Full Press Release Details
TONIX PHARMACEUTICALS HOLDING CORP 8-K
Tonix Pharmaceuticals and Makana Therapeutics
Announce Collaboration Combining Tonix's Anti-CD40L Monoclonal Antibody (TNX-1500) with Makana's Genetically Engineered Organs
Preclinical and Clinical Xenotransplantation Studies
Agreement includes the use of Tonix's
TNX-1500, as part of an immunomodulatory regimen to reduce rejection of Makana's genetically engineered pig organs in xenotransplantation
Establishes framework for Makana's kidney, heart and islet cell programs to utilize TNX-1500 for preclinical studies in support
of regulatory filings for potential use in human recipients
CHATHAM, N.J. and Miami, Fla., April 9,
2025 (GLOBE NEWSWIRE) - Tonix Pharmaceuticals Holding Corp. (Nasdaq: TNXP), ("Tonix") a fully-integrated biopharmaceutical
company with marketed products and a pipeline of development candidates, and Makana Therapeutics, Inc. ("Makana"), a global
leader in the field of xenotransplantation, today announced a collaborative research agreement under which Tonix and Makana will study
Tonix's anti-CD40L (CD40 ligand, also called CD154) monoclonal antibody candidate, TNX-1500, in combination with Makana's
human-compatible organs and cells for the treatment of organ failure. The preclinical research and development collaboration has the
potential to span multiple Makana programs including kidney, heart and islet cell transplant. The goal of the preclinical studies is
to support the submission of an investigational new drug application (IND) to the U.S. Food and Drug Administration (FDA) to support
compassionate use for patients undergoing xenotransplantation.
"We are excited to partner with Makana
in support of our mutual goal to offer novel solutions for patients requiring organ or cellular transplantation," said Seth Lederman,
M.D., Chief Executive Officer of Tonix. "We believe this strategic agreement is a promising step towards utilizing xenotransplantation
in the clinic. Makana's novel genetically engineered (GE) pigs, which have deleted swine leukocyte antigen (SLA)2, has
shown improved human compatibility and several other advantages over other technologies including high rates of fertility and birthing,
which potentially increases their ability to produce viable organs to satisfy a commercial market globally."
"Despite significant progress and momentum
in the field of xenotransplantation, improving organ compatibility to prevent rejection remains an ongoing challenge," said Joseph
Tector, M.D., Ph.D., Founder of Makana and a practicing transplant surgeon. "This collaboration
provides Makana the opportunity to combine its novel GE pig organs with TNX-1500 in our ongoing and future preclinical studies. We view
anti-CD40L as a critical part of an effective immunomodulatory regimen for successful xenotransplantation. This collaboration enables
us to pursue co-development of our GE organs with the TNX-1500, which has shown best-in-class pharmacokinetics and pharmacodynamics in
a human study after showing best-in-class results in preventing rejection in 6-month studies of allo- and xenotransplantation in animals.
Our mutual goal is to obtain the best human results as soon as possible."
"We are thrilled with this collaboration
utilizing TNX-1500 as an important element of our xenotransplant therapy. The collaboration with Tonix gives Makana the right product
and the right partner to bring Makana toward clinical development," said Mark Platt, President and Chief Executive Officer of Makana.
"Most organ-failure patients today will never receive a lifesaving/life-changing transplant. Our achievement in developing the SLA
DR knockout pig has yielded encouraging results with preclinical kidney xenografts and positions us to deliver strong outcomes in clinical
TNX-1500 is an investigational, humanized
Fc-modified IgG4 anti-CD40L antibody with high affinity for the CD40 ligand. CD40L is an attractive drug development target for transplant
immunomodulation since the engagement of the CD40L plays a pivotal role in immune system activation by modulating both antibody and cellular
About Makana's Genetically Engineered
Makana began developing pigs for xenotransplantation
in 2010. Makana's 2013 creation of the Triple Knockout (TKO) Pig, lacking three key glycans responsible for hyperacute and acute
organ rejection in humans, resulted in the first 1-year preclinical xeno-kidney survivor in animals1. This discovery revitalized
the xeno-field and today Makana's TKO genetics are employed across the xenotransplantation field.
Realizing that the first clinical xenografts
failed because of antibody mediated rejection, Makana deferred rushing to the clinic and employed the same stepwise scientific approach
to show that these early clinical failures occur because of the development of antibodies against SLA. The final result is that Makana
has developed the new TKO plus SLA DR KO pig that eliminates the next barrier to clinical success. Now Makana is poised to achieve longer
term clinical success.
Makana has achieved the field's longest
and most consistent preclinical survival without the need to insert human transgenes into its pig genetics. Rejection continues as a barrier
to survival in the limited number of emergency IND human transplants performed with transgenic pigs, further supporting Makana's
focus on antigen discovery and deletion in lieu of relying on inserted transgenes to evade the human immune response.
Without the need for transgenes, the future
commercialization of Makana's xeno-organs through breeding will be straightforward. When compared to transgenic animals, Makana's
knockout-only pigs will breed with greater efficiency and eliminate the challenge of retaining transgenic expression. This is an important
consideration, reducing both the cost of therapy and the complexity of GE pig production.
Makana's preclinical successes with
SLA-deleted pig kidneys in animal xenotransplantation has depended on the co-administration of primatized 5c8 anti-CD40L monoclonal antibody.
Tonix's TNX-1500 is an Fc-modified version of humanized 5c8, which maintains the activity of 5c8, while improving tolerability.
TNX-1500 (Fc-modified humanized anti-CD40L
mAb) is a humanized monoclonal antibody that binds and functionally inhibits the CD40-ligand (CD40L), also known as CD154 or 5c8 Ag.4
The combining sites of TNX-1500 are derived from humanized 5c8 or ruplizumab, which showed promise in treating systemic lupus erythematosus.5
Chimeric primatized 5c8 showed promise in preventing rejection of organ rejection in animals.6 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. 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 and renal xenografts.7-9
*TNX-1500 is an investigational new biologic and
is not approved for any indication
Tonix Pharmaceuticals Holding Corp.*
Tonix is a fully-integrated biopharmaceutical
company focused on transforming therapies for pain management and vaccines for public health challenges. Tonix's development portfolio
is focused on central nervous system (CNS) disorders. Tonix's priority is to advance TNX-102 SL, a product candidate for the management
of fibromyalgia, for which an NDA was submitted based on two statistically significant Phase 3 studies for the management of fibromyalgia
and for which a PDUFA (Prescription Drug User Fee act) goal date of August 15, 2025 has been assigned for a decision on marketing authorization.
The FDA has also granted Fast Track designation to TNX-102 SL for the management of fibromyalgia. TNX-102 SL is also being developed to
treat acute stress reaction and acute stress disorder under a Physician-Initiated IND at the University of North Carolina in the OASIS
study funded by the U.S. Department of Defense (DoD). Tonix's CNS portfolio includes TNX-1300 (cocaine esterase), a biologic in
Phase 2 development designed to treat cocaine intoxication that has FDA Breakthrough Therapy designation, and its development is supported
by a grant from the U.S. National Institute on Drug Abuse. Tonix's immunology development portfolio consists of biologics to address
organ transplant rejection, autoimmunity and cancer, including TNX-1500, which is an Fc-modified 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 infectious disease, including a vaccine for mpox, TNX-801. Tonix recently announced a contract
with the U.S. DoD's Defense Threat Reduction Agency (DTRA) for up to $34 million over five years to develop TNX-4200, small molecule
broad-spectrum antiviral agents targeting CD45 for the prevention or treatment of infections to improve the medical readiness of military
personnel in biological threat environments. Tonix owns and operates a state-of-the art infectious disease research facility in Frederick,
Md. 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; their efficacy and safety have not been established and have 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.
About Makana Therapeutics
Founded in 2009, Makana Therapeutics is focused
on developing swine with reduced xenoantigen expression, making human transplantation of cells, tissues and organs from these animals
possible. Makana's focus on scientifically validated genetics, optimized pig cloning techniques and careful patient selection is
expected to streamline product development and result in safer more efficacious products. For more information on Makana, please visit
Forward Looking Statements
Certain statements in this press release