ExCITE Awarded Technologies
The University of Louisville ExCITE Program is an NIH REACH Hub designed to turn biomedical innovations into commercial products that improve patient care and enhance human health. Each awarded technology has been through a competitive and stringent review by representatives from the pharmaceutical industry, NIH, FDA, CMS and USPTO. Awardees receive a grant of up to $200,000 for commercialization purposes while also receiving focused mentorship, training and access to the NIH REACH network.
Development of A Small Molecule Inhibitor Of PFKFB4 for Cancer Treatment
Category: Small Molecule
Disease: Lung Cancer
PI: Sucheta Telang
Technology Summary: Many cancers, especially lung cancers, have a high rate of sugar metabolism (glycolysis) compared to normal tissues. Studies at the University of Louisville (UofL) have determined that inhibition of PFKFB4, a key enzyme in glycolysis that is abundant in cancer cells, can decrease the metabolism and growth of tumors. Recently, UofL researchers used structure-based, virtual computational screening to identify a first-in-class, small molecule PFKFB4 inhibitor, named 5-MPN. This molecule inhibits the activity of recombinant human PFKFB4, decreases the steady-state concentration of the product of PFKFB4, and decreases glycolytic flux. Subsequent rounds of medicinal chemistry have produced improved inhibitors with high potency and low toxicity.
Cancer-Targeted Contrast Agent for MRI and CT Imaging
PI: Mohammad Tariq Malik
Technology Summary: Researchers at the University of Louisville have developed SpheraHance, an injectable cancer-targeted contrast agent that can be used for both CT and MRI scans.SpheraHance contains gold nanospheres (for CT contrast) coated with chelated gadolinium (for MRI contrast) and a universal cancer-targeting aptamer. Proof-of-concept data indicate that aptamer-linked nanospheres become concentrated in tumors while being cleared from normal tissues following intravenous injection in animal models. Importantly, SpheraHance is expected to have an excellent safety profile because its individual components have already been shown to be safe in humans.
Anti-Cancer Drug Targeting RAS
PI: Geoffrey Clark
Technology Summary: Ras is an important target for cancer therapeutics; however, previous attempts to inhibit Ras activity directly or through its effectors PI3K or Raf have had limited success.Researchers at the University of Louisville have developed C4, which specifically targets RalGDS, the third and possibly most important of the Ras-driven transformation pathways. C4 is a first-in-class inhibitor with nM activity, high specificity, and low toxicity. In vivo studies have demonstrated that C4 suppresses metastasis of Ras-driven cancer cell lines.Several novel compounds from an initial round of medicinal chemistry optimization show promising activity.
Next Generation Local Anesthetic Agent
Category: Small Molecule
PI: Jeffrey C Petruska
Technology Summary: Researchers at the University of Louisville have discovered a new application for an existing FDA-approved agent as a local anesthetic. Unlike currently available local anesthetics, which have significant limitations such as toxicity and temporary loss of motor function, this drug is not structurally related to cocaine. This may offer unique advantages for patients who may be resistant or allergic to existing drugs, and for use where cocaine-derived drugs cannot be used, such as for long-term corneal application. Moreover, this anesthetic may preferentially block sensory functions while partially-sparing associated motor function.
Intellectual Property: Provisional Application 62/251,162
Dry-Formulated Plant-Produced Cholera Toxin B Subunit
Disease: Ulcerative Colitis
PI: Krystal Hamorsky
Technology Summary: Researchers at the University of Louisville have discovered that oral administration of plant-made modified cholera toxin B subunit (CTBp) mitigates ulcerative colitis (UC) in a mouse model by facilitating mucosal wound healing via upregulation of TGFβ signaling pathways.These researchers are developing dry-formulated CTBp to be a novel, safe, and effective UC treatment.The attributes of this therapeutic will include effortless formulation for targeted delivery, ease of administration and higher patient acceptance, which will help assure higher treatment compliance in chronic therapy scenarios.
Intellectual Property: U.S. Patent Application Ser. No. 14/005,388, PCT/Us2016/40041
A Plasma microRNA Assay for Detecting Colorectal Neoplasm Diagnosis
Disease: Colorectal Cancer
PI: Susan Galandiuk
Technology Summary: In the US, approximately 140,000 patients are diagnosed annually with colorectal cancer (CRC), with approximately 51,000 CRC deaths annually. Many deaths could be prevented if precancerous polyps were detected with screening and removed prior to development of invasive cancer. Researchers at the University of Louisville are developing a minimally invasive method for early diagnosis with high sensitivity and specificity that may greatly improve early clinical diagnosis and patient compliance. The method consists of a point-of-care platform based on magnetic micro-bead extraction and electrochemical detection of a clinically-proven panel of plasma miRNAs capable of distinguishing between patients with and without colorectal cancer with high sensitivity and specificity. The team developing the project includes a colorectal surgeon, bioengineer, and biostatistician.
Intellectual Property: U.S. Non-Provisional Patent Application #15/062,419
Immunotherapeutic Agent for the Treatment of Cancer
Category: Biologic Drug
Disease: Advanced Melanoma
PI: Kavitha Yaddanapudi
Technology Summary: Malignant melanoma is a deadly form of skin cancer and current estimates are that 1 in 5 Americans will develop skin cancer in their lifetime. The five year survival rate for those diagnosed with stage IV metastatic disease has historically been 5-10%. While Immune checkpoint inhibitors (ICI) have revolutionized the treatment of unresectable late stage melanoma. Still, there remains an urgent need for new strategies because not all patients respond to ICIs, and resistance can occur in those who do. Overproduction of adenosine has been implicated as a causal factor in ICI resistance. This project will assess the efficacy of a cancer immunotherapy involving injection of adenosine deaminase (ADA), an enzyme that inactivates adenosine, directly into tumors.
Intellectual Property: U.S. Provisional Patent Application # 62/306,946,
Development 0f A Mutated Human Parvovirus B19 Vaccine
Disease: Parvovirus B19
PI: Alfred Bennett Jenson
Technology Summary: Human parvovirus B19 (B19) is a small DNA virus that infects rapidly dividing red blood cell (RBC) precursors, and is highly contagious. In healthy children, B19 infection causes unpleasant but rarely serious symptoms including fever, headache, and a “slapped cheek” rash that spreads to the trunk and extremities. However, in children or adults who have hereditary and acquired anemias, B19 is a very common cause of life-threatening aplastic crisis. These B19-associated life-threatening events could be almost completely prevented if a B19 parvovirus vaccine were available. Recently, two human clinical trials with conventional B19 vaccines consisting of virus like particles (VLPs) were discontinued due to adverse side effects and low responses. Dr. Jenson, who was part of the group that brought the world’s first successful cancer vaccine (Gardasil) to market, along with his team, have identified the likely cause of these previous shortcomings and developed a new approach with mutated VLPs. This approach is expected to not only avoid any adverse effects but also increase immunogenicity, thereby enabling development of a safe, efficacious B19 vaccine.
Non-invasive real-time assessment of coronary stenosis using RBC AGE
Category: Diagnostic Software
Disease: Coronary Artery Disease
PI: Eric Berson
Technology Summary: One million invasive coronary angiography (ICA) procedures are performed every year in patients who present with chest pain or are known to have stable coronary artery disease (CAD). The cardiologist performing the procedure determines the significance of the stenosis (blockage) by either “eyeballing” it, or by in by invasively measuring fractional flow reserve (i-FFR). While i-FFR is the Gold Standard test that has been demonstrated to improve outcomes and diminish the cost of healthcare, it is only performed in 10-20% of patients because it is invasive, expensive, time-consuming and requires additional radiation and contrast exposure. Dr. Eric Berson and his team are developing a non-invasive technique for quantifying the stenosis in real-time. This product uses Computational Fluid Dynamics (CFD) to model coronary blood flow across stenotic coronary lesions and assess the degree of stenosis severity. Successful development of this method would lead to benefits of i-FFR measurement in terms of cost savings and improvement in patient outcomes, while simultaneously avoiding the disadvantages such as extra cost for the procedure and time burden.
Development of Carbapenemase Detection Test
Category: Diagnostic Device
Disease: Antibiotic Resistance
PI: Gina K. Thomson
Technology Summary: Superbugs are antibiotic-resistant bacteria described by the CDC as causing mortality comparable to Ebola. Unlike most bacterial infections, superbug infections typically require at least two different active antibiotics to prevent the emergence and transmission of total antibiotic resistance and resulting death of the patient. The rapid and accurate detection of these superbugs is critical, as physicians may only have one chance to successfully treat the infection. Dr. Thomson and her team have developed a test that can rapidly detect gram-negative superbugs. The test works by detecting Carbapenemase, an enzyme produced by the majority of dangerous superbugs. Current tests for Carbapenemase on the market typically require overnight incubation while this solution is projected to produce results within 1-30 minutes. The test is miniaturized, suitable for automation, inexpensive, and more accurate than currently available tests.
Avaren-Fc Lectibody for liver graft protection against hepatitis C virus infection
Disease: Hepatitis C
PI: Nobuyuki Matoba
Technology Summary: This project aims to develop a new biologic drug for liver transplant recipients with chronic hepatitis C virus (HCV) infection. HCV poses a major health problem, with 3 to 6 million individuals infected in the USA and more than 180 million worldwide. HCV infection often leads to chronic liver disease, which can cause cirrhosis and death. Consequently, HCV-related end-stage liver disease is the leading indication for liver transplantation (LT). After patients undergo LT, antiviral therapy based on currently available drugs is not begun until the graft liver function becomes stable, which could take ~6 months post-LT. As a result, recurrent HCV infection is a universal problem, increasing the risk of accelerated cirrhosis, graft failure and death. Researchers from the University of Louisville have developed a chimeric antibody-like antiviral protein, Avaren-Fc lectibody, which would be infused during and after LT so that the graft liver is protected from HCV. Unlike other similar products under clinical development, Avaren-Fc lectibody is efficiently bioproduced in plants and exhibits potent inhibitory activity against HIV and cancer cells, in addition to HCV. Hence, if the safety and efficacy of Avaren-Fc isdemonstrated for the proposed use, the product may also offer a new treatment option for HIV/HCV co-infection.
Intellectual Property: Patent no. US 8802822 B2, and Patent no. US 9133252 B2