Tonix Pharmaceuticals and Massachusetts General Hospital Enter into Research Collaboration to Develop Tonix's Third Generation Anti-CD154 Monoclonal Antibody, TNX-1500, for the Treatment and Prevention of Organ Transplan

Pharmaceuticals Holding Corp. 8-K

Pharmaceuticals and Massachusetts General Hospital Enter into Research Collaboration to

Develop Tonix's Third Generation

Anti-CD154 Monoclonal Antibody, TNX-1500,

for the Treatment and Prevention of Organ Transplant Rejection

YORK, August 21, 2019 (GLOBE NEWSWIRE) -- Tonix Pharmaceuticals Holding Corp. (Nasdaq: TNXP) (Tonix or the Company), a clinical-stage

biopharmaceutical company, today announced the signing of a research collaboration agreement with Massachusetts General Hospital

(MGH), a teaching hospital of Harvard Medical School, to develop TNX-1500, a humanized monoclonal antibody (mAb) that targets

CD154 for the prevention and treatment of organ transplant rejection. TNX-1500 is another step in the strategic broadening of

Tonix's portfolio of high-value programs, whose risk is mitigated by previous clinical data and extensive preclinical science.

Although transplantation is the first targeted indication for TNX-1500, it is also a potential treatment for autoimmune conditions

including systemic lupus erythematosus, rheumatoid arthritis and multiple sclerosis.

and MGH have agreed to work jointly under a research agreement which will bring together Tonix's internally developed, proprietary

anti-CD154 mAb, TNX-1500, with transplantation experts from MGH, led by Richard N. Pierson III, M.D., scientific director of the

Center for Transplantation Sciences in the Department of Surgery at MGH and Professor of Surgery at Harvard Medical School (HMS).

The goal of the collaboration is to advance TNX-1500 as a potential first-in-class therapeutic for organ transplant rejection.

Transplant organ rejection occurs when the immune system of the organ recipient attacks the new organ as if it was an infection

President and Chief Executive Officer, Seth Lederman, M.D. said, "A substantial body of evidence in humans and animals indicates

that mAbs targeting CD154 have the potential to be an important therapeutic option for preventing or treating transplant organ

rejection and as a treatment for autoimmune disorders. Despite the recognized promise of anti-CD154 therapy, first generation

anti-CD154 mAbs were limited because their constant fragment (Fc) domain interacted with a receptor called Fc RII, which

raised concerns over an increased risk of thrombosis. Second generation anti-CD154 mAbs had dramatically reduced binding to Fc RII,

but had other issues, including decreased efficacy.1-3 TNX-1500 is a third generation anti-CD154 mAb that has been

designed by protein engineering to target CD154 therapeutically, while decreasing Fc RII binding and the potential for thrombosis."

Pierson of MGH and HMS said, "Anti-CD154 therapy has a unique activity in controlling the immune response to organ transplants.4,5

There remains a significant need for new treatments with improved activity and tolerability to prevent or treat organ transplant

rejection. Anti-CD154 has shown great promise to facilitate transplant tolerance' in multiple preclinical transplant

models. A safe, effective anti-CD154 also has potential to enable use of genetically modified or humanized' pig

organs to treat humans with advanced organ failure or diabetes, an emerging field known as xenotransplantation.'"

Lederman added, "Nearly 30 years ago, the laboratory that I directed as an Assistant Professor at Columbia University, discovered

and characterized CD154, generated the first anti-CD154 monoclonal antibody, 5c8, and elucidated the molecular basis of T cell

helper function.8 It is exciting to return to the anti-CD154 field and to bring forth a third generation anti-CD154

mAb potential biologic therapeutic for treating and preventing organ transplant rejection that stands on the shoulders of previous

work. We believe that TNX-1500 has the potential to maintain therapeutic activity of first generation anti-CD154 mAbs, but with

reduced risk of thrombosis. We believe that the combined expertise of Tonix and MGH will be strongly synergistic. Preventing and

treating organ rejection remains the greatest obstacles to long term survival in transplantation."

Waters J, Biocentury; October 26, (2018)

NCT02273960; ClinicalTrials.gov; "Study to Evaluate Safety and Efficacy

in Adult Subjects With ITP (ITP)"; results posted April 1, 2019, accessed July 29, 2019)

Ferrant JL et al., International Immunol. (11):1583 (2004)

O Neill NA, et al. Transplantation. 101(9): 2038 (2017)

Zhang T, et al. Immunotherapy. 7(8):899 (2015)

L ngin M, et al. Nature. 564(7736):430 (2018)

RN 3rd. J Thorac Cardiovasc Surg. Jun 13. pii: S0022-5223(19)31024-4. doi: 10.1016/j.jtcvs.2019.04.087. (2019)

Lederman, S. & al. J. Exp. Med. 175:1091-1101 (1992)

is a protein expressed on the surface of activated T lymphocytes that mediates T cell helper function. CD154 is also known as

the CD40-ligand (CD40-L), the T cell-B cell activating molecule (T-BAM), TRAP or gp39. CD154 is a member of the Tumor Necrosis

Factor (TNF) Super Family. No mAb against CD154 has been licensed anywhere in the world. Other TNF Super Family members have proven

to be targets for antagonist mAbs. Licensed mAbs against TNF include: infliximab (Remicade ), adalimumab (Humira ),

certolizumab pegol (Cimzia ), and golimumab (Simponi ) for the treatment of certain autoimmune conditions. Also, etanercept

(Enbrel ) is a TNF antagonist receptor fusion protein. A licensed mAb against RANKL (CD254) is denosumab (Prolia

or Xgeva ) for the treatment of osteoporosis, treatment-induced bone loss, metastases to bone, and giant cell tumor of bone.

and Simponi are trademarks of Janssen; Humira is a trademark of AbbVie Inc.; Cimzia is a trademark of UCB S. A.;

Enbrel , Prolia and Xgeva are trademarks of Amgen Inc.

Pharmaceuticals Holding Corp.

is a clinical-stage biopharmaceutical company focused on discovering and developing small molecules and biologics to treat psychiatric,

pain and addiction conditions, to improve biodefense through potential medical counter-measures and to prevent and treat organ

transplant rejection. Tonix's lead program is for the development of Tonmya* (TNX-102 SL), which is in Phase 3 development

as a bedtime treatment for PTSD. Tonix is also developing TNX-102 SL as a bedtime treatment for fibromyalgia, agitation in Alzheimer's

disease and alcohol use disorder, to be developed under separate Investigational New Drug applications (INDs) to support potential

pivotal efficacy studies. The fibromyalgia program is in Phase 3 development, the agitation in Alzheimer's program is Phase

2 ready and the alcohol use disorder program is in the pre-IND application stage. TNX-1300** (double-mutant cocaine esterase)

is being developed under an IND and is in Phase 2 development for the treatment of cocaine intoxication. Tonix

has two other programs in the pre-IND application stage of development for PTSD, but with different mechanisms than TNX-102 SL

and designed for daytime dosing: TNX-601 (tianeptine oxalate) and TNX-1600***, a triple reuptake inhibitor.

TNX-601 is also in development for a potential indication - neurocognitive dysfunction associated with corticosteroid use.

Data is expected in the second half of 2019 for a Phase 1 clinical formulation selection pharmacokinetic study of TNX-601 that

is being conducted outside of the U.S. TNX-801 (live virus vaccine for percutaneous (scarification) administration) is a potential

smallpox-preventing vaccine based on a live synthetic version of horsepox virus, currently in the pre-IND application stage. Finally,

TNX-1500 is being developed to prevent and treat organ transplant rejection, as well as to treat autoimmune conditions, and is

in the pre-IND application stage.

has been conditionally accepted by the U.S. Food and Drug Administration (FDA) as the proposed trade name for TNX-102 SL for the

treatment of PTSD. TNX-102 SL (cyclobenzaprine HCl sublingual tablets) is an investigational new drug and has not been approved

(T172R/G173Q double-mutant cocaine esterase 200 mg, i.v. solution) is an investigational new biologic and has not been approved

((2S,4R,5R)-5-(((2-aminobenzo[d]thiazol-6-yl)methyl)amino)-2-(bis(4-fluorophenyl)methyl)tetrahydro-2H-pyran-4-ol)

is an inhibitor of reuptake of three monoamine neurotransmitters (serotonin, norepinephrine and dopamine), or a "triple

reuptake" inhibitor.

press release and further information about Tonix can be found at www.tonixpharma.com.

Forward-Looking Statements

statements in this press release are forward-looking within the meaning of the Private Securities Litigation Reform Act of 1995.

These statements may be identified by the use of forward-looking words such as "anticipate," "believe,"

"forecast," "estimate," "expect," and "intend," among others. These forward-looking

statements are based on Tonix's current expectations and actual results could differ materially. There are a number of factors

that could cause actual events to differ materially from those indicated by such forward-looking statements. These factors include,

but are not limited to, risks related to failure to obtain FDA clearances or approvals and noncompliance with FDA regulations;

our need for additional financing; uncertainties of patent protection and litigation; uncertainties of government or third party

payor reimbursement; limited research and development efforts and dependence upon third parties; and substantial competition.

As with any pharmaceutical under development, there are significant risks in the development, regulatory approval and commercialization

of new products. Tonix does not undertake an obligation to update or revise any forward-looking statement. Investors should read

the risk factors set forth in the Annual Report on Form 10-K for the year ended December 31, 2018, as filed with the Securities

and Exchange Commission (the "SEC") on March 18, 2019, and periodic reports on Form 10-Q filed with the SEC on or

after the date thereof. Tonix does not undertake any obligation to update or revise any forward-looking statements, whether as

a result of new information, future events or otherwise, except as required by law.