LIXTE Product Pipeline

Pipeline Overview

LIXTE has developed two series of pharmacologically active drugs, the LB-100 series that inhibit serine/threonine phosphatases and the LB-200 series that inhibit histone deacetylases.

Our current focus is on the LB-100 series of which LB-100 is the lead clinical candidate. LB-100 exerts its activity by a novel mechanism and is the first of its type to be evaluated so broadly in multiple animal models of cancer and now in human beings. Serine/threonine phosphatases are ubiquitous enzymes that regulate many cell signaling networks important to cell growth, division and death. They have long been appreciated as potentially important targets for anti-cancer drugs. However, because of the multi- functionality of these enzymes, it had been widely held that pharmacologic inhibitors of these phosphatases would be too toxic to allow their development as anti-cancer treatments. We have shown that this is not the case. In a Phase 1 trial, LB-100 was well-tolerated at doses associated with objective regression (significant tumor shrinkage) and/or the arresting of tumor progression in patients with progressive cancers.

Lead Product Candidate: LB-100

Pre-clinical studies showed that LB-100 alone inhibits a spectrum of human cancers but when combined with standard cytotoxic drugs and/or radiation, LB-100 potentiates their effectiveness against hematologic and solid tumor cancers without enhancing toxicity. In addition, given at very low doses in animal models of cancer, LB-100 markedly increased the effectiveness of a PD-1 blocker, one of the widely used new immunotherapy drugs.

In the Phase 1 trial of LB-100, it was well tolerated at doses associated with antitumor activity. Responses included objective regression (tumor shrinkage) lasting for 11 months of a pancreatic cancer and cessation of growth (stabilization of disease) for 4 months or more of 9 other progressive solid tumors out of 20 patients who had measurable disease. As Phase 1 clinical trials are fundamentally designed to determine safety of a new compound in humans, we were encouraged by these results. The next step is to demonstrate in Phase 2 clinical trials the efficacy of LB-100 in one or more specific tumor types, against which the compound has well documented activity in pre-clinical models.

Current Studies of LB-100

Myelodysplastic (MDS) Syndromes is a group of cancers in which immature blood cells in the bone marrow do not mature or become healthy blood cells. PP2A inhibition enhances apoptosis (a form of programmed cell death) of MDS cells.

In November 2018, we received approval from the U.S. Food and Drug Administration (FDA) for our Investigational New Drug Application (IND) to conduct a Phase 1b/2 clinical trial to evaluate the therapeutic benefit of LB-100 in patients with low and intermediate-1 risk Myelodysplastic Syndrome (MDS) who have failed or are intolerant of standard treatment. The study is being conducted at the Moffitt NCI-designated Comprehensive Cancer Center, Tampa, FL.

Patients with MDS, although usually older, are generally well except for severe anemia requiring frequent blood transfusions. Our Phase 1b/2 clinical trial utilizes LB-100 as a single agent in the treatment of patients with low and intermediate-1 risk MDS, including patients with del(5q) myelodysplastic syndrome (del5qMDS) failing first line therapy (NCTO3886662). The bone marrow cells of patients with del5qMDS are deficient in PP2A by virtue of an acquired mutation and are especially vulnerable to further inhibition of PP2A by LB-100.

Advanced Soft Tissue Sarcomas (ASTS) are cancers that begin in the muscle, fat, fibrous tissue, blood vessels, or other supporting tissue of the body. The chemotherapy medication Doxorubicin is enhanced by LB-100.

In July 2019, we entered into a collaboration agreement for an Investigator-Initiated Clinical Trial with the Spanish Sarcoma Group (Grupo Español de Investigación en Sarcomas, or GEIS), Madrid, Spain, to carry out a clinical trial to obtain information about the efficacy and safety of LB-100 combined with doxorubicin in soft tissue sarcomas. Doxorubicin is the global standard for initial treatment of advanced soft tissue sarcomas (ASTS), a very aggressive disease. Doxorubicin alone has been the mainstay of first line treatment of ASTS for over 40 years, with little therapeutic gain from adding cytotoxic compounds to or substituting other cytotoxic compounds for doxorubicin. In animal models, LB-100 consistently enhances the anti-tumor activity of doxorubicin without apparent increases in toxicity.

GEIS has a network of referral centers in Spain and across Europe that have an impressive track record of efficiently conducting innovative studies in ASTS. We agreed to provide GEIS with a supply of LB-100 to be utilized in the conduct of this clinical trial, as well as to provide funding for the clinical trial. A positive study would have the potential to change the standard therapy for this disease after the medical industry’s four decades of failure to improve the marginal benefit of doxorubicin alone.

Small Cell Lung Cancer (SCLC) is the most aggressive lung cancer comprising 15% of the total number of cases in the world. A Phase 1b clinical trial will assess the combination of LB-100 with a standard regimen for untreated, extensive stage-disease small cell lung cancer (ED-SCLC).

In 2021, we initiated a Phase 1b clinical trial (NCT04560972) with world-renowned independent cancer research and treatment center City of Hope in previously untreated extensive stage SCLC patients to evaluate the effectiveness of a standard regimen of carboplatin/etoposide/atezolizumab with and without LB-100. The median survival of patients with this especially aggressive type of lung cancer, even with “best” therapy, is just over 12 months. The rationale for adding LB-100 to current standard treatment is that in preclinical studies the malignant cells of this uniformly fatal cancer are genetically sensitive to PP2A inhibition by a process termed synthetic lethality and the effectiveness of both carboplatin and etoposide is enhanced by LB-100.

Because of the rapid progression of small cell lung cancer, therapeutic benefit of adding LB-100 to standard treatment may be seen early on even in this Phase 1b clinical trial, generating enthusiasm by both clinicians and large pharmaceutical companies.

Glioblastoma Multiforme (GBM) is the most aggressive type of cancer that begins within the brain. Radiation and temozolomide (a medication used to treat some brain tumors including GBM) are enhanced by LB-100.

During the fourth quarter of 2019, the National Cancer Institute, or NCI, enrolled the first two patients of a planned eight patient pharmacologic study of the ability of LB-100 to enter the brain and penetrate recurrent brain tumors in patients where surgical removal of the cancers is indicated. This study (clinical trials registry NCT03027388) is being conducted and funded by the NCI under a cooperative research and development agreement (CRADA) with us; additional information will be reported by us as it is provided by the NCI.

Primary malignant brain tumors (gliomas) are very challenging to treat. Radiation combined with the chemotherapeutic drug temozolomide has been the mainstay of therapy of the most aggressive gliomas (glioblastoma multiforme or GBM) for decades, with some further benefit gained by the addition of one or more anti-cancer drugs, but without major advances in overall survival for the majority of patients. In animal models of GBM, LB-100 enhances the effectiveness of radiation, temozolomide chemotherapy treatments, and immunotherapy, indicating that LB-100 may improve outcomes of standard GBM treatment in the clinic. Although LB-100 has proven safe in patients at doses associated with apparent anti-tumor activity against several human cancers arising outside the brain, the ability of LB-100 to penetrate tumor tissue arising in the brain is not known. Unfortunately, many drugs potentially useful for GBM treatment do not enter the brain in amounts necessary for anti-cancer action.

The NCI study is designed to determine the extent to which LB-100 enters recurrent malignant gliomas. Patients having surgery to remove one or more tumors receive one dose of LB-100 prior to surgery. The patients have blood and tumor tissue analyzed to determine the amount of LB-100 present and to determine whether the cells in the tumors show the biochemical changes expected to be present if LB-100 reaches its molecular target. The goal is to obtain data in up to eight patients. As a result of the innovative design of the NCI study, data from so few patients should be sufficient to provide a sound rationale for conducting a clinical trial to determine the effectiveness of adding LB-100 to the standard treatment regimen for GBMs.

Future Clinical Trials

Given the extensive preclinical data supporting the hypothesis that LB-100 will potentiate the current most effective regimens for a number of additional cancers there are additional clinical trials we would to like to pursue when funding allows:

(1) A clinical trial in patients adding LB-100 to PD-1 inhibitors against one of several cancers in which PD-1 inhibitors alone have definite but modest activity. While the success of immunoblockers in cancer treatment is a major advance in cancer treatment, many patients do not have respond. Low doses of LB-100 have been shown to enhance the effectiveness of PD-1 blockade in mouse models of several different tumor types.

(2) A clinical trial to determine if, as shown in several animal models, LB-100 enhances the effectiveness of radiation therapy without enhancing toxicity. Even a modest improvement in the efficacy of radiation therapy allowing a reduction of in the number or dose radiation treatments required for cancer therapy in general would be a major benefit to patients and to the cost of treatment.


We have also developed another class of compounds that are novel histone deacetylase inhibitors (HDACi). Designated as our LB-200 series of compounds, these have potential use in the prevention and treatment of neurodegenerative diseases. The series has the potential to be the most effective in its class and may be useful for the treatment of chronic hereditary diseases, such as Gaucher’s disease, in addition to cancer and neurodegenerative diseases. LB-200 has not yet advanced to the clinical stage and would require additional capital to fund further development. Accordingly, because of our focus on the clinical development of LB-100 and analogs for cancer therapy, we have decided not to actively pursue the pre-clinical development of the LB-200 series of compounds at this time.