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
18 Outubro 2023 - 8:00AM
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 FcγRII 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 Sjögren’s
Syndrome.”
About TNX-1500
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 FcγRII 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, Sjögren’s syndrome and multiple sclerosis.8-10
CD40-L is a member of the TNFα super gene family. Other members
have been the targets of successful mAb: TNFα and RANKL for
autoimmune diseases and osteoporosis, respectively. Other TNFα
super gene family members are targeted by mAbs in development
including, TNF-like ligand 1A (TL1A) and CD30L for ulcerative
colitis.
- Anand R.P., et al. Nature. 2023. 622, 393–401.
- Mohiuddin M. Nature. News and Views. 2023. “Pig-to-primate
organ transplants require genetic modifications of donor.”
- Kozlov M. Nature. New, 2023. “Monkey survives two years after
gene-edited pig-kidney transplant.”
- Lederman S, et al. J Exp Med. 1992. 175(4):1091-101.
- NHPRRC anti-CD154 clone 5C8H1D MassBiologics PR-1547
- Lassiter G., et al. Am. J. Transplant.
2023. https://doi.org/10.1016/j.ajt.2023.03.022
- Miura S., et al. Am. J. Transplant. 2023.
https://doi.org/10.1016/j.ajt.2023.03.025
- UCB Pipeline - https://www.ucb.com/our-science/pipeline
- BioSpace. September 12, 2022 -
https://www.biospace.com/article/releases/horizon-therapeutics-plc-announces-phase-2-trial-evaluating-dazodalibep-for-the-treatment-of-sjoegren-s-syndrome-meets-primary-endpoint/
- Business Wire. January 18, 2023 -
https://www.businesswire.com/news/home/20230118005359/en/Horizon-Therapeutics-plc-Announces-Phase-2-Trial-Evaluating-Dazodalibep-for-the-Treatment-of-Sj%C3%B6gren%E2%80%99s-Syndrome-Meets-Primary-Endpoint-in-the-Second-Study-Population-Only-Phase-2-Trial-to-Meet-Primary-Endpoint-in-Both-Patient-Populations
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-β/δ 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 of clinical development of our product
candidates; 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, 2022, as filed
with the Securities and Exchange Commission (the “SEC”) on March
13, 2023, and periodic reports filed with the SEC on or after the
date thereof. All of Tonix's forward-looking statements are
expressly qualified by all such risk factors and other cautionary
statements. The information set forth herein speaks only as of the
date thereof.
Investor Contact
Jessica MorrisTonix
Pharmaceuticalsinvestor.relations@tonixpharma.com (862)
904-8182
Peter VozzoICR Westwickepeter.vozzo@westwicke.com (443)
213-0505
Media Contact
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Westwickeben.shannon@westwicke.com443-213-0495
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