Tonix Pharmaceuticals Announces Positive Phase 3 RELIEF Study Results for TNX-102 SL 5.6 mg in Fibromyalgia New 5.6 mg Dose Achieved Statistically Significant Pain Reduction Over Placebo at Week 14 (Primary Endpoint, p=0

Tonix Pharmaceuticals Holding Corp. 8-K

Tonix Pharmaceuticals Announces Positive

Phase 3 RELIEF Study Results for

TNX-102 SL 5.6 mg in Fibromyalgia

New 5.6 mg Dose Achieved Statistically Significant

Pain Reduction Over Placebo at Week 14

(Primary Endpoint, p=0.01)

TNX-102 SL Generally Well Tolerated with

Adverse Event Profile Comparable to Prior Studies;

No New Safety Signals Observed

Approximately 90% of Those Affected by Fibromyalgia

are Women; 95% of Participants in the

RELIEF Study were Women

Company to Host Conference Call Today at

CHATHAM, N.J., December 7, 2020 - Tonix Pharmaceuticals

Holding Corp. (Nasdaq: TNXP) (Tonix or the Company), a clinical-stage biopharmaceutical company, today announced that TNX-102

SL (cyclobenzaprine HCl sublingual tablets) met its pre-specified primary endpoint, significantly reducing daily pain compared

to placebo (p=0.01) in participants with fibromyalgia in the Phase 3 RELIEF study (Table 1). TNX-102 SL is a novel, non-opioid,

centrally-acting analgesic, taken once daily at bedtime, being developed for the management of fibromyalgia. RELIEF was a 14-week

randomized, double-blind, placebo-controlled trial of TNX-102 SL 5.6 mg, in which 503 participants with fibromyalgia were randomized

in a 1:1 ratio across 39 U.S. sites. All participants received one tablet of TNX-102 SL (2.8 mg) or placebo for the first two

weeks, which was increased to two tablets of TNX-102 SL (5.6 mg) or placebo for the remaining 12 weeks.

"Tonix is dedicated to improving the

lives of the millions suffering from fibromyalgia, approximately 90% of whom are female, and the results of the RELIEF trial bring

new hope to this community," said Seth Lederman, M.D., President and Chief Executive Officer of Tonix Pharmaceuticals. "TNX-102

SL at 5.6 mg showed statistically significant and clinically meaningful improvement on the primary endpoint of reducing daily

pain, as well as showed activity in key secondary endpoints of improving sleep and reducing fatigue. One of the biggest challenges

in drug development is finding a dose that balances efficacy and tolerability. We are pleased with the consistent effects of TNX-102

SL 5.6 mg on the primary endpoint of daily pain as well as the tolerability of this dose in the RELIEF study. We are also pleased

at the activity shown on all of the fibromyalgia specific, pre-specified secondary endpoints. We look forward to the results of

the currently enrolling, second potential pivotal Phase 3 study, RALLY, for which we expect to report topline data in the second

half of 2021. Based on the long term safety exposure data we have already collected, the mature stage of our Good Manufacturing

Practice (GMP) manufacturing processes and the established product stability at 36 months, we believe that upon achieving positive

results from the currently enrolling RALLY study, we may potentially be in a position to submit a New Drug Application (NDA) for

TNX-102 SL for fibromyalgia to the U.S. Food and Drug Administration (FDA) in 2022. Additionally, we believe that our commercial

manufacturing is on track to supply the U.S. market in 2022."

Table 1. Results of Primary and Secondary

Abbreviations: FIQ-R = Fibromyalgia Impact Questionnaire - Revised; PROMIS = Patient-Reported Outcomes Measurement Information System; LR = Logistic Regression (missing data considered non-responders);

NRS = Numeric Rating Scale

* statistically significant at p<0.0452

# nominally significant at p<0.0452

1 Analysis by Mixed Model Repeated Measures

with Multiple Imputation unless otherwise indicated.

2 Primary endpoint analysis for FDA approvals

of Cymbalta and Lyrica in fibromyalgia.

"These results support the proposed mechanism in which TNX-102

SL targets disturbed sleep in fibromyalgia and that improved sleep quality leads to improvement of fibromyalgia at the syndromal

level," continued Dr. Lederman. "The sleep disorder specific to fibromyalgia has been called non-restorative'

sleep. Dr. Harvey Moldofsky, Professor emeritus of Psychiatry and Medicine at the University of Toronto, founding Director of

the University of Toronto Center for Sleep and Chronobiology, and Member of the Tonix Scientific Advisory Board, first recognized

the central role of non-restorative sleep in the pathogenesis of fibromyalgia3,4. Our program is based on the subsequent

pioneering work of Dr. Iredell W. Iglehart III, Assistant Professor of Medicine, part-time, Division of Rheumatology, Johns Hopkins

School of Medicine, and Member of the Tonix Scientific Advisory Board, who recognized that a sleep-focused cyclobenzaprine treatment

protocol had the potential to target non-restorative sleep and lead to improvement of fibromyalgia at the syndromal level5.

Transforming this treatment paradigm into a potential product with the clinical activity described in the RELIEF study depended

on the invention of the Protectic and Angstro technologies. These technologies are integral to TNX-102 SL, which is

a sublingual tablet designed for transmucocal delivery of cyclobenzaprine with distinctive pharmacokinetic properties that include

bypassing first-pass hepatic metabolism. Teams led by Giorgio Reiner at APR Applied Pharma Research S.A. and Professor Marino

Nebuloni and Patrizia Colombo at Redox Analytical Science Srl invented and developed these underlying technologies in collaboration

pleased that TNX-102 SL has demonstrated statistically significant treatment effects on fibromyalgia pain," said Dr. Harvey

Moldofsky. "These results validate the mechanism that improving sleep

quality can lead to syndromal effects on fibromyalgia. The sublingual formulation of TNX-102 SL for transmucosal absorption

showed promise at the 2.8 mg dose in two prior studies, but now that the 5.6 mg dose has shown consistent efficacy, we are encouraged

in the outcome of future studies."

"TNX-102 SL has the potential to be

a new non-addictive, non-opiate analgesic for the management of fibromyalgia which is particularly important given that fibromyalgia

is a chronic pain condition," said Gregory Sullivan, M.D., Chief Medical Officer of Tonix. "Approximately one third

of fibromyalgia patients resort to opiates out of desperation and because of dissatisfaction with available therapies. Cyclobenzaprine,

the active ingredient of TNX-102 SL, has no recognized potential for addiction. Based on our previous discussions with FDA, we

expect to submit an NDA without new addiction liability studies. TNX-102 SL could potentially offer fibromyalgia patients, who

have multiple disabling fibromyalgia symptoms, a first-line monotherapy with broad symptom relief, and the compliance advantage

of being administered once-a-day (at bedtime)."

3Moldofsky H et al, Psychosom Med 1975;37:341-51.

4Moldofsky H and Scarisbrick P. Psychosom Med 1976;38:35-44.

5Iglehart IW. 2003; US Patent 6,541,523.

SUMMARY OF TOPLINE RESULTS OF THE RELIEF

The RELIEF study included a pre-specified

interim analysis that was conducted in September 2020. Due to the inclusion of the potential to stop for success for this interim

analysis, positive results required a two sided p-value of 0.0452 for both primary and secondary endpoints. Based on interim results,

the independent data monitoring committee (IDMC) made the non-binding recommendation that the trial continue to completion with

the addition of 210 participants to the original sample size of 470 participants, which was the maximum number of participants

that could be added under the interim statistical analysis plan. Given this information, the Company decided to complete the study

with the 503 enrolled participants and not to add additional participants. The first cohort of the study was enrolled between

December 2019 and April 2020 at a time when the COVID-19 pandemic struck the U.S. Due to the pandemic, the Company modified the

protocol in accordance with FDA guidelines to ensure patient safety and minimize risk in enrolling the first cohort. The modification

allowed sites to conduct remote study visits for select cases in which the COVID-19 pandemic made on-site visits unsafe or otherwise

not possible. The second cohort was enrolled between last week of April and July 2020 and, by this time, the sites' COVID-19-related

safety procedures for participants' attendance at clinic visits had become routine. At the time of the interim analysis

in September 2020, there were only 15 participants still active in the study, all of whom completed their last visit by the end

In analyzing the efficacy endpoints, a sequential

test procedure was applied to the primary and six key secondary efficacy endpoints such that each endpoint had to meet statistical

significance (below a two-sided 0.0452 p-value) in order for the subsequent endpoints to be considered for statistical significance.

The RELIEF study achieved statistical significance

on the pre-specified primary efficacy endpoint: change from baseline in the weekly average of daily diary pain severity numerical

rating scale (NRS) scores for TNX-102 SL 5.6 mg (LS mean [SE]: -1.9 [0.12] units) versus placebo (-1.5 [0.12] units), analyzed

by mixed model repeated measures with multiple imputation (LS mean [SE] difference: -0.4 [0.16] units, p=0.010, Table 1).

The statistically significant improvement

in pain is further substantiated when diary pain was analyzed by another standard statistical approach, a 30 percent responder

analysis, with 46.8% on active and 34.9% on placebo having a 30 percent or greater reduction in pain (logistic regression; odds