The Business
Cancer is the most pervasive and intractable group of diseases known to medicine. Currently in the United States there are more than 1.2 million cases of cancer diagnosed annually, with a death rate of more than 1,500 patients daily. Approximately 8 million Americans are suffering from one form or another of the disease. Over $180 billion is spent annually in the continuing battle against cancer. Today, more than two decades of research on the molecular basis of cancer is finally expected to usher in the era of targeted therapeutics for cancer and a departure from the traditional “slash and burn” approach of surgery and toxic chemotherapy. AACT Inc. (the “Company”) represents an example of this new approach.
AACT has developed several anticancer drugs that incorporate the latest genomic and genetic approaches to drug discovery and development. The Company’s most advanced and innovative compound, AA150030, has shown remarkable anticancer activity in laboratory and animal tests. The key findings from these tests indicate:
- AA150030 has the ability to kill Acute myeloid leukemia (AML) and chronic myelogenous leukemia (CML) cells that harbor a mutation in the FLT3 or BCRABL genes by inducing cell-suicide, or apoptosiswithout causing the typical side-effects of chemotherapy such as nausea, hair loss and weight loss.
- AA150030 enhances the activity of conventional chemotherapy when used in combination. Its ability to synergize with other therapeutics allows the use of lower doses of conventional chemotherapy in combination with AA150030,which drastically reduces the side effects without impairing the safety of the patients.
- Approximately 30% of AML patients harbor a mutation in FLT3 and >90% of CML patients harbor a chromosomal translocation which results in the production of the BCRABL protein by the leukemic cell. These two forms of leukemias constitute a large percentage human leukemias.
- Unlike most other anticancer agents, AA150030 is orally bioavailable allowing a convenient route of administration.
AA150030 has been extensively tested by the Company and independent experts and these studies shows that AA150030 exhibits extraordinary specificity towards FLT3+ and BCRABL+ cells, without affecting normal cells and other tumor cells that do not harbor these mutations. Animal experiments have been successfully performed usingAML cell lines.
A remarkable property of AA150030 is its unique mechanism of action. This drug affects a crucial step in the control of cell division by selectively blocking cancer cells from dividing and causing apoptosis (cell-suicide) in the treated cells. Since normal cells do not harbor mutations in the FLT3 or ABL genes, their viability and growth is unaffected by AA150030, thusproviding an escape mechanism for normal non-cancerous cells and protecting them from any damage. Because the mechanism of action of AA150030 is distinct from cytotoxic drugs such as daunorubicin, cytarabineandTaxolTM, it should be useful for the treatment of drug resistant cancers and for combination chemotherapy.
Although molecular biology has revealed common features in different types of cancers, no currently available drug is applicable to a majority of cancers. Most drugs work best against a single form of cancer, such as Tamoxifenâ for breast cancer. Consequently, most pharmaceutical companies have focused their research to develop drugs to treat specific types of cancer with well identified targets that are specifically mutated or amplified in these cancers. These types collectively account for about 50% of all new cases detected annually. Current data suggests that AA150030specifically targets AML and CML cells which specifically harbor mutant FLT3 or BCRABL genes.
AA150030 is the main thrust of AACT’s current development and commercialization activities. However, AACT is not a one-product company. The Company has developed and licensed, for future efforts, two additional therapeutic products and technologies. They include AA15040,a second generation of RAS mimeticsthat specifically target RAS-mutant cancer cells. Detailed genomic analyses of human tumors has identified that RAS gene family is the most frequently mutated oncogene (occurring in approximately 25-30% of all cancers) and is most often associated with patient death. The lethality associated with RAS activation appears to be due to the fact that RAS proteins interact with more than 50 different signaling molecules in the cell that drive cell proliferation and promotes their activation. Unfortunately, the development of RAS inhibitors has been unsuccessful due to the lack of well-defined pockets and cavities on the RAS surface.
AA150030 is orally bioavailable allowing a convenient route of administration.
To achieve inhibition of multiple signaling pathways activated by RAS, Dr. Reddy’s laboratory has undertaken a novel approach that exploits the observation that RAS bindsto these cellular proteins via a protein domain called the RAS-binding domain (RBD). Since all RAS-interacting proteins (called RAS-effector proteins), share this RAS-binding domain, they undertook a novel strategy of developing compounds that bind to RBDs of RAS-binding proteins with the hope that they could identify a molecule that could prevent the binding of RAS to its effectors. This effort led to the discovery of rigosertib (RGS) which binds to RBDs of multiple RAS effectors and blocks their interaction with RAS, thereby shutting down RAS function in tumor cells. Rigosertib is currently in clinical trials for the treatment of RAS-mutant cancers. Since the therapeutic activity of Rigosertib requires large and continuous infusion of the drug, Dr. Reddy’s lab undertook the task of developing second generation RAS mimetics that have greater potency in eliminating the growth of RAS-mutant cancers. This effort has led to the identification of a molecule, AA15040, that is approximately 10-100 fold more active than Rigosertib suggesting that RAS mimetics that are more potent than Rigosertib can be made.
In addition, AACT is in the process of developing AA108600, a kinase inhibitor which targets Cancer Stem Cells which have been shown to contribute to the lethality of Triple Negative Breast cancers and hormone-resistant prostate cancers. Preclinical studies have shown that AA108600 is lethal to Cancer Stem Cells that constitute a significant population of Triple Negative Breast Cancers (TNBC) and contribute to their metastatic and lethal properties. Dr. Reddy’s pre-clinical studies have shown that AA108600 inhibits the growth of TNBCs, overcomes chemotherapy resistance and in combination with paclitaxel eliminates the growth of metastatic lesions. As there is no approved therapy for TNBCs, AA108600 addresses an important unmet clinical need.
Following the advent of COVID-19, several studies have shown that SARS-Co-V-2 recruits the cooperation of a multitude of cellular proteins for its replication and pathogenesis. An important family of proteins required for the replication of SARS-Co-V-2 are the family of cellular kniases. Taking advantage of the possession of kinase inhibitor compound library, we screened this compound library for inhibitors of SARS-Co-V-2 replication. Our preliminary studies show that two compounds, AA108600 and AA108110 were potent inhibitors of SARS-Co-V-2 replication suggesting that these two compounds may find application in the treatment viral infections. Since these compounds act by inhibiting cellular proteins which are required for viral replication, mutations in the viral genome do not affect their ability to inhibit viral replication.
Dr. E. Premkumar Reddy, Ph.D., the principle founder of the Company and developer of AA150030, is a professor and director of Experimental Cancer Therapeutics at Icahn School of Medicine at Mount Sinai, New York. Before joining Mount Sinai, he served as the Director of the Fels Institute for Cancer Research and Molecular Biology (an affiliate of Temple University, Philadelphia). He has made seminal discoveries in the molecular biology of oncogenes and mechanism of action of protooncogenes, is the co-inventor of the most successful commercial diagnostic test for AIDS, and is the co-founder and editor of the premier journal of molecular biology, Oncogene. The Company is assisted by its SAB (Scientific Advisory Board), with experience in the areas of drug development and clinical trials.
AACT, a closely held Delaware corporation, was founded in 2018. Approximately $4 million have been invested in the development of AA150030, 108600 and the second generation RAS mimetics. Approximately one-fourth of this money came from the founders and four outsiders, and the rest from federal and non-federal grants. However, by virtue of its relationship with Fels and Mount Sinai, the actual total investment is appreciably higher. AACT’s primary source of technology is derived from research conducted at the Fels Institute and Mount Sinai School of Medicine or by contract laboratories. The Company owns the results of these activities or exclusively licenses them from Temple University and Mount Sinai School of Medicine (which will receive small royalties).
AACT now seeks to place up to $5M in Series B Convertible Preferred Stock (the “Financing”), which will be convertible into the Company’s common stock. The application of proceeds is described in the Financial Section.
Dr. E. Premkumar Reddy, Ph.D., the principle founder of the Company and developer of AA150030, is a professor and director of Experimental Cancer Therapeutics at Icahn School of Medicine at Mount Sinai, New York. Before joining Mount Sinai, he served as the Director of the Fels Institute for Cancer Research and Molecular Biology (an affiliate of Temple University, Philadelphia). He has made seminal discoveries in the molecular biology of oncogenes and mechanism of action of protooncogenes, is the co-inventor of the most successful commercial diagnostic test for AIDS, and is the co-founder and editor of the premier journal of molecular biology, Oncogene. The Company is assisted by its SAB (Scientific Advisory Board), with experience in the areas of drug development and clinical trials.
AACT, a closely held Delaware corporation, was founded in 2018. Approximately $4 million have been invested in the development of AA150030, 108600 and the second generation RAS mimetics. Approximately one-fourth of this money came from the founders and four outsiders, and the rest from federal and non-federal grants. However, by virtue of its relationship with Fels and Mount Sinai, the actual total investment is appreciably higher. AACT’s primary source of technology is derived from research conducted at the Fels Institute and Mount Sinai School of Medicine or by contract laboratories. The Company owns the results of these activities or exclusively licenses them from Temple University and Mount Sinai School of Medicine (which will receive small royalties).
AACT now seeks to place up to $5M in Series B Convertible Preferred Stock (the “Financing”), which will be convertible into the Company’s common stock. The application of proceeds is described in the Financial Section.