Tonix Pharmaceuticals Holding Corp. (Nasdaq: TNXP), a
biopharmaceutical company with marketed products and a pipeline of
development candidates, today announced the results of modeling key
human pharmacokinetic (PK) properties for TNX-1500 (Fc-modified
humanized anti-CD40L monoclonal antibody, or mAb)* from animal
studies. TNX-1500 is in development for the prevention of rejection
in solid organ and bone marrow transplantation and for the
treatment of autoimmune disorders.
“For more than 30 years, anti-CD40L therapy has
shown promise in transplantation and the treatment of autoimmunity,
but first-generation humanized mAbs were associated with an
increased risk of thrombosis and second-generation agents had poor
PK properties or reduced activity,” said Seth Lederman, M.D., Chief
Executive Officer of Tonix Pharmaceuticals. “Preclinical studies in
non-human primates have shown that TNX-1500 maintains the activity
of first generation mAbs, with reduced risk of thrombotic
complications.3-5 Today we are announcing that modeling studies
from animal PK data3, predict that a half-life of approximately
three weeks for TNX-1500 in humans6,7, which supports monthly
dosing. This PK analysis together with TNX-1500’s activity and
tolerability in animals, suggests that the protein engineering of
TNX-1500’s Fc region has achieved its design goals.”
Dr. Lederman continued, “Recently, positive
clinical data have been reported by Sanofi, with its Fc-modified
humanized anti-CD40L mAb frexalimab in treating relapsing multiple
sclerosis with monthly i.v. or biweekly s.c. dosing regimens.2
Based on its results in multiple sclerosis, Sanofi projects that
frexalimab will exceed €5B per year in peak sales1. TNX-1500 was
designed to reduce binding to the Fc-receptor for IgG type 2a, or
FcγR2a, which has been shown to play a role in the thrombosis
associated with first-generation anti-CD40L mAbs, similar to
frexalimab. In addition, Eledon Pharmaceuticals is in Phase 2
development for the prevention of rejection of kidney transplants
with tegoprubart, a non-covalent dimer antibody with no heavy-light
or heavy-heavy interchain disulfide bridges for the prevention of
rejection of kidney transplants.”8
“Anti-CD40L therapy has multiple possible
indications in addition to solid organ and bone marrow
transplantation, including autoimmune diseases,” Dr. Lederman
stated, “We look forward to the results of our Phase 1 PK and
pharmacodynamic trial in the third quarter of 2024 and to advancing
TNX-1500 as a promising candidate for prevention of organ and bone
marrow transplant rejection and for treating autoimmune
conditions.”
About the Translation of Human
Pharmacokinetic Parameters from Animal Data
Results of a single dose PK study in animals
were analyzed to predict human PK parameters. The PK study was
conducted in six healthy cynomolgus monkeys at 30, 100 and 300
mg/kg and revealed linear PK across those doses, consistent with an
antibody with no target mediated drug disposition.6,7 The half-life
in cynomolgus monkeys is approximately 14 days. Human half-life
prediction for TNX-1500 was based on allometric scaling for mAbs
with linear PK.6 Clearance in cynomolgus animals was 6.24 ml/day
(26.6% C.V.) and the predicted clearance in humans was 141 mL/day
(C.V. 22.9%).6,7 The predicted human half-life for TNX 1500 is 23.8
days (range of 18.3 to 27.6 days) which supports monthly dosing.
6,7
About TNX-1500
TNX-1500 (Fc-modified humanized anti-CD40L mAb)
is a humanized monoclonal antibody that binds and blocks the
CD40-ligand (CD40L), also known as CD154. TNX-1500 is being
developed for the prevention of allograft and xenograft rejection,
for the prevention of graft-versus-host disease (GvHD) after
hematopoietic stem cell transplantation (HCT) and for the treatment
of autoimmune diseases. A first-in-human Phase 1 trial of TNX-1500
has completed the clinical phase. Topline results are expected in
the third quarter of 2024. The primary objective of the Phase 1
trial is to assess the safety, tolerability, PK, and
pharmacodynamics of intravenous (i.v.) TNX-1500. Eligible
participants enrolled in the Phase 1 trial were distributed across
three dosing cohorts (3 mg/kg, 10 mg/kg, and 30 mg/kg,
respectively) and evaluated regularly over a 120-day period after
dosing. The Phase 1 trial is intended to support dosing in a
planned Phase 2 trial in kidney transplant recipients. Two
published articles in the American Journal of Transplantation
demonstrate TNX-1500 prevents rejection, prolongs survival and
preserves graft function as a single agent or in combination with
other drugs in non-human primate renal and heart allografts.3,4
About anti-CD40L Therapeutics in
Development
No anti-CD40L mAb has been approved in any
jurisdiction. In addition to TNX-1500, frexalimab and tegoprubart,
tn03 fusion protein dazodalibep is being developed by Amgen
(formerly Horizon Therapeutics Public Limited Company) for the
treatment of Sjögren's Syndrome.9,10 Dapirolizumab pegol, an
anti-CD40L pegylated Fab, is being developed by UCB for the
treatment of systemic lupus erythematosus.11
*TNX-1500 is an investigational new biologic and
is not approved for any indication
- Dunn, A.
Endpoints. December 7, 2023. “Sanofi CEO Paul Hudson pitches 12
blockbusters in a bid to convince investors on boosting R&D
spend”.
https://endpts.com/sanofi-rd-day-ceo-paul-hudson-touts-12-blockbusters-ups-rd-spend/
- Vermersch P., et al. N Engl J Med.
2024. 390(7):589-600 https://doi.org/10.1056/nejmoa2309439
- Lassiter G., et al. Am J
Transplantation.
2023. https://doi.org/10.1016/j.ajt.2023.03.022
- Miura S., et al. Am J
Transplantation.
2023. https://doi.org/10.1016/j.ajt.2023.03.025
- Anand, R.P., et al Nature. 622,
393–401 (2023). https://doi.org/10.1038/s41586-023-06594-4
- Deng R., et al. Mabs. 2011.
https://doi.org/10.4161/mabs.3.1.13799
- Tonix Pharmaceuticals – Data on
File
- Eledon press release. November 2,
2023.
https://ir.eledon.com/news-releases/news-release-details/eledon-reports-updated-data-ongoing-phase-1b-trial-evaluating
(accessed February 2024)
- 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
(accessed February 2024)
- BioSpace. January 18, 2023.
https://www.biospace.com/article/horizon-bags-second-phase-ii-win-in-sjoegren-s-syndrome
(accessed February 2024)
-
https://www.ucb.com/our-science/pipeline (accessed August
2023)
Tonix Pharmaceuticals Holding
Corp.*
Tonix is a biopharmaceutical company focused on
developing, licensing and commercializing therapeutics to treat and
prevent human disease and alleviate suffering. Tonix’s development
portfolio is focused on central nervous system (CNS) disorders.
Tonix’s priority is to submit a New Drug Application (NDA) to the
FDA in the second half of 2024 for Tonmya1, a product candidate for
which two positive Phase 3 studies have been completed for the
management of fibromyalgia. TNX-102 SL is also being developed to
treat acute stress reaction as well as fibromyalgia-type Long
COVID. Tonix’s CNS portfolio includes TNX-1300 (cocaine esterase) a
biologic designed to treat cocaine intoxication with Breakthrough
Therapy designation. Tonix’s immunology development portfolio
consists of 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. Tonix also has product candidates
in development in the areas of rare disease and infectious disease.
Tonix Medicines, our commercial subsidiary, markets Zembrace®
SymTouch® (sumatriptan injection) 3 mg and Tosymra® (sumatriptan
nasal spray) 10 mg for the treatment of acute migraine with or
without aura in adults.
*Tonix’s product development candidates are
investigational new drugs or biologics and have not been approved
for any indication.
1Tonmya™ is conditionally accepted by the U.S.
Food and Drug Administration (FDA) as the tradename for TNX-102 SL
for the management of fibromyalgia. Tonmya has not been approved
for any indication.
Zembrace SymTouch and Tosymra are registered
trademarks of Tonix Medicines. 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
Ben ShannonICR
Westwickeben.shannon@westwicke.com443-213-0495
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