and Human Services, Division M--Coronavirus Response and Relief Supplemental Appropriations Act, 2021,

of H.R. 133, The Consolidated Appropriations Act of 2021. The bill was enacted into law on 27 December 2020, becoming Public Law 116-260.

TNX-102 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 serotonin-5-HT2A, 1-adrenergic, histaminergic-H1, and muscarinic-M1

receptors, TNX-102 SL is in clinical development as a daily bedtime treatment for Long COVID, fibromyalgia, PTSD, alcohol use disorder,

and agitation in Alzheimer's disease. The U.S. Patent and Trademark Office (USPTO) has 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 these patents 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 2034/2035.

About Tonix Pharmaceuticals Holding Corp.

Tonix is a clinical-stage biopharmaceutical

company focused on discovering, licensing, acquiring and developing therapeutics and diagnostics to treat and prevent human disease and

alleviate suffering. Tonix's portfolio is composed of immunology, rare disease, infectious disease, and central nervous system (CNS)

product candidates. Tonix's immunology portfolio includes biologics to address organ transplant rejection, autoimmunity and cancer,

including TNX-15001 which is a humanized monoclonal antibody targeting CD40-ligand being developed for the prevention of allograft

and xenograft rejection and for the treatment of autoimmune diseases. A Phase 1 study of TNX-1500 is expected to be initiated in the second

half of 2022. Tonix's rare disease portfolio includes TNX-29002 for the treatment of Prader-Willi syndrome. TNX-2900

has been granted Orphan-Drug Designation by the FDA. Tonix's infectious disease pipeline includes a vaccine in development to prevent

smallpox and monkeypox called TNX-8013, next-generation vaccines to prevent COVID-19, and an antiviral to treat COVID-19. Tonix's

lead vaccine candidates for COVID-19 are TNX-1840 and TNX-18504, which are live virus vaccines based on Tonix's recombinant

pox vaccine (RPV) platform. TNX-35005 (sangivamycin, i.v. solution) is a small molecule antiviral drug to treat

acute COVID-19 and is in the pre-IND stage of development. TNX-102 SL, (cyclobenzaprine HCl sublingual tablets), is a small molecule drug

being developed to treat Long COVID that overlaps with fibromyalgia, a chronic post-COVID condition. Tonix expects to initiate a Phase

2 study in Long COVID in the second quarter of 2022. The Company's CNS portfolio includes both small molecules and biologics to

treat pain, neurologic, psychiatric and addiction conditions. Tonix's lead CNS candidate, TNX-102 SL, is in mid-Phase 3 development

for the management of fibromyalgia with a new Phase 3 study expected to start in the second quarter of 2022. Finally, TNX-13006

is a biologic designed to treat cocaine intoxication that is expected to start a Phase 2 trial in the second quarter of 2022.

1TNX-1500 is an investigational

new biologic at the pre-IND stage of development and has not been approved for any indication.

2TNX-2900 is an investigational

new drug at the pre-IND stage of development and has not been approved for any indication.

3TNX-801 is a live horsepox