Full Press Release Details
Tonix Pharmaceuticals Holding Corp. 8-K
Tonix Pharmaceuticals Announces Publication
of Data in the Journal Nature Involving TNX-1500 (Fc-modified dimeric anti-CD40L mAb) for the Prevention of Rejection in Kidney
Xenotransplantation in Animal Models
Research Directed by Faculty of the Center
for Transplantation Sciences, Massachusetts General Hospital
TNX-1500 is Enrolling in a Phase 1 Clinical
Tonix is Developing TNX-1500 for Prevention
of Kidney Allograft Rejection as the First Indication: Multiple Other Indications, including Autoimmune Disorders, are Planned
CHATHAM, N.J., October 18, 2023 (GLOBE NEWSWIRE) -
Tonix Pharmaceuticals Holding Corp. (Nasdaq: TNXP) (Tonix or the Company), a biopharmaceutical company with marketed products and a pipeline
of development candidates, today announced that a study published in the Journal Nature1 by faculty at the Center for
Transplantation Sciences, Massachusetts General Hospital (MGH) in collaboration with biotechnology company, eGenesis, utilized TNX-1500
(Fc-modified dimeric anti-CD40L monoclonal antibody [mAb]) as part of the immune modulating regimen to prevent organ transplant rejection.
Tonix's TNX-1500 is in development for the prevention of human kidney organ transplant rejection. The molecular target of TNX-1500
is CD40-ligand (CD40L), which is also known as CD154.
TNX-1500 was invented and developed in-house by Seth
Lederman, M.D., Chief Executive Officer of Tonix Pharmaceuticals, and colleagues. TNX-1500 is a third generation anti-CD40L monoclonal
antibody that has been designed by protein engineering to decrease Fc RII binding and to reduce the potential for thrombosis. Preclinical
studies in non-human primates demonstrated that TNX-1500 showed activity in preventing allograft and xenograft organ rejection and was
well tolerated. The research in the Nature paper was conducted at MGH, led by principal investigator Tatsuo Kawai, M.D., Professor
of Surgery, Harvard Medical School and the Center for Transplantation Science. A "News and Views" editorial2 and
a News3 story appeared in the same issue of Nature.
The Nature article titled, "Design and
testing of a humanized porcine donor for xenotransplantation" includes data that provide additional support for TNX-1500's
activity in preventing pig xenograft organ rejection and for its tolerability in non-human primates. Because anti-CD40L treatment is widely
recognized as critical to the success of xeno organ transplant, no animals were transplanted without anti-CD40L treatment. Four of the
transplanted animals received prophylactic treatment with TNX-1500. The other animals were treated with a primate-adapted version of mAb
5c8, which is an earlier antibody that was also discovered by Dr. Lederman, when he was an assistant professor at Columbia University.4
The primate-adapted 5c8 anti-CD40L mAb5 has been provided to qualified researchers at a nominal charge for more than 20 years
in an National Institute of Health (NIH)-funded program called the "Non-human Primate Reagent Resource Center" (NHPRRC).
"The animal study described in the Nature
publication1 supports the growing evidence that the protein engineering behind the invention of TNX-1500 resulted in a dimeric
antibody that retains activity to prevent rejection and preserve graft function. These and other data6,7 confirm the rationale
for us to pursue development of TNX-1500 to prevent rejection in human transplantation," said Dr. Lederman. "We are currently
enrolling in a Phase 1 trial with TNX-1500 in healthy volunteers to support the development of TNX-1500 for the prevention of allograft
rejection. There remains a significant need for new treatments with improved activity and tolerability to prevent organ transplant rejection.
We believe TNX-1500 has the potential for treating and preventing organ transplant rejection."
Dr. Lederman added, "Our primary focus of early
development will be allotransplantation in which the donor organ comes from a human volunteer or cadaver. However, long term we hope to
develop TNX-1500 for xenograft transplantation in which the donor organ comes from genetically engineered pigs. Several lines of research
indicate that anti-CD40L is required for long term xenograft acceptance. I believe it is unlikely for human xenotransplantation to proceed
without CD40L blockade. In addition, anti-CD40L monoclonal antibodies have demonstrated efficacy in autoimmune diseases like systemic
lupus erythematosus and Sj gren's Syndrome."
TNX-1500 (Fc-modified anti-CD40L mAb) is a
humanized dimeric monoclonal antibody that interacts with the CD40-ligand (CD40L), which is also known as CD154. TNX-1500 is being developed
for the prevention of allograft and xenograft rejection, for the treatment of autoimmune diseases including multiple sclerosis and for
the prevention of graft-versus-host disease (GvHD) after hematopoietic stem cell transplantation (HCT). A Phase 1 study of TNX-1500 is
currently enrolling. TNX-1500 is a third generation anti-CD40L mAb that has been designed by protein engineering to decrease Fc RII
binding and to reduce the potential for thrombosis. The disulfide-linked dimeric structure is similar to natural antibodies and in the
case of anti-CD40L is believed to confer to TNX-1500 a higher avidity for cell-associated CD40L, relative to soluble CD40L. Two articles
were recently published in the American Journal of Transplantation that demonstrate TNX-1500 prolongs nonhuman primate renal and
heart allograft survival6,7. Other anti-CD40L mAbs are in development for treating systemic lupus erythematosus, Sj gren's
syndrome and multiple sclerosis.8-10 CD40-L is a member of the TNF super gene family. Other members have been the targets
of successful mAb: TNF and RANKL for autoimmune diseases and osteoporosis, respectively. Other TNF super gene family members
are targeted by mAbs in development including, TNF-like ligand 1A (TL1A) and CD30L for ulcerative colitis.
Tonix Pharmaceuticals Holding Corp.*
Tonix 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, LLC 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 late
December 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 were reported 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 in the third quarter of 2023, with topline results expected in early November of 2023. TNX-4300
(estianeptine) is a single isomer version of TNX-601, a 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 mu-opioid receptor while maintaining
activity and the ability to activate PPAR- / and neuroplasticity in tissue culture. TNX-1900 (intranasal potentiated oxytocin),
is in development as a preventive treatment in chronic migraine, and enrollment has completed in a Phase 2 proof-of-concept study with
topline data expected in early December 2023. TNX-1900 is also being studied in binge eating disorder, pediatric obesity and social anxiety
disorder by academic collaborators under investigator-initiated INDs. TNX-1300 (cocaine esterase) is a biologic designed to treat cocaine
intoxication and has been granted Breakthrough Therapy designation by the FDA. A Phase 2 study of TNX-1300 is expected to be initiated
in the fourth quarter of 2023. Tonix's rare disease development portfolio includes TNX-2900 (intranasal potentiated oxytocin) for
the treatment of Prader-Willi syndrome. TNX-2900 has been granted Orphan Drug designation by the FDA. Tonix's immunology development
portfolio includes biologics to address organ transplant rejection, autoimmunity and cancer, including TNX-1500, which is a humanized
monoclonal antibody targeting CD40-ligand (CD40L or CD154) being developed for the prevention of allograft rejection and for the treatment
of autoimmune diseases. A Phase 1 study of TNX-1500 was initiated in the third quarter of 2023. Tonix's infectious disease pipeline
includes TNX-801, a vaccine in development to prevent smallpox and mpox. TNX-801 also serves as the live virus vaccine platform or recombinant
pox vaccine platform for other infectious diseases. The infectious disease development portfolio also includes TNX-3900 and TNX-4000,
which are classes of broad-spectrum small molecule oral antivirals.
*Tonix's product development candidates are
investigational new drugs or biologics and have not been approved for any indication.
Zembrace SymTouch and Tosymra are registered trademarks
of Tonix Medicines. Intravail is a registered trademark of Aegis Therapeutics, LLC, a wholly owned subsidiary of Neurelis, Inc. All other
marks are property of their respective owners.
This press release and further information about Tonix
can be found at www.tonixpharma.com.
Forward Looking Statements
Certain 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 the failure to obtain FDA clearances or approvals and noncompliance
with FDA regulations; risks related to the failure to successfully market any of our products; risks related to the timing and progress