PrimoCure Pharma’s KoDiscovery Anticancer Therapeutics - KAT 3-BP
PrimoCure Pharma has overcome the many challenges related to harnessing 3-BP as an anticancer therapy and has developed its KAT 3-BP solution.
KAT 3-BP is a patented formulation of 3-BP, that when combined with its proprietary administration protocols, has shown very promising preclinical results for treating pancreatic cancer with the potential of reducing tumor size and the metastatic spread of cancer cells.
How It Works
The KAT 3-BP formulation is administered to the patient and is carried to the cancer cells.
Within the cancer cells are mono-carboxylate transporters (MCTs), which are overexpressed in many cancer cells. These MCTs transport the KAT 3-BP formulation across the membrane of the cancer cell and into its nucleus.
Once KAT 3-BP penetrates the cancer cell's membrane and nucleus the formulation triggers multiple irreversible reactions with different cysteine residues of proteins, leading to loss of tertiary structure and function which causes the death of the cancer cell.
Specifically, KAT 3-BP irreversibly alkylates the glycolytic enzyme, Hexokinase II (HK2), resulting in the disruption of glucose metabolism leading to cancer cell death.
Advantages of KAT 3-BP
Due to its small molecular and chemical structure, the mechanism of action is well understood as evidenced by third parties studies.
Due to KAT’s mechanism of action, it can potentially target up to 95% of solid and liquid cancer types.
Multiple studies have demonstrated that KAT 3-BP can preferentially and effectively kill cancer stem cells, which can reduce, and possibly prevent the metastatic spread of existing cancers.
It is not only a metabolism-based therapy but is also an immunotherapy which can activate and help white blood cells to enhance immunological responses.
The method of entry into the cell minimizes cytotoxicity to normal cells and can be used in vivo.
It can be combined with existing standard-of-care therapies such as surgeries, immunotherapies, radiotherapies, and chemotherapies.
It is non-mutagenic
It does not induce drug resistance as 3BP is not a substrate for multidrug resistance (MDR) proteins
It can be effectively delivered through multiple routes of administration according to the cancer type and individual patient need.
It can be combined with alternative therapies such as oxygen therapy, heat therapy, traditional acupuncture and others.
To understand the full scope and potential of PrimoCure Pharma, Inc., as well as the vast potential for KAT 3-BP as a therapeutic drug for pancreatic and the majority of other cancers, it is necessary to take a step back to understand the roots of our heritage. First and foremost, PrimoCure Pharma is the sister closed corporation to Dr. Ko's first company, KoDiscovery, LLC, which was established as her research laboratory. Her groundbreaking discovery in 2000 of the unmatched potential 3-BP to rapidly kill cancer cells was followed by years of her painstaking research and development to carefully determine the optimum formulation, dosage, protocols and routes of administration that are safe and effective for human and animal use. Additionally, she has now successfully received numerous worldwide patents for KAT 3-BP to treat multiple cancers using multiple routes of administration, to potentially treat up to 95% of all cancers.
Below you may follow brief summaries of Dr. Ko's progress from her preclinical studies, animal and human case studies, the start of her first clinical trial and current plans through PrimoCure Pharma. You will also have access to many published studies validating her research and discoveries. Through this progression you will come to more fully understand the strengths of Dr. Ko's KAT 3-BP formulation and the vast potential it promises for the treatment of the majority of cancers across the globe.
KAT 3-BP DEVELOPMENT
First Preclinical Study
Dr. Ko's first preclinical study was more successful than anyone could have imagined. This mouse model seeded 34 mice with hepatocellular carcinoma with 19 mice treated with 3-BP and 15 untreated mice serving as controls. All 19 treated mice were completely cured and lived out a normal lifespan, while all 15 controls had to be euthanized.
Second Preclinical Study
Though the second preclinical study does not appear to be as dramatic or spectacular as the first, that understanding is far from true. In many ways, Dr. Ko feels that the significance of the second study was critical for her to validate the safety and potential toxicology of KAT 3-BP ultimately for human use.
Third Preclinical Study
This preclinical study was in partnership with the University of Maryland in 2018 and tested KAT’s effectiveness in conjunction with Radiation Therapy. These results have been particularly exciting, as it was designed to explore the effect of KAT 3-BP on tumor growth in non-small cell lung cancer.
Fourth Preclinical Study
3-Bromopyruvate Inhibits Pancreatic Tumor Growth by Stalling Glycolysis
and Dismantling Mitochondria in a Syngeneic Mouse Model
American Journal of Cancer Research Volume 12, Number 11:4879-5350; 2022
This study was completed as a collaborative project with the Radiation Oncology Research Department at the University of Maryland School of Medicine. For the last five years, the University of Maryland has been an important partner with Dr. Ko to provide independent confirmation of her work validating the efficacy of KAT 3-BP. A University of Maryland future study is currently in the planning stages, which will seek to determine the impact of a longer KAT 3-BP protocol on cancer stem cells and the metastatic spread of pancreatic cancer.
Highlights and key points from the Study Abstract
Pancreatic cancer (PC) is the fourth-most-deadly cancer in the United States with a 5-year survival rate of only 8%. The majority of patients with locally advanced pancreatic cancer undergo chemotherapy and/or radiation therapy (RT).
3-Bromopyruvate (3-BP) is a promising anticancer drug against pancreatic cancer. It exerts potent anticancer effects by inhibiting hexokinase II enzyme (HK2) of the glycolytic pathway in cancer cells while not affecting the normal cells.
KAT 3-BP killed 95% of Panc-2 cells... and severely inhibited ATP production by disrupting the interaction between HK2 and mitochondrial Voltage Dependent Anion Channel-1 (VDAC1) protein.
Electron microscopy data revealed that 3-BP severely damaged the mitochondrial membrane in cancer cells.
Immunohistochemistry data showed complete inhibition of hexokinase II (HK2) and TGFβ, in animals treated with 3-BP drug.
We also observed enhanced expression of active caspase-3 in tumor tissues exhibiting apoptotic death.
Importantly, we also observed inhibition in lactic acid production responsible for tumor aggression.
These results provide new evidence that 3-BP severely inhibits glucose metabolism in cancer cells by blocking hexokinase II, and disrupting mitochondria by suppressing BCL2L1 in pancreatic cancer.
First Human to Receive KAT 3-BP
This photograph of the first recipient of 3BP for cancer, Yvar Verhoeven, in this Case Report was poised with the novel anticancer agent, 3-bromopyruvate (3-BP) and his favorite legendary immortal bird, phoenix. The picture was taken on his 18th birthday, September 09, 2009, at his home in the Netherlands, after his 7th treatment with 3BP. This was a very special day as he had been told that he would never make it to his 17th birthday.
Hepatocellular Carcinoma - First KAT Clinical Trial
Embarking on its first success developing innovative anticancer therapeutics, in 2013, PrimoCure Pharma, Inc. received an FDA Orphan Drug Designation for KoDiscovery Anticancer Technology (KAT) to treat hepatocellular carcinoma. Moving forward from there, in May of 2019, assigning rights through its sister company, KoDiscovery LLC, closed a Licensing Agreement with NewG Lab Pharma, Inc. (NGLP) for the development and commercialization of KAT 3-BP for hepatocellular carcinoma. In the fourth quarter of 2021, NewG Lab Pharma received an FDA Investigational New Drug approval to begin a unique phase I/ II(a) clinical trial for hepatocellular carcinoma. This clinical trial will consist of three treatment arms with each group receiving an appropriate therapeutic dose of KAT 3-BP administered via oral, intratumoral, or oral & intratumoral combined. The phase I clinical trial was initiated in the last quarter of 2022 in South Korea with phase II projected to begin in the U.S. in 2023 or 2024.
We will provide updates on the status of the hepatocellular carcinoma clinical trial as we are given authorization, so please connect with us through our email list or Contact Page.
Breakthrough Study 3-Bromopyruvate Anti-cancer Agent
Glucose Catabolism in Rat Liver Tumors
Targeting Cancer Cell's Power Plants with 3BP