Our Technology
Overview
Short Chain Fatty Acid Derivative Therapeutics
Our founders discovered that short chain fatty acids possessed a variety of important biological effects that could be of therapeutic benefit in treating patients with a range of hematological disorders. They first discovered that short chain fatty acids, such as butyric acid, could be used to stimulate the synthesis of healthy fetal hemoglobin, which reversed the adverse effects of abnormal and deficient hemoglobin synthesis in the two most common hemoglobin diseases (hemoglobinopathies), sickle cell anemia and beta thalassemia, respectively. Further clinical studies demonstrated that patients with these two diseases, who were treated with intravenous infusions of arginine butyrate, showed significant and sustained increases in hemoglobin and red blood cell (RBC) levels that resulted in clinical improvement. However, butyrate therapy required intravenous infusions of large doses to achieve therapeutic effects making it impractical for widespread clinical application. In addition, butyrate was found to suppress, rather than stimulate, RBC production, limiting its usefulness to treat hemoglobinopathies and other kinds of anemias (e.g., secondary to cancer, kidney disease, HIV, autoimmune diseases, aging). Despite the limitations, proprietary regimens of butyrate were discovered that corrected anemia enough to make some patients with thalassemia free of their previous need for transfusions and significantly helped some previously seriously ill sickle cell patients.
Our Founders used a proprietary screening system to identify derivatives of short chain fatty acids (SCFADs) with increased potency, improved therapeutic effects and more favorable pharmacological properties compared to butyric acid. This led to the discovery of a series of compounds that not only induced hemoglobin F induction, but also stimulated the production of a variety of blood cells. These compounds appear to stimulate blood cell production through similar pathways to recombinant proteins, such as G-CSF (Neupogen, Neulasta) and erythropoietin (Epogen, Procrit). However, in contrast to these agents, the compounds can be orally-administered and thus should provide a significant advantage over the current recombinant proteins, which require injections. The first compound, HQK-1001 has now entered clinical development with an initial focus on treating sickle cell anemia and thalassemia. This and other compounds in development may also prove useful in treating other more common types of anemia associated with the elderly, HIV, cancer, kidney disease and other chronic illnesses.
Treatment for Virus-Associated Cancer
A large proportion of human cancers have been found to be associated with viruses, including human papilloma virus, Epstein-Barr virus, human immunodeficiency virus and hepatitis viruses. One of our Founders, Douglas Faller, Ph.D., M.D., discovered that it was possible to reactivate the expression of certain viral proteins that enabled the targeting and destruction of infected tumor cells, while sparing healthy cells. This discovery is backed by a series of patents that broadly cover the use of any agent to induce viral expression, followed by any second anti-viral agent used to treat cancer or other proliferative disorders.
The therapeutic potential of this approach was recently documented in a clinical trial in patients with advanced forms of Epstein-Barr viral associated lymphomas, who had failed treatment. Patients were treated with arginine butyrate, which induced the expression of the virus in the virally infected cells to express the viral enzyme, thymidine kinase. The patients were then treated with the anti-viral drug, ganciclovir, which is activated by this enzyme, and results in the destruction of virally-infected cells. As recently reported in the journal Blood, 10 out of 15 patients in this study showed a tumor response with several patients achieving complete remissions after failing numerous other therapies. The Company intends to continue to support Dr. Faller's work with the goal of partnering this technology to a biopharmaceutical company to continue the development of this promising new treatment approach for viral-associated cancers.
Pipeline - HQK-1001
The discovery of HQK-1001 originated from earlier studies by HemaQuest's Founders that derivatives of natural short chain fatty acids had increased potency, improved therapeutic effects and more favorable pharmacological properties compared to natural fatty acids, such as butyric acid. This led to the discovery of the short chain fatty acid derivative (SCFAD), known as HQK-1001, which is HemaQuest's first drug candidate and has many attractive attributes for drug development:
- Orally administered: High oral bioavailability (70-90%)
- Excellent pharmacokinetics: Once-a-day dosing
- Potent therapeutic effects: Effective in treating anemia in primates and rodents
- Strong safety record: Excellent therapeutic margins in safety studies
- Two-step inexpensive synthesis: Scaled for GMP manufacturing
In addition, studies in the laboratory in patients with anemia as well as in vivo studies in normal and anemic rodents and non-human primates demonstrated that HQK-1001:
- Induces fetal hemoglobin synthesis
- Prolongs survival of RBCs
- Potently stimulates production of RBCs (erythropoiesis) in a variety of human patients' cultures and in animal models
Therefore, HQK-1001 could prove useful in treating hemoglobinopathies, because the therapeutic effects listed above correct the major hemoglobin and RBC abnormalities that cause these diseases. In addition, HQK-1001's potent erythropoietic effects along with its oral activity make it an attractive alternative to erythropoietin and its derivatives, which are used to treat other kinds of anemia caused by kidney disease, cancer, HIV and autoimmune diseases.
HemaQuest plans to primarily focus its resources on developing HQK-1001 to treat hemoglobinopathies, because these diseases qualify for:
- Accelerated Approval, which provides a more rapid route to FDA approval for drugs used to treat illnesses with an unmet medical need.
- Orphan Drug Status designation, which provides seven years of market exclusivity and certain tax benefits for developing drugs to treat diseases affecting less than 200,000 patients in the U.S.
In December 2007, the FDA accepted the Company's IND for HQK-1001 for treating hemoglobinopathies. A Phase I clinical trial began in January 2008 testing the safety and pharmacokinetics of HQK-1001 in healthy volunteers. In addition, HQK-1001 may prove useful in treating more common types of anemia associated with aging, cancer, HIV, kidney disease and other illnesses.
Additional Drug Candidates
HemaQuest is also evaluating several additional SCFADs to treat a variety of hematological disorders characterized by deficiencies in hemoglobin or blood cells. Several of these compounds have shown therapeutic activities in stimulating RBC as well as white blood cell production in both the laboratory as well as animal models. These could prove useful to treat not only hemoglobinopathies and anemia, but also neutropenia, which is a decrease in neutrophils, the infection-fighting white blood cells. Commonly associated with cancer chemotherapy, neutropenia is a leading cause of infections in cancer patients. HemaQuest has preliminary data suggesting some of its SCFADs may be effective in treating this clinical condition. The Company is currently evaluating several drug candidates and expects to initiate development of one of these SCFADs within the next year